CHEMDNER_TRAIN_V01/0000755002344200234200000000000012176243316015155 5ustar mkrallingerBioinfoUnixCHEMDNER_TRAIN_V01/chemdner_abs_training.txt0000644002344200234200002261561512176224371022245 0ustar mkrallingerBioinfoUnix23104419 Transient gestational and neonatal hypothyroidism-induced specific changes in androgen receptor expression in skeletal and cardiac muscles of adult rat. The present study aims to identify the association between androgen status and metabolic activity in skeletal and cardiac muscles of adult rats with transient gestational/neonatal-onset hypothyroidism. Pregnant and lactating rats were made hypothyroid by exposing to 0.05% methimazole in drinking water; gestational exposure was from embryonic day 9-14 (group II) or 21 (group III), lactational exposure was from postnatal day 1-14 (group IV) or 29 (group V). Serum was collected for hormone assay. Androgen receptor status, Glu-4 expression, and enzyme activities were assessed in the skeletal and cardiac muscles. Serum testosterone and estradiol levels decreased in adult rats of groups II and III, whereas testosterone remained normal but estradiol increased in group IV and V, when compared to coeval control. Androgen receptor ligand binding activity increased in both muscle phenotypes with a consistent increase in the expression level of its mRNA and protein expressions except in the forelimb of adult rats with transient hypothyroidism (group II-V). Glut-4 expression remained normal in skeletal and cardiac muscle of experimental rats. Specific activity of hexokinase and lactate dehydrogenase increased in both muscle phenotypes whereas, creatine kinase activity increased in skeletal muscles alone. It is concluded that transient gestational/lactational exposure to methimazole results in hypothyroidism during prepuberal life whereas it increases AR status and glycolytic activity in skeletal and cardiac muscles even at adulthood. Thus, the present study suggests that euthyroid status during prenatal and early postnatal life is essential to have optimal AR status and metabolic activity at adulthood. 23550066 The CYP2B6*6 Allele Significantly Alters the N-demethylation of Ketamine Enantiomers In Vitro. Ketamine is primarily metabolized to norketamine by hepatic cytochrome P450 (CYP) 2B6 and CYP3A4-mediated N-demethylation. However, the relative contribution from each enzyme remains controversial. The CYP2B6*6 allele is associated with reduced enzyme expression and activity that may lead to interindividual variability in ketamine metabolism. We examined the N-demethylation of individual ketamine enantiomers using human liver microsomes (HLMs) genotyped for the CYP2B6*6 allele, insect cell expressed recombinant CYP2B6 and CYP3A4 enzymes and COS-1 cell expressed recombinant CYP2B6.1 and CYP2B6.6 protein variant. Effects of CYP-selective inhibitors on norketamine formation were also determined in HLMs. The two-enzyme Michaelis-Menten model best fitted the HLM kinetic data. The Km value for the high affinity enzyme and the low affinity enzyme were similar to those for the expressed CYP2B6 and CYP3A4, respectively. The intrinsic clearance for both ketamine enantiomers by the high affinity enzyme in HLMs with CYP2B6*1/*1 genotype were at least 2-fold and 6-fold higher, respectively, than those for CYP2B6*1/*6 genotype and CYP2B6*6/*6 genotype. The Vmax and Km values for CYP2B6.1 were approximately 160% and 70% of those for CYP2B6.6, respectively. ThioTEPA (CYP2B6 inhibitor, 25 μM) and the monoclonal antibody against CYP2B6 but not troleandomycin (CYP3A4 inhibitor, 25 μM) or the monoclonal antibody against CYP3A4 inhibited ketamine N-demethylation at clinically relevant concentrations. The degree of inhibition was significantly reduced in HLMs with the CYP2B6*6 allele (gene-dose P<0.05). These results indicate a major role of CYP2B6 in ketamine N-demethylation in vitro and a significant impact of the CYP2B6*6 allele on enzyme-ketamine binding and catalytic activity. 23164152 Metal-mediated targeting in the body. Metal ions are important for many biological processes and are steadily available in the human body. Metal concentrations can be extremely high in diseased areas of various pathological conditions. Some synthetic and natural drugs need to be activated by metal ions as prodrugs. In this review, we provide a few examples to illustrate how metal ions activate and mediate drug targeting in the body. This knowledge may be helpful for the development of more effective drugs and pharmaceutical formulations. 23477346 Follicular Variant of Papillary Thyroid Carcinoma is a Unique Clinical Entity: A Population-Based Study of 10,740 Cases. Background: Follicular variant of papillary thyroid carcinoma (FV-PTC) has been increasingly diagnosed in recent years. However, little is known about its clinical behavior. The purpose of this study was to determine the disease characteristics of FV-PTC, and to compare it with classical papillary thyroid carcinoma (C-PTC) and follicular thyroid carcinoma (FTC). Methods: All cases of C-PTC, FV-PTC and FTC larger than 1 cm in the Surveillance, Epidemiology and End Results (SEER) Cancer Database from 1988 to 2007 were identified. Tumor behavior and patient survival were compared among these three groups. Different risk factors for disease-specific mortality in each group were evaluated by multivariate analysis. Results: A total over 36,000 surgical cases were identified including 21,796 C-PTCs, 10,740 FV-PTCs and 3,958 FTCs. Extrathyroidal extension and lymph node metastases were more common in FV-PTC than in FTC, but significantly less common than in C-PTC (p<0.0001). Distant metastasis rate were present in 2% of patients with FV-PTC, 1% in C-PTC and 4% in FTC (p<0.0001). The 10-year disease-specific survival for patients with FV-PTC was 98%, similar to C-PTC (97%), but better than FTC (94%, p<0.0001). Age greater than 45 years remained a strong risk factor for disease-specific mortality in both FV-PTC and C-PTC, while the presence of extrathyroidal extension and distant metastases were stronger predictors of disease-specific mortality in FV-PTC than in C-PTC. Conclusions: FV-PTC is a common variant of PTC. Its clinical behavior is unique and represents an intermediate entity with clinical features that are between C-PTC and FTC. Interestingly, despite the variations in clinical behavior, the long-term outcome of these patients remains excellent and similar to C-PTC. 23530020 Prilocaine- and Lidocaine-induced Methemoglobinemia is Caused by Human Carboxylesterase-, CYP2E1- and CYP3A4-mediated Metabolic Activation. Prilocaine and lidocaine are classified as amide-type local anesthetics whose serious adverse effects include methemoglobinemia. Although the hydrolyzed metabolites of prilocaine (o-toluidine) and lidocaine (2,6-xylidine) have been suspected to induce methemoglobinemia, the metabolic enzymes that are involved remain uncharacterized. In the present study, we aimed to identify the human enzymes that are responsible for prilocaine- and lidocaine-induced methemoglobinemia. Our experiments revealed that prilocaine was hydrolyzed by recombinant human carboxylesterase (CES) 1A and CES2, whereas lidocaine was hydrolyzed only by human CES1A. When the parent compounds (prilocaine and lidocaine) were incubated with HLM, Met-Hb formation was lower than when the hydrolyzed metabolites were incubated with HLM. In addition, Met-Hb formation when prilocaine and o-toluidine were incubated with HLM was higher than that when lidocaine and 2,6-xylidine were incubated with HLM. Incubation with diisopropyl fluorophosphate and bis-(4-nitrophenyl) phosphate, which are general inhibitors of CES, significantly decreased Met-Hb formation when prilocaine and lidocaine were incubated with HLM. An anti-CYP3A4 antibody further decreased the residual formation of Met-Hb. Met-Hb formation following the incubation of o-toluidine and 2,6-xylidine with HLM was only markedly decreased by incubation with an anti-CYP2E1 antibody. o-Toluidine and 2,6-xylidine were further metabolized by CYP2E1 to 4- and 6-hydroxy-o-toluidine and 4-hydroxy-2,6-xylidine, respectively, and these metabolites were shown to more efficiently induce Met-Hb formation than the parent compounds. Collectively, we found that the metabolites produced by human CES-, CYP2E1- and CYP3A4-mediated metabolism were involved in prilocaine- and lidocaine-induced methemoglobinemia. 23122105 Non-target screening of Allura Red AC photodegradation products in a beverage through ultra high performance liquid chromatography coupled with hybrid triple quadrupole/linear ion trap mass spectrometry. The study deals with the identification of the degradation products formed by simulated sunlight photoirradiation in a commercial beverage that contains Allura Red AC dye. An UHPLC-MS/MS method, that makes use of hybrid triple quadrupole/linear ion trap, was developed. In the identification step the software tool information dependent acquisition (IDA) was used to automatically obtain information about the species present and to build a multiple reaction monitoring (MRM) method with the MS/MS fragmentation pattern of the species considered. The results indicate that the identified degradation products are formed from side-reactions and/or interactions among the dye and other ingredients present in the beverage (ascorbic acid, citric acid, sucrose, aromas, strawberry juice, and extract of chamomile flowers). The presence of aromatic amine or amide functionalities in the chemical structures proposed for the degradation products might suggest potential hazards to consumer health. 23494810 Spectroscopic Studies on Nicotine and Nornicotine in the UV Region. The UV absorption and electronic circular dichroism (ECD) spectra of (R)- and (S)-nicotine and (S)-nornicotine in aqueous solution were measured to a significantly lower wavelength range than previously reported, allowing the identification of four previously unobserved electronic transitions. The ECD spectra of the two enantiomers of nicotine were equal in magnitude and opposite in sign, while the UV absorption spectra were coincidental. In line with previous observations, (S)-nicotine exhibited a negative cotton effect centered on 263 nm with vibronic structure (π-π1 * transition) and a broad, positive ECD signal at around 240 nm associated with the n-π1 * transition. As expected this band disappeared when the pyridyl aromatic moiety was protonated. Four further electronic transitions are reported between 215 and 180 nm; it is proposed the negative maxima around 206 nm is either an n-σ* transition or a charge transfer band resulting from the movement of charge from the pyrrolidyl N lone pair to the pyridyl π* orbital. The pyridyl π-π2 * transition may be contained within the negative ECD signal envelope at around 200 nm. Another negative maximum at 188 nm is thought to be the pyridyl π-π3 * transition, while the lowest wavelength end-absorption and positive ECD may be associated with the π-π4 * transition. The UV absorption spectra of (S)-nornicotine was similar to that of (S)-nicotine in the range 280-220 nm and acidification of the aqueous solution enhanced the absorption. The ECD signals of (S)-nornicotine were considerably less intense compared to (S)-nicotine and declined further on acidification; in the far UV region the ECD spectra diverge considerably. Chirality 25:288-293, 2013. © 2013 Wiley Periodicals, Inc. 23567486 Variations in polyethylene glycol brands and their influence on the preparation process of hydrogel microspheres. Hydrogel microspheres, e.g. for the use as protein carriers, can be prepared without the use of organic solvents via an emulsified aqueous two-phase system (ATPS) that is based on two immiscible polymer solutions. The type and concentration of the polymers can affect the ATPS and finally the distribution of incorporated drugs between the aqueous phases. For the preparation of hydrogel microspheres based on hydroxyethyl starch-hydroxyethyl methacrylate (HES-HEMA), hydroxyethyl starch-methacrylate (HES-MA), and hydroxyethyl starch-polyethylene glycol methacrylate (HES-P(EG)6MA), polyethylene glycol 12,000 (PEG 12,000) was used as second polymer. The particle size distribution and encapsulation efficiency of the microspheres depended dramatically on the type of PEG 12,000 that was used in the second phase of the ATPS. Analysis of different PEG 12,000 brands by various methods revealed differences in the salt composition and molecular weight distribution of the polymers which can explain the results from the production process. The results illustrate that the range of product specifications may not always be tight enough to avoid variability in pharmaceutical processes like the preparation of hydrogel microspheres by an aqueous two-phase preparation process. 23639096 Bio-inspired, Calcium-free Alginate Hydrogels with Tunable Physical and Mechanical Properties and Improved Biocompatibility. Alginate hydrogels are for various biomedical applications including tissue engineering, cell therapy, and drug delivery. However, it is not easy to control swelling, or viscoelastic and biophysical properties of alginate hydrogels prepared by conventional crosslinking methods (ionic interaction using divalent cations). In this study, we describe a bio-inspired approach for preparing divalent ion-free alginate hydrogels that exhibit tunable physical and mechanical properties and improved biocompatibility due to the absence of cations in the gel matrices. We conjugated dopamine, a minimalized adhesive motif found in the holdfast pads of mussels, to alginate backbones (alginate-catechol) and the tethered catechols underwent oxidative crosslinking. This resulted in divalent cation-free alginate hydrogels. The swelling ratios and moduli of the alginate-catechol hydrogels are readily tunable, which is difficult to achieve in ionic bond-based alginate hydrogels. Furthermore, alginate-catechol hydrogels enhanced the survival of various human primary cells including stem cells in the three-dimensional gel matrix, indicating that intrinsic cytotoxicity caused by divalent cations becomes negligible when employing catechol oxidation for alginate crosslinking. The inflammatory response in vivo was also significantly attenuated compared to conventional alginate hydrogels with calcium crosslinking. This biomimetic approach for the preparation of alginate hydrogels may provide a novel platform technology to develop tunable, functional, biocompatible three-dimensional scaffolds for tissue engineering and cell therapy. 23198831 Hydrogen evolution from Pt/Ru-coated p-type WSe2 photocathodes. Crystalline p-type WSe(2) has been grown by a chemical vapor transport method. After deposition of noble metal catalysts, p-WSe(2) photocathodes exhibited thermodynamically based photoelectrode energy-conversion efficiencies of >7% for the hydrogen evolution reaction under mildly acidic conditions, and were stable under cathodic conditions for at least 2 h in acidic as well as in alkaline electrolytes. The open circuit potentials of the photoelectrodes in contact with the H(+)/H(2) redox couple were very close to the bulk recombination/diffusion limit predicted from the Shockley diode equation. Only crystals with a prevalence of surface step edges exhibited a shift in flat-band potential as the pH was varied. Spectral response data indicated effective minority-carrier diffusion lengths of ∼1 μm, which limited the attainable photocurrent densities in the samples to ∼15 mA cm(-2) under 100 mW cm(-2) of Air Mass 1.5G illumination. 23376090 Exposure to an organochlorine pesticide (chlordecone) and development of 18-month-old infants. Chlordecone is a persistent organochlorine pesticide that was used in the French West Indies until the early 1990s for banana weevil borer control. Human exposure to this chemical in this area still occurs nowadays due to consumption of contaminated food. Although adverse effects on neurodevelopment, including tremors and memory deficits, have been documented in experimental studies conducted with rodents exposed during the gestational and neonatal periods, no study has been conducted yet to determine if chlordecone alters child development. This study examines the relation of gestational and postnatal exposure to chlordecone to infant development at 18 months of age in a birth-cohort of Guadeloupean children. In a prospective longitudinal study conducted in Guadeloupe (Timoun mother-child cohort study), exposure to chlordecone was measured at birth from an umbilical cord blood sample (n=141) and from a breast milk sample collected at 3 months postpartum (n=75). Toddlers were assessed using an adapted version of the Ages and Stages Questionnaire. Higher chlordecone concentrations in cord blood were associated with poorer fine motor scores. When analyses were conducted separately for boys and girls, this effect was only observed among boys. These results suggest that prenatal exposure to chlordecone is associated with specific impairments in fine motor function in boys, and add to the growing evidence that exposure to organochlorine pesticides early in life impairs child development. 23530033 The Hyaluronan Receptor for Endocytosis (HARE) activates NF-κB mediated gene expression in response to 40-400 kDa, but not smaller or larger, hyaluronan. The Hyaluronan (HA) Receptor for Endocytosis (HARE) binds and clears 14 different ligands, including HA and heparin, via clathrin-mediated endocytosis. HA binding to HARE stimulates ERK1/2 activation (Kyosseva et al. J. Biol. Chem. 283, 15047, 2008). To assess a possible HA size-dependence for signaling, we tested purified HA fractions of different weight-average molar mass (Mw) and with narrow size distributions and Select-HA for stimulation of HARE-mediated gene expression using an NF-κB promoter-driven luciferase reporter system. Human HARE-mediated gene expression was stimulated in a dose-dependent manner with small HA (SHA) >40 kDa and intermediate HA (IHA) <400 kDa. The hyperbolic dose-response saturated at 20-50 nM with an apparent Km ~10 nM, identical to the Kd for HA-HARE binding. Activation was not detected with oligomeric HA (OHA), SHA <40 kDa, IHA >400 kDa or large HA (LHA). Similar responses occurred with rat HARE. Activation by SHA-IHA was blocked by excess nonsignaling SHA, IHA or LHA, deletion of the HA-binding LINK domain, or HA-blocking antibody. Endogenous NF-κB activation also occurred in the absence of luciferase plasmids, as assessed by degradation of IκB-α. ERK1/2 activation was also HA-size dependent. The results show that HA-HARE interactions stimulate NF-κB activated gene expression and that HARE senses a narrow size-range of HA degradation products. We propose a model in which optimal length HA binds multiple HARE proteins to allow cytoplasmic domain interactions that stimulate intracellular signaling. This HARE signaling system during continuous HA clearance could monitor the homeostasis of tissue biomatrix turnover throughout the body. 23223708 Hydrophobic asymmetric ultrafiltration PVDF membranes: an alternative separator for VFB with excellent stability. Polyvinylidene fluoride (PVDF) ultrafiltration membranes were investigated for the first time in vanadium redox flow battery (VFB) applications. Surprisingly, PVDF ultrafiltration membranes with hydrophobic pore walls and relatively large pore sizes of several tens of nanometers proved able to separate vanadium ions and protons efficiently, thus being suitable as a VFB separator. The ion selectivity of this new type of VFB membrane could be tuned readily by controlling the membrane morphology via changes in the composition of the membrane casting solution, and the casting thickness. The results showed that the PVDF membranes offered good performances and excellent stability in VFB applications, where it could, performance-wise, truly substitute Nafion in VFB applications, but at a much lower cost. 23499423 EBF2 Determines and Maintains Brown Adipocyte Identity. The master transcription factor Pparγ regulates the general differentiation program of both brown and white adipocytes. However, it has been unclear whether Pparγ also controls fat lineage-specific characteristics. Here, we show that early B cell factor-2 (Ebf2) regulates Pparγ binding activity to determine brown versus white adipocyte identity. The Ebf DNA-binding motif was highly enriched within brown adipose-specific Pparγ binding sites that we identified by genome-wide ChIP-Seq. Of the Ebf isoforms, Ebf2 was selectively expressed in brown relative to white adipocytes and was bound at brown adipose-specific Pparγ target genes. When expressed in myoblasts or white preadipose cells, Ebf2 recruited Pparγ to its brown-selective binding sites and reprogrammed cells to a brown fat fate. Brown adipose cells and tissue from Ebf2-deficient mice displayed a loss of brown-specific characteristics and thermogenic capacity. Together, these results identify Ebf2 as a key transcriptional regulator of brown fat cell fate and function. 23429043 Estimation of the safe use concentrations of the preservative 1,2-benzisothiazolin-3-one (BIT) in consumer cleaning products and sunscreens. 1,2-Benzisothiazolin-3-one (BIT; CAS # 2634-33-5) is a preservative used in consumer products. Dermal exposure to BIT at sufficient dose and duration can produce skin sensitization and allergic contact dermatitis in animals and susceptible humans.The purpose of this study is to derive a maximal concentration of BIT in various consumer products that would result in exposures below the No Expected Sensitization Induction Level (NESIL), a dose below which skin sensitization should not occur. A screening level exposure estimate was performed for several product use scenarios with sunscreen, laundry detergent, dish soap, and spray cleaner. We calculated that BIT concentrations below the following concentrations of 0.0075%, 0.035%, 0.035%, 0.021% in sunscreen, laundry detergent, dish soap, and spray cleaner, respectively, are unlikely to induce skin sensitization. We completed a pilot study consisting of bulk sample analysis of one representative product from each category labelled as containing BIT, and found BIT concentrations of 0.0009% and 0.0027% for sunscreen and dish soap, respectively. BIT was not detected in the laundry detergent and spray cleaner products above the limit of detection of 0.0006%. Based on publically available data for product formulations and our results, we were able to establish that cleaning products and sunscreens likely contain BIT at concentrations similar to or less than our calculated maximal safe concentrations and that exposures are unlikely to induce skin sensitization in most users. 23371488 Effect of wheel-running during abstinence on subsequent nicotine-seeking in rats. RATIONALE: Exercise appears to be a promising non-pharmacological treatment for nicotine addiction that may be useful for the vulnerable adolescent population. OBJECTIVES: The aim of this study is to determine if wheel-running, an animal model of aerobic exercise, during an abstinence period would decrease subsequent nicotine-seeking in rats that had extended access to nicotine self-administration during adolescence. METHODS: Male adolescent rats (n = 55) were trained to self-administer saline or nicotine infusions (5 or 10 μg/kg) under a fixed ratio 1 schedule with a maximum of 20 infusions/day beginning on postnatal day 30. After 5 days, access was extended to 23 h/day with unlimited infusions for a total of 10 days. After the last self-administration session, rats were moved to polycarbonate cages for a 10-day abstinence period where they either had access to a locked or unlocked running wheel for 2 h/day. Nicotine-seeking was examined following the 10th day of abstinence under a within-session extinction/cue-induced reinstatement paradigm. RESULTS: Intake was higher at the 10 μg/kg dose as compared to the 5 μg/kg dose; however, intake did not differ within doses prior to wheel assignment. Compared to saline controls, rats that self-administered nicotine at either dose showed a significant increase in drug-seeking during extinction, and consistent with our hypothesis, exercise during abstinence attenuated this effect. Nicotine led to modest but significant levels of cue-induced reinstatement; however, in this adolescent-onset model, levels were variable and not affected by exercise. CONCLUSIONS: Exercise may effectively reduce relapse vulnerability for adolescent-onset nicotine addiction. 23454299 Prediction and characterization of the linear IgE epitopes for the major soybean allergen β-conglycinin using immunoinformatics tools. The α subunit of β-conglycinin is a major allergen in soybean. The objective of this study was to predict and identify the linear immunoglobulin (Ig)E epitopes of the soybean α subunit of β-conglycinin. Three immunoinformatics tools were used to predict the potential epitopes and were confirmed by dot-blot inhibition using sera from soybean allergic subjects. As a result, 15 peptides were predicted and assembled by solid-phase synthesis. Eleven epitopes were identified by the dot-blot inhibition test. Moreover, peptide 3 had IgE binding capability with all sera(5/5) tested, while peptide 1, 4, 6, 8 and12 could bind to 4/5 of the sera samples. Secondary structure prediction of peptide 3 and circular dichroism test validated that the structure of peptide 3 was a random coil. 23537597 Antioxidant and micronutrient-rich milk formula reduces lead poisoning and related oxidative damage in lead-exposed mice. Lead poisoning is a global environmental disease that induces lifelong adverse health effects. The effect of a milk formula consisting of antioxidant of bamboo leaves (AOB), vitamin C (Vc), calcium lactate (CaLac), ferrous sulfate (FeSO4) and zinc sulfate (ZnSO4) on the reduction of lead and lead-induced oxidative damage in lead-exposed mice was studied. The lead-reducing effect of milk formula was investigated via a 7-week toxicokinetics study and a tissue distribution level examination. The ameliorating effect of milk formula on lead-induced oxidative damage was investigated. Results demonstrated current milk formula could effectively reduce blood lead levels (BLLs) and lead distribution levels of liver, kidneys, thighbones and brain in mice based on metal ion-mediated antagonism and chelation mechanisms. This milk formula could not only protect lead-susceptible tissues against lead poisoning, but also maintain normal absorption and distribution of essential elements in vivo. Meanwhile, current milk formula could prevent the reduction of δ-aminolevulinic acid dehydratase (δ-ALAD) activity and enhancement of free erythrocyte protoporphyrins (FEP) levels in blood erythrocytes of mice. Also, this formula could indirectly protect blood cell membranes against lead-induced lipid peroxidation. We conclude that current optimized milk formula effectively reduces lead poisoning and lead-induced in vivo oxidative damage in lead-exposed mice. 23511311 SEVERE HYPOGLYCEMIC EPISODES: A PERSISTENT THREAT FOR CHILDREN WITH TYPE 1 DIABETES MELLITUS AND THEIR FAMILIES. Background: As lowering HbA1c levels is still the main goal of insulin treatment, severe hypoglycaemia (SH) remains a common experience in children with type 1 diabetes mellitus (T1DM) and their families. Aim: This study aims to evaluate the incidence and the clinical features of SH episodes in our Centre in the last 20 years. Subjects and Methods: We analysed SH incidence in 269 patients diagnosed from 1990 to 2010 (total follow-up 2212.9 patient-years). Inclusion criteria: at least 3 visits/year and 1 year of follow-up. SH episode was defined as any condition of low blood glucose requiring third-party assistance. Results: 50.2% of patients experienced at least 1 SH episode for a total of 345 episodes. Whole incidence was 15.6/100 pts/yr, slightly different between first and second decade (12.6 vs 16.5, p=0.047). HbA1c at the time of SH was lower in the non-BB group (7.4±1.3 vs 8.2±1.4; p=0.0001) and worsened 3 months later (p=0.0001). Impaired awareness was the main or only symptom in 43.5%. SH occurred at night in 32% of patients and they were significantly younger than those with SH at other times. 5 SH episodes or more occurred in 8.1% of patients who presented a lower HbA1c, a younger age and shorter disease duration than the other patients. HbA1c at first SH was negatively correlated with number of SH (r=-0.20; p=0.05). Conclusions: Despite the advent of new insulin regimens, we confirm that SH still represents a relevant risk and a current threat for patients with T1DM and their families. 23568512 Toxicokinetics of acrylamide in primary rat hepatocytes: coupling to glutathione is faster than conversion to glycidamide. Acrylamide (AA), classified as class 2A carcinogen (probably carcinogenic to humans) by the International Agency for Research on Cancer (IARC), is formed during heating of food from reducing carbohydrates and asparagine by Maillard reaction chemistry. After dietary uptake, AA is in part metabolically converted into the proximate genotoxic phase I metabolite glycidamide (GA). GA reacts with nucleophilic base positions in DNA, primarily forming N7-(2-carbamoyl-2-hydroxyethyl)guanine (N7-GA-Gua) adducts. In a competing phase II biotransformation pathway AA, as well as its phase I metabolite GA, is coupled to glutathione (GSH). The GSH coupling products are further biotransformed and excreted via urine as mercapturic acids (MA), N-acetyl-S-(2-carbamoylethyl)cysteine (AAMA), and N-acetyl-S-(2-hydroxy-2-carbamoylethyl)cysteine (GAMA). In the present study, hepatic biotransformation pathways and DNA adduct formation were studied in primary rat hepatocytes, incubated with AA (0.2-2,000 μM) for up to 24 h. Contents of AA-GSH, GA, AAMA, and GAMA were measured in the cell culture medium after solid phase extraction (SPE). N7-GA-Gua adducts in DNA of hepatocytes were determined by HPLC-ESI-MS/MS after lysis of the cells and neutral thermal hydrolysis. Formation of AA-GSH was linear with AA concentration and incubation time and became detectable already at 0.2 μM (4 h). In contrast to AA, GA was not detected before 16 h incubation at 10-fold higher AA concentration (2 μM). In summary, the rate of AA-GSH formation was found to be about 1.5-3 times higher than that of GA formation. N7-GA-Gua adducts were found only at the highest AA concentration tested (2,000 μM). 23632158 Attack of the nervous system by Clostridium perfringens Epsilon toxin: From disease to mode of action on neural cells. Epsilon toxin (ET), produced by Clostridium perfringens types B and D, ranks among the four most potent poisonous substances known so far. ET-intoxication is responsible for enterotoxaemia in animals, mainly sheep and goats. This disease comprises several manifestations indicating the attack of the nervous system. This review aims to summarize the effects of ET on central nervous system. ET binds to endothelial cells of brain capillary vessels before passing through the blood-brain barrier. Therefore, it induces perivascular oedema and accumulates into brain. ET binding to different brain structures and to different component in the brain indicates regional susceptibility to the toxin. Histological examination has revealed nerve tissue and cellular lesions, which may be directly or indirectly caused by ET. The naturally occurring disease caused by ET-intoxication can be reproduced experimentally in rodents. In mice and rats, ET recognizes receptor at the surface of different neural cell types, including certain neurons (e.g. the granule cells in cerebellum) as well as oligodendrocytes, which are the glial cells responsible for the axons myelination. Moreover, ET induces release of glutamate and other transmitters, leading to firing of neural network. The precise mode of action of ET on neural cells remains to be determined. 23462380 Non-front-fanged colubroid snakes: A current evidence-based analysis of medical significance. Non-front-fanged colubroid snakes (NFFC; formerly and artificially taxonomically assembled as "colubrids") comprise about 70% of extant snake species and include several taxa now known to cause lethal or life threatening envenoming in humans. Although the medical risks of bites by only a handful of species have been documented, a growing number of NFFC are implicated in medically significant bites. The majority of these snakes have oral products (Duvernoy's secretions, or venoms) with unknown biomedical properties and their potential for causing harm in humans is unknown. Increasingly, multiple NFFC species are entering the commercial snake trade posing an uncertain risk. Published case reports describing NFFC bites were assessed for evidence-based value, clinical detail and verified species identification. These data were subjected to meta-analysis and a hazard index was generated for select taxa. Cases on which we consulted or personally treated were included and subjected to the same assessment criteria. Cases involving approximately 120 species met the selection criteria, and a small subset designated Hazard Level 1 (most hazardous), contained 5 species with lethal potential. Recommended management of these cases included antivenom for 3 species, Dispholidus typus, Rhabdophis tiginis, Rhabdophis subminiatus, whereas others in this subset without commercially available antivenoms (Thelotornis spp.) were treated with plasma/erythrocyte replacement therapy and supportive care. Heparin, antifibrinolytics and/or plasmapheresis/exchange transfusion have been used in the management of some Hazard Level 1 envenomings, but evidence-based analysis positively contraindicates the use of any of these interventions. Hazard Level 2/3 species were involved in cases containing mixed quality data that implicated these taxa (e.g. Boiga irregularis, Philodryas olfersii, Malpolon monspessulanus) with bites that caused rare systemic effects. Recommended management may include use of acetylcholinesterase inhibitors (e.g. neostigmine) and wound care on a case-by-case basis. Hazard level 3 species comprised a larger group capable of producing significant local effects only, often associated with a protracted bite (eg Heterodon nasicus, Borikenophis (Alsophis) portoricensis, Platyceps (Coluber) rhodorachis). Management is restricted to wound care. Bites by Hazard level 4 species comprised the majority of surveyed taxa and these showed only minor effects of no clinical importance. This study has produced a comprehensive evidence-based listing of NFFC snakes tabulated against medical significance of bites, together with best-practice management recommendations. This analysis assumes increasing importance, as there is growing exposure to lesser-known NFFC snakes, particularly in captive collections that may uncover further species of significance in the future. Careful and accurate documentation of bites by verified species of NFFC snakes is required to increase the evidence base and establish the best medical management approach for each species. 23463336 Effects of dried Citrus unshiu peels on gastrointestinal motility in rodents. Aqueous extracts of the dried mature (ANP-W) and immature Citrus unshiu peels (CUP-W) have been used as a traditional folk medicine for the treatment of gastrointestinal (GI) motility disorders in Korea. In the present study, neither ANP-W nor CUP-W exhibited significant toxicity even at an oral dose of 5 g/kg to mice. The effects of ANP-W and CUP-W on GI motor function were investigated by measuring the intestinal transit rate (ITR) of Evans blue in normal mice and rats with experimental GI motility dysfunctions (GMDs). In normal mice, the ITR was significantly increased by ANP-W (0.1-1 g/kg) in a dose dependent manner, whereas CUP-W elicited no significant change. GMD was induced by appropriate surgery or an intraperitoneal injection of acetic acid to the rats. The ITR in the GMD rats was significantly retarded compared to that in normal rats. However, the retardation was significantly inhibited by ANP-W (0.1-1 g/kg) in a dose dependent manner. The above results suggest that ANP-W has the potential for development as a prokinetic agent that may prevent or alleviate GMD in human patients. 23497898 Stability of sunflower 2S albumins and LTP to physiologically relevant in vitro gastrointestinal digestion. In order for a protein to elicit a systemic allergic response it must reach the circulatory system through the intestinal mucosa as a sufficiently large fragment with adequate structural integrity. Sunflower LTP and 2S albumins (SFA8 and three mixed fractions of Alb1 and Alb2) were digested in simulated gastric fluid (SGF) for 2h and the conditions were then changed to mimic the intestinal environment for a further 2h digestion. The effects of phosphatidylcholine (PC) and emulsification on the digestibility of the proteins were investigated. PC protected all of the proteins studied against both gastric and intestinal digestive enzymes but to different extents. Emulsification of SFA8 resulted in strong protection against digestion, which was further enhanced by the presence of PC in the SGF. These results highlight the importance of considering real food structures such as emulsified systems and also the gastrointestinal environment that proteins are exposed to once consumed when assessing allergenicity. 23122085 Discrimination against diacylglycerol ethers in lipase-catalysed ethanolysis of shark liver oil. Lipase-catalysed ethanolysis of squalene-free shark liver oil was investigated. The mentioned shark liver oil was comprised mainly of diacylglycerol ether and triacylglycerols. In order to test discrimination against diacylglycerol ether, up to 10 different lipases were compared. The ratio of oil to ethanol and lipase stability were also evaluated. Surprisingly, lipase from Pseudomonas stutzeri was the fastest biocatalyst among all assayed, although poor discrimination against diacylglycerol ether was observed. The best results in terms of selectivity and stability were obtained with immobilised lipase from Candida antarctica (Novozym 435). Ethanolysis reaction after 24h in the presence of Novozym 435 produced total disappearance of triacylglycerol and a final reaction mixture comprised mainly of diacylglycerol ethers (10.6%), monoacylglycerol ethers (32.9%) and fatty acid ethyl esters (46.0%). In addition, when an excess of ethanol was used, diacylglycerol ethers completely disappeared after 15 h, giving a final product mainly composed of monoacylglycerol ethers (36.6%) and fatty acid ethyl esters (46.4%). 23250357 The effect of a bile acid sequestrant on glucose metabolism in subjects with type 2 diabetes. We designed an experiment to examine the effect of bile acid sequestration with Colesevelam on fasting and postprandial glucose metabolism in type 2 diabetes. To do so, we tested the hypothesis that Colesevelam increases the disposition index (DI), and this increase is associated with increased glucagon-like peptide-1 (GLP-1) concentrations. Thirty-eight subjects on metformin monotherapy were studied using a double-blind, placebo-controlled, parallel-group design. Subjects were studied before and after 12 weeks of Colesevelam or placebo using a labeled triple-tracer mixed meal to measure the rate of meal appearance (Meal Ra), endogenous glucose production (EGP), and glucose disappearance (Rd). Insulin sensitivity and β-cell responsivity indices were estimated using the oral minimal model and then used to calculate DI. Therapy with Colesevelam was associated with a decrease in fasting (7.0 ± 0.2 vs. 6.6 ± 0.2 mmol/L; P = 0.004) and postprandial glucose concentrations (3,145 ± 138 vs. 2,896 ± 127 mmol/6 h; P = 0.01) in the absence of a change in insulin concentrations. Minimal model-derived indices of insulin secretion and action were unchanged. Postprandial GLP-1 concentrations were not altered by Colesevelam. Although EGP and Rd were unchanged, integrated Meal Ra was decreased by Colesevelam (5,191 ± 204 vs. 5,817 ± 204 μmol/kg/6 h; P = 0.04), suggesting increased splanchnic sequestration of meal-derived glucose. 23334583 Effects of aging on apoptosis gene expression in oral mucosal tissues. Apoptotic processes are important for physiologic renewal of an intact epithelial barrier and contribute some antimicrobial resistance for bacteria and viruses, as well as anti-inflammatory effects that benefits the mucosa. The oral cavity presents a model of host-bacterial interactions at mucosal surfaces, in which a panoply of microorganisms colonizes various niches in the oral cavity and creates complex multispecies biofilms that challenge the gingival tissues. This report details gene expression in apoptotic pathways that occur in oral mucosal tissues across the lifespan, using a nonhuman primate model. Macaca mulatta primates from 2 to 23 years of age (n = 23) were used in a cross-sectional study to obtain clinical healthy gingival tissues specimens. Further, mRNA was prepared and evaluated using the Affymetrix Rhesus GeneChip and 88 apoptotic pathway genes were evaluated. The results identified significant positive correlations with age in 12 genes and negative correlations with an additional five genes. The gene effects were predicted to alter apoptosis receptor levels, extrinsic apoptotic pathways through caspases, cytokine effects on apoptotic events, Ca(+2)-induced death signaling, cell cycle checkpoints, and potential effects of survival factors. Both the positively and negatively correlated genes within the apoptotic pathways provided evidence that healthy tissues in aging animals exhibit decreased apoptotic potential compared to younger animals. The results suggested that decreased physiologic apoptotic process in the dynamic septic environment of the oral mucosal tissues could increase the risk of aging tissues to undergo destructive disease processes through dysregulated inflammatory responses to the oral microbial burden. 23493569 Adipose Tissue Macrophages Function as Antigen Presenting Cells and Regulate Adipose Tissue CD4+ T Cells in Mice. The pro-inflammatory activation of leukocytes in adipose tissue contributes to metabolic disease. How crosstalk between immune cells initiates and sustains adipose tissue inflammation remains an unresolved question. We have examined the hypothesis that adipose tissue macrophages (ATMs) interact with and regulate the function of T cells. Dietary obesity was shown to activate the proliferation of effector memory CD4(+) T cells in adipose tissue. Our studies further demonstrate that ATMs are functional antigen presenting cells that promote the proliferation of IFN-γ producing CD4(+) T cells in adipose tissue. ATMs from both lean and obese visceral fat process and present MHC class II-restricted antigens. ATMs were sufficient to promote proliferation and IFN-γ production from antigen-specific CD4(+) T cells in vitro and in vivo. Diet-induced obesity increased the expression of MHC II and T cell costimulatory molecules on ATMs in visceral fat, which correlated with an induction of T cell proliferation in that depot. Collectively, these data indicate that ATMs provide a functional link between the innate and adaptive immune systems within visceral fat in mice. 23085994 Actinin-4 in keratinocytes regulates motility via an effect on lamellipodia stability and matrix adhesions. During wound repair, epidermal cells at the edge of an injury establish front-rear polarity through orchestrated changes in their cytoskeleton and adhesion structures. The polarity and directed migration of such cells is determined by the assembly, extension, and stabilization of a lamellipodium. Actinin-4 associates with lamellipodia and has been implicated in regulating lamellipodial structure, function and assembly. To study the functions of actinin-4 in human keratinocytes, we used shRNA to generate knockdown cells and compared their motility behavior and matrix adhesion assembly to scrambled shRNA treated control keratinocytes. Actinin-4 knockdown keratinocytes lack polarity, assemble multiple lamellipodia with a 2× increased area over controls, display reduced activity of the actin remodeling protein cofilin, and fail to migrate in a directional manner. This motility defect is rescued by plating knockdown cells on preformed laminin-332 matrix. In actinin-4-knockdown keratinocytes, focal contact area is increased by 25%, and hemidesmosome proteins are mislocalized. Specifically, α6β4 integrin localizes to large lamellipodial extensions, displays reduced dynamics, and fails to recruit its bullous pemphigoid antigen binding partners. Together, our data indicate a role for actinin-4 in regulating the steering mechanism of keratinocytes via profound effects on their matrix adhesion sites. 23214926 Total synthesis of AMF-26, an antitumor agent for inhibition of the Golgi system, targeting ADP-ribosylation factor 1. An effective method for the total synthesis of 1 (AMF-26), a potentially promising new anticancer drug that disrupts the Golgi system by inhibiting the ADP-ribosylation factor 1 (Arf1) activation, has been developed for the first time. The construction of the chiral linear precursor (a key to the synthesis) was achieved by the asymmetric aldol reaction followed by the computer-assisted predictive stereoselective intramolecular Diels-Alder reaction. The global antitumor activity of the totally synthetic 1 against a variety of human cancer cells was assessed using a panel of 39 human cancer cell lines (JFCR39), and it was shown that the synthetic 1 strongly inhibited the growth of several cancer cell lines at concentrations of less than 0.04 μM. Biological assays of novel derivatives, 26 and 31, which have different side-chains at the C-4 positions in the Δ¹,²-octalin backbone, disclosed the importance of the suitable structure of the side-chain containing conjugated multidouble bonds. 22728761 D-Serine facilitates the effectiveness of extinction to reduce drug-primed reinstatement of cocaine-induced conditioned place preference. Addiction is a disease that is characterized by compulsive drug-seeking and use despite negative health and social consequences. One obstacle in treating addiction is a high susceptibility for relapse which persists despite prolonged periods of abstinence. Relapse can be triggered by drug predictive stimuli such as environmental context and drug associated cues, as well as the addictive drug itself. The conditioned place preference (CPP) behavioral model is a useful paradigm for studying the ability of these drug predictive stimuli to reinstate drug-seeking behavior. The present study investigated the dose-dependent effects of D-serine (10 mg/kg, 30 mg/kg and 100 mg/kg) on extinction training and drug-primed reinstatement in cocaine-conditioned rats. In the first experiment, D-serine had no effect on the acquisition or development of cocaine-induced locomotor sensitization or CPP. In the second experiment, D-serine treatment resulted in significantly decreased time spent in the drug-paired compartment following completion of an extinction protocol. A cocaine-primed reinstatement test indicated that the combination of extinction training along with D-serine treatment resulted in a significant reduction of drug-seeking behavior. The third experiment assessed D-serine's long-term effects to diminish drug-primed reinstatement. D-serine treatment given during extinction was effective in reducing drug-seeking for more than four weeks of abstinence after the last cocaine exposure. These findings demonstrate that D-serine may be an effective adjunct therapeutic agent along with cognitive behavioral therapy for the treatment of cocaine addiction. This article is part of a Special Issue entitled 'Cognitive Enhancers'. 23229055 Microwave synthesis, characterization and bio-efficacy evaluation of novel chalcone based 6-carbethoxy-2-cyclohexen-1-one and 2H-indazol-3-ol derivatives. Novel chalcone based 6-carbethoxy-2-cyclohexen-1-one and 2H-indazol-3-ol derivatives were synthesized and characterized by using spectral techniques like IR, (1)H NMR, (13)C NMR, COSY, DEPT, and GC-MS. All these compounds were screened for anti-fungal, anti-bacterial and anti-oxidant activity. Cyclohexenone derivatives, in general, showed better anti-fungal and anti-bacterial activity than parent chalcones. Whereas, all the Indazole derivatives showed very good anti-oxidant activity and some were also found to be active as anti-bacterial agent. Among the screened compounds, 15 was found to be most active as anti-fungal agent (against Rhizoctonia solani, LC(50) = 2.36 μg mL(-1)), 15b was found to be most active anti-bacterial agent (against Klebsiella pneumonia, MIC = 24.68 μg mL(-1)) and 14b emerged as most active anti-oxidant (IC(50) = 19.81 μg mL(-1)). 23474382 Multiple dosing of simvastatin inhibits airway mucus production of epithelial cells: Implications in the treatment of chronic obstructive airway pathologies. BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by mucus hyper-production. This pathology, together with other inflammatory contributions, leads to airway obstruction and breathing complications. Newer therapeutic approaches are of increased interest, including the use of HMG-CoA reductase inhibitors. Retrospective studies have shown that statins are effective in reducing patient mortality and blood cytokines levels. These findings suggest statins may also provide a new therapeutic approach in COPD treatment. PURPOSE: The aim of the present work was to study the transport of SV across Calu-3 epithelial cells and to investigate its pharmacological action with respect to reduction in mucus production. METHODS: Calu-3 cells were grown under liquid covered culture (LCC) conditions for transport studies in order to demonstrate the ability of SV to transport across the monolayer. For mucus detection, cells were grown under air interface culture (AIC) conditions. Samples collected for microscope analysis were stained with alcian blue; images of the stained cell surface were acquired and the mucus was quantified as the RGBB ratio. RESULTS: SV was transported through the cell monolayer and 'retained' inside the Calu-3 cells. Colour analysis of stained Calu-3 monolayers microscope-images showed that chronic administration of SV for 14days caused a significant inhibition in mucus production. CONCLUSION: These findings suggest that local delivery of SV directly to the lungs may provide a promising treatment and potential disease management approach of COPD, with significant effects on mucus reduction. 23193183 Transferability and fine mapping of type 2 diabetes loci in African Americans: the Candidate Gene Association Resource Plus Study. Type 2 diabetes (T2D) disproportionally affects African Americans (AfA) but, to date, genetic variants identified from genome-wide association studies (GWAS) are primarily from European and Asian populations. We examined the single nucleotide polymorphism (SNP) and locus transferability of 40 reported T2D loci in six AfA GWAS consisting of 2,806 T2D case subjects with or without end-stage renal disease and 4,265 control subjects from the Candidate Gene Association Resource Plus Study. Our results revealed that seven index SNPs at the TCF7L2, KLF14, KCNQ1, ADCY5, CDKAL1, JAZF1, and GCKR loci were significantly associated with T2D (P < 0.05). The strongest association was observed at TCF7L2 rs7903146 (odds ratio [OR] 1.30; P = 6.86 × 10⁻⁸). Locus-wide analysis demonstrated significant associations (P(emp) < 0.05) at regional best SNPs in the TCF7L2, KLF14, and HMGA2 loci as well as suggestive signals in KCNQ1 after correction for the effective number of SNPs at each locus. Of these loci, the regional best SNPs were in differential linkage disequilibrium (LD) with the index and adjacent SNPs. Our findings suggest that some loci discovered in prior reports affect T2D susceptibility in AfA with similar effect sizes. The reduced and differential LD pattern in AfA compared with European and Asian populations may facilitate fine mapping of causal variants at loci shared across populations. 23614652 Conversion of Aristolochic Acid I into Aristolic Acid by Reaction with Cysteine and Glutathione: Biological Implications. Aristolochic acid I (AA-I), naturally occurring in Aristolochia plants, is a potent nephrotoxin and carcinogen. Here we report that AA-I suffers hydrogenolysis with loss of the nitro group by reaction with cysteine or glutathione to give aristolic acid. Since the reaction can proceed in aqueous solutions at pH 7.0 and 37 °C, it is inferred that it may also occur in biological systems and contribute to the nephrotoxic effects induced by AA-I. 23355489 Ataxia telangiectasia mutated (ATM) is dispensable for endonuclease I-SceI-induced homologous recombination in mouse embryonic stem cells. Ataxia telangiectasia mutated (ATM) is activated upon DNA double strand breaks (DSBs) and phosphorylates numerous DSB response proteins, including histone H2AX on serine 139 (Ser-139) to form γ-H2AX. Through interaction with MDC1, γ-H2AX promotes DSB repair by homologous recombination (HR). H2AX Ser-139 can also be phosphorylated by DNA-dependent protein kinase catalytic subunit and ataxia telangiectasia- and Rad3-related kinase. Thus, we tested whether ATM functions in HR, particularly that controlled by γ-H2AX, by comparing HR occurring at the euchromatic ROSA26 locus between mouse embryonic stem cells lacking either ATM, H2AX, or both. We show here that loss of ATM does not impair HR, including H2AX-dependent HR, but confers sensitivity to inhibition of poly(ADP-ribose) polymerases. Loss of ATM or H2AX has independent contributions to cellular sensitivity to ionizing radiation. The ATM-independent HR function of H2AX requires both Ser-139 phosphorylation and γ-H2AX/MDC1 interaction. Our data suggest that ATM is dispensable for HR, including that controlled by H2AX, in the context of euchromatin, excluding the implication of such an HR function in genomic instability, hypersensitivity to DNA damage, and poly(ADP-ribose) polymerase inhibition associated with ATM deficiency. 23624862 Coordinated conformational and compositional dynamics drive ribosome translocation. During translation elongation, the ribosome compositional factors elongation factor G (EF-G; encoded by fusA) and tRNA alternately bind to the ribosome to direct protein synthesis and regulate the conformation of the ribosome. Here, we use single-molecule fluorescence with zero-mode waveguides to directly correlate ribosome conformation and composition during multiple rounds of elongation at high factor concentrations in Escherichia coli. Our results show that EF-G bound to GTP (EF-G-GTP) continuously samples both rotational states of the ribosome, binding with higher affinity to the rotated state. Upon successful accommodation into the rotated ribosome, the EF-G-ribosome complex evolves through several rate-limiting conformational changes and the hydrolysis of GTP, which results in a transition back to the nonrotated state and in turn drives translocation and facilitates release of both EF-G-GDP and E-site tRNA. These experiments highlight the power of tracking single-molecule conformation and composition simultaneously in real time. 23444833 Isolation, Structure Elucidation, and Iron-Binding Properties of Lystabactins, Siderophores Isolated from a Marine Pseudoalteromonas sp. The marine bacterium Pseudoalteromonas sp. S2B, isolated from the Gulf of Mexico after the Deepwater Horizon oil spill, was found to produce lystabactins A, B, and C (1-3), three new siderophores. The structures were elucidated through mass spectrometry, amino acid analysis, and NMR. The lystabactins are composed of serine (Ser), asparagine (Asn), two formylated/hydroxylated ornithines (FOHOrn), dihydroxy benzoic acid (Dhb), and a very unusual nonproteinogenic amino acid, 4,8-diamino-3-hydroxyoctanoic acid (LySta). The iron-binding properties of the compounds were investigated through a spectrophotometric competition. 23208007 Polysialic acid enhances the migration and invasion of human cytotrophoblasts. Polysialic acid (polySia) is a large, cell-surface linear homopolymer composed of α2,8-linked sialic acid residues. Most extensively studied in the nervous system, this unique glycan modulates development by enhancing cell migration and regulating differentiation. PolySia also functions in developing and adult immune systems and is a signature of many cancers. In this study, we demonstrated that human placental trophoblasts, an epithelial lineage, also display this glycan. Cytotrophoblasts and syncytiotrophoblasts expressed polySia in the first trimester and downregulated it during the course of pregnancy. PolySia promoted cytotrophoblast migration in an explant model of chorionic villous growth. Removal of this glycan also reduced cytotrophoblast penetration of basement membranes in an in vitro model of invasion. Finally, we showed that polySia was overexpressed in biopsies from patients with gestational trophoblastic diseases, including benign molar pregnancies and malignant choriocarcinomas. These results demonstrated, for the first time, functional roles for polySia during normal human placental development and implicated these unusual oligosaccharides in the unrestrained invasion of trophoblast tumors. 22991234 Acute effect of calcium citrate on serum calcium and cardiovascular function. Calcium supplements have been associated with an increased risk of cardiovascular events. However, the validity of these findings has been questioned. A major concern is that the mechanism underlying an increase in cardiovascular events has not been demonstrated. Calcium initiates cardiac and vascular contraction following influx of calcium into cardiac and smooth muscle from extracellular fluid. We have investigated whether the acute rise in serum calcium following calcium supplement administration is associated with adverse changes in cardiovascular function. In an open interventional study, we recruited 25 volunteers (16 female, age 60.3 ± 6.5 years, body mass index 25.7 ± 2.7 kg/m2) from the community who were not taking calcium supplements. Participants were studied before and 3 hours after a single oral dose of 1000 mg calcium citrate. We assessed well-validated markers of arterial stiffness (pulse wave velocity [PWV]), arterial wave reflection (augmentation index [AIx]), and myocardial perfusion (subendocardial viability ratio [SEVR]) by pulse wave analysis and endothelial function (reactive hyperemia index [RHI]) by peripheral arterial tonometry. Total and ionized serum calcium were acutely increased by 0.10 ± 0.07 and 0.06 ± 0.03 mmol/L, respectively, 3 hours after calcium citrate administration (p < 0.0001 for both comparisons). Following administration of calcium citrate there was a fall in AIx from a median of 29.7% (23.8% to 34.0%) to 26.4% (22.7% to 34.0%, p = 0.03) and an increase in SEVR from 163% (148% to 174%) to 170% (149% to 185%, p = 0.007). PWV and RHI were not significantly altered. The change in total calcium was negatively correlated with the change in AIx (r = -0.48, p = 0.02). In summary, the acute increase in serum calcium following calcium supplement administration is associated with reduced arterial wave reflection and a marker of increased myocardial perfusion. If maintained long-term, these changes would be expected to reduce cardiovascular risk. Acute serum calcium-mediated changes in these parameters of cardiovascular function are unlikely to underlie an association between calcium supplementation and cardiovascular events. 23256503 Ballistic InAs nanowire transistors. Ballistic transport of electrons at room temperature in top-gated InAs nanowire (NW) transistors is experimentally observed and theoretically examined. From length dependent studies, the low-field mean free path is directly extracted as ~150 nm. The mean free path is found to be independent of temperature due to the dominant role of surface roughness scattering. The mean free path was also theoretically assessed by a method that combines Fermi's golden rule and a numerical Schrödinger-Poisson simulation to determine the surface scattering potential with the theoretical calculations being consistent with experiments. Near ballistic transport (~80% of the ballistic limit) is demonstrated experimentally for transistors with a channel length of ~60 nm, owing to the long mean free path of electrons in InAs NWs. 23429282 Sources of secondary metabolite variation in Dysidea avara (Porifera: Demospongiae): the importance of having good neighbors. Several studies report temporal, geographical, and intra-individual variation in sponge metabolite yields. However, the internal and/or external factors that regulate the metabolite production remain poorly understood. Dysidea avara is a demosponge that produces sesquiterpenoids (avarol and derivatives) with interesting medical properties, which has prompted addressed studies to obtain enough amounts of these metabolites for research on drug discovery. Within this framework, specimens of Dysidea avara from a population of the Northwest Mediterranean were sampled and their secondary metabolites quantified to assess their variability and the possible relationship with external (seasonality, interactions with neighbors) and internal (reproductive stages) factors. The results show a variation of the amount of both avarol and its monoacetate derivative with time, with no clear relationship with seawater temperature. A trade-off with sponge reproduction was not found either. However, our results showed for the first time that sponges are able to increase production or accumulation of secondary metabolites in their peripheral zone depending on the nature of their neighbors. This finding could explain part of the high variability in the amount of secondary metabolites usually found in chemical ecology studies on sponges and opens new biotechnological approaches to enhance the metabolite yield in sponge cultures. 23418059 Forty-seven days of decay does not change persistent organic pollutant levels in loggerhead sea turtle eggs. Reptile and bird eggs are priority samples for specimen banking programs that assess spatial and temporal trends of environmental contaminants. From endangered species, such as sea turtles, nonlethal sampling is required (e.g., unhatched eggs collected postemergence). Previous contaminant monitoring studies have used unhatched sea turtle eggs, but no study has tested whether their concentrations represent levels found in fresh eggs (e.g., eggs collected within 24 h of oviposition). The author analyzed three fresh eggs from different nest depths and up to three unhatched eggs from 10 loggerhead sea turtle (Caretta caretta) nests in South Carolina, USA, for a suite of persistent organic pollutants (POPs). Lipid-normalized POP concentrations were not significantly different (p > 0.05) between fresh and unhatched eggs or among different depths from the same nest. The POP concentrations in loggerhead eggs from South Carolina were higher than previously measured concentrations in eggs from Florida and slightly lower than concentrations in eggs from North Carolina. This pattern agrees with previously observed trends of increasing POP concentrations in loggerhead turtles inhabiting northern latitudes along the U.S. East Coast. Contaminant profiles are discussed, including a higher chlorinated pattern of polychlorinated biphenyls possibly associated with a Superfund site in nearby Brunswick, Georgia, USA, and unusual polybrominated diphenylether patterns seen in this and previous sea turtle studies. Concentrations correlated with one of eight measurements of reproductive success; levels were negatively correlated with egg mass (p < 0.05), which may have implications for hatchling fitness. The present study suggests that unhatched eggs can be used for POP-monitoring projects. 23214990 Protein adsorption mechanisms determine the efficiency of thermally controlled cell adhesion on poly(N-isopropyl acrylamide) brushes. This study investigated the impact of the protein adsorption mechanism(s) on the efficiency of thermally controlled cell adhesion and release from poly(N-isopropyl acrylamide) brushes. Large format polymer gradients were used to screen for grafting densities and substrate chemistries that alter both cell adhesion at 37 °C and rapid cell release at 25 °C. In particular, the grafting conditions investigated allowed protein adsorption to the underlying substrate, penetration of the brush only, or adsorption to the outer edge of the film. At an average molecular weight of 30 kDa (degree of polymerization N ∼ 270), the results show that robust protein adsorption to polymer brushes impairs rapid cell release below the lower critical solution temperature. Conversely, grafting conditions that permit protein penetration of the brush but block strong adsorption to the underlying substrate support cell adhesion above the transition temperature and ensure efficient cell recovery at lower temperature. These findings demonstrate the impact of protein adsorption mechanisms, surface chemistry, and polymer properties on thermally controlled cell capture and release. 23524195 Compound promiscuity: what can we learn from current data? The specificity paradigm that assigns central relevance to achieving target specificity of drug candidates has recently been revisited. Evidence is mounting that polypharmacological drug behavior is often responsible for therapeutic efficacy suggesting the consideration of new drug development strategies. Target promiscuity of compounds is at the origin of polypharmacology. For many bioactive compounds, multiple target annotations are available indicating that compound promiscuity is a general phenomenon. However, careful analysis of compound activity data reveals that the degree of apparent promiscuity is strongly influenced by data selection criteria and the type of activity measurements that are considered. Furthermore, promiscuity involving unrelated targets is less common. Apparent target promiscuity might often better be interpreted as activity promiscuity in different assays. 23588312 A DPYD Variant (Y186C) in Individuals of African Ancestry Is Associated With Reduced DPD Enzyme Activity. 5-Fluorouracil (5-FU) is used to treat many aggressive cancers, such as those of the colon, breast, and head and neck. The responses to 5-FU, with respect to both toxicity and efficacy, vary among racial groups, potentially because of variability in the activity levels of the enzyme dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene). In this study, the genetic associations between DPYD variations and circulating mononuclear-cell DPD enzyme activity were evaluated in 94 African-American and 81 European-American volunteers. The DPYD-Y186C variant was unique to individuals of African ancestry, and DPD activity was 46% lower in carriers as compared with noncarriers (279 ± 35 vs. 514 ± 168 pmol 5-FU min(-1) mg(-1); P = 0.00029). In this study, 26% of the African Americans with reduced DPD activity were carriers of Y186C. In the African-American cohort, after excluding Y186C carriers, homozygous carriers of C29R showed 27% higher DPD activity as compared with noncarriers (609 ± 152 and 480 ± 152 pmol 5-FU min(-1) mg(-1), respectively; P = 0.013).Clinical Pharmacology & Therapeutics (2013); advance online publication 1 May 2013. doi:10.1038/clpt.2013.69. 23554335 Vibrational sum-frequency generation activity of a 2,4-dinitrophenyl phospholipid hybrid bilayer: retrieving orientational parameters from a DFT analysis of experimental data. The vibrational nonlinear activity of films of 2,4-dinitrophenyl phospholipid (DNP) at the solid interface is measured by sum-frequency generation spectroscopy (SFG). Hybrid bilayers are formed by a Langmuir-Schaefer approach in which the lipid layer is physisorbed on top of a self-assembled monolayer of dodecanethiol on Pt with the polar heads pointing out from the surface. The SFG response is investigated in two vibrational frequency domains, namely, 3050-2750 and 1375-1240 cm(-1) . The first region probes the CH stretching modes of DNP films, and the latter explores the vibrational nonlinear activity of the 2,4-dinitroaniline moiety of the polar head of the lipid. Analysis of the CH stretching vibrations suggests substantial conformational order of the aliphatic chains with only a few gauche defects. To reliably assign the detected SFG signals to specific molecular vibrations, DFT calculations of the IR and Raman activities of molecular models are performed and compared to experimental solid-state spectra. This allows unambiguous assignment of the observed SFG vibrations to molecular modes localized on the 2,4-dinitroaniline moiety of the polar head of DNP. Then, SFG spectra of DNP in the 1375-1240 cm(-1) frequency range are simulated and compared with experimental ones, and thus the 1,4-axis of the 2,4-dinitrophenyl head is estimated to have tilt and rotation angles of 45±5° and 0±30°, respectively. 23095244 Subacute effects of ecstasy on mood: an exploration of associated risk factors. Ecstasy use may result in lowered mood, anxiety or aggression in the days following use. Yet, few studies have investigated what factors increase the risk of experiencing such symptoms. Ecstasy users (at least once in the last 12 months) who subsequently took ecstasy (n=35) over the period of one week, were compared on measures of mood, sleep, stress and drug use, with those who abstained from ecstasy (n=21) that week. Measures were administered the week prior to ecstasy use and one and three days following use, or the equivalent day for abstainers. Mood symptoms were assessed using the Kessler-10 self-report psychological distress scale, a subjective mood rating (1-10), and using the depression, anxiety and hostility items from the clinician-rated Brief Psychiatric Rating Scale. Timeline Followback methods were used to collect information on drug use and life stress in the past month. Self-reported sleep quality was also assessed. Ecstasy use was not associated with subacute depressive, anxiety or aggressive symptoms. Rather, lowered mood and increased psychological distress were associated with self-reported hours and quality of sleep obtained during the three-day follow-up. These findings highlight the importance of considering sleep disruption in understanding the short-term mood effects of ecstasy use. 23443165 Regulation of Translation Initiation under Biotic and Abiotic Stresses. Plants have developed versatile strategies to deal with the great variety of challenging conditions they are exposed to. Among them, the regulation of translation is a common target to finely modulate gene expression both under biotic and abiotic stress situations. Upon environmental challenges, translation is regulated to reduce the consumption of energy and to selectively synthesize proteins involved in the proper establishment of the tolerance response. In the case of viral infections, the situation is more complex, as viruses have evolved unconventional mechanisms to regulate translation in order to ensure the production of the viral encoded proteins using the plant machinery. Although the final purpose is different, in some cases, both plants and viruses share common mechanisms to modulate translation. In others, the mechanisms leading to the control of translation are viral- or stress-specific. In this paper, we review the different mechanisms involved in the regulation of translation initiation under virus infection and under environmental stress in plants. In addition, we describe the main features within the viral RNAs and the cellular mRNAs that promote their selective translation in plants undergoing biotic and abiotic stress situations. 23282576 A micro-cantilever sensor chip based on contact angle analysis for a label-free troponin I immunoassay. Cantilever sensors have been extensively explored as a promising technique for real-time and label-free analyses in biological systems. A major sensing principle utilized by state-of-the-art cantilever sensors is based on analyte-induced surface stress changes, which result in static bending of a cantilever. The sensor performance, however, suffers from the intrinsically small change in surface stress induced by analytes, especially for molecular recognition such as antigen-antibody binding. Through the contact angle change on a tailored solid surface, it is possible to convert a tiny surface stress into a capillary force-a much larger physical quantity needed for a practical sensor application. In this work, a micro-cantilever sensor based on contact angle analysis (CAMCS) was proposed to effectively enhance the sensitivity of a sensor in proportion to the square of the length to thickness ratio of the cantilever structure. CAMCS chips were fabricated using a standard complementary-metal-oxide-semiconductor (CMOS) process to demonstrate a 1250-fold enhancement in the sensitivity of surface stress to bioanalyte adsorption using a piezoresistive sensing method. A real-time and label-free troponin I (cTnI) immunoassay, which is now widely used in clinics and considered a gold standard for the early diagnosis and prognosis of cardiovascular disease, was performed to demonstrate cTnI detection levels as low as 1 pg mL(-1). The short detection time of this assay was within several minutes, which matches the detection time of commercially available instruments that are based on fluorescence-labeling techniques. 23581993 Engineering bacterial efflux pumps for solar-powered bioremediation of surface waters. Antibiotics are difficult to selectively remove from surface waters by present treatment methods. Bacterial efflux pumps have evolved the ability to discriminately expel antibiotics and other noxious agents via proton and ATP driven pathways. Here, we describe light-dependent removal of antibiotics by engineering the bacterial efflux pump AcrB into a proteovesicle system. We have created a chimeric protein with the requisite proton motive force by coupling AcrB to the light-driven proton pump Delta-rhodopsin (dR) via a glycophorin A transmembrane domain. This creates a solar powered protein material capable of selectively capturing antibiotics from bulk solutions. Using environmental water and direct sunlight, our AcrB-dR vesicles removed almost twice as much antibiotic as the treatment standard, activated carbon. Altogether, the AcrB-dR system provides an effective means of extracting antibiotics from surface waters as well as potential antibiotic recovery through vesicle solubilization. 23210790 Plant metabolomics: from holistic data to relevant biomarkers. Metabolomics is playing an increasingly important role in plant science. It aims at the comprehensive analysis of the plant metabolome which consists both of primary and secondary metabolites. The goal of metabolomics is ultimately to identify and quantify this wide array of small molecules in biological samples. This new science is included in several systems biology approaches and is based primarily on the unbiased acquisition of mass spectrometric (MS) or nuclear magnetic resonance (NMR) data from carefully selected samples. This approach provides the most ''functional'' information of the 'omics' technologies of a given organism since metabolites are the end products of the cellular regulatory processes. The application of state-of-the-art data mining, that includes various untargeted and targeted multivariate data analysis methods, to the vast amount of data generated by this data-driven approach leads to sample classification and the identification of relevant biomarkers. The biological areas that have been successfully studied by this holistic approach include global metabolite composition assessment, mutant and phenotype characterisation, taxonomy, developmental processes, stress response, interaction with the environment, quality control assessment, lead finding and mode of action of botanicals. This review summarises the main MS- and NMR-based approaches that are used to perform these studies and discusses the potential and current limitations of the various methods. The intent is not to provide an exhaustive overview of the field, which has grown considerably over the past decade, but to summarise the main strategies that are used and to discuss the potential and limitations of the different approaches as well as future trends. 23335565 Mimicking native extracellular matrix with phytic Acid-crosslinked protein nanofibers for cardiac tissue engineering. A functional scaffold fabricated is developed from natural polymers, favoring regeneration of the ischemic myocardium. Hemoglobin/gelatin/fibrinogen (Hb/gel/fib) nanofibers are fabricated by electrospinning and are characterized for morphology, scaffold composition, functional groups and hydrophilicity. It is hypothesized that ex vivo pretreatment of mesenchymal stem cells (MSCs) using 5-azacytidine and such a functional nanofibrous construct having a high oxygen-carrying potential could lead to enhanced cardiomyogenic differentiation of MSCs and result in superior biological and functional effects. The combination of a functional nanofibrous scaffold composed of natural polymers and crosslinked with a natural crosslinking agent, phytic acid, and stem cell biology may prove to be a novel therapeutic device for treatment of myocardial infarction. 23258742 A three-generational study of In ovo exposure to PBDE-99 in the zebra finch. Based on a literature review of avian data for polybrominated diphenyl ethers (PBDEs), ecologically relevant doses, low (10 ng/egg), medium (100 ng/egg), and high (1,000 ng/egg) of the 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) congener along with dimethylsulfoxide (DMSO) control were injected into the yolk sac of un-incubated eggs of zebra finch, Taeniopygia guttata. Offspring development and adult phenotype were followed over three generations. No effects of in ovo PBDE exposure on hatching success, chick growth, thyroid hormone levels, or hematological traits were measured at sexual maturity (90 d posthatching). However, the authors did detect significant effects of BDE-99 treatment on adult phenotype of in ovo-exposed birds by breeding observations, in which clutch size was significantly smaller in all PBDE-dosed birds (low, medium, and high) compared with controls. A trend was also seen for longer laying intervals in PBDE-dosed birds (13-14 d) compared with control birds (8 d). In addition, a significant effect of PBDE was found on growth of the second-generation offspring of in ovo-treated females; body mass was significantly lower in the high-PBDE dosed birds compared with controls from hatch through to fledging (day 30). The authors found no evidence of effects over the longer term and in successive generations, whether in adult, reproductive phenotype of the second-generation offspring of in ovo-treated birds, or in the growth of their (third-generation) offspring. Their results suggest that egg levels as low as 10 ng/g BDE-99 may affect reproduction in small passerines by reducing clutch size. 23252421 Lightweight and strong cellulose materials made from aqueous foams stabilized by nanofibrillated cellulose. A lightweight and strong porous cellulose material has been prepared by drying aqueous foams stabilized with surface-modified nanofibrillated cellulose (NFC). This material differs from other dry, particle stabilized foams in that renewable cellulose is used as stabilizing particles. Confocal microscopy and high speed video imaging show that the octylamine-coated, rod-shaped NFC nanoparticles residing at the air-liquid interface prevent the air bubbles from collapsing or coalescing. Stable wet foams can be achieved at solids content around 1% by weight. Careful removal of the water results in a cellulose-based material with a porosity of 98% and a density of 30 mg cm(-3). These porous cellulose materials have a higher Young's modulus than porous cellulose materials made from freeze-drying, at comparable densities, and have a compressive energy absorption of 56 kJ m(-3) at 80% strain. Measurement with the aid of an autoporosimeter revealed that most pores are in the range of 300 to 500 μm. 22836881 Hospitalized osteoporotic vertebral fracture increases the risk of stroke: a population-based cohort study. The association between osteoporosis and cardiovascular diseases has been demonstrated. Higher cardiovascular risk has also been correlated with vertebral fractures. However, the association between osteoporotic vertebral fracture and the possibly higher risk of stroke remains uncertain. This study aimed to evaluate the incidence, risk, and type of stroke in patients with osteoporotic vertebral fracture. Patients with osteoporotic vertebral fracture were identified (n = 380) and 10 age- and sex-matched controls per case (comparison group, n = 3795) were chosen from a nationwide representative cohort of 999,997 people from 1998 to 2005. Both groups were followed-up for stroke events for 3 years, matched by propensity scores with adjustments for covariates such as comorbidities (ie, hypertension, diabetes, arrhythmia, or coronary heart diseases) and exposure to medications (ie, aspirin, lipid lowering drug, or nitrates), and assessed by Kaplan-Meier and Cox regression analyses. The incidence rate of stroke in the osteoporotic vertebral fracture group (37.5 per 1000 person-years; 95% confidence interval [CI], 27.5-51.2) was significantly higher than in the comparison group (14.0 per 1000 person-years; 95% CI, 12.0-16.4, p < 0.001). Stroke was more likely to occur in the osteoporotic vertebral fracture patients than in the normal controls (crude hazard ratio [HR] 2.68, 95% CI 1.89-3.79, p < 0.001; adjusted HR 2.71, 95% CI 1.90-3.86, p < 0.001). In conclusion, patients with osteoporotic vertebral fracture have a higher risk of stroke (ie, both ischemic and hemorrhagic) and require stroke prevention strategies. 23044047 The early mouse 3D osteocyte network in the presence and absence of mechanical loading. Osteocytes are considered to act as mechanosensory cells in bone. They form a functional synctia in which their processes become interconnected to constitute a three-dimensional (3D) network. Previous studies reported that in mice, the two-dimensional osteocyte network becomes progressively more regular as they grow, although the key factors governing the arrangement of the osteocyte network during bone growth remain unknown. In this study, we characterized the 3D formation of the osteocyte network during bone growth. Morphological skeletal changes have been reported to occur in response to mechanical loading and unloading. In order to evaluate the effect of mechanical unloading on osteocyte network formation, we subjected newborn mice to sciatic neurectomy in order to immobilize their left hind limb as an unloading model. The osteocyte network was visualized by staining osteocyte cell bodies and processes with fluorescently labeled phalloidin. First, we compared the osteocyte network in the femora of embryonic and 6-week-old mice in order to understand the morphological changes that occur with normal growth and mechanical loading. In embryonic mice, the osteocyte network in the femur cortical bone displayed a random cell body distribution, non-directional orientation of cell processes, and irregularly shaped cells. In 6-week-old mice, the 3D network contained spindle-shaped osteocytes, which were arranged parallel to the longitudinal axis of the femur. In addition, more and longer cell processes radiated from each osteocyte. Second, we compared the cortical osteocyte networks of 6-week-old mice that had or had not undergone sciatic neurectomy in order to evaluate the effect of unloading on osteocyte network formation. The osteocyte network formation in both cortical bone and cancellous bone was affected by mechanical loading. However, there were differences in the extent of network formation between cortical bone and cancellous bone in response to mechanical loading with regard to the orientation, nuclear shape and branch formation. 23418674 Development of a cell-based high-throughput peroxisome proliferator-activated receptors (PPARs) screening model and its application for evaluation of the extracts from Rhizoma Coptis. To date, peroxisome proliferator-activated receptors (PPARs) are becoming the new therapeutic targets for the treatment of metabolic diseases, such as Type 2 diabetes, obesity, and cardiovascular disease. In this study, a cell-based high-throughput PPARs (PPARα/β/γ) model was developed for the screening of PPARs agonists. The screening conditions were evaluated through analyzing the expression value of luciferase. Finally, 24 h of drug acting time, 5 times of the dilution factor of luciferase zymolyte, and about 2 × 10(4) cells/ well on HeLa cells in 96-well plates were used, respectively. Furthermore, the quality of high-throughput screening (HTS) in stability and reliability was evaluated by the Z'-factor. Additionally, different extracts of Rhizoma Coptis and berberine were tested by the developed method. The results suggested that both the EtOAc extract and berberine were able to activate PPARα/β/γ, and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. In conclusion, the developed HTS assay is a simple, rapid, stable, and specific method for the screening of PPARs natural agonists. 23518040 The life history of a botulinum toxin molecule. There is an emerging literature describing the absorption, distribution, metabolism and elimination of botulinum toxin. This work reveals that the toxin can be absorbed by both the oral and inhalation routes. The primary mechanism for absorption is binding and transport across epithelial cells. Toxin that enters the body undergoes a distribution phase, which is quite short, and an elimination phase, which is comparatively long. During the distribution phase, botulinum toxin migrates to the peri-neuronal microcompartment in the vicinity of vulnerable cells, such as cholinergic nerve endings. Only these cells have the ability to selectively accumulate the molecule. When the toxin moves from the cell membrane to the cell interior, it undergoes programmed death. This is coincident with release of the catalytically active light chain that paralyzes transmission. Intraneuronal metabolism of light chain is via the ubiquitination-proteasome pathway. Systemic metabolism and elimination is assumed to be via the liver. The analysis of absorption, distribution, metabolism and elimination of the toxin helps to create a life history of the molecule in the body. This has many benefits, including: a) clarifying the mechanisms that underlie the disease botulism, b) providing insights for development of medical countermeasures against the toxin, and c) helping to explain the meaning of a lethal dose of toxin. It is likely that work intended to enhance understanding of the fate of botulinum toxin in the body will intensify. These efforts will include new and powerful analytic tools, such as single molecule-single cell analyses in vitro and real time, 3-dimensional pharmacokinetic studies in vivo. 23500334 Sphaerospora sensu stricto: Taxonomy, diversity and evolution of a unique lineage of myxosporeans (Myxozoa). Myxosporeans (Myxozoa) are eukaryotic parasites, primarily of fish, whose classification is in a state of flux as taxonomists attempt to synthesize the traditional morphology-based system with emerging DNA sequence-based phylogenies. The genus Sphaerospora Thélohan, 1892, which includes pathogenic species that cause significant impacts on fisheries and aquaculture, is one of the most polyphyletic taxa and exemplifies the current challenges facing myxozoan taxonomists. The type species, S. elegans, clusters within the Sphaerospora sensu stricto clade, members of which share similar tissue tropism and long insertions in their variable rRNA gene regions. However, other morphologically similar sphaerosporids lie in different branches of myxozoan phylogenetic trees. Herein, we significantly extend taxonomic sampling of sphaerosporids with SSU+LSU rDNA and EF-2 sequence data for 12 taxa including three representatives of the morphologically similar genus Polysporoplasma Sitjà-Bobadilla et Álvarez-Pellitero, 1995. These taxa were sampled from different vertebrate host groups, biogeographic realms and environments. Our phylogenetic analyses and statistical tests of single and concatenated datasets revealed Sphaerospora s. s. as a strongly supported monophyletic lineage, that clustered sister to the whole myxosporean clade (freshwater+marine lineages). Generally, Sphaerospora s. s. rDNA sequences (up to 3.7kb) are the longest of all myxozoans and indeed metazoans. The sphaerosporid clade has two lineages, which have specific morphological, biological and sequence traits. Lineage A taxa (marine Sphaerospora spp.) have a single binucleate sporoplasm and shorter AT-rich rDNA inserts. Lineage B taxa (freshwater/brackish Sphaerospora spp.+marine/brackish Polysporoplasma spp.) have 2-12 uninucleate sporoplasms and longer GC-rich rDNA inserts. Lineage B has four subclades that correlate with host group and habitat; all Polysporoplasma species, including the type species, cluster together in one of these subclades. We thus suppress the genus Polysporoplasma and the family Polysporoplasmidae and emend the generic diagnosis of the genus Sphaerospora. The combination of morphological, biological and DNA sequence data applied in this study helped to elucidate an important part of the taxonomic puzzle within the phylum Myxozoa. 23528390 Antibacterial action of quinolones: From target to network. Quinolones are widely used broad-spectrum antibacterials with incomplete elucidated mechanism of action. Here, molecular basis for the antibacterial action of quinolones, from target to network, is fully discussed and updated. Quinolones trap DNA gyrase or topoisomerase IV to form reversible drug-enzyme-DNA cleavage complexes, resulting in bacteriostasis. Cell death arises from chromosome fragmentation in protein synthesis-dependent or -independent pathways according to distinguished quinolone structures. In the former pathway, irreversible oxidative DNA damage caused by reactive oxygen species kills bacteria eventually. Toxin-antitoxin mazEF is triggered as an additional lethal action. Bacteria survive and develop resistance by SOS and other stress responses. Enlarged knowledges of quinolone actions and bacterial response will provide new targets for drug design and approaches to prevent bacterial resistance. 23545458 Total saponins of Panax notoginseng enhance VEGF and relative receptors signals and promote angiogenesis derived from rat bone marrow mesenchymal stem cells. ETHNOPHARMACOLOGICAL RELEVANCE: Total saponins of Panax notoginseng (tPNS), main constituents extracted from Panax Notoginseng, a highly valued traditional Chinese medicine, has been shown to increase protein expression and the secretion of vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells. AIMS OF THE STUDY: The effects of tPNS on angiogenesis were studied in rat bone marrow mesenchymal stem cells (rBMSCs). MATERIALS AND METHODS: rBMSCs were stimulated by tPNS of 48h. The mRNA expression levels of VEGF-A, Flt-1 and Kdr in rBMSCs were determined by quantitative real time PCR (qRT-PCR). rBMSCs were induced to differentiate into endothelial-like cells and the effects of tPNS on the angiogenesis ability of rBMSCs and rBMSCs after endothelial differentiation were assayed by a Matrigel model in vivo and in vitro. RESULTS: tPNS (100μg/ml) significantly enhanced the mRNA expression level of VEGF-A and Kdr compared to the control group, while they had no obvious effect on the expression of Flt-1. tPNS (1μg/ml and 100μg/ml) significantly increased capillary network forming of rBMSCs after endothelial differentiation in Matrigel in vitro. tPNS (50μg/kg, 100μg/kg and 150μg/kg) also significantly increased angiogenesis induced by the combination with implantation of rBMSCs and Matrigel in vivo. CONCLUSION: tPNS up-regulate VEGF-A and Kdr expression, and promote angiogenesis in rat bone marrow mesenchymal stem cells. 23320521 Novel antiviral activity of l-dideoxy bicyclic nucleoside analogues versus vaccinia and measles viruses in vitro. Dideoxy bicyclic pyrimidine nucleoside analogues (ddBCNAs) with d-chirality have previously been described by us to inhibit replication of human cytomegalovirus. We herein report for the first time that activity against vaccinia virus (VACV) was achieved using novel l-analogues. A structure-activity relationship was established: Antiviral activity versus VACV was highest with an ether side chain with an optimum of n-C(9)H(18)-O-n-C(5)H(11). This gave an IC(50) of 190 nM, a 60-fold enhancement over the FDA-approved antiviral cidofovir. Interestingly, l-ddBCNAs also inhibit wild type measles virus syncytia formation with a TCID(50) of 7.5 μM for the lead compound. We propose that l-ddBCNAs represent significant innovative antiviral candidates versus measles and poxviruses, and we suggest a mechanism of action versus one or more cellular targets that are essential for viral replication. 23511016 Synthesis of a DOTA (Gd(3+))-conjugate of proton-pump inhibitor pantoprazole for gastric wall imaging studies. Magnetic resonance imaging (MRI) is used to evaluate gastrointestinal (GI) structure and functions in humans. Despite filling the viscus lumen with a contrast agent, visualization of the viscus wall is limited. To overcome this limitation, we de novo synthesized a conjugate that covalently combines a Gd-based MRI contrast agent, encaged with a chelating agent (DOTA), with pantoprazole, which is a widely used proton pump inhibitor that binds to proton pumps in the stomach and colon. The DOTA linkage was installed at a mechanism-based strategic location in the pantoprazole molecule to minimize a possible negative effect of the structural modification on the drug. It is anticipated that by defining the wall of the stomach and colon, this compound will facilitate functional MRI of the GI tract in humans. 23537661 Effects of lactational and/or in utero exposure to environmental contaminants on the glucocorticoid stress-response and DNA methylation of the glucocorticoid receptor promoter in male rats. Perinatal events can reprogram the hypothalamo-pituitary-adrenal axis for the entire lifespan leading to abnormal glucocorticoid stress-response (GSR) in adulthood: a phenomenon reported to be mediated by changes in DNA methylation of the glucocorticoid receptor (GR) gene promoter. We examined whether in utero and/or lactational exposure to mixtures of environmental contaminants can also induce abnormal GSR during adulthood. The experiment included nine treatment groups. From gestation day (GD) 0 until postnatal day (PND) 20, dams were fed daily with a cookie laced with corn oil (control) or a chemical mixture (M) [polychlorinated biphenyls (PCBs), organochlorine pesticides, and methylmercury] at 0.5 or 1.0mg/kg/day (0.5M, and M). At birth, some control (C) and M litters were cross-fostered to create four groups with the following in utero/postnatal exposure: C/C, M/C, C/M, M/M. Other dams received 1.8ng/kg/day of a mixture of aryl hydrocarbon receptor (AhR) agonists (non-ortho PCBs, PC-dibenzodioxins and PC-dibenzofurans) without or with 0.5M (0.5MAhR). In adult male offspring the abundance of GR in treated groups was not different from the control, but the AhR and M groups were significantly different from each other with opposite effects in the hippocampus and liver. There was no change in DNA methylation of the GR promoter (exon-17 and -110). Abnormal GSRs were detected in the AhR, 0.5MAhR, CM, and MM groups. The literature associates abnormal GSR with metabolic and mental health impairments, thus these results support further investigation of the influence of developmental exposure to environmental contaminants and predisposition to stress-induced diseases. 23416326 Levels of PAH-DNA adducts in placental tissue and the risk of fetal neural tube defects in a Chinese population. We examined the relationship between PAH-DNA adduct levels in the placental tissue, measured by a highly sensitive (32)P-postlabeling assay, and the risk of fetal neural tube defects (NTDs). We further explored the interaction between PAH-DNA adducts and placental PAHs with respect to NTD risk. Placental tissues from 80 NTD-affected pregnancies and 50 uncomplicated normal pregnancies were included in this case-control study. Levels of PAH-DNA adducts were lower in the NTD group (8.12 per 10(8) nucleotides) compared to controls (9.92 per 10(8) nucleotides). PAH-DNA adduct concentrations below the median was associated with a 3-fold increased NTD risk. Women with a low PAH-DNA adduct level in concert with a high placental PAH level resulted in a 10-fold elevated risk of having an NTD-complicated pregnancy. A low level of placental PAH-DNA adducts was associated with an increased risk of NTDs; this risk increased dramatically when a low adduct level was coupled with a high placental PAH concentration. 23311700 Poorly differentiated thyroid carcinoma presenting with gross extrathyroidal extension: 1986-2009 Memorial Sloan-Kettering Cancer Center experience. To describe the outcome of patients with poorly differentiated thyroid cancer (PDTC) presenting with gross extrathyroidal extension (ETE). After IRB approval we performed retrospective review of consecutive series of thyroid cancer patients treated by primary surgical resection with or without adjuvant therapy at MSKCC from 1986-2009. Out of 91 PDTC patients, 27 (30%) had gross ETE (T4a) and they formed the basis of our study. Of 27 patients, 52% were female. The median age was 70 (range 27-87). Ten patients (37%) presented with distant metastases; four to the bone, three to lung and three had both bone and lung metastases. All patients had extended total thyroidectomy except two who had subtotal thyroidectomy. 20 patients (74%) had central compartment neck dissection and 11 also had lateral neck dissection. Four patients had pN0, 6 (30%) pN1a and 10 (50%) pN1b neck disease. 21 patients (77%) had adjuvant therapy: 15 (55%) RAI only, 3 (11%) postoperative external beam radiation (PORT) only and 3 (11%) had both RAI and PORT. Overall survival (OS), disease specific survival (DSS), local recurrence free survival (LRFS) and regional recurrence free survival (RRFS) were calculated by the Kaplan Meier method. Median follow-up time was 57 months (range 1-197 months). The 5 year OS and DSS were 47% and 49% respectively. This poor outcome was due to distant metastatic disease; 10 patients had distant metastases at presentation and a further 6 developed distant metastases during follow up. Locoregional control was good with 5 year LRFS and RRFS of 70% and 62% respectively. Overall, 8 patients (30%) had recurrences: 2 had distant alone, 2 regional, 2 regional and distant, 1 local and distant, and 1 had local, regional and distant recurrence. Aggressive surgery in patients with PDTC showing gross ETE resulted in satisfactory locoregional control. Due to the small proportion of patients who received PORT (22%), it is not possible to analyze its benefit on locoregional control. Of significance is the observation that the majority of patients (60%) who presented with or subsequently developed distant metastases eventually died of distant disease. New systemic therapies to target distant metastatic disease are required for improvements in outcome. 23474972 Energetic contribution to hydration shells in one-dimensional aqueous electrolyte solution by anomalous hydrogen bonds. The hydration structure of NaCl aqueous solution was elucidated in carbon nanotubes (CNTs) on the basis of canonical ensemble Monte Carlo simulations. Hydration shells were preferentially formed even in narrow CNTs to gain stabilization energy, whereas hydrogen bonding between water molecules in such CNTs was sacrificed. Nanoscale-confined aqueous electrolyte solutions therefore prioritize hydration shell formation between ions and water rather than hydrogen-bond formation between water molecules. 23357311 Introducing new dimensions in MIA-QSAR: A case for chemokine receptor inhibitors. Multivariate image analysis applied to quantitative structure-activity relationships (MIA-QSAR) is a very simple correlative method that uses pixels (binaries) of chemical structures built from 2D viewer programs as descriptors; structural changes correspond to different pixel coordinates, which explain the variance in the bioactivities block. The MIA-QSAR method has shown to be predictive and capable of encoding some chemical information, but introduction of more descriptive information, such as atom size and colors to differentiate atom types, would improve predictability and interpretability. The bioactivities of a series of chemokine receptor (CCR2) inhibitors have been modeled using both conventional and atom color/size-dependent MIA-QSAR (namely aug-MIA-QSAR); the latter showed to be better. Moreover, the results were comparable to those obtained by 3D methodologies, indicating that 2D shape and substituent size are more significant descriptors than the conformational profiles required by field fit techniques. 23588316 Regulatory and Scientific Issues Regarding Use of Foreign Data in Support of New Drug Applications in the United States: An FDA Perspective. Globalization of clinical research has led to an increase in clinical trials conducted outside of the United States that are submitted to the US Food and Drug Administration (FDA) in new drug applications. This article discusses the FDA's experience with these submissions in specific therapeutic areas, including the extent of this practice, differences between the effectiveness and safety outcomes of studies conducted inside and outside the United States, and the FDA's approach to acceptance of these trials.Clinical Pharmacology & Therapeutics (2013); advance online publication 1 May 2013. doi:10.1038/clpt.2013.70. 22838394 Three new diarylbutane lignans from the resin of Bursera fagaroides. Three new diarylbutane lignans, named 9-acetyl-9'-pentadecanoil-dihydroclusin (1), 2,3-demethoxy-secoisolintetralin monoacetate (4) and dihydroclusin monoacetate (5), have been isolated from the resin of Bursera fagaroides, together with two known ones, 2,3-demethoxy-secoisolintetralin diacetate (2) and dihydroclusin diacetate (3). The complete structure assignments were obtained by means of (1)H and (13)C NMR spectra. 23085368 In vivo-in vitro comparison of acute respiratory tract toxicity using human 3D airway epithelial models and human A549 and murine 3T3 monolayer cell systems. The usefulness of in vitro systems to predict acute inhalation toxicity was investigated. Nineteen substances were tested in three-dimensional human airway epithelial models, EpiAirway™ and MucilAir™, and in A549 and 3T3 monolayer cell cultures. IC(50) values were compared to rat four-hour LC(50) values classified according to EPA and GHS hazard categories. Best results were achieved with a prediction model distinguishing toxic from non-toxic substances, with satisfactory specificities and sensitivities. Using a self-made four-level prediction model to classify substances into four in vitro hazard categories, in vivo-in vitro concordance was mediocre, but could be improved by excluding substances causing pulmonary edema and emphysema in vivo. None of the test systems was outstanding, and there was no evidence that tissue or monolayer systems using respiratory tract cells provide an added value. However, the test systems only reflected bronchiole epithelia and alveolar cells and investigated cytotoxicity. Effects occurring in other cells by other mechanisms could not be recognised. Further work should optimise test protocols and expand the set of substances tested to define applicability domains. In vivo respiratory toxicity data for in vitro comparisons should distinguish different modes of action, and their relevance for human health effects should be ensured. 23412078 Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion: Results of a randomized, placebo-controlled study. OBJECTIVECanagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption.RESEARCH DESIGN AND METHODSThis two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, (3)H-glucose, (14)C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (R(a)O) in plasma, endogenous glucose production, and glucose disposal.RESULTSCompared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC(0-2h)] reductions of 35% and 43%, respectively; P < 0.001 for both), increased 0- to 6-h urinary glucose excretion (UGE(0-6h), 18.2 ± 5.6 vs <0.2 g; P < 0.001), and delayed R(a)O. Canagliflozin reduced AUC R(a)O by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P < 0.001) and by 20% over 0 to 2 h (576 vs. 723 mg/kg; P = 0.002). Over 2 to 6 h, canagliflozin increased R(a)O such that total AUC R(a)O over 0 to 6 h was <6% lower versus placebo (960 vs. 1,018 mg/kg; P = 0.003). A modest (∼10%) reduction in acetaminophen absorption was observed over the first 2 h, but this difference was not sufficient to explain the reduction in R(a)O. Total glucose disposal over 0 to 6 h was similar across groups.CONCLUSIONSCanagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying R(a)O, likely due to intestinal SGLT1 inhibition. 23433812 Reduction of dNTP levels enhances DNA replication fidelity in vivo. ATP is the most important energy source for the maintenance and growth of living cells. Here we report that the impairment of the aerobic respiratory chain by inactivation of the ndh gene, or the inhibition of glycolysis with arsenate, both of which reduce intracellular ATP, result in a significant decrease in spontaneous mutagenesis in Escherichia coli. The genetic analyses and mutation spectra in the ndh strain revealed that the decrease in spontaneous mutagenesis resulted from an enhanced accuracy of the replicative DNA polymerase. Quantification of the dNTP content in the ndh mutant cells and in the arsenate-treated cells showed reduction of the dNTP pool, which could explain the observed broad antimutator effects. In conclusion, our work indicates that the cellular energy supply could affect spontaneous mutation rates and that a reduction of the dNTP levels can be antimutagenic. 23364884 Anti-inflammatory activity of Bromelia hieronymi: comparison with bromelain. Some plant proteases (e. g., papain, bromelain, ficin) have been used as anti-inflammatory agents for some years, and especially bromelain is still being used as alternative and/or complementary therapy to glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. Bromelain is an extract rich in cysteine endopeptidases obtained from Ananas comosus. In this study the anti-inflammatory action of a partially purified extract of Bromelia hieronymi fruits, whose main components are cysteine endopeptidases, is presented. Different doses of a partially purified extract of B. hieronymi were assayed on carrageenan-induced and serotonine-induced rat paw edema, as well as in cotton pellet granuloma model. Doses with equal proteolytic activity of the partially purified extract and bromelain showed significantly similar anti-inflammatory responses. Treatment of the partially purified extract and bromelain with E-64 provoked loss of anti-inflammatory activity on carrageenan-induced paw edema, a fact which is consistent with the hypothesis that the proteolytic activity would be responsible for the anti-inflammatory action. 23515934 Mechanisms involved in the antinociceptive effects of orally administered oleanolic acid in the mouse. The antinociceptive effects of oleanolic acid were examined in ICR mice. Oleanolic acid administered orally (1, 5 and 10 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. In the time- course study, duration of antinociceptive action of oleanolic acid maintained at least for 60 min. In addition, the cumulative nociceptive response time for intraplantar formalin injection (2nd phase), intrathecal injection of substance P (0.7 μg) or glutamate (20 μg) was diminished by oleanolic acid. Intraperitoneal (i.p.) pretreatment with naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) attenuated antinociceptive effect induced by oleanolic acid in the writhing test. However, yohimbine (adrenergic receptor antagonist) did not affect antinociception induced by oleanolic acid. The results indicate that oleanolic acid shows an antinociceptive property in various pain models such as writhing, formalin, substance P and glutamate pain tests. Furthermore, this antinociceptive effect of oleanolic acid may be mediated by opioidergic and serotonergic receptors, but not adrenergic receptors. 23449308 Targeting pathological B cell receptor signalling in lymphoid malignancies. Signalling through the B cell receptor (BCR) is central to the development and maintenance of B cells. In light of the numerous proliferative and survival pathways activated downstream of the BCR, it comes as no surprise that malignant B cells would co-opt this receptor to promote their own growth and survival. However, direct evidence for BCR signalling in human lymphoma has only come to light recently. Roles for antigen-dependent and antigen-independent, or tonic, BCR signalling have now been described for several different lymphoma subtypes. Furthermore, correlative data implicate antigen-dependent BCR signalling in many other forms of lymphoma. A host of therapeutic agents targeting effectors of the BCR signalling pathway are now in clinical trials and have shown initial success against multiple forms of lymphoma. 23470867 Human induced pluripotent stem cells and their use in drug discovery for toxicity testing. Predicting human safety risks of novel xenobiotics remains a major challenge, partly due to the limited availability of human cells to evaluate tissue-specific toxicity. Recent progress in the production of human induced pluripotent stem cells (hiPSCs) may fill this gap. hiPSCs can be continuously expanded in culture in an undifferentiated state and then differentiated to form most cell types. Thus, it is becoming technically feasible to generate large quantities of human cell types and, in combination with relatively new detection methods, to develop higher-throughput in vitro assays that quantify tissue-specific biological properties. Indeed, the first wave of large scale hiSC-differentiated cell types including patient-derived hiPSCS are now commercially available. However, significant improvements in hiPSC production and differentiation processes are required before cell-based toxicity assays that accurately reflect mature tissue phenotypes can be delivered and implemented in a cost-effective manner. In this review, we discuss the promising alignment of hiPSCs and recently emerging technologies to quantify tissue-specific functions. We emphasize liver, cardiovascular, and CNS safety risks and highlight limitations that must be overcome before routine screening for toxicity pathways in hiSC-derived cells can be established. 23340331 Implications of pH manipulation methods for metal toxicity: not all acidic environments are created equal. The toxicity of many metals is impacted by environmental pH, through both competition and complexation by hydroxide and carbonate ions. To establish safe environmental regulation it is important to properly define the relationship between pH and metal toxicity, a process that involves manipulating the pH of test water in the lab. The current study compares the effects of the three most common pH manipulation methods (carbon dioxide, acid-base addition, and chemical buffers) on acute Pb toxicity of a model fish species, Pimephales promelas. Acidification of test water revealed that the Pb and Pb(2+) LC50 values were impacted by the pH manipulation method, with the following order of effects: HCl stems (16.4 μg g(-1)) > roots (15.5 μg g(-1)). The accumulation potential was fourfold higher than the plant available concentration of 15.2 μg g(-1) of Se g(-1) of soil (diethylenetriaminepentaacetic acid extracted). Although the plant was able to accumulate Se in their tissues, increase in Se concentrations in soil caused a concentration-dependent decrease in the growth rate of plants (regeneration of leaves, number of leaves, number of roots, root length, stem length and biomass). 23412841 Computational Investigation of Cancer-Associated Molecular Mechanism in Aurora A (S155R) Mutation. Centrosomes are the key-regulating element of cell cycle progression. Aberrations in their functional mechanism lead to several cancer-related disorders. Aurora A protein is a centrosome-associated protein that regulates the centriole duplication and its abberations are associated with multiple cases of aneuploidy and cancer-related disorders. S155R mutation in Aurora A is reported to induce cancer like phenotype and disrupt its binding with TPX2 protein. In this study, we have demonstrated the structural consequences of Aurora A S155R mutation and the atomic changes that influenced the loss of TPX2-binding affinity. Docking and molecular dynamics simulation results suggested significant loss in atomic contacts between mutant Aurora A and TPX2 protein. Further, we observed a notable changes in conformation of mutant Aurora A-TPX2 docked complex as compared to the native. Loss of binding affinity rendered the TPX2 domain free which then induced unfolding in its coiled region and enabled the overall expansion of mutant complex as compared to the native. The significant outcomes obtained from this study will facilitate in future cancer researches and in developing the potent drug therapies. 23391096 Paclitaxel-conjugated PAMAM dendrimers adversely affect microtubule structure through two independent modes of action. Paclitaxel (Taxol) is an anticancer drug that induces mitotic arrest via microtubule hyperstabilization but causes side effects due to its hydrophobicity and cellular promiscuity. The targeted cytotoxicity of hydrophilic paclitaxel-conjugated polyamidoamine (PAMAM) dendrimers has been demonstrated in cultured cancer cells. Mechanisms of action responsible for this cytotoxicity are unknown, that is, whether the cytotoxicity is due to paclitaxel stabilization of microtubules, as is whether paclitaxel is released intracellularly from the dendrimer. To determine whether the conjugated paclitaxel can bind microtubules, we used a combination of ensemble and single microtubule imaging techniques in vitro. We demonstrate that these conjugates adversely affect microtubules by (1) promoting the polymerization and stabilization of microtubules in a paclitaxel-dependent manner, and (2) bundling preformed microtubules in a paclitaxel-independent manner, potentially due to protonation of tertiary amines in the dendrimer interior. Our results provide mechanistic insights into the cytotoxicity of paclitaxel-conjugated PAMAM dendrimers and uncover unexpected risks of using such conjugates therapeutically. 23278633 Self-Assembly of N(3)-Substituted Xanthines in the Solid State and at the Solid-Liquid Interface. The self-assembly of small molecular modules interacting through noncovalent forces is increasingly being used to generate functional structures and materials for electronic, catalytic, and biomedical applications. The greatest control over the geometry in H-bond supramolecular architectures, especially in H-bonded supramolecular polymers, can be achieved by exploiting the rich programmability of artificial nucleobases undergoing self-assembly through strong H bonds. Here N(3)-functionalized xanthine modules are described, which are capable of self-associating through self-complementary H-bonding patterns to form H-bonded supramolecular ribbons. The self-association of xanthines through directional H bonding between neighboring molecules allows the controlled generation of highly compact 1D supramolecular polymeric ribbons on graphite. These architectures have been characterized by scanning tunneling microscopy at the solid-liquid interface, corroborated by dispersion-corrected density functional theory (DFT) studies and X-ray diffraction. 23274746 Artichoke induces genetic toxicity in the cytokinesis-block micronucleus (CBMN) cytome assay. Artichoke leaves are used in traditional medicine as an herbal medicament for the treatment of hepatic related diseases, as well as choleretic and diuretic. The aim of the present study was to evaluate the capacity of Cynara scolymus L. leaves extract (LE) to cause chromosomal instability and cytotoxicity in Chinese hamster ovary cells (CHO) employing the cytokinesis-block micronucleus (CBMN) cytome assay. Cells were treated with four concentrations of C. scolymus for two exposure times: 1h and 24h. Our findings showed that LE did not increase the frequencies of nucleoplasmic bridges (NPBs) and nuclear bud (NBUD). However, all concentrations of the extract produced increments in micronuclei frequencies (MNi) in both exposure times, when compared to the negative control. No significant differences were observed in the nuclear division cytotoxicity index (NDCI), reflecting the absence of cytotoxic effects associated to LE. The results demonstrated the ability of C. scolymus LE to promote chromosomal mutations which are, probably, a result of the pro-oxidant activity of LE constituents such as flavonoids and chlorogenic acids. The data obtained in this study suggests that high concentrations of artichoke can pose a risk associated to its consumption. 23289403 Influence of polyelectrolyte film stiffness on bacterial growth. Photo-cross-linkable polyelectrolyte films, whose nanomechanical properties can be varied under UV light illumination, were prepared from poly(l-lysine) (PLL) and a hyaluronan derivative modified with photoreactive vinylbenzyl groups (HAVB). The adhesion and the growth of two model bacteria, namely Escherichia coli and Lactococcus lactis , were studied on non-cross-linked and cross-linked films to investigate how the film stiffness influences the bacterial behavior. While the Gram positive L. lactis was shown to grow slowly on both films, independently of their rigidity, the Gram negative E. coli exhibited a more rapid growth on non-cross-linked softer films compared to the stiffer ones. Experiments performed on photopatterned films showing both soft and stiff regions, confirmed a faster development of E. coli colonies on softer regions. Interestingly, this behavior is opposite to the one reported before for mammalian cells. Therefore, the photo-cross-linked (PLL/HAVB) films are interesting coatings for tissue engineering since they promote the growth of mammalian cells while limiting the bacterial colonization. 23384042 Two-photon circular-linear dichroism of perylene in solution: a theoretical-experimental study. Herein, we report on the theoretical-experimental analysis of the two-photon absorption (TPA) and two-photon circular-linear dichroism (TPCLD) spectra of a highly conjugated, rigid, and centrosymmetric molecule in solution, that is, perylene/CH2Cl2. We show how a three-energy-level diagram, under the sum-over-essential states approach, assists in the determination of the magnitude of transition electric dipole moments and the angle between them for the main TPA transitions. We demonstrate the potential of TPCLD to reveal the symmetry of excited states and the angles between their transition electric dipole moments and that of the ground state. By means of TPCLD, we explain how the overwhelming contribution of certain TPA transitions can mask important spectral features in regions where the transition electric dipole moments are perpendicular. TPCLD is expected to enhance the understanding of the photophysical properties of materials that are not accessible using conventional linear and two-photon spectroscopy. TPA and TPCLD measurements were performed employing the open-aperture Z-scan technique using an amplified femtosecond system. Time-dependent density functional theory (TD-DFT) calculations were carried out using response theory at the B3LYP level with the aug-cc-pVDZ basis set. Solvent effects were included through the polarizable continuum model (PCM). 23561147 The effect of interesterification on the bioavailability of fatty acids in structured lipids. Fatty acid (FA) profile is a critical factor in the nutritional properties of fats, but, stereochemistry may also play a fundamental role in the rate and extent to which FAs are absorbed and become available. To better understand this phenomenon, we evaluated the bioavailability of FAs in linseed-oil and palm-stearin blends compared to their interesterified mix, using a sn-1,3 stereospecific lipase, to determine if there was any difference in terms of FA availability when using this technology. Test meals were fed through an intragastric feeding tube on Sprague-Dawley male rats after 18h fasting. Postprandial blood samples were collected after meal or physiological serum (control) administration and the FA profile of plasma lipids was determined. Results showed that modification of the melting profile through interesterification, without altering the bioavailability determined by sn-2 stereochemistry, could delay lipid absorption at the beginning, but had no effect on total lipid absorption. 23453067 Synthesis and evaluation against hepatitis C virus of 7-deaza analogues of 2'-C-methyl-6-O-methyl guanosine nucleoside and L-Alanine ester phosphoramidates. 7-Deazapurines are known to possess broad antiviral activity, however the 2'-C-methylguanosine analogue displays poor cell permeation and limited phosphorylation, thus is not an efficient inhibitor of hepatitis C virus (HCV) replication. We previously reported the 6-O-methyl entity as a prodrug moiety to increase liphophilicity of guanine nucleosides and the ProTide approach applied to 2'-C-methyl-6-O-methylguanosine has lead to potent HCV inhibitors now in clinical trials. In this Letter, we report the synthesis and biological evaluation of 2'-C-methyl-6-O-methyl-7-deaza guanosine and ProTide derivatives. In contrast to prior studies, removal of the N-7 of the nucleobase entirely negates anti-HCV activity compared to the 2'-C-methyl-6-O-methylguanosine analogues. To understand better this significant loss of activity, enzymatic assays and molecular modeling were carried out and suggested 2'-C-methyl-6-O-methyl-7-deaza guanosine and related ProTides do not act as efficient prodrugs of the free nucleotide, in marked contrast to the case of the parent guanine analogue. 23434445 Mucous hypersecretion and relationship to cough. A variety of foreign "invaders" such as viruses, bacteria and other particulates e.g., cigarette smoke, are inhaled, deposit on the airway surface and invade the "host." Mucins produced by the surface airway epithelium and by the submucosal glands are secreted into the airway lumen. Deposited particulates adhere to the mucus and are cleared via mucociliary transport and via cough. Mucins are major constituents of mucus, which is important in the clearance of inhaled materials. Normally, secreted mucus is cleared without symptoms or interference with lung function. However, in obstructive airway diseases such as COPD, asthma, and cystic fibrosis, excessive mucus is produced. Because of the prominence of mucous hypersecretion as a cause of cough, this discussion focuses on mechanisms regulating normal production of mucins and the mechanisms underlying exaggerated mucin secretion in chronic obstructive airway diseases. Mucins are produced by airway epithelial cells via a cascade of signals (the Epidermal Growth Factor Cascade) and secreted on the luminal epithelial surface, often in response to the deposition of inhaled irritants. Normally, only minimal amounts of mucins are secreted, which assist in clearance of the inhaled particulates. However, in disease, additional pathways are induced via positive feedback systems, which lead to mucous hypersecretion. In the large conducting airways, where cough receptors are concentrated, mucous hypersecretion causes stimulation of neural receptors that result in cough. However, in small airways (e.g., bronchioles), because of their small diameters, mucous hypersecretion leads to plugging of the airways. Because there are so many small airways, their plugging is difficult to detect early, and this locus is known as a "silent zone." In chronic obstructive airway diseases, plugging of small airways may persist and increase over time, finally resulting in severe airway obstruction. Different obstructive airway diseases induce inflammatory signaling (including mucous hypersecretion) via different stimuli, but often via similar signaling pathways. Application of present knowledge of signaling that occurs with mucous hypersecretion can lead to novel therapies for hypersecretion and cough induced in conducting airways and could prevent plugging in small airways that can lead to clinical deterioration and death. 22766173 Correlation between iodide dosimetry and terephthalic acid dosimetry to evaluate the reactive radical production due to the acoustic cavitation activity. Acoustic cavitation plays an important role in sonochemical processes and the rate of sonochemical reaction is influenced by sonication parameters. There are several methods to evaluate cavitation activity such as chemical dosimetry. In this study, to comparison between iodide dosimetry and terephthalic acid dosimetry, efficacy of sonication parameters in reactive radical production has been considered by iodide and terephthalic acid dosimetries. For this purpose, efficacy of different exposure parameters on cavitations production by 1 MHz ultrasound has been studied. The absorbance of KI dosimeter was measured by spectrophotometer and the fluorescence of terephthalic acid dosimeter was measured using spectrofluorometer after sonication. The result of experiments related to sonication time and intensity showed that with increasing time of sonication or intensity, the absorbance is increased. It has been shown that the absorbance for continuous mode is remarkably higher than for pulsing mode (p-value < 0.05). Also results show that with increasing the duty cycles of pulsed field, the inertial cavitation activity is increased. With compensation of sonication time or intensity in different duty cycles, no significant absorbance difference were observed unless 20% duty cycle. A significant correlation between the absorbance and fluorescence intensities (count) at different intensity (R = 0.971), different sonication time (R = 0.999) and different duty cycle (R = 0.967) were observed (p-value < 0.05). It is concluded that the sonication parameters having important influences on reactive radical production. These results suggest that there is a correlation between iodide dosimetry and terephthalic acid dosimetry to examine the acoustic cavitation activity in ultrasound field. 22594605 A new pyrimidinedione derivative from the gorgonian coral Verrucella umbraculum. A new pyrimidinedione derivative, 9-acetyl-1,3,7-trimethyl-pyrimidinedione (1), was isolated from the gorgonian coral Verrucella umbraculum, together with two known compounds, caffeine (2) and 1,3-dimethylpyrimidine-2,4(1H,3H)-dione (3). The structure of 1 was elucidated by the aid of 1D, 2D NMR and MS experiments. The structures of the known compounds were identified by comparison of their spectroscopic data with those reported in the literature. 23297762 Risk of completed suicide after bariatric surgery: a systematic review. Bariatric surgery is one of the most effective treatments for morbid obesity, and a large body of research indicates significant long-term weight loss. While overall mortality decreases in patients who received bariatric surgery, a number of studies have shown that suicide rates are higher in bariatric patients than in control groups. The objective of this study was to present a systematic review of suicide mortality after bariatric surgery and calculate an estimate for the suicide rate. Literature researches of the databases PubMed, Web of Knowledge, PsychInfo, ScienceDirect and Google Scholar were conducted. Thirty studies concerning bariatric surgery and completed suicides met the inclusion criteria. We included 28 studies in the estimation of a suicide rate for the bariatric population. Only one study (Tindle et al.) put a main focus on suicide after bariatric surgery; this was therefore chosen as an adequate reference figure for comparison. The other 27 chosen studies were compared with World Health Organization data and the suicide rate reported by Tindle et al. Twenty-three thousand eight hundred eighty-five people were included in the analysis. In the literature, we found a total of 95 suicides when examining 190,000 person-years of post-bariatric surgery data. Little information was provided describing the reasons for suicide and the time-point of these events after surgery. We estimated a suicide rate of 4.1/10,000 person-years (95% confidence interval [3.2, 5.1]/10,000 person-years). A comparison with Tindle et al. demonstrates that their rate is significantly higher than our estimate (P = 0.03). Bariatric surgery patients show higher suicide rates than the general population. Therefore, there is a great need to identify persons at risk and post-operative psychological monitoring is recommended. 23206990 ESR1 polymorphisms, daily hassles, anger expression, and depressive symptoms in adolescent boys and girls. Studies reporting associations between genetic factors and mood-related traits have often been criticized (i) for failing to take into account the role of the social environment in which individuals act and (ii) for not maintaining a 'transparent narrative connection' between genes and outcomes. In a sample of adolescents, we analyzed whether PvuII and XbaI, two polymorphisms on the ESR1 (Estrogen Receptor Gene α) were related to depressive symptoms, and considered whether daily hassles moderated this relationship and whether anger expression style mediated this relationship. Analyses suggested that ESR1 polymorphisms are relevant to the intra-sexual variability in depressive symptoms in boys and that the experience of daily hassles moderated this relationship. No such relationships were found in girls. Additionally, ESR1 polymorphisms are related to anger expression styles in girls. Anger-related variables, however, did not mediate the relationship between ESR1 polymorphisms and depressive symptoms, in boys nor in girls. 23410163 The economics of polypharmacology: fixed dose combinations and drug cocktails. The history of Fixed Dose Combination (FDC) oral drug products has been tumultuous over its history. Some FDCs were prepared for marketing purposes and others for clinical improvements. Often, the products prepared for marketing advantage ended up causing negative outcomes. However, in recent years, there has been a resurgence of FDCs as clinicians have found them adventitious for treatment of AIDS/HIV and for oral contraceptives, just to name two examples. International regulatory Agencies and most major drug regulatory agencies have established guidelines along with regulations concerning preparation, labeling and marketing for FDCs. The advantages of FDCs are said to be in the clinical realm where simplified therapy regimens are thought to enhance patient's medication taking compliance. On the financial side, health insurers and other payers normally save money from a decreased number of dispensing fees, the use of fewer bottles, labels, etc., and from the possible situation where the price of the FDC is less than the medication price of the two separate ingredients dispensed individually. Overall, there is a great deal of evidence in favor of appropriate FDCs. 23125070 Contribution of Leydig and Sertoli cells to testosterone production in mouse fetal testes. Testosterone is a final product of androgenic hormone biosynthesis, and Leydig cells are known to be the primary source of androgens. In the mammalian testis, two distinct populations of Leydig cells, the fetal and the adult Leydig cells, develop sequentially, and these two cell types differ both morphologically and functionally. It is well known that the adult Leydig cells maintain male reproductive function by producing testosterone. However, it has been controversial whether fetal Leydig cells can produce testosterone, and the synthetic pathway of testosterone in the fetal testis is not fully understood. In the present study, we generated transgenic mice in which enhanced green fluorescence protein was expressed under the control of a fetal Leydig cell-specific enhancer of the Ad4BP/SF-1 (Nr5a1) gene. The transgene construct was prepared by mutating the LIM homeodomain transcription factor (LHX9)-binding sequence in the promoter, which abolished promoter activity in the undifferentiated testicular cells. These transgenic mice were used to collect highly pure fetal Leydig cells. Gene expression and steroidogenic enzyme activities in the fetal Leydig cells as well as in the fetal Sertoli cells and adult Leydig cells were analyzed. Our results revealed that the fetal Leydig cells synthesize only androstenedione because they lack expression of Hsd17b3, and fetal Sertoli cells convert androstenedione to testosterone, whereas adult Leydig cells synthesize testosterone by themselves. The current study demonstrated that both Leydig and Sertoli cells are required for testosterone synthesis in the mouse fetal testis. 23451797 Structural Investigation and Biological Activity of Sesquiterpene Lactones from the Traditional Chinese Herb Inula racemosa. Five new sesquiterpene lactones, racemosalactones A-E (1-5), along with 19 known sesquiterpene latones (6-24), were isolated from the roots of Inula racemosa. Their structures were elucidated by extensive spectroscopic analysis, and the absolute configuration of 2 was deduced from X-ray diffraction analysis. Compounds 1, 6, 8, 10, 12, 14, and 17 exhibited antiproliferative activities with IC50 values ranging from 0.38 to 4.19 μg/mL against human non-small-cell lung cancer A549, hepatocellular carcinoma HepG2, and human fibrosarcoma HT1080 cells. Compounds 6 and 8 exhibited antiproliferative activities against endothelial cells with IC50 values of 2.4 and 2.5 μg/mL, respectively. Furthermore, compounds 6 and 8 both inhibited endothelial cell tube formation at 1.0 μg/mL. A method for the rapid and straightforward preparative-scale isolation of compound 6 from alantolides is described. 23111282 Analysis of gene expression changes to elucidate the mechanism of chilling injury in precision-cut liver slices. The exact mechanism of chilling injury (by a decrease of temperature to sub-physiological values), especially in the intact organ, is yet unknown. Precision-cut liver slices (PCLS), which closely resemble the organ from which they are derived, are an ideal in vitro model to study the mechanism of chilling injury in the intact organ. In the present study we were able to separate chilling injury from other damaging events such as cryoprotectant toxicity and ice-crystal injury and performed micro-array analysis of regulated genes. Pathway analysis revealed that different stress responses, lipid/fatty acid and cholesterol biosynthesis and metabolism were affected by chilling. This indicates that the cell-membrane might be the primary site and sensor for chilling, which may initiate and amplify downstream intracellular signaling events. Most importantly, we were able to identify gene expression responses from stellate cells and Kupffer cells suggesting the involvement of all liver cell types in the injury. In conclusion, a broad spectrum of previously unknown gene expression changes induced by chilling was identified in the tissue. This is the first report of a systematic investigation on the mechanism of chilling injury in integrated tissue by micro-array analysis under conditions in which other sources of injury are minimal. 23402364 Role of nitric oxide in the chemistry and anticancer activity of etoposide (VP-16,213). Originally identified as an innate cytotoxin, nitric oxide ((·)NO) formation in tumors can influence chemotherapy and exacerbate cancer progression. Here, we examined the hypothesis that (·)NO generation contributes to cancer cell drug resistance toward the widely used anticancer drug Etoposide (VP-16). The UV-vis spectrum of VP-16 was not changed by exposure of VP-16 to (·)NO in aqueous buffer. In contrast, reddish-orange compound(s) characteristic of o-quinone- and nitroso-VP-16 were readily generated in a hydrophobic medium (chloroform) in an oxygen-dependent manner. Similar products were also formed when the VP-16 radical, generated from VP-16 and horseradish peroxidase/H2O2, was exposed directly to (·)NO in chloroform in the presence of oxygen. Separation and spectral analysis of VP-16 reaction extracts by electron spin resonance and UV-vis indicated the generation of the phenoxy radical and the o-quinone of VP-16, as well as putative nitroxide, iminoxyl, and other nitrogen oxide intermediates. Nitric oxide products of VP-16 displayed significantly diminished topoisomerase II-dependent cleavage of DNA and cytotoxicity to human HL-60 leukemia cells. LPS-mediated induction of nitric oxide synthase in murine macrophages resulted in VP-16 resistance compared to Raw cells. Furthermore, (·)NO products derived from iNOS rapidly reacted with VP-16 leading to decreased DNA damage and cytotoxicity. Together, these observations suggest that the formation of (·)NO in tumors (associated macrophages) can contribute to VP-16 resistance via the detoxification of VP-16. 23416070 Glucagon-induced acetylation of Foxa2 regulates hepatic lipid metabolism. Circulating levels of insulin and glucagon reflect the nutritional state of animals and elicit regulatory responses in the liver that maintain glucose and lipid homeostasis. The transcription factor Foxa2 activates lipid metabolism and ketogenesis during fasting and is inhibited via insulin-PI3K-Akt signaling-mediated phosphorylation at Thr156 and nuclear exclusion. Here we show that, in addition, Foxa2 is acetylated at the conserved residue Lys259 following inhibition of histone deacetylases (HDACs) class I-III and the cofactors p300 and SirT1 are involved in Foxa2 acetylation and deacetylation, respectively. Physiologically, fasting states and glucagon stimulation are sufficient to induce Foxa2 acetylation. Introduction of the acetylation-mimicking (K259Q) or -deficient (K259R) mutations promotes or inhibits Foxa2 activity, respectively, and adenoviral expression of Foxa2-K259Q augments expression of genes involved in fatty acid oxidation and ketogenesis. Our study reveals a molecular mechanism by which glucagon signaling activates a fasting response through acetylation of Foxa2. 22579656 Neuroendocrine aspects of catamenial epilepsy. This review describes the neuroendocrinological aspects of catamenial epilepsy, a menstrual cycle-related seizure disorder in women with epilepsy. Catamenial epilepsy is a multifaceted neuroendocrine condition in which seizures are clustered around specific points in the menstrual cycle, most often around perimenstrual or periovulatory period. Three types of catamenial seizures (perimenstrual, periovulatory and inadequate luteal) have been identified. The molecular pathophysiology of catamenial epilepsy remains unclear. Cyclical changes in the circulating levels of estrogens and progesterone (P) play a central role in the development of catamenial epilepsy. Endogenous neurosteroids such as allopregnanolone (AP) and allotetrahydrodeoxycorticosterone (THDOC) that modulate seizure susceptibility could play a critical role in catamenial epilepsy. In addition, plasticity in GABA-A receptor subunits could play a role in the enhanced seizure susceptibility in catamenial epilepsy. P-derived neurosteroids such as AP and THDOC potentiate synaptic GABA-A receptor function and also activate extrasynaptic GABA-A receptors in the hippocampus and thus may represent endogenous regulators of catamenial seizure susceptibility. Experimental studies have shown that neurosteroids confer greater seizure protection in animal models of catamenial epilepsy, especially without evident tolerance to their actions during chronic therapy. In the recently completed NIH-sponsored, placebo controlled phase 3 clinical trial, P therapy proved to be beneficial only in women with perimenstrual catamenial epilepsy but not in non-catamenial subjects. Neurosteroid analogs with favorable profile may be useful in the treatment of catamenial epilepsy. 23552264 Evaluation of in vitro and in vivo genotoxicity of single-walled carbon nanotubes. Single-walled carbon nanotubes (SWCNTs) have extensive potential industrial applications due to their unique physical and chemical properties; yet this also increases the chance of human and environment exposure to SWCNTs. Due to the current lack of hazardous effect information on SWNCTs, a standardized genotoxicity battery test was conducted to clarify the genetic toxicity potential of SWCNTs (diameter: 1-1.2 nm, length: ∼20 μm) according to Organization for Economic Cooperation and Development test guidelines 471 (bacterial reverse mutation test), 473 (in vitro chromosome aberration test), and 474 (in vivo micronuclei test) with a good laboratory practice system. The test results showed that the SWCNTs did not induce significant bacterial reverse mutations at 31.3-500 μg/plate in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 or in Escherichia coli strain WP2uvrA, with and without a metabolic activation system. Furthermore, the in vitro chromosome aberration test showed no significant increase in structural or numerical chromosome aberration frequencies at SWCNT dose levels of 12.5-50 μg/ml in the presence and absence of metabolic activation. However, dose-dependent cell growth inhibition was found at all the SWCNT dose levels and statistically significant cytotoxic effects observed at certain concentrations in the presence and absence of metabolic activation. Finally, the SWCNTs did not evoke significant in vivo micronuclei frequencies in the polychromatic erythrocytes of an imprinting control region mice at 25-100 mg/kg. Thus, according to the results of the present study, the SWCNTs were not found to have a genotoxic effect on the in vitro and in vivo test systems. 23184951 ATP hydrolysis enhances RNA recognition and antiviral signal transduction by the innate immune sensor, laboratory of genetics and physiology 2 (LGP2). Laboratory of genetics and physiology 2 (LGP2) is a member of the RIG-I-like receptor family of cytoplasmic pattern recognition receptors that detect molecular signatures of virus infection and initiate antiviral signal transduction cascades. The ATP hydrolysis activity of LGP2 is essential for antiviral signaling, but it has been unclear how the enzymatic properties of LGP2 regulate its biological response. Quantitative analysis of the dsRNA binding and enzymatic activities of LGP2 revealed high dsRNA-independent ATP hydrolysis activity. Biochemical assays and single-molecule analysis of LGP2 and mutant variants that dissociate basal from dsRNA-stimulated ATP hydrolysis demonstrate that LGP2 utilizes basal ATP hydrolysis to enhance and diversify its RNA recognition capacity, enabling the protein to associate with intrinsically poor substrates. This property is required for LGP2 to synergize with another RIG-I-like receptor, MDA5, to potentiate IFNβ transcription in vivo during infection with encephalomyocarditis virus or transfection with poly(I:C). These results demonstrate previously unrecognized properties of LGP2 ATP hydrolysis and RNA interaction and provide a mechanistic basis for a positive regulatory role for LGP2 in antiviral signaling. 23608109 Novel therapeutic targets in non-small cell lung cancer. Oncogenic driver mutations frequently occur in lung cancer and play role in carcinogenesis. These mutations are usually associated with distinct clinical and histological features and are attractive targets for anticancer therapy. Recently, several molecularly distinct phenotypes of NSCLC based on specific and mutually exclusive genetic derangements have been described. Few targets like epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with EGFR tyrosine kinase inhibitors (TKIs) and crizotinib, respectively. Many more inhibitors of specific driver mutations involving genes like ROS, c-MET, FGFR, mTOR, IGFR and RET are currently under development. However, efforts to target some mutated genes like K-RAS have been unsuccessful. Moreover, the emerging challenge of acquired resistance to initially effective therapy is becoming another major concern. In this review recent data on novel molecular targets and their future prospects are discussed. 22788700 Polyphenol distribution in plant organs of tomato introgression lines. The content of total polyphenols, chlorogenic, caffeic (CaA) and ferulic acids, and rutin, was investigated in plant organs of three introgression lines (IL7-3, IL10-1 and IL12-4) of Solanum pennellii in Solanum lycopersicum cv M82 and compared with that of cropped parental. Such study aims to evidence factors associated to the introgressions that can affect polyphenol distribution in plant. Among genotypes few differences in polyphenols were recorded on fresh weight basis. IL7-3 showed higher total polyphenols in fruits and lower rutin in leaves than the other genotypes. IL12-4 showed an increasing trend of total polyphenol concentration in fresh vegetative organs; however, this seems to depend on the lower water content rather than on a higher polyphenol biosynthesis in the genotype. IL10-1 sowed higher CaA and lignin contents in leaves. Such differences agree with the morphological and physiological traits of the genotypes. 22956630 Effects of parabens on adipocyte differentiation. Parabens are a group of alkyl esters of p-hydroxybenzoic acid that include methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben. Paraben esters and their salts are widely used as preservatives in cosmetics, toiletries, food, and pharmaceuticals. Humans are exposed to parabens through the use of such products from dermal contact, ingestion, and inhalation. However, research on the effects of parabens on health is limited, and the effects of parabens on adipogenesis have not been systematically studied. Here, we report that (1) parabens promote adipogenesis (or adipocyte differentiation) in murine 3T3-L1 cells, as revealed by adipocyte morphology, lipid accumulation, and mRNA expression of adipocyte-specific markers; (2) the adipogenic potency of parabens is increased with increasing length of the linear alkyl chain in the following potency ranking order: methyl- < ethyl- < propyl- < butylparaben. The extension of the linear alkyl chain with an aromatic ring in benzylparaben further augments the adipogenic ability, whereas 4-hydroxybenzoic acid, the common metabolite of all parabens, and the structurally related benzoic acid (without the OH group) are inactive in promoting 3T3-L1 adipocyte differentiation; (3) parabens activate glucocorticoid receptor and/or peroxisome proliferator-activated receptor γ in 3T3-L1 preadipocytes; however, no direct binding to, or modulation of, the ligand binding domain of the glucocorticoid receptor by parabens was detected by glucocorticoid receptor competitor assays; and lastly, (4) parabens, butyl- and benzylparaben in particular, also promote adipose conversion of human adipose-derived multipotent stromal cells. Our results suggest that parabens may contribute to obesity epidemic, and the role of parabens in adipogenesis in vivo needs to be examined further. 23123945 Repeated exposure to the herbicide atrazine alters locomotor activity and the nigrostriatal dopaminergic system of the albino rat. Atrazine (ATR) is used as a pre- and post-emergent herbicide; although banned in several countries of the European Community, it is still used extensively around the world. A recent study in rats has shown that chronic, daily exposure to 10 mg ATR/kg BW causes hyperactivity, disrupts motor coordination and learning of behavioral tasks, and decreases dopamine levels in the brain. In order to evaluate the short-term effect of ATR exposure on locomotor activity, monoamine markers, and antioxidants, adult male Sprague-Dawley rats received six IP injections of 100 mg ATR/kg BW or vehicle over two weeks. After every ATR injection we found hypoactivity that lasted up to five days, and it was accompanied by reductions in levels of striatal DA, DOPAC, and HVA without any alteration in the striatal expression of the mRNAs for Mn-SOD, Trx-1, DAR-D(1), or DAR-D(2). In contrast, in the nucleus accumbens no changes in monoamine markers were observed, and a down-regulation of Trx-1 expression was detected shortly after the ATR treatment. Moreover, in the ventral midbrain, we found that ATR induced a down-regulation of mRNA for Th and DAT, but it increased VMAT2 mRNA expression. Decreases of monoamine levels and of locomotor activity disappeared three months after ATR treatment; however, an amphetamine challenge (1 mg/kg) given two months after the ATR treatment resulted in a significant stimulation in the exposed group, revealing hidden effects of ATR on dopaminergic systems. These results indicate that ATR exposure differentially modifies the dopaminergic systems, and these modifications may underlie the behavioral changes observed. 23347684 Synthesis of 2-aminomethyl-4-phenyl-1-azabicyclo[2.2.1]heptanes via LiAlH₄-induced reductive cyclization of 2-(4-chloro-2-cyano-2-phenylbutyl)aziridines and evaluation of their antimalarial activity. 2-(4-Chloro-2-cyano-2-phenylbutyl)aziridines were employed for the one-step stereoselective construction of both endo- and exo-2-aminomethyl-4-phenyl-1-azabicyclo[2.2.1]heptanes as new azaheterobicyclic scaffolds via a double LiAlH(4)-induced reductive cyclization protocol. Antiplasmodial assessment of these 1-azabicyclo[2.2.1]heptanes revealed moderate to good activities in the micromolar range, with the exo-isomers being the most promising structures. Furthermore, the proposed mode of action was supported by ligand docking studies, pointing to a strong binding interaction with the enzyme plasmepsin II. 23362923 Biselectivity of isoDGR Peptides for Fibronectin Binding Integrin Subtypes α5β1 and αvβ6: Conformational Control through Flanking Amino Acids. Integrins are the major class of cell adhesion proteins. Their interaction with different ligands of the extracellular matrix is diverse. To get more insight into these interactions, artificial ligands endowed with a well-defined activity/selectivity profile are necessary. Herein, we present a library of cyclic pentapeptides, based on our previously reported peptide motif c(-phg-isoDGR-X-), in which high activity toward fibronectin binding integrins α5β1 and αvβ6 and not on vitronectin binding integrins αvβ3 and αvβ5 has been achieved by changing the flanking amino acids. The structure of the most promising candidates has been determined using a combined approach of NMR, distance geometry, and molecular dynamics simulations, and docking studies have been further used to elucidate the peptide-integrin interactions at the molecular level. The peptides' binding affinity has been characterized by enzyme linked immunosorbent assay experiments, and the results have been verified by cell adhesion experiments on specifically functionalized surfaces. 23464990 A General Strategy for Biocompatible, High-Effective Upconversion Nanocapsules Based on Triplet-Triplet Annihilation. A general strategy for constructing high-effective upconversion nanocapsules based on triplet-triplet annihilation (TTA) was developed by loading both sensitizer and annihilator into BSA-dextran stabilized oil droplets. This strategy can maintain high translational mobility of the chromophores, avoid luminescence quenching of chromophore by aggregation, and decrease the O2-induced quenching of TTA-based upconversion emission. Pt(II)-tetraphenyl-tetrabenzoporphyrin (PtTPBP) and BODIPY dyes (BDP-G and BDP-Y with the maximal fluorescence emission at 528 and 546 nm, respectively) were chosen as sensitizer/annihilator couples to fabricate green and yellow upconversion luminescent emissive nanocapsules, named UCNC-G and UCNC-Y, respectively. In water under the atmospheric environment, interestingly, UCNC-G and UCNC-Y exhibit intense upconversion luminescence (UCL) emission (λex = 635 nm) with the quantum efficiencies (ΦUCL) of 1.7% and 4.8%, respectively, whereas very weak UCL emission (ΦUCL < 0.1%) was observed for the corresponding previous reported SiO2-coating nanosystems because of aggregation-induced fluorescence quenching of annihilators. Furthermore, application of theses upconversion nanocapsules for high-contrast UCL bioimaging in vivo of living mice without removing the skin was demonstrated under 635-nm excitation with low power density of 12.5 mW cm(-2). 23469688 8-(Tosylamino)quinoline inhibits tumour progression through targeting phosphoinositide-3-kinase/Akt pathway. We examined whether 8-(tosylamino)quinoline (8-TQ), a structural analogue of BAY 11-7082, is able to modulate various tumourigenic responses using various in vitro and in vivo experimental conditions. 8-TQ exhibited the strongest suppressive activity on the proliferation of C6, A431, HeLa and MDA-MB-231 cells with IC550 values ranging from 10 to 30 microM. According to the analysis of level of active caspase-3, and morphologies of C6, HeLa and MDA-MB-231 cells, it was revealed that 8-TQ is able to induce apoptosis. Furthermore, this compound strongly diminished the invasion of MDA-MB-231 cells, the migration of HeLa cells, and the new generation of blood vessels under non-toxic conditions. Reduction of the phospho-form levels of intracellular signalling enzymes by 8-TQ strongly indicated that molecular signalling machineries composed of phosphoinositide 3-kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/Akt and extracellular-signal-regulated kinase (ERK) could be targeted by 8-TQ treatment. Indeed, the specific inhibitors (LY294002 and U0126) of PI3K/PDK1/Akt and ERK showed similar anti-cancer properties to 8-TQ. Finally, 8-TQ intraperitoneally injected suppressed the increase of tumour volume up to 40% compared to vehicle-treated control. Taken together, our results clearly suggest that 8-TQ might have applications as a novel anti-cancer drug or may be served as a lead compound to be further optimized. 23411342 Synthesis and characterisation of nano structure lead (II) ion-imprinted polymer as a new sorbent for selective extraction and preconcentration of ultra trace amounts of lead ions from vegetables, rice, and fish samples. This paper describes the preparation of new Pb(II)-imprinted polymeric particles using 2-vinylpyridine as a functional monomer, ethylene glycol dimethacrylate as the cross-linker, 2,2'- azobisisobutyronitrile as the initiator, diphenylcarbazone as the ligand, acetonitril as the solvent, and Pb(NO(3))(2) as the template ion, through bulk polymerisation technique. The imprinted lead ions were removed from the polymeric matrix using 5 mL of HCl (2 mol.L(-1)) as the eluting solvent. The lead ion concentration was determined by flame atomic absorption spectrometry. Optimum pH for maximum sorption was obtained at 6.0. Sorption and desorption of Pb(II) ions on the IIP particles were quite fast and achieved fully over 5 min. In the proposed method, the maximum sorbent capacity of the ion-imprinted polymer was calculated to be 75.4 mg g(-1). The preconcentration factor, relative standard deviation, and limit of detection of the method were found to be 245, 2.1%, and 0.42 ng mL(-1), respectively. The prepared ion-imprinted polymer particles have an increased selectivity toward Pb(II) ions over a range of competing metal ions with the same charge and similar ionic radius. This ion-imprinted polymer is an efficient solid phase for extraction and preconcentration of lead ions in complex matrixes. For proving that the proposed method is reliable, a wide range of food samples with different and complex matrixes was used. 23633529 Characterization of Recombinantly Expressed Rat and Monkey Intestinal Alkaline Phosphatases: In Vitro Studies and In Vivo Correlations. Intestinal alkaline phosphatases (IALPs) are widely expressed in the brush border of epithelial cells of the intestinal mucosa. Although their physiological role is unclear, they are very significant when it comes to the release of bioactive parent from orally dosed phosphate prodrugs. Such prodrugs can be resistant to cleavage by IALP, or alternatively undergo rapid cleavage leading to the release and precipitation of the less soluble parent. Because purified IALPs from pre-clinical species are not commercially available, and species differences have not been investigated to date, an effort was made to recombinantly express, purify and characterize rat and cynomolgus monkey IALP (rIALP). Specifically, rIALP-catalyzed cleavage of five prodrugs (fosphenytoin, clindamycin phosphate, dexamethasone phosphate, ritonavir phosphate and ritonavir oxymethyl phosphate) was tested in vitro and parent exposure was assessed in vivo (rat only) following an oral dose of each prodrug. It was determined that the rate of phosphate cleavage in vitro varied widely; direct phosphates were more resistant to bioconversion, whereas faster conversion was observed with oxymethyl linked prodrugs. Overall, the rat rIALP-derived data were qualitatively consistent with in-vivo data; prodrugs that were readily cleaved in vitro rendered higher parent drug exposure in vivo. Of the five prodrugs tested, one (ritonavir phosphate) showed no conversion in vitro and minimal parent exposure in vivo. Finally, the apparent Km values obtained for fosphenytoin and clindamycin phosphate in vitro suggest that IALP is not likely to be saturated at therapeutic doses. 23624240 In vitro assessment of cobalt oxide particle toxicity: Identifying and circumventing interference. The continuing development of nanotechnology necessitates the reliable assessment of potential adverse health consequences associated with human exposures. The physicochemical properties of nanomaterials can be responsible for unexpected interactions with components of classical toxicity assays, which may generate erroneous interpretations. In this paper, we describe how particle interference can be observed in in vitro toxicity tests (CellTiter Blue, CyQUANT, WST-1 and CellTiter-Glo assay) and in cell biology tests using flow cytometry (cell cycle analysis). We used cobalt oxide (Co3O4) particles as an example, but these assays can be performed, in principle, regardless of the nanoparticle considered. We have shown that cobalt particles interfere with most of these tests. We adapted the protocol of the CellTiter-Glo assay to circumvent this interference and demonstrated that, using this protocol, the toxicity level is consistent with results obtained using the clonogenic assay, which is considered to be the reference test. Before assessing particle toxicity using in vitro toxicity tests, interference testing should be performed to avoid false interpretations. Furthermore, in some cases of interference, protocol adaptation can be considered to allow the reliable use of these quick and convenient in vitro tests. 23606278 Beyond Statins: Lipid Management to Reduce Cardiovascular Risk. The discovery that elevated total cholesterol levels and the subsequent understanding that low-density lipoprotein cholesterol levels are associated with higher risk for cardiovascular disease (CVD) has led to the development of lipid management strategies that seek to reduce the burden of CVD. Although substantive progress has been made in reducing death and cardiovascular events, questions remain regarding the optimal approach to further reduce CVD-associated death and disability. Based on current evidence, statins are the clear first-line agents for the management of hyperlipidemia in patients at high risk for cardiovascular events. However, due to the failure of recent clinical trials evaluating antihyperlipidemic drugs, the most appropriate lipid management strategy in patients who cannot tolerate statin therapy or who warrant antihyperlipidemic therapies in addition to statins is a major therapeutic controversy. In this review, we summarize the clinical trial evidence evaluating the efficacy of second-line antihyperlipidemic drug classes for reducing cardiovascular risk, provide recommendations for appropriate use of nonstatin lipid-altering drugs, and identify key areas of future research to support evidence-based lipid management. Given the complexity, magnitude, and burden of CVD, opportunities to improve processes of care and identify new therapeutic options clearly exist. 23584541 Synthesis of 3-O-propargylated betulinic acid and its 1,2,3-triazoles as potential apoptotic agents. Cytotoxic agents from nature are presently the mainstay of anticancer chemotherapy, and the need to reinforce the arsenal of anticancer agents is highly desired. Chemical transformation studies carried out on betulinic acid, through concise 1,2,3-triazole synthesis via click chemistry approach at C-3position in ring A have been evaluated for their cytotoxic potentiation against nine human cancer cell lines. Most of the derivatives have shown higher cytotoxic profiles than the parent molecule. Two compounds i.e. 3{1N(2-cyanophenyl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid (7) and 3{1N(5-hydroxy-naphth-1yl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid (13) displayed impressive IC50 values (2.5 and 3.5 μM respectively) against leukemia cell line HL-60 (5-7-fold higher potency than betulinic acid). As evident from various biological end points, inhibition of cell migration and colony formation, mitochondrial membrane disruption followed by DNA fragmentation and apoptosis, is demonstrated. 22903180 RETRACTED: Effects of nanometer-sized silver materials on survival response of Caspian roach (Rutilus rutilus caspicus). RETRACTED. 23426718 Anti-inflammatory profile of paricalcitol in hemodialysis patients: a prospective, open-label, pilot study. Inflammation is a strong predictor of increased morbidity and mortality in hemodialysis (HD) patients. Paricalcitol, a selective vitamin D receptor activator used for prevention and treatment of secondary hyperparathyroidism, has shown anti-inflammatory properties in experimental studies, although clinical data are scarce. In an open-label, prospective, single center, pilot study, 25 stable HD patients, previously receiving calcitriol, completed 12 weeks of therapy with oral paricalcitol. Serum and peripheral blood mononuclear cell (PBMC) expression profiles of inflammatory cytokines were analyzed. Serum interleukin (IL)-1, IL-10, and IL-18 did not change, unlike high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and IL-6, which experienced a significant mean percent decrease of 14.3%, 4.7%, and 5%, respectively. There was a significant reduction in the TNF-α/IL-10 and the IL-6/IL-10 ratios (P < .05). Serum intact parathyroid hormone concentration experienced a mild but significant reduction. In addition, expression levels of TNF-α and IL-6 decreased by 19.1% (P < .01) and 17.5% (P < .001), respectively, whereas expression of IL-10 increased by 17.7% (P < .01) after treatment. In conclusion, paricalcitol administration to HD patients is associated with a beneficial effect on the inflammatory cytokine serum and gene expression profile of PBMC. This effect may contribute to the survival benefits of paricalcitol observed in clinical studies. 23232461 Toxicity of organotin compounds: shared and unshared biochemical targets and mechanisms in animal cells. Most biochemical effects of organotin compounds leading to toxicity are astonishingly similar in different animal species. In vitro tests, designed to explore organotin action modes at cell level by minimizing interfering factors, point out akin responses to these man-made environmental pollutants from prokaryotes to mammals. On the other hand, a broad susceptibility range to organotin toxicants of animal cells and variegated action mechanisms of these compounds have been reported both in vitro and in vivo studies. Endocrine and lipid homeostasis perturbations span from mollusks to mammals, in which organotins mainly favor fat accumulation. Lipid changes were also found in Bacteria. Organotin are immunotoxic both in invertebrates and humans. Mitochondria and membrane functions seem to be a preferred target of these lipophilic pollutants. The inhibition of key membrane-bound enzyme complexes such as Na,K-and F0F1-ATPases, accompanied by perturbation of hydromineral balance, membrane potential and bioenergetics, has been widely reported. Highly conserved mechanisms could be involved in organotin binding to nuclear receptors, membrane components and intracellular proteins as well as in promoting DNA damage, all widely shared action modes of these toxicants. Accordingly, the different responsiveness/refractoriness to organotins, here overviewed, may mirror the biochemical-physiological selectivity of biomembranes, signalling pathways and intracellular protein components. 23286198 Using binary surfactant mixtures to simultaneously improve the dimensional tunability and monodispersity in the seeded growth of gold nanorods. We report a dramatically improved synthesis of colloidal gold nanorods (NRs) using a binary surfactant mixture composed of hexadecyltrimethylammonium bromide (CTAB) and sodium oleate (NaOL). Both thin (diameter <25 nm) and thicker (diameter >30 nm) gold NRs with exceptional monodispersity and broadly tunable longitudinal surface plasmon resonance can be synthesized using seeded growth at reduced CTAB concentrations (as low as 0.037 M). The CTAB-NaOL binary surfactant mixture overcomes the difficulty of growing uniform thick gold NRs often associated with the single-component CTAB system and greatly expands the dimensions of gold NRs that are accessible through a one-pot seeded growth process. Gold NRs with large overall dimensions and thus high scattering/absorption ratios are ideal for scattering-based applications such as biolabeling as well as the enhancement of optical processes. 23395826 Support vector machine: Classifying and predicting mutagenicity of complex mixtures based on pollution profiles. Powerful, robust in silico approaches offer great promise for classifying and predicting biological effects of complex mixtures and for identifying the constituents of greatest concern. Support vector machine (SVM) methods can deal with high dimensional data and small sample size and examine multiple interrelationships among samples. In this work, we applied SVM methods to examine pollution profiles and mutagenicity of 60 water samples obtained from 6 cities in China during 2006-2011. Pollutant profiles were characterized in water extracts by gas chromatography-mass spectrometry (GC/MS) and mutagenicity examined by Ames assays. We encoded feature vectors of GS-MS peaks in the mixtures and used 48 samples as the training set, reserving 12 samples as the test set. The SVM model and regression were constructed from whole pollution profiles that ranked compounds in relation to their correlation to the mutagenicity. Both classification and prediction performance were evaluated. The SVM model based on whole pollution profiles showed lower performance (sensitivity, specificity, accuracy and correlation coefficient were 69.5-70.7%, 70.6-73.2%, 69.9-72.1%, and 0.55-0.59%, respectively) than one based on compounds with highest association with mutagenicity. A SVM model with the top 10 compounds had the highest performance (sensitivity, specificity, accuracy, and correlation coefficient were 89.8-90.3%, 90.1-92.1%, 90.1-91.3%, and 0.80-0.82%, respectively), with negligible decreases in performance between the test and training set. SVM can be a powerful, robust classifier of the relationship of pollutants and mutagenicity in complex real-world mixtures. The top 14 compounds have the greatest contribution to mutagenicity and deserve further studies to identify these constituents. 23603293 Toluquinol, a marine fungus metabolite, is a new angiosuppresor that interferes the Akt pathway. Toluquinol, a methylhydroquinone produced by a marine fungus, was selected in the course of a blind screening for new potential inhibitors of angiogenesis. In the present study we provide the first evidence that toluquinol is a new anti-angiogenic-compound. In a variety of experimental systems, representing the sequential events of the angiogenic process, toluquinol treatment of activated endothelial cells resulted in strong inhibitory effect. Toluquinol inhibited the growth of endothelial and tumor cells in culture in the micromolar range. Our results indicate that the observed growth inhibitory effect could be due, at least in part, to an induction of apoptosis. Toluquinol induced endothelial cell death is mediated via apoptosis after a cell cycle block and caspase activation. Capillary tube formation on Matrigel and migratory, invasive and proteolytic capabilities of endothelial cells were inhibited by addition of toluquinol at subtoxic concentrations. Inhibition of the mentioned essential steps of in vitro angiogenesis agrees with the observed inhibition of the in vivo angiogenesis, substantiated by using the chick chorioallatoic membrane assay and confirmed by the murine Matrigel plug, the zebrafish embryo neovascularization and the zebrafish caudal fin regeneration assays. Data here shown altogether indicate that toluquinol has antiangiogenic effects both in vitro and in vivo that are exerted partly by suppression of the VEGF and FGF-induced Akt activation of endothelial cells. These effects are carried out at lower concentrations to those required for other inhibitors of angiogenesis, what makes toluquinol a promising drug candidate for further evaluation in the treatment of cancer and other angiogenesis-related pathologies. 23447132 Exchange protein directly activated by cAMP (epac): a multidomain cAMP mediator in the regulation of diverse biological functions. Since the discovery nearly 60 years ago, cAMP is envisioned as one of the most universal and versatile second messengers. The tremendous feature of cAMP to tightly control highly diverse physiologic processes, including calcium homeostasis, metabolism, secretion, muscle contraction, cell fate, and gene transcription, is reflected by the award of five Nobel prizes. The discovery of Epac (exchange protein directly activated by cAMP) has ignited a new surge of cAMP-related research and has depicted novel cAMP properties independent of protein kinase A and cyclic nucleotide-gated channels. The multidomain architecture of Epac determines its activity state and allows cell-type specific protein-protein and protein-lipid interactions that control fine-tuning of pivotal biologic responses through the "old" second messenger cAMP. Compartmentalization of cAMP in space and time, maintained by A-kinase anchoring proteins, phosphodiesterases, and β-arrestins, contributes to the Epac signalosome of small GTPases, phospholipases, mitogen- and lipid-activated kinases, and transcription factors. These novel cAMP sensors seem to implement certain unexpected signaling properties of cAMP and thereby to permit delicate adaptations of biologic responses. Agonists and antagonists selective for Epac are developed and will support further studies on the biologic net outcome of the activation of Epac. This will increase our current knowledge on the pathophysiology of devastating diseases, such as diabetes, cognitive impairment, renal and heart failure, (pulmonary) hypertension, asthma, and chronic obstructive pulmonary disease. Further insights into the cAMP dynamics executed by the Epac signalosome will help to optimize the pharmacological treatment of these diseases. 23568274 Pediatric relapsed or refractory leukemia: new pharmacotherapeutic developments and future directions. Over the past 50 years, numerous advances in treatment have produced dramatic increases in the cure rates of pediatric leukemias. Despite this progress, the majority of children with relapsed leukemia are not expected to survive. With current chemotherapy regimens, approximately 15 % of children with acute lymphoblastic leukemia and 45 % of children with acute myeloid leukemia will have refractory disease or experience a relapse. Advances in the treatment of pediatric relapsed leukemia have not mirrored the successes of upfront therapy, and newer treatments are desperately needed in order to improve survival in these challenging patients. Recent improvements in our knowledge of cancer biology have revealed an extensive number of targets that have the potential to be exploited for anticancer therapy. These advances have led to the development of a number of new treatments that are now being explored in children with relapsed or refractory leukemia. Novel agents seek to exploit the same molecular aberrations that contribute to leukemia development and resistance to therapy. Newer classes of drugs, including monoclonal antibodies, tyrosine kinase inhibitors and epigenetic modifiers are transforming the treatment of patients who are not cured with conventional therapies. As the side effects of many new agents are distinct from those seen with conventional chemotherapy, these treatments are often explored in combination with each other or combined with conventional treatment regimens. This review discusses the biological rationale for the most promising new agents and the results of recent studies conducted in pediatric patients with relapsed leukemia. 23552899 High responsivity, fast ultraviolet photodetector fabricated from ZnO nanoparticle-graphene core-shell structures. We report a simple, efficient and versatile method for assembling metal oxide nanomaterial-graphene core-shell structures. An ultraviolet photodetector fabricated from the ZnO nanoparticle-graphene core-shell structures showed high responsivity and fast transient response, which are attributed to the improved carrier transport efficiency arising from graphene encapsulation. 23147837 Experimental exposure of eggs to polybrominated diphenyl ethers BDE-47 and BDE-99 in red-eared sliders (Trachemys scripta elegans) and snapping turtles (Chelydra serpentina) and possible species-specific differences in debromination. Polybrominated diphenyl ethers (PBDEs) are a bioaccumulative, persistent, and toxic class of flame retardants that can potentially impact turtles in natural habitats via exposure through maternal transfer. To simulate maternal transfer in the present study, PBDE congeners BDE-47 and BDE-99 were topically applied to the eggshell and were allowed to diffuse into the egg contents of the red-eared slider (Trachemys scripta elegans) and snapping turtle (Chelydra serpentina). Eggs were topically dosed over 8 d to achieve a target concentration of 40 ng/g in the egg contents. Transfer efficiency was higher for BDE-47 than for BDE-99 in the red-eared sliders (25.8 ± 1.9% vs 9.9 ± 1.1%) and snapping turtles (31.3 ± 1.6% vs 12.5 ± 1.4%), resulting in greater BDE-47 and lower BDE-99 egg content concentrations relative to the 40 ng/g target. However, only 25.8 and 31.3% of the total BDE-47 and 9.9 and 12.5% of the total BDE-99 dose applied could be accounted for in the red-eared slider and snapping turtle egg contents, respectively. Additionally, increased BDE-47 in red-eared slider egg contents dosed with only BDE-99 indicate that BDE-99 might have been debrominated to BDE-47. The efficacy of topical dosing for administering desired embryonic exposures is clearly affected by the chemical properties of the applied compounds and was more successful for BDE-47 in both species. 23512409 Impact of DNA Sequence and Oligonucleotide Length on a Polythiophene-Based Fluorescent DNA Biosensor. DNA hybridization is a universal and specific mechanism for the recognition of biological targets. Some cationic polythiophene transducers sensitive to DNA structure have been previously utilized to detect such biomolecules. Further characterization of these systems indicates that both DNA sequence composition and length modulate the biosensor performance. It appears that different repeated sequence patterns cause different conformational changes of the polythiophene, from a more relaxed form to an extremely rigid one. A length difference between the DNA oligonucleotide probe and target has a detrimental effect on the fluorescent signal, but it can be attenuated by changing the sequence composition of the protruding target sequence. This demonstrates that the nature of DNA can be critical for hybridization-based detection systems. 23631732 Hydrodynamic Effects on the Relative Rotational Velocity of Associating Proteins. Hydrodynamic steering effects on the barnase-barstar association were studied through the analysis of the proteins' relative rotational velocity. We considered the two proteins approaching each other in a response to their electrostatic attraction and employed a method that accounts for the long range and the many-body character of hydrodynamic interactions as well as complicated shapes of proteins. Hydrodynamic steering effects are clearly seen when attractive forces are applied to proteins geometric centers (resulting in zero torques) and the attraction acts along the line that connects centers of geometry of proteins in their crystallographic complex. When we rotate barstar relative to barnase around this line by an angle in the range of (-90(o),60(o)), the rotational velocity arising solely due to hydrodynamic interactions restores orientation of proteins that is observed in the crystal structure. However, as in reality both electrostatic forces and torques act on proteins, and these forces and torques depend on protein-protein distance and the relative orientation of binding partners, we investigated also more realistic situations employing continuum electrostatics calculations based on atomistic proteins models. Overall, we conclude that hydrodynamic interactions aid barnase and barstar in assuming a proper relative orientation upon complex formation. 23542720 Leptin as regulator of pulmonary immune responses: Involvement in respiratory diseases. Leptin is an adipocyte-derived hormone, recognized as a critical mediator of the balance between food intake and energy expenditure by signalling through its functional receptor (Ob-Rb) in the hypothalamus. Structurally, leptin belongs to the long-chain helical cytokine family, and is now known to have pleiotropic functions in both innate and adaptive immunity. The presence of the functional leptin receptor in the lung together with evidence of increased airspace leptin levels arising during pulmonary inflammation, suggests an important role for leptin in lung development, respiratory immune responses and eventually pathogenesis of inflammatory respiratory diseases. The purpose of this article is to review our current understanding of leptin and its functional role on the different resident cell types of the lung in health as well as in the context of three major respiratory conditions being chronic obstructive pulmonary disease (COPD), asthma, and pneumonia. 23238783 The influence of sex, ethnicity, and CYP2B6 genotype on bupropion metabolism as an index of hepatic CYP2B6 activity in humans. The effects of sex, ethnicity, and genetic polymorphism on hepatic CYP2B6 (cytochrome P450 2B6) expression and activity were previously demonstrated in vitro. Race/ethnic differences in CYP2B6 genotype and phenotype were observed only in women. To identify important covariates associated with interindividual variation in CYP2B6 activity in vivo, we evaluated these effects in healthy volunteers using bupropion (Wellbutrin SR GlaxoSmithKline, Research Triangle Park, NC) as a CYP2B6 probe substrate. A fixed 150-mg oral sustained-release dose of bupropion was administered to 100 healthy volunteers comprising four sex/ethnicity cohorts (n = 25 each): Caucasian men and Caucasian, African American, and Hispanic women. Blood samples were obtained at 0 and 6 hours postdose for the measurement of serum bupropion (BU) and hydroxybupropion (HB) concentrations. Whole blood was obtained at baseline for CYP2B6 genotyping. To characterize the relationship between CYP2B6 activity and ethnicity, sex, and genotype when accounting for serum BU concentrations (dose-adjusted log(10)-transformed), analysis of covariance model was fitted in which the dependent variable was CYP2B6 activity represented as the log(10)-transformed, metabolic ratio of HB to BU concentrations. Several CYP2B6 polymorphisms were associated with CYP2B6 activity. Evidence of dependence of CYP2B6 activity on ethnicity or genotype-by-ethnicity interactions was not detected in women. These results suggest that CYP2B6 genotype is the most important patient variable for predicting the level of CYP2B6 activity in women, when measured by the metabolism of bupropion. The bupropion metabolic ratio appears to detect known differences in CYP2B6 activity associated with genetic polymorphism, across different ethnic groups. Prospective studies will be needed to validate the use of bupropion as a probe substrate for clinical use. 23238235 Mutagenic/recombinogenic effects of four lipid peroxidation products in Drosophila. The human diet is an important factor in the development of different diseases. Lipid peroxidation during frying in edible vegetable liquid oils of food components is a mechanism leading to the formation of free radicals. Such radicals induce tissue damage and are implicated in diverse pathological conditions, including aging, atherosclerosis, brain disorders, cancer, lung disorders and various liver disorders. In the present study, we decided to investigate the genotoxic effects of four lipid peroxidation products in the in vivo Drosophila wing somatic mutation and recombination test. In this test, point mutation, chromosome breakage and mitotic recombination produce single spots; while twin spots are produced only by mitotic recombination. Drosophila is a suitable eukaryotic organism for mutagenicity studies and also its metabolism is quite similar to that of mammalians. Since conflicting data exist on the possible risk of several lipid peroxidation products for humans, we have selected four of them, namely acrolein, crotonaldehyde, 4-hydroxy-hexenal (4-HHE) and 4-oxo-2-nonenal (4-ONE). Especially at the highest concentrations tested all exert both mutagenic and recombinogenic effects in the Drosophila SMART assay, showing a direct dose-effect relationship. This is the first study reporting genotoxicity data in Drosophila for these compounds. 23578610 Inhibitory effect of skullcap (Scutellaria baicalensis) extract on ovalbumin permeation in vitro and in vivo. Scutellaria baicalensis Georgi (skullcap) has been widely used as a dietary ingredient. The purpose of this study was to reveal novel function of skullcap and its mechanism on allergen permeation in intestinal epithelial cells. Intestinal epithelial Caco-2 cell monolayers were used to evaluate the inhibitory effect of skullcap on ovalbumin (OVA) permeation by measuring transepithelial electrical resistance (TEER) and the quantity of permeated OVA. TEER increased and the OVA flux decreased in a dose-dependent manner through up-regulating tight junction-related proteins in cells incubated with increasing concentrations of skullcap extract. In the in vivo study, the amounts of OVA from orally ingested albumen reduced on administration of the skullcap extract. We also revealed for the first time that the active component of skullcap extract for inhibition of OVA permeation was baicalein. These findings demonstrated that skullcap extract might attenuate a food allergic response by inhibiting allergen permeation in vitro and in vivo. 23376712 Comparison of the effects of the GABAB receptor positive modulator BHF177 and the GABAB receptor agonist baclofen on anxiety-like behavior, learning, and memory in mice. γ-Aminobutyric acid B (GABAB) receptor activation is a potential therapeutic approach for the treatment of drug addiction, pain, anxiety, and depression. However, full agonists of this receptor induce side-effects, such as sedation, muscle relaxation, tolerance, and cognitive disruption. Positive allosteric modulators (PAMs) of the GABAB receptor may have similar therapeutic effects as agonists with superior side-effect profiles. The present study behaviorally characterized N-([1R,2R,4S]-bicyclo[2.2.1]hept-2-yl)-2-methyl-5-(4-[trifluoromethyl]phenyl)-4-pyrimidinamine (BHF177), a GABAB receptor PAM, in mouse models of anxiety-like behavior, learning and memory. In addition, the effects of BHF177 were compared with the agonist baclofen. Unlike the anxiolytic chlordiazepoxide, baclofen (0.5, 1.5, and 2.5 mg/kg, intraperitoneally) and BHF177 (10, 20, and 40 mg/kg, orally) had no effect on anxiety-like behavior in the elevated plus maze, light/dark box, or Vogel conflict test. Baclofen increased punished drinking in the Vogel conflict test, but this effect may be attributable to the analgesic actions of baclofen. At the highest dose tested (2.5 mg/kg), baclofen-treated mice exhibited sedation-like effects (i.e., reduced locomotor activity) across many of the tests, whereas BHF177-treated mice exhibited no sedation-like effects. BHF177 exhibited pro-convulsion properties only in mice, but not in rats, indicating that this effect may be species-specific. At doses that were not sedative or pro-convulsant, baclofen and BHF177 had no selective effects on fear memory retrieval in contextual and cued fear conditioning or spatial learning and memory in the Barnes maze. These data suggest that BHF177 has little sedative activity, no anxiolytic-like profile, and minimal impairment of learning and memory in mice. 23373544 Schisandra lignans-loaded enteric nanoparticles: preparation, characterization, and in vitro-in vivo evaluation. Schisandrae lignans (SL) have been well proven to possess hepatoprotective effect against the hepatic dysfunction induced by various chemical hepatotoxins. Deoxyschisandrin (DA) and schisantherin A (SA) are both considered as the major active components in SL. The objective of the study was to prepare and evaluate Schisandra lignans (composed of DA and SA)-loaded enteric nanoparticles produced by a novel toxic solvent-free modified spontaneous emulsification solvent diffusion (SESD) method. An organic Schisandra lignans/Eudragit(®) S100 solution was injected into an aqueous poloxamer 188 solution under a agitation. The nanoparticles were characterized with respect to particle size distribution, morphology, encapsulation efficiency (EE) and physical stability of the drug, wettability, in vitro release and in vivo bioavailability. Nanoparticles with a smooth surface and dense structure were obtained with high EE (EE(DA) >90%; EE(SA) >85%). The drug was in a noncrystalline state in the matrix and physically stable for 120 days at room temperature. In vitro drug release study, the drug dissolution rate from the nanoparticles was significantly enhanced compared to the physical mixture and to the pure drug; the release profile of the nanoparticles was stable after 120 days. The appropriate size of nanoparticles (~93 nm), the solubilization of the surfactant, the noncrystalline state of the drug in the matrix and the fast dissolution rate contributed to a significantly enhanced oral bioavailability from the nanoparticles when compared to pure drug suspension. 23602903 Monoterpene pyridine alkaloids and phenolics from Scrophularia ningpoensis and their cardioprotective effect. Scrophularianines A-C (1-3), three new unusual monoterpene pyridine alkaloids with cyclopenta [c] pyridine skeleton reported from the genus Scrophularia for the first time, together with 15 known compounds (4-18), were isolated from the extract of Scrophularia ningpoensis. Their structures were elucidated on the basis of extensive analyses of spectroscopic evidences. The biogenetic relationship between monoterpene pyridine alkaloids and iridoids was proposed preliminarily. The myocardial protective bioassay indicated that compounds 13 and 14 with a concentration of 10(-4)M exhibited significantly protective effect against H2O2-induced apoptosis in cardiomyocytes. 23603339 Dehydroepiandrosterone post-transcriptionally modifies CYP1A2 induction involving androgen receptor. The pharmacological dosage of dehydroepiandrosterone (DHEA) protects against chemically induced carcinogenesis. The chemoprotective activity of DHEA is attributed to its inhibitory potential for the expression of CYP1A enzymes, which are highly responsible for metabolic activation of several mutagenic and carcinogenic chemicals. The present work investigated whether the chemoprevention by DHEA was due to diminished transcriptional activation of CYP1A genes or to the post-transcriptional modulation of CYP1A expression. In primary human hepatocytes, DHEA diminished the increase in CYP1A activities (7-ethoxyresorufin O-dealkylation and phenacetin O-dealkylation) and in CYP1A2 mRNA level induced by 3-methylcholanthrene, but did not alter the amount of CYP1A1 and CYP1B1 mRNA. The androgen receptor seemed to be involved in DHEA-mediated diminishment of CYP1A2 induction, which was attenuated in the presence of bicalutamide, the androgen receptor antagonist. The potential role of the glucocorticoid receptor and estrogen receptor in DHEA-mediated decrease in CYP1A2 induction was excluded. The developed computational model of CYP1A2 induction kinetics and CYP1A2 mRNA degradation proposed that a post-transcriptional mechanism was likely to be the primary mechanism of the DHEA-mediated diminishment of CYP1A2 induction. The hypothesis was confirmed by the results of actinomycin D-chase experiments in MCF-7 and LNCaP cells, displaying that the degradation rates of CYP1A2 mRNA were significantly higher in the cells exposed to DHEA. The novel findings on DHEA-mediated modulation of CYP1A2 mRNA stability may account for the beneficial effects of DHEA by decreasing the metabolic activation of pro-carcinogenic compounds. 23296100 Manganese-induced oxidative DNA damage in neuronal SH-SY5Y cells: attenuation of thymine base lesions by glutathione and N-acetylcysteine. Manganese (Mn) is an essential trace element required for normal function and development. However, exposure to this metal at elevated levels may cause manganism, a progressive neurodegenerative disorder with neurological symptoms similar to idiopathic Parkinson's disease (IPD). Elevated body burdens of Mn from exposure to parental nutrition, vapors in mines and smelters and welding fumes have been associated with neurological health concerns. The underlying mechanism of Mn neurotoxicity remains unclear. Accordingly, the present study was designed to investigate the toxic effects of Mn(2+) in human neuroblastoma SH-SY5Y cells. Mn(2+) caused a concentration dependent decrease in SH-SY5Y cellular viability compared to controls. The LD50 value was 12.98 μM Mn(2+) (p<0.001 for control vs. 24h Mn treatment). Both TUNEL and annexin V/propidium iodide (PI) apoptosis assays confirmed the induction of apoptosis in the cells following exposure to Mn(2+) (2 μM, 62 μM or 125 μM). In addition, Mn(2+) induced both the formation and accumulation of DNA single strand breaks (via alkaline comet assay analysis) and oxidatively modified thymine bases (via gas chromatography/mass spectrometry analysis). Pre-incubation of the cells with characteristic antioxidants, either 1mM N-acetylcysteine (NAC) or 1mM glutathione (GSH) reduced the level of DNA strand breaks and the formation of thymine base lesions, suggesting protection against oxidative cellular damage. Our findings indicate that (1) exposure of SH-SY5Y cells to Mn promotes both the formation and accumulation of oxidative DNA damage, (2) SH-SY5Y cells with accumulated DNA damage are more likely to die via an apoptotic pathway and (3) the accumulated levels of DNA damage can be abrogated by the addition of exogenous chemical antioxidants. This is the first known report of Mn(2+)-induction and antioxidant protection of thymine lesions in this SH-SY5Y cell line and contributes new information to the potential use of antioxidants as a therapeutic strategy for protection against Mn(2+)-induced oxidative DNA damage. 23147415 Mice heterozygous for AChE are more sensitive to AChE inhibitors but do not respond to BuChE inhibition. An impaired central cholinergic system is at least partly involved in Alzheimer's disease (AD) pathogenesis, with cholinergic markers such as acetylcholinesterase (AChE) activity and protein levels decreasing as cognitive decline progresses. AD patients receive AChE inhibitor drugs to enhance cholinergic responses in the brain. The present study characterises the cholinergic system of mice heterozygous for AChE (HZ) as a suitable in vivo model for permanently reduced AChE activity. In comparison to homozygous, wild type (WT) mice, HZ mice show a 40% reduction of AChE activity in the brain, while their hippocampal ACh levels are increased by 56% as measured by microdialysis; choline acetyltransferase levels remain unaltered, and choline uptake increases 2-fold. We demonstrate that HZ mice are significantly more sensitive to local AChE inhibition (BW284c51), but remain insensitive to butyrylcholinesterase (BuChE) inhibition (bambuterol). HZ mice are also more sensitive to the peripheral application of the selective AChE inhibitor donepezil or the mixed inhibitor physostigmine; extracellular ACh levels rise significantly after administration of both drugs; also glucose levels are moderately increased indicating potentially non-cholinergic effects of donepezil. Behavioural tests show comparable cognitive function in both mouse strains. Our results are discussed in relation to the use of AChE/BuChE inhibitors in AD patients. 23017389 Studies on the antioxidant potential of flavones of Allium vineale isolated from its water-soluble fraction. The aim of this work was to examine the chemical constituents and antioxidant potential of water-soluble fractions from the commonly consumed vegetable, Allium vineale. The water-soluble fraction, containing phenolic compounds, was extracted with ethyl acetate to obtain flavonoids which were separated and purified by repeated column chromatography over Sephadex LH-20, RP C18 and silica gel. The isolated compounds were identified according to their physicochemical properties and spectral data (UV, HPLC-TOF/MS, (1)H NMR, (13)C NMR and 2D NMR). Three flavonoids were isolated and identified as chrysoeriol-7-O-[2″-O-E-feruloyl]-β-d-glucoside (1), chrysoeriol (2), and isorhamnetin-3-β-d-glucoside (3). Antioxidant studies of the aqueous extract and three isolated compounds, 1, 2, 3, were undertaken and they were found to have significant antioxidant activity. Antioxidant activities were evaluated for total antioxidant activity by the ferric thiocyanate method, ferric ion (Fe(3+)) reducing antioxidant power assay (FRAP), ferrous ion (Fe(2+)) metal chelating activity, and DPPH free radical-scavenging activity. The water-soluble ethyl acetate and methanol extraction methods were also compared using HPLC-TOF/MS. 23290724 Zinc drives a tertiary fold in the prion protein with familial disease mutation sites at the interface. The cellular prion protein PrP(C) consists of two domains--a flexible N-terminal domain, which participates in copper and zinc regulation, and a largely helical C-terminal domain that converts to β sheet in the course of prion disease. These two domains are thought to be fully independent and noninteracting. Compelling cellular and biophysical studies, however, suggest a higher order structure that is relevant to both PrP(C) function and misfolding in disease. Here, we identify a Zn²⁺-driven N-terminal to C-terminal tertiary interaction in PrP(C). The C-terminal surface participating in this interaction carries the majority of the point mutations that confer familial prion disease. Investigation of mutant PrPs finds a systematic relationship between the type of mutation and the apparent strength of this domain structure. The structural features identified here suggest mechanisms by which physiologic metal ions trigger PrP(C) trafficking and control prion disease. 23465066 Highly Responsive Ultrathin GaS Nanosheet Photodetectors on Rigid and Flexible Substrates. The first GaS nanosheet-based photodetectors are demonstrated on both mechanically rigid and flexible substrates. Highly crystalline, exfoliated GaS nanosheets are promising for optoelectronics due to strong absorption in the UV-visible wavelength region. Photocurrent measurements of GaS nanosheet photodetectors made on SiO2/Si substrates and flexible polyethylene terephthalate (PET) substrates exhibit a photoresponsivity at 254 nm up to 4.2 AW(-1) and 19.2 AW(-1), respectively, which exceeds that of graphene, MoS2, or other 2D material-based devices. Additionally, the linear dynamic range of the devices on SiO2/Si and PET substrates are 97.7 dB and 78.73 dB, respectively. Both surpass that of currently exploited InGaAs photodetectors (66 dB). Theoretical modeling of the electronic structures indicates that the reduction of the effective mass at the valence band maximum (VBM) with decreasing sheet thickness enhances the carrier mobility of the GaS nanosheets, contributing to the high photocurrents. Double-peak VBMs are theoretically predicted for ultrathin GaS nanosheets (thickness less than five monolayers), which is found to promote photon absorption. These theoretical and experimental results show that GaS nanosheets are promising materials for high-performance photodetectors on both conventional silicon and flexible substrates. 23069619 A case study of real-time monitoring of solid-state phase transformations in acoustically levitated particles using near infrared and Raman spectroscopy. The objective of this study was to monitor the amorphous-to-crystalline solid-state phase transformation kinetics of the model drug ibuprofen with spectroscopic methods during acoustic levitation. Chemical and physical information was obtained by real-time near infrared (NIRS) and Raman spectroscopy measurements. The recrystallisation kinetic parameters (overall recrystallisation rate constant β and the time needed to reach 50% of the equilibrated level t(50)), were determined using a multivariate curve resolution approach. The acoustic levitation device coupled with non-invasive spectroscopy enabled monitoring of the recrystallisation process of the difficult-to-handle (adhesive) amorphous sample. The application of multivariate curve resolution enabled isolation of the underlying pure spectra, which corresponded well with the reference spectra of amorphous and crystalline ibuprofen. The recrystallisation kinetic parameters were estimated from the recrystallisation profiles. While the empirical recrystallisation rate constant determined by NIR and Raman spectroscopy were comparable, the lag time for recrystallisation was significantly lower with Raman spectroscopy as compared to NIRS. This observation was explained by the high energy density of the Raman laser beam, which might have led to local heating effects of the sample and thus reduced the recrystallisation onset time. It was concluded that acoustic levitation with NIR and Raman spectroscopy combined with multivariate curve resolution allowed direct determination of the recrystallisation kinetics of amorphous drugs and thus is a promising technique for monitoring solid-state phase transformations of adhesive small-sized samples during the early phase of drug development. 23216335 Platelet-derived microparticles in overweight/obese women with the polycystic ovary syndrome. A substantial proportion of women with the polycystic ovary syndrome (PCOS) are obese and obesity is considered as a prothrombotic state. Platelet-derived microparticles (PMPs) might be implicated in the activation of the coagulation cascade. We aimed to assess plasma PMPs in overweight/obese women with PCOS. We measured plasma PMPs and determined anthropometric, metabolic, hormonal and ultrasonographic features of PCOS in 67 overweight/obese women with PCOS (with body mass index [BMI] >25.0 kg/m(2)) and in 21 BMI-matched healthy women. Circulating androgens and markers of insulin resistance (IR) were higher in women with PCOS than in controls. Plasma PMPs were also higher in women with PCOS than in controls (p = 0.046). In women with PCOS, plasma PMPs correlated with the mean number of follicles in the ovaries (r = 0.343; p = 0.006). In controls, plasma PMPs did not correlate with any of the studied parameters. In conclusion, plasma PMPs are elevated in overweight/obese women with PCOS compared with BMI-matched controls. The cause of this increase is unclear but both IR and hyperandrogenemia might be implicated. More studies are required to elucidate the pathogenesis of the elevation of PMPs in PCOS and to assess its implications on the cardiovascular risk of these patients. 23408270 Anthelmintic activity of the natural compound (+)-limonene epoxide against Schistosoma mansoni. Blood fluke of the genus Schistosoma are the etiological agents of human schistosomiasis, an important neglected tropical disease that afflicts over 200 million people worldwide. The treatment for this disease relies heavily on a single drug, praziquantel. Recent reports of praziquantel resistance raise concerns about future control of the disease and show the importance of developing new antischistosomal drugs. Currently, natural products have been a good source for drug development. (+)-Limonene epoxide is a mixture of cis and trans isomers found in many plants. Here, we report the in vitro effect of this natural compound on the survival time of Schistosoma mansoni adult worms. In addition, we examined alterations on the tegumental surface of adult schistosomes by means of confocal laser scanning microscopy. The effects of (+)-limonene epoxide at 25 µg/mL on S. mansoni adult worms were similar to those of the positive control (praziquantel), with reduction in motility and death of all worms after 120 h. Confocal laser scanning microscopy revealed that (+)-limonene epoxide-mediated worm killing was associated with tegumental destruction. Our results, along with the low toxicity of the (+)-limonene epoxide, suggest that this natural compound might be promising for the development of new schistosomicidal agents. 23644200 Glycosylation enhances the anti-migratory activities of isomalyngamide A analogs. Three, new, fully synthetic glycosylated isomalyngamide A analogs 4-6 were prepared and evaluated for their anti-migratory activities in human breast cancer cells. The results of the study show that two glycosylated derivatives 4 and 5, containing mannose and galactose appendages, suppress metastatic events (e.g., migration, invasion and adhesion) in human breast adenocarcinoma MDA-MB-231 cells at "nontoxic" concentration levels. In contrast, derivative 6 that contains a lactose moiety, displays a less potent activity. The findings show that monosaccharide rather than disaccharide appendages to the isomalyngamide A backbone more greatly influence cell migration and invasive ability. Evidence has been gained for a mechanism for inhibition of metastatic activities in MDA-MB-231 cells by 4 and 5, involving inactivation of the expression of p-FAK and paxillin through the integrin-mediated antimetastatic pathway. 23361383 Role of diuretics and lipid formulations in the prevention of amphotericin B-induced nephrotoxicity. PURPOSE: To collect available clinical data to define the role of diuretics and lipid formulations in the prevention of amphotericin B (AmB)-induced nephrotoxicity (AIN) in human populations. METHOD: A literature search was performed in the following databases: Scopus, Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. RESULTS AND CONCLUSION: Co-administration of mannitol failed to show any clinically significant benefit in preventing AIN. Potassium-sparing diuretics, such as amiloride and spironolactone, have been shown to have beneficial effects as an alternative or adjunct to oral/parenteral potassium supplements in preventing hypokalemia due to AmB. Lipid-based formulations of AmB are clinically effective and safe in preventing AIN. However, due to their high cost and limited accessibility, these formulations are generally used as second-line antifungal therapy in cases of conventional AmB refractoriness and/or intolerance or pre-existing renal dysfunction. The potential effects of other nephroprotective agents, such as N-acetylcysteine, AIN merit further considerations and investigations. 23295582 Novel topical formulations of Terbinafine-HCl for treatment of onychomycosis. Terbinafine hydrochloride (TBF-HCl) is an active substance that is using for treatment of onychomycosis. Onychomycosis is a fungal infection which is the most common disease of nail plate. The nail plate is a barrier which prevents effective topical treatment of ungual disorders. In this study, TBF-HCl loaded liposome and ethosome formulations and also gel form of these formulations were prepared. The formulations were characterized and in vitro and ex vivo release studies were performed. Nail characterization studies were also performed to examine the effect of formulations and experimental conditions on nail surface. As a result, all formulations can serve as efficient formulations for ungual application of TBF-HCl. By the way, the results of the accumulation studies suggested that liposome poloxamer gel formulation could be promising system for ungual drug delivery due to the better accumulation and easier application of the formulation. 23609445 YidC occupies the lateral gate of the SecYEG translocon and is sequentially displaced by a nascent membrane protein. Most membrane proteins are co-translationally inserted into the lipid bilayer via the universally conserved SecY complex and they access the lipid phase presumably via a lateral gate in SecY. In bacteria, the lipid transfer of membrane proteins from the SecY channel is assisted by the SecY-associated protein YidC, but details on the SecY-YidC interaction are unknown. By employing an in vivo and in vitro site-directed cross-linking approach, we have mapped the SecY-YidC interface and found YidC in contact with all four transmembrane domains of the lateral gate. This interaction did not require the SecDFYajC complex and was not influenced by SecA binding to SecY. In contrast, ribosomes dissociated the YidC contacts to lateral gate helices 2b and 8. The major contact between YidC and the lateral gate was lost in the presence of ribosome-nascent chains and new SecY-YidC contacts appeared. These data demonstrate that the SecY-YidC interaction is influenced by nascent-membrane induced lateral gate movements. 23220412 Comparative responses of two species of marine phytoplankton to metolachlor exposure. Metolachlor, a chloroacetanilide herbicide, has been frequently detected in coastal waters. This study examined the growth, photosynthesis, and detoxification responses of chlorophyte Dunaliella tertiolecta (DT) and brown tide alga Aureococcus anophagefferens (AA) upon 5-day exposure to 0.5-5 mg L(-1) metolachlor. Growth was assessed with exponential growth rate, and 5th day in vivo chlorophyll fluorescence, chlorophyll a, b or c, cell density and cell size. The photosynthesis function was assessed with photochemical parameters of photosystem II (PSII) during the mid-exponential growth phase (i.e. 2-4 day metolachlor exposure). The biochemical detoxification was analyzed with glutathione production and metolachlor degradation. Results show that metolachlor caused up to ∼9% inhibition in growth rate in both species and an expected ∼35% and 25% inhibition in chlorophyll based endpoints in DT and AA respectively. DT had an up to 70% inhibition in cell density, but AA a 35% hormesis at 1 mg L(-1) metolachlor and no significant inhibition, as compared to the controls. Both DT and AA's cell sizes were enlarged by metolachlor exposure, but greater in DT (1.2% per mg L(-1)) than in AA (0.68% per mg L(-1)). On PSII photochemistry, maximum quantum yield was not affected in both species; PSII optical cross section and connectivity factor increased in DT but decreased in AA, suggesting species specific impact on PSII function. On detoxification responses, glutathione production, when normalized to total chlorophyll a, was not affected by metolachlor in both species; further, despite of heterotrophic capacity of A. anophagefferens metolachlor was not significantly degraded by this alga during the 5-day incubation. The species specific effects on algal growth have ecological implications of potential selective inhibition of chlorophytes by metolachlor herbicide. 23466874 Anti-diabetic effects of brown algae derived phlorotannins, marine polyphenols through diverse mechanisms. Marine algae are popular and abundant food ingredients mainly in Asian countries, and also well known for their health beneficial effects due to the presence of biologically active components. The marine algae have been studied for biologically active components and phlorotannins, marine polyphenols are among them. Among marine algae, brown algae have extensively studied for their potential anti-diabetic activities. Majority of the investigations on phlorotannins derived from brown algae have exhibited their various anti-diabetic mechanisms such as α-glucosidase and α-amylase inhibitory effect, glucose uptake effect in skeletal muscle, protein tyrosine phosphatase 1B (PTP 1B) enzyme inhibition, improvement of insulin sensitivity in type 2 diabetic db/db mice, and protective effect against diabetes complication. In this review, we have made an attempt to discuss the various anti-diabetic mechanisms associated with phlorotannins from brown algae that are confined to in vitro and in vivo. 23338525 Highly effective Ir(x)Sn(1-x)O2 electrocatalysts for oxygen evolution reaction in the solid polymer electrolyte water electrolyser. We developed an advanced surfactant-assistant method for the Ir(x)Sn(1-x)O(2) (0 < x ≤ 1) nanoparticle (NP) preparation, and examined the OER performances by a series of half-cell and full-cell tests. In contrast to the commercial Ir black, the collective data confirmed the outstanding activity and stability of the fabricated Ir(x)Sn(1-x)O(2) (x = 1, 0.67 and 0.52) NPs, which could be ascribed to the amorphous structure, good dispersion, high pore volume, solid-solution state and Ir-rich surface for bi-metal oxides, and relatively large size (10-11 nm), while Ir(0.31)Sn(0.69) exhibited poor electro-catalytic activity because of the separated two phases, a SnO(2)-rich phase and an IrO(2)-rich phase. Furthermore, compared with highly active IrO(2), the improved durability, precious-metal Ir utilization efficiency and correspondingly reduced Ir loading were realized by the addition of Sn component. When the Ir(0.52)Sn(0.48)O(2) cell operated at 80 °C using Nafion® 115 membrane and less than 0.8 mg cm(-2) of the noble-metal Ir loading, the cell voltages we achieved were 1.631 V at 1000 mA cm(-2), and 1.821 V at 2000 mA cm(-2). The IR-free voltage at the studied current density was very close to the onset voltage of oxygen evolution. The only 50 μV h(-1) of voltage increased for the 500 h durability test at 500 mA cm(-2). In fact, these results are exceptional compared to the performances for OER in SPEWE cells known so far. This work highlights the potential of using highly active and stable IrO(2)-SnO(2) amorphous NPs to enhance the electrolysis efficiency, reduce the noble-metal Ir loading and thus the cost of hydrogen production from the solid polymer electrolyte water electrolysis. 23427064 Interactive effects of contaminants and climate-related stressors: High temperature increases sensitivity to cadmium. An emerging issue in environmental toxicology is in understanding how climate change will alter responses of organisms to chemical contaminants. The objective of the present study was to characterize the interactive effects of cadmium and elevated temperature on life-stage-specific responses in the freshwater snail Physa pomilia. We exposed developing eggs, juveniles, and adults to Cd (5 µg/L, 15 µg/L, and 25 µg/L for eggs, and 250 µg/L for juveniles and adults) and 2 temperatures of 25 °C (control) and 35 °C (upper range of tolerance). In the absence of Cd, time to hatch was shorter at 35 °C compared with 25 °C, demonstrating a stimulatory effect of the higher temperature. However, when egg masses were reared at 35 °C and exposed to Cd, hatching success was significantly lower, and time-to-hatching was significantly longer. The effects of the higher temperature and Cd on newly hatched neonate survival were additive, except at the highest Cd concentration, at which effects of the 2 stressors were greater than additive. Overall, within the combined stressor treatments, adult snails generally survived significantly longer than did juvenile snails, and both were more tolerant than developing snails. Many climate projection models predict future increases in global temperatures. The present study shows that combined stressors may produce greater-than-additive effects, challenging predictive power. More studies are needed to better characterize the interactive effects of chemical contaminants and stressors related to climate change. Environ Toxicol Chem 2013;32:1337-1343. © 2013 SETAC. 23290050 On the preparation of indoxyl red from indican and some new characteristics. An indole compound with a strong purple-red color was produced by boiling a solution of indican under acidic conditions and purified by chromatographies on DEAE-650S Toyopearl TSK-gel and silica-gel columns. The purple-red compound purified was identified as indoxyl red, on the basis of FAB Mass, (13)C NMR, (1)H NMR, UV-visible spectra, and IR spectra. Although indoxyl red was first synthesized by Seidel(9) 70 years ago, very little information has been available on its characteristics. We repot here that the compound was purple-red colored at acidic pH and green at pH 13, and showed antiproliferative and cytotoxic activities to the mouse B cell lymphoma cell line NSF202. 22507666 mGlu5R promotes glutamate AMPA receptor phosphorylation via activation of PKA/DARPP-32 signaling in striatopallidal medium spiny neurons. Group I metabotropic glutamate receptors (mGluRs), which comprise mGlu1Rs and mGlu5Rs, are enriched in striatal medium spiny neurons (MSNs), where they modulate glutamatergic transmission. Here, we have examined the effect of group I mGluRs on the regulation of the state of phosphorylation of the GluA1 subunit of the AMPA glutamate receptor. We found that incubation of mouse striatal slices with the group I mGluR agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) promotes GluA1 phosphorylation at the cAMP-dependent protein kinase (PKA) site, Ser845. This effect is prevented by 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), a selective mGlu5R antagonist. The increase in GluA1 phosphorylation produced by DHPG is also prevented by blockade of adenosine A2A receptors (A2ARs), which are known to promote cAMP signaling specifically in striatopallidal MSNs, as well as by enzymatic degradation of endogenous adenosine, achieved with adenosine deaminase. The ability of DHPG to increase PKA-dependent phosphorylation of GluA1 depends on concomitant activation of the dopamine- and cAMP-regulated phosphoprotein of 32kDa (DARPP-32). Thus, inactivation of the PKA phosphorylation site of DARPP-32 abolishes the effect of DHPG. Moreover, cell-specific knock out of DARPP-32 in striatopallidal, but not in striatonigral, MSNs prevents the increase in Ser845 phosphorylation induced by DHPG. These results indicate that activation of mGlu5Rs promotes PKA/DARPP-32-dependent phosphorylation of downstream target proteins in striatopallidal MSNs and that this effect is exerted via potentiation of tonic A2AR transmission. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. 23641955 Using human recombinant UDP-glucuronosyltransferase isoforms and a relative activity factor approach to model total body clearance of laropiprant (MK-0524) in humans. Abstract 1.  A major pathway of elimination of the prostaglandin D2 receptor 1 antagonist laropiprant in humans is by uridine diphosphate-glucuronosyltransferase (UGT)-mediated biotransformation. In this study, liver and kidney relative activity factors were developed for UGT1A1, 1A9 and 2B7 to allow for in vitro-in vivo extrapolation of intrinsic clearance data to whole organ clearance using recombinant human UGT isoforms applying this to laropiprant as a model substrate. 2.  The total body metabolic clearance of laropiprant determined using this approach (5.0 L/hr) agreed well with the value determined in vivo following intravenous administration to healthy human volunteers (5.1 L/hr). 3.  The results suggest that approximately 36%, 36% and 28% of the hepatic metabolic clearance of laropiprant was mediated by UGT1A1, 1A9 and 2B7, respectively. Likewise, 80% and 20% of the renal metabolic clearance was mediated by UGT1A9 and 2B7, respectively. Furthermore, the data suggested that the contribution of the kidney to the overall total metabolic clearance was minor relative to the liver (∼ 12%). 23206503 Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy. N-palmitoylethanolamine (PEA), an endogenous fatty acid ethanolamide, plays a key role in the regulation of the inflammatory response and pain through, among others, activation of nuclear peroxisome proliferator-activated receptors (PPAR-α). Endogenous cannabinoids play a protective role in several central nervous system (CNS) disorders, particularly those associated with neuronal hyperexcitability. We investigated the effects of PEA and the role of PPAR-α in absence epilepsy using the WAG/Rij rat model. PEA, anandamide (AEA), a PPAR-α antagonist (GW6471) and a synthetic CB1 receptor antagonist/inverse agonist (SR141716) were administered to WAG/Rij rats in order to evaluate the effects on epileptic spike-wave discharges (SWDs) on EEG recordings. We studied also the effects of PEA co-administration with SR141716 and GW6471 and compared these effects with those of AEA to evaluate PEA mechanism of action and focusing on CB1 receptors and PPAR-α. Both PEA and AEA administration significantly decreased SWDs parameters (absence seizures). In contrast, GW6471 was devoid of effects while SR141716 had pro-absence effects. The co-administration of SR141716 with PEA or AEA completely blocked the anti-absence effects of these compounds. GW6471 antagonized PEA's effects whereas it did not modify AEA's effects. Furthermore, we have also measured PEA, AEA and 2-AG (2-arachidonoylglycerol) brain levels identifying significant differences between epileptic and control rats such as decreased PEA levels in both thalamus and cortex that might contribute to absence epilepsy. Our data demonstrate that PEA has anti-absence properties in the WAG/Rij rat model and that such properties depend on PPAR-α and indirect activation of CB1 receptors. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'. 23530765 Electron Paramagnetic Resonance Spectroscopic Study of Copper Hopping in Doped Bis(l-histidinato)cadmium Dihydrate. Electron paramagnetic resonance (EPR) spectroscopy was used to study Cu(II) dynamic behavior in a doped biological model crystal, bis(l-histidinato)cadmium dihydrate, in order to gain better insight into copper site stability in metalloproteins. Temperature-dependent changes in the low temperature X-band EPR spectra became visible around 100 K and continued up to room temperature. The measured 298 K g-tensor (principal values: 2.17, 2.16, 2.07) and copper hyperfine coupling tensor (principal values: -260, -190, -37 MHz) were similar to the average of the 77 K tensor values pertaining to two neighboring histidine binding sites. The observed temperature dependence was interpreted using Anderson's theory of motional narrowing, where the magnetic parameters for the different states are averaged as the copper rapidly hops between sites. The EPR pattern was also found to undergo a sharp sigmoidal-shaped, temperature-dependent conversion between two species with a critical temperature Tc ≈ 160 K. The species below Tc hops between the two low temperature site patterns, and the one above Tc represents an average of the molecular spin Hamiltonian coupling tensors of the two 77 K sites. In addition, the low and high temperature species hop between one another, contributing to the dynamic averaging. Spectral simulations using this 4-state model determined a hop rate between the two low temperature sites νh4 = 4.5 × 10(8) s(-1) and between the low and high temperature states νh2 = 1.7 × 10(8) s(-1) at 160 K. An Arrhenius relationship of hop rate and temperature gave energy barriers of ΔE4 = 389 cm(-1) and ΔE2 = 656 cm(-1) between the two low temperature sites and between the low and high temperature states, respectively. 22985953 Ultrasonic treatment and synthesis of sugar alcohol modified Na+-montmorillonite clay. Na(+)-montmorillonite clay (generally referred to as MMT) is very useful for reinforcing polymeric matrix at very low concentrations (typically, 2-5% wt). These clay particles are typically exfoliated before they can demonstrate the significant gains in heat deflection temperature, modulus, and elongation properties. In the case of hydrophilic biopolymer based matrices, such as carbohydrates and chitosan, exfoliating these nanoclay particles needs greater attention because the exfoliation is typically carried out using hydrophobic oligomers through ion-exchange. This study reports a new method of synthesizing completely hydrophilic MMT-assemblages using hydrophilic plasticizers for biopolymers. We used sugar alcohols (glycerol, xylitol with 3 and 5 hydroxyl groups) and polysaccharide maltodextrin to exfoliate the MMT. Sonication was conducted for MMT nanoclay and plasticizers at different weight ratios. It was confirmed that all plasticizer/modifier led to expansion of MMT gallery spacing (d-spacing) and the change in d-spacing could be related to the molecular structure of the plasticizer. Meanwhile, the extent of exfoliation was maximum with maltodextrin (fully exfoliation with 1:10 and 1:20 ratio of MMT:plasticizer) across all test samples and interestingly, glycerol and xylitol samples quickly established within the MMT galleries and exhibited minimal influence with further increase in relative concentrations. 23327557 Interactions between pectic compounds and procyanidins are influenced by methylation degree and chain length. The interactions between procyanidins and pectic compounds are of importance in food chemistry. Procyanidins with low (9) and high (30) average degrees of polymerization (DP9 and DP30) were extracted from two cider apple varieties. Commercial apple and citrus pectins, as well as three pectin subfractions (homogalacturonans, partially methylated homogalacturonans with degree of methylation 30 and 70) at 30 mM galacturonic acid equivalent, were titrated with the two procyanidin fractions (at 30 mM (-)-epicatechin equivalent) by isothermal titration calorimetry and UV-vis spectrophotometry. Slightly stronger affinities were recorded between commercial apple or citrus pectins and procyanidins of DP30 (Ka = 1460 and 1225 M(-1) respectively, expressed per monomer units) compared to procyanidins of DP9 (Ka = 1240 and 1085 M(-1), respectively), but stoichiometry and absorbance maxima differed between apple and citrus pectins. It was proposed that methylated homogalacturonans interacted with procyanidins DP30 mainly through hydrophobic interactions. The stronger association was obtained with the longer procyanidin molecules interacting with highly methylated pectins. 23538868 Diketopiperazine Derivatives from the Marine-Derived Actinomycete Streptomyces sp. FXJ7.328. Five new diketopiperazine derivatives, (3Z,6E)-1-N-methyl-3-benzy lidene-6-(2S-methyl-3-hydroxypropylidene)piperazine-2,5-dione (1), (3Z,6E)-1-N-methyl-3-benzylidene-6-(2R-methyl-3-hydroxypropylidene)piperazine-2,5-dione (2), (3Z,6Z)-3- (4-hydroxybenzylidene)-6-isobutylidenepiperazine-2,5-dione (3), (3Z,6Z)-3-((1H-imidazol-5-yl)-methylene)-6-isobutylidenepiperazine-2,5-dione (4), and (3Z,6S)-3-benzylidene-6-(2S-but-2-yl)piperazine-2,5-dione (5), were isolated from the marine-derived actinomycete Streptomyces sp. FXJ7.328. The structures of 1-5 were determined by spectroscopic analysis, CD exciton chirality, the modified Mosher's, Marfey's and the C3 Marfey's methods. Compound 3 showed modest antivirus activity against influenza A (H1N1) virus with an IC50 value of 41.5 ± 4.5 μM. In addition, compound 6 and 7 displayed potent anti-H1N1 activity with IC50 value of 28.9 ± 2.2 and 6.8 ± 1.5 μM, respectively. Due to the lack of corresponding data in the literature, the 13C NMR data of (3Z,6S)-3-benzylidene-6-isobutylpiperazine-2,5-dione (6) were also reported here for the first time. 23571308 Quantification of the Young's modulus of the primary plant cell wall using Bending-Lab-On-Chip (BLOC). Biomechanical and mathematical modeling of plant developmental processes requires quantitative information about the structural and mechanical properties of living cells, tissues and cellular components. A crucial mechanical property of plant cells is the mechanical stiffness or Young's modulus of its cell wall. Measuring this property in situ at single cell wall level is technically challenging. Here, a bending test is implemented in a chip, called Bending-Lab-On-a-Chip (BLOC), to quantify this biomechanical property for a widely investigated cellular model system, the pollen tube. Pollen along with culture medium is introduced into a microfluidic chip and the growing pollen tube is exposed to a bending force created through fluid loading. The flexural rigidity of the pollen tube and the Young's modulus of the cell wall are estimated through finite element modeling of the observed fluid-structure interaction. An average value of 350 MPa was experimentally estimated for the Young's modulus in longitudinal direction of the cell wall of Camellia pollen tubes. This value is in agreement with the result of an independent method based on cellular shrinkage after plasmolysis and with the mechanical properties of in vitro reconstituted cellulose-callose material. 23507573 Minireview: Nuclear Insulin and Insulin-like Growth Factor-1 Receptors: A Novel Paradigm in Signal Transduction. The specificity of the insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF1R) signaling pathways has been the focus of significant debate over the past few years. Recent evidence showing nuclear import and a direct transcriptional role for both InsR and IGF1R adds a new layer of complexity to this dialog. Hence, in addition to the classical roles associated with cell-surface receptors (eg, ligand binding, autophosphorylation of the tyrosine kinase domain, activation of insulin receptor substrate 1 (IRS-1) and additional substrates, protein-protein interactions with membrane and cytoplasm components), new data are consistent with nuclear (genomic) role(s) for both InsR and IGF1R. The present review provides a brief overview of the physical and functional similarities and differences between InsR and IGF1R and describes data from a number of laboratories providing evidence for a new layer of signaling regulation (ie, the ability of InsR and IGF1R to translocate to the cell nucleus and to elicit genomic activities usually associated with transcription factors). The ability of InsR and IGF1R to function as transcription factors, although poorly understood, constitutes a new paradigm in signal transduction. Although research on the role of nuclear InsR/IGF1R is still in its infancy, we believe that this rapidly developing area may have a major basic and translational impact on the fields of metabolism, diabetes, and cancer. 23261590 Neoechinulin A suppresses amyloid-β oligomer-induced microglia activation and thereby protects PC-12 cells from inflammation-mediated toxicity. A pathological hallmark of Alzheimer's disease (AD), aggregation and deposition of amyloid-β peptides, has been recognized as a potent activator of microglia-mediated neuroinflammation and neuronal dysfunction. Therefore, downregulation of microglial activation has a significant therapeutic demand. In this study, focus was given to evaluate the ability of neoechinulin A, an indole alkaloid isolated from marine-derived Microsporum sp., to attenuate microglial activation by oligomeric amyloid-β 1-42 (Aβ42). Neoechinulin A treatment significantly inhibited the generation of reactive oxygen and nitrogen species in Aβ42-activated BV-2 microglia cells. In addition, we found that neoechinulin A significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells. Moreover, the treatment downregulated the protein and gene expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β and IL-6. Further, activated microglia-mediated apoptosis of PC-12 pheochromocytoma cells was significantly repressed by neoechinulin A. The molecular mechanism studies suggested that neoechinulin A may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits. Regulation of these signalling pathways have most probably contributed to the anti-inflammatory activity of neoechinulin A. Collectively, these results suggest that with further studies neoechinulin A have a potential to be developed as a modulator of neuroinflammatory process in AD. 23611338 Reaction between peroxynitrite and triphenylphosphonium-substituted arylboronic acid isomers - Identification of diagnostic marker products and biological implications. Aromatic boronic acids react rapidly with peroxynitrite (ONOO-) to yield phenols as major products. This reaction was used to monitor ONOO- formation in cellular systems. Previously, we proposed that the reaction between ONOO- and arylboronates (PhB(OH)2) yields a phenolic product (major pathway) and a radical pair PhB(OH)2O•-…•NO2 (minor pathway). [Sikora A. et al., Chem Res Toxicol 24, 687-97]. In this study, we investigated the influence of a bulky triphenylphosphonium (TPP) group on the reaction between ONOO- and mitochondria-targeted arylboronate isomers (o-, m-, and p-MitoPhB(OH)2). Results from the electron paramagnetic resonance (EPR) spin-trapping experiments unequivocally showed the presence of a phenyl radical intermediate from meta and para isomers, and not from the ortho isomer. The yield of o-MitoPhNO2 formed from the reaction between o-MitoPhB(OH)2 and ONOO- was not diminished by phenyl radical scavengers, suggesting a rapid fragmentation of the o-MitoPhB(OH)2O•- radical anion with subsequent reaction of the resulting phenyl radical with •NO2 in the solvent cage. The DFT quantum mechanical calculations showed that the energy barrier for the dissociation of o-MitoPhB(OH)2O•- radical anion is significantly lower than that of m-MitoPhB(OH)2O•- and p-MitoPhB(OH)2O•- radical anions. We conclude that the reaction of ONOO- with ortho-MitoPhB(OH)2 forming the minor nitrated product, o-MitoPhNO2, and the corresponding major phenolic product (o-MitoPhOH) can be employed as a diagnostic tool to specifically detect ONOO- in biological systems. 23578633 Pilot study on levels of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in selected foodstuffs and human milk from Italy. Despite the health risks associated with perfluorinated compounds (PFC) exposure and the detection of these compounds in many countries around the world, little is known on their occurrence in Italy. The results of a study on levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), analysed by HPLC-ESI-MS, in human milk and food samples from the city of Siena and its province (central Italy) are here reported. PFOS was found in 13 out of 49 breast milk samples (0.76±1.27ng/g), while PFOA was detected in one sample (8.04ng/g). Only PFOS was found in food samples. Fish were the most contaminated samples (7.65±34.2ng/g); mean concentrations in meat and milk and dairy products were similar (1.43±7.21ng/g and 1.35±3.45ng/g, respectively). In all cereal-based food, eggs, vegetables, honey and beverages PFOS concentration was 10-fold) in the absence of Oatp1a/1b transporters. After intravenous administration (5 mg/kg), systemic exposure was 3-fold higher in Oatp1a/1b-null mice than in the wild-type mice. Liver, small intestinal, and kidney exposure were slightly, but not significantly, increased in Oatp1a/1b-null mice. The biliary excretion of rosuvastatin was very fast, with 60% of the dose eliminated within 15 minutes after intravenous administration, and also not significantly altered in Oatp1a/1b-null mice. Rosuvastatin renal clearance, although still minor, was increased ∼15-fold in Oatp1a/1b-null males, suggesting a role of Oatp1a1 in the renal reabsorption of rosuvastatin. Absence of Oatp1a/1b uptake transporters increases the systemic exposure of rosuvastatin by reducing its hepatic extraction ratio. However, liver concentrations are not significantly affected, most likely due to the compensatory activity of high-capacity, low-affinity alternative uptake transporters at higher systemic rosuvastatin levels and the absence of efficient alternative rosuvastatin clearance mechanisms. 22989703 Comparative antioxidant effects of lycopene, apo-10'-lycopenoic acid and apo-14'-lycopenoic acid in human macrophages exposed to H2O2 and cigarette smoke extract. Much of the beneficial effects of tomato lycopene in the prevention of chronic diseases has been attributed to its antioxidant properties, which could be mediated by its metabolites and/or oxidation products. However, the biological functions of these lycopene derivatives remain still unknown. In the present study, we evaluated and compared the antioxidant efficacy of the lycopene eccentric cleavage products apo-10'-lycopenoic acid and apo-14'-lycopenoic acid in counteracting the oxidative effects of H(2)O(2) and cigarette smoke extract (CSE) in THP-1 macrophages. Both apo-10'-lycopenoic acid and apo-14'-lycopenoic acid were able to inhibit spontaneous and H(2)O(2)-induced ROS production in a dose-dependent manner. Such an effect was accompanied by an inhibition of MAPK phosphorylation, by NF-κB inactivation, and by inhibition of hsp-70 and hsp-90 expressions. Both apo-lycopenoic acids also decreased CSE-induced ROS production, 8-OHdG formation and reduced the increase in NOX-4 and COX-2 expressions caused by CSE. However, in both the models of oxidative stress, apo-14'-lycopenoic acid was much more potent as an antioxidant than apo-10'-lycopenoic acid, showing antioxidant properties similar to lycopene. These data strongly suggest that apo-lycopenoic acids, and particularly apo-14'-lycopenoic acid, may mediate some of the antioxidant functions of lycopene in cells. 23548896 Identification of a new interaction mode between the Src homology 2 (SH2) domain of C-terminal Src kinase (Csk) and Csk-binding protein (Cbp)/phosphoprotein associated with glycosphingolipid microdomains (PAG). Proteins with Src homology 2 (SH2) domains play major roles in tyrosine kinase signaling. Structures of many SH2 domains have been studied, and the regions involved in their interactions with ligands have been elucidated. However, these analyses have been performed using short peptides comprising phosphotyrosine followed by a few amino acids, which are described as the canonical recognition sites. Here we report the solution structure of the SH2 domain of C-terminal Src kinase (Csk) in complex with a longer phosphopeptide from Csk-binding protein (Cbp). This structure, together with biochemical experiments, revealed the existence of a novel binding region in addition to the canonical phosphotyrosine-314 binding site of Cbp. Mutational analysis of this second region in cells showed that both canonical and novel binding sites are required for tumor suppression through the Cbp-Csk interaction. Furthermore, the data indicate an allosteric connection between Cbp binding and Csk activation that arises from residues in the βB/βC loop of the SH2 domain. 23443025 The influence of clan structure on the genetic variation in a single Ghanaian village. Socioeconomic and cultural factors are thought to have an important role in influencing human population genetic structure. To explain such population structure differences, most studies analyse genetic differences among widely dispersed human populations. In contrast, we have studied the genetic structure of an ethnic group occupying a single village in north-eastern Ghana. We found a markedly skewed male population substructure because of an almost complete lack of male gene flow among Bimoba clans in this village. We also observed a deep male substructure within one of the clans in this village. Among all males, we observed only three Y-single-nucleotide polymorphism (SNP) haplogroups: E1b1a*-M2, E1b1a7a*-U174 and E1b1a8a*-U209, P277, P278. In contrast to the marked Y-chromosomal substructure, mitochondrial DNA HVS-1 sequence variation and autosomal short-tandem repeats variation patterns indicate high genetic diversities and a virtually random female-mediated gene flow among clans. On the extreme micro-geographical scale of this single Bimoba village, correspondence between the Y-chromosome lineages and clan membership could be due to the combined effects of the strict patrilocal and patrilineal structure. If translated to larger geographic scales, our results would imply that the extent of variation in uniparentally inherited genetic markers, which are typically associated with historical migration on a continental scale, could equally likely be the result of many small and different cumulative effects of social factors such as clan membership that act at a local scale. Such local scale effects should therefore be considered in genetic studies, especially those that use uniparental markers, before making inferences about human history at large.European Journal of Human Genetics advance online publication, 27 February 2013; doi:10.1038/ejhg.2013.12. 23368884 Potent and Selective Inhibition of Histone Deacetylase 6 (HDAC6) Does Not Require a Surface-Binding Motif. Hydroxamic acids were designed, synthesized, and evaluated for their ability to selectively inhibit human histone deacetylase 6 (HDAC6). Several inhibitors, including compound 14 (BRD9757), exhibited excellent potency and selectivity despite the absence of a surface-binding motif. The binding of these highly efficient ligands for HDAC6 is rationalized via structure-activity relationships. These results demonstrate that high selectivity and potent inhibition of HDAC6 can be achieved through careful choice of linker element only. 23109068 Proximal femoral density distribution and structure in relation to age and hip fracture risk in women. Hip fracture risk rises exponentially with age, but there is little knowledge about how fracture-related alterations in hip structure differ from those of aging. We employed computed tomography (CT) imaging to visualize the three-dimensional (3D) spatial distribution of bone mineral density (BMD) in the hip in relation to age and incident hip fracture. We used intersubject image registration to integrate 3D hip CT images into a statistical atlas comprising women aged 21 to 97 years (n = 349) and a group of women with (n = 74) and without (n = 148) incident hip fracture 4 to 7 years after their imaging session. Voxel-based morphometry was used to generate Student's t test statistical maps from the atlas, which indicated regions that were significantly associated with age or with incident hip fracture. Scaling factors derived from intersubject image registration were employed as measures of bone size. BMD comparisons of young, middle-aged, and older American women showed preservation of load-bearing cortical and trabecular structures with aging, whereas extensive bone loss was observed in other trabecular and cortical regions. In contrast, comparisons of older Icelandic fracture women with age-matched controls showed that hip fracture was associated with a global cortical bone deficit, including both the superior cortical margin and the load-bearing inferior cortex. Bone size comparisons showed larger dimensions in older compared to younger American women and in older Icelandic fracture women compared to controls. The results indicate that older Icelandic women who sustain incident hip fracture have a structural phenotype that cannot be described as an accelerated pattern of normal age-related loss. The fracture-related cortical deficit noted in this study may provide a biomarker of increased hip fracture risk that may be translatable to dual-energy X-ray absorptiometry (DXA) and other clinical images. 23589501 Direct Bio-electrocatalysis of O2 Reduction by Streptomyces coelicolor Laccase Orientated at Promoter-Modified Graphite Electrodes. Bacterial laccase from Streptomyces coelicolor (SLAC) has been immobilised and orientated at promoter (pyrene and neocuproine)-modified electrodes productively both for direct electron transfer (ET) between the electrode and the T1 Cu site of SLAC and direct (unmediated) bio-electrocatalysis of dioxygen reduction. Its T1 Cu potential ranges between 471 and 318 mV versus the normal hydrogen electrode, at pH 5.5 and 8, respectively; this value is dependent both on the solution pH and electrode modification. In the presence of O2 , Cu of the T2/T3 trinuclear centre is distinguished electrochemically at 748-623 mV. Depending on the promoter nature, different orientations of SLAC at pyrene- and neocuproine-modified electrodes can be followed from the kinetic analysis of the ET rates. Bio-electrocatalytic reduction of oxygen starts from the T1 Cu potentials of SLAC, and is most efficient at the promoter-modified electrodes, thereby demonstrating good performance both in neutral and basic media and in solutions with a high NaCl content, such as sea water. The obtained results allow consideration of a broader bioenergetic application of laccases as biocathodes operating directly in such environmental media as sea water and physiological fluids. 23404509 α1A-Adrenergic Receptors Regulate Cardiac Hypertrophy In Vivo Through Interleukin-6 Secretion. The role of α1-adrenergic receptors (ARs) in the regulation of cardiac hypertrophy is still unclear, because transgenic mice demonstrated hypertrophy or the lack of it despite high receptor overexpression. To further address the role of the α1-ARs in cardiac hypertrophy, we analyzed unique transgenic mice that overexpress constitutively active mutation (CAM) α1A-ARs or CAM α1B-ARs under the regulation of large fragments of their native promoters. These constitutively active receptors are expressed in all tissues that endogenously express their wild-type counterparts as opposed to only myocyte-targeted transgenic mice. In this study, we discovered that CAM α1A-AR mice in vivo have cardiac hypertrophy independent of changes in blood pressure, corroborating earlier studies, but in contrast to myocyte-targeted α1A-AR mice. We also found cardiac hypertrophy in CAM α1B-AR mice, in agreement with previous studies, but hypertrophy only developed in older mice. We also discovered unique α1-AR-mediated hypertrophic signaling that was AR subtype-specific with CAM α1A-AR mice secreting atrial naturietic factor and interleukin-6 (IL-6), whereas CAM α1B-AR mice expressed activated nuclear factor-κB (NF-κB). These particular hypertrophic signals were blocked when the other AR subtype was coactivated. We also discovered that crossbreeding the two CAM models (double CAM α1A/B-AR) inhibited the development of hypertrophy and was reversible with single receptor activation, suggesting that coactivation of the receptors can lead to novel antagonistic signal transduction. This was confirmed by demonstrating antagonistic signals that were even lower than normal controls in the double CAM α1A/B-AR mice for p38, NF-κB, and the IL-6/glycoprotein 130/signal transducer and activator of transcription 3 pathway. Because α1A/B double knockout mice fail to develop hypertrophy in response to IL-6, our results suggest that IL-6 is a major mediator of α1A-AR cardiac hypertrophy. 23389956 Glucocorticoid programming of the fetal male hippocampal epigenome. The late-gestation surge in fetal plasma cortisol is critical for maturation of fetal organ systems. As a result, synthetic glucocorticoids (sGCs) are administered to pregnant women at risk of delivering preterm. However, animal studies have shown that fetal exposure to sGC results in increased risk of behavioral, endocrine, and metabolic abnormalities in offspring. Here, we test the hypothesis that prenatal GC exposure resulting from the fetal cortisol surge or after sGC exposure results in promoter-specific epigenetic changes in the hippocampus. Fetal guinea pig hippocampi were collected before (gestational day [GD52]) and after (GD65) the fetal plasma cortisol surge (Term∼GD67) and 24 hours after (GD52) and 14 days after (GD65) two repeat courses of maternal sGC (betamethasone) treatment (n = 3-4/gp). We identified extensive genome-wide alterations in promoter methylation in late fetal development (coincident with the fetal cortisol surge), whereby the majority of the affected promoters exhibited hypomethylation. Fetuses exposed to sGC in late gestation exhibited substantial differences in DNA methylation and histone h3 lysine 9 (H3K9) acetylation in specific gene promoters; 24 hours after the sGC treatment, the majority of genes affected were hypomethylated or hyperacetylated. However, 14 days after sGC exposure these differences did not persist, whereas other promoters became hypermethylated or hyperacetylated. These data support the hypothesis that the fetal GC surge is responsible, in part, for significant variations in genome-wide promoter methylation and that prenatal sGC treatment profoundly changes the epigenetic landscape, affecting both DNA methylation and H3K9 acetylation. This is important given the widespread use of sGC in the management of women in preterm labor. 23386597 Ezogabine: a novel antiepileptic for adjunctive treatment of partial-onset seizures. Epilepsy is defined as a tendency toward recurrent seizures unprovoked by any systemic or acute neurologic insults. It is a disruption of the electrical conductivity or activity in the brain, resulting in a seizure. In the United States, approximately 120 of every 100,000 people seek medical attention due to new seizure activity. Ezogabine, known as retigabine in Europe, is an ethyl N-(2-amino-4-[{fluorophenyl}methlamino]phenylcarbamate). The drug has been approved by the United States Food and Drug Administration (FDA) and European Medicines Agency for adjunctive treatment of partial-onset seizures in adults. Ezogabine exerts its therapeutic effect by enhancing transmembrane potassium channels (KCNQ ion channels), which is a novel mechanism in comparison with other antiepileptics. There are no specific documented contraindications to ezogabine. Warnings target patients that have benign prostatic hyperplasia or are receiving concomitant anticholinergic drugs due to a risk of urinary retention (2%). The FDA has required that ezogabine be part of a risk evaluation and mitigation strategy program in order to inform health care professionals of the risk of urinary retention. Prescribers should inform patients that ezogabine can cause urinary retention, including urinary hesitation, and instruct them to seek immediate medical attention if these symptoms occur. A medication guide has been developed for distribution to patients. 23017423 Light exposure during storage preserving soluble sugar and l-ascorbic acid content of minimally processed romaine lettuce (Lactuca sativa L.var. longifolia). Minimally processed romaine lettuce (MPRL) leaves were stored in light condition (2500lux) or darkness at 4°C for 7d. Light exposure significantly delayed the degradation of chlorophyll and decrease of glucose, reducing sugar, and sucrose content, and thus preserved more total soluble solid (TSS) content at the end of storage in comparison with darkness. While, it did not influenced starch content that progressively decreased over time. The l-ascorbic acid (AA) accumulated in light-stored leaves, but deteriorated in dark-stored leaves during storage. The dehydroascorbic acid (DHA) increased in all leaves stored in both light and dark condition, of which light condition resulted in less DHA than darkness. In addition, the fresh weight loss and dry matter significantly increased and these increases were accelerated by light exposure. Conclusively, light exposure in applied intensity effectively alleviated MPRL quality deterioration by delaying the decreases of pigments, soluble sugar, TSS content and accumulating AA. 22889612 Chemoprevention of benzo(a)pyrene-induced colon polyps in ApcMin mice by resveratrol. Human dietary exposure to benzo(a)pyrene (BaP) has generated interest with regard to the association of BaP with gastrointestinal carcinogenesis. Since colon cancer ranks third among cancer-related mortalities, it is necessary to evaluate the effect of phytochemicals on colon cancer initiation and progression. In this study, we investigated the preventive effects of resveratrol (RVT) on BaP-induced colon carcinogenesis in Apc(Min) mouse model. For the first group of mice, 100 μg BaP/kg body weight was administered to mice in peanut oil via oral gavage over a 60-day period. For the second group, RVT was coadministered with BaP at a dose of 45 μg/kg. For the third group, RVT was administered for 1 week prior to BaP exposure for 60 days. Jejunum, colon and liver were collected at 60 days post BaP and RVT exposure; adenomas in jejunum and colon were counted and subjected to histopathology. RVT reduced the number of colon adenomas in BaP+RVT-treated mice significantly compared to that in mice that received BaP alone. While dysplasia of varying degrees was noted in colon of BaP-treated mice, the dysplasias were of limited occurrence in RVT-treated mice. To ascertain whether the tumor inhibition is a result of altered BaP-induced toxicity of tumor cells, growth, apoptosis and proliferation of adenocarcinoma cells were assessed posttreatment with RVT and BaP. Cotreatment with RVT increased apoptosis and decreased cell proliferation to a greater extent than with BaP alone. Overall, our observations reveal that RVT inhibits colon tumorigenesis when given together with BaP and holds promise as a therapeutic agent. 23403184 The PprA protein is required for accurate cell division of γ-irradiated Deinococcus radiodurans bacteria. Deinococcus radiodurans, one of the most radioresistant organisms known to date is able to reconstruct an intact genome from hundreds of DNA fragments. Here, we investigate the in vivo role of PprA, a radiation-induced Deinococcus specific protein. We report that DNA double strand break repair in cells devoid of PprA and exposed to 3800Gy γ-irradiation takes place efficiently with a delay of only 1h as compared to the wild type, whereas massive DNA synthesis begins 90min after irradiation as in the wild type, a phenotype insufficient to explain the severe radiosensitivity of the ΔpprA mutant. We show that the slow kinetics of reassembly of DNA fragments in a ΔpprA ΔrecA double mutant was the same as that observed in a ΔrecA single mutant demonstrating that PprA does not play a major role in DNA repair through RecA-independent pathways. Using a tagged PprA protein and immunofluorescence microscopy, we show that PprA is recruited onto the nucleoid after γ-irradiation before DNA double strand break repair completion, and then is found as a thread across the septum in dividing cells. Moreover, whereas untreated cells devoid of PprA displayed a wild type morphology, they showed a characteristic cell division abnormality after irradiation not found in other radiosensitive mutants committed to die, as DNA is present equally in the two daughter cells but not separated at the division septum. We propose that PprA may play a crucial role in the control of DNA segregation and/or cell division after DNA double strand break repair. 23640962 Anti-inflammatory Activities of an Active Fraction Isolated from the root of Astragalus membranaceus in RAW 264.7 Macrophages. The root of Astragalus membranaceus (AR), which has been widely used in Traditional Chinese herbal formulae for treating foot ulcer, was found to exhibit anti-inflammatory property, but its molecular mechanism still remains unknown. We previously identified the anti-inflammatory sub-fraction using bioassay-guided fractionation. The objective of the present study was to investigate the anti-inflammatory mechanism of the major active fraction (MAF) (0.039 to 0.156 mg/mL) using lipopolysaccharide (LPS)-stimulated mouse macrophage RAW 264.7 cells. MAF was shown to inhibit LPS-induced mRNA and protein expression of inducible nitric oxide synthase by 54.7% and 65.1%, respectively. Additionally, MAF down-regulated the protein expression of cyclooxygenase-2 and MAPK regulator by 45.0% to 74.6%, as well as the reduction of DNA binding activity of nuclear factor kappa B (NFκB) by 66.5%. It also attenuated the production of prostaglandin E2 , interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor alpha by 21.2% to 86.2%. Furthermore, the chemical constituents of MAF were identified. A total of 13 known chemical compounds were found in MAF, including five isoflavonoids and eight saponins. In conclusion, a bioactive fraction of AR was identified which possessed anti-inflammatory property by reducing the release of inflammatory mediators and inactivation of NFκB through MAPK signalling pathway. Copyright © 2013 John Wiley & Sons, Ltd. 23256819 HR-MAS NMR Spectroscopy of Reconstructed Human Epidermis: Potential for the in Situ Investigation of the Chemical Interactions between Skin Allergens and Nucleophilic Amino Acids. High-resolution magic angle spinning (HR-MAS) is a nuclear magnetic resonance (NMR) technique that enables the characterization of metabolic phenotypes/metabolite profiles of cells, tissues, and organs, under both normal and pathological conditions, without resorting to time-consuming extraction techniques. In this article, we explore a new domain of application of HR-MAS, namely, reconstructed human epidermis (RHE) and the in situ observation of chemical interactions between skin sensitizers and nucleophilic amino acids. First, the preparation, storage, and analysis of RHE were optimized, and this work demonstrated that HR-MAS NMR was well adapted for investigating RHE with spectra of good quality allowing qualitative as well as quantitative studies of metabolites. Second, in order to study the response of RHE to chemical sensitizers, the ((13)C)methyldodecanesulfonate was chosen as an NMR probe, and we compared adducts formed on human serum albumin (HSA) in solution and adducts formed in RHE. Thus, while the modification of proteins or peptides in solution takes several days to lead to a significant amount of modification, in RHE the modifications of nucleophilic amino acids were observable already at 24 h. The chemioselectivity also appeared to be different with major modifications taking place on histidine, methionine, and cysteine residues in RHE, while on HSA, significant modifications were observed on lysine residues with the formation of methylated and dimethylated amino groups. We thus demonstrated that RHE could be used to investigate in situ chemical interactions taking place between skin sensitizers and nucleophilic amino acids. This opens perspectives for the molecular understanding of the skin immune system activation by sensitizing chemicals. 23525662 The nuclear receptors COUP-TF: a long-lasting experience in forebrain assembly. Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are nuclear receptors belonging to the superfamily of the steroid/thyroid hormone receptors. Members of this family are internalized to the nucleus both in a ligand-dependent or -independent manner and act as strong transcriptional regulators by binding to the DNA of their target genes. COUP-TFs are defined as orphan receptors, since ligands regulating their activity have not so far been identified. From the very beginning of metazoan evolution, these molecules have been involved in various key events during embryonic development and organogenesis. In this review, we will mainly focus on their function during development and maturation of the central nervous system, which has been well characterized in various animal classes ranging from ctenophores to mammals. We will start by introducing the current knowledge on COUP-TF mechanisms of action and then focus our discussion on the crucial processes underlying forebrain ontogenesis, with special emphasis on mammalian development. Finally, the conserved roles of COUP-TFs along phylogenesis will be highlighted, and some hypotheses, worth exploring in future years to gain more insight into the mechanisms controlled by these factors, will be proposed. 23625750 The effects of the adenosine A3 receptor agonist IB-MECA on sodium taurocholate-induced experimental acute pancreatitis. The role of adenosine A3 receptors and their distribution in the gastrointestinal tract have been widely investigated. Most of the reports discuss their role in intestinal inflammations. However, the role of adenosine A3 receptor agonist in pancreatitis has not been well established. The aim of this study is (Ed note: Purpose statements should be in present tense) to evaluate the effects of the adenosine A3 receptor agonist on the course of sodium taurocholate-induced experimental acute pancreatitis (EAP). The experiments were performed on 80 male Wistar rats, 58 of which survived, subdivided into 3 groups: C-control rats, I-EAP group, and II-EAP group treated with the adenosine A3 receptor agonist IB-MECA (1-deoxy-1-6[[(3-iodophenyl) methyl]amino]-9H-purin-9-yl)-N-methyl-B-D-ribofuronamide at a dose of 0.75 mg/kg b.w. i.p. at 48, 24, 12 and 1 h before and 1 h after the injection of 5 % sodium taurocholate solution into the biliary-pancreatic duct. Serum for α-amylase and lipase determinations and tissue samples for morphological examinations were collected at 2, 6, and 24 h of the experiment. In the IB-MECA group, α-amylase activity was decreased with statistically high significance compared to group I. The activity of lipase was not significantly different among the experimental groups but higher than in the control group. The administration of IB-MECA attenuated the histological parameters of inflammation as compared to untreated animals. The use of A3 receptor agonist IB-MECA attenuates EAP. Our findings suggest that stimulation of adenosine A3 receptors plays a positive role in the sodium taurocholate-induced EAP in rats. 23603385 How to measure hazards/risks following exposures to nanoscale or pigment-grade titanium dioxide particles. Due to its multifunctional applications, titanium dioxide particles have widespread use in commerce. The particle-types function as sources of pigment color, in food products, anti-bacterial components, ultraviolet radiation scavengers, catalysts, as well as in cosmetics. Because of its inherent properties in a diverse number of products, exposures may occur via any of the major point-of-entry routes, i.e., inhalation, oral or dermal. Although the majority of TiO2 applications are known to exist in the pigment-grade form, nanoscale forms of TiO2 are also common components in several products. This brief review is designed to identify relevant toxicology and risk-related issues which inform health effects assessments on the various forms of titanium dioxide particles. While there has been an abundance of hazard data generated on titanium dioxide particulates, many of the published reports have limited informational value for assessing health effects due, in large part, to shortcomings in experimental design issues, such as: (1) inadequate material characterization of test samples; (2) questionable relevance of experimental systems employed to simulate human exposures; (3) applications of generally high doses, exclusive focus on acute toxicity endpoints, and a lack of reference benchmark control materials, to afford interpretation of measured results; and/or (4) failure to recognize fundamental differences between hazard and risk concepts. Accordingly, a number of important toxicology issues are identified and integrated herein to provide a more comprehensive assessment of the health risks of different forms of pigment-grade and nanoscale titanium dioxide particles. It is important to note that particle-types of different TiO2 compositions may have variable toxicity potencies, depending upon crystal structure, particle size, particle surface characteristics and surface coatings. In order to develop a more robust health risk evaluation of TiO2 particle exposures, this review focuses on the following issues: A comprehensive evaluation of the existing animal and human health data is a necessary prerequisite for facilitating accurate assessments of human health risks to TiO2 exposures. 23239015 Poly-Ortho-Functionalizable Tetraarylporphycene Platform-Synthesis of Octacationic Derivatives Towards the Layer-by-Layer Design of Versatile Graphene Oxide Photoelectrodes. The most highly charged water-soluble poly-ortho-substituted tetraarylporphycene (Pc(8+) ) has been synthetized. The latter, which interacts in aqueous solutions with graphene oxide (GO) forming a photoactive ensemble Pc(8+) /GO, is immobilized by means of the Layer-by-Layer (LbL) technique onto ITO electrodes to afford novel solar energy conversion devices. 23287045 Toxicity of copper salts is dependent on solubility profile and cell type tested. Copper (Cu) is considered an essential metal for living organisms. However, disruption of Cu homeostasis is toxic and can lead to disorders such as Menkes and Wilson's diseases. The brain appears to be a vulnerable target organ. This study investigated the toxicity of Cu based on its solubility profile and cell type tested. Human A-172 (glioblastoma), SK-N-SH (neuroblastoma) and CCF-STTG1 (astrocytoma) cells were assessed after exposure to different concentrations (0.5-500μM) of copper sulfate (CuSO4) or copper (II) oxide (CuO). Since Cu is a redox active transition metal, we hypothesized that oxidative stress would be the main mechanism underlying cell toxicity. Therefore, cell viability was correlated with the extent of reactive oxygen species (ROS) formation. Cell viability decreased at the higher concentrations of the Cu salts and CuO was more toxic compared to CuSO4. The astrocytoma and glioblastoma cells were more vulnerable compared to the neuronal cells. Furthermore, it appears that oxidative stress only partially accounts for Cu-induced cell toxicity. Further studies are needed to better understand the unique susceptibility of glial cells and determine the physicochemical properties of insoluble Cu which accounts for its enhanced toxicity. 23239045 Perspectives and potential applications of nanomedicine in breast and prostate cancer. Nanomedicine is a branch of nanotechnology that includes the development of nanostructures and nanoanalytical systems for various medical applications. Among these applications, utilization of nanotechnology in oncology has captivated the attention of many research endeavors in recent years. The rapid development of nano-oncology raises new possibilities in cancer diagnosis and treatment. It also holds great promise for realization of point-of-care, theranostics, and personalized medicine. In this article, we review advances in nano-oncology, with an emphasis on breast and prostate cancer because these organs are amenable to the translation of nanomedicine from small animals to humans. As new drugs are developed, the incorporation of nanotechnology approaches into medicinal research becomes critical. Diverse aspects of nano-oncology are discussed, including nanocarriers, targeting strategies, nanodevices, as well as nanomedical diagnostics, therapeutics, and safety. The review concludes by identifying some limitations and future perspectives of nano-oncology in breast and prostate cancer management. 23561178 Home conservation strategies for tomato (Solanum lycopersicum): Storage temperature vs. duration - Is there a compromise for better aroma preservation? Expression of dissatisfaction with tomato aroma prompted us to lead this study on the impact of domestic storage conditions on volatile compounds. Two storage modalities (20 and 4°C) and two cultivars (Levovil and LCx) were used. Volatile compounds were analysed by gas chromatography-mass spectrometry detection after accelerated solvent extraction. Physical characteristics, lipoxygenase activity, hydroperoxide lyase activity; linoleic acid and linolenic acid were monitored. Storing tomatoes at 4°C induced a drastic loss in volatiles, whatever their biosynthetic origin. After 30days at 4°C, the concentration of volatiles had decreased by 66%. Reconditioning for 24h at 20°C was able to recover some aroma production after up to 6days storage at 4°C. Volatile degradation products arising from carotenoids and amino acids increased when tomatoes were kept at 20°C, while lipid degradation products did not vary. Storing tomatoes at fridge temperature, even for short durations, was detrimental for their aroma. This should be taken into account to formulate practical advice for consumers. 23411208 Alteration of α-tocopherol-associated protein (TAP) expression in human breast epithelial cells during breast cancer development. Breast cancer is the most common malignancy among women and has an age-specific incidence profile. Over the last decade, many studies have demonstrated the anticancer activity of α-tocopherol, the main and most active form of natural vitamin E. α-Tocopherol-associated protein (TAP) was found to be one of the major α-tocopherol binding proteins in human serum and in liver, brain, and prostate tissues. In this study, we found that reduced TAP expression was significantly correlated with Her2/neu receptor expression, breast cancer stage and nodal stage in paired normal and cancerous breast tissue samples from 93 patients using real-time PCR analysis. A cell viability assay showed that α-tocopheryl succinate (α-TOS), a synthetic derivative of α-tocopherol, enhanced the cells' sensitivity to doxorubicin and resulted in a reduction in cell viability in breast cancers. Taken together, these data suggest that the use of vitamin E or its analogue as a dietary supplement may be beneficial for the treatment of cancer. 23296368 Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature. Increased urinary 3-methylglutaconic acid excretion is a relatively common finding in metabolic disorders, especially in mitochondrial disorders. In most cases 3-methylglutaconic acid is only slightly elevated and accompanied by other (disease specific) metabolites. There is, however, a group of disorders with significantly and consistently increased 3-methylglutaconic acid excretion, where the 3-methylglutaconic aciduria is a hallmark of the phenotype and the key to diagnosis. Until now these disorders were labelled by roman numbers (I-V) in the order of discovery regardless of pathomechanism. Especially, the so called "unspecified" 3-methylglutaconic aciduria type IV has been ever growing, leading to biochemical and clinical diagnostic confusion. Therefore, we propose the following pathomechanism based classification and a simplified diagnostic flow chart for these "inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature". One should distinguish between "primary 3-methylglutaconic aciduria" formerly known as type I (3-methylglutaconyl-CoA hydratase deficiency, AUH defect) due to defective leucine catabolism and the-currently known-three groups of "secondary 3-methylglutaconic aciduria". The latter should be further classified and named by their defective protein or the historical name as follows: i) defective phospholipid remodelling (TAZ defect or Barth syndrome, SERAC1 defect or MEGDEL syndrome) and ii) mitochondrial membrane associated disorders (OPA3 defect or Costeff syndrome, DNAJC19 defect or DCMA syndrome, TMEM70 defect). The remaining patients with significant and consistent 3-methylglutaconic aciduria in whom the above mentioned syndromes have been excluded, should be referred to as "not otherwise specified (NOS) 3-MGA-uria" until elucidation of the underlying pathomechanism enables proper (possibly extended) classification. 23222849 Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma. Low-grade brain tumors (pilocytic astrocytomas) arising in the neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations. However, genetically engineered mice (GEM) in which mono-allelic germline Nf1 gene loss is coupled with bi-allelic somatic (glial progenitor cell) Nf1 gene inactivation develop brain tumors that do not fully recapitulate the neuropathological features of the human condition. These observations raise the intriguing possibility that, while loss of neurofibromin function is necessary for NF1-associated low-grade astrocytoma development, additional genetic changes may be required for full penetrance of the human brain tumor phenotype. To identify these potential cooperating genetic mutations, we performed whole-genome sequencing (WGS) analysis of three NF1-associated pilocytic astrocytoma (PA) tumors. We found that the mechanism of somatic NF1 loss was different in each tumor (frameshift mutation, loss of heterozygosity, and methylation). In addition, tumor purity analysis revealed that these tumors had a high proportion of stromal cells, such that only 50%-60% of cells in the tumor mass exhibited somatic NF1 loss. Importantly, we identified no additional recurrent pathogenic somatic mutations, supporting a model in which neuroglial progenitor cell NF1 loss is likely sufficient for PA formation in cooperation with a proper stromal environment. 23337941 Exciton diffusion in near-infrared absorbing solution-processed organic thin films. We report on singlet-singlet annihilation and exciton diffusion in as-prepared p-type and annealed n-type thin films of the low-bandgap quinoidal quaterthiophene [QQT(CN)4] using ultrafast transient absorption measurements. The decay dynamics of exciton populations are well described by a one-dimensional diffusion-limited bimolecular recombination, indicating that the singlet excitons migrate preferentially along the stacking direction. Our results show that the exciton diffusion constants in QQT(CN)4 films do not vary significantly upon thermal annealing. Exciton diffusion lengths are measured to be as high as 4 and 5 nm in as-prepared and annealed QQT(CN)4 films, respectively. We also observe an influence of the excitation densities on the singlet exciton diffusion, which is attributed to phonon scattering. Because of the possibility of patterning p-n regions in QQT(CN)4 films by thermal nanolithography techniques, this study provides important insight not only into the photophysical properties of quinoidal oligothiophene derivatives but also for their future integration into high-performance p-n nanostructured near infrared light-sensing devices. 23256816 The evolution of S100B inhibitors for the treatment of malignant melanoma. Malignant melanoma continues to be an extremely fatal cancer due to a lack of viable treatment options for patients. The calcium-binding protein S100B has long been used as a clinical biomarker, aiding in malignant melanoma staging and patient prognosis. However, the discovery of p53 as a S100B target and the consequent impact on cell apoptosis redirected research efforts towards the development of inhibitors of this S100B-p53 interaction. Several approaches, including computer-aided drug design, fluorescence polarization competition assays, NMR, x-ray crystallography and cell-based screens have been performed to identify compounds that block the S100B-p53 association, reactivate p53 transcriptional activities and induce cancer cell death. Eight promising compounds, including pentamidine, are presented in this review and the potential for future modifications is discussed. Synthesis of compound derivatives will likely exhibit increased S100B affinity and mimic important S100B-target dynamic properties that will result in high specificity. 23473664 Variations on glutamate binding in channel-gated receptors. In this issue of Structure, Lomash and colleagues report on the crystal structure and ligand binding properties of a primitive eukaryote glutamate-gated ion channel: AvGluR1. 23194559 Suitability of elemental fingerprinting for assessing the geographic origin of pumpkin (Cucurbita pepo var. styriaca) seed oil. An analytical method was developed and validated for the classification of the geographical origin of pumpkin seeds and oil from Austria, China and Russia. The distribution of element traces in pumpkin seed and pumpkin seed oils in relation to the geographical origin of soils of several agricultural farms in Austria was studied in detail. Samples from several geographic origins were taken from parts of the pumpkin, pumpkin flesh, seeds, the oil extracted from the seeds and the oil-extraction cake as well as the topsoil on which the plants were grown. Plants from different geographical origin show variations of the elemental patterns that are significantly large, reproducible over the years and ripeness period and show no significant influence of oil production procedure, to allow to a discrimination of geographical origin. A successful differentiation of oils from different regions in Austria, China and Russia classified with multivariate data analysis is demonstrated. 23508106 Loss of an igκ gene enhancer in mature B cells results in rapid gene silencing and partial reversible dedifferentiation. We address here whether there is cellular memory of a transcriptional enhancer once it has served its purpose to establish an active chromatin state. We have previously shown that the mouse Igκ gene's downstream enhancers, E3' and Ed, are essential but play redundant roles for establishing transcriptional activity in the locus during B cell development. To determine whether these enhancers are also necessary for the maintenance of transcriptional activity, we conditionally deleted E3' in mature B cells that possessed Ed(-/-) alleles. Upon E3' deletion, the locus became rapidly silenced and lost positive histone epigenetic marks, and the mature B cells partially dedifferentiated, induced RAG-1 and -2 along with certain other pro-B cell makers, and then redifferentiated after triggering Igλ gene rearrangements. We conclude that the Igκ gene's downstream enhancers are essential for both the establishment and maintenance of transcriptional activity and that there is no cellular memory of previous transcriptional activity in this locus. Furthermore, upon enhancer loss, the mature B cells unexpectedly underwent reversible retrograde differentiation. This result establishes that receptor editing can occur in mature B cells and raises the possibility that this may provide a tolerance mechanism for eliminating autoreactive B cells in the periphery. 23402549 Polymerase chain reaction-free variable-number tandem repeat typing using gold nanoparticle-DNA monoconjugates. In this work, we report a novel polymerase chain reaction (PCR)-free variable-number tandem repeat (VNTR) typing method using a T-shaped gold nanoparticle-DNA monoconjugate, called the "watching-gene assay". The T-shaped DNA probe was synthesized by "click" chemistry and linked with the gold nanoparticle to form the gold nanoparticle-DNA monoconjugate (a VNTR probe). Through a simple annealing and ligation reaction of the VNTR probe on a synthetic DNA template mimicking the human D1S80 VNTR locus, the number of tandem repeat units could be deciphered by counting the self-assembled gold nanoparticles. The number of tandem repeat units could be identified with more than 50% yield if the repeat number was less than four. In the case of the real human genomic DNA, the 18 repeat unit number could be successfully revealed by observing the 18-gold-nanoparticle cluster, which exactly corresponded to the number of tandem repeats of the real sample. Our "watching-gene assay" is rapid, simple, and direct for data interpretation, thereby providing an advanced PCR-free genetic polymorphism analysis platform. 23616238 Common variation in PPARGC1A/B and progression to diabetes or change in metabolic traits following preventive interventions: the Diabetes Prevention Program. AIMS/HYPOTHESIS: PPARGC1A and PPARGC1B encode transcriptional coactivators that regulate numerous type 2 diabetes-related metabolic processes. Common genetic variation across PPARGC1A/B was characterised by genotyping tagging variants. We then tested associations of these variants with diabetes incidence or change in quantifiable metabolic traits directly or via interactions (with metformin treatment or intensive lifestyle modification) in the Diabetes Prevention Program (DPP), a randomised controlled trial in persons at high risk of type 2 diabetes. METHODS: We used Tagger software to select 75 PPARGC1A and 94 PPARGC1B tag single nucleotide polymorphisms (SNPs) for analysis. These SNPs were tested for association with diabetes incidence using Cox proportional hazards regression models, and a range of relevant metabolic quantifiable traits, using generalised linear models. RESULTS: Eight PPARGC1A variants were nominally (p < 0.05) associated with diabetes incidence, of which one (rs3736265/Thr612Met) was associated with diabetes in the DPP (HR 1.31, 95% CI 1.05, 1.63 per copy of the 612Met allele) and in the DIAGRAM database (OR 1.11, 95% CI 1.01, 1.21). Consistent with earlier reports, the Gly482Ser (rs8192678) variant showed nominally significant effects on 1 year accumulation of adiposity and worsening insulin resistance (both p < 0.05). A third PPARGC1A variant (rs2970852) modified the effects of metformin on triacylglycerol levels (p interaction = 0.04; p = 0.0001 for association of SNP with triacylglycerol concentrations in metformin-treated participants). A number of other PPARGC1A/B variants were nominally directly associated with diabetes incidence or modified treatment effects on diabetes incidence. CONCLUSIONS/INTERPRETATION: These findings provide some novel and confirmatory insights into the roles of PPARGC1A/B variation in type 2 diabetes and related metabolic traits. TRIAL REGISTRATION: ClinicalTrials.gov NCT00004992. 23643933 Induction of the liver cancer-down-regulated long noncoding RNA uc002mbe.2 mediates trichostatin-induced apoptosis of liver cancer cells. Differential expression of long non-coding RNAs (lncRNAs) plays critical roles in hepatocarcinogenesis. Considerable attention has focused on the antitumor effect of histone deacetylase inhibitor (Trichostatin A, TSA) as well as the coding gene expression-induced apoptosis of cancer cells. However, it is not known whether lncRNA has a role in TSA-induced apoptosis of human hepatocellular carcinoma (HCC) cells. The global expression of lncRNAs and coding genes was analyzed with the Human LncRNA Array V2.0 after 24h treatment. Expression was verified in cell lines and tissues by quantitative real-time PCR. The data showed that 4.8% (959) of lncRNA and 6.1% (1849) of protein coding gene were significantly differentially expressed. The differential expressions of lncRNA and protein coding genes had distinguishable hierarchical clustering expression profiling pattern. Among these differentially expressed lncRNAs, the greatest change was noted for uc002mbe.2, which had more than 300 folds induction upon TSA treatment. TSA selectively induced uc002mbe.2 in four studied HCC cell lines. Compared with normal human hepatocytes and adjacent noncancerous tissues, uc002mbe.2 expression level was significantly lower in the HCC cell lines and liver cancer tissues. The TSA-induced uc002mbe.2 expression was positively correlated with the apoptotic effect of TSA in HCC cells. In addition, knockdown the expression of uc002mbe.2 significantly reduced TSA-induced apoptosis of Huh7cells. Therefore, TSA-induced apoptosis of HCC cells is uc002mbe.2 dependent and reduced expression of uc002mbe.2 may be associated with liver carcinogenesis. 23504356 Pharmacotherapy for the core symptoms in autistic disorder: current status of the research. The current review covers extant literature on pharmacotherapy for core symptoms of autism. The core symptoms of autism include impairments in social interaction and communication, as well as the presence of restricted and repetitive behaviors. There are no known efficacious treatments for the core social symptoms, although effects on repetitive behaviors are indicated with some data. While studies of fenfluramine, secretin, opiates, and mood stabilizers generally find no effect, mixed results suggest more research is needed on antidepressants and atypical antipsychotics. Newer lines of research, including cholinergic and glutamatergic agents and oxytocin, will be of considerable interest in the future. However, research on the treatment of core symptoms is plagued by limitations in study design, statistical power, and other issues inherent to the study of treatments for autism (e.g., heterogeneity of the disorder) that continue to prevent the elucidation of efficacious treatments. 23471561 Synthesis of novel bis-anthraquinone derivatives and their biological evaluation as antitumor agents. Cancer has become a major worldwide problem and drug resistance now is one of the most important problems in treatment of cancer. Anthraquinone derivatives represent one of the most important drugs that can be used in treatment of many types of cancer. In this study two series of novel bis-anthraquinone derivatives have been synthesized. Five of these compounds were chosen to be evaluated for their antitumor activity against human cancer cell lines by the National Cancer Institute (NCI, USA). Marked activity was shown for the tested compounds(2-6). The most active one was compound 6 with mean value -67.00 against all cell lines. Compounds 7 and 8 were found inactive. 22945305 Type 2 diabetes and cardiovascular disease in women. Cardiovascular disease is the leading cause of death in both men and women. This is also true for patients with diabetes. In general, differences between the sexes are present in several areas, such as epidemiology, pathophysiology, diagnostics, treatment response and prognosis, as well as the way in which disease is experienced and expressed. Cardiovascular disease presents later in life in women, who are therefore more likely to suffer from comorbidities. However, this age-related difference is attenuated in women with diabetes, who suffer their first myocardial infarction at about the same age as men with diabetes. Diabetes mellitus increases the risk of cardiovascular disease by three to four times in women and two to three times in men, after adjusting for other risk factors. This paper describes the differences in cardiovascular disease in men and women and the special situation of women with type 2 diabetes when it comes to risk factors, symptoms and the setting of acute coronary syndromes. Furthermore, it highlights the importance of sex-specific analyses in clinical research to improve our knowledge of cardiovascular disease in women in general and in women with diabetes in particular. The importance of taking sex into account when treating women and men at risk of cardiovascular disease is discussed. 23421331 Once-daily initiation of basal insulin as add-on to metformin: a 26-week, randomized, treat-to-target trial comparing insulin detemir with insulin glargine in patients with type 2 diabetes. AIMS: This study assessed the efficacy and safety of once-daily insulin initiation using insulin detemir (detemir) or insulin glargine (glargine) added to existing metformin in type 2 diabetes (T2D). METHODS: This 26-week, multinational, randomized, treat-to-target trial involved 457 insulin-naïve adults with T2D (HbA1c 7-9%). Detemir or glargine was added to current metformin therapy [any second oral antidiabetic drug (OAD) discontinued] and titrated to a target fasting plasma glucose (FPG) ≤90 mg/dl (≤5.0 mmol/l). Primary efficacy endpoint was change in HbA1c. RESULTS: Mean (s.d.) HbA1c decreased with detemir and glargine by 0.48 and 0.74%-points, respectively, to 7.48% (0.91%) and 7.13% (0.72%) [estimated between-treatment difference, 0.30 (95% CI: 0.14-0.46)]. Non-inferiority for detemir at the a priori level of 0.4%-points was not established. The proportions of patients reaching HbA1c ≤ 7% at 26 weeks were 38% and 53% (p = 0.026) with detemir and glargine, respectively. FPG decreased ∼43.2 mg/dl (∼2.4 mmol/l) in both groups [non-significant (NS)]. Treatment satisfaction was good for both insulins. Hypoglycaemia, which occurred infrequently, was observed less with detemir than glargine [rate ratio 0.73 (95% CI 0.54-0.98)]. The proportions of patients reaching HbA1c ≤ 7% without hypoglycaemia in the detemir and glargine groups were 32% and 38% (NS), respectively. Weight decreased with detemir [-0.49 (3.3) kg] and increased with glargine [+1.0 (3.1) kg] (95% CI for difference: -2.17 to -0.89 kg). CONCLUSION: While both detemir and glargine, when added to metformin therapy, improved glycaemic control, glargine resulted in greater reductions in HbA1c, while detemir demonstrated less weight gain and hypoglycaemia. 23000250 Three-finger toxins, a deadly weapon of elapid venom--milestones of discovery. Three-finger toxins (TFTs) are the main venom components of snakes from Elapidae family. Amino acid sequences of more than five hundreds TFTs are determined; these toxins form one of the largest protein families present in snake venoms. The first TFT α-bungarotoxin was isolated almost half a century ago and so far it remains a valuable tool in the study of nicotinic acetylcholine receptors. TFTs possess diverse biological activities; for example, α-neurotoxins bind specifically with high affinity to nicotinic acetylcholine receptors, while cytotoxins induce non-specific lysis in great variety of cells. These toxins are widely used as instruments in different branches of life sciences. In this review the main landmarks in TFT study are considered. These are the discovery and isolation of TFTs, determination of their structure and mode of action as well as evolution and relationship within the family. 23010165 A brief review of the scientific history of several lesser-known snake venom proteins: l-amino acid oxidases, hyaluronidases and phosphodiesterases. When considering the proteins and toxins in snake venom one's thoughts generally migrate to the proteinases, neurotoxins and phospholipases since these families of proteins are comprised by many of the toxins found in venom. However as modern proteomic and transcriptomic venom research has abundantly shown snake venoms are complex and containing numerous families of protein beyond the "big three". In this brief review we will discuss three of the lesser discussed proteins typically found in snake venoms: l-amino acid oxidases (LAAO); hyaluronidases and phosphodiesterases. These proteins have long been known to be part of many venoms' proteomes with reports appearing in the literature as early as 1944 for LAAO, 1947 for hyaluronidase (spreading factor), and 1932 for venom phosphodiesterase. These are more or less contemporary with the first reports (circa 1950) on snake venom proteases. Thus, the relatively modest literature on these snake venom proteins stems not from lack of early discovery but rather more likely to their ostensibly minor role in snake venom pathophysiology. In this review we will provide an overview of the experimental history of these venom proteins, their biochemical and structural features and their role in snake venom toxinology with the aim of bringing a fuller, more comprehensive, understanding of the history of laboratory research on snake venoms. In addition, there are some comments on these proteins from investigators who were actively engaged in their investigation. 23017404 Sugar metabolism in relation to chilling tolerance of loquat fruit. The relationship between chilling injury and sugar metabolism was investigated in loquat fruit stored at 1°C for 35days. No symptoms of chilling injury occurred in the fruit, of 'Ninghaibai' cultivar, during the whole storage whereas, in 'Dahongpao' fruit, severe chilling symptoms were observed after 20days of storage at 1°C. 'Ninghaibai' fruit had higher levels of glucose and fructose and higher activities of sucrose hydrolyzing enzymes, such as sucrose synthase-cleavage and invertase, than had 'Dahongpao'. Furthermore, the chilling resistant 'Ninghaibai' fruit also showed higher activities of hexokinase and fructokinase, involved in hexose phoshorylation and sugar signal generation. These results suggest that the higher content of hexoses and activities of hexose sensors were likely part of the mechanism for chilling tolerance of loquat fruit. 23623416 Synthesis and antifungal evaluation of pentyloxyl-diphenylisoxazoloyl pneumocandins and echinocandins. Echinocandins and pneumocandins are classes of lipocyclohexapeptides that are broad spectrum antifungal agents. They inhibit fungal specific 1,3-β-glucan synthase activity which is an essential component of the fungal cell wall. Chemical modifications of these two leads have produced three clinical agents namely caspofungin, micafungin and anidulafungin. The presence of hydroxy-glutamine versus threonine and unsaturated linear fatty acid versus branched chain saturated fatty acid differentiate the two classes of compounds with profound differences in their hemolytic properties. In the current study, we have replaced the side chain of the cyclohexapeptides with a common aromatic heterocyclic acyl side chain and compared the biological activities of the cores head-to-head and for the first time demonstrated the role played by the acyl chain and the hydroxy-glutamine for the antifungal potency. 23333900 Preparation of carbamazepine-Soluplus® solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting. Hot-melt extrusion (HME) is a dust- and solvent-free continuous process enabling the preparation of a variety of solid dosage forms containing solid dispersions of poorly soluble drugs into thermoplastic polymers. Miscibility of drug and polymer is a prerequisite for stable solid dispersion formation. The present study investigates the feasibility of forming solid dispersions of carbamazepine (CBZ) into polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus®) by hot-melt extrusion. Physicochemical properties of the raw materials, extrudates, co-melted products, and corresponding physical mixtures were characterized by thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC), attenuated total reflectance infrared (ATR-FTIR) spectroscopy and hot stage microscopy (HSM), while miscibility of CBZ and Soluplus® was estimated on the basis of the Flory-Huggins theory, Hansen solubility parameters, and solid-liquid equilibrium equation. It was found that hot-melt extrusion of carbamazepine and Soluplus® is feasible on a single-screw hot-melt extruder without the addition of plasticizers. DSC analysis and FTIR spectroscopy revealed that a molecular dispersion is formed when the content of CBZ does not exceed ∼5% w/w while higher CBZ content results in a microcrystalline dispersion of CBZ form III crystals, with the molecularly dispersed percentage increasing with extrusion temperature, at the risk of inducing transformation to the undesirable form I of CBZ. Thermodynamic modeling elucidated potential limitations and temperature dependence of solubility/dispersibility of carbamazepine in Soluplus® hot-melt extrudates. The results obtained by thermodynamic models are in agreement with the findings of the HME processing, encouraging therefore their further application in the HME process development. 23153959 Three-dimensional imaging of collagen fibril organization in rat circumferential lamellar bone using a dual beam electron microscope reveals ordered and disordered sub-lamellar structures. Lamellar bone is a major component of most mammalian skeletons. A prominent component of individual lamellae are parallel arrays of mineralized type I collagen fibrils, organized in a plywood like motif. Here we use a dual beam microscope and the serial surface view (SSV) method to investigate the three dimensional collagen organization of circumferential lamellar bone from rat tibiae after demineralization and osmium staining. Fast Fourier transform analysis is used to quantitatively identify the mean collagen array orientations and local collagen fibril dispersion. Based on collagen fibril array orientations and variations in fibril dispersion, we identify 3 distinct sub-lamellar structural motifs: a plywood-like fanning sub-lamella, a unidirectional sub-lamella and a disordered sub-lamella. We also show that the disordered sub-lamella is less mineralized than the other sub-lamellae. The hubs and junctions of the canalicular network, which connect radially oriented canaliculi, are intimately associated with the disordered sub-lamella. We also note considerable variations in the proportions of these 3 sub-lamellar structural elements among different lamellae. This new application of Serial Surface View opens the way to quantitatively compare lamellar bone from different sources, and to clarify the 3-dimensional structures of other bone types, as well as other biological structural materials. 23614904 Bile Acid and Sterol Metabolism with Combined HMGCoA Reductase and PCSK9 Suppression. PCSK9 inhibition markedly augments the LDL lowering action of statins. The combination is being evaluated for long-term effects on atherosclerotic disease outcomes. However, effects of combined treatment on hepatic cholesterol and bile acid metabolism have not yet been reported. To study this, PCSK9-Y119X mutant (knockout) and wild type mice were treated ± atorvastatin for 12 wks. Atorvastatin progressively lowered plasma LDL in each group, but no differences in liver cholesterol, cholesterol ester, or total bile acid concentrations, or in plasma total bile acid levels were seen. In contrast, atorvastatin increased fecal total bile acids (~2-fold, P<0.01) and cholesterol concentrations (~3-fold, P<0.01) vs. controls for both PCSK9-Y119X and wild type mice. All 14 individual bile acids resolved by LC-MS, including primary, secondary, and conjugated species, reflected similar increases. Expression of key liver bile acid synthesis genes CYP7A1 and CYP8B1 were ~2.5-fold higher with atorvastatin in both strains, but mRNA for liver bile acid export and reuptake transporters and conjugating enzymes were not unaffected. The data suggest that hepatocyte cholesterol and bile acid homeostasis is maintained with combined PCSK9 and HMGCoA reductase inhibition through efficient liver enzymatic conversion of LDL-derived cholesterol into bile acids and excretion of both, with undisturbed enterohepatic recycling. 23553944 Bone stiffness and failure load are related with clinical parameters in men with chronic obstructive pulmonary disease. Osteoporosis is frequently seen in patients with chronic obstructive pulmonary disease (COPD). Since research on bone structure and bone strength in COPD patients is limited, the objectives of this pilot study were: 1. To compare bone structure, stiffness and failure load, measured at the peripheral skeleton, between men with and without COPD after stratification for areal bone mineral density (aBMD), and 2. To relate clinical parameters with bone stiffness and failure load in men with COPD. We included 30 men with COPD (normal aBMD n = 18, osteoporosis n = 12) and 17 men without COPD (normal aBMD n = 9, osteoporosis n = 8). We assessed pack-years of smoking, body mass index (BMI), fat free mass index (FFMI), pulmonary function (FEV1 , FEV1 /FVC, DLCO and KCO) and extent of emphysema. Bone structure of the distal radius and tibia was assessed by high resolution peripheral quantitative computed tomography (HR-pQCT), and bone stiffness and failure load of the distal radius and tibia were estimated from micro finite element analysis (µFEA). After stratification for aBMD and COPD, men with osteoporosis showed abnormal bone structure (p < 0.01), lower bone stiffness (p < 0.01) and lower failure load (p < 0.01) compared with men with normal aBMD, and men with COPD had comparable bone structure, stiffness and failure load compared with men without COPD. In men with COPD, lower FFMI was related with lower bone stiffness and failure load of the radius and tibia and lower DLCO and KCO were related with lower bone stiffness and failure load of the tibia after normalization with respect to femoral neck aBMD. Thus, this pilot study could not detect differences in bone structure, stiffness and failure load between men with and without COPD after stratification for aBMD. FFMI and gas transfer capacity of the lung were significantly related with bone stiffness and failure load in men with COPD after normalization with respect to femoral neck aBMD. © 2013 American Society for Bone and Mineral Research. 23474321 Effects of salinity stress on Bufo balearicus and Bufo bufo tadpoles: Tolerance, morphological gill alterations and Na(+)/K(+)-ATPase localization. Freshwater habitats are globally threatened by human-induced secondary salinization. Amphibians are generally poorly adapted to survive in saline environments. We experimentally investigated the effects of chronic exposure to various salinities (5%, 10%, 15%, 20%, 25%, 30% and 35% seawater, SW) on survival, larval growth and metamorphosis of tadpoles from two amphibian populations belonging to two species: the green toad Bufo balearicus and the common toad Bufo bufo. In addition, gill morphology of tadpoles of both species after acute exposure to hypertonic conditions (20%, 25%, and 30% SW) was examined by light and electron microscopy. Tadpoles experienced 100% mortality above 20% SW in B. balearicus while above 15% SW in B. bufo. We detected also sublethal effects of salinity stress on growth and metamorphosis. B. bufo cannot withstand chronic exposure to salinity above 5% SW, tadpoles grew slower and were significantly smaller than those in control at metamorphosis. B. balearicus tolerated salinity up to 20% SW without apparent effects during larval development, but starting from 15% SW tadpoles metamorphosed later and at a smaller size compared with control. We also revealed a negative relation between increasing salt concentration and gill integrity. The main modifications were increased mucous secretion, detachment of external layer, alteration of epithelial surface, degeneration phenomena, appearance of residual bodies, and macrophage immigration. These morphological alterations of gill epithelium can interfere with respiratory function and both osmotic and acid-base regulation. Significant variations in branchial Na(+)/K(+)-ATPase activity were also observed between two species; moreover an increase in enzyme activity was evident in response to SW exposure. Epithelial responses to increasing salt concentration were different in the populations belonging to two species: the intensity of histological and ultrastructural pathology in B. bufo was greater and we noticed the appearance in exposed samples of the tubular vesicle cells (TVCs). Taken together, our results demonstrated that increased salinity of freshwater may give cause for concern and must be considered a stressor for amphibians as well as other pollutants. 23609606 In vitro exploration of potential mechanisms of toxicity of the human hepatotoxic drug fenclozic acid. The carboxylic acid NSAID fenclozic acid exhibited an excellent preclinical safety profile and promising clinical efficacy, yet was withdrawn from clinical development in 1971 due to hepatotoxicity observed in clinical trials. A variety of modern in vitro approaches have been used to explore potential underlying mechanisms. Covalent binding studies were undertaken with [(14)C]-fenclozic acid to investigate the possible role of reactive metabolites. Time-dependent covalent binding to protein was observed in NADPH-supplemented liver microsomes, although no metabolites were detected in these incubations or in reactive metabolite trapping experiments. In human hepatocytes, covalent binding was observed at lower levels than in microsomes and a minor uncharacterizable metabolite was also observed. In addition, covalent binding was observed in incubations undertaken with dog and rat hepatocytes, where a taurine conjugate of the drug was detected. Although an acyl glucuronide metabolite was detected when liver microsomes from human, rat and dog were supplemented with UDPGA, there was no detectable UDPGA-dependent covalent binding. No effects were observed when fenclozic acid was assessed for P450-dependent and P450-independent cytotoxicity to THLE cell lines, time-dependent inhibition of five major human cytochrome P450 enzymes, inhibition of the biliary efflux transporters BSEP and MRP2 or mitochondrial toxicity to THLE or HepG2 cells. These data suggest that Phase 1 bioactivation plays a role in the hepatotoxicity of fenclozic acid and highlight the unique insight into mechanisms of human drug toxicity that can be provided by investigations of biotransformation and covalent binding to proteins. 23448202 Large enhancement of nonlinear optical response in a hybrid nanobiomaterial consisting of bacteriorhodopsin and cadmium telluride quantum dots. We report wavelength-dependent enormous enhancement of the nonlinear refractive index of wild-type bacteriorhodopsin in the presence of semiconductor quantum dots. The effect is strongest in the region just below the absorption edge of both constituents of this hybrid material and in samples that show strong Förster resonance energy transfer. We show that enhancements of up to 4000% can be achieved by controlled engineering of the hybrid structure involving variations of the molar ratio of the constituents. This new hybrid material with exceptional nonlinear properties will have numerous photonic and optoelectronic applications employing its photochromic, energy transfer, and conversion properties. 23410078 Isolation and structures of axistatins 1-3 from the Republic of Palau marine sponge Agelas axifera Hentschel . An investigation begun in 1979 directed at the Republic of Palau marine sponge Agelas axifera Hentschel for cancer cell growth inhibitory constituents subsequently led to the isolation of three new pyrimidine diterpenes designated axistatins 1 (1), 2 (2), and 3 (3), together with the previously reported formamides 4, 5, and agelasine F (6). The structures were elucidated by analysis of 2D-NMR spectra and by HRMS. All of the isolated compounds were found to be moderate inhibitors of cancer cell growth. Axistatins 1-3 (1-3), formamide 4, and agelasine F (6) also exhibited antimicrobial activity. 23435179 Botulinum toxins: Mechanisms of action, antinociception and clinical applications. Botulinum toxin (BoNT) is a potent neurotoxin that is produced by the gram-positive, spore-forming, anaerobic bacterium, Clostridum botulinum. There are 7 known immunologically distinct serotypes of BoNT: types A, B, C1, D, E, F, and G. Clostridum neurotoxins are produced as a single inactive polypeptide chain of 150kDa, which is cleaved by tissue proteinases into an active di-chain molecule: a heavy chain (H) of ∼100kDa and a light chain (L) of ∼50kDa held together by a single disulfide bond. Each serotype demonstrates its own varied mechanisms of action and duration of effect. The heavy chain of each BoNT serotype binds to its specific neuronal ecto-acceptor, whereby, membrane translocation and endocytosis by intracellular synaptic vesicles occurs. The light chain acts to cleave SNAP-25, which inhibits synaptic exocytosis, and therefore, disables neural transmission. The action of BoNT to block the release of acetylcholine botulinum toxin at the neuromuscular junction is best understood, however, most experts acknowledge that this effect alone appears inadequate to explain the entirety of the neurotoxin's apparent analgesic activity. Consequently, scientific and clinical evidence has emerged that suggests multiple antinociceptive mechanisms for botulinum toxins in a variety of painful disorders, including: chronic musculoskeletal, neurological, pelvic, perineal, osteoarticular, and some headache conditions. 23111374 Syntheses and in vitro evaluations of uncharged reactivators for human acetylcholinesterase inhibited by organophosphorus nerve agents. Organophosphorus nerve agents (OPNAs) are highly toxic compounds that represent a threat to both military and civilian populations. They cause an irreversible inhibition of acetylcholinesterase (AChE), by the formation of a covalent P-O bond with the catalytic serine. Among the present treatment of nerve agents poisoning, pyridinium and bis-pyridinium aldoximes are used to reactivate this inhibited enzyme but these compounds do not readily cross the blood brain barrier (BBB) due to their permanent cationic charge and thus cannot efficiently reactivate cholinesterases in the central nervous system (CNS). In this study, a series of seven new uncharged oximes reactivators have been synthesized and their in vitro ability to reactivate VX and tabun-inhibited human acetylcholinesterase (hAChE) has been evaluated. The dissociation constant KD of inhibited enzyme-oxime complex, the reactivity rate constant kr and the second order reactivation rate constant kr2 have been determined and have been compared to reference oximes HI-6, Obidoxime and 2-Pralidoxime (2-PAM). Regarding the reactivation of VX-inhibited hAChE, all compounds show a better reactivation potency than those of 2-PAM, nevertheless they are less efficient than obidoxime and HI-6. Moreover, one of seven described compounds presents an ability to reactivate tabun-inhibited hAChE equivalent to those of 2-PAM. 23214430 Structure enhancement factor relationships in single gold nanoantennas by surface-enhanced Raman excitation spectroscopy. Determining the existence of any direct spectral relationship between the far-field scattering properties and the near-field Raman-enhancing properties of surface-enhanced Raman spectroscopy (SERS) substrates has been a challenging task with only a few significant results to date. Here, we prove that hot spot dominated systems show little dependence on the far-field scattering properties because of differences between near- and far-field localized surface plasmon resonance (LSPR) effects as well as excitation of new plasmon modes via a localized emitter. We directly probe the relationship between the near- and far-field light interactions using a correlated LSPR-transmission electron microscopy (TEM) surface-enhanced Raman excitation spectroscopy (SERES) technique. Fourteen individual SERS nanoantennas, Au nanoparticle aggregates ranging from dimers to undecamers, coated in a reporter molecule and encased in a protective silica shell, were excited using eight laser wavelengths. We observed no correlation between the spectral position of the LSPR maxima and the maximum enhancement factor (EF). The single nanoantenna data reveal EFs ranging from (2.5 ± 0.6) × 10(4) to (4.5 ± 0.6) × 10(8) with maximum enhancement for excitation wavelengths of 785 nm and lower energy. The magnitude of maximum EF was not correlated to the number of cores in the nanoantenna or the spectral position of the LSPR, suggesting a separation between near-field SERS enhancement and far-field Rayleigh scattering. Computational electrodynamics confirms the decoupling of maximum SERS enhancement from the peak of the scattering spectrum. It also points to the importance of a localized emitter for radiating Raman photons to the far-field which, in nonsymmetric systems, allows for the excitation of radiative plasmon modes that are difficult to excite with plane waves. Once these effects are considered, we are able to fully explain the hot spot dominated SERS response of the nanoantennas. 23411311 Determination of the degree of oxidation in highly-oxidised lipids using profile changes of fatty acids. The degree of highly oxidised lipids was determined by a modified method using profile changes of fatty acids in lard and soybean oil heated at 180°C. The usefulness of the modified method was compared through conjugated dienoic acid (CDA) and/or p-anisidine value (p-AV) methods. Absolute values, which were expressed as equivalent to an internal standard (C11:0), of both unsaturated fatty acids (UFAs) and saturated fatty acids (SFAs) decreased significantly during thermal oxidation (p<0.05) while relative percentage of SFA increased and those of UFA decreased significantly (p<0.05). The content of caprylic acid (C8:0) increased significantly (p<0.05) as thermal oxidation time increased. The ratio of total saturated over total unsaturated fatty acids (SFAs/UFAs) or caprylic acid (C8:0) over UFAs could be useful markers to determine the degree of oxidation. Antioxidant capacity of sesamol, a free radical scavenger, was determined using the ratio of fatty acids. The modified method can be applied to determine the quality control of fried foods containing highly oxidised and abused oils, which may not be measured correctly using CDA and p-AV. 23369343 Evaluation of in vivo anti-hyperglycemic and antioxidant potentials of α-santalol and sandalwood oil. Sandalwood finds numerous mentions across diverse traditional medicinal systems in use worldwide. The objective of this study was to evaluate the in vivo anti-hyperglycemic and antioxidant potential of sandalwood oil and its major constituent α-santalol. The in vivo anti-hyperglycemic experiment was conducted in alloxan-induced diabetic male Swiss albino mice models. The in vivo antioxidant experiment was performed in d-galactose mediated oxidative stress induced male Swiss albino mice models. Intraperitoneal administration of α-santalol (100mg/kg BW) and sandalwood oil (1g/kg BW) for an week modulated parameters such as body weight, blood glucose, serum bilirubin, liver glycogen, and lipid peroxides contents to normoglycemic levels in the alloxan-induced diabetic mice. Similarly, intraperitoneal administration of α-santalol (100mg/kg BW) and sandalwood oil (1g/kg BW) for two weeks modulated parameters such as serum aminotransferases, alkaline phosphatase, bilirubin, superoxide dismutase, catalase, free sulfhydryl, protein carbonyl, nitric oxide, liver lipid peroxide contents, and antioxidant capacity in d-galactose mediated oxidative stress induced mice. Besides, it was observed that the beneficial effects of α-santalol were well complimented, differentially by other constituents present in sandalwood oil, thus indicating synergism in biological activity of this traditionally used bioresource. 23174746 Orofacial dyskinesia induced by nasal Ritalin(R) (methylphenidate) sniffing: a rare case report from Switzerland. Ritalin® (methylphenidate) is an amphetamine-like prescription stimulant commonly used in the treatment of attention deficit hyperactivity disorder in children and adults. Recently, the recreational use of Ritalin has increased, particularly among young adults. Well-known symptoms of intoxication include signs of sympathetic nervous stimulation, such as agitation, anxiety, tachycardia, hypertension, headache, tremor, and dizziness. This case report describes oral dyskinesia as a rare presentation of Ritalin intoxication, with the review of pathophysiology and some epidemiological data. 23416191 Fragment-based drug design and identification of HJC0123, a novel orally bioavailable STAT3 inhibitor for cancer therapy. Fragment-based drug design (FBDD) is a promising approach for the generation of lead molecules with enhanced activity and especially drug-like properties against therapeutic targets. Herein, we report the fragment-based drug design, systematic chemical synthesis and pharmacological evaluation of novel scaffolds as potent anticancer agents by utilizing six privileged fragments from known STAT3 inhibitors. Several new molecules such as compounds 5, 12, and 19 that may act as advanced chemical leads have been identified. The most potent compound 5 (HJC0123) has demonstrated to inhibit STAT3 promoter activity, downregulate phosphorylation of STAT3, increase the expression of cleaved caspase-3, inhibit cell cycle progression and promote apoptosis in breast and pancreatic cancer cells with low micromolar to nanomolar IC50 values. Furthermore, compound 5 significantly suppressed estrogen receptor (ER)-negative breast cancer MDA-MB-231 xenograft tumor growth in vivo (p.o.), indicating its great potential as an efficacious and orally bioavailable drug candidate for human cancer therapy. 23305127 Enhanced redifferentiation of chondrocytes on microperiodic silk/gelatin scaffolds: toward tailor-made tissue engineering. Direct-write assembly allows rapid fabrication of complex three-dimensional (3D) architectures, such as scaffolds simulating anatomical shapes, avoiding the need for expensive lithographic masks. However, proper selection of polymeric ink composition and tailor-made viscoelastic properties are critically important for smooth deposition of ink and shape retention. Deposition of only silk solution leads to frequent clogging due to shear-induced β-sheet crystallization, whereas optimized viscoelastic property of silk-gelatin blends facilitate the flow of these blends through microcapillary nozzles of varying diameter. This study demonstrates that induction of controlled changes in scaffold surface chemistry, by optimizing silk-gelatin ratio, can govern cell proliferation and maintenance of chondrocyte morphology. Microperiodic silk-gelatin scaffolds can influence postexpansion redifferentiation of goat chondrocytes by enhancing Sox-9 gene expression, aggregation, and driving cartilage matrix production, as evidenced by upregulation of collagen type II and aggrecan expression. The strategy for optimizing redifferentiation of chondrocytes can offer valuable consideration in scaffold-based cartilage repair strategies. 23357633 Antimycobacterial activity evaluation, time-kill kinetic and 3D-QSAR study of C-(3-aminomethyl-cyclohexyl)-methylamine derivatives. A series of C-(3-aminomethyl-cyclohexyl)-methylamine derivatives were synthesized and evaluated for their antitubercular activity. Some of the compounds exhibited potent activity against Mycobacterium tuberculosis H37Rv. One of the compound having t-butyl at para position of the benzene ring showed excellent activity even better than the standard drug ethambutol with MIC value 1.1 ± 0.2 μM. The time-kill kinetics study of two most active compounds showed rapid killing of the M. tuberculosis within 4 days. Additionally atom-based quantitative structure-activity relationship (QSAR) model was developed that gave a statistically satisfying result (R(2))=0.92, Q(2)=0.75, Pearson-R=0.96 and effectively predicts the anti-tuberculosis activity of training and test set compounds. 23598462 Sub-picometer structural information of graphene hidden in a 50 pm resolved image. In a 2D self-organized crystalline structure more than 1000 unit-cells can be observed in a single image. Here we exploit the benefits from having a large number of observations of the same unit cell utilizing an image processing methodology. We obtain sub-picometer resolution data from a 50 pm image of graphene, revealing a 1% axial elongation and a 3 fold symmetry, indicating a chair conformation. 23313379 The effects of natural disturbances, reef state, and herbivorous fish densities on ciguatera poisoning in Rarotonga, southern Cook Islands. Ciguatera poisoning is a critical public-health issue among Pacific island nations. Accurately predicting ciguatera outbreaks has become a priority, particularly in Rarotonga in the southern Cook Islands, which has reported the highest incidence of ciguatera poisoning globally. Since 2006, however, cases of ciguatera poisoning have declined, and in 2011 ciguatera cases were the lowest in nearly 20 years. Here we examined the relationships between cases of ciguatera poisoning, from 1994 to 2011, and: (i) coral cover, used as a proxy of reef state, (ii) the densities of herbivorous fishes, and (iii) reef disturbances. We found that coral cover was not a good predictor of cases of ciguatera poisoning, but high densities of the herbivorous fish Ctenochaetus striatus and reef disturbances were both strong predictors of ciguatera poisoning. Yet these two predictors were correlated, because the densities of C. striatus increased only after major cyclones had disturbed the reefs. Since 2006, the number of cyclones has decreased considerably in Rarotonga, because of the climatic shift toward the negative phase of the Pacific Decadal Oscillation. We suggest that fewer cyclones have led to decreases in both the densities of C. striatus and of the number of reported cases of ciguatera poisoning in Rarotonga. 23354727 Osteoporosis in men: recent progress. As osteoporosis in men has been recognized as an important clinical problem, new information is being accumulated on its scope, pathophysiology, evaluation, and treatment. Fracture risk calculators, such as FRAX, identify a large proportion of the older male population to be at heightened risk for fracture. The classification of osteoporosis into primary and secondary forms, while still useful, is affected by the fact that many men have multiple contributing factors to their fracture risk. The role of sex steroids is being better defined as other risk factors for fracture are delineated. As longevity continues to increase in men and until osteoporotic fracture is truly recognized as a potentially fatal disorder, many men will be undiagnosed and untreated. Two recent studies provide more evidence that treatments which decrease fracture risk in women do the same in men. With the publication of guidelines and increasing strength of evidence for treatment efficacy, it is hoped that more men will be evaluated and treated for this often neglected disorder. 23644525 Solution-processed organic spin-charge converter. Conjugated polymers and small organic molecules are enabling new, flexible, large-area, low-cost optoelectronic devices, such as organic light-emitting diodes, transistors and solar cells. Owing to their exceptionally long spin lifetimes, these carbon-based materials could also have an important impact on spintronics, where carrier spins play a key role in transmitting, processing and storing information. However, to exploit this potential, a method for direct conversion of spin information into an electric signal is indispensable. Here we show that a pure spin current can be produced in a solution-processed conducting polymer by pumping spins through a ferromagnetic resonance in an adjacent magnetic insulator, and that this generates an electric voltage across the polymer film. We demonstrate that the experimental characteristics of the generated voltage are consistent with it being generated through an inverse spin Hall effect in the conducting polymer. In contrast with inorganic materials, the conducting polymer exhibits coexistence of high spin-current to charge-current conversion efficiency and long spin lifetimes. Our discovery opens a route for a new generation of molecular-structure-engineered spintronic devices, which could lead to important advances in plastic spintronics. 23066949 Protein-ligand interaction study of CpOGA in complex with GlcNAcstatin. The GlcNAcstatin is a potent inhibitor of O-glycoprotein 2-acetamino-2-deoxy-β-D-glucopyranosidase, which has been related with type II diabetes and neurodegenerative disorders. Herein, hybrid quantum mechanics/molecular mechanics, molecular dynamics simulations, and potential of mean force were employed to study the interactions established between GlcNAcstatin and a bacterial O-GlcNAcase enzyme from Clostridium perfringens. The results reveal that the imidazole nitrogen atom of GlcNAcstatin has shown a better interaction with the active site of Clostridium perfringens in its protonated form, which is compatible with a substrate-assisted reaction mechanism involving two conserved aspartate residues (297 and 298). Furthermore, the quantum mechanics/molecular mechanics-molecular dynamics simulations appointed a strong interaction between Asp401, Asp298, and Asp297 residues and the GlcNAcstatin inhibitor, which is in accordance with experimental data. Lastly, these results may contribute to understand the molecular mechanism of inhibition of Clostridium perfringens by GlcNAcstatin inhibitor and, consequently, this study might be useful to design new molecules with more interesting inhibitory activity. 23401139 Toxicity and toxicokinetics of binary combinations of petroleum hydrocarbon distillates with the earthworm Eisenia andrei. Petroleum hydrocarbons (PHCs) act via narcosis and are expected to have additive toxicity. However, previous work has demonstrated less-than-additive toxicity with PHC distillates and earthworms. A study was initiated to investigate this through toxicity and toxicokinetic studies with the earthworm Eisenia andrei. Three petroleum distillate fractions, F2 (>C10-C16), F3a (>C16-C23), and F3b (>C23-C34), were used in two binary combinations, F2F3a and F3aF3b. In the toxicity study, clean soil was spiked with equitoxic combinations of the two distillates ranging from 0.5 to 2.5 toxic units. In the toxicokinetic study, a binary combination consisting of one concentration of each distillate was used. On a soil concentration basis, the toxicity of the binary combinations of distillates was less than additive. Accumulation of the individual distillates, however, was generally reduced when a second distillate was present, resulting in lower body burden. This is thought to be due to the presence of a nonaqueous-phase liquid at the soil concentrations used. On a tissue concentration basis, toxicity was closer to additive. The results demonstrate that tissue concentrations are the preferred metric for toxicity for earthworms. They also demonstrate that the Canada-wide soil standards based on individual distillates are likely protective. Environ. Toxicol. Chem. 2013;32:1016-1026. © 2013 SETAC. 23220586 Effect of polyethylene glycol conjugation on the circulatory stability of plasma-derived human butyrylcholinesterase in mice. Exogenously administered human serum butyrylcholinesterase (Hu BChE) was demonstrated to function as a bioscavenger of highly toxic organophosphorus (OP) compounds in several animal species. Since the enzyme is isolated from human serum, it is currently the most suitable pretreatment for human use. A dose of 200-300mg/70kg human adult is projected to provide protection from 2 X LD50 of soman. Due to the limited supply of Hu BChE, strategies aimed at reducing the dose of enzyme are being explored. In this study, we investigated the effect of modification with polyethylene glycol (PEG) on the in vivo stability of Hu BChE. Mice were given two injections of either Hu BChE or Hu BChE modified with PEG-5K or PEG-20K, six weeks apart. Pharmacokinetic parameters, such as mean residence time (MRT), maximal concentration (Cmax), elimination half-life (T1/2), and area under the plasma concentration time curve extrapolated to infinity (AUC), were determined. For the first injection, values for MRT, T1/2, Cmax, and AUC for PEG-5K-Hu BChE and PEG-20K-Hu BChE were similar to those for Hu BChE. These values for the second injection of Hu BChE as well as PEG-Hu BChEs were lower as compared to those for the first injections, likely due to antibody-mediated clearance. 23401291 Novel Schiff-base-derived FabH inhibitors with dioxygenated rings as antibiotic agents. Fatty acid biosynthesis plays a vital role in bacterial survival and several key enzymes involved in this biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents. Of these promising targets, β-ketoacyl-acyl carrier protein (ACP) synthase III (FabH) is the most attractive target that could trigger the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and -negative bacteria. Designing small molecules with FabH inhibitory activity displays great significance for developing antibiotic agents, which should be highly selective, nontoxic and broad-spectrum. In this manuscript, a series of novel Schiff base compounds were designed and synthesized, and their biological activities were evaluated as potential inhibitors. Among these 21 new compounds, (E)-N-((3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)methylene)hexadecan-1-amine (10) showed the most potent antibacterial activity with a MIC value of 3.89-7.81 μM(-1) against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with an IC(50) value of 1.6 μM. Docking simulation was performed to position compound 10 into the E. coli FabH active site to determine the probable binding conformation. 23281242 Mesoporous metallic cells: design of uniformly sized hollow mesoporous pt-ru particles with tunable shell thicknesses. A new class of hollow mesoporous Pt-Ru and Pt particles with uniform size, named 'mesoporous metallic cells', are synthesized through a dual-templating approach using colloidal silica particles and non-ionic surfactants. To realize the full potential of mesoporous metals as electrocatalysts, the shell thicknesses, compositions, and hollow cavity sizes are precisely controlled. 23297346 Hydrogen sulfide, the next potent preventive and therapeutic agent in aging and age-associated diseases. Hydrogen sulfide (H(2)S) is the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide. It is physiologically generated by cystathionine-γ-lyase, cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase. H(2)S has been gaining increasing attention as an important endogenous signaling molecule because of its significant effects on the cardiovascular and nervous systems. Substantial evidence shows that H(2)S is involved in aging by inhibiting free-radical reactions, activating SIRT1, and probably interacting with the age-related gene Klotho. Moreover, H(2)S has been shown to have therapeutic potential in age-associated diseases. This article provides an overview of the physiological functions and effects of H(2)S in aging and age-associated diseases, and proposes the potential health and therapeutic benefits of H(2)S. 23417790 Determination of mercury speciation in fish tissue with a direct mercury analyzer. Knowledge of Hg speciation in tissue is valuable for assessing potential toxicological effects in fish. Direct Hg analyzers, which use thermal decomposition and atomic absorption spectrometry, have recently gained popularity for determining organic Hg after procedural solvent extraction from some environmental media, although quantitative recovery from lipid-rich materials, such as fish liver, has been problematic. The authors developed a new method by which organic Hg in fish liver and muscle is estimated by the difference between direct measurements of inorganic Hg in an acid extract and total Hg in whole tissue. The method was validated by analysis of a certified reference material (DOLT-4 dogfish liver) and naturally contaminated fish tissues with comparison to an established Hg speciation method (gas chromatography cold vapor atomic fluorescence spectrometry). Recovery of organic Hg from DOLT-4, estimated by difference, averaged 99 ± 5% of the mean certified value for methylmercury. In most liver samples and all muscle samples, estimates of organic Hg from the proposed method were indiscernible from direct speciation measurements of methylmercury (99% ± 6%). Estimation of organic Hg by the difference between total Hg and inorganic Hg was less accurate in liver samples with a high percentage of inorganic Hg (90%). This was because of the increased uncertainty that results from estimating a third value (i.e., organic Hg) by using the difference between two large concentrations (inorganic and total Hg). The proposed method is a useful tool for examining the speciation of Hg in fish muscle and liver, and by extension, potentially other tissues and environmental media. Environ Toxicol Chem 2013;32:1237-1241. © 2013 SETAC. 23379353 Impairment of regulatory T cell function in autoimmune thyroid disease. Background: Autoimmune thyroid disease (AITD) pathogenesis may result from a loss of immune tolerance to thyroid antigens. Regulatory T cells (Tregs) control immune responses, prevent excessive inflammation, and may be dysfunctional in AITD. We investigated the role of Tregs in Hashimoto's thyroiditis (HT) and Graves' disease (GD). Our goal was to identify differences in CD4+CD25hi Treg function or number in patients with GD and HT, compared to healthy controls (HC). Methods: Treg number was assessed by flow cytometric analysis in samples from twenty AITD patients (7 GD, 13 HT), 9 HC, and 7 individuals with Down syndrome (DS), a genetic disorder associated with multiple autoimmune disorders including AITD. Treg function was assessed by the inhibition of proliferation (radioactive thymidine incorporation into DNA) of blood-derived T effector cells (Teff) by Tregs in a co-culture. Various methods of stimulation were contrasted. Cytokine levels were determined in conditioned media from the co-cultures. Results: No differences were found in the frequency of Tregs as a percentage of CD4+ cells between AITD and HC. AITD Tregs were less capable of inhibiting the proliferation of Teff cells when compared to HC, however, the impairment was dependent on the type of stimulation used. DS patients without AITD exhibited normal Treg function. We observed few differences in cytokine production between HC and AITD patients. Conclusions: Tregs from AITD patients are partly dysfunctional, possibly explaining their autoimmunity. Future work will elucidate the diagnostic potential and pathophysiology of Tregs in AITD. 23151611 Antidepressant-like effect of oleanolic acid in mice exposed to the repeated forced swimming test. The study aimed to explore the antidepressant-like effect of oleanolic acid and its possible mechanism related to the monoaminergic system and neurotrophin in mice exposed to the repeated forced swimming test (FST). Both the duration and the latency of immobility affected by oleanolic acid (10, 20 and 40 mg/kg) were evaluated in the FST repeated at intervals on days 1, 7 and 14, followed by neurochemical and brain-derived neurotrophic factor (BDNF) analyses in the mouse brain regions of frontal cortex and whole hippocampus. A repeated analysis of variance (ANOVA) indicated that over retesting the immobility time increased, whereas latency to immobility tended to decrease. Minute-by-minute analysis showed that immobility time also increased during the 4-min course of the test. In addition, post-hoc Dunnett's test demonstrated that sub-chronic and chronic, but not acute, oleanolic acid treatment reduced the immobility time (sub-chronic: 20 mg/kg, 43.5%; chronic: 10 mg/kg, 19.3%; 20 mg/kg, 31.8%) and increased the latency to immobility (sub-chronic: 10 mg/kg, 60.6%; 20 mg/kg, 80.1%; chronic: 10 mg/kg, 121.8%; 20 mg/kg, 140.8%; 40 mg/kg, 80.0%). Furthermore, chronic administration of oleanolic acid significantly increased serotonin (5-HT) levels (frontal cortex: 44.5%, 41.9%, 27.5% for 10, 20, 40 mg/kg; hippocampus: 57.2%, 80.9% for 10, 20 mg/kg), decreased 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio (frontal cortex: 31.6%, 30.1%, 23.5%; hippocampus: 40.6%, 47.7%, 29.2% for 10, 20, 40 mg/kg) and elevated norepinephrine (NE) levels (hippocampus: 20 mg/kg, 45.4%) but did not alter dopamine (DA) levels. Moreover, BDNF levels in the two brain regions were also elevated by chronic oleanolic acid treatment (frontal cortex: 20 mg/kg, 67.2%; hippocampus: 10 mg/kg, 36.4%; 20 mg/kg, 55.1%). Taken together, these findings imply that functions of 5-HT, NE and BDNF may be involved in the antidepressant-like effect of oleanolic acid. 23561171 Rapid chemical profiling of saponins in the flower buds of Panax notoginseng by integrating MCI gel column chromatography and liquid chromatography/mass spectrometry analysis. The flower buds of Panax notoginseng (Notoginseng flower, FBP) are used as the traditional Chinese medicine San-Qi-Hua. In this study, we conducted column chromatography fractionation and liquid chromatography/mass spectrometry (LC/MS) analysis to comprehensively profile bioactive notoginseng saponins (ginsenosides) in FBP. MCI gel column chromatography allowed separation and enrichment of minor saponins. Electrospray ionization tandem mass spectrometry of [M-H](-) and [M+Na](+) precursor ions of the saponins provided reliable structural information for the sapogenin, and sequence of sugar chains. Confirmed by high-accuracy Q-TOF analysis, 170 notoginseng saponins were characterized from FBP, and 91 of them were reported from Panax species for the first time. The new ginsenosides contain acyl groups on α-chain, malonyl group at 20-OH, or di-malonyl groups. This study also indicated that the flower buds of P. notoginseng contained more protopanaxadiol-type but less protopanaxatriol-type ginsenosides than the roots. 23489629 N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11β-hydroxysteroid dehydrogenase type 1: strategies to eliminate reactive metabolites. N-(Pyridin-2-yl) arylsulfonamides 1 and 2 (PF-915275) were identified as potent inhibitors of 11β-hydroxysteroid dehydrogenase type 1. A screen for bioactivation revealed that these compounds formed glutathione conjugates. This communication presents the results of a risk benefit analysis carried out to progress 2 (PF-915275) to a clinical study and the strategies used to eliminate reactive metabolites in this series of inhibitors. Based on the proposed mechanism of bioactivation and structure-activity relationships, design efforts led to N-(pyridin-2-yl) arylsulfonamides such as 18 and 20 that maintained potent 11β-hydroxysteroid dehydrogenase type 1 activity, showed exquisite pharmacokinetic profiles, and were negative in the reactive metabolite assay. 23561089 The enhancement of antioxidant compounds extracted from Thymus vulgaris using enzymes and the effect of extracting solvent. We evaluate the total phenolic compounds (TPC) content and the antioxidant activity (AA) of extracts obtained from ground fresh thyme (FT) and depleted thyme (DT), a by-product of the process of essential oil extraction. In addition, enzymatic treatments were evaluated to improve the extraction yields of polyphenolic compounds from thyme. Extractions were performed using several solvents as methanol, ethanol, and water. Enzymes were applied prior to extraction or during the extraction process. The best results were obtained using a mixture of methanol and water, resulting in 2790 and 220mg Gallic acid equivalent (GAE)/L of TPC for FT and DT, respectively. A similar result was observed for AA. With regard to enzymatic treatment, application of Grindamyl CA 150 enzyme as a pre-treatment resulted in the production of an extract from DT with 614mg TE (trolox equivalent)/L of AA, 70% more than the control, and an AA of 621mg TE/L (74% more than the control sample) was obtained using Grindamyl CA 150 during the extraction process. These results suggest that enzymatic treatment is an interesting alternative for producing antioxidant extracts from DT. 23497882 Structural characterisation of polysaccharides from Tricholoma matsutake and their antioxidant and antitumour activities. In this study, polysaccharides from Tricholoma matsutake (TM-P) were purified using a DEAE-Sepharose fast flow column and three polysaccharide fractions (TM-P1, TM-P2 and TM-P3) were obtained. The chemical composition and structural characteristics of TM-P2 were quite different from those of TM-P1 and TM-P3. TM-P2 consisted of glucose, galactose and mannose with a molar ratio of 5.9:1.1:1.0. The glycosidic linkages were mainly composed of 1,6- and 1-linked glucose. Furthermore, TM-P2 showed the strongest in vitro antioxidant and antitumour activities. The oxygen radical absorbance capacity (ORAC) of TM-P2 was 2100.44 μmol Trolox/g. The antiproliferative activities of TM-P2 (4.0mg/ml) on the growth of HepG2 and A549 cells were 67.98% and 59.04%, respectively. 23194528 Characterisation of tequila according to their major volatile composition using multilayer perceptron neural networks. Differentiation of silver, gold, aged and extra-aged tequila using 1-propanol, ethyl acetate, 2-methyl-1-propanol, 3-methyl-1-butanol and 2-methyl-1-butanol and furan derivatives like 5-(hydroxymethyl)-2-furaldehyde and 2-furaldehyde has been carried out. The content of 1-propanol, ethyl acetate, 2-methyl-1-propanol, 3-methyl-1-butanol and 2-methyl-1-butanol was determined by means of head space solid phase microextraction gas chromatography mass-spectrometry. 5-(Hydroxymethyl)-2-furaldehyde and 2-furaldehyde were determined by high performance liquid chromatography with diode array detection. Kruskal-Wallis test was used to highlight significant differences between types of tequila. Principal component analysis was applied as visualisation technique. Linear discriminant analysis and multilayer perceptron artificial neural networks were used to construct classification models. The best classification performance was obtained when multilayer perceptron model was applied. 23537897 The birth and early years of INA, the International Neurotoxicology Association. The International Neurotoxicology Association (INA) is a scientific society whose members have interest and expertise in the discipline of neurotoxicology. The idea of forming INA was born in 1984, as a follow-up to a NATO-sponsored meeting on Toxicology of the Nervous System. INA held its first meeting in the Netherlands in 1987 and has had continuous meetings every other year since then. INA is registered as a scientific society in the Netherlands, and is an affiliated society of IUTOX. This paper presents a personal account of the events that led to the birth of INA, and of the first fifteen years of this association. 23352748 Rhododendron tomentosum (Ledum palustre). A review of traditional use based on current research. Rhododendron tomentosum Harmaja (previously: Ledum palustre) is a fragrant evergreen shrub found in peaty soils in northern Europe, Asia and North America, commonly referred to as wild rosemary, marsh tea, marsh rosemary or northern Labrador tea. At least since the eighteenth century it has been used in ethnomedicine for the treatment of various ailments, such as rheumatism, cough, cold and insect bites, as well as a repellent. The essential oil of wild rosemary with the rich polyphenolic fraction possesses analgesic, anti-inflammatory, antimicrobial, antiviral, antifungal and insecticidal potential, demonstrated by in vivo and in vitro studies. In addition, recent scientific research reported the promising antidiabetic, antioxidant and anticancer properties. This review summarizes the information concerning taxonomy, botany, ecology, chemical composition, biological activities, toxicology and traditional and contemporary application of Rhododendron tomentosum plants. 23460347 Arraying Cell Cultures Using PEG-DMA Micromolding in Standard Culture Dishes. A robust and effortless procedure is presented, which allows for the microstructuring of standard cell culture dishes. Cell adhesion and proliferation are controlled by three-dimensional poly(ethylene glycol)-dimethacrylate (PEG-DMA) microstructures. The spacing between microwells can be extended to millimeter size in order to enable the combination with robotic workstations. Cell arrays of microcolonies can be studied under boundary-free growth conditions by lift-off of the PEG-DMA layer in which the growth rate is accessible via the evolution of patch areas. Alternatively, PEG-DMA stencils can be used as templates for plasma-induced patterning. 23225780 N-cyano sulfoximines: COX inhibition, anticancer activity, cellular toxicity, and mutagenicity. From insects to cancer: N-Cyano sulfoximines were evaluated for COX inhibition and antiproliferative activity against a panel of cancer cell lines. The most active compound exhibited potent COX-2 inhibition, some selectivity for COX-2 over COX-1, only slight cytotoxicity towards healthy cells (HaCaT skin cells), and no mutagenic potential (as determined by an Ames assay). 23454308 Cytotoxicity of aluminium oxide nanoparticles towards fresh water algal isolate at low exposure concentrations. The growing commercial applications had brought aluminium oxide nanoparticles under toxicologists' purview. In the present study, the cytotoxicity of two different sized aluminium oxide nanoparticles (ANP(1), mean hydrodynamic diameter 82.6±22nm and ANP(2), mean hydrodynamic diameter 246.9±39nm) towards freshwater algal isolate Chlorella ellipsoids at low exposure levels (≤1μg/mL) using sterile lake water as the test medium was assessed. The dissolution of alumina nanoparticles and consequent contribution towards toxicity remained largely unexplored owing to its presumed insoluble nature. Herein, the leached Al(3+) ion mediated toxicity has been studied along with direct particulate toxicity to bring out the dynamics of toxicity through colloidal stability, biochemical, spectroscopic and microscopic analyses. The mean hydrodynamic diameter increased with time both for ANP(1) [82.6±22nm (0h) to 246.3±59nm (24h), to 1204±140nm (72h)] and ANP(2) [246.9±39nm (0h) to 368.28±48nm (24h), to 1225.96±186nm (72h)] signifying decreased relative abundance of submicron sized particles (<1000nm). The detailed cytotoxicity assays showed a significant reduction in the viability dependent on dose and exposure. A significant increase in ROS and LDH levels were noted for both ANPs at 1μg/mL concentration. The zeta potential and FT-IR analyses suggested surface chemical interaction between nanoparticles and algal cells. The substantial morphological changes and cell wall damage were confirmed through microscopic analyses (SEM, TEM, and CLSM). At 72h, significant Al(3+) ion release in the test medium [0.092μg/mL for ANP(1), and 0.19μg/mL for ANP(2)] was noted, and the resulting suspension containing leached ions caused significant cytotoxicity, revealing a substantial ionic contribution. This study indicates that both the nano-size and ionic dissolution play a significant role in the cytotoxicity of ANPs towards freshwater algae, and the exposure period largely determines the prevalent mode of nano-toxicity. 23543014 Commentary to Gebel 2012: a quantitative review should apply meta-analytical methods. Gebel (2012) performed a quantitative review of inhalation rat studies on the association of granular biopersistent dust exposures and lung cancer risk. The analytical methods applied are unreliable because they do not fulfil the requirements of current meta-analytical methods. 22982206 Verrucarin A sensitizes TRAIL-induced apoptosis via the upregulation of DR5 in an eIF2α/CHOP-dependent manner. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most promising candidates for new cancer therapeutics. However, resistance to TRAIL in some cancers remains a current problem in recent. The protein-folding compartment of the endoplasmic reticulum (ER) is particularly sensitive to disturbances, which, if severe, may trigger apoptosis. Therefore, we examined whether verrucarin A (VA) sensitize TRAIL-induced apoptosis in cancer cells by induction of ER stress. We first found that VA induces a major molecule of ER stress, CCAAT/enhancer binding protein homologous protein (CHOP)-dependent DR5 induction and subsequently increases TRAIL-induced cleavage of caspases and PARP in TRAIL-resistant Hep3B cells. Importantly, the transient knockdown using siRNA for CHOP abrogated VA-induced DR5 expression and attenuated TRAIL-induced apoptosis. Treatment with VA also increased the levels of phosphorylation of eukaryotic translation initiation factor-2α (eIF2α), which is a common cellular response of ER stress. Furthermore, salubrinal, a specific eIF2α phosphorylation-inducing agent, increased CHOP and DR5 expression in the presence of VA. In contrast, transfection of mutant-eIF2α significantly reversed VA-induced apoptosis with downregulation of CHOP-dependent DR5 expression. Therefore, VA-induced eIF2α phosphorylation seemed to be important for CHOP and DR5 upregulation and TRAIL-induced apoptosis. In addition, generation of reactive oxygen species (ROS) is an effector molecular in sensitization of VA-induced ER stress. We concluded that VA triggers TRAIL-induced apoptosis by eIF2α/CHOP-dependent DR5 induction via ROS generation. 23265880 A new single-photon emission computed tomography (SPECT) imaging agent for serotonin transporters: [(125)I]Flip-IDAM, (2-((2-((dimethylamino)methyl)-4-iodophenyl)thio)phenyl)methanol. New ligands for in vivo brain imaging of serotonin transporter (SERT) with single photon emission tomography (SPECT) were prepared and evaluated. An efficient synthesis and radiolabeling of a biphenylthiol, FLIP-IDAM, 4, was accomplished. The affinity of FLIP-IDAM was evaluated by an in vitro inhibitory binding assay using [(125)I]-IDAM as radioligand in rat brain tissue homogenates (K(i) = 0.03 nM). New [(125)I]Flip-IDAM exhibited excellent binding affinity to SERT binding sites with a high hypothalamus to cerebellum ratio of 4 at 30 min post iv injection. The faster in vivo kinetics for brain uptake and a rapid washout from non-specific regions provide excellent signal to noise ratio. This new agent, when labeled with (123)I, may be a useful imaging agent for mapping SERT binding sites in the human brain. 22986217 Soy isoflavones modulate adipokines and myokines to regulate lipid metabolism in adipose tissue, skeletal muscle and liver of male Huanjiang mini-pigs. Although a growing body of evidence suggests that soy isoflavones help regulate lipid metabolism, the underlying mechanism has not yet been thoroughly clarified. The present study was undertaken to determine the effects of soy isoflavones on the expression of genes involved in lipid metabolism in different adipose tissue depots, skeletal muscle and liver of male Huanjiang mini-pigs, as well as the expression of adipokines and myokines. A total of 36 male Huanjiang mini-pigs were fed basal diet (control, Con), low-dose soy isoflavones (LSI) and high-dose soy isoflavones (HSI). The results showed that LSI and HSI regulated the expression of genes involved in the anabolism and catabolism of fatty acids in dorsal subcutaneous (DSA), abdominal subcutaneous (ASA) and perirenal (PRA) adipose tissue depots, as well as longissimus dorsi muscle (LDM) and liver. LSI and HSI also regulated the expression of adipokines in DSA, ASA and PRA, and the expression of myokines in LDM in male Huanjiang mini-pigs. In addition, soy isoflavones regulated plasma glucose, leptin and adiponectin contents after treatment for two months. Our results indicate that soy isoflavones, by regulating the expression of adipokines and myokines, may regulate the metabolism of lipids and could have potential therapeutic applications in lipid abnormalities. 23210851 Recent advances in the development of catalytic inhibitors of human DNA topoisomerase IIα as novel anticancer agents. DNA topoisomerases comprise an important family of enzymes that catalyse the induction of topological changes (e.g. relaxation/ supercoiling, catenation/decatenation and knotting/unknotting) in the DNA molecule. These enzymes perform their functions by creating transient either single-stranded or double-stranded breaks in the DNA molecule. Due to their ability to modulate the topology of the DNA molecule, DNA topoisomerases play vital roles in replication, transcription, chromosome separation and segregation, and thus represent an important collection of design targets for novel anticancer drugs. The aim of this review is to provide an overview of the development of catalytic inhibitors of the human topoisomerase IIα enzyme--an important member of the DNA topoisomerase family--as potential novel anticancer agents. The group of catalytic topoII inhibitors is classified into four types according to their molecular mechanism of action: inhibitors that bind to the ATP binding site, inhibitors that prevent the ATP hydrolysis step and trap the enzyme in a closed clamp, inhibitors that block the DNA cleavage and inhibitors that prevent the enzyme binding to the DNA. One of the important considerations highlighted throughout this review is the structure-based perspective of inhibitor design, giving the reader a medicinal chemist's perspective on this vibrant and active field of drug design research. 23217961 Structure-activity relationship study on benzoic acid part of diphenylamine-based retinoids. Based on structure-activity relationship studies of the benzoic acid part of diphenylamine-based retinoids, the potent RXR agonist 4 was derivatized to obtain retinoid agonists, synergists, and an antagonist. Cinnamic acid derivatives 5 and phenylpropionic acid derivatives 6 showed retinoid agonistic and synergistic activities, respectively. The difference of the activities is considered to be due to differences in the flexibility of the carboxylic acid-containing substituent on the diphenylamine skeleton. Compound 7, bearing a methyl group at the meta position to the carboxyl group, was an antagonist, dose-dependently inhibiting HL-60 cell differentiation induced by 3.3 × 10(-10)M Am80. 23106482 Chemical constituents of Arisaema franchetianum tubers. A novel pyrrolidine alkaloid, (2R*,3S*,5S*)-N,2-dimethyl-3-hydroxy-5-(10-phenyldecyl)pyrrolidine (1), and 17 known compounds were isolated from Arisaema franchetianum Engl. (Araceae) tubers. The 17 compounds were bergenin (2), emodin (3), caffeic acid (4), nobiletin (5), 3-O-β-d-galactopyranosyl-hederagenin 28-O-β-d-xylopyranosyl(1 → 6)-β-d-galactopyranosyl ester (6), coniferin (7), qingyangshengenin (8), methylconiferin (9), syringaresinol 4'-O-β-d-glucopyranoside (10), gagaminine (11), perlolyrine (12), (S)-1-(1'-hydroxyethyl)-β-carboline (13), 1-(β-carboline-1-yl)-3,4,5-trihydroxy-1-pentanone (14), 1-methoxycarbonyl-β-carboline (15), indolo[2,3-α]carbazole (16), 4-hydroxycinnamic acid methyl ester (17), and methyl 4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethyl] ferulate (18). The inhibitory activities of compound 1 and its N-methyl derivative (1a) against porcine respiratory and reproductive syndrome virus (PRRSV), human leukemic K562 cells, and human breast cancer MCF-7 cells were evaluated. Compounds 1 [50% inhibited concentration (IC(50)) = 12.5 ± 0.6 μM] and 1a (IC(50) = 15.7 ± 0.9 μM) were cytotoxic against K562 cells. Compound 1a also had a weak effect on PRRSV with an IC(50) value of 31.9 ± 6.0 μM [selectivity index (SI) = 18.7]. 23122140 Carotenoid compositions of coloured tomato cultivars and contribution to antioxidant activities and protection against H(2)O(2)-induced cell death in H9c2. The carotenoid compositions, antioxidant activities and the potential cardio-protective role of 13 tomato cultivars with distinct colour were studied. Colour coordinates were evaluated by colorimeter and the carotenoid compositions were analysed by UPLC. Red tomatoes had the highest total carotenoid contents (TCC) and antioxidant activities, followed by purple, orange, pink and yellow ones. The TCC were 120.5-278.0 μg/gDW, and the antioxidant activities were 21.32-40.07 μmolTE/gDW (PCL), 64.42-89.98% (DPPH) and 10.47-13.76 μmolTE/g DW (ORAC), respectively. The lipophilic extracts were also found to prevent cell death in a cell-based model system using cardiac H9c2 cells and H(2)O(2), via attenuation of the caspase-3 and matrix metalloproteinase-2 activities. The extracts of different tomatoes showed strong but different antioxidant activities. Roles of total and individual carotenoids in the antioxidant activities were studied and lycopene showed the highest correlation. Results of this study can be used to guide the development of new tomato cultivars and functional foods, and benefit the consumers. 23207477 Cobalt whole blood concentrations in healthy adult male volunteers following two-weeks of ingesting a cobalt supplement. Recently, there has been an increase in the marketing and sales of dietary supplements, energy drinks, and other consumer products that may contain relatively high concentrations of essential elements. Cobalt-containing supplements are readily available in the U.S. and have been marketed to consumers as energy enhancers. However, little information is available regarding cobalt (Co) body burden and steady-state blood concentrations following the intake of Co dietary supplements. We assessed Co whole blood concentrations in four healthy adult male volunteers who ingested a commercially available Co supplement (0.4 mg Co/day) for 15 or 16 days. Pre-supplementation blood Co concentrations were less than the reporting limit of 0.5 μg/L, consistent with background concentrations reported to range between 0.1 and 0.4 μg/L. The mean whole blood Co concentration in the volunteers after 15 or 16 days of dosing was 3.6 μg Co/L and ranged from 1.8 to 5.1 μg Co/L. The mean observed concentration in the study group was approximately 9-36 times greater than background concentrations. Further studies of Co whole blood concentrations following supplementation over longer time periods with additional monitoring of physiological parameters may provide useful information for evaluating the health of persons who take various doses of Co. 23580169 A XAS study of the luminescent Eu centers in thiosilicate phosphors. Due to its bright yellow-to-red emission, europium doped Ca2SiS4 is a very interesting material for phosphor converted light emitting diodes. The emission spectrum is highly dependent on the Eu concentration and can consist of more than one emission band. We combined X-ray absorption fine structure and photoluminescence measurements to analyze the structure of europium centers in (Ca,Eu)2SiS4 luminescent powders. This paper provides an explanation for the concentration dependency of the emission spectra. We find that at low dopant concentrations a large fraction of trivalent europium ions is unexpectedly present in the powders. These trivalent europium ions tend to form defect clusters in the luminescent powders. Furthermore we observe a preferential substitution of the europium ions over the two different substitutional Ca sites, which changes upon increasing the dopant concentration. At high dopant concentration, the powder crystallizes in the monoclinic Eu2SiS4 structure. Once more a preferential substitution of the europium ions is observed. Summarizing, the influence of the concentration on the emission spectrum is explained by a difference in preferential occupation of the Eu ions in the lattice. 23540713 Asymmetric Collapse in Biomimetic Complex Coacervates Revealed by Local Polymer and Water Dynamics. Complex coacervation is a phenomenon characterized by the association of oppositely charged polyelectrolytes into micrometer-scale liquid condensates. This process is the purported first step in the formation of underwater adhesives by sessile marine organisms, as well as the process harnessed for the formation of new synthetic and protein-based contemporary materials. Efforts to understand the physical nature of complex coacervates are important for developing robust adhesives, injectable materials, or novel drug delivery vehicles for biomedical applications; however, their internal fluidity necessitates the use of in situ characterization strategies of their local dynamic properties, capabilities not offered by conventional techniques such as X-ray scattering, microscopy, or bulk rheological measurements. Herein, we employ the novel magnetic resonance technique Overhauser dynamic nuclear polarization enhanced nuclear magnetic resonance (DNP), together with electron paramagnetic resonance (EPR) line shape analysis, to concurrently quantify local molecular and hydration dynamics, with species- and site-specificity. We observe striking differences in the structure and dynamics of the protein-based biomimetic complex coacervates from their synthetic analogues, which is an asymmetric collapse of the polyelectrolyte constituents. From this study we suggest charge heterogeneity within a given polyelectrolyte chain to be an important parameter by which the internal structure of complex coacervates may be tuned. Acquiring molecular-level insight to the internal structure and dynamics of dynamic polymer complexes in water through the in situ characterization of site- and species-specific local polymer and hydration dynamics should be a promising general approach that has not been widely employed for materials characterization. 23490078 The effect of a unique halide-stabilizing residue on the catalytic properties of haloalkane dehalogenase DatA from Agrobacterium tumefaciens C58. Haloalkane dehalogenases catalyze the hydrolysis of carbon-halogen bonds in various chlorinated, brominated and iodinated compounds. These enzymes have a conserved pair of halide-stabilizing residues that are important in substrate binding and stabilization of the transition state and the halide ion product via hydrogen bonding. In all previously known haloalkane dehalogenases, these residues are either a pair of tryptophans or a tryptophan-asparagine pair. The newly-isolated haloalkane dehalogenase DatA from Agrobacterium tumefaciens C58 (EC 3.8.1.5) possesses a unique halide-stabilizing tyrosine residue, Y109, in place of the conventional tryptophan. A variant of DatA with the Y109W mutation was created and the effects of this mutation on the structure and catalytic properties of the enzyme were studied using spectroscopy and pre-steady-state kinetic experiments. Quantum mechanical and molecular dynamics calculations were used to obtain a detailed analysis of the hydrogen-bonding patterns within the active sites of the wild-type and the mutant, as well as of the stabilization of the ligands as the reaction proceeds. Fluorescence quenching experiments suggested that replacing the tyrosine with tryptophan improves halide binding by 3.7-fold, presumably as a result of the introduction of an additional hydrogen bond. Kinetic analysis revealed that the mutation affected the substrate specificity of the enzyme and reduced its K0.5 for selected halogenated substrates by a factor of 2-4, without impacting the rate-determining hydrolytic step. We conclude that DatA is the first natural haloalkane dehalogenase that stabilizes its substrate in the active site using only a single hydrogen bond, which is a new paradigm in catalysis by this enzyme family. 22424117 Antioxidant and lipoxygenase inhibiting new iridoid glucosides from Caryopteris odorata. The phytochemical investigation of the ethylacetate-soluble fraction of Caryopteris odorata (Ham. ex Roxb.) led to the isolation of four new iridoid glucosides (1-4): 8-O-trans-cinnamoyl caryoptoside (1), 8-O-trans-cinnamoyl shanzhiside methylester (2), 8-O-trans-cinnamoyl mussaenoside (3) and 8-O-cafeoyl massenoside (4). The structures of these compounds were determined by FAB-MS, IR, 1D and 2D-NMR spectroscopy and by comparing with the published data of the closely related compounds. The antioxidant potential of the isolated iridoids (1-4) was evaluated relative to conventionally used standards and these molecules exhibited good antioxidant potential. Moreover, their inhibitory potential was also screened against three enzymes, namely acetyl cholinesterase, butyrylcholinesterase and lipoxygenase. These iridoid glucosides were found to be inactive against acetyl and butyrylcholinesterases but active against lipoxygenase. 23530018 Chalcogenopyrylium Dyes as Differential Modulators of Organic Anion Transport by MRP1, MRP2 and MRP4. Multidrug resistance proteins (MRPs) mediate the ATP-dependent efflux of structurally diverse compounds, including anticancer drugs and physiological organic anions. Five classes of chalcogenopyrylium dyes (CGPs) were examined for their ability to modulate transport of [(3)H]estradiol glucuronide (E217βG) (a prototypical MRP substrate) into MRP-enriched inside-out membrane vesicles. Additionally, some CGPs were tested in intact transfected cells using a calcein efflux assay. Sixteen of 34 CGPs inhibited MRP1-mediated E217βG uptake by >50% (IC50's 0.7-7.6 μM). Of 9 CGPs with IC50's ≤2 μM, two belonged to Class I, two to Class III and five to Class V. When tested in the intact cells, only 4 of 16 CGPs (at 10 μM) inhibited MRP1-mediated calcein efflux by >50% (III-1, V-3, -4, -6) while a fifth (I-5) inhibited efflux by just 23%. These five CGPs also inhibited [(3)H]E217βG uptake by MRP4. In contrast, their effects on MRP2 varied with two (V-4, V-6) inhibiting E217βG transport (IC50's 2.0, 9.2 μM), two (V-3, III-1) stimulating transport (>2-fold), while CGP I-5 had no effect. Strikingly, although V-3 and V-4 had opposite effects on MRP2 activity, they are structurally identical except for their chalcogen atom (Se versus Te). This study is the first to identify Class V CGPs with their distinctive methine or trimethine linkage between two disubstituted pyrylium moieties as a particularly potent class of MRP modulators and also show that within this core structure, differences in the electronegativity associated with a chalcogen atom can be the sole determinant of whether a compound will stimulate or inhibit MRP2. 23639430 When a good taste turns bad: Neural mechanisms underlying the emergence of negative affect and associated natural reward devaluation by cocaine. An important feature of cocaine addiction in humans is the emergence of negative affect (e.g., dysphoria, irritability, anhedonia), postulated to play a key role in craving and relapse. Indeed, the DSM-IV recognizes that social, occupational and/or recreational activities become reduced as a consequence of repeated drug use where previously rewarding experiences (e.g., food, job, family) become devalued as the addict continues to seek and use drug despite serious negative consequences. Here, research in the Carelli laboratory is reviewed that examined neurobiological mechanisms that may underlie these processes using a novel animal model. Oromotor responses (taste reactivity) were examined as rats learned that intraoral infusion of a sweet (e.g., saccharin) predicts impending but delayed access to cocaine self-administration. We showed that rats exhibit aversive taste reactivity (i.e., gapes/rejection responses) during infusion of the sweet paired with impending cocaine, similar to aversive responses observed during infusion of quinine, a bitter tastant. Critically, the expression of this pronounced aversion to the sweet predicted the subsequent motivation to self-administer cocaine. Electrophysiology studies show that this shift in palatability corresponds to an alteration in nucleus accumbens (NAc) cell firing; neurons that previously responded with inhibition during infusion of the palatable sweet shifted to excitatory activity during infusion of the cocaine-devalued tastant. This excitatory response profile is typically observed during infusion of quinine, indicating that the once palatable sweet becomes aversive following its association with impending but delayed cocaine, and NAc neurons encode this aversive state. We also review electrochemical studies showing a shift (from increase to decrease) in rapid NAc dopamine release during infusion of the cocaine-paired tastant as the aversive state developed, again, resulting in responses similar to quinine infusion. Collectively, our findings suggest that cocaine-conditioned cues elicit a cocaine-need state that is aversive, is encoded by a distinct subset of NAc neurons and rapid dopamine signaling, and promotes cocaine-seeking behavior. Finally, we present data showing that experimentally induced abstinence (30 days) exacerbates this natural reward devaluation by cocaine, and this effect is correlated with a greater motivation to lever press during extinction. Dissecting the neural mechanisms underlying these detrimental consequences of addiction is critical since it may lead to novel treatments that ameliorate negative affective states associated with drug use and decrease the drive (craving) for the drug. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. 23201442 Raloxifene affects fatty acid oxidation in livers from ovariectomized rats by acting as a pro-oxidant agent. Estrogen deficiency accelerates the development of several disorders including visceral obesity and hepatic steatosis. The predisposing factors can be exacerbated by drugs that affect hepatic lipid metabolism. The aim of the present work was to determine if raloxifene, a selective estrogen receptor modulator (SERM) used extensively by postmenopausal women, affects hepatic fatty acid oxidation pathways. Fatty acids oxidation was measured in the livers, mitochondria and peroxisomes of ovariectomized (OVX) rats. Mitochondrial and peroxisomal β-oxidation was inhibited by raloxifene at a concentration range of 2.5-25 μM. In perfused livers, raloxifene reduced the ketogenesis from endogenous and exogenous fatty acids and increased the β-hydroxybutyrate/acetoacetate ratio. An increase in ¹⁴CO₂ production without a parallel increase in the oxygen consumption indicated that raloxifene caused a diversion of NADH from the mitochondrial respiratory chain to another oxidative reaction. It was found that raloxifene has a strong ability to react with H₂O₂ in the presence of peroxidase. It is likely that the generation of phenoxyl radical derivatives of raloxifene in intact livers led to the co-oxidation of NADH and a shift of the cellular redox state to an oxidised condition. This change can perturb other important liver metabolic processes dependent on cellular NADH/NAD⁺ ratio. 22780426 New long-chain aliphatic compounds from Peperomia dindygulensis. Three long-chain aliphatic compounds, including one new polyketide derivative, dindygulerione C (1), one new octaketide derivative, dindygulerione D (2) and one new acylresorcinol derivative dindyguleranone (3) were isolated from the whole plant of the Chinese anticancer folk medicine Peperomia dindygulensis Miq. (Piperaceae). Dindygulerione C is an unprecedented example of a N-containing polyketide. The chemical structures and configurations of 1-3 were elucidated as (-)-(4S)-2-[(Z)-1'-(6″,7″-dihydroxyphenethyl-amino)octadec-11'-enylidene]-4-hydroxycyclohexane-1,3-dione (1), (+)-2-heptadecyl-4-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (2) and 2-(1,3-dihydroxyphenyl)-octacosan-1'-one (3), respectively, by comparing with the literature data and extensive spectroscopic methods, including 2-D NMR and circular dichroism spectroscopic analysis. The cytotoxicity of 1-3 was evaluated against Hep3B and HepG2 liver cancer cell lines. 23116112 Stem cell lineage commitment by electrical fields and the potential application in drug discovery. Stem cells may be applied to improve the efficiency of drug discovery, but more effective protocols are first required to control the differentiation. Recent researches have revealed that physical stimulation is an important avenue for stem cell lineage commitment, such as electrical field stimulation. Here, we review literatures about stem cell differentiation by electrical field stimulation. Various forms of electrical fields with soluble induction factors have shown to produce a synergistic effect in order to enhance the osteogenic commitment. Moreover, electrical field stimulation alone shows marked effects of pre-commitment to cardiomyocyte and neuron. However, the related precise molecular regulatory mechanism is unclear. As cardiomyocyte and neuron are crucial factors in drug development process, electrical field stimulation may be proposed as an effect important for stem cell differentiation, exhibiting a potential application in drug discovery. 23497866 Application of response surface methodology to optimise extraction of flavonoids from fructus sophorae. Response surface methodology (RSM) based on a central composite design (CCD) was applied to optimise the extraction conditions for flavonoids from fructus sophorae with advantages in terms of resisting flavonoids during the whole process and maximising of extraction yield. Three aglycon forms of the flavonoids, namely, quercetin, kaempferol and isorhamnetin were quantified by high-performance liquid chromatography with ultraviolet detection (HPLC-UV) to estimate extraction yield. The combined effects of independent variables were studied and the optimal extraction conditions were obtained as ethanol concentration, 74.47%; solid-liquid ratio, 17.99 ml/g; temperature, 89.13°C; and extraction time, 2.10h. The reliability of the method was confirmed by recovery experiments, performed under optimal conditions. Recoveries indicated that flavonoids resisted the extraction conditions. The experimental extraction yield under optimal conditions was found to be 10.459%, which was well matched with the predicted values of 10.461%. 23561137 Anti-inflammatory and anticancer activities of extracts and compounds from the mushroom Inonotus obliquus. Mushroom Inonotus obliquus (I. obliquus) has been used as functional food and traditional Chinese herbs for long time. An efficient method for bioassay-guided preparative isolation was used for identifying the anti-inflammatory and anticancer constituents in I. obliquus. The petroleum ether and ethyl acetate fractions were found to have significant inhibition effects on NO production and NF-κB luciferase activity in macrophage RAW 264.7 cells and cytotoxicity against human prostatic carcinoma cell PC3 and breast carcinoma cell MDA-MB-231. Six main constituents were isolated from these two fractions and they were identified as lanosterol (1), 3β-hydroxy-8,24-dien-21-al (2), ergosterol (3), inotodiol (4), ergosterol peroxide (5) and trametenolic acid (6). Compound ergosterol, ergosterol peroxide and trametenolic acid showed anti-inflammatory activities and ergosterol peroxide and trametenolic acid showed obviously cytotoxicity on human prostatic carcinoma cell PC3 and breast carcinoma MDA-MB-231 cell. The results obtained in this work might contribute to understanding the biological activity of mushroom I. obliquus for food and drug application. 23552398 Modeling CO2 reduction on Pt(111). Density functional theory was used to model the electrochemical reduction of CO2 on Pt(111) with an explicit solvation layer and the presence of extra hydrogen atoms to represent a negatively charged electrode. We focused on the electronic energy barriers for the first four lowest energy proton-electron transfer steps for reducing CO2 on Pt(111) beginning with adsorbed *CO2 and continuing with *COOH, *CO + H2O, *COH, and ending with *C + H2O. We find that simple elementary steps in which a proton is transferred to an adsorbate (such as the protonation of *CO to *COH) have small barriers on the order of 0.1 eV. Elementary steps in which a proton is transferred and a C-O bond is simultaneously cleaved show barriers on the order of 0.5 eV. All barriers calculated for these steps show no sign of being insurmountable at room temperature. To explain why these barriers are so small, we analyze the charge density and the density of states plots to see that first, the electron transfer is decoupled from the proton transfer so that in the initial state, the surface and adsorbate are already charged up and can easily accept the proton from solution. Also, we see that in the cases where barriers are on the order of 0.1 eV, electron density in the initial state localizes on the oxygen end of the adsorbate, while electron density is more spread out on the surface for initial states of the C-O bond cleaving elementary steps. 23458422 Thermoresponsive Bacterial Cellulose Whisker/Poly(NIPAM-co-BMA) Nanogel Complexes: Synthesis, Characterization, and Biological Evaluation. Dispersions of poly(N-isopropylacrylamide-co-butyl methacrylate) (PNB) nanogels are known to exhibit reversible thermosensitive sol-gel phase behavior and can consequently be used in a wide range of biomedical applications. However, some dissatisfactory mechanical properties of PNB nanogels can limit their applications. In this paper, bacterial cellulose (BC) whiskers were first prepared by sulfuric acid hydrolysis and then nanosized by high-pressure homogenization for subsequent use in the preparation of BC whisker/PNB nanogel complexes (designated as BC/PNB). The mechanical properties of PNB was successfully enhanced, resulting in good biosafety. The BC/PNB nanogel dispersions exhibited phase transitions from swollen gel to shrunken gel with increasing temperature. In addition, differential scanning calorimetry (DSC) data showed that the thermosensitivity of PNB nanogels was retained. Rheological tests also indicated that BC/PNB nanogel complexes had stronger gel strengths when compared with PNB nanogels. The concentrated dispersions showed shear thinning behavior and improved toughness, both of which can play a key role in the medical applications of nanogel complexes. Furthermore, the BC/PNB nanogel complexes were noncytotoxic according to cytotoxicity and hemolysis tests. Concentrated BC/PNB nanogel dispersion displayed gel a forming capacity in situ by catheter injection, which indicates potential for a wide range of medical applications. 22304302 Three new steroidal glycosides from roots of Reineckia carnea. Two new spirostanols and a new furostanol, reinocarnoside A (1), B (2) and C (3), were isolated from the roots of Reineckia carnea, together with two known compounds, (25S)-1β,3β,4β-trihydroxyspirostan-5β-yl-O-β-D-glucopyranoside (4), kitigenin-5β-O-β-D-glucopyranoside (5). The structures of three new compounds were elucidated by spectroscopic methods including 1-D NMR, 2-D NMR and MS spectrums, and their anticancer activities were evaluated by MTT method. 23327360 Physicochemical characterization of phosphopeptide/titanium dioxide interactions employing the quartz crystal microbalance technique. The rapidly growing field of phosphoproteomics has led to a strong demand for procedures enabling fast and reliable isolation and enrichment of phosphorylated proteins and peptides. During the past decade, several novel phosphopeptide enrichment methods based on the affinity of phosphoryl groups for titanium dioxide (TiO(2)) have been developed and tested. The ultimate goal of obtaining comprehensive phosphoproteomes has, however, been found difficult to achieve and the obtained results often vary, dependent on the enrichment method and protocol used. In the present study, the physical chemistry of the phosphopeptide binding to TiO(2) is investigated by means of measurements using a quartz crystal microbalance with dissipation monitoring (QCM-D). Special emphasis is put on the effect of the degree of phosphorylation of the phosphopeptide, the impact of the primary amino acid structure, and the role of electrostatic interactions. The results show that, in general, adsorption of phosphopeptides follows the Langmuir model and that the affinity for the TiO(2) surface increases in a nonlinear fashion with increasing degree of phosphorylation. An exception was detected, however, where positive cooperativity between the peptides existed and the Langmuir model no longer applied. The source behind the cooperativity could be traced back to the primary amino acid structure and, more specifically, the presence of positively charged amino acids in positions that enable electrostatic interaction with phosphoryl groups on neighboring peptides. Regardless of the net peptide charge, the TiO(2)-phosphopeptide interaction was for all phosphopeptides investigated found to be mainly of electrostatic origin. This study highlights and explains some of the most common problems with the TiO(2)-based enrichment methods used today. 22940283 Relation between dynamics, activity and thermal stability within the cholinesterase family. Incoherent neutron scattering is one of the most powerful tools for studying dynamics in biological matter. Using the cold neutron backscattering spectrometer IN16 at the Institut Laue Langevin (ILL, Grenoble, France), temperature dependence of cholinesterases' dynamics (human butyrylcholinesterase from plasma: hBChE; recombinant human acetylcholinesterase: hAChE and recombinant mouse acetylcholinesterase: mAChE) was examined using elastic incoherent neutron scattering (EINS). The dynamics was characterized by the averaged atomic mean square displacement (MSD), associated with the sample flexibility at a given temperature. We found MSD values of hAChE above the dynamical transition temperature (around 200K) larger than for mAChE and hBChE, implying that hAChE is more flexible than the other ChEs. Activation energies for thermodynamical transition were extracted through the frequency window model (FWM) (Becker et al. 2004) [1] and turned out to increase from hBChE to mAChE and finally to hAChE, inversely to the MSDs relations. Between 280 and 316K, catalytic studies of these enzymes were carried out using thiocholine esters: at the same temperature, the hAChE activity was systematically higher than the mAChE or hBChE ones. Our results thus suggest a strong correlation between dynamics and activity within the ChE family. We also studied and compared the ChEs thermal inactivation kinetics. Here, no direct correlation with the dynamics was observed, thus suggesting that relations between enzyme dynamics and catalytic stability are more complex. Finally, the possible relation between flexibility and protein ability to grow in crystals is discussed. 23350621 Leptin levels and adipose tissue percentage in adolescents with polycystic ovary syndrome. The main purpose of the research is to compare serum leptin (Lep) levels and adipose tissue percentage in adolescents diagnosed with polycystic ovary syndrome (PCOS) and those in healthy subjects. The results showed a greater percentage of patients with increased adipose tissue and significantly higher serum Lep levels in the PCOS group compared to the healthy controls. It was proved that there is a correlation between Lep and body mass index, body adipose tissue, waist circumference and HOMA index. PCOS in adolescents is a condition related to highly predominant overweight and obesity with exceeding level of body adipose tissue and higher serum Lep levels compared to healthy age-matched controls. 23294895 Aspirin and aspirin resistance in coronary artery disease. Aspirin is still the mainstay of antiplatelet therapy in the secondary prevention of coronary artery disease. However certain patients do not benefit from the antithrombotic effects of aspirin. The phenomenon of so-called aspirin resistance can be considered from the clinical and laboratory perspective. A variety of methods have emerged for the laboratory diagnosis of aspirin resistance. None of them is considered ideal as they provide conflicting information with significant inter-individual variability and weak correlation between them. With the mechanisms of aspirin resistance not fully understood and the phenomenon commonly observed in individuals with poor compliance, the existence of aspirin resistance has been challenged. The aim of this review is to present recent data on the impact of aspirin resistance in primary and secondary prevention of coronary artery disease. 23174519 An unusual marine envenomation following a rope contact: a report on nine cases of dermatitis caused by Pennaria disticha. We would like to present the clinical course of nine patients who had an acute, painful dermatitis following contact with a rope used as a swimming area liner in the sea. The macroscopic and microscopic analysis of the fouling on the rope retrospectively, revealed Pennaria disticha as the causative organism. To our knowledge, there is no previous report on P. disticha envenomation in medical literature. P. disticha is a benthic hydrozoa belonging to Cnidaria phylum. Cnidaria are well known for their envenomation with their venomous organelle, "cnidocyst". The contact with cnidaria can result in a wide range of cytotoxic or anaphylactic reactions. While there is a large body of data in the literature from studies at molecular and cellular levels, there is limited data about the in vivo effects of cnidaria toxins. We think the clinical aspects of the dermatologic reactions caused by P. disticha and the diagnostic work-up to reveal the contamination on this unusual medium would be of interest to the readers. 23633532 Regulation of Lipid Metabolism by Glucocorticoids and 11β-HSD1 in Skeletal Muscle. The prevalence of insulin resistance and type 2 diabetes mellitus are rising dramatically and as a consequence there is an urgent need to understand the pathogenesis underpinning these conditions to develop new and more efficacious treatments.We have tested the hypothesis that glucocorticoid-mediated changes in insulin sensitivity may be associated with changes in lipid flux. Furthermore, pre-receptor modulation of glucocorticoid availability by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may represent a critical regulatory step.Dexamethasone decreased lipogenesis in both murine C2C12 and human LHC-NM2 myotubes. Inactivating p-Ser-79/218 of acetyl-CoA carboxylase 1/2 (ACC1/2) and activating p-Thr-172 of AMP-activated protein kinase (AMPK) were both increased following dexamethasone treatment in C2C12 myotubes. By contrast, dexamethasone increased β-oxidation. Selective 11β-HSD1 inhibition blocked the 11-dehydrocorticosterone (11DHC)-mediated decrease in lipogenic, and increase in lipolytic gene expression. Lipogenic gene expression was decreased, whilst lipolytic and β-oxidative genes expression increased in corticosterone (CORT) and 11DHC treated wild-type mice, and CORT (but not 11DHC) treated 11β-HSD1(-/-) mice. Furthermore, CORT and 11DHC treated wild-type mice, and CORT (but not 11DHC) treated 11β-HSD1(-/-) mice had increased p-Ser-79/218 ACC1/2, p-Thr-172 AMPK and intramyocellular diacylglyderide content.In summary, we have shown that glucocorticoids have potent actions upon intramyocellular lipid homeostasis by decreasing lipid storage, increasing lipid mobilisation and utilisation and increasing diacylglyderide content. It is plausible that dysregulated intramyocellular lipid metabolism may underpin GC-induced insulin resistance of skeletal muscle. 23444429 Defective DNA damage response and repair in liver cells expressing hepatitis B virus surface antigen. Hepatitis B virus (HBV) is implicated in liver cancer. The aim of this study was to find out whether HBV or its components [HBV surface antigen (HBsAg), HBV core protein (HBc), and HBV X protein (HBx)] could interfere with the host DNA damage response and repair pathway. The full HBV genome or individual HBV open-reading frame (ORF) was introduced into HepG2 cells to examine the effect on host genomic stability, DNA repair efficacy in response to double-strand DNA damage, and DNA damage-induced cell death. Responses to apoptosis induction in the HBV ORF-transfected HepG2 cells were also compared with those in HBV-positive and HBV-negative human hepatocellular carcinoma (HCC) cells. In the absence of HBV replication, accumulation of HBsAg in liver cells without other HBV proteins enhanced DNA repair protein and tumor suppressor promyelocytic leukemia (PML) degradation, which resulted in resistance to apoptosis induction and deficient double-strand DNA repair. However, HBsAg-positive cells exhibited increased cell death with exposure to the poly(ADP-ribose) polymerase inhibitor that blocks single-strand DNA repair. These results indicate that suppression of PML by HBsAg disrupts cellular mechanisms that respond to double-strand DNA damage for DNA repair or apoptosis induction, which may facilitate hepatocarcinogenesis and open up a synthetic lethality strategy for HBsAg-positive HCC treatment.-Chung, Y.-L. Defective DNA damage response and repair in liver cells expressing hepatitis B virus surface antigen. 23327532 Cooperative effects for CYP2E1 differ between styrene and its metabolites. Abstract 1. Cooperative interactions are frequently observed in the metabolism of drugs and pollutants by cytochrome P450s; nevertheless, the molecular determinants for cooperativity remain elusive. Previously, we demonstrated that steady-state styrene metabolism by CYP2E1 exhibits positive cooperativity. 2. We hypothesized that styrene metabolites have lower affinity than styrene toward CYP2E1 and limited ability to induce cooperative effects during metabolism. To test the hypothesis, we determined the potency and mechanism of inhibition for styrene and its metabolites toward oxidation of 4-nitrophenol using CYP2E1 Supersomes® and human liver microsomes. 3. Styrene inhibited the reaction through a mixed cooperative mechanism with high affinity for the catalytic site (67 µM) and lower affinity for the cooperative site (1100 µM), while increasing substrate turnover at high concentrations. Styrene oxide and 4-vinylphenol possessed similar affinity for CYP2E1. Styrene oxide behaved cooperatively like styrene, but 4-vinylphenol decreased turnover at high concentrations. Styrene glycol was a very poor competitive inhibitor. Among all compounds, there was a positive correlation with binding and hydrophobicity. 4. Taken together, these findings for CYP2E1 further validate contributions of cooperative mechanisms to metabolic processes, demonstrate the role of molecular structure on those mechanisms and underscore the potential for heterotropic cooperative effects between different compounds. 23633651 Prevalence of MAGI in patients with type 2 diabetes mellitus. Background. MAGI is an acronym that identifies the "male accessory gland inflammations/infections", a potential cause of male infertility. Type 2 diabetes mellitus (DM2) prevalence is going to increase among men of reproductive age. Due to the high prevalence of these two conditions, we could suppose that they might appear together in the same patient. Aim. To evaluate MAGI prevalence in patients with DM2 in fertile age. Subjects and Methods. A cross-sectional study carried out on patients with DM2 of fertile age. All patients underwent andrological evaluation for the identification of conventional MAGI diagnostic criteria. Results. DM2 patients showed a frequency of MAGI about 43%, significantly lower (p<0.05) than in infertile patients of the same age without diabetes, which showed a MAGI overall frequency of 61%. Among examined diabetic patients the prevalence of MAGI did not significantly differ between patients attending for diabetes care problems (glycemic control) and patients with andrological disorders. Finally, no significant difference in seminal inflammatory signs frequency was detected between patients with DM2 and infertile patients without diabetes. Finally, the correlation analysis showed a significant direct correlation between duration of diabetes and glycemic control with the prevalence of MAGI. Conclusion. MAGI prevalence in DM2 is lower than the one detected in age matched infertile non-diabetic patients, however, as in infertile patients, there is a high frequency of seminal inflammatory signs. Moreover, the observed prevalence among diabetic patients with diabetes care problems and diabetic patients with andrological problems is not statistically different. 23239825 Differentiation of opioid drug effects by hierarchical multi-site phosphorylation. Differences in the ability of opioid drugs to promote regulated endocytosis of μ-opioid receptors are related to their tendency to produce drug tolerance and dependence. Here we show that drug-specific differences in receptor internalization are determined by a conserved, 10-residue sequence in the receptor's carboxyl-terminal cytoplasmic tail. Diverse opioids induce receptor phosphorylation at serine (S)375, present in the middle of this sequence, but opioids differ markedly in their ability to drive higher-order phosphorylation on flanking residues [threonine (T)370, T376, and T379]. Multi-phosphorylation is required for the endocytosis-promoting activity of this sequence and occurs both sequentially and hierarchically, with S375 representing the initiating site. Higher-order phosphorylation involving T370, T376, and T379 specifically requires GRK2/3 isoforms, and the same sequence controls opioid receptor internalization in neurons. These results reveal a biochemical mechanism differentiating the endocytic activity of opioid drugs. 23578634 Effect of salt solutions applied during wheat conditioning on lipase activity and lipid stability of whole wheat flour. Lipolytic activity in whole wheat flour (WWF) is largely responsible for the loss in baking quality during storage. Metal ions affect the activity of seed lipases; however, no previous studies have applied this information to WWF in a way that reduces lipase activity, is practical for commercial manufacture, and uses common food ingredients. NaCl, KCl, Ca-propionate, or FeNa-ethylenediaminetetraacetic acid (FeNa-EDTA) were applied to hard red winter (HRW) and hard white spring (HWS) wheats during conditioning as aqueous solutions at concentrations that would be acceptable in baked goods. Salts affected lipase activity to different degrees depending on the type of wheat used. Inhibition was greater in HRW compared with HWS WWF, probably due to higher lipase activity in HRW wheat. In HRW WWF, 1% NaCl (flour weight) reduced hydrolytic and oxidative rancidity and resulted in higher loaf volume and lower firmness than untreated WWF after 24weeks of storage. 23411248 Antioxidant and antimicrobial activity of xylan-chitooligomer-zinc complex. In this study, a ternary complex based on natural polysaccharides was explored as a novel food preservative. Chitooligomer was obtained by enzyme hydrolysis of chitosan with immobilised neutral protease, and the degree of polymerisation (DP) was mainly from 2 to 5. Chitooligomer-zinc complex (CGZC) was first produced and then co-heated with xylan to prepare xylan-chitooligomer-zinc complex (XCGZC). XCGZC showed higher antioxidant and antibacterial activity than chitooligomer, chitooligomer-zinc and xylan-chitooligomer. The IC(50) of XCGZC was 5.37 mg/mL, which was equal to the antioxidant ability of 3.28 mg/mL BHT. The diameter of the inhibition zone for XCGZC against Escherichia coli and Staphylococcus aureus was 17.2 ± 0.4 and 30.3 ± 0.6mm vs. control of 6.0mm. Besides, XCGZC had excellent antibacterial activity against Bacillus subtilis, Salmonella typhimurium, Bacillus megaterium. Therefore, XCGZC can be used as a novel promising preservative with antibacterial and antioxidant properties in the food industry. 23611507 Links between obesity, diabetes and ethnic disparities in breast cancer among Hispanic populations. Breast cancer is the most prevalent malignancy in women worldwide and is a growing concern due to rising incidence and ongoing ethnic disparities in both incidence and mortality. A number of factors likely contribute to these trends including rising rates of obesity and diabetes across the globe and differences in genetic predisposition. Here, we emphasize Hispanic populations and summarize what is currently known about obesity, diabetes and individual genetic predisposition as they relate to ethnic disparities in breast cancer incidence and mortality. In addition, we discuss potential contributions to breast cancer aetiology from molecular mechanisms associated with obesity and diabetes including dyslipidemia, hyperglycaemia, hyperinsulinaemia, endocrine dysfunction and inflammation. We propose that unique differences in diet and lifestyle coupled with individual genetic predisposition and endocrine/immune dysfunction explain most of the ethnic disparities seen in breast cancer incidence and mortality. 23194540 Method development and validation for boscalid in blueberries by solid-phase microextraction gas chromatography, and their degradation kinetics. Analytical method for the residues of boscalid in blueberries was developed. Fungicide residues were determined by solid-phase microextraction (SPME) coupled to gas chromatography with micro-electron capture (μ-ECD) detector. The effect of pH values and fiber coatings were studied. The SPME fiber coating selected was 100 μm PDMS. The method is selective with adequate precision and high accuracy and sensitivity. Recoveries ranged within the 98-104% range, and detection and quantification limits were 1.33 and 4.42 μg/kg, respectively. Statistical parameters indicated the occurrence of matrix effect; consequently calibration was performed on spiked samples. Degradation of boscalid was studied in a blueberry field located in Concordia, Argentina, with fruits from Emerald and Jewel varieties. The degradation of boscalid in both blueberry varieties studied followed a first order rate kinetics and the half-life for boscalid was 5.3 and 6.3 days for Emerald and Jewel cultivars, respectively. 23359520 Pycnogenol® Supplementation Improves Health Risk Factors in Subjects with Metabolic Syndrome. This open, controlled study evaluated the effects of 6 month supplementation with Pycnogenol® maritime pine bark extract on health risk factors in subjects with metabolic syndrome. Pycnogenol® was used with the aim of improving risk factors associated with metabolic syndrome, central obesity, elevated triglycerides (TG), low HDL cholesterol, high blood pressure and fasting blood glucose. Sixty-four subjects (range 45-55 years) presenting with all five risk factors of metabolic syndrome were included, and Pycnogenol® was administered for 6 months. A group of 66 equivalent subjects were followed up as controls. In the 6-month study Pycnogenol® supplementation 150 mg/day decreased waist circumference, TG levels, blood pressure and increased the HDL cholesterol levels in subjects. Pycnogenol lowered fasting glucose from baseline 123 ± 8.6 mg/dl to 106.4 ± 5.3 after 3 months and to 105.3 ± 2.5 at the end of the study (p < 0.05 vs controls). Men's waist circumference decreased with Pycnogenol from 106.2 ± 2.2 cm to 98.8 ± 2.3 cm and to 98.3 ± 2.1 after 3 and 6 months. Women's waist decreased from 90.9 ± 1.6 cm to 84.6 ± 2.1 cm and to 83.6 ± 2.2 cm after 3 and 6 months. Both genders waist circumference reduction was significant as compared to controls at both time points. In addition, plasma free radicals decrease in the Pycnogenol group was more effective than in the control group (-34.6%; p < 0.05). In conclusion, this study indicates a role for Pycnogenol® for improving health risk factors in subjects with metabolic syndrome. Copyright © 2013 John Wiley & Sons, Ltd. 23361517 Structural and up-conversion properties of Er3+ and Yb3+ co-doped Y2Ti2O7 phosphors. Y(2)Ti(2)O(7) (YTO) and Er(3+)/Yb(3+) co-doped Y(2)Ti(2)O(7) (EYYTO) phosphors have been prepared by solid-state reaction method. Structures of YTO and EYYTO phosphors are identified as face centered cubic pyrochlores. Up-conversion emission spectra of EYYTO under 976 nm excitation is studied, which revealed three prominent emission lines at ~524, 548 and 661 nm originating from (2)H(11/2)→(4)I(15/2), (4)S(3/2)→(4)I(15/2) and (4)F(9/2)→(4)I(15/2) electronic transitions of Er(3+) ion, respectively in green and red regions. The power dependence study suggests that these bands arise due to two photon absorption. The monodispersed laser ablated colloidal solution of EYYTO shows strong red and green emissions on excitation with 976 nm laser. The variation of luminescence intensity at different laser excitation powers is observed and thus a color can be tuned. The photoluminescence lifetime of green band at 548 nm ((4)S(3/2) level) has been found to be ~446 μs. 22628265 Ethanol extract of Magnolia officinalis prevents lipopolysaccharide-induced memory deficiency via its antineuroinflammatory and antiamyloidogenic effects. Magnolia bark contains several compounds such as magnolol, honokiol, 4-O-methylhonokiol, obovatol, and other neolignan compounds. These compounds have been reported to have various beneficial effects in various diseases. There is sufficient possibility that ethanol extract of Magnolia officinalis is more effective in amyloidogenesis via synergism of these ingredients. Neuroinflammation has been known to play a critical role in the pathogenesis of Alzheimer's disease (AD). We investigated whether the ethanol extract of M. officinalis (10 mg/ kg in 0.05% ethanol) prevents memory dysfunction and amyloidogenesis in AD mouse model by intraperitoneal lipopolysaccharide (LPS, 250 µg/ kg/day for seven times) injection. We found that ethanol extract of M. officinalis prevented LPS-induced memory deficiency as well as inhibited the LPS-induced elevation of inflammatory proteins, such as inducible nitric oxide synthase and cyclooxygenase 2, and activation of astrocytes and microglia. In particular, administration of M. officinalis ethanol extract inhibited LPS-induced amyloidogenesis, which resulted in the inhibition of amyloid precursor protein, beta-site amyloid-precursor-protein-cleaving enzyme 1 and C99. Thus, this study shows that ethanol extract of M. officinalis prevents LPS-induced memory impairment as well as amyloidogenesis via inhibition of neuroinflammation and suggests that ethanol extract of M. officinalis might be a useful intervention for neuroinflammation-associated diseases such as AD. Copyright © 2012 John Wiley & Sons, Ltd. 23404739 Optimization of marine triterpene sipholenols as inhibitors of breast cancer migration and invasion. Sipholenol A, a sipholane triterpene isolated from the Red Sea sponge Callyspongia siphonella, has the ability to reverse multidrug resistance in cancer cells that overexpress P-glycoprotein (P-gp). Here, the antimigratory activity of sipholenol A and analogues are reported against the highly metastatic human breast cancer cell line MDA-MB-231 in a wound-healing assay. Sipholenol A and sipholenone A were semisynthetically optimized using ligand-based strategies to generate structurally diverse analogues in an attempt to maximize their antimigratory activity. A total of 22 semisynthetic ester, ether, oxime, and carbamate analogues were generated and identified by extensive one- and two-dimensional NMR spectroscopy and high-resolution mass spectrometry analyses. Sipholenol A 4β-4-chlorobenzoate and 19,20-anhydrosipholenol A 4β-4-chlorobenzoate esters were the most potent of all tested analogues in the wound-healing assay, with IC(50) values of 5.3 and 5.9 μM, respectively. Generally, ester derivatives showed better antimigratory activities than the carbamate analogues. A KINOMEscan of 19,20-anhydrosipholenol A 4β-benzoate ester against 451 human protein kinases identified protein tyrosine kinase 6 (PTK6) as a potential target. In breast tumor cells, PTK6 promotes growth factor signaling and migration, and as such the semisynthetic sipholanes were evaluated for their ability to inhibit PTK6 phosphorylation in vitro. The two analogues with the highest antimigratory activities, sipholenol A 4β-4-chlorobenzoate and 19,20-anhydrosipholenol A 4β-4-chlorobenzoate esters, also exhibited the most potent inhibition of PTK6 phosphorylation inhibition. None of the compounds exhibited cytotoxicity in a normal epithelial breast cell line. These derivatives were evaluated in an in vitro invasion assay, where sipholenol A succinate potently inhibited MDA-MB-231 cell invasion at 10 μM. These results highlight sipholane triterpenoids as novel antimigratory marine natural products with potential for further development as agents for the control of metastatic breast malignancies. 23432151 Five new secondary metabolites from Monascus purpureus-fermented Hordeum vulgare and Sorghum bicolor. Long grains of Hordeum vulgare and Sorghum bicolor were individually fermented with Monascus purpureus MTCC 369 under solid state fermentation. The aqueous extract of Monascus which fermented H. vulgare and S. bicolor was found to contain five different new metabolites. Silica gel column chromatography of the aqueous extract with a linear gradient of ethyl acetate, acetonitrile and carbon tetrachloride (v/v) yielded five new metabolites named benzopranyl capriate (9H-1-isoprenyl-benzopyran-5-isopropanoic acid-6-ol-6-n-decanoate), shorghumoic acid (n-octadec-8,11-dien-7α-ol-1-oic acid) and sorghumflavin A (2-n-butyloxo-6-β-hydroxy-7-β-isoprenyl ankaflavin) from Monascus-fermented S. bicolor, while hordeumflavin B (2-n-undecanyloxo-7-β-isoprenyl ankaflavin) and vulgaredilone (2-dodecanyl-7-β isopranyl monoscodilone) from Monascus-fermented H. vulgare. 23535394 An overview on the marine neurotoxin, saxitoxin: genetics, molecular targets, methods of detection and ecological functions. Marine neurotoxins are natural products produced by phytoplankton and select species of invertebrates and fish. These compounds interact with voltage-gated sodium, potassium and calcium channels and modulate the flux of these ions into various cell types. This review provides a summary of marine neurotoxins, including their structures, molecular targets and pharmacologies. Saxitoxin and its derivatives, collectively referred to as paralytic shellfish toxins (PSTs), are unique among neurotoxins in that they are found in both marine and freshwater environments by organisms inhabiting two kingdoms of life. Prokaryotic cyanobacteria are responsible for PST production in freshwater systems, while eukaryotic dinoflagellates are the main producers in marine waters. Bioaccumulation by filter-feeding bivalves and fish and subsequent transfer through the food web results in the potentially fatal human illnesses, paralytic shellfish poisoning and saxitoxin pufferfish poisoning. These illnesses are a result of saxitoxin's ability to bind to the voltage-gated sodium channel, blocking the passage of nerve impulses and leading to death via respiratory paralysis. Recent advances in saxitoxin research are discussed, including the molecular biology of toxin synthesis, new protein targets, association with metal-binding motifs and methods of detection. The eco-evolutionary role(s) PSTs may serve for phytoplankton species that produce them are also discussed. 23397032 Parathyroid hormone (1-34) counteracts the suppression of interleukin-11 expression by glucocorticoid in murine osteoblasts: a possible mechanism for stimulating osteoblast differentiation against glucocorticoid excess. Glucocorticoid (GC) excess causes a rapid loss of bone with a reduction in bone formation. Intermittent PTH (1-34) administration stimulates bone formation and counteracts the inhibition of bone formation by GC excess. We have previously demonstrated that mechanical strain enhances interleukin (IL)-11 gene transcription by a rapid induction of ΔFosB expression and protein kinase C (PKC)-δ-mediated phosphorylation of phosphorylated mothers against decapentaplegic (Smad)-1. Because IL-11 suppresses the expression of dickkopf-1 and -2 and stimulates Wnt signaling, IL-11 appears to mediate at least a part of the effect of mechanical strain on osteoblast differentiation and bone formation. The present study was undertaken to examine the effect of PTH(1-34) and GCs on IL-11 expression in murine primary osteoblasts (mPOBs). PTH(1-34) treatment of mPOBs enhanced IL-11 expression in a time- and dose-dependent manner. PTH(1-34) also stimulated ΔFosB expression and Smad1 phosphorylation, which cooperatively stimulated IL-11 gene transcription. PTH(1-34)-induced Smad1 phosphorylation was mediated via PKCδ and was abrogated in mPOBs from PKCδ knockout mice. Dexamethasone suppressed IL-11 gene transcription enhanced by PTH(1-34) without affecting ΔFosB expression or Smad1 phosphorylation, and dexamethasone-GC receptor complex was bound to JunD, which forms heterodimers with ΔFosB. High doses of PTH(1-34) counteracted the effect of dexamethasone on apoptosis of mPOBs, which was blunted by neutralizing anti-IL-11 antibody or IL-11 small interfering RNA. These results demonstrate that PTH(1-34) and GCs interact to regulate IL-11 expression in parallel with osteoblast differentiation and apoptosis and suggest that PTH(1-34) and dexamethasone may regulate osteoblast differentiation and apoptosis via their effect on IL-11 expression. 22743159 Role of metabotropic glutamate receptors in persistent forms of hippocampal plasticity and learning. Storage and processing of information at the synaptic level is enabled by the ability of synapses to persistently alter their efficacy. This phenomenon, known as synaptic plasticity, is believed to underlie multiple forms of long-term memory in the mammalian brain. It has become apparent that the metabotropic glutamate (mGlu) receptor is critically required for both persistent forms of memory and persistent synaptic plasticity. Persistent forms of synaptic plasticity comprise long-term potentiation (LTP) and long-term depression (LTD) that last at least for 4 h but can be followed in vivo for days and weeks. These types of plasticity are believed to be analogous to forms of memory that persist for similar time-spans. The mGlu receptors are delineated into three distinct groups based on their G-protein coupling and agonist affinity and also exercise distinct roles in the way they regulate both long-term plasticity and long-term hippocampus-dependent memory. Here, the mGlu receptors will be reviewed both in general, and in the particular context of their role in persistent (>4 h) forms of hippocampus-dependent synaptic plasticity and memory, as well as forms of synaptic plasticity that have been shown to be directly regulated by memory events. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. 23194750 Reversible inhibition of vasoconstriction by thiazolidinediones related to PI3K/Akt inhibition in vascular smooth muscle cells. Thiazolidinediones (also referred to as glitazones), agonists for Peroxisome Proliferator-Activated Receptor gamma (PPARγ), are used for treating type 2 diabetes mellitus, where they decrease insulin resistance and cardiovascular risk. Compounds bearing the thiazolidinedione structure have also been shown to inhibit phosphoinositide 3-kinase (PI3K). Here we tried to elucidate the poorly defined role of PI3K/Akt in the physiology of vascular smooth muscle cell contraction and tested the hypothesis that thiazolidinediones, by affecting the PI3K/Akt pathway, may influence vascular physiology. Isolated rat femoral arteries segments were mounted in a wire myograph and challenged with 100mM KCl or phenylephrine (PE), in the absence or presence of troglitazone, rosiglitazone, pioglitazone, LY294002 (PI3K inhibitor) and 10-DEBC (Akt inhibitor). All these compounds dose-dependently inhibited vasoconstriction to KCl or PE; their effect was reversible (after 60-120 min washout) and not affected by GW9662 (a PPARγ antagonist) or by N(G)-nitro-L-arginine (LNNA, an inhibitor of NO biosynthesis). Analysis of phospho-Akt (ser 473) in lysates from rat arteries (by immunoblot) revealed that thiazolidinediones, LY294002 and 10-DEBC, at the same concentration and kinetics inhibiting vasoconstriction, produced a similar decrease of Akt phosphorylation. PI3K/Akt pathway therefore appears to be an important, fast acting, modulator of contraction of vascular smooth muscle. Thiazolidinediones decrease vasoconstriction of isolated vessels possibly by inhibiting PI3K/Akt pathway. Such an effect of glitazones, if occurring in vivo, may impact cardiovascular syndromes related to vasospasm in diabetic patients. 23298158 Enhanced Electrical Conductivity in Poly(3-hexylthiophene)/Fluorinated Tetracyanoquinodimethane Nanowires Grown with a Porous Alumina Template. We report on improved electrical conductivity in poly(3-hexylthiophene) (P3HT)/2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ) composite nanowires grown using an anodized aluminum oxide (AAO) template. The electrical conductivity of individual nanowire measured by four-probe scanning tunneling microscopy shows that F4-TCNQ molecules are effectively doped into P3HT by capillary force. The resistivity is tuned in the 0.1-10 Ω cm range by changing the F4-TCNQ concentration from 10 to 0.1 wt % and is 2-4 orders of magnitude smaller than that of the corresponding P3HT/F4-TNCQ thin film composites. The AAO template-assisted synthesis approach thus appears to be effective for high chemical doping and for improving the electrical conductivity of the molecular wires. 23266447 Depth-resolved characterization of diffusion properties within and across minimally-perturbed skin layers. We examine by both experimental and computational means the diffusion of macromolecules through the skin strata (both the epidermis and dermis). Using mouse skin as a test case, we present a novel high-resolution technique to characterize the diffusion properties of heterogeneous biomaterials using 3D imaging of fluorescent probes, precisely-deposited in minimally-perturbed in vivo skin layers. We find the diffusivity of the delivered macromolecules (70 kDa and 2 MDa rhodamine-dextrans) low within the packed cellular arrangement of the epidermis, while gradually increasing (by ~an order of magnitude) through the dermis--as pores in the fibrillar network enlarge from the papillary to the reticular dermis. Our experimental and computational approaches for investigating the diffusion through skin strata help in the assessment and optimization of controlled delivery of drugs (e.g. vaccines) to specific sites (e.g. antigen presenting cells). 23585235 Kinetic Evidence for a Non-Langmuir-Hinshelwood Surface Reaction: H/D Exchange over Pd Nanoparticles and Pd(111). The mechanism of hydrogen recombination on a Pd(111) single crystal and well-defined Pd nanoparticles is studied using pulsed multi-molecular beam techniques and the H2 /D2 isotope exchange reaction. The focus of this study is to obtain a microscopic understanding of the role of subsurface hydrogen in enhancing the associative desorption of molecular hydrogen. HD production from H2 and D2 over Pd is investigated using pulsed molecular beams, and the temperature dependence and reaction orders are obtained for the rate of HD production under various reaction conditions designed to modulate the amount of subsurface hydrogen present. The experimental data are compared to the results of kinetic modeling based on different mechanisms for hydrogen recombination. We found that under conditions where virtually no subsurface hydrogen species are present, the HD formation rate can be described exceptionally well by a classic Langmuir-Hinshelwood model. However, this model completely fails to reproduce the experimentally observed high HD formation rates and the reaction orders under reaction conditions where subsurface hydrogen is present. To analyze this phenomenon, we develop two kinetic models that account for the role of subsurface hydrogen. First, we investigate the possibility of a change in the reaction mechanism, where recombination of one subsurface and one surface hydrogen species (known as a breakthrough mechanism) becomes dominant when subsurface hydrogen is present. Second, we investigate the possibility of the modified Langmuir-Hinshelwood mechanism with subsurface hydrogen lowering the activation energy for recombination of two hydrogen species adsorbed on the surface. We show that the experimental reaction kinetics can be well described by both kinetic models based on non-Langmuir-Hinshelwood-type mechanisms. 23238236 Chemical assessment and antioxidant capacity of pepper (Capsicum annuum L.) seeds. Capsicum annuum L. is reported to be the most widely cultivated species. Recently, waste of vegetable processing, like seeds, has been the subject of many studies as an attempt to find new, alternative and cheap resources of bioactive compounds with application in several industries. Despite their chemical, biological and ecological importance, C. annuum seeds are still poorly studied. To improve the knowledge on the metabolic profile of this matrix, a targeted metabolite analysis was performed in "sweet Italian" and "Reus long pairal" pepper seeds. Sterols, triterpenes, organic acids, fatty acids and volatile compounds were determined by different chromatographic methods. The antioxidant activity was assessed against DPPH(·), superoxide and nitric oxide radicals. A concentration-dependent activity was noticed against all radicals. Acetylcholinesterase inhibitory capacity was also evaluated, but no effect was found. Data provide evidence of great similarities between "sweet Italian" and "Reus long pairal" pepper seeds. The present study indicates that C. annuum seeds are a potential source of valuable bioactive compounds that could be used in food industry. 23223857 Biofunctionalized carbon nanotubes in neural regeneration: a mini-review. Carbon nanotubes (CNTs) have become an intriguing and promising biomaterial platform for the regeneration and functional recovery of damaged nerve tissues. The unique electrical, structural and mechanical properties, diversity of available surface chemistry and cell-penetrating ability of CNTs have made them useful implantable matrices or carriers for the delivery of therapeutic molecules. Although there are still challenges being faced in the clinical applications of CNTs mainly due to their toxicity, many studies to overcome this issue have been published. Modification of CNTs with chemical groups to ensure their dissolution in aqueous media is one possible solution. Functionalization of CNTs with biologically relevant and effective molecules (biofunctionalization) is also a promising strategy to provide better biocompatibility and selectivity for neural regeneration. Here, we review recent advances in the use of CNTs to promote neural regeneration. 22788542 Quality assessment and scavenging activity of Siamese neem flower extract. Young leaves and flowers of Siamese neem tree (Azadirachta indica A. Juss. var. siamensis Valeton) are commonly consumed as a bitter tonic vegetable. Active antioxidant components in the flowers are rutin and quercetin flavonoids. The aqueous extracts of young flowers collected from 14 different locations in Thailand were quantitatively analysed using high-performance liquid chromatography for the contents of rutin and quercetin, and were determined for the loss on drying, heavy metals and pesticide residues, microbial contamination, solubility, chromatographic fingerprints and acute toxicity. The extracts contained rutin and quercetin in the ranges from 388 to 1178 mg% dry weight (average 772 mg%), and 1 to 10 mg% dry weight (average 5 mg%), respectively. EC50 of the scavenging activity of all extracts was found in the range of 27-133 µg mL(-1). Loss on drying of the extracts was less than 7% w/w and no sign of toxicity (LD50 > 5 g kg(-1)) was found. 23330789 Facile fabrication of "dual click" one- and two-dimensional orthogonal Peptide concentration gradients. Peptides, proteins, and extracellular matrix act synergistically to influence cellular function at the biotic-synthetic interface. However, identifying the individual and cooperative contributions of the various combinations and concentration regimes is extremely difficult. The confined channel deposition method we describe affords highly tunable orthogonal reactive concentration gradients that greatly expand the dynamic range, spatial control, and chemical versatility of the reactive silanes that can be controllably deposited. Using metal-free "dual click" immobilization chemistries, multiple peptides with a variety of functionality can be immobilized efficiently and reproducibly enabling optimal concentration profiling and the assessment of synergistic interactions. 23305993 Chemical synthesis, docking studies and biological effects of a pan peroxisome proliferator-activated receptor agonist and cyclooxygenase inhibitor. The compound (5Z)-5-[(5-bromo-1H-indol-3-yl)methylene]-3-(4-chlorobenzyl)-thiazolidine-2,4-dione (LYSO-7) was synthesised in order to obtain a new type of anti-inflammatory drug, designed with hybrid features to inhibit cyclooxygenase (COX) and also to activate peroxisome proliferator-activated receptor (PPAR). Results obtained from docking (in silico) studies corroborated with experimental data, showing the potential affinity between the studied ligand and targets. The specificity of LYSO-7 for COX-enzymes was detected by the inhibition of COX-1 and COX-2 activities by 30% and 20%, respectively. In transactivation reporter gene assays LYSO-07 showed a pan partial agonist effect on the three PPAR subtypes (PPARγ, PPARα and PPARβ/δ). The agonist action on PPARγ was also observed by a pharmacological approach, as the reduction in the Escherichia coli lipopolysaccharide (LPS)-induced interleukin 1 beta (IL-1β) secretion and nitric oxide (NO) production by mouse neutrophils was blocked by GW9962, a specific PPARγ antagonist. Additionally, the in vivo effect was measured by reduced carrageenan-induced neutrophil influx into the subcutaneous tissue of mice. Taken together, these data show that LYSO-7 displays a potent in vivo anti-inflammatory effect during the innate acute response, which is dependent on its associated COX inhibitory activities and PPAR activation. 23041510 Effects of combined treatment with eldecalcitol and alendronate on bone mass, mechanical properties, and bone histomorphometry in ovariectomized rats: a comparison with alfacalcidol and alendronate. Eldecalcitol (ELD), a 2β-hydroxypropyloxy derivative of 1α,25 (OH) 2D3, inhibits bone resorption more potently than alfacalcidol (ALF) while maintaining osteoblastic function in an ovariectomized (OVX) osteoporosis rat model. Alendronate (ALN), which is the most common bisphosphonate used for the treatment of osteoporosis, increases the bone mineral density (BMD) by suppressing bone resorption. In this study, we investigated the effects of combination treatments with ELD and ALN or with ALF and ALN on bone mass and strength in OVX rats. Seventy female rats, 32 weeks old, were assigned to seven groups: (1) a sham-operated control group; (2) an OVX-control group; (3) an ELD group; (4) an ALF group; (5) an ALN group; (6) an ELD+ALN group; and (7) an ALF+ALN group. OVX rats were orally treated with ELD (0.015 μg/kg), ALF (0.0375 μg/kg), or ALN (0.2mg/kg) daily for 12 weeks. In both the lumbar spine and the femur, ELD and ALF monotherapy significantly increased the BMD, and ELD+ALN and ALF+ALN significantly increased the BMD, compared with ALN monotherapy, as an additive effect. In particular, ELD+ALN resulted in a significantly higher BMD than ALF+ALN in the femur. On mechanical testing of the lumbar spine, ELD and ALF monotherapy significantly increased the ultimate load, and ELD+ALN and ALF+ALN significantly increased the ultimate load compared with ALN monotherapy. In the femur, ELD, ELD+ALN, and ALF+ALN treatment significantly increased the ultimate load, compared with the OVX-control group, and ELD+ALN resulted in a significantly higher ultimate load than ALN monotherapy. A histomorphometric analysis showed that ELD monotherapy and ELD+ALN combination therapy had a potent inhibitory effect on bone resorption parameters (osteoclast surface and eroded surface), while maintaining bone formation parameters (osteoblast surface and osteoid surface). By contrast, ALF and ALF+ALN significantly lowered the histological parameters of both bone resorption and formation. These results suggested that ELD or ALF used in combination with ALN has therapeutic advantages over ALN monotherapy, with ELD+ALN combination treatment producing an especially beneficial anti-osteoporotic effect by inhibiting osteoclastic bone resorption and maintaining osteoblastic function, compared with ALF+ALN combination treatment. 23411255 Understanding the degradation of ascorbic acid and glutathione in relation to the levels of oxidative stress biomarkers in broccoli (Brassica oleracea L. italica cv. Bellstar) during storage and mechanical processing. The purpose of this research was to understand the degradation of ascorbic acid and glutathione content in broccoli florets (Brassica oleracea L. italica cv. Bellstar) during prolonged storage and subsequent mechanical processing. The initial content of total ascorbic acid and glutathione in broccoli florets averaged at 5.18 ± 0.23 and 0.70 ± 0.03 μmol/g fresh weight, respectively. Results showed that the content of ascorbic acid and glutathione in broccoli degraded during storage at 23°C, for at least 4.5-fold after 6 days of storage. On each day of storage, broccoli florets were mechanically processed, but the content of total ascorbic acid and glutathione was not significantly affected. When the mechanically processed broccoli florets were further incubated for up to 6h, the amount of ascorbic acid was greatly reduced as compared to glutathione. To obtain an in-depth understanding on the degradation of ascorbic acid and glutathione, the activity of enzymes involved in plant antioxidative system via ascorbate-glutathione cycle, as a response towards oxidative stress that took place during storage was determined in this study. The content of total ascorbic acid and glutathione in broccoli florets before and after mechanical processing were found to decrease concurrently with the activity of ascorbic acid peroxidase and glutathione reductase over the experimental storage duration. Meanwhile, the effect of oxidative stress on the content of ascorbic acid and glutathione was apparent during the 6h of incubation after mechanical processing. This phenomenon was demonstrated by the level of oxidative stress biomarkers examined, in which the formation of lipid peroxides, protein carbonyls and DNA oxidised products was positively associated with the degradation of total ascorbic acid and glutathione. 23517470 Light-Triggered Cross-Linking of Alginates with Caged Ca(2+) A strategy to light-trigger ionic cross-linking of alginates by incorporating a photosensitive Ca(2+) cage (nitr-T) is presented. Upon irradiation, free Ca(2+) was released, and this caused gelation of the alginate solution. Addition of Ca(2+) "on-demand" allowed us to obtain homogeneous alginate (ALG) gels using concentrated initial ALG solutions (10%), not possible with other ionic gelation approaches. The cross-linking degree and derived mechanical properties of the hydrogel were modulated by the exposure dose. The light-mediated cross-linked alginate hydrogel displayed a significant improvement in the mechanical properties and homogeneity when compared to mixtures of alginate and soluble Ca(2+) at comparable concentrations. 23163696 The octadecaneuropeptide stimulates somatolactin release from cultured goldfish pituitary cells. The present study aimed to investigate the distribution of the octadecaneuropeptide (ODN) in the goldfish brain and to look for a possible effect of ODN on somatolactin (SL) release from pituitary cells. A discrete population of ODN-immunoreactive neurones was localised in the lateral part of the nucleus lateralis tuberis. These neurones sent projections through the neurohypophyseal tract towards the neurohypophysis, and nerve fibres were seen in the close vicinity of SL-producing cells in the pars intermedia. Incubation of cultured goldfish pituitary cells with graded concentrations of ODN (10(-9) -10(-5 ) m) induced a dose-dependent stimulation of SL-β, but not SL-α, release. ODN-evoked SL release was blocked by the metabotrophic endozepine receptor antagonist cyclo(1-8) [DLeu(5) ]OP but was not affected by the central-type benzodiazepine receptor antagonist flumazenil. ODN-induced SL release was suppressed by treatment with the phospholipase C (PLC) inhibitor U-73122 but not with the protein kinase A (PKA) inhibitor H-89. These results indicate that, in fish, ODN produced by hypothalamic neurones acts as a hypophysiotrophic neuropeptide stimulating SL release. The effect of ODN is mediated through a metabotrophic endozepine receptor positively coupled to the PLC/inositol 1,4,5-trisphosphate/protein kinase C-signalling pathway. 23411181 In vitro biological activity of essential oils and isolated furanosesquiterpenes from the neglected vegetable Smyrnium olusatrum L. (Apiaceae). Smyrnium olusatrum, better known as Alexanders or wild celery, is a biennal herb used in cuisine for many centuries by Romans in many dishes, where it has now been replaced by celery. In order to provide additional evidences so that this forgotten vegetable can be reconsidered in the human diet, as well as in pharmaceutics, the essential oils obtained from different parts and its main isolated furanosesquiterpenes were in vitro biologically assayed for antiproliferative activity on human tumor cell lines by MTT assay, for antioxidant potential by DPPH, ABTS and FRAP assays, and for antimicrobial activity by the agar disc diffusion method. The essential oils showed cytotoxic effects on tested human tumor cell lines, related to the furanosesquiterpenoid content; the IC(50) values on colon carcinoma, glioblastoma, and breast adenocarcinoma cells were 8.51, 13.35, and 14.81 μg/ml, respectively. Isofuranodiene and 1β-acetoxyfuranoeudesm-4(15)-ene resulted the most active constituents. The essential oils possessed also radical scavenging activity. 23458621 Luminescent silica nanoparticles for cancer diagnosis. Fluorescence imaging techniques are becoming essential for preclinical investigations, necessitating the development of suitable tools for in vivo measurements. Nanotechnology entered this field to help overcome many of the current technical limitations, and luminescent nanoparticles (NPs) are one of the most promising materials proposed for future diagnostic implementation. NPs also constitute a versatile platform that can allow facile multi-functionalization to perform multimodal imaging or theranostics (simultaneous diagnosis and therapy). In this contribution we have mainly focused on dye doped silica or silica-based NPs conjugated with targeting moieties to enable imaging of specific cancer cells. We also cite and briefly discuss a few non-targeted systems for completeness. We summarize common synthetic approaches to these materials, and then survey the most recent imaging applications of silica-based nanoparticles in cancer. The field of theranostics is particularly important and stimulating, so, even though it is not the central topic of this paper, we have included some significant examples. We conclude with a short section on NP-based systems already in clinical trials and examples of specific applications in childhood tumors. This review aims to describe and discuss, through focused examples, the great potential of these materials in the medical field, with the aim to encourage further research to implement applications, which today are still rare. 23281340 Chemerin and vaspin: possible targets to treat obesity? Obesity is one of the main human epidemics today. The increase in fat accumulation, which is associated with obesity, may significantly change the expression of several bioactive molecules known as adipokines. These adipokines interact not only with adipose tissue, but also with metabolically relevant organs such as liver and muscle. Understanding the molecular basics of potential novel targets might help to improve the therapeutic treatment of people who suffer from obesity. Herein we summarize the state of the art of two novel adipokines and their impaired or protective action in obesity: chemerin and vaspin. Their expression patterns, signal transduction activity, and resulting functions within the human body are introduced. We also discuss various possibilities to target these adipokines, which may represent promising new targets for the treatment of obesity by small and synthetic compounds. 23104982 Identification of inhibitory scFv antibodies targeting fibroblast activation protein utilizing phage display functional screens. Fibroblast activation protein (FAP) is a serine protease selectively expressed on tumor stromal fibroblasts in epithelial carcinomas and is important in cancer growth, adhesion, and metastases. As FAP enzymatic activity is a potent therapeutic target, we aimed to identify inhibitory antibodies. Using a competitive inhibition strategy, we used phage display techniques to identify 53 single-chain variable fragments (scFvs) after three rounds of panning against FAP. These scFvs were expressed and characterized for binding to FAP by surface plasmon resonance and flow cytometry. Functional assessment of these antibodies yielded an inhibitory scFv antibody, named E3, which could attenuate 35% of FAP cleavage of the fluorescent substrate Ala-Pro-7-amido-4-trifluoromethylcoumarin compared with nonfunctional scFv control. Furthermore, a mutant E3 scFv was identified by yeast affinity maturation. It had higher affinity (4-fold) and enhanced inhibitory effect on FAP enzyme activity (3-fold) than E3. The application of both inhibitory anti-FAP scFvs significantly affected the formation of 3-dimensional FAP-positive cell matrix, as demonstrated by reducing the fibronectin fiber orientation from 41.18% (negative antibody control) to 34.06% (E3) and 36.15% (mutant E3), respectively. Thus, we have identified and affinity-maturated the first scFv antibody capable of inhibiting FAP function. This scFv antibody has the potential to disrupt the role of FAP in tumor invasion and metastasis. 23300000 Influence of rare earth elements on metabolism and related enzyme activity and isozyme expression in Tetrastigma hemsleyanum cell suspension cultures. The effects of rare earth elements (REEs) not only on cell growth and flavonoid accumulation of Tetrastigma hemsleyanum suspension cells but also on the isoenzyme patterns and activities of related enzymes were studied in this paper. There were no significant differences in enhancement of flavonoid accumulation in T. hemsleyanum suspension cells among La(3+), Ce(3+), and Nd(3+). Whereas their inductive effects on cell proliferation varied greatly. The most significant effects were achieved with 100 μM Ce(3+)and Nd(3+). Under treatment over a 25-day culture period, the maximal biomass levels reached 1.92- and 1.74-fold and the total flavonoid contents are 1.45- and 1.49-fold, than that of control, respectively. Catalase, phenylalanine ammonia-lyase (PAL), and peroxidase (POD) activity was activated significantly when the REE concentration range from 0 to 300 μM, whereas no significant changes were found in superoxide dismutase activity. Differences of esterase isozymes under REE treatment only laid in expression level, and there were no specific bands. The expression level of some POD isozymes strengthened with increasing concentration of REEs within the range of 50-200 μM. When REE concentration was higher than 300 μM, the expression of some POD isozymes was inhibited; meanwhile, some other new POD isozymes were induced. Our results also showed REEs did not directly influence PAL activity. So, we speculated that 50-200 μM REEs could activate some of antioxidant enzymes, adjust some isozymes expression, trigger the defense responses of T. hemsleyanum suspension cells, and stimulate flavonoid accumulation by inducing PAL activity. 23267862 Simultaneous addition of two ligands: a potential strategy for estimating divalent ion affinities in EF-hand proteins by isothermal titration calorimetry. Capable of providing a detailed thermodynamic picture of noncovalent association reactions, isothermal titration calorimetry (ITC) has become a popular method for studying protein-ligand interactions. We routinely employ the technique to study divalent ion-binding by two-site EF-hand proteins from the parvalbumin- and polcalcin lineages. The combination of high Ca(2+) affinity and relatively low Mg(2+) affinity, and the attendant complication of parameter correlation, conspire to make the simultaneous extraction of binding constants and -enthalpies for both ions challenging. Although global analysis of multiple ITC experiments can overcome these hurdles, our current experimental protocol includes upwards of 10 titrations - requiring a substantial investment in labor, machine time, and material. This paper explores the potential for using a smaller suite of experiments that includes simultaneous titrations with Ca(2+) and Mg(2+) at different ratios of the two ions. The results obtained for four proteins, differing substantially in their divalent ion-binding properties, suggest that the approach has merit. The Ca(2+)- and Mg(2+)-binding constants afforded by the streamlined analysis are in reasonable agreement with those obtained from the standard analysis protocol. Likewise, the abbreviated analysis provides comparable values for the Ca(2+)-binding enthalpies. However, the streamlined analysis can yield divergent values for the Mg(2+)-binding enthalpies - particularly those for lower affinity sites. This shortcoming can be remedied, in large measure, by including data from a direct Ca(2+) titration in the presence of a high, fixed Mg(2+) concentration. 23273225 Controlling Porphyrin Nanoarchitectures at Solid Interfaces. Two complementary examples of porphyrin nanoarchitectonics are presented. The fabrication of binary molecular monolayers using two different porphyrin molecules, tetrakis(3,5-di-t-butyl-4-hydroxyphenyl)porphyrin (1) and tetrakis(4-pyridyl)porphyrin (2), by deposition in ultrahigh vacuum was demonstrated. Two unusual heteromolecular monolayer structures were observed, with one exhibiting good separation of 1 molecules within the monolayer. Also, a synthetic nanoarchitectonic approach was used to prepare self-assembled molecular nanowires at a mica substrate. The nanowires could be observed to grow using atomic force microscopy (AFM), and the network structures of the nanowires could be influenced by manipulation using the AFM probe tip. 23570998 Assessment of the role of flavonoids for inducing osteoblast differentiation in isolated mouse bone marrow derived mesenchymal stem cells. Quercetin and rutin are common flavonoids in fruit and vegetables, and have been reported to affect bone development. However, the effect of flavonoids on osteoblast differentiation remains a matter of controversy. In the present study, mouse bone marrow mesenchymal stem cells (BMMSCs) were isolated and characterized for their use in osteoblast differentiation using two flavonoids, quercetin and rutin. BMMSCs were cultured in various concentrations of quercetin and rutin during the osteoblast differentiation period of 10 days. Both quercetin and rutin were found to up regulate the osteoblast differentiation in dose dependent manner, albeit to lesser extent in case of former than that of latter. Quercetin and rutin also increased alkaline phosphatase activity by about 150 and 240% and demonstrated mineralization up to 110 and 200% respectively as compared to control (which was considered as 100%). Further, both the flavonoids were also found to increase the expression of some of the prominent markers for differentiation of osteoblast like osteopontin, osterix, RunX2, osteoprotegerin and osteocalcin. The current data suggests that certain classes of flavonoids like rutin and quercetin can be used in the cure and management of osteodegenerative disorders due to their osteoblast specific differentiation activities. 23122137 Hypotriglyceridemic and hypoglycemic effects of vescalagin from Pink wax apple [Syzygium samarangense (Blume) Merrill and Perry cv. Pink] in high-fructose diet-induced diabetic rats. Vescalagin, an active component from Pink wax apple [Syzygium samarangense (Blume) Merrill and Perry cv. Pink] fruit, with glucose uptake enhancing ability in insulin-resistant FL83B mouse hepatocytes, as shown in our previous study, was further evaluated for its hypotriglyceridemic and hypoglycemic effects in high-fructose diet (HFD)-induced diabetic rats. Wistar rats were fed HFD for 16 weeks and orally administered with vescalagin from Pink wax apple daily during the last 4 weeks. The results of biochemical parameters showed that fasting blood glucose, C-peptide, fructosamine, triglyceride and free fatty acid contents decreased by 44.7%, 46.2%, 4.0%, 42.5%, and 10.8%, respectively, in the HFD-induced diabetic rats administered with vescalagin at 30 mg/kg body weight in comparison with those of control HFD-induced diabetic rats. However, high-density-lipoprotein-cholesterol content increased by 14.4% in the HFD rats treated with vescalagin. The present study reveals that vescalagin could have therapeutic value against diabetic progression via its anti-hypertriglyceridemic and anti-hyperglycemic effects. 23215238 Encapsulation of living E. coli cells in hollow polymer microspheres of highly defined size. Here, we report the preparation and characterization of hollow polymer microspheres based on the preprecipitation of porous calcium carbonate cores with an average size of 5 μm and their use for encapsulation of living microorganisms. The microspheres filled with individual living E. coli cells were prepared by layer-by-layer (LbL) deposition of different polyelectrolytes and proteins onto the porous calcium carbonate cores leading to the formation of matrix-like complexes of the compounds followed by calcium carbonate core dissolution using EDTA. Both the influence of the encapsulation process as well as of the used polyelectrolytes on the survival rate of the cells were determined by confocal laser scanning microscopy (CLSM) and microtiter plate fluorescence tests. After the encapsulation process ~40% of the cells were alive. Cultivation tests indicated that the lag phase of cells treated with polyelectrolytes increases and the encapsulated E. coli cells were able to produce green fluorescent protein inside the microcapsules. 23549285 Spongiatriol inhibits nuclear factor kappa B activation and induces apoptosis in pancreatic cancer cells. Pancreatic cancer, the fourth leading cause of cancer death in the US, is highly resistant to all current chemotherapies, and its growth is facilitated by chronic inflammation. The majority of pro-inflammatory cytokines initiate signaling cascades that converge at the activation of the Nuclear Factor Kappa B (NFκB), a signal transduction molecule that promotes cell survival, proliferation and angiogenesis. In an effort to identify novel inhibitors of NFκB, the HBOI library of pure compounds was screened using a reporter cell line that produces luciferin under the transcriptional control of NFκB. Seven compounds were identified through this screen, but in the case of five of them, their reported mechanism of action made them unlikely to be specific NFκB inhibitors. Spongiatriol, a marine furanoditerpenoid that was first isolated in the 1970s, is shown here to inhibit NFκB transcriptional activity in a reporter cell line, to reduce levels of phosphorylated (active) NFκB in the AsPC-1 cell line, to have an IC50 for cytotoxicity in the low micromolar range against the AsPC-1, BxPC-3, MiaPaCa-2 and Panc-1 pancreatic cancer cell lines, and to induce moderate but significant apoptosis in both the AsPC-1 and the Panc-1 cell lines. 23296837 Neuroprotective and anti-inflammatory properties of a coffee component in the MPTP model of Parkinson's disease. Consumption of coffee is associated with reduced risk of Parkinson's disease (PD), an effect that has largely been attributed to caffeine. However, coffee contains numerous components that may also be neuroprotective. One of these compounds is eicosanoyl-5-hydroxytryptamide (EHT), which ameliorates the phenotype of α-synuclein transgenic mice associated with decreased protein aggregation and phosphorylation, improved neuronal integrity and reduced neuroinflammation. Here, we sought to investigate if EHT has an effect in the MPTP model of PD. Mice fed a diet containing EHT for four weeks exhibited dose-dependent preservation of nigral dopaminergic neurons following MPTP challenge compared to animals given control feed. Reductions in striatal dopamine and tyrosine hydroxylase content were also less pronounced with EHT treatment. The neuroinflammatory response to MPTP was markedly attenuated, and indices of oxidative stress and JNK activation were significantly prevented with EHT. In cultured primary microglia and astrocytes, EHT had a direct anti-inflammatory effect demonstrated by repression of lipopolysaccharide-induced NFκB activation, iNOS induction, and nitric oxide production. EHT also exhibited a robust anti-oxidant activity in vitro. Additionally, in SH-SY5Y cells, MPP(+)-induced demethylation of phosphoprotein phosphatase 2A (PP2A), the master regulator of the cellular phosphoregulatory network, and cytotoxicity were ameliorated by EHT. These findings indicate that the neuroprotective effect of EHT against MPTP is through several mechanisms including its anti-inflammatory and antioxidant activities as well as its ability to modulate the methylation and hence activity of PP2A. Our data, therefore, reveal a strong beneficial effect of a novel component of coffee in multiple endpoints relevant to PD. 23500537 Oxyphytosterol formation in humans: Identification of high vs. low oxidizers. Animal studies suggest that oxyphytosterols are atherogenic. However, we have previously shown that plasma oxyphytosterol concentrations did not increase after consuming a diet enriched in plant sterol esters (3g/day), while minor reductions were seen after consuming a plant stanol ester-enriched diet. Large variations in oxyphytosterol concentrations between individuals however existed. The aim of this study was to identify factors that may explain inter-individual differences in plasma oxyphytosterol concentrations. For this, 43 subjects consumed for 4 weeks in random order a plant sterol, stanol and control margarine. Plasma oxyphytosterol concentrations were determined in butylated hydroxytoluene (BHT)-enriched EDTA plasma via GC-MS and serum oxidized low-density lipoprotein (oxLDL) concentrations were analyzed via ELISA. Trolox equivalent antioxidant capacity (TEAC) values, α-tocopherol concentrations and iron/copper status were determined to assess plasma oxidative and anti-oxidative capacity. Serum (non-oxidized) sitosterol and campesterol concentrations did not correlate with plasma oxysitosterol and oxycampesterol concentrations during any of the three dietary interventions. Moreover, plasma oxyphytosterol concentrations remained relatively stable over time. Six subjects could be arbitrarily classified as having consistent low or high plasma oxyphytosterol concentrations, which was also reflected in oxLDL concentrations. However, oxidative and anti-oxidative capacity markers, such as iron/copper status, α-tocopherol concentrations and TEAC values, could not explain these differences. In conclusion, subjects seem to have consistent plasma oxyphytosterol concentrations, which resulted in the identification of 'low and high oxidizers'. Differences, however, could not be attributed to the oxidative and anti-oxidative capacity markers analyzed. 23590189 Inflammation-Responsive Antioxidant Nanoparticles Based on a Polymeric Prodrug of Vanillin. Oxidative stress is induced by accumulation of hydrogen peroxide (H2O2), and therefore, H2O2 could serve as a potential biomarker of various oxidative stress-associated inflammatory diseases. Vanillin is one of the major components of natural vanilla and has potent antioxidant and anti-inflammatory activities. In this work, we developed a novel inflammation-responsive antioxidant polymeric prodrug of vanillin, termed poly(vanillin oxalate) (PVO). In design, PVO incorporates H2O2-reacting peroxalate ester bonds and bioactive vanillin via acid-responsive acetal linkages in its backbone. Therefore, in cells undergoing damages by oxidative stress, PVO readily degrades into three nontoxic components, one of which is antioxidant and anti-inflammatory vanillin. PVO nanoparticles exhibit potent antioxidant activities by scavenging H2O2 and inhibiting the generation of ROS (reactive oxygen species) and also reduce the expression of pro-inflammatory cytokines in activated macrophages in vitro and in vivo. We, therefore, anticipate that PVO nanoparticles have great potential as novel antioxidant therapeutics and drug delivery systems for ROS-associated inflammatory diseases. 22818587 Influence of low ultrasound intensity on the degradation of dextran catalyzed by dextranase. In our current research work, the effect of ultrasound irradiation on the enzymatic activity and enzymatic hydrolysis kinetic parameters of dextran catalysis by dextranase were investigated. Furthermore, the effects of ultrasound irradiation on the structure of dextranase were investigated with the aid of fluorescence spectroscopy and circular dichroism (CD) spectroscopy. The maximum activity of dextranase was observed when the sample was treated with ultrasound at 25 kHz, 40 W for 15 min, under which the enzyme activity increased by 13.43% compared the routine thermal incubation at 50 °C. Experimental Kinetics results, demonstrated that, both the V(max) and K(M) values of dextranase increased with ultrasound-treated compared with the incubation at 50 °C. Likewise, both the catalytic and specificity constants were higher under the effects of an ultrasonic field, indicating that, the substrate is converted into the product at an increased rate when compared with the incubation at 50 °C. On the other hand, fluorescence and CD spectra reflected that the ultrasound irradiation had increased the number of tryptophan on dextranase surface with increased α-helix by 15.74% and reduced random coil by 5.41% upon ultrasound-treated dextranase protein compared to the control, which were helpful for the improvement of its activity. 23317498 Small-molecule inhibitors for the treatment of hepatitis B virus documented in patents. Hepatitis B virus (HBV) infection is a serious health problem worldwide, and the current treatment methods including vaccines, immunomodulators, interferons and nucleoside analogs are far from satisfactory. For the search of new anti-HBV agents, much investigation has revealed a large number of small-molecule compounds with various skeletons and promising anti-HBV activities. Although some reviews on anti-HBV progress have been published, they are mainly concentrated on the results reported in journal articles. This review provides an overview of the structural features and anti-HBV properties of the small-molecule anti-HBV inhibitors claimed in recent patents (from 2001 to 2010). These small-molecules can be structurally classified as two main types, nucleoside analogs (cyclic and acyclic nucleosides) and non-nucleosides (natural and synthesized compounds), which are declared with the activity inhibiting the secretion of HBsAg and HBeAg and HBV DNA replication in vitro, as well as anti-DHBV DNA in vivo. Especially, the non-nucleosides with diverse skeletons and novel mechanism offer prolific candidates for anti-HBV drug discovery, which are preferred to be used as adjuvant therapy for HBV infection. This paper will provide valuable information for understanding the current anti-HBV investigation and developing new anti-HBV agents. 23434669 Chemical Inhibitors and microRNAs (miRNA) Targeting the Mammalian Target of Rapamycin (mTOR) Pathway: Potential for Novel Anticancer Therapeutics. The mammalian target of rapamycin (mTOR) is a critical regulator of many fundamental features in response to upstream cellular signals, such as growth factors, energy, stress and nutrients, controlling cell growth, proliferation and metabolism through two complexes, mTORC1 and mTORC2. Dysregulation of mTOR signalling often occurs in a variety of human malignant diseases making it a crucial and validated target in the treatment of cancer. Tumour cells have shown high susceptibility to mTOR inhibitors. Rapamycin and its derivatives (rapalogs) have been tested in clinical trials in several tumour types and found to be effective as anticancer agents in patients with advanced cancers. To block mTOR function, they form a complex with FKBP12 and then bind the FRB domain of mTOR. Furthermore, a new generation of mTOR inhibitors targeting ATP-binding in the catalytic site of mTOR showed potent and more selective inhibition. More recently, microRNAs (miRNA) have emerged as modulators of biological pathways that are essential in cancer initiation, development and progression. Evidence collected to date shows that miRNAs may function as tumour suppressors or oncogenes in several human neoplasms. The mTOR pathway is a promising target by miRNAs for anticancer therapy. Extensive studies have indicated that regulation of the mTOR pathway by miRNAs plays a major role in cancer progression, indicating a novel way to investigate the tumorigenesis and therapy of cancer. Here, we summarize current findings of the role of mTOR inhibitors and miRNAs in carcinogenesis through targeting mTOR signalling pathways and determine their potential as novel anti-cancer therapeutics. 23606629 Synthesis and Anti-herpetic Activity of Phosphoramidate ProTides. Among the many prodrug approaches aimed at delivering nucleoside monophosphates into cells, the phosphoramidate ProTide approach is one that has shown success, which has made it possible for some of the phosphoramidates to enter into clinical trials. Herein, we report the synthesis and antiviral activity of a series of phosphoramidate ProTides designed to bypass the thymidine kinase (TK) dependence of the parent nucleoside analogues. Phosphoramidate derivatives of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) that contain L-alanine or pivaloyloxymethyl iminodiacetate (IDA-POM) exhibit anti-HSV-1 and anti-VZV activity in cell cultures, but they largely lost antiviral potency against TK-deficient virus strains. Among deazapurine nucleosides and their phosphoramidate derivatives, the 7-deazaadenine containing nucleosides and their phosphoramidate triester derivatives showed weak antiviral activity against VZV. Apparently, intracellular nucleotide delivery with these phosphoramidates is partly successful. However, none of the compound prodrugs showed superior activity to their parent drugs. 23139019 The utility of modeling and simulation approaches to evaluate immunogenicity effect on the therapeutic protein pharmacokinetics. While therapeutic proteins (TP), particularly recombinant human proteins and fully human monoclonal antibodies, are designed to have a low immunogenic potential in humans, a clinical immune response does sometimes occur and cannot be predicted from preclinical studies. Changes in TP pharmacokinetics may be perceived as an early indication of antibody formation and serve as a surrogate for later changes in efficacy and safety in individual subjects. Given the substantial increase in number of biological products, including biosimilars, there is an urgent need to quantitatively predict and quantify the immune response and any consequential changes in TP pharmacokinetics. The purpose of this communication is to review the utility of population-based modeling and simulation approaches developed to date for investigating the development of an immune response and assessing its impact on TP pharmacokinetics. Two examples of empirical modeling approaches for pharmacokinetic assessment are presented. The first example presents methods to analyze pharmacokinetic data in the presence of anti-drug antibody (ADA) and confirm the effect of immunogenicity on TP pharmacokinetics in early phases of drug development. The second example provides a framework to analyze pharmacokinetic data in the absence or with very low incidence of ADA and confirm with enough power the lack of an immunogenicity effect on TP pharmacokinetics in late phases of drug development. Finally, a theoretical mechanism-based modeling framework is presented to mathematically relate the complex interaction among TP, their targets, and ADA. 22929022 Genetic perspectives on the origin of clicks in Bantu languages from southwestern Zambia. Some Bantu languages spoken in southwestern Zambia and neighboring regions of Botswana, Namibia, and Angola are characterized by the presence of click consonants, whereas their closest linguistic relatives lack such clicks. As clicks are a typical feature not of the Bantu language family, but of Khoisan languages, it is highly probable that the Bantu languages in question borrowed the clicks from Khoisan languages. In this paper, we combine complete mitochondrial genome sequences from a representative sample of populations from the Western Province of Zambia speaking Bantu languages with and without clicks, with fine-scaled analyses of Y-chromosomal single nucleotide polymorphisms and short tandem repeats to investigate the prehistoric contact that led to this borrowing of click consonants. Our results reveal complex population-specific histories, with female-biased admixture from Khoisan-speaking groups associated with the incorporation of click sounds in one Bantu-speaking population, while concomitant levels of potential Khoisan admixture did not result in sound change in another. Furthermore, the lack of sequence sharing between the Bantu-speaking groups from southwestern Zambia investigated here and extant Khoisan populations provides an indication that there must have been genetic substructure in the Khoisan-speaking indigenous groups of southern Africa that did not survive until the present or has been substantially reduced. 23095167 Kainate receptor signaling in pain pathways. Receptors and channels that underlie nociceptive signaling constitute potential sites of intervention for treatment of chronic pain states. The kainate receptor family of glutamate-gated ion channels represents one such candidate set of molecules. They have a prominent role in modulation of excitatory signaling between sensory and spinal cord neurons. Kainate receptors are also expressed throughout central pain neuraxis, where their functional contributions to neural integration are less clearly defined. Pharmacological inhibition or genetic ablation of kainate receptor activity reduces pain behaviors in a number of animal models of chronic pain, and small clinical trials have been conducted using several orthosteric antagonists. This review will cover kainate receptor function and participation in pain signaling as well as the pharmacological studies supporting further consideration as potential targets for therapeutic development. 23497875 Mild Fe-deficiency improves biomass production and quality of hydroponic-cultivated spinach plants (Spinacia oleracea L.). It is of great practical importance to improve yield and quality of vegetables in soilless cultures. This study investigated the effects of iron-nutrition management on yield and quality of hydroponic-cultivated spinach (Spinacia oleracea L.). The results showed that mild Fe-deficient treatment (1 μM FeEDTA) yielded a greater biomass of edible parts than Fe-omitted treatment (0 μM FeEDTA) or Fe-sufficient treatments (10 and 50 μM FeEDTA). Conversely, mild Fe-deficient treatment had the lowest nitrate concentration in the edible parts out of all the Fe treatments. Interestingly, all the concentrations of soluble sugar, soluble protein and ascorbate in mild Fe-deficient treatments were higher than Fe-sufficient treatments. In addition, both phenolic concentration and DPPH scavenging activity in mild Fe-deficient treatments were comparable with those in Fe-sufficient treatments, but were higher than those in Fe-omitted treatments. Therefore, we concluded that using a mild Fe-deficient nutrition solution to cultivate spinach not only would increase yield, but also would improve quality. 23255050 Intrinsically green iron oxide nanoparticles? From synthesis via (eco-)toxicology to scenario modelling. Iron oxide nanoparticles (IONP) are currently being studied as green magnet resonance imaging (MRI) contrast agents. They are also used in huge quantities for environmental remediation and water treatment purposes, although very little is known on the consequences of such applications for organisms and ecosystems. In order to address these questions, we synthesised polyvinylpyrrolidone-coated IONP, characterised the particle dispersion in various media and investigated the consequences of an IONP exposure using an array of biochemical and biological assays. Several theoretical approaches complemented the measurements. In aqueous dispersion IONP had an average hydrodynamic diameter of 25 nm and were stable over six days in most test media, which could also be predicted by stability modelling. The particles were tested in concentrations of up to 100 mg Fe per L. The activity of the enzymes glutathione reductase and acetylcholine esterase was not affected, nor were proliferation, morphology or vitality of mammalian OLN-93 cells although exposure of the cells to 100 mg Fe per L increased the cellular iron content substantially. Only at this concentration, acute toxicity tests with the freshwater flea Daphnia magna revealed slightly, yet insignificantly increased mortality. Two fundamentally different bacterial assays, anaerobic activated sludge bacteria inhibition and a modified sediment contact test with Arthrobacter globiformis, both rendered results contrary to the other assays: at the lowest test concentration (1 mg Fe per L), IONP caused a pronounced inhibition whereas higher concentrations were not effective or even stimulating. Preliminary and prospective risk assessment was exemplified by comparing the application of IONP with gadolinium-based nanoparticles as MRI contrast agents. Predicted environmental concentrations were modelled in two different scenarios, showing that IONP could reduce the environmental exposure of toxic Gd-based particles by more than 50%. Application of the Swiss "Precautionary Matrix for Synthetic Nanomaterials" rendered a low precautionary need for using our IONP as MRI agents and a higher one when using them for remediation or water treatment. Since IONP and (considerably more reactive) zerovalent iron nanoparticles are being used in huge quantities for environmental remediation purposes, it has to be ascertained that these particles pose no risk to either human health or to the environment. 23601409 Improvement of the AOAC 2009.01 total dietary fibre method for bread and other high starch containing matrices. The dietary fibre (DF) content in wheat grain based food products have been established with both the classical AOAC 985.29 dietary fibre and the new AOAC 2009.01 total dietary fibre protocol. There is a good agreement between the high molecular weight dietary fibre (HMWDF) contents measured with the AOAC 2009.01 method and (DF) content measured with the classical AOAC 985.29 method in wheat grain based food products. With the AOAC 2009.01 method also a significant amount of low molar weight dietary fibre (LMWDF), ranging from 1% to 3% w/w, was measured which is not quantified with the AOAC 985.29 method. With semi-preparative GPC the LMWDF (DP⩾3) fractions in the wheat grain based food products were isolated. The monosaccharide composition of the dissolved LMWDF constituents was determined. Glucose was by far the most abundant monosaccharide present with arabinose, galactose, xylose and mannose as minor constituents. It appeared that the LMWDF contains still not fully converted digestible starch/malto-oligosaccharide fragments with DP⩾3, which are erroneously quantified as LMWDF. By introducing an extra AMG hydrolysis step in the AOAC 2009.01 protocol after evaporation of the ethanol and dissolving the residue in deionised water, these malto-oligosaccharides are fully hydrolysed resulting in that way in a correct and lower LMWDF content. 23153054 A new approach to predicting human hepatic clearance of CYP3A4 substrates using monkey pharmacokinetic data. 1. Focusing on the genetic similarity of CYP3A subfamily enzymes (CYP3A4 and CYP3A5) between monkeys and humans, we have attempted to provide a single-species approach to predicting human hepatic clearance (CLh) of CYP3A4 substrates using pharmacokinetic parameters in cynomolgus monkeys following intravenous administrations. 2. Hepatic intrinsic clearance (CLint,h) of six CYP3A4 substrates (alprazolam, clonazepam, diltiazem, midazolam, nifedipine, and quinidine), covering a wide range of clearance, in monkeys correlated well with that cited in literature for humans (R = 0.90) with a simple equation of Y = 0.165X (Y: human CLint,h, X: monkey CLint,h, represented in mL/min/kg). 3. To verify the predictability of human CLint,h, monkey CLint,h of a test set of CYP3A4 substrates cited in literature (dexamethasone, nifedipine, midazolam, quinidine, tacrolimus, and verapamil) was applied to the equation and human CLint,h was calculated. The human CLint,h of all the substrates was predicted within 3-fold error (fold error: 0.35-2.77). 4. The predictability of human CLh by our method was superior to common in vivo prediction methods (allometry and liver blood flow method). These results suggest that human hepatic clearance of CYP3A4 substrates can be predicted by applying cynomolgus monkey CLint,h obtained following intravenous administrations in each laboratory to the simple equation. 23178182 UCCB01-125, a dimeric inhibitor of PSD-95, reduces inflammatory pain without disrupting cognitive or motor performance: comparison with the NMDA receptor antagonist MK-801. Excessive N-Methyl-d-aspartate receptor (NMDAR)-dependent production of nitric oxide (NO) is involved in the development and maintenance of chronic pain states, and is mediated by postsynaptic density protein-95 (PSD-95). By binding to both the NMDAR and neuronal NO synthase (nNOS), PSD-95 mediates a specific coupling between NMDAR activation and NO production. NMDAR antagonism shows anti-nociceptive action in humans and animal models of chronic pain but is associated with severe disturbances of cognitive and motor functions. An alternative approach to modulate the NMDAR-related activity is to perturb the NMDAR/PSD-95/nNOS complex by targeting PSD-95, thereby decreasing NO production without interfering with the NMDAR ion channel function. Here, we compared the effects of a dimeric PSD-95 inhibitor, UCCB01-125, and the NMDAR antagonist, MK-801, on mechanical hypersensitivity in the complete Freund's adjuvant (CFA) model of inflammatory pain. To examine side-effect profiles we also compared the effects of UCCB01-125 and MK-801 in tests of attention, long-term memory, and motor performance. When administered concurrently with CFA, both MK-801 and UCCB01-125 prevented the development of CFA-induced mechanical hypersensitivity 1 and 24 h after treatment. Moreover, UCCB01-125 was found to reverse CFA-induced hypersensitivity when administered 24 h after CFA treatment, an effect lasting for at least 3 days. At the dose reducing hypersensitivity, MK-801 disrupted attention, long-term memory, and motor performance. By contrast, even high doses of UCCB01-125 were devoid of side-effects in these tests. The data suggest that PSD-95 inhibition is a feasible strategy to prevent both development and maintenance of chronic inflammatory pain, while avoiding NMDAR antagonism-related side-effects. 23411265 Phytosteryl sinapates and vanillates: chemoenzymatic synthesis and antioxidant capacity assessment. Phytosterols and their derivatives have attracted much attention because of their health benefits to humans and are widely used in food, pharmaceuticals, and cosmetics in the past decades. While most of the research has focused on free phytosterols and phytosteryl esters of fatty acids, few researches reported on phytosteryl phenolates, the esters of phytosterols with phenolic acids. Two novel group phytosteryl phenolates, namely phytosteryl sinapates and vanillates, were successfully chemoenzymatically synthesised in this work and their structures confirmed. Fourier transform infrared (FTIR) and high performance chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) using atmospheric pressure chemical ionisation (APCI) under both positive and negative ion modes were employed for this purpose. High antioxidant capacity of phytosteryl sinapates was observed using both oxygen radical absorbance capacity (ORAC) assay and cooked ground meat model system. Although phytosteryl vanillates showed lower antioxidant capacity than phytosteryl sinapates, they were stronger antioxidants than vanillic acid and vinyl vanillate in both assays employed. Conjugation of phytosterols with sinapic or vanillic acid rendered higher antioxidant capacity. Further studies on health benefits of phytosteryl sinapates and vanillates are necessary. 23389625 Carbon-coated LiFePO4-porous carbon composites as cathode materials for lithium ion batteries. This work introduces a facile strategy for the synthesis of carbon-coated LiFePO(4)-porous carbon (C-LiFePO(4)-PC) composites as a cathode material for lithium ion batteries. The LiFePO(4) particles obtained are about 200 nm in size and homogeneously dispersed in porous carbon matrix. These particles are further coated with the carbon layers pyrolyzed from sucrose. The C-LiFePO(4)-PC composites display a high initial discharge capacity of 152.3 mA h g(-1) at 0.1 C, good cycling stability, as well as excellent rate capability (112 mA h g(-1) at 5 C). The likely contributing factors to the excellent electrochemical performance of the C-LiFePO(4)-PC composites could be related to the combined effects of enhancement of conductivity by the porous carbon matrix and the carbon coating layers. It is believed that further carbon coating is a facile and effective way to improve the electrochemical performance of LiFePO(4)-PC. 23497864 Determination of chemical variability of phenolic and monoterpene glycosides in the seeds of Paeonia species using HPLC and profiling analysis. A rapid, sensitive, and accurate HPLC-DAD method was developed and validated for simultaneous determination of one phenolic glycoside and seven monoterpene glycosides, including 1-O-β-d-(4-hydroxybenzoyl)glucose (1), pyridylpaeoniflorin (2), (8R)-piperitone-4-en-9-O-β-d-glucopyranoside (3), oxypaeoniflorin (4), 6'-O-β-glucopyranosylalbiflorin (5), albiflorin (6), β-gentiobiosylpaeoniflorin (7), and paeoniflorin (8), in 44 batches of peony seeds from nine Paeonia species collected from different areas. Using the optimised method, separations were conducted with a YMC-pack ODS-A column with water/formic acid and methanol as the mobile phase. All eight analytes demonstrated good linearity (r(2)>0.9993). The recoveries, measured at three concentration levels, varied from 98.20% to 103.81%. Six compounds including 1 and 4-8 occur ubiquitously in all the seeds of nine Paeonia species, and compounds 2 and 3 showed undetectable levels or very low content in several samples. The seed samples were classified into several groups, which coincide with the taxonomy of Paeonia at the section level. Peony seed might be a useful resource in developing new herbal or food products. 22862926 Incretin and pancreatic hormone secretion in Caucasian non-diabetic carriers of the TCF7L2 rs7903146 risk T allele. We characterised 62 non-diabetic, middle-aged, Caucasians with and without the T risk allele of rs7903146 in transcription factor 7-like 2 (TCF7L2) with regard to secretion of insulin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) as well as insulin sensitivity and endogenous glucose production. All participants had a 3-h oral glucose tolerance test (OGTT), an intravenous glucose tolerance test and a euglycaemic, hyperinsulinaemic clamp. After adjustment for age and sex, risk T allele carriers had higher haemoglobin A1c levels (p = 0.030), reduced first-phase insulin response (p = 0.048), higher peripheral insulin sensitivity (p = 0.050) and lower fasting GIP concentrations (p = 0.003) than CC allele carriers. The latter was also reflected by lower total GIP secretion during the OGTT (p = 0.018). We found no significant differences in endogenous glucose production, hepatic insulin sensitivity or fasting concentrations of glucose, insulin, glucagon and GLP-1 between the groups. The findings suggest that the effect of TCF7L2 on diabetes risk may include reduced secretion of GIP. 23313380 Preclinical assessment of a polyspecific antivenom against the venoms of Cerrophidion sasai, Porthidium nasutum and Porthidium ophryomegas: Insights from combined antivenomics and neutralization assays. A polyspecific antivenom is used in Central America for the treatment of envenomings by viperid snakes. This antivenom is generated in horses hyperimmunized with a mixture of venoms from Bothrops asper, Crotalus simus and Lachesis stenophrys. The present study analyzed the ability of this antivenom to neutralize the venoms of three Central American viperid species of the 'Porthidium group', i.e. Porthidium nasutum, Porthidium ophryomegas and Cerrophidion sasai, formerly classified as Cerrophidion godmani. In addition, the immunorecognition of the components of these venoms was assessed by immunoaffinity antivenomics. The antivenom proved effective in neutralizing the lethal, hemorrhagic, myotoxic, phospholipase A(2) (PLA(2)) and proteinase activities of the three venoms, albeit exhibiting quantitative differences in the values of the Median Effective Doses (ED(50)). Excepting for certain low molecular mass bands corresponding to disintegrins, and some PLA(2)s and PI-metalloproteinases, Western blotting and immunoaffinity chromatography revealed immunorecognition of most Porthidium and Cerrophidion venom proteins. In agreement with in vivo neutralization assays, immobilized antivenom IgGs showed higher immunocapturing activity of toxins from both Porthidium taxa than from C. sasai. Overall our results demonstrate a significant paraspecific protection of the Costa Rican polyspecific antivenom against the three venoms sampled. They also stress the need to search for novel ways to enhance the immune response of horses against several weakly immunogenic venom components. 23411177 Influence of seasonality on the chemical composition of oysters (Crassostrea rhizophorae). This paper aimed to evaluate the influence of seasonality on the chemical composition of oysters (Crassostrea rhizophorae). Samples were collected during summer and winter from the estuary and lagoon complex of the municipality of Barra de São Miguel, Alagoas, Brazil. Statistical differences (p<0.05) between summer and winter were observed in relation to chemical composition. The oysters cultivated in the winter presented some nutritional advantages because of the higher levels of proteins and functional nutrients, such as the eicosapentaenoic-docosahexaenoic acid combination and percentages of polyunsaturated fatty acids (n-3 and n-6), and the lower levels of saturated fatty acids. Therefore, the animals in winter presented a higher content of cholesterol oxides. The levels of cholesterol oxides found in these products during winter may encourage researchers to investigate the composition of oysters cultivated in different climates all over the world. 23295223 A novel transcriptional repressor PhaR for the steroid-inducible expression of the 3,17β-hydroxysteroid dehydrogenase gene in Comamonas testosteroni ATCC11996. Comamonas testosteroni is able to catabolize a variety of steroids and polycyclic aromatic hydrocarbons and might be used in the bioremediation of contaminated environments. 3,17β-Hydroxysteroid dehydrogenase (3,17β-HSD) from C. testosteroni is a member of the short-chain dehydrogenase/reductase (SDR) superfamily and a key enzyme in steroid degradation. The genome of C. testosteroni ATCC11996 was sequenced in our previous work. In addition to the gene coding for 3,17β-HSD (βhsd), a novel transcriptional repressor phaR gene (phaR) which locates 2290 bp upstream of the βhsd gene was found. PhaR knock-out mutants of C. testosteroni were prepared and shown to grow better than wild-type C. testosteroni in the presence of 1 mM testosterone, 0.5 mM estradiol or 0.5 mM cholesterol in both Standard 1 Nutrient (SIN) medium and 1:10 diluted SIN medium. After 1 mM testosterone induction, 3,17β-HSD expression in the mutant was 2.5 times higher than in wild type C. testosteroni. Accordingly, PhaR is a repressor that controls 3,17β-HSD expression. Moreover, phaR knock-out mutants grow at higher rates and produce more protein in the presence of steroids as carbon source. However, ELISA results showed that 0.5 mM estradiol and cholesterol could not induce βhsd gene expression in both wild-type and mutant C. testosteroni. Probably, in addition to the βhsd gene, PhaR regulates some other genes that relate to steroid degradation. The genes coding for PhaR and 3,17β-HSD together with their promoter domains were cloned into plasmids pK18 and pUC19. Escherichia coli HB101 was co-transformed with these plasmids. The results suggest that PhaR is a repressor, which might bind on a special βhsd promoter domain (214 bp). A 2509 bp DNA fragment that contained a putative promoter for the βhsd gene (without the phaR gene) was cloned into plasmid pUC2.5-3. The plasmid was transformed into HB101 (E. coli) and induced with testosterone. As a result, 3,17β-HSD expression was at a high level, but could not be further enhanced by testosterone. Taken together, phaR knock-out mutants have better ability to degrade steroids than wild-type C. testosteroni ATCC11996 and might therefore be used in bioremediation. 23517474 Cations Bind Only Weakly to Amides in Aqueous Solutions. We investigated salt interactions with butyramide as a simple mimic of cation interactions with protein backbones. The experiments were performed in aqueous metal chloride solutions using two spectroscopic techniques. In the first, which provided information about contact pair formation, the response of the amide I band to the nature and concentration of salt was monitored in bulk aqueous solutions via attenuated total reflection Fourier transform infrared spectroscopy. It was found that molar concentrations of well-hydrated metal cations (Ca(2+), Mg(2+), Li(+)) led to the rise of a peak assigned to metal cation-bound amides (1645 cm(-1)) and a decrease in the peak associated with purely water-bound amides (1620 cm(-1)). In a complementary set of experiments, the effect of cation identity and concentration was investigated at the air/butyramide/water interface via vibrational sum frequency spectroscopy. In these studies, metal ion-amide binding led to the ordering of the adjacent water layer. Such experiments were sensitive to the interfacial partitioning of cations in either a contact pair with the amide or as a solvent separated pair. In both experiments, the ordering of the interactions of the cations was: Ca(2+) > Mg(2+) > Li(+) > Na(+) ≈ K(+). This is a direct cationic Hofmeister series. Even for Ca(2+), however, the apparent equilibrium dissociation constant of the cation with the amide carbonyl oxygen was no tighter than ∼8.5 M. For Na(+) and K(+), no evidence was found for any binding. As such, the interactions of metal cations with amides are far weaker than the analogous binding of weakly hydrated anions. 23450752 Enantiomeric separation of racemic 4-aryl-1,4-dihydropyridines and 4-aryl-1,2,3,4-tetrahydropyrimidines on a chiral tetraproline stationary phase. The chromatographic chiral resolution of 4-aryl-1,4-dihydropyridines (1-32), 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines (33-38), and 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines (39-41) was studied on a tetraproline-immobilized chiral column synthesized in our lab. This tetraproline chiral stationary phase can resolve most of these compounds. The 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines (33-38) and 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines (39-41) were more efficiently resolved than the racemic 4-aryl-1,4-dihydropyridines on the tetraproline chiralstationary phase. Analytes with 5,5-dimethyl groups (39-41) were less efficiently resolved than analytes without 5,5-dimethyl substituents (1-16). The 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines (39-41) without a sulfur atom were much more efficiently resolved than 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines (33-38). No obvious electronic effects on the resolution of any of these analytes (1-41) were observed on the tetraproline chiral stationary phase. The tetraproline chiral stationary phase separated enantiomers mainly via hydrogen bonding interactions. 23292768 Microwave spectroscopic and atoms in molecules theoretical investigations on the Ar···propargyl alcohol complex: Ar···H-O, Ar···π, and Ar···C interactions. The structure of the Ar···propargyl alcohol (Ar···PA) complex is determined from the rotational spectra of the parent complex and its two deuterated isotopologues, namely Ar···PA-D(OD) and Ar···PA-D(CD). The spectra confirm a geometry in which PA exists in the gauche form with Ar located in between -OH and -C≡C-H groups. All a, b and c types of transitions show small splitting due to some large-amplitude motion dominated by C-OH torsion, as in the monomer. Splittings in a- and b-type transitions are of the order of a few kilohertz, whereas splitting in the c-type transitions is relatively larger (0.9-2.6 MHz) and decreases in the order Ar···PA>Ar···PA-D(CD)>Ar···PA-D(OD). The assignments are well supported by ab initio calculations. Atoms in molecules (AIM) and electrostatic potential calculations are used to explore the nature of the interactions in this complex. AIM calculations not only reveal the expected O-H···Ar and π···Ar interactions in the Ar···gauche-PA complex, but also novel C···Ar (of CH2OH group) and O-H···Ar interactions in the Ar···trans-PA complex. Similar interactions are also present in the Ar···methanol complex. 23002087 Arterial stiffness is inversely related to plasma adiponectin levels in young normotensive patients with type 1 diabetes. OBJECTIVE This study investigated the association between arterial stiffness and plasma adiponectin in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Participants were normotensive patients with type 1 diabetes who were up to age 40 years. Subjects on statins with macrovascular disease or overt nephropathy were excluded. Large artery stiffness was assessed by measurement of carotid-femoral pulse wave velocity (PWV), whereas plasma adiponectin was measured by radioimmunoassay. RESULTS Data from 80 patients (age 27.1 ± 6.1 years, BMI 24.2 ± 3.1 kg/m(2), HbA(1c) 7.5 ± 1.6%, 39 men, adiponectin 13.9 ± 6.7 μg/mL, and PWV 5.6 ± 0.9 m/s) were analyzed. Log adiponectin inversely correlated with age-adjusted PWV (r = -0.291, P = 0.009) and waist circumference (r = -0.427, P < 0.001). In a fully adjusted model, age, expiration/inspiration index, and log adiponectin were independently associated with PWV, explaining 39.6% of its variance. CONCLUSIONS Arterial stiffness is inversely related to adiponectin concentration in young patients with type 1 diabetes without major complications. 23192982 MLL histone methylases regulate expression of HDLR-SR-B1 in presence of estrogen and control plasma cholesterol in vivo. High-density lipoprotein receptors scavenger receptor class B type I [HDLR-SR-B1 (SR-B1)] is a key player in reverse cholesterol transport and maintaining blood cholesterol. We demonstrated that human SR-B1 is transcriptionally activated by 17β-estradiol (E2) in HEPG2 and JAR cells. SR-B1 promoter contains multiple estrogen response elements (ERE half-sites) along with some Sp1 binding sites. Knockdown of estrogen receptor (ER)α and ERβ down-regulated E2-induced SR-B1 expression. ERs were bound to SR-B1 promoter EREs in an E2-dependent manner. Along with ERs, mixed-lineage leukemia (MLL) histone methylases, especially MLL1 and MLL2, play key roles in E2-mediated SR-B1 activation. MLL1 and MLL2 bind to SR-B1 promoter in an E2-dependent manner and control the assembly of transcription pre-initiation complex and RNA polymerase II (RNAPII) recruitment. ERs and MLLs play critical roles in determining the cholesterol uptake by steroidogenic tissues/cells, and their knockdown suppressed the E2-induced cholesterol uptake efficiencies of the cells. Intriguingly, MLL2 knockdown in mice resulted in a 33% increase in plasma cholesterol level and also reduced SR-B1 expression in mice liver, demonstrating its crucial functions in controlling plasma cholesterol in vivo. 23172038 Predicting isosteric heats for gas adsorption. A method for predicting the isosteric heat of gas adsorption on solid materials is developed which requires the measurement of a single isotherm - where previous methods, such as the Clausius-Clapeyron approach, require either multiple isotherms or complex calorimetric measurement. The Tóth potential function, stemming from the Polanyi potential function, is evaluated using the Langmuir and Tóth isotherm equations to generate new equations for the isosteric heat. These new isosteric heat equations share common parameters with the isotherm equations and are determined from isotherm fitting. This method is demonstrated in the literature for gas adsorption onto solid adsorbates including zeolites of various surface charge character and non-porous rutile phase titanium dioxide. Predictions are made using the new isosteric heat equations and then compared to calorimetric data. 23087261 Lysine 48-linked polyubiquitination of organic anion transporter-1 is essential for its protein kinase C-regulated endocytosis. Organic anion transporter-1 (OAT1) mediates the body's disposition of a diverse array of environmental toxins and clinically important drugs. Therefore, understanding the regulation of this transporter has profound clinical significance. We had previously established that OAT1 undergoes constitutive internalization from and recycling back to the cell surface and that acute activation of protein kinase C (PKC) inhibits OAT1 activity by reducing OAT1 cell-surface expression through accelerating its internalization from cell surface to intracellular compartments. However, the underlying mechanisms are poorly understood. In the current study, we provide novel evidence that acute activation of PKC significantly enhances OAT1 ubiquitination both in vitro and ex vivo. We further show that ubiquitination of cell-surface OAT1 increases in cells transfected with dominant negative mutant of dynamin-2, a maneuver blocking OAT1 internalization, which suggests that OAT1 ubiquitination proceeds before OAT1 internalization. Mass spectroscopy has revealed that ubiquitination of OAT1 consists of polyubiquitin chains, primarily through lysine 48 linkage. Transfection of cells with the dominant negative mutant of ubiquitin Ub-K48R, which prevents the formation of Lys48-linked polyubiquitin chains, abolishes PKC-stimulated OAT1 ubiquitination and internalization. Together, our findings demonstrate for the first time that Lys48-linked polyubiquitination is essential for PKC-regulated OAT1 trafficking. 23320412 An adhesive bone marrow scaffold and bone morphogenetic-2 protein carrier for cartilage tissue engineering. A chondroitin sulfate-bone marrow (CS-BM) adhesive hydrogel was used to localize rhBMP-2 to enhance articular cartilage tissue formation. Chondrocyte pellet culture revealed that 0.1 and 1 μg/mL of rhBMP-2 enhanced sulfated-GAG content. rhBMP-2 localization within the hydrogels was investigated, and it was found that BM, CS-NHS, and rhBMP-2 levels and time affected rhBMP-2 retention. Retention was modulated from 82 to 99% over a 3-week period for the material formulations investigated. To evaluate carrier efficacy, rhBMP-2 and bovine articular chondrocytes were encapsulated within CS-BM, and biochemical evaluation revealed significant increases in total collagen production with rhBMP-2. Histological analysis revealed more robust tissue formation and greater type-II collagen production with encapsulated rhBMP-2. Subsequently, a subcutaneous culture of hydrogels revealed increased total collagen, type-II to type-I collagen ratio, and sulfated GAG in samples carrying rhBMP-2. These findings indicate the development of a multifunctional system capable of localizing rhBMP-2 to enhance repair tissue quality. 22510064 Physicochemical, pharmacokinetic and pharmacodynamic evaluations of novel ternary solid dispersion of rebamipide with poloxamer 407. This study was conducted primarily to improve the solubility of rebamipide, a poorly water-soluble anti-ulcer drug, using novel ternary solid dispersion (SD) systems and secondly to evaluate the effect of solubility enhancement on its pharmacokinetic (PK) and pharmacodynamic (PD) profile. After dissolving the three components in aqueous medium, ternary SD containing the drug, sodium hydroxide (NaOH) and PVP-VA 64 was achieved by spray drying method, which was used as primary SD. Poloxamer 407, a surfactant polymer, was incorporated in this primary SD by four different methods: co-grinding, physical mixing, melting or spray drying. SD was then characterized by dissolution test, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR). The spray dried SD of poloxamer 407 together with primary SD displayed highest dissolution rate of the drug of about 70% after 2 h. DSC, PXRD and FT-IR characterized the amorphous state and molecular dispersion of the drug in the SD. PK and PD studies in Sprague-Dawley rats revealed that the bioavailability of the drug using optimal SD was about twofold higher than that of reference product, and the irritation area of stomach was significantly reduced in the ulcer-induced rat model using optimal SD as compared to the reference product. 23265467 Sugarcane bagasse treated with hydrous ferric oxide as a potential adsorbent for the removal of As(V) from aqueous solutions. The mechanism of As(V) removal from aqueous solutions by means of hydrated ferric oxide (HFO)-treated sugarcane bagasse (SCB-HFO) (Saccharum officinarum L.) was investigated. Effects of different parameters, such as pH value, initial arsenic concentration, adsorbent dosage, contact time and ionic strength, on the As(V) adsorption were studied. The adsorption capacity of SCB-HFO for As(V) was found to be 22.1 mg/g under optimum conditions of pH 4, contact time 3h and temperature 22 °C. Initial As(V) concentration influenced the removal efficiency of SCB-HFO. The desorption of As(V) from the adsorbent was 17% when using 30% HCl and 85% with 1M NaOH solution. FTIR analyses evidenced two potential binding sites associated with carboxyl and hydroxyl groups which are responsible for As(V) removal. Adsorption, surface precipitation, ion exchange and complexation can be suggested as mechanisms for the As(V) removal from the solution phase onto the surface of SCB-HFO. 23147567 Uptake and toxicity of polycyclic aromatic hydrocarbons in terrestrial springtails--studying bioconcentration kinetics and linking toxicity to chemical activity. Passive dosing applies a polymer loaded with test compound(s) to establish and maintain constant exposure in laboratory experiments. Passive dosing with the silicone poly(dimethylsiloxane) was used to control exposure of the terrestrial springtail Folsomia candida to six polycyclic aromatic hydrocarbons (PAHs) in bioconcentration and toxicity experiments. Folsomia candida could move freely on the PAH-loaded silicone, resulting in exposure via air and direct contact. The bioconcentration kinetics indicated efficient uptake of naphthalene, anthracene, and pyrene through air and (near) equilibrium partitioning of these PAHs to lipids and possibly the waxy layer of the springtail cuticle. Toxicities of naphthalene, phenanthrene, and pyrene were related to chemical activity, which quantifies the energetic level and drives spontaneous processes including diffusive biouptake. Chemical activity-response relationships yielded effective lethal chemical activities (La50s) well within the expected range for baseline toxicity (0.01-0.1). Effective lethal body burdens for naphthalene and pyrene exceeded the expected range of 2 to 8 mmol kg(-1) fresh weight, which again indicated the waxy layer to be a sorbing phase. Finally, chemical activities were converted into equilibrium partitioning concentrations in lipids yielding effective lethal concentrations for naphthalene and phenanthrene in good correspondence with the lethal membrane burden for baseline toxicity (40-160 mmol kg(-1) lipid). Passive dosing was a practical approach for tightly controlling PAH exposure, which in turn provided new experimental possibilities and findings. 23500610 Pharmacokinetics and the drug-target residence time concept. The concept of drug-target residence time has been in focus in recent drug discovery literature. However, few studies consider the combined effect of pharmacokinetics (PK) and binding kinetics (BK) on the duration of effect of a drug. Using a simple model that takes both PK and BK into account, we found that prolongation of binding owing to a long drug-target residence time can only occur when the binding dissociation is slower than the PK elimination. Data for several drugs and/or drug candidates in the literature indicate that the opposite is observed, that is, they have a slower elimination compared with dissociation. These observations greatly reduce the usability of drug-target residence times for estimating the duration of effect of a drug in vivo. 23452254 TDDFT studies on the determination of the absolute configurations and chiroptical properties of Strandberg-type polyoxometalates. The electronic circular dichroism (ECD) and UV-visible absorption (UV-vis) spectra of Strandberg-type polyoxometalates (POMs) (R, R)-[(R*PO3)2M5O15](2-) (R* = CH3CH(NH3), (M = Mo, W)) have been explored using the time-dependent density functional theory (TDDFT) method. It demonstrates that the absolute configurations of chiral systems can be determined by chiroptical spectroscopic methods combined with DFT calculations. The calculated ECD spectra of the Strandberg-type molybdate were produced over the range of 3.3-6.5 eV, which are generally in agreement with the experimental spectra. In addition, the ECD spectra of (R, R)-[(R*PO3)2W5O15](2-) (R* = CH3CH(NH3)) were produced over the range of 4.5-8.5 eV. The Becke's half-and-half hybrid exchange-correlation functional (BHandHLYP) with the HF exchange fraction to 55% hybrid functional was found to well predict the excitation energies of studied systems. The origins of the ECD bands of two systems are mainly ascribed to charge-transfer (CT) transitions from oxygen atoms to metal atoms in polyanion. The results suggest that the polyanion are chiroptical chromophores. The polyanion plays a role as an optically active chromophore and contribute to the absorptions of ECD spectra. The difference of the UV-vis/ECD spectra between two systems shows that the transition metal atom significantly influences on the chiroptical properties of the studied Strandberg-type POMs. 23275110 PHEA-graft-polymethacrylate supramolecular aggregates for protein oral delivery. Salmon calcitonin (sCT) is characterized by a poor oral availability. A new copolymer, β-poly(N-2-hydroxyethyl)-graft-{N-2-ethylene[2-poly(methacrylic acid sodium salt)isobutyrate]}-d,l-aspartamide (PHEA-IB-p(MANa(+))), was designed for the oral administration of sCT through the formation of supramolecular aggregates (SAs) based on electrostatic interactions. Several sCT/PHEA-IB-p(MANa(+)) weight ratios were characterized by turbidimetry, DLS, zeta potential, and microscopy analysis. After the incubation of sCT/PHEA-IB-p(MANa(+)) complex with digestive enzymes, 10% (w/w) of loaded sCT was released in the native form. In vitro investigation was carried out to determine the copolymer effect on the permeability of sCT in Caco-2 cell monolayers. sCT pharmacokinetic profile and the pharmacodynamic effect on calcium plasma level were determined following an oral administration of the lead sCT/PHEA-IB-p(MANa(+)) SA (1/5 ratio) in rats. The SA yielded a marked prolongation of the sCT lowering calcium effect. The maximum decrease, 35% with respect the basal calcium plasma level at time 0h, was achieved after 4h post-administration, and after 7h, a decrease of 20% was still present. Differently, sCT yielded a transient calcium decrease that was completely restored after 5h. The higher bioavailability of sCT administered as SA was confirmed by the pharmacokinetic studies. In fact, the AUC and the Cmax were about 15 times higher for the sCT formulated as SA than the free sCT. This study indicates the potentials of PHEA-IB-p(MANa(+)) as carrier of sCT for oral delivery. 23294277 Hedgehog pathway inhibitors: a patent review (2009--present). INTRODUCTION: The hedgehog (Hh) pathway is a developmental signaling pathway that plays a key role in directing cellular growth and tissue patterning during embryonic development. Dysregulation of Hh signaling has been linked to the development of a variety of human tumors, and numerous drug development programs in both academia and industry are actively exploring inhibitors of the pathway as anti-cancer agents. AREAS COVERED: This review surveys the recent patent literature (2009 - 2012) for Hh pathway inhibitors as treatments for a variety of human malignancies. EXPERT OPINION: To date, all of the pathway inhibitors that have entered clinical trials and the majority of compounds identified via high-throughput screens target smoothened (Smo), a transmembrane protein that is essential for pathway signaling. While these compounds have shown initial promise in preclinical and clinical trials, several mechanisms of resistance to Smo inhibitors have been identified. Even with this knowledge, the majority of small-molecule pathway inhibitors disclosed in the recent patent literature directly target Smo. The continued identification of Hh pathway inhibitors that function either upstream or downstream is warranted not only to combat these emerging resistance mechanisms, but also to help elucidate the various cellular mechanisms that control both normal and oncogenic pathway signaling. 22658648 Chronic treatment with myo-inositol reduces white adipose tissue accretion and improves insulin sensitivity in female mice. Type 2 diabetes is a complex disease characterized by a state of insulin resistance in peripheral tissues such as skeletal muscle, adipose tissue or liver. Some inositol isomers have been reported to possess insulin-mimetic activity and to be efficient in lowering blood glucose level. The aim of the present study was to assess in mice the metabolic effects of a chronic treatment with myo-inositol, the most common stereoisomer of inositol. Mice given myo-inositol treatment (0.9 or 1.2 mg g(-1) day(-1), 15 days, orally or intraperitoneally) exhibited an improved glucose tolerance due to a greater insulin sensitivity. Mice treated with myo-inositol exhibited a decreased white adipose tissue accretion (-33%, P<.005) compared with controls. The decrease in white adipose tissue deposition was due to a decrease in adipose cell volume (-33%, P<.05), while no change was noticed in total adipocyte number. In skeletal muscle, in vivo as well as ex vivo myo-inositol treatment increased protein kinase B/Akt phosphorylation under baseline and insulin-stimulated conditions, suggesting a synergistic action of myo-inositol treatment and insulin on proteins of the insulin signalling pathway. Myo-inositol could therefore constitute a viable nutritional strategy for the prevention and/or treatment of insulin resistance and type 2 diabetes. 23470079 MicroRNAs and the Heart: Small Things Do Matter. MicroRNAs are small RNA molecules and constitute a relatively novel class of gene expression regulators, found in the great majority of eukaryotic cells. Their role in human physiology and pathology is actively being researched with new exciting discoveries continuously coming to the forefront. MicroRNAs play a crucial role in the biogenesis and function of the cardiovascular system and act as important regulators of various metabolic and signaling pathways in cardiovascular disease. In this review there will be a summary on current knowledge about the expression, regulation and function of microRNAs in the most common diseases of the cardiovascular system as well as a presentation of and discussion about their promising future role as new biomarkers and therapeutic targets. 23265899 Synthesis of DNA oligonucleotides containing C5-ethynylbenzenesulfonamide-modified nucleotides (EBNA) by polymerases towards the construction of base functionalized nucleic acids. C5-Ethynylbenzenesulfonamide-modified nucleotide (EBNA) was investigated as substrate of various DNA polymerases. The experiments revealed that KOD, Phusion and Klenow DNA polymerases successfully accepted EBNA-T nucleotide as a substrate and yielded the fully extended DNA. KOD DNA polymerase was found to be the most efficient enzyme to furnish EBNA-T containing DNA in good yields. Phusion DNA polymerase efficiently amplified the template containing EBNA-T nucleotides by PCR. 23589462 (13) C-Detected Through-Bond Correlation Experiments for Protein Resonance Assignment by Ultra-Fast MAS Solid-State NMR. We present two sequences which combine ((1) H,(15) N) and ((15) N,(13) C) selective cross-polarization steps with an efficient variant of the J-based homonuclear transfer scheme, in which a spin-state-selective (S(3) E) block is incorporated to improve both resolution and sensitivity in the direct (13) C dimension. We propose these two sequences as a part of a suite of four N-C correlation experiments allowing for the assignment of protein backbone resonances in the solid state. We illustrate these experiments under ultra-fast magic angle spinning conditions on two samples of microcrystalline dimeric human superoxide dismutase (SOD, 153×2 amino acids), in its diamagnetic ("empty", Zn(II) ) and paramagnetic (Cu(II) , Zn(II) ) states. 23290262 Alkyladenine DNA glycosylase (AAG) localizes to mitochondria and interacts with mitochondrial single-stranded binding protein (mtSSB). Due to a harsh environment mitochondrial genomes accumulate high levels of DNA damage, in particular oxidation, hydrolytic deamination, and alkylation adducts. While repair of alkylated bases in nuclear DNA has been explored in detail, much less is known about the repair of DNA alkylation damage in mitochondria. Alkyladenine DNA glycosylase (AAG) recognizes and removes numerous alkylated bases, but to date AAG has only been detected in the nucleus, even though mammalian mitochondria are known to repair DNA lesions that are specific substrates of AAG. Here we use immunofluorescence to show that AAG localizes to mitochondria, and we find that native AAG is present in purified human mitochondrial extracts, as well as that exposure to alkylating agent promotes AAG accumulation in the mitochondria. We identify mitochondrial single-stranded binding protein (mtSSB) as a novel interacting partner of AAG; interaction between mtSSB and AAG is direct and increases upon methyl methanesulfonate (MMS) treatment. The consequence of this interaction is specific inhibition of AAG glycosylase activity in the context of a single-stranded DNA (ssDNA), but not a double-stranded DNA (dsDNA) substrate. By inhibiting AAG-initiated processing of damaged bases, mtSSB potentially prevents formation of DNA breaks in ssDNA, ensuring that base removal primarily occurs in dsDNA. In summary, our findings suggest the existence of AAG-initiated BER in mitochondria and further support a role for mtSSB in DNA repair. 23535334 Impact of cell wall composition on maize resistance to pests and diseases. In cereals, the primary cell wall is built of a skeleton of cellulosic microfibrils embedded in a matrix of hemicelluloses and smaller amounts of pectins, glycoproteins and hydroxycinnamates. Later, during secondary wall development, p-coumaryl, coniferyl and sinapyl alcohols are copolymerized to form mixed lignins. Several of these cell wall components show a determinative role in maize resistance to pest and diseases. However, defense mechanisms are very complex and vary among the same plant species, different tissues or even the same tissue at different developmental stages. Thus, it is important to highlight that the role of the cell wall components needs to be tested in diverse genotypes and specific tissues where the feeding or attacking by the pathogen takes place. Understanding the role of cell wall constituents as defense mechanisms may allow modifications of crops to withstand pests and diseases. 23438860 A network model of the molecular organization of chromatin in Drosophila. Chromatin governs gene regulation and genome maintenance, yet a substantial fraction of the chromatin proteome is still unexplored. Moreover, a global model of the chromatin protein network is lacking. By screening >100 candidates we identify 42 Drosophila proteins that were not previously associated with chromatin, which all display specific genomic binding patterns. Bayesian network modeling of the binding profiles of these and 70 known chromatin components yields a detailed blueprint of the in vivo chromatin protein network. We demonstrate functional compartmentalization of this network, and predict functions for most of the previously unknown chromatin proteins, including roles in DNA replication and repair, and gene activation and repression. 23143674 Using chimeric mice with humanized livers to predict human drug metabolism and a drug-drug interaction. Interspecies differences in drug metabolism have made it difficult to use preclinical animal testing data to predict the drug metabolites or potential drug-drug interactions (DDIs) that will occur in humans. Although chimeric mice with humanized livers can produce known human metabolites for test substrates, we do not know whether chimeric mice can be used to prospectively predict human drug metabolism or a possible DDI. Therefore, we investigated whether they could provide a more predictive assessment for clemizole, a drug in clinical development for the treatment of hepatitis C virus (HCV) infection. Our results demonstrate, for the first time, that analyses performed in chimeric mice can correctly identify the predominant human drug metabolite before human testing. The differences in the rodent and human pathways for clemizole metabolism were of importance, because the predominant human metabolite was found to have synergistic anti-HCV activity. Moreover, studies in chimeric mice also correctly predicted that a DDI would occur in humans when clemizole was coadministered with a CYP3A4 inhibitor. These results demonstrate that using chimeric mice can improve the quality of preclinical drug assessment. 23210481 Development of vizantin, a safe immunostimulant, based on the structure-activity relationship of trehalose-6,6'-dicorynomycolate. Vizantin, 6,6'-bis-O-(3-nonyldodecanoyl)-α,α'-trehalose, was developed as a safe immunostimulator on the basis of a structure-activity relationship (SAR) study with trehalose 6,6'-dicorynomycolate (TDCM). It was possible to synthesize vizantin on a large scale more easily than in the case of TDCM, and the compound exhibited more potent prophylactic effect on experimental lung metastasis of B16-F0 melanoma cells. Because vizantin stimulated human macrophages, it is a promising candidate for clinical application. 23553677 A Localized Surface Plasmon Resonance-Based Multicolor Electrochromic Device with Electrochemically Size-Controlled Silver Nanoparticles. The first localized surface plasmon resonance (LSPR)-based multicolor electrochromic device with reversible five optical states is demonstrated. In this device, the size of deposited silver nanoparticles is electrochemically controlled using a voltage-step method in which two different voltages are applied successively. The electrochemically size-controlled silver nanoparticles enable a reversible multiple-color change by a shift of the LSPR band. 22980124 Something's got to give: psychiatric disease on the rise and novel drug development on the decline. Research and development of drugs for psychiatric disease is currently in a state of decline. Despite the increasing prevalence and healthcare costs of psychiatric disease, the costly and unpredictable drug development process has led to decreased public and investor confidence in the abilities of companies to develop safe and efficacious drugs. Industrial research in this disease area is therefore being scaled back owing to various scientific, corporate, financial and legal factors. This review will consider how these factors contribute to the current status of psychiatric drug development and offer several avenues forward to spur reinvestment in this type of research. Such a shift is needed to reduce the burden psychiatric disease imposes on the healthcare system and its patient populations. 23544463 Aqua Mediated Synthesis of Bio-active Compounds. Recently the aqueous medium has attracted the interest of organic chemists, and many. Moreover, in the past 20 years, the drug-discovery process has undergone extraordinary changes, and high-throughput biological screening of potential drug candidates has led to an ever-increasing demand for novel drug-like compounds. Noteworthy advantages were observed during the course of study on aqua mediated synthesis of compounds of medicinal importance. The established advantages of water as a solvent for reactions are, water is the most abundant and available resource on the planet and many biochemical processes occur in aqueous medium. This review will focus on describing new developments in the application of water in medicinal chemistry for the synthesis of bio-active compounds possessing various biological properties. 23437766 Discovery of Novel Dual Inhibitors of the Wild-Type and the Most Prevalent Drug-Resistant Mutant, S31N, of the M2 Proton Channel from Influenza A Virus. Anti-influenza drugs, amantadine and rimantadine, targeting the M2 channel from influenza A virus are no longer effective because of widespread drug resistance. S31N is the predominant and amantadine-resistant M2 mutant, present in almost all of the circulating influenza A strains as well as in the pandemic 2009 H1N1 and the highly pathogenic H5N1 flu strains. Thus, there is an urgent need to develop second-generation M2 inhibitors targeting the S31N mutant. However, the S31N mutant presents a huge challenge to drug discovery, and it has been considered undruggable for several decades. Using structural information, classical medicinal chemistry approaches, and M2-specific biological testing, we discovered benzyl-substituted amantadine derivatives with activity against both S31N and WT, among which 4-(adamantan-1-ylaminomethyl)-benzene-1,3-diol (44) is the most potent dual inhibitor. These inhibitors demonstrate that S31N is a druggable target and provide a new starting point to design novel M2 inhibitors that address the problem of drug-resistant influenza A infections. 23210662 Dendronized albumin core-shell transporters with high drug loading capacity. We describe the synthesis of a core-shell biohybrid consisting of a human serum albumin (HSA) core that serves as a reservoir for lipophilic molecules and a cationized shell region consisting of ethynyl-G2.0-PAMAM or ethynyl-G3.0-PAMAM dendrons. The binding capacity of lipophilic guests was quantified applying electron paramagnetic resonance (EPR) spectroscopy, and five to six out of seven pockets were still available compared with HSA. The attachment of ethynyl-G2.0-PAMAM dendrons to HSA yielded a nontoxic core-shell macromolecule that was clearly uptaken by A549 human epithelial cells due to the presence of the dendritic PAMAM shell. Significantly higher loading of doxorubicin was observed for dendronized G2-DHSA compared with the native protein due to the availability of binding pockets of the HSA core, and interaction with the dendritic shell. Dendronized G2-DHSA-doxorubicin displayed significant cytotoxicity resulting from high drug loading and high stability under different conditions, thus demonstrating its great potential as a transporter for drug molecules. 23010695 Enantioselective apoptosis induction in histiocytic lymphoma cells and acute promyelocytic leukemia cells. The aim of this study was to identify valproic acid (VPA) analogs with a broad spectrum of anti-cancer activities and an increased apoptosis-inducing potential compared with the parent VPA, which is enrolled as histone deacetylase (HDAC) inhibitor in a large number of clinical trials. We identified a chiral VPA derivative, (S)-2-pentyl-4-pentynoic acid, previously characterized as HDAC inhibitor that induced massive programmed cell death in a strongly enantioselective manner in U937 histiocytic lymphoma cells and NB4 acute promyelocytic leukemia cells. By performing fluorescence-activated cell sorting and Western blotting analyses, we established that enantiomer (S)-2-pentyl-4-pentynoic acid has higher apoptosis-inducing potential than VPA itself. The optic antipode (R)-2-pentyl-4-pentynoic acid and VPA caused under the same conditions only a weak growth inhibition without inducing cell differentiation and apoptosis. (S)-2-pentyl-4-pentynoic acid is more apoptogenic than VPA and displays enantioselective anti-cancer properties that warrant further research regarding the mechanistic basis of its activity and its potential use in cancer therapy. 23220560 Low level prenatal exposure to methylmercury disrupts neuronal migration in the developing rat cerebral cortex. We determined the effects of low-level prenatal MeHg exposure on neuronal migration in the developing rat cerebral cortex using in utero electroporation. We used offspring rats born to dams that had been exposed to saline or various doses of MeHg (0.01 mg/kg/day, 0.1 mg/kg/day, and 1 mg/kg/day) from gestational day (GD) 11-21. Immunohistochemical examination of the brains of the offspring was conducted on postnatal day (PND) 0, PND3, and PND7. Our results showed that prenatal exposure to low levels of MeHg (0.1 mg/kg/day or 1 mg/kg/day) during the critical stage in neuronal migration resulted in migration defects of the cerebrocortical neurons in offspring rats. Importantly, our data revealed that the abnormal neuronal distribution induced by MeHg was not caused by altered proliferation of neural progenitor cells (NPCs), induction of apoptosis of NPCs and/or newborn neurons, abnormal differentiation of NPCs, and the morphological changes of radial glial scaffold, indicating that the defective neuronal positioning triggered by exposure to low-dose of MeHg is due to the impacts of MeHg on the process of neuronal migration itself. Moreover, we demonstrated that in utero exposure to low-level MeHg suppresses the expression of Rac1, Cdc42, and RhoA, which play key roles in the migration of cerebrocortical neurons during the early stage of brain development, suggesting that the MeHg-induced migratory disturbance of cerebrocortical neurons is likely associated with the Rho GTPases signal pathway. In conclusion, our results provide a novel perspective on clarifying the mechanisms underlying the impairment of neuronal migration induced by MeHg. 23362942 Chiral selective transmembrane transport of amino acids through artificial channels. Peptide-appended pillar[n]arene (n = 5, 6) derivatives have been synthesized. (1)H NMR and IR studies revealed that the molecules adopt a tubular conformation in solution and lipid bilayer membranes. Kinetic measurements using the fluorescent labeling method with lipid vesicles revealed that these molecules can efficiently mediate the transport of amino acids across lipid membranes at a very low channel-to-lipid ratio (EC(50) = 0.002 mol %). In several cases, chiral selectivity for amino acid enantiomers was achieved, which is one of the key functions of natural amino acid channels. 23584426 Combined toxicity of ferroferric oxide nanoparticles and arsenic to the ciliated protozoa Tetrahymena Pyriformis. Fe3O4 nanoparticles (NPs) have a high affinity for arsenic. As a result of this association, Fe3O4 NPs loaded with high concentration of arsenic can enter into organisms and produce locally high concentrations of arsenic, which may lead to some unexpected toxicity to aquatic organisms. The objectives of this research were to investigate the toxic effect of Fe3O4 NPs in combination with As(V). Cultured Tetrahymena pyriformis was chosen as a research model organism to evaluate the toxic effects of the combined agents. The results showed that after 24h of As(V) exposure, the median effective concentration of As(V) to T. pyriformis was 1.29mg/L. Fe3O4 NPs alone were not only non-toxic, but actually promoted the growth of T. pyriformis at the experimental doses. After 24h exposure, the cell number increased by 32.2% at an exposure level of 3mg/L Fe3O4 NPs. After 24h exposure to 1.0mg/L As(V), the survival rate increased from 60.5% in the absence of Fe3O4 NPs to 73.8% and 83.8% in the presence of 13mg/L and 19mg/L Fe3O4 NPs, respectively. However, after 30h, the combined toxic effect of As(V) and Fe3O4 NPs on T. pyriformis was significantly enhanced and the survival rates for co-exposure to 1.5mg/L As(V) and 13mg/L Fe3O4 NPs decreased from 92.3% after 18h to 45.3% after 30h. After 18h of exposure to Fe3O4 NPs alone, the intracellular ROS levels were markedly increased and achieved steady state. Compared with the control group, the intracellular ROS levels were significantly increased (2.56-fold) by the combination of 19mg/L Fe3O4 NPs and 1.0mg/L As(V). Accumulation of As(V) in T. pyriformis led to an increase in trivalent arsenics as a result of the saturation of the cellular arsenic methylation capability or/and redox reactions. These exposures also resulted in an imbalance between oxidants and antioxidants, resulting in oxidative damage and cell death. 22906569 Extracellular and intracellular anti-mutagenic effects of bile pigments in the Salmonella typhimurium reverse mutation assay. In vitro anti-genotoxic properties of bile pigments have been explored and confirmed recently. Despite these reports mechanisms to explain DNA protection by endogenous bile pigments remain unclear. Surprisingly, the quantification of cellular pigment absorption which could represent a fundamental prerequisite for intracellular (e.g., anti-mutagenic) effects, has not been explored. Therefore, we aimed to measure the amounts of un-/conjugated bilirubin as well as biliverdin absorbed into colonies of Salmonella typhimurium, utilising HPLC analyses, and to observe whether intracellular compound concentrations could predict anti-genotoxic effects. HPLC analyses confirmed that bacterial bile pigment absorption was concentration-dependent. Plate bile pigment concentrations were inversely associated with genotoxicity of all tested mutagens, irrespective of strain and test conditions. However, protection against frame-shift mutation in strain TA98 most strongly depended on the bacterial absorption of bilirubin and biliverdin, which indicates that bile pigments can protect by intercepting mutations extracellularly and specifically inhibit frame-shift mutations intracellularly. 23611538 Toward the Molecular Mechanism(s) by Which EGCG Treatment Remodels Mature Amyloid Fibrils. Protein misfolding and/or aggregation has been implicated as the cause of several human diseases, such as Alzheimer's and Parkinson's diseases and familial amyloid polyneuropathy. These maladies are referred to as amyloid diseases, named after the cross-β-sheet amyloid fibril aggregates or deposits common to these disorders. Epigallocatechin-3-gallate (EGCG), the principal polyphenol present in green tea, has been shown to be effective at preventing aggregation and is able to remodel amyloid fibrils comprising different amyloidogenic proteins, although the mechanistic underpinnings are unclear. Herein, we work toward an understanding of the molecular mechanism(s) by which EGCG remodels mature amyloid fibrils made up of Aβ1-40, IAPP8-24, or Sup35NM7-16. We show that EGCG amyloid remodeling activity in vitro is dependent on auto-oxidation of the EGCG. Oxidized and unoxidized EGCG binds to amyloid fibrils, preventing the binding of thioflavin T. This engagement of the hydrophobic binding sites in Aβ1-40, IAPP8-24, or Sup35NMAc7-16 Y→F amyloid fibrils seems to be sufficient to explain the majority of the amyloid remodeling observed by EGCG treatment, although how EGCG oxidation drives remodeling remains unclear. Oxidized EGCG molecules react with free amines within the amyloid fibril through the formation of Schiff bases, cross-linking the fibrils, which may prevent dissociation and toxicity, but these aberrant post-translational modifications do not appear to be the major driving force for amyloid remodeling by EGCG treatment. These insights into the molecular mechanism of action of EGCG provide boundary conditions for exploring amyloid remodeling in more detail. 23360142 CO and CO-releasing molecules in medicinal chemistry. Since the discovery that CO acts as a cytoprotective and homeostatic molecule, increasing research efforts have been devoted to the exploitation of its therapeutic effects. Both endogenous and exogenous CO improves experimental lung, vascular and cardiac injuries and protects against several inflammatory states. The technology is now in place to bring CO to clinical applications, but the use of the gaseous molecule poses several problems. The challenges associated with the clinical implementation of the gas have in part been answered by the development of CO-releasing molecules (CO-RMs). As stable solid forms of CO, these molecules represent an alternative to the administration of carbon monoxide (orally or by injection). In this article, we present insights into the biochemical action of CO and discuss the efficacy of CO and CO-RMs in preclinical disease models. Recent advances in the CO-RMs field are critically addressed. 23331618 4-Aminoquinoline-Triazine-Based Hybrids with Improved In Vitro Antimalarial Activity Against CQ-Sensitive and CQ-Resistant Strains of Plasmodium falciparum. A systematic chemical modification in the triazine moiety covalently attached via suitable linkers to 4-amino-7-chloroquinolines yielded a series of new 7-chloro-4-aminoquinoline-triazine hybrids exhibiting high in vitro activity against W2 (chloroquine-resistant) and D6 (chloroquine-sensitive) strains of Plasmodium falciparum without any toxicity against mammalian cell lines (Vero, LLC-PK11, HepG2). Many of the compounds (6, 8, 10, 11, 13, 14, 16, 27, 29 and 33) showed excellent potency against chloroquine sensitive and resistant strains. In particular, compounds 6, 8, 14, 16 and 29 were found to be significantly more active than chloroquine against the chloroquine-resistant strains (W2 clone) of P. falciparum. 23607869 Hierarchy of relative bond dissociation enthalpies and their use to efficiently compute accurate absolute bond dissociation enthalpies for C-h, C-C, and C-f bonds. We have used the high-level W1X-2 and G4(MP2)-6X procedures to examine the performance of a variety of computationally less demanding quantum chemistry methods for the calculation of absolute bond dissociation enthalpies (BDEs) and a hierarchy of relative bond dissociation enthalpies. These include relative bond dissociation enthalpies (RBDEs), deviations from additivity of RBDEs (DARBDEs), and deviations from pairwise additivity of RBDEs (DPARBDEs). The absolute magnitudes of these quantities decrease in the order BDE > RBDE > DARBDE > DPARBDE, and overall, theoretical procedures are better able to describe these quantities in the same order. In general, the performance of the various types of procedures improves in the order pure DFT → hybrid DFT → double-hybrid DFT → composite procedures, as expected. Overall, we find M06-L to be the best-performing pure DFT procedure and M06-2X to be the best among the hybrid DFT methods. A promising observation is that even many pure and hybrid DFT procedures give DARBDE and DPARBDE values that are reasonably accurate. This can be exploited by using reference BDEs calculated at a higher-level of theory, in combination with DARBDE or DPARBDE values obtained at a lower level, to produce BDEs and RBDEs with an accuracy that is close to the directly calculated higher-level values. Strongly π-electron-withdrawing or π-electron-donating groups, however, sometimes represent challenges to these approximation methods when the substrate contains several of these substituents. 23271742 Arsenic suppresses cell survival via Pirh2-mediated proteasomal degradation of ΔNp63 protein. Transcription factor p63, a member of the p53 family, shares a high degree of sequence similarity with p53. Because of transcription from two distinct promoters, the p63 gene encodes two isoforms, TAp63 and ΔNp63. Although TAp63 acts as a tumor suppressor, ΔNp63 functions as an oncogene and is often overexpressed in squamous cell carcinomas. Thus, therapeutic agents targeting ΔNp63 might be used to manage tumors that overexpress ΔNp63. Here we found that arsenic trioxide, a frontline agent for acute promyelocytic leukemia, inhibits ΔNp63 but not TAp63 expression in time- and dose-dependent manners. In addition, we found that arsenic trioxide decreases the stability of ΔNp63 protein via a proteasome-dependent pathway but has little effect on the level of ΔNp63 transcript. Furthermore, we found that arsenic trioxide activates the Pirh2 promoter and consequently induces Pirh2 expression. Consistent with this, we found that knockdown of Pirh2 inhibits, whereas ectopic expression of Pirh2 enhances, arsenic-induced degradation of ΔNp63 protein. Importantly, we found that knockdown of ΔNp63 sensitizes, whereas ectopic expression of ΔNp63 inhibits, growth suppression induced by arsenic. Together, these data suggest that arsenic degrades ΔNp63 protein at least in part via Pirh2-dependent proteolysis and that inhibition of ΔNp63 expression facilitates tumor cells to arsenic-induced death. 23586839 Structures of the Dehydrogenation Products of Methane Activation by 5d Transition Metal Cations. The activation of methane by gas-phase transition metal cations (M+) has been studied extensively, both experimentally and using density functional theory (DFT). Methane is exothermically dehydrogenated by several 5d metal ions to form [M,C,2H]+ and H2. However, the structure of the dehydrogenation product has not been established unambiguously. Two types of structures have been considered: a carbene structure where an intact CH2 fragment is bound to the metal (M+-CH2) and a carbyne (hydrido-methylidyne) structure with both a CH and a hydrogen bound to the metal separately (H-M+-CH). For metal ions with empty d-orbitals, an agostic interaction can occur that could influence the competition between carbene and carbyne structures. In this work, the gas phase [M,C,2H]+ (M = Ta, W, Ir, Pt) products are investigated by infrared multiple-photon dissociation (IR-MPD) spectroscopy using the Free Electron Laser for IntraCavity Experiments (FELICE). Metal cations are formed in a laser ablation source and react with methane pulsed into a reaction channel downstream. IRMPD spectra of the [M,C,2H]+ species are measured in the 300 - 3500 cm-1 spectral range by monitoring the loss of H (2H in the case of [Ir,C,2H]+). For each system, the experimental spectrum closely resembles the calculated spectrum of the lowest energy structure calculated using DFT: for Pt, a classic C2v carbene structure; for Ta and W, carbene structures that are distorted by agostic interactions; and a carbyne structure for the Ir complex. The Ir carbyne structure was not considered previously. To obtain this agreement, the calculated harmonic frequencies are scaled with a scaling factor of 0.939, which is fairly low and can be attributed to the strong redshift induced by the IR multiple-photon excitation process of these small molecules. These four-atomic species are among the smallest systems studied by IR-FEL based IR-MPD spectroscopy and their spectra demonstrate the power of IR spectroscopy in resolving long-standing chemical questions. 23146871 Manganese transport via the transferrin mechanism. Excessive manganese (Mn) uptake by brain cells, particularly in regions like the basal ganglia, can lead to toxicity. Mn(2+) is transported into cells via a number of mechanisms, while Mn(3+) is believed to be transported similarly to iron (Fe) via the transferrin (Tf) mechanism. Cellular Mn uptake is therefore determined by the activity of the mechanisms transporting Mn into each type of cell and by the amounts of Mn(2+), Mn(3+) and their complexes to which these cells are exposed; this complicates understanding the contributions of each transporter to Mn toxicity. While uptake of Fe(3+) via the Tf mechanism is well understood, uptake of Mn(3+) via this mechanism has not been systematically studied. The stability of the Mn(3+)Tf complex allowed us to form and purify this complex and label it with a fluorescent (Alexa green) tag. Using purified and labeled Mn(3+)Tf and biophysical tools, we have developed a novel approach to study Mn(3+)Tf transport independently of other Mn transport mechanisms. This approach was used to compare the uptake of Mn(3+)Tf into neuronal cell lines with published descriptions of Fe(3+) uptake via the Tf mechanism, and to obtain quantitative information on Mn uptake via the Tf mechanism. Results confirm that in these cell lines significant Mn(3+) is transported by the Tf mechanism similarly to Fe(3+)Tf transport; although Mn(3+)Tf transport is markedly slower than other Mn transport mechanisms. This novel approach may prove useful for studying Mn toxicity in other systems and cell types. 22698957 An optogenetic approach in epilepsy. Optogenetic tools comprise a variety of different light-sensitive proteins from single-cell organisms that can be expressed in mammalian neurons and effectively control their excitability. Two main classes of optogenetic tools allow to either depolarize or hyperpolarize, and respectively generate or inhibit action potentials in selective populations of neurons. This opens unprecedented possibilities for delineating the role of certain neuronal populations in brain processing and diseases. Moreover, optogenetics may be considered for developing potential treatment strategies for brain diseases, particularly for excitability disorders such as epilepsy. Expression of the inhibitory halorhodopsin NpHR in hippocampal principal cells has been recently used as a tool to effectively control chemically and electrically induced epileptiform activity in slice preparations, and to reduce in vivo spiking induced by tetanus toxin injection in the motor cortex. In this review we give a comprehensive summary of what has been achieved so far in the field of epilepsy using optogenetics, and discuss some of the possible strategies that could be envisaged in the future. We also point out some of the challenges and pitfalls in relation to possible outcomes of using optogenetics for controlling network excitability, and associated brain diseases. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'. 23292753 Fluorescent live-cell imaging of metabolically incorporated unnatural cyclopropene-mannosamine derivatives. Sugar coated: We recently developed methylcyclopropenes as low-molecular-weight tetrazine coupling partners. Here, we demonstrate that methylcyclopropenes can meet the stringent steric demands required for metabolic imaging of unnatural mannosamines on live cells. Using sequential azide-alkyne chemistry, we also demonstrate multicolor imaging of two different metabolically incorporated unnatural sugars. 23567046 Recent advances in theranostic nanocarriers of doxorubicin based on iron oxide and gold nanoparticles. Hybrid (organic/inorganic) nanoparticles emerged as a simple solution to build "theranostic" systems. Due to their physical properties, superparamagnetic iron oxide nanoparticles (SPIONs) and plasmonic gold nanoparticles (Au-NPs) are extensively studied as a part of diagnostic and therapeutic strategies in cancer treatments. They can be used as agents for in vitro or in vivo imaging, for magnetic drug targeting and/or thermal therapy. Their functionalization with organic shells enhances their potential performance in tumor targeting and drug delivery. The advances in such hybrid nanocarriers are well illustrated with the example of the anticancer drug doxorubicin (DOX). The aim of this review is to give a multidisciplinary overview of such smart nanosystems loaded with DOX, based on examples taken from recent publications. From a physico-chemical point of view, we discuss the choices for the strategies for loading DOX and the consequences on drug release. From a biological point of view, we analyze the in vitro and in vivo assays concerning tumor imaging, targeted drug delivery and anticancer efficiency. Future opportunities and challenges are also addressed. 23638985 Ginsenjilinol, a new protopanaxatriol-type saponin with inhibitory activity on LPS-activated NO production in macrophage RAW 264.7 cells from the roots and rhizomes of Panax ginseng. One new dammarane triterpene saponin named ginsenjilinol (1) was isolated from the roots and rhizomes of Panax ginseng C.A. Mey., together with two known saponins ginsenoside Rf (2) and ginsenoside Re5 ( = panajaponol A, 3). Based on IR, HR-ESI-MS, and 1D as well as 2D NMR ((1)H-(1)H COSY, NOESY, HSQC, and HMBC) spectral data, the chemical structure of the new saponin was elucidated as 3β,12β,20S,26-tetrahydroxydammar-24E-en-6α-O-β-d-glucopyranosyl-(1 → 2)-O-β-d-glucopyranoside. The ability of the isolated saponins to inhibit nitric oxide production by lipopolysaccharide-activated RAW 264.7 cells was also assayed. All of the isolated saponins exhibited the significant activity in a concentration-dependent manner at concentrations of 60-200 μM with the half maximal inhibitory concentration (IC50) values of 70.96 ± 2.05 μM for 1, 74.14 ± 2.65 μM for 2, and 79.83 ± 1.78 μM for 3, respectively, whereas indomethacin had an IC50 of 63.75 ± 3.33 μM as a positive control drug. 23535360 Reactivity of Chemical Sensitizers Toward Amino Acids In Cellulo Plays a Role in the Activation of the Nrf2-ARE Pathway in Human Monocyte Dendritic Cells and the THP-1 Cell Line. Allergic contact dermatitis resulting from skin sensitization is an inflammatory skin disease linked to the use of chemicals termed haptens. Chemical reactivity is necessary for a chemical to be a sensitizer, allowing both covalent binding to proteins and maturation of dendritic cells (DCs) by mimicking "danger signals." The aim of this study was to evaluate how the reactivity of chemical sensitizers toward amino acids translates into a biological response using the activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway, which was assessed by the induction of three Nrf2 target genes (ho-1, nqo1, and il-8) and Nrf2 protein accumulation. Nrf2 activation is known to play a role in numerous detoxification mechanisms that could regulate danger signal outcomes in myeloid cells. Monocyte-derived DCs and THP-1 cells were exposed to (a) haptens with cysteine, lysine, or cysteine/lysine reactivity, (b) pro-/prehaptens, and (c) nonsensitizing molecules with reducing or oxidative properties (17 molecules in total). Chemicals were classified as "Nrf2 pathway activators" when at least two Nrf2 target genes associated with Nrf2 protein expression were induced. Results showed that most chemical sensitizers having cysteine and cysteine/lysine affinities were inducers of the Nrf2 pathway in both cell models, whereas lysine-reactive chemicals were less efficient. In THP-1 cells, the Nrf2 pathway was also activated by pro-/prehaptens. Regression analysis revealed that ho-1 and nqo1 expressions were found to be associated with chemical sensitizer reactivity to cysteine, providing evidence of the importance of chemical reactivity, as a part of danger signals, in DC biology. 23411315 Near-infrared hyperspectral imaging and partial least squares regression for rapid and reagentless determination of Enterobacteriaceae on chicken fillets. Bacterial pathogens are the main culprits for outbreaks of food-borne illnesses. This study aimed to use the hyperspectral imaging technique as a non-destructive tool for quantitative and direct determination of Enterobacteriaceae loads on chicken fillets. Partial least squares regression (PLSR) models were established and the best model using full wavelengths was obtained in the spectral range 930-1450 nm with coefficients of determination R(2)≥ 0.82 and root mean squared errors (RMSEs) ≤ 0.47 log(10)CFUg(-1). In further development of simplified models, second derivative spectra and weighted PLS regression coefficients (BW) were utilised to select important wavelengths. However, the three wavelengths (930, 1121 and 1345 nm) selected from BW were competent and more preferred for predicting Enterobacteriaceae loads with R(2) of 0.89, 0.86 and 0.87 and RMSEs of 0.33, 0.40 and 0.45 log(10)CFUg(-1) for calibration, cross-validation and prediction, respectively. Besides, the constructed prediction map provided the distribution of Enterobacteriaceae bacteria on chicken fillets, which cannot be achieved by conventional methods. It was demonstrated that hyperspectral imaging is a potential tool for determining food sanitation and detecting bacterial pathogens on food matrix without using complicated laboratory regimes. 23583641 Seasonal variation in the toxicological properties of size-segregated indoor and outdoor air particulate matter. Ambient air particulate matter (PM) as well as microbial contaminants in the indoor air are known to cause severe adverse health effects. It has been shown that there is a clear seasonal variation in the potency of outdoor air particles to evoke inflammation and cytotoxicity. However, the role of outdoor sources in the indoor air quality, especially on its toxicological properties, remains largely unknown. In this study, we collected size segregated (PM10-2.5, PM2.5-0.2 and PM0.2) particulate samples with a high volume cascade impactor (HVCI) on polyurethane foam and fluoropore membrane filters. The samples were collected during four different seasons simultaneously from indoor and outdoor air. Thereafter, the samples were weighed and extracted with methanol from the filters before undergoing toxicological analyses. Mouse macrophages (RAW264.7) were exposed to particulate sample doses of 50, 150 and 300μg/ml for 24h. Thereafter, the levels of the proinflammatory cytokine (TNF-α), NO-production, cytotoxicity (MTT-test) and changes in the cell cycle (SubG1, G1, S and G2/M phases) were investigated. PM10-2.5 particles evoked the highest inflammatory and cytotoxic responses. Instead, PM2.5-0.2 samples exerted the greatest effect on apoptotic activity in the macrophages. With respect to the outdoor air samples, particles collected during warm seasons had a stronger potency to induce inflammatory and cytotoxic responses, whereas no such clear effect was seen with the corresponding indoor air samples. Outdoor air samples were associated with higher inflammatory potential, whereas indoor air samples had overall higher cytotoxic properties. This indicates that the outdoor air has a limited influence on the indoor air quality in a modern house. Thus, the indoor sources dominate the toxicological responses obtained from samples collected inside house. 23295943 Apoptotic transcriptional profile remains activated in late remodeled left ventricle after myocardial infarction in swine infarcted hearts with preserved ejection fraction. Apoptosis is involved in both acute and chronic loss of cardiomyocytes after myocardial infarction (MI). To date, the pathophysiological significance of an apoptotic transcriptional profile activated in the post-ischemic remodeled myocardium, in the absence of hemodynamic factors secondary to left ventricular (LV) dysfunction, still remains to be determined. The mRNA expression of pro- and anti-apoptotic factors was determined in a swine model of non-reperfused MI with preserved LV ejection fraction. The extent of cell death was evaluated by histological analysis. Male adult farm pigs with MI (n=5), induced by permanent surgical ligation of the left anterior descending coronary artery and sham-operated adult farm pigs as control (n=7) were studied. Tissue samples were collected from the border (BZ) and remote zone (RZ) of the infarcted area to identify possible regional effects. After 4 weeks post-MI, the infarct size was 13±1% of the LV wall mass in absence of contractile dysfunction. In BZ, there was increased mRNA expression of Casp-3 (BZ vs Controls: 0.51±0.15 vs 1.39±0.04, p<0.001), a significant decrease in Bcl-2 (by 63%), associated with an increase in apoptotic cells, as revealed by TUNEL staining and cleaved-Casp-3 presence. In contrast, in the RZ there was a significant reduction of pro-apoptotic factors compared to BZ (by 80% for Casp-3), in presence of scattered apoptotic cells, increased gene expression of Hsp72 (1.82±0.21 vs 1.34±0.08, p=0.037) and iNOS (1.51±0.14 vs 1.19±0.05, p<0.05) compared to control. In conclusion, the LV distribution of apoptotic transcriptional profile revealed that apoptotic cell death is highly detectable in BZ, possibly explaining the local abnormalities of myocardial cell survival in a porcine model of MI with normal overall function. 23402270 Binding between proteins and cationic spherical polyelectrolyte brushes: effect of pH, ionic strength, and stoichiometry. Cationic spherical polyelectrolyte brushes (SPBs) were synthesized by photoemulsion polymerization, consisting of a polystyrene core with a diameter around 80 nm and a poly(2-aminoethylmethacrylate hydrochloride) (PAEMH) shell with a thickness from 10 to 50 nm densely grafted on the core surface. The binding of various proteins onto SPBs was observed by turbidimetric titration, dynamic light scattering (DLS), zeta potential, and isothermal titration calorimetry (ITC). The binding, aggregation, and releasing of proteins by SPB can be tuned by modulating pH. The pH regions of binding for bovine serum albumin (BSA), β-lactoglobulin (BLG), and papain onto SPBs are markedly different and tunable by ionic strength and stoichiometry between protein and SPB. Binding energetics, affinity, and amount of various proteins onto cationic SPBs were determined by ITC. These findings lay the foundation for SPB applications in the protein purification and selective immobilization of different proteins, enzymes, and antibodies. 22616577 Cytotoxicity of semisynthetic acetal triterpenes from one-pot vicinal diol cleavage following by lactolization: Reaction promoted by NaIO4/SiO2 gel in THF. In situ C-C bond cleavage of vicinal diol following by the lactolisation resulted from separated treatment of Arjunolic acid (1), 24-hydroxytormentic acid (2) and 3-O-β-D-glucopyranosylsitosterol (3) with sodium periodate and silica gel in dried THF according to the strategic position of hydroxyl functions in the molecule. The reaction led to a lactol pentacyclic triterpenes 1A, 2A and a bicyclotriacetal of β-sitosterol 3A. These products were further acetylated and the cytotoxicity of all molecules was evaluated against human fibrosarcoma HT1080 cancer cells lines. 23030680 In vitro metabolism of the 5-hydroxytryptamine1B receptor antagonist elzasonan. The metabolism of elzasonan has been examined in vitro using hepatic microsomes from human and recombinant heterologously expressed P450 enzymes (rCYP). Metabolism occurs primarily via oxidative N-demethylation to form M4 and oxidation reactions to form elzasonan N-oxide (M5) and 5-hydroxyelzasonan metabolite (M3). Additionally, elzasonan was shown to be metabolized to the novel cyclized indole metabolite (M6) which undergoes subsequent oxidation to form the iminium ion metabolite (M3a). The rCYP data was normalized relative to the levels of each CYP form in native human liver microsomes to better assess the contribution of each rCYP in the metabolism of elzasonan. Results demonstrated the involvement of CYP3A4 in the pathways leading to M3a, M3, M5 and M6 and CYP2C8 in the formation of M4. Kinetic constants for the formation of M3 were determined and correlation and inhibition studies suggested that CYP3A4 is primarily responsible for the formation of M3 and CYP2C19 plays a very minor role in its formation. Cytochrome b5 has shown to be an essential component in P450 3A4 catalyzed 5-hydroxyelzasonan formation and provides insights on the disconnect between human liver microsomes data and that of rCYP. Furthermore, rCYP3A4 containing b5 are useful models for predicting the rates for liver microsomes P450-dependent drug oxidations and should be utilized routinely. 23123743 Estrogen receptor ESR1 regulates the phospholipase C-inositol phosphate signaling in the hippocampus from rats in proestrous and estrous phases. The aim of the present study was to investigate the involvement of estrogen receptors in the activation of phospholipase C (PLC)-phosphoinositide hydrolysis in the hippocampus from rats in estrous and proestrous phases. 17β-Estradiol (E2) and ESR1-selective agonist PPT, but not ESR2-selective agonist DPN, induced a rapid increase on total [³H]-inositol phosphate accumulation in the hippocampus from both rats. These effects are mediated by PLC activation, since the inhibition of this protein decreased the total [³H]-inositol phosphate accumulation. The pretreatment with ESR1 and ESR2 antagonist ICI 182,780, but not with GPER antagonist G-15, blocked the total [³H]-inositol phosphate accumulation induced by E2 and PPT, confirming that ESR1 is upstream component regulating this rapid effect. SRC family of protein tyrosine kinases inhibitor PP2 blocked the total [³H]-inositol phosphate accumulation induced by E2 and PPT in hippocampus, suggesting that ESR1 undergoes translocation from the nuclei to the plasma membrane region via SRC to activate rapid signaling pathways. Furthermore, the magnitude of the response to E2 and PPT was higher in hippocampus from rats in proestrous than in estrous. On the other hand, the expression of the ESR1 is higher in hippocampus from rats in estrous than in proestrous, indicating that the regulation of this receptor by estrous cycle does not play a role in the magnitude of the response to E2 and PPT in hippocampus. In conclusion, our results indicate that E2 activates SRC-mediated translocation of ESR1 to the plasma membrane, which results in the activation of PLC-inositol phosphate signaling pathway in rat hippocampus. Thus, these rapid estrogen actions in hippocampus might be a key step mediating cellular events important for learning and memory. 22981737 Specific binding of collagen Q to the neuromuscular junction is exploited to cure congenital myasthenia and to explore bases of myasthenia gravis. Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ) in the form of asymmetric AChE (AChE/ColQ). The C-terminal domain of ColQ binds to MuSK, the muscle-specific receptor tyrosine kinase, that mediates a signal for acetylcholine receptor (AChR) clustering at the NMJ. ColQ also binds to heparan sulfate proteoglycans including perlecan. Congenital defects of ColQ cause endplate AChE deficiency. A single intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to Colq-/- mice rescued motor functions, synaptic transmission, and the ultrastructure of NMJ. We also injected AAV1-COLQ-IRES-EGFP to the left tibialis anterior and observed colocalization of AChE/ColQ at all the examined NMJs of the non-injected limbs. Additionally, injection of purified recombinant AChE/ColQ protein complex into gluteus maximus accumulated AChE in non-injected forelimbs. These observations suggest that the tissue-targeting signal of ColQ can be exploited to specifically deliver the transgene product to the target tissue. MuSK antibody-positive myasthenia gravis (MG) accounts for 5-15% of autoimmune MG. As AChR deficiency is typically mild and as cholinesterase inhibitors are generally ineffective or worsen myasthenic symptoms, we asked if the patient's MuSK-IgG interferes with binding of ColQ to MuSK. In vitro overlay of AChE/ColQ to muscle sections of Colq-/- mice revealed that MuSK-IgG blocks binding of ColQ to the NMJ. In vitro plate-binding of MuSK to ColQ disclosed that MuSK-IgG exerts a dose-dependent block of MuSK-ColQ interaction. In addition, passive transfer of MuSK-IgG to mice reduced the size and density of ColQ to ∼10% of controls and had a lesser effect on the sizes and densities of AChR and MuSK. Elucidation of molecular mechanisms of specific binding of ColQ to the NMJ enabled us to ameliorate devastating myasthenic symptoms of Colq-/- mice and to reveal bases of anti-MuSK MG. 23363574 Purification and characterization of glucose 6-phosphate dehydrogenase enzyme from rainbow trout (Oncorhynchus mykiss) liver and investigation of the effects of some metal ions on enzyme activity. Glucose 6-phosphate dehydrogenase (d-glucose 6-phosphate: NADP(+) oxidoreductase, EC 1.1.1.49; G6PD) is a key enzyme that is localized in all mammal tissues, especially in cytoplasmic sections and that catalyzes the first step of pentose phosphate metabolic pathway. In this study, G6PD enzyme was purified 1444-fold with a yield of 77% from rainbow trout liver using 2',5'-ADP-sepharose-4B affinity chromatography. Moreover, a purity check of the enzyme was performed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Some characteristic features like optimal pH, stable pH, optimal temperature and optimal ionic strength were determined for the purified enzyme. In addition to this, in vitro effects of ions like silver nitrate (Ag(+)), thallium sulphate (TI(+)), cobalt (II) nitrate (Co(2+)) and arsenic (V) oxide (As(5+)) on enzyme activity were researched. Half-maximal inhibitory concentration (IC(50)) values of Ag(+), Co(2+) and As(5+) metal ions, which showed an inhibitory effect, were found to be 0.0044, 0.084 and 4.058 mM, respectively; and their inhibition constants (K(i)) were found to be 0.0052 ± 0.00042, 0.087 ± 0.015700 and 4.833 ± 1.753207 mM, respectively. Tl(+) not exhibited inhibitory effect on the enzyme activity. 23354755 Impact assessment of dredging to remove coal fly ash at the Tennessee Valley Authority Kingston Fossil plant using fathead minnow elutriate exposures. On December 22, 2008, failure of an earthen containment structure resulted in the release of approximately 4.1 million m(3) of coal fly ash into the Emory River and the surrounding area from the Tennessee Valley Authority Kingston Fossil Plant near Kingston, Tennessee, USA. The purpose of the present study was to assess the potential of dredging activities performed to remove the fly ash from the river to result in increased risk to pelagic fish, with special consideration of mobilization of metals. Elutriates were created using two sources of fly ash by bubbling with air over 10 d. This elutriate preparation method was designed to represent worst-case conditions for oxidation, metal release, and dissolution. Larval and juvenile Pimephales promelas underwent 10-d exposures to these elutriates. Larval end points included survival and biomass, and juvenile end points included survival, length, biomass, liver somatic index, and bioaccumulation. No significant toxicity was observed. Bioaccumulation of metals in juveniles was found to be primarily attributable to metals associated with particles in the gut. Results suggest little potential for toxicity to related fish species due to fly ash removal dredging activities given the extreme conditions represented by the elutriates in the present study. 23524254 Mechanochemical activation of vincamine mediated by linear polymers: Assessment of some "critical" steps. The aim of the research was to investigate three "critical steps" that deserve particular attention during the mechanochemical activation of vincamine. The first step consisted in the selection of the best polymeric carrier/most affine stabiliser between linear PVP and NaCMC by using the GRID and the GRID based AutoDock software packages which permit to calculate their surface features and interactions. Moreover, the calculation of the partial and total solubility parameters supported the results obtained by GRID and AutoDock software. Then, after the selection of linear PVP-K30 as the suitable carrier, the influence of process and formulation variables on the amorphisation degree and solubility enhancement was studied, to select the most suitable process conditions and formulation parameters. Subsequently, the best performing samples were widely characterised using XRPD, TEM and SSNMR (including the proton relaxation ((1)H T1 NMR) time) techniques. These studies highlighted that all the coground samples were nanocrystalline solid dispersions indicating a dramatic difference between the amorphisation capacities of linear PVP-K30 and cross-linked PVP, used in previous analogous experiences. In particular, (13)C, (15)N and (1)H T1 NMR data point to a description of the system as a dispersion of nanocrystals in the polymer. In these dispersions vincamine is in a disordered crystalline state due to extensive interactions and contacts with PVP-K30 but the main hydrogen bonding motif characterising its packing remains. Again, differently from cross-linked PVP, dissolution studies revealed that linear PVP-K30 was able to promote a complete in vitro solubilisation of vincamine in some coground samples. What is more important, by using a linear polymer, drug-to-polymer and milling time variables appeared less influent on the solid state and in vitro properties of the composites. Finally, stability studies conducted for a period of 1year highlighted the high physical stability of the selected samples. 23538998 A simple and versatile microfluidic cell density gradient generator for quantum dot cytotoxicity assay. In this work, a simple and versatile microfluidic cell density gradient generator was successfully developed for cytotoxicity of quantum dots (QDs) assay. The microfluidic cell density gradient generator is composed of eight parallel channels which are respectively surrounded by 1-8 microwells with optimized length and width. The cells fall into microwells by gravity and the cell densities are obviously dependent of microwell number. In a case study, HepG2 and MCF-7 cells were successfully utilized for generating cell density gradients on the microfluidic chip. The microfluidic cell density gradient generator was proved to be easily handled, cell-friendly and could be used to conduct the subsequent cell-based assay. As a proof-of-concept, QD cytotoxicity was evaluated and the results exhibited obvious cell density-dependence. For comparison, QD cytotoxicity was also investigated with a series of cell densities infused by pipette tips. Higher reproducibility was observed on the microfluidic cell density gradient generator and cell density was demonstrated to be a vital factor in cytotoxic study. With higher efficiency, controllability and reproducibility, the microfluidic cell density gradient generator could be integrated into microfluidic analysis systems to promote chip-based biological assay. 23480597 A Novel CUG(exp)·MBNL1 Inhibitor with Therapeutic Potential for Myotonic Dystrophy Type 1. Myotonic dystrophy type 1 (DM1) is caused by an expanded CUG repeat (CUG(exp)) that sequesters muscleblind-like 1 protein (MBNL1), a protein that regulates alternative splicing. CUG(exp) RNA is a validated drug target for this currently untreatable disease. Herein, we develop a bioactive small molecule (1) that targets CUG(exp) RNA and is able to inhibit the CUG(exp)·MBNL1 interaction in cells that model DM1. The core of this small molecule is based on ligand 2, which was previously reported to be active in an in vitro assay. A polyamine-derivative side chain was conjugated to this core to make it aqueous-soluble and cell-penetrable. In a DM1 cell model this conjugate was found to disperse CUG(exp) ribonuclear foci, release MBNL1, and partially reverse the mis-splicing of the insulin receptor pre-mRNA. Direct evidence for ribonuclear foci dispersion by this ligand was obtained in a live DM1 cell model using time-lapse confocal microscopy. 23631351 Novel acetylated chalcone and biflavonoid glycosides from Trigonosciadium brachytaenium (Boiss.) Alava. A new acetylated chalcone glycoside, trans-2',6'-dihydroxy-4'-O-(4″-acetyl-rhamnoside)-4-methoxychalcone (1) and a new biflavonoid glycosides, 5,3',5″,4″'-tetrahydroxy-3″',5″'dimethoxy-biflavone (4' → 8″)-7-O-((2-rhamnoside) rhamnoside) (2) were isolated from the ethyl acetate soluble fraction of the methanol extract obtained from Trigonosciadium brachytaenium and have been purified by column chromatography and preparative TLC. Those structures were elucidated by UV, (1)H NMR and (13)C NMR, HMBC, EI-MS and IR spectra. The antioxidant activity of ethyl acetate extract was evaluated by 1,1-diphenyl-2-picrylhydrazyl method. The results indicate that ethyl acetate extract from aerial part of T. brachytaenium possesses considerable antioxidant activity. 23500065 The interaction of a polymeric persimmon proanthocyanidin fraction with Chinese cobra PLA2 and BSA. To elucidate the anti-venom mechanism of persimmon tannin, the interaction between a polymeric persimmon proanthocyanidin fraction (PT40) and phospholipase A2 (PLA2) or bovine serum albumin (BSA) were studied using a competitive binding assay and spectroscopic methods including Fourier transform infrared spectroscopy (FT-IR), circular dichroism (CD), and resonance light scattering (RLS) spectroscopy. The results revealed that PT40 has a higher affinity for PLA2 than for BSA at physiological pH and induced greater conformational changes in PLA2 than in BSA. PT40 covalently bound to PLA2 in a reaction probably involving Lys residues. We propose that the high affinity of PT40 for PLA2 and the covalent modification of PLA2 by PT40 may be responsible for the ability of the tannin to irreversibly inhibit PLA2 catalytic activity, to prevent edema, and to neutralize the lethality of Chinese cobra PLA2in vivo. 23587048 Trapping of a Cross-Link Formed by a Major Purine Adduct of a Metabolite of the Carcinogen N-Nitrosomorpholine by Inorganic and Biological Reductants. 3-Hydroperoxy-N-nitrosomorpholine in buffered aqueous media in the presence of calf thymus DNA was treated with a phosphine reductant to generate the transient α-hydroxynitrosamine and subsequent diazonium ion that alkylated the DNA, as previously reported. Subsequent addition of hydride donors, for 30 min, followed by acid hydrolysis of the mixture allowed detection and quantification of 6-(2-{2-[(9H-purin-6-yl)amino]ethoxy}ethoxy)-9H-purin-2-amine, the reduced cross-link formed from deposition, via the diazonium ion, of a 3-oxapentanal fragment on O(6)-Gua, and condensation with N(6)-Ade, presumably in the vicinity. Decreasing the temperature of the reaction mixtures and decreasing the pH modestly increased the yields of the trapped cross-link. Among three borohydride reductants, NaNCBH3 is superior, being ∼4 times more effective on a molar basis, as opposed to a hydride equivalent basis, than NaBH4 or Na(AcO)3BH. For trapping with NaNCBH3, it is deduced that the reaction likely occurs with the iminium ion that is in protonic equilibrium with its conjugate base imine. In an experiment in which the hydroperoxide was decomposed and NaNCBH3 was introduced after various periods of time, the amount of cross-link was observed to increase, nearly linearly, by ∼4-fold over 1 week. These data indicate that there are a minimum of two populations of cross-links, one that forms rapidly, in minutes, and another that grows in with time, over days. Reduced nicotinamide cofactors and ascorbate are observed to effect reduction (over 3 days) of the cross-links, confirming the possibility that otherwise reversible cross-links might be immortalized under biological conditions. 23161866 Effects of mutated pregnancy-associated plasma protein-a on atherosclerotic lesion development in mice. Pregnancy-associated plasma protein-A (PAPP-A) is a large multidomain metalloprotease involved in cleavage of IGF binding protein (IGFBP)-4 and -5 thereby causing release of bioactive IGF. Individual domains of PAPP-A have been characterized in vitro, including the metzincin proteolytic domain important for IGFBP proteolytic activity, short consensus repeats critical for cell surface association, and Lin-12/Notch repeat module demonstrated to determine IGFBP substrate specificity. To test the hypothesis that specific cleavage of IGFBP-4 by PAPP-A in close proximity to the cell surface is required for development of lesions in a murine model of atherosclerosis, the following PAPP-A transgenic (Tg) mice were generated: Tg(E483A), which lacks all PAPP-A proteolytic activity; Tg(D1499A), which selectively lacks proteolytic activity against IGFBP-4; and Tg(K1296A/K1316A), in which cell surface binding is compromised. Following cross-breeding with apolipoprotein E (ApoE) knockout (KO) mice, ApoE KO/Tg mice were fed a high-fat diet to promote aortic lesion development. Lesion area was increased 2-fold in aortas from ApoE KO/Tg wild-type compared with ApoE KO mice (P < 0.001). However, there was no significant increase in the lesion area in any of the ApoE KO/Tg mutant mice. We conclude that PAPP-A proteolytic activity is required for the lesion-promoting effect of PAPP-A and that its specificity must be directed against IGFBP-4. Furthermore, our data demonstrate that cleavage of IGFBP-4 at a distance from the cell surface, and hence from the IGF receptor, is not effective in promoting the development of the atherosclerotic lesions. Thus, PAPP-A exerts its effect while bound to the cell surface in vivo. 23440959 Associations of gender and age with the reporting of drug-induced hepatic failure: data from the VigiBase™. Patient gender and age are considered to be the risk factors for developing drug-induced liver injury (DILI). The aim of this study was to analyze gender and age differences in reporting of drug-induced hepatic failure (HF) to the VigiBase™. VigiBase™ was screened for the HF reports submitted from 2000 to 2009. The information retrieved referred to the suspected drug, age, gender, and a reporting country. Variables were examined by using descriptive statistics and the binomial test. During the 10-year period there were in total 6,370 HF reports from 38 countries. After the exclusion of cases with missing gender data (379 cases), females counted for 54.03%. The largest portion of HF cases referred to age <55 (42.57%) with female predominance (56.81%), whereas age ≥55 (32.57%) showed almost even gender distribution. Overall, there were 941 different drugs or their combinations reported. Females significantly predominated in HF cases associated with analgesics, antiepileptics, antiinflamatory and antirheumatic drugs, psychoanaleptics, antibacterials for systemic use, and antidiabetic drugs. Males were significantly overrepresented in HF cases associated with antivirals for systemic use. Differences between genders and/or age groups in the reporting of drug-induced HF depend on drug and/or drug class but may be influenced by multiple factors. 23545846 Determination of the mutagenic and genotoxic potential of simulated leachate from an automobile workshop soil on eukaryotic system. Contamination of soil and water bodies with spent engine oil and petroleum products is a serious ecological problem, primarily in the automobile workshops and garages. This has potential short and chronic adverse health risks. Information is currently scarce on the potential mutagenicity and genotoxicity of such wastes. In this study, the potential mutagenic and genotoxic effects of simulated leachate from automobile workshop soil in Sagamu, Ogun state, Nigeria, were investigated. The assays utilized were bone marrow micronucleus (MN) and chromosome aberration (CA), sperm morphology and sperm count in mice. The physicochemical analysis of the leachate was also carried out. Experiments were carried out at concentrations of 1, 5, 10, 25, 50, 75 and 100% (volume per volume; leachate:distilled water) of the leachate sample. MN analysis showed a concentration-dependent induction of micronucleated polychromatic erythrocytes across the treatment groups. In the CA test, there was concentration-dependent significant reduction in mitotic index and induction of different types of CAs. Assessment of sperm shape showed a significant increase in sperm abnormalities with significant decrease in mean sperm count in treated groups. Heavy metals analyzed in the tested sample are believed to contribute significantly to the observed genetic damage. This indicates that automobile workshop soil-simulated leachate contains potential genotoxic agents and constitutes a genetic risk in exposed human population. 23420400 Theoretical studies on the thermodynamic properties, densities, detonation properties, and pyrolysis mechanisms of trinitromethyl-substituted aminotetrazole compounds. Trinitromethyl-substituted aminotetrazoles with -NH(2), -NO(2), -N(3), and -NHC(NO(2))(3) groups were investigated at the B3LYP/6-31G(d) level of density functional theory. Their sublimation enthalpies, thermodynamic properties, and heats of formation were calculated. The thermodynamic properties of these compounds increase with temperature as well as with the number of nitro groups attached to the tetrazole ring. In addition, the detonation velocities and detonation pressures of these compounds were successfully predicted using the Kamlet-Jacobs equations. It was found that these compounds exhibit good detonation properties, and that compound G (D = 9.2 km/s, P = 38.8 GPa) has the most powerful detonation properties, which are similar to those of the well-known explosive HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazocine). Finally, the electronic structures and bond dissociation energies of these compounds were calculated. The BDEs of their C-NO(2) bonds were found to range from 101.9 to 125.8 kJ/mol(-1). All of these results should provide useful fundamental information for the design of novel HEDMs. 23441843 Epigenetic reactivation of Nrf2 in murine prostate cancer TRAMP C1 cells by natural phytochemicals Z-ligustilide and Radix angelica sinensis via promoter CpG demethylation. Cancer development has been linked to epigenetic modifications of cancer oncogenes and tumor suppressor genes; in advanced metastatic cancers, severe epigenetic modifications are present. We previously demonstrated that the progression of prostate tumors in TRAMP mice is associated with methylation silencing of the Nrf2 promoter and a reduced level of transcription of Nrf2 and Nrf2 target genes. Radix Angelicae Sinensis (RAS; Danggui) is a medicinal herb and health food supplement that has been widely used in Asia for centuries. Z-Ligustilide (Lig) is one of the bioactive components of RAS. We investigated the potential of Lig and RAS to restore Nrf2 gene expression through epigenetic modification in TRAMP C1 cells. Lig and RAS induced the mRNA and protein expression of endogenous Nrf2 and Nrf2 downstream target genes, such as HO-1, NQO1, and UGT1A1. Bisulfite genomic sequencing revealed that Lig and RAS treatment decreased the level of methylation of the first five CpGs of the Nrf2 promoter. A methylation DNA immunoprecipitation assay demonstrated that Lig and RAS significantly decreased the relative amount of methylated DNA in the Nrf2 gene promoter region. Lig and RAS also inhibited DNA methyltransferase activity in vitro. Collectively, these results suggest that Lig and RAS are able to demethylate the Nrf2 promoter CpGs, resulting in the re-expression of Nrf2 and Nrf2 target genes. Epigenetic modifications of genes, including Nrf2, may therefore contribute to the overall health benefits of RAS, including the anticancer effect of RAS and its bioactive component, Lig. 23499237 Exploring the UDP pocket of LpxC through amino acid analogs. Lipopolysaccharide (LPS) biosynthesis is an attractive antibacterial target as it is both conserved and essential for the survival of key pathogenic bacteria. Lipid A is the hydrophobic anchor for LPS and a key structural component of the outer membrane of Gram-negative bacteria. Lipid A biosynthesis is performed in part by a unique zinc dependent metalloamidase, LpxC (UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase), which catalyzes the first non-reversible step in lipid A biosynthesis. The UDP portion of the LpxC substrate-binding pocket has been relatively unexplored. We have designed and evaluated a series of hydroxamate based inhibitors which explore the SAR of substitutions directed into the UDP pocket with a range of substituted α-amino acid based linkers. We also provide the first wild type structure of Pseudomonas aeruginosa LpxC which was utilized in the design of many of these analogs. 22670797 Preformulation and formulation of newly synthesized QNT3-18 for development of a skin whitening agent. New molecules having the structure of (E)-2-(4-tert-butylbenzylidene) hydrazinecarbothioamide (QNT3-18) or 4-tert-butylphenylthiourea (QNT3-20) was synthesized and presupposed to inhibit melanogenesis through the inhibition of tyrosinase, which is involved in melanin formation. Therefore, we seek to develop these new molecules as skin whitening agents in topical formulations based on preformulation studies. QNT3-18 or QNT3-20 showed a strong single endothermic peak at 159.34°C with 10.79 μm-sized or at 150.69°C with 9.0 μm-sized aggregated particles, respectively. Both QNT3-18 and QNT3-20 did not show cytotoxicity at effective concentration range (0.4 µM) against keratinocyte cells and QNT3-18 was more retained than QNT3-20 in the skin instead of permeating through the skin. QNT3-18 or QNT3-20 was practically insoluble in water; the aqueous solubility was 3.8 ± 0.37 or 130.6 ± 2.52 μg/mL, respectively. Also, the partition coefficient value (log P) corresponding to the quotient between aqueous and octanol concentration of the molecule was 3.9 or 2.6, respectively. The skin retention amount of QNT3-18 was 1.7-fold higher than that of QNT3-20. When the optimal SLN cream (J3 formulation) containing 4 μM QNT3-18 was applied on the backs of hairless rats for 4 days after UV irradiation for 7 days and the skin color was checked by reflectance spectrophotometer, the rat skin treated with SLN cream with QNT3-18 quickly recovered to normal compared to skin treated with SLN cream without QNT3-18. Taken together, this study suggests that topical formulations such as creams including SLNs with QNT3-18 might be appropriate carriers for skin whitening agents. 23411182 Quantification of organic acids using voltammetric tongues. Recently, electronic tongues (ET) have appeared as an excellent alternative to traditional techniques for the evaluation of food quality and processes. ET systems are based on arrays of low selectivity sensors that are simultaneously sensitive to several components in a measured sample (cross-sensitivity). The aim of this study was to determine the ability of an ET based on pulse voltammetry to quantify organic acids (ascorbic, citric and malic acids) in simple (SS) and binary solutions (BS) using different electrodes. The most significant electrodes for ascorbic acid prediction were Ni and Ag for SS, and Ag and Ir for BS where positive pulses were more suitable than negative ones. The prediction of citric and malic acids in SS and BS were suitable using Ir, Rh, Pt, Ag and Cu electrodes, using both positive and negative pulses. 23333575 Genistein protection against acetaminophen-induced liver injury via its potential impact on the activation of UDP-glucuronosyltransferase and antioxidant enzymes. The purpose of this study was to investigate genistein's influence on the relationship between the activation of uridine diphosphate glucuronosyltransferase (UGTs) and the protection against acetaminophen-induced liver toxicity. Animal experimental results revealed that genistein (50, 100 or 200mg/BWkg) significantly ameliorated the biomarkers alanine aminotransferase, alanine aminotransferase, lactate dehydrogenase and malondialdehyde, as indicators of acute liver damage caused by APAP (200mg/BWkg). The level of GSH declined sharply after treatment with APAP within 1h in both the liver and blood with and without genistein. However, after 16h, the levels approached or returned to the original level. Genistein may accelerate and promote APAP glucuronidation as the results showed that APAP-glucuronide increased by 18.44%, 46.79%, and 66.49% for 4h of treatment with genistein dosages of 50, 100 or 200mg/BWkg, respectively, compared with the APAP-only treatment. The activation of UGTs and glutathione peroxidase and the inhibition of CYP2E1 by genistein were observed, and UGTs mRNA expression level with genistein was measured. These findings suggest that genistein can prevent and protect against APAP-induced liver toxicity due to the inhibition of APAP biotransformation and the resistance to oxidative stress via the modulation of the activities of metabolism and the antioxidant enzyme. 23402859 Chlorpyrifos induced hepatotoxic and hematologic changes in rats: the role of quercetin and catechin. Chlorpyrifos is an organophosphorus insecticide which is widely used throughout in the world and it caused toxic effects on nontarget organisms especially mammalian. In the present study, catechin, quercetin, chlorpyrifos, catechin+chlorpyrifos, quercetin+chlorpyrifos were given to male rats through gavage for 4weeks. Serum total protein, albumin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, trigliceride, total cholesterol levels, hematological changes, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase activities and malondialdehyde content in liver tissues and also histopathological changes of liver were investigated in the rats compared to control group. No significant differences in all investigated parameters were observed between control, catechin and quercetin groups. There were statistically significantly changes in liver function tests, some hematological parameters, antioxidant enzyme activities and malondialdehyde levels in chlorpyrifos treated group compared to control group. In catechin+chlorpyrifos treated group and quercetin+chlorpyrifos treated group we observed the protective effects of catechin and quercetin on examining parameters but not completely. While some histopathological changes detected in liver tissues in chlorpyrifos treated group, less histopathological changes were observed in catechin+chlorpyrifos and quercetin+chlorpyrifos treated groups at the end of the 4thweek. As a result, catechin and quercetin significantly reduce chlorpyrifos induced hepatotoxicity in rats. 23395689 Manganese-loaded lipid-micellar theranostics for simultaneous drug and gene delivery to lungs. Gadolinium (Gd) contrast agents are predominantly used for T(1) MR imaging. However, the high toxicity of Gd(3+) and potential side effects including nephrogenic systemic fibrosis have led to the search for alternative T(1) contrast agents. Since manganese (Mn) has paramagnetic properties with five unpaired electrons that permit high spin number, long electronic relaxation times, and labile water exchange, we evaluated Mn as a T(1) magnetic resonance imaging (MRI) contrast agent for lung imaging. Here we report on the design and synthesis of multifunctional lipid-micellar nanoparticles (LMNs) containing Mn oxide (M-LMNs) for MRI that can also be used for DNA and drug delivery. Oleic acid-coated MnO nanoparticles were encapsulated in micelles composed of polyethylene glycol (PEG-2000), phosphatidylethanolamine (PE), DC-cholesterol, and dioleoyl-phosphatidylethanolamine (DOPE). The particles are taken up in vitro by human embryonic kidney (HEK293), Lewis lung carcinoma (LLC1), and A549 cells and are devoid of cytotoxicity. When administered to mice intranasally, they preferentially accumulate in the lungs. In vitro phantom and ex vivo lung MRI results confirmed that M-LMNs are able to enhance T(1) MRI contrast. M-LMNs loaded with plasmid DNA and/or doxorubicin are efficiently taken up by HEK293 cells in vitro and by target cells in vivo. Taken together, these results demonstrate that M-LMNs are capable of simultaneously providing MRI contrast and DNA and/or drug delivery to target cells in the lung and therefore may prove useful as a lung theranostic, especially for lung cancers. 22981667 Oral delivery of anticancer drugs III: formulation using drug delivery systems. In the past few years, the growth of nanometric size drug delivery systems (DDS) has burst into challenging innovations enabling real progresses to achieve oral delivery of anticancer drugs. DDS, such as polymeric nanoparticles, micelles, dendrimers and lipid-based formulations enable physico-chemical properties of cytotoxic agents to be improved and oral bioavailability to be enhanced. In this review we highlight current DDS used for the oral delivery of anticancer drugs. 23047001 Design, synthesis and biological evaluation of benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of glycogen synthase kinase-3β (GSK-3β). Glycogen synthase kinase-3β (GSK-3β) plays a key role in type II diabetes and Alzheimer's diseases, to which non-ATP competitive inhibitors represent an effectively therapeutical approach due to their good specificity. Herein, a series of small molecules benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of GSK-3β have been designed and synthesized. The in vitro evaluation performed by luminescent assay showed most BTZ derivatives have inhibitory effects in micromolar scale. Among them compounds 6l, 6t and 6v have the IC50 values of 25.0 μM, 27.8 μM and 23.0 μM, respectively. Moreover 6v is devoid of any inhibitory activity in the assays to other thirteen protein kinases. Besides, SAR is analyzed and a hypothetical enzymatic binding mode is proposed by molecular docking study, which would be useful for new candidates design. 23265458 Defatted Jatropha curcas flour and protein isolate as materials for protein hydrolysates with biological activity. Jatropha curcas L. protein hydrolysates were produced by treatment of a non-toxic genotype with Alcalase as well as the digestive enzymes pepsin and pancreatin. The J. curcas protein hydrolysate produced with the pepsin-pancreatin system from protein isolate had the highest TEAC value and was shown to undergo single-electron transfer reactions in the ABTS(+) reduction assay, demonstrating its antioxidant capacity. Testing of antimicrobial activity in the J. curcas protein hydrolysates against seven bacterial pathogens showed no growth inhibitory effect in Gram-negative and Gram-positive bacteria. More ACE-I inhibitory active peptides were produced in the Alcalase hydrolysates obtained from J. curcas protein isolate. The protein hydrolysate obtained with Alcalase from defatted J. curcas flour as well as from the protein isolate showed the highest inhibitory effect of ADP-induced aggregation of human platelets in platelet-rich plasma. It is expected that the information collated will facilitate new applications of proteins present in Jatropha plant. 23479318 Association of cadmium and lead with antioxidant status and incidence of benign prostatic hyperplasia in patients of Western India. The association of cadmium (Cd) and lead (Pb) in the pathophysiology and progression of benign prostate hyperplasia (BPH) has been evaluated in an epidemiological study with 116 BPH patients of the western part of India. The prostatic acid phosphatase activity, prostate-specific antigen, maximum urinary flow rate (Q max), and redox status of BPH patients were correlated with Cd and Pb contents. Additionally, patients were also separated on the basis of their age, genetic lineage, and additive habits and correlated with the Cd, Pb, and Q max levels. Our results suggest that the accumulation of toxic metals in prostate tissue has a significant positive correlation with the pathogenesis of BPH. Cd and Pb exert their effects through altered antioxidant defense mechanisms, ultimately leading to increased BPH severity. Progression of the pathogenesis also depends on other factors such as additive habits, genetic lineage, and age of the patients. 23291503 Embryonic stem cell-derived trophoblast differentiation: a comparative review of the biology, function, and signaling mechanisms. The development of the placenta is imperative for successful pregnancy establishment, yet the earliest differentiation events of the blastocyst-derived trophectoderm that forms the placenta remain difficult to study in humans. Human embryonic stem cells (hESC) display a unique ability to form trophoblast cells when induced to differentiate either by the addition of exogenous BMP4 or by the formation of cellular aggregates called embryoid bodies. While mouse trophoblast stem cells (TSC) have been isolated from blastocyst outgrowths, mouse ESC do not spontaneously differentiate into trophoblast cells. In this review, we focus on addressing the similarities and differences between mouse TSC differentiation and hESC-derived trophoblast differentiation. We discuss the functional and mechanistic diversity that is found in different species models. Of central importance are the unique signaling events that trigger downstream gene expression that create specific cellular fate decisions. We support the idea that we must understand the nuances that hESC differentiation models display so that investigators can choose the appropriate model system to fit experimental needs. 23127599 Alleviative effects of resveratrol on nonalcoholic fatty liver disease are associated with up regulation of hepatic low density lipoprotein receptor and scavenger receptor class B type I gene expressions in rats. Lipid metabolic disorders are widely considered to be one of the most critical and basic link in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to illustrate the alleviation function of resveratrol (Res) on NAFLD and the roles of hepatic fatty acid synthase (FAS), low density lipoprotein receptor (LDLr), scavenger receptor class B type I (SR-BI), and thyroid hormone receptor β1 (TRβ1), which are the key molecules involved in lipid metabolism. Adult male Wistar rats were fed a normal diet or high fat/sucrose diet (HFS) with or without resveratrol for 13 weeks. HFS induced NAFLD formation and increased the lipids concentrations in serum and livers of rats, while noticeable improvement has been reached by Res intervention. Moreover, Res protected against HFS-induced decrease in hepatic LDLr and SR-BI mRNA and protein expressions, whereas TRβ1 expressions were impervious with/without Res. Unexpectedly, hepatic FAS gene expressions were markedly diminished in NAFLD rats and were gradually increased by treatment with Res. These data indicate that the alleviative effects of Res on NAFLD are associated with up regulation of hepatic LDLr and SR-BI gene expressions, which provide new insights into the pharmacological targets of Res in the prevention of NAFLD. 23525112 Nuclear Factor κB Mediates Suppression of Canonical Transient Receptor Potential 6 Expression by Reactive Oxygen Species and Protein Kinase C in Kidney Cells. This study was carried out to explore the molecular mechanism for down-regulation of TRPC6 expression in the reactive oxygen species (ROS)/PKC signaling in kidney cells. In cultured human mesangial cells, H2O2 and TNF-α inhibited TRPC6 mRNA expression in a time-dependent manner. Inhibition of NF-κB reversed both H2O2- and phorbol 12-myristate 13-acetate (PMA)-induced decrease in TRPC6 protein expression. Activation of NF-κB by knocking down IκBα using siRNA could mimic the suppressive effect of ROS/PKC on TRPC6. a Ca(2+) imaging study showed that activation and inhibition of NF-κB significantly decreased and increased the TRPC6-mediated Ca(2+) entry, respectively. Further experiments showed that PMA, but not its inactive analog 4α-phorbol 12, 13-didecanoate (4α-PDD), caused phosphorylation of IκBα and stimulated the nuclear translocation of NF-κB p50 and p65 subunits. The PMA-dependent IκBα phosphorylation was significantly inhibited by Gö6976. Electrophoretic mobility shift assay revealed that PMA stimulated DNA binding activity of NF-κB. Furthermore, specific knockdown of p65, but not p50, prevented an H2O2 inhibitory effect on TRPC6 protein expression, suggesting p65 as a predominant NF-κB subunit repressing TRPC6. In agreement with a major role of p65, chromatin immunoprecipitation assays showed that PMA treatment induced p65 binding to the TRPC6 promoter. Moreover, PMA treatment increased the association of p65 with histone deacetylase (HDAC) and decreased histone acetylation at the TRPC6 promoter. Consistently, knockdown of HDAC2 by siRNA or inhibition of HDAC with trichostatin A prevented a H2O2-induced decrease in TRPC6 mRNA and protein expressions, respectively. Taken together, our findings imply an important role of NF-κB in a negative regulation of TRPC6 expression at the gene transcription level in kidney cells. 23194518 Development and characterisation of composite films made of kefiran and starch. In this study, new edible composite films were prepared by blending kefiran with corn starch. Film-forming solutions of different ratios of kefiran to corn starch (100/0, 70/30, 50/50, 30/70) were cast at room temperature. The effects of starch addition on the resulting films' physical, mechanical and water-vapor permeability (WVP) properties were investigated. Increasing starch content from 0% to 50% (v/v) decreased the WVP of films; however, with further starch addition the WVP increased. Also, this increase in starch content increased the tensile strength and extensibility of the composite films. However, these mechanical properties decreased at higher starch contents. Dynamic mechanical thermal analysis (DMTA) curves showed that addition of starch at all levels increased the glass transition temperature of films. The electron scanning micrograph for the composite film was homogeneous, without signs of phase separation between the components. Thus, it was observed that these two film-forming components were compatible, and that an interaction existed between them. 23368091 Primary hepatocyte cultures as prominent in vitro tools to study hepatic drug transporters. Abstract Before any drug can be placed on the market, drug efficacy and safety must be ensured through rigorous testing. Animal models are used for this purpose, though currently increasing attention goes to the use of alternative in vitro systems. In particular, liver-based testing platforms that allow the prediction of pharmacokinetic (PK) and pharmacotoxicological properties during the early phase of drug development are of interest. They also enable the screening of potential effects on hepatic drug transporters. The latter are known to affect drug metabolism and disposition, thereby possibly underlying drug-drug interactions, which, in turn, may result in liver toxicity. Clearly, stable in vivo-like functional expression of drug transporters in hepatic in vitro settings is a prerequisite to be applicable in routine PK and pharmacotoxicological testing. In the first part of the article, an updated overview of hepatic drug transporters is provided, followed by a state-of-the-art review of drug-transporter production and activity in primary hepatocyte cultures (PHCs), being the gold-standard in vitro system. Specific focus is hereby put on strategies to maintain long-term functional expression, in casu of drug transporters, in these systems. In the second part, the use of PHCs to assess hepatobiliary transport and transporter-mediated interactions is outlined. 23132334 In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor. Dolutegravir (DTG; S/GSK1349572) is a potent HIV-1 integrase inhibitor with a distinct resistance profile and a once-daily dose regimen that does not require pharmacokinetic boosting. This work investigated the in vitro drug transport and metabolism of DTG and assessed the potential for clinical drug-drug interactions. DTG is a substrate for the efflux transporters P-glycoprotein (Pgp) and human breast cancer resistance protein (BCRP). Its high intrinsic membrane permeability limits the impact these transporters have on DTG's intestinal absorption. UDP-glucuronosyltransferase (UGT) 1A1 is the main enzyme responsible for the metabolism of DTG in vivo, with cytochrome P450 (P450) 3A4 being a notable pathway and UGT1A3 and UGT1A9 being only minor pathways. DTG demonstrated little or no inhibition (IC(50) values > 30 μM) in vitro of the transporters Pgp, BCRP, multidrug resistance protein 2, organic anion transporting polypeptide 1B1/3, organic cation transporter (OCT) 1, or the drug metabolizing enzymes CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, UGT1A1, or 2B7. Further, DTG did not induce CYP1A2, 2B6, or 3A4 mRNA in vitro using human hepatocytes. DTG does inhibit the renal OCT2 (IC(50) = 1.9 μM) transporter, which provides a mechanistic basis for the mild increases in serum creatinine observed in clinical studies. These in vitro studies demonstrate a low propensity for DTG to be a perpetrator of clinical drug interactions and provide a basis for predicting when other drugs could result in a drug interaction with DTG. 23583928 Pleiotropic effect of histamine H4 receptor modulation in the central nervous system. The histamine H4 receptor (H4R) is expressed primarily on cells involved in inflammation and immune responses. Recently, it has been reported the functional expression of H4R within neurons of the central nervous system, but their role has been poorly understood. The present study aimed to elucidate the physiopathological role of cerebral H4R in animal models by the intracerebroventricular administration of the H4R agonist VUF 8430 (20-40 μg per mouse). Selectivity of results was confirmed by the prevention of the effects produced by the H4R antagonist JNJ 10191584 (3-9 mg/kg p.o.). Neuronal H4R activation induced acute thermal antinociception, indicating that neuronal histamine H4R might be involved in the production of antinociception in the absence of an inflammatory process. An anxiolytic-like effect of intensity comparable to that exerted by diazepam, used as reference drug, was produced in the light-dark box test. VUF 8430 reversed the scopolamine-induced amnesia in the passive avoidance test and showed anorexant activity in food deprived mice. Conversely, the H4R activation did not modify the immobility time in the tail suspension test. Rotarod performance test was employed to demonstrate that the effects observed following the administration of VUF 8430 and JNJ 10191584 were not due to impaired motor function of animals. Furthermore, both compounds did not alter spontaneous mobility and exploratory activity in the hole board test. These results show the antinociceptive, antiamnesic, anxiolytic and anorexant effects induced by neuronal H4R agonism, suggesting that H4 modulators may have broader utility further the control of inflammatory and immune processes. 23378627 Identification and characterization of novel alternative splice variants of human constitutive androstane receptor in liver samples of Koreans and Caucasians. Human constitutive androstane receptor (hCAR, NR1I3) is a member of the orphan nuclear receptor family and regulates the transcription of many drug-metabolizing enzymes and drug transporters. Previous studies have shown that the hCAR gene produces a number of different kinds of mRNA splicing variants (SVs) in non-Asian ethnicities. In the present study, we identified 18 hCAR SVs (SV1-SV18), including four novel SVs in Korean human livers. Among the four novel SVs, SV2 showed enhanced transactivation activity when cotransfected with CYP2B6 reporter gene, whereas other SVs were nonfunctional. When profiles of major hCAR SVs were compared among 30 livers from Korean patients and 20 livers from Caucasian patients, the relative composition of each SV showed interethnic variation as well as interindividual variation. The most predominant form of hCAR SV was not wild type, but either SV4 or SV7. The summed relative amounts of SV4 and SV7 ranged from 34.5 to 57.6% in the 30 Korean livers and from 47.2 to 82.6% in the 20 Caucasian livers, suggesting large interindividual variation. The mean relative amount of nonfunctional SV9 was significantly higher in Koreans (29.8%) than in Caucasians (12.8%). The mean relative amount of novel SV2 was 9.7% in Korean livers and 3.5% in Caucasian livers. Expression profiling of hCAR proteins in human livers also supported large interindividual variation in the expressional ratio of wild-type and SVs. Our results describe for the first time the direct comparison of hCAR SV profiles between Koreans and Caucasians. The functional relevance of these interindividual and interethnic variations of hCAR mRNA expression needs to be further characterized. 23403537 Accurate quantum chemical energies for tetrapeptide conformations: why MP2 data with an insufficient basis set should be handled with caution. High-level quantum chemical calculations have been carried out for biologically-relevant conformers of tetrapeptides. Our results indicate potential problems if the widely-applied MP2 approach is used in such situations with basis sets of insufficient size. Efficient alternatives are discussed. 23542041 In vivo and in vitro anti-inflammatory activity of Lentinus polychrous extract. ETHNOPHARMACOLOGICAL RELEVANCE: Lentinus polychrous is a Thai local edible mushroom, traditionally used for the treatments of fever and inflammation due to snake or scorpion envenomation. AIM OF STUDY: The present study aimed to investigate an anti-inflammatory effect of Lentinus polychrous mycelial extract (LPME) both in vitro and in vivo. MATERIALS AND METHODS: The cytotoxicity and suppressive effects of LPME on nitric oxide production, intracellular O2(-) production, pro-inflammatory mediator expression, TNF-α production were determined by using LPS-activated RAW 264.7 cells. In addition, Anti-inflammatory effect of LPME was evaluated by using carageenan-induced paw edema in rats. RESULTS: The LPME exhibited cytotoxicity with 50% inhibitory concentration (IC50) of 280.25±10.10μg/ml and significantly suppressed the productions of NO and intracellular O2(-) with dose-dependent manner. LPME decreased the expressions of iNOS, IL-1β, IL-6, TNF-α and COX-2 and significantly decreased the TNF-α production in LPS-activated macrophage with dose-dependent manners. Moreover, LPME showed significant suppressive effect on paw edema in rats. CONCLUSION: The results clearly revealed that the LPME inhibited NO and pro-inflammatory productions by down-regulating the gene expressions of pro-inflammatory mediators leading to the decrease paw edema in rat which support the traditional use. 22080037 Mercury induces the expression of cyclooxygenase-2 and inducible nitric oxide synthase. Nuclear factor-κB (NF-κB) is a transcription factor that mediates the inducible expression of a variety of genes involved in immune and inflammatory responses. NF-κB activation induces numerous proinflammatory gene products including cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). The divalent heavy metal mercury has been used for thousands of years. Although mercury is clearly toxic to most mammalian organ systems, especially the immune system, exposure has still increased in some areas of the world. However, the underlying toxic mechanism is not clearly identified. Here, we report biochemical evidence that mercury alone induces NF-κB activation, resulting in the induced expression of COX-2 and iNOS. The results suggest that mercury can induce inflammatory diseases by lowering host defense. 23219658 Immunotherapy blocking the tissue plasminogen activator-dependent activation of N-methyl-d-aspartate glutamate receptors improves hemorrhagic stroke outcome. Ischemic and hemorrhagic strokes have different etiologies, but share some pathogenic mechanisms, including a pro-neurotoxic effect of endogenous tissue plasminogen activator (tPA) via N-methyl-d-Aspartate (NMDA) receptors. Thus, in a model of intracerebral hemorrhage in rats, we investigated the therapeutic value of a strategy of immunotherapy (αATD-GluN1 antibody) preventing the interaction of tPA with NMDA receptors. We found that a single intravenous injection of αATD-GluN1 reduced brain edema, neuronal death, microglial activation and functional deficits following intracerebral hemorrhage, without affecting the hematoma volume. 23294566 Anterior gradient 2 and 3--two prototype androgen-responsive genes transcriptionally upregulated by androgens and by oestrogens in prostate cancer cells. Androgens and oestrogens have been implicated in prostatic carcinogenesis and tumour progression. Although the actions of androgens have been studied extensively, the mechanisms underlying oestrogen signalling in prostate cancer are not fully understood. In the present study, we analyzed the effect of androgens and oestrogens on the expression of anterior gradient 2 (AGR2) and anterior gradient 3 (AGR3), comprising two highly-related genes encoding secretory proteins that are expressed in prostate cancer and one of which (AGR2) has been associated with tumour metastasis. Quantitative reverse-transcriptase PCR and western blot analysis showed androgen induction of AGR2 and AGR3 in three androgen receptor positive cell lines, starting at concentrations of 0.1 nm. Both AGR genes were also transcriptionally activated by ≥ 5 nM oestradiol but not by isotype selective or nonselective oestrogen receptor agonists in DUCaP cells that harbour a high-level of wild-type androgen receptor. A functional androgen receptor but not oestrogen receptor turned out to be required for both androgen and oestrogen regulation. This pattern of androgen and oestrogen regulation was confirmed in VCaP cells and was also observed for FKBP5, a well-characterized androgen-regulated gene. Genome-wide chromatin-immunoprecipitation studies coupled with deep sequencing identified androgen receptor binding sites localized in the distal promoter and intron regions of the AGR2 and AGR3 genes, respectively. The androgen responsiveness of these enhancers was verified by luciferase reporter gene assays and site-directed mutagenesis analysis. Androgen treatment also induced p300 and RNA Pol II recruitment to androgen receptor enhancers of AGR2 and initiated local chromatin remodelling and the formation of RNA Pol II-containing androgen receptor transcription complexes. 23362960 DNA origami nanopillars as standards for three-dimensional superresolution microscopy. Nanopillars are promising nanostructures composed of various materials that bring new functionalities for applications ranging from photovoltaics to analytics. We developed DNA nanopillars with a height of 220 nm and a diameter of ~14 nm using the DNA origami technique. Modifying the base of the nanopillars with biotins allowed selective, upright, and rigid immobilization on solid substrates. With the help of site-selective dye labels, we visualized the structure and determined the orientation of the nanopillars by three-dimensional fluorescence superresolution microscopy. Because of their rigidity and nanometer-precise addressability, DNA origami nanopillars qualify as scaffold for the assembly of plasmonic devices as well as for three-dimensional superresolution standards. 23537133 Efficient anodic allylation and benzylation of carbons using allyl and benzyl trimethylsilanes. An easy process for allylation and benzylation of different carbon materials, primarily of glassy carbon, in acetonitrile solutions containing tetraalkyammonium salts is described. The method relies on the capability of C(sp(2)) zones of glassy carbon (graphite and fullerene-like inclusions) to be anodically charged at potentials >1.5 V versus Ag/AgCl to form electrophilic centers reacting with substituted trimethylsilanes RSiMe3. Great propensity of the trimethylsilyl group (TMS(+)) to act as a cationic leaving group facilitates electrophilic reactions of the charged anodic surface with R-carrying silylated precursors, permitting efficient grafting of a large variety of R groups. The present preliminary work focuses only on the efficient grafting of benzyl and allyl moieties. 23609070 Similarities and differences between sexes in regional loss of cortical and trabecular bone in the mid-femoral neck: The AGES-Reykjavik Longitudinal Study. The risk of hip fracture rises rapidly with age, and is notably higher in women. After falls and prior fragility fractures, the main clinically recognized risk factor for hip fracture is reduced bone density. To better understand the extent to which femoral neck density and structure change with age in each sex, we have carried out a longitudinal study in subjects not treated with agents known to influence bone mineral density to investigate changes in regional cortical thickness, as well as cortical and trabecular bone mineral density at the mid-femoral neck. Segmental QCT analysis was used to assess bone measurements in two anatomic sub-regions, the supero-lateral (superior) and infero-medial (inferior). A total of 400 older individuals (100 men and 300 women, aged 66-90 years) who were participants in the AGES-Reykjavik study, were studied. Participants had two QCT scans of the hip over a median follow-up of 5.1 yr. (mean baseline age 74 yr.). Changes in bone values during follow-up were estimated from mixed effects regression models. At baseline women had lower bone values in the superior region than men. At follow-up all bone values were lower in women, except cortical vBMD inferiorly. The relative losses in all bone values estimated in the superior region were substantially (about threefold) and significantly greater compared to those estimated in the inferior region in both sexes. Women lost cortical thickness and cortical vBMD more rapidly than men in both regions; and this was only weakly reflected in total femoral neck DXA-like results. The higher rate of bone loss in women at critical locations may contribute materially to the greater femoral neck fracture incidence among women than men. 23223023 Increase of palmitic acid concentration impairs endothelial progenitor cell and bone marrow-derived progenitor cell bioavailability: role of the STAT5/PPARγ transcriptional complex. Metabolic profiling of plasma nonesterified fatty acids discovered that palmitic acid (PA), a natural peroxisome proliferator-activated receptor γ (PPARγ) ligand, is a reliable type 2 diabetes biomarker. We investigated whether and how PA diabetic (d-PA) concentrations affected endothelial progenitor cell (EPC) and bone marrow-derived hematopoietic cell (BM-HC) biology. PA physiologic (n-PA) and d-PA concentrations were used. Proliferating cell nuclear antigen content and signal transducer and activator of transcription 5 (STAT5), PPARγ, cyclin D1, and p21(Waf) expression were evaluated. Small interfering RNA technology, gene reporter luciferase assay, electrophoretic mobility shift assay, chromatin immunoprecipitation assay, and coimmunoprecipitation were exploited. In vivo studies and migration assays were also performed. d-PA, unlike n-PA or physiological and diabetic oleic and stearic acid concentrations, impaired EPC migration and EPC/BM-HC proliferation through a PPARγ-mediated STAT5 transcription inhibition. This event did not prevent the formation of a STAT5/PPARγ transcriptional complex but was crucial for gene targeting, as p21(Waf) gene promoter, unlike cyclin D1, was the STAT5/PPARγ transcriptional target. Similar molecular events could be detected in EPCs isolated from type 2 diabetic patients. By expressing a constitutively activated STAT5 form, we demonstrated that STAT5 content is crucial for gene targeting and EPC fate. Finally, we also provide in vivo data that d-PA-mediated EPC dysfunction could be rescued by PPARγ blockade. These data provide first insights on how mechanistically d-PA drives EPC/BM-HC dysfunction in diabetes. 23420770 Potential Genotoxicity of Traditional Chinese Medicinal Plants and Phytochemicals: An Overview. In the last decades, cases of poisoning due to herbal medicines have occurred in many countries; Chinese herbal medicines (CHMs) are occasionally involved. The experience gained from traditional use is efficient to detect immediate or near-immediate relationship between administration and toxic effects but is quite unlikely to detect medium- to long-term toxicities; thorough investigations of herbal medicines (toxicity assessments, active pharmacovigilance) appear then essential for their safe use. Genotoxicity is an especially insidious toxicity that may result in carcinoma development years after exposure; it can arise from multiple compounds, with or without metabolic activation. The present work reviews traditional CHMs and phytochemicals that have been shown to present a genotoxic hazard. Copyright © 2013 John Wiley & Sons, Ltd. 23249181 Progress of pharmacological studies on alkaloids from Apocynaceae. Alkaloid was a kind of biological active ingredient. There were various types of alkaloids in Apocynaceae. This paper reviewed the progress on alkaloids from Apocynaceae, which contained origin, structure, and pharmacological activity. 23620162 Structural changes in supercooled Al2O3-Y2O3 liquids. Structural changes in liquids between Al2O3 and Y2O3 are investigated as a function of the composition and during supercooling using high energy X-ray diffraction (HEXRD) techniques combined with containerless aerodynamic levitation. Many-body molecular dynamics simulation techniques utilizing potential models that incorporate anion polarization effects are applied to study the same liquid systems. The X-ray scattering experiments indicate a change in liquid structure during supercooling around a composition 20% Y2O3 (AlY20) that occurs over a narrow temperature interval. We have associated this change in structure with the onset of a liquid-liquid phase transformation. Analysis of the MD simulated structures has allowed the structure changes to be interpreted in terms of Al(3+) and Y(3+) coordination environments and particularly the Y(3+)-Y(3+) structural correlations. We show that the incipient liquid-liquid phase transition behaviour is correlated with local density fluctuations that represent different coordination polyhedra surrounding oxygen ions. The difference in energy and volume associated with this sampling of high and low density basins in the underlying energy landscape is consistent with independent verifications of the volume and enthalpy differences between different amorphous forms. The differences in the high- and low-density configurations match the difference in diffraction patterns observed experimentally. 23044045 A temporary decrease in mineral density in perinatal mouse long bones. Fetal and postnatal bone development in humans is traditionally viewed as a process characterized by progressively increasing mineral density. Yet, a temporary decrease in mineral density has been described in the long bones of infants in the immediate postnatal period. The mechanism that underlies this phenomenon, as well as its causes and consequences, remain unclear. Using daily μCT scans of murine femora and tibiae during perinatal development, we show that a temporary decrease in tissue mineral density (TMD) is evident in mice. By monitoring spatial and temporal structural changes during normal growth and in a mouse strain in which osteoclasts are non-functional (Src-null), we show that endosteal bone resorption is the main cause for the perinatal decrease in TMD. Mechanical testing revealed that this temporary decrease is correlated with reduced stiffness of the bones. We also show, by administration of a progestational agent to pregnant mice, that the decrease in TMD is not the result of parturition itself. This study provides a comprehensive view of perinatal long bone development in mice, and describes the process as well as the consequences of density fluctuation during this period. 23561177 Effects of industrial processing on folate content in green vegetables. Folates are described to be sensitive to different physical parameters such as heat, light, pH and leaching. Most studies on folates degradation during processing or cooking treatments were carried out on model solutions or vegetables only with thermal treatments. Our aim was to identify which steps were involved in folates loss in industrial processing chains, and which mechanisms were underlying these losses. For this, the folates contents were monitored along an industrial canning chain of green beans and along an industrial freezing chain of spinach. Folates contents decreased significantly by 25% during the washing step for spinach in the freezing process, and by 30% in the green beans canning process after sterilisation, with 20% of the initial amount being transferred into the covering liquid. The main mechanism involved in folate loss during both canning green beans and freezing spinach was leaching. Limiting the contact between vegetables and water or using steaming seems to be an adequate measure to limit folates losses during processing. 22625411 Recent advances in medicinal chemistry of sulfonamides. Rational design as anti-tumoral, anti-bacterial and anti-inflammatory agents. Now-a-days, cancer is becoming one of the major problems of public health in the world. Pharmacology treatment is a way to increase quality and long life. Predominantly, in last decade sulfonamide derivatives have been described as potential carbonic anhydrase inhibitors. In the present work, we describe recent advances during the last decade in medicinal chemistry of sulfonamides derivatives with some examples of rational design as anti-tumoral, antibacterial and anti-inflammatory agents. We show strategy design, structure-activity relationship, biological activity and advances of new sulfonamide compounds that have more health significance than some clinically used sulfonamides. 23496349 Probing the Electronic Properties of W3Ox(-/0) (x = 0-2) and W3(2-) Clusters: The Aromaticity of W3 and W3(2-). Density functional theory (DFT) calculations are employed to investigate the structural and electronic properties of bare tritungsten clusters (W3, W3(-), W3(2-)) and tritungsten oxide clusters W3Ox(-/0) (x = 1, 2). Generalized Koopmans' theorem is applied to predict the vertical detachment energies and simulate the photoelectron spectra (PES) for W3Ox(-) (x = 0-2) clusters. Extensive DFT calculations are performed in search of the lowest energy structures for both the anions and the neutrals. The bare tritungsten clusters are predicted to be triangular structures with D3h ((3)A1'), C2v ((2)A1) and D3h ((1)A1') symmetry for W3, W3(-) and W3(2-), respectively. For W3O(-) and W3O clusters, the oxygen atom occupies the terminal site, while the next added oxygen atom is found to be a bridging one in both W3O2(-) and W3O2 clusters. Molecular orbital analyses are carried out to elucidate the chemical bonding of these clusters and provide insights into the sequential oxidation from W3(-) to W3O2(-). Partial σ- and δ-aromaticity are revealed in the neutral W3 (D3h, (3)A1'), while the anion W3(2-) (D3h, (1)A1') possesses only δ-aromaticity. 23606463 Regulation of Conjugated Hemoglobin on Micelles through Copolymer Chain Sequences and the Protein's Isoelectric Aggregation. Amphiphilic triblock copolymers with carbonyl groups located either in the middle segment or in the third side block are synthesized by adjusting feeding sequence of the comonomers. The conjugation of hemoglobin (Hb) on the copolymer micelles is realized by condensation reactions of carbonyl with the amino groups of Hb, and the gas-binding capacity of Hb is well preserved. Interestingly, the reassembly behavior of Hb-conjugated micelles (HbM) is explored by adjusting the pH. As for triblock copolymers with a carbonyl-functionalized segment as the third block, Hb is rearranged into the inner core of micelles when the pH is adjusted close to the isoelectric point of Hb. Therefore, it may provide a new needed route for fabrication of protein carriers, which is different from the traditional encapsulation technique. 23439131 Microfluidic synthesis of cell-type-specific artificial extracellular matrix hydrogels. Droplet microfluidic technology is applied for the high-throughput synthesis via Michael-type addition of reactive, micrometer-sized poly(ethylene glycol) (PEG) hydrogels ("microgels") with precisely controlled dimension and physicochemical properties. A versatile chemical scheme is used to modify the reactive PEG microgels with tethered biomolecules to tune their bioactive properties for the bioreactor culture and manipulation of various (stem) cell types. 23634899 Isotopic Spectra of the Hydroxyl Radical. Rotational spectra of OH and its isotopologues have been precisely measured using high efficiency Terahertz (THz) sources. The measurements are compared with existing data and are useful for global modeling. For the first time microwave measurements of the $\Lambda$-doubling transitions of $^{17}$OH isotopologue are combined with THz data successfully. Precise rotational, fine-structure and hyperfine structure parameters for the $^{17}$OH isotopologue are reported. An isotopically independent Dunham model for all isotopologues of $^2\Pi$ OH v $ < $ 3 is presented. 23448620 Multiple targeted drugs carrying biodegradable membrane barrier: anti-adhesion, hemostasis, and anti-infection. A multiple targeted drug carrying bilayer membrane for preventing an abdominal adhesion is prepared by electrospinning. Two bioactive drugs were successfully incorporated into this bilayer membrane and can be independently released from nanofibrous scaffolds without losing structural integrity and functionality of the anti-adhesion membrane. Besides, the drug release profile could be easily adjusted by optimizing the swelling behavior of the fibrous scaffold. The inner layer of the bilayered fibrous membranes loaded with carbazochrome sodium sulfonate (CA) showed an excellent vascular hemostatic efficacy and formed little clot during in vivo experiment. The outer layer loaded with tinidazole (TI) had outstanding antibacterial effect against the anaerobe. We believe this approach could serve as a model technique to guide the design of implants with drug delivery functions. 23488748 Molecular dynamics simulation of nanosized water droplet spreading in an electric field. Molecular dynamics (MD) simulations are performed for the spreading of a nanosized water droplet on a solid substrate subject to a parallel electric field. A combined electrostatic and Lennard-Jones potential is employed to represent the intermolecular interactions. Results show that in response to the applied field, polar water molecules realign themselves and this microscopic reorientation of molecular dipoles combines with the intermolecular forces to produce a macroscopic deformation of a free spherical water droplet into an ellipsoid. The applied field has a strong effect on the spreading of the water droplet on a solid substrate. For a weaker parallel field, the droplet spreading is asymmetric with the leading contact angle being greater than the trailing contact angle. With an increase in field strength, this asymmetry continues to increase, culminates, and then decreases until it disappears. The symmetric spreading remains with a further increase in the field strength until the saturation point is reached. This transition from the asymmetric to symmetric spreading is a manifestation of the interaction of the electric field with polar water molecules and the intermolecular forces within the droplet and between the water and solid; the interaction also leads to a change in hydrogen bonds along the droplet surface. The dynamics of the droplet spreading is entailed by the electrically induced motion of molecules along the liquid surface toward the solid substrate and is controlled by a competing mechanism among the electric, water-water, and water-solid intermolecular forces. 23292985 Structural aspects of gut peptides with therapeutic potential for type 2 diabetes. Gut hormones represent a niche subset of pharmacologically active agents that are rapidly gaining importance in medicine. Due to their exceptional specificity for their receptors, these hormones along with their analogues have attracted considerable pharmaceutical interest for the treatment of human disorders including type 2 diabetes. With the recent advances in the structural biology, a significant amount of structural information for these hormones is now available. This Minireview presents an overview of the structural aspects of these hormones, which have roles in physiological processes such as insulin secretion, as well as a discussion on the relevant structural modifications used to improve these hormones for the treatment of type 2 diabetes. 23444785 Incision wound healing activity of pine bark extract containing topical formulations: a study with histopathological and biochemical analyses in albino rats. The present study was designed to identify and compare the in vivo wound healing capacity of a bark extract from Pinus brutia and Pycnogenol in an incision wound model in rats. O/W cream formulations were prepared incorporating 2% Pycnogenol and P. brutia bark extract. The rats were divided into three groups (n = 8). Subsequently placebo and test formulations were applied to animals once a day from day "0" until the 9th day. Malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) were studied in addition to histopathological examinations. Treatment with F. brutia extract containing cream inhibited lipid peroxidation by a 35% decrease in MDA and 46.8% increase in SOD activity, whereas 19.3% decrease in MDA and 34.7% increase in SOD activity were attained with Pynogenol compared to control. The histological data revealed a better performance of P. brutia extract enriched formulation in terms of degeneration of hair roots, increased vascularization and a decrease in necrotic area. Consequently, a high wound healing activity was observed in animals treated with P. brutia extract significantly accelerating the wound healing process. 23019139 A comparative analysis of computational approaches to relative protein quantification using peptide peak intensities in label-free LC-MS proteomics experiments. Liquid chromatography coupled with mass spectrometry (LC-MS) is widely used to identify and quantify peptides in complex biological samples. In particular, label-free shotgun proteomics is highly effective for the identification of peptides and subsequently obtaining a global protein profile of a sample. As a result, this approach is widely used for discovery studies. Typically, the objective of these discovery studies is to identify proteins that are affected by some condition of interest (e.g. disease, exposure). However, for complex biological samples, label-free LC-MS proteomics experiments measure peptides and do not directly yield protein quantities. Thus, protein quantification must be inferred from one or more measured peptides. In recent years, many computational approaches to relative protein quantification of label-free LC-MS data have been published. In this review, we examine the most commonly employed quantification approaches to relative protein abundance from peak intensity values, evaluate their individual merits, and discuss challenges in the use of the various computational approaches. 23357627 Phosphonic analogues of glutamic acid as irreversible inhibitors of Staphylococcus aureus endoproteinase GluC: an efficient synthesis and inhibition of the human IgG degradation. Endoproteinase GluC (V8 protease) is one of many virulence factors released by the Staphylococcus aureus species in vivo. The V8 protease is able to hydrolyze some serpins and all classes of mammalian immunoglobulins. The application of specific and potent inhibitors of V8 protease may lead to the development of new antibacterial agents. Herein, we present the synthesis and the inhibitory properties of novel peptidyl derivatives of a phosphonic glutamic acid analogue. One of the compounds Boc-Phe-Leu-Glu(P)(OC(6)H(4))(2) displayed an apparent second-order inhibition rate value of 8540 M(-1)s(-1). The Boc-Phe-Leu-Glu(P)(OC(6)H(4))(2) compound with the highest inhibitory potency showed the ability to prevent V8-mediated human IgG proteolysis in vitro. 23454309 Food web analysis reveals effects of pH on mercury bioaccumulation at multiple trophic levels in streams. Biomagnification processes and the factors that govern them, including those for mercury (Hg), are poorly understood in streams. Total and methyl Hg concentrations and relative trophic position (using δ(15)N) were analyzed in biofilm and invertebrates from 21 streams in New Brunswick, Canada to assess food web biomagnification leading to the common minnow blacknose dace (Rhinichthys atratulus), a species known to have Hg concentrations that are higher in low pH waters. Biomagnification slopes within stream food webs measured using Hg vs. δ(15)N or corresponding trophic levels (TL) differed depending on the chemical species analyzed, with total Hg exhibiting increases of 1.3-2.5 per TL (mean slope of total Hg vs. δ(15)N=0.14±0.06 S.D., range=0.06-0.20) and methyl Hg showing a more pronounced increase of 2.8 to 6.0 per TL (mean slope of methyl Hg vs. δ(15)N=0.30±0.08 S.D., range=0.22-0.39). While Hg biomagnification slopes through the entire food web (Trophic Magnification Factors, TMFs) were not influenced by water chemistry (pH), dietary concentrations of methyl Hg strongly influenced biomagnification factors (BMFs) for consumer-diet pairs within the food web at lower trophic levels, and BMFs between dace and predatory invertebrates were significantly higher in low pH waters. These analyses, coupled with observations of higher Hg in primary producers in streams with low pH, suggest that pH influences both baseline concentrations and biomagnification of Hg in these systems. Because higher Hg concentrations in the diets of primary consumers and predatory insects in lower pH waters led to lower BMFs, these feeding groups showed insignificant relationships between Hg and pH; thus, altered BMFs associated with dietary concentrations can dampen the effects of environmental conditions on Hg concentrations. 22859660 Effects of fenofibrate, a PPAR-α ligand, on the haemodynamics of glycerol-induced renal failure in rats. The modulating effect of peroxisome proliferator-activated receptor α ligand on haemodynamic effects of phenylepherine (PE), angiotensin II (AII), endothelin 1 (ET1), acetylcholine (Ach), sodium nitroprusside (SNP) and isoproterenol (ISO) were evaluated in glycerol-induced acute kidney injury in rats. The effect of PE on fenofibrate-treated animals was a dose-dependent increase in mean arterial blood pressure (MAP). For AII and ET1, MAP was also increased for the fenofibrate group but not in a dose-dependent fashion. On the medullary blood flow (MBF), while the lower doses of PE and AII increased the perfusion unit on the fenofibrate-treated group, the higher doses decreased the perfusion unit. The ET1 increased the perfusion unit on this group but not in dose-dependent fashion. The effects of PE and AII on the cortical blood flow (CBF) of fenofibrate-treated group is similar to that of MBF for the same group but not for ET1. The effect of Ach, SNP and ISO in all the groups was the decrease in MAP. ISO caused dose-dependent increase in MBF of fenofibrate-treated group. The effect of Ach, SNP and ISO on the CBF perfusion unit was that of the increase for the fenofibrate-treated group. The study showed that fenofibrate did not attenuate increased blood pressure induced by PE, AII and ET1 but caused enhanced vasodilation by Ach, SNP and ISO. 23333093 Green tea catechin leads to global improvement among Alzheimer's disease-related phenotypes in NSE/hAPP-C105 Tg mice. Amyloid β (Αβ) has been reported to be responsible for the functional and structural abnormalities of Alzheimer's disease (AD) through the induction of oxidative stress. The aim of this study was to determine whether or not treatment of transgenic (Tg) mice with green tea catechin (GTC), a radical scavenger, improves AD phenotypes. To test this, 7-month-old Tg mice were treated with a low (1 mg) or high (10 mg) dose of GTC for 6 months. Surprisingly, GTC-treated Tg mice exhibited significant decreases in behavioral impairment, Aβ-42 production, APP-C99/89 expression, γ-secretase component and Wnt protein levels, γ-secretase activity and MAPK activation. In contrast, the levels of APP-C83 protein and enzyme activities (α-secretase, neprilysin and Pin1) were elevated in the GTC-treated groups. Moreover, GTC-treated groups showed lower levels of total cholesterol and low-density lipoprotein cholesterol, whereas the level of high-density lipoprotein cholesterol increased. These results provide the first experimental evidence that GTC improves AD phenotypes, thereby suggesting that GTC can be used in the prevention of AD or treatment of AD patients. 23625779 Mesoporous Silica Nanoparticles Act as a Self-Adjuvant for Ovalbumin Model Antigen in Mice. Immunization to the model protein antigen ovalbumin (OVA) is investigated using MCM-41 mesoporous silica nanoparticles as a novel vaccine delivery vehicle and adjuvant system in mice. The effects of amino surface functionalization and adsorption time on OVA adsorption to nanoparticles are assessed. Amino-functionalized MCM-41 (AM-41) shows an effect on the amount of OVA binding, with 2.5-fold increase in binding capacity (72 mg OVA/g AM-41) compared to nonfunctionalized MCM-41 (29 mg OVA/g MCM-41). Immunization studies in mice with a 10 μg dose of OVA adsorbed to AM-41 elicits both antibody and cell-mediated immune responses following three subcutaneous injections. Immunizations at a lower 2 μg dose of OVA adsorbed to AM-41 particles results in an antibody response but not cell-mediated immunity. The level of antibody responses following immunization with nanoformulations containing either 2 μg or 10 μg of OVA are only slightly lower than that in mice which receive 50 μg OVA adjuvanted with QuilA, a crude mixture of saponins extracted from the bark of the Quillaja saponaria Molina tree. This is a significant result, since it demonstrates that AM-41 nanoparticles are self-adjuvanting and elicit immune responses at reduced antigen doses in vivo compared to a conventional delivery system. Importantly, there are no local or systemic negative effects in animals injected with AM-41. Histopathological studies of a range of tissue organs show no changes in histopathology of the animals receiving nanoparticles over a six week period. These results establish the biocompatible MCM-41 silica nanoparticles as a new method for vaccine delivery which incorporates a self-adjuvant effect. 23464520 Microvascular complications and diabetic retinopathy: recent advances and future implications. Retinal microvascular alterations have been observed during diabetic retinopathy (DR) due to the retinal susceptibility towards subtle pathological alterations. Therefore, retinal microvascular pathology is essential to understand the nature of retinal degenerations during DR. In this review, the role of retinal microvasculature complications during progression of DR, along with recent efforts to normalize such alterations for better therapeutic outcome, will be underlined. In addition, current therapeutics and future directions for advancement of standard treatment for DR patients will be discussed. 23179351 Changes of the serum cytokine contents in broilers fed on diets supplemented with nickel chloride. Cytokines are immunoregulatory proteins which play an important role in the immune system. The purpose of this study was to examine the serum cytokine contents including interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) induced by dietary nickel chloride in broilers by enzyme-linked immunospecific assay. A total of 240 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as control diet or the same basal diet supplemented with 300, 600, and 900 mg/kg of nickel chloride. During the experimental period of 42 days, the results showed that the serum IL-2, IL-4, IL-6, IL-10, IFN-γ and TNF-α contents were lower (p < 0.05 or p < 0.01) in the 300, 600, 900 mg/kg groups than those in the control group. It was concluded that dietary nickel chloride in the range of 300 to 900 mg/kg could reduce the serum cytokine contents, which could finally impact the immune function in broilers. 23155052 Matrix metalloproteinase-1-mediated up-regulation of vascular endothelial growth factor-2 in endothelial cells. Matrix metalloproteinase-1 (MMP-1) is a collagenase that is highly active in extracellular matrix and vascular remodeling, angiogenesis, and tumor progression. Vascular endothelial growth factor receptor-2 (VEGFR2), the main receptor for VEGF-A, is expressed on endothelial cells and promotes cell survival, proliferation, and other functions. Although MMP-1 and VEGFR2 co-exist in many normal and pathophysiological conditions, the effect of MMP-1 on cellular VEGFR2 that can promote the above processes is unknown. In this study we test the hypothesis that stimulation of endothelial cells with MMP-1 increases their levels of VEGFR2. The increased VEGFR2 is then available to bind VEGF-A, resulting in increased response. Indeed we found that endothelial cells incubated with active MMP-1 had higher mRNA and protein levels of VEGFR2. Furthermore, VEGF-A-dependent phosphorylation of intracellular signaling molecules and endothelial proliferation were elevated after MMP-1 treatment. MMP-1 caused activation of the nuclear factor-κB (NF-κB) pathway (p65/RelA) in endothelial cells, and this response was dependent upon activation of protease activated receptor-1 (PAR-1). Chromatin immunoprecipitation was used to confirm NF-κB-mediated active transcription of the VEGFR2 (KDR) gene. Elevation in VEGFR2 after MMP-1 stimulation was inhibited by PAR-1 knockdown and NF-κB specific inhibition. We conclude that MMP-1 promotes VEGFR2 expression and proliferation of endothelial cells through stimulation of PAR-1 and activation of NF-κB. These results suggest a mechanism by which MMP-1 may prime or sensitize endothelial cell functions. 23535821 Global increases in both common and rare copy number load associated with autism. Children with autism have an elevated frequency of large, rare copy number variants (CNVs). However, the global load of deletions or duplications, per se, and their size, location and relationship to clinical manifestations of autism have not been documented. We examined CNV data from 516 individuals with autism or typical development from the population-based Childhood Autism Risks from Genetics and Environment (CHARGE) study. We interrogated 120 regions flanked by segmental duplications (genomic hotspots) for events >50 kbp and the entire genomic backbone for variants >300 kbp using a custom targeted DNA microarray. This analysis was complemented by a separate study of five highly dynamic hotspots associated with autism or developmental delay syndromes, using a finely tiled array platform (>1 kbp) in 142 children matched for gender and ethnicity. In both studies, a significant increase in the number of base pairs of duplication, but not deletion, was associated with autism. Significantly elevated levels of CNV load remained after the removal of rare and likely pathogenic events. Further, the entire CNV load detected with the finely tiled array was contributed by common variants. The impact of this variation was assessed by examining the correlation of clinical outcomes with CNV load. The level of personal and social skills, measured by Vineland Adaptive Behavior Scales, negatively correlated (Spearman's r = -0.13, P = 0.034) with the duplication CNV load for the affected children; the strongest association was found for communication (P = 0.048) and socialization (P = 0.022) scores. We propose that CNV load, predominantly increased genomic base pairs of duplication, predisposes to autism. 23295740 Tamoxifen represses miR-200 microRNAs and promotes epithelial-to-mesenchymal transition by up-regulating c-Myc in endometrial carcinoma cell lines. Although tamoxifen (TAM), a selective estrogen receptor modulator, has been widely used in the treatment of hormone-responsive breast cancer, its estrogen-like effect increases the risk of endometrial cancer. However, the molecular mechanisms of TAM-induced endometrial carcinoma still remain unclear. In this report, we explored the role of microRNAs (miRNAs) in TAM-induced epithelial-mesenchymal transition (EMT) in ECC-1 and Ishikawa endometrial cancer cell lines and found miR-200 is involved in this process via the regulation of c-Myc. When treated with TAM, ECC-1 and Ishikawa cells were characterized by higher invasiveness and motility and underwent EMT. miR-200, a miRNA family with tumor suppressive functions in a wide range of cancers, was found reduced in response to TAM treatment. Consistent with zinc finger E-box binding homeobox 2, which was confirmed as a direct target of miR-200b in endometrial cancer cell lines, some other key factors of EMT such as Snail and N-cadherin increased, whereas E-cadherin decreased in the TAM-treated cells, contributing to TAM-induced EMT in these endometrial cancer cells. In addition, we showed that c-Myc directly binds to and represses the promoter of miR-200 miRNAs, and its up-regulation in TAM-treated endometrial cancer cells leads to the down-regulation of miR-200 and eventually to EMT. Collectively, our data suggest that TAM can repress the miR-200 family and induce EMT via the up-regulation of c-Myc in endometrial cancer cells. These findings describe a possible mechanism of TAM-induced EMT in endometrial cancer and provide a potential new therapeutic strategy for it. 23413033 Fine-tuning of Voltage Sensitivity of the Kv1.2 Potassium Channel by Interhelix Loop Dynamics. Many proteins function by changing conformation in response to ligand binding or changes in other factors in their environment. Any change in the sequence of a protein, for example during evolution, which alters the relative free energies of the different functional conformations changes the conditions under which the protein will function. Voltage-gated ion channels are membrane proteins that open and close an ion-selective pore in response to changes in transmembrane voltage. The charged S4 transmembrane helix transduces changes in transmembrane voltage into a change in protein internal energy by interacting with the rest of the channel protein through a combination of non-covalent interactions between adjacent helices and covalent interactions along the peptide backbone. However, the structural basis for the wide variation in the V50 value between different voltage-gated potassium channels is not well defined. To test the role of the loop linking the S3 helix and the S4 helix in voltage sensitivity, we have constructed a set of mutants of the rat Kv1.2 channel that vary solely in the length and composition of the extracellular loop that connects S4 to S3. We evaluated the effect of these different loop substitutions on the voltage sensitivity of the channel and compared these experimental results with molecular dynamics simulations of the loop structures. Here, we show that this loop has a significant role in setting the precise V50 of activation in Kv1 family channels. 23200246 Anti-inflammatory norditerpenoids from the soft coral Sinularia maxima. Chemical investigation of the soft coral Sinularia maxima resulted in the isolation of seven norditerpenoids, including two new compounds, 12-hydroxy-scabrolide A (2) and 13-epi-scabrolide C (6). The structures of the isolated compounds were elucidated based on extensive spectroscopic evidence including Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and both one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR, respectively), in comparison with reported data. Compound 6 potently inhibited IL-12 and IL-6 production in LPS-stimulated bone marrow derived dendritic (BMDCs) with IC(50) values of 5.30 ± 0.21 and 13.12 ± 0.64 μM, respectively. Compound 1 exhibited moderate inhibitory activity against IL-12 and IL-6 production with IC(50) values of 23.52 ± 1.37 and 69.85 ± 4.11 μM, respectively. 23514620 Hyaluronic Acid nanoparticles titrate the viscoelastic properties of viscosupplements. Hyaluronic acid (HA) is a glycosaminoglycan with diverse biomedical applications including viscosupplementation of synovial fluid for the treatment osteoarthritis. Current HA viscosupplements such as Synvisc, Orthovisc, and Hyalgan have shown positive effects of reducing pain and improving joint function. The therapeutic efficacy, however, is highly transient, and these viscous fluids suffer from poor injectability. HA nanoparticles were found to modify the rheological properties of a model of the HA viscosupplement Orthovisc. Nanoparticles were successfully synthesized from 17 and 1500 kDa HA. Nanoparticle suspensions of HA were studied at different concentrations and in blends with the model viscosupplement. Nanoparticles made from 1500 kDa HA reduced the viscosupplement viscosity and elasticity to a much greater degree than nanoparticles made from 17 kDa HA. The difference in the nanoparticle effect on viscoelasticity suggested that nanoparticles made from 17 kDa HA may have dangling surface polymers that facilitated interactions with HA in solution. This hypothesis was supported by the greater compressibility of 17 kDa nanoparticles as determined by ultrasonic vibrational spectroscopy. Rheological investigations showed that the viscoelasticity of viscosupplements could be discretely titrated by modulating the concentration and type of HA nanoparticle additive (hard sphere or hairy). Thus, the injectability of viscosupplements may be enhanced while maintaining high elasticity. 22824788 Telomere shortening and DNA damage of embryonic stem cells induced by cigarette smoke. Embryonic stem cells (ESCs) provide a valuable in vitro model for testing toxicity of chemicals and environmental contaminants including cigarette smoke. Mouse ESCs were acutely or chronically exposed to smoke components, cigarette smoke condensate (CSC), or cadmium, an abundant component of CSC, and then evaluated for their self-renewal, apoptosis, DNA damage and telomere function. Acute exposure of ESCs to high dose of CSC or cadmium increased DNA damage and apoptosis. Yet, ESCs exhibited a remarkable capacity to recover following absence of exposure. Chronic exposure of ESCs to low dose of CSC or cadmium resulted in shorter telomeres and DNA damage. Together, acute exposure of ESCs to CSC or cadmium causes immediate cell death and reduces pluripotency, while chronic exposure of ESCs to CSC or cadmium leads to DNA damage and telomere shortening. Notably, a sub-proportion of ESCs during passages is selected to resist to smoke-induced oxidative damage to telomeres. 23330984 Development of a natural products database from the biodiversity of Brazil. We describe herein the design and development of an innovative tool called the NuBBE database (NuBBEDB), a new Web-based database, which incorporates several classes of secondary metabolites and derivatives from the biodiversity of Brazil. This natural product database incorporates botanical, chemical, pharmacological, and toxicological compound information. The NuBBEDB provides specialized information to the worldwide scientific community and can serve as a useful tool for studies on the multidisciplinary interfaces related to chemistry and biology, including virtual screening, dereplication, metabolomics, and medicinal chemistry. The NuBBEDB site is at http://nubbe.iq.unesp.br/nubbeDB.html . 23546601 Estrogen Receptor-α Variant, ER-α36, is Involved in Tamoxifen Resistance and Estrogen Hypersensitivity. Antiestrogens such as tamoxifen provided a successful treatment for ER-positive breast cancer for the past two decades. However, most breast tumors are eventually resistant to tamoxifen therapy. The molecular mechanisms underlying tamoxifen resistance have not been well established. Recently, we reported that breast cancer patients with tumors expressing high concentrations of ER-α36, a variant of ER-α, benefited less from tamoxifen therapy than those with low concentrations of ER-α36, suggesting that increased ER-α36 concentration is one of the underlying mechanisms of tamoxifen resistance. Here, we investigated the function and underlying mechanism of ER-α36 in tamoxifen resistance. We found that tamoxifen increased ER-α36 concentrations and tamoxifen-resistant MCF7 cells expressed high concentrations of ER-α36. In addition, MCF7 cells with forced expression of recombinant ER-α36 and H3396 cells expressing high concentrations of endogenous ER-α36 were resistant to tamoxifen. ER-α36 downregulation in tamoxifen-resistant cells with the shRNA method restored tamoxifen sensitivity. We also found tamoxifen acted as a potent agonist by activating phosphorylation of the AKT kinase in ER-α36 expressing cells. Finally, we found that cells with high concentration of ER-α36 protein were hypersensitive to estrogen; activating ERK phosphorylation at pM range. Our results thus demonstrated that elevated ER-α36 concentration is one of the mechanisms by which ER-positive breast cancer cells escape tamoxifen therapy and provided a rational to develop novel therapeutic approaches for tamoxifen resistant patients by targeting ER-α36. 23361914 [(3)H]UR-PLN196: a selective nonpeptide radioligand and insurmountable antagonist for the neuropeptide Y Y(2) receptor. Radioing in on NPY: Attachment of a [2,3-(3)H]propionyl group through an appropriate linker to the guanidine group of an (S)-argininamide-type neuropeptide Y (NPY) Y(2) receptor antagonist resulted in a subtype-selective radioligand. 23228193 A new antibacterial phenanthrenequinone from Dendrobium sinense. A new phenanthrenequinone, named denbinobin B (1), together with three known phenanthrenes was isolated from the whole plant of Dendrobium sinense T. Tang et F.T. Wang, an endemic and endangered orchid to Hainan Island. The new compound was elucidated using a combination of 1D, 2D NMR (COSY, HMQC, and HMBC) techniques, and HR-ESI-MS analyses. Compound 1 exhibited moderate antibacterial activity against Staphylococcus aureus with the diameter of the inhibition zone of 16.5 mm. 23160003 Biomimetic diversity-oriented synthesis of benzannulated medium rings via ring expansion. Nature has exploited medium-sized 8- to 11-membered rings in a variety of natural products to address diverse and challenging biological targets. However, owing to the limitations of conventional cyclization-based approaches to medium-ring synthesis, these structures remain severely underrepresented in current probe and drug discovery efforts. To address this problem, we have established an alternative, biomimetic ring expansion approach to the diversity-oriented synthesis of medium-ring libraries. Oxidative dearomatization of bicyclic phenols affords polycyclic cyclohexadienones that undergo efficient ring expansion to form benzannulated medium-ring scaffolds found in natural products. The ring expansion reaction can be induced using three complementary reagents that avoid competing dienone-phenol rearrangements and is driven by rearomatization of a phenol ring adjacent to the scissile bond. Cheminformatic analysis of the resulting first-generation library confirms that these molecules occupy chemical space overlapping with medium-ring natural products and distinct from that of synthetic drugs and drug-like libraries. 23265456 Fast HPLC-DAD quantification of nine polyphenols in honey by using second-order calibration method based on trilinear decomposition algorithm. This paper describes the use of second-order calibration for development of HPLC-DAD method to quantify nine polyphenols in five kinds of honey samples. The sample treatment procedure was simplified effectively relative to the traditional ways. Baselines drift was also overcome by means of regarding the drift as additional factor(s) as well as the analytes of interest in the mathematical model. The contents of polyphenols obtained by the alternating trilinear decomposition (ATLD) method have been successfully used to distinguish different types of honey. This method shows good linearity (r>0.99), rapidity (t<7.60 min) and accuracy, which may be extremely promising as an excellent routine strategy for identification and quantification of polyphenols in the complex matrices. 23439241 pH-gradient PAMPA-based in vitro model assay for drug-induced phospholipidosis in early stage of drug discovery. In the present study we validated a widely used, high-throughput in vitro permeability model (PAMPA) to be used at the early stage of drug discovery for the phospholipidosis (PLD) prediction of drug-like compounds. Regarding the mechanism of action of PLD, our pH-gradient PAMPA system is the first noncell based model to mimic one-way transport of cationic amphiphilic drugs (CADs) from cytosol to the lysosome. Moreover, due to the fact that PLD can mainly occur in lung, liver, brain, kidney and heart, we have used similar commercially available original tissue-derived lipid fractions (heart, liver, brain), and in the case mimicking membrane of kidney and lung tissue we prepared tissue-mimetic artificial lipid mixtures in house. Metabolism of a drug can change the degree of PLD depending on the physicochemical properties of metabolites and the rate of metabolism. Our data from 57 drugs and 4 metabolites of earlier and 2 metabolites of newly recognized outliers (phenacetin and bupropion) using our pH-gradient PAMPA system show a good correlation with in vivo PLD data. Moreover, predictive ability of our best system, the lung specific pH-gradient PAMPA model was significantly better than widely used in silico models and it was also slightly better than that of the known noncell based models on our selection of compounds. Our pH-gradient PAMPA systems therefore offer mechanistically alternative, accurate and cost-effective screening tools for the early prediction of PLD potential of drug-like compounds. 23558950 E2f2 induces cone photoreceptor apoptosis independent of E2f1 and E2f3. The 'activating' E2fs (E2f1-3) are transcription factors that potently induce quiescent cells to divide. Work on cultured fibroblasts suggested they were essential for division, but in vivo analysis in the developing retina and other tissues disproved this notion. The retina, therefore, is an ideal location to assess other in vivo adenovirus E2 promoter binding factor (E2f) functions. It is thought that E2f1 directly induces apoptosis, whereas other activating E2fs only induce death indirectly by upregulating E2f1 expression. Indeed, mouse retinoblastoma (Rb)-null retinal neuron death requires E2f1, but not E2f2 or E2f3. However, we report an entirely distinct mechanism in dying cone photoreceptors. These neurons survive Rb loss, but undergo apoptosis in the cancer-prone retina lacking both Rb and its relative p107. We show that while E2f1 killed Rb/p107 null rod, bipolar and ganglion neurons, E2f2 was required and sufficient for cone death, independent of E2f1 and E2f3. Moreover, whereas E2f1-dependent apoptosis was p53 and p73-independent, E2f2 caused p53-dependent cone death. Our in vivo analysis of cone photoreceptors provides unequivocal proof that E2f-induces apoptosis independent of E2f1, and reveals distinct E2f1- and E2f2-activated death pathways in response to a single tumorigenic insult.Cell Death and Differentiation advance online publication, 5 April 2013; doi:10.1038/cdd.2013.24. 23396442 Structural and mechanical properties of individual human telomeric G-quadruplexes in molecularly crowded solutions. Recent experiments provided controversial observations that either parallel or non-parallel G-quadruplex exists in molecularly crowded buffers that mimic cellular environment. Here, we used laser tweezers to mechanically unfold structures in a human telomeric DNA fragment, 5'-(TTAGGG)4TTA, along three different trajectories. After the end-to-end distance of each unfolding geometry was measured, it was compared with PDB structures to identify the best-matching G-quadruplex conformation. This method is well-suited to identify biomolecular structures in complex settings not amenable to conventional approaches, such as in a solution with mixed species or at physiologically significant concentrations. With this approach, we found that parallel G-quadruplex coexists with non-parallel species (1:1 ratio) in crowded buffers with dehydrating cosolutes [40% w/v dimethyl sulfoxide (DMSO) or acetonitrile (ACN)]. In crowded solutions with steric cosolutes [40% w/v bovine serum albumin (BSA)], the parallel G-quadruplex constitutes only 10% of the population. This difference unequivocally supports the notion that dehydration promotes the formation of parallel G-quadruplexes. Compared with DNA hairpins that have decreased unfolding forces in crowded (9 pN) versus diluted (15 pN) buffers, those of G-quadruplexes remain the same (20 pN). Such a result implies that in a cellular environment, DNA G-quadruplexes, instead of hairpins, can stop DNA/RNA polymerases with stall forces often <20 pN. 22677475 Effect of tetrabrombisphenol A on induction of apoptosis in the testes and changes in expression of selected testicular genes in CD1 mice. Tetrabromobisphenol A (TBBPA) is a substance widely used in industry as a flame retardant. TBBPA was found in the environment and was detected even in the human body. The effect of this chemical was observed in different cell lines in vitro and it is supposed that TBBPA may affect various hormonal systems in vivo. In this study we examined the effect of TBBPA on the reproductive parameters of two generations of outbred mice in vivo. Experimental and control animals of F1 generation were bred in various conditions to enable evaluation of the possible trans-generational effect. An increased incidence of apoptosis in the testes and changes in the morphometry of seminiferous tubules was detected in the experimental animals. In addition, changes in the expression pattern of selected genes encoding proteins that play an important role during spermatogenesis were observed. In contrast, sperm quality and reproduction were not affected by TBBPA. 23590386 Fibrillar Morphology of Derivatives of Poly(3-alkylthiophene)s by Solvent Vapor Annealing: Effects of Conformational Transition and Conjugate Length. A fibrillar morphology was obtained, compared to the featherless pristine films, via solvent annealing the films of a series of derivatives of poly(3-alkylthiophene)s (P3ATs): poly(3-dodecylthiophene) (P3DDT), poly(3,3‴-didodecyl-quaterthiophene) (PQT12), and poly(2,5-bis(3-dodecylthiophen-2-yl)thieno[3,2-b]thiophene) (pBTTT12). Among the solvents used, including dichloromethane, chloroform, tetrahydrofuran, and carbon disulfide (CS2), CS2 was the best to induce fibril formation because its solubility parameter is closest to those of the P3AT derivatives. It was found that higher critical CS2 vapor pressures were needed to form crystal nuclei with increasing conjugation length and molecular weight of the P3AT derivatives; i.e., the critical vapor pressures for P3DDT 13.9k and PQT12 15.5k were 59.0% and 80.7%, respectively, and there were no nuclei of fibrils for pBTTT12 15.6k with the highest conjugation length, even at a CS2 vapor pressure of 98.3%. Meanwhile, at the highest vapor pressure, the fibril density decreased with increasing conjugation length and molecular weight of the P3AT derivatives. This is attributed to the rod-like conformation prevailing for polymers with larger conjugation length and higher molecular weight during solvent annealing, making the conformational transition toward coils more difficult and hindering diffusion of molecules. The results presented here are expected to be helpful for the design and processing of conjugated semiconductor polymers. 22628017 Direct Effects of Vaccinium myrtillus L. Fruit Extracts on Rat Heart Mitochondrial Functions. In this study, the direct influence of bilberry (Vaccinium myrtillus) fruit extracts (aqueous and ethanolic) rich in anthocyanins on the oxidative phosphorylation of isolated rat heart mitochondria was investigated in vitro. Higher concentrations of bilberry extracts concentration-dependently inhibited mitochondrial state 3 respiration (by 23%-61%) with pyruvate plus malate, mildly (by 1.2- to 1.3-fold) uncoupled the oxidative phosphorylation, and increased (by 30%-87%) the state 4 respiration rate in the presence of exogenous cytochrome c. Succinate oxidation was less affected. Pure anthocyanins, the main components of used extracts, malvidin-3-glucoside, malvidin-3-galactoside, and cyanidin-3-galactoside, had no effect on oxidation of pyruvate plus malate. A statistically significant decrease in H2 O2 production by mitochondria was found in the presence of bilberry fruit extracts. Our findings show that bilberry fruit anthocyanin-rich extracts possess direct effects on rat heart mitochondrial function in vitro. These findings give the first insights into the mechanism(s) of their action on cellular energy metabolism. Copyright © 2012 John Wiley & Sons, Ltd. 23355287 Electrospun TiO2 nanorods with carbon nanotubes for efficient electron collection in dye-sensitized solar cells. A high power conversion efficiency of 10.24% can be obtained in a dye-sensitized solar cell by incorporating multiwall carbon nanotubes inside a TiO2 nanorod photoanode. The multiwall carbon nanotubes in the nanorod can effectively collect and transport photogenerated electrons reducing the recombination as well as improving efficiency of the device. 23500768 Astaxanthin ameliorates lung fibrosis in vivo and in vitro by preventing transdifferentiation, inhibiting proliferation, and promoting apoptosis of activated cells. Astaxanthin, a member of the carotenoid family, is the only known ketocarotenoid transported into the brain by transcytosis through the blood-brain barrier. However, whether astaxanthin has antifibrotic functions is unknown. In this study, we investigated the effects of astaxanthin on transforming growth factor β1-mediated and bleomycin-induced pulmonary fibrosis in vitro and in vivo. The results showed that astaxanthin significantly improved the structure of the alveoli and alleviated collagen deposition in vivo. Compared with the control group, the astaxanthin-treated groups exhibited downregulated protein expressions of α-smooth muscle actin, vimentin, hydroxyproline, and B cell lymphoma/leukemia-2 as well as upregulated protein expressions of E-cadherin and p53 in vitro and in vivo. Astaxanthin also inhibited the proliferation of activated A549 and MRC-5 cells at median inhibitory concentrations of 40 and 30μM, respectively. In conclusion, astaxanthin could relieve the symptoms and halt the progression of pulmonary fibrosis, partly by preventing transdifferentiation, inhibiting proliferation, and promoting apoptosis of activated cells. 23474323 Evaluation of some selected blood parameters and histopathology of liver and kidney of rats fed protein-substituted mucuna flour and derived protein rich product. This comparative study reports the nutritional and toxicological characteristics of Mucuna pruriens flour and a protein-rich product developed from it. The protein-rich mucuna product (PRMP) was obtained by the three steps procedure: protein solubilization, heat-coagulation and sieving. Three weeks rats (n=6 per group) were fed for 28days on standard protein-substituted rat feed with mucuna flour or PRMP. The experimental design was a factorial design with three mucuna accessions (Velvet, Black and White) and two treatments (flour and PRMP). The protein content ranged 27.2-31.5g/100g for flour and 58.8-61.1% for PRMP. Processing flour into PRMP led to a significant (p<0.05) reduction of tannins (50%), total polyphenols (50%) and trypsin inhibitors (94%). The rats fed PMRP diets witnessed weight gain similar to casein, while those fed mucuna flour lost weight. The levels of total cholesterol, HDL-cholesterol and LDL-cholesterol observed in animals groups fed mucuna flour and PRMP were significantly lower (p<0.05) than the control group. In addition lymphocytes, granulocytes, red blood cells, hemoglobin and hematocrit of rats fed mucuna flour were significantly (p<0.05) lower than values in other rats groups. Kidneys glomerular sclerosis and high creatinine levels were observed in group fed mucuna flour. PRMP then represents a good alternative of using mucuna proteins for human nutrition. 23023024 The effects of α-tocopherol on oxidative damage and serum levels of Clara cell protein 16 in aspiration pneumonitis induced by bile acids. Our aim in this study is to examine the effects of α-tocopherol (AT) on rats with aspiration pneumonitis induced with bile acids (BAs). The animals were divided in to four groups, namely saline group (n = 7), saline + AT group (n = 7), BA group (n = 7), and BA + AT group (n = 7). Saline and BA groups aspirated intratracheally with 1 ml/kg saline and 1 ml/kg bile acids, respectively. AT was given at 20 mg/kg/day dosage for 7 days to the groups. AT group was given 20 mg/kg/day AT for 7 days. Malondialdehyde (MDA), Clara cell protein 16 (CC-16), catalase (CAT), superoxide dismutase (SOD), as well as peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, and necrosis were evaluated. The CAT activity of the BA group was significantly lower than the saline group. In the BA + AT group, there was a significant increase in SOD and CAT activities when compared with that of the BA group. The CC-16 and MDA contents in the BA group were significantly higher than in the saline group. The CC-16 and MDA levels of the BA + AT group were significantly lower than BA group. Histopathologic changes were seen in BA group, and there was a significant decrease in the BA + AT group. In conclusion, AT might be beneficial in the treatment of aspiration pneumonitis induced by BAs because AT decreased oxidative damage and resulted in a decrease in CC-16 levels. 23237305 Influence of glass scaffolds macroporosity on the bioactive process. Little is known about the ideal morphology for three-dimensional (3D) porous scaffolds to be used in bone tissue engineering. The present study will supply useful data about the dependence of the mineralization process upon macroporous features of bioactive glass scaffolds. It also points out the difficulty in distinguishing between the bioactive properties of scaffolds if using common characterization techniques often considered as standard techniques to assess in vitro bioactivity. Here, two bioactive glass foams with different porosities (porous diameters and interconnection sizes) were successfully synthesized by varying the surfactant quantity in the sol-gel foaming process. The two foams had porosities apparently sufficient to serve as a bone tissue engineering scaffold and exhibited no significant difference when studied for the releasing or the taking up of ionic species when immersed in simulated body fluid (SBF). However, thanks to microion beam analysis, it was possible to highlight key differences in the mineralization reaction taking place at the surface of the pores. It is clearly evident that the homogeneity of reaction inside the 3D-scaffolds is particularly dependent upon porosity. In particular, it is demonstrated that inadequate porous features can result in limited circulation of the fluid inside the pores. Careful attention must be paid to the pore size distribution and interconnection sizes when designing scaffolds for bone tissue engineering, in order to induce homogeneous mineralization inside the porous material and for the scaffold to be efficiently alimented with nutrients or growth factors while allowing a free circulation of the bone cells. 23178178 Subtle alterations in swimming speed distributions of rainbow trout exposed to titanium dioxide nanoparticles are associated with gill rather than brain injury. The effects of engineered nanomaterials on fish behaviours are poorly understood. The present study aimed to determine the locomotor behaviours of trout during waterborne exposure to titanium dioxide nanoparticles (TiO(2) NPs) as well as inform on the underlying physiological mechanisms involved. Trout were exposed to either control (without TiO(2)), 1 mg l(-1) TiO(2) NPs or 1 mg l(-1) bulk TiO(2) for 14 days. Titanium dioxide exposure resulted in 31 (bulk) and 22 fold (nano) increases in the Ti concentrations of gill tissue compared to controls, but there were no measurable increases of Ti in the internal organs including the brain. Gill pathologies were observed in both TiO(2) treatments. Locomotor behaviours were quantified using video tracking software and the proportion of time spent swimming at high speed (>20 cms(-1)) was significantly decreased in fish exposed to TiO(2) NPs, compared to controls, but not fish exposed to bulk TiO(2). The shift in swimming speed distribution in the TiO(2) NP-exposed fish was associated with decreased area of red pulp in the spleen, increases in haematocrit and whole blood haemoglobin, all consistent with a compensation for respiratory hypoxia without the accumulation of plasma lactate. Fish exposed to TiO(2) NPs also retained competitive abilities when paired with controls in aggressive social encounters. The duration of competitive contests, the level of aggression and contest outcome were not affected by NP exposure. Neurological injury did not explain the changes in locomotor behaviour, although there was some apparent enlargement of the blood vessels on the brain. Whole brain homogenates showed a statistically significant increase in oxidative stress defences such as the total glutathione pool, but without loss of Na(+)K(+)-ATPase or acetylcholinesterase activities. 23238352 New insight into the ZnO sulfidation reaction: mechanism and kinetics modeling of the ZnS outward growth. Zinc oxide based materials are commonly used for the final desulfurization of synthesis gas in Fischer-Tropsch based XTL processes. Although the ZnO sulfidation reaction has been widely studied, little is known about the transformation at the crystal scale, its detailed mechanism and kinetics. A model ZnO material with well-determined characteristics (particle size and shape) has been synthesized to perform this study. Characterizations of sulfided samples (using XRD, TEM and electron diffraction) have shown the formation of oriented polycrystalline ZnS nanoparticles with a predominant hexagonal form (wurtzite phase). TEM observations also have evidenced an outward development of the ZnS phase, showing zinc and oxygen diffusion from the ZnO-ZnS internal interface to the surface of the ZnS particle. The kinetics of ZnO sulfidation by H(2)S has been investigated using isothermal and isobaric thermogravimetry. Kinetic tests have been performed that show that nucleation of ZnS is instantaneous compared to the growth process. A reaction mechanism composed of eight elementary steps has been proposed to account for these results, and various possible rate laws have been determined upon approximation of the rate-determining step. Thermogravimetry experiments performed in a wide range of H(2)S and H(2)O partial pressures have shown that the ZnO sulfidation reaction rate has a nonlinear variation with H(2)S partial pressure at the same time no significant influence of water vapor on reaction kinetics has been observed. From these observations, a mixed kinetics of external interface reaction with water desorption and oxygen diffusion has been determined to control the reaction kinetics and the proposed mechanism has been validated. However, the formation of voids at the ZnO-ZnS internal interface, characterized by TEM and electron tomography, strongly slows down the reaction rate. Therefore, the impact of the decreasing ZnO-ZnS internal interface on reaction kinetics has been taken into account in the reaction rate expression. In this way the void formation at the interface has been modeled considering a random nucleation followed by an isotropic growth of cavities. Very good agreement has been observed between both experimental and calculated rates after taking into account the decrease in the ZnO-ZnS internal interface. 23439561 NADPH Oxidase NOX5-S and Nuclear Factor κB1 Mediate Acid-Induced Microsomal Prostaglandin E Synthase-1 Expression in Barrett's Esophageal Adenocarcinoma Cells. The mechanisms of progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA) are not known. Cycloxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) has been shown to be important in esophageal tumorigenesis. We have shown that COX-2 mediates acid-induced PGE2 production. The prostaglandin E synthase (PGES) responsible for acid-induced PGE2 production in BE, however, is not known. We found that microsomal PGES1 (mPGES1), mPGES2, and cytosolic PGES (cPGES) were present in FLO EA cells. Pulsed acid treatment significantly increased mPGES1 mRNA and protein levels but had little or no effect on mPGES2 or cPGES mRNA. Knockdown of mPGES1 by mPGES1 small interfering RNA (siRNA) blocked acid-induced increase in PGE2 production and thymidine incorporation. Knockdown of NADPH oxidase, NOX5-S, a variant lacking calcium-binding domains, by NOX5 siRNA significantly inhibited acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production. Overexpression of NOX5-S significantly increased the luciferase activity in FLO cells transfected with a nuclear factor κB (NF-κB) in vivo activation reporter plasmid pNF-κB-Luc. Knockdown of NF-κB1 p50 by p50 siRNA significantly decreased acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production. Two novel NF-κB binding elements, GGAGTCTCCC and CGGGACACCC, were identified in the mPGES1 gene promoter. We conclude that mPGES1 mediates acid-induced increase in PGE2 production and cell proliferation. Acid-induced mPGES1 expression depends on activation of NOX5-S and NF-κB1 p50. Microsomal PGES1 may be a potential target to prevent or treat EA. 23194510 Formation of carcinogenic 4(5)-methylimidazole in caramel model systems: a role of sulphite. Aqueous caramel model systems consisted the D-glucose/NH(3)/sulphite were heated at 100°C for 2 h and amounts of carcinogenic 4(5)-methylimidazole (4-MI) formed were determined. The amount formed ranged from 7.0 to 155.0 ppm. A system with 0.1 M sulphite yielded the greatest amount of 4-MI, which was 54% more than that yielded from a system without sulphite. When the amount of sulphite increased over 0.1 M, the amount of 4-MI reduced. The greatest reduction was achieved with 0.2 M sulphite by 68% compared to 0 M sulphite, suggesting that sulphite plays an important role in the formation of carcinogenic 4-MI in caramel colour. Also, a system with 0.1 M sulphite yielded the most intense caramel colour but the other levels of sulphite did not change the colour intensity significantly. Sulphite contributed slightly to the level of flavour chemicals evaluated using pyrazine formation. The results suggest that sulphite addition at appropriate amount reduces 4-MI formation in caramel colour without sacrificing flavour and colour formation. 23376608 Apigenin induces c-Myc-mediated apoptosis in FRO anaplastic thyroid carcinoma cells. Apigenin promotes apoptosis in cancer cells. We studied the effect of apigenin on cell survival and c-Myc expression in FRO anaplastic thyroid carcinoma (ATC) cells. Apigenin caused apoptosis via the elevation of c-Myc levels in conjunction with the phosphorylation of p38 and p53. In the c-Myc siRNA-transfected and apigenin-treated cells, compared with the apigenin-treated control cells, apoptosis and phosphorylation of p38 and p53 were ameliorated. In the presence of apigenin, diminution of p38 and p53 did not affect cell survival although apigenin activated the phosphorylation of p38 and p53 via increased c-Myc levels. In conclusion, our results indicate that apigenin induces apoptosis mediated via c-Myc with concomitant phosphorylation of p53 and p38 in FRO ATC cells. These findings suggest that augmented c-Myc acts as a core regulator and is necessary for apigenin-induced apoptosis in FRO ATC cells. 23214439 Fibril formation by pH and temperature responsive silk-elastin block copolymers. In this report, we study the self-assembly of two silk-elastin-like proteins: one is a diblock S(24)E(40) composed of 24 silk-like (S) repeats and 40 elastin-like (E) repeats; the other is a triblock S(12)C(4)E(40), in which the S and E blocks are separated by a random coil block (C(4)). Upon lowering the pH, the acidic silk-like blocks fold and self-assemble into fibrils by a nucleation-and-growth process. While silk-like polymers without elastin-like blocks form fibrils by heterogeneous nucleation, leading to monodisperse populations, the elastin-like blocks allow for homogeneous nucleation, which gives rise to polydisperse length distributions, as well as a concentration-dependent fibril length. Moreover, the elastin-like blocks introduce temperature sensitivity: at high temperature, the fibrils become sticky and tend to bundle and aggregate in an irreversible manner. Concentrated solutions of S(12)C(4)E(40) form weak gels at low pH that irreversibly lose elasticity in temperature cycling; this is also attributed to fibril aggregation. 23512438 Pesticide tolerant and phosphorus solubilizing Pseudomonas sp. strain SGRAJ09 isolated from pesticides treated Achillea clavennae rhizosphere soil. In this study, an attempt was made to identify an effective phosphate solubilizing bacteria from pesticide polluted field soil. Based on the formation of solubilization halo on Pikovskaya's agar, six isolates were selected and screened for pesticide tolerance and phosphate (P) solubilization ability through liquid assay. The results showed that only one strain (SGRAJ09) obtained from Achillea clavennae was found to tolerate maximum level of the pesticides tested and it was phylogenetically identified as Pseudomonas sp. It possessed a wide range of pesticide tolerance, ranging from 117 μg mL(-1) for alphamethrin to 2,600 μg mL(-1) for endosulfan. The available P concentrations increased with the maximum and double the maximum dose of monocrotophos and imidacloprid, respectively. On subjected to FT-IR and HPLC analysis, the presence of organic acids functional group in the culture broth and the production of gluconic acid as dominant acid aiding the P solubilization were identified. On comparison with control broth, monocrotophos and imidacloprid added culture broth showed quantitatively high organic acids production. In addition to gluconic acid production, citric and acetic acids were also observed in the pesticide amended broth. Furthermore, the Pseudomonas sp. strain SGRAJ09 possessed all the plant growth promoting traits tested. In presence of monocrotophos and imidacloprid, its plant growth promoting activities were lower than that of the pesticides unamended treatment. 23360230 Surface-enhanced Raman scattering dye-labeled Au nanoparticles for triplexed detection of leukemia and lymphoma cells and SERS flow cytometry. The labeling of cell surface receptors by fluorescent markers is an established method for the identification of cell phenotype in both research and clinical settings. Fluorescence dye labeling has inherent constraints, most notably the upper limit of labels per cell that may be probed using a single excitation source, in addition to a physical limit to the number of broad emission spectra that can be distinctly collected within the visible wavelength region. SERS labeling has the potential to mitigate these shortfalls. Herein, antibody-targeted, PEG-coated surface-enhanced Raman scattering (SERS) Au nanoparticles are used simultaneously to label three cell surface markers of interest on malignant B cells from the LY10 lymphoma cell line. The SERS probes were characterized by multiple methods to confirm their monodispersity and functionalization with both PEG and monoclonal antibodies. The specificity of the particles' cell labeling was demonstrated on both primary chronic lymphocytic leukemia and LY10 cells using SERS from cell suspensions and confocal Raman mapping, respectively. Fluorescence flow cytometry was employed to confirm the binding of SERS probes to LY10 over large cell populations, and the particles' SERS was collected directly from labeled cells using a commercial flow cytometer. To the best of our knowledge, this is the first demonstration of SERS flow cytometry from cells tagged with targeted SERS probes. 23560989 Star Polymers with a Cationic Core Prepared by ATRP for Cellular Nucleic Acids Delivery. Poly(ethylene glycol) (PEG)-based star polymers with a cationic core were prepared by atom transfer radical polymerization (ATRP) for in vitro nucleic acid (NA) delivery. The star polymers were synthesized by ATRP of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and ethylene glycol dimethacrylate (EGDMA). Star polymers were characterized by gel permeation chromatography, zeta potential, and dynamic light scattering. These star polymers were combined with either plasmid DNA (pDNA) or short interfering RNA (siRNA) duplexes to form polyplexes for intracellular delivery. These polyplexes with either siRNA or pDNA were highly effective in NA delivery, particularly at relatively low star polymer weight or molar ratios, highlighting the importance of NA release in efficient delivery systems. 23244178 Generic methods for micrometer- and nanometer-scale surface derivatization based on photochemical coupling of primary amines to monolayers of aryl azides on gold and aluminum oxide surfaces. A series of aryl azide terminated thiols and phosphonic acids has been synthesized, and used to prepare self-assembled monolayers on (respectively) gold and aluminum oxide surfaces. The rates of photoactivation were determined using contact angle measurement and X-ray photoelectron spectroscopy (XPS). The behavior of a diazirine functionalized aryl thiol was also studied. The rates of activation were found to be similar for all five adsorbates. However, the extent of photochemical coupling of a primary amine was significantly greater for the aryl azides than for the diazirine. A range of primary amines was successfully coupled to all of the azides with high yield. Little difference in reactivity was observed following perfluorination of the aromatic ring. Micrometer-scale patterns were fabricated by carrying out exposures of the aryl azide terminated SAMs through a mask submerged under a film of primary amine. Contrasting amines could be introduced to unreacted regions in a subsequent maskless step. A scanning near-field optical microscope was used to fabricate nanopatterns. Exposure of the azides to irradiation at 325 nm in air enabled selective deactivation of azides. The surrounding surface was functionalized with a primary amine in a maskless process; when a protein-resistant oligo(ethylene glycol) functionalized amine was used it was possible to produce protein nanopatterns, by adsorbing protein to features defined using near-field exposure. 23190172 17β-Oestradiol anti-inflammatory effects in primary astrocytes require oestrogen receptor β-mediated neuroglobin up-regulation. Neuroglobin (Ngb), so named after its initial discovery in brain neurones, has received great attention as a result of its neuroprotective effects both in vitro and in vivo. Recently, we demonstrated that, in neurones, Ngb is a 17β-oestradiol (E(2) ) inducible protein that is pivotal for hormone-induced anti-apoptotic effects against H(2) O(2) toxicity. The involvement of Ngb in other brain cell populations, as well as in other neuroprotective effects of E(2) , is completely unknown at present. We demonstrate Ngb immunoreactivity in reactive astrocytes located in the proximity of a penetrating cortical injury in vivo and the involvement of Ngb in the E(2) -mediated anti-inflammatory effect in primary cortical astrocytes. Upon binding to oestrogen receptor (ER)β, E(2) enhances Ngb levels in a dose-dependent manner. Although with a lesser degree than E(2) , the pro-inflammatory stimulation with lipopolysaccharide (LPS) also induces the increase of Ngb protein levels via nuclear factor-(NF)κB signal(s). Moreover, a negative cross-talk between ER subtypes and NFκB signal(s) has been demonstrated. In particular, ERα-activated signals prevent the NFκB-mediated Ngb increase, whereas LPS impairs the ERβ-induced up-regulation of Ngb. Therefore, the co-expression of both ERα and ERβ is pivotal for mediating E(2) -induced Ngb expression in the presence of NFκB-activated signals. Interestingly, Ngb silencing prevents the effect of E(2) on the expression of inflammatory markers (i.e. interleukin 6 and interferon γ-inducible protein 10). Ngb can be regarded as a key mediator of the different protective effects of E(2) in the brain, including protection against oxidative stress and the control of inflammation, both of which are at the root of several neurodegenerative diseases. 23548025 Artificial Neural Networks for Efficient Clustering of Conformational Ensembles and their Potential for Medicinal Chemistry. The biological function of proteins is strictly related to their molecular flexibility and dynamics: enzymatic activity, protein-protein interactions, ligand binding and allosteric regulation are important mechanisms involving protein motions. Computational approaches, such as Molecular Dynamics (MD) simulations, are now routinely used to study the intrinsic dynamics of target proteins as well as to complement molecular docking approaches. These methods have also successfully supported the process of rational design and discovery of new drugs. Identification of functionally relevant conformations is a key step in these studies. This is generally done by cluster analysis of the ensemble of structures in the MD trajectory. Recently Artificial Neural Network (ANN) approaches, in particular methods based on Self-Organising Maps (SOMs), have been reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data-mining problems. In the specific case of conformational analysis, SOMs have been successfully used to compare multiple ensembles of protein conformations demonstrating a potential in efficiently detecting the dynamic signatures central to biological function. Moreover, examples of the use of SOMs to address problems relevant to other stages of the drug-design process, including clustering of docking poses, have been reported. In this contribution we review recent applications of ANN algorithms in analysing conformational and structural ensembles and we discuss their potential in computer-based approaches for medicinal chemistry. 23348754 A brief history of oxytocin and its role in modulating psychostimulant effects. Over the past century, the polypeptide oxytocin has played an important role in medicine with major highlights including the identification of its involvement in parturition and the milk let-down reflex. Oxytocin is now implicated in an extensive range of psychological phenomena including reward and memory processes and has been investigated as a treatment for several psychiatric disorders including addiction, anxiety, autism, and schizophrenia. In this review, we first provide an historical overview of oxytocin and describe key aspects of its physiological activity. We then outline some pharmacological limitations in this field of research before highlighting the role of oxytocin in a wide range of behavioral and neuronal processes. Finally, we review evidence for a modulatory role of oxytocin with regard to psychostimulant effects. Key findings suggest that oxytocin attenuates a broad number of cocaine and methamphetamine induced behaviors and associated neuronal activity in rodents. Evidence also outlines a role for oxytocin in the prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in both rodents and humans. Clinical trials should now investigate the effectiveness of oxytocin as a novel intervention for psychostimulant addiction and should aim to determine its specific role in the therapeutic properties of MDMA that are currently being investigated. 23302583 Design, synthesis and biological evaluation of novel 7-mercaptocoumarin derivatives as α(1)-adrenoceptor antagonists. Study on the pharmacophore model of α(1)-adrenoceptor (α(1)-AR) antagonists led to design a series of novel 7-mercaptocoumarin derivatives as α(1)-AR antagonists. All designed compounds have been synthesized and biologically evaluated. The results showed that most of them exhibited strong antagonistic activity. Especially compound 6 showed excellent activity, which was better than that of the reference compound prazosin. Structure-activity relationship studies revealed that small hydrophobic group at the terminal heterocyclic ring and ortho substituents on the phenyl ring of phenylpiperazine moiety were the essential structural factors for α(1)-AR antagonistic activity. The pharmacophore modeling studies further clarified their structural contributions to antagonistic activity and also demonstrated that 7-mercaptocoumarin moiety could be a useful scaffold for design of α(1)-AR antagonists. 23636584 A tuneable array of unique steady-state microfluidic gradients. We report an on-chip gradient generator that has been designed, modelled, fabricated, and characterized to facilitate temporal tuning of several unique gradients in parallel for multiple applications. This design allows for steady state programming of the intensities across multiple orders of magnitude while producing exponential, linear, and logarithmic gradient profiles. The magnitude of the gradients is controlled through regulating the ratio of the two on-chip flow inlets without the need for valves or other active mixers. On-chip binding of biotin by a fluorescent streptavidin complex creates a diffusive barrier that regulates access to the gradient inlets, providing a second orthogonal mechanism for regulating the microgradient intensities. The device is also characterized using an on-chip enzymatic reaction to produce an array of tuneable product concentrations within the various microchannels. 23537339 Enantioselective Iron-Catalyzed Azidation of β-Keto Esters and Oxindoles. The first example of Fe-catalyzed enantioselective azidations of β-keto esters and oxindoles using a readily available N3-transfer reagent is reported. A number of α-azido-β-keto esters were obtained with up to 93% ee, and this methodology also generates 3-substitued 3-azidooxindoles with high enantioselectivities (up to 94%). 23333899 Surface functionalization of doxorubicin-loaded liposomes with octa-arginine for enhanced anticancer activity. Doxorubicin-loaded PEGylated liposomes (commercially available as DOXIL® or Lipodox®) were surface functionalized with a cell-penetrating peptide, octa-arginine (R8). For this purpose, R8-peptide was conjugated to the polyethylene glycol-dioleoyl phosphatidylethanolamine (PEG-DOPE) amphiphilic co-polymer. The resultant R8-PEG-PE conjugate was introduced into the lipid bilayer of liposomes at 2mol% of total lipid amount via spontaneous micelle-transfer technique. The liposomal modification did not alter the particle size distribution, as measured by Particle Size Analyzer and transmission electron microscopy (TEM). However, surface-associated cationic peptide increased zeta potential of the modified liposomes. R8-functionalized liposomes (R8-Dox-L) markedly increased the intracellular and intratumoral delivery of doxorubicin as measured by flow cytometry and visualizing by confocal laser scanning microscopy (CLSM) compared to unmodified Doxorubicin-loaded PEGylated liposomes (Dox-L). R8-Dox-L delivered loaded Doxorubicin to the nucleus, being released from the endosomes at higher efficiency compared to unmodified liposomes, which had marked entrapment in the endosomes at tested time point of 1h. The significantly higher accumulation of loaded drug to its site of action for R8-Dox-L resulted in improved cytotoxic activity in vitro (cell viability of 58.5±7% for R8-Dox-L compared to 90.6±2% for Dox-L at Dox dose of 50μg/mL for 4h followed by 24h incubation) and enhanced suppression of tumor growth (348±53mm(3) for R8-Dox-L, compared to 504±54mm(3) for Dox-L treatment) in vivo compared to Dox-L. R8-modification has the potential for broadening the therapeutic window of pegylated liposomal doxorubicin treatment, which could lead to lower non-specific toxicity. 23295999 Poor definitions threaten drug trial safety in India. India has become a hotbed of clinical trials, but recent reports of safety lapses have prompted calls for better regulation in this area. Currently, trial requirements can be relaxed if doing so is in the 'public interest', but a clearer definition of what this means is needed before this provision should be used. 23033256 DNA methylation and histone modification profiles of mouse organic anion transporting polypeptides. Organic anion transporting polypeptides (rodents, Oatps; human, OATPs) are primarily involved in the transmembrane transportation of a wide range of endogenous and exogenous compounds. Multiple mouse Oatp1 isoforms are closely located on chromosome 6, where each isoform shows distinct tissue distribution; Oatp1b2, Oatp1a6, and Oatp1c1 are expressed exclusively in the liver, kidney, and cerebrum, respectively; Oatp1a1 in the liver and kidney; and Oatp1a4 in the liver and cerebrum. We have identified tissue-dependent differentially methylated region (T-DMR) around the transcriptional start site (TSS) of Oatp1b2, which correlates with its liver-specific expression. Bisulfite sequencing also demonstrated the presence of T-DMRs around the TSS in other Oatp1 genes: CpG dinucleotides at +149 relative to the TSS for Oatp1c1; -48, +101, and +356 for Oatp1a4; -572 and -550 for Oatp1a1; and -122 and +216 for Oatp1a6 were differentially methylated among the liver, kidney, and cerebrum. These methylation profiles were largely consistent with the tissue distribution of Oatp1 mRNAs. Chromatin immunoprecipitation assay revealed that the mRNA expression of Oatp1 genes was accompanied by acetylated histone H3. Human OATP1B1 and OATP1B3 are located on chromosome 12p12 in the OATP1 cluster; both show predominant expression in the liver. These genes also contained T-DMRs that were hypomethylated in the liver, compared with kidney cortex: -511, -411, and +92 relative to the TSS for OATP1B1 and -331, +70, and +73 for OATP1B3. These results suggest that the difference in epigenetic profiles comprising DNA methylation and histone acetylation determines the distinct tissue distribution of Oatp/OATP mRNAs. 23518857 Non-bonding interactions and internal dynamics in CH2F2H2CO: a rotational and model calculations study. The rotational spectra of three isotopologues of the 1 : 1 complex between difluoromethane and formaldehyde have been observed and assigned using pulsed jet Fourier transform microwave spectroscopy. The formaldehyde lies in the FCF plane of difluoromethane, linked through a C-HF and a bifurcated CH2O weak hydrogen bonds. The rotational transitions are split into two component lines with a relative intensity ratio of 1 : 3, due to the internal rotation of the formaldehyde moiety along its symmetry axis. The barrier to this motion has been estimated by using a flexible model to be V2 = 180(10) cm(-1). 23265902 A-ring modification of SCH 900229 and related chromene sulfone γ-secretase inhibitors. Attempts to block metabolism by incorporating a 9-fluoro substituent at the A-ring of compound 1 (SCH 900229) using electrophilic Selectfluor™ led to an unexpected oxidation of the A-ring to give difluoroquinone analog 1a. Oxidation of other related chromene γ-secretase inhibitors 2-8 resulted in similar difluoroquinone analogs 2a-8a, respectively. These quinone products exhibited comparable in vitro potency in a γ-scretase membrane assay, but were several fold less potent in a cell-based assay in lowering Aβ40-42, compared to their parent compounds. 23017385 Phenolic profiles of cultivated, in vitro cultured and commercial samples of Melissa officinalis L. infusions. Melissa officinalis L. (lemon balm) is normally consumed as an infusion and presents therapeutic properties, such as sedative, carminative and antispasmodic, also being included in some pharmaceutical preparations. The phenolic profiles of different samples of lemon balm, prepared as infusions, were evaluated by HPLC-DAD-ESI/MS. The profiles were compared in order to understand the differences between cultivated, in vitro cultured and commercial (bags and granulated) samples. All the samples showed a similar phenolic profile, presenting differences only in the quantities found of each compound. Rosmarinic acid was the most abundant compound, being higher in commercial samples, especially in tea bag sample (55.68mg/g of infusion) and lower in in vitro cultured sample (15.46mg/g). Moreover, dimers, trimers and tetramers of caffeic acid were identified and quantified for the first time in lemon balm. Only one flavonoid, luteolin-3'-O-glucuronide was found in all the samples, ranging from 8.43mg/g in commercial granulate sample to 1.22mg/g in in vitro cultured sample. Overall, cultivated and in vitro cultured samples presented the lowest amounts of phenolic compounds (59.59 and 30.21mg/g, respectively); otherwise, commercial samples showed the highest contents (109.24mg/g for tea bag and 101.03mg/g for granulate sample). The present study shows that infusion of lemon balm can be a source of phenolic compounds, known for their bioactive effects. 23401324 Plant consumption by grizzly bears reduces biomagnification of salmon-derived polychlorinated biphenyls, polybrominated diphenyl ethers, and organochlorine pesticides. The present study characterizes the uptake and loss of persistent organic pollutants (POPs) in grizzly bears (Ursus arctos horribilis) by sampling and analyzing their terrestrial and marine foods and fecal material from a remote coastal watershed in British Columbia, Canada. The authors estimate that grizzly bears consume 341 to 1,120 µg of polychlorinated biphenyls (PCBs) and 3.9 to 33 µg of polybrominated diphenyl ethers daily in the fall when they have access to an abundant supply of returning salmon. The authors also estimate that POP elimination by grizzly bears through defecation is very low following salmon consumption (typically <2% of intake) but surprisingly high following plant consumption (>100% for PCBs and organochlorine pesticides). Excretion of individual POPs is largely driven by a combination of fugacity (differences between bear and food concentrations) and the digestibility of the food. The results of the present study are substantiated by a principal components analysis, which also demonstrates a strong role for log KOW in governing the excretion of different POPs in grizzly bears. Collectively, the present study's results reveal that grizzly bears experience a vegetation-associated drawdown of POPs previously acquired through the consumption of salmon, to such an extent that net biomagnification is reduced. Environ. Toxicol. Chem. 2013;32:995-1005. © 2013 SETAC. 23543321 RNAi silencing of three homologues of S-adenosylmethionine decarboxylase gene in tapetal tissue of tomato results in male sterility. Polyamines play very important role in various cellular metabolic functions, including floral induction, floral differentiation and fertility regulation. In the present study, S-adenosylmethionine decarboxylase (SAMDC), a key gene involved in polyamine biosynthesis, has been targeted in tapetal tissue of tomato using RNAi to examine its effect on tapetum development and pollen viability. The target SAMDC gene fragments of three homologues were cloned in a hairpin RNA construct under the control of tapetal-specific A9 promoter, which was used to generate several RNAi tomato plants. These RNAi lines expressed the intended small interfering RNAs in the anther and showed the aborted and sterile pollen exhibiting shrunken and distorted morphology. These RNAi tomato plants having sterile pollen, failed to set fruits but female fertility of the plants remained unaffected as cross pollination resulted in fruit setting. Expression profiling of SAMDC genes showed considerable decrease in transcripts of SAMDC1 (5-8 fold) and SAMDC2 and SAMDC3 (2-3 fold) in the anthers of RNAi plants. The other polyamine biosynthesis genes, ADC and SPDSYN exhibited ~1.5 fold decrease in their transcript levels. Presence of siRNA molecules specific to SAMDC homologues in anther and tapetal-specific activity of A9 promoter as shown with GUS reporter system of RNAi plants suggested down-regulation of the target genes in tapetum by RNAi. These observations indicate the importance of SAMDC, in turn polyamines in pollen development, and thus tapetum-specific down-regulation of SAMDC genes using RNAi can be used for developing male sterile plants. 23210547 An explicit formula for optical oscillator strength of excitons in semiconducting single-walled carbon nanotubes: family behavior. The sensitive structural dependence of the optical properties of single-walled carbon nanotubes, which are dominated by excitons and tunable by changing diameter and chirality, makes them excellent candidates for optical devices. Because of strong many-electron interaction effects, the detailed dependence of the optical oscillator strength f(s) of excitons on nanotube diameter d, chiral angle θ, and electronic subband index P (the so-called family behavior), however, has been unclear. In this study, based on results from an extended Hubbard Hamiltonian with parameters derived from ab initio GW plus Bethe-Salpeter equation (GW-BSE) calculations, we have obtained an explicit formula for the family behavior of the oscillator strengths of excitons in semiconducting single-walled carbon nanotubes (SWCNTs), incorporating environmental screening. The formula explains recent measurements well and is expected to be useful in the understanding and design of possible SWCNT optical and optoelectronic devices. 23529571 Recent progress in nanosensors for sensitive detection of biomolecules. Developing sensitive, rapid, and cost-effective methods for detection of biomolecules is important for both clinical and numerous non-clinical applications. During the last two decades, functional nanomaterials with unique physical and chemical properties have provided significant advantages for biological detection. In this feature article, we introduce recent progress in nanobiosensor development by exploiting the optical, electrical and catalytic properties of a range of nanomaterials, with a focus on gold nanoparticles, carbon nanotubes, graphene and carbon dots. In addition, the perspectives on future opportunities and unsolved challenges are also discussed. 23330848 Acetylcholinesterase immobilized capillary reactors-tandem mass spectrometry: an on-flow tool for ligand screening. The use of immobilized capillary enzyme reactors (ICERs) for online ligand screening has been adopted as a new technique for high-throughput screening (HTS). In this work, the selected target was the enzyme acetylcholinesterase (AChE), and the AChE-ICERs produced were used in a liquid chromatograph-tandem ion-trap mass spectrometer. The activity and kinetic parameters were evaluated by monitoring the choline's precursor ion (M + H)(+)m/z 104.0 and its ion fragment (C2H3OH) - (M + H)(+)m/z 60.0. The assay method was validated using the reference AChE inhibitors tacrine and galanthamine. Two new ligands, out of a library of 17 coumarin derivatives, were identified, and the half-maximal inhibitory concentration (IC50), inhibition constant (K(i)), and the inhibition mechanism were determined. A coumarin derivative with IC50 similar to tacrine was highlighted. 23099811 Influence of dietary carbon on mercury bioaccumulation in streams of the Adirondack Mountains of New York and the Coastal Plain of South Carolina, USA. We studied lower food webs in streams of two mercury-sensitive regions to determine whether variations in consumer foraging strategy and resultant dietary carbon signatures accounted for observed within-site and among-site variations in consumer mercury concentration. We collected macroinvertebrates (primary consumers and predators) and selected forage fishes from three sites in the Adirondack Mountains of New York, and three sites in the Coastal Plain of South Carolina, for analysis of mercury (Hg) and stable isotopes of carbon (δ(13)C) and nitrogen (δ(15)N). Among primary consumers, scrapers and filterers had higher MeHg and more depleted δ(13)C than shredders from the same site. Variation in δ(13)C accounted for up to 34 % of within-site variation in MeHg among primary consumers, beyond that explained by δ(15)N, an indicator of trophic position. Consumer δ(13)C accounted for 10 % of the variation in Hg among predatory macroinvertebrates and forage fishes across these six sites, after accounting for environmental aqueous methylmercury (MeHg, 5 % of variation) and base-N adjusted consumer trophic position (Δδ(15)N, 22 % of variation). The δ(13)C spatial pattern within consumer taxa groups corresponded to differences in benthic habitat shading among sites. Consumers from relatively more-shaded sites had more enriched δ(13)C that was more similar to typical detrital δ(13)C, while those from the relatively more-open sites had more depleted δ(13)C. Although we could not clearly attribute these differences strictly to differences in assimilation of carbon from terrestrial or in-channel sources, greater potential for benthic primary production at more open sites might play a role. We found significant variation among consumers within and among sites in carbon source; this may be related to within-site differences in diet and foraging habitat, and to among-site differences in environmental conditions that influence primary production. These observations suggest that different foraging strategies and habitats influence MeHg bioaccumulation in streams, even at relatively small spatial scales. Such influence must be considered when selecting lower trophic level consumers as sentinels of MeHg bioaccumulation for comparison within and among sites. 23601371 Physicochemical and biological characterization of Pep-1/elastin complexes. Transdermal drug delivery of proteins is challenging because the skin acts as a natural and protective barrier. Several techniques including using the cell penetrating peptides (CPPs) have been studied to increase the penetration of therapeutic proteins into and through the skin. CPPs facilitate and improve the transduction of large and hydrophilic cargo molecules through plasma membrane. We have recently reported an efficient skin delivery of elastin protein in complex with a CPP called Pep-1. Since the biophysical characteristics of CPP/protein complexes have been linked with their biological responses, in the present study, we investigated biophysical properties of Pep-1/elastin complexes (ratio 10:1) stored in three temperatures (-20°C, 4°C and 25°C) by Photon Correlation Spectroscopy (PCS), Circular Dichroism (CD) and isothermal denaturation. We also evaluated the ability of transduction of this complex into cells and skin tissue using both fluorescence microscopy and Kodak In-Vivo FX Pro Imaging System. This article is protected by copyright. All rights reserved. 23427076 Addressable organic structure by anisotropic wetting. The anisotropic wetting of functional organic molecules on a patterned surface and the development of a photolithography-compatible method to fabricate addressable organic structures is reported. For example, DtCDQA is grown on a SiO2 surface with a Au prepattern, achieving a high resolution cross-over organic structure. 23447427 Ion-induced synthesis of uniform single-crystalline sulphide-based quaternary-alloy hexagonal nanorings for highly efficient photocatalytic hydrogen evolution. Uniform single-crystalline quaternary sulphide nanoring photocatalysts are synthesized via the copper-ion-induced Kirkendall effect and is followed by a cation exchange reaction. The obtained Cu(2+) -doped ZnIn2 S4 nanorings show highly preserved morphology, and demonstrate high visible-light-driven photocatalytic activity for H2 evolution in water splitting. 23585311 The effect of PTH(1-34) on fracture healing during different loading conditions. Parathyroid hormone (PTH) and PTH(1-34) have been shown to promote bone healing in several animal studies. It is known that the mechanical environment is important in fracture healing. Furthermore, PTH and mechanical loading has been suggested to have synergistic effects on intact bone. The aim of the present study was to investigate whether the effect of PTH(1-34) on fracture healing in rats was influenced by reduced mechanical loading. For this purpose we used female, 25-week-old ovariectomized rats. Animals were subjected to closed midshaft fracture of the right tibia ten weeks after ovariectomy. Five days before fracture, half of the animals received Botulinum Toxin A-injections in the muscles of the fractured leg to induce muscle paralysis (unloaded group), while the other half received saline injections (control group). For the following eight weeks, half of the animals in each group received injections of hPTH(1-34) (20 µg/kg/day) and the other half received vehicle treatment. Fracture healing was assessed by radiology, DXA, histology and bone strength analysis. We found that unloading reduced callus area significantly, while no effects of PTH(1-34) on callus area were seen in neither normally nor unloaded animals. PTH(1-34) increased callus bone mineral density (BMD) and bone mineral content (BMC) significantly, while unloading decreased callus BMD and BMC significantly. PTH(1-34)-treatment increased bone volume of the callus in both unloaded and control animals. PTH(1-34)-treatment increased ultimate force of the fracture by 63% in both control and unloaded animals and no interaction of the two interventions could be detected. PTH(1-34) was able to stimulate bone formation in normally loaded as well as unloaded intact bone. In conclusion, the study confirms the stimulatory effect of PTH(1-34) on fracture healing and our data suggest that PTH(1-34) is able to promote fracture healing, as well as intact bone formation during conditions of reduced mechanical loading. 23160964 1,25-Dihydroxyvitamin D3 upregulates leptin expression in mouse adipose tissue. Leptin is an adipose tissue-derived hormone that plays a critical role in energy homeostasis. Vitamin D has been shown to regulate energy metabolism, but the relationship between vitamin D and leptin is unclear. Leptin expression and secretion was reduced in vitamin D receptor (VDR)-null mice and increased in transgenic (Tg) mice overexpressing the VDR in adipocytes; however, as leptin is mainly determined by fat mass, it is unclear whether the vitamin D hormone directly regulates leptin expression. To address this question, we determined the effect of vitamin D on leptin expression in vivo and ex vivo. One-week treatment of WT mice with the vitamin D analog RO-27-5646 led to a significant increase in adipose leptin mRNA transcript and serum leptin levels. Moreover, in adipose tissue cultures, 1,25-dihydroxyvitamin D markedly stimulated mRNA expression and secretion of leptin, but not resistin, in adipose tissues obtained from WT mice, but not from VDR-null mice, and leptin upregulation induced by 1,25-dihydroxyvitamin D was more robust in adipose tissues obtained from VDR Tg mice compared with WT mice. These data demonstrate that 1,25-dihydroxyvitamin D stimulates adipose leptin production in a VDR-dependent manner, suggesting that vitamin D may affect energy homeostasis through direct regulation of leptin expression. 22641218 TGF-β and NF-κB signal pathway cross-talk is mediated through TAK1 and SMAD7 in a subset of head and neck cancers. Transforming growth factor-beta (TGF-β) has a dual role in epithelial malignancies, including head and neck squamous cell carcinoma (HNSCC). Attenuation of canonical TGF-β signaling enhances de novo tumor development, whereas TGF-β overexpression and signaling paradoxically promotes malignant progression. We recently observed that TGF-β-induced growth arrest response is attenuated, in association with aberrant activation of nuclear factor-κB (NF-κB), a transcription factor, which promotes malignant progression in HNSCC. However, what role cross-talk between components of the TGF-β and NF-κB pathways plays in altered activation of these pathways has not been established. Here, we show TGF-β receptor II and TGF-β-activated kinase 1 (TAK1) are predominantly expressed in a subset of HNSCC tumors with nuclear activation of NF-κB family member RELA (p65). Further, TGF-β1 treatment induced sequential phosphorylation of TAK1, IKK, IκBα and RELA in human HNSCC lines. TAK1 enhances TGF-β-induced NF-κB activation, as TAK1 siRNA knockdown decreased TGF-β1-induced phosphorylation of IKK, IκB and RELA, degradation of IκBα, RELA nuclear translocation and DNA binding, and NF-κB-induced reporter and target gene transcription. Functionally, TAK1 siRNA inhibited cell proliferation, migration and invasion. Celastrol, a TAK1 inhibitor and anti-inflammatory compound used in traditional Chinese medicine, also decreased TGF-β1-induced phosphorylation of TAK1 and RELA, and suppressed basal, TGF-β1- and tumor necrosis factor-alpha (TNF-α)-induced NF-κB reporter gene activity. Celastrol also inhibited cell proliferation, while increasing sub-G0 DNA fragmentation and Annexin V markers of apoptosis. Furthermore, TGF-β and RELA activation promoted SMAD7 expression. In turn, SMAD7 preferentially suppressed TGF-β-induced SMAD and NF-κB reporters when compared with constitutive or TNF-α-induced NF-κB reporter gene activation. Thus, cross-talk by TGF-β via TAK1 and NF-κB promotes the malignant phenotype of HNSCC. Moreover, NF-κB may contribute to the downstream attenuation of canonical TGF-β signaling through increased SMAD7 expression. Celastrol highlights the therapeutic potential of agents targeting TAK1 as a key node in this pro-oncogenic TGF-β-NF-κB signal pathway. 23098993 The role of transient receptor potential A 1 (TRPA1) in the development and maintenance of carrageenan-induced hyperalgesia. Transient receptor potential ankyrin 1 (TRPA1) is a nonselective cation channel important in setting nociceptive threshold. It is expressed in nociceptive C-fibers and in non-neuronal cells involved in pro-inflammatory mediators' release. We asked whether TRPA1 contributes to carrageenan-induced hyperalgesia in rats, and if so, whether this contribution is mediated by mechanisms involved in inflammation such as cytokine release and neutrophil migration and/or by a direct sensitization of the primary afferent nociceptors. Pharmacological blockade of local TRPA1 by its selective antagonist HC 030031 prevented and reversed carrageenan-induced hyperalgesia, which was detected either by a mechanical or chemical (low dose of capsaicin) stimulus. However, it did not affect either carrageenan-induced cytokines expression or neutrophil migration. The neuronal TRPA1 gene silencing induced by intrathecal pre-treatment with antisense oligodoexynucleotide completely prevented carrageenan-induced hyperalgesia over 24 h and significantly reduced TRPA1 expression in the dorsal root ganglia cells (L5-6), which was not affected by carrageenan treatment. We conclude that TRPA1 plays an important role in the development and maintenance of carrageenan-induced inflammatory hyperalgesia by directly contributing to nociceptor excitability. 23499925 The importance of early bedside echocardiography in children with scorpion envenomation. Scorpion sting may cause myocardial injury and heart failure (HF). Clinical signs of failure may develop several hours or even days after the sting, while electrocardiography (ECG) and blood examination soon after the sting may be normal. We sought to examine whether normal echocardiographic (echo) examination performed shortly after hospital arrival would exclude subsequent HF. We also sought to check if blood troponin and natriuretic peptide values measured shortly after arrival may predict or exclude subsequent HF. Natriuretic peptide activities have not been measured in scorpion sting victims. We also wanted to check if HF occurs in envenomated young infants. In a 3-year prospective study we looked at the demographic, clinical, laboratory, ECG, and echo data of all patients with general envenomation who arrived at the emergency department (ED) after scorpion sting. Clinical, laboratory, ECG, and echo results on arrival and 24 h after arrival were checked and compared between groups of patients with normal and abnormal echo on arrival. We then looked for differences in clinical course, therapy, and outcome between groups. The study included 98 children aged 80 days to 19 years (median 53.1 months), 25 were below the age of 2 years. Envenomation by the "yellow scorpion"Leiurus quinquestriatus was suspected in 74 cases. Median time between sting and ED arrival was 80 min. Echo was performed on arrival in 93 of the 98 patients, (in 5 occasions it was not performed or not recorded) 74 were normal and 19 were abnormal. Abnormal echo included hypokinesia and low fractional shortening and ejection fraction of the left ventricle. Clinical signs, abnormal ECG, and laboratory results were not discriminative between groups on arrival. Mean troponin T was higher in patients with abnormal echo, but within normal range in 13 of the 19 patients with abnormal echo and above normal in 2 of the 74 patients with normal echo - missing sensitivity and specificity. Mean N-terminal pro B-type natriuretic peptide was above normal in both groups but within normal range in 5 patients with abnormal echo and above normal range in 24 patients with normal echo - missing sensitivity and specificity. None of the patients with normal echo had subsequent HF and none of the children younger than 2 years of age had HF. All patients survived the intoxication and were discharged home without sequel. We conclude that early echo examination is an important procedure. In our study, normal examination excluded subsequent HF. Abnormal examination accelerated cardiac therapy which might have contributed to our favorable outcome. HF did not occur in infants younger than two years of age. 23570993 Additional Histopathologic Examination of the Lungs from a 3-Month Inhalation Toxicity Study with Multiwall Carbon Nanotubes in Rats. For hazard assessment of multiwalled carbon nanotubes (MWCNTs), a 90-day inhalation toxicity study has been performed with Nanocyl NC 7000 in accordance with OECD 413 test guideline. MWCNTs produced no systemic toxicity. However, increased lung weights, multifocal granulomatous inflammation, diffuse histiocytic and neutrophilic infiltrates, and intra-alveolar lipoproteinosis were observed in lung and lung-associated lymph nodes at 0.5 and 2.5mg/m(3). Additional investigations of the lungs were performed, including special stains for examination of connective tissue, and electron microscopy was performed to determine the location of the MWCNTs. The alveolar walls revealed no increase of collagen fibers, whereas within the microgranulomas a slight increase of collagen fibers was observed. The pleura did not reveal any increase in collagen fibers. Only a slight increase in reticulin fibers in the alveolar walls in animals of the 0.5 and 2.5mg/m(3) concentration group was noted. In the 0.1mg/m(3) group, the only animal revealing minimal granulomas exhibited a minimal increase in collagen within the granuloma. No increase in reticulin was observed. Electron microscopy demonstrated entangled MWCNTs within alveolar macrophages. Occasionally electron dense particles/detritus were observed within membrane-bound vesicles (interpreted as phagosomes), which could represent degraded MWCNTs. If so, MWCNTs were degradable by alveolar macrophages and not persistent within the lung. Inhalation of MWCNTs caused granulomatous inflammation within the lung parenchyma but not the pleura in any of the concentration groups. Thus, there are some similarities to effects caused by inhaled asbestos, but the hallmark effects, namely pleural inflammation and/or fibrosis leading to mesotheliomas, are absent. 23416264 In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Tobacco smoke consists of thousands of harmful components. A major class of chemicals found in tobacco smoke is formed by aldehydes, in particular formaldehyde, acetaldehyde and acrolein. The present study investigates the gene expression changes in human lung alveolar epithelial cells upon exposure to formaldehyde, acrolein and acetaldehyde at sub-cytotoxic levels. We exposed A549 cells in vitro to aldehydes and non-aldehyde chemicals (nicotine, hydroquinone and 2,5-dimethylfuran) present in tobacco smoke and used microarrays to obtain a global view of the transcriptomic responses. We compared responses of the individual aldehydes with that of the non-aldehydes. We also studied the response of the aldehydes when present in a mixture at relative concentrations as present in cigarette smoke. Formaldehyde gave the strongest response; a total of 66 genes were more than 1.5-fold differentially expressed mostly involved in apoptosis and DNA damage related processes, followed by acetaldehyde (57 genes), hydroquinone (55 genes) and nicotine (8 genes). For acrolein and the mixture only one gene was upregulated involved in oxidative stress. No gene expression effect was found for exposure to 2,5-dimethylfuran. Overall, aldehyde responses are primarily indicative for genotoxicity and oxidative stress. These two toxicity mechanisms are linked to respiratory diseases such as cancer and COPD, respectively. The present findings could be important in providing further understanding of the role of aldehydes emitted from cigarette smoke in the onset of pulmonary diseases. 23609452 TIP60 Positively Regulates ThPOK-Mediated Repression of Eomesodermin in Human CD4+ T Cells. The abundant expression of IFNγ in ThPOK-deficient CD4+ T cells requires the activation of Eomesodermin (Eomes); however, the underlying mechanism of this phenomenon remains unclear. Here we report that ThPOK directly binds to the promoter region of the Eomes gene to repress its expression in CD4+ T cells. We identified the histone acetyltransferase TIP60 as a corepressor of ThPOK-target genes, where ectopically expressed TIP60 increased ThPOK protein stability by promoting its acetylation at its K360 residue to then augment the transcriptional repression of Eomes. Moreover, knockdown of endogenous TIP60 abolished the stabilization of ThPOK in CD4+ T cells, which led to the transcriptional activation of Eomes and increased production of IFNγ. Our results reveal a novel pathway by which TIP60 and ThPOK synergistically suppresses Eomes function and IFNγ production, which could contribute to the regulation of inflammation. 23617226 Solvent Induced Luminescence Quenching: Static and Time-Resolved X-Ray Absorption Spectroscopy of a Copper(I) Phenanthroline Complex. We present a static and picosecond X-ray absorption study at the Cu K-edge of Bis(2,9-dimethyl-1,10-phenanthroline)copper(I) ([Cu(dmp)2]+; dmp = 2,9-dimethyl-1,10-phenanthroline) dissolved in acetonitrile and dichloromethane. The steady state photoluminescence spectra in dichloromethane and acetonitrile are also presented and show a shift to longer wavelengths for the latter, which points to a stronger stabilisation of the excited complex. The fine structure features of the static and transient X-ray spectra allow an unambiguous assignment of the electronic and geometric structure of the molecule in both its ground and excited 3MLCT states. Importantly, the transient spectra are remarkably similar for both solvents and the spectral changes can be rationalised using the optimised ground and excited state structures of the complex. The proposed assignment of the lifetime shortening of the excited state in donor solvents (acetonitrile) to a metal centred exciplex is not corroborated here. Molecular dynamics simulations confirm the lack of complexation, however in both solvents the molecules come close to the metal but undergo rapid exchange with the bulk. The shortening of the lifetime of the title complex and nine additional related complexes can be rationalised by the decrease of the 3MLCT energy. Deviations from this trend may be explained by means of the effects of the dihedral angle between the ligand planes, the solvent and the 3MLCT-1MLCT energy gap. 23434422 Euryspongins A-C, three new unique sesquiterpenes from a marine sponge Euryspongia sp. Three new unique sesquiterpenes, euryspongins A-C (1-3), were isolated from a marine sponge Euryspongia sp. collected at Iriomote Island, Okinawa, Japan. Compound 1 possessed a bicyclic furanosesquiterpene structure with six- and eight-membered rings, whereas compounds 2 and 3 had an α,β-unsaturated-γ-lactone ring instead of the furan ring in 1. Only five natural products in this class have been reported, and compounds 1-3 are the sixth-eighth examples of natural products. Compounds 1-3 had no inhibition effect against PTP1B, an important target enzyme for the treatment of diabetes, while the dehydro derivative of 1 [dehydroeuryspongin A (4)] exhibited inhibitory activity (IC(50)=3.6 μM). 23391207 Controllable adhesive superhydrophobic surfaces based on PDMS microwell arrays. This paper presents a one-step method to fabricate superhydrophobic surfaces with extremely controllable adhesion based on PDMS microwell arrays. The microwell array structures are rapidly produced on PDMS films by a point-by-point femtosecond laser scanning process. The as-prepared superhydrophobic surfaces show water controllable adhesion that ranges from ultrahigh to ultralow by adjusting the extent of overlap of the adjacent microwells, on which the sliding angle can be controlled from 180° (a water droplet can not slide down even when the as-prepared surface is turned upside down) to 3°. A "micro-airbag effect" is introduced to explain the adhesion transition phenomenon of the microwell array structures. This work provides a facile and promising strategy to fabricate superhydrophobic surfaces with controllable adhesion. 23258537 The RNA polymerase of marine cyanophage Syn5. A single subunit DNA-dependent RNA polymerase was identified and purified to apparent homogeneity from cyanophage Syn5 that infects the marine cyanobacteria Synechococcus. Syn5 is homologous to bacteriophage T7 that infects Escherichia coli. Using the purified enzyme its promoter has been identified by examining transcription of segments of Syn5 DNA and sequencing the 5'-termini of the transcripts. Only two Syn5 RNAP promoters, having the sequence 5'-ATTGGGCACCCGTAA-3', are found within the Syn5 genome. One promoter is located within the Syn5 RNA polymerase gene and the other is located close to the right genetic end of the genome. The purified enzyme and its promoter have enabled a determination of the requirements for transcription. Unlike the salt-sensitive bacteriophage T7 RNA polymerase, this marine RNA polymerase requires 160 mm potassium for maximal activity. The optimal temperature for Syn5 RNA polymerase is 24 °C, much lower than that for T7 RNA polymerase. Magnesium is required as a cofactor although some activity is observed with ferrous ions. Syn5 RNA polymerase is more efficient in utilizing low concentrations of ribonucleotides than T7 RNA polymerase. 22585425 The antioxidant activity of allylpyrocatechol is mediated via decreased generation of free radicals along with escalation of antioxidant mechanisms. Allylpyrocatechol (APC) is responsible for the antiinflammatory activity exhibited by the methanolic extract of leaves of Piper betle. As antiinflammatory compounds may display antioxidant properties and vice versa, we investigated the antioxidant effect of APC. APC effectively reduced phorbol-myristate-acetate-induced generation of reactive oxygen species and superoxide in murine peritoneal macrophages as well as inhibited Escherichia-coli-induced phagocytic activity of macrophages. Furthermore, pBluescript SK(+) plasmid DNA damage induced by addition of sodium ascorbate was attenuated by APC as it inhibited transformation of the supercoiled form to a relaxed form. In addition, APC increased the enzymatic (catalase) and nonenzymatic (GSH) antioxidant components of murine macrophages. Taken together, APC exhibited an antioxidant activity which was mediated both via decreased generation of free radicals along with increase in cellular antioxidants. Copyright © 2012 John Wiley & Sons, Ltd. 23600646 Cyclodextrin-Functionalized Fe3O4@TiO2: Reusable, Magnetic Nanoparticles for Photocatalytic Degradation of Endocrine-Disrupting Chemicals in Water Supplies. Water-dispersible, photocatalytic Fe3O4@TiO2 core-shell magnetic nanoparticles have been prepared by anchoring cyclodextrin cavities to the TiO2 shell, and their ability to capture and photocatalytically destroy endocrine-disrupting chemicals, bisphenol A and dibutyl phthalate, present in water, has been demonstrated. The functionalized nanoparticles can be magnetically separated from the dispersion after photocatalysis and hence reused. Each component of the cyclodextrin-functionalized Fe3O4@TiO2 core-shell nanoparticle has a crucial role in its functioning. The tethered cyclodextrins are responsible for the aqueous dispersibility of the nanoparticles and their hydrophobic cavities for the capture of the organic pollutants that may be present in water samples. The amorphous TiO2 shell is the photocatalyst for the degradation and mineralization of the organics, bisphenol A and dibutyl phthalate, under UV illumination, and the magnetism associated with the 9 nm crystalline Fe3O4 core allows for the magnetic separation from the dispersion once photocatalytic degradation is complete. An attractive feature of these "capture and destroy" nanomaterials is that they may be completely removed from the dispersion and reused with little or no loss of catalytic activity. 23631493 Effect of Lycopene Supplementation on Oxidative Stress: An Exploratory Systematic Review and Meta-Analysis of Randomized Controlled Trials. Abstract Lycopene is a potentially useful compound for preventing and treating cardiovascular diseases and cancers. Studies on the effects of lycopene on oxidative stress offer insights into its mechanism of action and provide evidence-based rationale for its supplementation. In this analysis, randomized controlled trials of the effects of oral lycopene supplementation on any valid outcomes of oxidative stress were identified and pooled through a search of international journal databases and reference lists of relevant publications. Two reviewers extracted data from each of the identified studies. Only studies of sufficient quality were included. Twelve parallel trials and one crossover trial were included in the systematic review, and six trials provided data for quantitative meta-analysis. Our results indicate that lycopene supplementation significantly decreases the DNA tail length, as determined using comet assays, with a mean difference (MD) of -6.27 [95% confidence interval (CI) -10.74, -1.90] (P=.006) between the lycopene intervention groups and the control groups. Lycopene supplementation does not significantly prolong the lag time of low-density lipoprotein (MD 3.76 [95% CI -2.48, 10.01]; P=.24). Lycopene possibly alleviates oxidative stress; however, biomarker research for oxidative stress needs be more consistent with the outcomes in lycopene intervention trials for disease prevention. 23627275 Dual-Responsive Capsules with Tunable Low Critical Solution Temperatures and Their Loading and Release Behavior. Dual-responsive capsules sensitive to pH and temperature changes were successfully prepared by grafting random copolymer brushes of 2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA) and oligo(ethylene glycol) methacrylate (OEGMA) from polydopamine (Pdop)-coated SiO2 via a surface-initiated atom-transfer radical polymerization (SI-ATRP) method with subsequent removal of the SiO2 core. The uptake and release properties of the resulting capsules are highly affected by changes in the pH values and temperature of the solution. The capsules can take up cationic dye rhodamine 6G (Rh6G) at high pH and T < LCST but not at low pH and T > LCST. In contrast, the capsules can release Rh6G at pH < 7 and temperature below the LCST, but release is less efficient under the opposite conditions. This dual-responsive property was also observed for the anionic dye methyl orange. 23303785 A Myc-microRNA network promotes exit from quiescence by suppressing the interferon response and cell-cycle arrest genes. The transition of mammalian cells from quiescence to proliferation is accompanied by the differential expression of several microRNAs (miRNAs) and transcription factors. However, the interplay between transcription factors and miRNAs in modulating gene regulatory networks involved in human cell proliferation is largely unknown. Here we show that the miRNA miR-22 promotes proliferation in primary human cells, and through a combination of Argonaute-2 immunoprecipitation and reporter assays, we identified multiple novel targets of miR-22, including several cell-cycle arrest genes that mediate the effects of the tumor-suppressor p53. In addition, we found that miR-22 suppresses interferon gene expression by directly targeting high mobility group box-1 and interferon regulatory factor (IRF)-5, preventing activation of IRF3 and NF-κB, which are activators of interferon genes. The expression of interferon genes is elevated in quiescent cells and their expression is inhibitory for cell proliferation. In addition, we find that miR-22 is activated by the transcription factor Myc when quiescent cells enter proliferation and that miR-22 inhibits the Myc transcriptional repressor MXD4, mediating a feed-forward loop to elevate Myc expression levels. Our results implicate miR-22 in downregulating the anti-proliferative p53 and interferon pathways and reveal a new transcription factor-miRNA network that regulates the transition of primary human cells from quiescence to proliferation. 22664910 Nuclear Receptors in atherosclerosis: a superfamily with many 'Goodfellas'. Nuclear Receptors form a superfamily of 48 transcription factors that exhibit a plethora of functions in steroid hormone signaling, regulation of metabolism, circadian rhythm and cellular differentiation. In this review, we describe our current knowledge on the role of Nuclear Receptors in atherosclerosis, which is a multifactorial disease of the vessel wall. Various cell types are involved in this chronic inflammatory pathology in which multiple cellular processes and numerous genes are dysregulated. Systemic risk factors for atherosclerosis are among others adverse blood lipid profiles, enhanced circulating cytokine levels, as well as increased blood pressure. Since many Nuclear Receptors modulate lipid profiles or regulate blood pressure they indirectly affect atherosclerosis. In the present review, we focus on the functional involvement of Nuclear Receptors within the atherosclerotic vessel wall, more specifically on their modulation of cellular functions in endothelial cells, smooth muscle cells and macrophages. Collectively, this overview shows that most of the Nuclear Receptors are athero-protective in atherosclerotic lesions. 23554463 Comprehensive prediction in 78 human cell lines reveals rigidity and compactness of transcription factor dimers. The binding of transcription factors (TFs) to their specific motifs in genomic regulatory regions is commonly studied in isolation. However, in order to elucidate the mechanisms of transcriptional regulation, it is essential to determine which TFs bind DNA cooperatively as dimers, and to infer the precise nature of these interactions. So far, only a small number of such dimeric complexes are known. Here, we present an algorithm for predicting cell-type-specific TF-TF dimerization on DNA on a large scale, using DNase I hypersensitivity data from 78 human cell lines. We represented the universe of possible TF complexes by their corresponding motif complexes, and analyzed their occurrence at cell-type-specific DNase I hypersensitive sites. Based on ~1.4 billion tests for motif complex enrichment, we predicted 603 highly significant cell-type-specific TF dimers, the vast majority of which are novel. Our predictions included 76% (19/25) of the known dimeric complexes and showed significant overlap with an experimental database of protein-protein interactions. They were also independently supported by evolutionary conservation, as well as quantitative variation in DNase I digestion patterns. Notably, the known and predicted TF dimers were almost always highly compact and rigidly spaced, suggesting that TFs dimerize in close proximity to their partners, which results in strict constraints on the structure of the DNA-bound complex. Overall, our results indicate that chromatin openness profiles are highly predictive of cell-type-specific TF-TF interactions. Moreover, cooperative TF dimerization seems to be a widespread phenomenon, with multiple TF complexes predicted in most cell types. 22660443 Azole interactions with multidrug therapy in pediatric oncology. Patients with cancer receive multidrug therapy. Antineoplastic agents and supportive care drugs are often administered together, leading to potential drug-drug interactions. These interactions may have significant clinical implications in terms of toxicity or a decrease in the efficacy of the treatment administered. Here, we focus on the role of azoles and their main pharmacokinetic interactions with the principal classes of drugs used in pediatric oncology. The co-administration of azoles and antineoplastic agents, corticosteroids, immunosuppressants, antacids, antiemetics, antiepileptic drugs and analgesics was investigated, and a practical guide on the management of these drugs when administered together is provided. 23599006 Pharmacological and Chemical Study to Identify Wound-Healing Active Compounds in Ageratina pichinchensis. The aerial parts of Ageratina pichinchensis are used in Mexican traditional medicine for the treatment of skin wounds. Recently, it was demonstrated that the aqueous extract of this plant reduced the time required to cicatrize a wound induced in the rat. The same extract showed a capability to induce overgrowth in normal fetal lung cells (MRC-5). The objective of the present study was isolating and identifying the active compounds in A. pichinchensis that are capable of inducing cellular overgrowth, as well as performing a preliminary evaluation of their anti-inflammatory and toxic effects. By means of bioguided chemical separation of an aqueous extract of A. pichinchensis, the most active compound capable of inducing cellular overgrowth was identified as 7-O-(β-D-glucopyranosyl)-galactin. In vivo inflammation induced with carrageenan in mice was significantly reduced by the aqueous extract of A. pichinchensis, reaching a decrease of up to 60.6 %. Acute (2 g/kg) and subchronic (1 g/kg for 28 days) oral administration of the aqueous extract of this plant did not affect hepatic function (through alanine aminotransferase and aspartate aminotransferase activity evaluation), while no alterations of the histologic samples of liver and kidney were evidenced. 23504645 Solar-Powered Nanomechanical Transduction from Crystalline Molecular Rotors. A photoinduced solid-state SO2 isomerism drives a larger mechanical change (benzene-ring rotation) in a neighbouring ion (i.e., the system acts as a solar-powered molecular transducer). The ring rotation and SO2 photoisomerisation are observed using in situ X-ray crystallography and are controllable, reproducible, and metastable at low temperatures. This discovery presents a new range of materials for solar-energy-based molecular transduction. 23497881 Evaluation of sequential inoculation of Saccharomyces cerevisiae and Oenococcus oeni strains on the chemical and aromatic profiles of cherry wines. The current study was carried out to elucidate the effect of sequential inoculation of Saccharomyces cerevisiae (RC212, D254) and Oenococcus oeni (SG26, Lalvin 31 and Uvaferm Alpha) on the production of cherry wines, especially on the chemical and aromatic characteristics. SI-D culture required the shortest period (23 d) to complete the fermentation, while other inoculations needed longer time. Analysis from chemical composition showed that titratable acidity and content of l-malic acid exhibited evident differences among the samples after MLF. For volatile compounds, 49 major components were identified, mostly comprising of alcohols, acids and esters. Cherry wines obtained from SI-B and SI-C showed higher contents of total volatile alcohols, and SI-D wines produced the greatest amount of volatile acids. According to the odour active value (OAV), 9 out of 49 studied volatile components had OAV >1 in all the analyzed wines, while six volatile components showed OAV >1 only for some of them. Furthermore, a sensory analysis was performed to compare the sensory profile of these cherry wines, and results evidenced that wines resulting from different inoculations presented diverse sensory profiles. These findings suggest that sequential inoculations posed a great potential in affecting and modulating the aromatic profile of cherry wines. 23052195 Neuropeptide Y Y1 receptor knockdown can modify glutathione peroxidase and c-AMP response element-binding protein in phenylpropanolamine-treated rats. It has been reported that antioxidative enzymes, neuropeptide Y (NPY), and c-AMP response element-binding protein (CREB) are involved in regulating phenylpropanolamine (PPA)-mediated appetite suppression. Here, we investigated whether Y1 receptor (Y1R) might be involved in this regulation. Rats were daily treated with PPA for 4 days. Changes in the contents of NPY, Y1R, glutathione peroxidase (GP), and CREB were assessed and compared. Results showed that Y1R, GP, and CREB increased, with a maximal increase about 100, 200, and 150 %, respectively, on Day 2. By contrast, NPY decreased with a biggest reduction about 48 % on Day 2 and the pattern of expression during PPA treatment was opposite to those of Y1R, GP, and CREB. Central knockdown (using antisense) or inhibition (using antagonist) of Y1R expression modulated the anorectic response of PPA and the reciprocal regulation between NPY and GP (or CREB), revealing an essential role of Y1R in regulating NPY, GP, and CREB. These results suggest that Y1R participates in the reciprocal regulation of NPY, GP, and CREB in the hypothalamus during PPA treatment in conscious rats. The present results may aid the therapeutic research of PPA and related antiobesity drugs. 23356987 Male mice housed in groups engage in frequent fighting and show a lower response to additional bone loading than females or individually housed males that do not fight. Experiments to investigate bone's physiological adaptation to mechanical loading frequently employ models that apply dynamic loads to bones in vivo and assess the changes in mass and architecture that result. It is axiomatic that bones will only show an adaptive response if the applied artificial loading environment differs in a significant way from that to which the bones have been habituated by normal functional loading. It is generally assumed that this normal loading is similar between experimental groups. In the study reported here we found that this was not always the case. Male and female 17-week-old C57BL/6 mice were housed in groups of six, and a single episode (40 cycles) of non-invasive axial loading, engendering 2,200 με on the medial surface of the proximal tibiae in sample mice, was applied to right tibiae on alternate days for two weeks. This engendered an adaptive increase in bone mass in females, but not males. Observation revealed the main difference in behaviour between males and females was that males were involved in fights 1.3 times per hour, whereas the females never fought. We therefore housed all mice individually. In females, there was a similar significant osteogenic response to loading in cortical and trabecular bone of both grouped and individual mice. In contrast, in males, adaptive increases in the loaded compared with non-loaded control bones was only apparent in animals housed individually. Our interpretation of these findings is that the frequent vigorous fighting that occurs between young adult males housed in groups could be sufficient to engender peak strains and strain rates that equal or exceed the stimulus derived from artificial loading. This indicates the importance of ensuring that physical activity is consistent between groups. Reducing the background level of the naturally engendered strain environment allows adaptive responses to artificial loading to be demonstrated at lower loads. 23159662 Ex vivo permeation characteristics of venlafaxine through sheep nasal mucosa. Venlafaxine, a dual acting antidepressant is a new therapeutic option for chronic depression. Depression is a common mental disorder associated with the abnormalities in neuronal transport in the brain. Since the nose-to-brain pathway has been indicated for delivering drugs to the brain, we analyzed the transport of venlafaxine through sheep nasal mucosa. Transmucosal permeation kinetics of venlafaxine were examined using sheep nasal mucosa mounted onto static vertical Franz diffusion cells. Nasal mucosa was treated with venlafaxine in situ gel (100 μl; 1% w/v) for 7h. Amount of venlafaxine diffused through mucosa was measured using validated RP-HPLC method. After the completion of the study histopathological investigation of mucosa was carried out. Ex vivo studies through sheep nasal mucosa showed sustained diffusion of venlafaxine with 66.5% permeation in 7h. Transnasal transport of venlafaxine followed a non-Fickian diffusion process. Permeability coefficient and steady state flux were found to be 21.11×10(-3) cmh(-1) and 21.118 μg cm(-2)h(-1) respectively. Cumulative amount permeated through mucosa at 7h was found to be 664.8 μg through an area of 3.14 cm(2). Total recovery of venlafaxine at the end of the permeation study was 87.3% of initial dose distributed (i) at the mucosal surface (208.4 μg; 20.8%) and (ii) through mucosa (664.8 μg; 66.5%). Histopathological examinations showed no significant adverse effects confirming that the barrier function of nasal mucosa remains unaffected even after treatment with venlafaxine in situ gel. Permeation through sheep nasal mucosa using in situ gel demonstrated a harmless nasal delivery of venlafaxine, providing new dimension to the treatment of chronic depression. 23484490 High Purity Isolation and Quantification of Semiconducting Carbon Nanotubes via Column Chromatography. The isolation of semiconducting carbon nanotubes (CNTs) to ultrahigh (ppb) purity is a prerequisite for their integration into high-performance electronic devices. Here, a method employing column chromatography is used to isolate semiconducting nanotubes to 99.9% purity. The study finds that by modifying the solution preparation step, both the metallic and semiconducting fraction are resolved and elute using a single surfactant system, allowing for multiple iterations. Iterative processing enables a far more rapid path to achieving the level of purities needed for high performance computing. After a single iteration, the metallic peak in the absorption spectra is completely attenuated. Although absorption spectroscopy is typically used to characterize CNT purity, it is found to be insufficient in quantifying solutions of high purity (>98 to 99%) due to low signal-to-noise in the metallic region of ultrahigh purity solutions. Therefore, a high throughput electrical testing method was developed to quantify the degree of separation by characterizing ∼4000 field-effect transistors fabricated from the separated nanotubes after multiple iterations of the process. The separation and characterization methods described here provide a path to produce the ultrahigh purity semiconducting CNT solutions needed for high performance electronics. 23194825 Neurotoxicity of "ecstasy" and its metabolites in human dopaminergic differentiated SH-SY5Y cells. "Ecstasy" (3,4-methylenedioxymethamphetamine or MDMA) is a widely abused recreational drug, reported to produce neurotoxic effects, both in laboratory animals and in humans. MDMA metabolites can be major contributors for MDMA neurotoxicity. This work studied the neurotoxicity of MDMA and its catechol metabolites, α-methyldopamine (α-MeDA) and N-methyl-α-methyldopamine (N-Me-α-MeDA) in human dopaminergic SH-SY5Y cells differentiated with retinoic acid and 12-O-tetradecanoyl-phorbol-13-acetate. Differentiation led to SH-SY5Y neurons with higher ability to accumulate dopamine and higher resistance towards dopamine neurotoxicity. MDMA catechol metabolites were neurotoxic to SH-SY5Y neurons, leading to caspase 3-independent cell death in a concentration- and time-dependent manner. MDMA did not show a concentration- and time-dependent death. Pre-treatment with the antioxidant and glutathione precursor, N-acetylcysteine (NAC), resulted in strong protection against the MDMA metabolites' neurotoxicity. Neither the superoxide radical scavenger, tiron, nor the inhibitor of the dopamine (DA) transporter, GBR 12909, prevented the metabolites' toxicity. Cells exposed to α-MeDA showed an increase in intracellular glutathione (GSH) levels, which, at the 48 h time-point, was not dependent in the activity increase of γ-glutamylcysteine synthetase (γ-GCS), revealing a possible transient effect. Importantly, pre-treatment with buthionine sulfoximine (BSO), an inhibitor of γ-GCS, prevented α-MeDA induced increase in GSH levels, but did not augment this metabolite cytotoxicity. Even so, BSO pre-treatment abolished NAC protective effects against α-MeDA neurotoxicity, which were, at least partially, due to GSH de novo synthesis. Inversely, pre-treatment of cells with BSO augmented N-Me-α-MeDA-induced neurotoxicity, but only slightly affected NAC neuroprotection. In conclusion, MDMA catechol metabolites promote differential toxic effects to differentiated dopaminergic human SH-SY5Y cells. 23561203 A micellar improved method for trace levels selenium quantification in food samples, alcoholic and nonalcoholic beverages through CPE/FAAS. A useful preconcentration and determination method was proposed for trace selenium in food samples. The procedure is based on complex formation of Pyronine B with Se(IV) ions in the presence of sodium dodecyl sulphate (SDS) and Ponpe 7.5. The variables affecting complex formation, extraction and phase separation were studied and optimised. Under the experimental conditions used, the calibration graph was linear in the range of 20-1700μgL(-1) for Se(IV) ions. The limit of detection was 3.81μgL(-1) of Se(IV) and the relative standard deviation for 5 replicate determinations at 250μgL(-1)concentration level was 2.45%. Recovery values were obtained between 97.8% and 102.8% for spiked samples. The method was successfully applied to the determination of total selenium in some food samples and alcoholic and nonalcoholic beverages. Its validity was checked by the analysis of four certified reference materials. The results obtained by the proposed method were quantitatively in good agreement with the certified values. 23394286 Resolving stable axial trapping points of nanowires in an optical tweezers using photoluminescence mapping. Axially resolved microphotoluminescence mapping of semiconductor nanowires held in an optical tweezers reveals important new experimental information regarding equilibrium trapping points and trapping stability of high aspect ratio nanostructures. In this study, holographic optical tweezers are used to scan trapped InP nanowires along the beam direction with respect to a fixed excitation source and the luminescent properties are recorded. It is observed that nanowires with lengths on the range of 3-15 μm are stably trapped near the tip of the wire with the long segment positioned below the focus in an inverted trapping configuration. Through the use of trap multiplexing we investigate the possibility of improving the axial stability of the trapped nanowires. Our results have important implication for applications of optically assisted nanowire assembly and optical tweezers based scanning probes microscopy. 23635023 Monolithic Barrier-All-Around High Electron Mobility Transistor with Planar GaAs Nanowire Channel. High quality growth of planar GaAs nanowires (NWs) with widths as small as 35 nm is realized by comprehensively mapping the parameter space of group III flow, V/III ratio, and temperature as the size of the NWs scale down. Using a growth mode modulation scheme for the NW and thin film barrier layers, monolithically integrated AlGaAs barrier-all-around planar GaAs NW high electron mobility transistors (NW-HEMTs) are achieved. The peak extrinsic transconductance, drive current, and effective electron velocity are 550 µS/µm, 435 µA/µm, and ~2.9 ×〖10〗^7 cm/s, respectively, at 2V supply voltage with a gate length of 120 nm. The excellent DC performance demonstrated here shows the potential of this bottom-up planar NW technology for low-power high-speed very-large-scale-integration (VLSI) circuits. 23198958 Triggered indistinguishable single photons with narrow line widths from site-controlled quantum dots. In this Letter, we present narrow line width (7 μeV), nearly background-free single-photon emission (g((2))(0) = 0.02) and highly indistinguishable photons (V = 0.73) from site-controlled In(Ga)As/GaAs quantum dots. These excellent properties have been achieved by combining overgrowth on ex situ pit-patterned substrates with vertical stacking of spectrally distinct quantum dot layers. Our study paves the way for large-scale integration of quantum dots into quantum photonic circuits as indistinguishable single-photon sources. 23535934 Challenges and approaches for the development of safer immunomodulatory biologics. Immunomodulatory biologics, which render their therapeutic effects by modulating or harnessing immune responses, have proven their therapeutic utility in several complex conditions including cancer and autoimmune diseases. However, unwanted adverse reactions--including serious infections, malignancy, cytokine release syndrome, anaphylaxis and hypersensitivity as well as immunogenicity--pose a challenge to the development of new (and safer) immunomodulatory biologics. In this article, we assess the safety issues associated with immunomodulatory biologics and discuss the current approaches for predicting and mitigating adverse reactions associated with their use. We also outline how these approaches can inform the development of safer immunomodulatory biologics. 23455057 Microwave-assisted synthesis of arene ruthenium(II) complexes that induce S-phase arrest in cancer cells by DNA damage-mediated p53 phosphorylation. A series of arene ruthenium(II) complexes coordinated by phenanthroimidazole derivates, [(C6H6)Ru(L)Cl]Cl·2H2O (1b L = IP, 2b L = p-NMe2PIP, 3b L = p-MeOPIP, 4b L = p-HOPIP, 5b L = p-COOHPIP, 6b L = p-CF3PIP, 7b L = p-BrPIP) have been synthesized in yields of 89-92% under microwave irradiation in 30 min, and the crystal structure of 1b by XRD gives a typical "piano stool" conformation. The antitumor activity of these complexes against various tumor cells have been evaluated by MTT assay, and the results show that this type of arene Ru(II) complexes exhibit acceptable inhibitory effect against all of these tumor cells, especially osteosarcoma MG-63 cells, but with low toxicity toward HK-2 human normal cells. Studies on the mechanism revealed that cell cycle arrest at S-phase in MG-63 cells induced by the arene Ru(II) complex 2b, which was confirmed by the increase in the percentage of cells at S-phase and down-regulator of cyclin A. The further studies by Comet assay at single cell level indicated that DNA damage in MG-63 cells was triggered by 2b, following with the up-regulation of phosphorylated p53 and histone. The studies by spectroscopy in vitro also indicate that 2b bind to DNA molecule by intercalative mode to disturb the bio-function of tumor cells. In conclusion, the synthetic arene Ru(II) complexes could serve as novel p53 activator with potential application in cancer chemotherapy. 23628332 Anti-adipogenic activity of compounds isolated from Idesia polycarpa on 3T3-L1 cells. Recently, obesity is a complex multifactorial chronic disease increasing the risk for type 2 diabetes, coronary heart disease and hypertension, and has become a major worldwide health problem. In the course of screening natural products employing 3T3-L1 cells as an in vitro system, the methanol extract of Idesia polycarpa Maxim. Fruits (Flacourtiaceae) significantly inhibited adipocyte differentiation by measuring lipid contents using oil red O staining. One new compound, 6-(oxymethyl)-2-hydroxyphenyl-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside (8), was isolated along with nine known compounds (1-7 and 9-10) from CHCl3 and n-BuOH fractions of the methanol extract of I. polycarpa fruits. Among them, idescarpin (1) with 1-hydroxy-6-oxo-2-cyclohexenecarboxylate moiety showed the most potent inhibitory activity on adipocyte differentiation with IC50 values of 23.2μM. Idescarpin (1) dramatically suppressed the induction of C/EBPα expression, whereas it significantly increased the induction of PPARγ expression, supported by quantitative real time PCR and Western blot analysis. The down-regulation in mRNA levels of SREBP1c, SCD-1, and FAS by idescarpin (1) during adipocyte differentiation revealed that the inhibition of adipocyte differentiation was mediated by the regulation of lipogenesis. Taken together, we suggest that idescarpin (1) shows a great potential against obesity and diabetes though the anti-adipogenic activity and the up-regulation of PPARγ. 23091169 Identification of Dlk1-Dio3 imprinted gene cluster noncoding RNAs as novel candidate biomarkers for liver tumor promotion. The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, suggesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds. 23592747 EPITOPE RECOGNITION IN HLA-DR3 TRANSGENIC MICE IMMUNIZED TO TSH-R PROTEIN OR PEPTIDES. Development of Graves' disease (GD) is related to HLA-DR3. The extracellular domain (ECD) of human TSH receptor (hTSH-R) is a crucial antigen in GD. hTSH-R peptide 37 (AA 78-94) is an important immunogenic peptide in DR3 transgenic mice immunized to hTSH-R. This study 1) examines epitope recognition in DR3 transgenic mice immunized to hTSH-R protein, and 2) evaluates ability of a mutant hTSH-R peptide to attenuate immunogenicity of hTSH-R peptide 37.DR3 transgenic mice were immunized to recombinant hTSH-R-ECD protein or peptides. A mutant hTSH-R 37 peptide (ISRIYVSIDATLSQLES: 37m), in which DR3 binding motif position 5 was mutated V>A, and position 8 Q>S, was synthesized. 37m should bind to HLA-DR3, but not bind T-cell receptors. DR3 transgenic mice were immunized to hTSH-R 37 and 37m.Mice immunized to hTSH-R-ECD protein developed strong anti hTSH-R antibody, and antisera reacted strongly with hTSH-R peptides 1-5 (20-94), 21(258-277), 41(283-297), 36(376-389), and 31(399-418). Strikingly, antisera raised to hTSH-R peptide 37 bound to hTSH-R peptides 1-7(20-112), 10(132-50), 33(137-150), 41, 23(286-305), 24(301-320), 36, and 31, as well as to hTSH-R-ECD protein. Both antibody titers to hTSH-R 37, and reaction of splenocytes to hTSH-R 37, were significantly reduced in mice immunized to hTSH-R 37 plus 37m, compare to mice immunized to hTSH-R 37 alone.The ability of immunization to a single peptide to induce antibodies that bind hTSH-R-ECD protein, and multiple unrelated peptides, is a unique observation. Immunogenic reaction to hTSH-R peptide 37 was partially suppressed by 37m, and this may contribute to immunotherapy of AITD. 22625416 Flax terpenoid pathway as a source of health promoting compounds. Flax is an important crop plant grown mainly for its fiber and seeds, which are also rich in omega-3 fatty acids and valuable antioxidants derived from the terpenoid pathways including carotenoids, tocochromanols and sterols. Many of those components found in flax have been recently shown to positively influence human health. Although terpenes vary greatly in their chemical structure, mainly two mechanisms of their biological activity can be considered: direct antioxidation, and a recently explored one, connected to specific receptor and cell signaling pathway activation. Recent studies show that many of the health promoting agents derived from flax act through both of the mentioned mechanisms, resulting in synergistic physiological effects. The work summarizes the two mechanisms, focusing mainly on the one involving cell signaling, as a promising target for medicine and pharmacotherapy. 23363576 Hepatoprotective effect of carob against acute ethanol-induced oxidative stress in rat. The present study was undertaken to determine whether subacute treatment with aqueous extract of carob (Ceratonia siliqua L.) pods (AECPs) protects against ethanol (EtOH)-induced oxidative stress in rat liver. Animals were divided into four groups: control, carob, EtOH and EtOH + carob. Wistar rats were intraperitoneally pretreated with AECP (600 mg/kg body weight (bw)) during 7 days and intoxicated for 6 h by acute oral administration of EtOH (6 g/kg bw) 24 h after the last injection. We found that acute administration of EtOH leads to hepatotoxicity as monitored by the increase in the levels of hepatic marker aspartate aminotransferase and alanine aminotransferase as well as hepatic tissue injury. EtOH also increased the formation of malondialdehyde in the liver, indicating an increase in lipid peroxidation and depletion of antioxidant enzyme activities as superoxide dismutase, catalase and glutathione peroxidase. Subacute carob pretreatment prevented all the alterations induced by EtOH and returned their levels to near normal. Importantly, we showed that acute alcohol increased hepatic and plasmatic hydrogen peroxide and free iron levels. The carob pretreatment reversed EtOH effects to near control levels. These data suggest that carob could have a beneficial effect in inhibiting the oxidative damage induced by acute EtOH administration and that its mode of action may involve an opposite effect on plasma and tissue-free iron accumulation. Indeed, carob can be offered as a food additive to protect against EtOH-induced oxidative damage. 23611124 Preliminary Structure-Activity Relationships and Biological Evaluation of Novel Antitubercular Indolecarboxamide Derivatives Against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains. Tuberculosis (TB) remains one of the leading causes of mortality and morbidity worldwide, with approximately one-third of the world's population infected with latent TB. This is further aggravated by HIV coinfection and the emergence of multidrug- and extensively drug-resistant (MDR and XDR, respectively) TB; hence the quest for highly effective antitubercular drugs with novel modes of action is imperative. We report herein the discovery of an indole-2-carboxamide analogue, 3, as a highly potent antitubercular agent, and the subsequent chemical modifications aimed at establishing a preliminary body of structure-activity relationships (SARs). These efforts led to the identification of three molecules (12-14) possessing an exceptional activity in the low nanomolar range against actively replicating Mycobacterium tuberculosis , with minimum inhibitory concentration (MIC) values lower than those of the most prominent antitubercular agents currently in use. These compounds were also devoid of apparent toxicity to Vero cells. Importantly, compound 12 was found to be active against the tested XDR-TB strains and orally active in the serum inhibition titration assay. 23295739 Adaptive changes in basal and stress-induced HPA activity in lactating and post-lactating female rats. Lactation represents a period of marked adaptation of the hypothalamo-pituitary-adrenal HPA axis. We characterized basal and stress-induced HPA activity during lactation and experimental weaning using dynamic blood sampling in rats. Pulsatile and diurnal corticosterone release occurred at all reproductive stages studied (virgin; day 10 of lactation; 3 and 14 days after experimental weaning on day 10 of lactation). However, in lactating rats the diurnal peak was significantly reduced, resulting in a flattened rhythm, and three days after weaning, basal HPA activity was markedly suppressed: the number of pulses and underlying basal levels of corticosterone were reduced and the diurnal rise phase delayed. Marked changes in the HPA response to 10 min noise stress also occurred at these times: being completely absent in lactating animals, but restored and highly prolonged in early weaned animals. Injection of methylprednisolone (2 mg, iv) was used to determine whether changes in fast glucocorticoid suppression correlated with these adaptive changes. Methylprednisolone induced a rapid suppression of corticosterone in virgin animals, but this effect was markedly attenuated in lactating and early weaned animals and was accompanied by significant changes in relative expression of hippocampal glucocorticoid and mineralocorticoid receptor mRNA. All effects were reversed or partially reversed 14 days after experimental weaning. Thus, the presence of the pups has an important influence on regulation of the HPA axis, and while postpartum adaptations are reversible, acute weaning evokes marked reorganisation of basal and stress-induced HPA activity. 23556446 Association of ATP-binding cassette transporter variants with the risk of Alzheimer's disease. Aim: A number of studies have demonstrated that ABCB1 and BCRP (ABCG2) actively transport Aβ. We aimed to investigate the association of genetic variants of selected multidrug transporters with Alzheimer's disease (AD) in histopathologically confirmed AD cases and controls. Materials & methods: DNA from brain tissue of 71 AD cases with Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropathological stages B/C and 81 controls was genotyped for selected variants in ABCA1, ABCA7, ABCB1, ABCC2 and ABCG2. In addition, the APOE4 status was analyzed. Results: The novel ABCA7 SNP, rs3752246, tended to be associated with AD in our study. Variants in ABCB1 were significantly less frequent in AD cases older than 65 years of age and among females. This association of ABCB1 2677G>T (rs2032582) was more pronounced in APOE4-negative cases (p = 0.005). However, only ABCC2 3972C>T (rs3740066) was significantly associated with AD risk after logistic regression analysis including all variants. Other transporters showed a lack of association. Conclusion: Our results support the hypothesis that ABCB1 and possibly other ABC-transporters are involved in the process of Aβ accumulation in the aging brain and may modulate the risk for AD in an allele-specific manner, and thus might represent a new target for prevention and treatment of AD. Original submitted 8 October 2012; Revision submitted 22 January 2013. 23484622 UVA Radiation Induced Ultrafast Electron Transfer from a Food Carcinogen Benzo[a]pyrene to Organic Molecules, Biological Macromolecules, and Inorganic Nano Structures. Reactions involving electron transfer (ET) and reactive oxygen species (ROS) play a pivotal role in carcinogenesis and cancer biochemistry. Our present study emphasizes UVA radiation induced ET reaction as one of the key aspects of a potential carcinogen, benzo[a]pyrene (BP), in the presence of a wide variety of molecules covering organic p-benzoquinone (BQ), biological macromolecules like calf-thymus DNA (CT-DNA), human serum albumin (HSA) protein, and inorganic zinc oxide (ZnO) nanorods (NRs). Steady-state and picosecond-resolved fluorescence spectroscopy have been used to monitor such ET reactions. Physical consequences of BP association with CT-DNA have been investigated through temperature-dependent circular dichroism (CD) spectroscopy. The temperature-dependent steady-state, picosecond-resolved fluorescence lifetime and anisotropy studies reveal the effect of temperature on the perturbation of such ET reactions from BP to biological macromolecules, highlighting their temperature-dependent association. Furthermore, the electron-donating property of BP has been corroborated by measuring wavelength-dependent photocurrent in a BP-anchored ZnO NR-based photodevice, offering new physical insights for the carcinogenic study of BP. 23275440 Ribosomal protein S25 dependency reveals a common mechanism for diverse internal ribosome entry sites and ribosome shunting. During viral infection or cellular stress, cap-dependent translation is shut down. Proteins that are synthesized under these conditions use alternative mechanisms to initiate translation. This study demonstrates that at least two alternative translation initiation routes, internal ribosome entry site (IRES) initiation and ribosome shunting, rely on ribosomal protein S25 (RPS25). This suggests that they share a mechanism for initiation that is not employed by cap-dependent translation, since cap-dependent translation is not affected by the loss of RPS25. Furthermore, we demonstrate that viruses that utilize an IRES or a ribosome shunt, such as hepatitis C virus, poliovirus, or adenovirus, have impaired amplification in cells depleted of RPS25. In contrast, viral amplification of a virus that relies solely on cap-dependent translation, herpes simplex virus, is not hindered. We present a model that explains how RPS25 can be a nexus for multiple alternative translation initiation pathways. 23449201 Influence of binder droplet dimension on granulation rate during fluidized bed granulation. Here, we statistically identified the critical factor of the granulation rate during the fluidized bed granulation process. Lactose was selected as the excipient and was granulated with several binders, including hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and polyvinylpyrrolidone. The viscosity, density, and surface tension of the binder solution, contact angle, and the work done during adhesion and cohesion between the binder and lactose, mist diameter, Stokes number, and the dimension of the droplet were considered. The Stokes number was defined as the ratio of the inertial force to the viscous-damping force of a particle. We confirmed that droplet diameter after adhesion had the highest correlation coefficient with the granulation rate constant in our investigated parameters. Partial least squares regression revealed two critical principal components of the granulation rate: one relating to the droplet dimension, which is composed of mist diameter and diameter and thickness of the droplet after adhesion of the binder to the lactose surface; and the other relating to wettability, which involves the work done during adhesion and cohesion, surface tension, and the thickness of the droplet after adhesion of the binder to the lactose surface. 23553679 Validation of a Novel Approach for Dose Individualization in Pharmacotherapy Using Gabapentin in a Proof of Principles Study. STUDY OBJECTIVE: To demonstrate the premise of individualized dosing charts (IDCs) as a clinical-bedside decision-support tool to individualize dosage regimens for drugs in which the interpatient variability is controlled by the pharmacokinetic (PK) behavior of the patient, to calculate the optimal sampling schedule (OSS), which minimizes the number of blood samples per patient. The approach is illustrated with available PK data for gabapentin. DESIGN: Retrospective proof of principles study using gabapentin PK data from a published clinical trial. PATIENTS: Nineteen subjects in a trial designed to uncover the importance of the genetic contributions to variability in gabapentin absorption, renal elimination, and transport; subjects were monitored for 36 hours after administration of a single dose of gabapentin 400 mg, and plasma concentrations were determined at 14 time points. MEASUREMENTS AND MAIN RESULTS: When the PK profiles were different between subjects, the IDCs are dramatically different from each other and from the IDC for an "average" patient representing the patient population. The dose amount and dosing interval must be adjusted to maximize the probability of staying within the target concentration range. An optimal sampling methodology based on the assumption-free Bayesian approach is used to distinguish the PK profile of an individual patient from the patient population. In the case of gabapentin, only two optimally selected test blood samples, at 1.5 and 6 hours after administration of a single doses, were necessary. The average sensitivity and the average specificity of the OSS was 99% and 96%, respectively. CONCLUSION: IDCs display the risk of a patient violating the target concentration range for any dosage regimen. They can be used as a clinical-bedside decision-support tool in a patient-physician partnership to decide on a dose amount and dosing interval that are medically acceptable while practical and convenient to ensure compliance. By using the assumption-free Bayesian approach and the OSS, the number of samples required from a new patient to individualize the dosage regimen can be reduced significantly while preserving high levels of sensitivity and specificity. Prospective studies are being planned to validate the encouraging results. This approach can be extended to any drug if PK data and a target concentration range are available for either therapeutic drug monitoring or target concentration intervention. 23296122 A RASSCF study of free base, magnesium and zinc porphyrins: accuracy versus efficiency. The restricted-active-space self-consistent-field methodology is successfully applied to the study of free base- and regular metalloporphyrins, the latter containing magnesium and zinc central ions. It is shown that inclusion of all excitations involving the Gouterman frontier orbitals in the RAS2 subspace results in a numerically stable approach, producing highly accurate results at a fraction of the computational cost of the complete-active-space self-consistent-field method, whereas increasing RAS2 beyond this size leads to only modest improvement. Topological and orbital analysis shows that the approach is also able to give a highly accurate description of the electronic wavefunction. Inclusion of the entire π-conjugated subsystem in the active space results in more accurate excitation energies and a reduction in the dependence on the exact form of the perturbational Hamiltonian used to include dynamic correlation. The larger active space also resolves a quantitative disagreement in results obtained with and without the inclusion of dynamic correlation. 23521014 Barriers to superfast water transport in carbon nanotube membranes. Carbon nanotube (CNT) membranes hold the promise of extraordinary fast water transport for applications such as energy efficient filtration and molecular level drug delivery. However, experiments and computations have reported flow rate enhancements over continuum hydrodynamics that contradict each other by orders of magnitude. We perform large scale molecular dynamics simulations emulating for the first time the micrometer thick CNTs membranes used in experiments. We find transport enhancement rates that are length dependent due to entrance and exit losses but asymptote to 2 orders of magnitude over the continuum predictions. These rates are far below those reported experimentally. The results suggest that the reported superfast water transport rates cannot be attributed to interactions of water with pristine CNTs alone. 23253441 The discovery of fused oxadiazepines as gamma secretase modulators for treatment of Alzheimer's disease. In an attempt to further improve overall profiles of the oxadiazine series of GSMs, in particular the hERG activity, conformational modifications of the core structure resulted in the identification of fused oxadiazepines such as 7i which had an improved hERG inhibition profile and was a highly efficacious GSM in vitro and in vivo in rats. These SAR explorations offer opportunities to identify potential drugs to treat Alzheimer's disease. 23588997 Modelling zirconium hydrides using the special quasirandom structure approach. The study of the structure and properties of zirconium hydrides is important for understanding the embrittlement of zirconium alloys used as cladding in light water nuclear reactors. Simulation of the defect processes is complicated due to the random distribution of the hydrogen atoms. We propose the use of the special quasirandom structure approach as a computationally efficient way to describe this random distribution. We have generated six special quasirandom structure cells based on face centered cubic and face centered tetragonal unit cells to describe ZrH2-x (x = 0.25-0.5). Using density functional theory calculations we investigate the mechanical properties, stability, and electronic structure of the alloys. 23218713 Inhibition of norovirus 3CL protease by bisulfite adducts of transition state inhibitors. Noroviruses are the most common cause of acute viral gastroenteritis, accounting for >21 million cases annually in the US alone. Norovirus infections constitute an important health problem for which there are no specific antiviral therapeutics or vaccines. In this study, a series of bisulfite adducts derived from representative transition state inhibitors (dipeptidyl aldehydes and α-ketoamides) was synthesized and shown to exhibit anti-norovirus activity in a cell-based replicon system. The ED(50) of the most effective inhibitor was 60 nM. This study demonstrates for the first time the utilization of bisulfite adducts of transition state inhibitors in the inhibition of norovirus 3C-like protease in vitro and in a cell-based replicon system. The approach described herein can be extended to the synthesis of the bisulfite adducts of other classes of transition state inhibitors of serine and cysteine proteases, such as α-ketoheterocycles and α-ketoesters. 23118019 In vivo and in vitro characterization of naltrindole-derived ligands at the κ-opioid receptor. Accumulating evidence supports a role for κ-opioid receptor antagonists in the treatment of mood disorders. Standard κ-antagonists have an unusual pharmacodynamic action, with a single injection blocking receptor signaling for several weeks. Here, we have characterized the κ-selective properties of two ligands, 5'-(2-aminomethyl) naltrindole (5'-AMN) and N-((Naltrindol-5-yl) methyl) pentanimidamide (5'-MABN), to identify whether modifications of the naltrindole side chain produces short-acting κ-antagonists. Opioid receptor binding affinity and activity were assessed using [(3)H]-diprenorphine binding, guanosine-5'-O-(3-[35S]-thio) triphosphate ([(35)S]-GTPγS) binding and isolated guinea-pig ileum. Pharmacodynamic profiles of 5'-AMN and 5'-MABN (1-10 mg/kg) were investigated using the tail-withdrawal assay and diuresis. Efficacy was also determined in depression- and anxiety-related behavioral paradigms in CD-1 mice. Both 5'-AMN and 5'-MABN had high affinity for κ-receptors (K (i) 1.36 ± 0.98 and 0.27 ± 0.08, respectively) and were revealed as potent κ-antagonists (pA(2) 7.43 and 8.18, respectively) and μ-receptor antagonists (pA(2) 7.62 and 7.85, respectively) in the ileum. Contrary to our hypothesis, in vivo, 5'-AMN and 5'-MABN displayed long-lasting antagonist effects in mice, reducing the antinociceptive actions of U50,488 (10 mg/kg) at 28 and 21 days post-injection, respectively. Interestingly, while 5'-AMN and 5'-MABN were not κ-selective, both compounds did show significant antidepressant- and anxiolytic-like effects at 7-14 days post-injection in mice. 23232059 Cynaropicrin from Cynara scolymus L. suppresses photoaging of skin by inhibiting the transcription activity of nuclear factor-kappa B. Aging of skin is characterized by skin wrinkling, laxity, and pigmentation induced by several environmental stress factors. Histological changes during the photoaging of skin include hyperproliferation of keratinocytes and melanocytes causing skin wrinkles and pigmentation. Nuclear factor kappa B (NF-κB) is one of the representative transcription factors active in conjunction with inflammation. NF-κB is activated by stimulation such as ultraviolet rays and inflammatory cytokines and induces the expression of various genes such as those of basic fibroblast growth factor (bFGF) and matrix metalloprotease-1 (MMP-1). We screened several plant extracts for their possible inhibitory effect on the transcriptional activity of NF-κB. One of them, an extract from Cynara scolymus L., showed a greatest effect on the suppression of NF-κB transactivation. As a result, we found that cynaropicrin, which is a sesquiterpene lactone, inhibited the NF-κB-mediated transactivation of bFGF and MMP-1. Furthermore, it was confirmed that in an in vivo mouse model cynaropicrin prevented skin photoaging processes leading to the hyperproliferation of keratinocytes and melanocytes. These findings taken together indicate that cynaropicrin is an effective antiphotoaging agent that acts by inhibiting NF-κB-mediated transactivation. 23583036 Structure and T Cell Inhibition Properties of B7 Family Member, B7-H3. T cell activity is controlled by a combination of antigen-dependent signaling through the T cell receptor and a set of auxiliary signals delivered through antigen-independent interactions, including the recognition of the B7 family of ligands. B7-H3 is a recently identified B7 family member that is strongly overexpressed in a range of cancers and correlates with poor prognosis. We report the crystal structure of murine B7-H3 at a 3 Å resolution, which provides a model for the organization of the IgV and IgC domains within the ectodomain. We demonstrate that B7-H3 inhibits T cell proliferation and show that the FG loop of the IgV domain plays a critical role in this function. B7-H3 crystallized as an unusual dimer arising from the exchange of the G strands in the IgV domains of partner molecules. This arrangement, in combination with previous reports, highlights the dynamic nature and plasticity of the immunoglobulin fold. 23346898 Giant Ising-type magnetic anisotropy in trigonal bipyramidal Ni(II) complexes: experiment and theory. This paper reports the experimental and theoretical investigations of two trigonal bipyramidal Ni(II) complexes, [Ni(Me(6)tren)Cl](ClO(4)) (1) and [Ni(Me(6)tren)Br](Br) (2). High-field, high-frequency electron paramagnetic resonance spectroscopy performed on a single crystal of 1 shows a giant uniaxial magnetic anisotropy with an experimental D(expt) value (energy difference between the M(s) = ± 1 and M(s) = 0 components of the ground spin state S = 1) estimated to be between -120 and -180 cm(-1). The theoretical study shows that, for an ideally trigonal Ni(II) complex, the orbital degeneracy leads to a first-order spin-orbit coupling that results in a splitting of the M(s) = ± 1 and M(s) = 0 components of approximately -600 cm(-1). Despite the Jahn-Teller distortion that removes the ground term degeneracy and reduces the effects of the first-order spin-orbit interaction, the D value remains very large. A good agreement between theoretical and experimental results (theoretical D(theor) between -100 and -200 cm(-1)) is obtained. 23562597 Structure-activity relationship of cytochrome bc1 reductase inhibitor broad spectrum antifungal ilicicolin H. Ilicicolin H is a broad spectrum antifungal agent showing sub micro g/mL MICs against Candida spp., Aspergillus fumigatus and Cryptococcus spp. It is a potent inhibitor (C50 2-3ng/mL) of the mitochondrial cytochrome bc1 reductase with over 1000-fold selectivity against rat liver cytochrome bc1 reductase. Structure-activity relationship of semisynthetic derivatives by chemical modification of ilicicolin H and its 19-hydroxy derivative produced by biotransformation have been described. Basic 4'-esters and moderately polar N- and O-alkyl derivatives retained antifungal and the cytochrome bc1 reductase activities. 4',19-Diacetate and 19-cyclopropyl acetate retained antifungal and enzyme activity and selectivity with over 20-fold improvement of plasma protein binding. 23340646 A rationally designed dual role anode material for lithium-ion and sodium-ion batteries: case study of eco-friendly Fe3O4. Identifying dual role electrode materials capable of storing both lithium and sodium are thought to be highly relevant, as these materials could find potential applications simultaneously in lithium and sodium ion batteries. In this regard, the concept of dual alkali storage is demonstrated in Fe(3)O(4) anode material undergoing conversion reaction. To enable improved storage, a rational active material and electrode design is proposed. Accordingly, the following features were simultaneously incorporated into the design: (i) an optimal particle size, (ii) a conducting matrix, (iii) adequately large active material surface area and (iv) strong electrode material-current collector integrity. Electrodes incorporating this rational design exhibit excellent high rate performance and impressive cyclability during lithium storage. For instance, Fe(3)O(4) electrodes deliver a charge capacity of 950 mAh g(-1) at 1.2 C (~2.6 times higher than graphite and 5.4 times higher than Li(4)Ti(5)O(12)). Further, these electrodes show no signs of capacity fade even up to 1100 cycles. Impressively, the cells could also be charged-discharged to 65% of their theoretical capacity in just 5 min or 12 C (11.11 A g(-1)). The rate performance and cyclability of lithium storage achieved here are amongst the highest reported values in the literature for the conversion reaction in Fe(3)O(4). Besides lithium storage, the dual role of this anode is shown by demonstrating its sodium storage ability by conversion reaction for the first time. 23579333 Co-Ni layered double hydroxides for water oxidation in neutral electrolyte. The electrochemical properties of Co-Ni layered double hydroxides (LDHs) as efficient electrocatalysts for water oxidation were investigated in potassium phosphate electrolyte under neutral pH condition. The Co-Ni LDHs with a core-shell structure were fabricated using a facile route from a Co-Ni hydroxide precursor with iodine as a topotactic oxidizer. The unique core-shell morphology is likely due to the enrichment of Co(iii) hydroxide in the inner core indicated by selected area electron diffraction and energy-dispersive spectroscopy. Through a self-assembling process at the organic/inorganic interface and dip-coating, the Co-Ni LDHs were deposited onto FTO glass substrates to prepare composite electrodes. Low over-potential and high current density was achieved in the oxygen evolution reaction. The excellent electrocatalytic activity of Co-Ni LDHs may be attributed to more accessible Co active sites and rapid movement of interlayer ions within their layered structure. 23411335 Physicochemical responses and microbial characteristics of shiitake mushroom (Lentinus edodes) to gum arabic coating enriched with natamycin during storage. Physicochemical responses and microbial characteristics of shiitake mushroom (Lentinus edodes) to gum arabic (GA) coating incorporating natamycin (NA) during storage were investigated. Mushroom weight loss, firmness, total soluble solids, total sugar, reducing sugar, ascorbic acid, and microbial and sensory quality were measured. Mushroom coated with gum arabic+natamycin (GANA) maintained tissue firmness and showed reduction in microbial counts from yeasts and moulds compared with the control. In addition, GANA coating also delayed changes in the soluble solids concentration, total sugar and ascorbic acid. Sensory evaluation proved the efficacy of GANA coating by maintaining the overall quality of shiitake mushroom during the storage period. The efficiency was better than that of GA or NA treatment alone. Our study suggests that GANA has the potential to improve the quality of shiitake mushroom and extend its shelf-life up to 16d. 23435649 Marine ecosystem health status assessment through integrative biomarker indices: a comparative study after the Prestige oil spill "Mussel Watch". Five integrative biomarker indices are compared: Bioeffects Assessment Index (BAI), Health Status Index (HSI), integrated biological response (IBR), ecosystem health condition chart (EHCC) and Integrative Biomarker Index (IBI). They were calculated on the basis of selected biomarker data collected in the framework of the Prestige oil spill (POS) Mussel Watch monitoring (2003-2006) carried out in Galicia and the Bay of Biscay. According to the BAI, the health status of mussels was severely affected by POS and signals of recovery were evidenced in Galicia after April-04 and in Biscay Bay after April-05. The HSI (computed by an expert system) revealed high levels of environmental stress in 2003 and a recovery trend from April-04 to April-05. In July-05, the health status of mussels worsened but in October-05 and April-06 healthy condition was again recorded in almost all localities. IBR/n and IBI indicated that mussel health was severely affected in 2003 and improved from 2004 onwards. EHCC reflected a deleterious environmental condition in 2003 and a recovery trend after April-04, although a healthy ecosystem condition was not achieved in April-06 yet. Whereas BAI and HSI provide a basic indication of the ecosystem health status, star plots accompanying IBR/n and IBI provide complementary information concerning the mechanisms of biological response to environmental insult. Overall, although the integrative indices based on biomarkers show different sensitivity, resolution and informative output, all of them provide coherent information, useful to simplify the interpretation of biological effects of pollution in marine pollution monitoring. Each others' advantages, disadvantages and applicability for ecosystem health assessment are discussed. 23122141 Medium chain and behenic acid incorporated structured lipids from sal, mango and kokum fats by lipase acidolysis. Medium chain (MC) and behenic fatty acids were incorporated into kokum, sal and mango fats using 1,3-specific lipase catalysed acidolysis. The incorporation of fatty acids increased with increase in concentration of fatty acids and duration of reaction. The order of incorporation of fatty acids was C22:0>C10:0>C8:0, to the extent of 53%, 42.5%, 35.8%, respectively, after 16 h, using kokum as substrate. The same trend was observed with sal or mango fats as substrates though the percentages incorporated were different. The modified products with higher contents of MC were liquids with no solid fats, even at 0°C, and which showed low cloud point due to an increase in triacylglycerols containing lower chain fatty acids. The modified products after incorporating both MC and C22:0 showed long melting ranges and were suitable for use in bakery, confectionery, etc. as vanaspati substitutes. 23509853 Enhanced Catalytic Four-Electron Dioxygen (O2) and Two-Electron Hydrogen Peroxide (H2O2) Reduction with a Copper(II) Complex Possessing a Pendant Ligand Pivalamido Group. A copper complex, [(PV-tmpa)Cu(II)](ClO4)2 (1) [PV-tmpa = bis(pyrid-2-ylmethyl){[6-(pivalamido)pyrid-2-yl]methyl}amine], acts as a more efficient catalyst for the four-electron reduction of O2 by decamethylferrocene (Fc*) in the presence of trifluoroacetic acid (CF3COOH) in acetone as compared with the corresponding copper complex without a pivalamido group, [(tmpa)Cu(II)](ClO4)2 (2) (tmpa = tris(2-pyridylmethyl)amine). The rate constant (kobs) of formation of decamethylferrocenium ion (Fc*(+)) in the catalytic four-electron reduction of O2 by Fc* in the presence of a large excess CF3COOH and O2 obeyed first-order kinetics. The kobs value was proportional to the concentration of catalyst 1 or 2, whereas the kobs value remained constant irrespective of the concentration of CF3COOH or O2. This indicates that electron transfer from Fc* to 1 or 2 is the rate-determining step in the catalytic cycle of the four-electron reduction of O2 by Fc* in the presence of CF3COOH. The second-order catalytic rate constant (kcat) for 1 is 4 times larger than the corresponding value determined for 2. With the pivalamido group in 1 compared to 2, the Cu(II)/Cu(I) potentials are -0.23 and -0.05 V vs SCE, respectively. However, during catalytic turnover, the CF3COO(-) anion present readily binds to 2 shifting the resulting complex's redox potential to -0.35 V. The pivalamido group in 1 is found to inhibit anion binding. The overall effect is to make 1 easier to reduce (relative to 2) during catalysis, accounting for the relative kcat values observed. 1 is also an excellent catalyst for the two-electron two-proton reduction of H2O2 to water and is also more efficient than is 2. For both complexes, reaction rates are greater than for the overall four-electron O2-reduction to water, an important asset in the design of catalysts for the latter. 23348514 Effects of metformin on burn-induced hepatic endoplasmic reticulum stress in male rats. Severe burn injury causes hepatic dysfunction that results in major metabolic derangements including insulin resistance and hyperglycemia and is associated with hepatic endoplasmic reticulum (ER) stress. We have recently shown that insulin reduces ER stress and improves liver function and morphology; however, it is not clear whether these changes are directly insulin mediated or are due to glucose alterations. Metformin is an antidiabetic agent that decreases hyperglycemia by different pathways than insulin; therefore, we asked whether metformin affects postburn ER stress and hepatic metabolism. The aim of the present study is to determine the effects of metformin on postburn hepatic ER stress and metabolic markers. Male rats were randomized to sham, burn injury and burn injury plus metformin and were sacrificed at various time points. Outcomes measured were hepatic damage, function, metabolism and ER stress. Burn-induced decrease in albumin mRNA and increase in alanine transaminase (p < 0.01 versus sham) were not normalized by metformin treatment. In addition, ER stress markers were similarly increased in burn injury with or without metformin compared with sham (p < 0.05). We also found that gluconeogenesis and fatty acid metabolism gene expressions were upregulated with or without metformin compared with sham (p < 0.05). Our results indicate that, whereas thermal injury results in hepatic ER stress, metformin does not ameliorate postburn stress responses by correcting hepatic ER stress. 23363407 Highly luminescent and photostable quantum dot-silica monolith and its application to light-emitting diodes. A highly luminescent and photostable quantum dot-silica monolith (QD-SM) substance was prepared by preliminary surface exchange of the QDs and base-catalyzed sol-gel condensation of silica. The SM was heavily doped with 6-mercaptohexanol exchanged QDs up to 12 vol % (26 wt %) without particle aggregation. Propylamine catalyst was important in maintaining the original luminescence of the QDs in the SM during sol-gel condensation. The silica layer was a good barrier against oxygen and moisture, so that the QD-SM maintained its initial luminescence after high-power UV radiation (∼1 W) for 200 h and through the 150 °C LED encapsulant curing process. Green and red light-emitting QD-SMs were applied as color-converting layers on blue LEDs, and the external quantum efficiency reached up to 89% for the green QD-SM and 63% for the red one. A white LED made with a mixture of green and red QDs in the SM, in which the color coordinate was adjusted at (0.23, 0.21) in CIE1931 color space for a backlight application, showed an efficacy of 47 lm/W, the highest value yet reported. 23161804 Enantiomeric discrimination of isoxazoline fused β-amino acid derivatives using (18-crown-6)-2,3,11,12-tetracarboxylic acid as a chiral NMR solvating agent. (18-Crown-6)-2,3,11,12-tetracarboxylic acid is a useful chiral NMR solvating agent for isoxazoline-fused β-amino acid derivatives. Isoxazoline substrates are analyzed as their hydrochloride salts in methanol-d(4). The crown ether and substrate associate through the formation of three hydrogen bonds between the protonated amine and crown ether oxygen atoms. Enantiomeric discrimination is observed for two or more resonances of every substrate. At least one of these resonances is free of overlap with other resonances in the spectrum and has large enough enantiomeric discrimination to enable the determination of enantiomeric purity. 2D COSY methods can be used to identify additional resonances that exhibit enantiomeric discrimination in the NMR spectrum. 23600648 Two new glycosides from the florets of Carthamus tinctorius. Two new glycoside compounds, named saffloquinoside C (1) and (-)-4-hydroxybenzoic acid-4-O-[6'-O-(2″-methylbutyryl)-β-D-glucopyranoside] (2), were isolated from the florets of Carthamus tinctorius. Their structures were elucidated by detailed spectroscopic means including UV, IR, HR-ESI-MS, 1D and 2D NMR, and CD data. Compound 1 was a rare quinochalcone glycoside with six five-membered dioxaspirocycle. 23631553 Bio-based Chitosan/Polybenzoxazine Crosslinked Films: Preparation in Aqueous Media and Synergistic Improvements in Thermal and Mechanical Properties. A novel class of polymer blends has been prepared from main-chain type benzoxazine polymer (MCBP) and chitosan (CTS), a modified biomacromolecule. A water-soluble, main-chain type benzoxazine polymer, MCBP(BA-tepa), was synthesized from the reaction of bisphenol-A (BA), tetraethylenepentamine (TEPA) and formalin. The structure of the MCBP(BA-tepa) was confirmed by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FT-IR). The polymer blends were prepared by mixing MCBP(BA-tepa) and chitosan (CTS) in aqueous acetic acid solution (1%). The CTS/MCBP(BA-tepa) films are crosslinked by thermal treatment via the ring-opening polymerization of benzoxazine structures in the main chain to produce AB-crosslinked network. Differential scanning calorimetry and FT-IR were used to study the effects of chitosan on the polymerization behavior of benzoxazine. Hydrogen bonding between polybenzoxazine and chitosan structures was also observed. The mechanical and thermal properties of crosslinked CTS/MCBP(BA-tepa) films were evaluated and the results show unusual levels of synergism. In particular, the tensile strength and thermal stability were significantly enhanced in a non-linear fashion. Keywords: Polybenzoxazine; chitosan; crosslinked films; mechanical and thermal properties. 23643528 Cross-protection by co-immunization with influenza hemagglutinin DNA and inactivated virus vaccine using coated microneedles. The need for annual revaccination against influenza is a burden on the healthcare system, leads to low vaccination rates and makes timely vaccination difficult against pandemic strains, such as during the 2009 H1N1 influenza pandemic. In an effort toward achieving a broadly protective vaccine that provides cross-protection against multiple strains of influenza, this study developed a microneedle patch to co-immunize with A/PR8 influenza hemagglutinin DNA and A/PR8 inactivated virus vaccine. We hypothesize that this dual component vaccination strategy administered to the skin using microneedles will provide cross-protection against other strains of influenza. To test this hypothesis, we developed a novel coating formulation that did not require additional excipients to increase coating solution viscosity by using the DNA vaccine itself to increase viscosity and thereby enable thick coatings of DNA vaccine and inactivated virus vaccine on metal microneedles. Co-immunization in this way not only generated robust antibody responses against A/PR8 influenza but also generated robust heterologous antibody responses against pandemic 2009 H1N1 influenza in mice. Challenge studies showed complete cross-protection against lethal challenge with live pandemic 2009 H1N1 virus. Control experiments using A/PR8 inactivated influenza virus vaccine with placebo DNA coated onto microneedles produced lower antibody titers and provided incomplete protection against challenge. Overall, this is the first study showing DNA solution as a microneedle coating agent and demonstrating cross-protection by co-immunization with inactivated virus and DNA vaccine using coated microneedles. 23394542 Interfacing quantum dots and graphitic surfaces with chlorine atomic ligands. The performance of devices based on semiconductor nanocrystals (NCs) improves both with stronger interface interactions among NCs and between NCs and solid electrode surfaces. The combination of X-ray photoelectron spectroscopy (XPS) and solid (31)P CP/MAS NMR (cross-polarization/magic angle spinning nuclear magnetic resonance) shows that the selective substitution of long organic chains by chlorine atomic ligands during the colloidal synthesis by the hot injection method promotes the adsorption of CdSe NCs to carbon sp(2) surfaces, leading to the formation of well-ordered NC monolayers on graphitic materials. 23565060 Promoter Sequence Determines the Relationship between Expression Level and Noise. The ability of cells to accurately control gene expression levels in response to extracellular cues is limited by the inherently stochastic nature of transcriptional regulation. A change in transcription factor (TF) activity results in changes in the expression of its targets, but the way in which cell-to-cell variability in expression (noise) changes as a function of TF activity, and whether targets of the same TF behave similarly, is not known. Here, we measure expression and noise as a function of TF activity for 16 native targets of the transcription factor Zap1 that are regulated by it through diverse mechanisms. For most activated and repressed Zap1 targets, noise decreases as expression increases. Kinetic modeling suggests that this is due to two distinct Zap1-mediated mechanisms that both change the frequency of transcriptional bursts. Notably, we found that another mechanism of repression by Zap1, which is encoded in the promoter DNA, likely decreases the size of transcriptional bursts, producing a unique transcriptional state characterized by low expression and low noise. In addition, we find that further reduction in noise is achieved when a single TF both activates and represses a single target gene. Our results suggest a global principle whereby at low TF concentrations, the dominant source of differences in expression between promoters stems from differences in burst frequency, whereas at high TF concentrations differences in burst size dominate. Taken together, we show that the precise amount by which noise changes with expression is specific to the regulatory mechanism of transcription and translation that acts at each gene. 23462379 Ribosome-inactivating proteins: From toxins to useful proteins. Ribosome-inactivating proteins (RIPs) either single-chain (type 1) or two-chain (type 2) are frequent in plants, often in multiple forms. They are RNA N-glycosidases, have antiviral, antifungal and insecticidal activity. Their expression in plants is increased under stressful conditions. They are investigated for practical applications in medicine and in agriculture. In medicine, RIPs have been linked to, or fused with, appropriate antibodies or other carriers to form "immunotoxins" or other conjugates specifically toxic to the cells target of the carrier, with the aim of eliminating malignant or other undesired cells. In agriculture, it has been observed that an enhanced expression of RIPs confers to plants an increased resistance to viruses, fungi, insects, and also to drought and salinity. 23147032 Understanding the role of gut microbes and probiotics in obesity: how far are we? Obesity has been associated with structural alterations in the gut microbiota, suggesting potential causality between specific microbial taxa and this disorder. Studies in animal models have also provided evidence for plausible gut microbiota mechanisms of action underlying body weight regulation. Yet evidence identifying which specific microbes contribute to or predict obesity is not completely consistent across studies. More recently, diet has also been shown to be primarily involved in regulating the microbiota structure initially related to obesity, suggesting that the role of microbes in energy balance is under the influence of diet. Controversy over the role of components of the gut microbiota in obesity has extended to bacteria, which although weakly related to body weight in observational and human intervention studies, are of interest due to their use as probiotics. This review focuses exclusively on human observational studies and probiotic intervention trials, excluding animal studies and studies in infants at early developmental stages, since such results cannot be extrapolated to human obesity at later stages in life. In this context, evidence for relationships between the gut microbiota composition and obesity and the possible role of probiotics is reviewed, discussing the strengths and weaknesses of the studies conducted to date. 23322648 Structure-activity relationships of glucosamine-derived glycerolipids: the role of the anomeric linkage, the cationic charge and the glycero moiety on the antitumor activity. The potent antitumor activity of 1-O-hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (1) was previously shown to arise through an apoptosis-independent pathway. Here, a systematic structure-activity study in which the effects of the anomeric linkage, the cationic charge and the glycero moiety on the antitumor activity is described. Eight analogues of 1 were synthesized, and their antitumor activity against breast (JIMT1 and BT549), pancreas (MiaPaCa2) and prostate (DU145, PC3) cancer was determined. 1-O-Hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-α-D-glucopyranosyl)-sn-glycerol (2) consistently displayed the most potent activity against all five cell lines with CC(50) values in the range of 6-10 μM. However, replacement of the O-glycosidic linkage by a thioglycosidic linkage or replacement of the amino group by an azide or guanidino group leads to a threefold or greater decrease in potency. The glycero moiety also contributes to the overall activity of 1 and 2 but its effects are of lesser importance. Investigation into the mode of action of this class of compounds revealed that, in agreement with previous findings, the cytotoxic effects arise through induction of large acid vacuoles. 23432203 Development and characterization of monomeric N-end rule inhibitors through in vitro model substrates. In the N-end rule pathway, a set of N-terminal amino acids, called N-degrons, are recognized and ubiquitinated by the UBR proteins. Here we examined various N-end rule inhibitors to identify essential structural components of the system. Our study using in vitro biochemical assay indicated that the l-conformation and protonated α-amino group of the first residue were critical for N-degrons to properly interact with the UBR proteins. The monomeric molecules with minimum interacting motifs showed endopeptidase resistance and better inhibitory activities than traditional dipeptide inhibitors. Collectively, our study identifies a pharmacophore of N-end rule inhibitors, which provides a structural platform to improve the efficiency and druggable properties of inhibitors. Considering that the N-end rule has been implicated in many pathophysiological processes in cells, inhibitors of this pathway, such as p-chloroamphetamine, are potentially of clinical interest in a novel aspect of action mechanisms. 23391441 Ultrasound-aided microbubbles facilitate the delivery of drugs to the inner ear via the round window membrane. The round window membrane (RWM) acts as a barrier between the middle ear and cochlea and can serve as a crucial route for therapeutic medications entering the inner ear via middle ear applications. In this study, we targeted the practical application of microbubbles (MBs) ultrasound on increasing the RWM permeability for facilitating drug or medication delivery to the inner ear. Using biotin-fluorescein isothiocyanate conjugates (biotin-FITC) as delivery agents and guinea pig animal models, we showed that MB ultrasound exposure can improve the inner ear system use of biotin-FITC delivery via the RWM by approximately 3.5 to 38 times that of solely soaking biotin-FITC around the RWM for spontaneous diffusion. We also showed that there was significant enhancement of hair cell uptake of gentamicin in animals whose tympanic bullas were soaked with MB-mixed gentamicin-Texas Red or gentamicin and exposed to ultrasound. Furthermore, increased permeability of the RWM from acoustic cavitation of MBs could also be visualized immediately following ultrasound exposure by using Alexa Fluor 488-conjugated phalloidin as a tracer. Most importantly, such applications had no resulting damage to the integrity of the RWM or deterioration of the hearing thresholds assessed by auditory brainstem responses. We herein provide a basis for MB ultrasound-mediated techniques with therapeutic medication delivery to the inner ear for future application in humans. 23600735 Chemical and preclinical studies on Hedyotis diffusa with anticancer potential. This paper presents the chemical and preclinical anticancer research on Hedyotis diffusa Willd. in detail, one of the most renowned herbs often prescribed in the polyherbal formulas for cancer treatment in traditional Chinese medicine. Anthraquinones, flavonoids, and terpenoids constitute the majority of the 69 compounds that have been isolated and identified from H. diffusa. The anticancer effects of the methanolic, ethanolic, and aqueous extracts in various preclinical cancer models have been described. This review also summarized the anticancer activity of constituents of the herb and the mechanisms of action. All the studies suggest that H. diffusa has enormous potential in the therapy of cancer and warrants further chemical and pharmacological investigation. 23348501 Formation, reactivity, and antiplatelet activity of mixed disulfide conjugates of clopidogrel. In this work, we investigated the formation, reactivity, and antiplatelet activity of various mixed disulfide conjugates of clopidogrel. Our results showed that the production of the active metabolite (AM) from 2-oxoclopidogrel by human liver microsomes (HLMs) is greatly affected by the thiol reductants used. Among the 10 thiol compounds tested, glutathione (GSH) is most efficient in producing the AM at a rate of 167 pmoles AM/min/mg HLM. Interestingly, no AM but only the mixed disulfide conjugates were formed in the presence of 6-chloropyridazine-3-thiol (CPT), 2,5-dimethylfuran-3-thiol, and 3-nitropyridine-2-thiol (NPT). The mass spectrometry (MS) and MS(2) spectra of the conjugates of these thiol compounds confirmed the presence of a mixed disulfide bond linkage between the AM and the thiol reductants. Kinetic studies revealed that the mixed disulfide conjugates were capable of exchanging thiols with GSH to release the AM with second order rate constants ranging from 1.2 to 28 M(-1)s(-1). The mixed disulfide conjugates of CPT and NPT showed potent inhibition of platelet aggregation after pretreatment with 1 mM GSH, confirming that the AM is responsible for the antiplatelet activity of clopidogrel. Collectively, our results provide strong support for a cytochrome P450 (P450)-mediated bioactivation mechanism involving the initial formation of a glutathionyl conjugate, followed by thiol-disulfide exchange with another GSH molecule to release the AM. Furthermore, the stable mixed disulfide conjugates identified in this study provide a platform to quantitatively generate the therapeutic AM without the need for P450-mediated bioactivation. This property can be further explored to overcome the interindividual variability in clopidogrel therapy. 23616387 Click To Bind: Metal Sensors. The copper-catalyzed azide-alkyne "click" cycloaddition reaction is an efficient coupling reaction that results in the formation of a triazole ring. The wide range of applicable substrates for this reaction allows the construction of a variety of conjugated systems. The additional function of triazoles as metal-ion ligands has led to the click reaction being used for the construction of optical sensors for metal ions. The triazoles are integral binding elements, which are formed in an efficient modular synthesis. Herein, we review recent examples of triazoles as a metal-binding element in conjugated metal-ion sensors. 23480798 Are the intramolecular o-h···f and o-h···cl hydrogen bonds maintained in solution? A theoretical study. The present case study aims at calculating the equilibrium conformer compositions for 2X-ethanol and 2X-phenol (X = F, Cl) in solution, and exploring the effect of the applied theoretical method and basis set on the obtained results, as well as considering the usefulness of the continuum solvent approach in comparison with the explicit solvent Monte Carlo model utilizing the free energy perturbation method. Gas-phase optimizations at the DFT/B97D/aug-cc-pvtz and ab initio MP2/aug-cc-pvtz levels predicted structures in good agreement with the available experimental data for three test molecules. Because in-solution geometries change only slightly according to the IEF-PCM continuum solvent calculations in carbon tetrachloride and water, the two theoretical levels were applied further on, and complete basis set (CBS) relative internal free energies were estimated for the conformers under study. The predicted OCCF gauche/trans ratio for 2F-ethanol was well reproduced in comparison with available experimental compositions. The predominant gauche structure maintains an intramolecular hydrogen bond in carbon tetrachloride (HB structure), whereas HB and NoHB gauche conformers appear in nearly the same fraction in aqueous solution. The internally hydrogen-bonded conformer is predominant also for 2X-phenol species, as calculated on the basis of relative CBS internal free energies and IEF-PCM and FEP/MC solvation free energies. Use of a trihydrate supermolecule model for 2F-ethanol conformers leads to the prediction of the aqueous-solution composition in contrast to the experiment. Solution structure modeling predicts weak hydrogen-bond formation capacity for both the covalently bound F and Cl atoms, even in conformations where they are fully exposed to hydration. 23333650 A success in Toxinology translational research in Brazil: Bridging the gap. Basic research is fundamental for discovering potential diagnostic and therapeutic tools, including drugs, vaccines and new diagnostic techniques. On this basis, diagnosis and treatment methods for many diseases have been developed. Presently, discovering new candidate molecules and testing them in animals are relatively easy tasks that require modest resources and responsibility. However, crossing the animal-to-human barrier is still a great challenge that most researchers tend to avoid. Thus, bridging this current gap between clinical and basic research must be encouraged and elucidated in training programmes for health professionals. This project clearly shows the challenges faced by a group of Brazilian researchers who, after discovering a new fibrin sealant through 20 years of painstaking basic work, insisted on having the product applied clinically. The Brazilian government has recently become aware of this challenge and has accordingly defined the product as strategic to the public health of the country. Thus, in addition to financing research and development laboratories, resources were invested in clinical trials and in the development of a virtual platform termed the Virtual System to Support Clinical Research (SAVPC); this platform imparts speed, reliability and visibility to advances in product development, fostering interactions among sponsors, physicians, students and, ultimately, the research subjects themselves. This pioneering project may become a future model for other public institutions in Brazil, principally in overcoming neglected diseases, which unfortunately continue to afflict this tropical country. 23521567 Molecular Dynamics Simulations of DPPC Bilayers Using "LIME", a New Coarse-Grained Model. A new intermediate resolution model for phospholipids, LIME, designed for use with discontinuous molecular dynamics (DMD) simulations is presented. The implicit-solvent model was developed using a multiscale modeling approach in which the geometric and energetic parameters are obtained by collecting data from atomistic simulations of a system composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) molecules and explicit water. In the model, 14 coarse-grained sites that are classified as 1 of 6 types represent DPPC. DMD simulations performed on a random solution of DPPC resulted in the formation of a defect-free bilayer in less than 4 h. The bilayer formed quantitatively reproduces the main structural properties (e.g., area per lipid, bilayer thickness, bond order parameters) that are observed experimentally. In addition, the bilayer transitions from a liquid-crystalline phase to a tilted gel phase when the temperature is reduced. Transbilayer movement of a lipid from the bottom leaflet to the top leaflet is observed when the temperature is increased. 23122168 Optimisation of resistant starch II and III levels in durum wheat pasta to reduce in vitro digestibility while maintaining processing and sensory characteristics. Foods with elevated levels of resistant starch (RS) may have beneficial effects on human health. Pasta was enriched with commercial resistant starches (RSII, Hi Maize™ 1043; RSIII, Novelose 330™) at 10%, 20% and 50% substitution of semolina for RSII and 10% and 20% for RSIII and compared with pasta made from 100% durum wheat semolina to investigate technological, sensory, in vitro starch digestibility and structural properties. The resultant RS content of pasta increased from 1.9% to ∼21% and was not reduced on cooking. Significantly, the results indicate that 10% and 20% RSII and RSIII substitution of semolina had no significant effects on pasta cooking loss, texture and sensory properties, with only a minimal reduction in pasta yellowness. Both RS types lowered the extent of in vitro starch hydrolysis compared to that of control pasta. X-ray diffraction and small-angle scattering verified the incorporation of RS and, compared to the control sample, identified enhanced crystallinity and a changed molecular arrangement following digestion. These results can be contrasted with the negative impact on pasta resulting from substitution with equivalent amounts of more traditional dietary fibre such as bran. The study suggests that these RS-containing formulations may be ideal sources for the preparation of pasta with reduced starch digestibility. 22445601 Differentiating the roles of mGlu2 and mGlu3 receptors using LY541850, an mGlu2 agonist/mGlu3 antagonist. Despite the potential therapeutic relevance of group II metabotropic glutamate (mGlu) receptors, there has been a lack of pharmacological tools for separating the roles of mGlu2 and mGlu3 receptor subtypes. LY541850 was claimed from human mGlu receptors expressed in non-neuronal cells to be a selective orthosteric mGlu2 agonist and mGlu3 antagonist. We have verified this pharmacological profile of LY541850 in hippocampal slices. Field excitatory post-synaptic potentials (fEPSPs) evoked by stimulation of the temporo-ammonic path (TAP) input to CA1 stratum lacunosum moleculare (SLM) were inhibited by LY541850 in mGlu3-/- mice (EC(50) 38 nM) and wild-type littermates (EC(50) 42 nM) to a similar extent but were not significantly affected in mGlu2-/- mice. The group II agonist, DCG-IV, inhibited the fEPSP in all three genotypes. Co-application of DCG-IV and LY541850 in mGlu3-/- and wild-type littermates resulted in an additive effect, whereas in mGlu2-/- mice, LY541850 reversed the inhibitory action of DCG-IV. These results confirm the selective mGlu2 agonist and mGlu3 antagonist actions of LY541850. A similar profile of activity was seen in medial perforant path synapse to the dentate gyrus. Systemic administration of LY541850 to wild-type mice, reduced the increase in locomotor activity following both phencyclidine and amphetamine administration. These data support the hypothesis that mGlu2 receptors mediate the antipsychotic effects of mixed group II agonists. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. 23521318 Bioassay-guided isolation and identification of antitermitic active compound from the leaf of Chinese cedar (Cryptomeria fortunei Hooibrenk). The persistent use of synthetic termiticides is at present of environmental concern and has resulted in the need to search for plant-derived compounds as an alternative for termite control. Antitermitic activity of Chinese cedar (Cryptomeria fortunei Hooibrenk) against Reticulitermes chinensis was demonstrated in laboratory tests. Bioactivity tests against the termite R. chinensis demonstrate that the lethal concentration (LC50) value of leaf essential oil is 2.80 mg/mL. Furthermore, α-terpineol, which was responsible for the antitermitic property and isolated from Chinese cedar that exhibited very strong antitermitic activity, was found to be significantly effective against R. chinensis with median LC50 values of 0.86 mg/mL. The findings suggested that the essential oil from Chinese cedar leaf and α-terpineol might be considered as a potent source for the production of effective, environmentally friendly and safe termiticides. 23146692 Purification and determination of two novel antioxidant peptides from flounder fish (Paralichthys olivaceus) using digestive proteases. We investigated the effects of bioactive-peptides from hydrolysates of flounder fish muscle (FFM) on antioxidant activity. The hydrolysates were prepared by enzymatic reactions of FFM using eight commercial proteases such as papain, pepsin, trypsin, neutrase, alcalase, kojizyme, protamex, and α-chymotrypsin. The α-chymotrypsin hydrolysate showed the strongest antioxidant activity among the eight enzymatic hydrolysates. Further separation of the α-chymotrypsin hydrolysate was performed by ultrafiltration, gel filtration, and reverse-phase high performance liquid chromatography. Consequently, two novel peptides with high antioxidant activity were purified, and their amino acid sequences were determined (Val-Cys-Ser-Val [VCSV] and Cys-Ala-Ala-Pro [CAAP], respectively). The two peptides showed good scavenging activity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical (IC(50) values, 111.32 and 26.89 μM, respectively) and high cytoprotective activities against 2,2-azobis-(2-amidino-propane) dihydrochloride (AAPH) without cytotoxicity and scavenged total reactive oxygen species in Vero cells. In particular, apoptotic bodies produced by AAPH dose-dependently decreased following treatment with the CAAP peptide. These results revealed firstly the two peptides with strong antioxidative effects from FFM. 23454208 Induction of endoplasmic reticulum stress-mediated apoptosis and non-canonical autophagy by luteolin in NCI-H460 lung carcinoma cells. In this study, we investigated the anti-cancer effects of luteolin, a member of the flavonoid family, in NCI-H460 human lung carcinoma cells. It was shown that luteolin induces apoptotic cell death through modulating both the extrinsic pathway and intrinsic pathways, which are suppressed by z-VAD-fmk, indicating that luteolin triggers caspase-dependant apoptosis. Furthermore, we found that the α subunit of the eukaryotic initiation factor 2 (eIF2α/C/EBP homologous protein pathway, but not the c-Jun N-terminal kinase pathway, played a critical role in induction of apoptosis by luteolin. The data indicated that luteolin also induces autophagy; evidence for this is the accumulation of microtubule-associated protein light chain-3 (LC3) II protein, the increase of LC3 puncta as well as an enhanced autophagy flux. In addition, inhibiting autophagy by bafilomycin A1 reduced apoptotic cell death, suggesting that luteolin-induced autophagy functions as a cell death mechanism. Notably, the activated caspases that appeared with luteolin treatment cleaved Beclin-1, and the expression of LC3II remained the same even after cells were challenged with Beclin-1 siRNA, demonstrating that luteolin induces Beclin-1-independent autophagy. Taken together, our findings showed that luteolin triggers both endoplasmic reticulum stress-related apoptosis and non-canonical autophagy, which function as a cell death mechanism in NCI-H460 human lung cancer cells. 22370634 MNK kinases facilitate c-myc IRES activity in rapamycin-treated multiple myeloma cells. When mTOR inhibitor rapalogs prevent cap-dependent translation of cell-cycle proteins like c-myc, continuing tumor cell growth depends on cap-independent translation, which is mediated by internal ribosome entry sites (IRESes) located in the 5'-UTR (untranslated region) of transcripts. To investigate if rapalog-induced activation of MNK kinases had a role in such IRES activity, we studied multiple myeloma (MM) cells. Rapamycin (RAP)-activated MNK1 kinase activity in MM cell lines and primary specimens by a mitogen-activated protein kinase-dependent mechanism. Pharmacological inhibition of MNK activity or genetic silencing of MNK1 prevented a rapalog-induced upregulation of c-myc IRES activity. Although RAP, used alone, had little effect on myc protein expression, when combined with a MNK inhibitor, myc protein expression was abrogated. In contrast, there was no inhibition of myc RNA, consistent with an effect on myc translation. In a RAP-resistant MM cell lines as well as a resistant primary MM specimen, co-exposure to a MNK inhibitor or MNK1 knockdown significantly sensitized cells for RAP-induced cytoreduction. Studies in MNK-null murine embryonic fibroblasts additionally supported a role for MNK kinases in RAP-induced myc IRES stimulation. These results indicate that MNK kinase activity has a critical role in the fail-safe mechanism of IRES-dependent translation when mTOR is inhibited. As kinase activity also regulated sensitivity to RAP, the data also provide a rationale for therapeutically targeting MNK kinases for combined treatment with mTOR inhibitors. 23143039 Temperature dependence of long-term cadmium toxicity in the zebrafish is not explained by liver oxidative stress: evidence from transcript expression to physiology. Standard ecotoxicity tests are performed at species' specific standard temperatures, but temperature is known to affect chemical toxicity. A temperature increase has been shown to increase cadmium toxicity in several aquatic species but information in fish is scarce. Based on literature we hypothesize that with increasing temperature, cadmium accumulation and oxidative stress increase, resulting in increased toxicity. In this study zebrafish acclimated to 12, 18, 26 (standard temperature) or 34°C for one month, were exposed to 5 μM cadmium for 4 or 28 days at the respective acclimation temperature. Cadmium toxicity (mortality) increased with increasing temperature. PCA showed that the high mortality at 34°C was closely correlated to an increasing tissue cadmium accumulation with increasing temperature, but not to liver oxidative damage under the form of protein carbonyl content or lipid peroxidation (measured as malondialdehyde levels) or liver antioxidative potential. Instead, acclimation to 12°C induced the highest oxidative damage to liver proteins and lipids, and transcript levels of glucose-6P-dehydrogenase, 6P-gluconate-dehydrogenase and glutathione peroxidase were particularly good markers of cold-induced oxidative stress. At this low temperature there was no interaction with cadmium exposure and there was no sign of cadmium sensitivity. Contrastingly, the combined effect of high temperature and cadmium exposure on mortality proved synergistic. Therefore we conclude that interactions between temperature and cadmium toxicity increased with increasing temperature and that this probably played part in increasing cadmium sensitivity. Increased cadmium compartmentalization and protein carbonyl content in liver of zebrafish acclimated to the standard temperature of 26°C probably played part in increased sensitivity towards the same cadmium body burden compared to lower temperatures. On the one hand we recognize and this study even confirms the importance of applying standard temperatures in standard ecotoxicity tests to ensure inter-study comparability. On the other hand temperatures in the field may deviate from standard temperatures and accounting for deviating temperatures, which can alter chemical sensitivity, in regulation can improve environmental protection. 23314276 Effects of 17β-trenbolone on Eastern and Western mosquitofish (Gambusia holbrooki and G. affinis) anal fin growth and gene expression patterns. The Eastern and Western mosquitofish (Gambusia holbrooki and G. affinis) are potential bioindicator organisms for endocrine disruptors. Male mosquitofish have an elongated anal fin (gonopodium) used for internal fertilization whose formation is driven by androgens. Normal female mosquitofish have a normal, rounded anal fin which undergoes elongation into a gonopodium structure when female mosquitofish are exposed to androgenic chemicals. Significant issues with using mosquitofish as a bioindicator include the lack of knowledge on how anal fin growth in females corresponds to endpoints relevant to biological integrity and the lack of information on the molecular pathways that regulate anal fin growth. The objectives of this study were to understand how androgen-induced anal fin elongation relates to changes in endpoints related to the female reproductive system and to understand how anal fin elongation occurs in androgen-exposed female mosquitofish. To achieve these objectives, adult female G. holbrooki were exposed to a vehicle control or one of three doses of the androgen 17β-trenbolone (TB) at nominal concentrations of 0.1, 1 or 10 μg TB/L. Anal fin measurements were taken and livers were used for quantitative polymerase chain reaction analysis of vitellogenin (vtg) mRNA expression at multiple time points. 10 μg TB/L induced anal fin elongation after 7 days of treatment (one-way ANOVA, p<0.05) as did 0.1 and 1 μg TB/L at later time points (one-way ANOVA, p<0.05). 10 μg TB/L significantly reduced hepatic vtg gene expression at all time points assessed (one-way ANOVA, p<0.05). There was no correlation between anal fin elongation levels and vtg gene expression (Spearman's ρ, p>0.05). In a separate experiment, female G. holbrooki and G. affinis were exposed to the vehicle control or 1 μg TB/L. Anal fins were used for qualitative gene expression analysis of the genes sonic hedgehog (shh), muscle segment homeobox C (msxC), and fibroblast growth factor receptor 1 (fgfr1) by in situ hybridization. Shh was expressed in the distal tip of the gonopodium while msxC and fgfr1 were more widely expressed along the same anal fin rays during androgen exposure. These data provide insight into the molecular pathways involved in anal fin elongation and pave the way for future work toward developing the mosquitofish into a bioindicator organism for endocrine disruptors. 22750050 AMPK signalling and the control of substrate use in the heart. All mammalian cells rely on adenosine triphosphate (ATP) to maintain function and for survival. The heart has the highest basal ATP demand of any organ due to the necessity for continuous contraction. As such, the ability of the cardiomyocyte to monitor cellular energy status and adapt the supply of substrates to match the energy demand is crucial. One important serine/threonine protein kinase that monitors cellular energy status in the heart is adenosine monophosphate activated protein kinase (AMPK). AMPK is also a key enzyme that controls multiple catabolic and anabolic biochemical pathways in the heart and indirectly plays a crucial role in regulating cardiac function in both physiological and pathophysiological conditions. Herein, we review the involvement of AMPK in myocardial fatty acid and glucose transport and utilization, as it relates to basal cardiac function. We also assess the literature amassed on cardiac AMPK and discuss the controversies surrounding the role of AMPK in physiological and pathophysiological processes in the heart. The work reviewed herein also emphasizes areas that require further investigation for the purpose of eventually translating this information into improved patient care. 23411075 Arylglycine derivatives as potent transient receptor potential melastatin 8 (TRPM8) antagonists. A series of arylglycine-based analogs was synthesized and tested for TRPM8 antagonism in a cell-based functional assay. Following structure-activity relationship studies in vitro, a number of compounds were identified as potent TRPM8 antagonists and were subsequently evaluated in an in vivo pharmacodynamic assay of icilin-induced 'wet-dog' shaking in which compound 12 was fully effective. TRPM8 antagonists of the type described here may be useful in treating pain conditions wherein cold hypersensitivity is a dominant feature. 23393216 Decreased serum concentrations of 25-hydroxycholecalciferol are associated with increased risk of progression to impaired fasting glucose and diabetes. OBJECTIVE To study the association between vitamin D status and the risk of incident impaired fasting glucose (IFG) and diabetes in a population-based cohort of diabetes-free subjects. RESEARCH DESIGN AND METHODS In a historical prospective cohort study of subjects from the Clalit Health Services database, which includes information on nearly 4 million people, diabetes-free subjects aged 40-70 years with serum 25-hydroxycholecalciferol (25-OHD) measurements available were followed for 2 years to assess the development of IFG and diabetes in five 25-OHD subgroups: ≥25, 25.1-37.5, 37.6-50, 50.1-75, and >75 nmol/L. RESULTS The baseline cohort included 117,960 adults: 83,526 normoglycemic subjects and 34,434 subjects with IFG. During follow-up, 8,629 subjects (10.3% of the normoglycemic group) developed IFG, and 2,162 subjects (1.8% of the total cohort) progressed to diabetes. A multivariable model adjusted for age, sex, population group, immigrant status, BMI, season of vitamin D measurement, LDL and HDL cholesterol, triglycerides, estimated glomerular filtration rate, history of hypertension or cardiovascular disease, Charlson comorbidity index, smoking, and socioeconomic status revealed an inverse association between 25-OHD and the risk of progression to IFG and diabetes. The odds of transitioning from normoglycemia to IFG, from normoglycemia to diabetes, and from IFG to diabetes in subjects with a 25-OHD level ≤25 nmol/L were greater than those of subjects with a 25-OHD level >75 nmol/L [odds ratio 1.13 (95% CI 1.03-1.24), 1.77 (1.11-2.83), and 1.43 (1.16-1.76), respectively]. CONCLUSIONS Vitamin D deficiency appears to be an independent risk factor for the development of IFG and diabetes. 23195960 A specific and essential role for Na,K-ATPase α3 in neurons co-expressing α1 and α3. Most neurons co-express two catalytic isoforms of Na,K-ATPase, the ubiquitous α1, and the more selectively expressed α3. Although neurological syndromes are associated with α3 mutations, the specific role of this isoform is not completely understood. Here, we used electrophysiological and Na(+) imaging techniques to study the role of α3 in central nervous system neurons expressing both isoforms. Under basal conditions, selective inhibition of α3 using a low concentration of the cardiac glycoside, ouabain, resulted in a modest increase in intracellular Na(+) concentration ([Na(+)](i)) accompanied by membrane potential depolarization. When neurons were challenged with a large rapid increase in [Na(+)](i), similar to what could be expected following suprathreshold neuronal activity, selective inhibition of α3 almost completely abolished the capacity to restore [Na(+)](i) in soma and dendrite. Recordings of Na,K-ATPase specific current supported the notion that when [Na(+)](i) is elevated in the neuron, α3 is the predominant isoform responsible for rapid extrusion of Na(+). Low concentrations of ouabain were also found to disrupt cortical network oscillations, providing further support for the importance of α3 function in the central nervous system. The α isoforms express a well conserved protein kinase A consensus site, which is structurally associated with an Na(+) binding site. Following activation of protein kinase A, both the α3-dependent current and restoration of dendritic [Na(+)](i) were significantly attenuated, indicating that α3 is a target for phosphorylation and may participate in short term regulation of neuronal function. 23639739 In vivo administration of VEGF- and GDNF-releasing biodegradable polymeric microspheres in a severe lesion model of Parkinson's disease. In this work, the neuroregenerative potentials of microencapsulated VEGF, GDNF and their combination on a severely lesioned rat model were compared with the aim of developing a new strategy to treat advanced stages of Parkinson's disease. Both neurotrophic factors were separately encapsulated into polymeric microspheres (MS) to obtain a continuous drug release over time. The regenerative effects of these growth factors were evaluated using a rotation behaviour test and quantified by the number of surviving TH+ cells. The biological activities of encapsulated vascular endothelial growth factor (VEGF) and glial cell line derived neurotrophic factor (GDNF) were investigated in HUVEC and PC12 cells, respectively. The treatment of 6-OHDA-lesioned rats with GDNF microspheres and with both VEGF and GDNF microspheres resulted in improved results in the rotation behaviour test. Both groups also showed higher levels of neuroregeneration/neuroreparation in the substantia nigra than the control group did. These results were confirmed by the pronounced TH + neuron recovery in the group receiving VEGF+GDNF-MS, demonstrating regenerative effects. 23328072 Dose-dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells. Fat infiltration within muscle is one of a number of features of vitamin D deficiency, which leads to a decline in muscle functionality. The origin of this fat is unclear, but one possibility is that it forms from myogenic precursor cells present in the muscle, which transdifferentiate into mature adipocytes. The current study examined the effect of the active form of vitamin D₃, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), on the capacity of the C2C12 muscle cell line to differentiate towards the myogenic and adipogenic lineages. Cells were cultured in myogenic or adipogenic differentiation media containing increasing concentrations (0, 10⁻¹³, 10⁻¹¹, 10⁻⁹, 10⁻⁷ or 10⁻⁵  M) of 1,25(OH)₂D₃ for up to 6 days and markers of muscle and fat development measured. Mature myofibres were formed in both adipogenic and myogenic media, but fat droplets were only observed in adipogenic media. Relative to controls, low physiological concentrations (10⁻¹³ and 10⁻¹¹  M) of 1,25(OH)₂D3 increased fat droplet accumulation, whereas high physiological (10⁻⁹  M) and supraphysiological concentrations (≥10⁻⁷  M) inhibited fat accumulation. This increased accumulation of fat with low physiological concentrations (10⁻¹³ and 10⁻¹¹  M) was associated with a sequential up-regulation of PPARγ2 (PPARG) and FABP4 mRNA, indicating formation of adipocytes, whereas higher concentrations (≥10⁻⁹  M) reduced all these effects, and the highest concentration (10⁻⁵  M) appeared to have toxic effects. This is the first study to demonstrate dose-dependent effects of 1,25(OH)₂D₃ on the transdifferentiation of muscle cells into adipose cells. Low physiological concentrations (possibly mimicking a deficient state) induced adipogenesis, whereas higher (physiological and supraphysiological) concentrations attenuated this effect. 23223551 Quantum chemical study of the catalytic activation of methane by copper oxide and copper hydroxide cations. The activation of methane and its subsequent conversion into more valuable feedstocks under ambient conditions are regarded as one of the major challenges in contemporary catalysis, due to its thermodynamically strong and kinetically inert C-H bond. Several enzymes and synthetic bioinorganic systems perform the activation of C-H bonds in methane and small hydrocarbons, mediated by transition metal mononuclear centers. Among them, monocopper cores and, in particular, CuO(+) and CuOH(+) have been suggested as efficient catalytic centers; this activity has not been experimentally proven until very recently, mainly due to the difficulty to produce sufficient amounts of active species to demonstrate the bond activation processes. The theoretical study presented here provides a thorough quantum chemical description of the activity of both species, together with molecular level insight into the elementary steps of the experimentally observed reactions. Post-HF (CCSD(T), CASPT2) and Density Functional Theory (DFT) methods have been used to unravel detailed electronic and mechanistic aspects of the reaction paths. Our study reveals the decisive role of the oxygen-centered radical in the reactivity of both species, and the improvement of the reactivity as a result of the protonation of the active species. 23375004 Chemometrics-Based Approach to Feature Selection of Chromatographic Profiles and its Application to Search Active Fraction of Herbal Medicine. In our previous report (J Pharmaceut Biomed 56 (2011) 443-447), a support vector machine (SVM)-based pharmacodynamic model was established for predicting active fractions of herbal medicines (HMs), where information contents embedded in the chromatograms of the fractions were represented with the peak areas. However, in this representation the global characteristics of the chromatograms were completely missed, which is definitely contrary to the global and holistic views in theories of HMs and undoubtedly reduce the success rate of this model. To deal with the challenge, two chemometrics methods, that is, minimum redundancy maximum relevance (mRMR) and particle swarm optimizer (PSO), were applied in this article for feature selection of the whole chromatograms, and the PSO was also used to tune the SVM parameters. As a case, a sample HM, that is, Xiangdan injection, was investigated. The predictive accuracy was fully evaluated and compared with those by other popular and reported methods. Furthermore, the confirmation on the independent predicting set exhibited that the predicted bioactivities were well consistent with the experimental values. The important potential application of the present model is to be extended to help search active fractions of other HMs. 23643542 Water extract of licorice had anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines. ETHNOPHARMACOLOGICAL RELEVANCE: Licorice (Glycyrrhiza uralensis Fisch., Leguminosae) has been used in herbal medicine and food supplement worldwide for centuries. Licorice is a common ingredient of several prescriptions of traditional Chinese medicine which have been proved to inhibit infection of human respiratory syncytial virus (HRSV). There are two preparations of licorice, Radix Glycyrrhizae and Radix Glycyrrhizae Preparata. However, it is unknown whether licorice or which preparation of licorice is effective against HRSV, nor is its active constituent. AIM OF THE STUDY: We tested the hypothesis that Radix Glycyrrhizae can effectively decrease HRSV-induced plaque formation in respiratory mucosal cell lines. We also tried to find out the active constituent. MATERIALS AND METHODS: Anti-HRSV activities of hot water extracts of preparations of licorice, glycyrrhizin and 18β-glycyrrhetinic acid (18β-GA), the active constituents of licorice, were examined by plaque reduction assay in both human upper (HEp-2) and low (A549) respiratory tract cell lines. Abilities of crude licorice to inhibit viral replication and to stimulate IFN-β were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: Radix Glycyrrhizae and Radix Glycyrrhizae Preparata dose-dependently inhibited HRSV-induced plaque formation in both HEp-2 and A549 cell lines (p<0.0001). The effect of Radix Glycyrrhizae was better than that of Radix Glycyrrhizae Preparata on HEp-2 cells. However, there was no difference of their anti-HRSV effects on A549 cells. Besides, glycyrrhizin was ineffective at all. Nevertheless, 18β-GA showed a potent anti-HRSV activity. Radix Glycyrrhizae was more effective when given before viral inoculation (p<0.0001) which may be due to its inhibition of viral attachment on (p<0.0001) and penetration (p<0.0001) into the host cells. The anti-HRSV activity of Radix Glycyrrhizae was further confirmed by RT-PCR and qRT-PCR. 300μg/ml Radix Glycyrrhizae markedly decreased the viral amounts within the cells and in the suspension. Radix Glycyrrhizae might further stimulate mucosal cells to secrete IFN-β to counteract viral infection. CONCLUSIONS: Both Radix Glycyrrhizae and Radix Glycyrrhizae Preparata are effective against HRSV infection on airway epithelial cells. Radix Glycyrrhizae inhibited HRSV mainly by preventing viral attachment, internalization, and by stimulating IFN secretion. 18β-GA may be one of its active constituents. 23587426 Synthesis and antimicrobial activity of novel amphiphilic aromatic amino alcohols. We report in this work the preparation and in vitro antimicrobial evaluation of novel amphiphilic aromatic amino alcohols synthesized by reductive amination of 4-alkyloxybenzaldehyde with 2-amino-2-hydroxymethyl-propane-1,3-diol. The antibacterial activity was determined against four standard strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa) and 21 clinical isolates of methicillin-resistant Staphylococcus aureus. The antifungal activity was evaluated against four yeast (Candida albicans, Candida tropicalis, Candida glabrata and Candida parapsilosis). The results obtained showed a strong positive correlation between the lipophilicity and the antibiotic activity of the tested compounds. The best activities were obtained against the Gram-positive bacteria (MIC=2-16μgml(-1)) for the five compounds bearing longer alkyl chains (4c-g; 8-14 carbons), which were also the most active against Candida (MIC=2-64μgml(-1)). Compound 4e exhibited the highest levels of inhibitory activity (MIC=2-16μgml(-1)) against clinical isolates of MRSA. A concentration of twice the MIC resulted in bactericidal activity of 4d against 19 of the 21 clinical isolates. 23625769 A 7-Year Case of Furosemide-Induced Immune Thrombocytopenia. Immune thrombocytopenia has been attributed to many causes. Several drugs have been implicated as culprits in causing drug-induced thrombocytopenia. Although the mechanism for this type of thrombocytopenia is not well understood, at least three types of antibodies appear to be involved: drug-dependent antibodies, hapten-dependent antibodies, and drug-induced platelet-reactive autoantibodies. In this report, we describe a case in which furosemide was identified as the probable cause of drug-induced thrombocytopenia in an 84-year-old man with chronic symptomatic idiopathic thrombocytopenia for seven years before discovery. The patient's platelet count and daily furosemide dose, both intravenous and oral, were documented throughout his medical history. A dose-dependent change in platelet count was observed in association with the furosemide dose. His platelet count increased on discontinuation of furosemide and beginning of torsemide. Several months after discontinuation of furosemide, his platelet count increased to a 9-year high of 206 × 10(3) /mm(3) from a low of 36 × 10(3) /mm(3) while receiving furosemide therapy. Based on the observations of this case report, clinicians should more readily consider furosemide as a potential cause of thrombocytopenia. 23325631 Caged CO(2) for the direct observation of CO(2)-consuming reactions. CO(2)-consuming reactions, in particular carboxylations, play important roles in technical processes and in nature. Their kinetic behavior and the reaction mechanisms of carboxylating enzymes are difficult to study because CO(2) is inconvenient to handle as a gas, exists in equilibrium with bicarbonate in aqueous solution, and typically yields products that show no significant spectroscopic differences from the reactants in the UV/Vis range. Here we demonstrate the utility of 3-nitrophenylacetic acid and related compounds (caged CO(2)) in conjunction with infrared spectroscopy as widely applicable tools for the investigation of such reactions, permitting convenient measurement of the kinetics of CO(2) consumption. The use of isotopically labeled caged CO(2) provides a tool for the assignment of infrared absorption bands, thus aiding insight into reaction intermediates and mechanisms. 23356791 Formaldehyde metabolism and formaldehyde-induced stimulation of lactate production and glutathione export in cultured neurons. Formaldehyde is endogenously produced in the human body and brain levels of this compound are elevated in neurodegenerative conditions. Although the toxic potential of an excess of formaldehyde has been studied, little is known on the molecular mechanisms underlying its neurotoxicity as well as on the ability of neurons to metabolize formaldehyde. To address these topics, we have used cerebellar granule neuron cultures as model system. These cultures express mRNAs of various enzymes that are involved in formaldehyde metabolism and were remarkably resistant toward acute formaldehyde toxicity. Cerebellar granule neurons metabolized formaldehyde with a rate of around 200 nmol/(h × mg) which was accompanied by significant increases in the cellular and extracellular concentrations of formate. In addition, formaldehyde application significantly increased glucose consumption, almost doubled the rate of lactate release from viable neurons and strongly accelerated the export of the antioxidant glutathione. The latter process was completely prevented by inhibition of the known glutathione exporter multidrug resistance protein 1. These data indicate that cerebellar granule neurons are capable of metabolizing formaldehyde and that the neuronal glycolysis and glutathione export are severely affected by the presence of formaldehyde. 23057692 A comprehensive study to evaluate the effect of constant low voltage iontophoresis on transungual delivery. Treatment of nail diseases by topical drug delivery continues to draw much attention in the recent days. This study aims to systematically investigate the effect of constant voltage iontophoresis in the transungual drug delivery, using ciclopirox as a model drug. Preliminary permeation studies were carried out by applying constant voltage (6 V for 24 h) using a gel formulation across the human nail plate in a Franz diffusion cell. Different protocols have been studied to authenticate the potential of the proposed technique. Antifungal studies were carried out to assess the pharmacodynamic effect of drug depot formed in the nail plate. Initial studies revealed that application of constant voltage iontophoresis enhanced the permeation by an order of magnitude (p = 0.019) and delivered significant amount of drug into the deeper nail layers. Noticeably higher permeation was observed during the active phase in on-off studies. Excellent correlation was observed in permeation (r(2) = 0.98) and drug load (r(2) = 0.97) with the increase in applied voltage (3-12 V), indicating that the current technique is predictable. The data observed suggest that any further increase in voltage could eventually lead to increase in the permeation and drug load, as the saturation level is very distant. Furthermore, the enhancement in permeation with the applied voltage (3-12 V) was found to be 6-20 folds, compared to the passive process. Results of step up and step down studies substantiated the viability of the current technique. Zone of inhibition measured during the antifungal studies demonstrated that the drug molecules loaded into the nail plate by low voltage iontophoresis is active and releases over an extended period of time (~32 days). Given the excellent results, the current technique could be used as an effective approach for the delivery of antimycotics, which would localize the drug at the infection site and potentially offer higher patient compliance. 23357362 Testing of Perilla frutescens extract and Vicenin 2 for their antispasmodic effect. Gastrointestinal discomfort is frequently observed. The effects of Perilla frutescens extract and Vicenin 2 (a compound in this extract) were assayed in rat ileum with or without stimulation with acetylcholine or Ba(2+). Both had no direct spasmolytic effect, but both decreased acetylcholine- or Ba(2+)-induced contraction of rat ileum indicating an antispasmodic effect. This is valuable because effects were only observed when spasms were induced and may disturb the patient. The extract and the compound may be used to maintain and improve gut health. 22989705 Pioglitazone protects against cisplatin induced nephrotoxicity in rats and potentiates its anticancer activity against human renal adenocarcinoma cell lines. Cisplatin-induced nephrotoxicity is a serious problem that limits its use in cancer treatment. The present study aimed to investigate the renal protective capacity of pioglitazone to reduce the cisplatin- induced nephrotoxicity. The underlying suggested mechanism(s) and whether this nephroprotective effect (if any) interferes with the cytotoxic effect of cisplatin on cancer cells were also investigated. Pioglitazone, Bisphenol A diglycidyl ether, BADGE, IP injected (Peroxisome proliferator- activated receptor gamma (PPAR-γ) antagonist), or their combination were administered to rats one hour before cisplatin injection. Moreover, their effects on the cell viability of human renal adenocarcinoma cell models (ACHN) were studied. The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB) genes expression in cisplatin injected rats. It increased both renal reduced glutathione (GSH) content and PPAR-γ gene expression. In contrast to the data obtained by prior administration of BADGE. Pioglitazone also potentiated the cytotoxic effect of cisplatin on human renal adenocarcinoma cells and this effect was abolished by BADGE co administration. In conclusion, these results suggested that pioglitazone protected against cisplatin- induced nephrotoxicity through its interaction with PPAR-γ receptors and antioxidant effects. Furthermore, pioglitazone did not interfere but rather potentiated the cytotoxic effects of cisplatin on human renal adenocarcinoma cells. 23503923 Composite dissolving microneedles for coordinated control of antigen and adjuvant delivery kinetics in transcutaneous vaccination. Transcutaneous administration has the potential to improve therapeutics delivery, providing an approach that is safer and more convenient than traditional alternatives, while offering the opportunity for improved therapeutic efficacy through sustained/controlled drug release. To this end, we demonstrate a microneedle materials platform for rapid implantation of controlled-release polymer depots into the cutaneous tissue. Arrays of microneedles comprised of drug-loaded poly(lactide-co-glycolide) (PLGA) microparticles or solid PLGA tips were prepared with a supporting and rapidly water-soluble poly(acrylic acid) (PAA) matrix. Upon application of microneedle patches to the skin of mice, the microneedles perforated the stratum corneum and epidermis. Penetration of the outer skin layers was followed by rapid dissolution of the PAA binder on contact with the interstitial fluid of the epidermis, implanting the microparticles or solid polymer microneedles in the tissue, which were retained following patch removal. These polymer depots remained in the skin for weeks following application and sustained the release of encapsulated cargos for systemic delivery. To show the utility of this approach we demonstrated the ability of these composite microneedle arrays to deliver a subunit vaccine formulation. In comparison to traditional needle-based vaccination, microneedle delivery gave improved cellular immunity and equivalent generation of serum antibodies, suggesting the potential of this approach for vaccine delivery. However, the flexibility of this system should allow for improved therapeutic delivery in a variety of diverse contexts. 23518472 Estrogenic and androgenic effects in mosquitofish (Gambusia affinis) from streams contaminated by municipal effluent in Guangzhou, China. The study reported in this paper used mosquitofish to investigate the estrogenic and androgenic effects of municipal wastewater contamination on the stream system in Guangzhou, China. Western mosquitofish collected from a reference site and five study sites in streams forming part of the Pearl River network were dissected and analyzed for their morphological characteristics (anal fin and hemal spine characteristics) and target mRNA expression of genes (VTGα and ERα mRNA expression). Increased VTGα mRNA expression in males and decreased VTGα mRNA expression in females were observed in samples taken from four of the five study sites, with no such observations being made at the reference site. Correlation analysis indicated a significant correlation between the hemal spine morphology index and the gene transcription relative to the reference site. The multiple index also indicated that both male and female mosquitofish in contaminated streams were altered by discharged wastewater, as reflected in their morphological changes and relative induction of mRNA expression of genes in comparison to fish collected from the reference site. 23000449 Characterization of acetylcholinesterase in Hong Kong oyster (Crassostrea hongkongensis) from South China Sea. Acetylcholinesterase (AChE) activity has been used to evaluate the exposure of mollusk bivalves to organophosphates, carbamate pesticides, and heavy metals. Crassostrea hongkongensis is a Hong Kong endemic oyster, and has a high commercial value along the coastal area of South China. The use of this species as a bio-indicator of the marine environment, and the use of AChE activity measurements in tissues of C. hongkongensis require prior characterization of AChE in this species. Here, we report that gill tissue contains the highest AChE activity in C. hongkongensis, and that the molecular form of AChE is most likely to be a dimeric form. In addition, the effect of the pesticide acephate on AChE activity in the gill of C. hongkongensis was analyzed, and the mean inhibition concentration (IC50) value was determined. This study suggests that AChE activity in the gill tissue of C. hongkongensis might be used as a biomarker in monitoring organophosphate contamination in the marine fauna of South China. 23279802 Synthesis and quantum chemical studies of new 4-aminoquinazoline derivatives as Aurora A/B kinase inhibitors. Nine novel 4-aminoquinazoline derivatives were designed and synthesized. Biochemical and cellular analyses demonstrated that most of the derivatives exhibited a strong activity to inhibit Aurora A and B kinases and to suppress the proliferation of a panel of human tumor cell lines (U937, K562, A549, LoVo, and HT29). Quantum chemical studies were also carried out to determine the structural features of these compounds engaged in the inhibition of Aurora kinases. 23536315 Regulation of neutrophil extracellular trap formation by anti-inflammatory drugs. The formation of neutrophil extracellular traps (NETs) is a newly described phenomenon that increases the bacteria killing ability and the inflammatory response of neutrophils. Because NET generation occurs in an inflammatory microenvironment, we examined its regulation by anti-inflammatory drugs. Treatment of neutrophils with dexamethasone had no effect while acetylsalicylic acid (ASA) treatment prevented NET formation. NETosis was also abrogated by the presence of BAY 11-7082 and Ro 106-9920, two structurally unrelated NF-κB inhibitors. The decrease in NET formation mediated by ASA, BAY-11-7082 and Ro 106-9920 was correlated with a significant reduction in the phosphorylation of NF-κB p65 subunit, indicating that the activation of this transcription factor is a relevant signaling pathway involved in the generation of DNA traps. The inhibitory effect of these drugs was also observed when NET generation was induced under acidic or hyperthermic conditions, two stress signals of the inflammatory microenvironment. In a mouse peritonitis model, while pretreatment of animals with ASA or BAY 11-7082 resulted in a marked suppression of NET formation along with increased bacteremia, dexamethasone had no effect. Our results show that NETs have an important role in the local control of infection and that ASA and NF-κB blockade could be useful therapies to avoid undesired effect of persistent neutrophil activation. 23563049 Molecular dynamics in liquid and glassy states of non-steroidal anti-inflammatory drug: Ketoprofen. Ketoprofen is a well known nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects. It acts by inhibiting the body's production of prostaglandin. The molecular mobility of amorphous ketoprofen has been investigated by broadband dielectric spectroscopy (BDS) covering wide temperature and frequency range. Multiple relaxation processes were observed. Besides the primary α-relaxation, one secondary relaxation, γ-have been identified. The γ-process visible in the dielectric spectra at very low temperature is non-JG relaxation, and has an activation energy E=37.91kJ/mol typical for local mobility. Based on Ngai's coupling model smaller n or a larger Kohlrausch exponent (1-n) of the α-relaxation associated with larger τβ (Tg). In the case of ketoprofen we conclude that the secondary relaxation (β) emerging from intermolecular motions, is hidden under the dominant α-peak. The temperature dependence of the relaxation time of the α-process can be described over the entire measured range by a single Vogel-Fulcher-Tammann (VFT) equation. From VFT fits, the glass transition temperature (Tg) was estimated as 267.07K, and a fragility or steepness index m=86.57 was calculated, showing that ketoprofen is a fragile glass former. Our differential scanning calorimetry (DSC) study shows that ketoprofen is a non-crystallizing compound. To confirm the hydrogen bond patterns of ketoprofen FTIR spectroscopy was applied in both crystalline and amorphous phases. Solubility test performed at 37°C proved that amorphous phase is more soluble than the crystalline phase. 23561091 Flavonoids from the capitula of Eriocaulon australe. A flavan, eriocaulin A (1), and three flavone acyl glucosides, eriocaulosides A-C (2-4) were isolated from the capitula of Eriocaulon australe R. Br. (Eriocaulaceae), a Chinese medicine and an herb for health care beverages, together with seven known flavones and three isoflavones (5-14). The new flavonoids were elucidated as (2S)-3',4'-methylenedioxy-5-methoxy-7-hydroxyflavan (1), hispidulin 7-O-β-d-(6-O-cinnamoyl)glucopyranoside (2), jaceosidin 7-O-β-d-(6-O-p-coumaroyl)glucopyranoside (3), jaceosidin 7-O-β-d-(6-O-p-hydroxybenzoyl)glucopyranoside (4) based on their spectroscopic data. All the 14 flavonoids were obtained from this species for the first time. The in vitro cytotoxicity of compounds 1-14 against human lung adenocarcinoma A549, human breast adenocarcinoma MCF-7, and human cervical carcinoma HeLa cell lines was evaluated using the MTT colourimetric assay. Compounds 1, 7, and 9 were cytotoxic to A549, compounds 1, 2, 7, 9, 12, and 14 to MCF-7, and compounds 7, 9, and 14 to HeLa cells, with IC50 values ranging from 7.17 to 29.57μg/ml, while the others were inactive (IC50>50μg/ml). 23281847 Spreading and structuring of water on superhydrophilic polyelectrolyte brush surfaces. The wetting behavior of superhydrophilic polyelectrolyte brushes was investigated. Reflection interference contrast microscopy demonstrated that the contact angles of water on the polyelectrolyte brushes were extremely low but remained finite in the range of <3°. The presence of water molecules was evident, even outside the macroscopic water droplet. These water molecules were confined to the thin brush layers and contained a highly ordered hydrogen bond network, which was identified as structural water. The presence of the thin film and the structural water changed the surface energies, which prevented the complete wetting of the surface. 23461825 Signal transducer and activator of transcription 6 directly regulates human ORMDL3 expression. Orosomucoid-like 3 (ORMDL3) has been associated with asthma and a series of autoimmune disorders, and is involved in endoplasmic reticulum-mediated inflammatory responses. However, its clinical significance and the molecular mechanism underlying its expression are still largely unclear. To elucidate the mechanisms of human ORMDL3 transcriptional regulation, we cloned a 1.5 kb genomic DNA fragment containing the putative promoter region and evaluated its transcriptional activity in a luciferase reporter system by deletion analysis. We identified a 68 bp region that functions as a minimal promoter. Bioinformatics analysis predicted that the -64 to -56 bp region contained a signal transducer and activator of transcription 6 (STAT6) binding site. Electrophoretic mobility shift assay and chromatin immunoprecipitation demonstrated that STAT6 bound to its binding site within the ORMDL3 promoter. STAT6 over-expression or knockdown trans-activated or trans-inhibited, respectively, the ORMDL3 promoter containing the STAT6-binding motif. Treatment with interleukins 4 or 13 increased ORMDL3 promoter activity as well as endogenous ORMDL3 expression. Immunoprecipitation and ChIP/Re-ChIP assays revealed that STAT6 and p300 exist in the same protein complex that binds to the ORMDL3 promoter. Our study confirmed that STAT6 plays important roles in regulating the expression of human ORMDL3 by directly binding to the promoter region, which may shed light on a possible role in various human diseases. STRUCTURED DIGITAL ABSTRACT: p300 physically interacts with STAT6 by anti bait coimmunoprecipitation (View Interaction: 1, 2). 23584358 Agomelatine: An antidepressant with new potent hepatoprotective effects on paracetamol-induced liver damage in rats. Paracetamol was shown to induce hepatotoxicity or more severe fatal acute hepatic damage. Agomelatine, commonly known as melatonin receptor agonist, is a new antidepressant, which resynchronizes circadian rhythms with subjective and objective improvements in sleep quality and architecture, as melatonin does. In the present study, it was aimed to evaluate the hepatoprotective activity of agomelatine on paracetamol-induced hepatotoxicity and to understand the relationship between the hepatoprotective mechanism of agomelatine and antioxidant system and proinflammatory cytokines. A total of 42 rats were divided into 7 groups as each composed of 6 rats: (1) intact, (2) 40 mg/kg agomelatine, (3) 140 mg/kg N-acetylcysteine (NAC), (4) 2 g/kg paracetamol, (5) 2 g/kg paracetamol + 140 mg/kg NAC, (6) 2 g/kg paracetamol + 20 mg/kg agomelatine, and (7) 2 g/kg paracetamol + 40 mg/kg agomelatine groups. Paracetamol-induced hepatotoxicity was applied and liver and blood samples were analyzed histopathologically and biochemically. There were statistically significant increases in the activities of aspartate aminotransferase, alanine aminotransferase, levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and 8-iso-prostane, and decreases in the activity of superoxide dismutase and level of glutathione in the group treated with paracetamol. Administration of agomelatine and NAC separately reversed these changes significantly. In conclusion, agomelatine administration protects liver cells from paracetamol-induced hepatotoxicity via antioxidant activity and reduced proinflammatory cytokines, such as TNF-α and IL-6. 23278398 X-ray crystallography and computational docking for the detection and development of protein-ligand interactions. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterised by the selective dysfunction and death of the upper and lower motor neurons. Median survival rates are between 3 and 5 years after diagnosis. Mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) have been linked to a subset of familial forms of ALS (fALS). Herein, we describe a fragment- based drug discovery (FBDD) approach for the investigation of small molecule binding sites in SOD1. X-ray crystallography has been used as the primary screening method and has been shown to directly detect protein-ligand interactions which cannot be unambiguously identified using other biophysical methods. The structural requirements for effective binding at Trp32 are detailed for a series of quinazoline-containing compounds. The investigation of an additional site that binds a range of catecholamines and the use of computational modelling to assist fragment evolution is discussed. This study also highlights the importance of ligand solubility for successful Xray crystallographic campaigns in lead compound design. 23200901 The role of efflux transporters on the transport of highly toxic aconitine, mesaconitine, hypaconitine, and their hydrolysates, as determined in cultured Caco-2 and transfected MDCKII cells. Aconitum alkaloids including aconitine (AC), mesaconitine (MA), hypaconitine (HA), are highly toxic. Their hydrolysates, such as benzoylaconine (BAC), benzoylmesaconine (BMA), benzoylhypaconine (BHA), aconine, and mesaconine, are considerably less toxic. Efflux transporters, including P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein isoform 2 (MRP2), act as a first line of defence and play key roles in toxicity prevention. The aim of the present study was to determine the role of efflux transporters in the transport of Aconitum alkaloids using cultured Caco-2, MDR1-MDCKII and BCRP-MDCKII cells. Bidirectional transport assays of the Aconitum alkaloids were performed with or without P-gp (cyclosporine A and verapamil), BCRP (Ko143) and MRP2 (MK571) inhibitors. The efflux ratios (Er) of AC, MA, and HA in Caco-2 cells were 34.6±4.2, 29.7±2.1, and 15.6±2.1, respectively; those of BAC, BMA, and BHA were approximately 4, and those of aconine and mesaconine were equal to 1. The Er values of AC, MA, and HA in MDR1-MDCKII and BCRP-MDCKII cells were significantly higher than those in parental MDCKII cells. Taken together the results of Er values and intracellular amounts in the presence of inhibitors, P-gp and BCRP were involved in the transport of AC, MA and HA; and MRP2 might transport AC, MA, HA, BAC, BMA and BHA. 23373463 Reaction-diffusion framework: the mechanism of the polymorphic transition of α- to β-cobalt hydroxide. A new and simple method is proposed to explore the mechanism of the intercalation/deintercalation of a variety of anions throughout the formation of α-Co(OH)2 crystals and their polymorphic conversion to β-Co(OH)2. This method is based on the reaction-diffusion of hydroxide ions in a gel matrix containing the cobalt salt. The spatiotemporal evolution of each polymorph and their interaction is revealed by tracking the location of the two sharp interfaces between the two polymorphs (conversion zone) and between the gel and α-Co(OH)2 (formation zone) and by measuring the weight composition of each zone. We thereby find that the dynamics of the transformation reaction are correctly described by the two-dimensional Avrami-Erofe'ev equation at different temperatures. The data suggest that the structural redistribution of the atoms inside the α-Co(OH)2 particles plays the fundamental role in establishing the overall rate of the reaction. On the other hand, we notice that other factors such as the nature of the intercalated anions and the concentration of the polymer matrix alter considerably the final rate of the transition reaction through increasing the stability of the α phase. 22397600 Comparison of pharmacokinetics in beagle dogs of nimesulide bilayer tablets with dispersible tablets. The purpose of this study was to compare the in vitro release and the in vivo pharmacokinetics of bilayer tablets with the conventional dispersible tablets of nimesulide. The tablets were administered to beagle dogs and the plasma levels of nimesulide were determined by high-performance liquid chromatography-MS/MS. The pharmacokinetic parameters were calculated using a noncompartmental model. The bilayer tablets showed a biphasic in vitro release pattern with initial burst release and sustained release following the quasi-Fickian diffusion-based release mechanism. The C(max), t(max), mean residence time (MRT), and area under the curve from 0 to 36 h were 10.8 ± 4.2 μg/mL, 2.3 ± 1.0 h, 6.7 ± 2.1 h, 81.5 ± 26.7 μg·h/mL for the bilayer tablets and 14.8 ± 5.8 μg/mL, 2.7 ± 0.8 h, 5.6 ± 0.9 h, 95.4 ± 44.2 μg·h/mL for the dispersible tablets. Compared with the dispersible tablets, the bilayer tablets have lower C(max), similar t(max), and longer MRT. The aforementioned pharmacokinetic parameters, especially the MRT demonstrated to be valuable for evaluating the biphasic characteristics. This study provides a promising in vivo evaluation method for the bilayer tablets with biphasic release pattern. 23547757 Potent Proteasome Inhibitors Derived from the Unnatural Cis-Cyclopropane Isomer of Belactosin A: Synthesis, Biological Activity, and Mode of Action. The natural product belactosin A (1) with a trans-cyclopropane structure is a useful prototype compound for developing potent proteasome (core particle, CP) inhibitors. To date, 1 and its analogs are the only CP ligands bind to both the non-primed S1 pocket as well as the primed substrate binding channel, however, these molecules harbor a high IC50 value of more than 1 µM. We have performed structure activity relationship studies, hereby elucidating unnatural cis-cyclopropane derivatives of 1 that exhibit high potency to primarily block the chymotrypsin-like active site of the human constitutive (cCP) and immunoproteasome (iCP). The most active compound 3e reversibly inhibits cCP and iCP similarly with an IC50 of 5.7 nM. X-ray crystallographic analysis of the yeast proteasome in complex with 3e revealed that the ligand accommodates predominantly to the primed substrate binding channel and covalently binds to the active site threonine residue via its β-lactone ring-opening. 23558747 Impaired in vivo binding of MeCP2 to chromatin in the absence of its DNA methyl-binding domain. MeCP2 is a methyl-CpG-binding protein that is a main component of brain chromatin in vertebrates. In vitro studies have determined that in addition to its specific methyl-CpG-binding domain (MBD) MeCP2 also has several chromatin association domains. However, the specific interactions of MeCP2 with methylated or non-methylated chromatin regions and the structural characteristics of the resulting DNA associations in vivo remain poorly understood. We analysed the role of the MBD in MeCP2-chromatin associations in vivo using an MeCP2 mutant Rett syndrome mouse model (Mecp2(tm)(1)(.)(1)(Jae)) in which exon 3 deletion results in an N-terminal truncation of the protein, including most of the MBD. Our results show that in mutant mice, the truncated form of MeCP2 (ΔMeCP2) is expressed in different regions of the brain and liver, albeit at 50% of its wild-type (wt) counterpart. In contrast to the punctate nuclear distribution characteristic of wt MeCP2, ΔMeCP2 exhibits both diffuse nuclear localization and a substantial retention in the cytoplasm, suggesting a dysfunction of nuclear transport. In mutant brain tissue, neuronal nuclei are smaller, and ΔMeCP2 chromatin is digested faster by nucleases, producing a characteristic nuclease-resistant dinucleosome. Although a fraction of ΔMeCP2 is found associated with nucleosomes, its interaction with chromatin is transient and weak. Thus, our results unequivocally demonstrate that in vivo the MBD of MeCP2 together with its adjacent region in the N-terminal domain are critical for the proper interaction of the protein with chromatin, which cannot be replaced by any other of its protein domains. 23265469 Enzymatic synthesis of fructooligosaccharides by inulinases from Aspergillus niger and Kluyveromyces marxianus NRRL Y-7571 in aqueous-organic medium. This work is focused on the synthesis of the fructooligosaccharides (FOS) from sucrose and inulin, using free, immobilized and pre-treated immobilized inulinase from Kluyveromyces marxianus NRRL Y 7571 and Aspergillus niger in an aqueous-organic system. Initially, the influence of pre-treatment using four different gases, propane, n-butane, CO(2) and liquefied petroleum gas (LPG), was investigated towards FOS production and best results were found when both enzymes were previously treated with LPG. The best reaction yields were obtained when the immobilized enzymes were treated with LPG. Considering FOS synthesis using the enzyme from A. niger, yields of 26.62% of GF2 (kestose), 30.62% of GF3 (nystose) and 8.47% of GF4 (fructosyl nystose) were achieved using sucrose as substrate. Using inulinases from K. marxianus NRRL Y 7571, 11.89% of GF2 and 20.83% of GF3 were obtained, using inulin as substrate. However, promising results were achieved using the free form of inulinase from A. niger (77.19% of GF2; 14.03% of GF3 and 0.07% of GF4) using inulin as substrate. 23265506 EC50 estimation of antioxidant activity in DPPH· assay using several statistical programs. DPPH(·) assay is a reliable method to determine the antioxidant capacity of biological substrates. The DPPH(·) radical scavenging activity is generally quantified in terms of inhibition percentage of the pre-formed free radical by antioxidants, and the EC(50) (concentration required to obtain a 50% antioxidant effect) is a typically employed parameter to express the antioxidant capacity and to compare the activity of different compounds. In this study, the EC(50) estimation was performed using a comparative approach based on various regression models implemented in six specialized computer programs: GraphPad Prism® version 5.01, BLeSq, OriginPro® 8.5.1, SigmaPlot® 12, BioDataFit® 1.02, and IBM SPSS Statistics® Desktop 19.0. For this project, quercetin, catechin, ascorbic acid, caffeic acid, chlorogenic acid and acetylcysteine were screened as antioxidant standards with DPPH(·) assay to define the EC(50) parameters. All the statistical programs gave similar EC(50) values, but GraphPad Prism® five-parameter analysis pointed out a best performance, also showing a minor variance in relation to the actual EC(50). 22610853 Effects of supplementation with curcuminoids on dyslipidemia in obese patients: a randomized crossover trial. Dyslipidemia is a leading risk factor for cardiovascular disease and is also a common feature of obesity. Curcumin is a bioactive phytochemical with well-known antioxidant, anti-inflammatory, and cardioprotective properties. The present study investigated the hypolipidemic activity of curcumin in obese individuals. Participants (n = 30) were treated with curcuminoids (1 g/day), or placebo in a randomized, double-blind, placebo-controlled, crossover trial. Serum concentrations of total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, together with anthropometric parameters and high-sensitivity C-reactive protein were measured before and after each treatment period. Anthropometric parameters including weight, BMI, waist circumference, hip circumference, arm circumference, and body fat remained statistically unchanged by the end of trial (p > 0.05). As for the lipid profile parameters, serum triglycerides were significantly reduced following curcumin supplementation (p = 0.009). However, curcuminoids were not found to affect serum levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein (p > 0.05). In summary, the findings of the present study indicated that curcuminoid supplementation (1 g/day for 30 days) leads to a significant reduction in serum triglycerides concentrations but do not have a significant influence on other lipid profile parameters as well as body mass index and body fat. Copyright © 2012 John Wiley & Sons, Ltd. 23323763 Two new stemona alkaloids from Stemona tuberosa Lour. Two new pyrrolo[1,2-α]azepine-type stemona alkaloids, named as tuberostemonoxirine (1) and 9α-epi-tuberospironine (2), were isolated from the roots of Stemona tuberosa. The structures and relative configurations of new compounds were established on the basis of extensive spectroscopic evidences, especially 1D and 2D NMR and HR-MS experiments. 23428347 Bortezomib enhances antigen-specific cytotoxic T cell responses against immune-resistant cancer cells generated by STAT3-ablated dendritic cells. Dendritic cell (DC)-based vaccines have received attention as a new therapeutic modality against cancer. However, increased STAT3 activity in the tumor microenvironment makes DCs tolerogenic and suppresses their antitumor activity. In this study, we explored the effects of a combination treatment consisting of a proteasome inhibitor, bortezomib, and an antigen specific STAT3-ablated (STAT3(-/-)) DC-based vaccine on the control of TC-1(P3) tumors, a p53-degraded immune resistant cancer cells. We found that E7-antigen expressing STAT3(-/-) DC (E7-DC-1STAT3(-/-)) vaccination enhanced generation of E7-specific CD8(+) T cells, but was not enough to control TC-1(P3) cancer cells. Therefore, we investigated whether bortezomib could create a synergistic effect with E7-DC-1STAT3(-/-) vaccination. We found that apoptosis via down-regulation of STAT3 and NF-κB and up-regulation of Fas and death receptor 5 (DR5) expression in TC-1(P3) induced by bortezomib was independent of p53 status. We also observed that TC-1(P3) cells pretreated with bortezomib had markedly enhanced anti-tumor effects on E7-specific CD8(+) T cells through a Fas/DR5-mediated mechanism. In addition, TC-1(P3) tumor-bearing mice treated with bortezomib prior to vaccination with E7-DC-1STAT3(-/-) demonstrated enhanced generation of E7-specific CD8(+) T cells and prolonged survival compared to those treated with monotherapy. These results suggest that the anti-tumor effects against a p53-degraded immune resistant variant generated by antigen-expressing STAT3-ablated mature DCs may be enhanced by bortezomib via death receptor-mediated apoptosis. 23494187 Brentuximab vedotin: a review of its use in patients with hodgkin lymphoma and systemic anaplastic large cell lymphoma following previous treatment failure. Brentuximab vedotin (ADCETRIS(®)) is an antibody-drug conjugate that is specifically targeted against CD30-positive cancer cells such as those in Hodgkin lymphoma or systemic anaplastic large cell lymphoma (ALCL). Intravenous brentuximab vedotin was associated with an overall objective response rate (primary endpoint) of 75 % in 102 patients with Hodgkin lymphoma who had relapsed after high-dose chemotherapy and autologous haematopoietic stem cell transplantation, in a noncomparative, multicentre, phase II trial. In 58 patients with relapsed systemic ALCL after at least one prior treatment, intravenous brentuximab vedotin was associated with an overall objective response rate (primary endpoint) of 86 % in a noncomparative, multicentre, phase II trial. Tumour reductions were observed in 94 % of patients with Hodgkin lymphoma and 97 % of patients with systemic ALCL, and most tumours decreased in size by >65 % and >85 %, respectively. The estimated 12-month survival rates were 89 % and 52 %, respectively. Brentuximab vedotin was generally well tolerated in these trials. The most common adverse event was peripheral neuropathy; approximately one-half of patients with this adverse event experienced complete resolution. 23258708 The comprehensive epigenome map of piRNA clusters. PIWI-interacting RNA (piRNA) clusters act as anti-transposon/retrovirus centers. Integration of selfish jumping elements into piRNA clusters generates de novo piRNAs, which in turn exert trans-silencing activity against these elements in animal gonads. To date, neither genome-wide chromatin modification states of piRNA clusters nor a mode for piRNA precursor transcription have been well understood. Here, to understand the chromatin landscape of piRNA clusters and how piRNA precursors are generated, we analyzed the transcriptome, transcription start sites (TSSs) and the chromatin landscape of the BmN4 cell line, which harbors the germ-line piRNA pathway. Notably, our epigenomic map demonstrated the highly euchromatic nature of unique piRNA clusters. RNA polymerase II was enriched for TSSs that transcribe piRNA precursors. piRNA precursors possessed 5'-cap structures as well as 3'-poly A-tails. Collectively, we envision that the euchromatic, opened nature of unique piRNA clusters or piRNA cluster-associated TSSs allows piRNA clusters to capture new insertions efficiently. 23597490 Anti-diabetic activity of embelin: Involvement of cellular inflammatory mediators, oxidative stress and other biomarkers. Embelin (benzoquinone), an active constituent of methanolic extracts of the fruit of Embelia basal (Myrsinaceae), was studied in high fat diet (HFD)+streptozotocin (STZ) diabetic rats. Treatment of embelin (25 and 50mg/kg/day, p.o.) for 3 weeks to HFD+STZ diabetic rats elicited insignificant increase in body weight, reduced the elevated plasma glucose, glycosylated haemoglobin and pro-inflammatory mediators (interleukin 6 and tumour necrosis factor α) significantly. Furthermore, embelin treatment at both the doses significantly decreased the elevated malondialdehyde, restored depleted glutathione, antioxidant enzymes, superoxide dismutase and catalase in liver. The increased lipid profiles in HFD+STZ diabetic rats were also reduced by embelin treatment significantly. Embelin treatment to HFD+STZ diabetic rats also improved the altered histoarchitecture of β-islets of pancreas and hepatocytes. The embelin effect on progression of type 2 diabetes mellitus in rats appears to be through the inhibition of intracellular pro-inflammatory mediators, lowering of lipid profile and amelioration of oxidative stress. Considering the pharmacological activity profile of embelin, it is suggested that embelin be a useful diabetic modulator or adjuvant along with clinically effective anti-diabetic drugs in the treatment of type 2 diabetes mellitus and needs to be clinically evaluated on human subjects. 23146765 1H NMR-based metabonomics approach in a rat model of acute liver injury and regeneration induced by CCl4 administration. The administration of carbon tetrachloride (CCl(4)) has been established as a model of toxin-induced acute and chronic liver injury. In the present study, we investigate the progression of the biochemical response to acute CCl(4)-induced liver injury, capturing metabolic variations during both toxic insult and regeneration using NMR-based metabonomic analysis of liver tissue and plasma. A single dose of CCl(4) (1 mL/kg BW) was intraperitoneally administered to male Wister rats sacrificed every 12h up to 72 h post treatment, while healthy animals served as controls. Acquired (1)H NMR spectra of liver tissue extracts and plasma samples were explored with multivariate analysis and the resulted models were correlated with conventional biochemical and histopathological indices of toxicity for monitoring the progression of experimental injury. The metabonomic analysis resulted in discrimination between the subjects under toxic insult (up to 36 h) and those at the regenerative phase (peaked at 48 h). At 72 h normalization of liver's pathology similar to the controls group was apparent. Principal component analysis (PCA) trajectories highlighted the time points of the greater degree of toxic insult and the regenerative state. A number of metabolites such as glucose, lactate, choline, formate exhibited variations suggesting CCl(4) induced impairment in essential biochemical pathways as energy metabolism, lipid biosynthesis and transmethylation reactions. The latter provides new evidence of B12 and folate pathways deficiency, indicative of new mechanistic implications possibly by direct inhibition of B12 dependent enzymes by the chlorinated radicals of CCl(4) metabolism. 23524983 Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. In contrast to studies on class I histone deacetylase (HDAC) inhibitors, the elucidation of the molecular mechanisms and therapeutic potential of class IIa HDACs (HDAC4, HDAC5, HDAC7 and HDAC9) is impaired by the lack of potent and selective chemical probes. Here we report the discovery of inhibitors that fill this void with an unprecedented metal-binding group, trifluoromethyloxadiazole (TFMO), which circumvents the selectivity and pharmacologic liabilities of hydroxamates. We confirm direct metal binding of the TFMO through crystallographic approaches and use chemoproteomics to demonstrate the superior selectivity of the TFMO series relative to a hydroxamate-substituted analog. We further apply these tool compounds to reveal gene regulation dependent on the catalytic active site of class IIa HDACs. The discovery of these inhibitors challenges the design process for targeting metalloenzymes through a chelating metal-binding group and suggests therapeutic potential for class IIa HDAC enzyme blockers distinct in mechanism and application compared to current HDAC inhibitors. 23065696 Rapid estimation of nuclear magnetic resonance experiment time in low-concentration environmental samples. Nuclear magnetic resonance (NMR) spectroscopy is an essential tool for studying environmental samples but is often hindered by low sensitivity, especially for the direct detection of nuclei such as(13) C. In very heterogeneous samples with NMR nuclei at low abundance, such as soils, sediments, and air particulates, it can take days to acquire a conventional(13) C spectrum. The present study describes a prescreening method that permits the rapid prediction of experimental run time in natural samples. The approach focuses the NMR chemical shift dispersion into a single spike, and, even in samples with extremely low carbon content, the spike can be observed in two to three minutes, or less. The intensity of the spike is directly proportional to the total concentration of nuclei of interest in the sample. Consequently, the spike intensity can be used as a powerful prescreening method that answers two key questions: (1) Will this sample produce a conventional NMR spectrum? (2) How much instrument time is required to record a spectrum with a specific signal-to-noise (S/N) ratio? The approach identifies samples to avoid (or pretreat) and permits additional NMR experiments to be performed on samples producing high-quality NMR data. Applications in solid- and liquid-state(13) C NMR are demonstrated, and it is shown that the technique is applicable to a range of nuclei. 23194531 Pulsed-electric-field-assisted extraction of anthocyanins from purple-fleshed potato. The influence of pulsed electric field (PEF) treatment on the anthocyanin extraction yield (AEY) from purple-fleshed potato (PFP) at different extraction times (60-480 min) and temperatures (10-40°C) using water and ethanol (48% and 96%) as solvents has been investigated. Response surface methodology was used to determine optimal PEF treatment and optimise anthocyanin extraction. A PEF treatment of 3.4 kV/cm and 105 μs (35 pulses of 3 μs) resulted in the highest cell disintegration index (Z(p)=1) at the lowest specific energy requirements (8.92 kJ/kg). This PEF treatment increased the AEY, the effect being higher at lower extraction temperature with water as solvent. After 480 min at 40°C, the AEY obtained for the untreated sample using 96% ethanol as the solvent (63.9 mg/100 g fw) was similar to that obtained in the PEF-treated sample using water (65.8 mg/100 g fw). Therefore, PEF was possible with water, a more environmental-friendly solvent than ethanol, without decreasing the AEY from PFP. 23357308 Synthesis of some new 2-(3-pyridyl)-4,5-disubstituted thiazoles as potent antimicrobial agents. As a part of ongoing studies in developing new potent antimicrobial agents, a series of novel 2-(3-pyridyl)-4,5-disubstituted thiazoles was efficiently synthesized and characterized by spectral and elemental analyses. The newly synthesized compounds were evaluated for their in vitro antimicrobial activity against ten bacterial and five fungal human pathogenic strains using the disc diffusion assay. Among the synthesized compounds, 5-acetyl-4-methyl-2-(3-pyridyl)thiazole (5) exhibited twofold antibacterial activity of ampicillin in inhibiting the growth of Staphylococcus epidermidis (MIC 0.24 μg/mL) and also showed equipotent antifungal activity with amphotricin B against Geotricum candidum (MIC 0.48 μg/mL). From structure-activity relationship (SAR) point of view, increasing the size of the substitutions either at position 4 or 5 on the thiazole nucleus decreased the antimicrobial activity. 23331539 Fragment-based design of novel quinazolinon derivatives as human acrosin inhibitors. Human acrosin is a promising target for the male contraceptives. On the basis of the active site of human acrosin, a series of novel quinazolinon compounds were designed by a fragment docking and growing strategy. In vitro anti-acrosin assay revealed that all the compounds showed potent human acrosin inhibitory activities. In particular, compounds 5c and 5g are more active than the known inhibitors. Molecular docking studies revealed that the quinazolinon inhibitors interacted with human acrosin mainly through hydrogen bonding and hydrophobic interactions. The binding mode was also consistent with the structure-activity relationships. The quinazolinon derivatives in this study can serve as new lead structure for the development of novel male contraceptives. 23564211 The role of P-glycoprotein in CNS antihistamine effects. RATIONALE: P-glycoprotein (P-gp) is a drug efflux pump expressed, amongst others, on the luminal surface of the cerebral endothelial cells forming the blood-brain barrier. Studies in rodents have demonstrated that antihistamines that are substrates of the P-gp transporter display no or minor central nervous system (CNS) effects as compared to antihistamines that are not P-gp transporter substrates. OBJECTIVES: The present study explored whether P-gp contributes in similar ways to the occurrence of sedative effects of antihistamines in humans. METHODS: An fMRI study was conducted according to a double-blind, randomized, placebo-controlled, cross-over design in 13 healthy volunteers. Participants received cetirizine 15 mg (an antihistamine), verapamil 120 mg (a P-gp blocker), a combination of cetirizine + verapamil, and a placebo. Brain activity was assessed while conducting the attention network test (ANT) in a 3T magnetic resonance scanner. The ANT measures three independent attention domains: i.e., alerting, orienting, and executive attention. It was expected that the combined treatment of cetirizine with verapamil would prevent efflux of cetirizine from the CNS, thus increasing attentional impairment, as compared to cetirizine administered alone. RESULTS: The present study provides evidence that the P-gp transporter is involved in central antihistamine effects in humans. Participants were less alert during the combined treatment of cetirizine and verapamil as indicated by longer reaction times and decreased blood oxygen level-dependent response in the right superior temporal gyrus. CONCLUSION: It is concluded that the affinity for the P-gp transporter may contribute to the lower incidence of CNS side effects of certain antihistamines. 23509904 Structure-Based Design of β-Site APP Cleaving Enzyme 1 (BACE1) Inhibitors for the Treatment of Alzheimer's Disease. The amyloid hypothesis asserts that excess production or reduced clearance of the amyloid-β (Aβ) peptides in the brain initiates a sequence of events that ultimately lead to Alzheimer's disease and dementia. The Aβ hypothesis has identified BACE1 as a therapeutic target to treat Alzheimer's and led to medicinal chemistry efforts to design its inhibitors both in the pharmaceutical industry and in academia. This review summarizes two distinct categories of inhibitors designed based on conformational states of "closed" and "open" forms of the enzyme. In each category the inhibitors are classified based on the core catalytic interaction group or the aspartyl binding motif (ABM). This review covers the description of inhibitors in each ABM class with X-ray crystal structures of key compounds, their binding modes, related structure-activity data highlighting potency advances, and additional properties such as selectivity profile, P-gp efflux, pharmacokinetic, and pharmacodynamic data. 23260032 Exploring the Toxicity of a Bismuth-Asparagine Coordination Polymer on the Early Development of Zebrafish Embryos. Nanoparticles are widely used in nanomedicine, raising concerns about their toxicity. In this study, the toxicity of bismuth-asparagine coordination polymer spheres (BACP-2) was assessed in zebrafish embryos. Injection of 1-4 cell stage embryos with BACP-2 resulted in smaller head size (particularly smaller eye size), shorter body length, and pericardial edemas. The severity and occurrence of the resulting phenotype were concentration-dependent. The expression of genes such as krox20, orthodenticle homeobox 2 (otx2), and cardiac myosin light chain-2 (cmlc2) indicates that the effects of BACP-2 on the head and heart were related to changes in gene expression patterns. A delay in epiboly was observed, and the expression levels of the no tail (ntl) gene indicated that the delay in epiboly resulted both from the effect of BACP-2 on cell migration during epiboly and from slow growth. These findings indicate that BACP-2 exhibits concentration-dependent developmental toxicity, providing insight into the nanotoxicity of bismuth derivatives, which must be rigorously evaluated with respect to toxicity before their application in nanomedicine. 22497567 Evaluation of the physicochemical and biopharmaceutical properties of fluoro-indomethacin. Drug nanocarriers have shown great potential in therapy and as diagnostic probes, e.g. in imaging of cancer and inflammation. Imaging can be applied to localize the carrier or the drug itself in the body and/or tissues. In this particular case it is important that drug molecules have the characteristics for possible detection, e.g. after modification with positron emission tomography compliant radioisotopes, without affecting their pharmacological behavior. In order to easily and efficiently follow the ADME profile of the drug after loaded into nanocarriers, the drug can be radiolabelled with, e.g. 18F-label, in order to assess its biodistribution after enteral and parenteral administration in rats. However, this is only possible if the derivative compound behaves similarly to the parent drug compound. In this study, indomethacin (a poorly water-soluble drug) was chosen as a model compound and aimed to evaluate the physicochemical and biopharmaceutical properties of an analog of indomethacin (IMC), fluoro-indomethacin (F-IMC). Although some of the physicochemical and biopharmaceutical properties of IMC are already known, in order to establish a feasible comparison between IMC and F-IMC, the behavior of the former was also investigated in the same conditions as for F-IMC. In this context, both IMC and F-IMC were thermally and morphologically studied. Furthermore, the following properties were also studied for both compounds: pKa and logP, solubility and dissolution profiles at physiological pH values, and toxicity at different concentrations in Caco-2 cells. Finally, the transport across Caco- 2 monolayers of the IMC and F-IMC at physiological pH range was also investigated. The results obtained showed similar values in pKalogP, solubility, dissolution, cytotoxicity, and permeability for both compounds. Thus, there might be strong evidence that both IMC and F-IMC should have a similar ADME behavior and profiles in vivo. The results provide fundamental tools and ideas for further research with nanocarriers of 18F-IMC. 23333641 Effects of methoxychlor and its metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane on 11β-hydroxysteroid dehydrogenase activities in vitro. Methoxychlor (MXC) is primarily used as a pesticide and widely present in the environment. The objective of the present study is to investigate the direct effects of MXC and its metabolite 2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) on two isoforms of 11β-hydroxysteroid dehydrogenase (11β-HSD1 and 11β-HSD2) in vitro. Human liver microsome, rat testis microsome and adult Leydig cells were used for the measurement of 11β-HSD1 activity. Human placental and rat kidney microsomes were used for 11β-HSD2 activity. The IC(50) values on human 11β-HSD1 by MXC and HPTE were 1.91±0.07 and 8.88 ± 0.08 μM, respectively. HPTE inhibited rat 11β-HSD1 with IC(50) of 9.15±0.05μM, while MXC did not inhibit the enzyme. MXC and HPTE were competitive inhibitors of 11β-HSD1. HPTE also inhibited human and rat 11β-HSD2 with IC(50) values of 55.57 ± 0.08 and 12.96 ± 0.11 μM, respectively, while MXC did not inhibit 11β-HSD2. In summary, our results showed that MXC and its metabolite HPTE inhibited both isoforms of 11β-HSD in a species- and chemical structure-dependent manner. 23567040 Photochemical internalization (PCI) of immunotoxins targeting CD133 is specific and highly potent at femtomolar levels in cells with cancer stem cell properties. CD133 is a putative cancer stem cell (CSC) marker for a number of different cancers and is suggested to be a therapeutic target. Since also normal stem cells express CD133 it is of paramount importance that targeting strategies provide a specific and efficient delivery of cytotoxic drugs in only CD133-positive CSCs. In this study, we have employed photochemical internalization (PCI), a minimally invasive method for light-controlled, specific delivery of membrane-impermeable macromolecules from endocytic vesicles to the cytosol, to specifically target CD133-positive cancer cells. We demonstrate that PCI increases the cytotoxic effect of an immunotoxin (IT) targeting CD133-expressing cancer cells of colon (WiDr and HCT116) and pancreas (BxPC-3) origin. The IT consisted of the mAb CD133/1 (AC133) bound to the ribosome inactivating plant toxin saporin (anti-CD133/1-sap). We show that TPCS2a-PCI of anti-CD133/1-sap is specific, and highly cytotoxic at femto-molar concentrations. Specific binding and uptake of CD133/1, was shown by fluorescence microscopy and co-localization with TPCS2a in endosomes/lysosomes was determined by confocal microscopy. CD133(high) WiDr cells, isolated by fluorescence activated cell sorting, had a 7-fold higher capacity to initiate spheroids than CD133(low) cells (P<0.001) and were resistant to photodynamic therapy (PDT). However, PDT-resistance was bypassed by the PCI strategy. Tumor initiation and aggressive growth in athymic nude mice was obtained with only 10 CD133(high) cells in contrast to CD133(low) cells where substantially higher cell numbers were needed. The excellent high efficacy and selectivity of eliminating CD133-expressing cells by PCI warrant further pre-clinical evaluations of this novel therapeutic approach. 23523949 Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure. This study was designed to evaluate the effectiveness of crocin, main component of Crocus sativus L. (Saffron) against subchronic diazinon (DZN) induced cardiotoxicity in rats. METHODS: Rats were divided into 7 groups; control (corn oil, gavage), DZN (15mg/kg/day, gavage,), crocin (12.5, 25 or 50mg/kg/day, i.p) plus DZN, vitamin E (200IU/kg, i.p, three times per week) plus DZN and crocin (50mg/kg/day, i.p) groups. Treatments were continued for 4weeks. Creatine phosphokinase MB (CK-MB), malondealdehyde (MDA) and glutathione (GSH) levels were evaluated in heart tissue at the end of treatments. Levels of apoptotic proteins (Bax, Bcl2, caspase 3) and cytosolic cytochrome c were analyzed by Western blotting. Transcript levels of Bax and Bcl2 were also determined using qRT PCR. RESULTS: DZN induced histophatological damages and elevated the level of cardiac marker CK-MB. These effects were associated with increased MDA level, lower level of reduced GSH and induction of apoptosis through elevation of Bax/Bcl2 ratio (both protein and mRNA levels), cytochrome c release to the cytosol and activation caspase 3 in cardiac tissue. Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN. In summary, DZN induced mitochondrial-mediated apoptosis in heart tissue of rat following subchronic exposure. Crocin, as an antioxidant, showed protective effects against DZN cardiotoxicity by reducing lipid peroxidation and alleviating apoptosis. 23535915 Comparing the sensitivity of geographically distinct Lemna minor populations to atrazine. The objectives of this study were to compare the sensitivities of field populations and a laboratory culture of a duckweed species (Lemna minor) to the herbicide atrazine using three different endpoints and to determine whether sensitivity to atrazine was affected by past exposure to the herbicide. L. minor cultures were purchased commercially or collected from field sites within an agricultural watershed and exposed to atrazine for 7 days under greenhouse conditions. Populations differed significantly in their sensitivity to atrazine. Biomass was more sensitive than frond number, while chlorophyll fluorescence was not a sensitive endpoint. Overall, the sensitivity of the various populations to atrazine was not strongly related to measures of past exposure to agriculture stressors. Positive correlations between biomass twenty-five percent inhibition concentrations (IC25s), biomass estimated marginal means and in-stream atrazine concentrations were observed, providing evidence that atrazine exposure is linked to a decrease in sensitivity to atrazine. However, IC25s generated for each population were similar, ranging from 19 to 40 and 57 to 92 μg/L atrazine for biomass and frond data respectively, and likely do not represent biologically significant differences in atrazine sensitivity. Given the small range in sensitivity observed between populations, commercial laboratory cultures appear to provide a good estimate of the sensitivity of field populations of L. minor to atrazine and should continue to be used in regulatory phytotoxicity testing. 23061607 Organosilicon molecules with medicinal applications. The incorporation of silicon and synthesis of organosilicon small molecules provide unique opportunities for medicinal applications. The biological investigation of organosilicon small molecules is particularly interesting because of differences in their chemical properties that can contribute to enhanced potency and improved pharmacological attributes. Applications such as inhibitor design, imaging, drug release technology, and mapping inhibitor binding are discussed. 23391598 Essential trace and toxic element concentrations in organic and conventional milk in NW Spain. Dietary composition and husbandry practices largely determine essential trace element status and toxic element exposure of livestock, and consequently their concentrations in animal products. This study evaluates the main essential trace (Co, Cr, Cu, Fe, I, Mn, Mo, Ni, Se and Zn) and toxic (As, Cd, Hg and Pb) element concentrations in milk from organic and conventional farms in NW Spain (n=50). Milk samples were acid digested and analyzed by ICP-MS. Essential trace element concentrations in organic milk were significantly lower compared to conventional milk, this was especially evident for elements that are routinely supplemented at high concentrations in the conventional concentrate feed: Cu (41.0 and 68.9μg/L in organic and conventional milk, respectively), Zn (3326 and 3933μg/L), I (78 and 265μg/L) and Se (9.4 and 19.2μg/L). Toxic metal concentrations in milk were in general very low and no statistically significant differences were observed between organic and conventional milk. In addition, the mineral content of organic milk showed a seasonal pattern, the significantly higher As (65%) and Fe (13%) concentrations found in the winter sampling possibly being related to a higher consumption of concentration feed and soil ingestion when grazing. 23318730 Platinum folate nanoparticles toxicity: cancer vs. normal cells. Almost for two decades metallic nanoparticles are successfully used for cancer detection, imaging and treatment. Due to their high electron density they can be easily observed by electron microscopy and used in laser and radiofrequency therapy as energy releasing agents. However, the limitation for this practice is an inability to generate tumor-specific heating in a minimally invasive manner to the healthy tissue. To overcome this restraint we proposed to use folic acid coated metallic nanoparticles and determine whether they preferentially penetrate cancer cells. We developed technique for synthesizing platinum nanoparticles using folic acid as stabilizing agent which produced particles of relatively narrow size distribution, having d=2.3 ± 0.5 nm. High resolution TEM and zeta potential analysis indicated that the particles produced by this method had a high degree of crystalline order with no amorphous outer shell and a high degree of colloidal stability. The keratinocytes and mammary breast cells (cancer and normal) were incubated with platinum folate nanoparticles, and the results showed that the IC50 was significantly higher for the normal cells than the cancer cells in both cases, indicating that these nanoparticles preferentially target the cancer cells. TEM images of thin sections taken from the two types of cells indicated that the number of vacuoles and morphology changes after incubation with nanoparticles was also larger for the cancer cells in both types of tissue studied. No preferential toxicity was observed when folic acid receptors were saturated with free folic acid prior to exposure to nanoparticles. These results confirm our hypothesis regarding the preferential penetration of folic acid coated nanoparticles to cancer cells due to receptor mediated endocytosis. 23109183 Microfluidic investigation of BDNF-enhanced neural stem cell chemotaxis in CXCL12 gradients. In vivo studies have suggested that gradients of CXCL12 (aka stromal cell-derived factor 1α) may be critical for neural stem cell (NSC) migration during brain development and neural tissue regeneration. However, traditional in vitro chemotaxis tools are limited by unstable concentration gradients and the inability to decouple cell migration directionality and speed. These limitations have restricted the reproducible and quantitative analysis of neuronal migration, which is required for mechanism-based studies. Using a microfluidic gradient generator, nestin and Sox-2 positive human embryonic NSC chemotaxis is quantified within a linear and stable CXCL12 gradient. While untreated NSCs are not able to chemotax within CXCL12 gradients, pre-treatment of the cells with brain-derived neurotrophic factor (BDNF) results in significant chemotactic, directional migration. BDNF pre-treatment has no effect on cell migration speed, which averages about 1 μm min(-1). Quantitative analysis determines that CXCL12 concentrations above 9.0 nM are above the minimum activation threshold, while concentrations below 14.7 nM are below the saturation threshold. Interestingly, although inhibitor studies with AMD 3100 revealed that CXCL12 chemotaxis requires receptor CXCR4 activation, BDNF pre-treatment is found to have no profound effects on the mRNA levels or surface presentation of CXCR4 or the putative CXCR7 scavenger receptor. The microfluidic study of NSC migration within stable chemokine concentration profiles provides quantitative analysis as well as new insight into the migratory mechanism underlying BDNF-induced chemotaxis towards CXCL12. 23584484 miR-194 suppresses metastasis of non-small cell lung cancer through regulating expression of BMP1 and p27(kip1.) MicroRNAs (miRNAs) are increasingly implicated in regulating tumor malignance through their capacity to coordinately repress expression of tumor-related genes. Here, we show that overexpression of miR-194 in lung cancer cell lines, results in suppressing metastasis of lung cancer cells, while inhibiting its expression through 'miRNA sponge' promotes the cancer cells to metastasize. miR-194 expression is also found to be in strongly negative association with metastasis in clinical specimens of non-small cell lung cancer. We demonstrate that miR-194 directly targets both BMP1 and p27(kip1). The resulting downregulation of BMP1 leads to suppression of TGFβ activity and, thus, to downregulation of the expression of key oncogenic genes (matrix metalloproteinases MMP2 and MMP9). This leads, in turn, to decreased tumor invasion. In addition, the miRNA-194-induced suppression of p27(kip1) activates the RhoA pathway, producing enhanced development of actin stress fibers and impaired migration of cancer cells. These findings reveal two structurally independent but functionally linked branches of the regulatory and signaling pathway that together provide a bridge between the metastasis-depressing miRNA and the key genes that govern the malignancy of lung cancers.Oncogene advance online publication, 15 April 2013; doi:10.1038/onc.2013.108. 23470152 Ideal redox behavior of the high-density self-assembled monolayer of a molecular tripod on a au(111) surface with a terminal ferrocene group. A dyad consisting of a tripod-shaped trithiol with an adamantane core and a terminal ferrocenyl group linked through ap-phenyleneethynylene bridge was synthesized. The trithiol formed a stable self-assembled monolayer (SAM) on Au(111), wherein each molecule is bound to the surface by three-point adsorption using all sulfur atoms, with confirmation by PM-IRRAS and XPS analyses. Cyclic voltammetry of the SAM showed a line shape typical of an ideal adsorbed system, that is, a monolayer with negligible electrostatic interaction among the terminal ferrocenyl groups. Thus, a rare SAM was achieved, in which the component molecules were isolated from adjacent molecules without the coadsorption of nonelectroactive molecules. 23473066 Going where traditional markers have not gone before: utility of and promise for RAD sequencing in marine invertebrate phylogeography and population genomics. Characterization of large numbers of single-nucleotide polymorphisms (SNPs) throughout a genome has the power to refine the understanding of population demographic history and to identify genomic regions under selection in natural populations. To this end, population genomic approaches that harness the power of next-generation sequencing to understand the ecology and evolution of marine invertebrates represent a boon to test long-standing questions in marine biology and conservation. We employed restriction-site-associated DNA sequencing (RAD-seq) to identify SNPs in natural populations of the sea anemone Nematostella vectensis, an emerging cnidarian model with a broad geographic range in estuarine habitats in North and South America, and portions of England. We identified hundreds of SNP-containing tags in thousands of RAD loci from 30 barcoded individuals inhabiting four locations from Nova Scotia to South Carolina. Population genomic analyses using high-confidence SNPs resulted in a highly-resolved phylogeography, a result not achieved in previous studies using traditional markers. Plots of locus-specific FST against heterozygosity suggest that a majority of polymorphic sites are neutral, with a smaller proportion suggesting evidence for balancing selection. Loci inferred to be under balancing selection were mapped to the genome, where 90% were located in gene bodies, indicating potential targets of selection. The results from analyses with and without a reference genome supported similar conclusions, further highlighting RAD-seq as a method that can be efficiently applied to species lacking existing genomic resources. We discuss the utility of RAD-seq approaches in burgeoning Nematostella research as well as in other cnidarian species, particularly corals and jellyfishes, to determine phylogeographic relationships of populations and identify regions of the genome undergoing selection. 23288589 Electrolyte-gated organic field-effect transistor sensors based on supported biotinylated phospholipid bilayer. Anchored, biotinylated phospholipids forming the capturing layers in an electrolyte-gated organic field-effect transistor (EGOFET) allow label-free electronic specific detection at a concentration level of 10 nM in a high ionic strength solution. The sensing mechanism is based on a clear capacitive effect across the PL layers involving the charges of the target molecules. 23371965 The inactivation of human CYP2E1 by phenethyl isothiocyanate, a naturally occurring chemopreventive agent, and its oxidative bioactivation. Phenethylisothiocyanate (PEITC), a naturally occurring isothiocyanate and potent cancer chemopreventive agent, works by multiple mechanisms, including the inhibition of cytochrome P450 (P450) enzymes, such as CYP2E1, that are involved in the bioactivation of carcinogens. PEITC has been reported to be a mechanism-based inactivator of some P450s. We describe here the possible mechanism for the inactivation of human CYP2E1 by PEITC, as well as the putative intermediate that might be involved in the bioactivation of PEITC. PEITC inactivated recombinant CYP2E1 with a partition ratio of 12, and the inactivation was not inhibited in the presence of glutathione (GSH) and not fully recovered by dialysis. The inactivation of CYP2E1 by PEITC is due to both heme destruction and protein modification, with the latter being the major pathway for inactivation. GSH-adducts of phenethyl isocyanate (PIC) and phenethylamine were detected during the metabolism by CYP2E1, indicating formation of PIC as a reactive intermediate following P450-catalyzed desulfurization of PEITC. Surprisingly, PIC bound covalently to CYP2E1 to form protein adducts but did not inactivate the enzyme. Liquid chromatography mass spectroscopy analysis of the inactivated CYP2E1 apo-protein suggests that a reactive sulfur atom generated during desulfurization of PEITC is involved in the inactivation of CYP2E1. Our data suggest that the metabolism of PEITC by CYP2E1 that results in the inactivation of CYP2E1 may occur by a mechanism similar to that observed with other sulfur-containing compounds, such as parathion. Digestion of the inactivated enzyme and analysis by SEQUEST showed that Cys 268 may be the residue modified by PIC. 23265896 Regioselective synthesis of 5- and 6-methoxybenzimidazole-1,3,5-triazines as inhibitors of phosphoinositide 3-kinase. Phosphoinositide 3-kinases (PI3K) hold significant therapeutic potential as novel targets for the treatment of cancer. ZSTK474 (4a) is a potent, pan-PI3K inhibitor currently under clinical evaluation for the treatment of cancer. Structural studies have shown that derivatisation at the 5- or 6-position of the benzimidazole ring may influence potency and isoform selectivity. However, synthesis of these derivatives by the traditional route results in a mixture of the two regioisomers. We have developed a straightforward regioselective synthesis that gave convenient access to 5- and 6-methoxysubstituted benzimidazole derivatives of ZSTK474. While 5-methoxy substitution abolished activity at all isoforms, the 6-methoxy substitution is consistently 10-fold more potent. This synthesis will allow convenient access to further 6-position derivatives, thus allowing the full scope of the structure-activity relationships of ZSTK474 to be probed. 22310170 Drought episode modulates the response of river biofilms to triclosan. The consequences of global change on rivers include altered flow regime, and entrance of compounds that may be toxic to biota. When water is scarce, a reduced dilution capacity may amplify the effects of chemical pollution. Therefore, studying the response of natural communities to compromised water flow and to toxicants is critical for assessing how global change may affect river ecosystems. This work aims to investigate how an episode of drought might influence the response of river biofilms to pulses of triclosan (TCS). The objectives were to assess the separate and combined effects of simulated drought (achieved through drastic flow alteration) and of TCS exposure on biofilms growing in artificial channels. Thus, three-week-old biofilms were studied under four conditions: Control (normal water flow); Simulated Drought (1 week reduced flow+2 days interrupted flow); TCS only (normal water flow plus a 48-h pulse of TCS); and Simulated Drought+TCS. All channels were then left for 2 weeks under steady flow conditions, and their responses and recovery were studied. Several descriptors of biofilms were analyzed before and after each step. Flow reduction and subsequent interruption were found to provoke an increase in extracellular phosphatase activity, bacterial mortality and green algae biomass. The TCS pulses severely affected biofilms: they drastically reduced photosynthetic efficiency, the viability of bacteria and diatoms, and phosphate uptake. Latent consequences evidenced significant combined effects caused by the two stressors. The biofilms exposed only to TCS recovered far better than those subjected to both altered flow and subsequent TCS exposure: the latter suffered more persistent consequences, indicating that simulated drought amplified the toxicity of this compound. This finding has implications for river ecosystems, as it suggests that the toxicity of pollutants to biofilms may be exacerbated following a drought. 23116643 Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice. The aim of this study was to investigate the therapeutic potential of rosmarinic acid (RA), a natural phenolic, in the treatment of acute liver toxicity. RA at 10, 25 and 50mg/kg was administered by gavage once daily for 2 consecutive days, 6h after CCl(4) intoxication. CCl(4) intoxication caused hepatic necrosis and increased serum ALT activity. In the livers, oxidative/nitrosative stress was evidenced by increased 3-nitrotyrosine (3-NT) and thiobarbituric acid reactive substances (TBARS) formation and a significant decrease in Cu/Zn superoxide dismutase (SOD) activity. CCl(4) administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). RA improved histological and serum markers of liver damage and significantly ameliorated oxidative/nitrosative stress and inflammatory response in liver tissue. Additionally, RA prevented transforming growth factor-beta1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) expression, suggesting suppression of profibrotic response. Furthermore, RA significantly inhibited the CCl(4)-induced apoptosis, which was evident from decreased cleavage of caspase-3. The hepatoprotective activity of RA coincided with enhanced NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. The results of this study indicates that RA possesses antioxidant, anti-inflammatory, antiapoptotic and antifibrotic activity against acute liver toxicity. 23644214 Synthetic tactics of new class of 4-aminothieno[2,3-d]pyrimidine-6-carbonitrile derivatives acting as antimicrobial agents. Thermal selective reactions were studied on oxothieno[2,3-d]pyrimidine-6-carboxamide 3 with POCl3 and PCl5. At 25-50 °C, the C7-amide rearranges to nitrile furnished compound 4 in 85-90% yield, while at 80-110 °C furnished mixture of products 4 and 5 in 28-68% yields. The chloro displacement with amines in compound 5 yielded 4-aminothieno[2,3-d]pyrimidine-6-carbonitrile derivatives 8(a-h) and 9(a-e). Antimicrobial activity of new compounds was studied against several bacteria such as Staphylococcus aureus MTCC-96, Escherichia coli MTCC-443, Pseudomonas aeruginosa MTCC-4 41, Streptococcus pyogenes MTCC-442 and fungi Aspergillus niger MTCC-282, Aspergillus clavatus MTCC-1323, Candida albicans MTCC-227 using broth microdilution method. Compounds 4, 8b, 8d, 8e, 8h and 9a showed promising antibacterial activity compared to ampicillin and compounds 8b, 8h showed better antifungal activity compared to greseofulvin. 23086198 Importance of UDP-glucuronosyltransferases 2A2 and 2A3 in tobacco carcinogen metabolism. UDP-glucuronosyltransferase A1 (UGT2A1) is expressed in the lung and exhibits activity against polycyclic aromatic hydrocarbons (PAHs), suggesting UGT2A1 involvement in the local metabolism of PAH tobacco carcinogens. The goal of the present study was to investigate the importance of two additional UGT2A enzymes, UGT2A2 and UGT2A3, in tobacco carcinogen metabolism. Real-time polymerase chain reaction suggested that wild-type UGT2A2 had the highest expression in the breast, followed by trachea > larynx > kidney. A novel splice variant of UGT2A2 lacking exon 3 (termed UGT2A2Δexon3) was investigated, with UGT2A2Δexon3 expression determined to be 25-50% that of wild-type UGT2A2 in all tissues examined. UGT2A3 was determined to be well expressed in the liver and colon, followed by pancreas > kidney > lung > tonsil > trachea > larynx. Cell homogenates prepared from human embryonic kidney (HEK)293 cells overexpressing wild-type UGT2A2 (termed UGT2A2_i1) exhibited glucuronidation activity, as observed by reverse-phase ultra-pressure liquid chromatography, against 1-hydroxy-(OH)-pyrene, 1-naphthol, and hydroxylated benzo(a)pyrene metabolites, whereas homogenates prepared from HEK293 cells overexpressing UGT2A3 only showed activity against simple PAHs like 1-OH-pyrene and 1-naphthol. Activity assays showed the UGT2A2Δexon3 protein (termed UGT2A2_i2) exhibited no detectable glucuronidation activity against all substrates examined; however, coexpression studies suggested that UGT2A2_i2 negatively modulates UGT2A2_i1 activity. Both UGT2A2 and UGT2A3 exhibited no detectable activity against complex PAH proximate carcinogens, tobacco-specific nitrosamines, or heterocyclic amines. These data suggest that, although UGT2A1 is the only UGT2A enzyme active against PAH proximate carcinogens (including PAH diols), both UGTs 2A1 and 2A2 play an important role in the local detoxification of procarcinogenic monohydroxylated PAH metabolites. 23307548 Ambulatory blood pressure monitoring: recent evidence and clinical pharmacy applications. Conventional office blood pressure readings are a well-established surrogate for the prediction of cardiovascular risk. It is assumed that these readings reflect an underlying average level of blood pressure exposure occurring in an individual over a period of time. But because blood pressure is not static, important additional prognostic information about the diurnal blood pressure profile, including within-day and between-day variability, is not easily ascertained from conventional measurements. Ambulatory blood pressure monitoring provides a more thorough depiction of the underlying blood pressure level and predicts cardiovascular risk more robustly than do conventional blood pressure measurements. Although the technology has been available for more than 30 years, there has been an expansion of the research base in the past decade supporting its role in the evaluation and management of patients with hypertension and as an important surrogate in research trials. This review summarizes recent evidence supporting the predictive ability of ambulatory blood pressure monitoring and briefly highlights opportunities for clinical pharmacists to adopt this important clinical and research tool. 22294443 Detection of polycyclic aromatic hydrocarbons in different types of processed foods. Polycyclic aromatic hydrocarbons (PCAHs), particularly those with a high molecular weight, have been classified as probable carcinogens to humans. The aim of the present study is to determine the levels of PCAHs in samples of meat, fish, chicken, fried potato, and toasted bread, which will be thermally processed using conventional and microwave ovens. Different samples will be collected and analyzed for five PCAHs including pyrene, benzo(a)anthracene, benzo(e)pyrene, benzoflouroanthene, and benzo(a)pyrene. The analytical method involves saponification with methanolic potassium hydroxide, extraction with cyclohexane, and determination by high-performance liquid chromatography. The obtained results showed that there is a variation in the detected PCAHs in different foodstuffs. Fried potato processed by conventional oven or microwave oven showed none of the selected studied PCAHs. It was found that, chicken showed higher content levels of total PCAHs than the meat and fish. Data are the highest mean concentrations of fluoranthene and benzo(a)pyrene but within low limit. The obtained results were compared with international permissible levels to avoid pollution, which may cause hazardous effects on individual and society. 22972222 Factors associated with the glucose-lowering effect of vildagliptin identified from the results of the oral glucose tolerance test in Japanese patients with type 2 diabetes. In order to investigate the factors contributing to the glucose-lowering effect of vildagliptin, we analyzed the results of the oral glucose tolerance test together with several clinical parameters in Japanese patients with type 2 diabetes before and after 24 weeks of treatment with vildagliptin. The data of the 13 patients who satisfactorily completed the follow-up examinations were included. After 24 weeks treatment with vildagliptin, the patients were classified into a responder group (69.2%) and a non-responder group (30.8%); the responders consisting of subjects whose HbA1c decreased following 24 weeks treatment with vildagliptin, and the non-responders consisting of subjects who did not show any significant decrease of HbA1c. There were no differences in baseline characteristics between the two groups before administration of vildagliptin. After 24 weeks of treatment, HbA1c was significantly reduced from 7.3 ± 0.5% to 6.7 ± 0.5% in the responder group (P = 0.0077), while it tended to rather increased from 7.1 ± 0.6% to 7.5 ± 0.7% in the non-responder group (P = 0.0679). Also, parameters reflecting the glucose-stimulated insulin secretion, such as the insulinogenic index and oral disposition index, were significantly higher in the responder group than in the non-responder group, whereas insulin sensitivity was similar between the two groups. These results suggest that the difference in the degree of improvement of the glucose tolerance between the responder group and non-responder group in this study could be associated with the effect of vildagliptin on the glucose-stimulated insulin secretion, but not on the insulin sensitivity. 22687520 Non-invasive brain stimulation in neurological diseases. Non-invasive brain stimulation has shown its potential to modulate brain plasticity in humans. Endeavour has been made to utilize brain stimulation in neurological diseases to enhance adaptive processes and prevent potential maladaptive ones. In stroke for instance both sensorimotor and higher cognitive impairment, such as aphasia and neglect, has been addressed to facilitate functional recovery. In Parkinson's disease, brain stimulation has been evaluated to improve motor and non-motor symptoms. In the present review we provide an update of the field of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) as non-invasive brain stimulation techniques to improve motor and higher cognitive functions in patients suffering from stroke and Parkinson's disease. Rather than attempting to be comprehensive in regard of the reviewed scientific field, this article may be considered as a present day's framework of the application of non-invasive brain stimulation on selected examples of common neurological diseases. At the end we will briefly discuss open controversies and future directions of the field which has to be addressed in upcoming studies. This article is part of a Special Issue entitled 'Cognitive Enhancers'. 23042728 Exposure to valproic acid inhibits chondrogenesis and osteogenesis in mid-organogenesis mouse limbs. In utero exposure to valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, causes neural tube, heart, and limb defects. Valpromide (VPD), the amide derivative of VPA, does not inhibit HDAC activity and is a weak teratogen in vivo. The detailed mechanism of action of VPA as a teratogen is not known. The goal of this study was to test the hypothesis that VPA disrupts regulation of the expression of genes that are critical in chondrogenesis and osteogenesis during limb development. Murine gestation day-12 embryonic forelimbs were excised and exposed to VPA or VPD in a limb bud culture system. VPA caused a significant concentration- dependent increase in limb abnormalities, which was correlated with its HDAC inhibitory effect. The signaling of both Sox9 and Runx2, key regulators of chondrogenesis, was downregulated by VPA. In contrast, VPD had little effect on limb morphology and no significant effect on HDAC activity or the expression of marker genes. Thus, VPA exposure dysregulated the expression of target genes directly involved in chondrogenesis and osteogenesis in the developing limb. Disturbances in these signaling pathways are likely to be a consequence of HDAC inhibition because VPD did not affect their expressions. 23578627 A study of the precursors of the natural antioxidant phenol 3,4-dihydroxyphenylglycol in olive oil waste. 3,4-Dihydroxyphenylglycol (DHPG) is a potent antioxidant recently found in the free form in olive oil and table olives. DHPG can be recovered from olive oil solid waste by a hydrothermal treatment. It was observed that an increase in the concentration of DHPG occurred when alperujo aqueous extracts were subjected to mild thermal conditions (post-treatment). This fact indicates that certain solubilized compounds or precursors containing DHPG which is released with the post-treatment. In the present study, the precursors of DHPG were identified and characterized after extraction from alperujo using thermal treatment and purification by fractionation on Amberlite® XAD16 polyamide and semi-preparative reverse-phase HPLC columns. Their structures were elucidated using HPLC coupled to diode array detector (DAD) and electrospray ionization mass spectrometry (ESI-MS). The results identified three compounds as precursors, and their structures can be attributed to the diastereoisomeric forms of the two β-hydroxy derivatives of verbascoside and isoverbascoside (β-hydroxyacteoside and β-hydroxyisoacteoside), and 2″-hydroxyoleuropein, all of which contain a DHPG moiety, potentially explaining the increases in the concentration of this phenolic compound in olive oil waste. 23420471 TiO2 nanowire electron transport pathways inside organic photovoltaics. Charge transport is one of the five main steps in the operation of organic photovoltaics, but achieving balanced hole and electron transport with high mobility has been challenging in devices. Here, we report improved charge transport in organic photovoltaics via incorporation of nanostructured inorganic electron transport materials into the active layers of devices. Co-depositing TiO2 nanowires with the organic active layer solution embeds the nanowires directly within active layers of the solar cell. The ability of these nanowires to transport electrons is compared with neat P3HT:PCBM active layers and also devices containing TiO2 nanotube aggregates. Incorporation of TiO2 nanowires yields a six-fold increase in the electron mobility relative to unmodified devices, leading to a 19% improvement in the power conversion efficiency. Lower energetic disorder of the film and more balanced charge transport are also observed upon incorporating TiO2 nanowires. These advantageous effects correlate with the TiO2 nanowire length. 23416847 A review of mouse critical size defect models in weight bearing bones. Current and future advances in orthopedic treatment are aimed at altering biological interactions to enhance bone healing. Currently, several clinical scenarios exist for which there is no definitive treatment, specifically segmental bone loss from high-energy trauma or surgical resection - and it is here that many are aiming to find effective solutions. To test experimental interventions and better understand bone healing, researchers employ critical size defect (CSD) models in animal studies. Here, an overview of CSDs is given that includes the specifications of varying models, a discussion of current scaffold and bone graft designs, and current outcome measures used to determine the extent of bone healing. Many promising graft designs have been discovered along with promising adjunctive treatments, yet a graft that offers biomechanical support while allowing for neovascularization with eventual complete resorption and remodeling remains to be developed. An overview of this important topic is needed to highlight current advances and provide a clear understanding of the ultimate goal in CSD research - develop a graft for clinical use that effectively treats the orthopedic conundrum of segmental bone loss. 23350972 Laboratory adapted Escherichia coli K-12 becomes a pathogen of Caenorhabditis elegans upon restoration of O antigen biosynthesis. Escherichia coli has been the leading model organism for many decades. It is a fundamental player in modern biology, facilitating the molecular biology revolution of the last century. The acceptance of E. coli as model organism is predicated primarily on the study of one E. coli lineage; E. coli K-12. However, the antecedents of today's laboratory strains have undergone extensive mutagenesis to create genetically tractable offspring but which resulted in loss of several genetic traits such as O antigen expression. Here we have repaired the wbbL locus, restoring the ability of E. coli K-12 strain MG1655 to express the O antigen. We demonstrate that O antigen production results in drastic alterations of many phenotypes and the density of the O antigen is critical for the observed phenotypes. Importantly, O antigen production enables laboratory strains of E. coli to enter the gut of the Caenorhabditis elegans worm and to kill C. elegans at rates similar to pathogenic bacterial species. We demonstrate C. elegans killing is a feature of other commensal E. coli. We show killing is associated with bacterial resistance to mechanical shear and persistence in the C. elegans gut. These results suggest C. elegans is not an effective model of human-pathogenic E. coli infectious disease. 23128829 Induction of nuclear anomalies in exfoliated buccal cells of coca chewers: results of a field study. The leaves of coca (Erythroxylum coca var. coca), a South American shrub which contains cocaine, other alkaloids and phenolics are widely used by indigenous populations of the Andes. It is currently not known if coca consumption causes genotoxic effects in humans. This information is important to predict potential long-term toxic effects such as cancer induction. Therefore, the buccal cytome assay was used to analyze oral cells from 45 uni- and bilateral chewers and 23 controls living in the Altiplano of the Peruvian Andes. In total, 123,471 cells were evaluated from chewers and 57,916 from controls. Information concerning the consumption levels and habits and also use of lime were collected with questionnaires. Chewing of the leaves did not induce nuclear anomalies reflecting genetic damage such as micronuclei (MNi) and nuclear buds; in the highest exposure group (but not in the overall group) even a significant decrease in the frequencies of cells with MNi (by 64 %) was observed. However, we found significantly elevated levels of other nuclear anomalies (karyorrhexis and karyolysis) which reflect cytotoxic effects in the coca users. The frequencies of these anomalies increased with the daily consumption and when lime was used to improve the release of the alkaloids. In contrast to other chewing habits (betel, tobacco and khat), consumption of coca leaves does not induce genetic instability in cells from the oral cavity and our findings indicate that no adverse health effects take place in chewers which are associated with DNA damage. However, the significant increase in certain anomalies shows that acute toxic effects are caused by coca consumption. 22301816 Effect of Thiovit(R) Jet on the structure of thoracic microtrichia/trichomes in Drosophila melanogaster. Widely used fungicides and pesticides are known to have profound effect on several nontarget organisms, which is a cause of concern. The present study aims to demonstrate the effect of a fungicide, Thiovit(®) Jet on the structure of epidermal microtrichia (trichome) of the dorsal thorax in Drosophila melanogaster. External morphology and structural variations of thoracic appendages have been extensively studied using scanning electron microscope from flies treated with different concentrations of Thiovit Jet (20, 30, 40 or 200 μg/ml). Similar to the effect of other fungicides like captan and captafol which are reported to produce somatic mutations in the same organism, the present study successfully demonstrates variation in the trichome/microtrichia structure of the dorsal thorax of D. melanogaster. Structural variations were observed to be associated with different concentrations of Thiovit Jet (30, 40 and 200 μg/ml), but the maximum notable change was found with 40 μg/ml treatment. The gross abnormality in the trichome structure may be due to mutation in proteins associated with normal cuticular deposition. 23374872 Potent and selective tariquidar bioisosters as potential PET radiotracers for imaging P-gp. Compounds 8a-d have been designed as bioisosters of tariquidar for imaging P-gp expression and density by PET. The results displayed that compounds 8b and 8d could be considered potential P-gp/BCRP ligands suitable as (11)C and (18)F radiotracers, respectively. 23645248 Oestrogen action on thyroid progenitor cells: relevant for the pathogenesis of thyroid nodules? Benign and malignant thyroid nodules are more prevalent in females than in men. Experimental data suggest that the proliferative effect of oestrogen rather than polymorphisms is responsible for this gender difference. This study analysed whether both differentiated thyroid cells and thyroid stem and progenitor cells are a target of oestrogen action. In thyroid stem/progenitor cells derived from nodular goitres the ability of 17beta-oestradiol to induce thyrosphere formation, the expression of oestrogen receptors and the effect of 17beta-oestradiol on growth, expression of marker of stem cells and thyroid differentiation (TSH receptor, thyroperoxidase, thyroglobulin, sodium iodide symporter expression) were analysed. 17beta-oestradiol induced thyrosphere formation, albeit to lower extent than other growth factors. Thyroid stem and progenitor cells expressed oestrogen receptor alpha and beta with an 8 time higher expression level of oestrogen receptor alpha mRNA compared to differentiated thyrocytes. 17beta-oestradiol was a potent stimulator of thyroid stem/ progenitor cell growth. In contrast, TSH-induced differentiation of progenitor cells, in particular the expression of the sodium iodide symporter, was significantly inhibited by 17beta-oestradiol.In conclusion, oestrogen stimulated growth and simultaneously inhibited differentiation of thyroid nodules derived stem/progenitor cells. From these data and based on the concept of cellular heterogeneity, we hypothesize a supportive role of oestrogen in the propagation of thyroid stem/progenitor cells leading to a selection of a progeny of growth-prone cells with a decreased differentiation. These cells may be the origin of hypo- or non-functioning thyroid nodules in females. 23375260 Structural basis for autoinhibition of the guanine nucleotide exchange factor FARP2. FARP2 is a Dbl-family guanine nucleotide exchange factor (GEF) that contains a 4.1, ezrin, radixin and moesin (FERM) domain, a Dbl-homology (DH) domain and two pleckstrin homology (PH) domains. FARP2 activates Rac1 or Cdc42 in response to upstream signals, thereby regulating processes such as neuronal axon guidance and bone homeostasis. How the GEF activity of FARP2 is regulated remained poorly understood. We have determined the crystal structures of the catalytic DH domain and the DH-PH-PH domains of FARP2. The structures reveal an auto-inhibited conformation in which the GEF substrate-binding site is blocked collectively by the last helix in the DH domain and the two PH domains. This conformation is stabilized by multiple interactions among the domains and two well-structured inter-domain linkers. Our cell-based activity assays confirm the suppression of the FARP2 GEF activity by these auto-inhibitory elements. 23489976 Light at Night Alters Daily Patterns of Cortisol and Clock Proteins in Female Siberian Hamsters. Humans and other organisms have adapted to a 24-h solar cycle in response to life on Earth. The rotation of the planet on its axis and its revolution around the sun cause predictable daily and seasonal patterns in day length. In order to successfully anticipate and adapt to these patterns in the environment, a variety of biological processes oscillate with a daily rhythm approximately 24 h in length. These rhythms arise from hierarchally-coupled cellular clocks generated by positive and negative transcription factors of core circadian clock gene expression. From these endogenous cellular clocks, overt rhythms in activity and patterns in hormone secretion and other homeostatic processes emerge. These circadian rhythms in physiology and behavior can be organized by a variety of cues, but they are most potently entrained by light. In recent history, there has been a major change from naturally occurring light cycles set by the sun, to artificial and sometimes erratic light cycles determined by the use of electric lighting. Virtually every individual living in an industrialized country experiences light at night (LAN), but despite its prevalence, the biological effects of such unnatural lighting have not been fully considered. Using female Siberian hamsters (Phodopus sungorus), we investigated the effects of chronic nightly exposure to dim light on daily rhythms in locomotor activity, serum cortisol concentrations, and brain expression of circadian clock proteins (i.e., PER1, PER2, BMAL1). Although locomotor activity remained entrained to the light cycle, the diurnal fluctuation of cortisol concentrations was blunted and the expression patterns of clock proteins in the SCN and hippocampus were altered. These results demonstrate that chronic exposure to dim LAN can dramatically affect fundamental cellular function and emergent physiology. © 2013 British Society for Neuroendocrinology. 22424088 Comparative chemical composition and in vitro antioxidant activities of essential oil isolated from the leaves of Cinnamomum tamala and Pimenta dioica. Cinnamomum tamala Nees and Eberm (tejpat) and Pimenta dioica (L.) Merr (pimento) leaves are commonly used for flavouring food and widely used in pharmaceutical preparations because of their hypoglycemic, carminative and stimulant properties. In this study, we compared the chemical composition and antioxidant activities of tejpat and pimento essential oils by employing various in vitro methods. GC and GC-MS analyses were done to find out the chemical composition, and the main constituent identified in tejpat and pimento leaf oils was eugenol. Both the oils showed significant radical scavenging activity against DPPH and superoxide radicals with a potent metal chelating activity and were compared with that of standard compound, eugenol. Among the two oils, tejpat oil showed better activity in terms of antioxidative potential. 23360361 Vesicles composed of fatty acid and N-[3-(dimethylamino)propyl]-octadecanamide: effect of fatty acid chain length on physicochemical properties of vesicles. Abstract Background and objectives: Vesicles, recently claimed as drug delivery carriers, were prepared by taking advantage of an electrostatic interaction between the carboxylic groups of fatty acids (FAs) and the amino groups of N-[3-(Dimethylamino)propyl]-Octadecanamide (DMAPODA). The study is to find out the effect of FAs' chain length on physicochemical properties of vesicles. Methods: Decanoic acid (DA), myristic acid (MA), stearic acid (SA) and behenic acid (BA) were used as FAs. Vesicles composed of them and DMAPODA were studied about formation on microscope, calorimetric analysis, size and zeta potential. Results: On microphotographs, all of FAs could form vesicles when mixed with DMAPODA in an equi-molar ratio. However, DA/DMAPODA vesicles were disintegrated during the homogenization. Due to the asymmetry of DA/DMAPODA associate, it seems to hardly form a stable and well-packed bilayer. On thermograms, the vesicles exhibited one strong peak, indicating that FAs can be homogeneously mixed with the cationic amphiphile. The sizes of the four kinds of vesicles suspended in an aqueous solution (final pH 7.5) were in the same order (hundreds of nanometer) on microphotographs. But, on a light scattering machine, the mean size of MA/DMAPODA vesicle was measured to be much greater than those of the other vesicles, possibly because of the low absolute value of the zeta potential. In addition, the medium pH value had a significant effect on the size of BA/DMAPODA vesicle possibly because the zeta potential was strongly dependent on the pH value. Conclusion: FAs' chain length would affect the physicochemical properties of vesicles composed of them and DMAPODA. 23616376 Flexible Low-Voltage Organic Transistors with High Thermal Stability at 250 °C. Low-operating-voltage flexible organic thin-film transistors with high thermal stability using DPh-DNTT and SAM gate dielectrics are reported. The mobility of the transistors are decreased by 23% after heating to 250 °C for 30 min. Furthermore, flexible organic pseudo-CMOS inverter circuits, which are functional after heating to 200 °C. 23458575 Targeting mitochondria for cardiac protection. The critical role of mitochondria in cardiomyocyte survival and death has become an exciting field of research in cardiac biology. Indeed, it is accepted that mitochondrial dysfunction plays a crucial role in the pathogenesis of multiple cardiac diseases. Besides the obvious relevance of mitochondria in energy production, calcium homeostasis, and reactive oxygen species (ROS) production, new processes like mitochondrial fusion/fission, phosphorylation and nitrosylation modifications in mitochondrial proteins have been suggested to form part of a cast of key players in cardiac disease. This review describes currently studied drugs and compounds that target mitochondria in the scenario of cardiovascular diseases. 23092136 A metabolomic study reveals novel plasma lyso-Gb3 analogs as Fabry disease biomarkers. Fabry disease is an X-linked, multisystemic lysosomal storage disorder due to alpha-galactosidase A deficiency. It is characterized by the accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb(3)), in biological fluids, vascular endothelium, heart, and kidneys. Treatment by enzyme replacement therapy has been shown to be beneficial in both males and females affected with the disease. In addition to Gb(3), increased concentrations of globotriaosylsphingosine (lyso-Gb(3)) have recently been reported in urine and plasma of Fabry patients. The overall objective of this metabolomic study was to identify and characterize new potential plasma biomarkers in treated and untreated males and females affected with Fabry disease which might better reflect disease severity and progression. We employed a time-of-flight mass spectrometry metabolomic approach using plasma samples of Fabry patients compared to age-matched controls. We found three new lyso-Gb(3) analogs in Fabry patients presenting m/z ratios at 802, 804, and 820. As previously detected by our group, we also found a m/z ratio of 784 corresponding to the lyso-Gb(3) molecule minus two hydrogen atoms. Using exact mass measurements and tandem mass spectrometry, we confirmed that these analogs result from modifications of the lyso-Gb(3) sphingosine moiety. We evaluated the relative plasma concentration by measuring area counts for each lyso-Gb(3) analog. None of these analogs was detected in the majority of healthy controls. The relative concentration of each analog was higher in males compared to female Fabry patients. We demonstrated that mass spectrometry combined to a metabolomic approach is a powerful tool to detect and identify new potential biomarkers. 23099645 Association of NDRG1 Gene Promoter Methylation with Reduced NDRG1 Expression in Gastric Cancer Cells and Tissue Specimens. NDRG1 (N-myc downstream-regulated gene 1) plays a role in cell differentiation and suppression of tumor metastasis. This study aims to determine the expression of NDRG1 mRNA and protein in gastric cancer cell lines and tissue specimens and then assess the possible cause of its aberrant expression. Six gastric cancer cell lines and 20 pairs of normal and gastric cancer tissue samples were used to assess NDRG1 expression using Real-time PCR and Western blot. High-resolution melting analysis (HRM) and methylation-specific PCR (MSP) were performed to detect gene mutation and methylation, respectively, in cell lines and tissues samples. Expression of NDRG1 mRNA and protein was downregulated in gastric cancer cell lines and tissues. Specifically, expression of NDRG1 mRNA and protein was lower in all six gastric cancer cell lines than that of normal gastric cells, while 15 out of 20 cases of gastric cancer tissues had the reduced levels of NDRG1 mRNA and protein. HRM data showed that there was no mutation in NDRG1 gene, but MSP data showed high levels of NDRG1 gene promoter methylation in the CpG islands in both cell lines and tissue samples. Moreover, treatment with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine upregulated NDRG1 expression in gastric cancer HGC27 cells, but not in the histone deacetylase inhibitor trichostatin A-treated HGC27 cells. In conclusion, this study has shown that expression of NDRG1 mRNA and protein was reduced in gastric cancer cell lines and tissues, which is due to methylation of NDRG1 gene promoter. Further study will unearth the clinical significance of the reduced NDRG1 protein in gastric cancer. 23418006 Versatile Nanostructured Materials via Direct Reaction of Functionalized Catechols. A facile one-step polymerization strategy is explored to achieve novel catechol-based materials. Depending on the functionality of the catechol, the as-prepared product can be used to modify at will the surface tension of nano and bulk structures, from oleo-/hydrophobic to highly hydrophilic. A hydrophobic catechol prepared thus polymerized shows the ability to self-assemble as solid nanoparticles with sticky properties in polar solvent media. Such a versatile concept is ideal for the development of catechol-based multifunctional materials. 23484974 Preferential adsorption and activity of monocomponent cellulases on lignocellulose thin films with varying lignin content. Understanding the enzymatic hydrolysis of cellulose and the influence of lignin in the process are critical for viable production of fuels and chemicals from lignocellulosic biomass. The interactions of monocomponent cellulases with cellulose and lignin substrates were investigated by using thin films supported on quartz crystal microgravimetry (QCM) resonators. Trichoderma reesei exoglucanase (CBH-I) and endoglucanase (EG-I) bound strongly to both cellulose and lignin but EG-I exhibited a distinctive higher affinity with lignin, causing a more extensive inhibition of the cellulolytic reactions. CBH-I was found to penetrate into the bulk of the cellulose substrate increasing the extent of hydrolysis and film deconstruction. In the absence of a cellulose binding domain (CBD) and a linker, the CBH-I core adsorbed slowly and was not able to penetrate into the film. Conversely to CBH-I, EG-I exhibited activity only on the surface of the lignocellulose substrate even when containing a CBD and a linker. Interestingly, EG-I displayed a clearly different interaction profile as a function of contact time registered by QCM. 23375049 Activity cliffs: facts or artifacts? The fact that similar compounds may have very different properties has a large impact in several areas of chemistry. In drug discovery, almost every medicinal chemist working on lead optimization has faced unexpected large 'jumps' in activity due to small changes in structure, that is, activity cliffs. A number of computational approaches have been developed to detect and quantify activity cliffs and help to understand, and eventually predict, structure-activity relationships (SAR) in compound data sets. Although activity cliffs do exist, the identification and quantification of cliffs have to proceed with caution because one may identify 'false positive cliffs'. In addition to apparent cliffs due to inaccurate determinations of activity, computationally identified cliffs can be artifacts attributed to the molecular representation and quantitative definition of 'high' structural similarity. This paper brings together and discusses, in a brief and integrated manner, some of the major aspects that raise the question whether all the activity cliffs detected in compound data sets are facts or artifacts. 22830982 Evaluation of seven drug metabolisms and clearances by cryopreserved human primary hepatocytes cultivated in microfluidic biochips. We present characterization of the metabolic performance of human cryopreserved hepatocytes cultivated in a platform of parallelized microfluidic biochips. The RTqPCR analysis revealed that the mRNA levels of the cytochromes P450 (CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4) were reduced after the adhesion period (when compared to the post-thawing step). The microfluidic perfusion played a part in stabilizing and partially recovering the levels of the HNF4α, PXR, OAPT2, CYP 1A2, 2B6, 2C19 and 3A4 mRNA on contrary to non-perfused cultures. Fluorescein diacetate staining and P-gp mRNA level illustrated the hepatocytes' polarity in the biochips. Drug metabolism was assessed using midazolam, tolbutamide, caffeine, omeprazole, dextromethorphan, acetaminophen and repaglinide as probes. Metabolite detection and quantification revealed that CYP1A2 (via the detection of paraxanthine), CYP3A4 (via 1-OH-midazolam, and omeprazole sulfone detection), CYP2C8 (via hydroxyl-repaglinide detection), CYP2C19 (via hydroxy-omeprazole detection) and CYP2D6 (via dextrorphan detection) were functional in our microfluidic configurations. Furthermore, the RTqPCR analysis showed that the drugs acted as inductors leading to overexpression of mRNA levels when compared to post-thawing values (such as for HNF4α, PXR and CYP3A4 by dextromethorpahn and omeprazole). Finally, intrinsic in vitro biochip clearances were extracted using a PBPK model for predictions. The biochip predictions were compared to literature in vitro data and in vivo situations. 23337397 Inhibition of leukemic U937 cell growth by induction of apoptosis, cell cycle arrest and suppression of VEGF, MMP-2 and MMP-9 activities by cytotoxin protein NN-32 purified from Indian spectacled cobra (Naja naja) venom. A cytotoxin NN-32 (6.7 kDa) from Indian cobra (Naja naja) venom inhibited human leukemic U937 cell growth as observed by Trypan blue dye exclusion method and cytotoxicity was confirmed by MTT assay. NN-32 induced apoptosis of U937 cell and cell cycle arrest of sub-G1 phase were revealed by FACS analysis. Increased Bax/Bcl-2 ratio, increased caspase 3 and 9 activities, cleaved PARP, decreased VEGF, MMP-2 and MMP-9 activities were observed after NN-32 treatment of U937 cell. Antileukemic activity of NN-32 on U937 cell may be due to activation of apoptosis, arresting cell cycle and antiangiogenesis activities. 23042953 Hydrophobic amino acids in the hinge region of the 5A apolipoprotein mimetic peptide are essential for promoting cholesterol efflux by the ABCA1 transporter. The bihelical apolipoprotein mimetic peptide 5A effluxes cholesterol from cells and reduces inflammation and atherosclerosis in animal models. We investigated how hydrophobic residues in the hinge region between the two helices are important in the structure and function of this peptide. By simulated annealing analysis and molecular dynamics modeling, two hydrophobic amino acids, F-18 and W-21, in the hinge region were predicted to be relatively surface-exposed and to interact with the aqueous solvent. Using a series of 5A peptide analogs in which F-18 or W-21 was changed to either F, W, A, or E, only peptides with hydrophobic amino acids in these two positions were able to readily bind and solubilize phospholipid vesicles. Compared with active peptides containing F or W, peptides containing E in either of these two positions were more than 10-fold less effective in effluxing cholesterol by the ABCA1 transporter. Intravenous injection of 5A in C57BL/6 mice increased plasma-free cholesterol (5A: 89.9 ± 13.6 mg/dl; control: 38.7 ± 4.3 mg/dl (mean ± S.D.); P < 0.05) and triglycerides (5A: 887.0 ± 172.0 mg/dl; control: 108.9 ± 9.9 mg/dl; P < 0.05), whereas the EE peptide containing E in both positions had no effect. Finally, 5A increased cholesterol efflux approximately 2.5-fold in vivo from radiolabeled macrophages, whereas the EE peptide was inactive. These results provide a rationale for future design of therapeutic apolipoprotein mimetic peptides and provide new insights into the interaction of hydrophobic residues on apolipoproteins with phospholipids in the lipid microdomain created by the ABCA1 transporter during the cholesterol efflux process. 23347547 Quercetin-loaded microcapsules ameliorate experimental colitis in mice by anti-inflammatory and antioxidant mechanisms. Quercetin (1) is an anti-inflammatory and antioxidant flavonoid. However, the oral administration of 1 did not lead to beneficial effects in experimental animal colitis models, which involve cytokines and oxidative stress. A possible explanation is that the absorption profile of 1 prevents its activity. Therefore, it was reasoned that the controlled release of 1 would improve its therapeutic effect. Thus, the therapeutic effect and mechanisms of 1-loaded microcapsules in acetic acid-induced colitis in mice were evaluated. Microcapsules were prepared using pectin/casein polymer and 1. The oral administration of 1-loaded microcapsules decreased neutrophil recruitment, attenuated histological alterations, and reduced macroscopical damage, edema, and IL-1β and IL-33 production in the colon samples. Microcapsules loaded with 1 also prevented the reduction of anti-inflammatory cytokine IL-10 and the antioxidant capacity of the colon. These preclinical data indicate that pectin/casein polymer microcapsules loaded with 1 improved the anti-inflammatory and antioxidant effects of 1 compared to the nonencapsulated drug. Therefore, quercetin seems to be a promising active molecule in inflammatory bowel disease if provided with adequate controlled release. 23458730 Concentration-dependent inhibitory effects of baicalin on the metabolism of dextromethorphan, a dual probe of CYP2D and CYP3A, in rats. Baicalin has been shown to possess many pharmacological effects, including antiviral, antioxidant, anti-cancer and anti-inflammatory properties. In the current study, we reveal the inhibitory effects of baicalin on the metabolism of dextromethorphan (DXM), a dual probe substrate of CYP2D and CYP3A, in rats. Lineweaver-Burk plots demonstrated that baicalin inhibited the activities of CYP2D and CYP3A in a non-competitive manner in rat liver microsomes (RLMs). Concomitant administration of baicalin (0.90g/kg, i.v.) and DXM (10mg/kg, i.v.) increased the maximum drug concentration (Cmax) (37%) and the area under concentration-time curve (AUC) (42%) and decreased the clearance (CL) (27%) of DXM in a randomised, crossover study in rats (P<0.01). The change in the AUC of DXM was significantly correlated with the Cmax and AUC of baicalin (P<0.05). The inhibitory effects of multiple doses of baicalin (0.90g/kg, i.v., 12days) on the metabolism of DXM were similar to those observed following a single dose in rats. The activity of CYP3A in excised liver samples from rats following multiple baicalin treatment was significantly decreased compared to that of the control group (P<0.05), whereas multiple doses of baicalin had no obvious effect on the activity of CYP2D. Taken together, these data demonstrate that baicalin inhibits the metabolism of DXM in a concentration-dependent manner in rats, possibly through inhibiting hepatic CYP2D and CYP3A activities. 23411272 Oligomeric procyanidins of lotus seedpod inhibits the formation of advanced glycation end-products by scavenging reactive carbonyls. It has been reported that oligomeric procyanidins of lotus seedpod (LSOPC) is effective in the alleviation of Alzheimer's disease and diabetes through its antioxidant and insulin-potentiating activities. This study investigated the anti-glycative activity of LSOPC in a bovine serum albumin (BSA)-glucose model. The level of glycation and conformational alterations were assessed by specific fluorescence, Congo red binding assay and circular dichroism. The results show that LSOPC has a significant anti-glycative activity in vitro and it can also effectively protect the secondary structure of BSA during glycation. LSOPC or catechin (a major constituent unit of LSOPC), were used to react with methylglyoxal. The structures of their carbonyl adducts were tentatively identified using HPLC-MS(2). Their capacity to scavenge methylglyoxal suggested carbonyl scavenging as a major mechanism of antiglycation. Therefore, LSOPC could be helpful to prevent AGEs-associated diseases, and with the potential to be used as functional food ingredients. 23413803 Tumor necrosis factor receptor-associated factor 5 is an essential mediator of ischemic brain infarction. Tumor necrosis factor receptor-associated factor 5 (TRAF5) is an adaptor protein of the tumor necrosis factor (TNF) receptor superfamily and the interleukin-1 receptor/Toll-like receptor superfamily and plays important roles in regulating multiple signaling pathways. This study was conducted to investigate the role of TRAF5 in the context of brain ischemia/reperfusion (I/R) injury. Transient occlusion of the middle cerebral artery was performed on TRAF5 knockout mice (KO), neuron-specific TRAF5 transgene (TG), and the appropriate controls. Compared with the WT mice, the TRAF5 KO mice showed lower infarct volumes and better outcomes in the neurological tests. A low neuronal apoptosis level, an attenuated blood-brain barrier (BBB) disruption and an inhibited inflammatory response were exhibited in TRAF5 KO mice. TRAF5 TG mice exhibited an opposite phenotype. Moreover, the Akt/FoxO1 signaling pathway was enhanced in the ischemic brains of the TRAF5 KO mice. These results provide the first demonstration that TRAF5 is a critical mediator of I/R injury in an experimental stroke model. The Akt /FoxO1 signaling pathway probably plays an important role in the biological function of TRAF5 in this model. 23261667 Long-term incubation of adult Nereis virens (Annelida: Polychaeta) in copper-spiked sediment: the effects on adult mortality, gametogenesis, spawning and embryo development. Late gametogenic Nereis virens were incubated for up to 2.5 months in environmentally relevant concentrations of copper-spiked sediment. Sequential extraction confirmed that much more labile copper (in actual and percentage terms) was present as spiked concentrations increased, although the residual fractions contained similar amounts across concentrations. This is also reflected in the tissue concentration of the worms which increased in line with the sediment concentrations. Adult mortality was not dependent on the exposure time, but higher concentrations usually induced greater mortality for both sexes. Oocytes were significantly smaller at higher concentrations although pairwise comparisons did not show specific differences. Spawning of males occurred a number of days earlier in the higher concentrations. Differences in the number of embryos developing normally after in vitro fertilizations of oocytes fertilized with sperm from exposed males and non-exposed males showed that sperm were more susceptible to toxicity, but oocytes were also affected at the highest concentration. These results show that there are direct and indirect reproductive consequences of parental exposure to copper with implications for recruitment and subsequent colonization of polluted sediments for this ecologically and commercially important species. 23585383 Surface Matters: Enhanced Bactericidal Property of Core-Shell Ag-Fe2 O3 Nanostructures to Their Heteromer Counterparts from One-Pot Synthesis. A facile one-pot synthesis of Ag@Fe2 O3 core-shell and Ag-Fe2 O3 heteromer nanoparticles is developed, and the core-shell nanoparticles have shown superior antibacterial properties compared to their heteromer counterparts and plain Ag nanoparticles. The mechanism for the increased efficiency is proposed to be due to the enhanced Ag ion release from the iron oxide shell-protected pristine Ag surface. 23277230 Fisetin averts oxidative stress in pancreatic tissues of streptozotocin-induced diabetic rats. Persistent hyperglycemia is associated with chronic oxidative stress which contributes to the development and progression of diabetes-associated complications. The sensitivity of pancreatic β-cells to oxidative stress has been attributed to their low content of antioxidants compared with other tissues. Bioactive compounds with potent antidiabetic properties have been shown to ameliorate hyperglycemia mediated oxidative stress. Recently, we have reported that oral administration of fisetin (10 mg/Kg b.w.), a bioflavonoid found to be present in strawberries, persimmon, to STZ-induced experimental diabetic rats significantly improved normoglycemia. The present study was aimed to evaluate the antioxidant potential of fisetin in both in vitro and in vivo. Diabetes was induced by single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Fisetin was administered orally for 30 days. At the end of the study, all animals were killed. Blood samples were collected for the biochemical estimations. The antioxidant status was evaluated. Histological examinations were performed on pancreatic tissues. Fisetin treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), NF-kB p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin. The treatment also improved the antioxidant status in pancreas as well as plasma of diabetic rats indicating the antioxidant potential of fisetin. In addition, the results of DPPH and ABTS assays substantiate the free radical scavenging activity of fisetin. Histological studies of the pancreas also evidenced the tissue protective nature of fisetin. It is concluded that, fisetin possesses antioxidant and anti-inflammatory property and may be considered as an adjunct for the treatment of diabetes. 23588562 The prevalence and incidence of medicinal cannabis on prescription in The Netherlands. BACKGROUND: A growing number of countries are providing pharmaceutical grade cannabis to chronically ill patients. However, little published data is known about the extent of medicinal cannabis use and the characteristics of patients using cannabis on doctor's prescription. This study describes a retrospective database study of The Netherlands. METHODS: Complete dispensing histories were obtained of all patients with at least one medicinal cannabis prescription gathered at pharmacies in The Netherlands in the period 2003-2010. Data revealed prevalence and incidence of use of prescription cannabis as well as characteristics of patients using different cannabis varieties. RESULTS: Five thousand five hundred forty patients were identified. After an initial incidence of about 6/100,000 inhabitants/year in 2003 and 2004, the incidence remained stable at 3/100,000/year in 2005-2010. The prevalence rate ranged from 5 to 8 per 100,000 inhabitants. Virtually all patients used some form of prescription medication in the 6 months preceding start of cannabis use, most particularly psycholeptics (45.5 %), analgesics (44.3 %), anti-ulcer agents (35.9 %) and NSAIDs (30.7 %). We found no significant association between use of medication of common indications for cannabis (pain, HIV/AIDS, cancer, nausea, glaucoma) and variety of cannabis used. CONCLUSIONS: This is the first nationwide study into the extent of prescription of medicinal cannabis. Although the cannabis varieties studied are believed to possess different therapeutic effects based on their different content of tetrahydrocannabinol (THC) and cannabidiol (CBD), no differences in choice of variety was found associated with indication. 23463634 All-graphene core-sheath microfibers for all-solid-state, stretchable fibriform supercapacitors and wearable electronic textiles. Unique all-graphene core-sheath fibers composed of a graphene fiber core with a sheath of 3D graphene network have been developed. Used as flexible electrodes, all-solid-state fiber supercapacitors have been fabricated, which can be managed to highly compressible and stretchable spring supercapacitors and can also be woven into a textile for wearable electronics. 23418880 A new antibacterial denitroaristolochic acid from the tubers of Stephania succifera. A new denitroaristolochic acid, demethylaristofolin C (1), together with six known alkaloids, crebanine N-oxide (2), (-)-sukhodianine-β-N-oxide (3), palmatine (4), corydalmine (5), dehydrocorydalmine (6), and corynoxidine (7), was isolated from the tubers of Stephania succifera. The structure of demethylaristofolin C was elucidated by spectroscopic techniques (UV, IR, 1D, and 2D NMR) and HR-ESI-MS analyses. These compounds exhibited antibacterial activities against Staphylococcus aureus and methicillin-resistant S. aureus strains in different degrees. 23460508 Association of polymorphisms in the leptin and leptin receptor genes with inflammatory mediators in patients with osteoporosis. Bone mass and inflammation are implicated in the pathogenesis of osteoporosis. We hypothesized that leptin and leptin receptor gene might be associated with osteoporosis by activating the inflammatory pathway. Therefore, we analyzed polymorphisms of the leptin (gene symbol, LEP) and leptin receptor (gene symbol, LEPR) genes and determined their associations with proinflammatory cytokine levels in patients with osteoporosis. We assessed polymorphisms in LEP (-2548G > A) and LEPR (Lys109Arg, Gln223Arg, and Lys656Asn) and calculated odds ratios for the genotype and allele distributions between patients and controls. Serum leptin, soluble leptin receptor, interleukin (IL)-1, IL-6, IL-7, and tumor necrosis factor (TNF) levels were measured by enzyme-linked immunosorbent assays (ELISA) and were verified by in vitro lymphocyte proliferation assays and ELISAs. We found a higher frequency of the A allele for LEP at -2548 in patients with osteoporosis compared with the control group. The A allele was associated with differences in serum leptin, soluble leptin receptor, IL-1, IL-6, and TNF levels compared with the wild-type G allele (p < 0.05). The G allele in Lys109Arg and Gln223Arg was associated with increased risk of osteoporosis and with differences in serum leptin, soluble leptin receptor, IL-1, IL-6, and TNF levels compared with the wild-type A allele (p < 0.05). The Lys656Asn genotype was not associated with the risk of osteoporosis. In vitro lymphocyte proliferation assays and ELISAs confirmed these results. Polymorphisms in LEP and LEPR are associated with increased risk of osteoporosis, possibly by increasing the expression of proinflammatory cytokines. 23559276 Kinetics of Apoptosis and Expression of Apoptosis-Related Proteins in Rat CA3 Hippocampus Cells After Experimental Diffuse Brain Injury. The present study examined kinetics of apoptosis and expression of apoptosis-related proteins Bcl-2, Bax, and caspase-3 in the CA3 hippocampus cells after diffuse brain injury (DBI) induced experimentally in rats. Percentage of apoptotic cells and expressions of above proteins were examined by flow cytometry and immunohistochemistry. Substantial neuronal apoptosis was documented in the CA3 hippocampus cells after DBI (22.26 ± 2.97 % at 72 h after DBI vs. 2.92 ± 0.88 % in sham-operated animals). Expression of Bc1-2 decreased, while expression of Bax and caspase-3 increased after DBI, with caspase-3 expression peaking after that of Bax (72 vs. 48 h, respectively). Further, the Bc1-2/Bax expression ratio decreased prior to increase of caspase-3 expression. In conclusion, cell apoptosis and altered expressions of Bcl-2, Bax, and caspase-3 are present in the CA3 region of hippocampus after experimental DBI. Changes in the Bc1-2/Bax expression ratio may facilitate activation of caspase-3 and aggravate neuronal apoptosis after brain injury. 23600914 24(S)-hydroxycholesterol is actively eliminated from neuronal cells by ABCA1. High cholesterol turnover catalyzed by cholesterol 24-hydroxylase is essential for neural functions, especially learning. Because 24(S)-hydroxycholesterol (24-OHC), produced by 24-hydroxylase, induces apoptosis of neuronal cells, it is vital to eliminate it rapidly from cells. Here, using differentiated SH-SY5Y neuron-like cells as a model, we examined whether 24-OHC is actively eliminated via transporters induced by its accumulation. The expression of ABCA1 and ABCG1 was induced by 24-OHC, as well as TO901317 and retinoic acid, which are ligands of the nuclear receptors LXR/RXR. When the expression of ABCA1 and ABCG1 was induced, 24-OHC efflux was stimulated in the presence of high density lipoprotein (HDL), whereas apolipoprotein A-I was not an efficient acceptor. The efflux was suppressed by the addition of siRNA against ABCA1, but not by ABCG1 siRNA. To confirm the role of each transporter, we analyzed HEK293 cells stably expressing human ABCA1 or ABCG1; we clearly observed 24-OHC efflux in the presence of HDL, whereas efflux in the presence of apolipoprotein A-I was marginal. Furthermore, the treatment of primary cerebral neurons with LXR/RXR ligands suppressed the toxicity of 24-OHC. These results suggest that ABCA1 actively eliminates 24-OHC in the presence of HDL as a lipid acceptor and protects neuronal cells. This article is protected by copyright. All rights reserved. 23523991 Effect of naloxone on ischemic acute kidney injury in the mouse. Renal ischemia produces sympathoexcitation, which is responsible for the development of ischemic acute kidney injury. Stimulation of central opioid receptors activates the renal sympathetic nerve. The present study examined the effect of an opioid receptor antagonist naloxone on the ischemia/reperfusion-induced renal dysfunction in mice. Blood urea nitrogen (BUN) and plasma creatinine increased 24 h after the renal ischemia/reperfusion. Intraperitoneal or intracerebroventricular, but not intrathecal, pretreatment with naloxone suppressed the renal ischemia/reperfusion-induced increases in BUN and plasma creatinine. This effect of naloxone was reversed by subcutaneous pretreatment with morphine. Selective MOP receptor antagonist β-funaltrexamine (FNA) also suppressed the renal ischemia/reperfusion-induced increases in BUN and plasma creatinine. Moreover, tyrosine hydroxylase expression in the renal tissue increased 24 h after renal ischemia/reperfusion, which was abolished by intraperitoneal or intracerebroventricular pretreatment with naloxone and FNA. Immunohistochemical experiments revealed a significant increase in the number of the Fos family proteins (c-Fos, FosB, Fra-1, and Fra-2) positive cells in the paraventricular nucleus of hypothalamus and supraoptic nucleus 24 h after the renal ischemia/reperfusion. Intracerebroventricular pretreatment with naloxone attenuated the renal ischemia/reperfusion-induced increase in the number of the Fos family proteins positive cells in these areas. Finally, we observed that i.c.v. pretreatment with antiserum against β-endorphin also suppressed the increased blood urea and plasma creatinine. These results suggest that the blockade of central opioid receptors can attenuate the ischemic acute kidney injury through the inhibition of renal sympathoexcitation. The central opioid receptors may thus be a new target for the treatment of ischemic organ failures. 23546003 Synthesis of 2,3-Bis(halomethyl)quinoxaline Derivatives and Evaluation of Their Antibacterial and Antifungal Activities. Quinoxaline derivatives having bis(fluoromethyl), bis(chloromethyl), or bis(iodomethyl) groups at the 2- and 3-positions, and various electron-donating/withdrawing substituents at the 6- and/or 7-positions, were synthesized. Their antibacterial and antifungal activities were evaluated by means of minimum inhibitory concentration assays. The relationships between the substituents and the antimicrobial activities of the quinoxaline derivatives indicate that the electrophilicity of the halomethyl units plays an important role in generating the antimicrobial activity. 23174457 Mn(2+) modulates the kinetic properties of an archaeal member of the PLL family. Recently we reported on the characterization of an archaeal member of the amidohydrolase superfamily, namely Sulfolobus acidocaldarius lactonase, showing low but significant and extremely thermostable paraoxonase activity. This enzyme, that we have named SacPox, is a member of the new described family of phosphotriesterase-like lactonases (PLLs). In this family the binuclear metal centre, which is involved in the catalytic machinery, has been poorly studied up to now. In this work we describe the expression of the protein in presence of different metals showing Mn(2+) to support the higher activity. The enzyme has been over-expressed, purified and characterized as a Mn(2+)-containing enzyme by inductive plasma coupled mass spectrometry (ICP-MS), showing also surprising kinetic differences in comparison with the cadmium-containing enzyme. The Mn(2+) containing enzyme was about 30-fold more efficient with paraoxon as substrate and more stable than the Cd(2+) counterpart, even though the Mn(2+) affinity for the binuclear metal centre is apparently lower. These results increase our knowledge of the biochemical characteristics of SacPox mainly with regard to the metal-ions modulation of function. 23327534 Characterisation of the essential oil from different aerial parts of Lindera chunii Merr. (Lauraceae). The essential oils from three organs (i.e. flowers, leaves and stems) of wild Lindera chunii Merr. in Dinghu Mountain (China) were obtained by microwave-assisted hydrodistillation. The essential oils were analysed by gas chromatography with flame ionisation detection and gas chromatography with mass spectrometry. The yields of essential oil varied from 0.06% to 0.59% and showed a remarkable variation among the plant organs. A total of 43 compounds accounting for 95.4-96.3% of the total essential oil were identified, and the major compounds were germacrene B (0.7-43.2%), viridiflorene (trace to 14.6%), globulol (6.3-11.6%), α-cadinol (1.7-8.6%) and τ-cadinol (0.5-7.3%). This study shows that the chemical compositions of the essential oils from the different organs of L. chunii are very variable. 22780563 Hydrothermally mixed hydroxyapatite-multiwall carbon nanotubes composite coatings on biomedical alloys by electrophoretic deposition. Hydroxyapatite (HA) coatings have been used to improve biological and mechanical fixation of metallic prosthesis. Because of extraordinary features of carbon nanotubes (CNTs), they have a lot of facilities, such as extremely strong nanoreinforcement materials for composites. HA powders were synthesized and mixed with multiwalled carbon nanotubes (MWCNTs) by a hydrothermal process. Calcium acetate (Ca (CH(3)COO)(2)) and phosphoric acid (H(3)PO(4)) were used as starting materials for synthesizing nano-HA powders. HA-MWCNTs were treated together hydrothermally at 200 °C for 2 h to synthesize nano-HA powders mixed homogeneously with MWCNTs. Cathodic deposits were obtained on Ti-based alloys using suspensions containing nano-HA and MWCNTs dispersed in n-butanol solvent. It was shown that MWCNTs interacted with HA powders during hydrothermal processing, and therefore, they can easily be dispersed within aqueous-based suspensions. It was also shown that hydrothermal surface modification of MWCNTs with functional groups was achievable, which was a significant step toward eliminating nonwetting surface behavior of MWCNTs, resulting in obtaining homogeneous dispersion of them in liquids. 23228696 Metformin-mediated downregulation of p38 mitogen-activated protein kinase-dependent excision repair cross-complementing 1 decreases DNA repair capacity and sensitizes human lung cancer cells to paclitaxel. Metformin, an extensively used and well-tolerated drug for treating individuals with type 2 diabetes, has recently gained significant attention as an anticancer drug. On the other hand, paclitaxel (Taxol) is a new antineoplastic drug that has shown promise in the treatment of non-small cell lung cancer (NSCLC). High expression levels of excision repair cross-complementary 1 (ERCC1) in cancers have been positively associated with the DNA repair capacity and a poor prognosis in NSCLC patients treated with platinum-containing chemotherapy. In this current study, paclitaxel was found to increase phosphorylation of mitogen-activated protein kinase (MAPK) kinase 3/6 (MKK3/6)-p38 MAPK as well as protein and mRNA levels of ERCC1 in H1650 and H1703 cells. Moreover, paclitaxel-induced ERCC1 protein and mRNA levels significantly decreased via the downregulation of p38 activity by either a p38 MAPK inhibitor SB202190 or p38 knockdown with specific small interfering RNA (siRNA). Specific inhibition of ERCC1 with siRNA was found to enhance the paclitaxel-induced cytotoxic effect and growth inhibition. Furthermore, metformin was able to not only decrease the paclitaxel-induced p38 MAPK-mediated ERCC1 expression, but also augment the cytotoxic effect induced by paclitaxel. Finally, expression of constitutive activate MKK6 or HA-p38 MAPK vectors in lung cancer cells was able to abrogate ERCC1 downregulation by metformin and paclitaxel as well as cell viability and DNA repair capacity. Overall, our results suggest that inhibition of the p38 MAPK signaling by metformin coupled with paclitaxel therapy in human NSCLC cells may be a clinically useful combination, which however will require further validation. 23398145 White light from a single-emitter light-emitting electrochemical cell. We report a novel and generic approach for attaining white light from a single-emitter light-emitting electrochemical cell (LEC). With an active-layer comprising a multifluorophoric conjugated copolymer (MCP) and an electrolyte designed to inhibit MCP energy-transfer interactions during LEC operation, we are able to demonstrate LECs that emit broad-band white light with a color rendering index of 82, a correlated-color temperature of 4000 K, and a current conversion efficacy of 3.8 cd/A. It is notable that this single-emitter LEC configuration eliminates color-drift problems stemming from phase separation, which are commonly observed in conventional blended multiemitter devices. Moreover, the key role of the electrolyte in limiting undesired energy-transfer reactions is highlighted by the observation that an electrolyte-free organic light-emitting diode comprising the same MCP emits red light. 23449618 MAP/microtubule affinity-regulating kinases, microtubule dynamics, and spermatogenesis. During spermatogenesis, spermatids derived from meiosis simultaneously undergo extensive morphological transformation, to become highly specialized and metabolically quiescent cells, and transport across the seminiferous epithelium. Spermatids are also transported back-and-forth across the seminiferous epithelium during the epithelial cycle until they line up at the luminal edge of the tubule to prepare for spermiation at stage VIII of the cycle. Spermatid transport thus requires the intricate coordination of the cytoskeletons in Sertoli cells (SCs) as spermatids are nonmotile cells lacking the ultrastructures of lamellipodia and filopodia, as well as the organized components of the cytoskeletons. In the course of preparing this brief review, we were surprised to see that, except for some earlier eminent morphological studies, little is known about the regulation of the microtubule (MT) cytoskeleton and the coordination of MT with the actin-based cytoskeleton to regulate spermatid transport during the epithelia cycle, illustrating that this is a largely neglected area of research in the field. Herein, we summarize recent findings in the field regarding the significance of actin- and tubulin-based cytoskeletons in SCs that support spermatid transport; we also highlight specific areas of research that deserve attention in future studies. 22661401 Bioremoval of heavy metals from industrial effluent by fixed-bed column of red macroalgae. Three different species of nonliving red algal biomass Laurancia obtusa, Geldiella acerosa and Hypnea sp. were used to build three types of fixed-bed column for the removal of toxic heavy metal ions such as Cu(2+), Zn(2+), Mn(2+) and Ni(2+) from industrial effluent. In general, the highest efficiency of metal ion bioremoval was recorded for algal column of L. obtusa followed by G. acerosa and the lowest one was recorded for Hypnea sp., with mean removal values of 94%, 85% and 71%, respectively. The obtained results showed that biological treatments of industrial effluents with these algal columns, using standard algal biotest, Pseudokirchneriella subcapitata, were capable of reducing effluent toxicities from 75% to 15%, respectively. Red algal column may be considered as an inexpensive and efficient alternative treatment for conventional removal technology, for sequestering heavy metal ions from industrial effluents. 23147750 Assessing causation of the extirpation of stream macroinvertebrates by a mixture of ions. Increased ionic concentrations are associated with the impairment of benthic invertebrate assemblages. However, the causal nature of that relationship must be demonstrated so that it can be used to derive a benchmark for conductivity. The available evidence is organized in terms of six characteristics of causation: co-occurrence, preceding causation, interaction, alteration, sufficiency, and time order. The inferential approach is to weight the lines of evidence using a consistent scoring system, weigh the evidence for each causal characteristic, and then assess the body of evidence. Through this assessment, the authors found that a mixture containing the ions Ca(+), Mg(+), HCO 3(-), and SO 4(-), as measured by conductivity, is a common cause of extirpation of aquatic macroinvertebrates in Appalachia where surface coal mining is prevalent. The mixture of ions is implicated as the cause rather than any individual constituent of the mixture. The authors also expect that ionic concentrations sufficient to cause extirpations would occur with a similar salt mixture containing predominately HCO 3(-), SO 4(2-), Ca(2+), and Mg(2+) in other regions with naturally low conductivity. This case demonstrates the utility of the method for determining whether relationships identified in the field are causal. 23160961 Plasma ghrelin is positively associated with body fat, liver fat and milk fat content but not with feed intake of dairy cows after parturition. Ghrelin is a gastrointestinal peptide hormone that is present in blood mostly in a non-posttranslationally modified form, with a minor proportion acylated at Ser(3). Both ghrelin forms were initially assigned a role in the control of food intake but there is accumulating evidence for their involvement in fat allocation and utilization. We investigated changes in the ghrelin system in dairy cows, exhibiting differences in body fat mobilization and fatty liver, from late pregnancy to early lactation. Sixteen dairy cows underwent liver biopsy and were retrospectively grouped based on high (H) or low (L) liver fat content post-partum. Both groups had a comparable feed intake in week -6 (before parturition) and week 2 (after parturition). Only before parturition was preprandial total ghrelin concentration higher in L than in H cows and only after parturition was the basal plasma concentration of non-esterified fatty acids higher in H than in L cows. Both before and after parturition, H cows had higher preprandial plasma concentrations of acyl ghrelin, a higher acyl:total ghrelin ratio, lower plasma triacylglyceride concentrations and a lower respiratory quotient compared with L cows. These group differences could not be attributed to an allelic variant of the acyl ghrelin receptor. Rather, the ratio of acyl:total ghrelin correlated with several aspects of fat metabolism and with respiratory quotient but not with feed intake. These results show that endogenous ghrelin forms are associated with fat allocation, fatty liver, and utilization of fat during the periparturient period. 23194507 Analysis of Anabaena vaginicola and Nostoc calcicola from Northern Iran, as rich sources of major carotenoids. Four major carotenoids of high nutritional significance, including β-carotene, lycopene, lutein and zeaxanthin were determined in three isolates of heterocystous cyanobacteria, belonging to the genera Anabaena and Nostoc, isolated from Iranian terrestrial and aquatic ecosystems, for the first time. The ultrasonically extracted carotenoids were identified and quantified by a rapid and sensitive isocratic HPLC method and identification was further confirmed by spiking authentic standards and the pattern of the UV-Vis spectra obtained from photo-diode array detector. The results showed that these isolates contain large amounts of four major carotenoids, especially lycopene (up to 24,570 μg/g dry weight, DW) which appears to be the highest reported amount until present; and β-carotene (up to 8133 μg/g DW) which is comparable with the best natural sources of β-carotene. Meanwhile, they are rich in the cis-isomers of lycopene and β-carotene which is important in their bioavailability and health benefits. 23248196 Statins and Risk of Diabetes: An analysis of electronic medical records to evaluate possible bias due to differential survival. OBJECTIVE Two meta-analyses of randomized trials of statins found increased risk of type 2 diabetes. One possible explanation is bias due to differential survival when patients who are at higher risk of diabetes survive longer under statin treatment. RESEARCH DESIGN AND METHODS We used electronic medical records from 500 general practices in the U.K. and included data from 285,864 men and women aged 50-84 years from January 2000 to December 2010. We emulated the design and analysis of a hypothetical randomized trial of statins, estimated the observational analog of the intention-to-treat effect, and adjusted for differential survival bias using inverse-probability weighting. RESULTS During 1.2 million person-years of follow-up, there were 13,455 cases of type 2 diabetes and 8,932 deaths. Statin initiation was associated with increased risk of type 2 diabetes. The hazard ratio (95% CI) of diabetes was 1.45 (1.39-1.50) before adjusting for potential confounders and 1.14 (1.10-1.19) after adjustment. Adjusting for differential survival did not change the estimates. Initiating atorvastatin and simvastatin was associated with increased risk of type 2 diabetes. CONCLUSIONS In this sample of the general population, statin therapy was associated with 14% increased risk of type 2 diabetes. Differential survival did not explain this increased risk. 23303786 Space exploration by the promoter of a long human gene during one transcription cycle. An RNA polymerase has been thought to transcribe by seeking out a promoter, initiating and then tracking down the template. We add tumor necrosis factor α to primary human cells, switch on transcription of a 221-kb gene and monitor promoter position during the ensuing transcription cycle (using RNA fluorescence in situ hybridization coupled to super-resolution localization, chromosome conformation capture and Monte Carlo simulations). Results are consistent with a polymerase immobilized in a 'factory' capturing a promoter and reeling in the template, as the transcript and promoter are extruded. Initially, the extruded promoter is tethered close to the factory and so likely to re-initiate; later, the tether becomes long enough to allow re-initiation in another factory. We suggest close tethering underlies enhancer function and transcriptional 'bursting'. 23041661 Salt bridge switching from Arg290/Glu167 to Arg290/ATP promotes the closed-to-open transition of the P2X2 receptor. P2X receptors are trimeric adenosine-5'-triphosphate (ATP)-gated cation channels involved in fast signal transduction in many cell types. In this study, we used homology modeling of the rat P2X2 receptor with the zebrafish P2X4 X-ray template to determine that the side chains of the Glu167 and Arg290 residues are in close spatial vicinity within the ATP-binding pocket when the rat P2X2 channel is closed. Through charge reversal mutation analysis and mutant cycle analysis, we obtained evidence that Glu167 and Arg290 form an electrostatic interaction. In addition, disulfide trapping indicated the close proximity of Glu167 and Arg290 when the channel is in the closed state, but not in the ATP-bound open state. Consistent with a gating-induced movement that disrupts the Glu167/Arg290 salt bridge, a comparison of the closed and open rat P2X2 receptor models revealed a significant rearrangement of the protein backbone and the side chains of the Glu167 and Arg290 residues during the closed-to-open transition. The associated release of the Glu167/Arg290 salt bridge during channel opening allows a strong ionic interaction between Arg290 and a γ-phosphate oxygen of ATP. We conclude from these results that the state-dependent salt bridge switching from Arg290/Glu167 to Arg290/ATP fulfills a dual role: to destabilize the closed state of the receptor and to promote the ionic coordination of ATP in the ATP-binding pocket. 23159529 Nanobody-albumin nanoparticles (NANAPs) for the delivery of a multikinase inhibitor 17864 to EGFR overexpressing tumor cells. A novel, EGFR-targeted nanomedicine has been developed in the current study. Glutaraldehyde crosslinked albumin nanoparticles with a size of approximately 100nm were loaded with the multikinase inhibitor 17864-L(x)-a platinum-bound sunitinib analogue-which couples the drug to methionine residues of albumin and is released in a reductive environment. Albumin nanoparticles were surface-coated with bifunctional polyethylene glycol 3500 (PEG) and a nanobody-the single variable domain of an antibody-(Ega1) against the epidermal growth factor receptor (EGFR). EGa1-PEG functionalized nanoparticles showed a 40-fold higher binding to EGFR-positive 14C squamous head and neck cancer cells in comparison to PEGylated nanoparticles. 17864-L(x) loaded EGa1-PEG nanoparticles were internalized by clathrin-mediated endocytosis and ultimately digested in lysosomes. The intracellular routing of EGa1 targeted nanoparticles leads to a successful release of the kinase inhibitor in the cell and inhibition of proliferation whereas the non-targeted formulations had no antiproliferative effects on 14C cells. The drug loaded targeted nanoparticles were as effective as the free drug in vitro. These results demonstrate that multikinase inhibitor loaded nanoparticles are interesting nanomedicines for the treatment of EGFR-positive cancers. 23234313 Influence of surface groups on poly(propylene imine) dendrimers antiprion activity. Prion diseases are characterized by the accumulation of PrP(Sc), an aberrantly folded isoform of the host protein PrP(C). Specific forms of synthetic molecules known as dendrimers are able to eliminate protease-resistant PrP(Sc) in both an intracellular and in vitro setting. The properties of a dendrimer which govern this ability are unknown. We addressed the issue by comparing the in vitro antiprion ability of numerous modified poly(propylene-imine) dendrimers, which varied in size, structure, charge, and surface group composition. Several of the modified dendrimers, including an anionic glycodendrimer, reduced the level of protease resistant PrP(Sc) in a prion strain-dependent manner. This led to the formulation of a new working model for dendrimer/prion interactions which proposes dendrimers eliminate PrP(Sc) by destabilizing the protein and rendering it susceptible to proteolysis. This ability is not dependent on any particular charge of dendrimer, but does require a high density of reactive surface groups. 23127698 Conjunctival modifications induced by medical and surgical therapies in patients with glaucoma. Lowering intra-ocular pressure, either medically or surgically, is the proven strategy to control glaucoma, though profound changes to the ocular surface and conjunctiva are caused. Toxicity and allergy initiated by medical therapy induce modifications, which progressively worsen with the length of treatment and number of drugs. Conjunctival changes lead to symptoms of ocular surface disease, reduced quality of life, reduced therapeutic compliance and increased risk of surgical failure. Surgery modifies conjunctiva by inducing bleb formation in fistulizing techniques, and by activating secondary aqueous humour outflow pathways, such as trans-scleral routes, in both filtration and bleb-less approaches. The use of unpreserved medications, limitation of intra-operative conjunctival damage and development of bleb-less surgery are advisable. 23196320 Laser synthesis of ligand-free bimetallic nanoparticles for plasmonic applications. A picosecond laser ablation approach has been developed for the synthesis of ligand-free AuAg bimetallic NPs where the relative amount of Ag is controlled in situ through a laser shielding effect. Various measurements, such as optical spectroscopy, transmission electron microscopy combined with energy dispersive X-ray spectroscopy and inductively coupled plasma optical emission spectrometry, revealed the generation of homogenous 15 nm average size bimetallic NPs with different compositions and tunable localized surface plasmon resonance. Furthermore, ligand-free metallic nanoparticles with respect to chemically synthesized nanoparticles display outstanding properties, i.e. featureless Raman background spectrum, which is a basic requirement in many plasmonic applications such as Surface Enhanced Raman Spectroscopy. Various molecules were chemisorbed on the nanoparticle and SERS investigations were carried out, by varying the laser wavelength. The SERS enhancement factor for AuAg bimetallic NPs shows an enhancement factor of about 5.7 × 10(5) with respect to the flat AuAg surface. 23610077 Surface-Passivated SBA-15-Supported Gold Nanoparticles: Highly Improved Catalytic Activity and Selectivity toward Hydrophobic Substrates. Silanol groups on a silica surface affect the activity of immobilized catalysts because they can influence the hydrophilicity/hydrophobicity, matter transfer, or even transition state in a catalytic reaction. Previously, these silanol groups have usually been passivated by using surface-passivation reagents, such as alkoxysilanes, bis-silylamine reagents, chlorosilanes, etc., and surface passivation has typically been found in mesoporous-silicas-supported molecular catalysts and heteroatomic catalysts. However, this property has rarely been reported in mesoporous-silicas-supported metal-nanoparticle catalysts. Herein, we prepared an almost-superhydrophobic SBA-15-supported gold-nanoparticle catalyst by using surface passivation, in which the catalytic activity increased more than 14 times for the reduction of nitrobenzene compared with non-passivated SBA-15. In addition, this catalyst can selectively catalyze hydrophobic molecules under our experimental conditions, owing to its high (almost superhydrophobic) hydrophobic properties. 23223345 The Effects of Carbohydrate, Unsaturated Fat, and Protein Intake on Measures of Insulin Sensitivity: Results from the OmniHeart Trial. OBJECTIVE Impaired insulin sensitivity increases the risk of cardiovascular disease. Although calorie restriction and weight loss increase insulin sensitivity, the effects of modifying macronutrient composition on insulin sensitivity are uncertain. The purpose of this study is to determine the effects on insulin sensitivity of a carbohydrate-rich diet (CARB; similar to the Dietary Approaches to Stop Hypertension [DASH] diet), a protein-rich diet (PROT; protein predominantly from plant sources), and an unsaturated fat-rich diet (UNSAT; predominantly monounsaturated). RESEARCH DESIGN AND METHODS This study was a randomized, controlled, three-period, crossover feeding study. The study participants were 164 individuals with prehypertension or stage 1 hypertension without diabetes. Diets were administered for 6 weeks each, with a washout period between diets of 2-4 weeks. Weight was held constant throughout the study. For our primary outcome, we calculated the quantitative insulin sensitivity check index (QUICKI) using the end-of-period fasting serum glucose and insulin. QUICKI is a validated measure of insulin sensitivity. The primary analyses used generalized estimating equations. RESULTS At baseline, mean (SD) BMI was 30.2 (6.1) kg/m(2), and mean (SD) QUICKI was 0.35 (0.04). The UNSAT diet increased QUICKI by 0.005, more than the CARB diet (P = 0.04). PROT had no significant effect compared with CARB. CONCLUSIONS A diet that partially replaces carbohydrate with unsaturated fat may improve insulin sensitivity in a population at risk for cardiovascular disease. Given the well-recognized challenges of sustaining weight loss, our results suggest an alternative approach for improving insulin sensitivity. 23228028 Controllable electrical properties of metal-doped In2O3 nanowires for high-performance enhancement-mode transistors. In recent years, In(2)O(3) nanowires (NWs) have been widely explored in many technological areas due to their excellent electrical and optical properties; however, most of these devices are based on In(2)O(3) NW field-effect transistors (FETs) operating in the depletion mode, which induces relatively higher power consumption and fancier circuit integration design. Here, n-type enhancement-mode In(2)O(3) NW FETs are successfully fabricated by doping different metal elements (Mg, Al, and Ga) in the NW channels. Importantly, the resulting threshold voltage can be effectively modulated through varying the metal (Mg, Ga, and Al) content in the NWs. A series of scaling effects in the mobility, transconductance, threshold voltage, and source-drain current with respect to the device channel length are also observed. Specifically, a small gate delay time (0.01 ns) and high on-current density (0.9 mA/μm) are obtained at 300 nm channel length. Furthermore, Mg-doped In(2)O(3) NWs are then employed to fabricate NW parallel array FETs with a high saturation current (0.5 mA), on/off ratio (>10(9)), and field-effect mobility (110 cm(2)/V·s), while the subthreshold slope and threshold voltage do not show any significant changes. All of these results indicate the great potency for metal-doped In(2)O(3) NWs used in the low-power, high-performance thin-film transistors. 23588390 Synergistic targeting/prodrug strategies for intravesical drug delivery - Lectin-modified PLGA microparticles enhance cytotoxicity of stearoyl gemcitabine by contact-dependent transfer. The direct access to the urothelial tissue via intravesical therapy has emerged as a promising means for reducing the high recurrence rate of bladder cancer. However, few advanced delivery concepts have so far been evaluated to overcome critical inherent efficacy limitations imposed by short exposure times, low tissue permeability, and extensive washout. This study reports on a novel strategy to enhance gemcitabine treatment impact on urothelial cells by combining a pharmacologically advantageous prodrug approach with the pharmacokinetic benefits of a glycan-targeted carrier system. The conversion of gemcitabine to its 4-(N)-stearoyl derivative (GEM-C18) allowed for stable, homogeneous incorporation into PLGA microparticles (MP) without compromising intracellular drug activation. Fluorescence-labeled GEM-C18-PLGA-MP were surface-functionalized with wheat germ agglutinin (WGA) or human serum albumin (HSA) to assess in direct comparison the impact of biorecognitive interaction on binding rate and anchoring stability. MP adhesion on urothelial cells of non-malignant origin (SV-HUC-1), and low- (5637) or high-grade (HT-1376) carcinoma was correlated to the resultant antiproliferative and antimetabolic effect in BrdU and XTT assays. More extensive and durable binding of the WGA-GEM-C18-PLGA-MP induced a change in the pharmacological profile and substantially higher cytotoxicity, allowing for maximum response within the temporal restrictions of instillative administration (120min). Mechanistically, a direct, contact-dependent transfer of stearoyl derivatives from the particle matrix to the urothelial membrane was found to account for this effect. With versatile options for future application, our results highlight the potential offered by the synergistic implementation of targeting/prodrug strategies in delivery systems tailored to the intravesical route. 23295156 L-Carnitine protects against arterial hypertension-related cardiac fibrosis through modulation of PPAR-γ expression. Cardiac fibrosis is a pathogenic factor in a variety of cardiovascular diseases and is characterized by an abnormal accumulation of extracellular matrix protein that leads to cardiac dysfunction. l-Carnitine (LC) plays an essential role in the β-oxidation of long-chain fatty acids in lipid metabolism. We have previously demonstrated the beneficial effects of LC in hypertensive rats. The aim of this study was to analyze the effect of LC on arterial hypertension-associated cardiac fibrosis and to explore the mechanisms of LC action. To this end, four groups of rats were used: Wistar (control), rats treated with 400mg/kg/day of LC, rats treated with 25mg/kg/day of l-NAME (to induce hypertension), and rats treated with LC+l-NAME simultaneously. We found an elevation in the myocardial expression of profibrotic factors (TGF-β1 and CTGF), types I and III of collagen, and NADPH oxidase subunits (NOX2 and NOX4), in hypertensive rats when compared with normotensive ones. In addition, an increase in myocardial fibrosis was also found in the l-NAME group. These results were accompanied by a down-regulation of PPAR-γ in the heart of hypertensive animals. When hypertensive rats were treated with LC, all these alterations were reversed. Moreover, a significant negative correlation was observed between myocardial interstitial fibrosis and mRNA expression of PPAR-γ. In conclusion, the reduction of cardiac fibrosis and the down-regulation of NOX2, NOX4, TGF-β1 and CTGF induced by LC might be, at least in part, mediated by an upregulation of PPAR-γ, which leads to a reduction on hypertension-related cardiac fibrosis. 23547776 Development of an ALK2-Biased BMP Type I Receptor Kinase Inhibitor. The bone morphogenetic protein (BMP) signaling pathway has essential functions in development, homeostasis, and the normal and pathophysiologic remodeling of tissues. Small molecule inhibitors of the BMP receptor kinase family have been useful for probing physiologic functions of BMP signaling in vitro and in vivo and may have roles in the treatment of BMP-mediated diseases. Here we describe the development of a selective and potent inhibitor of the BMP type I receptor kinases, LDN-212854, which in contrast to previously described BMP receptor kinase inhibitors exhibits nearly 4 orders of selectivity for BMP versus the closely related TGF-β and Activin type I receptors. In vitro, LDN-212854 exhibits some selectivity for ALK2 in preference to other BMP type I receptors, ALK1 and ALK3, which may permit the interrogation of ALK2-mediated signaling, transcriptional activity, and function. LDN-212854 potently inhibits heterotopic ossification in an inducible transgenic mutant ALK2 mouse model of fibrodysplasia ossificans progressiva. These findings represent a significant step toward developing selective inhibitors targeting individual members of the highly homologous BMP type I receptor family. Such inhibitors would provide greater resolution as probes of physiologic function and improved selectivity against therapeutic targets. 23561222 Separation and purification of the antioxidant compounds, caffeic acid phenethyl ester and caffeic acid from mushrooms by molecularly imprinted polymer. Caffeic acid phenethyl ester (CAPE) and caffeic acid (CA), two naturally occurring phenolic antioxidants, have been reported to have a diversity of biological activities. In this investigation, a novel approach to separate and enrich CAPE and CA from 25 species of mushrooms using molecularly imprinted polymers (MIPs) as the sorbent material is reported. The MIPs were synthesized using CAPE as the template, and its adsorption behavior was investigated in detail. In comparison with C18-solid phase extraction (SPE), MIP-SPE displayed high selectivity and good affinity for CAPE and CA. The antioxidant potential of the mushroom extracts, before and after preconcentration using MIPs, was assayed by inhibition of erythrocyte hemolysis and lipid peroxidation. Application of MIPs with a high affinity toward CAPE and CA provides a novel method for obtaining active compounds from natural products. 23416262 A cell-based, multiparametric sensor approach characterises drug-induced cytotoxicity in human liver HepG2 cells. Drug-induced toxicity is of considerable concern in drug discovery and development, placing emphasis on the need for predictive in vitro technologies that identify potential cytotoxic side effects of drugs. A label-free, real-time, multiparametric cytosensor system has therefore been established for in vitro assessment of drug-induced toxicity. The system is based on monitoring cellular oxygen consumption, acidification and impedance of human hepatocarcinoma-derived HepG2 cells. The read-out derived from the multiparametric cytosensor system has been optimised and permits sensitive, reliable, and simultaneous recording of cell physiological signals, such as metabolic activity, cellular respiration and morphological changes and cell adhesion upon exposure to a drug. Analysis of eight prototypic reference drugs revealed distinct patterns of drug-induced physiological signals. Effects proved to be rigidly concentration-dependent. Based on signal patterns and reversibility of the observed effects, compounds could be classified based as triggering mechanisms of respiratory or metabolic stress or conditions leading to cell death (necrosis-like and apoptosis-like). A test-flag-risk mitigation strategy is proposed to address potential risks for drug-induced cytotoxicity. 23389991 Impaired Postural Balance in Turner Syndrome. An impaired body balance has been found in Turner syndrome (TS) in clinical tests like Rombergs's test and walking on a balance beam. The aim of the study was to assess postural balance in TS subjects with specific balance testing using dynamic posturography and relate to body composition. Nineteen TS subjects (20-57 years) were included. Balance was measured with dynamic posturography (Equitest) and compared with 19 sex and age-matched controls (22-59 years). Equitest, visual, vestibular, and somatosensory systems were provoked with increasing difficulty (6 tests, SO1-SO6) and body sway was measured with a dual forceplate. Body composition was measured with DXA. No difference was found between the TS subjects and the controls on fixed platform with open eyes (SO1), with closed eyes (SO2), with stable platform and visual disorientation (SO3), or on unstable platform with open eyes (SO4). In the difficult tests on unstable platform the TS subjects did worse compared with controls both in the test with eyes closed (SO5), p<0.01, and in the test with visual disorientation (SO6), p<0.05. Composite (a merge of all six recordings) was significantly lower in the TS-group, p<0.05. In the TS group high total body weight was related to worse outcome on tests SO5, SO6, and composite, while total bone mass, age, height, or waist showed no significant association with balance scores. Our findings indicate that TS could have an increased risk for falling due to impaired ability to manage complex coordination tasks. 23201370 Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L). The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt.) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO. 23264030 Effects of fluoxetine on the swimming and behavioural responses of the Arabian killifish. The selective serotonin reuptake inhibitor fluoxetine has frequently been detected in surface waters around the world. Fluoxetine modulates levels of serotonin, a neurotransmitter that regulates several important physiological and behavioural processes including fear and anxiety, aggression, locomotion and feeding. In this study, groups of sub-adult Arabian killifish (Aphanius dispar) were exposed to either 0, 0.03, 0.3 or 3 μg/L fluoxetine hydrochloride for 7 days and their swimming behaviour and social interactions videotaped in a circular arena. The fish were subsequently exposed to a predator alarm chemical (from dragonfly larvae fed with A. dispar) and their short-term responses recorded. The video was analysed using the open-sourced software program Ctrax which objectively quantified swimming and social behaviours. Aggression (chasing behaviour was significantly reduced at 3.0 μg/L fluoxetine. After the addition of the predator alarm chemicals fish responded quickly, increasing the percentage of time spent drifting or motionless and reducing average swimming velocity. Controls and fish exposed to 0.03 or 3 μg/L fluoxetine reduced swimming speed by 20-30 % but returned to pre-exposure velocities within 6 min. Fish exposed to 0.3 μg/L fluoxetine reduced swimming speed by 38 % after addition of the predator alarm and did not return to pre-exposure speeds during the recording period (19 min). Schooling behaviour was also affected by fluoxetine and predator alarm with fish exposed to 0.3 μg/L fluoxetine significantly reducing nearest neighbour distance and swimming speed relative to nearest neighbour the following addition of the predator alarm. 23528252 Decreased androgen receptor expression may contribute to spermatogenesis failure in rats exposed to low concentration of bisphenol A. To investigate the effects of a low bisphenol A (BPA) concentration on male reproduction, adult rats were administered a concentration of BPA that was less than the no observable adverse effect level (0.0005-5mg/kg/bw) for 8 weeks. General toxicity, reproductive hormones, and spermatogenesis were then determined. The expression of genes related to hormone synthesis and spermatogenesis was also analyzed. These BPA concentrations generated no general toxicity and no significant changes on serum hormones. However, the testicular testosterone, hormone synthesis-related genes StAR and Cyp450scc increased, whereas 3β-HSD, 17β-HSD, and Cyp450arom decreased. Additionally, BPA significantly decreased the epithelial height and round spermatids in seminiferous tubules, sperm count, androgen receptor expression, and the expression of the spermatogenesis-related genes outer dense fiber protein 1 (ODF1) and transition protein 1. Our results indicate that a low BPA concentration can induce spermatogenesis disorders mainly through decreasing androgen receptor expression. The present results may bring attention to the risk of environmental BPA exposure. 23180382 Solvated graphenes: an emerging class of functional soft materials. From a materials science point of view, graphene is essentially a polymer having a giant, two-dimensional molecular configuration. In this Progress Report, solvated graphene and its derivatives are illustrated from the perspective of soft matter. Firstly, the key appealing features of graphene as a molecular building block for assembling bulk soft materials are highlighed. It is then demonstrated how the intersheet interactions in solution are correlated with the molecular structure of graphene, and how a combination of the unique molecular structure and colloidal interactions can lead to simple, solution-phase approaches for assembling graphenes into a variety of macroscopic nanoarchitectures. A number of new exciting functions and applications are also highlighted, which are enabled by the solvation effect and in particular, it is discussed why and how solvated graphenes can offer exciting functions that are unattainable with the dried, hard counterpart. The discussion is concluded with some personal perspectives on the future directions in which this emerging class of functional soft materials could be pursued. 23403904 Comparative study of artificial chromosome centromeres in human and murine cells. Human artificial chromosomes (HAC) are a valuable tool in the analysis of complex chromatin structures such as the human centromere because of their small size and relative simplicity compared with normal human chromosomes. This report includes a comprehensive study of the centromere and chromatin composition of HAC, expressing human genes, generated in human cells and transferred to murine cells. The analysis involved chromatin immuno-precipitation and immuno-FISH on metaphase chromosomes and chromatin fibres. In both the cell types, the HAC consisted of alphoid and non-alphoid DNA and were mainly euchromatic in composition, although a pericentromeric heterochromatic region was present on all the HAC. Fibre-FISH and chromatin immuno-precipitation data indicated that the position of the centromere differed between HAC in human cells and in murine cells. Our work highlights the importance and utilisation of HAC for understanding the epigenetic aspects of chromosome biology.European Journal of Human Genetics advance online publication, 13 February 2013; doi:10.1038/ejhg.2012.296. 23526231 Alkaloids from Lycoris caldwellii and their particular cytotoxicities against the astrocytoma and glioma cell lines. Phytochemical investigation of the ethanol extract of the bulbs of Lycoris caldwellii afforded four new alkaloids, (+)-N-methoxylcarbonyl-nandigerine (1), (+)-N-methoxycarbonyl-lindcarpine (2), (+)-10-O-methylhernovine N-oxide (3), and (+)-3-hydroxy-anhydrolycorine N-oxide (4). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D ((1)H-(1)H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. All the alkaloids were in vitro evaluated for their cytotoxic activities against eight tumor cell lines (BEN-MEN-1, CCF-STTG1, CHG-5, SHG-44, U251, BGC-823, HepG2, and SK-OV-3). Alkaloids 1 and 2 exhibited particular cytotoxic activities against astrocytoma and glioma cell lines with IC50 of 9.2-11.3 μM and 10.4-12.2 μM respectively. 23624029 Diagnosis and management of classical congenital adrenal hyperplasia. Congenital adrenal hyperplasia (CAH) is among the most common genetic disorders. Deficiency of adrenal steroid 21-hydroxylase deficiency due to mutations in the CYP21A2 gene accounts for about 95% cases of CAH. This disorder manifests with androgen excess with or without salt wasting. It also is a potentially life threatening disorder; neonatal screening with 17-hydroxyprogesterone measurement can diagnose the condition in asymptomatic children. Carefully monitored therapy with glucocorticoid and mineralocorticoid supplementation will ensure optimal growth and development for children with CAH. Genital surgery may be required for girls with CAH. Continued care is required for individuals with CAH as adults to prevent long-term adverse consequences of the disease, including infertility, metabolic syndrome and osteoporosis. 23578583 The potential role of T cell migration and chemotaxis as targets of glucocorticoids in multiple sclerosis and experimental autoimmune encephalomyelitis. Glucocorticoids (GCs) are the most commonly prescribed drugs for the treatment of acute disease bouts in multiple sclerosis (MS) patients. While T lymphocytes were shown to be essential targets of GC therapy, at least in animal models of MS, the mechanisms by which GCs modulate T cell function are less clear. Until now, apoptosis induction and repression of pro-inflammatory cytokines in T cells have been considered the most critical mechanisms in ameliorating disease symptoms. However, this notion is being challenged by increasing evidence that the control of T cell migration and chemotaxis by GCs might be even more important for the treatment of neuroinflammatory diseases. In this review we aim to provide an overview of how GCs impact the morphological alterations that T cells undergo during activation and migration as well as the influences that GCs have on the directed movement of T cells under the influence of chemokines. A deeper understanding of these processes should not only help to advance our understanding of how GCs exert their beneficial effects in MS therapy but may reveal future strategies to intervene in the pathogenesis of neuroinflammatory diseases. 23461784 Tough Germanium Nanoparticles under Electrochemical Cycling. Mechanical degradation of the electrode materials during electrochemical cycling remains a serious issue that critically limits the capacity retention and cyclability of rechargeable lithium-ion batteries. Here we report the highly reversible expansion and contraction of germanium nanoparticles under lithiation-delithiation cycling with in situ transmission electron microscopy (TEM). During multiple cycles to the full capacity, the germanium nanoparticles remained robust without any visible cracking despite ∼260% volume changes, in contrast to the size-dependent fracture of silicon nanoparticles upon the first lithiation. The comparative in situ TEM study of fragile silicon nanoparticles suggests that the tough behavior of germanium nanoparticles can be attributed to the weak anisotropy of the lithiation strain at the reaction front. The tough germanium nanoparticles offer substantial potential for the development of durable, high-capacity, and high-rate anodes for advanced lithium-ion batteries. 23468426 The interaction of isopenicillin N synthase with homologated substrate analogues δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-Xaa characterised by protein crystallography. Isopenicillin N synthase (IPNS) converts the linear tripeptide δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine (ACV) into bicyclic isopenicillin N (IPN) in the central step in the biosynthesis of penicillin and cephalosporin antibiotics. Solution-phase incubation experiments have shown that IPNS turns over analogues with a diverse range of side chains in the third (valinyl) position of the substrate, but copes less well with changes in the second (cysteinyl) residue. IPNS thus converts the homologated tripeptides δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-valine (AhCV) and δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-allylglycine (AhCaG) into monocyclic hydroxy-lactam products; this suggests that the additional methylene unit in these substrates induces conformational changes that preclude second ring closure after initial lactam formation. To investigate this and solution-phase results with other tripeptides δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-Xaa, we have crystallised AhCV and δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-S-methylcysteine (AhCmC) with IPNS and solved crystal structures for the resulting complexes. The IPNS:Fe(II):AhCV complex shows diffuse electron density for several regions of the substrate, revealing considerable conformational freedom within the active site. The substrate is more clearly resolved in the IPNS:Fe(II):AhCmC complex, by virtue of thioether coordination to iron. AhCmC occupies two distinct conformations, both distorted relative to the natural substrate ACV, in order to accommodate the extra methylene group in the second residue. Attempts to turn these substrates over within crystalline IPNS using hyperbaric oxygenation give rise to product mixtures. 23474356 Structure-property relationship for cellular accumulation of macrolones in human polymorphonuclear leukocytes (PMNs). Macrolones are a new class of antimicrobial compounds consisting of a macrolide scaffold linked to a 4-quinolone-3-carboxylic acid moiety via C(4″) position of a macrolide. As macrolides are known to possess favorable pharmacokinetic properties by accumulating in inflammatory cells, in this study we determined the intensity of accumulation in human polymorphonuclear leukocytes (PMNs) of 57 compounds of the macrolone class and analyzed the relationship between the molecular structure and this cellular pharmacokinetic property. Accumulation of macrolones ranged from 0 to 5.5-fold higher than the standard macrolide azithromycin. Distinct structural features in all three considered molecule parts: the macrolide scaffold, quinolone moiety and the linker, affect cellular accumulation. Interestingly, while the parent macrolide, azithromycin, accumulates approximately 3-fold more than clarithromycin, among macrolones all clarithromycin derivatives accumulated in PMNs significantly more than their azithromycin counterparts. Modeling cellular accumulation of macrolones with simple molecular descriptors, as well as with the measured octanol-water distribution coefficient, revealed that the number of hydrogen bond donors and secondary amide groups negatively contribute to macrolone accumulation, while lipophilicity makes a positive contribution. 23444335 A study on the effects of pica and iron-deficiency anemia on oxidative stress, antioxidant capacity and trace elements. Pica is defined as developmentally inappropriate consumption of nonnutritive substances for at least 1 month. There are a few studies on serum trace element levels of patients with pica. The literature contains contracting data on the levels of oxidative stress and antioxidant levels in patients with iron-deficiency anemia (IDA). The effect of pica on oxidative stress and antioxidant capacity has not been investigated yet. The present study evaluated the effects of pica and IDA on oxidative stress and antioxidant capacity as well as on the levels of trace elements including serum zinc and selenium in 47 children with IDA plus pica, 22 children with IDA only and 21 nonanemic children as controls. The results demonstrated significantly lower levels of serum selenium and zinc in pica and IDA groups compared to the control group. Total oxidant levels were highest in the pica group and consistently, the lowest total antioxidant capacity was observed again in the pica group. Comparison of pica and IDA groups yielded significantly lower levels of total antioxidant levels and significantly higher oxidative stress index in the pica group. Consequently, it is thought that the detrimental effects of pica within the organism were mediated by adverse impacts on antioxidant capacity and oxidative stress. These effects should be kept in mind while managing patients with pica. 23592779 Cubilin, a high affinity receptor for fibroblast growth factor 8, is required for cell survival in the developing vertebrate head. Cubilin (Cubn) is a multiligand endocytic receptor critical for the intestinal absorption of vitamin B12 and renal protein reabsorption. During mouse development Cubn is expressed in both embryonic and extra-embryonic tissues and Cubn gene inactivation results in early embryo-lethality most likely due to the impairment of the function of extra-embryonic Cubn. We here focus on the developmental role of Cubn expressed in the embryonic head. We report that Cubn is a novel, interspecies conserved Fgf receptor. Epiblast-specific inactivation of Cubn in the mouse embryo as well as Cubn silencing in the anterior head of frog or the cephalic neural crest of chick embryos show that Cubn is required during early somite stages to convey survival signals in the developing vertebrate head. Surface Plasmon resonance analysis reveals that fibroblast growth factor 8 (Fgf8), a key mediator of cell survival, migration, proliferation and patterning in the developing head is a high affinity ligand for Cubn. Cell uptake studies show that binding to Cubn is necessary for the phosphorylation of the Fgf signaling mediators MAPK and Smad1. Although Cubn may not form stable ternary complexes with Fgf receptors (FgfRs) it acts together with and/or is necessary for optimal FgfR activity. We propose that plasma membrane binding of Fgf8, and most likely of the Fgf8 family members Fgf17 and Fgf18, to Cubn improves Fgf ligand endocytosis and availability to FgfRs, thus modulating Fgf signaling activity. 23480196 Purification and sidewall functionalization of multiwalled carbon nanotubes and resulting bioactivity in two macrophage models. This study examined the consequences of surface carboxylation of multiwalled carbon nanotubes (MWCNT) on bioactivity. Since commercial raw MWCNT contain impurities that may affect their bioactivity, HCl refluxing was exploited to purify raw "as-received" MWCNT by removing the amorphous carbon layer on the MWCNT surface and reducing the metal impurities (e.g. Ni). The removal of amorphous carbon layer was confirmed by Raman spectroscopy and thermogravimetric analysis. Furthermore, the HCl-purified MWCNT provided more available reaction sites, leading to enhanced sidewall functionalization. The sidewall of HCl-purified MWCNT was further functionalized with the -COOH moiety by HNO(3) oxidation. This process resulted in four distinct MWCNT: raw, purified, -COOH-terminated raw MWCNT, and -COOH-terminated purified MWCNT. Freshly isolated alveolar macrophages from C57Bl/6 mice were exposed to these nanomaterials to determine the effects of the surface chemistry on the bioactivity in terms of cell viability and inflammasome activation. Inflammasome activation was confirmed using inhibitors of cathepsin B and Caspase-1. Purification reduced the cell toxicity and inflammasome activation slightly compared to raw MWCNT. In contrast, functionalization of MWCNT with the -COOH group dramatically reduced the cytotoxicity and inflammasome activation. Similar results were seen using THP-1 cells supporting their potential use for high-throughput screening. This study demonstrated that the toxicity and bioactivity of MWCNT were diminished by removal of the Ni contamination and/or addition of -COOH groups to the sidewalls. 23585058 NMDA Receptor Activation Down-Regulates Expression of δ Subunit-Containing GABA-A Receptors in Cultured Hippocampal Neurons. Neurosteroids are endogenous allosteric modulators of γ amino-butyric acid type A receptors (GABARs), and enhance GABAR-mediated inhibition. However, GABARs expressed on hippocampal dentate granule neurons of epileptic animals are modified such that their neurosteroid sensitivity is reduced and δ subunit expression is diminished. The molecular mechanisms triggering this GABAR plasticity were explored. In the cultured hippocampal neurons treatment with NMDA (10 μM) for 48 hrs reduced surface expression of δ and α4 subunits, but did not increase expression of γ2 subunits. The tonic current recorded from neurons in NMDA-treated cultures was reduced, and its neurosteroid modulation was also diminished. In contrast, synaptic inhibition and its modulation by neurosteroids were preserved in these neurons. The time course of NMDA effects on surface and total δ subunit expression were distinct; shorter (6 hrs) treatment decreased surface expression, whereas longer treatment reduced both surface and total expression. APV blocked NMDA effects on δ subunit expression. Chelation of calcium ions by BAPTA-AM or blockade of ERK1/2 activation by UO126 also prevented the NMDA effects. Thus prolonged activation of NMDA receptors in hippocampal neurons reduced GABAR δ subunit expression through Ca2+ entry and at least in part by ERK1/2 activation. 23458573 PET studies in nonhuman primate models of cocaine abuse: Translational research related to vulnerability and neuroadaptations. The current review highlights the utility of positron emission tomography (PET) imaging to study the neurobiological substrates underlying vulnerability to cocaine addiction and subsequent adaptations following chronic cocaine self-administration in nonhuman primate models of cocaine abuse. Environmental (e.g., social rank) and sex-specific influences on dopaminergic function and sensitivity to the reinforcing effects of cocaine are discussed. Cocaine-related cognitive deficits have been hypothesized to contribute to high rates of relapse and are described in nonhuman primate models. Lastly, the long-term consequences of cocaine on neurobiology are discussed. PET imaging and longitudinal, within-subject behavioral studies in nonhuman primates have provided a strong framework for designing pharmacological and behavioral treatment strategies to aid drug-dependent treatment seekers. Non-invasive PET imaging will allow for individualized treatment strategies. Recent advances in radiochemistry of novel PET ligands and other imaging modalities can further advance our understanding of stimulant use on the brain. This article is part of a Special Issue entitled 'Neuroimaging'. 23151003 Metabotropic purinergic receptors in lipid membrane microdomains. There is broad evidence that association of transmembrane receptors and signalling molecules with lipid rafts/caveolae provides an enriched environment for protein-protein interactions necessary for signal transduction, and a mechanism for the modulation of neurotransmitter and/or growth factor receptor function. Several receptors translocate into submembrane compartments after ligand binding, while others move in the opposite direction. The role of such a dynamic localization and functional facilitation is signalling modulation and receptor desensitization or internalization. Purine and pyrimidine nucleotides have been viewed as primordial precursors in the evolution of all forms of intercellular communication, and they are now regarded as fundamental extracellular signalling molecules. They propagate the purinergic signalling by binding to ionotropic and metabotropic receptors expressed on the plasma membrane of almost all cell types, tissues and organs. Here, we have illustrated the localization in lipid rafts/caveolae of G protein-coupled P1 receptors for adenosine and P2Y receptors for nucleoside tri- and di-phosphates. We have highlighted that microdomain partitioning of these purinergic GPCRs is cell-specific, as is the overall expression levels of these same receptors. Moreover, we have described that disruption of submembrane compartments can shift the purinergic receptors from raft/caveolar to non-raft/non-caveolar fractions, and then abolish their ability to activate lipid signalling pathways and to integrate with additional lipid-controlled signalling events. This modulates the biological response to purinergic ligands and most of all indicates that the topology of the various purinergic components at the cell surface not only organizes the signal transduction machinery, but also controls the final cellular response. 23565776 Amino Acid-nucleotide-lipids: effect of amino Acid on the self-assembly properties. Hybrid amphiphiles composed of a lipid covalently linked to biomolecules are attracting considerable attention, owing to their unique physicochemical and biological properties. Herein, we have synthesized novel amino acid-nucleotide-lipids (ANLs), presenting phenylalanine and thymidine residues and saturated or unsaturated diacyl glycerol lipid moieties to investigate the effect of the specific aminoacid moieties on both aggregation properties and interactions of ANLs with single strand polyA RNA. Physicochemical studies (DLS, cryo-TEM, and small angle X-ray scattering) indicate that phenylanaline amino acids inserted at the 5' position of the nucleotide-lipids stabilize multilamellar systems, whereas unilamellar vesicles are formed preferentially in the case of nucleotide-lipids (NLs). Both NLs and ANLs exhibit weak interactions with complementary polyA RNA as revealed by isothermal titration calorimetry investigations. The multilamellar vesicles obtained with ANLs could be used as a versatile carrier, suitable for both hydrophobic and hydrophilic therapeutic molecules. 23220635 The AhR twist: ligand-dependent AhR signaling and pharmaco-toxicological implications. The aryl hydrocarbon receptor (AhR) is a transcription factor which is activated by diverse compounds and regulates the expression of xenobiotic metabolism genes. Recent studies have unraveled unsuspected physiological roles and novel alternative ligand-specific pathways for this receptor. In this review, we discuss these novel aspects and focus on the different responses elicited by the diverse endogenous and/or exogenous AhR ligands. In addition to challenging the relevance of the 'agonist/antagonist' classification of ligands, we introduce the concept of AhR plasticity as a primordial factor in the generation of these pathways. Finally, we suggest several promising perspectives for the pharmacological modulation of these responses. 23246700 Phthalate and di-(2-ethylhexyl) adipate (DEHA) intake by German infants based on the results of a duplicate diet study and biomonitoring data (INES 2). Phthalates as well as di-(2-ethylhexyl) adipate (DEHA) are used as plasticizers in diverse applications and are of toxicological concern. The study was conducted with a study population of 25 German subjects aged between 15 and 21 months. Overall, 16 phthalates and DEHA were measured by gas chromatography-mass spectrometry in a total of 171 duplicate diet samples collected over 7 consecutive days, and 20 phthalate metabolites were analyzed in the urine samples collected over 7 consecutive days using a liquid chromatography-tandem mass spectrometry method. The median "high" daily dietary intake based on 95th percentiles was 4.66 μg/kg b.w. for di-2-ethylhexyl phthalate (DEHP), 1.03 μg/kg b.w. for di-isobutyl phthalate (DiBP), and 0.70 μg/kg b.w. for di-n-butyl phthalate (DnBP), and 1.0 μg/kg b.w. for DEHA. The "high" daily total intake from biomonitoring data was 4.9 μg/kg b.w. for DEHP, 2.2 μg/kg b.w. for DnBP, 3.9 μg/kg b.w. for DiBP, and 2.6 μg/kg b.w. for di-isononyl phthalate. The comparison of the two intake estimates indicates that the dominant intake source of DEHP was food ingestion, whereas other sources considerably contributed to the total intake of other phthalates. Using our "high" intake scenario, none of the analyzed phthalates reached the recommended tolerable daily intake levels. 23291927 Small-scale heat detection using catalytic microengines irradiated by laser. We demonstrate a novel approach to modulating the motion speed of catalytic microtubular engines via laser irradiation/heating with regard to small-scale heat detection. Laser irradiation on the engines leads to a thermal heating effect and thus enhances the engine speed. During a laser on/off period, the motion behaviour of a microengine can be repeatable and reversible, demonstrating a regulation of motion speeds triggered by laser illumination. Also, the engine velocity exhibits a linear dependence on laser power in various fuel concentrations, which implies an application potential as local heat sensors. Our work may hold great promise in applications such as lab on a chip, micro/nano factories, and environmental detection. 22766394 Association of a deficit of arousal with fatigue in multiple sclerosis: effect of modafinil. Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system, leading to chronic disability. Fatigue is a common and distressing symptom of MS which is unrelated to its clinical form, stage of development, the degree of disability, or the lesion load on magnetic resonance imaging. Fatigue in MS is associated with excessive daytime sleepiness and autonomic dysfunction. Recently it has been reported that the wakefulness-promoting drug modafinil may relieve fatigue in MS patients and ameliorate the associated cognitive difficulties. However, it is not clear to what extent the anti-fatigue effect of modafinil may be related to its alerting and sympathetic activating effects. We addressed this question by comparing three groups of subjects, MS patients with fatigue, MS patients without fatigue and healthy controls, matched for age and sex, on measures of alertness (self-ratings on the Epworth and Stanford Sleepiness Scales and on a battery of visual analogue scales; critical flicker fusion frequency; Pupillographic Sleepiness Test; choice reaction time) and autonomic function (systolic and diastolic blood pressure, heart rate, pupil diameter), and by examining the effect of a single dose (200 mg) of modafinil on these measures. MS patients with fatigue, compared with healthy controls, had reduced level of alertness on all the tests used; MS patients without fatigue did not differ from healthy controls. MS patients with fatigue had a reduced level of cardiovascular sympathetic activation compared to the other two groups. Modafinil displayed alerting and sympathomimetic effects in all three groups of subjects. As fatigue in MS is associated with reduced levels of alertness and sympathetic activity, modafinil may exert its anti-fatigue effect in MS by correcting these deficiencies. The anti-fatigue effect of modafinil may reflect the activation of the noradrenergic locus coeruleus (LC), since there is evidence that this wakefulness-promoting nucleus is damaged in MS, and that modafinil, probably via the dopaminergic system, can stimulate the LC. This article is part of a Special Issue entitled 'Cognitive Enhancers'. 23292881 3D nanoscale chemical imaging of the distribution of aluminum coordination environments in zeolites with soft X-ray microscopy. Which side are you on? Scanning transmission X-ray microscopy is used for the first time to elucidate the coordination and distribution of aluminum in industrial-relevant zeolites at the single-particle level. Extended regions of a few hundred nanometers, rich in higher aluminum coordination environments, are heterogeneously embedded within the zeolite particle, before and after a steaming post-treatment. 23047912 L-BMAA induced ER stress and enhanced caspase 12 cleavage in human neuroblastoma SH-SY5Y cells at low nonexcitotoxic concentrations. The cyanobacterial β-N-methylamino-L-alanine (L-BMAA) is described as a low-potency excitotoxin, possibly a factor in the increased incidence of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) in Guam. The latter association is intensively disputed, as L-BMAA concentrations required for toxic effects exceed those assumed to occur via food. The question thus was raised whether L-BMAA leads to neurodegeneration at nonexcitotoxic conditions. Using human SH-SY5Y neuroblastoma cells, L-BMAA-transport, incorporation into proteins, and subsequent impairment of cellular protein homeostasis were investigated. Binding of L-BMAA to intracellular proteins, but no clear protein incorporation was detected in response to (14)C-L-BMAA exposures. Nevertheless, low L-BMAA concentrations (≥ 0.1mM, 48 h) increased protein ubiquitination, 20S proteasomal and caspase 12 activity, expression of the endoplasmic reticulum (ER) stress marker CHOP, and enhanced phosphorylation of elf2α in SH-SY5Y cells. In contrast, high L-BMAA concentrations (≥ 1mM, 48 h) increased reactive oxygen species and protein oxidization, which were partially ameliorated by coincubation with vitamin E. L-BMAA-mediated cytotoxicity was observable 48 h following ≥ 2mM L-BMAA treatment. Consequently, the data presented here suggest that low L-BMAA concentrations result in a dysregulation of the cellular protein homeostasis with ensuing ER stress that is independent from high-concentration effects such as excitotoxicity and oxidative stress. Thus, the latter could be a contributing factor in the onset and slow progression of ALS/PDC in Guam. 23340977 Two-dimensional supramolecular electron spin arrays. A bottom-up approach is introduced to fabricate two-dimensional self-assembled layers of molecular spin-systems containing Mn and Fe ions arranged in a chessboard lattice. We demonstrate that the Mn and Fe spin states can be reversibly operated by their selective response to coordination/decoordination of volatile ligands like ammonia (NH3 ). 23466459 Dietary Chlorella protects against heterocyclic amine-induced aberrant gene expression in the rat colon by increasing fecal excretion of unmetabolized PhIP. The food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic amines formed by cooking meat and fish at high temperature. PhIP induces colorectal adenoma risk in male rats when administered orally. This study used male Fisher 344 rats to investigate the impact of dietary Chlorella on PhIP metabolism and aberrant colonic gene expression following short-term PhIP treatment. High-performance liquid chromatography analysis revealed that fecal excretion of unmetabolized PhIP was significantly increased in rats whose diets were supplemented with Chlorella compared to rats in a PhIP-only group (P<0.001). Quantitative realtime PCR confirmed that the increase in beta-catenin and cyclin D1 mRNA in the colon induced by PhIP was ameliorated in rats pre-fed with Chlorella (P=0.052 for beta-catenin; P=0.005 for cyclin D1). The increase in DNA shearing that is a hallmark of caspase-8-mediated apoptosis by PhIP was also significantly diminished in the colons of rats pre-fed Chlorella (P=0.012). These results suggested that administering dietary Chlorella with a Western-style diet concomitantly or immediately before mutagen exposure might be beneficial in blocking the absorption of food mutagens such as PhIP. 23265502 Ascorbic acid, nitrate, and nitrite concentration relationship to the 24hour light/dark cycle for spinach grown in different conditions. Nitrate, nitrite and ascorbic acid (vitamin C) concentrations were determined for spinach (Spinacia oleracea L.) over a 24 h period to determine if light intensity (including dark periods) at time of harvest impacts concentrations in raw vegetables. Nitrate, nitrate and ascorbic acid concentrations varied significantly over the 24 h period and appeared to be related to changes in light intensity. Light intensity at the time an experimental sample is collected may affect the concentration of some constituents that a researcher is studying. Also, nitrate and nitrite concentrations in raw spinach can be reduced by harvesting at the best time of day. The highest nitrate concentrations in spinach occurred in the dark just prior to an increase in light intensity. Ascorbic acid was near its highest level for the 24 h period when the light intensity initially increased, then decreased to its lowest level around 3-6 h later. 23589365 Crop seed oil bodies: From challenges in protein identification to an emerging picture of the oil body proteome. Oleaginous seeds store lipids in specialized structures called oil bodies (OBs). These organelles consist of a core of neutral lipids bound by proteins embedded in a phospholipid monolayer. OB proteins are well conserved in plants and have long been grouped into only two categories: structural proteins or enzymes. Recent work, however, which identified other classes of proteins associated with OBs, clearly shows that this classification is obsolete. Proteomics-mediated OB protein identification is facilitated in plants for which the genome is sequenced and annotated. However, it is not clear whether this knowledge can be dependably transposed to less well characterized plants, including the well-established commercial sources of seed oil as well as the many others being proposed as novel sources for biodiesel, especially in Africa and Asia. Towards an update of the current data available on OB proteins this review discusses (i) the specific difficulties for proteomic studies of organelles; (ii) a 2012 census of the proteins found in seed OBs from various crops; (iii) the oleosin composition of OBs and their role in organelle stability; (iv) post translational modification of OB proteins as an emerging field of investigation; and finally we describe the emerging model of the OB proteome from oilseed crops. 23246867 A p21-activated kinase (PAK1) signaling cascade coordinately regulates F-actin remodeling and insulin granule exocytosis in pancreatic β cells. Human islet studies implicate an important signaling role for the Cdc42 effector protein p21-activated kinase (PAK1) in the sustained/second-phase of insulin secretion. Because human islets from type 2 diabetic donors lack ∼80% of normal PAK1 protein levels, the mechanistic requirement for PAK1 signaling in islet function was interrogated. Similar to MIN6 β cells, human islets elicited glucose-stimulated PAK1 activation that was sensitive to the PAK1 inhibitor, IPA3. Given that sustained insulin secretion has been correlated with glucose-induced filamentous actin (F-actin) remodeling, we tested the hypothesis that a Cdc42-activated PAK1 signaling cascade is required to elicit F-actin remodeling to mobilize granules to the cell surface. Live-cell imaging captured the glucose-induced cortical F-actin remodeling in MIN6 β cells; IPA3-mediated inhibition of PAK1 abolished this remodeling. IPA3 also ablated glucose-stimulated insulin granule accumulation at the plasma membrane, consistent with its role in sustained/second-phase insulin release. Both IPA3 and a selective inhibitor of the Cdc42 GTPase, ML-141, blunted the glucose-stimulated activation of Raf-1, suggesting Raf-1 to be downstream of Cdc42→PAK1. IPA3 also inhibited MEK1/2 activation, implicating the MEK1/2→ERK1/2 cascade to occur downstream of PAK1. Importantly, PD0325901, a new selective inhibitor of MEK1/2→ERK1/2 activation, impaired F-actin remodeling and the sustained/amplification pathway of insulin release. Taken together, these data suggest that glucose-mediated activation of Cdc42 leads to activation of PAK1 and prompts activation of its downstream targets Raf-1, MEK1/2 and ERK1/2 to elicit F-actin remodeling and recruitment of insulin granules to the plasma membrane to support the sustained phase of insulin release. 23401039 Guidelines for Resident Teaching Experiences. Postgraduate year one (PGY1) and postgraduate year two (PGY2) residencies serve to develop pharmacists into skillful clinicians who provide advanced patient-centered care in various general and specialized areas of pharmacy practice. Pharmacy residencies are a minimum requirement for many clinical pharmacy positions, as well as for positions in academia. The role of clinical pharmacists typically includes teaching, regardless of whether they pursue an academic appointment. Common teaching duties of pharmacist-clinicians include giving continuing education or other invited presentations, providing education to colleagues regarding clinical initiatives, precepting pharmacy students (early and advanced experiences) and residents, and educating other health care professionals. Although ASHP provides accreditation standards for PGY1 and PGY2 residencies, the standards pertaining to teaching or education training are vague. Through the years, teaching certificate programs that develop residents' teaching skills and better prepare residents for a diverse pharmacy job market have increased in popularity; moreover, teaching certificate programs serve as an attractive recruitment tool. However, the consistency of requirements for teaching certificate programs is lacking, and standardization is needed. The Task Force on Residencies developed two sets of guidelines to define teaching experiences within residencies. The first guideline defines the minimum standards for teaching experiences in any residency-training program. The second guideline is for programs offering a teaching certificate program to provide standardization, ensuring similar outcomes and quality on program completion. One of the main differences between the guidelines is the recommendation that residency programs offering a teaching certificate program be affiliated with an academic institution to provide the pedagogy and variety of teaching experiences for the resident. Residency program directors should consider adopting these guidelines to offer consistent teaching experiences. In addition, residents should inquire about the elements of teaching in a program as an aid to selecting the training best suited to their needs. 23597133 Three-Dimensional Ab Initio Potential Energy Surface for H-CO(X̃(2)A'). We present an ab initio potential for the H-CO(X̃(2)A') complex in which the CO bond length is varied and the long-range interactions between H and CO are accurately represented. It was computed using the spin-unrestricted open-shell single and double excitation coupled cluster method with perturbative triples [RHF-UCCSD(T)]. Three doubly augmented correlation-consistent basis sets were utilized to extrapolate the correlation energy to the complete basis set limit. More than 4400 data points were calculated and used for an analytic fit of the potential: long-range terms with inverse power dependence on the H-CO distance R were fit to the data points for large R, the reproducing kernel Hilbert space (RKHS) method was applied to the data at smaller distances. Our potential was compared with previous calculations and with some data extracted from spectroscopy. Furthermore, it was used in three-dimensional discrete variable representation (DVR) calculations of the vibrational frequencies and rotational constants of HCO, which agree very well with the most recently measured data. Also the dissociation energy D0 = 0.623 eV of HCO into H + CO obtained from these calculations agrees well with experimental values. Finally, we made preliminary two-dimensional (2D) calculations of the cross sections for rotationally inelastic H-CO collisions with the CO bond length fixed and obtained good agreement with recently published 2D results. 23124950 Transparent nanowire network electrode for textured semiconductors. This work presents an inexpensive and easily manufacturable, highly conductive and transparent nanowire network electrode for textured semiconductors. It is based on lines of silver nanoparticles transformed into a nanowire network by microwave or furnace sintering. The nanonetwork electrode on crystalline silicon is demonstrated experimentally, with the nanoparticles self-assembling in the valleys between the pyramids of the textured surface. Optical experiments show that this conductive nanowire network electrode can be essentially 'invisible' when covered with the conventional anti-reflection coating (ARC), and thus could be employed in photovoltaic applications. 23318455 Axl/Gas6/NFκB signalling in schwannoma pathological proliferation, adhesion and survival. TAM family receptor tyrosine kinases comprising Tyro3 (Sky), Axl, and Mer are overexpressed in some cancers, correlate with multidrug resistance and contribute to tumourigenesis by regulating invasion, angiogenesis, cell survival and tumour growth. Mutations in the gene coding for a tumour suppressor merlin cause development of multiple tumours of the nervous system such as schwannomas, meningiomas and ependymomas occurring spontaneously or as part of a hereditary disease neurofibromatosis type 2. The benign character of merlin-deficient tumours makes them less responsive to chemotherapy. We previously showed that, amongst other growth factor receptors, TAM family receptors (Tyro3, Axl and Mer) are significantly overexpressed in schwannoma tissues. As Axl is negatively regulated by merlin and positively regulated by E3 ubiquitin ligase CRL4DCAF1, previously shown to be a key regulator in schwannoma growth we hypothesized that Axl is a good target to study in merlin-deficient tumours. Moreover, Axl positively regulates the oncogene Yes-associated protein, which is known to be under merlin regulation in schwannoma and is involved in increased proliferation of merlin-deficient meningioma and mesothelioma. Here, we demonstrated strong overexpression and activation of Axl receptor as well as its ligand Gas6 in human schwannoma primary cells compared to normal Schwann cells. We show that Gas6 is mitogenic and increases schwannoma cell-matrix adhesion and survival acting via Axl in schwannoma cells. Stimulation of the Gas6/Axl signalling pathway recruits Src, focal adhesion kinase (FAK) and NFκB. We showed that NFκB mediates Gas6/Axl-mediated overexpression of survivin, cyclin D1 and FAK, leading to enhanced survival, cell-matrix adhesion and proliferation of schwannoma. We conclude that Axl/FAK/Src/NFκB pathway is relevant in merlin-deficient tumours and is a potential therapeutic target for schwannoma and other merlin-deficient tumours.Oncogene advance online publication, 14 January 2013; doi:10.1038/onc.2012.587. 23001862 Gold nanoprisms as optoacoustic signal nanoamplifiers for in vivo bioimaging of gastrointestinal cancers. Early detection of cancer greatly increases the chances of a simpler and more effective treatment. Traditional imaging techniques are often limited by shallow penetration, low sensitivity, low specificity, poor spatial resolution or the use of ionizing radiation. Hybrid modalities, like optoacoustic imaging, an emerging molecular imaging modality, contribute to improving most of these limitations. However, this imaging method is hindered by relatively low signal contrast. Here, gold nanoprisms (AuNPrs) are used as signal amplifiers in multispectral optoacoustic tomography (MSOT) to visualize gastrointestinal cancer. PEGylated AuNPrs are successfully internalized by HT-29 gastrointestinal cancer cells in vitro. Moreover, the particles show good biocompatibility and exhibit a surface plasmon band centered at 830 nm, a suitable wavelength for optoacoustic imaging purposes. These findings extend well to an in vivo setting, in which mice are injected with PEGylated AuNPrs in order to visualize tumor angiogenesis in gastrointestinal cancer cells. Overall, both our in vitro and in vivo results show that PEGylated AuNPrs have the capacity to penetrate tumors and provide a high-resolution signal amplifier for optoacoustic imaging. The combination of PEGylated AuNPrs and MSOT represents a significant advance for the in vivo imaging of cancers. 23631427 Dual Targeting of the Adenosine A2A Receptors and Monoamine Oxidase B by 4H-3,1-Benzothiazin-4-ones. Blockade of A2A adenosine receptors (A2AARs) and inhibition of monoamine oxidase B (MAO-B) in brain are considered attractive strategies for the treatment of neurodegenerative diseases such as Parkinson's disease (PD). In the present study benzothiazinones, e.g. 2-(3-chlorophenoxy)-N-(4-oxo-4H-3,1-benzothiazin-2-yl)acetamide (13), were identified as a novel class of potent MAO-B inhibitors (IC50 human MAO-B: 1.63 nM). Benzothiazinones with large substituents in the 2-position, e.g. methoxy-cinnamoylamino, phenylbutyrylamino, or chlorobenzylpiperazinylbenzamido residues (14, 17, 27, 28) showed high affinity and selectivity for A2AARs (Ki human A2AAR: 39.5-69.5 nM). By optimizing benzothiazinones for both targets the first potent, dual-acting A2AAR/MAO-B inhibitors with a non-xanthine structure were developed. The best derivative was N-(4-oxo-4H-3,1-benzothiazin-2-yl)-4-phenylbutanamide (17, Ki human A2A 39.5 nM, IC50 human MAO-B 34.9 nM; selective versus other AR subtypes and MAO-A), which inhibited A2AAR-induced cAMP accumulation and showed competitive, reversible MAO B inhibition. The new compounds may be useful tools for validating the A2AAR/MAO-B dual target approach in PD. 23582235 Zinc Promotes the Death of Hypoxic Astrocytes by Upregulating Hypoxia-Induced Hypoxia-Inducible Factor-1alpha Expression via Poly(ADP-ribose) Polymerase-1. AIM: Pathological release of excess zinc ions has been implicated in ischemic brain cell death. However, the underlying mechanisms remain to be elucidated. In stroke, ischemia-induced zinc release and hypoxia-inducible factor-1 (HIF-1) accumulation concurrently occur in the ischemic tissue. The present study tests the hypothesis that the presence of high intracellular zinc concentration is a major cause of modifications to PARP-1 and HIF-1α during hypoxia, which significantly contributes to cell death during ischemia. METHODS: Primary cortical astrocytes and C8-D1A cells were exposed to different concentrations of zinc chloride. Cell death rate and protein expression of HIF-1 and Poly(ADP-ribose) polymerase (PARP)-1 were examined after 3-h hypoxic treatment. RESULTS: Although 3-h hypoxia or 100 μM of zinc alone did not induce noticeable cytotoxicity, their combination led to a dramatic increase in astrocytic cell death in a zinc-concentration-dependent manner. Exposure of astrocytes to hypoxia for 3 h remarkably increased the levels of intracellular zinc and HIF-1α protein, which was further augmented by added exogenous zinc. Notably, HIF-1α knockdown blocked zinc-induced astrocyte death. Moreover, knockdown of PARP-1, another important protein in the response of hypoxia, attenuated the overexpression of HIF-1α and reduced the cell death rate. CONCLUSIONS: Our studies show that zinc promotes hypoxic cell death through overexpression of the hypoxia response factor HIF-1α via the cell fate determine factor PARP-1 modification, which provides a novel mechanism for zinc-mediated ischemic brain injury. 23313961 Specific uptake of folate-decorated triamcinolone-encapsulating nanoparticles by retinal pigment epithelium cells enhances and prolongs antiangiogenic activity. We are proposing folate-decorated polymeric nanoparticles as carriers of poorly soluble drug molecules for intracellular and prolonged delivery to retinal pigment epithelium (RPE) cells. RPE is a monolayer of epithelial cells that forms the outer blood-retinal barrier in the posterior segment of the eye, and is also implicated in the pathology of, such as neovascularization in age-related macular degeneration (AMD). In this study, folate-functionalized poly(ethylene glycol)-b-polycaprolactone (folate-PEG-b-PCL) were synthesized for assembling into nanoparticles of ~130nm. These nanoparticles were internalized into ARPE-19 (human RPE cell line) via receptor-mediated endocytosis, and the cellular uptake was significantly higher than particles without folate modification. Triamcinolone acetonide (TA) was efficiently encapsulated (>97%) into the folate-decorated nanoparticles and was slowly released over a period of 4 weeks at pH 5.5 and 8 weeks at pH 7.4. The enhanced uptake and controlled release resulted in prolonged anti-angiogenic gene expression of RPE cells. In cell culture, the down-regulation of vascular endothelial growth factor (VEGF) and up-regulation of pigment epithelium derived factor (PEDF) lasted for at least 3 weeks. Unlike benzyl alcohol, the surfactant found in commercial formulation, folate-modified nanoparticles were non-toxic. Furthermore, TA became less cytotoxic by being encapsulated in the nanoparticles. Our findings suggest that folate-PEG-PCL nanoparticles are promising drug carriers for RPE targeting. 23470359 Testing for departures from additivity in mixtures of perfluoroalkyl acids (PFAAs). This study is a follow-up to a paper by Carr et al. that determined a design structure to optimally test for departures from additivity in a fixed ratio mixture of four perfluoroalkyl acids (PFAAs) using an in vitro transiently-transfected COS-1 PPARα reporter model with a mixing ratio that is based on average serum levels in NHANES subjects. Availability of information regarding potential for additivity of PFAAs in mixtures is critically important for risk assessors who are concerned with the ability of the compounds to affect human health and impact ecological systems. It is clear that exposures are not to single compounds, but to mixtures of the PFAAs. This paper presents the results from the data collected using the design from Carr et al. along with subsequent analyses that were performed to classify the relationships among mixtures of PFAAs. A non-linear logistic additivity model was employed to predict relative luciferase units (RLU), an indicator of PPARα activation. The results indicated a less than additive relationship among the four PFAAs. To determine if the possible "antagonism" is from the competition among or between carboxylates and sulfonates, four different binary mixtures were also studied. There was a less than additive relationship in all four binary mixtures. These findings are generally similar to two other reports of interfering interactions between PFAAs in mixtures. The most conservative interpretation for our data would be an assumption of additivity (and lack of a greater than additive interaction), with a potential for antagonistic interactions. 23175443 Oncogenic FGFR3 gene fusions in bladder cancer. FGF receptor 3 (FGFR3) is activated by mutation or over-expression in many bladder cancers. Here, we identify an additional mechanism of activation via chromosomal re-arrangement to generate constitutively activated fusion genes. FGFR3-transforming acid coiled coil 3 (TACC3) fusions resulting from 4p16.3 re-arrangements and a t(4;7) that generates a FGFR3-BAI1-associated protein 2-like 1 (BAIAP2L1) fusion were identified in 4 of 43 bladder tumour cell lines and 2 of 32 selected tissue samples including the tumour from which one of the cell lines was derived. These are highly activated and transform NIH-3T3 cells. The FGFR3 component is identical in all cases and lacks the final exon that includes the phospholipase C gamma 1 (PLCγ1) binding site. Expression of the fusions in immortalized normal human urothelial cells (NHUC) induced activation of the mitogen-activated protein kinase pathway but not PLCγ1. A protein with loss of the terminal region alone was not as highly activated as the fusion proteins, indicating that the fusion partners are essential. The TACC3 fusions retain the TACC domain that mediates microtubule binding and the BAIAP2L1 fusion retains the IRSp53/MIM domain (IMD) that mediates actin binding and Rac interaction. As urothelial cell lines with FGFR3 fusions are extremely sensitive to FGFR-selective agents, the presence of a fusion gene may aid in selection of patients for FGFR-targeted therapy. 23220589 In vitro investigation of efficacy of new reactivators on OPC inhibited rat brain acetylcholinesterase. Organophosphorus compounds (OPC) were developed as warfare nerve agents. They are also widely used as pesticides. The drug therapy of intoxication with OPC includes mainly combination of cholinesterase (ChE) reactivators and cholinolytics. There is no single ChE reactivator having an ability to reactivate sufficiently the inhibited enzyme due to the high variability of chemical structure of the inhibitors. The difficulties in reactivation of ChE activity and slight antidote effect regarding intoxication with some OPC are some of the reasons for continuous efforts to obtain new reactivators of ChE. The aim of the present study was to evaluate the efficacy of some ChE reactivators against OPC intoxication (tabun, paraoxon and dichlorvos) in in vitro experiments and to compare their activity to that known for some currently used oximes (obidoxime, HI-6, 2-PAM). Experiments were carried out using rat brain acetylcholinesterase (AChE). Reactivators showed different activity in the reactivation of rat brain AChE after dichlorvos, paraoxon and tabun inhibition. AChE was easier reactivated after paraoxon treatment. The best effect showed BT-07-4M, obidoxime, TMB-4 and BT-08 from the group of symmetric oximes, and Toxidin, BT-05 and BT-03 from asymmetric compounds. The reactivation of brain AChE inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure. All compounds showed low activity toward inhibition of AChE caused by dichlorvos. Comparison of two main structure types (symmetric/asymmetric) showed that the symmetric compounds reactivated better AChE, inhibited with this OPC, than asymmetric ones. 23496412 Formation of Aragonitic Layered Structures from Kaolinite and Amorphous Calcium Carbonate Precursors. Clay materials have been an ever-present accoutrement of modern civilization; improvements to process these materials have quickened their utilization for use in complex multiaxial load-bearing structures. Specifically, with better methods to organize the constituent metal oxide components in clay, the distribution of characteristic nematic and smectic phases can be controlled. In this work, we utilize the interactions of an amorphous calcium carbonate phase with kaolinite to form a complex composite that can be organized into distinct hierarchical structures. We demonstrate that these ACC-kaolinite composites can maintain characteristic long-range-ordered layer-by-layer structures across many length scales, from nano- to millimeter, through convenient and economical processing at room temperature. 23233034 Synthesis and NIR optical properties of hollow gold nanospheres with LSPR greater than one micrometer. Optical analysis in the near infrared region is of significant biological importance due to better tissue penetration and reduced autofluorescence. In this work, an improved synthesis of hollow gold nanospheres (HGNs), which provides a tunable localized surface plasmon resonance (LSPR) from 610 nm up to 1320 nm, is demonstrated. The scattering properties of these nanoparticles are shown using surface enhanced Raman scattering (SERS) at 1064 nm excitation wavelength and are compared to citrate reduced gold and silver nanoparticles of similar physical sizes and surface properties. After the addition of salts, a strong signal was observed from hollow gold with a LSPR of 650 nm and a weaker, yet observable, signal from HGNs with a LSPR of 775 nm. However, no obvious signals were observed in the case of standard citrate reduced gold, silver or HGNs with a LSPR of 1080 nm. The absorption properties of HGNs were investigated by monitoring their photothermal activity. In this case, different nanoparticle suspensions including citrate reduced gold, silver, and HGNs were illuminated by a continuous laser at 785 nm excitation wavelength and the absorption efficiency of HGNs with a LSPR of 775 nm was calculated to be 0.81% which is more than 5 times higher than the absorption efficiency of citrate reduced gold nanoparticles under similar conditions. 23613425 A Biodegradable Polymersome Containing Bcl-xL siRNA and Doxorubicin as a Dual Delivery Vehicle for a Synergistic Anticancer Effect. Combined cancer treatment via co-delivery of siRNAs and an anticancer drug can be a promising strategy due to the synergistic effect of simultaneously minimizing gene/drug administration. In this study, Bcl-xL siRNA and doxorubicin (DOX) are encapsulated into designed methoxy-poly(ethylene glycol)-block-poly(D,L-lactic acid) (mPEG-b-PLA) block copolymer polymersomes (PSomes). A study of the cytotoxicity of Bcl-xL siRNA and DOX co-encapsulated PSomes (CPSomes) shows more inhibited proliferation of MKN-45 and MKN-28 human gastric cancer cell lines than only gene- and drug-loaded ones. Consequently, these results demonstrate that co-delivery of genes and drugs using PSomes results in a synergistic efficacy and indicates the potential of PSomes as efficient nanocarriers for combined cancer therapy. 22644836 Insulin resistance is not necessarily an essential element of metabolic syndrome. Type 2 diabetes is frequently associated with metabolic syndrome (MetS). Insulin resistance (IR) is thought to be the underlying pathophysiology of MetS. The purpose of this study is to examine the association of MetS with IR and beta cell function. This is a cross-sectional study in NHANES 1999-2000 participants who were at least 18 years old, including 911 non-Hispanic whites (NHW), 398 non-Hispanic blacks (NHB), and 595 Mexican-Americans (MA). MetS was defined based on the revised ATP III. IR and beta cell function were calculated using homeostasis model assessment (HOMA-IR and HOMA-B). The high-risk tertile was defined as the highest HOMA-IR and lowest HOMA-B. The odds ratio (OR) was calculated against the other two tertiles. The relationship of HOAM-IR and HOMA-B with the components of MetS was also examined. IR was a risk factor of MetS in all three ethnic groups (OR 4.17-12.01, P < 0.0001). Fasting glucose, triglycerides, and HDL cholesterol were associated with IR (P < 0.001) and correlated with HOMA-IR (P < 0.001), while inconsistent results were noted in blood pressure and waist circumference among three racial/ethnic groups. However, in the MetS subjects, 32 % of NHW, 28 % of NHB, and 44 % of MA were not in the IR tertile and in the IR subjects, 25 % of NHW, 36 % NHB, and 30 % of MA did not have MetS. No relationship was found between beta cell function and MetS. Although IR is a risk factor for MetS, IR is neither necessary nor required for MetS. 23273993 Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell-type plasticity within a tumor has recently been suggested to cause a bidirectional conversion between tumor-initiating stem cells and nonstem cells triggered by an inflammatory stroma. NF-κB represents a key transcription factor within the inflammatory tumor microenvironment. However, NF-κB's function in tumor-initiating cells has not been examined yet. Using a genetic model of intestinal epithelial cell (IEC)-restricted constitutive Wnt-activation, which comprises the most common event in the initiation of colon cancer, we demonstrate that NF-κB modulates Wnt signaling and show that IEC-specific ablation of RelA/p65 retards crypt stem cell expansion. In contrast, elevated NF-κB signaling enhances Wnt activation and induces dedifferentiation of nonstem cells that acquire tumor-initiating capacity. Thus, our data support the concept of bidirectional conversion and highlight the importance of inflammatory signaling for dedifferentiation and generation of tumor-initiating cells in vivo. 23410172 Rationally designed multitarget agents against inflammation and pain. Arachidonic acid (ARA) undergoes enzyme-mediated oxidative metabolism, resulting in the formation of a number of biologically active metabolites. For over a century, these biochemical transformations have been the target of numerous pharmacological drugs for inflammation and pain. In particular, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors (coxibs) are widely used in the treatment of inflammation and pain. However, gastrointestinal (GI) and cardiovascular adverse effects of NSAIDs and coxibs, and recent findings demonstrating that there are significant risks from the disruption of oxylipin levels when pharmacologically inhibiting a single ARA cascade metabolic pathway, have led to studies involving the simultaneous inhibition of multiple pathways in ARA cascade. These studies suggest that multitarget inhibition represents a new and valuable option to enhance efficacy or reduce side-effects in the treatment of inflammation and pain. This review focuses on the crosstalk within the three pathways of the ARA cascade (cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450)), and summarizes the current and future approaches of multitarget inhibitors for the treatment of eicosanoid driven inflammation and pain. 23454529 New quinazoline derivatives for telomeric G-quadruplex DNA: Effects of an added phenyl group on quadruplex binding ability. To improve the selectivity of indoloquinoline or benzofuroquinoline derivatives, we previously reported several quinazoline derivatives [17]. These compounds could mimic a tetracyclic aromatic system through intramolecular hydrogen bond. Studies showed that these quinazoline derivatives were effective and selective telomeric G-quadruplex ligands. With this encouragement, here we synthesized a series of N-(2-(quinazolin-2-yl)phenyl)benzamide (QPB) compounds as modified quinazoline derivatives. In this modification, a phenyl group was introduced to the aromatic core. The evaluation results showed that part of QPB derivatives had stronger binding ability and better selectivity for telomeric G-quadruplex DNA than LZ-11, the most potential compound of reported quinazoline derivatives. Furthermore, telomerase inhibition of QPB derivatives and their cellular effects were studied. 23468310 Sarothrin from Alkanna orientalis is an antimicrobial agent and efflux pump inhibitor. An Alkanna orientalis leaf and flower extract inhibited the growth of Staphylococcus aureus, a pathogen that causes an estimated 478 000 hospitalizations in the US annually. Bioassay-guided fractionation of A. orientalis resulted in isolation of the flavonoid sarothrin (5,7,4'-trihydroxy-3,6,8-trimethoxyflavone), which inhibited the growth of Mycobacterium smegmatis (MIC 75 µM) and S. aureus (MIC > 800 µM), and possessed efflux pump inhibitory activity. This is the first report of antimicrobial or efflux pump inhibitory activity of sarothrin, and of its presence in A. orientalis. Our findings suggest that the effectiveness of A. orientalis extracts is due to a combination of multiple constituents, including sarothrin. 23517729 Efficient induction of apoptosis in HeLa cells by a novel cationic porphycene photosensitizer. In the present study we analyze the photobiological properties of 2,7,12-tris(α-pyridinio-p-tolyl)-17-(p-(methoxymethyl)phenyl) porphycene (Py3MeO-TBPo) in Hela cells, in order to assess its potential as a new photosensitizer for photodynamic therapy of cultured tumor cells. Using 0.5 μM Py3MeO-TBPo, flow cytometry studies demonstrated an increase of intracellular drug levels related to the incubation time, reaching a maximum at 18 h. LysoTracker(®) Green (LTG) and MitoTracker(®) Green (MTG) probes were used to identify the subcellular localization. Upon exposure to ultraviolet excitation, red porphycene fluorescence was detected as red granules in the cytoplasm that colocalized with LTG. No significant toxic effects were detected for Py3MeO-TBPo in the dark at concentrations below 1 μM. In contrast, Py3MeO-TBPo combined with red-light irradiation induced concentration- and fluence-dependent HeLa cells inactivation. Besides, all photodynamic protocols assayed induced a clear effect of cell detachment inhibition after trypsin treatment. Both apoptotic and necrotic cell death mechanisms can occur in HeLa cells depending on the experimental protocol. After 18 h incubation with 0.5 μM Py3MeO-TBPo and subsequent red light irradiation (3.6 J/cm(2)), a high number of cells die by apoptosis, as evaluated by morphological alterations, immunofluorescent relocalization of Bax from cytosol to mitochondria, and TUNEL assay. Likewise, immunofluorescence techniques showed that cytochrome c is released from mitochondria into cytosol in cells undergoing apoptosis, which occurs immediately after relocation of Bax in mitochondria. The highest amount of apoptosis appeared 24 h after treatment (70%) and this cell death occurred without cell detachment to the substrate. In contrast, with 0.75 μM Py3MeO-TBPo and 3.6 J/cm(2) irradiation, morphological changes showed a preferential necrotic cell death. Singlet oxygen was identified as the cytotoxic agent involved in cell photoinactivation. Moreover, cell cultures pre-exposed to the singlet oxygen scavenger sodium azide showed pronounced protection against the loss of viability induced by Py3MeO-TBPo and light. Different changes in distribution and organization of cytoskeletal elements (microtubules and actin microfilaments) as well as the protein vinculin, after apoptotic and necrotic photodynamic treatments have been analyzed. Neither of these two cell death mechanisms (apoptosis or necrosis) induced cell detachment. In summary, Py3MeO-TBPo appears to meet the requirements for further scrutiny as a very good photosensitizer for photodynamic therapy: it is water soluble, has a high absorption in the red spectral region (where light penetration in tissue is higher), and is able to induce effective high apoptotic rate (70%) related to the more widely studied photosensitizers. 22634360 Metabotropic glutamate receptor 4 in the basal ganglia of parkinsonian monkeys: ultrastructural localization and electrophysiological effects of activation in the striatopallidal complex. Group III metabotropic glutamate receptors (mGluR4,7,8) are widely distributed in the basal ganglia. Injection of group III mGluR agonists into the striatopallidal complex alleviates parkinsonian symptoms in 6-hydroxydopamine-treated rats. In vitro rodent studies have suggested that this may be partly due to modulation of synaptic transmission at striatopallidal and corticostriatal synapses through mGluR4 activation. However, the in vivo electrophysiological effects of group III mGluRs activation upon basal ganglia neurons activity in nonhuman primates remain unknown. Thus, in order to examine the anatomical substrates and physiological effects of group III mGluRs activation upon striatal and pallidal neurons in monkeys, we used electron microscopy immunohistochemistry to localize mGluR4, combined with local administration of the group III mGluR agonist L-AP4, or the mGluR4 positive allosteric modulator VU0155041, to assess the effects of group III mGluR activation on the firing rate and pattern of striatal and pallidal neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated parkinsonian monkeys. At the ultrastructural level, striatal mGluR4 immunoreactivity was localized in pre- (60%) and post-synaptic (30%) elements, while in the GPe, mGluR4 was mainly expressed pre-synaptically (90%). In the putamen, terminals expressing mGluR4 were evenly split between putative excitatory and inhibitory terminals, while in the GPe, most labeled terminals displayed the ultrastructural features of striatal-like inhibitory terminals, though putative excitatory boutons were also labeled. No significant difference was found between normal and parkinsonian monkeys. Extracellular recordings in awake MPTP-treated monkeys revealed that local microinjections of small volumes of L-AP4 resulted in increased firing rates in one half of striatal cells and one third of pallidal cells, while a significant number of neurons in both structures showed either opposite effects, or did not display any significant rate changes following L-AP4 application. VU0155041 administration had little effect on firing rates. Both compounds also had subtle effects on bursting and oscillatory properties, acting to increase the irregularity of firing. The occurrence of pauses in firing was reduced in the majority (80%) of GPe neurons after L-AP4 injection. Our findings indicate that glutamate can mediate multifarious physiological effects upon striatal and pallidal neurons through activation of pre-synaptic group III mGluRs at inhibitory and excitatory synapses in parkinsonian monkeys. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. 22809387 Development and characterization of composite YSZ-PEI electrophoretically deposited membrane for Li-ion battery. In this work, the electrophoretic-deposition (EPD) method was used to fabricate pristine and composite ceramic-polymer membranes for application in planar and 3D microbattery configurations. The major focus was on the effect of polyethyleneimine additive on the morphology, composition, and electrochemical properties of the membrane. The ionic conductivity, cycleability, and charge/discharge behavior of planar LiFePO(4)/Li cells comprising composite porous YSZ-based membrane with impregnated LiPF(6) EC:DEC electrolyte were found to be similar to the cells with commercial Celgard membrane. Conformal EPD coating of the electrode materials by a thin-film ceramic separator is advantageous for high-power operation and safety of batteries. 22898132 Assessment of developmental delay in the zebrafish embryo teratogenicity assay. In this study we analyzed some aspects of the assessment of developmental delay in the zebrafish embryotoxicity/teratogenicity test and explored the suitability of acetylcholinesterase (AChE) activity as a biochemical marker and as a higher throughput alternative to morphological endpoints such as head-trunk angle, tail length and morphological score. Embryos were exposed from 4 to 52 h post-fertilization (hpf) to a selection of known embryotoxic/teratogen compounds (valproic acid, retinoic acid, caffeine, sodium salicylate, glucose, hydroxyurea, methoxyacetic acid, boric acid and paraoxon-methyl) over a concentration range. They were evaluated for AChE activity, head-trunk angle, tail length and several qualitative parameters integrated in a morphological score. In general, the different patterns of the concentration-response curves allowed distinguishing between chemicals that produced growth retardation (valproic and methoxyacetic acid) and chemicals that produced non-growth-delay related malformations. An acceptable correlation between the morphological score, AChE activity and head-trunk angle as markers of developmental delay was observed, being AChE activity particularly sensitive to detect delay in the absence of malformations. 23159479 The impact of oxytocin administration and maternal love withdrawal on event-related potential (ERP) responses to emotional faces with performance feedback. This is the first experimental study on the effect of oxytocin administration on the neural processing of facial stimuli conducted with female participants that uses event-related potentials (ERPs). Using a double-blind, placebo-controlled within-subjects design, we studied the effects of 16 IU of intranasal oxytocin on ERPs to pictures combining performance feedback with emotional facial expressions in 48 female undergraduate students. Participants also reported on the amount of love withdrawal they experienced from their mothers. Vertex positive potential (VPP) and late positive potential (LPP) amplitudes were more positive after oxytocin compared to placebo administration. This suggests that oxytocin increased attention to the feedback stimuli (LPP) and enhanced the processing of emotional faces (VPP). Oxytocin heightened processing of the happy and disgusted faces primarily for those reporting less love withdrawal. Significant associations with LPP amplitude suggest that more maternal love withdrawal relates to the allocation of attention toward the motivationally relevant combination of negative feedback with a disgusted face. 23561190 Preparative separation of triterpene alcohol ferulates from rice bran oil using a high performance counter-current chromatography. A novel method for the separation of two major triterpene alcohol ferulates from rice bran oil (RBO) was developed using a high performance counter-current chromatography (HPCCC). A two-phase solvent system of n-hexane-acetonitrile (1:1, v/v) was applied to purify cycloartenyl ferulate (CAF) and 24-methylene cycloartanyl ferulate (24-mCAF) from RBO. The yields were 20.50±2.60mg CAF and 12.62±1.15mg 24-mCAF from 390mg RBO through a two-step separation procedure. The purities of the two compounds were 97.97±0.90% and 95.50±0.75%, respectively, as determined by high performance liquid chromatography (HPLC). Their chemical structures were confirmed by ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and (1)H, (13)C and 2D nuclear magnetic resonance (NMR). This represents the first report on direct separation of CAF and 24-mCAF from RBO by HPCCC. 23201309 Selectivity of kinases on the activation of tenofovir, an anti-HIV agent. Nucleoside analogues, used in HIV-therapy, need to be phosphorylated by cellular enzymes in order to become potential substrates for HIV reverse transcriptase. After incorporation into the viral DNA chain, because of lacking of their 3'-hydroxyl groups, they stop the elongation process and lead to the death of the virus. Phosphorylation of the HIV-drug derivative, tenofovir monophosphate was tested with the recombinant mammalian nucleoside diphosphate kinase (NDPK), 3-phosphoglycerate kinase (PGK), creatine kinase (CK) and pyruvate kinase (PK). Among them, only CK was found to phosphorylate tenofovir monophosphate with a reasonable rate (about 45-fold lower than with its natural substrate, ADP), while PK exhibits even lower, but still detectable activity (about 1000-fold lower compared to the value with ADP). On the other hand, neither NDPK nor PGK has any detectable activity on tenofovir monophosphate. The absence of activity with PGK is surprising, since the drug tenofovir competitively inhibits both CK and PGK towards their nucleotide substrates, with similar inhibitory constants, K(I) of 2.9 and 4.8mM, respectively. Computer modelling (docking) of tenofovir mono- or diphosphate forms to these four kinases suggests that the requirement of large-scale domain closure for functioning (as for PGK) may largely restrict their applicability for phosphorylation/activation of pro-drugs having a structure similar to tenofovir monophosphate. 23568578 Differential levels of brain amino acids in rat models presenting learned helplessness or non-learned helplessness. RATIONALE: Glutamatergic and γ-aminobutyric acid (GABA)ergic abnormalities have recently been proposed to contribute to depression. The learned helplessness (LH) paradigm produces a reliable animal model of depression that expresses a deficit in escape behavior (LH model); an alternative phenotype that does not exhibit LH is a model of resilience to depression (non-LH model). OBJECTIVES: We measured the contents of amino acids in the brain to investigate the mechanisms involved in the pathology of depression. METHODS: LH and non-LH models were subjected to inescapable electric footshocks at random intervals following a conditioned avoidance test to determine acquirement of predicted escape deficits. Tissue amino acid contents in eight brain regions were measured via high-performance liquid chromatography. RESULTS: The non-LH model showed increased GABA levels in the dentate gyrus and nucleus accumbens and increased glutamine levels in the dentate gyrus and the orbitofrontal cortex. The LH model had reduced glutamine levels in the medial prefrontal cortex. Changes in the ratios of GABA, glutamine, and glutamate were detected in the non-LH model, but not in the LH model. Reductions in threonine levels occurred in the medial prefrontal cortex in both models, whereas elevated alanine levels were detected in the medial prefrontal cortex in non-LH animals. CONCLUSIONS: The present study demonstrates region-specific compensatory elevations in GABA levels in the dentate gyrus and nucleus accumbens of non-LH animals, supporting the implication of the GABAergic system in the recovery of depression. 23329588 Operationalizing value-based pricing of medicines : a taxonomy of approaches. The UK Government is proposing a novel form of price regulation for branded medicines, which it has dubbed 'value-based pricing' (VBP). The specifics of how VBP will work are unclear. We provide an account of the possible means by which VBP of medicines might be operationalized, and a taxonomy to describe and categorize the various approaches. We begin with a brief discussion of the UK Government's proposal for VBP and proceed to define a taxonomy of approaches to VBP. The taxonomy has five main dimensions: (1) what is identified as being of value, (2) how each element is measured, (3) how it is valued, (4) how the different elements of value are aggregated, and (5) how the result is then used to determine the price of a medicine. We take as our starting point that VBP will include a measure of health gain and that, as proposed by the UK Government, this will be built on the QALY. Our principal interest is in the way criteria other than QALYs are taken into account, including severity of illness, the extent of unmet need, and wider societal considerations such as impacts on carers. We set out to: (1) identify and describe the full range of alternative means by which 'value' might be measured and valued, (2) identify and describe the options available for aggregating the different components of value to establish a maximum price, and (3) note the challenges and relative advantages associated with these approaches. We review the means by which aspects of VBP are currently operationalized in a selection of countries and place these, and proposals for the UK, in the context of our taxonomy. Finally, we give an initial assessment of the challenges, pros and cons of each approach. We conclude that identifying where VBP should lie on each of the five dimensions entails value judgements: there are no simple 'right or wrong' solutions. If a wider definition of value than incremental QALYs gained is adopted, as is desirable, then a pragmatic way to aggregate the different elements of value, including both QALYs and benefits unrelated to QALYs, is to use a multi-criteria decision analysis (MCDA) approach. All approaches to VBP ultimately require the conversion of value, however assessed, into a monetary price. This requires assessment of the marginal values of all types of benefit, not just of QALYs. All stages of the VBP process are subject to uncertainty and margins of error. Consequently, the assessment of overall value can provide bounds to a price negotiation but cannot be expected to identify a precise value-based price. 23524305 Binding pattern and toxicological effects of lectins from genus Canavalia on bovine sperm. The aim of this study was to determine the binding patterns of Canavalia ensiformis (ConA), Canavalia boliviana (ConBol) and Canavalia brasiliensis (ConBr) lectins to bovine sperm and their effects on sperm motility, viability, lipid peroxidation, reactive oxygen species production and fertilization ability. ConA bound to whole spermatozoa, with the exception of the equatorial segment, ConBol did not interact with the acrosome region and ConBr exhibited a fragmented binding pattern. The three lectins decreased sperm motility but did not affect cell viability or lipid peroxidation. Nevertheless, ROS production was increased in comparison to controls and a reduction in the cleavage and blastocyst ratio was induced in comparison to controls. In conclusion, this study determined that structurally similar lectins interact differently with bovine sperm and affect sperm motility, viability, lipid peroxidation, ROS production and fertilization ability in various ways. 23391443 An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis. Prolonged inappropriate inflammatory responses contribute to the pathogenesis of rheumatoid arthritis (RA) and to aspects of osteoarthritis (OA). The orphan nuclear receptor, NR4A2, is a key regulator and potential biomarker for inflammation and represents a potentially valuable therapeutic target. Both salmon calcitonin (sCT) and hyaluronic acid (HA) attenuated activated mRNA expression of NR4A1, NR4A2, NR4A3, and matrix metalloproteinases (MMPs) 1, 3 and 13 in three human cell lines: SW1353 chondrocytes, U937 and THP-1 monocytes. Ad-mixtures of sCT and HA further down-regulated expression of NR4A2 compared to either agent alone at specific concentrations, hence the rationale for their formulation in nanocomplexes (NPs) using chitosan. The sCT released from NP stimulated cAMP production in human T47D breast cancer cells expressing sCT receptors. When NP were injected by the intra-articular (I.A.) route to the mouse knee during on-going inflammatory arthritis of the K/BxN serum transfer model, joint inflammation was reduced together with NR4A2 expression, and local bone architecture was preserved. These data highlight remarkable anti-inflammatory effects of sCT and HA at the level of reducing NR4A2 mRNA expression in vitro. Combining them in NP elicits anti-arthritic effects in vivo following I.A. delivery. 23468099 Effects of chronic social defeat stress on behavior and choline acetyltransferase, 78-kDa glucose-regulated protein, and CCAAT/enhancer-binding protein (C/EBP) homologous protein in adult mice. RATIONALE: Social defeat stress induces physiological and behavioral symptoms, including anxiety, anhedonia, immune deficits, and altered expression of key brain genes. OBJECTIVES: The present study investigated the effects of social defeat stress on the behaviors and expressions of Chat, Grp78, and chop in the brains of adult mice. METHODS: Adult mice were divided into susceptible and unsusceptible groups after 10 days of social defeat stress. In experiment 1, behavioral tests were conducted, and brains were processed for Western blotting at day 27 after stress. In experiment 2, social avoidance tests were conducted, and brains were processed for Western blotting at day 12 after stress. RESULTS: The results indicate decreased and increased locomotion and anxiety behavior in all defeated mice. Decrease in social interaction, increased immobility, and impaired memory performance were only observed in susceptible mice. A decrease in the Chat level at days 12 and 27 was noted in the prefrontal cortex (PFC), amygdala (Amyg), and dorsal hippocampus (HIP) in defeated mice. The expression levels of Grp78 and chop measured on days 12 and 27 were significantly greater in the Amyg of susceptible mice. In the PFC and HIP, defeated mice displayed different patterns in the levels of Grp78 and chop expressions measured on days 12 and 27. CONCLUSIONS: The present study demonstrated that chronic social defeat stress in mice produces stress-related behaviors. Different response patterns were noted for Grp78 and chop expression among the groups in terms of brain regions and time-course effects. 23161217 Suramin decreases injury and improves regeneration of ethanol-induced steatotic partial liver grafts. Steatotic grafts are excluded for use in partial liver transplantation (LT) because of the increased risk of primary nonfunction. This study investigated the effects of suramin, a polysulfonated naphthylurea, on the outcome of steatotic partial LT. Rat livers were harvested after acute ethanol treatment (6 g/kg, intragastric administration), reduced in size to ≈ 1/3, and transplanted. Serum alanine aminotransferase (ALT) and total bilirubin levels as well as hepatic necrosis and apoptosis were significantly higher after transplantation of fatty partial grafts (FPG) than lean partial grafts (LPG). Suramin (5 mg/kg, i.p.) decreased ALT by ≈ 60%, hyperbilirubinemia by 75%, necrosis by 83%, and apoptosis by 70% after FPG transplantation. Hepatic cellular 5-bromo-2'-deoxyuridine (BrdU) incorporation increased to 28% in LPG but was only 2% in FPG at 48 hours, and the mitotic index increased to 7% in LPG but was only 0.2% in FPG, indicating suppressed regeneration in FPG. Suramin increased BrdU incorporation and the mitotic index to 43% and 9%, respectively, in FPG. All FPG recipients died within 5 days. Suramin recovered survival of FPG to 62%. Tumor necrosis factor-α (TNF-α) mRNA was 2.2-fold higher in FPG than in LPG and was associated with activation of caspase-8 and caspase-3 in FPG. Suramin decreased TNF-α and caspase activation in FPG. Transforming growth factor-β (TGF-β), phospho-Smad2/3 and p21Cip1 were significantly higher in FPG than in LPG and suramin blocked TGF-β formation and its down-stream signaling pathway. Taken together, suramin improves the outcome of FPG transplantation, most likely by inhibition of TNF-α and TGF-β formation. 22397675 Injectable PLA-based in situ forming implants for controlled release of Ivermectin a BCS Class II drug: solvent selection based on physico-chemical characterization. In situ forming implants (ISI) prepared from biodegradable polymers such as poly(D,L-lactide) (PLA) and biocompatible solvents can be used to obtain sustained drug release after parenteral administration. The aim of this work was to study the effect of several biocompatible solvents with different physico-chemical properties on the release of ivermectin (IVM), an antiparasitic BCS II drug, from in situ forming PLA-based implants. The solvents evaluated were N-methyl-2-pyrrolidone (NMP), 2-pyrrolidone (2P), triacetine (TA) and benzyl benzoate (BB). Hansen's solubility parameters of solvents were used to explain polymer/solvent interactions leading to different rheological behaviours. The stability of the polymer and drug in the solvents were also evaluated by size exclusion and high performance liquid chromatography, respectively. The two major factors determining the rate of IVM release from ISI were miscibility of the solvent with water and the viscosity of the polymer solutions. In general, the release rate increased with increasing water miscibility of the solvent and decreasing viscosity in the following order NMP>2P>TA>BB. Scanning electron microscopy revealed a relationship between the rate of IVM release and the surface porosity of the implants, release being higher as implant porosity increased. Finally, drug and polymer stability in the solvents followed the same trends, increasing when polymer-solvent affinities and water content in solvents decreased. IVM degradation was accelerated by the acid environment generated by the degradation of the polymer but the drug did not affect PLA stability. 23620478 Diabetic Retinopathy and Microalbuminuria Can Predict Macroalbuminuria and Renal Function Decline in Japanese Type 2 Diabetic Patients: Japan Diabetes Complications Study. OBJECTIVETo examine the interactive relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in type 2 diabetic patients, and to elucidate the role of DR and microalbuminuria on the onset of macroalbuminuria and renal function decline.RESEARCH DESIGN AND METHODSWe explored the effects of DR and microalbuminuria on the progression of DN from normoalbuminuria and low microalbuminuria (<150 mg/gCr) to macroalbuminuria or renal function decline in the Japan Diabetes Complications Study (JDCS), which is a nationwide randomized controlled study of type 2 diabetic patients focusing on lifestyle modification. Patients were divided into four groups according to presence or absence of DR and MA: normoalbuminuria without DR [NA(DR-)] (n = 773), normoalbuminuria with DR [NA(DR+)] (n = 279), microalbuminuria without DR [MA(DR-)] (n = 277), and microalbuminuria with DR [MA(DR+)] (n = 146). Basal urinary albumin-to-creatinine ratio and DR status were determined at baseline and followed for a median of 8.0 years.RESULTSAnnual incidence rates of macroalbuminuria were 1.6/1,000 person-years (9 incidences), 3.9/1,000 person-years (8 incidences), 18.4/1,000 person-years (34 incidences), and 22.1/1,000 person-years (22 incidences) in the four groups, respectively. Multivariate-adjusted hazard ratios of the progression to macroalbuminuria were 2.48 (95% CI 0.94-6.50; P = 0.07), 10.40 (4.91-22.03; P < 0.01), and 11.55 (5.24-25.45; P < 0.01) in NA(DR+), MA(DR-), and MA(DR+), respectively, in comparison with NA(DR-). Decline in estimated glomerular filtration rate (GFR) per year was two to three times faster in MA(DR+) (-1.92 mL/min/1.73 m(2)/year) than in the other groups.CONCLUSIONSIn normo- and low microalbuminuric Japanese type 2 diabetic patients, presence of microalbuminuria at baseline was associated with higher risk of macroalbuminuria in 8 years. Patients with microalbuminuria and DR showed the fastest GFR decline. Albuminuria and DR should be considered as risk factors of renal prognosis in type 2 diabetic patients. An open sharing of information will benefit both ophthalmologists and diabetologists. 23317572 Radiolytic transformation of rotenone with potential anti-adipogenic activity. Radiolytic transformation of the isoflavonoid rotenone (1) with γ-irradiation afforded two new degraded products, rotenoisins A (2) and (3). The structures of the two new rotenone derivatives were elucidated on the basis of spectroscopic methods. The new products 2 and 3 exhibited significantly enhanced inhibitory activities against pancreatic lipase and adipocyte differentiation in 3T3-L1 cells when compared to parent rotenone. 23629515 Mitochondria as a Target of Environmental Toxicants. Enormous strides have recently been made in our understanding of the biology and pathobiology of mitochondria. Many diseases have been identified as caused by mitochondrial dysfunction, and many pharmaceuticals have been identified as previously unrecognized mitochondrial toxicants. A much smaller but growing literature indicates that mitochondria are also targeted by environmental pollutants. We briefly review the importance of mitochondrial function and maintenance for health, based on the genetics of mitochondrial diseases and the toxicities resulting from pharmaceutical exposure. We then discuss how the principles of mitochondrial vulnerability illustrated by those fields might apply to environmental contaminants, with particular attention to factors that may modulate vulnerability including genetic differences, epigenetic interactions, tissue characteristics, and developmental stages. Finally, we review the literature related to environmental mitochondrial toxicants, with a particular focus on those toxicants that target mitochondrial DNA. We conclude that the fields of environmental toxicology and environmental health should focus more strongly on mitochondria. 23604592 Developmental exposure to As, Cd and Pb-mixture diminishes skeletal growth and causes osteopenia at maturity via osteoblast and chondrocyte malfunctioning in female rats. We studied the effect of metal mixture (MM), comprising of As, Cd and Pb, in developing female rat skeleton from gestation day-5 until postnatal day-60 (P-60). MM resulted in synergistic inhibition in viability and differentiation of osteoblasts in vitro, likely induced by reactive oxygen species. MM, administered at their most frequently occurring concentrations present in the ground-water of India, i.e. As: 0.38ppm, Pb: 0.22 ppm and Cd: 0.098 ppm or 10× of the ratio to developing rats exhibited a synergistic decrease in ex vivo mineralization of bone marrow stromal (osteoprogenitor) cells. MM group showed a dose-dependent attenuation in weight and axial lengths, and shortening of tibias at P-60. Furthermore, the growth plate was shortened, which was associated with shorter proliferative- and hypertrophic zones, decreased parathyroid hormone-related protein and Indian hedgehog expression in the chondrocytes, reduced primary- and secondary spongiosa, and hypomineralized osteoids - a major characteristic of osteomalacia. In addition, compared to the control, MM treated rats were clearly osteopenic based on BMD, micro-architecture, biomechanical strength, and particularly the biochemical profile, that suggested high turnover bone loss. Finally, in comparison to the control, the fracture healing ability of MM group was delayed and accompanied by inferior quality of the healed bone. Together, these data demonstrated that the mixture of As, Cd and Pb induced synergistic toxicity to developing skeleton thereby diminishing modeling-directed bone accrual, inducing osteopenia and dampening fracture healing. 23497860 Pigment production by a new thermotolerant microalga Coelastrella sp. F50. Microalgae are good crops to produce natural pigments because of their high growth rates. Tropical zones are better locations than temperate areas for microalgal cultivation because they have longer duration of daylight and more stable temperatures throughout the year, but the high temperatures pose a challenge to microalgal cultivation. A newly isolated thermotolerant microalga produces reddish pigments under environmental stress. Morphological and molecular evidence including meridional ribs on the cell wall, pigment production, and its 18S rDNA sequence suggests that this microalga belongs to the genus Coelastrella. Salt stress and high light intensity accelerated biosynthesis of the pigments, and significant quantities of oil accumulated as the cells experienced stress due to nutrient deficiency. This microalga could withstand temperature of 50°C for more than 8h, which is a necessary trait for outdoor cultivation in tropical areas. The pigments contain astaxanthin, lutein, canthaxanthin, and β-carotene as analysed by using HPLC. 23552101 Cis-silencing of PIP5K1B evidenced in Friedreich's ataxia patient cells results in cytoskeleton anomalies. Friedreich's ataxia (FRDA) is a progressive neurodegenerative disease characterized by ataxia, variously associating heart disease, diabetes mellitus and/or glucose intolerance. It results from intronic expansion of GAA triplet repeats at the FXN locus. Homozygous expansions cause silencing of the FXN gene and subsequent decreased expression of the encoded mitochondrial frataxin. Detailed analyses in fibroblasts and neuronal tissues from FRDA patients have revealed profound cytoskeleton anomalies. So far, however, the molecular mechanism underlying these cytoskeleton defects remains unknown. We show here that gene silencing spreads in cis over the PIP5K1B gene in cells from FRDA patients (circulating lymphocytes and primary fibroblasts), correlating with expanded GAA repeat size. PIP5K1B encodes phosphatidylinositol 4-phosphate 5-kinase β type I (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. Accordingly, loss of pip5k1β function in FRDA cells was accompanied by decreased PI(4,5)P2 levels and was shown instrumental for destabilization of the actin network and delayed cell spreading. Knockdown of PIP5K1B in control fibroblasts using shRNA reproduced abnormal actin cytoskeleton remodeling, whereas over-expression of PIP5K1B, but not FXN, suppressed this phenotype in FRDA cells. In addition to provide new insights into the consequences of the FXN gene expansion, these findings raise the question whether PIP5K1B silencing may contribute to the variable manifestation of this complex disease. 23584556 Gene identification and comparative molecular modeling of a Trypanosoma rangeli major surface protease. Trypanosoma rangeli is a hemoflagellate parasite which is able to infect humans. Distinct from Trypanosoma cruzi, the causative agent of Chagas disease, T. rangeli is non-pathogenic to the vertebrate host. The manner by which the T. rangeli interacts with the host is still unknown, but it certainly depends on the surface molecules. Major surface proteins (MSP) are GPI-anchored, zinc-dependent metalloproteases present in the surface of all trypanosomatids studied so far, which are implicated as virulence factors in pathogenic trypanosomatids, such as Leishmania spp and T. cruzi. The aims of this work were to generate the complete sequence of a T. rangeli MSP (TrMSP) gene and to determine the 3D-structure of the predicted protein by homology modeling. The plasmid bearing a complete copy of a TrMSP gene was completely sequenced and the predicted protein was modeled using Modeller software. Results indicate that TrMSP open reading frame (ORF) codes for a predicted 588 amino acid protein and shows all elements required for its posttranslational processing. Multiple sequence alignment of TrMSP with other trypanosomatids' MSPs showed an extensive conservation of the N-terminal and central regions and a more divergent C-terminal region. Leishmania major MSP (LmMSP), which had its crystal structure previously determined, has an overall 35 % identity with TrMSP. This identity allowed the comparative molecular modeling of TrMSP, which demonstrated a high degree of structural conservation between MSPs from other trypanosomatids (TrypMSPs). All modeled MSPs have a conserved folding pattern, apart from structural divergences in the C-domain and discrete differences of charge and topology in the catalytic cleft, and present the same geometry of the canonical HEXXH zinc-binding motif. The determination of surface charges of the molecules revealed that TrMSP is a predominantly positive protein, whereas LmMSP and Trypanosoma cruzi MSP (TcMSP) are negative proteins, suggesting that substrates recognized by TcMSP and LmMSP could not interact with TrMSP. Moreover, the comparison between TrMSP and TcMSP protein sequences has revealed 45 non-neutral amino acid substitutions, which can be further assessed through protein engineering. The characteristics of TrMSP could explain, at least in part, the lack of pathogenicity of T. rangeli to humans and point to the necessity of identifying the biological targets of this enzyme. 23445497 Drug-initiated ring-opening polymerization of O-carboxyanhydrides for the preparation of anticancer drug-poly(O-carboxyanhydride) nanoconjugates. We report a novel synthetic strategy of polymer-drug conjugates for nanoparticulate drug delivery: hydroxyl-containing drug (e.g., camptothecin, paclitaxel, doxorubicin and docetaxel) can initiate controlled polymerization of phenyl O-carboxyanhydride (Phe-OCA) to afford drug-poly(Phe-OCA) conjugated nanoparticles, termed drug-PheLA nanoconjugates (NCs). Our new NCs have well-controlled physicochemical properties, including high drug loading, quantitative drug loading efficiency, controlled particle size with narrow particle size distribution, and sustained drug release profile over days without "burst" release effect as observed in conventional polymer/drug encapsulates. Compared with polylactide NCs, the PheLA NCs have increased noncovalent hydrophobic interchain interactions and thereby result in remarkable stability in human serum with negligible particle aggregation. Such distinctive properties can reduce the premature disassembly of NCs upon dilution in the bloodstream and prolong NCs' in vivo circulation with the enhancement of intratumoral accumulation of NCs, which has a bearing on therapeutic effectiveness. 22940855 Quantum chemical investigation of the intra- and intermolecular proton transfer reactions and hydrogen bonding interactions in 4-amino-5-(2-hydroxyphenyl)-2H-1,2,4-triazole-3(4H)-thione. The intramolecular thione-thiol tautomerism and intermolecular double proton transfer reaction of the hydrogen-bonded thione and thiol dimers in the title triazole compound were studied at the B3LYP level of theory using 6-311++G(d,p) basis function. The influence of the solvent on the single and double proton transfer reactions was examined in three solvents (chloroform, methanol and water) using the polarizable continuum model (PCM) approximation. The computational results show that the thione tautomer is the most stable isomer with a very high tautomeric energy barrier both in the gas phase and in solution phase, indicating a quite disfavored process. The solvent effect is found to be sizable with increasing polarity. In the double proton transfer reaction, the thione dimer is found to be more stable than thiol dimer both in the gas phase and in solution phase. The energetic and thermodynamic parameters of the double proton transfer process show that the double proton exchange from thione dimer to thiol dimer is thermodynamically unfavored. However, the exchange from thiol dimer to thione dimer for the gas phase and water phase seems to be feasible with a low barrier height and with a negative value in enthalpy and free energy changes. In addition, the hydrogen bonding interactions were analyzed in the gas phase regarding their geometries and energies. It is found that all complex formations are enthalpically favored, and the stability of the H-bonds comes in the order of S1-H2···N2>N2-H2···S1>N3-H3B···O1. Finally, non-linear optical properties were carried out at the same calculation level in the gas phase. 23587422 Recent advances in malaria drug discovery. This digest covers some of the most relevant progress in malaria drug discovery published between 2010 and 2012. There is an urgent need to develop new antimalarial drugs. Such drugs can target the blood stage of the disease to alleviate the symptoms, the liver stage to prevent relapses, and the transmission stage to protect other humans. The pipeline for the blood stage is becoming robust, but this should not be a source of complacency, as the current therapies set a high standard. Drug discovery efforts directed towards the liver and transmission stages are in their infancy but are receiving increasing attention as targeting these stages could be instrumental in eradicating malaria. 23586519 Self-Seeding in One Dimension: A Route to Uniform Fiber-like Nanostructures from Block Copolymers with a Crystallizable Core-Forming Block. One-dimensional micelles formed by the self-assembly of crystalline-coil poly(ferrocenyldimethylsilane) (PFS) block copolymers exhibit self-seeding behavior when solutions of short micelle fragments are heated above a certain temperature and then cooled back to room temperature. In this process, a fraction of the fragments (the least crystalline fragments) dissolves at elevated temperature, but the dissolved polymer crystallizes onto the ends of the remaining seed fragments upon cooling. This process yields longer nanostructures (up to 1 μm) with uniform width (ca. 15 nm) and a narrow length distribution. In this paper, we describe a systematic investigation of factors that affect the self-seeding behavior of PFS block copolymer micelle fragments. For PI1000-PFS50 (the subscripts refer to the number average degree of polymerization) in decane, these factors include the presence of a good solvent (THF) for PFS and the effect of annealing the fragments prior to the self-seeding experiments. THF promoted the dissolution of the micelle fragments, while preannealing improved their stability. We also extended our experiments to other PFS block copolymers with different corona-forming blocks. These included PI637-PFS53 in decane, PFS60-PDMS660 in decane (PDMS = polydimethylsiloxane), and PFS30-P2VP300 in 2-propanol (P2VP = poly(2-vinylpyridine)). The most remarkable result of these experiments is our finding that the corona-forming chain plays an important role in affecting how the PFS chains crystallize in the core of the micelles and, subsequently, the range of temperatures over which the micelle fragments dissolve. Our results also show that self-seeding is a versatile approach to generate uniform PFS fiber-like nanostructures, and in principle, the method should be extendable to a wide variety of crystalline-coil block copolymers. 23567269 A Review of the "Omics" Approach to Biomarkers of Oxidative Stress in Oryza sativa. Physiological and ecological constraints that cause the slow growth and depleted production of crops have raised a major concern in the agriculture industry as they represent a possible threat of short food supply in the future. The key feature that regulates the stress signaling pathway is always related to the reactive oxygen species (ROS). The accumulation of ROS in plant cells would leave traces of biomarkers at the genome, proteome, and metabolome levels, which could be identified with the recent technological breakthrough coupled with improved performance of bioinformatics. This review highlights the recent breakthrough in molecular strategies (comprising transcriptomics, proteomics, and metabolomics) in identifying oxidative stress biomarkers and the arising opportunities and obstacles observed in research on biomarkers in rice. The major issue in incorporating bioinformatics to validate the biomarkers from different omic platforms for the use of rice-breeding programs is also discussed. The development of powerful techniques for identification of oxidative stress-related biomarkers and the integration of data from different disciplines shed light on the oxidative response pathways in plants. 23201003 Inhibitory effect of 1α,25-dihydroxyvitamin D₃ on excretion of JBP485 via organic anion transporters in rats. The aim of this study was to investigate the pharmacokinetic mechanism of interaction between JBP485 and 1α,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. Rats were injected intraperitoneally with 0.64 nmol/kg/day 1,25(OH)(2)D(3) in 1 ml/kg corn oil for 5 days. The plasma and urine concentrations of JBP485 after intravenous administration and the uptake of JBP485 in kidney slices in vitro were determined by liquid chromatography/tandem mass spectrometry. Quantitative polymerase chain reaction, western blotting, immunohistochemical analysis and immunofluorescence were used to determine the changes in the expression of organic anion transporter (Oat)1 and Oat3 in rat kidney in response to 1,25(OH)(2)D(3) treatment. The plasma concentrations and AUCs of JBP485 were significantly increased, while the renal clearance of JBP485 and uptake of JBP485 in kidney slices were significantly decreased after 1,25(OH)(2)D(3) treatment. These results confirmed that 1,25(OH)(2)D(3) inhibited renal excretion of JBP485. Moreover, 1,25(OH)(2)D(3) decreased expression of Oat1 and Oat3 in rat kidney. Our results are novel in demonstrating an interaction between JBP485 and 1,25(OH)(2)D(3) when they are co-administered. The mechanism of interaction between JBP485 and 1,25(OH)(2)D(3) could be explained at least in part by inhibitory effect of 1,25(OH)(2)D(3) on expression of Oats in rat kidney. 23339572 Chemical reactivity and biological activity of chalcones and other α,β-unsaturated carbonyl compounds. Abstract 1. Chalcones are structural analogues of benzalacetophenone (BAP). Several derivatives have been identified in plants and anticarcinogenic and anti-inflammatory properties were attributed to the compounds, probably related to their direct antioxidant activity or stimulatory effects on the expression of endogenous defence enzymes like hemeoxygenase-1 (HO-1). HO-1 expression is triggered by the Nrf2-Keap1 signalling pathway, initiated by the addition of chalcones to thiol groups of Keap1 via Michael-type reaction. 2. The present study used a model system estimating the reactivity of different synthetic chalcones and other α,β-unsaturated carbonyl compounds with thiols and compared the chemical reactivity with the biological activity, measured by HO-1 expression in human dermal fibroblasts. 3. Chemical reactivity with the thiol group of N-acetylcysteine was determined with 5,5'-dithiobis-(2-nitrobenzoic acid) and followed chemical principles of structure-reactivity relationship. Most reactive were sulforaphane, dimethylfumarate, chalcone 3 ((2E)-1-phenyl-3-pyrimidin-2-ylprop-2-en-1-one) and chalcone 7 (1,3-diphenylprop-2-yn-1-one). This result demonstrates that α,β-unsaturated carbonyl derivatives react with thiols differently. All compounds were also biologically active; however, expression of HO-1 was not only related to the chemical reactivity but also to the lipophilicity of the molecules which likely affected transmembrane uptake. Most efficient inducers of HO-1 expression were BAP, 4-hydroxynonenal and chalcone 1 (4-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]benzonitrile), chalcone 5 ((2E)-1-phenyl-3-[4-(trifluoromethyl)-phenyl]prop-2-en-1-one) and chalcone 7. 23558446 Inhibition of PDGFRα by MEDI-575 Reduces Tumor Growth and Stromal Fibroblast Content in a Model of Non-Small Cell Lung Cancer. Platelet-derived growth factor receptor alpha (PDGFRα) is a receptor tyrosine kinase that promotes cell survival and is expressed in both the tumor and the stromal components of human cancers. We have developed a fully human monoclonal antibody, MEDI-575, that selectively binds to human PDGFRα with high affinity, with no observable affinity for murine PDGFRα. To more fully characterize the role of PDGFRα in the regulation of tumor stroma, we evaluated the in vivo antitumor effects of MEDI-575 in tumor-bearing SCID mice and in genetically altered SCID mice expressing human PDGFRα in place of murine PDGFRα. We utilized the Calu-6 non-small cell lung cancer model, because it lacks an in vitro proliferative response to PDGFRα activation. Antitumor activity was observed when the study was performed in mice expressing the human receptor, but no activity was observed in the mice expressing the murine receptor. Immunohistological analysis of tumors from mice expressing human PDGFRα showed a highly significant reduction in stromal fibroblast content and only minor changes in tumor proliferative index in tumors exposed to MEDI-575 compared to the results seen in vehicle-treated tumors or tumors from mice expressing murine PDGFRα. Additional in vitro studies indicated that exposure of primary cancer-associated fibroblasts to MEDI-575 can directly affect proliferation and key signaling pathways in these cells. These results highlight the potential for observing antitumor activity with MEDI-575 through modulation of the stromal component of tumors and confirm that the PDGFRα pathway can play a role in maintaining a tumor microenvironment conducive to tumor growth. 23469781 Quinolines as chemotherapeutic agents for leishmaniasis. The development of leishmanicidal quinolines and their in vitro (promastigote and amastigote) and, where applicable, in vivo activities are reviewed. This survey provides a direct comparison of bioactivity across different species(e.g. L. donovani, L. amazonensis, L. chagasi, L infantum), and in different animal models (e.g. L. donovani Balb/c mice and L. donovani infected hamsters). The progress of selected quinolines through pre-clinical development and phase I/II trials, and the lead quinoline drugs sitamaquinine and Imiquimod, are discussed in conjunction with delivery systems and combination therapies. 23524189 Mesenchymal stem cells as delivery vehicle of porphyrin loaded nanoparticles: Effective photoinduced in vitro killing of osteosarcoma. Mesenchymal stem cells (MSC) have the unique ability to home and engraft in tumor stroma. These features render them potentially a very useful tool as targeted delivery vehicles which can deliver therapeutic drugs to the tumor stroma. In the present study, we investigate whether fluorescent core-shell PMMA nanoparticles (FNPs) post-loaded with a photosensitizer, namely meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS) and uploaded by MSC could trigger osteosarcoma (OS) cell death in vitro upon specific photoactivation. In co-culture studies we demonstrate using laser confocal microscopy and time lapse imaging, that only after laser irradiation MSC loaded with photosensitizer-coated fluorescent NPs (TPPS@FNPs) undergo cell death and release reactive oxygen species (ROS) which are sufficient to trigger cell death of all OS cells in the culture. These results encourage further studies aimed at proving the efficacy of this novel tri-component system for PDT applications. 23471440 Exposure to phototoxic NSAIDs and quinolones is associated with an increased risk of melanoma. PURPOSE: Ultraviolet radiation exposure is the most important exogenous risk factor for cutaneous malignancies. It is possible that phototoxic drugs promote the development of cutaneous melanoma (CM) by intensifying the effect of ultraviolet light on the skin. We investigated the association between the use of common systemic phototoxic drugs and development of CM. METHODS: This study was a case-control study in a Dutch population-based cohort. The drug dispensing data was obtained from PHARMO, a Dutch drug dispensing and hospital admissions registry, and linked to PALGA, the nationwide pathology network of the Netherlands. The cases were patients diagnosed with pathologically confirmed primary CM between 1991 and 2004. Controls were sampled from the PHARMO population. Exposure to systemic phototoxic drugs was measured and included antimicrobial agents, diuretics, antipsychotic drugs, antidiabetic drugs, cardiac drugs, antimalarials and nonsteroidal anti-inflammatory drugs (NSAIDs). A multivariate conditional logistic regression analysis was performed to study the association between exposure to phototoxic drugs and CM. RESULTS: The study population included 1,318 cases and 6,786 controls. Any phototoxic drug during the study period was dispensed for 46 % of the cases and 43 % of the controls (p = 0.012). The use of quinolones [odds ratio (OR) 1.33, 95 % confidence interval (CI) 1.01-1.76] and propionic acid derivative NSAIDs (OR 1.33, 95 % CI 1.14-1.54) had a positive association with CM. CONCLUSIONS: Our study shows that the use of phototoxic drugs is associated with an increased risk of developing CM. Even a short-term use of phototoxic quinolones and propionic acid derivative NSAIDs may increase the risk for CM. Patient education to promote sun-protective behaviour is essential to avoid immediate adverse effects and possible long-term effects of phototoxic drugs. 23594296 Investigation of aqueous stability of taxol in different release media. Abstract In the present study, the aqueous stability of taxol in different aqueous media and immiscible aqueous/organic systems at 37 °C was investigated. The aqueous media included phosphate buffered saline (PBS) and PBS containing 10% methanol, 10% ethanol, 10% hydroxypropyl β-cyclodextrin (HP-βCD), 1% sodium citrate and 1% Tween 80. The immiscible systems consisted of PBS/octanol, PBS/dichloromethane, PBS/chloroform and PBS/ethyl acetate. The concentrations of taxol and related derivatives in each of the media were determined through the high-performance liquid chromatography assay. Results showed that hydrolysis and epimerization were two major types of degradation for taxol in the aqueous media starting from the initial hours of contact (6 hours). Addition of Tween 80 to PBS moderately increased the aqueous stability of taxol. As well, using PBS containing 10% HP-βCD inhibited the taxol hydrolysis, while epimerization still in process. In the case of immiscible systems, except for PBS/ethyl acetate system, no evidences of taxol hydrolysis were observed. Meanwhile, epimerization of taxol in PBS/dichloromethane and PBS/chloroform systems underwent due to the ability of C-Cl bonds to form hydrogen bonding with the hydroxyl group of C7 of taxol. 23529898 Multifunctional Hybrid Materials From Poly(3-Hydroxybutyrate), TiO2 Nanoparticles, and Chitosan Oligomers by Combining Electrospinning/Electrospraying and Impregnation. Several types of fibrous material containing poly(3-hydroxybutyrate) (PHB), nanosized TiO2 -anatase (nanoTiO2 ), and chitosan oligomers are prepared by combining the electrospinning, electrospraying, and impregnation techniques. Simultaneous electrospinning/electrospraying provides uniform distribution of electrosprayed nanoTiO2 along the PHB fibers and throughout the mat. Hybrid materials of different design manifest excellent photocatalytic activity, even after repeated use. They exhibit high bactericidal activity against Escherichia coli. In addition, the fibrous scaffolds are compatible with human mesenchymal stem cells and provide a favorable environment for their development. 23351040 How do metabolites differ from their parent molecules and how are they excreted? Understanding which physicochemical properties, or property distributions, are favorable for successful design and development of drugs, nutritional supplements, cosmetics, and agrochemicals is of great importance. In this study we have analyzed molecules from three distinct chemical spaces (i) approved drugs, (ii) human metabolites, and (iii) traditional Chinese medicine (TCM) to investigate four aspects determining the disposition of small organic molecules. First, we examined the physicochemical properties of these three classes of molecules and identified characteristic features resulting from their distinctive biological functions. For example, human metabolites and TCM molecules can be larger and more hydrophobic than drugs, which makes them less likely to cross membranes. We then quantified the shifts in physicochemical property space induced by metabolism from a holistic perspective by analyzing a data set of several thousand experimentally observed metabolic trees. Results show how the metabolic system aims to retain nutrients/micronutrients while facilitating a rapid elimination of xenobiotics. In the third part we compared these global shifts with the contributions made by individual metabolic reactions. For better resolution, all reactions were classified into phase I and phase II biotransformations. Interestingly, not all metabolic reactions lead to more hydrophilic molecules. We were able to identify biotransformations leading to an increase of logP by more than one log unit, which could be used for the design of drugs with enhanced efficacy. The study closes with the analysis of the physicochemical properties of metabolites found in the bile, faeces, and urine. Metabolites in the bile can be large and are often negatively charged. Molecules with molecular weight >500 Da are rarely found in the urine, and most of these large molecules are charged phase II conjugates. 23383594 An adsorbent performance indicator as a first step evaluation of novel sorbents for gas separations: application to metal-organic frameworks. An adsorbent performance indicator (API) is proposed in an effort to initially highlight porous materials of potential interest for PSA separation processes. This expression takes into account working capacities, selectivities, and adsorption energies and additionally uses weighting factors to reflect the specific requirements of a given process. To demonstrate the applicability of the API, we have performed the adsorption of carbon dioxide and methane at room temperature on a number of metal-organic frameworks, a zeolite and a molecular sieve carbon. The API is calculated for two different CO2/CH4 separation case scenarios: "bulk separation" and "natural gas purification". This comparison highlights how the API can be more versatile than previously proposed comparison factors for an initial indication of potential adsorbent performance. 23104245 Comparative study of equimolar doses of gamma-hydroxybutyrate (GHB), 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) on catalepsy after acute and chronic administration. Gamma-hydroxybutyrate (GHB), and its precursors 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) are known drugs of abuse. The ability of acute and chronic administration of equimolar doses of GHB (200mg/kg), 1,4-BD (174mg/kg) and GBL (166mg/kg) to produce catalepsy in male Swiss Webster mice was examined. GHB, 1,4-BD, GBL produced catalepsy when injected acutely. Drug treatment was then continued for 14days. Tolerance development was determined on days 6, 14, and challenged with a higher dose on day 15 in those chronically pretreated mice, and compared with naïve mice. Chronic GHB produced tolerance to catalepsy, as evidenced from area under the curve (AUC) of catalepsy versus time (min-sec) on days 6 (678±254), 14 (272±247), which were less than those on day 1 (1923±269). However, less tolerance was seen from GBL or 1,4-BD, as AUCs on days 6 and 14 were not significantly lower than that of day 1. In conclusion, although equimolar doses were used, expecting similar levels of GHB in the body, 1,4-BD and GBL shared only some of the in vivo effects of GHB. The rate of metabolic conversion of 1,4-BD and GBL into GHB might be responsible for the differences in the tolerance development to these drugs. 23122167 Schisarisanlactones A and B: a new class of nortriterpenoids from the fruits of Schisandra arisanensis. Two novel highly oxygenated nortriterpenoids, schisarisanlactones A (1) and B (2), have been isolated from the fruits of Schisandra arisanensis, an endemic plant of Taiwan. Compounds 1 and 2 possess an unprecedented 5/5/7/5/5-fused pentacyclic ring system. The structures of both compounds were determined on the basis of spectroscopic analyses, especially 2D NMR and MS. A plausible biogenetic pathway of 1 was proposed. Schisarisanlactone A (1) showed significant anti-HIV activity. 23430000 Inflammation and immune system interactions in atherosclerosis. Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for 16.7 million deaths each year. The underlying cause of the majority of CVD is atherosclerosis. In the past, atherosclerosis was considered to be the result of passive lipid accumulation in the vessel wall. Today's picture is far more complex. Atherosclerosis is considered a chronic inflammatory disease that results in the formation of plaques in large and mid-sized arteries. Both cells of the innate and the adaptive immune system play a crucial role in its pathogenesis. By transforming immune cells into pro- and anti-inflammatory chemokine- and cytokine-producing units, and by guiding the interactions between the different immune cells, the immune system decisively influences the propensity of a given plaque to rupture and cause clinical symptoms like myocardial infarction and stroke. In this review, we give an overview on the newest insights in the role of different immune cells and subtypes in atherosclerosis. 22614018 Promotion of DNA repair by nuclear IKKβ phosphorylation of ATM in response to genotoxic stimuli. Ataxia-telangiectasia mutated (ATM) is one of the key molecules involved in the cellular response to DNA damage. A portion of activated ATM is exported from the nucleus into the cytoplasm, where it activates the I kappa B kinase/nuclear factor kappa B (IKK/NF-κB) signaling pathway. It has been thought that activated IKKβ, which is a critical kinase for NF-κB activation, generally resides in the cytoplasm and phosphorylates cytoplasmic downstream molecules, such as IκBα. Here, we identified a new role for IKKβ during the response to DNA damage. ATM phosphorylation in response to alkylating agents consisted of two phases: the early phase (up to 3 h) and late phase (after 6 h). A portion of the activated IKKβ generated during the DNA damage response was found to translocate into the nucleus and directly phosphorylate ATM in the late phase. Furthermore, the phosphorylation of ATM by nuclear IKKβ was suggested to promote DNA repair. In parallel, activated IKKβ induced classical NF-κB activation and was involved in anti-apoptosis. Our findings define the function of IKKβ during the response to DNA damage, which promotes cell survival and DNA repair, and maintains cellular homeostasis. 23393217 Nurse-Community Health Worker Team Improves Diabetes Care in American Samoa: Results of a randomized controlled trial. OBJECTIVETo evaluate the effectiveness of a culturally adapted, primary care-based nurse-community health worker (CHW) team intervention to support diabetes self-management on diabetes control and other biologic measures.RESEARCH DESIGN AND METHODSTwo hundred sixty-eight Samoan participants with type 2 diabetes were recruited from a community health center in American Samoa and were randomly assigned by village clusters to the nurse-CHW team intervention or to a wait-list control group that received usual care.RESULTSParticipants had a mean age of 55 years, 62% were female, mean years of education were 12.5 years, 41% were employed, and mean HbA(1c) was 9.8% at baseline. At 12 months, mean HbA(1c) was significantly lower among CHW participants, compared with usual care, after adjusting for confounders (b = -0.53; SE = 0.21; P = 0.03). The odds of making a clinically significant improvement in HbA(1c) of at least 0.5% in the CHW group was twice the odds in the usual care group after controlling for confounders (P = 0.05). There were no significant differences in blood pressure, weight, or waist circumference at 12 months between groups.CONCLUSIONSA culturally adapted nurse-CHW team intervention was able to significantly improve diabetes control in the U.S. Territory of American Samoa. This represents an important translation of an evidence-based model to a high-risk population and a resource-poor setting. 23327794 Alkaloids from Microcos paniculata with cytotoxic and nicotinic receptor antagonistic activities. Microcos paniculata is a large shrub or small tree that grows in several countries in South and Southeast Asia. In the present study, three new piperidine alkaloids, microgrewiapines A-C (1-3), as well as three known compounds, inclusive of microcosamine A (4), 7'-(3',4'-dihydroxyphenyl)-N-[4-methoxyphenyl)ethyl]propenamide (5), and liriodenine (6), were isolated from cytotoxic fractions of the separate chloroform-soluble extracts of the stem bark, branches, and leaves of M. paniculata. Compounds 1-6 and 1a (microgrewiapine A 3-acetate) showed a range of cytotoxicity values against the HT-29 human colon cancer cell line. When evaluated for their effects on human α3β4 or α4β2 nicotinic acetylcholine receptors (nAChRs), several of these compounds were shown to be active as nAChR antagonists. As a result of this study, microgrewiapine A (1) was found to be a selective cytotoxic agent for colon cancer cells over normal colon cells and to exhibit nicotinic receptor antagonistic activity for both the hα3β4 and hα4β2 receptor subtypes. 23517379 Generating Long Supramolecular Pathways with a Continuous Density of States by Physically Linking Conjugated Molecules via Their End Groups. Self-assembly of conjugated 2,5-dialkoxy-phenylene-thienylene-based oligomers on epitaxial monolayer graphene was studied in ultrahigh vacuum by low-temperature scanning tunneling microscopy (STM). The formation of long one-dimensional (1D) supramolecular chain-like structures has been observed, associated to a physical linking of their ends which involved the rotation of the end thiophene rings in order to allow π-π stacking of these end-groups. dI/dV maps taken at an energy corresponding to the excited states showed a continuous electronic density of states, which tentatively suggests that within such molecular chains conjugation of electrons is preserved even across physically linked molecules. Thus, in a self-organization process conjugation may be extended by appropriately adapting conformations of neighboring molecules. Our STM results on such self-organized end-linked molecules potentially represent a direct visualization of J-aggregates. 23328127 Allele-Specific Transcriptional Activity at Type 2 Diabetes-Associated Single Nucleotide Polymorphisms in Regions of Pancreatic Islet Open Chromatin at the JAZF1 Locus. Translation of noncoding common variant association signals into meaningful molecular and biological mechanisms explaining disease susceptibility remains challenging. For the type 2 diabetes association signal in JAZF1 intron 1, we hypothesized that the underlying risk variants have cis-regulatory effects in islets or other type 2 diabetes-relevant cell types. We used maps of experimentally predicted open chromatin regions to prioritize variants for functional follow-up studies of transcriptional activity. Twelve regions containing type 2 diabetes-associated variants were tested for enhancer activity in 832/13 and MIN6 insulinoma cells. Three regions exhibited enhancer activity and only rs1635852 displayed allelic differences in enhancer activity; the type 2 diabetes risk allele T showed lower transcriptional activity than the nonrisk allele C. This risk allele showed increased binding to protein complexes, suggesting that it functions as part of a transcriptional repressor complex. We applied DNA affinity capture to identify factors in the complex and determined that the risk allele preferentially binds the pancreatic master regulator PDX1. These data suggest that the rs1635852 region in JAZF1 intron 1 is part of a cis-regulatory complex and that maps of open chromatin are useful to guide identification of variants with allelic differences in regulatory activity at type 2 diabetes loci. 22865292 The R740S mutation in the V-ATPase a3 subunit increases lysosomal pH, impairs NFATc1 translocation, and decreases in vitro osteoclastogenesis. Vacuolar H(+) -ATPase (V-ATPase), a multisubunit enzyme located at the ruffled border and in lysosomes of osteoclasts, is necessary for bone resorption. We previously showed that heterozygous mice with an R740S mutation in the a3 subunit of V-ATPase (+/R740S) have mild osteopetrosis resulting from an ∼90% reduction in proton translocation across osteoclast membranes. Here we show that lysosomal pH is also higher in +/R740S compared with wild-type (+/+) osteoclasts. Both osteoclast number and size were decreased in cultures of +/R740S compared with +/+ bone marrow cells, with concomitant decreased expression of key osteoclast markers (TRAP, cathepsin K, OSCAR, DC-STAMP, and NFATc1), suggesting that low lysosomal pH plays an important role in osteoclastogenesis. To elucidate the molecular mechanism of this inhibition, NFATc1 activation was assessed. NFATc1 nuclear translocation was significantly reduced in +/R740S compared with +/+ cells; however, this was not because of impaired enzymatic activity of calcineurin, the phosphatase responsible for NFATc1 dephosphorylation. Protein and RNA expression levels of regulator of calcineurin 1 (RCAN1), an endogenous inhibitor of NFATc1 activation and a protein degraded in lysosomes, were not significantly different between +/R740S and +/+ osteoclasts, but the RCAN1/NFATc1 ratio was significantly higher in +/R740S versus +/+ cells. The lysosomal inhibitor chloroquine significantly increased RCAN1 accumulation in +/+ cells, consistent with the hypothesis that higher lysosomal pH impairs RCAN1 degradation, leading to a higher RCAN1/NFATc1 ratio and consequently NFATc1 inhibition. Our data indicate that increased lysosomal pH in osteoclasts leads to decreased NFATc1 signaling and nuclear translocation, resulting in a cell autonomous impairment of osteoclastogenesis in vitro. 23293964 Single-molecule force spectroscopy identifies a small cold shock protein as being mechanically robust. Single-molecule force spectroscopy has emerged as a powerful approach to examine the stability and dynamics of single proteins. We have completed force extension experiments on the small cold shock protein B from Thermotoga maritima, using a specially constructed chimeric polyprotein. The protein's simple topology, which is distinct from the mechanically well-characterized β-grasp and immunoglobulin (Ig)-like folds, in addition to the wide range of structural homologues resulting from its ancient origin, provides an attractive model protein for single-molecule force spectroscopy studies. We have determined that the protein has mechanical stability, unfolding at greater than 70 pN at a pulling velocity of 100 nm s(-1). We reveal features of the unfolding energy landscape by measuring the dependence of the mechanical stability on pulling velocity, in combination with Monte Carlo simulations. We show that the cold shock protein has mechanically robust, yet malleable, features that may be important in providing the protein with stability and flexibility to function over a range of environmental conditions. These results provide insights into the relationship between the secondary structure and topology of a protein and its mechanical strength. This lays the foundation for the investigation of the effects of changes in environmental conditions on the mechanical and dynamic properties of cold shock proteins. 23438106 Consequences of Membrane Topography. The surface of mammalian cells is neither smooth nor flat and cells have several times more plasma membrane than the minimum area required to accommodate their shape. We discuss the biological function of this apparent excess membrane that allows the cells to migrate, undergo shape changes and probably plays a role in signal transduction. Methods for studying membrane folding and topography; atomic force microscopy, scanning ion conductance microscopy, fluorescence polarisation microscopy and linear dichroism, are described and evaluated. Membrane folding and topography is frequently ignored when interpreting microscopy data. This has resulted in several misconceptions for instance regarding colocalisation, membrane organisation and molecular clustering. We suggest simple ways to avoid these pitfalls and invoke Occam's razor - that simple explanations are preferable to complex ones. Topography, i. e. deviations from a smooth surface, should always be ruled out as the cause of anomalous data before other explanations are presented. © 2013 The Authors Journal compilation © 2013 FEBS. 22846225 Matching biochemical and functional efficacies confirm ZIP as a potent competitive inhibitor of PKMζ in neurons. PKMζ is an autonomously active, atypical protein kinase C (aPKC) isoform that is both necessary and sufficient for maintaining long-term potentiation (LTP) and long-term memory. The myristoylated ζ-pseudosubstrate peptide, ZIP, potently inhibits PKMζ biochemically in vitro, within cultured cells, and within neurons in hippocampal slices, and reverses LTP maintenance and erases long-term memory storage. A recent study (Wu-Zhang et al., 2012), however, suggested ZIP was not effective on a PKMζ fusion protein overexpressed in cultured cells. Chelerythrine, a redox-sensitive PKC inhibitor that inhibits PKMζ and disrupts LTP maintenance and memory storage, was also reported by Wu-Zhang et al. (2012) not to inhibit the expressed PKMζ fusion protein. However, the efficacy of inhibitors on endogenous enzymes in cells may not be adequately assessed in expression systems in which levels of expression of exogenous enzymes greatly exceed those of endogenous enzymes. Thus, we show, biochemically, that when PKMζ reaches a level beyond that necessary for substrate phosphorylation such that much of the enzyme is excess or 'spare' kinase, ZIP and chelerythrine do not effectively block substrate phosphorylation. We also show that the cellular overexpression techniques used by Wu-Zhang et al. (2012) increase kinase levels ~30-40 fold above normal levels in transfected cells. Using a mathematical model we show that at such level of overexpression, standard concentrations of inhibitor should have no noticeable effect. Furthermore, we demonstrate the standard concentrations of ZIP, but not scrambled ZIP, inhibit the ability of PKMζ to potentiate AMPAR responses at postsynaptic sites, the physiological function of the kinase. Wu-Zhang et al. (2012) had also claimed that staurosporine, a general kinase inhibitor that does not effectively inhibit PKMζ biochemically in vitro, nonetheless indirectly blocked the PKMζ fusion protein overexpressed in cultured cells by inhibiting phosphoinositide-dependent protein kinase-1 (PDK1). However, here we show that staurosporine does not affect PDK1 phosphorylation of the endogenous PKMζ in hippocampal slices. Thus, the biochemical in vitro effects of PKMζ inhibitors correspond with their intracellular effects, and ZIP and chelerythrine, together with scrambled ZIP and staurosporine as controls, are effective tools to examine the function of PKMζ in neurons. This article is part of a Special Issue entitled 'Cognitive Enhancers'. 23638621 A prospective, randomised, investigator-blind, controlled, clinical study on the clinical efficacy and tolerability of two highly purified hMG preparations administered subcutaneously in women undergoing IVF. Abstract The aim of this multicentre, prospective, randomised, investigator blind, controlled clinical trial was to evaluate the clinical efficacy and tolerability of a highly purified human menopausal gonadotrophin (hMG) preparation (Merional-HG) when administered to patients undergoing controlled ovarian stimulation (COS) for in-vitro fertilisation (IVF) procedure enrolled in hospital departments. One hundred fifty-seven patients were randomised in two parallel groups: 78 started COS with Merional-HG and 79 with Menopur. Results of the study showed that both highly purified hMG preparations were equivalent in terms of number of oocytes retrieved (primary endpoint: 8.8 ± 3.9 versus 8.4 ± 3.8, p = 0.54). In the patients treated with Merional-HG, we observed a higher occurrence of mature oocytes (78.3% versus 71.4%, p = 0.005) and a reduced quantity of gonadotrophins administered per cycle (2.556 ± 636 IU versus 2.969 ± 855 IU, p < 0.001). Fertilisation, cleavage, implantation rates and the number of positive β-human chorionic gonadotrophin (hCG; pregnancy) tests and the clinical pregnancy rate were comparable in the two groups. Both treatments were well tolerated. In conclusion, the results of this study support the efficacy and safety of Merional-HG administered subcutaneously for assisted reproduction techniques. Efficiency of Merional-HG appears to be higher due to reduced quantity of drug used and the higher yield of mature oocytes retrieved. 23395663 Lactose substituted zinc phthalocyanine: a near infrared fluorescence imaging probe for liver cancer targeting. A near infrared fluorescence probe, lactose substituted zinc phthalocyanine, [2,9(10),16(17),23(24)-tetrakis((1-(β-d-lactose-2-yl)-1H-1,2,3-triazol-4-yl)methoxyl)phthalocyaninato] zinc(II), was synthesized via click reaction. Structural characterization and optical experiment demonstrated its excellent biocompatibility and fluorescence imaging ability. Near infrared fluorescence imaging in vivo for liver cancer, lung cancer and melanoma cancer with tumor bearing nude mice as models demonstrated that lactose substituted zinc phthalocyanine has specifically targeting ability to liver cancer while no targeting to lung cancer or melanoma, which implied its potential in liver cancer diagnosis as a near infrared optical probe. 22966070 Tub has a key role in insulin and leptin signaling and action in vivo in hypothalamic nuclei. Mutation of tub gene in mice induces obesity, suggesting that tub could be an important regulator of energy balance. In the current study, we investigated whether insulin, leptin, and obesity can modulate Tub in vivo in hypothalamic nuclei, and we investigated possible consequences on energy balance, neuropeptide expression, and hepatic glucose metabolism. Food intake, metabolic characteristics, signaling proteins, and neuropeptide expression were measured in response to fasting and refeeding, intracerebroventricular insulin and leptin, and Tub antisense oligonucleotide (ASO). Tub tyrosine phosphorylation (Tub-p-tyr) is modulated by nutritional status. Tub is a substrate of insulin receptor tyrosine kinase (IRTK) and leptin receptor (LEPR)-Janus kinase 2 (JAK2) in hypothalamic nuclei. After leptin or insulin stimulation, Tub translocates to the nucleus. Inhibition of Tub expression in hypothalamus by ASO increased food intake, fasting blood glucose, and hepatic glucose output, decreased O(2) consumption, and blunted the effect of insulin or leptin on proopiomelanocortin, thyroid-releasing hormone, melanin-concentrating hormone, and orexin expression. In hypothalamus of mice administered a high-fat diet, there is a reduction in leptin and insulin-induced Tub-p-tyr and nuclear translocation, which is reversed by reducing protein tyrosine phosphatase 1B expression. These results indicate that Tub has a key role in the control of insulin and leptin effects on food intake, and the modulation of Tub may contribute to insulin and leptin resistance in DIO mice. 23154865 Enhanced heterodimerization of Bax by Bcl-2 mutants improves irradiated cell survival. B Cell Lymphoma-2 (Bcl-2) protein suppresses ionizing radiation-induced apoptosis in hemato-lymphoid system. To enhance the survival of irradiated cells, we have compared the effects and mechanism of Bcl-2 and its functional variants, D34A (caspase-3 resistant) and S70E (mimics phosphorylation on S70). Bcl-2 and its mutants were transfected into hematopoietic cell line and assessed for cell survival, clonogenicity and cell cycle perturbations upon exposure to ionizing radiation. The electrostatic potential of BH3 cleft of Bcl-2/mutants and their heterodimerization with Bcl-2 associated X protein (Bax) were computationally evaluated. Correspondingly, these results were verified by co-immunoprecipitation and western blotting. The mutants afford higher radioprotective effect than Bcl-2 in apoptotic and clonogenic assays at D(0) (radiation dose at which 37 % cell survival was observed). The computational and functional analysis indicates that mutants have higher propensity to neutralize Bax protein by heterodimerization and have increased caspase-9 suppression capability, which is responsible for enhanced survival. This study implies potential of Bcl-2 mutants or their chemical/peptide mimics to elicit radioprotective effect in cells exposed to radiation. 23566269 4-Hydroxypyridazin-3(2H)-one Derivatives as Novel d-Amino Acid Oxidase Inhibitors. d-Amino acid oxidase (DAAO) catalyzes the oxidation of d-amino acids including d-serine, a coagonist of the N-methyl-d-aspartate receptor. We identified a series of 4-hydroxypyridazin-3(2H)-one derivatives as novel DAAO inhibitors with high potency and substantial cell permeability using fragment-based drug design. Comparisons of complex structures deposited in the Protein Data Bank as well as those determined with in-house fragment hits revealed that a hydrophobic subpocket was formed perpendicular to the flavin ring by flipping Tyr224 in a ligand-dependent manner. We investigated the ability of the initial fragment hit, 3-hydroxy-pyridine-2(1H)-one, to fill this subpocket with the aid of complex structure information. 3-Hydroxy-5-(2-phenylethyl)pyridine-2(1H)-one exhibited the predicted binding mode and demonstrated high inhibitory activity for human DAAO in enzyme- and cell-based assays. We further designed and synthesized 4-hydroxypyridazin-3(2H)-one derivatives, which are equivalent to the 3-hydroxy-pyridine-2(1H)-one series but lack cell toxicity. 6-[2-(3,5-Difluorophenyl)ethyl]-4-hydroxypyridazin-3(2H)-one was found to be effective against MK-801-induced cognitive deficit in the Y-maze. 23349498 A link between GIP and osteopontin in adipose tissue and insulin resistance. Low grade inflammation in obesity is associated with accumulation of the macrophagederived cytokine osteopontin in adipose tissue and induction of local as well as systemic insulin resistance. Since GIP (glucose-dependent insulinotropic polypeptide) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate osteopontin (OPN) expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher in adipose tissue of obese individuals (0.13±}0.04 vs 0.04±}0.01, P<0.05) and correlated inversely with measures of insulin sensitivity (r=-0.24, P=0.001). A common variant of the GIP receptor (GIPR) (rs10423928) gene was associated with lower amount of the exon 9 containing isoform required for transmembrane activity. Carriers of the A-allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone, but also as a trigger of inflammation and insulin resistance in adipose tissue. Carriers of GIPR rs10423928 A-allele showed protective properties via reduced GIP effects. Identification of this unprecedented link between GIP and OPN in adipose tissue might open new avenues for therapeutic interventions. 23266311 The venom optimization hypothesis revisited. Animal venoms are complex chemical mixtures that typically contain hundreds of proteins and non-proteinaceous compounds, resulting in a potent weapon for prey immobilization and predator deterrence. However, because venoms are protein-rich, they come with a high metabolic price tag. The metabolic cost of venom is sufficiently high to result in secondary loss of venom whenever its use becomes non-essential to survival of the animal. The high metabolic cost of venom leads to the prediction that venomous animals may have evolved strategies for minimizing venom expenditure. Indeed, various behaviors have been identified that appear consistent with frugality of venom use. This has led to formulation of the "venom optimization hypothesis" (Wigger et al. (2002) Toxicon 40, 749-752), also known as "venom metering", which postulates that venom is metabolically expensive and therefore used frugally through behavioral control. Here, we review the available data concerning economy of venom use by animals with either ancient or more recently evolved venom systems. We conclude that the convergent nature of the evidence in multiple taxa strongly suggests the existence of evolutionary pressures favoring frugal use of venom. However, there remains an unresolved dichotomy between this economy of venom use and the lavish biochemical complexity of venom, which includes a high degree of functional redundancy. We discuss the evidence for biochemical optimization of venom as a means of resolving this conundrum. 23295229 Fluorescence lifetime analysis and effect of magnesium ions on binding of NADH to human aldehyde dehydrogenase 1. Aldehyde dehydrogenase 1 (ALDH1A1) catalyzes the oxidation of toxic aldehydes to carboxylic acids. Physiologic levels of Mg(2+) ions decrease ALDH1 activity in part by increasing NADH binding affinity to the enzyme. By using time-resolved fluorescence spectroscopy, we have resolved the fluorescent lifetimes (τ) of free NADH in solution (τ=0.4 ns) and two enzyme-bound NADH states (τ=2.0 ns and τ=7.7 ns). We used this technique to investigate the effects of Mg(2+) ions on the ALDH1A1-NADH binding characteristics and enzyme catalysis. From the resolved free and bound NADH fluorescence signatures, the KD values for both NADH conformations in ALDH1A1 ranged from about 24 μM to 1 μM for Mg(2+) ion concentrations of 0-6000 μM, respectively. The rate constants for dissociation of the enzyme-NADH complex ranged from 0.03 s(-1) (6000 μM Mg(2+)) to 0.30s(-1) (0 μM Mg(2+)) as determined by addition of excess NAD(+) to prevent re-association of NADH and resolving the real-time NADH fluorescence signal. During the initial reaction of enzyme with NAD(+) and butyraldehyde, there was an immediate rise in the NADH fluorescence, due to the formation of bound NADH complexes, with a constant steady-state rate of production of free NADH. As the Mg(2+) ion concentration was increased, there was a consistent decrease of the enzyme catalytic turnover from 0.31 s(-1) (0 μM Mg(2+)) to 0.050 s(-1) (6000 μM Mg(2+)) and a distinct shift in steady-state conformational population from one that favors the ALDH1-NADH complex with the shorter fluorescence lifetime (33% excess) in the absence of magnesium ion to one that favors the ALDH1-NADH complex with the longer fluorescence lifetime (13% excess) at 6000 μM Mg(2+). This shift in conformational population at higher Mg(2+) ion concentrations and to lower enzyme activity may be due to longer residence time of the NADH in the ALDH1 pocket. The results from monitoring enzyme catalysis in the absence of magnesium suggests that the ALDH1-NADH complex with the shorter fluorescence lifetime is the form initially produced, and the complex with the longer fluorescence lifetime is produced through isomerization. 23382380 Reconstitution of homomeric GluA2(flop) receptors in supported lipid membranes: functional and structural properties. AMPA receptors (AMPARs) are glutamate-gated ion channels ubiquitous in the vertebrate central nervous system, where they mediate fast excitatory neurotransmission and act as molecular determinants of memory formation and learning. Together with detailed analyses of individual AMPAR domains, structural studies of full-length AMPARs by electron microscopy and x-ray crystallography have provided important insights into channel assembly and function. However, the correlation between the structure and functional states of the channel remains ambiguous particularly because these functional states can be assessed only with the receptor bound within an intact lipid bilayer. To provide a basis for investigating AMPAR structure in a membrane environment, we developed an optimized reconstitution protocol using a receptor whose structure has previously been characterized by electron microscopy. Single-channel recordings of reconstituted homomeric GluA2(flop) receptors recapitulate key electrophysiological parameters of the channels expressed in native cellular membranes. Atomic force microscopy studies of the reconstituted samples provide high-resolution images of membrane-embedded full-length AMPARs at densities comparable to those in postsynaptic membranes. The data demonstrate the effect of protein density on conformational flexibility and dimensions of the receptors and provide the first structural characterization of functional membrane-embedded AMPARs, thus laying the foundation for correlated structure-function analyses of the predominant mediators of excitatory synaptic signals in the brain. 23194543 Effect of dry heating with ionic gums on physicochemical properties of starch. Corn starch, potato starch, pea starch were impregnated with ionic gums (sodium alginate, CMC, and xanthan, 1% based on starch solids) and heat-treated in a dry state for 0, 2, or 4 h at 130°C. Effects of the dry heating on paste viscosity (RVA), microstructure and thermal properties were examined. Dry heat treatment with ionic gums reduced the pasting temperature of the three starches. Heating with xanthan increased the paste viscosity of corn and potato starch. With heat treatment, the paste viscosity of all the starch-sodium alginate mixtures decreased. Heating with CMC increased the paste viscosity of potato starch, but decreased that of corn and pea starch. After dry-heating, To, Tp and Tc of potato starch with ionic gums decreased significantly. SEM of potato starch with CMC showed that the gel structure got compacter after drying-heating. Heat treatment obviously improved the functional properties of the three starches. 22614019 The Grainyhead transcription factor Grhl3/Get1 suppresses miR-21 expression and tumorigenesis in skin: modulation of the miR-21 target MSH2 by RNA-binding protein DND1. Epidermal differentiation and stratification, crucial for barrier formation, are regulated by a complex interplay of transcription factors, including the evolutionarily conserved Grainyhead-like 3 (Grhl3/Get1); Grhl3-deleted mice exhibit impaired epidermal differentiation and decreased expression of multiple differentiation genes. To test whether Grhl3 regulates epidermal genes indirectly by controlling the expression of specific microRNAs (miRs), we performed miR profiling and identified 11 miRs that are differentially regulated in Grhl3(-/-) skin, one of which is miR-21, previously shown to be upregulated in diseased skin, including in psoriasis and squamous cell skin cancer. We found that miR-21 is normally expressed in the post-mitotic suprabasal layers of the epidermis, overlapping with Grhl3. The miR-21 promoter is bound and repressed by Grhl3 indicating that these two factors are involved in a regulatory loop maintaining homeostasis in the epidermis. Although miR-21 overexpression in normal keratinocytes had mild effects on the expression of several known miR-21 targets, an enhanced downregulation of the miR-21 tumor-related targets, including MSH2, was observed in Ras-transformed keratinocytes. The increased sensitivity of transformed keratinocytes to miR-21's effects occurs in part through downregulation of the RNA-binding protein DND1 during the transformation process. Additionally, we observed increased tumorigenesis in mice subcutaneously injected with transformed keratinocytes lacking Grhl3. These findings indicate that decreased Grhl3 expression contributes to tumor progression and upregulation of the oncomir miR-21 in squamous cell carcinoma of the skin. 23356740 A comparison of the signalling properties of two tyramine receptors from Drosophila. In invertebrates, the phenolamines, tyramine and octopamine, mediate many functional roles usually associated with the catecholamines, noradrenaline and adrenaline, in vertebrates. The α- and β-adrenergic classes of insect octopamine receptor are better activated by octopamine than tyramine. Similarly, the Tyramine 1 subgroup of receptors (or Octopamine/Tyramine receptors) are better activated by tyramine than octopamine. However, recently, a new Tyramine 2 subgroup of receptors was identified, which appears to be activated highly preferentially by tyramine. We examined immunocytochemically the ability of CG7431, the founding member of this subgroup from Drosophila melanogaster, to be internalized in transfected Chinese hamster ovary (CHO) cells by different agonists. It was only internalized after activation by tyramine. Conversely, the structurally related receptor, CG16766, was internalized by a number of biogenic amines, including octopamine, dopamine, noradrenaline, adrenaline, which also were able to elevate cyclic AMP levels. Studies with synthetic agonists and antagonists confirm that CG16766 has a different pharmacological profile to that of CG7431. Species orthologues of CG16766 were only found in Drosophila species, whereas orthologues of CG7431 could be identified in the genomes of a number of insect species. We propose that CG16766 represents a new group of tyramine receptors, which we have designated the Tyramine 3 receptors. 23441878 Probing the Photoisomerization of CHBr3 and CHI3 in Solution with Transient Vibrational and Electronic Spectroscopy. Transient infrared absorption spectroscopy monitors condensed-phase photodissociation dynamics of 30 mM CHBr3 and 50 mM CHI3 in liquid CCl4. The experiments have picosecond time resolution and monitor the C-H stretch region of both the parent polyhalomethanes and their photolytically generated isomers. The C-H stretching transitions of these isomers, in which the emergent halogen atom returns to form a C-X-X bonding motif, appear about 9 ps after photolysis for iso-CHBr2-Br and in about 46 ps for iso-CHI2-I. These time scales are consistent with, but differ from, the time evolution of the transient electronic absorption spectra of the same samples, highlighting the subtle differences between monitoring the vibrational and electronic chromophores. The specificity of using vibrational transitions to track condensed-phase reaction dynamics permits reassessment of the transient electronic spectrum of photolysis in neat CHBr3, which has an additional prompt feature near 400 nm. Calculations show that this feature, which arises from a precursor to the isomer, is a charge-transfer transition of a contact pair between the nascent Br fragment and a nearby CHBr3 molecule. Dilution and solvent studies show that transition is independent of the solvent. The iso-CHBr2-Br transition wavelength, however, shifts over the range of 400 to 510 nm depending on the solvent. Time-dependent density functional calculations faithfully reproduce these trends. 23122136 Degradation kinetics of anthocyanins in acerola pulp: comparison between ohmic and conventional heat treatment. Degradation kinetics of monomeric anthocyanins in acerola pulp during thermal treatment by ohmic and conventional heating was evaluated at different temperatures (75-90°C). Anthocyanin degradation fitted a first-order reaction model and the rate constants ranged from 5.9 to 19.7 × 10(-3)min(-1). There were no significant differences between the rate constants of the ohmic and the conventional heating processes at all evaluated temperatures. D-Values ranged from 116.7 to 374.5 for ohmic heating and from 134.9 to 390.4 for conventional heating. Values of the free energy of inactivation were within the range of 100.19 and 101.35 kJ mol(-1). The enthalpy of activation presented values between 71.79 and 71.94 kJ mol(-1) and the entropy of activation ranged from -80.15 to -82.63 J mol(-1)K(-1). Both heating technologies showed activation energy of 74.8 kJ mol(-1) and close values for all thermodynamic parameters, indicating similar mechanisms of degradation. 23261527 Emerging targets in lipid-based therapy. The use of prostaglandins and NSAIDS in the clinic has proven that lipid mediators and their associated pathways make attractive therapeutic targets. When contemplating therapies involving lipid pathways, several basic agents come to mind. There are the enzymes and accessory proteins that lead to the metabolism of lipid substrates, provided through diet or through actions of lipases, the subsequent lipid products, and finally the lipid sensors or receptors. There is abundant evidence that molecules along this lipid continuum can serve as prognostic and diagnostic indicators and are in fact viable therapeutic targets. Furthermore, lipids themselves can be used as therapeutics. Despite this, the vernacular dialog pertaining to "biomarkers" does not routinely include mention of lipids, though this is rapidly changing. Collectively these agents are becoming more appreciated for their respective roles in diverse disease processes from cancer to preterm labor and are receiving their due appreciation after decades of ground work in the lipid field. By relating examples of disease processes that result from dysfunction along the lipid continuum, as well as examples of lipid therapies and emerging technologies, this review is meant to inspire further reading and discovery. 23563055 A possible role of partially pyrolysed essential oils in Australian Aboriginal traditional ceremonial and medicinal smoking applications of Eremophila longifolia (R. Br.) F. Muell (Scrophulariaceae). ETHNOPHARMACOLOGICAL SIGNIFICANCE: Eremophila longifolia is one of the most respected of the traditional medicines used by Australian Aboriginal people. Customary use involves smoldering the leaves over hot embers of a fire to produce an acrid smoke, believed to have therapeutic effects broadly consistent with antimicrobial, antifungal and anti-inflammatory capacity. AIM OF THE STUDY: The current study aims to examine the contribution of partially pyrolysed and non-pyrolysed essential oils in traditional usage of Eremophila longifolia. MATERIALS AND METHODS: Non-pyrolysed and partially pyrolysed essential oils were produced by hydrodistillation and part-wet/part-dry distillation, respectively. All samples were tested for antimicrobial activity by broth dilution. Some of these samples were further treated to an incrementally stepped temperature profile in a novel procedure employing a commercial thermocycler in an attempt to mimic the effect of temperature gradients produced during smoking ceremonies. Components from the pyrodistilled oils were compared with the non-pyrodistilled oils, using GC-MS, GC-FID and HPLC-PAD. The 2,2-diphenyl-1-picrylhydrazyl method, was used to compare free radical scavenging ability. RESULTS: Partially pyrolysed oils had approximately three or more times greater antimicrobial activity, enhanced in cultures warmed incrementally to 60°C and held for 30s and further enhanced if held for 2min. Partially pyrolysed oils showed a radical scavenging capacity 30-700 times greater than the corresponding non-pyrolysed oils. HPLC-PAD revealed the presence of additional constituents not present in the fresh essential oil. CONCLUSION: These results, by showing enhanced antimicrobial and antioxidant activities, provide the first known Western scientific justification for the smoking ceremonies involving leaves of Eremophila longifolia. During customary use, both partially pyrolysed as well as non-pyrolysed essential oils may contribute significantly to the overall intended medicinal effect. 23411076 Design, synthesis and structure-activity relationship of rhenium 2-arylbenzothiazoles as β-amyloid plaque binding agents. To continue our efforts toward the development of (99m)Tc PiB analogs, we have synthesized 24 neutral and lipophilic Re (as a surrogate of (99m)Tc) 2-arylbenzothiazoles, and explored their structure-activity relationship for binding to Aβ1-40 fibrils. These Re complexes were designed and synthesized via the integrated approach, so their (99m)Tc analogs would have a greater chance of crossing the blood-brain barrier. While the lipophilicities (logPC18=1.59-3.53) of these Re 2-arylbenzothiazoles were all within suitable range, their binding affinities (Ki=30-617nM) to Aβ1-40 fibrils varied widely depending on the selection and integration of the tetradentate chelator into the 2-phenylbenzothiazole pharmacophore. For potential clinical applications, further refinement to obtain Re 2-arylbenzothiazoles with better binding affinities (<10nM) will likely be needed. The integrated approach reported here to generate compact, neutral and lipophilic Re 2-arylbenzothiazoles could be applied to other potent pharmacophores as well to convert other current Aβ PET tracers to their (99m)Tc analogs for more widespread application via the use of SPECT scanners. 23395165 The Hunger Games: p53 regulates metabolism upon serine starvation. Cancer cells reprogram their metabolism to support a high proliferative rate. A new study shows that, upon serine starvation, the tumor suppressor p53 activates p21 to shift metabolic flux from purine biosynthesis to glutathione production, which enhances cellular proliferation and viability by combating ROS (Maddocks et al., 2013). 23153057 Assessment of cytochrome P450 (1A2, 2B6, 2C9 and 3A4) induction in cryopreserved human hepatocytes cultured in 48-well plates using the cocktail strategy. 1. A fast, straightforward and cost-effective assay was validated for the assessment of CYP induction in cryopreserved human hepatocytes cultured in 48-well plates. The cocktail strategy (in situ incubation) was used to assess the induction of CYP1A2, CYP2B6, CYP2C9 and CYP3A4 by using the recommended probe substrate, i.e. phenacetin, bupropion, diclofenac and midazolam, respectively. 2. Cryopreserved human hepatocytes were treated for 72 h with prototypical reference inducers, β-naphthoflavone (25 µM), phenobarbital (500 µM) and rifampicin (10 µM) as positive controls for CYP induction. The use of a cocktail strategy has been validated and compared to the classical approach (single incubation). The need of using phase II inhibitor (salicylamide) in CYP induction assay was also investigated. 3. By using three different batches of cryopreserved human hepatocytes and our conditions of incubations, we showed that there was no relevant drug-drug interaction using the cocktail strategy. The same conclusions were observed when a broad range of enzyme activity has to be assessed (wide range of reference inducers, i.e. EC50-Emax experiment). In addition, the interassay reproducibility assessment showed that the day-to-day variability was minimal. 4. In summary, the study showed that the conditions used (probe substrates, concentration of probe substrate and time of incubation) for the cocktail approach were appropriate for investigations of CYP induction potential of new chemical entities. In addition, it was also clear that the use of salicylamide in the incubation media was not mandatory and could generate drug-drug interactions. For this reason, we recommend to not use salicylamide in CYP induction assay. 23567293 Inhibition of proteases as a novel therapeutic strategy in the treatment of metabolic, inflammatory and functional diseases of the gastrointestinal tract. Proteases are widely distributed in the human body and are crucially involved in the modulation of physiological processes in the gastrointestinal (GI) tract. They also have a major role in the etiology and the course of GI diseases. This review discusses the pharmacology of proteases and medical application of their inhibitors in the GI tract. In particular, we focus on metabolic disorders, such as diabetes type 2, inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and abdominal pain. Based on recent papers in the field of pharmacology and documented clinical trials, we suggest future treatment options employing protease inhibitors. 23463732 Cyclodextrin Insulation Prevents Static Quenching of Conjugated Polymer Fluorescence at the Single Molecule Level. Conjugated polymers (CPs) are promising materials for fluorescence imaging application. However, a significant problem in this field is the unexplained abnormally low fluorescence brightness (or number of fluorescence photons detected per one excitation photon) exhibited by most of CP single chains in solid polymer hosts. Here it is shown that this detrimental effect can be fully avoided for short chains of polyfluorene-bis-vinylphenylene (PFBV) embedded in a host polymer matrix of PMMA, if the conjugated backbone is insulated by cyclodextrin rings to form a polyrotaxane (PFBV-Rtx). Fluorescence kinetics and quantum yields are measured for the polymers in liquid solutions, pristine films, and solid PMMA blends. The fluorescence brightness of PFBV-Rtx single chains dispersed in a solid PMMA is very close to that expected for a chain with 100% fluorescence quantum yield, while the unprotected PFBV chains of the same length possess 4 times lower brightness. Despite this, the fluorescence decay kinetics are the same for both polymers, suggesting the presence of static or ultrafast fluorescence quenching in the unprotected polymer. About 80% of an unprotected PFBV chain is estimated to be completely quenched. The hypothesis is that the cyclodextrin rings prevent the quenching by working as 'bumpers' reducing the mechanical forces applied by the host polymer to the conjugated backbone and help retaining its conformational freedom. While providing a recipe for making CP fluorescence bright at the single-molecule level, these results identify a lack of fundamental understanding in the community of the influence of the environment on excited states in conjugated materials. 23400796 The accumulation of metal (Co, Cr, Cu, Mn and Zn) in freshwater Ulva (Chlorophyta) and its habitat. The possibility of using freshwater Ulva (Chlorophyta) as a bioaccumulator of metals (Co, Cr, Cu, Mn and Zn) in lake and river water was examined weekly in the summer of 2010 in three types of samples: the water, the sediment and the thalli of Ulva. Samples of freshwater Ulva were collected from two aqueous ecosystems lie 250 km away from the basin of the Baltic Sea and 53 km from each other. A flow lake located in the centre of the big city was the first water reservoir (ten sites) and second, the suburban river (six sites). The mean metal concentrations in the Ulva tissue from the river and the lake decreased in the following order: Mn > Zn > Cr > Cu > Co and Mn > Cr > Zn > Cu > Co, respectively. Moreover, a negative and statistically significant correlation between Mn concentrations in the Ulva thalli and the river water was observed. Additionally, numerous correlations were noted between the different concentrations of metals within the Ulva thalli, in the water and in the sediment. The great concentrations of Mn and Zn and the smallest of Co were found in thalli of Ulva, irrespective of the type of the ecosystem from which samples of algal thalli originated. Freshwater Ulva populations examined in this study were clearly characterized a dozen or so times by the higher Mn and Cr accumulation than taxa from that genera coming from sea ecosystems. The calculated bioconcentration factor confirm the high potential for freshwater Ulva to be a bioaccumulator of trace metals in freshwater ecosystems. 23262203 Plasmonic photothermal therapy increases the tumor mass penetration of HPMA copolymers. Effective drug delivery to tumors requires both transport through the vasculature and tumor interstitium. Previously, it was shown that gold nanorod (GNR) mediated plasmonic photothermal therapy (PPTT) is capable of increasing the overall accumulation of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers in prostate tumors. In the present study, it is demonstrated that PPTT is also capable of increasing the distribution of these conjugates in tumors. Gadolinium labeled HPMA copolymers were administered to mice bearing prostate tumors immediately before treatment of the right tumor with PPTT. The left tumor served as internal, untreated control. Magnetic resonance imaging (MRI) of both tumors showed that PPTT was capable of improving the tumor mass penetration of HPMA copolymers. Thermal enhancement of delivery, roughly 1.5-fold, to both the tumor center and periphery was observed. Confocal microscopy of fluorescently labeled copolymers corroborates these findings in that PPTT is capable of delivering more HPMA copolymers to the tumor's center and periphery. These results further demonstrate that PPTT is a useful tool to improve the delivery of polymer-drug conjugates. 23001428 Chronic toxicity of tire and road wear particles to water- and sediment-dwelling organisms. Tire and road wear particles (TRWP) consist of a complex mixture of rubber, and pavement released from tires during use on road surfaces. Subsequent transport of the TRWP into freshwater sediments has raised some concern about the potential adverse effects on aquatic organisms. Previous studies have shown some potential for toxicity for tread particles, however, toxicity studies of TRWP collected from a road simulator system revealed no acute toxicity to green algae, daphnids, or fathead minnows at concentrations up to 10,000 mg/kg under conditions representative of receiving water bodies. In this study, the chronic toxicity of TRWP was evaluated in four aquatic species. Test animals were exposed to whole sediment spiked with TRWP at concentrations up to 10,000 mg/kg sediment or elutriates from spiked sediment. Exposure to TRWP spiked sediment caused mild growth inhibition in Chironomus dilutus but had no adverse effect on growth or reproduction in Hyalella azteca. Exposure to TRWP elutriates resulted in slightly diminished survival in larval Pimephales promelas but had no adverse effect on growth or reproduction in Ceriodaphnia dubia. No other endpoints in these species were affected. These results, together with previous studies demonstrating no acute toxicity of TRWP, indicate that under typical exposure conditions TRWP in sediments pose a low risk of toxicity to aquatic organisms. 22623520 Acute effects of methiocarb on oxidative damage and the protective effects of vitamin E and taurine in the liver and kidney of Wistar rats. Methiocarb (MC) is a widely used carbamate pesticide in agriculture and health programs. Although the main molecular mechanism of carbamate toxicity involves acetylcholinesterase inhibition, studies have also implicated the induction of oxidative stress. Therefore, the present study was aimed to evaluate the effect of acute MC exposure on lipid peroxidation, antioxidant defense systems, histological changes in Wistar rats and the protective effect of pretreatment with vitamin E and taurine. A total of 48 rats were randomly divided into six groups. Rats in group I were given corn oil, while those in group III were dosed with vitamin E (100 mg/kg body weight (b.w.)) and in group V were dosed with taurine (50 mg/kg b.w.). Rats in group II were administered with MC only (25 mg/kg b.w., 1/4 of median lethal dose (LD(50))), while those in groups IV and VI were pretreated with vitamin E (100 mg/kg b.w.) and taurine (50 mg/kg b.w.) for 20 days, respectively, and then exposed to MC (25 mg/kg b.w.). The rats administered with MC showed significant increase in the levels of malondialdehyde in the liver and kidney as an index of lipid peroxidation. Levels of glutathione and activities of superoxide dismutase, catalase and glutathione peroxidase were significantly increased, while activity of glutathione reductase remained unchanged in both the tissues after MC treatment. Mild degenerative histological changes were observed in liver tissue, while the changes in kidney tissue were more severe then liver after MC treatment. Pretreatment with vitamin E and taurine resulted in a significant decrease in the lipid peroxidation and alleviating effects on antioxidant defense systems in both the tissues, while protective effects on the histological changes were shown only in kidney when compared with liver. In conclusion, the study has demonstrated that the acute MC exposure in Wistar rats caused oxidative damage on liver and kidney, which were partly ameliorated by the pretreatment of vitamin E and taurine. 23419950 Optimization of cell receptor-specific targeting through multivalent surface decoration of polymeric nanocarriers. Treatment of tuberculosis is impaired by poor drug bioavailability, systemic side effects, patient non-compliance, and pathogen resistance to existing therapies. The mannose receptor (MR) is known to be involved in the recognition and internalization of Mycobacterium tuberculosis. We present a new assembly process to produce nanocarriers with variable surface densities of mannose targeting ligands in a single step, using kinetically-controlled, block copolymer-directed assembly. Nanocarrier association with murine macrophage J774 cells expressing the MR is examined as a function of incubation time and temperature, nanocarrier size, dose, and PEG corona properties. Amphiphilic diblock copolymers are prepared with terminal hydroxyl, methoxy, or mannoside functionality and incorporated into nanocarrier formulations at specific ratios by Flash NanoPrecipitation. Association of nanocarriers protected by a hydroxyl-terminated PEG corona with J774 cells is size dependent, while nanocarriers with methoxy-terminated PEG coronas do not associate with cells, regardless of size. Specific targeting of the MR is investigated using nanocarriers having 0-75% mannoside-terminated PEG chains in the PEG corona. This is a wider range of mannose densities than has been previously studied. Maximum nanocarrier association is attained with 9% mannoside-terminated PEG chains, increasing uptake more than 3-fold compared to non-targeted nanocarriers with a 5kgmol(-1) methoxy-terminated PEG corona. While a 5kgmol(-1) methoxy-terminated PEG corona prevents non-specific uptake, a 1.8kgmol(-1) methoxy-terminated PEG corona does not sufficiently protect the nanocarriers from nonspecific association. There is continuous uptake of MR-targeted nanocarriers at 37°C, but a saturation of association at 4°C. The majority of targeted nanocarriers associated with J774E cells are internalized at 37°C and uptake is receptor-dependent, diminishing with competitive inhibition by dextran. This characterization of nanocarrier uptake and targeting provides promise for optimizing drug delivery to macrophages for TB treatment and establishes a general route for optimizing targeted formulations of nanocarriers for specific delivery at targeted sites. 23547786 Bacteria-adsorbed palygorskite stabilizes the quaternary phosphonium salt with specific-targeting capability, long-term antibacterial activity, and lower cytotoxicity. In order to extend the antibacterial time of quaternary phosphonium salt in bacteria, palygorskite (PGS) is used as the carrier of dodecyl triphenyl phosphonium bromide (DTP), and a DTP-PGS hybrid is prepared. Antibacterial performance of this novel hybrid is investigated for both Gram-positive and Gram-negative bacteria. The results show that the DTP could be absorbed on the surface of PGS which had bacteria-adsorbed capability. The DTP-PGS hybrid, combining the advantages of PGS and DTP, display specific-targeting capability, long-term antibacterial activity, and lower cytotoxicity, suggesting the great potential application as PGS-based antibacterial powder. 23315683 Exciton Dissociation and Charge-Transport Enhancement in Organic Solar Cells with Quantum-Dot/N-doped CNT Hybrid Nanomaterials. The incorporation of InP quantum-dot/N-doped multiwalled carbon nanotube (QD:NCNT) nanohybrids in the active layer of poly(3-hexylthiophene)/indene-C60 bisadduct (P3HT/ICBA) bulk-heterojuction solar cells enhances VOC and JSC . The QDs encourage exciton dissociation by promoting electron transfer, while the NCNTs enhance the transport of the separated electrons and eventual charge collection. Such a synergistic effect successfully improves the power conversion efficiency (PCE) from 4.68% (reference cells) to 6.11%. 23411211 Cannabisin B induces autophagic cell death by inhibiting the AKT/mTOR pathway and S phase cell cycle arrest in HepG2 cells. This study investigates the anticancer properties of cannabisin B, purified from hempseed hull, in HepG2 human hepatoblastoma cells. The results indicate that cannabisin B significantly inhibited cell proliferation by inducing autophagic cell death rather than typical apoptosis. Cell viability transiently increased upon the addition of a low concentration of cannabisin B but decreased upon the addition of high concentrations. Cannabisin B-induced changes in cell viability were completely inhibited by pre-treatment with 3-methyladenine (3-MA), indicating that the induction of autophagy by cannabisin B caused cell death. Additionally, cannabisin B induced S phase cell cycle arrest in a dose-dependent manner. Moreover, cannabisin B was found to inhibit survival signaling by blocking the activation of AKT and down-stream targets of the mammalian target of rapamycin (mTOR). These findings suggest that cannabisin B possesses considerable antiproliferative activity and that it may be utilised as a promising chemopreventive agent against hepatoblastoma disease. 23561208 Effect of Saccharomyces strains on the quality of red wines aged on lees. Ageing on lees involves ageing the wine in contact with yeast cells after fermentation. If combined with the addition of oak chips, it can soften the wood flavour and increase the aromatic complexity of wine. The aim of the present work is to optimise both ageing techniques through selection of an adequate Saccharomyces cerevisiae strain. The study lasted 6months and content of polysaccharides, anthocyanins, proanthocyanidins, volatile compounds, colour parameters and sensory analysis, were periodically evaluated. Among the strains tested, G37 showed the highest release of polysaccharides (24.4±5.5mgl(-1)). Vanillin, syringaldehyde and furfuryl alcohol increased with ageing time in 7VA2 treatment. The wine aged with CTPL14 strain presented fewer monomeric and oligomeric proanthocyanidins (12.4±0.6 and 83.4±8.3mgl(-1), respectively), and showed the lowest astringency and bitterness sensations. Results show an improvement in the sensory profile of the red wine aged with a combination of these two techniques. 23373724 Enhancing the efficacy of Ara-C through conjugation with PAMAM dendrimer and linear PEG: a comparative study. 1β-d-Arabinofuranosylcytosine (Cytarabine, Ara-C) is a key drug in the treatment of acute myeloid leukemia. Ara-C has a number of limitations such as a rapid deactivation by cytidine deaminase leading to the formation of a biologically inactive metabolite, Ara-U (1β-d-arabinofuranosyluracil), a low lipophilicity, and fast clearance from the body. To address these problems, we developed a conjugate in which hydroxyl-terminated PAMAM dendrimer, G4-OH ["D"] and PEG were used as carriers for the drug (Ara-C). The conjugates were synthesized using an efficient multistep protection/deprotection method resulting in the formation of a covalent bond between the primary hydroxyl group of Ara-C and dendrimer/PEG. The structure, physicochemical properties, and drug release kinetics were characterized extensively. (1)H NMR and MALDI-TOF mass spectrometry suggested covalent attachment of 10 Ara-C molecules to the dendrimer. The release profile of Ara-C in human plasma and in PBS buffer (pH 7.4) showed that the conjugates released the drug over 14 days in PBS, with the release sped up in plasma. In PBS, while most of the drug is released from PEG-Ara-C, the dendrimer continues to release the drug in a sustained fashion. The results also suggested that the formation of the inactive form of Ara-C (Ara-U) was delayed upon conjugation of Ara-C to the polymers. The inhibition of cancer growth by the dendrimer-Ara-C and PEG-Ara-C conjugates was evaluated in A549 human adenocarcinoma epithelial cells. Both dendrimer- and PEG-Ara-C conjugates were 4-fold more effective in inhibition of A549 cells compared to free Ara-C after 72 h of treatment. 23259742 Short-channel transistors constructed with solution-processed carbon nanotubes. We develop short-channel transistors using solution-processed single-walled carbon nanotubes (SWNTs) to evaluate the feasibility of those SWNTs for high-performance applications. Our results show that even though the intrinsic field-effect mobility is lower than the mobility of CVD nanotubes, the electrical contact between the nanotube and metal electrodes is not significantly affected. It is this contact resistance which often limits the performance of ultrascaled transistors. Moreover, we found that the contact resistance is lowered by the introduction of oxygen treatment. Therefore, high-performance solution-processed nanotube transistors with a 15 nm channel length were obtained by combining a top-gate structure and gate insulators made of a high-dielectric-constant ZrO(2) film. The combination of these elements yields a performance comparable to that obtained with CVD nanotube transistors, which indicates the potential for using solution-processed SWNTs for future aggressively scaled transistor technology. 23542126 Oxidative status in ICU patients with septic shock. The aim of this pilot study was to investigate variability of oxidative stress during sepsis evolution. ICU patients with the diagnosis of septic shock were included. Thiobarbituric-acid reactive substances, total antioxidant capacity, protein carbonyls in plasma, reduced, oxidized glutathione and catalase activity in erythrocyte lysate were assessed in the 1st, 3rd, 5th and 8thday after sepsis appearance. A total of 17 patients were divided in two groups: survivors (n=7) and non-survivors (n=10). APACHE II was 11.5±5.4 and 19.9±4.97 in survivors and non-survivors respectively (p=0.005), while mean age and SOFA score at sepsis diagnosis, were similar between the two groups. GSH levels, catalase activity and protein carbonyls presented significant different course in time between survivors and non-survivors (p<0.05). Catalase activity was significantly higher in survivors (238.8±51.5) than non-survivors (166.4±40.2; p=0.005), while protein carbonyls levels were significantly lower in survivors (0.32±0.09) than non-survivors (0.48±0.16; p=0.036) on the 1stday. Yet, non-survivors exhibited a declining course in GSH levels during time, while GSH levels were maintained in survivors. Conclusively, a longstanding antioxidant deficiency in non-surviving patients was noted. This phenomenon was clearly prominent in patients' erythrocytes. 23180762 The nucleoid-associated protein Dan organizes chromosomal DNA through rigid nucleoprotein filament formation in E. coli during anoxia. Dan is a transcription factor that regulates the ttd operon encoding tartrate dehydratase. During anaerobic conditions, its copy number increases by 100-fold, making Dan an abundant nucleoid-associated protein. However, little is known about the mode of Dan-DNA interaction. To understand its cellular functions, we used single-molecule manipulation and imaging techniques to show that Dan binds cooperatively along DNA, resulting in formation of a rigid periodic nucleoprotein filament that strongly restricts accessibility to DNA. Furthermore, in the presence of physiologic levels of magnesium, these filaments interact with each other to cause global DNA condensation. Overall, these results shed light on the architectural role of Dan in the compaction of Escherichia coli chromosomal DNA under anaerobic conditions. Formation of the nucleoprotein filament provides a basis in understanding how Dan may play roles in both chromosomal DNA protection and gene regulation. 23447538 Mutational tail loss is an evolutionary mechanism for liberating marapsins and other type I serine proteases from transmembrane anchors. Human and mouse marapsins (Prss27) are serine proteases preferentially expressed by stratified squamous epithelia. However, mouse marapsin contains a transmembrane anchor absent from the human enzyme. To gain insights into physical forms, activities, inhibition, and roles in epithelial differentiation, we traced tail loss in human marapsin to a nonsense mutation in an ancestral ape, compared substrate preferences of mouse and human marapsins with those of the epithelial peptidase prostasin, designed a selective substrate and inhibitor, and generated Prss27-null mice. Phylogenetic analysis predicts that most marapsins are transmembrane proteins. However, nonsense mutations caused membrane anchor loss in three clades: human/bonobo/chimpanzee, guinea pig/degu/tuco-tuco/mole rat, and cattle/yak. Most marapsin-related proteases, including prostasins, are type I transmembrane proteins, but the closest relatives (prosemins) are not. Soluble mouse and human marapsins are tryptic with subsite preferences distinct from those of prostasin, lack general proteinase activity, and unlike prostasins resist antiproteases, including leupeptin, aprotinin, serpins, and α2-macroglobulin, suggesting the presence of non-canonical active sites. Prss27-null mice develop normally in barrier conditions and are fertile without overt epithelial defects, indicating that marapsin does not play critical, non-redundant roles in development, reproduction, or epithelial differentiation. In conclusion, marapsins are conserved, inhibitor-resistant, tryptic peptidases. Although marapsins are type I transmembrane proteins in their typical form, they mutated independently into anchorless forms in several mammalian clades, including one involving humans. Similar pathways appear to have been traversed by prosemins and tryptases, suggesting that mutational tail loss is an important means of evolving new functions of tryptic serine proteases from transmembrane ancestors. 23591111 A cyclodextrin-capped histone deacetylase inhibitor. We have synthesized a β-cyclodextrin (βCD)-capped histone deacetylase (HDAC) inhibitor 3 containing an alkyl linker and a zinc-binding hydroxamic acid motif. Biological evaluation (HDAC inhibition studies) of 3 enabled us to establish the effect of replacing an aryl cap (in SAHA (vorinostat,)) 1 by a large saccharidic scaffold "cap". HDAC inhibition was observed for 3, to a lesser extent than SAHA, and rationalized by molecular docking into the active site of HDAC8. However, compound 3 displayed no cellular activity. 23399931 The fundamental chemical equation of aromaticity. In the search for the chemical measure of molecular aromaticity, namely the energetic gain of a cyclic delocalized structure for just being cyclic, the numerous definitions of generic aromatic stabilisation energies proposed hitherto stand as approximates of the conceptual limit devised within the framework of spectral graph theory, i.e. the topological resonance energy (TRE). After a 36 year challenge, the TRE acyclic reference of any π-cyclic molecule, originally merely defined by an abstract matching polynomial, is now given a real chemical structure: the Möbius-twisted head-to-tail metathesis cyclo-dimer of the parent ring. The original treatment at the Hückel molecular orbital level of theory can now be extended to DFT or ab initio levels. The corresponding ring opening-closing-twisting chemical transformation provides the observable basis for the measure of aromaticity under either vertical or adiabatic conditions. 23440664 A practical and scalable manufacturing process for an anti-fungal agent, Nikkomycin Z. A scalable and reliable manufacturing process for Nikkomycin Z HCl on a 170 g scale has been developed and optimized. The process is characterized by a 2.3 g/L fermentation yield, 79% purification yield, and >98% relative purity of the final product. This method is suitable for further scale up and cGMP production. The Streptomyces tendae ΔNikQ strain developed during the course of this study is superior to any previously reported strain in terms of higher yield and purity of Nikkomycin Z. 23472840 Encapsulation of Hydrophobic Drugs in Pluronic F127 Micelles: Effects of Drug Hydrophobicity, Solution Temperature, and pH. Three drugs, ibuprofen, aspirin, and erythromycin, are encapsulated in spherical Pluronic F127 micelles. The shapes and the size distributions of the micelles in dilute, aqueous solutions, with and without drugs, are ascertained using cryo-scanning electron microscopy and dynamic light scattering (DLS) experiments, respectively. Uptake of drugs above a threshold concentration is seen to reduce the critical micellization temperature of the solution. The mean hydrodynamic radii and polydispersities of the micelles are found to increase with decrease in temperature and in the presence of drug molecules. The hydration of the micellar core at lower temperatures is verified using fluorescence measurements. Increasing solution pH leads to the ionization of the drugs incorporated in the micellar cores. This causes rupture of the micelles and release of the drugs into the solution at the highest solution pH value of 11.36 investigated here and is studied using DLS and fluorescence spectrocopy. 23305777 Neolignans from leaves of Miliusa mollis. From the leaves of Miliusa mollis Pierre (Annonaceae), five new dihydrobenzofuran neolignans, namely miliumollin, 7-methoxymiliumollin, 3'-methoxymiliumollin, 4'-O-methylmiliumollin and miliumollinone, and a new 8-O-4' neolignan named miliusamollin were isolated, and their structures were elucidated through analysis of spectroscopic data. Miliumollin, 3'-methoxymiliumollin, miliumollinone and decurrenal exhibited weak cytotoxicity against KB, MCF7 and NCI-H187 cells. Miliumollinone possessed weak inhibitory effects against herpes simplex virus types 1 and 2. None of the isolates displayed inhibitory activity against avian influenza H5N1 neuraminidase. 23584857 Induction of the metabolic regulator Txnip in fasting-induced and natural torpor. Torpor is a physiological state characterised by controlled lowering of metabolic rate and core body temperature, allowing substantial energy savings during periods of reduced food availability or harsh environmental conditions. The hypothalamus coordinates energy homeostasis and thermoregulation, and plays a key role in directing torpor. We recently showed that mice lacking the orphan G protein coupled receptor Gpr50 readily enter torpor in response to fasting, and have now used these mice to conduct a microarray analysis of hypothalamic gene expression changes related to the torpor state. This revealed a strong induction of thioredoxin interacting protein (Txnip) in the hypothalamus of torpid mice, which was confirmed by quantitative RT-PCR and Western blot analyses. In situ hybridisation identified the ependyma lining the third ventricle as the principal site of torpor-related expression of Txnip. To characterise further the relationship between Txnip and torpor, we profiled Txnip expression in mice during prolonged fasting, cold exposure, and 2-deoxyglucose-induced hypometabolism, as well as in naturally occurring torpor bouts in the Siberian hamster. Strikingly, pronounced upregulation of Txnip expression was only observed in WT mice when driven into torpor, and during torpor in the Siberian hamster. Increase of Txnip was not limited to the hypothalamus, with exaggerated expression in white adipose tissue, brown adipose tissue, and liver also demonstrated in torpid mice. Given the recent identification of Txnip as a molecular nutrient sensor important in the regulation of energy metabolism, our data suggest that elevated Txnip expression is critical to regulating energy expenditure and fuel utilisation during the extreme hypometabolic state of torpor. 23428841 Lecithin/chitosan controlled release nanopreparations of tamoxifen citrate: Loading, enzyme-trigger release and cell uptake. Tamoxifen citrate (TAM), an anticancer drug with amphiphilic properties, was loaded in lecithin/chitosan nanoparticles (LCN) with a view to oral administration. The influence of tamoxifen loading on the physico-chemical properties of nanoparticles was studied. Size, surface charge and morphological properties of tamoxifen-loaded nanoparticles (LCN-TAM) were assessed. The increase in the tamoxifen amount in the LCN-TAM preparation up to 60mg/100ml maintained the positive zeta potential value of about +45mV. A statistically significant decrease in particle size was observed for TAM amounts between 5 and 20mg. A strong influence of loaded tamoxifen on the structure of lecithin/chitosan nanoparticles was observed, supported by the quantification of free chitosan and morphological analysis. A loading of tamoxifen in nanoparticles of around 19% was obtained. The release of the drug from the LCN-TAM colloidal dispersion was measured, showing that tamoxifen citrate was released very slowly in simulated gastro-intestinal fluids without enzymes. When enzymes able to dismantle the nanoparticle structure were added to the dissolution medium, drug release was triggered and continued in a prolonged manner. Tamoxifen-loaded nanoparticles showed cytotoxicity towards MCF-7 cells comparable to that obtained with tamoxifen citrate solution, but the rate of this toxic effect was dependent on drug release. Caco-2 cells, used as a model of the intestinal epithelium, were shown to take up the TAM loaded nanoparticles extensively. 23470104 High-Resolution Direct-Absorption Spectroscopy of Hydroxymethyl Radical in the CH Symmetric Stretching Region. High-resolution, fully rotationally resolved direct absorption spectra of hydroxymethyl radical, CH2OH, are presented in the infrared CH stretching region. As a result of low rotational temperatures and sub-Doppler linewidths obtained in the slit supersonic expansion, the Ka = 0 ← 0 band of the symmetric CH stretch for CH2OH has been unambiguously identified and analyzed. By way of chemical confirmation, hydroxymethyl radical is generated via two different slit jet discharge syntheses: (i) direct dissociation of CH3OH to form CH2OH and (ii) dissociation of Cl2 followed by the radical H atom extraction reaction Cl + CH3OH → HCl + CH2OH. The identified transitions are fit to a Watson A-reduced symmetric top Hamiltonian to yield first precision experimental values for the ground state rotational constants as well as improved values for the symmetric stretch rotational constants and vibrational band origin. The results both complement and substantially improve upon spectral efforts via previous double resonance ionization detected infrared methods by Feng et al. [J. Phys. Chem. A, 2004, 108, 7093], as well as offer high-resolution predictions for laboratory and astronomical detection of hydroxymethyl radical in the millimeter-wave region. 23561120 A new process for obtaining hydroxytyrosol using transformed Escherichia coli whole cells with phenol hydroxylase gene from Geobacillus thermoglucosidasius. Phenol hydroxylase gene cloning from the thermophilic bacteria Geobacillus thermoglucosidasius was used to develop an effective method to convert tyrosol into the high-added-value compound hydroxytyrosol by hydroxylation. Phenol hydroxylase is a two-component enzyme encoded by pheA1 and pheA2 genes and strictly dependent on NADH and FAD. These two genes were subcloned together as a 2kb fragment into Escherichia coli Rosetta cells, and the transformants were able to grow and effectively transform up to 5mM of phenol and tyrosol using IPTG (isopropyl-β-d-thiogalactopyranoside) as inducer. In addition, when a new fragment with a 340pb upstream pheA1 gene was subcloned, a similar biotransformation rate was attained without IPTG, confirming that this fragment encodes for a phenol hydroxylase promoter that can be recognised by E. coli. Both transformants brought about the total bioconversion of monophenols at a high concentration (5mM), which represents an increase, both in concentration and in yield, compared with that previously described in the bibliography. The use of the transformant with its constitutive promoter was more interesting from a biotechnological point of view, since it is not necessary to use IPTG. It also gave rise to greater operational stability. 23139378 Analysis of the repaglinide concentration increase produced by gemfibrozil and itraconazole based on the inhibition of the hepatic uptake transporter and metabolic enzymes. The plasma concentration of repaglinide is reported to increase greatly when given after repeated oral administration of itraconazole and gemfibrozil. The present study analyzed this interaction based on a physiologically based pharmacokinetic (PBPK) model incorporating inhibition of the hepatic uptake transporter and metabolic enzymes involved in repaglinide disposition. Firstly, the plasma concentration profiles of inhibitors (itraconazole, gemfibrozil, and gemfibrozil glucuronide) were reproduced by a PBPK model to obtain their pharmacokinetic parameters. The plasma concentration profiles of repaglinide were then analyzed by a PBPK model, together with those of the inhibitors, assuming a competitive inhibition of CYP3A4 by itraconazole, mechanism-based inhibition of CYP2C8 by gemfibrozil glucuronide, and inhibition of organic anion transporting polypeptide (OATP) 1B1 by gemfibrozil and its glucuronide. The plasma concentration profiles of repaglinide were well reproduced by the PBPK model based on the above assumptions, and the optimized values for the inhibition constants (0.0676 nM for itraconazole against CYP3A4; 14.2 μM for gemfibrozil against OATP1B1; and 5.48 μM for gemfibrozil glucuronide against OATP1B1) and the fraction of repaglinide metabolized by CYP2C8 (0.801) were consistent with the reported values. The validity of the obtained parameters was further confirmed by sensitivity analyses and by reproducing the repaglinide concentration increase produced by concomitant gemfibrozil administration at various timings/doses. The present findings suggested that the reported concentration increase of repaglinide, suggestive of synergistic effects of the coadministered inhibitors, can be quantitatively explained by the simultaneous inhibition of the multiple clearance pathways of repaglinide. 23473030 Iron and diabetes risk. Iron overload is a risk factor for diabetes. The link between iron and diabetes was first recognized in pathologic conditions-hereditary hemochromatosis and thalassemia-but high levels of dietary iron also impart diabetes risk. Iron plays a direct and causal role in diabetes pathogenesis mediated both by β cell failure and insulin resistance. Iron also regulates metabolism in most tissues involved in fuel homeostasis, with the adipocyte in particular serving an iron-sensing role. The underlying molecular mechanisms mediating these effects are numerous and incompletely understood but include oxidant stress and modulation of adipokines and intracellular signal transduction pathways. 23296019 Combined analytical ultracentrifugation, light scattering and fluorescence spectroscopy studies on the functional associations of the bacterial division FtsZ protein. The combined application of different biophysical techniques - analytical ultracentrifugation, light scattering and fluorescence-based assays - to study the ligand-linked self-association and assembly properties of the cell division protein FtsZ from Escherichia coli is described. These reactions are thought to be important for the formation of the dynamic division ring that drives bacterial cytokinesis. In addition, the use of this orthogonal experimental approach to measure the interactions between FtsZ oligomers (GDP forms) and polymers (GTP forms) with two variants (a soluble form and a full-length protein incorporated in phospholipid bilayer nanodiscs) of the ZipA protein, which provides membrane tethering to FtsZ, is described as well. The power of a global analysis of the results obtained from complementary biophysical methods to discriminate among alternative self- and hetero-associating schemes and to propose a more robust description of the association reactions involved is emphasized. This orthogonal approach will contribute to complete our quantitative understanding of the initial events of bacterial division. 23385211 Basic N-interlinked imipramines show apoptotic activity against malignant cells including Burkitt's lymphoma. We here report the synthesis of ethylene glycol N-interlinked imipramine dimers of various lengths from the tricyclic antidepressant desipramine via an amide coupling reaction followed by reduction with lithium aluminium hydride. The target molecules were found to be potent inhibitors of cellular viability while inducing cell type specific death mechanisms in three cancer cell lines including a highly chemoresistant Burkitt's lymphoma cell line. Basic amine analogues were found to be important for increased potency. Imipramine and desipramine were also tested for apoptotic activity and were found to be much less active than the novel dimeric compounds. Imipramine dimers were only found to be moderate inhibitors of the human serotonin transporter (hSERT) having IC(50) values in the micromolar region whilst the induction of cell death occurred independently of hSERT expression. These results demonstrate the potential of newly designed and synthesised imipramines derivatives for use against malignant cells, including those resistant to standard chemotherapy. 23533220 Enhanced Striatal β1-Adrenergic Receptor Expression Following Hormone Loss in Adulthood Is Programmed by Both Early Sexual Differentiation and Puberty: A Study of Humans and Rats. After reproductive senescence or gonadectomy, changes occur in neural gene expression, ultimately altering brain function. The endocrine mechanisms underlying these changes in gene expression beyond immediate hormone loss are poorly understood. To investigate this, we measured changes in gene expression the dorsal striatum, where 17β-estradiol modulates catecholamine signaling. In human caudate, quantitative PCR determined a significant elevation in β1-adrenergic receptor (β1AR) expression in menopausal females when compared with similarly aged males. No differences were detected in β2-adrenergic and D1- and D2-dopamine receptor expression. Consistent with humans, adult ovariectomized female rats exhibited a similar increase in β1AR expression when compared with gonadectomized males. No sex difference in β1AR expression was detected between intact adults, prepubertal juveniles, or adults gonadectomized before puberty, indicating the necessity of pubertal development and adult ovariectomy. Additionally, increased β1AR expression in adult ovariectomized females was not observed if animals were masculinized/defeminized with testosterone injections as neonates. To generate a model system for assessing functional impact, increased β1AR expression was induced in female-derived cultured striatal neurons via exposure to and then removal of hormone-containing serum. Increased β1AR action on cAMP formation, cAMP response element-binding protein phosphorylation and gene expression was observed. This up-regulation of β1AR action was eliminated with 17β-estradiol addition to the media, directly implicating this hormone as a regulator of β1AR expression. Beyond having implications for the known sex differences in striatal function and pathologies, these data collectively demonstrate that critical periods early in life and at puberty program adult gene responsiveness to hormone loss after gonadectomy and potentially reproductive senescence. 23201223 Emerging role of primary cilia as mechanosensors in osteocytes. The primary cilium is a solitary, immotile microtubule-based extension present on nearly every mammalian cell. This organelle has established mechanosensory roles in several contexts including kidney, liver, and the embryonic node. Mechanical load deflects the cilium, triggering biochemical responses. Defects in cilium function have been associated with numerous human diseases. Recent research has implicated the primary cilium as a mechanosensor in bone. In this review, we discuss the cilium, the growing evidence for its mechanosensory role in bone, and areas of future study. This article is part of a Special Issue entitled "The Osteocyte". 23159888 Analysis of mammalian alcohol dehydrogenase 5 (ADH5): characterisation of rat ADH5 with comparisons to the corresponding human variant. Alcohol dehydrogenase 5 (ADH5) is a member of the mammalian alcohol dehydrogenase family of yet undefined functions. ADH5 was first identified at the DNA level in human and deer mouse. A rat alcohol dehydrogenase structure of similar type has been isolated at the cDNA level using human ADH5 as a screening probe, where the rat cDNA structure displayed several atypical properties. mRNA for rat ADH5 was found in multiple tissues, especially in the kidney. In vitro translation experiments indicated that rat ADH5 is expressed as efficiently as ADH1 and furthermore, rat ADH5 was readily expressed in COS cells fused to Green Fluorescent Protein. However, no soluble ADH5 protein could be heterologously expressed in Escherichia coli cells with expression systems successfully used for other mammalian ADHs, including fused to glutathione-S-transferase. Molecular modelling of the enzyme indicated that the protein does not fold in a productive way, which can be the explanation why no stable and active ADH5 has been isolated. These results indicate that ADH5, while readily expressed at the mRNA level, does not behave similarly to other mammalian ADHs investigated. The results, in vitro and in silico, suggest an unstable ADH5 structure, which can explain for why no active and stable protein can be isolated. Further possibilities are conceivable: the ADH5 protein may have to interact with a stabiliser, or the gene is actually a pseudogene. 23546004 Medicinal Flowers. XXXVIII. Structures of Acylated Sucroses and Inhibitory Effects of Constituents on Aldose Reducatase from the Flower Buds of Prunus mume. The methanolic extract from the flower buds of Prunus mume, cultivated in Zhejiang province, China, showed an inhibitory effect on aldose reductase. From the methanolic extract, five new acylated sucroses, mumeoses F-J, were isolated together with 29 known compounds. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of the isolated compounds on aldose reductase were also investigated. Acylated quinic acid analogs, which are one of the major compounds of the flower buds of P. mume, were shown to substantially inhibit aldose reductase. In particular, mumeic acid-A was found to exhibit a potent inhibitory effect [IC50=0.4 µm]. 23265901 Synthesis and evaluation of 8-oxoadenine derivatives as potent Toll-like receptor 7 agonists with high water solubility. We report the discovery of novel series of highly potent TLR7 agonists based on 8-oxoadenines, 1 and 2 by introducing and optimizing various tertiary amines onto the N(9)-position of the adenine moiety. The introduction of the amino group resulted in not only improved water solubility but also enhanced TLR7 agonistic activity. In particular compound 20 (DSR-6434) indicated an optimal balance between the agonistic potency and high water solubility. It also demonstrated a strong antitumor effect in vivo by intravenous administration in a tumor bearing mice model. 23154304 Synthesis of novel indole hydrazone derivatives and evaluation of their antiplatelet aggregation activity. Based on the existing reports regarding the antiplatelet aggregation activity of hydrazone derivatives, a series of indole hydrazone derivatives were considered as potential antiplatelet agents and synthesized. The structures of the synthesized compounds were confirmed by spectral data and elemental analysis. The new indole hydrazone derivatives were evaluated for their ability to inhibit platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid (AA). Compounds 1h and 3h exhibited remarkable activity against arachidonic acid induced platelet aggregation with IC(50) values comparable to that of indomethacin and compound 1i efficiently inhibited platelet aggregation induced by both ADP and AA. 23474386 Novel 5-(benzyloxy)pyridin-2(1H)-one derivatives as potent c-Met inhibitors. A series of novel 5-(benzyloxy)pyridin-2(1H)-ones were designed, synthesized and biologically evaluated for c-Met inhibition. Various amides and benzoimidazoles at C-3 position were investigated. A potent compound 12b with a c-Met IC50 of 12nM was identified. This compound exhibited potent inhibition of EBC-1 cell associated with c-Met constitutive activation and showed high selectivity for c-Met than other tested 11 kinases. The binding model 12b with c-Met was disclosed by docking analysis. 23561165 Chemical, rheological and surface morphologic characterisation of spent hen proteins extracted by pH-shift processing with or without the presence of cryoprotectants. The chemical and rheological properties of spent hen proteins recovered by acid and alkaline extraction have been studied with/without cryoprotectants (CP) after 3weeks of frozen storage. Four pH values (2.0, 2.5, 11.5, and 12.0) were used for extraction. CP addition prevented freeze-induced denaturation and oxidation in all extracted proteins, as revealed by significant increases in reactive sulphydryl groups (p<0.0001), and a decrease in the formation of carbonyl groups (p<0.0001). The alkaline extracted proteins with CP formed more viscoelastic gels compared to the others, while samples without CP failed to form a gel network. FTIR of the protein isolates with CP showed a protective effect on the secondary structure of the isolated proteins. Scanning electron micrographs showed a protective shield of CP around the isolated proteins. 23345171 Adjustment of Born-Oppenheimer electronic wave functions to simplify close coupling calculations. Technical problems connected with use of the Born-Oppenheimer clamped-nuclei approximation to generate electronic wave functions, potential energy surfaces (PES), and associated properties are discussed. A computational procedure for adjusting the phases of the wave functions, as well as their order when potential crossings occur, is presented which is based on the calculation of overlaps between sets of molecular orbitals and configuration interaction eigenfunctions obtained at neighboring nuclear conformations. This approach has significant advantages for theoretical treatments describing atomic collisions and photo-dissociation processes by means of ab initio PES, electronic transition moments, and nonadiabatic radial and rotational coupling matrix elements. It ensures that the electronic wave functions are continuous over the entire range of nuclear conformations considered, thereby greatly simplifying the process of obtaining the above quantities from the results of single-point Born-Oppenheimer calculations. The overlap results are also used to define a diabatic transformation of the wave functions obtained for conical intersections that greatly simplifies the computation of off-diagonal matrix elements by eliminating the need for complex phase factors. 23423243 Characterisation of non-warfarin-associated bleeding events reported to the Norwegian spontaneous reporting system. OBJECTIVE: The aim of the study was to analyse non-warfarin-associated bleeding adverse drug events reported to the Norwegian spontaneous reporting system, with characterisation of the bleeding locations, outcome and drug interactions. In addition, concordance in assessments between reporters and evaluators, trend shifts in reporting, and detection of potentially new adverse drug interaction signals were studied. METHODS: Data on bleeding events reported between 1 January 2003 and 31 December 2005 were retrieved from the Norwegian spontaneous reporting system database. RESULTS: Of 327 case reports of non-warfarin-associated bleeding events, 270 reports (82.6 %) were characterised as serious and 69 (21.1 %) had a fatal outcome. One hundred and eighty-seven bleeds (57.5 %) were gastrointestinal, 57 (17.4 %) were cerebral, and 81 (24.8 %) were from other bleeding sites. The bleeding sites differed with respect to the patient's age, drug use, diagnoses and outcomes. Of drugs associated with bleeding, nonsteroidal anti-inflammatory drugs (NSAIDs)/COX-2 inhibitors (145 reports) and acetylsalicylic acid (128 reports) were most frequently used. Only fibrinolytics were associated with increased mortality. There was a 67.4 % correlation between reporters and evaluators in assessment of drugs associated with bleeding (P < 0.001), with considerable variation in concordance between drug groups. CONCLUSION: Non-warfarin-associated bleeding events are associated with substantial mortality. Old age, cerebral bleeds, number of drugs used, and use of fibrinolytics are all independently associated with increased mortality. The recognition of the bleeding risk of commonly used drugs such as acetylsalicylic acid and heparins may be insufficient among prescribers. 23161648 Derivation of a benchmark for freshwater ionic strength. Because increased ionic strength has caused deleterious ecological changes in freshwater streams, thresholds for effects are needed to inform resource-management decisions. In particular, effluents from surface coal mining raise the ionic strength of receiving streams. The authors developed an aquatic life benchmark for specific conductance as a measure of ionic strength that is expected to prevent the local extirpation of 95% of species from neutral to alkaline waters containing a mixture of dissolved ions in which the mass of SO (4)2- + HCO (3)- ≥ Cl(-). Extirpation concentrations of specific conductance were estimated from the presence and absence of benthic invertebrate genera from 2,210 stream samples in West Virginia. The extirpation concentration is the 95th percentile of the distribution of the probability of occurrence of a genus with respect to specific conductance. In a region with a background of 116 µS/cm, the 5th percentile of the species sensitivity distribution of extirpation concentrations for 163 genera is 300 µS/cm. Because the benchmark is not protective of all genera and protects against extirpation rather than reduction in abundance, this level may not fully protect sensitive species or higher-quality, exceptional waters. 23344824 Phytotoxicity evaluation and phytochemical analysis of three medicinally important plants from Pakistan. This work examines the crude methanolic extracts of three medicinally important plants native to Pakistan for potent phytotoxic activities and important phytochemicals. These plants include Euphorbia wallichii, Bergenia ciliata and Phytolacca latbenia. The phytotoxic effects were checked at 10,000, 1000, and 100 µg/ml against two economically important standard target species, Triticum aestivum (monocot representative) and Brassica napus (dicot representative). The phytotoxicity effects on seed germination, seedling growth and seedling weight were checked. A simple, cost-effective in vitro phytotoxicity assay (that uses petri plates) was used to evaluate the allelopathic properties of crude extracts. At highest concentration, extracts from all the three plants showed phytotoxic activities such that P. latbenia > E. wallichii > B. ciliata. In seedling growth, root length was affected more than shoot length, whereas among the target species B. napus was found to be more sensitive towards extracts when compared with T. aestivum. Phytochemical analysis showed that P. latbenia is rich in saponins and terpenoids, while E. wallichii and B. ciliata are rich in tannins, terpenoids and cardiac glycoside. P. latbenia also carries a moderate amount of cardiac glycosides. 23556445 Genomic variation in the MAP3K5 gene is associated with β-thalassemia disease severity and hydroxyurea treatment efficacy. Aim: In this study we explored the association between genetic variations in MAP3K5 and PDE7B genes, residing on chromosome 6q23, and disease severity in β-hemoglobinopathy patients, as well as the association between these variants with response to hydroxyurea (HU) treatment. Furthermore, we examined MAP3K5 expression in the context of high fetal hemoglobin (HbF) and upon HU treatment in erythroid progenitor cells from healthy and KLF1 haploinsufficient individuals. Materials & methods: For this purpose, we genotyped β-thalassemia intermedia and major patients and healthy controls, as well as a cohort of compound heterozygous sickle cell disease/β-thalassemia patients receiving HU as HbF augmentation treatment. Furthermore, we examined MAP3K5 expression in the context of high HbF and upon HU treatment in erythroid progenitor cells from healthy and KLF1 haploinsufficient individuals. Results: A short tandem repeat in the MAP3K5 promoter and two intronic MAP3K5 gene variants, as well as a PDE7B variant, are associated with low HbF levels and a severe disease phenotype. Moreover, MAP3K5 mRNA expression levels are altered in the context of high HbF and are affected by the presence of HU. Lastly, the abovementioned MAP3K5 variants are associated with HU treatment efficacy. Conclusion: Our data suggest that these MAP3K5 variants are indicative of β-thalassemia disease severity and response to HU treatment. Original submitted 24 September 2012; Revision submitted 4 February 2013. 23449220 Development of modified siRNA molecules incorporating 5-fluoro-2'-deoxyuridine residues to enhance cytotoxicity. Therapeutic small interfering RNAs (siRNAs) are composed of chemically modified nucleotides, which enhance RNA stability and increase affinity in Watson-Crick base pairing. However, the precise fate of such modified nucleotides once the siRNA is degraded within the cell is unknown. Previously, we demonstrated that deoxythymidine release from degraded siRNAs reversed the cytotoxicity of thymidylate synthase (TS)-targeted siRNAs and other TS inhibitor compounds. We hypothesized that siRNAs could be designed with specific nucleoside analogues that, once released, would enhance siRNA cytotoxicity. TS-targeted siRNAs were designed that contained 5-fluoro-2'-deoxyuridine (FdU) moieties at various locations within the siRNA. After transfection, these siRNAs suppressed TS protein and messenger RNA expression with different efficiencies depending on the location of the FdU modification. FdU was rapidly released from the siRNA as evidenced by formation of the covalent inhibitory ternary complex formed between TS protein and the FdU metabolite, FdUMP. These modified siRNAs exhibited 10-100-fold greater cytotoxicity and induced multiple DNA damage repair and apoptotic pathways when compared with control siRNAs. The strategy of designing siRNA molecules that incorporate cytotoxic nucleosides represents a potentially novel drug development approach for the treatment of cancer and other human diseases. 23303441 Evaluation of hepatic disposition of paroxetine using sandwich-cultured rat and human hepatocytes. Paroxetine, a selective serotonin reuptake inhibitor, is metabolized in the liver and excreted into bile and urine as metabolites, but species differences have been observed in hepatic disposition between rats and humans. A major metabolite in rats is M1-glucuronide, whereas M1-glucuronide and M1-sulfate are found in humans. The primary excretion route of paroxetine-derived radioactivity in rats and humans is bile and urine, respectively. The aim of this study was to examine the usefulness of sandwich-cultured hepatocytes (SCH) to evaluate in vivo species differences of the hepatic disposition of paroxetine between rats and humans. The metabolite profile of [(3)H]paroxetine in SCH was similar to that in hepatocytes in suspension, and the in vitro metabolite profiles were similar to the published in vivo metabolic pathways for both species. Furthermore, the biliary excretion index (BEI) of formed M1-glucuronide in rat SCH (25.8-50.9%) was higher than that in human SCH (15.1-16.7%). The BEI of formed M1-sulfate (16.4-29.1%) was comparable to that of M1-glucuronide in human SCH, whereas the BEIs of paroxetine were negligible in SCH of both species. Moreover, M1-glucuronide was demonstrated to be a multidrug resistance-associated protein 2 substrate in both species, as determined by its uptake into ATP-binding cassette transporter-expressing membrane vesicles. SCH should prove to be useful to evaluate the processes of hepatic uptake and metabolism of parent drugs and the simultaneous examination of the biliary excretion of both parent drug and liver-derived metabolites. 23591660 Computer simulations of cluster impacts: effects of the atomic masses of the projectile and target. Cluster secondary ion mass spectrometry is now widely used for the characterization of nanostructures. In order to gain a better understanding of the physics of keV cluster bombardment of surfaces and nanoparticles (NPs), the effects of the atomic masses of the projectile and of the target on the energy deposition and induced sputtering have been studied by means of molecular dynamics simulations. 10 keV C60 was used as a model projectile and impacts on both a flat polymer surface and a metal NP were analyzed. In the first case, the mass of the impinging carbon atoms was artificially varied and, in the second case, the mass of the NP atoms was varied. The results can be rationalized on the basis of the different atomic mass ratios of the projectile and target. In general, the emission is at its maximum, when the projectile and target have the same atomic masses. In the case of the supported NP, the emission of the underlying organic material increases as the atomic mass of the NP decreases. However, it is always less than that calculated for the bare organic surface, irrespective of the mass ratio. The results obtained with C60 impacts on the flat polymer are also compared to simulations of C60 and monoatomic Ga impacts on the NP. 23219339 Neuroprotective effects of oxymatrine against excitotoxicity partially through down-regulation of NR2B-containing NMDA receptors. Oxymatrine (OMT) is a major bioactive component derived from Sophora flavescens Ait (kushen), which is widely used in Chinese medicine. Recent studies have shown that it has neuroprotective effects; however, its underlying mechanisms remain unclear. We focus on the mechanisms of pharmacologic action in OMT by detecting its pharmacological properties against focal cerebral ischemia in vivo and NMDA-induced neurotoxicity in vitro. OMT prevented cerebral ischemic injury in mice induced via a 2 h middle cerebral artery occlusion and a 24 h reperfusion, in vivo. In vitro cultured neurons challenged with N-methyl-D-aspartate (NMDA, 200 μM) for 30 min showed significant decrease in the viability of neurons; however, OMT was able to protect neurons against induced neurotoxicity via NMDA exposure. Western blot analysis revealed that OMT decreased the expression of Bax and repaired the balance of pro- and anti-apoptotic proteins. Furthermore, OMT significantly reversed the up-regulation of NR2B and inhibited the calcium overload in the cultured neurons after challenging the NMDA. OMT showed partial protection in the cortical neurons via down-regulation of NR2B containing NMDA receptors and up-regulation of Bcl-2 family. Our results provide new insights into the development of natural therapeutic anti-oxidants against ischemia. 23159790 Purification and structural characterisation of phospholipase A1 (Vespapase, Ves a 1) from Thai banded tiger wasp (Vespa affinis) venom. The Thai banded tiger wasp (Vespa affinis) is one of the most dangerous vespid species in Southeast Asia, and stinging accidents involving this species still cause fatalities. In the present study, four forms of V. affinis phospholipase A(1) were identified through a proteomics approach. Two of these enzymes were purified by reverse-phase chromatography, and their biochemical properties were characterised. These enzymes, designated Ves a 1s, are not glycoproteins and exist as 33441.5 and 33474.4 Da proteins, which corresponded with the 34-kDa band observed via SDS-PAGE. The thermal stabilities of these enzymes were stronger than snake venom. Using an in vivo assay, no difference was found in the toxicities of the different isoforms. Furthermore, the toxicity of these enzymes does not appear to be correlated with their PLA(1) activity. The cDNAs of the full-length version of Ves a 1s revealed that the Ves a 1 gene consists of a 1005-bp ORF, which encodes 334 amino acid residues, and 67- and 227-bp 5' and 3' UTRs, respectively. The two isoforms are different by three nucleotide substitutions, resulting in the replacement of two amino acids. Through sequence alignment, these enzymes were classified as members of the pancreatic lipase family. The structural modelling of Ves a 1 used the rat pancreatic lipase-related protein 2 (1bu8A) as a template because it has PLA(1) activity, which demonstrated that this enzyme belongs to the α/β hydrolase fold family. The Ves a 1 structure, which is composed of seven α-helixes and eleven β-strands, contains the β-strand/ɛSer/α-helix structural motif, which contains the Gly-X-Ser-X-Gly consensus sequence. The typical surface structures that play important roles in substrate selectivity (the lid domain and the β9 loop) were shortened in the Ves a 1 structure, which suggests that this enzyme may only exhibit phospholipase activity. Moreover, the observed insertion of proline into the lid domain of the Ves a 1 structure is rare. We therefore propose that this proline residue might be involved in the stability and activity of Ves a 1s. 23246531 The novel δ opioid receptor agonist KNT-127 produces distinct anxiolytic-like effects in rats without producing the adverse effects associated with benzodiazepines. We previously reported that a δ opioid receptor agonist SNC80 produced potent anxiolytic-like effects in rodents. Recently, we succeeded in synthesizing a novel δ opioid receptor agonist KNT-127. In this study, we investigated the anxiolytic-like effects of KNT-127 using three different rat models of innate anxiety. In an elevated plus-maze test, KNT-127 (0.3, 1, and 3.0 mg/kg, s.c.) significantly and dose-dependently increased the time rats spent in the open arms 30 min after administration. The magnitude of the KNT-127 (3.0 mg/kg, s.c.)-induced anxiolytic-like effects was similar to that produced by diazepam (1.0 mg/kg, s.c.), a benzodiazepine anxiolytic. The anxiolytic-like effects of KNT-127 (3.0 mg/kg, s.c.) were abolished by pretreatment with naltrindole (0.1 mg/kg, s.c.), a selective δ opioid receptor antagonist, suggesting that KNT-127-induced anxiolytic-like effects are mediated by δ opioid receptors. These findings were supported by results obtained from light/dark and open-field tests. Interestingly, in contrast to diazepam (1.0 mg/kg, s.c.), KNT-127 (3.0 mg/kg, s.c.) caused no significant performance changes in the Y-maze test, the ethanol-induced sleeping test, and footprint test. This is the first study to demonstrate that the novel δ opioid receptor agonist KNT-127 produces distinct anxiolytic-like effects in rats, without producing the adverse effects associated with benzodiazepines. 23131798 Discovery of novel cannabinoid receptor ligands by a virtual screening approach: further development of 2,4,6-trisubstituted 1,3,5-triazines as CB2 agonists. 3D ligand-based virtual screening was employed to identify novel scaffolds for cannabinoid receptor ligand development. A total of 112 compounds with diverse structures were purchased from commercial vendors. 12 CB1 receptor antagonists/inverse agonists and 10 CB2 receptor agonists were identified in vitro. One of the CB2 agonists, N-cyclopentyl-4-ethoxy-6-(4-methylpiperidin-1-yl)-1,3,5-triazin-2-amine (19, -logEC(50)=7.5, E(max)=255%) was selected for further development. As far as we are aware, the compound's 1,3,5-triazine scaffold represents a new core structure for CB2 agonists. A library of fifty-seven 2,4,6-trisubstituted-1,3,5-triazines was created to clarify the structure-activity relationship study of the analogs. 23228471 Facile regioselective synthesis of novel bioactive thiazolyl-pyrazoline derivatives via a three-component reaction and their antimicrobial activity. A series of novel 2-(3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles have been prepared by a three-component cyclo-condensation of various chalcones, thiosemicarbazide and phenacyl bromide. The easy work-up of the products, rapid reaction, and mild conditions are notable features of this protocol. The reaction was efficiently catalyzed in one-pot by a few drops of HCl in EtOH under reflux conditions providing the title compounds in moderate to high yields. The antibacterial activity of the selected products was examined. Some products exhibit promising activities. 23259866 Morphologies of ABC triblock terpolymer melts containing poly(cyclohexadiene): effects of conformational asymmetry. We have synthesized linear ABC triblock terpolymers containing poly(1,3-cyclohexadiene), PCHD, as an end block and characterized their morphologies in the melt. Specifically, we have studied terpolymers containing polystyrene (PS), polybutadiene (PB), and polyisoprene (PI) as the other blocks. Systematically varying the ratio of 1,2- /1,4-microstructures of poly(1,3-cyclohexadiene), we have studied the effects of conformational asymmetry among the three blocks on the morphologies using transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), and self-consistent field theory (SCFT) performed with PolySwift++. Our work reveals that the triblock terpolymer melts containing a high percentage of 1,2-microstructures in the PCHD block are disordered at 110 °C for all the samples, independent of sequence and volume fraction of the blocks. In contrast, the triblock terpolymer melts containing a high percentage of 1,4-microstructure form regular morphologies known from the literature. The accuracy of the SCFT calculations depends on calculating the χ parameters that quantify the repulsive interactions between different monomers. Simulations using χ values obtained from solubility parameters and group contribution methods are unable to reproduce the morphologies as seen in the experiments. However, SCFT calculations accounting for the enhancement of the χ parameter with an increase in the conformational asymmetry lead to an excellent agreement between theory and experiments. These results highlight the importance of conformational asymmetry in tuning the χ parameter and, in turn, morphologies in block copolymers. 23406348 Computational study of chain transfer to monomer reactions in high-temperature polymerization of alkyl acrylates. This article presents a computational study of chain transfer to monomer (CTM) reactions in self-initiated high-temperature homopolymerization of alkyl acrylates (methyl, ethyl, and n-butyl acrylate). Several mechanisms of CTM are studied. The effects of the length of live polymer chains and the type of monoradical that initiated the live polymer chains on the energy barriers and rate constants of the involved reaction steps are investigated theoretically. All calculations are carried out using density functional theory. Three types of hybrid functionals (B3LYP, X3LYP, and M06-2X) and four basis sets (6-31G(d), 6-31G(d,p), 6-311G(d), and 6-311G(d,p)) are applied to predict the molecular geometries of the reactants, products and transition sates, and energy barriers. Transition state theory is used to estimate rate constants. The results indicate that abstraction of a hydrogen atom (by live polymer chains) from the methyl group in methyl acrylate, the methylene group in ethyl acrylate, and methylene groups in n-butyl acrylate are the most likely mechanisms of CTM. Also, the rate constants of CTM reactions calculated using M06-2X are in good agreement with those estimated from polymer sample measurements using macroscopic mechanistic models. The rate constant values do not change significantly with the length of live polymer chains. Abstraction of a hydrogen atom by a tertiary radical has a higher energy barrier than abstraction by a secondary radical, which agrees with experimental findings. The calculated and experimental NMR spectra of dead polymer chains produced by CTM reactions are comparable. This theoretical/computational study reveals that CTM occurs most likely via hydrogen abstraction by live polymer chains from the methyl group of methyl acrylate and methylene group(s) of ethyl (n-butyl) acrylate. 23617753 Small-Molecule Inhibitors of Cytokine-Mediated STAT1 Signal Transduction In β-Cells With Improved Aqueous Solubility. We previously reported the discovery of BRD0476 (1), a small molecule generated by diversity-oriented synthesis that suppresses cytokine-induced β-cell apoptosis. Herein, we report the synthesis and biological evaluation of 1 and analogs with improved aqueous solubility. By replacing naphthyl with quinoline moieties, we prepared active analogs with up to a 1400-fold increase in solubility from 1. In addition, we demonstrated that compound 1 and analogs inhibit STAT1 signal transduction induced by IFN-γ. 23353659 Phenolic glycosides from Curculigo orchioides Gaertn. Five new chlorophenolic glucosides, curculigine E (1), curculigine F (2), curculigine G (3), curculigine H (5), curculigine I (6) and one new phenolic glycoside, orcinoside H (4), together with eight known phenolic glycosides (7-14) were isolated from the Curculigo orchioides Gaertn. Their structures were established by spectroscopic techniques (IR, UV, MS, 1D and 2D NMR). The isolated phenolic glycosides were evaluated for antiosteoporotic activity against MC3T3-E1 cell line using MTT assays. Compounds 1, 2, 3, and 5 showed moderate antiosteoporotic activity with the proliferation rate of 10.1-14.1%. 23487179 Rotational spectroscopy meets theory. Rotational spectroscopy is known to be a technique that is widely used to infer information on molecular structure and dynamics. In the last few decades, its role in the field of atmospheric and astrophysical investigations has rapidly grown. However, several are the challenging aspects in rotational spectroscopy, since the detection and analysis of spectra as well as interpretation of obtained results are not at all straightforward. Quantum chemistry has reached such an accuracy that can be used to disentangle these challenging situations by guiding the experimental investigation, assisting in the determination of the spectroscopic parameters, and extracting information of chemical interest. This perspective provides an overview of the theoretical background and computational requirements needed for the accurate evaluation of the spectroscopic parameters of relevance to rotational spectroscopy. The role of theory in guiding and supporting experiment is detailed through a few examples, and the interplay of experiment and theory is discussed in terms of the information of physical and chemical interest that can be derived. 23409842 Mechanistic insights into water-protein interactions of filamentous bacteriophage. Water plays a major structural and functional role around proteins. In an attempt to explore this mechanistic structural aspect of proteins, we present site-specific interaction of hydration water with the major coat protein subunit of filamentous virus Pf1 by magic angle spinning (MAS) solid-state NMR. The interaction of surrounding water with 36 MDa Pf1 virion is investigated in uniformly (13)C, (15)N isotopically labeled; polyethylene glycol precipitated fully hydrated samples by solid-state nuclear magnetic resonance spectroscopy. Dipolar edited two-dimensional (2D) (1)H-(15)N heteronuclear correlation (HETCOR) experiments lead to unambiguous assignments of cross-peaks originating exclusively from (1)H resonances of water molecules correlating to the protein amide nitrogen. An enhanced resolved (1)H chemical shift dimension in these experiments also precludes the need of perdeuteration. We report seven residues spanning the 40-residue continuous α-helical conformation assembly of Pf1 interacting with surrounding water. It shows a highly hydrated inner core inside this viral filamentous assembly. The results obtained also suggest the first evidence of a water-mediated interface cluster formed at the site of Arg44 with the single-stranded DNA genome of the filamentous phage supramolecular assembly. 23423942 Use of gene expression data to determine effects on gonad phenotype in japanese medaka after exposure to trenbolone or estradiol. Various aquatic bioassays using one of several fish species have been developed or are in the process of being developed by organizations like the US Environmental Protection Agency and the Office of Economic Cooperation and Development for testing potential endocrine-disrupting chemicals (EDCs). Often, these involve assessment of the gonad phenotype of individuals as a key endpoint that is inputted into a risk or hazard assessment. Typically, gonad phenotype is determined histologically, which involves specialized and time-consuming techniques. The methods detailed here utilize an entirely different methodology, reverse-transcription quantitative polymerase chain reaction, to determine the relative expression levels of 4 genes after exposure to either 17β-estradiol or 17β-trenbolone and, by extension, the effects of EDCs on the phenotypic status of the gonad. The 4 genes quantified, Sox9b, protamine, Fig1α, and ZPC1, are all involved in gonad development and maintenance in Japanese medaka (Oryzias latipes); these data were then inputted into a permutational multivariate analysis of variance to determine whether significant differences exist between treatment groups. This information in conjunction with the sexual genotype, which can be determined in medaka, can be used to determine adverse effects of exposure to EDCs in a similar fashion to the histologically determined gonad phenotype. Environ Toxicol Chem 2013;32:1344-1353. © 2013 SETAC. 23609438 The Intermediate-conductance Calcium-activated Potassium Channel KCa3.1 Regulates Vascular Smooth Muscle Cell Proliferation via Controlling Calcium-dependent Signaling. The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to a variety of cell activation processes in pathologies such as inflammation, carcinogenesis and vascular remodeling. We examined the electrophysiological and transcriptional mechanisms by which KCa3.1 regulates vascular smooth muscle cell (VSMC) proliferation. Platelet-derived growth factor-BB (PDGF)-induced proliferation of human coronary artery VSMCs was attenuated by lowering intracellular Ca(2+) concentration ([Ca(2+)]i) and was enhanced by elevating [Ca(2+)]i. KCa3.1 blockade or knockdown inhibited proliferation by suppressing the rise in [Ca(2+)]i and attenuating the expression of phosphorylated cAMP response element binding protein (CREB), c-fos and neuron-derived orphan receptor-1 (NOR-1). This anti-proliferative effect was abolished by elevating [Ca(2+)]i. KCa3.1 overexpression induced VSMC proliferation, and potentiated PDGF-induced proliferation, by inducing CREB phosphorylation, c-fos and NOR-1. Pharmacological stimulation of KCa3.1 unexpectedly suppressed proliferation by inhibiting the rise in [Ca(2+)]i and abolishing the expression and activity of KCa3.1 and PDGF β-receptors. The stimulation also attenuated the levels of phosphorylated CREB, c-fos and cyclins expression. After KCa3.1 blockade, the characteristic round shape of VSMCs expressing high l-caldesmon and low calponin-1 (dedifferentiation state) was maintained, whereas KCa3.1 stimulation induced a spindle-shape cellular appearance, with low l-caldesmon and high calponin-1. In conclusion, KCa3.1 plays an important role in VSMC proliferation via controlling Ca(2+)-dependent signaling pathways and its modulation may therefore constitute a new therapeutic target for cell proliferative diseases such as atherosclerosis. 23602400 Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors. 2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d]pyrimidine derivative (2) was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50=150nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivative (18) showed potent PDE4B inhibitory activity (IC50=25 nM). Finally, N-propylacetamide derivative (31b) was determined as a potent inhibitor for both PDE4B (IC50=7.5nM) and TNF-α production in mouse splenocytes (IC50=9.8nM) and showed good in vivo anti-inflammatory activity in the LPS-induced lung inflammation model in mice (ID50=18mg/kg). The binding mode of the new inhibitor (31e) in the catalytic site of PDE4B is presented based on an X-ray crystal structure of the ligand-enzyme complex. 22397835 Toxic effects of 50 Hz electromagnetic field on memory consolidation in male and female mice. In this study, the effect of exposure to an 8 mT, 50 Hz extremely low-frequency electromagnetic field (ELF EMF) on memory consolidation of adult male and female mice was studied. For this purpose male and female mice were randomly distributed among six groups (n = 10 in each group). Using passive avoidance task, despite its natural tendency, mouse learns to stay on a small platform to avoidant electric shock. Immediately after the learning session, laboratory animals in the experimental groups were placed in an 8 mT, 50 Hz sinusoidal EMF for 4 h. The second male and female groups were sham exposed (exposure device off) and the third groups were considered as the controls. Twenty-four hours after the learning session, the animals were placed on small platform again and step-down latency was measured as the memory consolidation index. Significant (p < 0.05) decreases were determined among groups in memory function and results showed that exposure to an 8 mT, 50 Hz EMF for 4 h has devastating effects on memory consolidation in male and female mice. 23435916 Anti-inflammatory effect of pristimerin on lipopolysaccharide-induced inflammatory responses in murine macrophages. Pristimerin, a quinonemethide triterpenoid derived from Celastraceae and Hippocrateaceae, has recently been found to suppress tumor promotion, metastasis and angiogenesis. In the present study, we evaluated the anti-inflammatory potentials of pristimerin in a cell culture system. Pristimerin suppressed not only the generation of nitric oxide (NO) and prostaglandin E2, but also the expression of inducible NO synthase and cyclooxygenase-2 induced by lipopolysacharide (LPS) in murine macrophage RAW264.7 cells. Similarly, pristimerin inhibited the release of pro-inflammatory cytokines, namely, tumor necrosis factor-α and interleukin-6, induced by LPS. The underlying mechanism of the anti-inflammatory action of pristimerin was correlated with down-regulation of nuclear factor-κB and the mitogen-activated protein kinase signal pathway. 23445362 Arylazanylpyrazolone derivatives as inhibitors of mutant superoxide dismutase 1 dependent protein aggregation for the treatment of amyotrophic lateral sclerosis. The arylsulfanylpyrazolone and aryloxanylpyrazolone scaffolds previously were reported to inhibit Cu/Zn superoxide dismutase 1 dependent protein aggregation and to extend survival in the ALS mouse model. However, further evaluation of these compounds indicated weak pharmacokinetic properties and a relatively low maximum tolerated dose. On the basis of an ADME analysis, a new series of compounds, the arylazanylpyrazolones, has been synthesized, and structure-activity relationships were determined. The SAR results showed that the pyrazolone ring is critical to cellular protection. The NMR, IR, and computational analyses suggest that phenol-type tautomers of the pyrazolone ring are the active pharmacophore with the arylazanylpyrazolone analogues. A comparison of experimental and calculated IR spectra is shown to be a valuable method to identify the predominant tautomer. 23511711 A Nanogram Dose of the CYP3A Probe Substrate Midazolam to Evaluate Drug Interactions. The objective of the study was to establish an in vivo method for assessing cytochrome P450 3A (CYP3A) activity using therapeutically inert nanogram doses of midazolam. We administered four escalating single doses of oral midazolam (0.0001-3 mg) to 12 healthy participants, stratified according to CYP3A5 carrier status, to assess pharmacokinetics linearity. We then evaluated the interactions with the CYP3A inhibitor ketoconazole (400 mg q.d.) after nanogram and regular doses of midazolam. Area under the plasma concentration-time curve (AUC) and peak plasma concentration (Cmax) were linear over the entire range of doses. Ketoconazole reduced midazolam oral clearance by 92.8%. AUC and Cmax increased by 1,540 and 363%, respectively. CYP3A5 carrier status had no influence on midazolam oral clearance or its inhibition by ketoconazole. This is the first study showing that midazolam pharmacokinetics is linear in a 30,000-fold concentration range, and therefore that nano- and microgram doses of midazolam can reliably predict the pharmacokinetics of midazolam in therapeutic doses and can be used to assess CYP3A activity even in the presence of strong CYP3A inhibitors.Clinical Pharmacology & Therapeutics (2013); advance online publication 20 March 2013. doi:10.1038/clpt.2013.27. 23405943 Design and evaluation of 4-aminophenol and salicylate derivatives as free-radical scavenger. This theoretical and experimental study describes the design and evaluation of the free-radical scavenging effect for the molecular association of 4-aminophenol and salicylate derivatives. For this purpose, we employed theoretical methods for the selection of antioxidant drugs and the rapid methods of evaluation: the 1,1-diphenyl-2-picrylhydrazyl radical and the thiobarbituric acid reactive substances in the lipid peroxidation initiated by Fe(2+) and ascorbic acid in human erythrocytes. The associate derivatives exhibited a more potent inhibition than the salicylic acid, while the benzoyl compound exhibited a more potent inhibition than paracetamol. The molecular parameters related to the electron distribution and structure (ionization potential and energy of the highest occupied molecular orbital) correlated very well with the antioxidant action of the compounds studied here in different tests. 23471504 Interindividual variability of carboxymethylenebutenolidase homolog, a novel olmesartan medoxomil hydrolase, in the human liver and intestine. Olmesartan medoxomil (OM) is a prodrug-type angiotensin II type 1 receptor antagonist. OM is rapidly converted into its active metabolite olmesartan by multiple hydrolases in humans, and we recently identified carboxymethylenebutenolidase homolog (CMBL) as one of the OM bioactivating hydrolases. In the present study, we further investigated the interindividual variability of mRNA and protein expression of CMBL and OM-hydrolase activity using 40 individual human liver and 30 intestinal specimens. In the intestinal samples, OM-hydrolase activity strongly correlated with the CMBL protein expression, clearly indicating that CMBL is a major contributor to the prodrug bioactivation in human intestine. The protein and activity were highly distributed in the proximal region (duodenum and jejunum) and decreased to the distal region of the intestine. Although there was high interindividual variability (16-fold) in both the protein and activity in the intestinal segments from the duodenum to colon, the interindividual variability in the duodenum and jejunum was relatively small (3.0- and 2.4-fold, respectively). In the liver samples, the interindividual variability in the protein and activity was 4.1- and 6.8-fold, respectively. No sex differences in the protein and activity were shown in the human liver or intestine. A genetically engineered Y155C mutant of CMBL, which was caused by a single nucleotide polymorphism rs35489000, showed significantly lower OM-hydrolase activity than the wild-type protein although no minor allele was genotyped in the 40 individual liver specimens. 23411210 Neuroprotective effects of oral gallic acid against oxidative stress induced by 6-hydroxydopamine in rats. Free radical-induced neural damage is implicated in neurodegenerative diseases and antioxidants have protective activity. In the present study, we examined the effect of gallic acid (GA; 50, 100 and 200mg/kg, p.o. for 10 days) on memory deficit and cerebral oxidative stress induced by 6-hydroxydopamine (6-OHDA; 8 μg/2 μL) injected into the medial forebrain bundle (MFB, full nigral lesion) as an animal model of Parkinson's disease (PD). The results showed that 6-OHDA significantly reduced the passive avoidance memory performance, non-enzymatic (total thiol) and enzymatic [glutathione peroxidase (GPx)] antioxidant contents and increased the level of malondialdehyde (MDA) in the hippocampus and striatum of vehicle-treated group as compared to sham-operated rats. Furthermore, oral administration of GA significantly increased the passive avoidance memory, total thiol and GPx contents and also decreased MDA levels in the above tissues. The results suggest that GA has neuroprotective activity against 6-OHDA-induced oxidative stress via enhancement of cerebral antioxidant defence. 23561197 Development of electrochemical biosensor with nano-interface for xanthine sensing - A novel approach for fish freshness estimation. Highly sensitive, selective and mediator-free electrochemical biosensor with nano-interface for sensing xanthine using xanthine oxidase (XOx) has been developed. Towards the preparation of nano-interface, Fe3O4 nanoparticles were synthesized by thermal co-precipitation method and structural, morphological characterizations were carried out using X-ray diffraction (XRD), field emission scanning electron microscope (FE-SEM) and field emission transmission electron microscope (FE-TEM) respectively. The modified electrode with the covalently linked XOx was confirmed by FT-IR. With the modified electrode as working electrode, electrochemical studies were carried out. The linear range was found to be from 0.4 to 2.4nM. The biosensor exhibited an optimum response in less than 2s and was not prone to interferences from ascorbic acid, urea and sucrose. The Michaelis-Menten constant (Km) was found to be 1.3nM. The limit of detection is found to be 2.5pM and limit of quantification as 8.3pM. The developed biosensor was used for the real time measurement of fish freshness. 23426954 Novel Insights into CB1 Cannabinoid Receptor Signaling: A Key Interaction Identified between the Extracellular-3 Loop and Transmembrane Helix 2. Activation of the cannabinoid CB1 receptor (CB1) is modulated by aspartate residue D2.63(176) in transmembrane helix (TMH) 2. Interestingly, D2.63 does not affect the affinity for ligand binding at the CB1 receptor. Studies in class A G protein-coupled receptors have suggested an ionic interaction between residues of TMH2 and 7. In this report, modeling studies identified residue K373 in the extracellular-3 (EC-3) loop in charged interactions with D2.63. We investigated this possibility by performing reciprocal mutations and biochemical studies. D2.63(176)A, K373A, D2.63(176)A-K373A, and the reciprocal mutant with the interacting residues juxtaposed D2.63(176)K-K373D were characterized using radioligand binding and guanosine 5'-3-O-(thio)triphosphate functional assays. None of the mutations resulted in a significant change in the binding affinity of N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A) or (-)-3cis -[2-hydroxyl-4-(1,1-dimethyl-heptyl)phenyl]-trans-4-[3-hydroxyl-propyl] cyclohexan-1-ol (CP55,940). Modeling studies indicated that binding-site interactions and energies of interaction for CP55,940 were similar between wild-type and mutant receptors. However, the signaling of CP55,940, and (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]-pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthalenyl)-methanone mesylate (WIN55,212-2) was impaired at the D2.63(176)A-K373A and the single-alanine mutants. In contrast, the reciprocal D2.63(176)K-K373D mutant regained function for both CP55,940 and WIN55,212-2. Computational results indicate that the D2.63(176)-K373 ionic interaction strongly influences the conformation(s) of the EC-3 loop, providing a structure-based rationale for the importance of the EC-3 loop to signal transduction in CB1. The putative ionic interaction results in the EC-3 loop pulling over the top (extracellular side) of the receptor; this EC-3 loop conformation may serve protective and mechanistic roles. These results suggest that the ionic interaction between D2.63(176) and K373 is important for CB1 signal transduction. 23122152 The influence of the malaxation temperature on the activity of polyphenoloxidase and peroxidase and on the phenolic composition of virgin olive oil. The effect of the malaxation temperature under sealed conditions on the qualitative and quantitative composition of the phenolic compounds in virgin olive oils produced from four Italian cultivars was assessed for two atmospheric conditions. In both cases, the results show a positive relationship between temperature and the concentration of the derivatives of the secoiridoid aglycones; the effect of the temperature on the oxidoreductases that promote oxidation (polyphenoloxidase and peroxidase) was investigated to determine their optimal temperatures and thermal stability. While olive peroxidase (POD) showed the highest activity at 37°C and high stability in the temperature range tested, polyphenoloxidase (PPO) exhibited the optimum activity at approximately 50°C, but showed low stability at 40°C, with a large variation in stability according to the olive cultivar. These results may contribute to an understanding of the increase in the phenol concentration found in virgin olive oils obtained following higher temperatures of malaxation. 23428212 Transparent, Conductive, and Printable Composites Consisting of TEMPO-Oxidized Nanocellulose and Carbon Nanotube. Ultrastrong, transparent, conductive and printable nanocomposites were successfully prepared by mixing single-walled carbon nanotubes (CNTs) with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized cellulose nanofibrils (TOCNs) with abundant sodium carboxyl groups on the crystalline nanocellulose surfaces. The surface-anionic cellulose nanofibrils had reinforcing and nanodispersing effects on the CNTs both in water used as the dispersed medium and in the dried composite film, providing highly conductive and printable nanocomposites with a small amount of CNTs. TOCNs are therefore expected as an effective flexible matrix that can be used as an alternative to conventional polymers for various electrical materials, when nanocomposited with CNTs and also graphene. Our findings provide a promising route to realize green and flexible electronics. 22733134 The Hedgehog processing pathway is required for NSCLC growth and survival. Considerable interest has been generated from the results of recent clinical trials using smoothened (SMO) antagonists to inhibit the growth of hedgehog (HH) signaling-dependent tumors. This interest is tempered by the discovery of SMO mutations mediating resistance, underscoring the rationale for developing therapeutic strategies that interrupt HH signaling at levels distinct from those inhibiting SMO function. Here, we demonstrate that HH-dependent non-small cell lung carcinoma (NSCLC) growth is sensitive to blockade of the HH pathway upstream of SMO, at the level of HH ligand processing. Individually, the use of different lentivirally delivered shRNA constructs targeting two functionally distinct HH-processing proteins, skinny hedgehog (SKN) or dispatched-1 (DISP-1), in NSCLC cell lines produced similar decreases in cell proliferation and increased cell death. Further, providing either an exogenous source of processed HH or a SMO agonist reverses these effects. The attenuation of HH processing, by knocking down either of these gene products, also abrogated tumor growth in mouse xenografts. Finally, we extended these findings to primary clinical specimens, showing that SKN is frequently overexpressed in NSCLC and that higher DISP-1 expression is associated with an unfavorable clinical outcome. Our results show a critical role for HH processing in HH-dependent tumors, identifies two potential druggable targets in the HH pathway, and suggest that similar therapeutic strategies could be explored to treat patients harboring HH ligand-dependent cancers. 23536728 Tumor Suppressor Protein p53 Negatively Regulates Human Pregnane X Receptor Activity. The human pregnane X receptor (PXR) regulates genes involved in drug metabolism and disposition. PXR associates with multiple corepressors that attenuate, and coactivators that enhance its activity. PXR plays a vital role in the drug metabolism pathway, and a comprehensive examination of PXR-associated proteins will provide greater insight into the regulation of the receptor and possible therapeutic implications. We performed a mass spectrometric screen to identify PXR-associated proteins. Here we report that the tumor suppressor protein p53 can associate with PXR and downregulate its activity. A loss-of-function p53 mutant (R175H) interacts with PXR but does not repress its activity. Mutant p53 can relieve the suppressive effect of wild-type p53 by competing with its interaction with PXR, suggesting that protein-protein interaction is required but not sufficient for p53 to repress PXR activity. Interestingly, a PXR variant with a naturally occurring deletion of a conserved, unique sequence in the ligand binding domain (PXR174-210) did not interact with p53, indicating that the PXR-p53 interaction is specific. Using a chromatin immunoprecipitation assay, we showed that p53 inhibits the binding of PXR to the CYP3A4 promoter. The loss of p53 function in tumor cells leads to aberrant cell proliferation, apoptosis, carcinogenesis, and altered sensitivity to chemotherapeutic drugs, while PXR contributes to chemoresistance in many cancer cells. Our findings show for the first time that wild-type p53 can negatively regulate PXR by physically associating with it. Thus, PXR and p53 appear to play important yet opposing roles in the sensitivity of tumor cells to chemotherapy. 23444284 Population pharmacokinetic analysis of a nevirapine-based HIV-1 prevention of mother-to-child transmission program in Uganda to assess the impact of different dosing regimens for newborns. Single-dose nevirapine for mothers and newborns at delivery is the simplest prevention strategy for vertical HIV-1 transmission and hence widely used in resource-constrained settings. HIV-1-positive mothers and newborns received single-dose nevirapine in a prevention of mother-to-child HIV-1 transmission (PMTCT) program in Uganda. In a pharmacokinetic investigation, breast milk and plasma samples of mothers and newborns were collected. The nonlinear mixed-effects modeling approach was suitable for analysis (average: 1.8 samples/matrix/individual). For describing the nevirapine pharmacokinetics in mothers and newborns, a 1-compartment model was demonstrated to be sufficient. The plasma-placenta transfer could be quantified, revealing a transfer fraction of 11% to 25% (with a significant influence of time span between maternal nevirapine intake and birth) and a high transfer rate constant from maternal drug administration. Interindividual variability was moderate between mothers and high between newborns. Simulations revealed that newborns born early (<1 hour) after maternal nevirapine intake would benefit from a 3-fold higher nevirapine dosage (6 mg/kg) after birth for analogous protective plasma concentrations over the first 2 weeks. In contrast, postnatal nevirapine dosage seemed to be dispensable for newborns born late (>24 hours) after maternal nevirapine intake. These dosing recommendations should be evaluated in prospective studies, including additional antiretroviral drugs in accordance with current PMTCT guidelines. 23549672 Is There Visceral Adipose Tissue (VAT) Intracellular Hypercortisolism in Human Obesity? The fact that obesity is a prominent feature of Cushing's syndrome (systemic hypercortisolism of adrenocortical origin) stimulated a 40-year search for evidence of systemic hypercortisolism in human obesity. That search has failed to find such evidence. For the past 15 years, however, studies have been done to evaluate a possible alternative type of hypercortisolism in obesity, namely visceral adipose tissue (VAT) intracellular hypercortisolism. The current review summarizes the evidence published so far about this possibility. There have been three types of evidence studied: direct measurement of the VAT levels of 11β-hydroxysteroid dehydrogenase type I (11-HSD-1), which converts biologically inactive cortisone to biologically active cortisol; direct measurement of splanchnic cortisol production; and evaluation of the effect of a specific inhibitor of 11-HSD-1 on metabolic abnormalities associated with obesity, particularly diabetes mellitus. The results are complex and difficult to interpret. Our conclusion is that the presence of VAT intracellular hypercortisolism in human obesity is possible but unlikely. 23411202 Effects of amylosucrase treatment on molecular structure and digestion resistance of pre-gelatinised rice and barley starches. Structural modification of rice and barley starches with Neisseria polysaccharea amylosucrase (NpAS) was conducted, and relationship between structural characteristics and resistant starch (RS) contents of NpAS-treated starches was investigated. Pre-gelatinised rice and barley starches were treated with NpAS. NpAS-treated starches were characterised with respect to morphology, X-ray diffraction pattern, amylopectin branch-chain distribution, and RS content, and their structural characteristics were correlated to RS contents. Regardless of amylose contents of native starches, NpAS-treated (relative to native) starches possessed lower and higher proportions of shorter (DP 6-12) and intermediate (DP 13-36) amylopectin (AP) branch-chains, respectively. RS contents were higher for NpAS-treated starches relative to native starches, and maximum RS contents were obtained for NpAS-treated starches of waxy rice and barley genotypes. Amylose contents were not associated with RS contents of NpAS-treated starches. However, shorter and intermediate AP branch-chain portions were negatively and positively correlated to RS contents of NpAS-treated starches, respectively. 23597450 Anti-inflammatory effect of prunetin via the suppression of NF-κB pathway. Prunetin is an O-methylated isoflavone, which is found in Prunus yedoensis. To date no report has been published on anti-inflammatory activities of prunetin. In the present study, the anti-inflammatory effect of prunetin on LPS-stimulated RAW 264.7 macrophage and LPS-induced septic shock model were investigated. Inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) expressions were determined by western blot and or realtime-PCR (RT-PCR). To elucidate its underlying mechanism, nuclear factor-kappa B (NF-κb) activation and its downstream pathways were investigated by NF-κB transcription factor assay, reporter gene expression, and western blot. In vivo anti-inflammatory effects of prunetin were evaluated in LPS-induced endotoxemia. Promoter assay revealed that prunetin inhibits LPS-induced nitric oxide and prostaglandin E2 production through the suppression of iNOS and COX-2 at the transcriptional level. In addition, prunetin inhibits NF-κB-dependent inflammatory responses by modulating IκB kinase (IKK)-inhibitor κBα (IκBα)-NF-κB signaling. Consistent with these results, prunetin significantly reduced serum levels of inflammatory cytokines and mortality in mice challenged with lipopolysaccharide. These findings offer a potential mechanism for the anti-inflammatory activity of prunetin. 22659473 Molecular mechanisms that desensitize metabotropic glutamate receptor signaling: an overview. The purpose of the present article is to review our actual knowledge on the desensitization of metabotropic glutamate receptors based on the literature available so far, with the attempt to emphasize all converging data and to give a possible explanation to those evidences that still remain controversial. 1. We review our knowledge on the regulation of mGlu receptors based on the available literature 2. We report converging data and we comment on issues that still remain controversial. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. 23341208 Simulations in evolution. III. Randomness as a generator of opportunities. In Neo-Darwinism, variation and natural selection are the two evolutionary mechanisms which propel biological evolution. Our previous reports presented a histogram model to simulate the evolution of populations of individuals classified into bins according to an unspecified, quantifiable phenotypic character, and whose number in each bin changed generation after generation under the influence of fitness, while the total population was maintained constant. The histogram model also allowed Shannon entropy (SE) to be monitored continuously as the information content of the total population decreased or increased. Here, a simple Perl (Practical Extraction and Reporting Language) application was developed to carry out these computations, with the critical feature of an added random factor in the percent of individuals whose offspring moved to a vicinal bin. The results of the simulations demonstrate that the random factor mimicking variation increased considerably the range of values covered by Shannon entropy, especially when the percentage of changed offspring was high. This increase in information content is interpreted as facilitated adaptability of the population. 23603053 Structure-dependent activities of hydroxylated polybrominated diphenyl ethers on human estrogen receptor. Polybrominated diphenyl ethers (PBDEs) have been shown to affect the estrogen receptor (ER) signaling pathway, and one of the proposed disruption mechanisms is direct binding of hydroxylated PBDE (OH-PBDE) to ER. In this paper, the binding affinity of 22 OH-PBDEs with different degrees of bromination to ER was assessed quantitatively using a surface plasmon resonance biosensor technique. Seven OH-PBDEs were found to bind directly with ER with KD ranging from 1.46×10(-7)M to 7.90×10(-6)M, and the affinity is in the order of 6-OH-BDE-047≧4'-OH-BDE-049>4'-OH-BDE-017>6'-OH-BDE-099≧5'-OH-BDE-099>2'-OH-BDE-007>3'-OH-BDE-028. In MVLN luciferase gene reporter assays, 10 low-brominated OH-PBDEs induced luciferase activity alone, but are 10(5) to 10(7) fold less potent than E2. Their estrogenic activity is in the order of 4'-OH-BDE-049>4'-OH-BDE-017>2'-OH-BDE-007>3'-OH-BDE-028>3-OH-BDE-047≧3'-OH-BDE-007. The good correlation between estrogenic activity and ER binding affinity of the low-brominated OH-PBDEs strongly suggest that these compounds induce ER transcriptional activity by binding directly with ER. The other 12 high-brominated OH-PBDEs inhibited luciferase activity of E2 to various degrees, demonstrating their antagonistic activity. Molecular docking analysis of the ER/OH-PBDE complexes revealed two distinctive binding modes between low- and high-brominated OH-PBDEs which provided rationale for the difference in their ER activity. 23238991 Snake (Walterinnesia aegyptia) venom-loaded silica nanoparticles induce apoptosis and growth arrest in human prostate cancer cells. Prostate cancer (PCa) is the most commonly diagnosed cancer in men. The progression and invasion of PCa are normally mediated by the overexpression of chemokine receptors (CKRs) and the interaction between CKRs and their cognate ligands. We recently demonstrated that venom extracted from Walterinnesia aegyptia (WEV) either alone or in combination with silica nanoparticles (WEV+NP) mediated the growth arrest and apoptosis of breast cancer cells. In the present study, we evaluated the impact of WEV alone and WEV+NP on the migration, invasion, proliferation and apoptosis of prostate cancer cells. We found that WEV alone and WEV+NP decreased the viability of all cell types tested (PCa cells isolated from patient samples, PC3 cells and LNCaP cells) using an MTT assay. The IC(50) values were determined to be 10 and 5 μg/mL for WEV alone and WEV+NP, respectively. WEV+NP decreased the surface expression of the CKRs CXCR3, CXCR4, CXCR5 and CXCR6 to a greater extent than WEV alone and subsequently reduced migration and the invasion response of the cells to the cognate ligands of the CKRs (CXCL10, CXCL12, CXCL13 and CXCL16, respectively). Using a CFSE proliferation assay, we found that WEV+NP strongly inhibited epidermal growth factor-mediated PCa cell proliferation. Furthermore, analysis of the cell cycle indicated that WEV+NP strongly altered the cell cycle of PCa cells and enhanced the induction of apoptosis. Finally, we demonstrated that WEV+NP robustly decreased the expression of anti-apoptotic effectors, such as B cell Lymphoma-2 (Bcl-2), B cell Lymphoma-extra large (Bcl-(XL)) and myeloid cell leukemia sequence-1 (Mcl-1), and increased the expression of pro-apoptotic effectors, such as Bcl-2 homologous antagonist/killer (Bak), Bcl-2-associated X protein (Bax) and Bcl-2-interacting mediator of cell death (Bim). WEV+NP also altered the membrane potential of mitochondria in the PCa cells. Our data reveal the potential of nanoparticle-sustained delivery of snake venom as effective treatments for prostate cancer. 23494834 Prospects and challenges of graphene in biomedical applications. Graphene materials have entered a phase of maturity in their development that is characterized by their explorative utilization in various types of applications and fields from electronics to biomedicine. Herein, we describe the recent advances made with graphene-related materials in the biomedical field and the challenges facing these exciting new tools both in terms of biological activity and toxicological profiling in vitro and in vivo. Graphene materials today have mainly been explored as components of biosensors and for construction of matrices in tissue engineering. Their antimicrobial activity and their capacity to act as drug delivery platforms have also been reported, however, not as coherently. This report will attempt to offer some perspective as to which areas of biomedical applications can expect graphene-related materials to constitute a tool offering improved functionality and previously unavailable options. 23456892 The effect of rosiglitazone on bone mass and fragility is reversible and can be attenuated with alendronate. Rosiglitazone (RSG) is an anti-diabetic drug that has been associated with increased peripheral fractures primarily in postmenopausal women. In this report, we investigated the underlying mechanisms of RSG-associated bone loss in ovariectomized (OVX) rats and determine whether changes in bone parameters associated with RSG administration are reversible on treatment cessation or preventable by co-administration with an antiresorptive agent. Nine-month-old Sprague-Dawley rats underwent OVX or sham operation. Sham-operated rats received oral vehicle only; OVX animals were randomized to receive vehicle, RSG, alendronate (ALN) or RSG plus ALN for 12 weeks. All treatment started the day after ovariectomy. After the 12 week treatment period, the OVX and RSG groups also underwent an 8-week treatment-free recovery period. Bone densitometry measurements, bone turnover markers, biomechanical testing and histomorphometric analysis were conducted. Micro-computed tomography was also used to investigate changes in microarchitecture. RSG significantly increased deoxypyridinoline levels compared with OVX. Significant exacerbation of OVX-induced loss of bone mass, strength and microarchitectural deteriorations was observed in RSG-treated OVX animals compared with OVX controls. These effects were observed predominantly at sites rich in trabecular bone with less pronounced effects in cortical bone. Co-administration of RSG and ALN prevented the bone loss associated with RSG treatment. Following cessation of RSG treatment, effects on bone mass and strength showed evidence of reversal. Thus, treatment of OVX rats with RSG results in loss of bone mass and strength, primarily at sites rich in trabecular bone mainly due to increased bone resorption. These effects can be prevented by concomitant treatment with ALN and may be reversed following discontinuation of RSG. © 2013 American Society for Bone and Mineral Research. 23535185 Galangin attenuates mast cell-mediated allergic inflammation. A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. In this study, we investigated anti-allergic inflammatory effect of galangin and underlying mechanisms of action using in vitro and in vivo models. Galangin inhibited histamine release by the reduction of intracellular calcium in phorbol 12-mystate 13-acetate plus calcium ionophore A23187-stimulated human mast cells (HMC-1). Galangin decreased expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8. The inhibitory effect of galangin on theses pro-inflammatory cytokines was related with c-Jun N-terminal kinases, and p38 mitogen-activated protein kinase, nuclear factor-κB, and caspase-1. Furthermore, galangin attenuated IgE-mediated passive cutaneous anaphylaxis and the expression of histamine receptor 1 at the inflamed tissue. The inhibitory effects of galangin were more potent than cromolyn, a known anti-allergic drug. Our results showed that galangin down-regulates mast cell-derived allergic inflammatory reactions by blocking histamine release and expression of pro-inflammatory cytokines. In light of in vitro and in vivo anti-allergic inflammatory effects, galangin could be a beneficial anti-allergic inflammatory agent. 23552908 Adsorption of diferrocenylacetylene on Au(111) studied by scanning tunneling microscopy. Scanning tunneling microscopy images of diferrocenylacetylene (DFA) coadsorbed with benzene on Au(111) show individual and close-packed DFA molecules, either adsorbed alongside benzene or on top of a benzene monolayer. Images acquired over a range of positive and negative tip-sample bias voltages show a shift in contrast, with the acetylene linker appearing brighter than the ferrocenes at positive sample bias (where unoccupied states primarily contribute) and the reverse contrast at negative bias. Density functional theory was used to calculate the electronic structure of the gas-phase DFA molecule, and simulated images produced through two-dimensional projections of these calculations approximate the experimental images. The symmetry of both experimental and calculated molecular features for DFA rules out a cis adsorption geometry, and comparison of experiment to simulation indicates torsion around the inter-ferrocene axis between 90° and 180° (trans); the cyclopentadienyl rings are thus angled with respect to the surface. 23542239 SPIO-PICsome: Development of a highly sensitive and stealth-capable MRI nano-agent for tumor detection using SPIO-loaded unilamellar polyion complex vesicles (PICsomes). Size controllable polyion complex vesicles (PICsomes), composed of biocompatible poly(ethylene glycol) (PEG) and poly(amino acid)s, have an extremely prolonged lifetime in the bloodstream that enables them to accumulate effectively in tumors via the enhanced permeability and retention (EPR) effect. The purpose of this study was to use PICsomes to synthesize a highly sensitive MRI contrast agent for more precise tumor detection. We synthesized SPIO-Cy5-PICsomes (superparamagnetic iron oxide nanoparticle-loaded Cy5-cross-linked Nano-PICsomes) and characterized them using dynamic light scattering and transmission electron microscopy in vitro and evaluated their ability to detect subcutaneously grafted tumors in vivo with MRI. The transverse relaxivity (r2) of the SPIO-Cy5-PICsomes (r2=663±28mM(-1)s(-1)) was 2.54 times higher than that of bare clinically-used SPIO. In in vivo MRI experiments on mice subcutaneously grafted with colon-26 tumor cells, the tumor signal was significantly altered at 3h after SPIO-Cy5-PICsome administration and persisted for at least 24h. Small and early-stage in vivo tumors (3days after grafting, approximately 4mm(3)) were also clearly detected with MRI. SPIO-loaded PICsomes are sensitive MRI contrast agents that can act as a powerful nanocarrier to detect small tumors for early diagnosis. 23234607 Reporter ligand NMR screening method for 2-oxoglutarate oxygenase inhibitors. The human 2-oxoglutarate (2OG) dependent oxygenases belong to a family of structurally related enzymes that play important roles in many biological processes. We report that competition-based NMR methods, using 2OG as a reporter ligand, can be used for quantitative and site-specific screening of ligand binding to 2OG oxygenases. The method was demonstrated using hypoxia inducible factor hydroxylases and histone demethylases, and K(D) values were determined for inhibitors that compete with 2OG at the metal center. This technique is also useful as a screening or validation tool for inhibitor discovery, as exemplified by work with protein-directed dynamic combinatorial chemistry. 23586638 Kinetics and Mechanism of the Tropospheric Oxidation of Vinyl Acetate Initiated by OH Radical: A Theoretical Study. Vinyl acetate [VA (CH3COOC2H3)] is an important unsaturated and oxygenated volatile organic compound responsible for atmospheric pollution. In this work, possible reaction mechanisms for the degradation of OH-initiated atmospheric oxidation of VA are investigated. The potential energy surfaces (PESs) for the reaction of OH radical with VA in the presence of O2 and NO have been studied using the M06-2X/6-311++G(d,p) method. The initial addition reactions of more and less substituted ethylenic C-atoms of VA are treated separately, followed by a conventional transition state theory (TST) calculation for reaction rates. The direct H-abstraction mechanism and kinetics have also been studied. The initial OH addition occurs through a prereactive complex, and the calculated rate constants in the temperature range 250-350 K for both the addition reactions are found to have negative temperature dependence. The calculation indicates that the reaction proceeds predominantly via the addition of OH radical to the double bond rather than the direct abstraction of H-atoms in VA. IM1 [CH3C(O)O(•)CHCH2OH] and IM2 [CH3C(O)OCH(OH)(•)CH2], the OH adduct complexes formed initially, react with ubiquitous O2 followed by NO before their rearrangement. The formation of the prereactive complex plays an important role in reaction mechanism and kinetics. The calculated rate constant, k298K = 1.61 × 10(-11) cm(3) molecule(-1) s(-1), is well harmonized with the previous experimental data, k298K = (2.48 ± 0.61) × 10(-11) cm(3) molecule(-1) s(-1) (Blanco et al.) and k298K = (2.3 ± 0.3) × 10(-11) cm(3) molecule(-1) s(-1) (Picquet-Varrult et al.). Additionally, consistent and reliable enthalpies of formation at 298.15 K (ΔfH°298.15) have been computed for all the species involved in the title reaction using the composite CBS-QB3 method. The theoretical results confirm that the major products are formic acetic anhydride, acetic acid, and formaldehyde in the OH-initiated oxidation of VA in the presence of O2 and NO, which are in excellent agreement with the experimental findings. 23643700 Vitamin C and Lifespan in Model Organisms. The process of ageing has been repeatedly associated with increasing oxidative damage which has led to the hypothesis that reducing oxidative stress through antioxidant dietary factors may prolong lifespan. Ascorbic acid is an essential antioxidant in human diets and is widely used for supplementation. However, it is rather unclear if and to what extent ascorbic acid may affect lifespan in humans and model organisms. In our review of literature on vitamin C supplementation and its effect on lifespan in different model organisms we found that some studies suggest an increase in lifespan, other studies failed to observe any beneficial effect of vitamin C on longevity and some studies even reported a decrease in lifespan following vitamin C supplementation. Of the 14 studies included in our analysis, 3 were carried out in worms, 4 in flies and 7 in rodents. The discrepancies between the studies may be related to species-specific differences, the concentration of vitamin C administered, the duration of supplementation and whether vitamin C was used alone or as part of a combined antioxidant diet. Potential underlying mechanisms through which vitamin C may influence lifespan and differences amongst species regarding the capacity to produce vitamin C endogenously are discussed. 23330564 Recent developments in emerging microimmunoassays. Creative and novel microimmunoassay approaches continue to proliferate across many platforms originating from several fields of study. These efforts are aimed at improving one or more metrics for clinical tests, including improved sensitivity, increased speed, reduced cost, smaller sample size, the ability to analyze multiple antigens in parallel and ease of use. Many approaches focus on the production of microarrays that accomplish standard assays in parallel, or mobile solid-support formats to overcome issues of high background noise and long incubation times. In this article, innovative developments beyond existing commercial tests in the microimmunoassay arena are reviewed, covering January 2008 to April 2012. These developing experimental platforms are discussed in terms of their ability to augment or replace current commercial approaches. 23223801 Lanthanide-doped luminescent nano-bioprobes: from fundamentals to biodetection. Trivalent lanthanide (Ln(3+))-doped luminescent inorganic nanoparticles (NPs), characterized by long-lived luminescence, large Stokes and/or anti-Stokes shifts, narrow emission bands and high photochemical stability, are considered to be promising candidates as luminescent bioprobes in biomedicine and biotechnology. In this feature article, we provide a brief overview of the most recent advances in Ln(3+)-doped luminescent inorganic NPs as sensors, which covers from their chemical and physical fundamentals to biodetection, such as controlled synthesis methodology, surface modification chemistry, optical physics, and their promising applications in diverse bioassays, with an emphasis on heterogeneous and homogeneous in vitro biodetection. Finally, some of the most important emerging trends and future efforts toward this active research field are also proposed. 23099339 Teratogenic effects of diabetic conditions in chick heart in ovo and in micromass culture may be prevented by addition of vitamin C and folic acid. Maternal diseases like diabetes mellitus may cause developmental defects. Supplementation with folic acid and vitamin C during the periconceptional period has been shown to prevent some neural tube and congenital heart defects. Hearts were dissected from 5 days-old White Leghorn chick embryos, the cells isolated and cultured in micromass under diabetic conditions, with and without folic acid and vitamin C. Contractile activity, cell viability (resazurin reduction) and protein assays were performed. Results indicated diabetic conditions reduced contractile activity and cell viability, whilst vitamin C (100 μM) and folic acid (1 mM) administered concurrently significantly improved them to values comparable with the control. Day 3 chick embryos in ovo were injected with glucose+hydroxybutyrate or a combination of these and vitamins. Diabetic conditions caused gross and histological malformations, but these effects were abrogated by vitamin supplement. Teratogenic effects on heart development could possibly be prevented by vitamin supplementation during pregnancy. 23479455 The 5-hydroxytryptamine (serotonin) receptor 6 agonist EMD 386088 ameliorates ketamine-induced deficits in attentional set shifting and novel object recognition, but not in the prepulse inhibition in rats. Preclinical data suggest that the 5-hydroxytryptamine (serotonin) 6 (5-HT6) receptor may be a potential target for the development of new therapies for treating cognitive dysfunctions in schizophrenia and other central nervous system disorders. Recent evidence indicates that not only blockade but also activation of 5-HT6 receptors exerts procognitive effects. Nevertheless, little is known about the potential efficacy of 5-HT6 receptor agonists in models of schizophrenia-like cognitive deficits. The aim of the present study was to evaluate the effects of the 5-HT6 receptor agonist, EMD 386088, on the ketamine-induced deficits in the attentional set-shifting task (ASST), novel object recognition (NOR) task and prepulse inhibition (PPI) task in rats. Acute administration of EMD 386088 (2.5 and 5 mg/kg, intraperitoneally) to Sprague-Dawley rats reversed the deficit in the ASST induced by repeated ketamine administration. Moreover, the ketamine-induced deficit in the NOR task was ameliorated by EMD 386088 at a dose of 5 mg/kg. However, in contrast to the antipsychotic drug clozapine, the 5-HT6 agonist did not affect PPI disrupted by ketamine. The present study demonstrated the beneficial effects of the 5-HT6 agonist in ameliorating some of the ketamine-induced deficits relevant to schizophrenia. It thus seems likely that the 5-HT6 receptor activation may represent a useful pharmacological approach to the treatment of cognitive disturbances observed in this disorder. 23149337 Gs-coupled adenosine receptors differentially limit antigen-induced mast cell activation. Mast cell activation results in the immediate release of proinflammatory mediators prestored in cytoplasmic granules, as well as initiation of lipid mediator production and cytokine synthesis by these resident tissue leukocytes. Allergen-induced mast cell activation is central to the pathogenesis of asthma and other allergic diseases. Presently, most pharmacological agents for the treatment of allergic disease target receptors for inflammatory mediators. Many of these mediators, such as histamine, are released by mast cells. Targeting pathways that limit antigen-induced mast cell activation may have greater therapeutic efficacy by inhibiting the synthesis and release of many proinflammatory mediators produced in the mast cell. In vitro studies using cultured human and mouse mast cells, and studies of mice lacking A(2B) receptors, suggest that adenosine receptors, specifically the G(s)-coupled A(2A) and A(2B) receptors, might provide such a target. Here, using a panel of mice lacking various combinations of adenosine receptors, and mast cells derived from these animals, we show that adenosine receptor agonists provide an effective means of inhibition of mast cell degranulation and induction of cytokine production both in vitro and in vivo. We identify A(2B) as the primary receptor limiting mast cell degranulation, whereas the combined activity of A(2A) and A(2B) is required for the inhibition of cytokine synthesis. 23077105 Induction of hepatic multidrug resistance-associated protein 3 by ethynylestradiol is independent of cholestasis and mediated by estrogen receptor. Multidrug resistance-associated protein 3 (Mrp3; Abcc3) expression and activity are up-regulated in rat liver after in vivo repeated administration of ethynylestradiol (EE), a cholestatic synthetic estrogen, whereas multidrug resistance-associated protein 2 (Mrp2) is down-regulated. This study was undertaken to determine whether Mrp3 induction results from a direct effect of EE, independent of accumulation of any endogenous common Mrp2/Mrp3 substrates resulting from cholestasis and the potential mediation of estrogen receptor (ER). In in vivo studies, male rats were given a single, noncholestatic dose of EE (5 mg/kg s.c.), and basal bile flow and the biliary excretion rate of bile salts and glutathione were measured 5 hours later. This treatment increased Mrp3 mRNA by 4-fold, detected by real-time polymerase chain reaction, despite the absence of cholestasis. Primary culture of rat hepatocytes incubated with EE (1-10 µM) for 5 hours exhibited a 3-fold increase in Mrp3 mRNA (10 µM), consistent with in vivo findings. The increase in Mrp3 mRNA by EE was prevented by actinomycin D, indicating transcriptional regulation. When hepatocytes were incubated with an ER antagonist [7α,17β-[9-[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol (ICI182/780), 1 µM], in addition to EE, induction of Mrp3 mRNA was abolished, implicating ER as a key mediator. EE induced an increase in ER-α phosphorylation at 30 minutes and expression of c-Jun, a well-known ER target gene, at 60 minutes, as detected by Western blotting of nuclear extracts. These increases were prevented by ICI182/780. In summary, EE increased the expression of hepatic Mrp3 transcriptionally and independently of any cholestatic manifestation and required participation of an ER, most likely ER-α, through its phosphorylation. 23434648 Structural Characterization of an LPA1 Second Extracellular Loop Mimetic with a Self-Assembling Coiled-Coil Folding Constraint. G protein-coupled receptor (GPCR) structures are of interest as a means to understand biological signal transduction and as tools for therapeutic discovery. The growing number of GPCR crystal structures demonstrates that the extracellular loops (EL) connecting the membrane-spanning helices show tremendous structural variability relative to the more structurally-conserved seven transmembrane α-helical domains. The EL of the LPA(1) receptor have not yet been conclusively resolved, and bear limited sequence identity to known structures. This study involved development of a peptide to characterize the intrinsic structure of the LPA(1) GPCR second EL. The loop was embedded between two helices that assemble into a coiled-coil, which served as a receptor-mimetic folding constraint (LPA(1)-CC-EL2 peptide). The ensemble of structures from multi-dimensional NMR experiments demonstrated that a robust coiled-coil formed without noticeable deformation due to the EL2 sequence. In contrast, the EL2 sequence showed well-defined structure only near its C-terminal residues. The NMR ensemble was combined with a computational model of the LPA(1) receptor that had previously been validated. The resulting hybrid models were evaluated using docking. Nine different hybrid models interacted with LPA 18:1 as expected, based on prior mutagenesis studies, and one was additionally consistent with antagonist affinity trends. 23614728 Adenovirus-delivered angiopoietin-1 treatment for phosgene-induced acute lung injury. Abstract Context: Exposure to phosgene can result in an acute lung injury, leading to pulmonary edema and even death. Angiopoietin-1 (Ang1) is a critical factor for vascular stabilization due to its ability to reduce endothelial permeability and inflammation. Objective: In this study, the histopathological changes of the lungs after exposure to phosgene and the effect of Ang1 treatment were examined. Materials and methods: Rats were exposed to phosgene gas at 8.33 g/m(3) for 5 min. Ang1 overexpressing rats were established by an intravenous injection of adenovirus-Ang1 (Ad/Ang1). The histological changes of the lung were examined by Haematoxylin-Eosin (H&E) staining and fluorescence microscopy. The inferior lobe was used for the determination of the ratio of wet weight to dry weight of the lung. The concentration of cytokines in the serum and bronchoalveolar lavage fluid was determined by enzyme-linked immunosorbent assay. Results: The pathological analysis showed signs of inflammation and edema, evident from a significant increase in the number of leukocytes in bronchoalveolar lavage fluid and the ratio of wet to dry weight of the lungs. The lung injury induced by phosgene was markedly reduced after the injection of Ad/Ang1. The increase of IL-1β and IL-17 and decrease of vascular endothelial growth factor in the serum and bronchoalveolar lavage fluid of phosgene-exposed animals were abolished by the administration of Ad/Ang1. Discussion and conclusions: Ang1 has the beneficial effects on phosgene-induced lung injury. The adenovirus-delivered Ang1 may have the potential as a novel approach for the treatment of the acute lung injury caused by phosgene gas inhalation in humans. 23230274 Stress granules inhibit apoptosis by reducing reactive oxygen species production. Cells can undergo two alternative fates following exposure to environmental stress: they either induce apoptosis or inhibit apoptosis and then repair the stress-induced alterations. These processes minimize cell loss and prevent the survival of cells with aberrant DNA and protein alterations. These two alternative fates are partly controlled by stress granules (SGs). While arsenite, hypoxia, and heat shock induce the formation of SGs that inhibit apoptosis, X-ray irradiation and genotoxic drugs do not induce SGs, and they are more prone to trigger apoptosis. However, it is unclear precisely how SGs control apoptosis. This study found that SGs suppress the elevation of reactive oxygen species (ROS), and this suppression is essential for inhibiting ROS-dependent apoptosis. This antioxidant activity of SGs is controlled by two SG components, GTPase-activating protein SH3 domain binding protein 1 (G3BP1) and ubiquitin-specific protease 10 (USP10). G3BP1 elevates the steady-state ROS level by inhibiting the antioxidant activity of USP10. However, following exposure to arsenite, G3BP1 and USP10 induce the formation of SGs, which uncovers the antioxidant activity of USP10. We also found that the antioxidant activity of USP10 requires the protein kinase activity of ataxia telangiectasia mutated (ATM). This work reveals that SGs are critical redox regulators that control cell fate under stress conditions. 23508887 DNA Methylation and Cancer Development: Molecular Mechanism. DNA methylation is a significant regulator of gene expression, and its role in carcinogenesis recently has been a subject of remarkable interest. The aim of this review is to analyze the mechanism and cell regulatory effects of both hypo- and hyper-DNA methylation on cancer. In this review, we report new developments and their implications regarding the effects of DNA methylation on cancer development. Indeed, alteration of the pattern of DNA methylation has been a constant finding in cancer cells of the same type and differences in the pattern of DNA methylation not only occur in a variety of tumor types, but also in developmental processes Furthermore, the pattern of histone modification appears to be a predicator of the risk of recurrence of human cancers. It is well known that hypermethylation represses transcription of the promoter sections of tumor-suppressor genes leading to gene silencing. However, hypomethylation also has been identified as a cause of oncogenesis. Furthermore, experiments concerning the mechanism of methylation and its control have led to the discovery of many regulatory enzymes and proteins. This review reports on methods developed for the detection of 5-hydroxymethylcytosine methylation at the 5-methylcytosine of protein domains in the CpG context compared to non-methylated DNA, histone modification, and microRNA change. 23265504 Physico-chemical and antioxidant properties of four mango (Mangifera indica L.) cultivars in China. Four principal mango cultivars (Tainong No.1, Irwin, JinHwang and Keitt) grown in southern China were selected, and their physico-chemical and antioxidant properties were characterized and compared. Of all the four cultivars, Tainong No.1 had highest content of total phenols, ρ-coumaric acid, sinapic acid, quercetin, titratable acidity, citric acid, malic acid, fructose, higher antioxidant activities (DPPH, FRAP) and L(*), lower pH, PPO activity and individual weight. Keitt mangoes showed significantly (p<0.05) higher contents of β-carotene, ρ-hydroxybenzoic acid, sucrose, total sugar, total soluble solid, catechin, succinic acid and higher PPO activity. JinHwang mangoes exhibited significantly (p<0.05) higher individual weight and PPO activity, but had lower content of total phenols, β-carotene and lower antioxidant activity. Principal component analysis (PCA) allowed the four mango cultivars to be differentiated clearly based on all these physico-chemical and antioxidant properties determined in the study. 23452042 Reversibly acetylated lysine residues play important roles in the enzymatic activity of Escherichia coli N-hydroxyarylamine O-acetyltransferase. CobB is a bacterial NAD(+) -dependent protein deacetylase. Although progress has been made in functional studies of this protein in recent years, its substrates and biological functions are still largely unclear. Using proteome microarray technology, potential substrates of Escherichia coli CobB were screened and nine proteins were identified, including N-hydroxyarylamine O-acetyltransferase (NhoA). In vitro acetylation/deacetylation of NhoA was verified by western blotting and mass spectrometry, and two acetylated lysine residues were identified. Site-specific mutagenesis experiments showed that mutation of each acetylated lysine decreased the acetylation level of NhoA in vitro. Further analysis showed that variant NhoA proteins carrying substitutions at the two acetylated lysine residues are involved in both the O-acetyltransferase and N-acetyltransferase activity of NhoA. Structural analyses were also performed to explore the effects of the acetylated lysine residues on the activity of NhoA. These results suggest that reversible acetylation may play a role in the activity of Escherichia coli NhoA. 23293921 Analytical model for the deformation of a fluid-fluid interface beneath an AFM probe. We present an analytical solution for the shape of a fluid-fluid interface near a nanoscale solid sphere, which is a configuration motivated by common measurements with an atomic force microscope. The forces considered are surface tension, gravity, and the van der Waals attraction. The nonlinear governing equation has been solved previously using the method of matched asymptotic expansions, and this requires that the surface tension forces far exceed those of gravity, i.e., the Bond number is much less than one. We first present this method using a physically relevant scaling of the equations, then offer a new analytical solution valid for all Bond numbers. We show that one configuration with a large effective Bond number, and thus one requiring our new solution, is a nanothick liquid film spread over a solid substrate. The scaling implications of both analytical methods are considered, and both are compared with numerical solutions of the full equation. 23159667 A novel approach to improve the pharmacokinetic properties of 8-chloro-adenosine by the dual combination of lipophilic derivatisation and liposome formulation. 8-Chloro-adenosine (8CA) has shown promise in hematologic and solid tumor models and is in a phase I clinical trial. However, 8CA is intensively metabolized shortly after i.v. administration, with a t(1/2β) of approximately 1h. Many carriers have failed to encapsulate 8CA efficiently. To improve its pharmacokinetic properties, 8-chloro-adenosine-5'-O-stearate (8CAS), a lipophilic octadecanoyl analogue of 8CA, was synthesized and incorporated into pegylated liposomes. The liposomes, comprising egg phosphatidylcholine, cholesterol and poly (ethylene glycol) 2000-distearoyl phosphatidylethanolamine (PEG-DSPE), had mean diameters of approximately 100 nm and an entrapment efficiency of 69-86%. MTT assays showed that the cytotoxicity of 8CAS and its pegylated liposomes (8CAS-PL) were retained, with IC(50) values of 1.0 μM and 1.9 μM at 72 h on MCF-7 cells, respectively, slightly higher than that of 8CA (0.6 μM). Pharmacokinetic studies in rats after i.v. injection showed that both 8CAS and 8 CAS-PL had increased elimination half-lives (t(1/2), 128.4, 249.2 vs. 74.7 min), decreased clearance rates (Cl, 0.0135, 0.00875 vs. 0.2398 L/min/kg) and increased area under the concentration-time curve (AUC(0-∞), 741.4, 1163.6 vs. 42.0 mg min/L) compared to 8CA. No obvious hematological toxicity was seen for Kunming mice receiving i.v. 8CA or 8CAS-PL at a dosage of 10mg/kg daily. These results indicate that the lipophilic derivation of 8CA and the incorporation of 8CAS is an effective strategy to improve the bioavailability of 8CA. 23565749 Silver Chloride as a Heterogeneous Nucleant for the Growth of Silver Nanowires. Various additives are employed in the polyol synthesis of silver nanowires (Ag NWs), which are typically halide salts such as NaCl. A variety of mechanistic roles have been suggested for these additives. We now show that the early addition of NaCl in the polyol synthesis of Ag NWs from AgNO3 in ethylene glycol results in the rapid formation of AgCl nanocubes, which induce the heterogeneous nucleation of metallic Ag upon their surfaces. Ag NWs subsequently grow from these nucleation sites. The conclusions are supported by studies using ex situ generated AgCl nanocubes. 23592516 Nrf2-activators Attenuate the Progression of Nonalcoholic Steatohepatitis-Related Fibrosis in a Dietary Rat Model. Oxidative stress is considered to be a key mechanism of hepatocellular injury and disease progression in patients with nonalcoholic steatohepatitis (NASH). The transcription factor Nrf2 plays a central role in stimulating expression of various antioxidant-associated genes in the cellular defense against oxidative stress. As the cytosolic repressor Keap1 negatively regulates Nrf2, activation of Nrf2 facilitated by its release from Keap1 may represent a promising strategy in the treatment of NASH. To test this hypothesis, we utilized two chemically distinct types of Nrf2-activator. One is the thiol-reactive agent oltipraz (OPZ), a typical Nrf2-activator, and the other is a novel biaryl urea compound, termed NK-252. NK-252 exhibits a greater Nrf2-activating potential than OPZ. Furthermore, in vitro binding studies revealed that NK-252 interacts with the domain containing the Nrf2-binding site of Keap1, whereas OPZ does not. This finding indicates that NK-252 is more potent than OPZ due to its unique mechanism of action. For in vivo animal model studies, we employed rats on a choline-deficient L-amino acid-defined (CDAA)-diet, which demonstrate pathological findings similar to those seen in human NASH. The administration of OPZ or NK-252 significantly attenuated the progression of histological abnormalities in rats on a CDAA diet, especially hepatic fibrosis. In conclusion, by using Nrf2-activators with independent mechanisms of action, we show in a rat model of NASH that the activation of Nrf2 is responsible for the anti-fibrotic effects of these drugs. This strategy of Nrf2 activation presents new opportunities for treatment of NASH patients with hepatic fibrosis. 23258773 Assessing ongoing sources of dissolved-phase polychlorinated biphenyls in a contaminated stream. Few studies assess the potential of ongoing sources of "fresh" polychlorinated biphenyls (PCBs) to aquatic systems when direct discharge to the environment has been eliminated. In the present study, the authors used single-layered, low-density polyethylene samplers (PEs) to measure total PCB concentrations, congener profiles, and enantiomeric fractions (EFs) in a contaminated stream and to provide multiple lines of evidence for assessing ongoing inputs of PCB. Concentrations were well above background levels that have been monitored for years. Concentrations significantly increased with distance, the farthest downstream PE concentrations being almost five times greater than those at 79 m downstream of a historical point source. The PCBs in the PEs at 79 m downstream of the contamination source were dominated by low K(OW) congeners, similar to those in the mixture of Aroclors 1016 and 1254 (4:1 v/v) historically released from the former capacitor manufacturer. The only two chiral congeners detected in the PEs downstream were PCBs 91 and 95. The EF values were nonracemic for PCB 91, while the values were either racemic or near racemic for PCB 95. Increased PCB concentrations with distance and a congener composition of predominantly low-weight congeners in the PEs at 79 m downstream of the plant site suggested an ongoing PCB source from the plant site. Chiral signatures suggested aerobic biotransformation of dissolved PCBs but did not shed any light on possible ongoing PCB inputs. 23335243 Genetic dissection of sesquiterpene biosynthesis by Fusarium fujikuroi. A treasure trove of terpenes: The products of two fungal sesquiterpene synthases from the rice pathogen Fusarium fujikuroi were identified by gene-knockout experiments, genetic engineering of the fungus for production optimization, isolation of the sesquiterpenes, and structure elucidation by spectroscopic methods. 23628333 Identification of substituted 2-thio-6-oxo-1,6-dihydropyrimidines as inhibitors of human lactate dehydrogenase. A novel 2-thio-6-oxo-1,6-dihydropyrimidine-containing inhibitor of human lactate dehydrogenase (LDH) was identified by high-throughput screening (IC50=8.1μM). Biochemical, surface plasmon resonance, and saturation transfer difference NMR experiments indicated that the compound specifically associated with human LDHA in a manner that required simultaneous binding of the NADH co-factor. Structural variation of the screening hit resulted in significant improvements in LDHA biochemical inhibition activity (best IC50=0.48μM). A crystal structure of an optimized compound bound to human LDHA was obtained and explained many of the observed structure-activity relationships. 23017406 GABA shunt and polyamine degradation pathway on γ-aminobutyric acid accumulation in germinating fava bean (Vicia faba L.) under hypoxia. GABA shunt and polyamine degradation pathway on γ-aminobutyric acid (GABA) accumulation in germinating fava bean under hypoxia was investigated. GABA content, GAD and DAO activity were significantly increased under hypoxia treatment. Glu and polyamine contents enhanced largely and thus supplied as sufficient substrates for GABA formation. In contrast, GABA content decreased, mainly in the embryo, after removing the hypoxia stress. DAO activity, Glu and polyamines contents decreased, while an increment of GAD activity was observed. This indicated that GAD activity can be not only regulated by hypoxia, but by the rapid growth of embryo after the recovery from hypoxia stress. When treated with AG, DAO activity was almost inhibited completely, and the GABA content decreased by 32.96% and 32.07% after treated for 3 and 5 days, respectively. Hence, it can be inferred that about 30% of GABA formed in germinating fava bean under hypoxia was supplied by polyamine degradation pathway. 23553811 Clinical update on the management of atrial fibrillation. Atrial fibrillation (AF) is a cardiac arrhythmia associated with significant morbidity and mortality, affecting more than 3 million people in the United States and 1-2% of the population worldwide. Its estimated prevalence is expected to double within the next 50 years. During the past decade, there have been significant advances in the treatment of AF. Studies have demonstrated that a rate control strategy, with a target resting heart rate between 80 and 100 beats/minute, is recommended over rhythm control in the vast majority of patients. The CHA2 DS2 ≥ (congestive heart failure, hypertension, age ≥ 65 yrs, diabetes mellitus, stroke or transient ischemic attack, vascular disease, female gender) scoring system is a potentially useful stroke risk stratification tool that incorporates additional risk factors to the commonly used CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke transient ischemic attack) scoring tool. Similarly, a convenient scheme, termed HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), to assess bleeding risk has emerged that may be useful in select patients. Furthermore, new antithrombotic strategies have been developed as potential alternatives to warfarin, including dual-antiplatelet therapy with clopidogrel plus aspirin and the development of new oral anticoagulants such as dabigatran, rivaroxaban, and apixaban. Vernakalant has emerged as another potential option for pharmacologic conversion of AF, whereas recent trials have better defined the role of dronedarone in the maintenance of sinus rhythm. Finally, catheter ablation represents another alternative to manage AF, whereas upstream therapy with inhibitors of the renin-angiotensin-aldosterone system, statins, and polyunsaturated fatty acids could potentially prevent the occurrence of AF. Despite substantial progress in the management of AF, significant uncertainty surrounds the optimal treatment of this condition. 23573990 Tailoring of morphology and surface properties of syndiotactic polystyrene aerogels. This study evaluates a method for rendering syndiotactic polystyrene (sPS) aerogels hydrophilic using polyethylene oxide (PEO) of different molecular weights. The highly porous sPS aerogels are inherently hydrophobic although applications involving absorption of moisture and removal of particulate solids may benefit from the high surface area of sPS aerogels provided some degree of hydrophilicity is induced in these materials. In this work, sPS gels are prepared by thermo-reversible gelation in tetrahydrofuran in the presence of PEO. The gels are dried under supercritical conditions to obtain aerogels. The aerogels are characterized by scanning electron microscopy, nitrogen-adsorption porosimetry, helium pycnometry, and contact angle measurements. The data reveal that the pore structures and surface energy can be controlled by varying the concentration and molecular weight of PEO and using different cooling rates during thermo-reversible gelation. In the first case, sPS aerogels, aerogels containing PEO of a low molecular weight or low concentration show superhydrophobic surface presenting the "lotus effect". In the second case, PEO at a higher concentration or with higher molecular weight forms phase-separated domains yielding new hydrophilic macropores (>10 μm) in the aerogel structures. These macropores contribute to the superhydrophobic surface with the "petal effect". The cooling rate during gelation shows a strong influence on these two cases. 23573957 HCV NS5A Replication Complex Inhibitors. Part 4. (1) Optimization for Genotype 1a Replicon Inhibitory Activity. A series of symmetrical E-stilbene prolinamides that originated from the library-synthesized lead 3 was studied with respect to HCV genotype 1a (G-1a) and genotype 1b (G-1b) replicon inhibition and selectivity against BVDV and cytotoxicity. SAR emerging from an examination of the prolinamide cap region revealed 11 to be a selective HCV NS5A inhibitor exhibiting submicromolar potency against both G-1a and G-1b replicons. Additional structural refinements resulted in the identification of 30 as a potent, dual G-1a/1b HCV NS5A inhibitor. 22872100 The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy. The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant. 22512590 Chitin synthase inhibitors as antifungal agents. Increased risk of fungal diseases in immunocompromised patients, emerging fungal pathogens, limited repertoire of antifungal drugs and resistance development against the drugs demands for development of new and effective antifungal agents. With greater knowledge of fungal metabolism efforts are being made to inhibit specific enzymes involved in different biochemical pathways for the development of antifungal drugs. Chitin synthase is one such promising target as it is absent in plants and mammals. Nikkomycin Z, a chitin synthase inhibitor is under clinical development. Chitin synthesis in fungi, chitin synthase as a target for antifungal agent development, different chitin synthase inhibitors isolated from natural sources, randomly synthesized and modified from nikkomycin and polyoxin are discussed in this review. 23561128 Effect of nitrite on the odourant volatile fraction of cooked ham. The aim of this work was to reliably identify the key odour compounds in cooked ham and acquire new knowledge on the role of sodium nitrite on the formation of its aroma. Gas chromatography coupled with mass spectrometry and (or) olfactometry was used. In all, 24 odourants were identified in the volatile fraction of cooked ham. Their main origins are discussed. Orthonasal sniffing of the hams was used to study how these substances contributed to the overall aroma of the product. The aroma of cooked ham is a balance between that of certain sulfur compounds produced during cooking and that of oxidation compounds commonly found in cooked meats. In the absence of nitrite, this balance is disturbed by extensive formation of oxidation compounds that mask the meaty notes induced by the sulfur compounds. 23360180 Combined effects of Ag nanoparticles and oxygen plasma treatment on PLGA morphological, chemical, and antibacterial properties. The purpose of this study is to investigate the combined effects of oxygen plasma treatments and silver nanoparticles (Ag) on PLGA in order to modulate the surface antimicrobial properties through tunable bacteria adhesion mechanisms. PLGA nanocomposite films, produced by solvent casting with 1 wt % and 7 wt % of Ag nanoparticles were investigated. The PLGA and PLGA/Ag nanocomposite surfaces were treated with oxygen plasma. Surface properties of PLGA were investigated by field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), static contact angle (CA), and high resolution X-ray photoelectron spectroscopy (XPS). Antibacterial tests were performed using an Escherichia coli RB (a Gram negative) and Staphylococcus aureus 8325-4 (a Gram positive). The PLGA surface becomes hydrophilic after the oxygen treatment and its roughness increases with the treatment time. The surface treatment and the Ag nanoparticle introduction have a dominant influence on the bacteria adhesion and growth. Oxygen-treated PLGA/Ag systems promote higher reduction of the bacteria viability in comparison to the untreated samples and neat PLGA. The combination of Ag nanoparticles with the oxygen plasma treatment opens new perspectives for the studied biodegradable systems in biomedical applications. 23451707 Discovery of allosteric modulators of factor XIa by targeting hydrophobic domains adjacent to its heparin-binding site. To discover promising sulfated allosteric modulators (SAMs) of glycosaminoglycan-binding proteins (GBPs), such as human factor XIa (FXIa), we screened a library of 26 synthetic, sulfated quinazolin-4(3H)-ones (QAOs) resulting in the identification of six molecules that reduced the Vmax of substrate hydrolysis without influencing the KM. Mutagenesis of residues of the heparin-binding site (HBS) of FXIa introduced a nearly 5-fold loss in inhibition potency supporting recognition of an allosteric site. Fluorescence studies showed a sigmoidal binding profile indicating highly cooperative binding. Competition with a positively charged, heparin-binding polymer did not fully nullify inhibition suggesting importance of hydrophobic forces to binding. This discovery suggests the operation of a dual-element recognition process, which relies on an initial Coulombic attraction of anionic SAMs to the cationic HBS of FXIa that forms a locked complex through tight interaction with an adjacent hydrophobic patch. The dual-element strategy may be widely applicable for discovering SAMs of other GBPs. 23632082 GIRK-like and TRPC-like conductances mediate thyrotropin-releasing hormone-induced increases in excitability in thalamic paraventricular nucleus neurons. The thalamic paraventricular nucleus (PVT), reported to participate in arousal and motivated behaviors, contains abundant receptors for thyrotropin-releasing hormone (TRH), a neuropeptide also known to modulate arousal and mood. To test the hypothesis that TRH could influence the excitability of PVT neurons, whole call patch clamp recordings obtained in rat brain slice preparations were evaluated during bath applied TRH. In the majority of neurons tested, TRH induced reversible TTX-resistant membrane depolarization. Under voltage-clamp, TRH induced a concentration-dependent G protein- mediated inward current. The mean net TRH-induced current exhibited a decrease in membrane conductance. Further analyses identified two concurrent conductances contributing to the TRH-induced response. One conductance featured a Na(+)-independent and K(+)-dependent net current that displayed rectification and was suppressed by micromolar concentrations of Ba(2+) and two GIRK antagonists, tertiapin Q and SCH 23390. The second conductance featured a Na(+)-dependent net inward current with an I-V relationship that exhibited double rectification with a negative slope conductance below -40 mV. This conductance was suppressed by nonselective TRPC channel blockers 2-APB, flufenamic acid and ML204, enhanced by La(3+) in a subpopulation of cells, and unchanged by the TRPV1 antagonist capsazepine or a Na(+) /Ca(2+) exchanger blocker KB-R7943. TRH also enhanced hyperpolarization-activated low threshold spikes, a feature that was sensitive to pretreatment with either 2-APB or ML204. Collectively, the data imply that TRH enhances excitability in PVT neurons via concurrently decreasing a G-protein-gated inwardly rectifying K(+) conductance and activating a cationic conductance with characteristics reminiscent of TRPC-like channels, possibly involving TRPC4/C5 subunits. 23395656 Synthesis and biological evaluation of new cytotoxic indazolo[4,3-gh]isoquinolinone derivatives. A series of indazolo[4,3-gh]isoquinolinones derivatives have been synthesized to decrease cardiotoxic side effects in comparison to Mitoxantrone. The antiproliferative effects of different side chains were investigated and tested on at least four different cell lines of cervix, ovarian, CNS, NSCLC (non-small-cell lung cancer) and colon carcinoma. In addition to antiproliferative activities, influence on cell cycle and intercalation behavior have been tested. 23523258 In vivo effect of Schisandrin B on cytochrome P450 enzyme activity. To investigate the possible drug interaction, this study is designed to evaluate the ability of Schisandrin B (Sch B) to modulate cytochrome P450 3A activity (CYP3A) in vivo and to alter the pharmacokinetic profiles of CYP3A substrate (midazolam) in treated rats. Rats were repeated administered with physiological saline (negative control group), ketoconazole (75mg/kg, positive control group) or varied doses of Sch B (experimental groups) for three consecutive days. Subsequently, changes in hepatic microsomal CYP3A activity and the pharmacokinetic profiles of midazolam and 1'-hydroxy midazolam in plasma were studied to evaluate CYP3A activity. The results indicated that Sch B significantly dose-dependently inhibited rat hepatic microsomal CYP3A activity with Ki value of 16.64mg/kg and showed the characteristic of a noncompetitive inhibitor. Oral administration of Sch B for 3 days in rats produced significant effect on the pharmacokinetics of oral midazolam. Sch B resulted in a significant, dose-dependent increase in midazolam AUC0-∞ except at the dose of 2mg/kg, while AUC0-∞ increased by 26.1% (8mg/kg) and 60.6% (16mg/kg), respectively. In the pharmacokinetic profiles of 1'-hydroxy midazolam, the significant, dose-dependent decrease in AUC0-∞ was observed except at the dose of 2mg/kg, while AUC0-∞ reduced by 44.5% (8mg/kg) and 49.2% (16mg/kg), respectively. These results suggested that 3-day treatment of Sch B could increase concentration and oral bioavailability of drug metabolized by CYP3A. When the drug, consisting of Sch B, is used in the clinic for more than 3 days, the possible drug-drug interactions should be taken into consideration. 23225764 Preparation of functional water-soluble low-cytotoxic poly(methacrylate)s with pendant cationic L-lysines for efficient gene delivery. In this work, we present the preparation of water-soluble poly(methacrylate)s with pendant cationic L-lysines PHMLs(6-30 K). Plasmid DNA binding affinity as well as particle sizes and zeta potentials of the polyplexes were examined for these PHML vectors, and their cytotoxicities were assayed with HeLa cells by CCK-8 and lactate dehydrogenase kits. Gene transfection efficacy and intracellular uptake of the polyplexes by the PHML vectors were also studied with HeLa cells. As a result, it was revealed that the low cytotoxic PHMLs tended to exhibit gene transfection efficiencies significantly higher than those of the linear structural PLL (15-30 K) control, in particular the molecular weight of a PHML vector remarkably influenced its pDNA binding affinity, transfection efficacy and intracellular uptake of the polyplexes. 23335320 Synthesis and characterization of conformationally rigid chiral pyridine-N-heterocyclic carbene-based palladacycles with an unexpected Pd-N bond cleavage. The versatility of a previously developed method for the synthesis of chiral carbene-based palladacycles is demonstrated through the synthesis of two new chiral pyridine-functionalized N-heterocyclic carbene palladacycles with different wingtip groups. The efficiency in their resolution with different counter anions and different chiral amino acid salt auxiliaries has been studied. The absolute stereochemistries of all the chiral compounds were confirmed by single crystal X-ray crystallography. An unexpected Pd-N bond cleavage that resulted in the racemization of the α-carbon center in these complexes has also been investigated. 23425605 The role of de novo catecholamine synthesis in mediating methylmercury-induced vesicular dopamine release from rat pheochromocytoma (PC12) cells. The purpose of this study was to characterize methylmercury (MeHg)-induced dopamine (DA) release from undifferentiated pheochromocytoma (PC12) cells and to examine the potential role for DA synthesis in this process. MeHg caused a significant increase in DA release that was both concentration- and time-dependent. DA release was significantly increased by 2µM MeHg at 60min and by 5µM MeHg at 30min; 1µM MeHg was without effect. Because DA release induced by 5µM MeHg was associated with a significant percentage of cell death at 60 and 120min, 2µM MeHg was chosen for further characterization of release mechanisms. MeHg-induced DA release was attenuated but not abolished in the absence of extracellular calcium, whereas the vesicular content depleting drug reserpine (50nM) abolished release. Thus, MeHg-induced DA release requires vesicular exocytosis but not extracellular calcium. MeHg also increased intracellular DA and the rate of DA storage utilization, suggesting a role for DA synthesis in MeHg-induced DA release. The tyrosine hydroxylase inhibitor α-methyltyrosine (300µM, 24h) completely abolished MeHg-induced DA release. MeHg significantly increased DA precursor accumulation in cells treated with 3-hydroxybenzylhydrazine (10µM), revealing that MeHg increases tyrosine hydroxylase activity. Overall, these data demonstrate that MeHg facilitates DA synthesis, increases intracellular DA, and augments vesicular exocytosis. 23633521 Loss of Kruppel-like Factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2). Krüppel-like Factor 3 (KLF3) is a transcriptional regulator that we have shown to be involved in the regulation of adipogenesis in vitro. Here we report that KLF3 null mice are lean and protected from diet-induced obesity and glucose intolerance. On a chow diet, plasma levels of leptin are decreased, and adiponectin is increased. Despite significant reductions in body weight and adiposity, wildtype and knockout animals show equivalent energy intake, expenditure and excretion. To investigate the molecular events underlying these observations, we used microarray analysis to compare gene expression in Klf3(+/+) and Klf3(-/-) tissues. We found that mRNA expression of Fam132a, which encodes a newly identified insulin-sensitizing adipokine, adipolin, is significantly upregulated in the absence of KLF3. We confirmed that KLF3 binds the Fam132a promoter in vitro and in vivo and that this leads to repression of promoter activity. Further, plasma adipolin levels were significantly increased in Klf3(-/-) mice compared to wild-type littermates. Boosting levels of adipolin via targeting of KLF3 offers a novel potential therapeutic strategy for the treatment of insulin resistance. 23495190 Artemisinin-polypyrrole conjugates: synthesis, DNA binding studies and preliminary antiproliferative evaluation. Greater than the sum of its parts: Artemisinins are currently in phase I-II clinical trials against breast, colorectal and non-small-cell lung cancers. In an attempt to offer increased specificity, a series of hybrid artemisinin-polypyrrole minor groove binder conjugates are described. DNA binding/modelling studies and preliminary biological evaluation give insights into their mechanism of action and the potential of this strategy. 23207328 Nasal administration of liquid crystal precursor mucoadhesive vehicle as an alternative antiretroviral therapy. The purpose of this study was to develop a mucoadhesive stimuli-sensitive drug delivery system for nasal administration of zidovudine (AZT). The system was prepared by formulating a low viscosity precursor of a liquid crystal phase, taking advantage of its lyotropic phase behavior. Flow rheology measurements showed that the formulation composed of PPG-5-CETETH-20, oleic acid and water (55, 30, 15% w/w), denominated P, has Newtonian flow behavior. Polarized light microscopy (PLM) revealed that formulation P is isotropic, whereas its 1:1 (w/w) dilution with artificial nasal mucus (ANM) changed the system to an anisotropic lamellar phase (PD). Oscillatory frequency sweep analysis showed that PD has a high storage modulus (G') at nasal temperatures. Measurement of the mucoadhesive force against excised porcine nasal mucosa or a mucin disk proved that the transition to the lamellar phase tripled the work of mucoadhesion. Ex vivo permeation studies across porcine nasal mucosa exhibited an 18-fold rise in the permeability of AZT from the formulation. The Weibull mathematical model suggested that the AZT is released by Fickian diffusion mechanisms. Hence, the physicochemical characterization, combined with ex vivo studies, revealed that the PPG-5-CETETH-20, oleic acid, and water formulation could form a mucoadhesive matrix in contact with nasal mucus that promoted nasal absorption of the AZT. For an in vivo assessment, the plasma concentrations of AZT in rats were determined by HPLC method following intravenous and intranasal administration of AZT-loaded P formulation (PA) and AZT solution, respectively, at a dose of 8mg/kg. The intranasal administration of PA resulted in a fast absorption process (Tmax=6.7min). Therefore, a liquid crystal precursor formulation administered by the nasal route might represent a promising novel tool for the systemic delivery of AZT and other antiretroviral drugs. In the present study, the uptake of AZT absorption in the nasal mucosa was demonstrated, providing new foundations for clinical trials in patients with AIDS. 23379346 Introduction of Target Cliffs as a Concept To Identify and Describe Complex Molecular Selectivity Patterns. The study of target specificity or selectivity of small molecules is an important task in drug design. In an ideal situation, a compound would exclusively interact with an individual target and hence be target specific. However, such exclusive binding events are likely to be rare, as increasing evidence suggests. Because many compounds are active against more than one target, apparent selectivity often results from potency differences, i.e., a compound that is highly potent against a given target and weakly potent against one or more others displays target selectivity. In a simple case, a compound might have known activity against a pair of targets and be selective for one over the other. Then, selectivity is straightforward to rationalize. However, there are many more complex selectivity relationships associated with multi-target activities of compounds that are difficult to analyze and compare in a consistent manner. For this purpose, we introduce herein target cliffs as a concept to describe complex selectivity patterns. A target cliff is defined as a pair of targets against which at least one compound displays a large difference in potency. As such, target cliffs are distinct from activity cliffs. However, qualifying target pairs (target cliffs) and compound pairs (activity cliffs) can be systematically extracted from the same data structure termed target-compound matrices. Furthermore, these two types of cliffs can be compared to identify and prioritize compounds that are selective and reveal structure-activity relationship (SAR) information. 23531160 Inflammation, serotonin and major depression. The understanding of the neurobiological processes leading to major depressive disorder (MDD) is an active field of research in the scientific community. For years, the alteration of monoamine neurotransmission, in particular serotonin (5-HT), has been considered the most significant pathophysiological mechanism of the disorder. However, biological data supporting the postulated MDD-related monoamine alterations have been inconclusive, and the use of monoaminergic antidepressants has not yielded the expected results. In the last few years, it has been demonstrated that inflammatory pathways have a significant role in the pathophysiology of MDD. According to the cytokine hypothesis, the disorder would be due to a stress-related increased production of cytokines, including interleukins, tumor necrosis factor- α and interferon- α and γ . These, in turns, would cause the activation of the indoleamine 2,3 dioxygenase (IDO), with subsequent production of tryptophan (TRP) catabolites along the IDO pathway (TRYCATs) and decreased availability of TRP and 5-HT. Besides monoamines, other molecular mechanisms, as those within the inflammatory pathways, should be taken into account in the attempt to clarify the pathophysiology of MDD and to improve its treatment. 23564918 NH2-Terminal Probrain Natriuretic Peptide Is a Stronger Predictor of Cardiovascular Mortality Than C-Reactive Protein and Albumin Excretion Rate in Elderly Patients With Type 2 Diabetes: The Casale Monferrato population-based study. OBJECTIVETo study whether NH2-terminal probrain natriuretic peptide (NT-proBNP) is a short-term independent predictor of both all-cause and cardiovascular (CV) mortality in type 2 diabetic patients and to establish whether albuminuria and C-reactive protein (CRP) affect this relationship.RESEARCH DESIGN AND METHODSThe prospective study included 1,825 type 2 diabetic patients from the population-based cohort of the Casale Monferrato study. CV risk factors, preexisting CVD, and NT-proBNP levels were evaluated at baseline. All-cause and CV mortality were assessed 5.5 years after baseline examination. Multivariate Cox proportional hazards modeling was used to estimate mortality hazard ratios (HRs).RESULTSDuring the follow-up period, 390 people died (175 for CVD) out of 9,101 person-years of observations. A significantly increased mortality risk by quartiles of NT-proBNP was observed (test for trend, P < 0.001). NT-proBN P values >91 pg/mL conferred HRs of 2.05 (95% CI 1.47-2.86) for all-cause and 4.47 (2.38-8.39) for CV mortality, independently of CV risk factors, including CRP and albumin excretion rate (AER). The association was also significant for modest rises in NT-proBNP levels and in patients without microalbuminuria and CVD at baseline (upper quartiles HRs 3.82 [95% CI 1.24-13.75]) and 3.14 [1.00-9.94]). Albuminuria and NT-proBNP had an additive effect on mortality, though the association was stronger for NT-proBNP.CONCLUSIONSNT-proBNP is a strong independent predictor of short-term CV mortality risk in elderly people with type 2 diabetes, including those without preexisting CVD. This association is evident even in people with slightly increased values, is not modified by CRP, and is additive to that provided by AER. 23500778 Protective effects of a compound isolated from Alnus japonica on oxidative stress-induced death in transformed retinal ganglion cells. Here, we investigated whether hirsutenone, a compound isolated from Alnus japonica, was able to attenuate oxidative stress-induced death in transformed retinal ganglion (RGC-5) cells. Hirsutenone effectively protected RGC-5 cells from oxidative insult induced by, l-buthionine-(S,R)-sulfoximine (BSO) plus glutamate in a concentration-dependent manner, as demonstrated by propidium iodide (PI)/Hoechst 33342 double staining, flow cytometry, and MTT assays. Moreover, hirsutenone inhibited the increase in apoptotic protein expression resulting from BSO plus glutamate. Hirsutenone also effectively inhibited sodium nitroprusside (SNP)-induced lipid peroxidation in rat brain homogenates. To investigate the effects of hirsutenone in vivo, we used N-methyl-d-aspartate (NMDA) as a negative insult on the retinas of rats. NMDA affects the thinning of the inner plexiform layer (IPL) and causes an increase in the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive ganglion cells in the ganglion cell layer (GCL). Hirsutenone treatment led to a reduction in NMDA-induced IPL and TUNEL staining of the GCL. In conclusion, hirsutenone isolated from A. japonica may act as neuroprotective agent for conditions such as glaucoma. 23400888 Abo-, inco-, ona-, and rima-botulinum toxins in clinical therapy: a primer. Botulinum neurotoxin (BoNT) is an acetylcholine release inhibitor and a neuromuscular-blocking agent used for the treatment of a variety of medical and cosmetic indications. Currently, in the United States, there are four BoNT formulations licensed for use: abobotulinumtoxinA, incobotulinumtoxinA, onabotulinumtoxinA, and rimabotulinumtoxinB. These revised name designations were established to reinforce the understanding that each BoNT product has an individual potency and is not interchangeable with any other BoNT product. The therapeutic use of BoNTs is expanding and new formulations are on the horizon. This article is a primer that describes distinctions among currently available, licensed BoNT formulations. Toxin pharmacology, product characteristics, storage, handling, preparation, and dosages will be reviewed. In addition, issues related to dose equivalency ratios, immunogenicity, potency, and toxin spread will be discussed. Therapeutic indications and safety are discussed briefly. Knowledge of the available and licensed BoNT formulations and the ability to make distinctions in toxin pharmacology, product characteristics, and indications are vital for product selection, preparation, drug information, avoidance of drug errors, quality assurance, and patient safety. 23411268 Characterization of oils and fats by 1H NMR and GC/MS fingerprinting: classification, prediction and detection of adulteration. The correct identification of oils and fats is important to consumers from both commercial and health perspectives. Proton nuclear magnetic resonance ((1)H NMR) spectroscopy, gas chromatography-mass spectrometry (GC/MS) fingerprinting and chemometrics were employed successfully for the quality control of oils and fats. Principal component analysis (PCA) of both techniques showed group clustering of 14 types of oils and fats. Partial least squares discriminant analysis (PLS-DA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) using GC/MS data had excellent classification sensitivity and specificity compared to models using NMR data. Depending on the availability of the instruments, data from either technique can effectively be applied for the establishment of an oils and fats database to identify unknown samples. Partial least squares (PLS) models were successfully established for the detection of as low as 5% of lard and beef tallow spiked into canola oil, thus illustrating possible applications in Islamic and Jewish countries. 23639545 Synthesis and ionophoric activities of functionalized bis(choloyl) conjugates with a rigid core. Three bis(choloyl) conjugates bearing a rigid p-phenylenediamine/p-bis(aminomethyl)benzene linker and amino/acetamido groups were synthesized, and fully characterized on the basis of (1)H NMR, ESI-MS and HRMS. Their ionophoric activities were investigated by means of pH discharge assay. The results indicate that these conjugates exhibit potent ionophoric activities across egg-yolk l-α-phosphatidylcholine (EYPC)-based liposomal membranes, via a cation/proton antiport mechanism. They show moderate ion selectivity among alkali metal ions. Of the three conjugates, the ones having amino groups transport alkali metal ions in the order of Na(+)>Li(+)>K(+)≈Rb(+)≈Cs(+), whereas the one having acetamido groups functions in the order of Li(+)>Na(+)>K(+)≈Rb(+)≈Cs(+). 23489624 Novel small molecules as apoptosis inducers: synthesis, preliminary structure-activity relationships, and in vitro biological evaluation. Inducing apoptosis is a promising therapeutic approach to overcome cancer. In this study, 30 compounds were synthesized and evaluated for their antiproliferative activity against three tumor cell lines in vitro: A875, H460 and Hela cancer cells by the MTT assay. The most potent analogue 7a, a novel compound was first reported by our group, inhibited the proliferation of A875 cells with an IC50 value of 98 nM. Flow cytometry analysis and morphological analysis suggested that compound 7a had potential anticancer efficacy via G2/M cell cycle arrest, which could be attributed to its proliferation and apoptosis, and also in a concentration-dependent manner. The SAR analysis indicated that the substituents R(2) played a crucial role in the antiproliferation activity. 23299909 Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART Body Composition substudy. Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17% female, 74% on ART) randomised to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline, months 4 and 12; BMD at the spine (dual X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared to the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (βCTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p<0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and βCTX at month 4 predicted decrease in hip BMD at month 12, while increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months. © 2013 American Society for Bone and Mineral Research. 23529671 Evaluation of body weight, insulin resistance, leptin and adiponectin levels in premenopausal women with hyperprolactinemia. The effects of hyperprolactinemia on metabolic parameters are not clear and a few data evaluating adiponectin levels in prolactinoma and idiopathic hyperprolactinemia exist. The aim of this study was to evaluate the effects of hyperprolactinemia on body weight, insulin resistance, beta cell function, and leptin and adiponectin levels in premenopausal women with hyperprolactinemia. Forty premenopausal women with prolactinoma or idiopathic hyperprolactinemia were compared to 41 age-matched healthy premenopausal women with regard to body weight, body mass index, waist and hip circumferences, waist to hip ratio, fasting plasma glucose, insulin levels, insulin resistance measured by homeostasis model assessment (HOMA)-insulin resistance index, beta cell function measured by HOMA-β index, leptin and adiponectin levels. Plasma insulin levels and HOMA indexes (both insulin resistance and beta indexes) were significantly higher in hyperprolactinemic women. The other parameters were similar between both groups. There was a positive correlation between prolactin levels and fasting plasma glucose in hyperprolactinemic women. The results of this study showed that high prolactin levels may be associated with hyperinsulinemia and insulin resistance in premenopausal women. This effect seems to be independent of body weight, leptin and adiponectin levels. High prolactin levels may directly stimulate insulin secretion from pancreas and directly cause hepatic and whole-body insulin resistance. 23412992 Cardiotonic steroids-mediated Na+/K+-ATPase targeting could circumvent various chemoresistance pathways. Many cancer patients fail to respond to chemotherapy because of the intrinsic resistance of their cancer to pro-apoptotic stimuli or the acquisition of the multidrug resistant phenotype during chronic treatment. Previous data from our groups and from others point to the sodium/potassium pump (the Na+/K+-ATPase, i.e., NaK) with its highly specific ligands (i.e., cardiotonic steroids) as a new target for combating cancers associated with dismal prognoses, including gliomas, melanomas, non-small cell lung cancers, renal cell carcinomas, and colon cancers. Cardiotonic steroid-mediated Na+/K+-ATPase targeting could circumvent various resistance pathways. The most probable pathways include the involvement of Na+/K+-ATPase β subunits in invasion features and Na+/K+-ATPase α subunits in chemosensitisation by specific cardiotonic steroid-mediated apoptosis and anoïkis-sensitisation; the regulation of the expression of multidrug resistant-related genes; post-translational regulation, including glycosylation and ubiquitinylation of multidrug resistant-related proteins; c-Myc downregulation; hypoxia-inducible factor downregulation; NF-κB downregulation and deactivation; the inhibition of the glycolytic pathway with a reduction of intra-cellular ATP levels and an induction of non-apoptotic cell death. The aims of this review are to examine the various molecular pathways by which the NaK targeting can be more deleterious to biologically aggressive cancer cells than to normal cells. 23265492 Three sulphated polysaccharides isolated from the mucilage of mud snail, Bullacta exarata philippi: characterization and antitumour activity. Three sulphated polysaccharides, coded as BEMPA, BEMPB(1), BEMPB(2), were extracted from the mucilage of mud snail of Bullacta exarata and purified by DEAE-cellulose ion-exchange and size-exclusion chromatography. Structural analysis of purified polysaccharides by chemical and biochemical methods revealed BEMPA was a high (1→3,4)-linked mannose-containing polysaccharide with molecular weight of 22,977 Da. BEMPB(1), with molecular weight of 64,117 Da, was a high (1→3)-linked arabinose-containing polysaccharide. BEMPB(2) was mainly composed of (1→3,4)-linked mannose with molecular weight of 47,507Da. The comparison between sulphated polysaccharides and their desulphated products showed that sulphate substitutions of BEMPB(1) were deduced to be at the C-3 of (1→4)-linked mannose, while sulphate substitutions of BEMPA and BEMPB(2) were at C-4 of (1→3)-linked mannose. Furthermore, BEMPA exhibited highest inhibitory effects on growth of B-16 melanoma cells, and IC(50) were 31.1 μg/mL. 22986456 Decreased serum chemerin levels in male Japanese patients with type 2 diabetes: sex dimorphism. Chemerin, a recently discovered adipocytokine plays an important role in obesity and obesity-associated metabolic complications. However, the role of chemerin in the pathogenesis of type 2 diabetes mellitus (T2DM) has not fully been elucidated. We compared the serum chemerin levels and metabolic parameters between 88 control subjects, 86 patients with metabolic syndrome (MS), and 147 patients with T2DM in a Japanese population and further analyzed their correlation. Enzyme-linked immunosorbent assay was used to measure the serum chemerin levels. The chemerin levels were significantly higher in male than in female control subjects (p < 0.005), with significant decreases in patients with T2DM compared with those with MS and control subjects (164.9 ± 6.3 ng/mL vs. 209.8 ± 7.7 and 218.7 ± 7.3 ng/mL; p < 0.0001 vs. p < 0.0001, respectively) but no significant differences in female subjects. The multiple regression analysis revealed that the chemerin levels negatively correlated with the fasting glucose and HbA1c levels in total and male subjects. In the patients with T2DM, the chemerin levels negatively correlated with fasting glucose and high-density lipoprotein cholesterol but positively correlated with body mass index (BMI), and total cholesterol and triglyceride levels. The negative correlation between the chemerin and fasting glucose levels remained significant after adjustment for age, sex, and BMI in the total and male subjects and those with T2DM. These results suggest the role of chemerin in sex dimorphism and a potential link between chemerin levels and T2DM pathogenesis in a Japanese population. 23394394 Uncertain prognosis for high-quality diagnostics: clinical challenges, economic barriers and needed reforms. Quality healthcare, as measured by outcomes and costs, needs high-quality diagnostics whose use governs the evidence-based flow of patients from screening to treatment to outcomes monitoring. The current patent, regulatory and reimbursement environment may be inadequate to spur their development, thereby placing in jeopardy the goals of healthcare reform and the aspirations of personalized medicine. Policy actions to ensure consistent quality standards and to increase development incentives through research support, reimbursement reform, increased intellectual property protection and market-making activities may be required to obtain the well-characterized, clinically proven diagnostics that US healthcare requires. 23540609 Molar Mass, Entanglement, and Associations of the Biofilm Polysaccharide of Staphylococcus epidermidis. Biofilms are microbial communities that are characterized by the presence of a viscoelastic extracellular polymeric substance (EPS). Studies have shown that polysaccharides, along with proteins and DNA, are a major constituent of the EPS and play a dominant role in mediating its microstructure and rheological properties. Here, we investigate the possibility of entanglements and associative complexes in solutions of extracellular polysaccharide intercellular adhesin (PIA) extracted from Staphylococcus epidermidis biofilms. We report that the weight average molar mass and radius of gyration of PIA isolates are 2.01 × 10(5) ± 1200 g/mol and 29.2 ± 1.2 nm, respectively. The coil overlap concentration, c*, was thus determined to be (32 ± 4) × 10(-4) g/mL. Measurements of the in situ concentration of PIA (cPIA,biofilm) was found to be (10 ± 2) × 10(-4) g/mL . Thus, cPIA,biofilm < c* and the amount of PIA in the biofilm is too low to cause polymer chain entanglements. In the pH range 3.0-5.5, PIA was found to both self-associate and to form complexes with bovine serum albumin (BSA). By static light scattering, both self-association and complex formation with 0.5% (w/v) BSA were found to occur at PIA concentrations of 0.30 × 10(-4) g/mL and greater, which is about 30 times lower than the measured cPIA,biofilm. These results suggest that the microscopic origin of EPS viscoelasticity is unlikely to be due to polysaccharide entanglements. Furthermore, the onset of self-association and protein complexation of PIA occurs at concentrations far lower than the native PIA concentration in biofilms. This finding therefore suggests a critical role for those two association mechanisms in mediating biofilm viscoelasticity. 23374869 Inhibition of monoamine oxidase by phthalide analogues. Based on recent reports that the small molecules, isatin and phthalimide, are suitable scaffolds for the design of high potency monoamine oxidase (MAO) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1(3H)-one] analogues. Phthalide is structurally related to isatin and phthalimide and it is demonstrated here that substitution at C6 of the phthalide moiety yields compounds endowed with high binding affinities to both human MAO isoforms. Among the nineteen homologues evaluated, the lowest IC(50) values recorded for the inhibition of MAO-A and -B were 0.096 and 0.0014 μM, respectively. In most instances, C6-substituted phthalides exhibit MAO-B specific inhibition. Among a series of 6-benzyloxyphthalides bearing substituents on the para position of the phenyl ring the general order of potency was CF(3) > I > Br > Cl > F > CH(3) > H. The results also show that the binding modes of representative phthalides are reversible and competitive at both MAO isoforms. Based on these data, C6-substituted phthalides may serve as leads for the development of therapies for neurodegenerative disorders such as Parkinson's disease. 23580404 Low Driving Voltage and High Mobility Ambipolar Field-Effect Transistors with PbS Colloidal Nanocrystals. PbS colloidal nanocrystals (NCs) are promising materials for optoelectronic devices, due to their size-tunable properties. However, there is still minimal understanding of their charge transport mechanism. Through a combination of ligand selections, ambipolar transistor structure optimization, and electrochemical gating usage, high carrier mobility is achieved. The outstanding device characteristics open possibility to investigate the intrinsic transport properties of PbS NCs. 23484851 Effect of sequence on the ionization behavior of a series of amphiphilic polypeptides. The behavior of five polypeptides made of hydrophilic and pH-responsive aspartic acid (Asp) and hydrophobic phenylalanine (Phe), which had been prepared by stitching together short well-defined sequences of Asp and Phe, was studied as a function of pH. The effect of pH on these polypeptides referred to as (Asp3Phe1)n, (Asp2Phe1)n, (Asp1Phe1)n, (Asp1Phe2)n, and (Asp1Phe3)n varied dramatically depending on their constituting sequence. The more hydrophobic polypeptides (Asp1Phe2)n and (Asp1Phe3)n behaved as if the Asp's were isolated from each other and showed an apparent pKa (pKa(app)) that remained constant with level of ionization (α = [Asp(-)]/[Asp]total) and equaled 5.4 and 6.4, respectively. The more hydrophilic polypeptides (Asp3Phe1)n and (Asp2Phe1)n behaved like weak polyacids showing a linear increase in pKa(app) with increasing α. The pKa(app) of (Asp1Phe1)n showed a trend as a function of α intermediate between the Asp-rich and Phe-rich polypeptides, behaving as if the Asp's were isolated at low α values (<0.35) but acting as a weak polyacid for large α values (>0.35). The effect that α, and thus the charge density of the polypeptides, had on the collapse and aggregation of the polypeptides was characterized by conducting static light scattering and fluorescence measurements. Static light scattering measurements demonstrated that all polypeptides precipitated and aggregated in solution at a critical charge density of 0.2. Fluorescence measurements with pyrene indicated that this behavior was due to the formation of Phe aggregates in water. Together, these experiments provide a complete description of how pH affects the behavior of a series of unique amphiphilic polypeptides designed with a well-defined sequence. 23399641 Creation and screening of a multi-family bacterial oxidoreductase library to discover novel nitroreductases that efficiently activate the bioreductive prodrugs CB1954 and PR-104A. Two potentially complementary approaches to improve the anti-cancer strategy gene-directed enzyme prodrug therapy (GDEPT) are discovery of more efficient prodrug-activating enzymes, and development of more effective prodrugs. Here we demonstrate the utility of a flexible screening system based on the Escherichia coli SOS response to evaluate novel nitroreductase enzymes and prodrugs in concert. To achieve this, a library of 47 candidate genes representing 11 different oxidoreductase families was created and screened to identify the most efficient activators of two different nitroaromatic prodrugs, CB1954 and PR-104A. The most catalytically efficient nitroreductases were found in the NfsA and NfsB enzyme families, with NfsA homologues generally more active than NfsB. Some members of the AzoR, NemA and MdaB families also exhibited low-level activity with one or both prodrugs. The results of SOS screening in our optimised E. coli reporter strain SOS-R2 were generally predictive of the ability of nitroreductase candidates to sensitise E. coli to CB1954, and of the kcat/Km for each prodrug substrate at a purified protein level. However, we also found that not all nitroreductases express stably in human (HCT-116 colon carcinoma) cells, and that activity at a purified protein level did not necessarily predict activity in stably transfected HCT-116. These results highlight a need for all enzyme-prodrug partners for GDEPT to be assessed in the specific context of the vector and cell line that they are intended to target. Nonetheless, our oxidoreductase library and optimised screens provide valuable tools to identify preferred nitroreductase-prodrug combinations to advance to preclinical evaluation. 23410634 Time series analysis of oxidative stress response patterns in HepG2: A toxicogenomics approach. Oxidative stress plays an important role in chemically induced liver injury, however, our insight into molecular responses to different oxygen radicals is fragmentary. Since these cellular responses will differ over time, examining time-dependent changes in gene expression, and correlating these with markers for oxidative stress, may provide new insights into responses to oxidants. We used the human hepatoma cell line HepG2 to investigate the effects of oxidative stress on the transcriptome level by micro-arrays at seven time points (0.5, 1, 2, 4, 6, 8 and 24h) following exposure to the oxidants menadione, hydrogen peroxide and tert-butyl hydroperoxide including the effects on cell cycle and apoptosis by flow cytometry, protein carbonyl formation by spectrophotometry and oxidative DNA damage by FPG-comet. In total, 3429 genes were differentially expressed, including 136 genes that were significantly modified by all oxidants. Time-dependent biological pathway analysis showed that these genes were particularly involved in inflammatory responses, cell cycle processes and glutathione signaling. These responses were confirmed and supported by phenotypic anchoring to the different cellular endpoints. In addition, using an innovative temporal analysis we established an oxidative stress-related gene expression time cluster. Altogether, this study provides new insights in temporal oxidative stress mechanisms and demonstrates sequential cellular responses that may contribute to a better hazard identification and the mechanisms of toxicological responses in the liver induced by oxidative stress. 23017399 Can the dietary element content of virgin argan oils really be used for adulteration detection? Levels of eight dietary elements were assessed by ICP-AES in virgin edible and beauty argan oil samples prepared from four remote locations of the argan forest, and over a three-year period. The data showed sufficiently little variability to assess that all argan oil samples present, in terms of dietary elements, a similar composition, independently from the tree location within the argan forest. Therefore, adulteration detection by trace element analysis in edible and beauty argan oil is a method that can be generalised. 23261524 Live-cell imaging of p53 interactions using a novel Venus-based bimolecular fluorescence complementation system. p53 plays an important role in regulating a wide variety of cellular processes, such as cell cycle arrest and/or apoptosis. Dysfunction of p53 is frequently associated with several pathologies, such as cancer and neurodegenerative diseases. In recent years substantial progress has been made in developing novel p53-activating molecules. Importantly, modulation of p53 interaction with its main inhibitor, Mdm2, has been highlighted as a promising therapeutic target. In this regard, bimolecular fluorescence complementation (BiFC) analysis, by providing direct visualization of protein interactions in living cells, offers a straightforward method to identify potential modulators of protein interactions. In this study, we developed a simple and robust Venus-based BiFC system to screen for modulators of p53-p53 and p53-Mdm2 interactions in live mammalian cells. We used nutlin-3, a well-known disruptor of p53-Mdm2 interaction, to validate the specificity of the assay. The reduction of BiFC signal mediated by nutlin-3 was correlated with an increase in Puma transactivation, PARP cleavage, and cell death. Finally, this novel BiFC approach was exploited to identify potential modulators of p53-Mdm2 complex formation among a commercially available chemical library of 33 protein phosphatase inhibitors. Our results constitute "proof-of-concept" that this model has strong potential as an alternative to traditional target-based drug discovery strategies. Identification of new modulators of p53-p53 and p53-Mdm2 interactions will be useful to achieve synergistic drug efficacy with currently used anti-tumor therapies. 23448196 The need for better insulin therapy. Insulin replacement therapy corrects a core defect of diabetes pathophysiology. Since its introduction as a therapeutic modality almost 100 years ago, insulin therapy has undergone remarkable changes in purity and ability to provide more physiologic control of blood glucose levels. With glucose-lowering potential limited only by risks of hypoglycaemia, which remains the major limitation in our ability to achieve glycaemic goals, insulin replacement therapy remains a cornerstone of therapy. Major progress in reducing the risks of hypoglycemia has occurred with the development of insulin analogs. This review article briefly chronicles the evolution of insulin replacement strategies, highlighting both challenges in pharmaceutical development and patient acceptance, underscoring achievements, as well as denoting what improvements are still needed. 23210485 Qualitative studies among obese children and adolescents: a systematic review of the literature. Childhood obesity is a complex condition involving medical, social, moral and cultural issues. Qualitative approaches are of great value in understanding this complexity. This meta-synthesis of 45 qualitative studies deals specifically with the issue of obesity in children and adolescents from different perspectives - those of obese children and adolescents, of parents, and of health professionals providing support to the family. Our aim was to obtain a coherent view of child and adolescent obesity, focused on clinical and personal experience. The themes derived from the synthesis process fall under three main axes: 'Seeing others, seeing oneself', 'Understanding others, understanding oneself', and 'Treating others, treating oneself'. It emerges that participants in all three groups had equal difficulty in perceiving and labelling obesity, mainly because of their lack of any real common ground. The insufficiency of shared representations destabilizes the therapeutic relationship and its construction: an important issue in the doctor-child-parent relationship in this context is the need to exchange their viewpoints of obesity. Health workers may also expand their understanding of obesity by incorporating the personal experiences of obese children and their parents in order to match treatment plans to their needs and expectations. 23456978 Plasminogen plays a crucial role in bone repair. The further development in research of bone regeneration is necessary to meet the clinical demand for bone reconstruction. Plasminogen is a critical factor of the tissue fibrinolytic system, which mediates tissue repair in the skin and liver. However, the role of the fibrinolytic system in bone regeneration remains unknown. Herein, we investigated bone repair and ectopic bone formation using plasminogen deficient (Plg(-/-) ) mice. Bone repair of the femur is delayed in Plg(-/-) mice, unlike that in the wild-type (Plg(+/+) ) mice. The deposition of cartilage matrix and osteoblast formation were both decreased in Plg(-/-) mice. Vessel formation, macrophage accumulation, and the levels of vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) were decreased at the site of bone damage in Plg(-/-) mice. Conversely, heterotopic ossification was not significantly different between Plg(+/+) and Plg(-/-) mice. Moreover, angiogenesis, macrophage accumulation, and the levels of VEGF and TGF-β were comparable between Plg(+/+) and Plg(-/-) mice in heterotopic ossification. Our data provide novel evidence that plasminogen is essential for bone repair. The present study indicates that plasminogen contributes to angiogenesis related to macrophage accumulation, TGF-β, and VEGF, thereby leading to the enhancement of bone repair. © 2013 American Society for Bone and Mineral Research. 23568579 On the persistence of cocaine-induced place preferences and aversions in rats. RATIONALE: Rats develop preferences for places associated with the immediate rewarding effects of cocaine and aversions for places paired with the drug's delayed negative effects. The motivation to seek cocaine should therefore depend upon the relative magnitude of these two opposing effects of the drug. OBJECTIVE: The current study tested this notion by assessing the relative persistence of the positive and negative associations formed between environmental cues and the immediate or delayed effects of cocaine. METHODS: Rats were administered 1.0 mg/kg intravenous cocaine and placed into a distinctive environment either immediately or 15-min after injection, alternating daily with pairings of a second environment with saline. After four drug-place and four saline-place pairings, rats were returned to their home cages for 1, 7, or 21 days after which a 15-min place preference test was conducted. In a second experiment, the effectiveness of a single reconditioning session (one drug-place and one saline-place pairing) to reactivate learned cocaine-place associations was assessed after 1 or 3 weeks of drug abstinence. RESULTS: Places associated with the immediate effects of cocaine were preferred (CPP), while places associated with the delayed effects of cocaine were avoided (CPA). The persistence of these effects differed with CPP remaining viable at 3 weeks of withdrawal, while CPA was no longer present after 1 week. Reconditioning with an additional cocaine-place pairing failed to reinstate the CPA. CONCLUSIONS: Cue-induced "relapse" of cocaine-seeking behavior may be fueled in part by an increased persistence of positive relative to negative associations with drug-paired stimuli. 22949397 Oral intake of beet extract provides protection against skin barrier impairment in hairless mice. The epidermis acts as a functional barrier against the external environment. Disturbances in the function of this barrier cause water loss and increase the chances of penetration by various irritable stimuli, leading to skin diseases such as dry skin, atopic dermatitis, and psoriasis. Ceramides are a critical natural element of the protective epidermal barrier. The aim of this study was to evaluate whether the oral intake of beet (Beta vulgaris) extract, a natural product rich in glucosylceramide (GlcCer), may prevent disturbance in skin barrier function. When HR-1 hairless mice were fed a special diet (HR-AD), transepidermal water loss (TEWL) from the dorsal skin increased, with a compensatory increase in water intake after 5 weeks. Mice fed with HR-AD had dry skin with erythema and showed increased scratching behaviour. Histological examinations revealed a remarkable increase in the thickness of the skin at 8 weeks. Supplemental addition of beet extract, which contained GlcCer at a final concentration of 0.1%, significantly prevented an increase TEWL, water intake, cumulative scratching time, and epidermal thickness at 8 weeks. These results indicate that oral intake of beet extract shows potential for preventing skin diseases associated with impaired skin barrier function. Copyright © 2012 John Wiley & Sons, Ltd. 23311718 Phase boundaries, structural characteristics, and NMR spectra of ionic liquid-in-oil microemulsions containing double chain surface active ionic liquid: a comparative study. A method developed for the first time, to create a huge number of ionic liquid (IL)-in-oil microemulsions has been discussed in our earlier publication (Rao, V. G.; Ghosh, S.; Ghatak, C.; Mandal, S.; Brahmachari, U.; Sarkar, N. J. Phys. Chem. B 2012, 116, 2850-2855). Here, we present facile methods to adjust the structural parameters of microemulsions using different ionic liquids (ILs) as additives (polar phase). We have characterized ILs/[C(4)mim][AOT]/benzene ternary system by performing a phase behavior study, dynamic light scattering (DLS) measurements, and (1)H NMR measurements. The IL loading capacity of microemulsions (area of single phase region) (i) increases with increase in alkyl chain length of cation of ILs and follows the trend [C(6)mim][TF(2)N] > [C(4)mim][TF(2)N] > [C(2)mim][TF(2)N], (ii) increases with decrease in cation anion interaction strength of added ILs and follows the trend [C(4)mim][TF(2)N] > [C(4)mim][PF(6)] > [C(4)mim][BF(4)]. So depending on the IL used, the amount of IL within the core of microemulsions can be easily manipulated to directly affect the size of aggregates in microemulsions. The size increase with increasing R value (R value is defined as the molar ratio of RTILs to [C(4)mim][AOT]) was found to be maximum in the case of [C(2)mim][TF(2)N]/[C(4)mim][AOT]/benzene microemulsions and follows the trend [C(2)mim][TF(2)N] > [C(4)mim][TF(2)N] > [C(6)mim][TF(2)N]. However, the size increase was almost the same with increase in R value in the case of ILs with different anions. The most promising fact about IL-in-oil microemulsions is their high thermal stability compared to that of aqueous microemulsions, so we investigated the effect of temperature on size of aggregates in microemulsions at R = 1.0. It is evident from dynamic light scattering measurements that the aggregates in microemulsions remain monodisperse in nature with increasing temperature, and in all the cases, the size of aggregates in microemulsions decreases with increasing temperature. The effect of water addition on IL-in-oil (IL/O) microemulsions was also studied in detail. By far, this is the first report where the effect of water addition on microemulsions containing hydrophobic ILs is being reported and compared with microemulsions containing hydrophilic ILs. We observed that the added water has a prominent effect on the microstructure of the microemulsions. In all the cases, (1)H NMR spectra provide more detailed information about intra/intermolecular interactions thus affording a clear picture of locations of (i) the RTILs in RTILs/[C(4)mim][AOT]/benzene microemulsions and (ii) the added water molecules in microemulsions. 23465072 New GABA/Glutamate Receptor Target for [(3)H]Isoxazoline Insecticide. The highly effective and selective isoxazoline insecticide A1443 is known to potently displace [(3)H]ethynylbicycloorthobenzoate ([(3)H]EBOB) binding to house fly head membranes with an IC50 of 0.2 nM in a manner characteristic of GABA-gated chloride channel antagonists. To further define its mode of action, we prepared phenyl-labeled [(3)H]A1443 as described with a specific activity of 14 Ci/mmol. This new radioligand with an apparent IC50 of about 0.4 nM is poorly displaced by most insecticides acting at the [(3)H]EBOB site. Interestingly, the isoxazoline binding site is directly coupled to the avermectin GABA/glutamate chloride channel activator site. These findings revive interest in the insect GABA/glutamate receptor as an insecticide target. 23288866 P-glycoprotein increases portal bioavailability of loperamide in mouse by reducing first-pass intestinal metabolism. P-glycoprotein (P-gp) and CYP3A (cytochrome P450 3A, generally; Cyp3a, rodent enzyme) in the intestine can attenuate absorption of orally administered drugs. While some suggest that P-gp enhances intestinal metabolism by CYP3A/Cyp3a during absorption of a dual substrate, others suggest that P-gp reduces the metabolism in the intestine when substrates are at subsaturating concentrations. Hence, to elucidate the cellular mechanisms that can address these divergent reports, we studied intestinal absorption of the dual substrate loperamide in portal vein-cannulated P-gp-competent and P-gp-deficient mice. These studies showed that at low doses of loperamide, which produced intestinal concentrations near the apparent K(m) for oxidative metabolism, the bioavailability across the intestine (F(G)) was 6-fold greater in the P-gp-competent mice than in P-gp-deficient mice. The higher F(G) of loperamide in the presence of P-gp was attributed to lower loperamide intestinal metabolism. However, at high doses of loperamide, the sparing of first-pass metabolism by P-gp was balanced against the attenuation of absorption by apical efflux, resulting in no net effect on F(G). In vitro studies with intestinal tissue from P-gp-competent and -deficient mice confirmed that P-gp reduced the metabolic rate of loperamide during absorptive flux at concentrations near K(m) but had little effect on metabolism at higher (saturating) concentrations. Further, studies in which Cyp3a was chemically inactivated by aminobenzotriazole in P-gp-competent and -deficient mice, showed that P-gp and Cyp3a individually attenuated F(G) by 8-fold and 70-fold, respectively. These results confirmed that P-gp effectively protects loperamide at low doses from intestinal first-pass metabolism during intestinal absorption. 23401281 Soluble metal pool as affected by soil addition with organic inputs. The potential impact of diverse inputs of organic matter (hay, maize straw, and peat) on the mobility and bioavailability of Cd, Cu, Pb, and Zn was examined at laboratory scale for three soils with contrasting properties and for two moisture regimes: field capacity and saturated conditions. Soil solution was characterized for total soluble metals, dissolved soil organic carbon, and ultraviolet absorbance at 254 nm. Speciation analyses were performed with WHAM VI. For field capacity conditions, metal mobility increased (Pb > Cu > Zn > Cd) for all soils and treatments compared with controls and was significantly correlated (p < 0.05) with dissolved organic matter (r = 0.540). Solubilization of organic matter was mostly driven by Al mobilization (r = 0.580, p < 0.05) and variations in solution pH. The bioavailable pool of metals, estimated as free ion activities, decreased with the increasing occurrence of metal-organic matter complexes, which was accompanied by an increase in solution of highly aromatic organic matter. Soil saturation generally decreased metal mobility and the ratio of metal-organo matter complexes in solution. Consistently, such effects were accompanied by a decrease in the solubilization of organic matter and lower mobilization of Al, Fe, and Mn. Environ Toxicol Chem 2013;32:1027-1032. © 2013 SETAC. 23241059 Pseudostatic and dynamic nanomechanics of the tunica adventitia in elastic arteries using atomic force microscopy. Tunica adventitia, the outer layer of blood vessels, is an important structural feature, predominantly consisting of collagen fibrils. This study uses pseudostatic atomic force microscopy (AFM) nanoindentation at physiological conditions to show that the distribution of indentation modulus and viscous creep for the tunica adventitia of porcine aorta and pulmonary artery are distinct. Dynamic nanoindentation demonstrates that the viscous dissipation of the tunica adventitia of the aorta is greater than the pulmonary artery. We suggest that this mechanical property of the aortic adventitia is functionally advantageous due to the higher blood pressure within this vessel during the cardiac cycle. The effects on pulsatile deformation and dissipative energy losses are discussed. 23387901 Tubulin inhibitors from an endophytic fungus isolated from Cedrus deodara. From an endophytic fungus, a close relative of Talaromyces sp., found in association with Cedrus deodara, four compounds including two new ones (2 and 4) were isolated and characterized. The structures of two compounds (1 and 4) were confirmed by X-ray crystallography. The compounds displayed a range of cytotoxicities against human cancer cell lines (HCT-116, A-549, HEP-1, THP-1, and PC-3). All the compounds were found to induce apoptosis in HL-60 cells, as evidenced by fluorescence and scanning electron microscopy studies. Also, the compounds caused significant microtubule inhibition in HL-60 cells. 23465594 Increased dietary fat contributes to dysregulation of the LKB1/AMPK pathway and increased damage in a mouse model of early-stage ethanol-mediated steatosis. OBJECTIVE: The objective of the study was to examine the interaction of moderate and high dietary fat and ethanol with respect to formation of steatosis and regulation of the AMP-activated protein kinase (AMPK) pathway in a mouse model of chronic ethanol consumption. METHODS: Male C57BL/6J mice were pair-fed a modified Lieber-DeCarli diet composed of either moderate fat [30% fat-derived calories (MF)] or high fat [45% fat-derived calories (HF)] combined with increasing concentrations of ethanol (2%-6%) for 6 weeks. RESULTS: Chronic ethanol consumption resulted in significant increases in plasma alanine aminotransferase in MF (1.84-fold) and HF mice (2.33-fold), yet liver triglycerides only increased significantly in the HF model (1.62-fold). Ethanol addition significantly increased plasma adiponectin under conditions of MF but not HF. In combination with MF, the addition of ethanol significantly decreased total and hepatic pThr(172)AMPKα and acetyl CoA Carboxylase (ACC). HF plus ethanol decreased pSer(108)AMPKβ, yet a marked 1.5-fold increase in pThr(172)AMPKα occurred. No change was evident in pSer(79)ACC under conditions of ethanol and HF ingestion. In both models, nuclear levels of sterol response element binding protein 1c and carbohydrate response element binding protein were decreased. Surprisingly, MF plus ethanol significantly elevated protein expression of medium-chain acyl-CoA dehydrogenase (MCAD), long-chain acyl-CoA dehydrogenase (LCAD) and very long chain acyl-CoA dehydrogenase but did not significantly affect mRNA expression of other proteins involved in β-oxidation and fatty acid synthesis. HF plus ethanol significantly reduced mRNA expression of both stearoyl CoA desaturase 1 and fatty acid elongase 5, but did not have an effect on MCAD or LCAD. CONCLUSION: These data suggest that, when co-ingested with ethanol, dietary fat differentially contributes to dysregulation of adiponectin-dependent activation of the AMPK pathway in the liver of mice. 23537700 Similar pyruvate kinase modifications in glioblastoma cells by 7β-hydroxycholesterol and glutamine withdrawal. Oxysterols possess anti-proliferative properties that may be used with much effect in the treatment of cancer. We have demonstrated previously that 7 beta-hydroxycholesterol (7b-HC) provokes both metabolic stress, as witnessed by AMPK activation, and changes in lipid raft composition in C6 glioblastoma cells. These observations suggested that glycolysis might have been changed. Here we will show that 7b-HC increases cell cycle time and that it changes the affinity of pyruvate kinase to its substrate, phosphoenol pyruvate. The latter effect is mimicked by glutamine withdrawal. 23524160 Synthesis and biological evaluation of novel pyrrolidine-2,5-dione derivatives as potential antidepressant agents. Part 1. A series of 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives was synthesized and their biological activity was evaluated. The chemical structures of the newly prepared compounds were confirmed by (1)H NMR, (13)C NMR and ESI-HRMS spectra data. All tested compounds proved to be potent 5-HT1A receptor and serotonin transporter protein (SERT) ligands. Among them, compounds 15, 18, 19 and 30 showed significant affinity for 5-HT1A and SERT. Computer docking simulations carried out for compounds 15, 31 and 32 to models of 5-HT1A receptor and SERT confirm the results of biological tests. Due to high affinity for the 5-HT1A receptor and moderate affinity for SERT, compounds 31, 32, 35, and 37 were evaluated for their affinity for D2L, 5-HT6, 5-HT7 and 5-HT2A receptors. In vivo tests, in turn, resulted in determining the functional activity of compounds 15, 18, 19 and 30 to the 5-HT1A receptor. The results of these tests indicate that all of the ligands possess properties characteristic of 5-HT1A receptor agonists. 23381882 Mechanisms of Pharmacokinetic Enhancement Between Ritonavir and Saquinavir; Micro/Small Dosing Tests Using Midazolam (CYP3A4), Fexofenadine (p-Glycoprotein), and Pravastatin (OATP1B1) as Probe Drugs. We investigated the mechanisms of ritonavir-mediated enhancement effect on the pharmacokinetics of saquinavir using in vivo probes for CYP3A4 (midazolam), p-glycoprotein (fexofenadine), and OATP1B1 (pravastatin) following oral micro/small dosing. A cocktail of the drugs (2 mg of saquinavir, 100 µg of each probe) was administered to eight healthy volunteers (phase 1), and then coadministered with 20 mg (phase 2) and 100 mg (phase 3) of ritonavir. Plasma concentrations of the drugs were measured by validated LC-MS/MS methods. The mean plasma AUC(0-24) (pg hour/mL) of saquinavir at phases 1, 2, and 3 was 101, 2 540, and 23 900 (P < .01), respectively. The relative area under the plasma concentration-time curve (AUC)(0-24) ratios of midazolam and fexofenadine at phases 1, 2, and 3 were 1:5.9:14.7 (P < .01), and 1:1.4:2.2 (P < .01-.05), respectively. In contrast, there was no difference in the pharmacokinetics of pravastatin. Inhibition of intestinal and hepatic CYP3A-mediated metabolism, and intestinal p-glycoprotein-mediated efflux of saquinavir, but not OATP1B1, is involved in the enhancement mechanism. Micro/small dosing is useful for examining the mechanism of drug interactions without safety concern. 23369833 Transformation of paralytic shellfish poisoning toxins in UK surf clams (Spisula solida) for targeted production of reference materials. The periodic occurrence of Paralytic Shellfish Poisoning (PSP) toxins in UK surf clams and the recent move away from biological assays for PSP testing resulted in the need to determine method performance characteristics for the replacement analytical method in this species. With the requirement for laboratory reference materials to aid this validation together with known issues relating to toxin transformation in live clams and homogenised tissue, there was the need to assess the toxin transformation characteristics of PSP toxins in surf clam tissue. Initial work examined the rates of toxin transformation in UK surf clam tissue incubated with toxin standards, showing rapid transformation of N-sulfocarbamoyl toxins with slower transformation of carbamate toxins. Full transformational pathways were determined using a combination of three different analytical methods and confirmed the major expected transformations involving decarbamoylation, with some evidence for additional reaction pathways. Results obtained from the analysis of surf clam and oyster tissues incubated with varying concentrations of toxic Alexandrium algae highlighted expected transformation reactions, although significant differences were observed in the extent of the transformations amongst the range of toxins studied, with less efficient transformation of N-hydroxylated toxins as compared with other carbamate and N-sulfocarbamoyl toxins. Analysis of PSP-toxic incurred oyster, scallop and mussel tissues incubated with variable proportions of surf clam tissue showed large differences in the extent of the transformations. Total conversion of N-sulfocarbamoyl toxins was confirmed at low relative proportions of surf clam tissue in all three species, whereas transformation of carbamate toxins was found to occur only in the presence of higher proportions of surf clam tissue in oysters and mussels in comparison with scallops. Results enabled the production of three laboratory reference materials prepared following incubation of incurred homogenates with optimum proportions of surf clam tissue, resulting in materials containing a large number of PSP toxins. Stability experiments provided good preliminary evidence for the stability of these targeted materials under storage conditions. The work therefore provides both additional information relating to the transformational activity in UK surf clams and highlights a good potential method for the targeted production of reference materials which include a wider range of toxins than normally present in naturally incurred shellfish. 23041538 Ischemia-induced synaptic plasticity drives sustained expression of calcium-permeable AMPA receptors in the hippocampus. Long lasting enhancement of synaptic transmission can be triggered by brief bursts of afferent stimulation, underlying long-term potentiation (LTP), and also by brief ischemia in a process known as i-LTP. The extent to which LTP and i-LTP rely on comparable cellular mechanisms remains unclear. Under physiological conditions, LTP induction drives transient expression of calcium-permeable AMPARs (CP-AMPARs) at synapses, whose ability to undergo plasticity is primed by endogenous activation of adenosine A(2A) receptors (A(2A)Rs). The present work thus addressed the contribution of CP-AMPARs and A(2A)Rs to i-LTP, which was induced in rat hippocampal slices by brief (10 min) oxygen/glucose deprivation (OGD). The amplitude of afferent-evoked excitatory postsynaptic currents (EPSCs) recorded from CA1 pyramidal neurons was decreased during OGD but gradually recovered toward values significantly above (157 ± 17%) the baseline (100%) 40-50 min after re-oxygenation. This i-LTP was precluded by CP-AMPAR blockade (internal spermine (500 μM) or extracellular NASPM (20 μM) application) as well as by A(2A)R blockade with a selective antagonist (SCH 58261, 100 nM). OGD prompted sustained (>70 min) facilitation of mEPSC amplitude and frequency, and decreased mEPSC decay time, all of which were prevented by SCH 58261 (100 nM). The ability of NASPM (20 μM) to acutely inhibit EPSCs 1 h after OGD, but not in control conditions nor in OGD-challenged slices when in the presence of SCH 58261 (100 nM), further supports sustained CP-AMPAR recruitment by i-LTP in an A(2A)R-dependent way. We propose that although i-LTP may initially mimic LTP, failure of auto-regulated CP-AMPAR removal from synapses could constitute an early divergent event between these forms of plasticity. 23258671 Super-stable ultrafine beta-tungsten nanocrystals with metastable phase and related magnetism. Ultrafine tungsten nanocrystals (average size of 3 nm) with a metastable phase (beta-tungsten with A15 structure, β-W) have been prepared by laser ablation of tungsten in liquid nitrogen. The as-prepared metastable nanocrystals exhibited super-stablity, and can keep the same metastable structure over a period of 6 months at room temperature. This super-stability is attributed to the nanosized confinement effect of ultrafine nanocrystals. The magnetism measurements showed that the β-W nanocrystals have weak ferromagnetic properties at 2 K, which may arise from surface defects and unpaired electrons on the surface of the ultrafine nanocrystals. These findings provided useful information for the application of ultrafine β-W nanocrystals in microelectronics and spintronics. 23315090 Hypolipidemic effect of fruit fibers in rats fed with high dietary fat. The hypolipidemic effect of 10% fruit fibers in rats fed with high-fat diet (HFD) was evaluated. This study was conducted on a total of 50 male Albino rats divided into 10 equal groups fed with different types of dietary fruits. The feeding period lasted for 24 weeks. Fasting blood samples were collected and sera separated and subjected to lipid profile assay and atherogenic index. In addition, total antioxidant activity of different fruits was determined. The results obtained showed that pomegranate had higher content of antioxidants followed by apple, strawberry and guava compared with other fruits. Rats fed with 20% coconut oil showed a highly significant elevation in the levels of serum total cholesterol, low-density lipoprotein cholesterol and atherogenic factor while the level of high-density lipoprotein cholesterol was significantly decreased when compared with control rats. Histological examination revealed that there was a large lipid and cholesterol deposition in the livers of rats fed with HFD. The potential in lowering the levels of plasma total cholesterol and triglyceride is in the following order: pomegranate > apple > strawberry > guava > papaya > mandarin and orange. Accumulation of hepatic lipid droplets was diminished when compared with the HFD group. Also, antiatherogenic is better than the untreated groups. Accordingly these hypolipidemic effects may be due to high-fiber content and antioxidant activity of these fruits. 23434934 From SNP to Transcriptional Mechanism: A Model for FRMD3 in Diabetic Nephropathy. Genome wide association studies (GWAS) have proven to be highly effective at defining causal relationships between single nucleotide polymorphisms (SNP) and clinical phenotypes in complex diseases. Establishing a mechanistic link between a non-coding SNP and the clinical outcome is a significant hurdle in translating associations into biological insight. We demonstrate an approach to assess the functional context of a diabetic nephropathy (DN) associated SNP located in the promoter region of the gene FRMD3. The approach integrates pathway analyses with transcriptional regulatory pattern based promoter modeling and allows the identification of a transcriptional framework impacted by the DN-associated SNP in the FRMD3 promoter. This framework provides a testable hypothesis for mechanisms of genomic variation and transcriptional regulation in the context of DN. Our model proposes a possible transcriptional link through which the polymorphism in the FRMD3 promoter could influence transcriptional regulation within the bone morphogenetic protein (BMP) signaling pathway. These findings provide the rationale to interrogate the biological link between FRMD3 and the BMP pathway, and serve as an example of functional genomics-based hypothesis generation. 23386616 Toll-like receptor 2 mediates peripheral nerve injury-induced NADPH oxidase 2 expression in spinal cord microglia. We have previously reported that NADPH oxidase 2 (Nox2) is up-regulated in spinal cord microglia after spinal nerve injury, demonstrating that it is critical for microglia activation and subsequent pain hypersensitivity. However, the mechanisms and molecules involved in Nox2 induction have not been elucidated. Previous studies have shown that Toll-like receptors (TLRs) are involved in nerve injury-induced spinal cord microglia activation. In this study, we investigated the role of TLR in Nox2 expression in spinal cord microglia after peripheral nerve injury. Studies using TLR knock-out mice have shown that nerve injury-induced microglial Nox2 up-regulation is abrogated in TLR2 but not in TLR3 or -4 knock-out mice. Intrathecal injection of lipoteichoic acid, a TLR2 agonist, induced Nox2 expression in spinal cord microglia both at the mRNA and protein levels. Similarly, lipoteichoic acid stimulation induced Nox2 expression and reactive oxygen species production in primary spinal cord glial cells in vitro. Studies on intracellular signaling pathways indicate that NF-κB and p38 MAP kinase activation is required for TLR2-induced Nox2 expression in glial cells. Conclusively, our data show that TLR2 mediates nerve injury-induced Nox2 gene expression in spinal cord microglia via NF-κB and p38 activation and thereby may contribute to spinal cord microglia activation. 23363425 Silica precipitation by synthetic minicollagens. Oligomeric Pro-Hyp-Gly- (POG-) peptides, wherein the collagenous triple helix is supported by C-terminal capping, exhibit silica precipitation properties (O, Hyp = (2S,4R)hydroxyproline). As quantified by a molybdate assay, the length of the covalently tethered triple helix (number of POG units) determines the amount of amorphous silica obtained from silicic acid solution. Although lacking charged side chains, the synthetic collagens precipitate large quantities of silicic acid resulting in micrometer-sized spheres of varying surface morphologies as analyzed by scanning electron microscopy. Similar precipitation efficiencies on a fast time scale of less than 10 min were previously described only for biogenic diatom proteins and sponge collagen, respectively, which have a considerably higher structural complexity and limited accessibility. The minicollagens described here provide an unexpected alternative to the widely used precipitation conditions, which generally depend on (poly-)amines in phosphate buffer. Collagen can form intimate connections with inorganic matter. Hence, silica-enclosed collagens have promising perspectives as composite materials. 22788743 The potential impact of strawberry on human health. The strawberry (Fragaria X ananassa, Duch.) represents a relevant source of micronutrients, such as minerals, vitamin C, folate and phenolic substances, most of which are natural antioxidants and contribute to the high nutritional quality of the fruit. All these compounds are essential for health and, in particular, strawberry phenolics are best known for their antioxidant and anti-inflammatory action, and possess directly and indirectly antimicrobial, anti-allergy and anti-hypertensive properties, as well as the capacity to inhibit the activities of some physiological enzymes and receptor properties. The main objective of this article is to review and update the current knowledge on the potential impact of the strawberry on human health, with particular attention on compounds and their possible mechanisms of action. 22580610 miR-34a functions as a tumor suppressor modulating EGFR in glioblastoma multiforme. Chromosome 1p36.23 is frequently deleted in glioblastoma multiforme (GBM). miR-34a localizes in this region. Our experiments found that miR-34a was often deleted and epidermal growth factor receptor (EGFR) was frequently amplified in genomic DNA of 55 GBMs using single-nucleotide polymorphism DNA microarray. Notably, we found that the mean survival time was significantly shortened for patients whose GBMs had both EGFR amplification and miR-34a deletion. Expression of miR-34a was significantly lower in GBM samples compared with normal brain tissue. Forced expression of miR-34a in GBM cells decreased their ability to migrate and profoundly decreased their levels of cyclin-A1, -B1, -D1, and -D3, as well as cyclin-dependent kinase and increased expression of cyclin kinase inhibitor proteins (p21, p27). Also, human GBM cells (U251) stable overexpressing mir-34a formed smaller tumors when growing as xenografts in immunodeficient mice compared with wild-type U251 GBM cells. Furthermore, the protein expression of EGFR decreased in the cells with forced overexpression of miR-34a. Additional studies showed that mir-34a targeted Yin Yang-1 (YY1) and YY1 is a transcription factor that can stimulate the expression of EGFR. Thus, our data suggest that miR-34a acts as a tumor suppressor by inhibiting growth of GBM cells in vitro and in vivo associated with moderating the expression of cell-cycle proteins and EGFR. Moreover, we discovered for the first time that both deletion of miR-34a and amplification of EGFR were associated with significantly decreased overall survival of GBM patients. 23374865 Synthesis and micellar mimic properties of bile acid trimers. Two fan-shaped bile acid trimers have been synthesized via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) 'click chemistry', and their extraction experiments of cresol red sodium (CR) and pyrene were investigated in the polar and non-polar solvents, respectively. The transmission electron microscopy (TEM) results showed that the homogenous hollow capsules formed with the diameter size range of 40-70 nm in a solution of water and acetone. Thus the amphiphilicity of fan-shaped bile acid trimers might be used as the promising candidate in biological and drug delivery applications. 23603112 Binding of new cationic porphyrin-tetrapeptide conjugates to nucleoprotein complexes. Ongoing research on DNA binding of cationic porphyrin derivatives and their conjugates is a subject of growing interest because of their possible DNA binding and demonstrated biological properties. In this study nucleoprotein binding of tri-cationic meso-tri(4-N-methylpyridyl)-mono-(4-carboxyphenyl)porphyrin (TMPCP) and tetrapeptides conjugated TMPCP (TMPCP-4P) and bi-cationic meso-5,10-bis(4-N-methylpyridyl)-15,20-di-(4-carboxyphenyl)porphyrin (BMPCP-4P2) was investigated with comprehensive spectroscopic methods. The key observation is that tetrapeptide-conjugates of cationic porphyrins with two or three positive charges bind to encapsidated DNA in T7 phage nucleoprotein complex. The binding modes were analyzed by fluorescent energy transfer, fluorescent life time and CD measurements. Intercalative binding is most feasible when tricationic ligands complex with DNA, especially when it is in close connection with protein capsid. It was found that larger ligand BMPCP-4P2 binds externally to encapsidated T7 DNA, and complex externally as well as by intercalation when the DNA accommodate to relaxed B-conformation. In the case of TMPCP and TMPCP-4P the intercalation is the predominant binding form both in nucleoprotein (NP) and preheated complexes. Further, melting experiments revealed that bound porphyrins do not influence the capsid stability or protein-DNA interactions, but efficiently stabilize the double helical structure of DNA without respect to binding form. A good correlation was found between porphyrin/base pair ration and DNA strand separation temperature. 23178170 Structure of a Ca(2+)/CaM:Kv7.4 (KCNQ4) B-helix complex provides insight into M current modulation. Calmodulin (CaM) is an important regulator of Kv7.x (KCNQx) voltage-gated potassium channels. Channels from this family produce neuronal M currents and cardiac and auditory I(KS) currents and harbor mutations that cause arrhythmias, epilepsy, and deafness. Despite extensive functional characterization, biochemical and structural details of the interaction between CaM and the channel have remained elusive. Here, we show that both apo-CaM and Ca(2+)/CaM bind to the C-terminal tail of the neuronal channel Kv7.4 (KCNQ4), which is involved in both hearing and mechanosensation. Interactions between apo-CaM and the Kv7.4 tail involve two C-terminal tail segments, known as the A and B segments, whereas the interaction between Ca(2+)/CaM and the Kv7.4 C-terminal tail requires only the B segment. Biochemical studies show that the calcium dependence of the CaM:B segment interaction is conserved in all Kv7 subtypes. X-ray crystallographic determination of the structure of the Ca(2+)/CaM:Kv7.4 B segment complex shows that Ca(2+)/CaM wraps around the Kv7.4 B segment, which forms an α-helix, in an antiparallel orientation that embodies a variation of the classic 1-14 Ca(2+)/CaM interaction motif. Taken together with the context of prior studies, our data suggest a model for modulation of neuronal Kv7 channels involving a calcium-dependent conformational switch from an apo-CaM form that bridges the A and B segments to a Ca(2+)/CaM form bound to the B-helix. The structure presented here also provides a context for a number of disease-causing mutations and for further dissection of the mechanisms by which CaM controls Kv7 function. 23159397 Systemic effects induced by the venom of the snake Bothrops caribbaeus in a murine model. Snakebite envenoming by Bothrops caribbaeus, an endemic viperid from the Lesser Antillean island of Saint Lucia, is clinically characterized by local tissue damage and systemic thrombosis that can lead to cerebral, myocardial or pulmonary infarctions and venous thromboses. Systemic effects (lethality, pulmonary hemorrhage, thrombocytopenia and coagulopathy) induced by intravenous (i.v.) administration of B. caribbaeus venom were studied in mice. The role of snake venom metalloproteinases (SVMPs) in these systemic alterations was assessed by inhibition with the chelating agent calcium disodium ethylenediaminetetraacetic acid (CaNa(2)EDTA). A snake C-type lectin-like (snaclec) and a type P-III hemorrhagic SVMP were isolated and characterized from this venom, and the effect of venom and the isolated snaclec on human platelet aggregation was studied in vitro. Results indicate that SVMPs play an important role in the overall toxicity of B. caribbaeus venom, being responsible for systemic hemorrhage and lethality, but not thrombocytopenia, whereas the isolated snaclec is involved in the thrombocytopenic effect. Both venom and snaclec induce platelet aggregation/agglutination. Moreover, the snaclec binds directly to glycoprotein Ib (GPIb) and induces agglutination in washed fixed platelets. On the other hand, B. caribbaeus venom hydrolyzed fibrinogen in vitro and induced a partial drop of fibrinogen levels with an increase in fibrin/fibrinogen degradation products (FDP) levels in vivo. The negative result for D-dimer (DD) in plasma is consistent with the lack of microscopic evidence of pulmonary thrombosis and endothelial cell damage. Likewise, no increments in plasma sE-selectin levels were detected. The absence of thrombosis in this murine model suggests that this effect may be species-specific. 23228697 Carboxylesterase-2 is a highly sensitive target of the antiobesity agent orlistat with profound implications in the activation of anticancer prodrugs. Orlistat has been the most used anti-obesity drug and the mechanism of its action is to reduce lipid absorption by inhibiting gastrointestinal lipases. These enzymes, like carboxylesterases (CESs), structurally belong to the α/β hydrolase fold superfamily. Lipases and CESs are functionally related as well. Some CESs (e.g., human CES1) have been shown to hydrolyze lipids. This study was designed to test the hypothesis that orlistat inhibits CESs with higher potency toward CES1 than CES2, a carboxylesterase with little lipase activity. Liver microsomes and recombinant CESs were tested for the inhibition of the hydrolysis of standard substrates and the anticancer prodrugs pentyl carbamate of p-aminobenzyl carbamate of doxazolidine (PPD) and irinotecan. Contrary to the hypothesis, orlistat at 1 nM inhibited CES2 activity by 75% but no inhibition on CES1, placing CES2 one of the most sensitive targets of orlistat. The inhibition varied among some CES2 polymorphic variants. Pretreatment with orlistat reduced the cell killing activity of PPD. Certain mouse but not rat CESs were also highly sensitive. CES2 is responsible for the hydrolysis of many common drugs and abundantly expressed in the gastrointestinal track and liver. Inhibition of this carboxylesterase probably presents a major source for altered therapeutic activity of these medicines if co-administered with orlistat. In addition, orlistat has been linked to various types of organ toxicities, and this study provides an alternative target potentially involved in these toxicological responses. 23466235 Discovery of non-peptide inhibitors of Plasmepsin II by structure-based virtual screening. Plasmepsin II (PM II) is an attractive target for anti-malaria drug discovery, which involves in host hemoglobin degradation in the acidic food vacuole. In this study, we demonstrated the successful use of structure-based virtual screening to identify inhibitors of PM II from two chemical database. Five novel non-peptide inhibitors were identified and revealed moderate inhibitory potencies with IC50 ranged from 4.62 ± 0.39 to 9.47 ± 0.71 μM. The detailed analysis of binding modes using docking simulations for five inhibitors showed that the inhibitors could be stabilized by forming multiple hydrogen bonds with catalytic residues (Asp 34 and Asp 214) and also with other key residues. 23146662 Comparison of transcriptional response to phorbol ester, bryostatin 1, and bryostatin analogs in LNCaP and U937 cancer cell lines provides insight into their differential mechanism of action. Bryostatin 1, like the phorbol esters, binds to and activates protein kinase C (PKC) but paradoxically antagonizes many but not all phorbol ester responses. Previously, we have compared patterns of biological response to bryostatin 1, phorbol ester, and the bryostatin 1 derivative Merle 23 in two human cancer cell lines, LNCaP and U937. Bryostatin 1 fails to induce a typical phorbol ester biological response in either cell line, whereas Merle 23 resembles phorbol ester in the U937 cells and bryostatin 1 in the LNCaP cells. Here, we have compared the pattern of their transcriptional response in both cell lines. We examined by qPCR the transcriptional response as a function of dose and time for a series of genes regulated by PKCs. In both cell lines bryostatin 1 differed primarily from phorbol ester in having a shorter duration of transcriptional modulation. This was not due to bryostatin 1 instability, since bryostatin 1 suppressed the phorbol ester response. In both cell lines Merle 23 induced a pattern of transcription largely like that of phorbol ester although with a modest reduction at later times in the LNCaP cells, suggesting that the difference in biological response of the two cell lines to Merle 23 lies downstream of this transcriptional regulation. For a series of bryostatins and analogs which ranged from bryostatin 1-like to phorbol ester-like in activity on the U937 cells, the duration of transcriptional response correlated with the pattern of biological activity, suggesting that this may provide a robust platform for structure activity analysis. 23570572 Self-Repair of a Biological Fiber Guided by an Ordered Elastic Framework. Incorporating sacrificial cross-links into polymers represents an exciting new avenue for the development of self-healing materials, but it is unclear to what extent their spatial arrangement is important for this functionality. In this respect, self-healing biological materials, such as mussel byssal threads, can provide important chemical and structural insights. In this study, we employ in situ small-angle X-ray scattering (SAXS) measurements during mechanical deformation to show that byssal threads consist of a partially crystalline protein framework capable of large reversible deformations via unfolding of tightly folded protein domains. The long-range structural order is destroyed by stretching the fiber but reappears rapidly after removal of load. Full mechanical recovery, however, proceeds more slowly, suggesting the presence of strong and slowly reversible sacrificial cross-links. One likely role of the highly ordered elastic framework is to bring sacrificial binding sites back into register upon stress release, facilitating bond reformation and self-repair. 23558682 Porphyromonas gingivalis virulence factor gingipain RgpB shows a unique zymogenic mechanism for cysteine peptidases. Zymogenicity is a regulatory mechanism which prevents inadequate catalytic activity in the wrong context. It plays a central role in maintaining microbial virulence factors in an inactive form inside the pathogen until secretion. Among these virulence factors is the cysteine peptidase gingipain B (RgpB), which is the major virulence factor secreted by the periodontopathogen Porphyromonas gingivalis that attacks host vasculature and defense proteins. The structure of the complex between soluble mature RgpB, consisting of a catalytic domain and an immunoglobulin-superfamily domain, and its 205-residue N-terminal pro-domain, the largest structurally characterized to date for a cysteine peptidase, reveals a novel fold for the pro-domain that is distantly related to sugar-binding lectins. It attaches laterally to the catalytic domain through a large concave surface. The main determinant for latency is a surface inhibitory loop, which approaches the active-site cleft of the enzyme on its non-primed side in a substrate-like manner. It inserts an arginine (R126) into the S1 pocket, thus matching the substrate specificity of the enzyme. Downstream of R126, the polypeptide leaves the cleft, thereby preventing cleavage. Moreover, the carbonyl group of R126 establishes a very strong hydrogen bond with the co-catalytic histidine, H440, pulling it away from the catalytic cysteine, C473, and towards E381, which probably plays a role orienting the side chain of H440 during catalysis. The present results provide the structural determinants of zymogenic inhibition of RgpB by way of a novel inhibitory mechanism for peptidases in general and open the field for the design of novel inhibitory strategies in the treatment of human periodontal disease. 21826085 DPP6 as a candidate gene for neuroleptic-induced tardive dyskinesia. We implemented a two-step approach to detect potential predictor gene variants for neuroleptic-induced tardive dyskinesia (TD) in schizophrenic subjects. First, we screened associations by using a genome-wide (Illumina HumanHapCNV370) SNP array in 61 Japanese schizophrenia patients with treatment-resistant TD and 61 Japanese schizophrenia patients without TD. Next, we performed a replication analysis in 36 treatment-resistant TD and 138 non-TD subjects. An association of an SNP in the DPP6 (dipeptidyl peptidase-like protein-6) gene, rs6977820, the most promising association identified by the screen, was significant in the replication sample (allelic P=0.008 in the replication sample, allelic P=4.6 × 10(-6), odds ratio 2.32 in the combined sample). The SNP is located in intron-1 of the DPP6 gene and the risk allele was associated with decreased DPP6 gene expression in the human postmortem prefrontal cortex. Chronic administration of haloperidol increased Dpp6 expression in mouse brains. DPP6 is an auxiliary subunit of Kv4 and regulates the properties of Kv4, which regulates the activity of dopaminergic neurons. The findings of this study indicate that an altered response of Kv4/DPP6 to long-term neuroleptic administration is involved in neuroleptic-induced TD. 23219525 Influence of sildenafil and tadalafil on the enzyme- and transporter-inducing effects of bosentan and ambrisentan in LS180 cells. The combinations of the endothelin-1 receptor antagonists bosentan or ambrisentan with the phosphodiesterase 5 inhibitors sildenafil or tadalafil are current standard therapies of advanced pulmonary arterial hypertension. However, these drugs have a number of drug interactions. Changes of bosentan pharmacokinetics by sildenafil are attributed to reduced hepatic uptake as a consequence of inhibition of organic anion transporting polypeptides. We therefore tested in vitro the hypothesis that sildenafil and tadalafil reduce the enzyme- and transporter-inducing effects of bosentan or ambrisentan by preventing cellular access. Although intracellular concentrations of bosentan and ambrisentan (measured by high pressure liquid chromatography coupled with tandem mass-spectrometry) after four days of incubation of LS180 cells were lower when sildenafil or tadalafil were present, quantification of mRNA expression in these cells by real-time reverse transcription polymerase chain reaction revealed that bosentan and ambrisentan-mediated induction was stable or even increased in combination with sildenafil or tadalafil. For the drug transporter P-glycoprotein this was confirmed at the protein and functional level with highly significant correlations between P-gp mRNA, protein, and function. Moreover, using a reporter gene assay in LS180 cells, our study demonstrates for the first time that tadalafil is a potent, ambrisentan a weak, and sildenafil no activator of pregnane X receptor. In conclusion, our study demonstrates that although sildenafil and tadalafil indeed reduce intracellular concentrations of bosentan and ambrisentan in LS180 cells, they do not mitigate the inducing effects of these endothelin-1 receptor antagonists. 23359555 Electrochemical Synthesis of Transparent, Amorphous, C(60) -Rich, Photoactive, and Low-Doped Film with an Interconnected Structure. An electrochemical synthesis is developed through quantitative electrochemical reaction of N-alkylcarbazole leading to a novel class of structurally interconnected high-C(60) content (60 wt%) polymer films with negligible doping and intrinsic physicochemical properties of pure C(60) . This strategy allows preparation of previously unavailable low-doped fullerene-containing non-conjugated polymers and broadens the potential applications of electrochemical synthesis for controlled polymer film structures. 23223234 The fidelity of transcription: RPB1 (RPO21) mutations that increase transcriptional slippage in S. cerevisiae. The fidelity of RNA synthesis depends on both accurate template-mediated nucleotide selection and proper maintenance of register between template and RNA. Loss of register, or transcriptional slippage, is particularly likely on homopolymeric runs in the template. Transcriptional slippage can alter the coding capacity of mRNAs and is used as a regulatory mechanism. Here we describe mutations in the largest subunit of Saccharomyces cerevisiae RNA polymerase II that substantially increase the level of transcriptional slippage. Alleles of RPB1 (RPO21) with elevated slippage rates were identified among 6-azauracil-sensitive mutants and were also isolated using a slippage-dependent reporter gene. Biochemical characterization of polymerase II isolated from these mutants confirms elevated levels of transcriptional slippage. 22317825 RETRACTED: Biochemical changes in the Beluga Huso huso exposed to acute crude diesel oil. RETRACTED. 23499823 Synthesis and molecular modeling of (4'R)- and (4'S)- 4'-substituted 2'-{[(E)-androst-5-en-17-ylidene]-methyl}oxazolines. Synthesis of four novel (4'R)- and (4'S)- 2'-{[(E)-3β-hydroxyandrost-5-en-17-ylidene]-methyl} oxazolines, comprising 4'-hydroxymethyl (1 and 2) and 4'-methoxycarbonyl (3 and 4) substituents is presented. Reaction of 17α-bromo-21-iodo-3β-acetoxypregn-5-en-20-one with either (L)-serine methyl ester, or (D)-serine methyl ester resulted in methyl N-[3β-acetoxy-21-oxopregna-5,17(20)-dien-21-yl]-(L)-serinate and methyl N-[3β-acetoxy-21-oxopregna-5,17(20)-dien-21-yl]-(D)-serinate (as mixtures of related [17(20)E]- and [17(20)Z]-isomers). Cyclization of obtained amides led to methyl 2'-{[(E)-3β-acetoxyandrost-5-en-17-ylidene]methyl}-(4'S)-4',5'-dihydro-1',3'-oxazole-4'-carboxylate and methyl 2'-{[(E)-3β-acetoxyandrost-5-en-17-ylidene]methyl}-(4'R)-4',5'-dihydro-1',3'-oxazole-4'-carboxylate which were transformed to titled compounds 1-4. The molecular docking of compounds 1-4 to ligand binding site of nuclear receptor LXRβ revealed significant differences due to stereochemical configuration of 4' atom and structure of 4'-substituent. 23416011 A nitrophenyl-based prodrug type for colorectal targeting of prednisolone, budesonide and celecoxib. Celecoxib is a COX-2 inhibitor drug that can be used to reduce the risk of colorectal adenocarcinoma. Glucocorticoids are used in the treatment of inflammatory bowel disease. A limitation to the use of both drug types is that they undergo absorption from the intestinal tract with serious side effects. The prodrug systems introduced here involve forming a nitro-substituted acylsulfonamide group in the case of celecoxib and a nitro-substituted 21-ester for the glucocorticoids. Drug release is triggered by the nitro reductase action of the colonic microflora, liberating a cyclization competent species. The release of the active parent drugs was evaluated in vitro using Clostridium perfringens and epithelial transport through Caco-2 monolayer evaluation was carried out to estimate the absorption properties of the prodrugs compared to the parental drugs. 23248191 Impact of restricted maternal weight gain on fetal growth and perinatal morbidity in obese women with type 2 diabetes. OBJECTIVE Since January 2008, obese women with type 2 diabetes were advised to gain 0-5 kg during pregnancy. The aim with this study was to evaluate fetal growth and perinatal morbidity in relation to gestational weight gain in these women. RESEARCH DESIGN AND METHODS A retrospective cohort comprised the records of 58 singleton pregnancies in obese women (BMI ≥30 kg/m(2)) with type 2 diabetes giving birth between 2008 and 2011. Birth weight was evaluated by SD z score to adjust for gestational age and sex. RESULTS Seventeen women (29%) gained ≤5 kg, and the remaining 41 gained >5 kg. The median (range) gestational weight gains were 3.7 kg (-4.7 to 5 kg) and 12.1 kg (5.5-25.5 kg), respectively. Prepregnancy BMI was 33.5 kg/m(2) (30-53 kg/m(2)) vs. 36.8 kg/m(2) (30-48 kg/m(2)), P = 0.037, and median HbA1c was 6.7% at first visit in both groups and decreased to 5.7 and 6.0%, P = 0.620, in late pregnancy, respectively. Gestational weight gain ≤5 kg was associated with lower birth weight z score (P = 0.008), lower rates of large-for-gestational-age (LGA) infants (12 vs. 39%, P = 0.041), delivery closer to term (268 vs. 262 days, P = 0.039), and less perinatal morbidity (35 vs. 71%, P = 0.024) compared with pregnancies with maternal weight gain >5 kg. CONCLUSIONS In this pilot study in obese women with type 2 diabetes, maternal gestational weight gain ≤5 kg was associated with a more proportionate birth weight and less perinatal morbidity. 23256719 Antioxidants and mucolytics in COPD management: when (if ever) and in whom? Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Oxidative stress is an important mechanism in the pathogenesis of this disease. The oxidant/ antioxidant imbalance occurring in smokers and patients with COPD is well established. Thus, therapeutic strategies targeting oxidative stress with pharmacological antioxidant agents or boosting the endogenous levels of antioxidants is likely to be beneficial as an adjunctive tool in the treatment of COPD patients. Thiol compounts such as N-acetyl-L-cysteine (NAC), carbocysteine, erdosteine, and fudosteine have been extensively studied. Although some results remain controversial, NAC and carbocysteine seem to have beneficial effect in patients not receiving inhaled corticosteroids who suffer from frequent exacerbations. In addition, other antioxidants like superoxide dismutase (SOD) mimetics and nuclear factor-erythroid 2 related factor 2 (Nrf2) are shown to decrease markers of oxidative stress in patients with emphysema, while others like glutathione peroxidase (GPx) mimetics and NO synthase (iNOS) can prevent both inflammation and oxidative stress in clinical trials in vivo (or in mouse models). In this article we review the effectiveness of various antioxidant factors in COPD and their potential beneficial effect in the treatment of the disease. 23341143 Regional inhibition of cholinesterase in free-ranging western pond turtles (Emys marmorata) occupying California mountain streams. The present study investigated the potential effects of cholinesterase (ChE)-inhibiting pesticides on western pond turtles (Emys marmorata) occupying streams in two regions of California, USA. The southern region was suspected of having increased exposure to atmospheric deposition of contaminants originating from Central Valley agriculture. The northern region represented reference ChE activities because this area was located outside of the prominent wind patterns that deposit pesticides into the southern region. Total ChE activity was measured in plasma from a total of 81 turtles from both regions. Cholinesterase activity of turtles was significantly depressed by 31% (p = 0.005) in the southern region after accounting for additional sources of variation in ChE activity. Male turtles had significantly increased ChE activity compared with females (p = 0.054). Cloaca temperature, length, mass, handling time, body condition, and lymph presence were not significant predictors of turtle ChE activity. In the southern region, 6.3% of the turtles were below the diagnostic threshold of two standard deviations less than the reference site mean ChE activity. Another diagnostic threshold determined that 75% of the turtles from the southern region had ChE activities depressed by 20% of the reference mean. The decrease in ChE activity in the southern region suggests sublethal effects of pesticide exposure, potentially altering neurotransmission, which can result in various deleterious behaviors. 23305444 Discovery and evaluation of novel inhibitors of mycobacterium protein tyrosine phosphatase B from the 6-Hydroxy-benzofuran-5-carboxylic acid scaffold. Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatase B (mPTPB) is a virulence factor secreted by the pathogen and mediates mycobacterial survival in macrophages by targeting host cell immune responses. Consequently, mPTPB represents an exciting new target to combat tuberculosis (TB) infection. We describe a medicinal chemistry oriented approach that transforms a benzofuran salicylic acid scaffold into a highly potent (IC(50) = 38 nM) and selective mPTPB inhibitor (>50 fold against a large panel of PTPs). Importantly, the inhibitor is capable of reversing the altered host immune responses induced by the bacterial phosphatase and restoring the macrophage's full capacity to secrete IL-6 and undergo apoptosis in response to interferon-γ stimulation, validating the concept that chemical inhibition of mPTPB may be therapeutically useful for novel TB treatment. The study further demonstrates that bicyclic salicylic acid pharmacophores can be used to deliver PTP inhibitors with high potency, selectivity, and cellular efficacy. 23410164 Polypharmacology in a single drug: multitarget drugs. Polypharmacology offers a model for the way drug discovery must evolve to develop therapies most suited to treating currently incurable diseases. It is driven by a worldwide demand for safer, more effective, and affordable medicines against the most complex diseases, and by the failures of modern drug discovery to provide these. Polypharmacology can involve combinations and/or multitarget drugs (MTD). Although not mutually exclusive, my premise is that MTDs have inherent advantages over combinations. This review article focuses on MTDs from a medicinal chemistry perspective. I will explore their use in current clinical practice, their likely application in the future, and the challenges to be overcome to achieve this goal. 23411312 Thermal stability of anthocyanins and colourless phenolics in pomegranate (Punica granatum L.) juices and model solutions. The present study aimed at a systematic assessment of the factors influencing the anthocyanin (AC) stability and colour retention of pomegranate juices and less complex model solutions with particular focus on the effects of colourless phenolic copigments (CP). The thermal stability of ACs in three pomegranate juices obtained from isolated arils and the entire fruit with and without previous steaming, in model solutions with AC:CP ratios ranging from 1:0 to 1:4 (m/m), and in two purified extracts from pomegranate juices characterised by different phenolic profiles, respectively, was investigated upon heating at 60, 70, 80 and 90°C for 15 min to 5h. The thermal impact on the AC and CP contents, and the formation of 5-hydroxymethylfurfural (HMF) and AC degradation products were monitored using HPLC-DAD-MS(n). Total phenolic contents, antioxidant capacity and colour properties were determined spectrophotometrically. Heating at 90°C for 5h resulted in total AC losses ranging from 76% to 87% of the initial AC levels in the juices, 78% in both extracts as well as 57% and ∼78% in the model solutions, showing the best stability at an AC:CP ratio of 1:2 and in juices having the highest initial AC contents, respectively. In contrast, the AC stability was independent of total phenolic contents, and low and high molecular pomegranate matrix components (such as organic acids and sugars). Good correlation of the AC contents with red colour (a(∗)) was observed for all samples at elevated temperatures (70-90°C). The stability of putative health-promoting polyphenols of pomegranate juices was not markedly affected by the thermal treatment. Unexpectedly, the HMF contents only slightly increased upon forced heating. Therefore, the visual appearance does not adequately reflect the quality and storage stability of pomegranate juices. 23000447 A 90-day feeding study of glyphosate-tolerant maize with the G2-aroA gene in Sprague-Dawley rats. Maize is not only a staple food crop but also an important raw material for feed and industry; however, the threat of weeds leads to a serious decline in its output and quality. The G2-aroA gene confers glyphosate herbicide tolerance to crops. In this study, the food safety of genetically modified (GM), glyphosate-tolerant maize with the G2-aroA gene was evaluated in a 90-day feeding study in Sprague-Dawley (SD) rats. Maize grain from GM or non-GM isogenic control lines were separately formulated into rodent diets at concentrations of 12.5% (low level), 25% (middle level), and 50% (high level). An additional group of rats were fed a commercialized diet as a control. The toxicological response variables, including body weights, food consumption, serum biochemistry, hematology, and absolute and relative organ weights, were compared between rats fed GM maize and those fed non-GM maize after consumption of test diets for 90days. In addition, gross and microscopic pathology were conducted among treatment groups. No adverse effects related to the consumption of GM maize were detected in the subchronic feeding study. These results indicated that the GM glyphosate-tolerant maize was as safe and nutritious as conventional maize. 23382105 Population pharmacokinetics and dose optimization of mycophenolic acid in HCT recipients receiving oral mycophenolate mofetil. We sought to create a population pharmacokinetic model for total mycophenolic acid (MPA), to study the effects of different covariates on MPA pharmacokinetics, to create a limited sampling schedule (LSS) to characterize MPA exposure (i.e., area under the curve or AUC) with maximum a posteriori Bayesian estimation, and to simulate an optimized dosing scheme for allogeneic hematopoietic cell transplantation (HCT) recipients. Four thousand four hundred ninety-six MPA concentration-time points from 408 HCT recipients were analyzed retrospectively using a nonlinear mixed effects modeling approach. MPA pharmacokinetics was characterized with a two-compartment model with first-order elimination and a time-lagged first-order absorption process. Concomitant cyclosporine and serum albumin were significant covariates. The median MPA clearance (CL) and volume of the central compartment were 24.2 L/hour and 36.4 L, respectively, for a 70 kg patient receiving tacrolimus with a serum albumin of 3.4 g/dL. Dosing simulations indicated that higher oral MMF doses are needed with concomitant cyclosporine, which increases MPA CL by 33.8%. The optimal LSS was immediately before and at 0.25 hours, 1.25 hours, 2 hours, and 4 hours after oral mycophenolate mofetil administration. MPA AUC in an individual HCT recipient can be accurately estimated using a five-sample LSS and maximum a posteriori Bayesian estimation. 23347616 5' C-rich telomeric overhangs are an outcome of rapid telomere truncation events. A subset of human tumors ensures indefinite telomere length maintenance by activating a telomerase-independent mechanism known as Alternative Lengthening of Telomeres (ALT). Most tumor cells of ALT origin share a constellation of unique characteristics, which include large stores of extra-chromosomal telomeric material, chronic telomere dysfunction and a peculiar enrichment in chromosome ends with 5' C-rich overhangs. Here we demonstrate that acute telomere de-protection and the subsequent DNA damage signal are not sufficient to facilitate formation of 5' C-overhangs at the chromosome end. Rather chromosome ends bearing 5' C-overhangs are a by-product of rapid cleavage events, processing of which occurs independently of the DNA damage response and is partly mediated through the XRCC3 endonuclease. 23448384 High-temperature and pressure-induced ferroelectricity in hydrogen-bonded supramolecular crystals of anilic acids and 2,3-di(2-pyridinyl)pyrazine. Cocrystallization of anilic acids (H2xa) and 2,3-di(2-pyridinyl)pyrazine (dppz) affords a variety of molecular geometries, including hydrogen-bonding and supramolecular structures. Proton-transferred 1:1 salts of [H-dppz][Hca] and [H-dppz][Hba] (H2ca = chloranilic acid, H2ba = bromanilic acid) were found to host room-temperature ferroelectricity with a spontaneous polarization of 3-4 μC/cm(2) along the hydrogen-bonded chains. Compared with the Curie points of other supramolecular ferroelectrics, those of the salts are relatively high (402 K and >420 K, respectively) because of the elongated hydrogen bonds, which stabilize the proton-ordered state against thermal agitation. In addition to the ferroelectric black (α) form, dppz and H2ba gave two different crystal forms with a 2:3 ratio: the brown β form of [H(1.5)-dppz]2[Hba]3 and the brownish-red γ form of [H-dppz]2[Hba]2[H2ba]. Mixed solutions of dppz with the less acidic fluoranilic acid (H2fa) exhibit valence instability; the H2fa molecules remain mostly neutral in absolute ethanol, whereas methanol (MeOH) solution apparently increases the deprotonated Hfa(-) content. Crystallizations of these solutions gave a neutral [dppz][H2fa] cocrystal and ionic [H-dppz(+)][Hfa(-)]·MeOH salt, respectively. The ferroelectricity induced by a modest hydrostatic pressure corroborates the conclusion that the ionic state with a dipolar [H-dppz(+)][Hfa(-)] chain is energetically close to the nonpolar neutral ground state of the [dppz][H2fa] crystal. 23422227 Cytotoxic sesquiterpenes from Hedychium spicatum: Isolation, structure elucidation and structure-activity relationship studies. Phytochemical investigation of chloroform extract from rhizomes of Hedychium spicatum resulted in the isolation of six new sesquiterpenes (1-6) along with fifteen known compounds (7-21). Their structures were elucidated on the basis of the extensive spectroscopic analyses (IR, Mass and NMR) and by comparison of the data with those reported in the literature. Further, cytotoxic activities of all the isolates were evaluated by determining their inhibitory effects against A-549, B-16, Hela, HT-29, NCI-H460, PC-3, IEC-6 and L-6 cancer cell lines. Results indicated that compounds 1 and 3 may serve as an important natural lead compounds for future development as they showed potent cytotoxic activity against Hela cell lines with an IC50 value of 0.3μg/mL and 1.80μg/mL, respectively. 23411217 Peyer's patch-mediated intestinal immune system modulating activity of pectic-type polysaccharide from peel of Citrus unshiu. An intestinal immune system modulating polysaccharide (CUI-3IIb-3-2, 18kDa) was purified from Citrus unshiu peel. CUI-3IIb-3-2 mainly comprised GalA, GlcA, Ara, Gal and Rha, and it consisted of 4-linked GalA, terminal Araf, 4- or 5-linked/3,4- or 3,5-branched Ara, terminal Gal, and 2-linked/2,4-branched Rha. After CUI-3IIb-3-2 digestion by endo-α-d-(1→4)-polygalacturonase, its hydrolysate was fractionated into PG-1 and PG-2. Methylation analyses of PG-1 and PG-2 using base-catalysed β-elimination suggested that CUI-3IIb-3-2 be assumed as pectic-type polysaccharide. Since the activities of PG-1 and PG-2 were potently decreased, the whole polysaccharide structure of CUI-3IIb-3-2 would be essential to maintain the activity. Meanwhile, when CUI-3IIb was orally administered in mice, bone marrow cell proliferation and GM-CSF/IL-6 production from Peyer's patch cell were significantly higher (1.76- and 2.03/2.51-fold, respectively) than a saline. Therefore, a pectic-type polysaccharide from citrus peel could stimulate Peyer's patches and produce hematopoietic growth factors resulted in bone marrow cell proliferation. 23317159 JAK inhibitors: pharmacology and clinical activity in chronic myeloprolipherative neoplasms. The Janus family kinases (JAKs), JAK1, JAK2, JAK3, and TYK2, are involved in cell growth, survival, development, and differentiation of a variety of cells, particularly immune cells and hematopoietic cells. They form a subgroup of the non-receptor protein tyrosine kinases. Activating mutations within each of the JAKs is associated with malignant transformations; the most common are mutations of JAK2 in polycythemia vera (PV) and other myeloproliferative neoplasms (MPN). Identification of the V617F mutation of the JAK2 gene (JAK2 V617F) led to an important breakthrough in the understanding of MPN disease pathogenesis. The JAK2 V617F mutation is present in the majority of PV patients, and about 50% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) are affected. This mutation leads to hyperactivation of JAK2, cytokine-independent signaling, and subsequent activation of downstream signaling networks. JAK2 ATP-competitive inhibitors that indirectly inhibit the JAK-STAT pathway are new candidates for the treatment of MPN. JAK2 inhibitors in development for the treatment of MPN have demonstrated clinical activity with minimal toxicity. These agents consistently alleviate constitutional symptoms and reduce spleen size in PMF and other MPN. However, some of these inhibitors have additional unique effects. Ruxolitinib causes a significant reduction in the level of pro-inflammatory cytokines. Another inhibitor, CYT387, improves anemia. Many other JAK2 inhibitors such as TG101348 or SAR302503, SB1518, CEP701 and LY2784544 are now under investigation for MPN development. In contrast tasocitinib, a predominantly JAK3 inhibitor, is being evaluated in a number of inflammatory and immunological diseases, including rheumatoid arthritis, psoriasis, ulcerative colitis, dry eye disease and in kidney transplant patients. In conclusion the use of JAK inhibitors in MPN and some of the immune-mediated disorders is a promising new strategy for therapy. However, definitive data from ongoing and future preclinical and clinical trials will aid in better defining the status of these drugs in the treatment of these diseases. 23639361 Ghrelin receptor is activated by naringin and naringenin, constituents of a prokinetic agent Poncirus fructus. ETHNOPHARMACOLOGICAL RELEVANCE: Poncirus fructus (PF), also known as a dried immature fruit of Poncirus trifoliata (L.) Raf, has long been traditionally used for the various gastrointestinal disorders in Eastern Asia. AIM OF STUDY: The aqueous extract of PF (PF-W) has the strong prokinetic effect, yet the underlying mechanism is still elusive. The present study investigated whether PF-W has any effect on motilin receptor or ghrelin receptor, since these receptors enhance intestinal motility when activated. MATERIALS AND METHODS: The effect of PF-W and its components on motilin or ghrelin receptor was determined by calcium imaging and whole-cell patch clamp methods. RESULTS: PF-W activates the ghrelin receptor, but not the motilin receptor, resulting in a transient increase of intracellular calcium levels. Furthermore, among various constituents of PF, only naringin and naringenin evoked the intracellular calcium augmentation via the ghrelin receptor. Moreover, cortistatin-8 - a ghrelin receptor inhibitor - specifically blocked naringin- and naringenin-induced calcium increases. In addition, naringin and naringenin induced inward currents in ghrelin receptor-expressing cells under whole-cell patch clamp configuration. CONCLUSION: PF-W activates the ghrelin receptor, and naringin and naringenin are key constituents responsible for the activation of ghrelin receptor. Therefore, the present study suggests that the ghrelin receptor is a molecular entity responsible for the strong prokinetic activity of PF-W. 23347937 Olfactory evolution: mice rethink stink. Animals use a vast array of chemicals to communicate with others. How such signals originate is poorly known. Now a study traces the emergence of a signal from a metabolic product and the evolution of its behavioural significance. 23423710 5-Aza-2'-deoxycytidine inhibited PDGF-induced rat airway smooth muscle cell phenotypic switching. Airway smooth muscle (ASM) cell phenotypic switching played an important role in airway remodeling in asthma. In vitro platelet-derived growth factor (PDGF) induced ASM cell phenotypic switching from a mature to pro-remodeling phenotype, but the mechanism remained incompletely understood. This study was to explore the effect of DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (Aza-CdR) on PDGF-induced rat ASM cell phenotypic switching and biological behaviors. Rat airway smooth muscle (RASM) cells were obtained by primary explant techniques. Western blot, 3-dimensional gel contraction, transwell and wound healing assay, and MTT were applied to detect cell phenotypic switching, contractility, migration and proliferation, respectively. Cytoskeleton rearrangement was observed by immunofluorescence. Results showed Aza-CdR inhibited PDGF-induced down-regulation of contractile markers in RASM cells and increased cell contractility. Aza-CdR inhibited PDGF-induced RASM cell migration by abrogating cell morphology change and cytoskeletal reorganization and attenuated the effect of PDGF on proliferating cell nuclear antigen expression and cell cycle progression, ultimately cell proliferation. PDGF-induced DNA methyltransferase 1 (DNMT1) expression was mediated by activation of PI3K/Akt and ERK signaling in RASM cells. Selective depletion of DNMT1 protein by Aza-CdR inhibited PDGF-induced RASM cell phenotypic switching, revealing DNMT1-mediated DNA methylation was implicated in asthmatic ASM remodeling. We proposed for the first time that DNMT1 played a key role in PDGF-induced RASM cell phenotypic switching and Aza-CdR is promising in intervening ASM remodeling in asthma. Although study of abnormal DNA methylation in PDGF-stimulated ASM cells is in its infancy, this work contributes to providing new insights into the mechanism of ASM remodeling and may be helpful for developing effective treatments for airway remodeling in asthma. 23491602 Evidence that YycJ is a novel 5'-3' double-stranded DNA exonuclease acting in Bacillus anthracis mismatch repair. The most important system for correcting replication errors that survive the built in editing system of DNA polymerase is the mismatch repair (MMR) system. We have identified a novel mutator strain yycJ in Bacillus anthracis. Mutations in the yycJ gene result in a spontaneous mutator phenotype with a mutational frequency and specificity comparable to that of MMR-deficient strains such as those with mutations in mutL or mutS. YycJ was annotated as a metallo-β-lactamase (MβL) super family member with unknown activity. In this study we carried out a biochemical characterization of YycJ and demonstrated that a recombinant YycJ protein possesses a 5'-3' exonuclease activity at the 5' termini and at nicks of double-stranded DNA. This activity requires a divalent metal cofactor Mn(2+) and is stimulated by 5'-phosphate ends of duplex DNA. The mutagenesis of conserved amino acid residues revealed that in addition to the five MβL family conserved motifs, YycJ appears to have its specific motifs that can be used to distinguish YycJ from other closely related MβL family members. A phylogenetic survey showed that putative YycJ homologs are present in several bacterial phyla as well as in members of the Methanomicrobiales and Thermoplasmales from Archaea. We propose that YycJ represents a new group of MβL fold exonucleases, which is likely to act in the recognition of MMR entry point and subsequent removal of the mismatched base in certain MutH-less bacterial species. 23495163 Variability of n-alkanes and nonacosan-10-ol in natural populations of Picea omorika. This is the first report of population variability of the contents of n-alkanes and nonacosan-10-ol in the needle epicuticular waxes of Serbian spruce (Picea omorika). The hexane extracts of needle samples originated from three natural populations in Serbia (Vranjak, Zmajevački potok, and Mileševka Canyon) were investigated by GC and GC/MS analyses. The amount of nonacosan-10-ol varied individually from 50.05 to 74.42% (65.74% in average), but the differences between the three investigated populations were not statistically confirmed. The results exhibited variability of the composition of n-alkanes in the epicuticular waxes with their size ranging from C(18) to C(35). The most abundant n-alkanes were C(29), C(31), and C(27) (35.22, 13.77, and 12.28% in average, resp.). The carbon preference index of all the n-alkanes (CPI(total)) of the P. omorika populations (average of populations I-III) ranged from 3.3 to 11.5 (mean of 5.9), while the average chain length (ACL) ranged from 26.6 to 29.2. The principal component and cluster analyses of the contents of nine n-alkanes showed the greatest difference for the population growing in the Mileševka Canyon. The obtained results were compared with previous literature data given for other Picea species, and this comparison was briefly discussed. 23092894 PET and SPECT tracers for glutamate receptors. Radioligands for PET imaging of glutamate receptors will have the potential for studying neurological and neuropsychiatric disorders and their diagnosis and therapeutic intervention. Glutamate is the major excitatory neurotransmitter in the brain and is implicated in the pathophysiology of many neurodegenerative and neuropsychiatric disorders. Glutamate and its receptors are potential targets in the treatment of these disorders. Glutamate signaling is mediated through ionotropic and metabotropic receptors. The abundant concentration of these receptors can facilitate their in vivo quantification using positron emission tomography (PET). Glutamate receptors are a potentially important set of targets for monitoring disease progression, for evaluating the effect of therapy and for new treatment development based on the quantification of receptor occupancy. Here, we review the PET and single-photon emission computed tomography (SPECT) radioligands that have been developed for imaging glutamate receptors in living brain. 23537748 Synergistic antibacterial effect of curcumin against methicillin-resistant Staphylococcus aureus. Methicillin-resistant Staphylococcus aureus (MRSA) are spread among infected patients, with infection rates increasing at an alarming rate. Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of infectious diseases worldwide. Under the selection pressure of exposure to antibiotics, microorganisms evolve to survive against the new conditions imposed by therapy. Therefore, there exists a need to develop alternative natural or combination drug therapies. Curcumin (CCM), a natural polyphenolic flavonoid isolated from the rhizome of a plant, Curcuma longa Linné., has been found to possess many beneficial biological activities. The aim of this study was to investigate the synergistic effect of curcumin and antibiotics as well as to determine the antibacterial activity of CCM against specific MRSA strains. The antibacterial activity of CCM was assessed by the broth microdilution method (by calculating the minimal inhibitory concentration [MIC]), checkerboard dilution test, and time-kill assay. Antimicrobial activity of CCM was observed against all tested strains. The MICs of CCM against 10 strains of S. aureus ranged from 125 to 250μg/ml. In the checkerboard test, CCM markedly reduced the MICs of the antibiotics oxacillin (OXI), ampicillin (AMP), ciprofloxacin (CIP), and norfloxacin (NOR) used against MRSA. The time-kill curves showed that a combined CCM and OXI treatment reduced the bacterial counts below the lowest detectable limit after 24h. This study suggested that CCM reduced the MICs of several antibiotics tested, notably of OXI, AMP, CIP, and NOR, and that CCM in combination with antibiotics could lead to the development of new combination of antibiotics against MRSA infection. 23353027 In vitro toxicological characterisation of the S-containing arsenic metabolites thio-dimethylarsinic acid and dimethylarsinic glutathione. Inorganic arsenic is a well-documented, exposure relevant human carcinogen. A promising starting point to further understand the mechanisms behind inorganic arsenic carcinogenicity might be a formation of reactive, highly toxic metabolites during human arsenic metabolism. This study characterises the toxicity of recently identified S-containing arsenic metabolites in cultured human A549 lung adenocarcinoma epithelium cells. In direct comparison to arsenite, thio-dimethylarsinic acid (thio-DMA(V)) and dimethylarsinic glutathione (DMAG) exerted a 5- to 20-fold stronger cytotoxicity and showed a 2- to 20-fold higher cellular bioavailability, respectively. All three arsenicals disturbed cell cycle progression at cytotoxic concentrations, but failed to increase the level of reactive oxygen and nitrogen species (RONS) in healthy A549 cells. However, a strong disturbance of the oxidative defense system was observed after incubation with absolutely sub-cytotoxic, pico- to nanomolar concentrations of arsenite and thio-DMA(V), respectively. Thus, both GSH and GSSG levels were significantly decreased by up to 40%. Accordingly, RONS levels of oxidatively (H2O2) stressed cells were strongly increased by the arsenicals. Since in vivo RONS are permanently endogenously and exogenously produced, this boost of the existing oxidative stress by arsenite and thio-DMA(V) might contribute to the process of inorganic arsenic induced carcinogenicity. 23000442 Selective inhibitory effects of mollugin on CYP1A2 in human liver microsomes. Mollugin originally isolated from Rubia cordifolia is a pharmacological compound for its anti-inflammation, anti-cancer, and anti-viral activity. In the present study, a cocktail probe assay was performed for determination of the selective inhibitory effect of mollugin on cytochrome P450 (CYP) enzymes in human liver microsomes (HLM). Incubation of isoform-specific substrate probes CYPs with mollugin (0-25μM) in HLM resulted in strong inhibition of CYP1A2-catalyzed phenacetin O-deethylation, showing IC(50) values of 1.03 and 3.55μM without and with pre-incubation, respectively. Mollugin-caused inhibition of phenacetin O-deethylation was concentration-dependent in HLMs, but not time-dependent. In addition, the Lineweaver-Burk plot indicated a typical competitive inhibition. Inhibitory effects of mollugin on human recombinant cDNA-expressed CYP1A1 and 1A2 were comparable. Taken together, the results suggested that mollugin might cause herb-drug interaction through selective inhibition of CYP1A2 in humans receiving herbal medications, including R. cordifolia. 23494831 Oxygen Activation of Apo-obelin-Coelenterazine Complex. Ca(2+) -regulated photoproteins use a noncovalently bound 2-hydroperoxycoelenterazine ligand to emit light in response to Ca(2+) binding. To better understand the mechanism of formation of active photoprotein from apoprotein, coelenterazine and molecular oxygen, we investigated the spectral properties of the anaerobic apo-obelin-coelenterazine complex and the kinetics of its conversion into active photoprotein after exposure to air. Our studies suggest that coelenterazine bound within the anaerobic complex might be a mixture of N7-protonated and C2(-) anionic forms, and that oxygen shifts the equilibrium in favor of the C2(-) anion as a result of peroxy anion formation. Proton removal from N7 and further protonation of peroxy anion and the resulting formation of 2-hydroperoxycoelenterazine in obelin might occur with the assistance of His175. It is proposed that this conserved His residue might play a key role both in formation of active photoprotein and in Ca(2+) -triggering of the bioluminescence reaction. 23017401 Genistein and dicarboximide fungicides in infant formulae from the EU market. A method based on ultrasonic extraction and purification by solid phase extraction followed by LC-MS/MS and GC-MS analysis was developed for the determination of genistein, genistin, iprodione, vinclozolin and procymidone in infant powdered formulas. The method was tested for different formulations: milk, soy and hypoallergenic, and was applied to European pooled samples. Spike recoveries ranged from 53.1% to 91.5% and the relative standard deviation values for repeatability ranged from 9.6% to 17.7%, except for iprodione in milk formula (22.3%). None of the fungicides were found in the European pooled formulae, while genistein was found at 9.7μg/g in soy formula and the concentration of genistin, its β-glycosylated form, was respectively 31.4ng/g and 476ng/g in milk and soy formula. 22815230 The antioxidant and anticancer effects of wild carrot oil extract. Daucus carota L. ssp. carota (Apiacea) is used in traditional medicine in Lebanon and in different regions throughout the world. The present study investigates the in vitro anticancer activities of Daucus carota oil extract (DCOE) on four human cancer cell lines as well as its in vitro antioxidant activity. DCOE was extracted from the dried umbels with 50:50 acetone-methanol. The oil extract was analyzed by gas chromatography-mass spectrometry and screened for its antioxidant properties in vitro using 1,1-diphenyl-2-picryl hydrazyl free radical scavenging assay (DPPH), ferrous ion chelating assay (FIC) and the ferric reducing antioxidant power assay (FRAP). The anticancer activity of the oil extract against human colon (HT-29, Caco-2) and breast (MCF-7, MDA-MB-231) cancer cell lines was evaluated using the trypan blue exclusion method and the WST-1 cell proliferation assay. DCOE exhibited antioxidant activity in all assays used. The FRAP value was 164 ± 5.5 µmol FeSO4 /g, and the IC50 values for DPPH and FIC assays were 2.1 ± 0.03 mg/ml and 0.43 ± 0.02 mg/ml, respectively. Also, DCOE demonstrated a significant increase in cell death and decrease in cell proliferation. The effect of DCOE on the cell lines exhibited time and dose-dependent responses. The present study established that DCOE possesses both antioxidant and promising anticancer activities. Copyright © 2012 John Wiley & Sons, Ltd. 23079231 Synergistic immunosuppressive effects of the mTOR inhibitor sirolimus and the phytochemical curcumin. The immunosuppressant sirolimus and curcumin, the main principle of the turmeric spice, have shown antiproliferative effects on many human and not-human cell lines. Whereas the antiproliferative effect of sirolimus is mainly mediated by inhibition of mTOR, curcumin is described to affect many molecular targets which makes it unpredictable to appraise if the effects of these both substances on cell proliferation and especially on immunosuppression are additive or synergistic. To answer this question we investigated the interaction of both these substances on OKT3-induced human peripheral blood mononuclear cell (PBMC) proliferation. OKT3-induced human PBMC proliferation was determined by measuring (3)H-thymidine incorporation. Influence of curcumin on interleukin-2 (IL-2) release and IκB-phosphorylation in PBMC was determined by ELISA and western blot, respectively. Curcumin-induced apoptosis and necrosis was analyzed by FACS analysis. Whereas curcumin completely inhibited OKT3-induced PBMC proliferation in a dose-dependent manner with an IC(50) of 2.8 μM, sirolimus could reduce PBMC proliferation dose-dependently only to a minimum of 28% at a concentration of 5 ng/ml (IC(50) 1.1 ng/ml). When curcumin was combined at concentrations of 1.25-2.5 μM with sirolimus at concentrations from 0.63 to 1.25 ng/ml the effects were synergistic. Combination of curcumin (1.25-2.5 μM) with sirolimus (5 ng/ml) showed additive effects. The effects after combination of curcumin at 5 μM with each sirolimus concentration and sirolimus at 10 ng/ml with each curcumin concentration were presumably antagonistic. We conclude that the immunosuppressive effects of curcumin and sirolimus in low concentrations are synergistic in OKT3-activated PBMC. Whether curcumin and sirolimus have also synergistic antiproliferative effects in tumor cells has to be shown in further experiments including animal models. 23480848 Effect of Solvent Polarity on the Vibrational Dephasing Dynamics of the Nitrosyl Stretch in an Fe(II) Complex Revealed by 2D IR Spectroscopy. The vibrational dephasing dynamics of the nitrosyl stretching vibration (νNO) in sodium nitroprusside (SNP, Na2[Fe(CN)5NO]·2H2O) are investigated using two-dimensional infrared (2D IR) spectroscopy. The νNO in SNP acts as a model system for the nitrosyl ligand found in metalloproteins which play an important role in the transportation and detection of nitric oxide (NO) in biological systems. We perform a 2D IR line shape study of the νNO in the following solvents: water, deuterium oxide, methanol, ethanol, ethylene glycol, formamide, and dimethyl sulfoxide. The frequency of the νNO exhibits a large vibrational solvatochromic shift of 52 cm(-1), ranging from 1884 cm(-1) in dimethyl sulfoxide to 1936 cm(-1) in water. The vibrational anharmonicity of the νNO varies from 21 to 28 cm(-1) in the solvents used in this study. The frequency-frequency correlation functions (FFCFs) of the νNO in SNP in each of the seven solvents are obtained by fitting the experimentally obtained 2D IR spectra using nonlinear response theory. The fits to the 2D IR line shape reveal that the spectral diffusion time scale of the νNO in SNP varies from 0.8 to 4 ps and is negatively correlated with the empirical solvent polarity scales. We compare our results with the experimentally determined FFCFs of other charged vibrational probes in polar solvents and in the active sites of heme proteins. Our results suggest that the vibrational dephasing dynamics of the νNO in SNP reflect the fluctuations of the nonhomogeneous electric field created by the polar solvents around the nitrosyl and cyanide ligands. The solute solvent interactions occurring at the trans-CN ligand are sensed through the π-back-bonding network along the Fe-NO bond in SNP. 23506624 BACE2 as a new diabetes target: a patent review (2010 - 2012). Introduction: When two novel aspartyl proteases were published in 1999 and 2000, beta-site APP-cleaving enzyme 1 (BACE1) was confirmed as the long sought after beta-secretase and Alzheimer's disease drug target. However, the role of its paralogue, BACE2, proved elusive until a 2011 publication implicated it as a Collectrin (TMEM27) secretase controlling pancreatic beta-cell proliferation and a new therapeutic intervention for diabetes. Areas covered: This review, using SureChemOpen, encompasses early validation compounds and small-molecule BACE2 inhibitors for diabetes. Since 2010, one assay patent and several chemical series have been published by Roche but these were followed by filings from Novartis and Schering in 2012. The patents from these three companies include BACE2-only filings but also some specifying both BACE1 and BACE2 inhibitors. Expert opinion: Roche's early collaborative target validation has given them a lead in BACE2 medicinal chemistry. However, the extensive data output for BACE1 in patents and papers over the last decade, plus liganded crystal structures for both proteases, should expedite the design of BACE2 inhibitors by other organisations. This may also shorten the development time for clinical candidates that, unlike those now entering Phase I trials for BACE1, would not need to be brain-penetrant. 23562073 Raggin' on T-bet. Although increasing adiposity is usually associated with adipose tissue infiltration by inflammatory cells and systemic insulin resistance, Stolarczyk et al. (2013) report in this issue that mice deficient in the T-box transcription factor, T-bet, display a dissociated phenotype with enhanced perigonadal adipose but enhanced insulin sensitivity. 23468408 Cell-Laden Hydrogels in Integrated Microfluidic Devices for Long-Term Cell Culture and Tubulogenesis Assays. A hydrogel biochip combining microfluidic mixing and orthogonal supplementation strategies is developed and validated to allow facile generation of libraries of optically transparent 3D culture microenvironments. Live, on-chip tracing of embryonic stem cell differentiation and endothelial cell tubulogenesis confirms that the platform can be used to both create communities of discrete 3D microenvironments as well as to locally monitor subsequent divergent responses at both single cell and multi-cell scales. 23570840 Goniolandrene A and B from Goniothalamus macrophyllus. Goniothalamus macrophyllus (Blume) Hook. f. & Thoms. is a plant widely distributed in Malaysia. The aim of this study is to identify compounds from the roots of G. macrophyllus. The ground roots were extracted with aqueous methanol and partitioned sequentially with n-hexane, chloroform and butanol. Purification from this extracts afforded six compounds with two new compounds, namely goniolandrene-A (1), -B (2). The absolute configuration of goniolandrene B (2) was established by circular dichrosim. The compounds were cytotoxic against the P388 cells with IC50 values ranging from 0.42 to 160μM. Goniothalamin (3) exhibited the highest inhibition of 0.42μM. 23612709 Signaling mechanisms in Mammalian myoblast fusion. Myoblast fusion is a critical process that contributes to the growth of muscle during development and to the regeneration of myofibers upon injury. Myoblasts fuse with each other as well as with multinucleated myotubes to enlarge the myofiber. Initial studies demonstrated that myoblast fusion requires extracellular calcium and changes in cell membrane topography and cytoskeletal organization. More recent studies have identified several cell-surface and intracellular proteins that mediate myoblast fusion. Furthermore, emerging evidence suggests that myoblast fusion is also regulated by the activation of specific cell-signaling pathways that lead to the expression of genes whose products are essential for the fusion process and for modulating the activity of molecules that are involved in cytoskeletal rearrangement. Here, we review the roles of the major signaling pathways in mammalian myoblast fusion. 23230281 Increased oxidized low-density lipoprotein causes blood-brain barrier disruption in early-onset preeclampsia through LOX-1. Early-onset preeclampsia (EPE) is a severe form of preeclampsia that involves life-threatening neurological complications. However, the underlying mechanism by which EPE affects the maternal brain is not known. We hypothesized that plasma from women with EPE increases blood-brain barrier (BBB) permeability vs. plasma from women with late-onset preeclampsia (LPE) or normal pregnancy (NP) and investigated its underlying mechanism by perfusing cerebral veins from nonpregnant rats (n=6-7/group) with human plasma from women with EPE, LPE, or NP and measuring permeability. We show that plasma from women with EPE significantly increased BBB permeability vs. plasma from women with LPE or NP (P<0.001). BBB disruption in response to EPE plasma was due to a 260% increase of circulating oxidized LDL (oxLDL) binding to its receptor, LOX-1, and subsequent generation of peroxynitrite (P<0.001). A rat model with pathologically high lipid levels in pregnancy showed symptoms of preeclampsia, including elevated blood pressure, growth-restricted fetuses, and LOX-1-dependent BBB disruption, similar to EPE (P<0.05). Thus, we have identified LOX-1 activation by oxLDL and subsequent peroxynitrite generation as a novel mechanism by which disruption of the BBB occurs in EPE. As increased BBB permeability is a primary means by which seizure and other neurological symptoms ensue, our findings highlight oxLDL, LOX-1, and peroxynitrite as important therapeutic targets in EPE. 23450777 Exfoliated graphitic carbon nitride nanosheets as efficient catalysts for hydrogen evolution under visible light. Graphitic carbon nitride nanosheets are extracted, produced via simple liquid-phase exfoliation of a layered bulk material, g-C3 N4 . The resulting nanosheets, having ≈2 nm thickness and N/C atomic ratio of 1.31, show an optical bandgap of 2.65 eV. The carbon nitride nanosheets are demonstrated to exhibit excellent photocatalytic activity for hydrogen evolution under visible light. 23289615 Freezing continuous-flow self-assembly in a microfluidic device: toward imaging of liposome formation. A new method is described that combines a microfluidic device for the controlled formation of liposomes with instantaneous immobilization by means of ultrarapid cooling. The microfluidic device is composed of capillaries to hydrodynamically focus a stream of lipids dissolved in 2-propanol by two adjacent aqueous buffer streams before rapidly cooling by propane jet-freezing. The capillary containing the frozen sheath-flow is subsequently separated from the flow-focusing unit and trimmed with cryo-ultramicrotomy for imaging with cryo-scanning electron microscopy (SEM). The emergence of liposomes could be visualized by cryo-SEM without the need for chemical fixation or labeling. We demonstrate that the method is capable of revealing in more detail the formation of nonequilibrium liposomes. Partially and completely formed liposomes were observed at the miscible alcohol-buffer interface. The number density of lipid vesicles varied along the focused interface, and we frequently found clusters of liposomes. Additionally, evidence for the formation of disclike transient intermediates is presented. The method is not limited to studying self-assembly processes only. It can be extended to other biochemical reactions, crystallization processes, and even systematic interfacial mixing studies between different solvents. 23439223 Post-partum variation in the expression of paternal care is unrelated to urinary steroid metabolites in marmoset fathers. The organization and activation of maternal care are known to be highly regulated by hormones and there is growing evidence that expression of paternal care is also related to endocrine substrates. We examined the relationship between paternal behavior and steroid hormones in marmoset fathers (Callithrix geoffroyi) and evaluated whether hormone-paternal behavior relationships were altered by previous offspring-care experience in males. Based on previous findings, we predicted that testosterone, estradiol, and cortisol would decrease following the birth of offspring and would be lowest during the period of maximal infant carrying. Furthermore, we predicted that post-partum changes in carrying effort and hormone levels would be influenced by the level of offspring-care experience. Carrying effort and other paternal care behaviors underwent temporal changes over the post-partum period, but these patterns were not related to variation in hormone concentrations over the same period. There was a limited effect of offspring-care experience on hormone concentrations, but experience was found to play a role in the expression of paternal care, with experienced fathers engaging in significantly more infant allogrooming than inexperienced fathers. Furthermore, inexperienced fathers increased the frequency of food sharing in response to infant begging across the post-partum period, while experienced fathers displayed consistently low levels. We posit that a combination of experiential factors and an increased role for alloparents in offspring-care led to these changes. However, it appears that hormonal changes may not influence paternal responsiveness in white-faced marmoset fathers and that hormone-paternal behavior relationships are not critically dependent on a male's previous offspring-care experience. 23028140 Autoinhibition of CYP3A4 leads to important role of CYP2C8 in imatinib metabolism: variability in CYP2C8 activity may alter plasma concentrations and response. Recent data suggest that the role of CYP3A4 in imatinib metabolism is smaller than presumed. This study aimed to evaluate the quantitative importance of different cytochrome P450 (P450) enzymes in imatinib pharmacokinetics. First, the metabolism of imatinib was investigated using recombinant P450 enzymes and human liver microsomes with P450 isoform-selective inhibitors. Thereafter, an in silico model for imatinib was constructed to perform pharmacokinetic simulations to assess the roles of P450 enzymes in imatinib elimination at clinically used imatinib doses. In vitro, CYP2C8 inhibitors and CYP3A4 inhibitors inhibited the depletion of 0.1 µM imatinib by 45 and 80%, respectively, and the formation of the main metabolite of imatinib, N-desmethylimatinib, by >50%. Likewise, recombinant CYP2C8 and CYP3A4 metabolized imatinib extensively, whereas other isoforms had minor effect on imatinib concentrations. In the beginning of imatinib treatment, the fractions of its hepatic clearance mediated by CYP2C8 and CYP3A4 were predicted to approximate 40 and 60%, respectively. During long-term treatment with imatinib 400 mg once or twice daily, up to 65 or 75% of its hepatic elimination was predicted to occur via CYP2C8, and only about 35 or 25% by CYP3A4, due to dose- and time-dependent autoinactivation of CYP3A4 by imatinib. Thus, although CYP2C8 and CYP3A4 are the main enzymes in imatinib metabolism in vitro, in silico predictions indicate that imatinib inhibits its own CYP3A4-mediated metabolism, assigning a key role for CYP2C8. During multiple dosing, pharmacogenetic polymorphisms and drug interactions affecting CYP2C8 activity may cause marked interindividual variation in the exposure and response to imatinib. 23520074 Opposite modulation of cell migration by distinct subregions of urokinase connecting Peptide. Functional analysis of isolated protein domains may uncover cryptic activities otherwise missed. The serine protease urokinase (uPA) has a clear-cut motogen activity that is catalytically independent and resides in its amino-terminal growth factor domain (GFD, residues 1-49) and connecting peptide region (CP, residues 132-158). To functionally dissect the CP region, we analysed the biological activity of two synthetic peptides corresponding to the N-terminal [uPA-(135-143), residues 135-143] and C-terminal [uPA-(144-158), residues 144-158] CP subregions. Most of the chemotactic activity of connecting peptide-derived peptide (CPp, [uPA-(135-158)]) for embryonic kidney HEK293/uPAR-25 cells is retained by uPA-(144-158) at nanomolar concentrations. In contrast, uPA-(135-143) inhibits basal, CPp -, vitronectin- and fibronectin-induced cell migration. Radioreceptor binding assays on intact HEK293 cells revealed that uPA-(135-143) and uPA-(144-158) are both able to compete with [(125) I]-CPp, albeit with different binding affinities. The consequences of phospho-mimicking, S138E substitution, were studied using [138E]uPA-(135-158) and [138E]uPA-(135-143) peptides. Unlike CPp, [138E]uPA-(135-158) and [138E]uPA-(135-143) exhibit remarkable inhibitory properties. Finally, analysis of the conformational preferences of the peptides allowed to identify secondary structure elements exclusively characterising the stimulatory CPp and uPA-(144-158) versus the inhibitory uPA-(135-143), [138E]uPA-(135-158) and [138E]uPA-(135-143) peptides. In conclusion, these data shed light on the cryptic activities of uPA connecting peptide, revealing the occurrence of two adjacent regions, both competing for binding to cell surface but conveying opposite signalling on cell migration. 23627282 Development and Therapeutic Implications of Selective Histone Deacetylase 6 Inhibitors. The ensuing Perspective provides an in depth look at the numerous disease states in which histone deacetylase 6 (HDAC6) has been implicated. The physiological pathways, protein-protein interactions and non-histone substrates relating to different pathological conditions are discussed with regard to HDAC6. Furthermore, the compounds and methods used to modulate HDAC6 activity are profiled. The latter half of this Perspective analyzes reported HDAC6 selective inhibitors in terms of structure, potency and selectivity over the other HDAC isoforms with the intent of providing a comprehensive overview of the molecular tools available. Potential obstacles and future directions of HDAC6 research are also presented. 23238233 Four new triterpenoid saponins from the leaves of Panax japonicus grown in southern Miyazaki Prefecture (4). Four new dammarane-type triterpenoid saponins such as chikusetsusaponin LM3 (1), chikusetsusaponin LM4 (2), chikusetsusaponin LM5 (3), chikusetsusaponin LM6 (4), and twenty known triterpenoid saponins such as ginsenoside Rb3 (5), ginsenoside Rc (6), ginsenoside Rd (7), ginsenoside Re (8), ginsenoside Rg1 (9), ginsenoside F3 (10), ginsenoside F5 (11), ginsenoside F6 (12), chikusetsusaponin IVa (13), chikusetsusaponin V (14), chikusetsusaponin L5 (15), chikusetsusaponin L9a (16), chikusetsusaponin L9bc (17), chikusetsusaponin L10 (18), chikusetsusaponin FK2 (19), chikusetsusaponin FK6 (20), chikusetsusaponin FK7 (21), chikusetsusaponin FT1 (22), chikusetsusaponin LM1 (23), and chikusetsusaponin LM2 (24), were isolated from the leaves of Panax japonicus C. A. MEYER collected in Miyazaki prefecture, Japan. The structures of new chikusetsusaponins were elucidated on the basis of spectral and physicochemical evidences. 23197296 RNF4 is required for DNA double-strand break repair in vivo. Unrepaired DNA double-strand breaks (DSBs) cause genetic instability that leads to malignant transformation or cell death. Cells respond to DSBs with the ordered recruitment of signaling and repair proteins to the sites of DNA lesions. Coordinated protein SUMOylation and ubiquitylation have crucial roles in regulating the dynamic assembly of protein complexes at these sites. However, how SUMOylation influences protein ubiquitylation at DSBs is poorly understood. We show herein that Rnf4, an E3 ubiquitin ligase that targets SUMO-modified proteins, accumulates in DSB repair foci and is required for both homologous recombination (HR) and non-homologous end joining repair. To establish a link between Rnf4 and the DNA damage response (DDR) in vivo, we generated an Rnf4 allelic series in mice. We show that Rnf4-deficiency causes persistent ionizing radiation-induced DNA damage and signaling, and that Rnf4-deficient cells and mice exhibit increased sensitivity to genotoxic stress. Mechanistically, we show that Rnf4 targets SUMOylated MDC1 and SUMOylated BRCA1, and is required for the loading of Rad51, an enzyme required for HR repair, onto sites of DNA damage. Similarly to inactivating mutations in other key regulators of HR repair, Rnf4 deficiency leads to age-dependent impairment in spermatogenesis. These findings identify Rnf4 as a critical component of the DDR in vivo and support the possibility that Rnf4 controls protein localization at DNA damage sites by integrating SUMOylation and ubiquitylation events. 23293966 Synthesis and characterization of quarteranthene: elucidating the characteristics of the edge state of graphene nanoribbons at the molecular level. The characteristics of the edge state, which is a peculiar magnetic state in zigzag-edged graphene nanoribbons (ZGNRs) that originates from electron-electron correlation in an edge-localized π-state, are investigated by preparing and characterizing quarteranthene molecules. The molecular geometry that was determined from the X-ray analysis is consistent with a zigzag-edge-localized structure of unpaired electrons. The localized electrons are responsible for the peculiar magnetic (room-temperature ferromagnetic correlation), optical (the lowest-lying doubly excited state), and chemical (peroxide bond formation) behaviors. On the basis of these distinguishing properties and a careful consideration of the valence bonding, insight into the edge state of ZGNRs can be gained. 23455373 Properties and self-assembled packing morphology of long alkyl-chained substituted polyhedral oligomeric silsesquioxanes (POSS) cages. Polyhedral oligomeric silsesquioxane (POSS) cubic cage systems (octa-n-octadecyloctasilsesquioxane, (T8C18) and octakis(n-octadecyldimethylsiloxy)octasilsesquioxane, (Q8C18)) were synthesised with eight long n-alkyl chain (R = C18H37) substituent arms, as model nano-functionalized compounds. The crystalline packing morphology of the cages was studied using time-resolved Small- and Wide-angle X-ray scattering (SAXS/WAXS), thermal and optical techniques. From thermal analysis the melting and crystallization temperatures of the Q8 cage were significantly less than those for the T8 cage. X-ray scattering showed that both cage systems have long-range crystalline ordering where the alkyl chains align in a parallel axial disposition from the POSS core giving a 'rod-like' self-assembled packing morphology. The packing length-scale can be directly related to the overall dimensions of the POSS molecules. Compared to the T8 cages, the Q8 cages pack more efficiently allowing the interdigitation of the alkyl chain arms. Different packing modes and thermal behaviour observed for the T8 and Q8 cages is directly attributed to their structural chemistry. For the Q8 cage, the presence of the OSiMe2 spacer groups which tether the alkyl chain arms to the cage (absent in the T8 cages) allows greater flexibility of the arms letting them interdigitate with each other when packing which is not observed for the analogous T8 cages. 23411351 Interactive effects of a bacterial parasite and the insecticide carbaryl to life-history and physiology of two Daphnia magna clones differing in carbaryl sensitivity. Natural and chemical stressors occur simultaneously in the aquatic environment. Their combined effects on biota are usually difficult to predict from their individual effects due to interactions between the different stressors. Several recent studies have suggested that synergistic effects of multiple stressors on organisms may be more common at high compared to low overall levels of stress. In this study, we used a three-way full factorial design to investigate whether interactive effects between a natural stressor, the bacterial parasite Pasteuria ramosa, and a chemical stressor, the insecticide carbaryl, were different between two genetically distinct clones of Daphnia magna that strongly differ in their sensitivity to carbaryl. Interactive effects on various life-history and physiological endpoints were assessed as significant deviations from the reference Independent Action (IA) model, which was implemented by testing the significance of the two-way carbaryl×parasite interaction term in two-way ANOVA's on log-transformed observational data for each clone separately. Interactive effects (and thus significant deviations from IA) were detected in both the carbaryl-sensitive clone (on survival, early reproduction and growth) and in the non-sensitive clone (on growth, electron transport activity and prophenoloxidase activity). No interactions were found for maturation rate, filtration rate, and energy reserve fractions (carbohydrate, protein, lipid). Furthermore, only antagonistic interactions were detected in the non-sensitive clone, while only synergistic interactions were observed in the carbaryl sensitive clone. Our data clearly show that there are genetically determined differences in the interactive effects following combined exposure to carbaryl and Pasteuria in D. magna. 23455314 Contribution of the m1 transmembrane helix and pre-m1 region to positive allosteric modulation and gating of N-methyl-d-aspartate receptors. N-methyl-d-aspartate (NMDA) receptors are glutamate-gated ion channels whose function is critical for normal excitatory synaptic transmission in the brain and whose dysfunction has been implicated in several neurologic conditions. NMDA receptor function is subject to extensive allosteric regulation both by endogenous compounds and by exogenous small molecules. Elucidating the structural determinants and mechanism of action by which allosteric regulators control gating will enhance our understanding of NMDA receptor activation and facilitate the development of novel therapeutics. Here, we investigated the structural determinants for (3-chlorophenyl)(6,7-dimethoxy-1-((4-methoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone (CIQ), a GluN2C/2D-selective positive allosteric modulator. We show that CIQ does not bind to the amino-terminal domain of the NMDA receptor and does not share structural determinants with modulators acting at the agonist-binding domain dimer interface or ion channel pore. Rather, we identified critical determinants of CIQ modulation in the region near the first transmembrane helix of GluN2D, including in a putative pre-M1 cuff helix that may influence channel gating. We also show that mutations within the GluN2D pre-M1 region alter open probability of the NMDA receptor. These results suggest a novel site of action for potentiation of NMDA receptors by small molecules and implicate the pre-M1 region in NMDA receptor gating. 23203454 Metabolism of the plasticizer and phthalate substitute diisononyl-cyclohexane-1,2-dicarboxylate (DINCH(®)) in humans after single oral doses. Hexamoll(®) DINCH(®) (diisononyl-cyclohexane-1,2-dicarboxylate) is a new high-molecular-weight plasticizer and a phthalate substitute. In this study, the metabolism of DINCH(®) was investigated by oral dosage of three male volunteers with approximately 50 mg Hexamoll(®) DINCH(®) (resulting in individual doses between 0.552 and 0.606 mg/kg body weight). Their urine samples were consecutively collected over 48 h. In analogy to di-iso-nonylphthalate (DINP) metabolism, we quantified the simple monoester mono-isononyl-cyclohexane-1,2-dicarboxylate (MINCH) and its secondary oxidized metabolites with HPLC-MS/MS via isotope dilution analysis. Additionally, we quantified the unspecific full breakdown product, cyclohexane-1,2-dicarboxylic acid (CHDA), via standard addition. All postulated metabolites were present in all samples analyzed. The unspecific CHDA was identified as the major urinary metabolite representing 23.7 % of the dose as the mean of the three volunteers (range 20.0-26.5 %). 14.8 % (11.3-16.7 %) of the dose was excreted as monoesters with oxidative modifications, in particular OH-MINCH 10.7 % (7.7-12.9 %), oxo-MINCH 2.0 % (1.5-2.6 %) and carboxy-MINCH 2.0 % (1.8-2.3 %). Less than 1 % was excreted as the simple monoester MINCH. In sum, 39.2 % (35.9-42.4 %) of the DINCH(®) dose was excreted as these metabolites in urine within 48 h. Over 90 % of the metabolites investigated were excreted within 24 h after application. The secondary oxidized metabolites, with elimination half-times between 10 and 18 h, proved to be apt and specific biomarkers to determine DINCH(®) exposure. With this study, we provide reliable urinary excretion factors to calculate DINCH(®) intakes based on these metabolites in environmental and occupational studies. 23588558 Adherence to preventive statin therapy according to socioeconomic position. AIM: To explore whether long-term adherence to preventive statin therapy depends on socioeconomic position (SEP). METHODS: A cohort of individuals without established cardiovascular disease (CVD) or diabetes initiating preventive statin therapy during 2002-2005 was followed in the individual-level Danish registries for 4 years or until censoring events (death, emigration, CVD or diabetes). Only individuals aged 40-84 years for whom information was available on the SEP indicators, education and income were included (N = 76,038). Two different aspects of poor adherence were applied as outcome measures: (1) Proportion of days covered (PDC) with medication below 80 %, assuming a daily dose of one tablet (continuity); (2) Discontinuation defined as a gap between two consecutive prescriptions exceeding 365 days (persistence). Stratum-specific logistic regression analyses were applied to estimate the odds ratio (OR) for PDC <80 % across SEP, adjusting for age and hypertension. Hazard ratio (HR) for discontinuation was estimated by Cox regression analyses. RESULTS: Adjusting mutually for income and education, the OR for PDC <80 % decreased with increasing income. Comparing the highest income quintile with the lowest, the OR were 0.64 (95 % Confidence Interval 0.64-0.65) and 0.73 (0.73-0.74) in men aged 40-64 and 65-84 years, respectively; in women, the figures were 0.79 (0.79-0.79) and 0.95 (0.94-0.95), respectively. While observed increases in adherence with longer education in unadjusted analyses were attenuated after adjustment for income among men, the potential inverse relationship between length of education and adherence was enhanced among women. Applying discontinuation as outcome, analogous differences were demonstrated. CONCLUSION: Adherence to preventive statin therapy in Denmark decreases with decreasing income-especially in men aged 40-64 years. 23232866 Integration of pre-aligned liquid metal electrodes for neural stimulation within a user-friendly microfluidic platform. Electrical stimulation of nervous tissue is used clinically for the treatment of multiple neurological disorders and experimentally for basic research. With the increase of optical probes to record neuronal activity, simple and user-friendly methods are desired to stimulate neurons and their subcellular compartments for biological experimentation. Here we describe the novel integration of liquid metal electrodes with microfluidic culture platforms to accomplish this goal. We integrated electrode and cell channels into a single poly(dimethylsiloxane) (PDMS) chip, eliminating entirely the need to align electrodes with microchannels. We designed the electrode channels such that the metal can be injected by hand and when the device is non-covalently bound to glass. We demonstrated the biocompatibility of the electrodes for long-term cultures (12 days) using hippocampal neurons. We demonstrated the use of these electrodes to depolarize neurons and recorded neuronal activity using the calcium indicator dye, Fluo-4. We established optimal stimulation parameters that induce neuronal spiking without inducing damage. We showed that the liquid metal electrode evoked larger calcium responses in somata than bath electrodes using the same stimulus parameters. Lastly we demonstrated the use of these liquid metal electrodes to target and depolarize axons. In summary, the integration of liquid metal electrodes with neuronal culture platforms provides a user-friendly and targeted method to stimulate neurons and their subcellular compartments, thus providing a novel tool for future biological investigations. 23335561 Shrinking hydrogel-DNA spots generates 3D microdots arrays. This report describes a straightforward approach for the achievement of sub-100 micrometers size hydrogel dots supporting DNA immobilization. Hydrogel-DNA spots are arrayed and UV-crosslinked on PolyShrink, an innovative polymer material having the remarkable property of isotropically shrinking under high temperature. Curing the microarray enables then spot miniaturization, resulting in 6 µm thick and 60 µm wide hydrogel dots in which oligonucleotides are immobilized in a 3D hydrophilic environment. The probe immobilization within the hydrogel network and its capacity to detect targets specifically and quantitatively is demonstrated using chemiluminescent as well as colorimetric detection techniques. The hydrogel material improves probe accessibility within the spot, leading to an enhanced sensitivity. 23411250 A critical study of use of the Fe(II)/3-hydroxy-4-nitroso-2,7-naphthalenedisulfonic acid complexes in the quantification of polyphenols in medicinal plants. A critical study of the use of the Fe(III)/3-hydroxy-4-nitroso-2,7-naphthalenedisulfonic acid (NRS) complexes on the quantification of the polyphenols content in aqueous extracts of plants, expressed as pyrogallic acid, [PA], is presented. The reaction used is based on the reduction of Fe(III) to Fe(II) by [PA] in the presence of NRS in a buffered medium (Tris; pH 8.0) with formation of Fe(II)/NRS complexes. A calibration curve of absorbance (at 730 nm) vs. [PA] is linear (r=0.998; n=7) from 1.0 to 7.0 μmolL(-1) [PA]. LD and RSD were 0.5 μmolL(-1) and 2.5% (6.0 μmolL(-1) [PA], n=10), respectively. The influence of pH, type of buffer solution and interfering species possibly present in the samples were evaluated. Aqueous extracts of twelve medicinal plants used in the Brazilian folk medicine were analysed by using both Fe(III)/NRS complexes and the Folin-Ciocalteu reagent. 23164711 On scaffold hopping: challenges in the discovery of sulfated small molecules as mimetics of glycosaminoglycans. The design of sulfated, small, nonsaccharide molecules as modulators of proteins is still in its infancy as standard drug discovery tools such as library of diverse sulfated molecules and in silico docking and scoring protocol have not been firmly established. Databases, such as ZINC, contain too few sulfate-containing nonsaccharide molecules, which severely limits the identification of new hits. Lack of a generally applicable protocol for scaffold hopping limits the development of sulfated small molecules as synthetic mimetics of the highly sulfated glycosaminoglycans. We explored a sequential ligand-based (LBVS) and structure-based virtual screening (SBVS) approach starting from our initial discovery of monosulfated benzofurans to discover alternative scaffolds as allosteric modulators of thrombin, a key coagulation enzyme. Screening the ZINC database containing nearly 1 million nonsulfated small molecules using a pharmacophore developed from the parent sulfated benzofurans followed by a genetic algorithm-based dual-filter docking and scoring screening identified a group of 10 promising hits, of which three top-scoring hits were synthesized. Each was found to selectively inhibit human alpha-thrombin suggesting the possibility of this approach for scaffold hopping. Michaelis-Menten kinetics showed allosteric inhibition mechanism for the best molecule and human plasma studies confirmed good anticoagulation potential as expected. Our simple sequential LBVS and SBVS approach is likely to be useful as a general strategy for identification of sulfated small molecules hits as modulators of glycosaminoglycan-protein interactions. 23517145 Anti-inflammatory Lanostanoids and Lactone Derivatives from Antrodia camphorata. Four new lanostanoids, ethyl lucidenate A (1), ethyl lucidenate F (2), 15-O-acetylganolucidate A (3), and 3,11,15,23-tetraoxo-27ξ-lanosta-8,16-dien-26-oic acid (4), and two new lactone derivatives, 5-hydroxy-5-(methoxymethyl)-4-methylfuran-2(5H)-one (5) and 3-(4-methoxy-2-oxo-2H-pyran-6-yl)propanoic acid (6), together with four known compounds, 11α-hydroxy-3,7-dioxolanost-8,24(E)-dien-26- oic acid (7), 3,7,11-trioxo-5α-lanosta-8,24(E)-dien-26-oic acid (8), methyl 3,7,11,12,15,23-hexaoxo-5α-lanost-8-en-26-oate (9), and ethyl 3,7,11,12,15,23-hexaoxo-5α-lanost-8-en-26-oate (10), were characterized from Antrodia camphorata. The structures of these new compounds were determined by analysis of their spectroscopic data, including 1D and 2D NMR experiments. Ten components were evaluated for anti-inflammatory activity by examining their effect on LPS-iNOS-dependent NO production in murine macrophage (RAW 264.7) cells. Among them, compounds 1, 3, 7, 8, 9, and 10 significantly suppressed the NO concentration in LPS-treated RAW 264.7 cells with IC50 values ≤ 10 μM. 23541950 Genome-wide association studies on serum sex steroid levels. Even though the levels of circulating sex steroid hormones are to a large extent heritable, their genetic determinants are largely unknown. With the advent of genome-wide association studies (GWAS), much progress has been made and several genetic loci have been identified to be associated with serum levels of dehydroepiandrosterone sulfate, testosterone and sex hormone-binding globulin. The variants identified so far only explain a small amount of the overall heritability, but may help to elucidate the role of sex steroid hormones in common disorders such as hypogonadism, type 2 diabetes and hormone-sensitive cancers. This review provides an overview of the current state of knowledge of the genetic determinants of sex steroid hormones, with a focus on recent GWAS and brief directions for elucidating the remaining heritability. 23262390 Manganese exposure induces α-synuclein aggregation in the frontal cortex of non-human primates. Aggregation of α-synuclein (α-syn) in the brain is a defining pathological feature of neurodegenerative disorders classified as synucleinopathies. They include Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Occupational and environmental exposure to manganese (Mn) is associated with a neurological syndrome consisting of psychiatric symptoms, cognitive impairment and parkinsonism. In this study, we examined α-syn immunoreactivity in the frontal cortex of Cynomolgus macaques as part of a multidisciplinary assessment of the neurological effects produced by exposure to moderate levels of Mn. We found increased α-syn-positive cells in the gray matter of Mn-exposed animals, typically observed in pyramidal and medium-sized neurons in deep cortical layers. Some of these neurons displayed loss of Nissl staining with α-syn-positive spherical aggregates. In the white matter we also observed α-syn-positive glial cells and in some cases α-syn-positive neurites. These findings suggest that Mn exposure promotes α-syn aggregation in neuronal and glial cells that may ultimately lead to degeneration in the frontal cortex gray and white matter. To our knowledge, this is the first report of Mn-induced neuronal and glial cell α-syn accumulation and aggregation in the frontal cortex of non-human primates. 23527317 Exploring the effect of N-substitution in nor-lobelane on the interaction with VMAT2: discovery of a potential clinical candidate for treatment of methamphetamine abuse. A series of N-substituted lobelane analogues was synthesized and evaluated for their [(3)H]dihydrotetrabenazine binding affinity at the vesicular monoamine transporter and for their inhibition of vesicular [(3)H]dopamine uptake. Compound 19a, which contains an N-1,2(R)-dihydroxypropyl group, had been identified as a potential clinical candidate for the treatment of methamphetamine abuse. 23141425 EGCG inhibits CTGF expression via blocking NF-κB activation in cardiac fibroblast. Connective tissue growth factor (CTGF) has been reported to play an important role in tissue fibrosis and presents a promising therapeutic target for fibrotic diseases. In heart, inappropriate increase in level of CTGF promotes fibroblast proliferation and extracellular matrix (ECM) accumulation, thereby exacerbating cardiac hypertrophy and subsequent failure. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac fibrosis. However, the molecular mechanism by which EGCG exerts its anti-fibrotic effects has not been well investigated. In this study, we found that EGCG could significantly reduce collagen synthesis, fibronectin (FN) expression and cell proliferation in rat cardiac fibroblasts stimulated with angiotensinII (AngII). It also ameliorated cardiac fibrosis in rats submitted to abdominal aortic constriction (AAC). Moreover, EGCG attenuated the excessive expression of CTGF induced by AAC or AngII, and reduced the nuclear translocation of NF-κB p65 subunit and degradation of IκB-α. Subsequently, we demonstrated that in cardiac fibroblasts NF-κB inhibition could suppress AngII-induced CTGF expression. Taken together, these findings provide the first evidence that the effect of EGCG against cardiac fibrosis may be attributed to its inhibition on NF-κB activation and subsequent CTGF overexpression, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy. 23506052 Detection of Nanosized Ordered Domains in DOPC/DPPC and DOPC/Ch Binary Lipid Mixture Systems of Large Unilamellar Vesicles Using a TEMPO Quenching Method. Nanosized ordered domains formed in 1,2-dioleoyl-sn-glycero-3-phosphocholine/1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DOPC/DPPC) and DOPC/cholesterol (Ch) liposomes were characterized using a newly developed (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) quenching method. The membrane fluidity of the DOPC/DPPC liposomes, evaluated by the use of 1,6-diphenyl-1,3,5-hexatriene (DPH), increased significantly above their phase-transition temperature. The fluorescence spectra of 6-lauroyl-2-dimethylamino naphthalene (Laurdan) indicated the formation of an immiscible ordered phase in the DOPC/DPPC (50/50) liposomal membrane at 30 °C. The analysis of the membrane polarity indicated that the surface of the liquid-disordered phase was hydrated whereas that of the ordered phase was dehydrated. DOPC/DPPC and DOPC/Ch (70/30) liposomes exhibited heterogeneous membranes, indicating that nanosized ordered domains formed on the surface of the DOPC/DPPC liposomes. The size of these nanosized ordered domains was estimated using the TEMPO quenching method. Because TEMPO can quench DPH distributed in the disordered phases, the remaining fluorescence from DPH is proportional to the size of the ordered domain. The domain sizes calculated for DOPC/DPPC (50/50), DOPC/DPPC (25/75), DOPC/Ch (70/30), and DOPC/DPPC/Ch (40/40/20) were 13.9, 36.2, 13.2, and 35.5 Å, respectively. 23350797 7-Chloro-4-quinolinyl Hydrazones: A Promising and Potent Class of Antileishmanial Compounds. In this work, we report the antileishmanial evaluation of twenty 7-chloro-4-quinolinyl hydrazone derivatives (1-20). Firstly, the compounds were tested against promastigotes of four different Leishmania species. After that, all derivatives were assayed against L. braziliensis amastigotes and murine macrophages. Furthermore, it was investigated whether the antiamastigote L. braziliensis effect of the compounds could be associated with nitric oxide production. Compounds 6 and 7 showed a strong leishmanicidal activity against intracellular parasite with IC50 in nanogram levels (30 and 20 ng/mL, respectively). Appreciable activity of three compounds tested can be considered an important finding for the rational design of new leads for antileishmanial compounds. 23291435 Thyroid disturbance related to chronic hepatitis C infection: role of CXCL10. Association between autoimmune thyroid diseases (AITD) and hepatitis C is controversial, but may occur or worsen during alpha-interferon treatment. The mechanism responsible for autoimmune diseases in infected patients has not been fully elucidated. This study aims to evaluate the frequency of AITD in chronic hepatitis C and the association of CXCL10 and AITD. One hundred and three patients with chronic hepatitis C and 96 controls were prospectively selected to clinical, hormonal, thyroid autoimmunity and ultrasound exams, besides thyroxine-binding globulin (TBG) and CXCL10 measurements and hepatic biopsies. The frequency of AITD among infected subjects was similar to controls. TT3 and TT4 distributions were right shifted, as was TBG, which correlated to both of them. Thyroid heterogeneity and hypoechogenicity were associated with AITD. Increased vascularization was more prevalent in chronic hepatitis C.CXCL10 was higher in infected patients (p=0.007) but was not related to thyroid dysfunction. Increase in CXCL10 levels were consistent with hepatic necroinflammatory activity (p=0.011). In summary, no association was found between chronic hepatitis C and AITD. Infected subjects had higher TT3 and TT4 which were correlated to TBG. Increased CXCL10 was not associated to thyroid dysfunction in HCV-infected population. 23289412 Novel 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives: a patent review (2008 - 2011). INTRODUCTION: The triazoles represent a class of five-membered heterocyclic compounds of great importance for the preparation of new drugs with diverse biological activities because they may present several structural variations with the same numbers of carbon and nitrogen atoms. Due to the success of various triazoles that entered the pharmaceutical market and are still being used in medicines, many companies and research groups have shown interest in developing new methods of synthesis and biological evaluation of potential uses for these compounds. In this review, the authors explored aspects of patents for the 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole families, including prototypes being considered in clinical studies between 2008 and 2011. AREAS COVERED: The triazoles have been studied for over a century as an important class of heterocyclic compounds and still attract considerable attention due to their broad range of biological activities. More recently, there has been considerable interest in the development of novel triazoles with anti-inflammatory, antiplatelet, antimicrobial, antimycobacterial, antitumoral and antiviral properties and activity against several neglected diseases. This review emphasizes recent perspective and advances in the therapeutically active 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivative patents between 2008 and 2011, covering the development of new chemical entities and new pharmaceuticals. Many studies have focused on these compounds as target structures and evaluated them in several biological targets. EXPERT OPINION: The preparation of 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives brings to light several issues. There is a need to find new, more efficient preparations for these triazoles that take into consideration current issues in green chemistry, energy saving and sustainability. New diseases are discovered and new viruses and bacteria continue to challenge mankind, so it is imperative to find new prototypes for these new diseases. Of great urgency is finding prototypes against bacteria that continue to increase resistance and for neglected diseases that affect a large part of humanity, especially the poor and vulnerable. 23287700 Cannabinoid discrimination and antagonism by CB(1) neutral and inverse agonist antagonists. Cannabinoid receptor 1 (CB(1)) inverse agonists (e.g., rimonabant) have been reported to produce adverse effects including nausea, emesis, and anhedonia that limit their clinical applications. Recent laboratory studies suggest that the effects of CB(1) neutral antagonists differ from those of such inverse agonists, raising the possibility of improved clinical utility. However, little is known regarding the antagonist properties of neutral antagonists. In the present studies, the CB(1) inverse agonist SR141716A (rimonabant) and the CB(1) neutral antagonist AM4113 were compared for their ability to modify CB(1) receptor-mediated discriminative stimulus effects in nonhuman primates trained to discriminate the novel CB(1) full agonist AM4054. Results indicate that AM4054 serves as an effective CB(1) discriminative stimulus, with an onset and time course of action comparable with that of the CB(1) agonist Δ(9)-tetrahydrocannabinol, and that the inverse agonist rimonabant and the neutral antagonist AM4113 produce dose-related rightward shifts in the AM4054 dose-effect curve, indicating that both drugs surmountably antagonize the discriminative stimulus effects of AM4054. Schild analyses further show that rimonabant and AM4113 produce highly similar antagonist effects, as evident in comparable pA(2) values (6.9). Taken together with previous studies, the present data suggest that the improved safety profile suggested for CB(1) neutral antagonists over inverse agonists is not accompanied by a loss of antagonist action at CB(1) receptors. 23265462 Transepithelial transport of 6-O-caffeoylsophorose across Caco-2 cell monolayers. The aim of this study was to clarify the transport behaviour and mechanism of caffeic acid analogue bearing a sugar-moiety, 6-O-caffeoylsophorose (CS), in Caco-2 cells. The absorption of CS was investigated by its transport across Caco-2 cell monolayers using a high-performance liquid chromatography-time-of-flight-mass spectrometry (LC-TOF-MS). The permeation of CS was concentration-dependent and reached the plateau at >6 mM. The apparent permeability (P(app)) of CS in the apical-to-basolateral direction was 5.4×10(-7) cm/s, while in the reversed direction the P(app) value was significantly reduced (1.9×10(-7) cm/s). CS transport was competitively inhibited by phloretin, an inhibitor of monocarboxylic acid transporter (MCT). Benzoic acid, an MCT substrate, also reduced CS transport. A less significant change of CS transport was observed across Caco-2 cell monolayers pretreated with quercetin, a suppressor of tight-junction. These findings strongly indicate that CS, a caffeic acid analogue bearing sophorose moiety, can be transported across Caco-2 cell monolayers via the MCT pathway. 23318645 Papillary thyroid carcinoma arising from a thyroglossal duct cyst: a single institution experience. Thyroid cancers arising from a thyroglossal duct cyst (TGDC) are rarely reported. No clear consensus exists regarding optimal management. In this light, TGDC carcinomas recently treated at Asan Medical Center, as well as previously reported cases in the literature, were reviewed. There were ten patients who were diagnosed with TGDC carcinoma at our institution. All patients underwent pre-operative fine-needle aspiration biopsy (FNAB). Nine patients were suspected of having papillary carcinoma following cytology. The Sistrunk operation (SO) was performed in four patients, SO with total thyroidectomy (SO/TT) was performed in three patients, and SO/TT with neck dissection was performed in three patients. Six patients who received total thyroidectomy underwent radioactive iodine (RAI) therapy and T4 suppression. With a median follow-up period of 28.5 months, two patients showed recurrence and one of them died of the disease. We analyzed 163 cases from 1990 to 2012 with three or more cases TGDC carcinoma, including the present study. Among 48 patients who underwent FNAB, 75% had papillary thyroid carcinoma (PTC). SO, SO/TT, or SO/TT with neck dissection was performed in 27%, 41%, and 32% of patients, respectively. Among 119 patients who received total thyroidectomy, 36% had concomitant PTC in the thyroid. Among 52 patients who received neck dissection, 69% had cervical nodal involvement. The results of our review suggest that when TGDC carcinoma is suspected, ultrasonography and, if necessary, FNAB should be performed. If these tests reveal a suspected lesion in the thyroid or lymph node, SO/TT and lymph node dissection should be performed. 23168915 Nanostructural transformations during the reduction of hollow and porous nickel oxide nanoparticles. Size-dependent nanostructural transformations occurring during the H(2)-mediated reduction of hollow and porous NiO nanoparticles were investigated for controlled nanoparticle sizes of ~10 to 100 nm. Transmission electron microscopy reveals that the location and number of reduction sites strongly depend on the nanoparticle size and structure. 23194517 Oxidative changes during ice storage of rainbow trout (Oncorhynchus mykiss) fed different ratios of marine and vegetable feed ingredients. Recently fish meal and oil have increasingly been replaced with proteins and oils from vegetable sources in the diets of farmed salmonids, but the consequences for the oxidative stability of the resulting fish products have not been investigated. The aim of the present study was to evaluate the influence of feeding regime on composition of rainbow trout fillets, as well as on lipid and protein oxidation during storage on ice. Rainbow trout were fed six different diets, which differed in their levels of marine oil and proteins vs. vegetable oil and protein. Fish fillets were characterised by measurement of fatty acid and amino acid composition, primary and secondary lipid oxidation products, astaxanthin and tocopherol content. Protein oxidation was assessed by measuring protein carbonyl content, oxidised amino acids, sulfhydryl groups and immuno-blotting against carbonyl groups. Feeding regimes significantly influenced fatty acid composition. Replacement of fish oil with vegetable oil reduced formation of primary oxidation products, but the effect on secondary oxidation products differed between different types of volatiles. The differences in protein and amino acid composition were not significant, and there were no clear effects of diets on protein oxidation, but data indicated that compounds present in the marine ingredients might have had an effect on protein oxidation. 22949511 Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen. Although biallelic mutations in non-collagen genes account for <10% of individuals with osteogenesis imperfecta, the characterization of these genes has identified new pathways and potential interventions that could benefit even those with mutations in type I collagen genes. We identified mutations in FKBP10, which encodes the 65 kDa prolyl cis-trans isomerase, FKBP65, in 38 members of 21 families with OI. These include 10 families from the Samoan Islands who share a founder mutation. Of the mutations, three are missense; the remainder either introduce premature termination codons or create frameshifts both of which result in mRNA instability. In four families missense mutations result in loss of most of the protein. The clinical effects of these mutations are short stature, a high incidence of joint contractures at birth and progressive scoliosis and fractures, but there is remarkable variability in phenotype even within families. The loss of the activity of FKBP65 has several effects: type I procollagen secretion is slightly delayed, the stabilization of the intact trimer is incomplete and there is diminished hydroxylation of the telopeptide lysyl residues involved in intermolecular cross-link formation in bone. The phenotype overlaps with that seen with mutations in PLOD2 (Bruck syndrome II), which encodes LH2, the enzyme that hydroxylates the telopeptide lysyl residues. These findings define a set of genes, FKBP10, PLOD2 and SERPINH1, that act during procollagen maturation to contribute to molecular stability and post-translational modification of type I procollagen, without which bone mass and quality are abnormal and fractures and contractures result. 23578763 Personalized medicine: predicting responses to therapy in patients with RA. Personalized medicine where each patient receives the right drug and the right intensity of drug treatment for as long as needed or safe is the goal of medicine. The identification of predictors of response is the first step toward this. In rheumatoid arthritis (RA), several prediction matrices were designed to predict the risk of rapid radiological progression (RRP) in the first year of treatment, on either disease modifying anti-rheumatic drug (DMARD) monotherapy or combination therapy with prednisone or a biological agent. Both clinical markers and biomarkers of response to either anti-TNF or different mode of action biological agents, and of successful discontinuation of these agents once the treatment goal has been achieved, have been identified in different studies. Most of these markers need validation in other cohorts. Research into combining clinical markers and biomarkers of response could lead to identification of risk profiles resulting in a new step toward personalized medicine in RA. 23619567 Zebrafish as a model organism to study host-pathogen interactions. Zebrafish have been extensively used in biomedical research as a model to study vertebrate development but it is only recently that it has also been adopted into varied fields such as immunology and host-pathogen interactions. Zebrafish have a rapid life cycle, small size and the adults exhibit no territorial behavior in relatively dense cages. Under standard conditions each female lays an average of a hundred eggs per clutch, providing a large number of larvae per week. Their transparency during early life stages allows real time visualization of the different organs, which makes them especially suitable for the study of bacterial host-pathogen interactions. Traditionally, these studies have been technically challenging in higher organisms, given the loss of control over the bacteria once the pathogen infects its host. Here we describe an emerging approach to monitor Salmonella typhimurium infection progression using in vivo fluorescence upon parenteral infection. We have engineered Salmonella with the Cascade expression system; an efficient method to voluntarily activate bacterial heterologous gene expression at any point during infection once inside the Zebrafish macrophages, using a non-toxic inducer. 23494232 Acute ketamine induces hippocampal synaptic depression and spatial memory impairment through dopamine D1/D5 receptors. RATIONALE: Subanesthetic doses of ketamine have been reported to induce psychotic states that may mimic positive and negative symptoms as well as cognitive and memory deficits similar to those observed in schizophrenia. The cognitive and memory deficits are persistent, and their underlying cellular mechanisms remain unclear. OBJECTIVES: We sought to investigate the roles of dopamine D1/D5 receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in hippocampal synaptic transmission and spatial memory impairment induced by ketamine. METHODS: We examined the effects of subanesthetic ketamine on hippocampal synaptic transmission in freely moving rats. Spatial memory was tested with the Morris water maze. Pretreatment with the D1/D5 receptors antagonist SCH23390 or the AMPA receptors endocytosis interfering peptide Tat-GluR23Y was conducted to examine their capacities to reverse ketamine-induced electrophysiological and behavioral alterations. A series of behavioral observations, including locomotion, prepulse inhibition, and social interaction, were also conducted after ketamine treatment. RESULTS: Ketamine induced synaptic depression lasting at least 4 h at hippocampal Schaffer collateral-CA1 synapses in freely moving rats and long-term spatial memory impairment. Both the effects were blocked by either SCH23390 or Tat-GluR23Y. Ketamine also elicited transient behavioral changes lasting less than 90 min, such as hyperlocomotion and prepulse inhibition deficits. These changes were ameliorated by SCH23390 but not by Tat-GluR23Y. Rats treated with ketamine showed social withdrawal that was also attenuated by either SCH23390 or Tat-GluR23Y. CONCLUSIONS: Our results indicate that hippocampal synaptic depression is involved in ketamine-induced memory impairment, and this is modulated by D1/D5 receptors activation and AMPA receptors endocytosis. 23122160 Feasibility and application of an HPLC/UVD to determine dinotefuran and its shorter wavelength metabolites residues in melon with tandem mass confirmation. A new analytical method was developed for dinotefuran and its metabolites, MNG, UF, and DN, in melon using high-performance liquid chromatography (HPLC) coupled with an ultraviolet detector (UVD). Due to shorter wavelength, lower sensitivity to UV detection, and high water miscibility of some metabolites, QuEChERs acetate-buffered version was modified for extraction and purification. Mobile phases with different ion pairing or ionisation agents were tested in different reverse phase columns, and ammonium bicarbonate buffer was found as the best choice to increase the sensitivity of target analytes to the UV detector. After failure of dispersive SPE clean-up with primary secondary amine, different solid phase extraction cartridges (SPE) were used to check the protecting capability of analytes against matrix interference. Finally, samples were extracted with a simple and rapid method using acetonitrile and salts, and purified through C(18)SPE. The method was validated at two spiking levels (three replicates for each) in the matrix. Good recoveries were observed for all of the analytes and ranged between 70.6% and 93.5%, with relative standard deviations of less than 10%. Calibration curves were linear over the calibration ranges for all the analytes with r(2)≥ 0.998. Limits of detection ranged from 0.02 to 0.05 mg kg(-1), whereas limits of quantitation ranged from 0.06 to 0.16 mg kg(-1) for dinotefuran and its metabolites. The method was successfully applied to real samples, where dinotefuran and UF residues were found in the field-incurred melon samples. Residues were confirmed via LC-tandem mass spectrometry (LC-MS/MS) in positive-ion electrospray ionisation (ESI(+)) mode. 23485441 Activity-based assay for human mono-ADP-ribosyltransferases ARTD7/PARP15 and ARTD10/PARP10 aimed at screening and profiling inhibitors. Poly(ADP-ribose) polymerases (PARPs) or diphtheria toxin like ADP-ribosyl transferases (ARTDs) are enzymes that catalyze the covalent modification of proteins by attachment of ADP-ribose units to the target amino acid residues or to the growing chain of ADP-ribose. A subclass of the ARTD superfamily consists of mono-ADP-ribosyl transferases that are thought to modify themselves and other substrate proteins by covalently adding only a single ADP-ribose moiety to the target. Many of the ARTD enzymes are either established or potential drug targets and a functional activity assay for them will be a valuable tool to identify selective inhibitors for each enzyme. Existing assays are not directly applicable for screening of inhibitors due to the different nature of the reaction and different target molecules. We modified and applied a fluorescence-based assay previously described for PARP1/ARTD1 and tankyrase/ARTD5 for screening of PARP10/ARTD10 and PARP15/ARTD7 inhibitors. The assay measures the amount of NAD(+) present after chemically converting it to a fluorescent analog. We demonstrate that by using an excess of a recombinant acceptor protein the performance of the activity-based assay is excellent for screening of compound libraries. The assay is homogenous and cost effective, making it possible to test relatively large compound libraries. This method can be used to screen inhibitors of mono-ARTDs and profile inhibitors of the enzyme class. The assay was optimized for ARTD10 and ARTD7, but it can be directly applied to other mono-ARTDs of the ARTD superfamily. Profiling of known ARTD inhibitors against ARTD10 and ARTD7 in a validatory screening identified the best inhibitors with submicromolar potencies. Only few of the tested ARTD inhibitors were potent, implicating that there is a need to screen new compound scaffolds. This is needed to create small molecules that could serve as biological probes and potential starting points for drug discovery projects against mono-ARTDs. 23336337 Enhancing macrocyclic diterpenes as multidrug-resistance reversers: structure-activity studies on jolkinol D derivatives. The phytochemical study of Euphorbia piscatoria yielded jolkinol D (1) in a large amount, whose derivatization gave rise to 12 ester derivatives (2-13) and hydrolysis to compound 14. The in vitro modulation of P-gp of compounds 1-14 was evaluated through a combination of transport and chemosensitivity assays, using the L5178 mouse T lymphoma cell line transfected with the human MDR1 gene. Apart from jolkinol D, all derivatives (2-14) showed potential as MDR reversal agents. In this small library of novel bioactive macrocyclic lathyrane diterpene derivatives, designed to evaluate structure-activity relationships essential in overcoming multidrug resistance (MDR), some correlations between MDR reversal and molecular weight, accessible solvent areas, and octanol/water partition coefficient were identified that can contribute to the development of new selective P-gp reversal agents. 23623743 A comparative study of protein carbonylation and mitochondrial dysfunction using the neurotoxicants 1,3-dinitrobenzene, 3-nitropropionic acid, and 3-chloropropanediol. This comparative evaluation of neurotoxicants previously identified as models of chemical-induced mitochondrial dysfunction and energy deprivation demonstrated that subtoxic concentrations of 1,3-dinitrobenzene (1,3-DNB), 3-nitropropionic acid (3-NPA), and 3-chloropropanediol (3-CPD) each led to concentration-dependent loss of the mitochondrial membrane potential (ΔΨm) associated with similar patterns of protein carbonylation. Subtoxic concentrations of each neurotoxicant were determined by measuring DI TNC1 cell viability using the MTS cell proliferation assay. Although exposure 1μM, 10μM, and 100μM concentrations of each toxicant did not result in loss of cell viability after 48h, exposure to each toxicant at these concentrations led to concentration-dependent loss of tetramethyl rhodamine methyl ester (TMRM) fluorescence over the same exposure period. Preincubation with the antioxidant, deferoxamine, was effective in preventing loss of TMRM flurorescence. Through the combined use of two-dimensional polyacrylamide gel electrophoresis (2D PAGE) and Oxyblot analysis, this study demonstrated that exposure to each toxicant resulted in the formation of distinctly similar patterns of protein carbonylation comprised of specific proteins identified with tandem MS/MS. Our results provide insight as to how exposure to different neurotoxicants that enhance oxidative stress may, in fact, lead to mitochondrial injury and subsequent toxicity through selective, yet shared, pathways of protein modification by oxidative carbonylation. 23561075 Proanthocyanidin profile of cowpea (Vigna unguiculata) reveals catechin-O-glucoside as the dominant compound. Proanthocyanidin (PA) profile and content can have important nutritional and health implications on plant foods. Six diverse cowpea phenotypes (black, red, green, white, light-brown and golden-brown) were investigated for PA composition using normal-phase HPLC and reversed-phase UPLC-TQD-MS. Catechin and (epi)afzelechin were the major flavan-3-ol units. Unusual composition was observed in all cowpea phenotypes with significant degrees of glycosylation in the monomers and dimers. The PA content of cowpea (dry basis) ranged between 2.2 and 6.3mg/g. Monomeric flavan-3-ols were the largest group of PA (36-69%) in cowpea, with catechin-7-O-glucoside accounting for most (about 88%) of the monomers. The oligomers with degree of polymerization (DP) 2-4 ranged from 0.41 to 1.3mg/g (15-20%), whereas DP>10 polymers accounted for only 13.5% of PA. Future studies that highlight the impact of the unusual cowpea PA profile on nutritional and bioactive properties of this important legume are warranted. 23265452 The determination of phenolic profiles of Serbian unifloral honeys using ultra-high-performance liquid chromatography/high resolution accurate mass spectrometry. Polyphenolic profiles of 44 unifloral Serbian honeys were analyzed using ultra-high-performance liquid chromatography (UHPLC) coupled with hybrid mass spectrometer which combines the Linear Trap Quadrupole (LTQ) and OrbiTrap mass analyzer. Rapid UHPLC method was developed in combination with a high sensitivity accurate mass scan and a simultaneous data dependent scan. The honey samples were of different botanical origin: acacia (Robinia pseudoacacia), sunflower (Helianthus annuus), linden (Tilia cordata), basil (Ocimum basilicum), buckwheat (Fagopyrum esculentum), oilseed rape (Brassica napus), and goldenrod (Solidago virgaurea). The presence of 43 compounds, mainly flavonoids, was proven in all honey samples by their characteristic mass spectra and fragmentation pattern. Relatively high amounts of chrysin, pinocembrin and galangin were identified in all honey extracts. p-Coumaric acid was not detected in basil, buckwheat and goldenrod honey extracts. A larger amount of gallic acid (max value 1.45 mg/kg) was found in the sunflower honey, while a larger amount of apigenin (0.97 mg/kg) was determined in the buckwheat honey in comparison with other honeys. The samples were classified according to the botanical origin using pattern recognition technique, Principal Component Analysis (PCA). The LTQ OrbiTrap technique was proven to be reliable for the unambiguous detection of phenolic acids, their derivatives, and flavonoid aglycones based on their molecular masses and fragmentation pattern. 23644884 HDAC6 and Ovarian Cancer. The special class IIb histone deacetylase, HDAC6, plays a prominent role in many cellular processes related to cancer, including oncogenesis, the cell stress response, motility, and myriad signaling pathways. Many of the lessons learned from other cancers can be applied to ovarian cancer as well. HDAC6 interacts with diverse proteins such as HSP90, cortactin, tubulin, dynein, p300, Bax, and GRK2 in both the nucleus and cytoplasm to carry out these cancerous functions. Not all pro-cancer interactions of HDAC6 involve deacetylation. The idea of using HDAC6 as a target for cancer treatment continues to expand in recent years, and more potent and specific HDAC6 inhibitors are required to effectively down-regulate the tumor-prone cell signaling pathways responsible for ovarian cancer. 23435913 Simple and sensitive liquid chromatography-tandem mass spectrometry methods for quantification of tadalafil in rat plasma: application to pharmacokinetic study in rats. A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated in rat plasma for quantification of tadalafil, a novel therapeutic agent for erectile dysfunction. Tadalafil and acebutolol (internal standard) were extracted by liquid-liquid extraction with tert-butyl methyl ether. The chromatographic separation was performed on a reverse phase C18 column with a mobile phase consisting of 0.1 % formic acid and acetonitrile (45:55, v/v) at a flow rate of 0.3 mL/min. The protonated analyte was quantitated by multiple reaction monitoring with a Waters Quattro micro™ API mass spectrometer. The calibration curve was linear over a concentration range of 2-2000 ng/mL, and the lower limit of quantification was 2 ng/mL with a precision (CV %) of 10.9 %. Acceptable intra-day and inter-day precision and accuracy were obtained at 3 concentration levels (3, 200, and 1500 ng/mL). Tadalafil was found to be stable in a battery of studies, including bench top, freeze-thaw, and autosampler conditions. The validated method was successfully used to determine tadalafil concentration in rat plasma samples after oral administration at a dose of 1 mg/kg. 23530011 Metabolic Effects of Chronic Cannabis Smoking. OBJECTIVEWe examined if chronic cannabis smoking is associated with hepatic steatosis, insulin resistance, reduced β-cell function, or dyslipidemia in healthy individuals.RESEARCH DESIGN AND METHODSIn a cross-sectional, case-control study, we studied cannabis smokers (n = 30; women, 12; men, 18; 27 ± 8 years) and control subjects (n = 30) matched for age, sex, ethnicity, and BMI (27 ± 6). Abdominal fat depots and intrahepatic fat content were quantified by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Insulin-sensitivity indices and various aspects of β-cell function were derived from oral glucose tolerance tests (OGTT).RESULTSSelf-reported cannabis use was: 9.5 (2-38) years; joints/day: 6 (3-30) [median (range)]. Carbohydrate intake and percent calories from carbohydrates, but not total energy intake, were significantly higher in cannabis smokers. There were no group differences in percent total body fat, or hepatic fat, but cannabis smokers had a higher percent abdominal visceral fat (18 ± 9 vs. 12 ± 5%; P = 0.004). Cannabis smokers had lower plasma HDL cholesterol (49 ± 14 vs. 55 ± 13 mg/dL; P = 0.02), but fasting levels of glucose, insulin, total cholesterol, LDL cholesterol, triglycerides, or free fatty acids (FFA) were not different. Adipocyte insulin resistance index and percent FFA suppression during an OGTT was lower (P < 0.05) in cannabis smokers. However, oral glucose insulin sensitivity index, measures of β-cell function, or incretin concentrations did not differ between the groups.CONCLUSIONSChronic cannabis smoking was associated with visceral adiposity and adipose tissue insulin resistance but not with hepatic steatosis, insulin insensitivity, impaired pancreatic β-cell function, or glucose intolerance. 23499236 Discovery of new potential hits of Plasmodium falciparum enoyl-ACP reductase through ligand- and structure-based drug design approaches. We here report the discovery of novel Plasmodium falciparum enoyl-ACP reductase (PfENR) inhibitors as new antimalarial hits through ligand- and structure-based drug design approaches. We performed 2D and 3D QSAR studies on a set of rhodanine analogues using hologram QSAR (HQSAR), comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. Statistical and satisfactory results were obtained for the best HQSAR (r(2) of 0.968 and qLOO(2) of 0.751), CoMFA (r(2) of 0.955 and qLOO(2) of 0.806) and CoMSIA (r(2) of 0.965 and qLOO(2) of 0.659) models. The information gathered from the QSAR models guided us to design new PfENR inhibitors. Three new hits were predicted with potency in the submicromolar range and presented drug-like properties. 23500547 HDL particle functionality as a primary pharmacological target for HDL-based therapies. Despite all existing pharmaceuticals aiming at effectively reducing LDL cholesterol, the steadily increasing prevalence of coronary heart disease (CHD) worldwide shifted focus on HDL as an alternative therapeutic target for the treatment of CHD. Indeed, based on the results from epidemiological studies, high HDL cholesterol (HDL-C) levels have been traditionally associated to atheroprotection. Therefore, current drug design considers plasma HDL-C levels as a primary pharmacological target for combating CHD. However, this approach does not take into consideration the fact that HDL is a rather heterogeneous mixture of lipoprotein particles with distinct apolipoprotein and lipid composition that dictate their atheroprotective or proatherogenic function. This may explain why simply raising HDL-C levels by pharmacological means has yet to yield the expected atheroprotection in recent clinical trials. In this review we argue that HDL particle functionality rather than HDL-C levels should be the primary target in the rational design of new HDL-based pharmaceuticals aiming at successfully treating CHD. 23256640 Enhancing biocompatibility of D-oligopeptide hydrogels by negative charges. Oligopeptide hydrogels are emerging as useful matrices for cell culture with commercial products on the market, but L-oligopeptides are labile to proteases. An obvious solution is to create D-oligopeptide hydrogels, which lack enzymatic recognition. However, D-oligopeptide matrices do not support cell growth as well as L-oligopeptide matrices. In addition to chiral interactions, many cellular activities are strongly governed by charge-charge interactions. In this work, the effects of chirality and charge on human mesenchymal stem cell (hMSC) behavior were studied using hydrogels assembled from oppositely charged oligopeptides. It was found that negative charges significantly improved hMSC viability and proliferation in D-oligopeptide gels but had little effect on their interactions with L-oligopeptide gels. This result points to the possibility of using charge and other factors to engineer biomaterials whose chirality is distinct from that of natural biomaterials, but whose performance is close to that of natural biomaterials. 23534695 Electrohydrodynamic Bubbling: An Alternative Route to Fabricate Porous Structures of Silk Fibroin Based Materials. Conventional fabrication techniques and structures employed in the design of silk fibroin (SF) based porous materials provide only limited control over pore size and require several processing stages. In this study, it is shown that, by utilizing electrohydrodynamic bubbling, not only can new hollow spherical structures of SF be formed in a single step by means of bubbles, but the resulting bubbles can serve as pore generators when dehydrated. The bubble characteristics can be controlled through simple adjustments to the processing parameters. Bubbles with diameters in the range of 240-1000 μm were fabricated in controlled fashion. FT-IR characterization confirmed that the rate of air infused during processing enhanced β-sheet packing in SF at higher flow rates. Dynamic mechanical analysis also demonstrated a correlation between air flow rate and film tensile strength. Results indicate that electrohydrodynamically generated SF and their composite bubbles can be employed as new tools to generate porous structures in a controlled manner with a range of potential applications in biocoatings and tissue engineering scaffolds. 23434491 Interaction of 17β-estradiol and ketoconazole on endocrine function in goldfish (Carassius auratus). An understanding of the effects of toxic mixtures of endocrine disrupting chemicals (EDCs) on aquatic organisms is challenging as these organisms are exposed to multiple classes of contaminants in their natural habitat. The aim of the present study was to evaluate the interactions of two classes of EDCs, 17β-estradiol (E2) and ketoconazole (KTC), on endocrine function in male goldfish (Carassius auratus), including vitellogenesis, metabolic capability and serum steroid synthesis. Changes in vitellogenin (VTG) concentration, liver 7-ethoxyresorufin-O-deethylase (EROD) activity and circulating serum E2 level were examined. The expression of related genes was also determined using quantitative real-time polymerase chain reaction. Exposure to E2 caused a significant increase in VTG concentrations which corresponded with the gene expression of VTG and estrogen receptor (ER) in males, which were further elevated after combined exposure to E2 and KTC, indicative of a synergetic relationship. Exposure to E2 also resulted in a distinct increase in serum steroid biosynthesis and associated cytochrome P450 (CYP) aromatase expression after 10 days. However, these changes were inhibited by the presence of KTC, which acted as a steroidogenic inhibitor in fish. Moreover, KTC significantly decreased liver EROD activity and increased the related gene expression of CYP1A. However, these KTC-mediated metabolic reactions in goldfish were up-regulated following exposure to KTC in combination with E2. These findings reveal complex interactions on endocrine functions in male goldfish when exposed to multiple contaminations and may provide a better understanding of the effects of toxic mixtures. 23330908 Structure-based design and synthesis of C-1- and C-4-modified analogs of zanamivir as neuraminidase inhibitors. In order to exploit the 430-cavity in the active sites of neuraminidases, 22 zanamivir analogs with C-1 and C-4 modification were synthesized, and their inhibitory activities against both group-1 (H5N1, H1N1) and group-2 neuraminidases (H3N2) were determined. Compound 9f exerts the most potency, with IC(50) value of 0.013, 0.001, and 0.09 μM against H3N2, H5N1, and H1N1, which is similar to that of zanamivir (H3N2 IC(50) = 0.0014 μM, H5N1 IC(50) = 0.012 μM, H1N1 IC(50) = 0.001 μM). Pharmacokinetic studies of compound 9f in rats showed a much longer plasma half-life (t(1/2)) than that of zanamivir following administration (po dose). Molecular modeling provided information about the binding model between the new inhibitors and neuraminidase, with the elongated groups at the C-1-position being projected toward the 430-loop region. This study may represent a novel starting point for the future development of improved antiflu agents. 23416229 Alpha neurotoxins. α-Neurotoxins have been isolated from hydrophid, elapid and, more recently, colubrid snake venoms. Also referred to as postsynaptic neurotoxins or 'curare mimetic' neurotoxins, they play an important role in the capture and/or killing of prey by binding to the nicotinic acetylcholine receptor on the skeletal muscle disrupting neurotransmission. They are also thought to cause respiratory paralysis in envenomed humans. This review will discuss the historical background into the discovery, isolation, structure and mechanism of action of the α-neurotoxins, including targets and cellular outcomes, and then will examine the potential uses of α-neurotoxins as pharmacological tools and/or as drug leads. 22516666 Evaluation of the effects of venlafaxine and pregabalin on the carbon dioxide inhalation models of Generalised Anxiety Disorder and panic. Previous studies have shown that subjective and objective symptoms of anxiety induced by 7.5% CO(2) inhalation can be attenuated by anxiolytics such as lorazepam and, to a lesser extent, paroxetine. Venlafaxine and pregabalin, two other licensed treatments for Generalised Anxiety Disorder, were used to further investigate the 7.5% and 35% CO(2) models of anxiety in healthy volunteers. Fifty-four participants were randomised to receive either placebo, venlafaxine or pregabalin. Study treatments were dosed incrementally over a three week period, to reach daily doses of 150 mg venlafaxine and 200mg pregabalin by the CO(2) challenge test day. Participants inhaled air 7.5% CO(2) for 20 minutes (single-blind presentation), and a non-blinded single vital capacity of 35% CO(2). Subjective ratings were recorded before and after each inhalation. Both 7.5% and 35% CO(2) inhalations produced the expected effects of increased ratings of symptoms of panic and anxiety, with increased blood pressure and heart rate. No significant treatment effects were found, although there were trends towards a reduction in feeling tense and nervous by both drugs compared with placebo during the 7.5% CO(2) challenge, and a reduction in alertness generally in the venlafaxine group compared with the pregabalin group. In contrast with the clear anxiolytic effects of benzodiazepines reported in several previous CO(2) studies, these findings suggest that the anxiogenic effects of CO(2) challenges are not significantly influenced by these serotonergic and GABAergic anxiolytics. This may be due to a lack of sensitivity of the CO(2) challenges in healthy volunteers to these drug types. 23402423 Conducting the temperature-dependent conformational change of macrocyclic compounds to the lattice dilation of quantum dots for achieving an ultrasensitive nanothermometer. We report a ligand decoration strategy to enlarge the lattice dilation of quantum dots (QDs), which greatly enhances the characteristic sensitivity of a QD-based thermometer. Upon a multiple covalent linkage of macrocyclic compounds with QDs, for example, thiolated cyclodextrin (CD) and CdTe, the conformation-related torsional force of CD is conducted to the inner lattice of CdTe under altered temperature. The combination of the lattice expansion/contraction of CdTe and the stress from CD conformation change greatly enhances the shifts of both UV-vis absorption and photoluminescence (PL) spectra, thus improving the temperature sensitivity. As an example, β-CD-decorated CdTe QDs exhibit the 0.28 nm shift of the spectra per degree centigrade (0.28 nm/°C), 2.4-fold higher than those of monothiol-ligand-decorated QDs. 23432004 Gd-based Macromolecules and Nanoparticles as Magnetic Resonance Contrast Agents for Molecular Imaging. As we move towards an era of personalized medicine, molecular imaging contrast agents are likely to see an increasing presence in routine clinical practice. Magnetic resonance (MR) imaging has garnered particular interest as a platform for molecular imaging applications due its ability to monitor anatomical changes concomitant with physiologic and molecular changes. One promising new direction in the development of MR contrast agents involves the labeling and/or loading of nanoparticles with gadolinium (Gd). These nanoplatforms are capable of carrying large payloads of Gd, thus providing the requisite sensitivity to detect molecular signatures within disease pathologies. In this review, we discuss some of the progress that has recently been made in the development of Gd-based macromolecules and nanoparticles and outline some of the physical and chemical properties that will be important to incorporate into the next generation of contrast agents, including high Gd chelate stability, high "relaxivity per particle" and "relaxivity density", and biodegradability. 23232056 Small molecule amides as potent ROR-γ selective modulators. The structure-activity relationship study of a diphenylpropanamide series of ROR-γ selective modulators is reported. Compounds were screened using chimeric receptor Gal4 DNA-binding domain (DBD)-NR ligand binding domain cotransfection assay in a two-step format. Three different regions of the scaffold were modified to assess the effects on repression of ROR-γ transcriptional activity and potency. The lead compound 1 exhibits modest mouse pharmacokinetics and an acceptable in vitro profile which makes it a suitable in vivo probe to interrogate the functions of ROR-γ in animal models of disease. 23455056 Novel oleanolic vinyl boronates: Synthesis and antitumor activity. A series of novel oleanane-type pentacyclic triterpenoids bearing a boronate ester moiety at C3 have been synthesized by palladium-catalyzed cross-coupling of bis(pinacolato)diboron with vinyl triflates, in the presence of base, and these compounds were fully characterized by 1D and 2D NMR techniques. Evaluation of their antiproliferative effects on a panel of hematological-based and solid tumor cell lines identified three active oleanolic vinyl boronates that inhibited the growth of leukemia (Jurkat, K562), Burkitt's lymphoma (Jijoye), cervix (Hela), colon (SW480), and ovary (SKOV-3) cancer cells without concomitant inhibition of non-tumoral human fibroblasts. Their mechanisms of action were investigated on the leukemia Jurkat cell line. The results show that the incorporation of boron in the oleanolic acid core combined with the presence of amide bonds afforded compounds with desirable biological effects such as apoptosis induction and inhibition of proteasomal activity on tumor cells, which makes them potential templates for further development in the anticancer drug setting. 23256643 Magnetostructural correlation for rational design of Mn(II) hybrid-spin complexes. The magnetic properties of a series of manganese(II) diacetylacetonate and dihexafluoroacetylacetonate hybrid-spin complexes with neutral pyridine-based organic radicals were characterized theoretically by DFT calculations. Three stable radicals, in which a radical group is bound in either para or meta position with respect to the pyridine nitrogen atom, were considered. The correct stable structures and multiplets of the complexes were obtained by full geometry optimization starting from an ideal structure. A total of three important geometry descriptors of the complexes were monitored and related to their magnetic characteristics. These structural parameters are (i) the torsion angle governing the conjugation of the organic radical m-PyNO (anti versus gauche), (ii) the coordination geometry of the acetyl acetonate ligands around the metal ion (square versus rhombic), and (iii) the relative orientation of the organic radical with respect to the acetyl acetonate plane (parallel versus perpendicular). It was found that the magnetic properties are not sensitive to the orientation of the radicals with respect to the equatorial plane but do depend on the conformation of the organic radicals. Even a spin switch between the ferromagnetic (S = (7)/(2)) and antiferromagnetic (S = (3)/(2)) ground state was found to be feasible for one of the complexes upon variation of the organic radical geometry, namely, the dihedral angle between the organic radical moiety and the pyridine ring. The pattern of molecular orbital overlap was determined to be the key factor governing the exchange coupling in the modeled systems. Bonding π-type overlap provides antiferromagnetic coupling in all complexes of the para radicals. In the meta analogues, the spins are coupled through the σ orbitals. A low-spin ground state occurs whenever a continuous σ-overlap pathway is present in the complex. Ferromagnetic interaction requires σ-π orthogonality of the pyridine atomic orbitals and/or π-antibonding Mn-pyridine natural orbital overlap. Using an estimate of the donor-acceptor energy stabilization, the affinity of a given Mn(II) d-orbital to mix with the sp(2) orbital from pyridine can be predicted. 23499758 Effect of UDP-glucuronosyltransferase 1A8 polymorphism on raloxifene glucuronidation. Raloxifene is an antiestrogen marketed for the treatment of osteoporosis. The major metabolic pathway of raloxifene is glucuronidation at 6- and/or 4'-positions, which is mainly catalyzed by UDP-glucuronosyltransferase 1A8 (UGT1A8) expressed in extrahepatic tissues such as the small intestine and colon. Two non-synonymous allelic variants, termed UGT1A8*2 (518C>G, A173G) and UGT1A8*3 (830G>A, C277Y), have been found in Caucasian, African-American and Asian populations. In this study, the effect of amino acid substitutions in UGT1A8 on raloxifene glucuronidation was studied using recombinant UGT1A8 enzymes of wild-type (UGT1A8.1) and variant UGT1A8 (UGT1A8.2 and UGT1A8.3) expressed in Sf9 cells. Raloxifene 6- and 4'-glucuronidation by UGT1A8.1 exhibited negative allosteric kinetics. The Km and Vmax values of UGT1A8.1 were 15.0μM and 111pmol/min/mg protein for 6-glucuronidation, and 9.35μM and 232pmol/min/mg protein for 4'-glucuronidation, respectively. The kinetics of raloxifene 6-glucuronidation by UGT1A8.2 was positive allosteric, whereas the kinetics of raloxifene 4'-glucuronidation was negative allosteric. The S50 value of raloxifene 6-glucuronidation was markedly low (1.2%) compared with the Km value of UGT1A8.1, and the Km value for raloxifene 4'-glucuronidation was 29% that of UGT1A8.1. The Vmax value for raloxifene 6-glucuronidation by UGT1A8.2 was comparable to that of UGT1A8.1, whereas the Vmax value for raloxifene 4'-glucuronidation was significantly lower (54%) than that of UGT1A8.1. The activities of raloxifene 6- and 4'-glucuronidation in UGT1A8.3 were markedly lower than those of UGT1A8.1. In mycophenolic acid glucuronidation, the kinetics by wild-type and variant UGT1A8s fitted the Michaelis-Menten model. The Km and Vmax values of UGT1A8.1 were 123μM and 4820pmol/min/mg protein, respectively. The Km and Vmax values of UGT1A8.2 were comparable to those of UGT1A8.1. The Km value of UGT1A8.3 was similar to that of UGT1A8.1, whereas the Vmax value was reduced to 2.4% of UGT1A8.1. These findings suggest that A173G and C277Y substitutions of UGT1A8 change the metabolic ability toward raloxifene, and that the polymorphic alleles of UGT1A8 may influence the clinical response and bioavailability of medicines metabolized mainly by UGT1A8. 23263987 Enhanced leptin sensitivity, reduced adiposity, and improved glucose homeostasis in mice lacking exchange protein directly activated by cyclic AMP isoform 1. The prototypic second messenger cyclic AMP (cAMP) is essential for controlling cellular metabolism, including glucose and lipid homeostasis. In mammals, the majority of cAMP functions are mediated by cAMP-dependent protein kinase (PKA) and exchange proteins directly activated by cAMP (Epacs). To explore the physiological functions of Epac1, we generated Epac1 knockout mice. Here we report that Epac1 null mutants have reduced white adipose tissue and reduced plasma leptin levels but display heightened leptin sensitivity. Epac1-deficient mice are more resistant to high-fat diet-induced obesity, hyperleptinemia, and glucose intolerance. Furthermore, pharmacological inhibition of Epac by use of an Epac-specific inhibitor reduces plasma leptin levels in vivo and enhances leptin signaling in organotypic hypothalamic slices. Taken together, our results demonstrate that Epac1 plays an important role in regulating adiposity and energy balance. 23601711 Preparation of S14161 and its analogues and the discovery of 6-bromo-8-ethoxy-3-nitro-2H-chromene as a more potent antitumor agent in vitro. The small chemical compound 8-ethoxy-2-(4-fluorophenyl)-3-nitro-2H-chromene (S14161) was recently identified as an inhibitor of the phosphoinositide 3-kinase (PI3K). In the present study, we designed a novel synthesis of S14161 and prepared a series of its analogues via the oxa-Michael-Henry reaction in the presence of catalytic amounts of l-proline and triethylamine. Further structural simplification led to the identification of 6-bromo-8-ethoxy-3-nitro-2H-chromene (BENC-511) that exhibited potent antiproliferative activities against a panel of 12 tumor cell lines. Compared with S14161, BENC-511 was more potent in blocking the AKT phosphorylation and inducing cancer cell apoptosis. BENC-511 also displayed more potent effects on human umbilical vein epithelial cells (HUVEC) migration, suggesting its anti-angiogenesis activity. 23074021 In vivo genotoxicity of methyleugenol in gpt delta transgenic rats following medium-term exposure. Methyleugenol (MEG), which is commonly used as a fragrance and flavoring agent, has been shown to induce hepatocellular tumors in rodents. However, the role of genotoxicity as a possible mechanism of action is not fully understood even though the DNA-reactive metabolite of MEG has been identified. In this study, a gpt delta transgenic rat model was used to clarify whether genotoxic mechanisms are involved in MEG-induced hepatocarcinogenesis following medium-term exposure. F344 gpt delta rats were subjected to repeated oral administration of MEG at dosages of 0, 10, 30, or 100mg/kg (a carcinogenic dose) for 13 weeks. The relative weight of the liver of the male and female rats that were administered 100mg/kg MEG and the absolute weight of the liver of the male rats that were administered 100mg/kg MEG were significantly increased. In addition, the number and area of glutathione S-transferase placental form (GST-P) positive foci and proliferating cell nuclear antigen (PCNA) positive cell ratios in the hepatocytes were significantly increased in the male and female rats that were administered 100mg/kg MEG compared with the control animals. In the in vivo mutation assays, a significant increase in the gpt and Spi(-) mutant frequencies was observed in both sexes at the carcinogenic dose. These results suggest the possible participation of genotoxic mechanisms in MEG-induced hepatocarcinogenesis. 23111879 Emergency do not consume/do not use concentrations for ferric chloride in drinking water. The U.S. Congress [PL 107-188] amended the Safe Drinking Water Act and required each community water system serving more than 3,000 people to conduct vulnerability assessments. These assessments address potential circumstances that could compromise the safety and reliability of municipal water. Ferric chloride is used in coagulation and flocculation, and it is used to treat raw water with high viral loads, elevated dissolved solids or high bromide. Iron is an essential nutrient, but elevated concentrations of FeCl3 are corrosive as a result of hydrolysis to HCl. Based on a no-observed-adverse effect level (NOAEL) of 0.5% FeCl3 • 6H2O administered in drinking water to male and female F344 rats for up to 2 years, a do not consume concentration of 200 mg FeCl3 /L can be derived. Since instillation of 0.3 M (48.7 g/L) FeCl3 in saline to rodent vagina failed to elicit damage, a topical do not use concentration of 2000 mg FeCl3/L (600 mg Fe/L) can be assigned. The only FeCl3 data available to quantify ocular toxicity involved a pH 1 solution in rabbit eyes, but HCl instillation (pH 2.5) to rabbit eyes found permanent corneal ulceration after 10 min. The pH of FeCl3 in water at the do not use limit (2.4-2.6) is near the pH (2.0) considered corrosive by regulatory agencies. As direct eye contact with water at pH 4.5 or below increases complaints of ocular discomfort, emergency response plans that address FeCl3 in drinking water must account for Fe levels and the pH of the affected water. 23386250 Upregulation of nuclear factor of activated T-cells by nerve injury contributes to development of neuropathic pain. Nerve injury induces long-term changes in gene expression in the nociceptive circuitry and can lead to chronic neuropathic pain. However, the transcriptional mechanism involved in neuropathic pain is poorly understood. Nuclear factor of activated T-cells (NFATc) is a transcriptional factor regulated by the Ca(2+)-dependent protein phosphatase calcineurin. In this study, we determined nerve injury-induced changes in the expression of NFATc1-c4 in the dorsal root ganglia (DRG) and spinal cords and their role in the development of neuropathic pain. The mRNA of NFATc1-c4 was detected in the rat DRG and dorsal spinal cord. Nerve injury transiently elevated NFATc1-c3 mRNA levels and persistently increased NFATc4 and C-C chemokine receptor type 2 (CCR2) mRNA levels in the DRG. However, NFATc1-c4 mRNA levels in the spinal cord were not altered significantly by nerve injury. Nerve injury also significantly increased the protein level of dephosphorylated NFATc4 in the DRG. Intrathecal injection of the specific NFATc inhibitor 11R-VIVIT or the calcineurin inhibitor FK-506 (tacrolimus) early after nerve injury significantly attenuated the development of tactile allodynia. In addition, treatment with FK-506 or 11R-VIVIT significantly reduced the mRNA levels of NFATc4 and CCR2 but not large-conductance Ca(2+)-activated K(+) channels, in the DRG after nerve injury. Our findings suggest that peripheral nerve injury causes a time-dependent change in NFATc1-c4 expression in the DRG. Calcineurin-NFATc-mediated expression of pronociceptive cytokines contributes to the transition from acute to chronic pain after nerve injury. 23541399 Androgen deprivation from pre-puberty to peripuberty interferes in proteins expression in pubertal and adult rat epididymis. Few studies have focused on experimental testosterone deprivation in immature animals. Therefore, this study used sexually immature rats aiming to evaluate the testes and epididymis histology and proteins expression in these organs on PND50 and 75, after premature antiandrogen exposure, from PND21 to 44. Although the androgen deprivation from pre-puberty up to peripuberty did not alter the histological organization of the testes and epididymis either at puberty or at adulthood, the treatment impaired the expression of specific proteins in epididymal tissue at puberty and adulthood (androgen receptor, calmodulin, Rab11A). These changes may be related to impaired epididymal function, sperm quality and fertility capacity as observed in a previous study. Further studies are necessary to better investigate the molecular mechanisms involved in the impairment on reproductive competence of male rats after precocious hormonal injury. 23582327 Type 2 innate signals stimulate fibro/adipogenic progenitors to facilitate muscle regeneration. In vertebrates, activation of innate immunity is an early response to injury, implicating it in the regenerative process. However, the mechanisms by which innate signals might regulate stem cell functionality are unknown. Here, we demonstrate that type 2 innate immunity is required for regeneration of skeletal muscle after injury. Muscle damage results in rapid recruitment of eosinophils, which secrete IL-4 to activate the regenerative actions of muscle resident fibro/adipocyte progenitors (FAPs). In FAPs, IL-4/IL-13 signaling serves as a key switch to control their fate and functions. Activation of IL-4/IL-13 signaling promotes proliferation of FAPs to support myogenesis while inhibiting their differentiation into adipocytes. Surprisingly, type 2 cytokine signaling is also required in FAPs, but not in myeloid cells, for rapid clearance of necrotic debris, a process that is necessary for timely and complete regeneration of tissues. 23245188 Catalase-like and peroxidase-like catalytic activities of silicon nanowire arrays. Silicon nanowire arrays (SiNWAs) were found to have catalytic activities similar to those of biological enzymes catalase and peroxidase. Thus not only can these materials catalyze the decomposition reaction of H(2)O(2) into water and oxygen, but they can also catalyze the oxidation of o-phenylenediamine (OPD), a common substrate for peroxidases, by H(2)O(2). The presence of Si-H bonds and the morphology of the SiNWAs are found to be crucial to the occurrence of such catalytic activity. When the SiNWAs are reacted with H(2)O(2), the data from Raman spectroscopy suggests the formation of (Si-H)(2)···(O species) ((Si-H)(2)···Os), which is presumably responsible for the catalytic activity. These findings suggest the potential use of SiNWAs as enzyme mimics in medicine, biotechnology, and environmental chemistry. 23008099 Lack of enantioselectivity in the SULT1A3-catalyzed sulfoconjugation of normetanephrine enantiomers: an in vitro and computational study. (1R)-Normetanephrine is the natural stereoisomeric substrate for sulfotransferase 1A3 (SULT1A3)-catalyzed sulfonation. Nothing appears known on the enantioselectivity of the reaction despite its potential significance in the metabolism of adrenergic amines and in clinical biochemistry. We confronted the kinetic parameters of the sulfoconjugation of synthetic (1R)-normetanephrine and (1S)-normetanephrine by recombinant human SULT1A3 to a docking model of each normetanephrine enantiomer with SULT1A3 and the 3'-phosphoadenosine-5'-phosphosulfate cofactor on the basis of molecular modeling and molecular dynamics simulations of the stability of the complexes. The K(M), V(max), and k(cat) values for the sulfonation of (1R)-normetanephrine, (1S)-normetanephrine, and racemic normetanephrine were similar. In silico models were consistent with these findings as they showed that the binding modes of the two enantiomers were almost identical. In conclusion, SULT1A3 is not substrate-enantioselective toward normetanephrine, an unexpected finding explainable by a mutual adaptability between the ligands and SULT1A3 through an "induced-fit model" in the catalytic pocket. 23541670 Discovery of a series of novel 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers, as potent JAK3 kinase inhibitors. We report the discovery of a novel series of ATP-competitive Janus kinase 3 (JAK3) inhibitors based on the 5H-pyrrolo[2,3-b]pyrazine scaffold. The initial leads in this series, compounds 1a and 1h, showed promising potencies, but a lack of selectivity against other isoforms in the JAK family. Computational and crystallographic analysis suggested that the phenyl ether moiety possessed a favorable vector to achieve selectivity. Exploration of this vector resulted in the identification of 12b and 12d, as potent JAK3 inhibitors, demonstrating improved JAK family and kinase selectivity. 23381681 Effects of supplementary selenium source on the blood parameters in beef cows and their nursing calves. Over 2 years, 32 beef cows nursing calves in southwest Arkansas were randomly selected from a herd of 120 that were managed in six groups and were assigned to six 5.1-ha bermudagrass (Cynodon dactylon [L.] Pers.) pastures. Treatments were assigned to pastures (two pastures/treatment) and cows had ad libitum access to one of three free-choice minerals: (1) no supplemental selenium (Se), (2) 26 mg of supplemental Se from sodium selenite per kilogram, and (3) 26 mg of supplemental Se from seleno-yeast per kilogram (designed mineral intake = 113 g/cow daily). Data were analyzed using a mixed model; year and pasture were the random effects and treatment was the fixed effect. At the beginning of the calving and breeding seasons, cows supplemented with Se had greater (P < 0.01) whole blood Se concentration (WBSe) and glutathione peroxidase activities (GSH-Px) than cows receiving no supplemental Se; cows fed seleno-yeast had greater (P ≤ 0.05) WBSe than cows fed sodium selenite, but GSH-Px did not differ (P ≥ 0.25) between the two sources. At birth and near peak lactation (late May), calves from cows supplemented with Se had greater (P < 0.01) WBSe than calves from cows fed no Se and calves from cows fed seleno-yeast had greater (P ≤ 0.01) WBSe and GSH-Px than calves from cows fed sodium selenite. Thyroxine (T4), triiodothyronine (T3), and the T4:T3 ratio in calves did not differ among treatments (P ≥ 0.35). At birth, insulin-like growth factor 1 (IGF-1) was greater (P = 0.02) in calves nursing cows with no supplemental Se than in ones with supplemental Se; in calves nursing cows with supplemental sodium selenite, IGF-1 did not differ (P = 0.96) from ones offered supplemental seleno-yeast. Selenium supplementation of gestating beef cows benefited cows and calves by increasing WBSe and GSH-Px. The use of seleno-yeast as a Se supplement compared to sodium selenite increased the WBSe of both cows and their calves without affecting the T4 to T3 conversion or IGF-1 concentrations. 23231809 Dopamine facilitates dendritic spine formation by cultured striatal medium spiny neurons through both D1 and D2 dopamine receptors. Variations of dopamine (DA) levels induced by drugs of abuse or in the context of Parkinson's disease modulate the number of dendritic spines in medium spiny neurons (MSNs) of the striatum, showing that DA plays a major role in the structural plasticity of MSNs. However, little is presently known regarding early spine development in MSNs occurring before the arrival of cortical inputs and in particular about the role of DA and D1 (D1R) and D2 (D2R) DA receptors. A cell culture model reconstituting early cellular interactions between MSNs, intrinsic cholinergic interneurons and DA neurons was used to study the role of DA in spine formation. After 5 or 10 days in vitro, the presence of DA neurons increased the number of immature spine-like protrusions. In MSN monocultures, chronic activation of D1R or D2R also increased the number of spines and spinophilin expression in MSNs, suggesting a direct role for these receptors. In DA-MSN cocultures, chronic blockade of D1R or D2R reduced the number of dendritic spines. Interestingly, the combined activation or blockade of both D1R and D2R failed to elicit more extensive spine formation, suggesting that both receptors act through a mechanism that is not additive. Finally, we found increased ionotropic glutamate receptor responsiveness and miniature excitatory postsynaptic current (EPSC) frequency in DA-MSN co-cultures, in parallel with a higher number of spines containing PSD-95, suggesting that the newly formed spines present functional post-synaptic machinery preparing the MSNs to receive additional glutamatergic contacts. These results represent a first step in the understanding of how dopamine neurons promote the structural plasticity of MSNs during the development of basal ganglia circuits. 23643824 Therapeutic cell encapsulation: Ten steps towards clinical translation. Since the conception of cell microencapsulation, many scientists bet on this biotechnology as they saw in it a promising alternative to protect transplanted cells from host immunoresponse. Some decades later, this initial enthusiasm is giving rise to a phase of certain conformism and lack of novel advances in the field. This perspective critically discusses current challenges needed to help this approach become a realistic clinical proposal. Alginate seems to be well established as the biomaterial of choice, but additional efforts are needed regarding current cross-linkers and coatings. Biofunctionalization of the matrices may provide the necessary biomimetic microenvironment to control cell behavior. Different alginate degradation rates would allow widening the applications of this biotechnology from drug delivery to cell delivery. In this sense, stem cells from stromal tissues could be the most suitable cell source due to their intrinsic hypoimmunogenicity, their immunomodulatory effets and their capacity to cell homing. The incorporation of suicide and reporter genes in the genome of enclosed cells may overcome some of the existing biosafety concerns. Administration and extraction by means of less invasive procedures also need to be developed to succeed in clinical translation. Finally, improving cost-effectiveness for the scale-up, together with establishing and fulfilling a series of strict regulatory aspects will be indispensable to make the final step to the clinic. 23262162 Antioxidant cosmeto-textiles: Skin assessment. Resveratrol, a natural product, has been reported to have antioxidant activities such as the scavenging of free radicals. This compound could be used in the dermocosmetic field to protect the skin from oxidative stress. In this work, the percutaneous profile of resveratrol in ethanol solutions through pig skin was determinated by an in vitro methodology. The percutaneous absorption of resveratrol was measured and compared with trolox, an analogous of Vitamin E. Both antioxidants were found in all skin sections (stratum corneum, epidermis, and dermis). Besides, the free radical scavenging activity of resveratrol and trolox has been evaluated using DPPH method. The effective dose (ED50) of compounds and DPPH radical inhibition in each skin layer were evaluated. Under the conditions used for these experiments, it can be deduced that resveratrol is more efficient than trolox as an antioxidant, also in the inner skin layers. The cosmeto-textiles with an active substance incorporated into their structure are increasingly used in the cosmetics and pharmaceutical industries. The action of several cosmeto-textiles on the skin was assessed by in vitro and in vivo methodologies. Samples of these cosmeto-textiles were prepared with resveratrol incorporated into cotton and polyamide fabrics. An in vitro percutaneous absorption was used to demonstrate the delivery of the resveratrol from the textile to the different skin layers (stratum corneum, epidermis, and dermis). Additionally, these cosmeto-textiles containing the antioxidant were applied onto the forearms of volunteers to evaluate the textiles' efficacy in skin penetration. The antioxidant's antiradical capacity was evaluated using the DPPH method. Results showed that resveratrol could be detected in the dermis, epidermis, and stratum corneum (SC) by an in vitro percutaneous absorption method and was also detected in the outermost layers of the SC by an in vivo method (stripping). A smaller amount of resveratrol was penetrated through the skin layers when cosmeto-textiles were used compared to direct topical application of the antioxidant solution. The cosmeto-textiles investigated can act as a reservoir system capable of progressively deliver the active substance to the skin layers. From the skin penetration profiles and the antioxidant efficacy assessment of resveratrol, it is possible to ameliorate the inherent antioxidant capacity of skin. 23273150 Preferred configurations of peptide-peptide interactions. The natural and fundamental proclivities of interaction between a pair of peptide units are examined using high-level ab initio calculations. The NH···O H-bonded structure is found to be the most stable configuration of the N-methylacetamide (NMA) model dimer, but only slightly more so than a stacked arrangement. The H-bonded geometry is destabilized by only a small amount if the NH group is lifted out of the plane of the proton-accepting amide. This out-of-plane motion is facilitated by a stabilizing charge transfer from the CO π bond to the NH σ* antibonding orbital. The parallel and antiparallel stacked dimers are nearly equal in energy, both only slightly less stable than the NH···O H-bonded structure. Both are stabilized by a combination of CH···O H-bonding and a π→π* transfer between the two CO bonds. There are no minima on the surface that are associated with O(lp)→π*(CO) transfers, due in large part to strong electrostatic repulsion between the two O atoms, which resists an approach of a carbonyl O from above the C=O bond of the other amide. 23570533 Laccase-mediated coupling of nonpolar chains for the hydrophobization of lignocellulose. We investigate the use of laccase enzymes for coupling short nonpolar chains containing aromatic rings onto flax fibers and nanofibrillated cellulose (NFC) with different lignin contents. Trametes villosa, Pycnoporus cinnabarinus and Myceliophthora thermophila were used to facilitate surface coupling and to produce materials with different levels of hydrophobicity. Heat treatment of fiber webs after lacccase-mediated coupling markedly increased the resistance to water absorption. The highest hydrophobization levels of flax fibers was achieved by coupling dodecyl 3,4,5-trihydroxybenzoate (HB-C12), which yielded water contact angles (WCA) of 80-96 degrees and water absorption times (drop tests) of ca. 73 min. The results from apparent aromatic content and FTIR analyses confirmed the laccase-mediated coupling of HB-C12 onto the cellulose fibers. Substrates consisting of ultrathin films of NFC were also used as substrates for enzyme-mediated hydrophobization with HB-C12. In these cases water contact angles in the range of 87-104 degrees were achieved, depending on the conditions. Quartz crystal microgravimetry (QCM) was used to study the dynamics and the extent of the coupling process onto cellulose. The results help to better understand the mechanisms involved in laccase-mediated hydrophobization and provide a proof of a biotechnological platform for the development of added-value fiber products. 23493374 Creb1-Mecp2-(m)CpG complex transactivates postnatal murine neuronal glucose transporter isoform 3 expression. The murine neuronal facilitative glucose transporter isoform 3 (Glut3) is developmentally regulated, peaking in expression at postnatal day (PN)14. In the present study, we characterized a canonical CpG island spanning the 5'-flanking region of the glut3 gene. Methylation-specific PCR and bisulfite sequencing identified methylation of this CpG ((m)CpG) island of the glut3 gene, frequency of methylation increasing 2.5-fold with a 1.6-fold increase in DNA methyl transferase 3a concentrations noted with advancing postnatal age (PN14 vs PN3). 5'-flanking region of glut3-luciferase reporter transient transfection in HT22 hippocampal neurons demonstrated that (m)CpGs inhibit glut3 transcription. Contrary to this biological function, glut3 expression rises synchronously with (m)CpGs in PN14 vs PN3 neurons. Chromatin immunoprecipitation (IP) revealed that methyl-CpG binding protein 2 (Mecp2) bound the glut3-(m)CpGs. Depending on association with specific coregulators, Mecp2, a dual regulator of gene transcription, may repress or activate a downstream gene. Sequential chromatin IP uncovered the glut3-(m)CpGs to bind Mecp2 exponentially upon recruitment of Creb1 rather than histone deacetylase 1. Co-IP and coimmunolocalization confirmed that Creb1 associated with Mecp2 and cotransfection with glut3-(m)CpG in HT22 cells enhanced glut3 transcription. Separate 5-aza-2'-deoxycytidine pretreatment or in combination with trichostatin A reduced (m)CpG and specific small interference RNAs targeting Mecp2 and Creb1 separately or together depleting Mecp2 and/or Creb1 binding of glut3-(m)CpGs reduced glut3 expression in HT22 cells. We conclude that Glut3 is a methylation-sensitive neuronal gene that recruits Mecp2. Recruitment of Creb1-Mecp2 by glut3-(m)CpG contributes towards transactivation, formulating an escape from (m)CpG-induced gene suppression, and thereby promoting developmental neuronal glut3 gene transcription and expression. 23561185 Modulating β-carotene bioaccessibility by controlling oil composition and concentration in edible nanoemulsions. Diets rich in carotenoids have been correlated with a reduced risk of developing certain types of chronic diseases, but these bioactive components have low intestinal absorption due to their hydrophobic nature. The aim of this work was to study the effect of carrier oil composition (medium-chain triglyceride (MCT) to long-chain triglyceride (LCT) ratio) and total carrier oil concentration (1% or 4% w/w) on the physical stability, lipid digestibility and bioaccessibility of β-carotene-loaded nanoemulsions, using a simulated digestion process. Lipolysis led to an appreciable increase in the size and negative charge on the particles in the system. The total fraction of triacylglycerols converted to free fatty acids decreased as the percentage of LCT within the lipid phase increased, particularly for the nanoemulsions with higher fat contents. There was an increase in β-carotene bioaccessibility as the LCT within the lipid phase increased for low fat nanoemulsions, which was attributed to the increased solubilisation capacity of mixed micelles formed by LCT. β-carotene bioaccessibility showed a complex relationship on LCT content for high fat nanoemulsions, due to the opposing effects of lipid digestion and micelle solubilisation. These results may facilitate the optimisation of delivery systems for lipophilic bioactive compounds for food or pharmaceutical applications. 23584636 Long single ZnO nanowire for logic and memory circuits: NOT, NAND, NOR gate, and SRAM. We demonstrate logic and static random access memory (SRAM) circuits using a 100 μm long and 100 nm thin single ZnO nanowire (NW), which acts as a channel of field-effect transistors (FETs) with Al2O3 dielectrics. NW FETs are thus arrayed in one dimension to consist of NOT, NAND, and NOR gate logic, and SRAM circuits. Two respective top-gate NW FETs with Au and indium-tin-oxide (ITO) were connected to form an inverter, the basic NOT gate component, since the former gate leads to an enhanced mode FET while the latter to depletion mode due to their work function difference. Our inverters showed a high voltage gain of 22 under a 5 V operational voltage, resulting in successful operation of all other devices. We thus conclude that our long single NW approach is quite promising to extend the field of nano-electronics. 23506741 A novel benzo[d]imidazole derivate prevents the development of dextran sulfate sodium-induced murine experimental colitis via inhibition of NLRP3 inflammasome. NLRP3 inflammasome has been reported to be associated with various kinds of immunological diseases including colitis. However, there are few drug candidates targeting inflammasomes for the treatment of colitis. In the present study, we aimed at examining the effect of 1-ethyl-5-methyl-2-phenyl-1H-benzo[d]imidazole, a synthetic small molecular compound also named Fc11a-2, for the treatment of dextran sulfate sodium (DSS)-induced experimental colitis in mice via targeting NLRP3 inflammasome. Treatment with Fc11a-2 dose-dependently attenuated the loss of body weight and shortening of colon length induced by DSS. In addition, the disease activity index, histopathologic scores and myeloperoxidase activity were also significantly reduced by Fc11a-2 treatment. Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF-α, IL-1β, IL-18, IL-17A and IFN-γ, were markedly suppressed by Fc11a-2. Furthermore, a decreased CD11c(+) macrophage infiltration in colons and inactivation of caspase-1 in peritoneal macrophages were detected in Fc11a-2-treated mice. The mechanism of action of Fc11a-2 was related to the inhibition of the cleavage of pro-caspase-1, pro-IL-1β and pro-IL-18 which in turn suppressed the activation of NLRP3 inflammasome. Taken together, our results demonstrate the ability of Fc11a-2 to inhibit NLRP3 inflammasome activation and its potential use in the treatment of inflammatory bowel diseases. 23601396 A review of composition studies of Cameroon traditional dishes: Macronutrients and minerals. This paper reviews published data that contributes to the knowledge of the ingredients and nutrients of Cameroon traditional dishes. Macronutrient (energy, carbohydrates, protein, total fat, fibre and ash) and mineral (iron, zinc, magnesium, calcium, phosphorus, copper, manganese, potassium, sodium and selenium) data are presented for 117 commonly consumed dishes from three eco-regions. Tables providing an overview of the main ingredients and nutrient values (range of means per 100g edible portion) are presented. Considerable variability in nutrient values has been reported among dishes. Water contents range from 29.8 to 95.9g/100g edible portion while energy values range from 12 to 403kcal/100g. Energy yielding-constituents are the major nutrients recorded in published data, followed by iron, zinc and magnesium. 22559719 Variation in the volatile oil composition of Eucalyptus citriodora produced by hydrodistillation and supercritical fluid extraction techniques. This work reports variations in the yields and quality of volatiles produced from Eucalyptus citriodora leaves by different hydrodistillation (HD) and supercritical carbon dioxide extraction (SCE) techniques. HD techniques (1.5%) produced higher yields compared to SCE (0.7%). Citronellal, the major component, was maximum in the extract produced by SCE (79%) followed by oil produced by water-steam distillation (WSD) (72.6%) and water distillation (WD) (62.4%) techniques. Chemical composition of glycoside-bound volatiles produced by acid hydrolysis during HD was found to be very different from free volatiles, although in a minor quantity. The extent of artefact formation and release of aglycones was more profound in the bound volatile oil produced by WD than WSD. Highest oxygenated monoterpenes were found in SCE and WSD (93% each) followed by WD (91.4%). Although the SCE produced lower yields than the HD techniques, its extract is superior in quality in terms of higher concentration of citronellal. 23265491 Evaluation of biological activities of a groundnut (Apios americana Medik) extract containing a novel isoflavone. Groundnut (Apios americana Medik) contains a novel isoflavone, genistein-7-O-gentiobioside. In the present study, we examined the biological activities of an alcohol extract of groundnut containing genistein-7-O-gentiobioside as the main component. Although the groundnut extract by itself did not show antioxidative activity, it drove the antioxidative system in cells. Pretreatment of human breast carcinoma MCF-7 cells for 24 h with the groundnut extract and soybean isoflavone increased gene expression of heme oxygenase-1 (HO-1), a major antioxidative stress enzyme. These groundnut extract-treated cells showed antioxidative activity against free radicals derived from a radical initiator. Pretreatment of cells with 100 μg/mL groundnut extract prevented the depletion of glutathione by the radical initiator; however, treatment with 100 μg/mL of soybean isoflavone injured the cell membrane, indicating that glutathione might be released to the extracellular environment. These results suggest that the groundnut extract had isoflavone-like activity. Like soybean, groundnuts are a good source of isoflavones. 23495001 Raphanus sativus L. var niger as a source of Phytochemicals for the Prevention of Cholesterol Gallstones. Raphanus sativus L. var niger (black radish) is a plant of the cruciferous family with important ethnobotanical uses for the treatment of gallstones in Mexican traditional medicine. It has been established that the juice of black radish decreases cholesterol levels in plasma and dissolves gallstones in mice. Glucosinolates, the main secondary metabolites of black radish, can hydrolyze into its respective isothiocyanates and have already demonstrated antioxidant properties as well as their ability to diminish hepatic cholesterol levels; such therapeutic effects can prevent the formation of cholesterol gallstones. This disease is considered a current problem of public health. In the present review, we analyze and discuss the therapeutic effects of the main glucosinolates of black radish, as well as the effects that this plant has on cholesterol gallstones disease. Copyright © 2013 John Wiley & Sons, Ltd. 23205778 Transferable potentials for phase equilibria. 10. Explicit-hydrogen description of substituted benzenes and polycyclic aromatic compounds. The explicit-hydrogen version of the transferable potentials for phase equilibria (TraPPE-EH) force field is extended to various substituted benzenes through the parametrization of the exocyclic groups -F, -Cl, -Br, -C≡N, and -OH and to polycyclic aromatic hydrocarbons through the parametrization of the aromatic linker carbon atom for multiple rings. The linker carbon together with the TraPPE-EH parameters for aromatic heterocycles constitutes a force field for fused-ring heterocycles. Configurational-bias Monte Carlo simulations in the Gibbs ensemble were carried out to compute vapor-liquid coexistence curves for fluorobenzene; chlorobenzene; bromobenzene; di-, tri-, and hexachlorobenzene isomers; 2-chlorofuran; 2-chlorothiophene; benzonitrile; phenol; dihydroxybenzene isomers; 1,4-benzoquinone; naphthalene; naphthalene-2-carbonitrile; naphthalen-2-ol; quinoline; benzo[b]thiophene; benzo[c]thiophene; benzoxazole; benzisoxazole; benzimidazole; benzothiazole; indole; isoindole; indazole; purine; anthracene; and phenanthrene. The agreement with the limited experimental data is very satisfactory, with saturated liquid densities and vapor pressures reproduced to within 1.5% and 15%, respectively. The mean unsigned percentage errors in the normal boiling points, critical temperatures, and critical densities are 0.9%, 1.2%, and 1.4%, respectively. Additional simulations were carried out for binary systems of benzene/benzonitrile, benzene/phenol, and naphthalene/methanol to illustrate the transferability of the developed potentials to binary systems containing compounds of different polarity and hydrogen-bonding ability. A detailed analysis of the liquid-phase structures is provided for selected neat systems and binary mixtures. 23159732 The specific interaction of the photosensitizer methylene blue with acetylcholinesterase provides a model system for studying the molecular consequences of photodynamic therapy. The photosensitizer, methylene blue (MB), generates singlet oxygen ((1)O2) that irreversibly inhibits Torpedo californica acetylcholinesterase (TcAChE). In the dark MB inhibits reversibly, binding being accompanied by a bathochromic shift that can be used to show its displacement by other reversible inhibitors binding to the catalytic 'anionic' subsite (CAS), the peripheral 'anionic' subsite (PAS), or bridging them. Data concerning both reversible and irreversible inhibition are here reviewed. MB protects TcAChE from thermal denaturation, and differential scanning calorimetry reveals a ∼8°C increase in the denaturation temperature. The crystal structure of the MB/TcAChE complex reveals a single MB stacked against W279 in the PAS, pointing down the gorge towards the CAS. The intrinsic fluorescence of the irreversibly inhibited enzyme displays new emission bands that can be ascribed to N'-formylkynurenine (NFK); this was indeed confirmed using anti-NFK antibodies. Mass spectroscopy revealed that two Trp residues, Trp84 in the CAS, and Trp279 in the PAS, were the only Trp residues, out of a total of 14, significantly modified by photo-oxidation, both being converted to NFK. In the presence of competitive inhibitors that displace MB from the gorge, their modification is completely prevented. Thus, photo-oxidative damage caused by MB involves targeted release of (1)O2 by the bound photosensitizer within the aqueous milieu of the active-site gorge. 23261820 The effect of triclosan on the uterotrophic response to extended doses of ethinyl estradiol in the weanling rat. Triclosan (TCS), an antibacterial, has been shown to be an endocrine disruptor in the rat. We reported previously that TCS potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth in rats exposed to EE and TCS in the uterotrophic assay, whereas TCS alone had no effect. To further characterize this potentiation, we evaluated the effect of co-exposure with lower doses of EE that are comparable to the concentrations in hormone replacement regimens and began to assess the mechanisms by which this potentiation occurs. Changes in uterine weight, epithelial cell growth, and estrogen-sensitive gene expression were assessed. TCS expectedly enhanced the uterotrophic response to EE, however at significantly lower doses of EE. Similarly, TCS increased the EE-induced stimulation of epithelial cell height following cotreatment. Cotreatment also enhanced the estrogen-induced change in gene expression, which was reversed with an ER antagonist. Furthermore, the TCS-induced potentiation was independent of ER activation, as no effects were observed in the ER TA assay. 23601391 Progress with a global branded food composition database. Excess energy, saturated fat, sugar and salt from processed and fast foods are a major cause of chronic disease worldwide. In 2010 The Food Monitoring Group established a global branded food composition database to track the nutritional content of foods and make comparisons between countries, food companies and over time. A protocol for the project was agreed and published in 2011 with 24 collaborating countries. Standardised tools and a website have been developed to facilitate data collection and entry. In 2010 data were obtained from nine countries, in 2011 from 12 and in 2012 data are anticipated from 10 additional countries. This collaborative approach to the collation of food composition data offers potential for cross-border collaboration and support in developed and developing countries. The project should contribute significantly to tracking progress of the food industry and governments towards commitments made at the recent UN high level meeting on chronic disease. 22732443 Hippocampal long-term depression mediates spatial reversal learning in the Morris water maze. Synaptic plasticity at hippocampal excitatory synapses has been proposed as the cellular mechanism underlying spatial learning and memory. However, most previous studies have focused on the role of long-term potentiation (LTP) in learning and memory, and much less is known about the role of long-term depression (LTD). Here, we report that hippocampal-dependent spatial learning in the Morris water maze facilitated hippocampal CA1 LTD induction in vivo. The LTD can be blocked by systemic application of the selective GluN2B antagonist Ro25-6981 (6 mg/kg, i.p.) or a synthetic peptide Tat-GluA2(3Y) (3 μmol/kg, i.p.) that interferes with the endocytosis of AMPA receptors. In addition, systemic or intrahippocampal administration of these two mechanistically and structurally distinct inhibitors impaired spatial reversal learning of a novel target location, when the hidden platform was moved to the quadrant opposite the initial target location. Notably, acute elevated-platform stress, which facilitates hippocampal LTD induction, enhanced both acquisition and retrieval of spatial reversal memory. The present study demonstrates that reversal learning is impaired by blocking hippocampal LTD, and enhanced by facilitating hippocampal LTD, suggesting that hippocampal LTD may be necessary and sufficient to mediate new information processing. This article is part of a Special Issue entitled 'Cognitive Enhancers'. 23592846 Using partial least squares regression to analyze cellular response data. This Teaching Resource provides lecture notes, slides, and a problem set for a lecture introducing the mathematical concepts and interpretation of partial least squares regression (PLSR) that were part of a course entitled "Systems Biology: Mammalian Signaling Networks." PLSR is a multivariate regression technique commonly applied to analyze relationships between signaling or transcriptional data and cellular behavior. 23178339 New approach to improve encapsulation and antitumor activity of doxorubicin loaded in solid lipid nanoparticles. This work aimed to develop solid lipid nanoparticles (SLNs) loaded with doxorubicin evaluating the influence of docosahexaenoic acid (DHA), a polyunsaturated fatty acid that enhances the activity of anticancer drugs, on drug encapsulation efficiency (EE). The SLN were characterized for size, zeta potential, entrapment efficiency (EE) and drug release. Studies of in vitro antitumor activity and cellular uptake were also conducted. The reduction in particle size (from 127 ± 14 to 94 ± 1 nm) and negative charges were obtained for SLN loaded with DHA and triethanolamine (TEA), amine used to increase the solubility of doxorubicin in melted lipid. The EE was significantly improved from 36 ± 4% to 99 ± 2% for SLN without and with DHA at 0.4%, respectively. The doxorubicin release in a slightly acid medium (pH 5.0) was higher than that observed at physiological pH. The in vitro studies clearly showed the higher cytotoxicity of doxorubicin-DHA-loaded SLN than free doxorubicin+DHA on human lung tumor cell line (A549) and the improved cellular uptake achieved with the drug encapsulation can be an explanation. These findings suggest that DHA-doxorubicin-loaded SLN is a promising alternative for the treatment of cancer. 22991330 Can peripheral blood γδ T cells predict osteonecrosis of the jaw? An immunological perspective on the adverse drug effects of aminobisphosphonate therapy. Nitrogen-bisphosphonates (n-BP), often referred to as aminobisphosphonates, are the most commonly prescribed drugs for the treatment of disorders of bone fragility. However, long-term continuous treatment predisposes certain individuals to serious rare side effects, such as bisphosphonate-associated osteonecrosis of the jaw (BAONJ). n-BP use is known to unintentionally activate a subset of innate T cells called Vγ9Vδ2 T cells, but the consequence of this chronic immune stimulation has remained unexplored. The primary objectives of this study were to 1) determine the fate of Vγ9Vδ2 T cells in osteoporotic patients on n-BP therapy as a function of time and type of therapy; 2) evaluate the proportion of Vγ9Vδ2 T cells in patients who had recently experienced n-BP-associated ONJ. We found there is a notable loss of Vγ9Vδ2 T cells over time in osteoporotic patients on n-BP therapy, particularly those on intravenous (iv) therapy (Spearman r = -0.55, p < 0.0001 iv; r = -0.3, p < 0.03 oral) (n = 68); no difference was observed in total T cells, monocytes, or granulocytes. Importantly, the observed negative effect on Vγ9Vδ2 T cells coincides with the reported route of administration and timing of the rare occurrence of BAONJ. Patients (n = 6) who had experienced BAONJ were all found to be significantly deficient in Vγ9Vδ2 T cells (median = 0.07%) in comparison to age- and sex-matched treatment-naïve controls (N = 11; median = 2.40%), U = 0, p = 0.001; this was the only consistent difference in the leukocytes assessed. All BAONJ cases had an underlying condition that further contributed to impaired immunity. We propose Vγ9Vδ2 T cells show a strong potential to serve as harbingers of possible adverse immune effects of n-BP therapy, particularly in those patients already having a compromised immune system as they may be most vulnerable to the development of conditions such as BAONJ. 23570914 Suppression of nuclear factor erythroid 2-related factor 2 via extracellular signal-regulated kinase contributes to bleomycin-induced oxidative stress and fibrogenesis. Pulmonary fibrosis is a serious and irreversible lung injury with obscure etiologic mechanisms and no effective treatment to date. This study explored a crucial link between oxidative stress and pulmonary fibrogenesis, focusing on nuclear factor erythroid 2-related factor 2 (Nrf2), a core transcription factor in antioxidative regulation systems. Treatment of C57 BL/6 mice with bleomycin increased fibroblast viability and collagen production and significantly downregulated Nrf2. In addition, prominent oxidative stress was indicated by changes in superoxide dismutase, catalase activity, and glutathione and thiobarbituric acid-reactive substance levels. In a cell-based model, bleomycin suppressed Nrf2 activation via extracellular signal-related kinase phosphorylation, enhancing intracellular reactive oxygen species in lung fibroblasts and stimulating abnormal cell proliferation and collagen secretion. To confirm this novel mechanism of bleomycin-induced fibrogenesis, we attempted to upregulate Nrf2 and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance. Collectively, these results disclose a potential regulatory mechanism in pulmonary fibrosis that will aid the development of new therapies. 23517008 Surface topography effects in protein adsorption on nanostructured carbon allotropes. We report a molecular dynamics (MD) simulation study of protein adsorption on the surface of nanosized carbon allotropes, namely single-walled carbon nanotubes (SWNT) considering both the convex outer surface and the concave inner surface, together with a graphene sheet for comparison. These systems are chosen to investigate the effect of the surface curvature on protein adsorption at the same surface chemistry, given by sp(2) carbon atoms in all cases. The simulations show that proteins do favorably interact with these hydrophobic surfaces, as previously found on graphite which has the same chemical nature. However, the main finding of the present study is that the adsorption strength does depend on the surface topography: in particular, it is slightly weaker on the outer convex surfaces of SWNT and is conversely enhanced on the inner concave SWNT surface, being therefore intermediate for flat graphene. We additionally find that oligopeptides may enter the cavity of common SWNT, provided their size is small enough and the tube diameter is large enough for both entropic and energetic reasons. Therefore, we suggest that proteins can effectively be used to solubilize in water single-walled (and by analogy also multiwalled) carbon nanotubes through adsorption on the outer surface, as indeed experimentally found, and to functionalize them after insertion of oligopeptides within the cavity of nanotubes of appropriate size. 23315005 Epigenetic and small RNA regulation of senescence. Leaf senescence is regulated through a complex regulatory network triggered by internal and external signals for the reprogramming of gene expression. In plants, the major developmental phase transitions and stress responses are under epigenetic control. In this review, the underlying molecular mechanisms are briefly discussed and evidence is shown that epigenetic processes are also involved in the regulation of leaf senescence. Changes in the chromatin structure during senescence, differential histone modifications determining active and inactive sites at senescence-associated genes and DNA methylation are addressed. In addition, the role of small RNAs in senescence regulation is discussed. 23511783 It is important research, but why is it necessary? The findings regarding cardiovascular actions of dietary supplements labeled as "ephedra free" reported by Foster et al. in the March issue reaffirm decades of research that began in the 1920s with K.K. Chen's study of naturally occurring adrenergic chemicals. Although the study by Foster et al. provides scientifically sound data needed by the US Food and Drug Administration (FDA) as it evaluates the safety of these products, we should ask, "Why was it necessary that these chemicals be studied again for their cardiovascular actions in humans?" 23628605 Steroid hormone synthesis in mitochondria. Mitochondria are essential sites for steroid hormone biosynthesis. Mitochondria in the steroidogenic cells of the adrenal, gonad, placenta and brain contain the cholesterol side-chain cleavage enzyme, P450scc, and its two electron-transfer partners, ferredoxin reductase and ferredoxin. This enzyme system converts cholesterol to pregnenolone and determines net steroidogenic capacity, so that it serves as the chronic regulator of steroidogenesis. Several other steroidogenic enzymes, including 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase and aldosterone synthase also reside in mitochondria. Similarly, the mitochondria of renal tubular cells contain two key enzymes participating in the activation and degradation of vitamin D. The access of cholesterol to the mitochondria is regulated by the steroidogenic acute regulatory protein, StAR, serving as the acute regulator of steroidogenesis. StAR action requires a complex multi-component molecular machine on the outer mitochondrial membrane (OMM). Components of this machine include the 18kDa translocator protein (TSPO), the voltage-dependent anion chanel (VDAC-1), TSPO-associated protein 7 (PAP7, ACBD3), and protein kinase A regulatory subunit 1α (PKAR1A). The precise fashion in which these proteins interact and move cholesterol from the OMM to P450scc, and the means by which cholesterol is loaded into the OMM, remain unclear. Human deficiency diseases have been described for StAR and for all the mitochondrial steroidogenic enzymes, but not for the electron transfer proteins or for the components of the cholesterol import machine. 23424028 Bioavailability-based chronic toxicity measurements of permethrin to Chironomus dilutus. Compared with acute toxicity, chronic exposures to low levels of contaminants are more environmentally relevant, but fewer data are available. In the present study, sediment toxicity of the pyrethoid permethrin to Chironomus dilutus was determined. The whole-life-cycle toxicity testing was conducted with the endpoints covering survival, growth, emergence, and reproduction. Permethrin caused 50% lethality in C. dilutus at 1.83 ± 1.13 µg/g organic carbon (OC) and 1.20 ± 0.55 µg/g OC after exposures of 20 d (before pupation) and 58 d (the end of the testing), respectively. The 5% and median effect concentrations (EC5 and EC50) represented the marginal and toxic levels of the sublethal effects, respectively, and effect data were all normalized to the controls before Probit analysis. The EC5s for growth, emergence, and reproduction were 0.034 ± 0.006 µg/g OC, 0.016 ± 0.008 µg/g OC, and 0.009 ± 0.008 µg/g OC, respectively; the respective EC50s were 1.09 ± 0.56 µg/g OC, 0.838 ± 0.077 µg/g OC, and 0.039 ± 0.105 µg/g OC. In addition, a 24-h Tenax extraction was employed to better assess permethrin bioavailability. Ultimately, response spectra with a series of endpoints were developed for permethrin using either OC-normalized bulk sediment concentrations or bioavailability-based Tenax extractable concentrations as the dose metric. The development of bioavailability-based chronic toxicity endpoints for sediment-associated permethrin would provide valuable benchmarks for evaluating ecological risk of this contaminant and contributing to improve sediment management policies. Environ Toxicol Chem 2013;32:1403-1411. © 2013 SETAC. 23219725 Budding yeast Wapl controls sister chromatid cohesion maintenance and chromosome condensation. The establishment of stable sister chromatid cohesion during DNA replication requires acetylation of the chromosomal cohesin complex by the replication fork-associated acetyltransferase Eco1. Cohesin acetylation is thought to facilitate replication fork progression by counteracting an as yet ill-defined cohesion "antiestablishment" activity imposed by the Wapl protein. Here, using budding yeast, we find no evidence that cohesin acetylation must overcome Wapl during replication fork progression. Instead, Wapl emerges as a negative regulator of cohesion maintenance in G2, a function that it likely exerts through its role as destabilizer of unacetylated, chromosome-bound cohesin. Our results suggest that acetylation renders cohesin Wapl-resistant from S phase onward until mitosis. In the absence of Wapl, sister chromatid cohesion functions well, suggesting that Wapl partakes in a cohesin function outside of sister chromatid cohesion. We find that Wapl is not required for cohesin's known role in transcriptional regulation. Rather, cells lacking Wapl display increased chromosome condensation in both interphase and mitosis. Thus, as a conserved regulator of cohesin dynamics on chromosomes, Wapl controls cohesion maintenance after its establishment in S phase and adjusts the chromosome condensation status. 23565585 In vitro evaluation of the effects of various additives and polymers on nerve growth factor microspheres. Abstract Objective: To evaluate the effects of various additives or polymers on the in vitro characteristics of nerve growth factor (NGF) microspheres. Materials and methods: NGF microspheres were fabricated using polyethylene glycol (PEG), ovalbumin (OVA), bovine serum albumin (BSA) or glucose as protein protectors, and poly(lactide-co-glycolide) (PLGA) or poly(lactic acid) (PLA)/PLGA blends as encapsulation materials. Results: Encapsulation efficiencies of the NGF microspheres with various additives or polymers were not more than 30%. A comparative study revealed that OVA was somewhat superior over others, and was thus chosen as the protective additive in subsequent experiments. Polymer analysis showed that NGF release from 1:1 PLA (η = 0.8):PLGA (75/25, η = 0.45) microspheres lasted for 90 d with a burst release rate of 12.7%. About 40% of the original bioactivity was retained on the 28th day, while 10% was left on the 90th day. Discussion and conclusion: The combination of OVA as an additive and the PLA/PLGA blend as the coating matrix is suitable for encapsulation of NGF in microspheres for extended release. 23643745 Pharmacological and genetic evidence for pre- and postsynaptic D2 receptor involvement in motor responses to nociceptin/orphanin FQ receptor ligands. A combined pharmacological and genetic approach was undertaken to investigate the contribution of endogenous dopamine to the motor actions of nociceptin/orphanin FQ (N/OFQ) receptor (NOP receptor) ligands. Motor activity was evaluated by a battery of behavioural tests in mice. The involvement of the various DA receptor subtypes in the motor effects of N/OFQ and NOP receptor antagonists was evaluated pharmacologically, using D1/D5 (SCH23390), D2/D3 (raclopride, amisulpride) and D3 (S33084) receptor antagonists, and by using D2 receptor knockout mice. Low doses of N/OFQ and NOP receptor antagonists promoted movement whereas higher doses inhibited it. Motor facilitation was selectively prevented by raclopride while motor inhibition was prevented by amisulpride. Amisulpride also attenuated the hypolocomotion induced by the D2/D3 receptor agonist pramipexole and dopamine precursor L-3,4-dihydroxyphenylalanine, whereas raclopride (and S33084) worsened it. To dissect out the contribution of pre- and postsynaptic D2 receptors, mice lacking the D2 receptor (D2R(-/-)) or its long isoform (D2L(-/-)) were used. Motor facilitation induced by N/OFQ and NOP receptor antagonists was lost in D2R(-/-) and D2L(-/-) mice whereas motor inhibition induced by NOP receptor antagonists (and pramipexole) was lost in D2R(-/-) but preserved in D2L(-/-) mice. N/OFQ-induced hypolocomotion was observed in both genotypes. We demonstrate that motor actions of NOP receptor ligands rely on the modulation of endogenous dopamine. Motor facilitation induced by NOP receptor antagonists as well as low dose N/OFQ is mediated through D2L postsynaptic receptors whereas motor inhibition observed with higher doses of N/OFQ occurs by direct inhibition of mesencephalic DA neurons. Motor inhibition seen with high doses of NOP receptor antagonists appears to be mediated through the D2 presynaptic autoreceptors. These data confirm that endogenous N/OFQ is a powerful modulator of dopamine transmission in vivo and that the effects of NOP receptor antagonists on motor function reflect the blockade of this endogenous N/OFQ tone. 23333834 RANKL targeted peptides inhibit osteoclastogenesis and attenuate adjuvant induced arthritis by inhibiting NF-κB activation and down regulating inflammatory cytokines. Peptides designed from osteoprotegerin (OPG) have previously been shown to inhibit receptor activator of NF-κB ligand (RANKL) and prevent bone loss without significantly inhibiting inflammation. The objective of this study was to develop a novel peptide with dual inhibitory activity against bone loss and inflammation using site-directed mutagenesis. Out of the three putative sites (i.e., Tyr70-Asp78, Tyr82-Glu96, and Leu113-Arg122) available on OPG for RANKL binding, Leu113-Arg122 was used as a template for peptide synthesis. Peptide mutants of the template sequence (112YLEIEFCLKHR122) were synthesized and initially screened for their inhibitory effect on RANK-RANKL binding by competitive ELISA. The most active peptide was further evaluated in vitro for RANKL induced osteoclastogenesis in mouse macrophage cells, and in vivo for Freund's complete adjuvant induced arthritis (AIA) in Lewis rats. The efficacy of the candidate peptide was compared with that of the standard drug celecoxib. The peptide YR-11 (YLEIEFSLKHR), obtained by direct substitution of cysteine with a serine residue in the template sequence, significantly (p<0.05) inhibited RANK-RANKL binding, and RANKL induced TRAP activity and formation of multinucleated osteoclasts without any cytotoxicity. Administration of YR-11 peptide at the dose of 30mg/kg (i.p.) ameliorated both bone loss and inflammation in AIA rats. To elucidate the mechanism for inhibition of inflammation in arthritic rats, serum and tissue cytokines (TNF-α, IL-1β, and IL-6) were analyzed by ELISA and RT-PCR methods. Results confirmed that YR-11 peptide inhibited pro-inflammatory cytokines in the sera and hind paw tissues of AIA rats through its suppressive effect on RANKL induced nuclear translocation of NF-κB. The results obtained in this study substantiate the therapeutic benefit of this novel peptide in the prevention of bone loss and inflammation in rheumatoid arthritis with reduced side effects. 23542652 The effects of 17-α-ethinylestradiol (EE2) on molecular signaling cascades in mummichog (Fundulus heteroclitus). Exposures to ≤10ng/L of 17-α-ethinylestradiol (EE2) will reduce or shut down egg production in freshwater fish models, while mummichog (Fundulus heteroclitus), an estuarine species, are able to produce eggs at EE2 concentrations >3000ng/L. The objective of this study was to gain mechanistic insight into how mummichog are able to produce eggs during exposures to high EE2. Mummichog were exposed to 0, 50 or 250ng/L of EE2 for 14d. There were no changes in gonadosomatic index, liversomatic index, gonad development, or plasma estradiol levels after exposure to EE2. However, testosterone significantly decreased with EE2 exposures (50, 250ng/L). Microarray analysis in the liver revealed that cell processes associated with lipids were affected by EE2 at the transcriptome level. Based on the transcriptomics data, we hypothesize that mummichog are able to maintain lipid transport and uptake into the ovary and this may be associated with apolipoproteins, facilitating normal oocyte development. Novel gene regulatory networks for protein modification targets were also constructed to learn more about the potential roles of estrogens in the teleost liver. Although post-translational modifications (PTMs) are important regulatory mechanisms, the roles of PTMs in protein regulation in fish and the susceptibility of PTMs to aquatic pollutants are largely unexplored and may offer novel insight into mechanisms of endocrine disruption. 23609770 Acquisition of responding with a remifentanil-associated conditioned reinforcer in the rat. RATIONALE: Drug-associated environmental stimuli may serve as conditioned reinforcers to enhance drug self-administration behaviors in humans and laboratory animals. However, it can be difficult to distinguish experimentally the conditioned reinforcing effects of a stimulus from other behavioral processes that can change rates of responding. OBJECTIVES: To characterize the conditioned reinforcing effects of a stimulus paired with the μ-opioid agonist, remifentanil, using a new-response acquisition procedure in the rat. METHODS: First, in Pavlovian conditioning (PAV) sessions, rats received response-independent IV injections of remifentanil and presentations of a light-noise compound stimulus. In paired PAV groups, injections and stimulus presentations always co-occurred. In random PAV control groups, injections and stimulus presentations occurred with no consistent relationship. Second, in instrumental acquisition (ACQ) sessions, all animals could respond in an active nose-poke that produced the stimulus alone or in an inactive nose-poke that had no scheduled consequences. RESULTS: During ACQ, rats made significantly more active nose-pokes than inactive nose-pokes after paired PAV, but not after random PAV. Between groups, rats also made more active nose-pokes after paired PAV than after random PAV. After paired PAV, increased active responding was obtained under different schedules of reinforcement, persisted across multiple ACQ sessions, and depended on the number of PAV sessions conducted. CONCLUSIONS: The remifentanil-paired stimulus served as a conditioned reinforcer for nose-poking: responding depended on both the contingency between the stimulus and remifentanil and the contingency between the nose-poke and the stimulus. Generally, new-response acquisition procedures may provide valid, flexible models for studying opioid-based conditioned reinforcement. 23325530 Diclofenac: New data on chronic toxicity and bioconcentration in fish. Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug that is regularly detected in surface waters. To support a robust aquatic risk assessment, two early life stage (ELS) tests, compliant with the Organisation for Economic Co-operation and Development (OECD) test guideline 210, were conducted in rainbow trout and in zebrafish. Population relevant endpoints, such as hatching, growth, and survival, and in the trout study, histopathological effects in potential target organs, were examined. The bioconcentration of DCF in rainbow trout was measured in a separate study according to OECD test guideline 305. The bioconcentration factor (BCF) in rainbow trout remained below 10, demonstrating no relevant bioconcentration of DCF in fish. In the rainbow trout ELS test, the no observed effect concentration (NOEC) including histopathology was 320 µg/L. The effect of DCF on zebrafish growth was less clear, and the NOEC can be interpreted as 10 µg/L. However, for a number of reasons, the authors consider the moderately reduced growth of zebrafish exposed to concentrations of up to 320 µg/L not a repeatable, treatment-related effect of DCF. This leads us to a conclusion that DCF has, with high probability, no adverse effect on both fish species up to 320 µg/L. This NOEC indicates a sufficient safety margin for fish populations, because concentrations of DCF in European rivers are in the range of ng/L to low µg/L. 22712621 Bearberry identification by a multidisciplinary study on commercial raw materials. Herbal species different from the official bearberry, Arctostaphylos uva-ursi, are sold through conventional markets and also through non-controlled Internet websites, putting consumer safety at risk owing to the lack of quality control. Recently, Arctostaphylos pungens has become one of the most used species as a raw material for herbal medicines and dietary supplements in the place of official bearberry, a plant used for the treatment of various urinary disorders. A fingerprint identification based on an integrated application of different analytical techniques (HPTLC, NMR, HPLC-DAD and LC-ESI-MS) is here described to distinguish A. uva-ursi from A. pungens. The HPTLC and HPLC-DAD fingerprints resulted the simplest methods to differentiate the two species, whereas LC-ESI-MS was more useful to quantify arbutin, the main component of bearberry, and to evaluate its different content in the two species. This multidisciplinary study showed for the first time a specific phytochemical fingerprint of the new species A. pungens. 23561176 Effect of flavonoid structure on the fluidity of model lipid membranes. We investigated how the structural properties of (+)-catechin, (-)-epicatechin, (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG) and butylated hydroxytoluene (BHT) correlate with structural changes of phosphatidylcholine plus sphingomyelin (2.4:1) model lipid membranes. Changes were measured by fluorescence anisotropy, electron paramagnetic resonance, and differential scanning calorimetry. Two fluorophores and two spin probes were used to monitor membrane characteristics close to water-lipid interface and in the middle of the bilayer. The data obtained were correlated to the amount of bounded compounds, the number of H-bonds, and the topological polar surface area (TPSA) of the compounds. These correlations reflect the behaviours of (+)-catechin, (-)-epicatechin, EGC, EGCG and BHT. Our results confirm that phenolics studied here are bounded to a membrane surface predominantly via hydrogen bonds, while BTH is inserted into the lipid bilayer. 23539511 Cardiac natriuretic Peptide gene expression and plasma concentrations during the first 72 hours of life in piglets. Plasma measurement of cardiac natriuretic peptides constitutes promising markers of congenital heart disease. However, concentrations change rapidly and dramatically during the first days after delivery even in healthy neonates, which complicates clinical interpretation. It is unknown whether these changes in plasma concentrations are explained by corresponding changes in the cardiac gene expression. We quantified the chamber-specific mRNA levels of ANP (A-type natriuretic peptide) and BNP (B-type natriuretic peptide) and plasma pro-ANP and BNP-32 concentrations in healthy piglets during the first 72 hours of life (from 2 litters, n = 44). Chamber-specific ANP and BNP mRNA levels reflected hemodynamic neonate changes at birth but did not correlate with circulating natriuretic peptide concentrations. However, plasma pro-ANP and creatinine concentrations were closely correlated (P < .0001; r = 0.73). Plasma pro-ANP levels were highest on the day of delivery (5580 pmol/L [4320-6786] decreasing to 2484 pmol/L [1602-2898] after 72 hours, P < .0001). During the 72 hours, gel chromatography suggested that the translational products in circulation and in atrial tissue were immature, ie, unprocessed pro-ANP. In contrast to pro-ANP, BNP-32 plasma concentrations were low at delivery and peaked after 48 hours (12 [10.5-20.6] vs. 88.8 [71.7-101.4] pmol/L, P < .0001). To conclude, ANP and BNP gene expression differs considerably between cardiac chambers in the first 72 hours of life in healthy piglets, resembling the transition from fetal to neonate circulation. However, the cardiac gene expression does not explain plasma concentrations. 23122118 CODEX-compliant eleven organophosphorus pesticides screening in multiple commodities using headspace-solid phase microextraction-gas chromatography-mass spectrometry. A headspace-solid phase microextraction-gas chromatography-mass spectrometric (HS-SPME-GC-MS, hereafter abbreviated as "SPME") method was developed for dedicated organophosphorus (OP) pesticides assessment in multiple vegetable and fruit commodities. Specific extraction variables were optimised to achieve harmonised extraction performance of eleven OPs in a great span of seven characteristic commodities cataloged in Codex Alimentarius Commission. Comprehensive validation study confirmed analytical robustness of the SPME treatment in turnip, green cabbage, French beans, eggplant, apple, nectarine and grapes. Based on range-specific evaluation, extraction of individual OPs was characterised by sub-ppb level sensitivity and a wide 0.01-2.5 mg L(-1) dynamic range. Effective sample clean-up afforded precise quantification (0.5-10.9% R.S.D.) within a 70-120% recovery range at the MRL levels specified for individual commodities. Compared to conventional methods currently used, the SPME treatment developed here is quick, accurate, and relatively environmental friendly; it represents an attractive, practical way to deliver international standards in OP screening routines. 23567242 Bisphenol A: Update on newly developed data and how they address NTP's 2008 finding of "Some Concern" Bisphenol A (BPA) is a component of polycarbonate plastics and epoxy resins used in many commercial products including coatings and liners of food containers. Low levels of BPA can be detected in over 90% of human urine samples in the US, indicating that exposure to BPA is widespread. In 2008, the US National Toxicology Program's Center for the Evaluation of Risks to Human Reproduction (NTP-CERHR) expressed concerns regarding BPA's potential health effects, and suggested improved study designs and methodologies that they believed would address those concerns. This paper discusses some of the controversial issues surrounding BPA, summarizes the current regulatory status of BPA, reviews recent pharmacokinetic studies, and describes ongoing and planned research on the effects of BPA. In addition, we evaluate two papers studying BPA neurobehavioral effects, identified by the European Food Safety Authority and the German Federal Institute for Risk Assessment as being valid for use in risk assessment, to determine whether they address the NTP-CERHR methodological concerns. The data from these studies would likely be sufficient for NTP to lower its concern level for neurobehavioral effects of BPA. At this time, many regulatory agencies from around the world support the use of BPA in food contact materials. 23249244 Multifaceted ultrafast intramolecular charge transfer dynamics of 4-(dimethylamino)benzonitrile (DMABN). Intramolecular charge transfer (ICT) of DMABN has been the subject of extensive investigations. Through the measurements of highly time-resolved fluorescence spectra (TRFS) over the whole emission region, we have examined the ICT dynamics of DMABN in acetonitrile free from the solvation dynamics and vibronic relaxation. The ICT dynamics was found to be characterized by a broad range of time scales; nearly instantaneous (<30 fs), 160 fs, and 3.3 ps. TRFS revealed that an ICT state with partially twisted geometry, ICT(P), is formed within a few hundred femtoseconds either directly from the initial photoexcited state or via the locally excited (LE) state. The ICT(P) state undergoes further relaxation along the intramolecular nuclear coordinate to reach the twisted ICT (TICT) state with the time constant of 4.8 ps. A conformational diversity along the rotation of the dimethylamino group was speculated to account for the observed diffusive dynamics. 23578968 Evaluation of a predictive in vitro Leydig cell assay for anti-androgenicity of phthalate esters in the rat. An in vitro assay using the rat Leydig cell line R2C was evaluated for its ability to quantitatively predict inhibition of testosterone synthesis. Results obtained for endocrine active phthalates (MEHP, MBP), and inactive phthalates (MMP and MEP) were highly consistent with in vivo results based on tissue and media concentrations. Statistically significant inhibition of testosterone synthesis (p<0.05, 1-way ANOVA) was observed at 1μM MBP and 3μM MEHP, while MEP and MMP did not affect inhibition of testosterone synthesis until much higher concentrations (≫100μM). Concentrations causing 50% inhibition of testosterone synthesis for MBP and MEHP (3 and 6μM respectively), were similar to in vivo values (3 and 7μM). The R2C assay was used to determine the relative potency of 14 structurally diverse monoesters and oxidative metabolites of MEHP. Monoesters with alkyl chains 4-5 carbons in length had the highest potency for testosterone inhibition, while 0-2 carbon alkyl chains were least potent. Phase I metabolism did not completely inactivate MEHP, underscoring the need for metabolism data when interpreting in vitro pharmacodynamic data. This steroid inhibition assay provides a predictive in vitro alternative to expensive and timeconsuming developmental rat studies for phthalate-induced antiandrogenicity. 22360797 Chemical constituents of the hemiparasitic plant Phoradendron brachystachyum DC Nutt (Viscaceae). Phoradendron brachystachyum is a hemiparasitic plant widely distributed in México that belongs to the Viscaceae family. It has been commonly used in folk medicine as a substitute for the European mistletoe. In this chemical study, morolic acid was isolated as the major component (47.54% of the total composition of acetone extract) of this plant. In addition, 19 known compounds were identified: β-sitosteryl and stigmasteryl linoleates, β-sitosterol, stigmasterol, triacontanol, squalene, α- and β-amyrin, lupeol, lupenone, betulin aldehyde, betulon aldehyde, oleanolic aldehyde, betulinic acid, betulonic acid, moronic acid, morolic acid, oleanolic acid, flavonoids acacetin and acacetin 7-methyl ether. There have been no previous reports in the literature on the chemical composition of this potential natural source of hypoglycaemic and antihypertensive compounds. 23643725 The use of antioxidant enzymes in freshwater biofilms: Temporal variability vs. toxicological responses. This study aims to investigate the potential of antioxidant enzyme activities (AEA) as biomarkers of oxidative stress in freshwater biofilms. Therefore, biofilms were grown in channels for 38 days and then exposed to different concentrations (0-150μgL(-1)) of the herbicide oxyfluorfen for 5 more weeks. Under control conditions, the AEA of biofilms were found to change throughout time with a significant increase in ascorbate peroxidase (APX) activity during the exponential growth and a more important role of catalase (CAT) and glutathione reductase (GR) activities during the slow growth phase. Chronic exposure to oxyfluorfen led to slight variations in AEA, however, the ranges of variability of AEA in controls and exposed communities were similar, highlighting the difficulty of a direct interpretation of AEA values. After 5 weeks of exposure to oxyfluorfen, no clear effects were observed on chl-a concentration or on the composition of other pigments suggesting that algal group composition was not affected. Eukaryotic communities were structured clearly by toxicant concentration and both eukaryotic and bacterial richness were reduced in communities exposed to the highest concentration. In addition, during acute exposure tests performed at the end of the chronic exposure, biofilms chronically exposed to 75 and 150μgL(-1) oxyfluorfen showed a higher CAT activity than controls. Chronic exposure to oxyfluorfen provoked then structural changes but also functional changes in the capacity of biofilm CAT activity to respond to a sudden increase in concentration, suggesting a selection of species with higher antioxidant capacity. This study highlighted the difficulty of interpretation of AEA values due to their temporal variation and to the absence of absolute threshold value indicative of oxidative stress induced by contaminants. Nevertheless, the determination of AEA pattern throughout acute exposure test is of high interest to compare oxidative stress levels undergone by different biofilm communities and thus determine their antioxidant capacity. 23455593 Neural substrates of acupuncture in the modulation of cravings induced by smoking-related visual cues: an FMRI study. RATIONALE: Cue reactivity is a key factor in modulating motivational and goal-directed behaviors associated with compulsive drug intake and relapse. Smoking-associated cues produce smoking urges and cravings and are accompanied by the activation of brain regions involved in attention, motivation, and reward. OBJECTIVES: We investigated whether acupuncture ameliorates cravings induced by smoking-related visual cues, and we explored the neural mechanisms underlying the effects of acupuncture on modulating smoking urges. METHODS: After 36 h of smoking abstinence, 25 right-handed male smokers underwent fMRI, during which smoking-related and neutral visual cues were presented. Twelve subjects were treated with real acupuncture (RA) at HT7 and 13 subjects received sham acupuncture (SA). During the scanning sessions, craving scores to smoking-related visual cues were assessed before and after RA or SA treatment. The differences in brain responses to smoking vs. neutral cues after treatment between the RA and SA groups were detected using three-way ANOVAs (Cue × Session × Group). RESULTS: After treatment, the craving scores were significantly decreased in the RA group, as compared to the SA group. When we explored the neural substrates of acupuncture on the modulation of cravings induced by smoking cues, significant differences were found in the medial prefrontal cortex, the premotor cortex, the amygdala, the hippocampus, and the thalamus. CONCLUSIONS: These findings suggest that acupuncture alleviates cue-induced cravings through the regulation of activity in brain regions involved in attention, motivation, and reward relative to craving scores in the initial abstinence phase. 23493317 PDE3 and PDE4 isozyme selective inhibitors are both required for synergistic activation of brown adipose tissue. Brown adipose tissue (BAT) is a highly thermogenic organ that converts lipids and glucose into heat. Many of the metabolic and gene transcriptional hallmarks of BAT activation, namely increased lipolysis, uncoupling protein-1 (UCP1) mRNA, and glucose uptake are regulated by the adrenergic second messenger, adenosine-3',5'-cyclic monophosphate (cAMP). Cyclic nucleotide phosphodiesterases (PDEs) catalyze the breakdown of cAMP, thereby regulating the magnitude and duration of this signaling molecule. In the absence of adrenergic stimulus, we found that it required a combination of a PDE3 and a PDE4 inhibitor to fully induce UCP1 mRNA and lipolysis in brown adipocytes, whereas neither PDE inhibitor alone had any substantial effect under basal conditions. Under submaximal β-adrenoceptor stimulation of brown adipocytes, a PDE3 inhibitor alone could potentiate induction of UCP1 mRNA, while a PDE4 inhibitor alone could augment lipolysis, indicating differential roles for each of these two PDEs. Neither induction of UCP1 nor lipolysis was altered by inhibition of PDE1, PDE2 or PDE8A. Finally, when injected into mice, the combination of PDE3 and PDE4 inhibitors stimulated glucose uptake in BAT under thermoneutral and fasted conditions, a response that was further potentiated by the global ablation of PDE8A. Taken together, these data illustrate that multiple PDEs work in concert to regulate three of the important pathways leading to BAT activation, a finding that may provide an improved conceptual basis for the development of therapies for obesity-related diseases. 23541948 Signaling pathways mediating the effects of insulin-like growth factor-I in bovine muscle satellite cells. The objective of this study was to identify the signaling pathways mediating the effects of IGF-I on muscle cell proliferation, protein synthesis, and protein degradation in a physiologically more relevant muscle cell model. We isolated muscle satellite cells from adult cattle and expanded them as myoblasts or induced them to form myotubes in culture. We determined the effects of IGF-I on proliferation of myoblasts and protein synthesis and degradation in myotubes in the presence or absence of specific signaling inhibitors. Our data suggest that both the MEK/ERK and PI3K/AKT pathways mediate the stimulatory effect of IGF-I on myoblast proliferation and that the PI3K/AKT pathway mediates this effect through cyclin D2. Our data also suggest that both the MEK/ERK and PI3K/AKT pathways mediate the stimulatory effect of IGF-I on protein synthesis through p70S6K and that the PI3K/AKT pathway mediates the inhibitory effect of IGF-I on protein degradation through FoxO3a. 23561139 Chemical profile and sensory properties of different foods cooked by a new radiofrequency oven. Radio frequency (RF) heating has been used for numerous applications in the food industry such as baking, thawing or pasteurisation. It reduces cooking time, and it helps to retain acceptable food colour and texture. In this paper, chemical and sensory data obtained from broccoli, potatoes, salmon and cocoa cakes cooked using an innovative RF oven were reported. The oven has an algorithm able to monitor the energy feedback from the cavity and to adjust the energy output accordingly. The different foods were cooked to the same end point and the concentration of phytochemicals, vitamins and acrylamide were assessed. Results demonstrated that RF oven preserved ascorbic acid and increased glucosinolates concentration in broccoli and it decreased the formation of acrylamide in roasted potatoes more than 50%. The total amount of vitamins B was 30% and 50% higher in RF cooked salmon than conventionally cooked salmon prepared at 55 and 75°C, respectively. 23320931 Reversible recruitment and emission of DO3A-derived lanthanide complexes at ligating molecular films on gold. The recruitment of DO3A-derived lanthanide complexes by ligation to isophthalic acid and catechol-modified gold surfaces, and their resulting sensitization, is reported herein. Predictably pH-dependent surface recruitment is associated with the expected fingerprint europium and terbium emission characteristics. The intensity of the lanthanide luminescence scales exponentially with spacer length, indicating a strong quenching interaction between the lanthanide and the gold surface. The switchable catechol oxidation state provides a means of electrochemically triggering the release of prior ligated complexes. 23164931 The perirhinal cortex of rats: an intricate area for microinfusion of anticonvulsants against soman-induced seizures. Microinfusion of anticonvulsants into the perirhinal cortex through 1 guide cannula in each hemisphere only invades a small area of this seizure controlling site in rats exposed to soman. The purpose of the present study was to examine whether infusions made through 2 cannulas in each perirhinal cortex may produce more efficacious anticonvulsant action against soman intoxication than the use of 1 cannula only in rats infused with the ionotropic antagonists procyclidine and caramiphen or the metabotropic glutamate modulators DCG-IV and MPEP. The results showed that the mere presence of indwelling double cannulas caused proconvulsant effect in response to subsequent systemic administration of soman. Both the control and caramiphen groups with double cannulas had significantly shorter latencies to seizure onset than the corresponding groups with single cannula. Procyclidine resulted in anticonvulsant efficacy, even in rats with double cannulas. In rats that received twin infusions of DCG-IV or MPEP, the anticonvulsant impact was very high, inasmuch as a majority of the rats in each group was protected against seizure activity. Drugs possessing powerful anticonvulsant potency can apparently counteract the proconvulsant effect of double cannulas, and some can even gain enhanced anticonvulsant capacity when invading a larger area of the perirhinal cortex. Perirhinal EEG recordings (electrodes in indwelling cannulas) in a separate set of rats not exposed to soman or drugs showed no differences in basal electrical activity (total power 0.5-25Hz or the theta band 4-12Hz) between groups with single or double cannulas. The intrinsic excitability and synaptic connectivity of the perirhinal cortex may be associated with the proconvulsant impact observed in rats with double cannulas when exposed to soman. 23271737 Molecular mechanism by which a potent hepatitis C virus NS3-NS4A protease inhibitor overcomes emergence of resistance. Although optimizing the resistance profile of an inhibitor can be challenging, it is potentially important for improving the long term effectiveness of antiviral therapy. This work describes our rational approach toward the identification of a macrocyclic acylsulfonamide that is a potent inhibitor of the NS3-NS4A proteases of all hepatitis C virus genotypes and of a panel of genotype 1-resistant variants. The enhanced potency of this compound versus variants D168V and R155K facilitated x-ray determination of the inhibitor-variant complexes. In turn, these structural studies revealed a complex molecular basis of resistance and rationalized how such compounds are able to circumvent these mechanisms. 23486635 Two Dimensional Window Exchange Umbrella Sampling for Transmembrane Helix Assembly. The method of window exchange umbrella sampling molecular dynamics (WEUSMD) with a pre-optimized parameter set was recently used to obtain the most probable conformations and the energetics of transmembrane (TM) helix assembly of a generic TM sequence. When applied to glycophorin A TM domain (GpA-TM) using the restraint potentials along the helix-helix distance, however, tight interfacial packing of GpA-TM resulted in insufficient conformational sampling at short helix-helix separation. This sampling issue is addressed by extending the WEUSMD into two dimensions with the restraint potentials along the helix-helix distance and crossing angle. The two-dimensional WEUSMD results demonstrate that the incomplete sampling in the one-dimensional WEUSMD arises from high barriers along the crossing angle between the GpA-TM helices. Together with the faster convergence in both the assembled conformations and the potential of mean force, the 2D-WEUSMD can be a general and efficient approach in computational studies of TM helix assembly. 23526919 Phospholipid/Carbocyanine Dye-Shelled Microbubbles as Ultrasound-Modulated Fluorescent Contrast Agents. Fluorescent microbubbles have been fabricated with the capacity to have their emission modulated by ultrasound. These contrast agent particles could potentially be used in the future to extract fluorescence modulation from a strong light background to increase imaging depth and resolution in scattering media. Fluorescence intensity modulation was demonstrated at the ultrasound driving frequency. 23425273 Clinical development of biosimilars: an evolving landscape. Biosimilars, or similar biological medicinal products, can provide a meaningful option for patients and physicians provided they deliver the therapeutic value of a reference product at a more modest cost. Unlike generic small-molecule drugs that require primarily the demonstration of pharmaceutical equivalence, the complex nature of protein therapeutics warrants a rigorous evaluation of both pharmaceutical and therapeutic equivalence to the reference product in an abbreviated clinical program. Furthermore, the lack of comprehensive structure-activity relationship data increases the burden on appropriately designed human clinical studies with predefined acceptance criteria to demonstrate the absence of clinically meaningful differences between the biosimilar and reference product. Although a number of biosimilar proteins have been approved, especially in Europe, issues on substitutability, extrapolation to other disease indications, and selection of reference standards and comparators, remains to be standardized at a global level. 23462666 Significant Coronary Stenosis in Asymptomatic Chinese With Different Glycemic Status. OBJECTIVE To evaluate coronary artery stenosis in early diabetes or prediabetes asymptomatic of myocardial ischemia in community-dwelling Chinese adults.RESEARCH DESIGN AND METHODS Age- and sex-matched participants with normal glucose regulation (NGR), prediabetes, or diabetes diagnosed within 5 years, asymptomatic of coronary artery disease (CAD), were randomly selected from a community-dwelling Chinese population aged 40-60 years. Dual-source computed tomography coronary angiography was used to evaluate the existence and extent of coronary stenosis, which was considered significant if >50% narrowing of vessel lumen was detected.RESULTS After excluding uninterpretable segments attributable to motion artifacts, a total of 135 participants with NGR, 132 with prediabetes, and 134 with diabetes participated in data analysis. Significant coronary stenosis was detected in 10 (7.4%), 10 (7.6%), and 22 (16.4%) individuals with NGR, prediabetes, and diabetes, respectively (P for trend = 0.029). Diabetes, rather than prediabetes, was associated with a significant 2.34-fold elevated risk [odds ratio (OR) 2.34 (95% CI 1.01-5.43); P = 0.047] of significant coronary stenosis as compared with that associated with NGR. Levels of glucose evaluation were independently and significantly associated with risks of significant coronary stenosis in diabetes. Each 1-SD increase in fasting plasma glucose, 2-h postload plasma glucose, and HbA1c conveyed 2.11-fold, 1.73-fold, and 1.81-fold higher risks of significant coronary stenosis, respectively, after adjustment for other conventional cardiovascular risk factors.CONCLUSIONSUsing a noninvasive CAD diagnostic modality such as dual-source computed tomography coronary angiography, we detected a markedly elevated risk of significant coronary stenosis with early diabetes in asymptomatic Chinese adults. 22849656 NT, NPY and PGP 9.5 presence in myomeytrium and in fibroid pseudocapsule and their possible impact on muscular physiology. The uterine myoma pseudocapsule is a neurovascular bundle surrounding fibroid, containing neuropeptides, probably involved in uterine scar healing. We studied neurotensin (NT), neuropeptide tyrosine (NPY), and protein gene product 9.5 (PGP 9.5) nerve fibres in the pseudocapsule neurovascular bundle of intramural uterine fibroids on 67 no pregnant women by intracapsular myomectomy sparing the neurovascular bundle, sampling full thickness specimens of the pseudocapsule of uterine fibroids (PUF) and normal myometrium (NM) obtained from the fundus uteri (FU) and the uterine body (UB). The samples were sent for histological and immunofluorescent analyses and compared by morphometrical quantification. The Conventional Unit (C.U.) difference of NT, NPY, and PGP 9.5 nerve fibres was statistically analyzed. Our results showed that NT, NPY, and PGP 9.5 neurofibers are almost equally present in PUF as in NM of a no pregnant uterus. As all of these neuropeptides are present in the uterine muscle and can affect muscle contractility, uterine peristalsis and muscular healing. A myomectomy respecting the pseudocapsule neurofibers should facilitate smooth muscle scarring and promote restoration of normal uterine peristalsis with a possible positive influence on fertility. 23462281 The Beneficial Role of Thiamine in Parkinson Disease. Parkinson disease (PD) is the second most common form of neurodegeneration among elderly individuals. PD is clinically characterized by tremors, rigidity, slowness of movement, and postural imbalance. In this paper, we review the evidence for an association between PD and thiamine. Interestingly, a significant association has been demonstrated between PD and low levels of serum thiamine, and thiamine supplements appear to have beneficial clinical effects against PD. Multiple studies have evaluated the connection between thiamine and PD pathology, and candidate pathways involve the transcription factor Sp1, p53, Bcl-2, caspase-3, tyrosine hydroxylase, glycogen synthase kinase-3β, vascular endothelial growth factor, advanced glycation end products, nuclear factor kappa B, mitogen-activated protein kinase, and the reduced form of nicotinamide adenine dinucleotide phosphate. Thus, a review of the literature suggests that thiamine plays a role in PD, although further investigation into the effects of thiamine in PD is needed. 23639992 Microfluidics on liquid handling stations (μF-on-LHS): an industry compatible chip interface between microfluidics and automated liquid handling stations. We describe a generic microfluidic interface design that allows the connection of microfluidic chips to established industrial liquid handling stations (LHS). A molding tool has been designed that allows fabrication of low-cost disposable polydimethylsiloxane (PDMS) chips with interfaces that provide convenient and reversible connection of the microfluidic chip to industrial LHS. The concept allows complete freedom of design for the microfluidic chip itself. In this setup all peripheral fluidic components (such as valves and pumps) usually required for microfluidic experiments are provided by the LHS. Experiments (including readout) can be carried out fully automated using the hardware and software provided by LHS manufacturer. Our approach uses a chip interface that is compatible with widely used and industrially established LHS which is a significant advancement towards near-industrial experimental design in microfluidics and will greatly facilitate the acceptance and translation of microfluidics technology in industry. 23410170 Rationally Designed Multitarget Anti-HIV Agents. Multitarget-directed ligands (MTDLs), an emerging and appealing drug discovery strategy, utilizing a single chemical entity to inhibit multitargets, was confirmed to be effective in reducing the likelihood of drug resistance, diminishing problems of dosing complexity, drug-drug interactions and toxicities, as well as improving patient compliance. The exploration of MTDL strategy should be valuable in anti-HIV drug discovery. In this article, current knowledge and strategies for the rational design of the multitarget and selective anti-HIV agents are described and a number of illustrative examples are given. Moreover, the challenges, limitations and outlook of such novel drug design strategies are also presented, with a goal to highlight the representative paradigms in the rational design of MTDLs, and to help medicinal chemists discover the next generation of multitarget anti-HIV agents. 23400270 Self-templating synthesis of hollow mesoporous silica and their applications in catalysis and drug delivery. Hollow mesoporous silica materials have been intensively pursued because of their unique properties for various applications. Yolk/shell structured hollow mesoporous silica with functional cores inside their hollow interior can further broaden the applications of hollow mesoporous silica. The self-templating strategy has been developed as one of the most important strategies to effectively fabricate hollow mesoporous silicas and their yolk/shell counterparts. In this feature article, we provide an overview of advances in the self-templating synthesis of hollow mesoporous silica based on the following three strategies: surface-protected etching, structural difference-based selective etching, and cationic surfactant assisted self-templating. We then discuss some important applications of these self-templating strategy-derived hollow mesoporous silicas, such as nanoreactors for confined catalysis and multifunctional platforms for combined therapy. Finally, some perspectives for the future development of this active research field are provided. 23248173 TGFβ receptor signaling is essential for inflammation-induced but not β-cell workload-induced β-cell proliferation. Protection and restoration of a functional β-cell mass are fundamental strategies for prevention and treatment of diabetes. Consequently, knowledge of signals that determine the functional β-cell mass is of immense clinical relevance. Transforming growth factor β (TGFβ) superfamily signaling pathways play a critical role in development and tissue specification. Nevertheless, the role of these pathways in adult β-cell homeostasis is not well defined. Here, we ablated TGFβ receptor I and II genes in mice undergoing two surgical β-cell replication models (partial pancreatectomy or partial duct ligation), representing two triggers for β-cell proliferation, increased β-cell workload and local inflammation, respectively. Our data suggest that TGFβ receptor signaling is necessary for baseline β-cell proliferation. By either provision of excess glucose or treatment with exogenous insulin, we further demonstrated that inflammation and increased β-cell workload are both stimulants for β-cell proliferation but are TGFβ receptor signaling dependent and independent, respectively. Collectively, by using a pancreas-specific TGFβ receptor-deleted mouse model, we have identified two distinct pathways that regulate adult β-cell proliferation. Our study thus provides important information for understanding β-cell proliferation during normal growth and in pancreatic diseases. 23418362 The sorting of proglucagon to secretory granules is mediated by carboxypeptidase E and intrinsic sorting signals. Proglucagon is expressed in pancreatic alpha cells, intestinal L cells and brainstem neurons. Tissue-specific processing of proglucagon yields the peptide hormones glucagon in the alpha cell and glucagon-like peptide (GLP)-1 and GLP-2 in L cells. Both glucagon and GLP-1 are secreted in response to nutritional status and are critical for regulating glycaemia. The sorting of proglucagon to the dense-core secretory granules of the regulated secretory pathway is essential for the appropriate secretion of glucagon and GLP-1. We examined the roles of carboxypeptidase E (CPE), a prohormone sorting receptor, the processing enzymes PC1/3 and PC2 and putative intrinsic sorting signals in proglucagon sorting. In Neuro 2a cells that lacked CPE, PC1/3 and PC2, proglucagon co-localised with the Golgi marker p115 as determined by quantitative immunofluorescence microscopy. Expression of CPE, but not of PC1/3 or PC2, enhanced proglucagon sorting to granules. siRNA-mediated knockdown of CPE disrupted regulated secretion of glucagon from pancreatic-derived alphaTC1-6 cells, but not of GLP-1 from intestinal cell-derived GLUTag cells. Mutation of the PC cleavage site K70R71, the dibasic R17R18 site within glucagon or the alpha-helix of glucagon, all significantly affected the sub-cellular localisation of proglucagon. Protein modelling revealed that alpha helices corresponding to glucagon, GLP-1 and GLP-2, are arranged within a disordered structure, suggesting some flexibility in the sorting mechanism. We conclude that there are multiple mechanisms for sorting proglucagon to the regulated secretory pathway, including a role for CPE in pancreatic alpha cells, initial cleavage at K70R71 and multiple sorting signals. 23138333 The effect of copper on different phototrophic microorganisms determined in vivo and at cellular level by confocal laser microscopy. Microbial mats are coastal ecosystems that consist mainly of cyanobacteria, primary producers in these habitats that play an important role in stabilising delta sediments. However, these ecosystems are subject to various kinds of pollution, including metal contamination, placing their survival at risk. Among heavy metals, copper is an essential metal at low doses and toxic at high doses. This metal is present in different pesticides used in rice production, a thriving agro-industry in the Ebro Delta (Spain). For several years, our group has been studying the Ebro Delta microbial mats and has developed a method for determining the effect that metals cause on cyanobacteria populations. This method is based on confocal laser microscopy coupled to a spectrofluorometer, which rapidly provides simultaneous three-dimensional information on photosynthetic microorganisms and their fluorescence spectra profiles. The current study determines the copper effect on different photosynthetic microorganisms from culture collection (Chroococcus sp. PCC 9106 and Spirulina sp. PCC 6313) and isolated from the environment (Microcoleus-like and the microalga DE2009). Comparing all results obtained it can be observed that the minimum dose of Cu that is capable of significantly altering chlorophyll a (chl a) fluorescence intensity were 1 × 10(-7) M in Chroococcus sp. PCC 9106; 1 × 10(-7) M in Spirulina sp. PCC 6313; 3 × 10(-7) M in Microcoleus and 5 × 10(-6) M in the microalga DE2009. Moreover, the sensitivity of the technique used was 1 × 10(-7) M. 23587647 Role of BDNF epigenetics in activity-dependent neuronal plasticity. Brain-derived neurotrophic factor (BDNF) is a key mediator of the activity-dependent processes in the brain that have a major impact on neuronal development and plasticity. Impaired control of neuronal activity-induced BDNF expression mediates the pathogenesis of various neurological and psychiatric disorders. Different environmental stimuli, such as the use of pharmacological compounds, physical and learning exercises or stress exposure, lead to activation of specific neuronal networks. These processes entail tight temporal and spatial transcriptional control of numerous BDNF splice variants through epigenetic mechanisms. The present review highlights recent findings on the dynamic and long-term epigenetic programming of BDNF gene expression by the DNA methylation, histone-modifying and microRNA machineries. The review also summarizes the current knowledge on the activity-dependent BDNF mRNA trafficking critical for rapid local regulation of BDNF levels and synaptic plasticity. Current data open novel directions for discovery of new promising therapeutic targets for treatment of neuropsychiatric disorders. This article is part of a Special Issue entitled 'BDNF'. 23383723 Interactions between Pluronics (F127 and F68) and bile salts (NaTDC) in the aqueous phase and the interface of oil-in-water emulsions. Pluronics are being introduced in food research in order to delay lipid digestion, with the length of hydrophilic and hydrophobic chains playing an important role in the rate of such a process. Since bile salts play a crucial role in the lipid digestion process, the aim of this work is to analyze the interactions between Pluronic F127 or F68 and the bile salt NaTDC when the latter is added at physiological concentrations. These interactions are studied at the Pluronic-covered oil-water interface and in the aqueous phase of Pluronic-stabilized emulsions. This work has been carried out with techniques such as differential scanning calorimetry, interfacial tension, dilatational rheology, and scanning electron microscopy. As a result, Pluronic F127 was shown to be more resistant to displacement by bile salt than F68 at the oil-water interface due to the larger steric hindrance and interfacial coverage provided. In addition, Pluronics have the ability to compete for the oil-water interface and interact in the bulk with the bile salt. Concretely, Pluronic F127 seems to interact with more molecules of bile salt in the bulk, thus hindering their adsorption onto the oil-water interface. As a conclusion, Pluronic F127 affects to a larger extent the ability of bile salt to promote the further cascade of lipolysis in the presence of lipase owing to a combination of interfacial and bulk events. 23315791 N-Boc-protected 1,2-diphenylethylenediamine-based dendritic organogels with multiple-stimulus-responsive properties. A new class of poly(benzyl ether) dendrimers, decorated in their cores with N-Boc-protected 1,2-diphenylethylenediamine groups, were synthesized and fully characterized. It was found that the gelation capability of these dendrimers was highly dependent on dendrimer generation, and the second-generation dendrimer (R,R)-G(2)DPENBoc proved to be a highly efficient organogelator. A number of experiments (SEM, TEM, FTIR spectroscopy, (1)H NMR spectroscopy, rheological measurements, UV/Vis absorption spectroscopy, CD, and XRD) revealed that these dendritic molecules self-assembled into elastically interpenetrating one-dimensional nanostructures in organogels. The hydrogen bonding, π-π, and solvophobic interactions were found to be the main driving forces for formation of the gels. Most interestingly, these dendritic organogels exhibited smart multiple-stimulus-responsive behavior upon exposure to environmental stimuli such as temperature, anions, and mechanical stress. 23514599 GC-Targeted C8-Linked Pyrrolobenzodiazepine-Biaryl Conjugates with Femtomolar in Vitro Cytotoxicity and in Vivo Antitumor Activity in Mouse Models. DNA binding 4-(1-methyl-1H-pyrrol-3-yl)benzenamine (MPB) building blocks have been developed that span two DNA base pairs with a strong preference for GC-rich DNA. They have been conjugated to a pyrrolo[2,1-c][1,4]benzodiazepine (PBD) molecule to produce C8-linked PBD-MPB hybrids that can stabilize GC-rich DNA by up to 13-fold compared to AT-rich DNA. Some have subpicomolar IC50 values in human tumor cell lines and in primary chronic lymphocytic leukemia cells, while being up to 6 orders less cytotoxic in the non-tumor cell line WI38, suggesting that key DNA sequences may be relevant targets in these ultrasensitive cancer cell lines. One conjugate, 7h (KMR-28-39), which has femtomolar activity in the breast cancer cell line MDA-MB-231, has significant dose-dependent antitumor activity in MDA-MB-231 (breast) and MIA PaCa-2 (pancreatic) human tumor xenograft mouse models with insignificant toxicity at therapeutic doses. Preliminary studies suggest that 7h may sterically inhibit interaction of the transcription factor NF-κB with its cognate DNA binding sequence. 23612720 Control of one-dimensional magnetism in graphene via spontaneous hydrogenation of the grain boundary. We propose that control of one-dimensional (1D) magnetism in graphene could be made easier by spontaneous hydrogenation of chemically reactive grain boundaries (GBs) in polycrystalline graphenes. Unlike pristine graphene, where hydrogen adsorption favors the formation of zero-dimensional (0D) clusters, the defect cores (pentagon, heptagon and octagon) at the GBs in polycrystalline graphene promote hydrogenation along the GBs. The hydrogenation in polycrystalline graphene starts at the GBs, proceeds gradually towards the grain interior (GI) and results in smooth 1D graphane-graphene interfaces. Our calculations show that the type (ferro- or antiferro-magnetism) and strength of the magnetism can be controlled by controlling the orientation of GBs. Since GBs in single-layer graphenes can be fabricated in a controllable way in experiments, the hydrogenation of GBs could be a unique method to realize large-area magnetic graphenes for future spintronic applications. 22303963 Determination of three steroidal saponins from Ophiopogon japonicus (Liliaceae) via high-performance liquid chromatography with mass spectrometry. A simple and accurate analytical method was developed for simultaneous quantification of three steroidal saponins in the roots of Ophiopogon japonicus via high-performance liquid chromatography (HPLC) with mass spectrometry (MS) in this study. Separation was performed on a Tigerkin C(18) column and detection was performed by mass spectrometry. A mobile phase consisted of 0.02% formic acid in water (v/v) and 0.02% formic acid in acetonitrile (v/v) was used with a flow rate of 0.5 mL min(-1). The quantitative HPLC-MS method was validated for linearity, precision, repeatability, stability, recovery, limits of detection and quantification. This developed method provides good linearity (r >0.9993), intra- and inter-day precisions (RSD <4.18%), repeatability (RSD <5.05%), stability (RSD <2.08%) and recovery (93.82-102.84%) for three steroidal saponins. It could be considered as a suitable quality control method for O. japonicus. 23542440 Sensitization of restraint-induced corticosterone secretion after chronic restraint in rats: Involvement of 5-HT7 receptors. Serotonin (5-HT) modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress. We examined the effect of chronic restraint stress (CRS; 20 min/day) as compared to control (CTRL) conditions for 14 days, on: 1) restraint-induced ACTH and corticosterone (CORT) secretion in rats pretreated with vehicle or SB-656104 (a 5-HT7 receptor antagonist); 2) 5-HT7 receptor-like immunoreactivity (5-HT7-LI) and protein in the hypothalamic paraventricular nucleus (PVN) and adrenal glands (AG); 3) baseline levels of 5-HT and 5-hydroxyindolacetic acid (5-HIAA), and 5-HIAA/5-HT ratio in PVN and AG; and 4) 5-HT-like immunoreactivity (5-HT-LI) in AG and tryptophan hydroxylase (TPH) protein in PVN and AG. On day 15, animals were subdivided into Treatment and No treatment groups. Treatment animals received an i.p. injection of vehicle or SB-656104; No Treatment animals received no injection. Sixty min later, Treatment animals were either decapitated with no further stress (0 min) or submitted to acute restraint (10, 30, 60 or 120 min); hormone serum levels were measured. No Treatment animals were employed for the rest of measurements. CRS decreased body weight gain and increased adrenal weight. In CTRL animals, acute restraint increased ACTH and CORT secretion in a time of restraint-dependent manner; both responses were inhibited by SB-656104. Exposure to CRS abolished ACTH but magnified CORT responses to restraint as compared to CTRL conditions; SB-656104 had no effect on ACTH levels but significantly inhibited sensitized CORT responses. In CTRL animals, 5-HT7-LI was detected in magnocellular and parvocellular subdivisions of PVN and sparsely in adrenal cortex. Exposure to CRS decreased 5-HT7-LI and protein in the PVN, but increased 5-HT7-LI in the adrenal cortex and protein in whole AG. Higher 5-HT and 5-HIAA levels were detected in PVN and AG from CRS animals but 5-HIAA/5-HT ratio increased in AG only. Finally, whereas 5-HT-LI was sparsely observed in the adrenal cortex of CTRL animals, it strongly increased in the adrenal cortex of CRS animals. No TPH protein was detected in AG from both animal groups. Results suggest that CRS promotes endocrine disruption involving decreased ACTH and sensitized CORT responses to acute restraint. This phenomenon may be associated with increased function and expression of 5-HT7 receptors as well as 5-HT turnover in AG. 23395957 Cellular Mechanisms of Nociceptin/Orphanin FQ (N/OFQ) Peptide (NOP) Receptor Regulation and Heterologous Regulation by N/OFQ. The nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor is the fourth and most recently discovered member of the opioid receptor superfamily that also includes μ, δ, and κ opioid receptor subtypes (MOR, DOR, and KOR, respectively). The widespread anatomic distribution of the NOP receptor enables the modulation of several physiologic processes by its endogenous agonist, N/OFQ. Accordingly, the NOP receptor has gained a lot of attention as a potential target for the development of ligands with therapeutic use in several pathophysiological states. NOP receptor activation frequently results in effects opposing classic opioid receptor action; therefore, regulation of the NOP receptor and conditions affecting its modulatory tone are important to understand. Mounting evidence reveals a heterologous interaction of the NOP receptor with other G protein-coupled receptors, including MOR, DOR, and KOR, which may subsequently influence their function. Our focus in this review is to summarize and discuss the findings that delineate the cellular mechanisms of NOP receptor signaling and regulation and the regulation of other receptors by N/OFQ and the NOP receptor. 23604719 Simultaneous determination of five flavonoids during the growth of Fructus Sophorae by capillary electrophoresis. A method of simultaneous determination of five flavonoids during the growth of Fructus Sophorae by β-cyclodextrin (β-CD-) modified capillary zone electrophoresis was developed. The effects of various parameters such as buffer concentration, pH, applied voltage, and β-CD concentrations were investigated. After a series of optimization processes, the determination of five flavonoids in Fructus Sophorae was successfully achieved in 20 mmol/L borax buffer (pH 9.5), 25 kV applied voltage, and 8 mmol/L β-CD. The linearity, detection limits, repeatability, and recovery were satisfactory. Thus, the proposed β-CD-modified capillary zone electrophoresis method was satisfactorily used to analyze Fructus Sophorae samples. The results can be useful for the quality control and medicinal resource development of Fructus Sophorae. 23339480 Dendrimer and cancer: a patent review (2006-present). INTRODUCTION: Dendrimers were widely used in cancer diagnosis and therapy during the past decade. The surface functionalities allow bioactive molecules such as imaging probes, therapeutic compounds, targeting ligands to be present on dendrimer surface in a multivalent fashion. In addition, the interior pockets as well as the charged surface of dendrimer can be encapsulated/bound with anti-cancer drugs or therapeutic DNAs/siRNAs. AREAS COVERED: The combination of dendrimer chemistry and new cancer therapy techniques such as radiotherapy, photodynamic therapy, neuron capture therapy, and photothermal therapy provides promising strategies in future cancer therapy. Here, we focused on recent advances on this topic in the patents (2006 - present) and discussed the advantages of dendrimer technology in these inventions. EXPERT OPINION: The challenges and perspectives of dendrimer-based theranostics for cancer diagnosis and therapy are discussed. Future efforts in this area should be focused on designing materials to solve problems such as cancer metastasis, multidrug resistance (MDR) in cancer cells, and early-stage cancer diagnosis. 23221633 Novel Smad proteins localize to IR-induced double-strand breaks: interplay between TGFβ and ATM pathways. Cellular damage from ionizing radiation (IR) is in part due to DNA damage and reactive oxygen species, which activate DNA damage response (DDR) and cytokine signaling pathways, including the ataxia telangiectasia mutated (ATM) and transforming growth factor (TGF)β/Smad pathways. Using classic double-strand breaks (DSBs) markers, we studied the roles of Smad proteins in DDR and the crosstalk between TGFβ and ATM pathways. We observed co-localization of phospho-Smad2 (pSmad2) and Smad7 with DSB repair proteins following low and high linear energy transfer (LET) radiation in human fibroblasts and epithelial cells. The decays of both foci were similar to that of γH2AX foci. Irradiation with high LET particles induced pSmad2 and Smad7 foci tracks indicating the particle trajectory through cells. pSmad2 foci were absent in S phase cells, while Smad7 foci were present in all phases of cell cycle. pSmad2 (but not Smad7) foci were completely abolished when ATM was depleted or inactivated. In contrast, a TGFβ receptor 1 (TGFβR1) inhibitor abrogated Smad7, but not pSmad2 foci at DSBs sites. In summary, we suggest that Smad2 and Smad7 contribute to IR-induced DSB signaling in an ATM or TGFβR1-dependent manner, respectively. 23364615 Adsorption and Self-Assembly of Large Polycyclic Molecules on the Surfaces of TiO2 Single Crystals. Titanium dioxide is one of the most frequently studied metal oxides, and its (110) rutile surface serves as a prototypical model for the surface science of such materials. Recent studies have also shown that the (011) surface is relatively easy for preparation in ultra-high vacuum (UHV) and that both the (110) and (011) surfaces could be precisely characterized using scanning tunneling microscopy (STM). The supramolecular self-assembly of organic molecules on the surfaces of titanium dioxide plays an important role in nanofabrication, and it can control the formation and properties of nanostructures, leading to wide range of applications covering the fields of catalysis, coatings and fabrication of sensors and extends to the optoelectronic industry and medical usage. Although the majority of experiments and theoretical calculations are focused on the adsorption of relatively small organic species, in recent years, there has been increasing interest in the properties of larger molecules that have several aromatic rings in which functional units could also be observed. The purpose of this review is to summarize the achievements in the study of single polycyclic molecules and thin layers adsorbed onto the surfaces of single crystalline titanium dioxide over the past decade. 23471029 Controlled formation of mono- and dihydroxy-resolvins from EPA and DHA using soybean 15-lipoxygenase. Resolvins and protectins are important anti-inflammatory and pro-resolution compounds derived from the enzymatic oxidation of omega-3 fatty acids all-cis-5,8,11,14,17-eicosapentaenoic acid (EPA) and all-cis-4,7,10,13,16,19-docosahexaenoic acid (DHA). We have developed a simple, controlled method to synthesize an array of resolvin and protectin analogs from fatty acid starting materials using soybean 15-lipoxygenase. The conditions were optimized for the production of both mono- and dihydroxy derivatives, with enzyme concentration and pH found to have a significant effect on the reaction products. The methods were applied to five biologically important omega-3 and omega-6 fatty acid substrates. Mono- and dihydroxy compounds were successfully synthesized from all substrates and the products were characterized by normal phase (NP) HPLC, GC-MS, TOF-MS, UV-visible (UV-vis) spectroscopy, and NMR spectroscopy. The methods could be further applied to any polyunsaturated fatty acids containing the cis-1,4,7,10-undecatetraene moiety to produce a range of novel compounds with potential biological activity. 23103282 Social networks, web-based tools and diseases: implications for biomedical research. Advances in information technology have improved our ability to gather, collect and analyze information from individuals online. Social networks can be seen as a nonlinear superposition of a multitude of complex connections between people where the nodes represent individuals and the links between them capture a variety of different social interactions. The emergence of different types of social networks has fostered connections between individuals, thus facilitating data exchange in a variety of fields. Therefore, the question posed now is "can these same tools be applied to life sciences in order to improve scientific and medical research?" In this article, I will review how social networks and other web-based tools are changing the way we approach and track diseases in biomedical research. 23377115 Evaluation of genotoxic effects of five flavour enhancers (glutamates) on the root meristem cells of Allium cepa. The effects of different treatments with flavour enhancers monosodium glutamate, monopotassium glutamate, calcium diglutamate, monoammonium glutamate, and magnesium diglutamate on the cytology, DNA content, and interphase nuclear volume (INV) of A. cepa were investigated. Three concentrations of these additives - 20, 40, and 60 ppm - were applied for 6, 12, and 24 h. All the concentrations of these chemicals showed an inhibitory effect on cell division in root tips of A. cepa and caused a decrease in mitotic index values. Additionally, all the treatments changed the frequency of mitotic phases when compared with the control groups. These compounds increased chromosome abnormalities, among them are micronuclei, c-mitosis, anaphase bridges, stickiness, binucleus, laggards, and breaks. The nuclear DNA content and INV decreased when compared with control groups. 23111885 Low cytotoxic elastic niosomes loaded with salmon calcitonin on human skin fibroblasts. A low cytotoxic elastic niosomal formulation loaded with salmon calcitonin was developed. The elastic niosomes were prepared from Tween 61 mixed with cholesterol at various concentrations of the edge activators (sodium cholate (NaC) and sodium deoxycholate (NaDC); 0.25, 0.5, 2.5, 5 and 10% mole) or ethanol (10-30% v/v). The effects of the niosomal concentrations (5, 10 and 20 mM) and phosphate buffer at pH 7.0 (5, 10, 20 and 30 mM) on the physical characteristics of niosomes were investigated. The 5 mM elastic niosomes in 5 mM phosphate buffer containing calcitonin 0.22 mg/mL gave the highest elasticity (deformability index (DI)) at 6.79 ± 2.03 determined by the extrusion method. The blank elastic niosomes comprised 2.5% mole NaDC, 5% mole NaC or 20% v/v ethanol showed the highest elasticity. The 5% mole NaC elastic niosomes loaded with calcitonin gave the highest DI (21.59 ± 0.91) and percentages of calcitonin entrapment efficiency (60.11 ± 4.98). This study has demonstrated that this NaC elastic niosome did not only reduce the cytotoxicity of the loaded calcitonin but also gave superior cell viability to the ethanolic elastic niosome as well. 23545002 Ultralow friction induced by tribochemical reactions: a novel mechanism of lubrication on steel surfaces. The tribological properties of two steel surfaces rubbing against each other are measured while they are in contact with 1,3-diketones of varying structure. Such systems show after a short running-in period ultralow friction properties with a coefficient of friction of as low as μ = 0.005. It is suggested that the extremely favorable friction properties are caused by a tribochemical reaction between the 1,3-diketones and the steel surfaces, leading to formation of a chelated iron-diketo complex. The influence of temperature and the molecular structure of the 1,3 diketo-lubricants onto the friction properties of the system is elucidated under both static and dynamic conditions. With progression of the tribochemical reaction, the sliding surfaces become very conformal and smooth, so that the pressure is greatly reduced and further wear is strongly reduced. All iron particles potentially generated by wear during the initial running-in period are completely dissolved through complex formation. It is proposed that the tribochemical polishing reaction causes a transition from boundary lubrication to fluid lubrication. 22992330 Genetic correlate of cognitive training response in schizophrenia. Intensive computerized auditory training results in improved cognition for schizophrenia patients, but participants show variation in their cognitive gains and the biological factors that affect the response to training are unknown. Single nucleotide polymorphisms (SNPs) in the catechol-O-methyltransferase (COMT) gene have been related to cognitive function. Here we asked if functional variation in this gene has an impact on the response of schizophrenia patients to cognitive training. We genotyped 48 schizophrenia patients who completed 50 h of computerized cognitive training and analyzed the association between DNA variants in the COMT gene and the improvement in global cognition. Although conventional analyses did not reveal any significant associations, a set-based analysis examining the aggregate effect of common variation in the COMT gene (42 SNPs) suggested association with improvement in global cognition. Eight SNPs, mostly located in the 3' end of the COMT gene, were nominally associated with improvement in cognition. These data suggest that genotype influences the response to intensive cognitive training in schizophrenia, and may indicate that cognitive training regimens need to be personalized to the underlying biosignatures of each individual patient. This article is part of a Special Issue entitled 'Cognitive Enhancers'. 23608241 The effect of mitragynine on cAMP formation and mRNA expression of mu-opioid receptors mediated by chronic morphine treatment in SK-N-SH neuroblastoma cell. ETHOPHARMACOLOGICAL RELEVANCE: Mitragynine is an indole alkaloid compound of Mitragyna speciosa (M. speciosa) Korth. (Rubiaceae). This plant is native to the southern regions of Thailand and northern regions of Malaysia and is frequently used to manage the withdrawal symptoms in both countries. AIM OF STUDY: To investigate the effect of mitragynine after chronic morphine treatment on cyclic AMP (cAMP) level and mRNA expression of mu-opioid receptor (MOR) in human neuroblastoma SK-N-SH cell. METHOD AND MATERIALS: Mitragynine was isolated from the Mitragyna speciosa plant using the acid-base extraction method. The cAMP level upon forskolin stimulation in the cells was determined using the Calbiochem(®) Direct Immunoassay Kit. The mRNA expression of the MOR was carried out using quantitative RT-PCR. RESULT: Cotreatment and pretreatment of morphine and mitragynine significantly reduced the production of cAMP level at a lower concentration of nitrogen while the higher concentration of this compound could lead to the development of tolerance and dependence as shown by the increase of the cAMP level production in foskolin stimulation. In MOR mRNA expression study, cotreatment of morphine with mitragynine significantly reduced the down-regulation of MOR mRNA expression as compared to morphine treatment only. CONCLUSION: These finding suggest that mitragynine could possibly avoid the tolerance and dependence on chronic morphine treatment by reducing the up-regulation of cAMP level as well as reducing the down-regulation of MOR at a lower concentration of mitragynine. 23323677 Synthesis, characterization, and cure chemistry of renewable bis(cyanate) esters derived from 2-methoxy-4-methylphenol. A series of renewable bis(cyanate) esters have been prepared from bisphenols synthesized by condensation of 2-methoxy-4-methylphenol (creosol) with formaldehyde, acetaldehyde, and propionaldehyde. The cyanate esters have been fully characterized by infrared spectroscopy, (1)H and (13)C NMR spectroscopy, and single crystal X-ray diffraction. These compounds melt from 88 to 143 °C, while cured resins have glass transition temperatures from 219 to 248 °C, water uptake (96 h, 85 °C immersion) in the range of 2.05-3.21%, and wet glass transition temperatures from 174 to 193 °C. These properties suggest that creosol-derived cyanate esters may be useful for a wide variety of military and commercial applications. The cure chemistry of the cyanate esters has been studied with FTIR spectroscopy and differential scanning calorimetry. The results show that cyanate esters with more sterically demanding bridging groups cure more slowly, but also more completely than those with a bridging methylene group. In addition to the structural differences, the purity of the cyanate esters has a significant effect on both the cure chemistry and final Tg of the materials. In some cases, post-cure of the resins at 350 °C resulted in significant decomposition and off-gassing, but cure protocols that terminated at 250-300 °C generated void-free resin pucks without degradation. Thermogravimetric analysis revealed that cured resins were stable up to 400 °C and then rapidly degraded. TGA/FTIR and mass spectrometry results showed that the resins decomposed to phenols, isocyanic acid, and secondary decomposition products, including CO2. Char yields of cured resins under N2 ranged from 27 to 35%, while char yields in air ranged from 8 to 11%. These data suggest that resins of this type may potentially be recycled to parent phenols, creosol, and other alkylated creosols by pyrolysis in the presence of excess water vapor. The ability to synthesize these high temperature resins from a phenol (creosol) that can be derived from lignin, coupled with the potential to recycle the composites, provides a possible route to the production of sustainable, high-performance, thermosetting resins with reduced environmental impact. 23562075 Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Mitochondrial fusion, fission, and mitophagy form an essential axis of mitochondrial quality control. However, quality control might not be the only task carried out by mitochondrial dynamics. Recent studies link mitochondrial dynamics to the balance between energy demand and nutrient supply, suggesting changes in mitochondrial architecture as a mechanism for bioenergetic adaptation to metabolic demands. By favoring either connected or fragmented architectures, mitochondrial dynamics regulates bioenergetic efficiency and energy expenditure. Placement of bioenergetic adaptation and quality control as competing tasks of mitochondrial dynamics might provide a new mechanism, linking excess nutrient environment to progressive mitochondrial dysfunction, common to age-related diseases. 23360619 The relative protein abundance of UGT1A alternative splice variants as a key determinant of glucuronidation activity in vitro. Alternative splicing (AS) is one of the most significant components of the functional complexity of human UDP-glucuronosyltransferase enzymes (UGTs), particularly for the UGT1A gene, which represents one of the best examples of a drug-metabolizing gene regulated by AS. Shorter UGT1A isoforms [isoform 2 (i2)] are deficient in glucuronic acid transferase activity but function as negative regulators of enzyme activity through protein-protein interaction. Their abundance, relative to active UGT1A enzymes, is expected to be a determinant of the global transferase activity of cells and tissues. Here we tested whether i2-mediated inhibition increases with greater abundance of the i2 protein relative to the isoform 1 (i1) enzyme, using the extrahepatic UGT1A7 as a model and a series of 23 human embryonic kidney 293 clonal cell lines expressing variable contents of i1 and i2 proteins. Upon normalization for i1, a significant reduction of 7-ethyl-10-hydroxycamptothecin glucuronide formation was observed for i1+i2 clones (mean of 53%) compared with the reference i1 cell line. In these clones, the i2 protein content varied greatly (38-263% relative to i1) and revealed two groups: 17 clones with i2 < i1 (60% ± 3%) and 6 clones with i2 ≥ i1 (153% ± 24%). The inhibition induced by i2 was more substantial for clones displaying i2 ≥ i1 (74.5%; P = 0.001) compared with those with i2 < i1 (45.5%). Coimmunoprecipitation supports a more substantial i1-i2 complex formation when i2 exceeds i1. We conclude that the relative abundance of regulatory i2 proteins has the potential to drastically alter the local drug metabolism in the cells, particularly when i2 surpasses the protein content of i1. 23403080 Synthesis and anti-Candida activity of novel 2-hydrazino-1,3-thiazole derivatives. Eighteen new hydrazino-1,3-thiazole derivatives were evaluated against 8 strains of multi-resistant Candida spp. Introduction of an indolyl moiety linked to the hydrazone function enhanced the in vitro anti-Candida activity, with an activity spectrum towards Candida albicans strains. Introduction of a (S)-2-aminoethyl chain on the thiazole nucleus largely enhanced the in vitro antifungal activity, with a selectivity oriented towards non-C. albicans species. 23577749 In vitro antimicrobial activity of 20 selected climber species from the Bignoniaceae family. Hydroalcoholic and aqueous extracts of some climber species from the Bignoniaceae family that grow in the north of Argentina were evaluated for in vitro antibacterial activity against Gram-positive and Gram-negative strains. By means of bioautography and disc diffusion methods, it could be determined that all infusions were not active, whereas the hydroalcoholic extracts of seven species were able to inhibit bacterial growth. The minimum inhibitory concentration and minimum bactericidal concentration observed were between 62.5 and 1000 μg gallic acid equivalent (GAE)/mL and between 125 and 1000 μg GAE/mL, respectively. The tested extracts were more active against Gram-positive microorganisms. Time-kill experiments indicated that all extracts have bacteriostatic activity. Phytochemical screening showed the presence of terpenoids, phenols and flavonoids. The amount of phenolic compounds and flavonoids was higher in tinctures when compared with infusions. These results suggest the presence of antibacterial substances in the hydroalcoholic extracts, which could be used for the treatment of infections. 22961200 A convective replica-exchange method for sampling new energy basins. Replica-exchange is a powerful simulation method for sampling the basins of a rugged energy landscape. The replica-exchange method's sampling is efficient because it allows replicas to perform round trips in temperature space, thereby visiting both low and high temperatures in the same simulation. However, replicas have a diffusive walk in temperature space, and the round trip rate decreases significantly with the system size. These drawbacks make convergence of the simulation even more difficult than it already is when bigger systems are tackled. Here, we present a simple modification of the exchange method. In this method, one of the replicas steadily raises or lowers its temperature. We tested the convective replica-exchange method on three systems of varying complexity: the alanine dipeptide in implicit solvent, the GB1 β-hairpin in explicit solvent and the Aβ(25-35) homotrimer in a coarse grained representation. For the highly frustrated Aβ(25-35) homotrimer, the proposed "convective" replica-exchange method is twice as fast as the standard method. It discovered 24 out of 27 free-energy basins in less than 500 ns. It also prevented the formation of groups of replicas that usually form on either side of an exchange bottleneck, leading to a more efficient sampling of new energy basins than in the standard method. 23249338 Light-harvesting and ultrafast energy migration in porphyrin-based metal-organic frameworks. Given that energy (exciton) migration in natural photosynthesis primarily occurs in highly ordered porphyrin-like pigments (chlorophylls), equally highly ordered porphyrin-based metal-organic frameworks (MOFs) might be expected to exhibit similar behavior, thereby facilitating antenna-like light-harvesting and positioning such materials for use in solar energy conversion schemes. Herein, we report the first example of directional, long-distance energy migration within a MOF. Two MOFs, namely F-MOF and DA-MOF that are composed of two Zn(II) porphyrin struts [5,15-dipyridyl-10,20-bis(pentafluorophenyl)porphinato]zinc(II) and [5,15-bis[4-(pyridyl)ethynyl]-10,20-diphenylporphinato]zinc(II), respectively, were investigated. From fluorescence quenching experiments and theoretical calculations, we find that the photogenerated exciton migrates over a net distance of up to ~45 porphyrin struts within its lifetime in DA-MOF (but only ~3 in F-MOF), with a high anisotropy along a specific direction. The remarkably efficient exciton migration in DA-MOF is attributed to enhanced π-conjugation through the addition of two acetylene moieties in the porphyrin molecule, which leads to greater Q-band absorption intensity and much faster exciton-hopping (energy transfer between adjacent porphyrin struts). The long distance and directional energy migration in DA-MOF suggests promising applications of this compound or related compounds in solar energy conversion schemes as an efficient light-harvesting and energy-transport component. 23464618 Photoexcitation dynamics of coupled semiconducting carbon nanotube thin films. Carbon nanotubes are a promising means of capturing photons for use in solar cell devices. We time-resolved the photoexcitation dynamics of coupled, bandgap-selected, semiconducting carbon nanotubes in thin films tailored for photovoltaics. Using transient absorption spectroscopy and anisotropy measurements, we found that the photoexcitation evolves by two mechanisms with a fast and long-range component followed by a slow and short-range component. Within 300 fs of optical excitation, 20% of nanotubes transfer their photoexcitation over 5-10 nm into nearby nanotube fibers. After 3 ps, 70% of the photoexcitation resides on the smallest bandgap nanotubes. After this ultrafast process, the photoexcitation continues to transfer on a ∼10 ps time scale but to predominantly aligned tubes. Ultimately the photoexcitation hops twice on average between fibers. These results are important for understanding the flow of energy and charge in coupled nanotube materials and light-harvesting devices. 23544698 Theoretical Strategy to Build Structural Models of Microhydrated Inorganic Systems for the Knowledge of Their Vibrational Properties: The Case of the Hydrated Nitrate Aerosols. This study provides theoretical anharmonic calculations for microhydrated NaNO3-labeled (NaNO3, nH2O)x with a water-to-solute ratio (n) ranging from 1 to 3. A representative geometrical model of these forms was first investigated by simulating the molecular clusters as (NaNO3,1H2O)x with x = 1 to 4. The comparison between the calculated time independent anharmonic frequencies using the B3LYP-D/6-311+G(d,p) method and their experimental counterparts led to the choice of a supercluster model. The most probable structures of (NaNO3,nH2O)3 molecular system were investigated by using our global search algorithm we developed recently (GSAM code) both at the B3LYP/6-311+G(d,p) and the B3LYP-D/6-311+G(d,p) levels of theory. The quality of the structural model is illustrated by comparing the B3LYP/6-311+G(d,p) and B3LYP-D/6-311+G(d,p) anharmonic vibrational signatures with those obtained from IR experiments. While an average deviation of 16 cm(-1) is observed in the case of the B3LYP computations, the deviation is reduced to 7 cm(-1) for the B3LYP-D computations. 23380520 Early steps of double-strand break repair in Bacillus subtilis. All organisms rely on integrated networks to repair DNA double-strand breaks (DSBs) in order to preserve the integrity of the genetic information, to re-establish replication, and to ensure proper chromosomal segregation. Genetic, cytological, biochemical and structural approaches have been used to analyze how Bacillus subtilis senses DNA damage and responds to DSBs. RecN, which is among the first responders to DNA DSBs, promotes the ordered recruitment of repair proteins to the site of a lesion. Cells have evolved different mechanisms for efficient end processing to create a 3'-tailed duplex DNA, the substrate for RecA binding, in the repair of one- and two-ended DSBs. Strand continuity is re-established via homologous recombination (HR), utilizing an intact homologous DNA molecule as a template. In the absence of transient diploidy or of HR, however, two-ended DSBs can be directly re-ligated via error-prone non-homologous end-joining. Here we review recent findings that shed light on the early stages of DSB repair in Firmicutes. 23245512 Synthesis of acylated glycoconjugates as templates to investigate in vitro biopharmaceutical properties. A series of novel glycopyranosyl azides were synthesised wherein the carbohydrate moiety was peracylated with four acetyl, propionyl, butanoyl, pentanoyl (valeryl) or 3-methylbutanoyl (isovaleryl) ester linked groups. A panel of glycoconjugates was synthesised from these glycopyranosyl azides using copper-catalysed azide-alkyne cycloaddition. The in vitro metabolic stability, plasma stability and plasma protein binding was then measured to establish the impact of the different acyl group when presented on a common scaffold. The acetyl, propionyl and butanoyl esters exhibited metabolism consistent with esterase processing, and various mono-, di- and tri-acylated hydrolysis products as well as the fully hydrolysed compound were detected. In contrast, the pentanoyl and 3-methylbutanoyl esters were stable. 23446230 CYP2J2 overexpression increases EETs and protects against angiotensin II-induced abdominal aortic aneurysm in mice. Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acids to form epoxyeicosatrienoic acids (EETs), which possess various beneficial effects on the cardiovascular system. However, whether increasing EETs production by CYP2J2 overexpression in vivo could prevent abdominal aortic aneurysm (AAA) remains unknown. Here we investigated the effects of recombinant adeno-associated virus (rAAV)-mediated CYP2J2 overexpression on angiotensin (Ang) II-induced AAA in apoE-deficient mice. rAAV-CYP2J2 delivery led to an abundant aortic CYP2J2 expression and increased EETs generation. It was shown that CYP2J2 overexpression attenuated matrix metalloproteinase expression and activity, elastin degradation, and AAA formation, which was associated with reduced aortic inflammation and macrophage infiltration. In cultured vascular smooth muscle cells (VSMCs), rAAV-mediated CYP2J2 overexpression and EETs markedly suppressed Ang II-induced inflammatory cytokine expression. Moreover, overexpressed CYP2J2 and EETs inhibited Ang II-induced macrophage migration in a VSMC-macrophage coculture system. We further indicated that these protective effects were mediated by peroxisome proliferator-activated receptor (PPAR)γ activation. Taken together, these results provide evidence that rAAV-mediated CYP2J2 overexpression prevents AAA development which is likely via PPARγ activation and anti-inflammatory action, suggesting that increasing EETs levels could be considered as a potential strategy to prevent and treat AAA. 23561140 Changes in polyphenol content during production of grape juice concentrate. The production of grape juice concentrate on an industrial scale was evaluated and samples from the main steps of processing have been collected and analyzed. The sampling steps included the selection and washing of grapes (Nevsehir Patlak variety), pressing in order to obtain the juice separate from the seed and the skin fraction, pasteurization, clarification, filtration, evaporation, and filling-packing at 27°C with a Brix of 45°. Samples from each of the processing steps were analyzed by a number of spectrophotometric analyses. A series of anthocyanin compounds was identified using HPLC-MS, and the fate of anthocyanins, quercetin rutinoside and procyanidins was followed using HPLC. The results indicate that the removal of seed and fruit skin removes most of the procyanidins and anthocyanins, while subsequent clarification and filtration treatments further reduce the anthocyanin content. 23201331 Protective effects of sweroside on human MG-63 cells and rat osteoblasts. Herbal Fructus Corni is a folk medicine with a long history of safe use for treating osteoporosis in postmenopausal women or elderly men in Asia. Sweroside is a bioactive herbal ingredient isolated from Fructus Corni, which has been widely used for the treatment of osteoporosis in traditional Chinese medicine (TCM). Unfortunately, the working mechanisms of this compound are difficult to determine and thus remain unclear. The aim of the study was performed to determine the potential molecular mechanism of the anti-osteoporotic effect of sweroside on the human MG-63 cells and rat osteoblasts. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used to observe the effect of sweroside on cell proliferation. The activity of alkaline phosphatase (ALP) and the amount of osteocalcin were also assayed the cell differentiation. Sweroside significantly increased the proliferation of human MG-63 cells and rat osteoblasts (P<0.01). It increased the activity of ALP, and osteocalcin was also elevated in response to sweroside (P<0.05). Of note, flowcytometer assay showed that sweroside can attenuate and inhibit apoptosis. Sweroside has a direct osteogenic effect on the proliferation and differentiation of cultured human MG-63 cells and rat osteoblasts in vitro. These data will help in understanding the molecular mechanisms of therapeutic efficacy of sweroside, and highlight insights into drug discovery. In the current study, sweroside has been suggested to be a promising osteoporosis therapeutic natural product. 23058997 Non-enzymatic proteins from snake venoms: a gold mine of pharmacological tools and drug leads. Non-enzymatic proteins from snake venoms play important roles in the immobilization of prey, and include some large and well-recognized families of toxins. The study of such proteins has expanded not only our understanding of venom toxicity, but also the knowledge of normal and disease states in human physiology. In many cases their characterization has led to the development of powerful research tools, diagnostic techniques, and pharmaceutical drugs. They have further yielded basic understanding of protein structure-function relationships. Therefore a number of studies on these non-enzymatic proteins had major impact on several life science and medical fields. They have led to life-saving therapeutics, the Nobel prize, and development of molecular scalpels for elucidation of ion channel function, vasoconstriction, complement system activity, platelet aggregation, blood coagulation, signal transduction, and blood pressure regulation. Here, we identify research papers that have had significant impact on the life sciences. We discuss how these findings have changed the course of science, and have also included the personal recollections of the original authors of these studies. We expect that this review will provide impetus for even further exciting research on novel toxins yet to be discovered. 23639192 Puerarin stimulates proliferation and differentiation and protects against cell death in human osteoblastic MG-63 cells via ER-dependent MEK/ERK and PI3K/Akt activation. Puerarin, the main isoflavone glycoside found in the Chinese herb radix of Pueraria lobata (Willd.) Ohwi, has received increasing attention because of its possible role in the prevention of osteoporosis. Previously, we showed that puerarin could inhibit the bone absorption of osteoclasts and promote long bone growth in fetal mouse in vitro. Further study confirmed that puerarin stimulated proliferation and differentiation of osteoblasts in rat. However, the mechanisms underlying its actions on human bone cells have not been well defined. Here we show that puerarin increases proliferation and differentiation and opposes cisplatin-induced apoptosis in human osteoblastic MG-63 cells containing two estrogen receptor (ER) isoforms. Puerarin promotes proliferation by altering cell cycle distribution whereas puerarin-mediated survival may be associated with up-regulation of Bcl-xL expression. Treatment with the ER antagonist ICI 182,780 abolishes the above actions of puerarin on osteoblast-derived cells. Using small interfering double-stranded RNA technology, we further demonstrate that the effects of puerarin on proliferation, differentiation and survival are mediated by both ERα and ERβ. Moreover, we also demonstrate that puerarin functions at least partially through activation of MEK/ERK and PI3K/Akt signaling. This agent also shows much weaker effect on breast epithelial cell growth than that of estrogen. Therefore, puerarin will be a promising agent that prevents or retards osteoporosis. 23529894 Biomimetic Synthesis and Studies Toward Enantioselective Synthesis of Flindersial Alkaloids. A strategy allowing both stereocontrol and control over structural isomer formation has been defined for the antimalarial flindersial alkaloids. The recently reported flinderoles were demonstrated to be derived from the natural product borrerine. The structural isomers of flinderoles, the borreverines, were also produced in vitro along with the flinderoles through the dimerization of borrerine in acidic conditions. This result is thought to replicate the biosynthesis of these compounds. Flinderoles A, B, and C, desmethylflinderole C, isoborreverine, and dimethylisoborreverine can each be synthesized in three steps from tryptamine. Furthermore, progress toward a concise enantioselective synthesis of flinderoles A, B, and C is described. This work includes enantioselective conjugate addition to an unprotected indole-appended enone. Chirality 00:000-000, 2013. © 2013 Wiley Periodicals, Inc. 23435910 Effect of sinapic acid against dimethylnitrosamine-induced hepatic fibrosis in rats. Sinapic acid is a member of the phenylpropanoid family and is abundant in cereals, nuts, oil seeds, and berries. It exhibits a wide range of pharmacological properties. In this study, we investigated the hepatoprotective and antifibrotic effects of sinapic acid on dimethylnitrosamine (DMN)-induced chronic liver injury in rats. Sinapic acid remarkably prevented DMN-induced loss of body weight. This was accompanied by a significant increase in levels of serum alanine transaminase, aspartate transaminase, and liver malondialdehyde content. Furthermore, sinapic acid reduced hepatic hydroxyproline content, which correlated with a reduction in the expression of type I collagen mRNA and histological analysis of collagen in liver tissue. Additionally, the expression of hepatic fibrosis-related factors such as α-smooth muscle actin and transforming growth factor-β1 (TGF-β1), were reduced in rats treated with sinapic acid. Sinapic acid exhibited strong scavenging activity. In conclusion, we find that sinapic acid exhibits hepatoprotective and antifibrotic effects against DMN-induced liver injury, most likely due to its antioxidant activities of scavenging radicals, its capacity to suppress TGF-β1 and its ability to attenuate activation of hepatic stellate cells. This suggests that sinapic acid is a potentially useful agent for the protection against liver fibrosis and cirrhosis. 23104244 Cytochrome P450-mediated herb-drug interaction potential of Galgeun-tang. We evaluated the herb-drug interaction potential of Galgeun-tang (GGT) extracts, mediated by cytochrome P450 (CYP) inhibition/induction. Further, the effects of fermentation on the CYP-mediated herb-drug interaction potential of GGT extracts were determined. As measured by LC-ESI/MS/MS, GGT extracts (0-300μg/mL) showed no inhibitory activity toward eight CYP isoforms (1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4) in pooled human liver microsomes, suggesting that GGT may have low potential for herb-drug interactions mediated by CYP inhibition. Hepatic CYP expression and activity in rats treated with GGT extracts twice per day for 1week was examined. Among the tested CYP isoforms (1A1, 1A2, 1B1, 2B1, 2C11, 2E1, 3A1, 3A2, and 4A1), CYP1B1 and 4A1 were increased by GGT extracts. Hepatic activities of 7-ethoxyresorufin-O-deethylase, 7-pentoxyresorufin-O-depentylase, and chlorzoxazone 6-hydroxylase, but not midazolam hydroxylase were also elevated. These results raise the possibility that GGT extracts may increase the toxicity of environmental toxicants through the elevating CYP-dependent metabolic activation. Interestingly, the increases in CYP1B1 and CYP4A1 levels, and 7-ethoxyresorufin-O-deethylase, 7-pentoxyresorufin-O-depentylase, and chlorzoxazone 6-hydroxylase activities were attenuated by fermentation of GGT extract using Lactobacillus plantarum KFRI 402, but not 144. Further studies are needed to identify the CYP regulatory component(s) from GGT and determination its metabolism. 23266719 Immunomodulatory properties of multi-walled carbon nanotubes in peripheral blood mononuclear cells from healthy subjects and allergic patients. In the present study, we investigated the immunomodulatory activity of multi-walled carbon nanotubes (MWCNTs) in peripheral blood mononuclear cells (PBMCs) from healthy donors and mite-allergic subjects. Freshly prepared PBMCs, stimulated or not with Toll-like receptor (TLR)1-9 agonists, a T cell mitogen (phytohemagglutinin A) or mite allergen extract were cultured in the presence or absence of MWCNTs. Secretion of TNF-α, IL-2, IL-5, IL-6, IL-12/23p40 or IFN-γ was quantified in the culture supernatants by ELISA. Basal secretion of all the cytokines was not altered by MWCNTs in PBMCs from both healthy donors and allergic subjects. In PBMCs from healthy donors, TNF-α, IL-6 and IL-12/23p40 secretion in response to the TLR4 agonist, lipopolysaccharide was however increased in a dose-dependent manner by MWCNTs. Significant increases in the release of these cytokines were also observed in PBMCs stimulated with a TLR2 or TLR3 agonist. MWCNTs also increased the release of IL-2 and IFN-γ by PBMCs stimulated with a T cell mitogen. In contrast, MWCNTs inhibited allergen-induced IL-5 secretion by PBMCs from mite-allergic subjects. As well, MWCNTs altered the capacity of PBMC-derived monocytes to differentiate into functional dendritic cells. All together, our data suggest that according to its immune cell target, MWCNTs may either promote or suppress immune responses in humans. Further investigations are necessary to fully understand the complexity behind interactions of engineered nanoparticles with the immune system. 23628154 Novel pharmacokinetic studies of the Chinese formula Huang-Lian-Jie-Du-Tang in MCAO rats. Our previous studies showed that after oral administration of an Huang-Lian-Jie-Du-Tang (HLJDT) decoction, there is a higher concentration of the pure components, berberine, baicalin and gardenoside in the plasma of Middle cerebral artery occlusion (MCAO) rats than in sham-operated rats, The aim of the present study was to determine whether these components could be reliably measured in MCAO rat tissues. First, the plasma concentration-time profiles of berberine, palmatine, baicalin, baicalein and gardenoside were characterised in MCAO rats after oral administration of the aqueous extract of HLJDT. Subsequently, liver, lung and kidney tissues were obtained from sudden death MCAO rats in the absorption phase (0.25h), the distribution phase (1.0h) and the elimination phase (8.0h) after administration of the HLJDT aqueous extract. An HPLC method was developed and validated for the determination of the distribution characteristics of berberine, palmatine, baicalin, baicalein and gardenoside simultaneously from the above-mentioned rat tissues. The results indicated that berberine, palmatine, baicalin and baicalein distributed rapidly and accumulated at high levels in the lung, while gardenoside distributed widely in the lung and the kidney. To the best of our knowledge, this is the first report to describe the distribution of the active ingredients derived from HLJDT in MCAO rat tissues. The tissue distribution results provide a biopharmaceutical basis for the design of the clinic application of HLJDT in cerebrovascular disease. 22827894 Structural requirements for effective oximes - Evaluation of kinetic in vitro data with phosphylated human AChE and structurally different oximes. Treatment of poisoning by various organophosphorus (OP) nerve agents with established acetylcholinesterase (AChE) reactivators (oximes) is insufficient. In consequence, extensive research programs have been undertaken in various countries in the past decades to identify more effective oximes. The efficacy of new compounds has been investigated with different in vitro and in vivo models which hamper the comparison of results from different laboratories. The crucial mechanism of action of oximes is the reactivation of phosphylated AChE. The kinetic properties of these compounds can be quantified in vitro with isolated AChE from different origin. It was tempting to evaluate the reactivation kinetics of a series of oximes with various OP inhibitors performed under identical experimental conditions in order to get insight into structural requirements for adequate affinity and reactivity towards inhibited AChE. The determination of reactivation rate constants with bispyridinium oximes having different linkers, bearing oxime group(s) at different positions and having in part additional substituents revealed that (a) the reactivating potency was dependent on the position of the oxime groups and of additional substituents, (b) small modifications of the oxime structure had an in part marked effect on the kinetic properties and (c) no single oxime had an adequate reactivating potency with AChE inhibited by structurally different OP. These and previous studies underline the necessity to investigate in detail the kinetic properties of novel oximes and that the identification of a single oxime being effective against a broad range of structurally different OP will remain a major challenge. 23199992 Discrimination of cabbage (Brassica rapa ssp. pekinensis) cultivars grown in different geographical areas using ¹H NMR-based metabolomics. Cabbage (Brassica rapa ssp. pekinensis) is one of the most popular foods in Asia and is widely cultivated in many countries for the production of lightly fermented vegetables. In this study, metabolomic analysis was performed to distinguish two cultivars of cabbage grown in different geographical areas, Korea and China, using ¹H NMR spectroscopy coupled with multivariate statistical analysis. Principal component analysis (PCA) showed clear discrimination between extracts of cabbage grown in Korea and China for two different cultivars (Chunmyeong and Chunjung). The major biochemicals (metabolites) that contributed to discrimination between cabbages grown in the two regions were 4-aminobutyrate (GABA), acetate, asparagine, leucine, isoleucine, O-phosphocholine, phenylacetate, phenylalanine, succinate, sucrose, tyrosine, and valine. These results suggest that the levels of the major metabolites that differ significantly between cabbages grown in these two areas were influenced by environmental factors such as climate and geology. Our study demonstrates that ¹H NMR based on metabolomics, coupled with multivariate statistics, can be applied to identify the regions of cultivation of various cabbage cultivars. 23164674 Early life exposure to air pollution: how bad is it? Increasing concentrations of air pollution have been shown to contribute to an enormity of adverse health outcomes worldwide, which have been observed in clinical, epidemiological, and animal studies as well as in vitro investigations. Recently, studies have shown that air pollution can affect the developing fetus via maternal exposure, resulting in preterm birth, low birth weight, growth restriction, and potentially adverse cardiovascular and respiratory outcomes. This review will provide a summary of the harmful effects of air pollution exposure on the developing fetus and infant, and suggest potential mechanisms to limit the exposure of pregnant mothers and infants to air pollution. 23340332 Individual and combined effects of copper and parasitism on osmoregulation in the European eel Anguilla anguilla. The European eel (Anguilla anguilla), a catadromous species, breeds in the sea and migrates to estuarine, lagoon or freshwater habitats for growth and development. Yellow eels, exposed to low or fluctuating salinities, are also exposed to multiple other stressors as pollution, over-fishing and parasitism, which contribute to the dramatic decrease of eel populations in several European countries. The objective of this study was to evaluate the single and combined effects of waterborne copper and experimental infestation of eels with the nematode Anguillicoloides crassus after a salinity challenge from nearly isotonic (18ppt) to hypo- (5ppt) and hypertonic (29ppt) conditions, in order to investigate the osmoregulatory capacity of eels exposed to these stressors. In a nearly isotonic condition (18ppt), blood osmolality remained constant over the 6 weeks contamination to Cu(2+) and Anguillicoloides crassus. In fish exposed to a salinity challenge of 29ppt for 2 weeks, no significant effect was recorded in blood osmolality, Na(+)/K(+)-ATPase (NKA) activity, Na(+) and Cl(-) concentrations. After 2 weeks at 5ppt however, a significant blood osmolality decrease was detected in fish exposed to Anguillicoloides crassus infestation with or without Cu(2+) addition. This decrease may originate from lower Cl(-) levels measured in eels exposed to both stressors. Blood Na(+) levels remained relatively stable in all tested animals, but gill NKA activities were lower in eels exposed to combined stress. No apparent branchial lesions were detected following the different treatments and immunolocalization of NKA revealed well-differentiated ionocytes. Thus, the 5ppt challenge in eels exposed to copper and Anguillicoloides crassus seems to clearly enhance iono/osmoregulatory disturbances. Funded by ANR CES/CIEL 2008-12. 23344820 Biochemical modulation of cell energy by 2-deoxyglucose and malonate in 7,12-dimethylbenz(a)anthracene-induced carcinogenesis in rats. The goal of this study was to explore the impact of 2-deoxglucose or malonate individually or in combination on the level of cell energy (adenosine-5'-triphosphate) and oxidative stress in 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary proliferation in rats. A total of 60 adult female Sprague Dawley rats were randomly divided into five groups (12 rats each): group I serves as the control group. Rats in groups (II-V) were administrated intragastrically a single dose of 50 mg/kg body weight (bw) of DMBA. A day after DMBA administration, rats in group III were injected intraperitoneally (ip) with 100 mg 2-deoxyglucose (2-DG)/kg bw daily. Rats in group IV were injected ip with 10 mg sodium malonate/kg bw daily. Rats in group V were injected ip with 100 mg 2-DG/kg bw and 10 mg sodium malonate/kg bw (treatment for 90 days). The results obtained showed that DMBA induced oxidative stress by decreasing the activities of glutathione reductase (GRase) and superoxide dismutase (SOD), glutathione peroxidase (GPx) and elevating the levels of malondialdehyde (MDA) and nitric oxide (NO) in mammary tissues when compared with control. The combined treatment protected against the previous deleterious changes by a significant elevation in the activities of GRase and SOD, GPx and lowering the levels of MDA and NO more potentially when compared with individual treatment. Apoptosis, as indicated by a significant release of cytochrome c from mitochondria into the cytosol, observed in DMBA-injected rats was positively significantly correlated with the elevation of the level of NO. These data explained the possible additive effect of 2-DG and malonate by depleting the cell energy by their protective effects against the earlier stages of carcinogenesis. 23445125 Vectorization efforts to increase gram-negative intracellular drug concentration: a case study on HldE-K inhibitors. In this paper, we present different strategies to vectorize HldE kinase inhibitors with the goal to improve their gram-negative intracellular concentration. Syntheses and biological effects of siderophoric, aminoglycosidic, amphoteric, and polycationic vectors are discussed. While siderophoric and amphoteric vectorization efforts proved to be disappointing in this series, aminoglycosidic and polycationic vectors were able for the first time to achieve synergistic effects of our inhibitors with erythromycin. Although these effects proved to be nonspecific, this study provides information about the required stereoelectronic arrangement of the polycationic amines and their basicity requirements to fulfill outer membrane destabilization resulting in better erythromycin synergies. 23472886 Design, synthesis, and biological evaluation of indenoisoquinoline rexinoids with chemopreventive potential. Nuclear receptors, such as the retinoid X receptor (RXR), are proteins that regulate a myriad of cellular processes. Molecules that function as RXR agonists are of special interest for the prevention and control of carcinogenesis. The majority of these ligands possess an acidic moiety that is believed to be key for RXR activation. This communication presents the design, synthesis, and biological evaluation of both acidic and nonacidic indenoisoquinolines as new RXR ligands. In addition, a comprehensive structure-activity relationship study is presented that identifies the important features of the indenoisoquinoline rexinoids. The ease of modification of the indenoisoquinoline core and the lack of the necessity of a carboxyl group for activity make them an attractive and unusual family of RXR agonists. This work establishes a structural foundation for the design of new and novel rexinoid cancer chemopreventive agents. 23470105 Light reflection control in biogenic micro-mirror by diamagnetic orientation. As has become known, most materials, such as proteins and DNA, show orientation under strong magnetic fields. However, the critical threshold for the magnetic field of the magnetomechanical phenomena is still unknown. We demonstrate that a thin micro-mirror from a fish scale with high reflectivity exhibits a distinct magnetic response at 100 mT. A dramatic event under a magnetic field is the decrease of light scattering from guanine crystals as well as rapid rotation against the applied magnetic field. Enhancement of light scattering intensity is also observed when the three vectors of light incidence, magnetic field, and observation are orthogonally directed. The results indicate that biogenic guanine crystals have a large diamagnetic anisotropy along the surface parallel and normal directions. The micrometer to submicrometer scale of thin biogenic plates can act as a noninvasively, magnetically controlled micro-mirror for light irradiation control in the micrometer-scale region. 23562765 Bisphenol A affects androgen receptor function via multiple mechanisms. Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2μM), did not compete with R1881 for AR binding, when tested at 30μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR. 22580035 The high affinity IgE receptor (FcεRI) expression and function in airway smooth muscle. The airway smooth muscle (ASM) is no longer considered as merely a contractile apparatus and passive recipient of growth factors, neurotransmitters and inflammatory mediators signal but a critical player in the perpetuation and modulation of airway inflammation and remodeling. In recent years, a molecular link between ASM and IgE has been established through Fc epsilon receptors (FcεRs) in modulating the phenotype and function of these cells. Particularly, the expression of high affinity IgE receptor (FcεRI) has been noted in primary human ASM cells in vitro and in vivo within bronchial biopsies of allergic asthmatic subjects. The activation of FcεRI on ASM cells suggests a critical yet almost completely ignored network which may modulate ASM cell function in allergic asthma. This review is intended to provide a historical perspective of IgE effects on ASM and highlights the recent updates in the expression and function of FcεRI, and to present future perspectives of activation of this pathway in ASM cells. 23227887 Central nervous system disposition and metabolism of Fosdevirine (GSK2248761), a non-nucleoside reverse transcriptase inhibitor: an LC-MS and Matrix-assisted laser desorption/ionization imaging MS investigation into central nervous system toxicity. The CNS disposition and metabolism of Fosdevirine (FDV), an HIV non-nucleoside reverse transcriptase inhibitor, was investigated in four patients who unexpectedly experienced seizures after at least 4 weeks of treatment in a Phase IIb, HIV-1 treatment experienced study. In addition, the CNS disposition and metabolism of FDV was examined in samples from rabbit, minipig, and monkey studies. LC-MS was used to characterize and estimate the concentrations of FDV and its metabolites in cerebral spinal fluid (seizure patients, rabbit, and monkey) and brain homogenate (rabbit, minipig, and monkey). The application of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) provided the spatial distribution of FDV and its metabolites in brain tissue (rabbit, minipig, and monkey). A cysteine conjugate metabolite resulting from an initial glutathione (GSH) Michael addition to the trans-phenyl acrylonitrile moiety of FDV was the predominant drug-related component in the samples from seizure patients, rabbits, and minipigs. This metabolite persisted in the CNS for an extended period of time after the last dose in both seizure patients and minipigs. Furthermore, the localization of this metabolite was found to be highly associated with the white matter in rabbit and minipig brain sections by MALDI IMS. In contrast, the predominant component in monkey CNS was FDV, which was shown to be highly associated with the gray matter. On the basis of these data, several hypothesizes are considered, which might provide insights into species differences in CNS toxicity/seizures observed after FDV dosing. 22841391 Methylselenol, a selenium metabolite, modulates p53 pathway and inhibits the growth of colon cancer xenografts in Balb/c mice. It is has been hypothesized that methylselenol is a critical selenium metabolite for anticancer activity in vivo. In this study, we used a protein array which contained 112 different antibodies known to be involved in the p53 pathway to investigate the molecular targets of methylselenol in human HCT116 colon cancer cells. The array analysis indicated that methylselenol exposure changed the expression of 11 protein targets related to the regulation of cell cycle and apoptosis. Subsequently, we confirmed these proteins with the Western blotting approach, and found that methylselenol increased the expression of GADD 153 and p21 but reduced the level of c-Myc, E2F1 and Phos p38 MAP kinase. Similar to our previous report on human HCT116 colon cancer cells, methylselenol also inhibited cell growth and led to an increase in G1 and G2 fractions with a concomitant drop in S-phase in mouse colon cancer MC26 cells. When the MC26 cells were transplanted to their immune-competent Balb/c mice, methylselenol-treated MC26 cells had significantly less tumor growth potential than that of untreated MC26 cells. Taken together, our data suggest that methylselenol modulates the expression of key genes related to cell cycle and apoptosis and inhibits colon cancer cell proliferation and tumor growth. 23241831 Information hierarchies optimize patient-centered solutions. Enabling science and information technologies has catalyzed a surge of biological, clinical, demographic, health services, and comparative-effectiveness data. While accelerating the deconvolution of complex pathophysiological, medical, social, and environmental networks and systems, these platforms have produced informational quanta devoid of contextualization. Therapeutic innovation is thus now challenged with moving beyond knowledge generation and curation to integrated solution-seeking paradigms that organize functionally related information, producing system-level insights into health and disease for optimized patient-centered outcomes. This annual issue on therapeutics innovations highlights emerging considerations for the generation and hierarchical organization of scientific and clinical information and its translation to advancing next-generation disease management. 23330971 Highly transparent low resistance ZnO/Ag nanowire/ZnO composite electrode for thin film solar cells. We present an indium-free transparent conducting composite electrode composed of silver nanowires (AgNWs) and ZnO bilayers. The AgNWs form a random percolating network embedded between the ZnO layers. The unique structural features of our ZnO/AgNW/ZnO multilayered composite allow for a novel transparent conducting electrode with unprecedented excellent thermal stability (∼375 °C), adhesiveness, and flexibility as well as high electrical conductivity (∼8.0 Ω/sq) and good optical transparency (>91% at 550 nm). Cu(In,Ga)(S,Se)₂ (CIGSSe) thin film solar cells incorporating this composite electrode exhibited a 20% increase of the power conversion efficiency compared to a conventional sputtered indium tin oxide-based CIGSSe solar cell. The ZnO/AgNW/ZnO composite structure enables effective light transmission and current collection as well as a reduced leakage current, all of which lead to better cell performance. 23411079 Steroidal constituents from the leaves of Hosta longipes and their inhibitory effects on nitric oxide production. Hosta longipes (FR. et SAV.) MATSUMURA (Liliaceae) is an edible vegetable in Korea. This study was conducted with the aim of evaluating the potential of H. longipes as a functional food for the treatment of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. In this respect, the study resulted in the identification of three new steroidal compounds, longipenane (1), longipenane 26-O-β-d-glucopyranoside (2) and neogitogenin 3-O-α-l-rhamnopyranosyl-(1→2)-O-[β-d-glucopyranosyl-(1→4)]-β-d-galactopyranoside (3), along with two known steroidal saponins (4 and 5). The identification and structural elucidation of these compounds were based on 1D and 2D NMR measurements, high-resolution FAB mass spectroscopy (HR-FAB-MS), and chemical methods. A proinflammatory mediator, nitric oxide (NO), in murine microglial BV-2 cells was used to assess the anti-neuroinflammatory effect of the isolated compounds from H. longipes. Among them, compounds 4 and 5 showed strong inhibitory effects on NO production without high cell toxicity in lipopolysaccharide-activated BV-2 cells (IC50=17.66 and 13.16μM, respectively). 23361101 Multiple dosing of ephedra-free dietary supplements: hemodynamic, electrocardiographic, and bacterial contamination effects. Four popular ephedra-free dietary supplements were evaluated for their effects on heart rate (HR), blood pressure (BP), and electrocardiographic (ECG) parameters. Twelve healthy men participated in a study randomized for product sequence, with a 21-day washout period between supplement-administration phases. Throughout the study, Holter monitors were used to assess ECG and HR activity. BP was assessed automatically on multiple occasions. The supplements were ingested three times daily for 3 days. Caffeine content, microbial load, and serum caffeine concentrations were determined. Mean systolic (SBP) and diastolic BP (DBP) readings showed significant increases relative to baseline (10.8 ± 2.5 and 5.3 ± 3.1 mm Hg, respectively; P < 0.05). All supplements significantly increased HR and decreased bradycardia runs; abnormal atrial/ventricular events were frequently noted. Gastrointestinal and sympathomimetic symptoms were also common. Two supplements were heavily contaminated with Bacillus species. In light of these findings, the use of ephedra-free dietary supplements should be discouraged in individuals with hypertension, diabetes, or other cardiovascular diseases. 22939943 Osteocyte control of osteoclastogenesis. Multiple lines of evidence support the idea that osteocytes act as mechanosensors in bone and that they control bone formation, in part, by expressing the Wnt antagonist sclerostin. However, the role of osteocytes in the control of bone resorption has been less clear. Recent studies have demonstrated that osteocytes are the major source of the cytokine RANKL involved in osteoclast formation in cancellous bone. The goal of this review is to discuss these and other studies that reveal mechanisms whereby osteocytes control osteoclast formation and thus bone resorption. This article is part of a Special Issue entitled "The Osteocyte". 23223639 Patterned polymer nanowire arrays as an effective protein immobilizer for biosensing and HIV detection. We report an array of polymeric nanowires for effectively immobilizing biomolecules on biochips owing to the large surface area. The nanowires were fabricated in predesigned patterns using an inductively coupled plasma (ICP) etching process. Microfluidic biochips integrated using the substrates with arrays of nanowires and polydimethylsiloxane channels have been demonstrated to be effective for detecting antigens, and a detection limit of antigens at 0.2 μg mL(-1) has been achieved, which is improved by a factor of 50 compared to that based on flat substrates without the nanowires. In addition, the high sensitivity for clinical detection of human immunodeficiency virus (HIV) antibody has also been demonstrated, showing a 20 times enhancement in fluorescent signal intensity between the samples with positive and negative HIV. 23588681 Emodin-6-O-β-D-glucoside down-regulates endothelial protein C receptor shedding. Endothelial protein C receptor (EPCR) plays an important role in the protein C anticoagulation pathway and in the cytoprotective pathway. Previously, EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-α converting enzyme (TACE). Soluble EPCR levels are increased in patients with systemic inflammatory diseases. Recently, we reported that a new active compound, emodin-6-O-β-D-glucoside (EG) from Reynoutria japonica, has anti-inflammatory activities. However, little is known of the effects of EG on EPCR shedding. Here, we investigated this issue by monitoring the effects of EG on the phorbol-12-myristate 13-acetate (PMA) or the cecal ligation and puncture (CLP)-mediated EPCR shedding and its underlying mechanisms. Data showed that EG potently inhibited the PMA and CLP-induced EPCR shedding by suppressing TACE expression. Given these results, EG could be used as a candidate therapeutic for the treatment of vascular inflammatory diseases. 23557487 New Analysis of the ν3 and ν4 Bands of HNO3 in the 7.6 μm Region. A new line position analysis of the nu3 and nu4 bands of nitric acid (HNO3) at 1326.186 and 1303.072 cm-1 together with its associated interacting bands is presented. The 3^1 and 4^1 energy levels were obtained from an extended analysis of high resolution Fourier transform spectra recorded at Giessen in the 7.6 µm region. The energy levels of 3^1 and 4^1 upper states of nitric acid are strongly interacting with those of the 9^3, 6^2, 5^19^1 and 7^18^1 dark states centered at 1288.899, 1289.46, 1341.05 and 1343.78 cm-1, respectively. Informations on these perturbing dark states were achieved through previous partial investigations of hot bands in high resolution Fourier transform spectra recorded at 22 µm in Giessen (for 3nu9-2nu9 and 3nu9-nu5), at 12 µm in Denver (for 3nu9-nu9), and at 11 µm in Orsay (for nu5+nu9-nu9). The energy levels calculation accounts for the various Fermi, anharmonic, A-type, B-type and C-type Coriolis resonances which couple together the {6^2,9^3,4^1,3^1,5^19^1,7^18^1} interacting energy levels. For nitric acid the nu9 mode (OH torsion relative to the -NO2 moiety) is a large amplitude motion. The theoretical model used in this work accounts also for large amplitude effects in the 93 dark state which lead to a splitting of the 93 energy levels of about 0.060 cm-1. In this way the existence of "torsional" splittings for several nu4 perturbed lines was explained by the occurrence of local A-type and B-type Coriolis resonances coupling the 4^1 energy levels with those of 93. Because four dark bands had to be accounted for in the model, the results of the energy levels calculations are reasonable, although not perfect. However a very significant improvement was achieved in term of understanding the 7.6 µm absorbing bands of nitric acid as compared to the analysis of the nu3 and nu4 bands performed several years ago [Perrin, A.; Lado-Bordowski, O.; Valentin, A. Mol. Phys. 1989, 67, 249-267]. Finally the present analysis also features, for the first time, the nu3+nu9-nu9 hot band located at 1331.09 cm-1. 23245514 Synthesis of perylene bisimide-centered glycodendrimer and its interactions with concanavalin A. A novel glycodendrimer based on 18 peripheral α-D-mannoses functionalized perylene bisimide derivative PBI-18-Man was synthesized and its selectively binding interactions for Con A were investigated by CD spectra and turbidity assay, which exhibited strong binding affinity for Con A with the binding constant of 1.3×10(8) M(-1) (7.2×10(6) M(-1) for monomeric mannose, valency corrected), 3 orders of magnitude higher affinity than the monovalent mannose ligand. Furthermore, the inhibitory activity for Con A was studied by ELLA experiment, showed 2 times inhibitor activity than the reference compound (α-MMP). 23377100 Chemically differentiating ascorbate-mediated dissolution of quantum dots in cell culture media. To investigate the dynamic dissolution of quantum dots (QDs) in cell culture media, in this study we constructed an online automatic analytical system comprising a sequential in-tube solid phase extraction (SPE) device and an inductively coupled plasma (ICP) mass spectrometer. By means of selectively extracting QDs and cadmium ions (Cd(2+)) onto the interior surface of the polytetrafluoroethylene (PTFE) tube, this novel SPE device could be used to determine the degree of QD dissolution through a simple adjustment of sample acidity. To the best of our knowledge, this study is the first to exploit PTFE tubing as a selective SPE adsorbent for the online chemical differentiation of QDs and Cd(2+) ions with the goal of monitoring the phenomenon of QD dissolution in complicated biological matrices. We confirmed the analytical reliability of this system through comparison of the measured Cd-to-QD ratios to the expected values. When analyzing QDs and Cd(2+) ions at picomolar levels, a temporal resolution of 8 min was required to load sufficient amounts of the analytes to meet the sensitivity requirements of the ICP mass spectrometer. To demonstrate the practicability of this developed method, we measured the dynamic variations in the Cd-to-QD705 ratio in the presence of ascorbate as a physiological stimulant to generate reactive oxygen species in cell culture media and trigger the dissolution of QDs; our results suggest that the ascorbate-induced QD dissolution was dependent on the time, treatment concentration, and nature of the biomolecule. 23588093 Artemisia copa aqueous extract as vasorelaxant and hypotensive agent. ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia copa Phil. (Asteraceae) is a medicinal plant commonly used in traditional medicine in Argentina. AIM OF THE STUDY: The vasorelaxant and hypotensive activities of the aqueous extract of Artemisia copa have been investigated. MATERIALS AND METHODS: The in vitro effect of the extract and isolated compounds from Artemisia copa was investigated using isolated rat aortic rings. The acute effect caused by the intravenous (i.v.) infusion (0.1-300mg/kg) on blood pressure and heart rate was evaluated in spontaneous hypertensive rats. In addition, a phytochemical analysis of the extract was performed by HPLC. RESULTS: Artemisia copa had a relaxant effect in endothelium-intact aortic rings that had been pre-contracted with 10(-7)M phenylephrine (Emax=96.7±1.3%, EC50=1.1mg/ml), 10(-5)M 5-hydroxytriptamine (Emax=96.7±3.5%, EC50=1.5mg/ml) and 80mM KCl (Emax=97.9± 4.4%, EC50=1.6mg/ml). In denuded aortic rings contracted by phenylephrine, a similar pattern was observed (Emax=92.7±6.5%, EC50=1.8mg/ml). l-NAME, indomethacin, tetraethylammonium and glibenclamide were not able to block the relaxation induced by the extract. Nevertheless, the pre-treatment with Artemisia copa attenuated the CaCl2-induced contraction in a concentration-dependent manner (Emax: 86% of inhibition for 3mg/ml and 52% de-inhibition for 1mg/ml). This pre-treatment also induced a significant attenuation of the norepinephrine-induced contraction in a concentration-dependent manner (Emax: 72.7% of inhibition for 3mg/ml and 27% de inhibition for 1mg/ml) in a Ca(2+) free medium. Upon analyzing the composition of the extract, the presence of p-coumaric acid, isovitexin, luteolin and chrysoeriol were found. Luteolin (CE50: 1.5μg/ml), chrysoeriol (CE50: 13.2μg/ml) and p-coumaric acid (CE50: 95.2μg/ml), isolated from the aqueous extract, caused dilatation of thoracic aortic rings pre-contracted with phenylephrine. Artemisia copa administered i.v. also induced a decrease in the mean arterial pressure but did not affect the heart rate in hypertensive rats. CONCLUSIONS: The aqueous extract of Artemisia copa proved to have vasorelaxing and hypotensive effects through the inhibition of Ca(2+) influx via membranous calcium channels and intracellular stores. The presence of luteolin, chrysoeriol and p-coumaric acid found in this plant could be involved in this effect. 23011663 Comparative analysis of the protective effects of caffeic acid phenethyl ester (CAPE) on pulmonary contusion lung oxidative stress and serum copper and zinc levels in experimental rat model. The aim of this study was to investigate the effects of caffeic acid phenethyl ester (CAPE) in the lungs by biochemical and histopathological analyses in an experimental isolated lung contusion model. Eighty-one male Sprague-Dawley rats were used. The animals were divided randomly into four groups: group 1 (n = 9) was defined as without contusion and without CAPE injection. Group 2 (n = 9) was defined as CAPE 10 μmol/kg injection without lung contusion. Group 3 (n = 36) was defined as contusion without CAPE-administrated group which consisted of four subgroups that were created according to analysis between days 0, 1, 2, and 3. Group 4 (n = 27) was defined as CAPE 10 μmol/kg administrated after contusion group divided into three subgroups according to analysis on days 1, 2, and 3. CAPE 10 μmol/kg was injected intraperitoneally 30 min after trauma and on days 1 and 2. Blood samples were obtained to measure catalase (CAT) and superoxide dismutase (SOD) activities and level of malondialdehyde (MDA) and for blood gas analysis. Trace elements such as zinc and copper were measured in serum. The lung tissue was also removed for histopathological examination. Isolated lung contusion increased serum and tissue SOD and CAT activities and MDA levels (p < 0.05). Both serum and tissue SOD, MDA, and CAT levels on day 3 were lower in group 4 compared to group 3 (p < 0.05). Further, the levels of SOD, MDA, and CAT in group 4 were similar compared to group 1 (p > 0.05). CAPE also had a significant beneficial effect on blood gases (p < 0.05). Both serum zinc and copper levels were (p < 0.05) influenced by the administration of CAPE. Histopathological examination revealed lower scores in group 4 compared to group 3 (p < 0.05) and no significant differences compared to group 1 (p > 0.05). CAPE appears to be effective in protecting against severe oxidative stress and tissue damage caused by pulmonary contusion in an experimental setting. Therefore, we conclude that administration of CAPE may be used for a variety of conditions associated with pulmonary contusion. Clinical use of CAPE may have the advantage of prevention of pulmonary contusion. 23315938 Research resource: tissue- and pathway-specific metabolomic profiles of the steroid receptor coactivator (SRC) family. The rapidly growing family of transcriptional coregulators includes coactivators that promote transcription and corepressors that harbor the opposing function. In recent years, coregulators have emerged as important regulators of metabolic homeostasis, including the p160 steroid receptor coactivator (SRC) family. Members of the SRC family have been ascribed important roles in control of gluconeogenesis, fat absorption and storage in the liver, and fatty acid oxidation in skeletal muscle. To provide a deeper and more granular understanding of the metabolic impact of the SRC family members, we performed targeted metabolomic analyses of key metabolic byproducts of glucose, fatty acid, and amino acid metabolism in mice with global knockouts (KOs) of SRC-1, SRC-2, or SRC-3. We measured amino acids, acyl carnitines, and organic acids in five tissues with key metabolic functions (liver, heart, skeletal muscle, brain, plasma) isolated from SRC-1, -2, or -3 KO mice and their wild-type littermates under fed and fasted conditions, thereby unveiling unique metabolic functions of each SRC. Specifically, SRC-1 ablation revealed the most significant impact on hepatic metabolism, whereas SRC-2 appeared to impact cardiac metabolism. Conversely, ablation of SRC-3 primarily affected brain and skeletal muscle metabolism. Surprisingly, we identified very few metabolites that changed universally across the three SRC KO models. The findings of this Research Resource demonstrate that coactivator function has very limited metabolic redundancy even within the homologous SRC family. Furthermore, this work also demonstrates the use of metabolomics as a means for identifying novel metabolic regulatory functions of transcriptional coregulators. 23282017 X-ray absorption near edge structure spectroscopy to resolve the in vivo chemistry of the redox-active indazolium trans-[Tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019). Indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (1, KP1019) and its analogue sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (2, KP1339) are promising redox-active anticancer drug candidates that were investigated with X-ray absorption near edge structure spectroscopy. The analysis was based on the concept of the coordination charge and ruthenium model compounds representing possible coordinations and oxidation states in vivo. 1 was investigated in citrate saline buffer (pH 3.5) and in carbonate buffer (pH 7.4) at 37 °C for different time intervals. Interaction studies on 1 with glutathione in saline buffer and apo-transferrin in carbonate buffer were undertaken, and the coordination of 1 and 2 in tumor tissues was studied too. The most likely coordinations and oxidation states of the compound under the above mentioned conditions were assigned. Microprobe X-ray fluorescence of tumor thin sections showed the strong penetration of ruthenium into the tumor tissue, with the highest concentrations near blood vessels and in the edge regions of the tissue samples. 23644201 Synthesis, characterization and in vitro pharmacological evaluation of new water soluble Ni(II) complexes of 4N-substituted thiosemicarbazones of 2-oxo-1,2-dihydroquinoline-3-carbaldehyde. Four new Ni(II) complexes of general formula [Ni(H2-Qtsc-R)2](NO3)2 (H2-Qtsc-R = 4N-substituted thiosemicarbazones of 2-oxo-1,2-dihydroquinoline-3-carbaldehyde, where R = H (1), Me (2), Et (3), or Ph (4)) have been synthesized and characterized. The geometry of the complexes was confirmed by single crystal X-ray crystallography for one of the complexes (3). The binding affinity of the complexes with DNA and protein have been studied which indicate that they could interact with calf thymus DNA and bovine serum albumin protein. Investigations of antioxidative properties showed that all the complexes have strong radical scavenging properties. Cytotoxic studies showed that the complexes exhibited effective cytotoxic activity against a panel of human cancer cells without affecting the normal cells much. 23086038 PAQR3 modulates insulin signaling by shunting phosphoinositide 3-kinase p110α to the Golgi apparatus. Phosphoinositide 3-kinase (PI3K) mediates insulin actions by relaying signals from insulin receptors (IRs) to downstream targets. The p110α catalytic subunit of class IA PI3K is the primary insulin-responsive PI3K implicated in insulin signaling. We demonstrate here a new mode of spatial regulation for the p110α subunit of PI3K by PAQR3 that is exclusively localized in the Golgi apparatus. PAQR3 interacts with p110α, and the intracellular targeting of p110α to the Golgi apparatus is reduced by PAQR3 downregulation and increased by PAQR3 overexpression. Insulin-stimulated PI3K activity and phosphoinositide (3,4,5)-triphosphate production are enhanced by Paqr3 deletion and reduced by PAQR3 overexpression in hepatocytes. Deletion of Paqr3 enhances insulin-stimulated phosphorylation of AKT and glycogen synthase kinase 3β, but not phosphorylation of IR and IR substrate-1 (IRS-1), in hepatocytes, mouse liver, and skeletal muscle. Insulin-stimulated GLUT4 translocation to the plasma membrane and glucose uptake are enhanced by Paqr3 ablation. Furthermore, PAQR3 interacts with the domain of p110α involved in its binding with p85, the regulatory subunit of PI3K. Overexpression of PAQR3 dose-dependently reduces the interaction of p85α with p110α. Thus, PAQR3 negatively regulates insulin signaling by shunting cytosolic p110α to the Golgi apparatus while competing with p85 subunit in forming a PI3K complex with p110α. 23270527 Recyclable thermoresponsive polymer-cellulase bioconjugates for biomass depolymerization. Here we report the construction and characterization of a recoverable, thermoresponsive polymer-endoglucanase bioconjugate that matches the activity of unmodified enzymes on insoluble cellulose substrates. Two copolymers exhibiting a thermoresponsive lower critical solution temperature (LCST) were created through the copolymerization of an aminooxy-bearing methacrylamide with N-isopropylacrylamide (NIPAm) or N-isopropylmethacrylamide (NIPMa). The aminooxy group provided a handle through which the LCST was adjusted through small-molecule quenching. This allowed materials with LCSTs ranging from 20.9 to 60.5 °C to be readily obtained after polymerization. The thermostable endoglucanase EGPh from the hypothermophilic Pyrococcus horikoshii was transaminated with pyridoxal-5'-phosphate to produce a ketone-bearing protein, which was then site-selectively modified through oxime linkage with benzylalkoxyamine or 5 kDa-poly(ethylene glycol)-alkoxyamine. These modified proteins showed activity comparable to the controls when assayed on an insoluble cellulosic substrate. Two polymer bioconjugates were then constructed using transaminated EGPh and the aminooxy-bearing copolymers. After 12 h, both bioconjugates produced an equivalent amount of free reducing sugars as the unmodified control using insoluble cellulose as a substrate. The recycling ability of the NIPAm copolymer-EGPh conjugate was determined through three rounds of activity, maintaining over 60% activity after two cycles of reuse and affording significantly more soluble carbohydrates than unmodified enzyme alone. When assayed on acid-pretreated Miscanthus, this bioconjugate increased the amount of reducing sugars by 2.8-fold over three rounds of activity. The synthetic strategy of this bioconjugate allows the LCST of the material to be changed readily from a common stock of copolymer and the method of attachment is applicable to a variety of proteins, enabling the same approach to be amenable to thermophile-derived cellulases or to the separation of multiple species using polymers with different recovery temperatures. 23430368 The metabolic effects of growth hormone in adipose tissue. There is a general consensus that a reduction in growth hormone (GH) secretion results in obesity. However, the pathophysiologic role of GH in the metabolism of lipids is yet to be fully understood. The major somatic targets of GH are bones and muscles, but GH stimulates lipolysis and seems to regulate lipid deposition in adipose tissue. Patients with isolated GH deficiency (GHD) have enlarged fat depots due to higher fat cell volume, but their fat cell numbers are lower than those of matched controls. The treatment of patients with GH results in a relative loss of body fat and shifts both fat cell number and fat cell volume toward normal, indicating an adipogenic effect of GH. Adults with GHD are characterized by perturbations in body composition, lipid metabolism, cardiovascular risk profile, and bone mineral density. It is well established that GHD is usually accompanied by an increase in fat accumulation; GH replacement in GHD results in the reduction of fat mass, particularly abdominal fat mass. In addition, abdominal obesity results in a secondary reduction in GH secretion that is reversible with weight loss. However, whereas GH replacement in patients with GHD leads to specific depletion of intra-abdominal fat, administering GH to obese individuals does not seem to result in a consistent reduction or redistribution of body fat. Although administering GH to obese non-GHD subjects has only led to equivocal results, more recent studies indicate that GH still remains a plausible metabolic candidate. 23561192 Modifications of Kyoho grape berry quality under long-term NaCl treatment. Different concentrations of a sodium chloride spray were applied to the grapevine cultivar Kyoho to determine the effects of salinity on berry quality. The fruit's fresh weight, relative water content, hardness and titratable acid were gradually enhanced with increased salt concentrations. Anthocyanin and soluble solids increased after treatment with moderate salinity (20 and 60mM); however, the results were reversed under high salinity (100 and 150mM). The soluble sugars glucose, fructose and sucrose increased after treatment with moderate salinity, whereas glucose and fructose declined under high salinity. For the six organic acids tested, their total levels were elevated by salinity, which increased the production of tartaric and malic acids. The aroma of the berry was extremely sensitive to salinity and showed a considerable decline in abundance and variety at 20mM NaCl. In summary, moderate salinity enhanced the overall berry quality, but decreased the aroma quality, whereas high salinity decreased the berry quality. 23294699 Pentacyclic hemiacetal sterol with antifouling and cytotoxic activities from the soft coral Nephthea sp. A novel unusual pentacyclic hemiacetal sterol nephthoacetal (1), was isolated from soft coral Nephthea sp. The structure of this sterol was inferred from its two acetyl derivatives (2) and (3), by means of spectroscopic methods, and quantum chemical calculations. Anti-fouling activity of compounds 1-3 against Bugula neritina larvae was evaluated, sterol (1) exhibited significant inhibitory effect with EC(50) value of 2.5 μg/mL, while having low toxicity with LC(50)>25.0 μg/mL. The in vitro cytotoxic activity of compounds 1-3 against HeLa cells was also evaluated, all of them exhibited moderate cytotoxicity with IC(50) values of 12.3 (1), 10.1 (2), and 19.6 μg/mL (3), respectively. 23594310 Signatures of Fano Interferences in the Electron Energy Loss Spectroscopy and Cathodoluminescence of Symmetry-Broken Nanorod Dimers. Through numerical simulation, we predict the existence of the Fano interference effect in the electron energy loss spectroscopy (EELS) and cathodoluminescence (CL) of symmetry-broken nanorod dimers that are heterogeneous in material composition and asymmetric in length. The differing selection rules of the electron probe in comparison to the photon of a plane wave allow for the simultaneous excitation of both optically bright and dark plasmons of each monomer unit, suggesting that Fano resonances will not arise in EELS and CL. Yet, interferences are manifested in the dimer's scattered near- and far-fields and are evident in EELS and CL due to the rapid π-phase offset in the polarizations between super-radiant and subradiant hybridized plasmon modes of the dimer as a function of the energy loss suffered by the impinging electron. Depending upon the location of the electron beam, we demonstrate the conditions under which Fano interferences will be present in both optical and electron spectroscopies (EELS and CL) as well as a new class of Fano interferences that are uniquely electron-driven and are absent in the optical response. Among other things, the knowledge gained from this work bears impact upon the design of some of the world's most sensitive sensors, which are currently based upon Fano resonances. 23439649 E6AP/UBE3A Ubiquitin Ligase Harbors Two E2~ubiquitin Binding Sites. By exploiting (125)I-polyubiquitin chain formation as a functional readout of enzyme activity, we have quantitatively examined the mechanism of human E6AP/UBE3A for the first time. Initial rate studies identify UbcH7 as the cognate E2 carrier protein for E6AP, although related Ubc5 isoforms and the ISG15-specific UbcH8 paralog also support E6AP with reduced efficacy due to impaired binding and catalytic competence. Initial rates of polyubiquitin chain formation displayed hyperbolic kinetics with respect to UbcH7 concentration (Km = 57.6 ± 5.7 nm and kcat = 0.032 ± 0.001 s(-1)) and substrate inhibition above 2 μm. Competitive inhibition by an isosteric UbcH7C86S-ubiquitin oxyester substrate analog (Ki = 64 ± 18 nm) demonstrates that Km reflects intrinsic substrate affinity. In contrast, noncompetitive inhibition by a UbcH7C86A product analog (Ki = 7 ± 0.7 μm) and substrate inhibition at high concentrations require two functionally distinct E2∼ubiquitin substrate binding sites. The kinetics of polyubiquitin chain formation reflect binding at a cryptic Site 1 not previously recognized that catalyzes E6AP∼ubiquitin thioester formation. Subsequent binding of E2∼ubiquitin at the canonical Site 2 present in the extant crystal structure is responsible for polyubiquitin chain elongation. Other rate studies show that the conserved -4 Phe(849) residue is required for polyubiquitin chain formation rather than target protein conjugation as originally suggested. The present studies unambiguously preclude earlier models for the mechanism of Hect domain-catalyzed conjugation through the canonical binding site suggested by the crystal structure and define a novel two-step mechanism for formation of the polyubiquitin degradation signal. 23282999 Zinc sulphate and vitamin E alleviate reproductive toxicity caused by aluminium sulphate in male albino rats. This study was designed to investigate the reproductive toxicity of aluminium sulphate and the therapeutic effects of administration of zinc sulphate and vitamin E individually or in combination against the toxic effect caused by aluminium (Al) in male albino rats. The animals were divided into five groups: group 1 received distilled water and served as control; group 2 received only aluminium sulphate (50 mg/kg body weight (b.w.)); group 3 received aluminium sulphate (50 mg/kg b.w.) plus zinc sulphate (50 mg/kg b.w.); group 4 received aluminium sulphate (50 mg/kg b.w.) and vitamin E (15 mg/kg b.w.); group 5 received aluminium sulphate plus a combination of zinc sulphate and vitamin E in similar doses as above. Doses were administered orally once daily for 45 consecutive days. The results revealed that aluminium sulphate induced significant decrease in body weight gain and testis weight and significant increase in Al level in both serum and testes of male rats. Biochemical analysis showed significant decrease in serum total protein and phospholipids levels, while serum total lipid was significantly elevated post Al treatment. In addition, significant decrease in total protein, phospholipids and cholesterol levels in the testes of Al-treated rats was recorded. The data also showed significant decrease in the levels of serum testosterone, leutinizing hormone and follicle stimulating hormone and significant increase in the level of serum prolactin in Al-intoxicated rats. Moreover, histological examination showed that aluminium sulphate caused apparent alterations in the testicular structure of the treated animals. Treatment with zinc sulphate and vitamin E individually or in combination ameliorated the harmful effects of Al, which was proved histopathologically by the noticeable improvement in the testicular tissues. We can conclude that the tested dose of aluminium sulphate induced toxic effect on the reproductive system of male albino rats and the treatment with zinc sulphate and/or vitamin E alleviated these toxic effects. In some cases, vitamin E exerted a more potent effect, while in other cases, the more potent effect is related to zinc sulphate and the combination of both at most of the recorded data. 23634786 Lanostane Triterpenoids from the Mushroom Naematoloma fasciculare. In our continuing search for structurally interesting and bioactive metabolites from Korean wild mushrooms, bioassay-guided fractionation and a chemical investigation of the MeOH extracts of the fruiting bodies of the mushroom Naematoloma fasciculare resulted in the isolation of four new lanostane triterpenoids (1-4), together with 11 known compounds (5-15). The structures of 1-5 were determined by a combination of 1D and 2D NMR and HRMS. The absolute configuration of the 3-hydroxy-3-methylglutaryl group as a side chain in 1 and 2 was determined by the alkaline methanolysis method. The full NMR data assignment of the known compound fasciculol G (5) is reported for the first time. Compounds 1-15 were tested for their antiproliferative activities against four human cancer cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) and evaluated for their inhibitory effects on nitric oxide production in a lipopolysaccharide-activated murine microglial cell line. 23289646 Living unimodal growth of polyion complex vesicles via two-dimensional supramolecular polymerization. Understanding the dynamic behavior of molecular self-assemblies with higher-dimensional structures remains a key challenge to obtaining well-controlled and monodispersed structures. Nonetheless, there exist few systems capable of realizing the mechanism of supramolecular polymerization at higher dimensions. Herein, we report the unique self-assembling behavior of polyion complexes (PICs) consisting of poly(ethylene glycol)-polyelectrolyte block copolymer as an example of two-dimensional supramolecular living polymerization. Monodispersed and submicrometer unilamellar PIC vesicles (nano-PICsomes) displayed time-dependent growth while maintaining a narrow size distribution and a unilamellar structure. Detailed analysis of the system revealed that vesicle growth proceeded through the consumption of unit PICs (uPICs) composed of a single polycation/polyanion pair and was able to restart upon the further addition of isolated uPICs. Interestingly, the resulting vesicles underwent dissociation into uPICs in response to mechanical stress. These results clearly frame the growth as a two-dimensional supramolecular living polymerization of uPICs. 23009741 Ocular perfusion pressure and ocular blood flow in glaucoma. Glaucoma is a progressive optic neuropathy of unknown origin. It has been hypothesized that a vascular component is involved in glaucoma pathophysiology. This hypothesis has gained support from studies showing that reduced ocular perfusion pressure is a risk factor for the disease. The exact nature of the involvement is, however, still a matter of debate. Based on recent evidence we propose a model including primary and secondary insults in glaucoma. The primary insult appears to happen at the optic nerve head. Increased intraocular pressure and ischemia at the post-laminar optic nerve head affects retinal ganglion cell axons. Modulating factors are the biomechanical properties of the tissues and cerebrospinal fluid pressure. After this primary insult retinal ganglion cells function at a reduced energy level and are sensitive to secondary insults. These secondary insults may happen if ocular perfusion pressure falls below the lower limit of autoregulation or if neurovascular coupling fails. Evidence for both faulty autoregulation and reduced hyperemic response to neuronal stimulation has been provided in glaucoma patients. The mechanisms appear to involve vascular endothelial dysfunction and impaired astrocyte-vessel signaling. A more detailed understanding of these pathways is required to direct neuroprotective strategies via the neurovascular pathway. 23421758 Colloidal nanoplasmonics: from building blocks to sensing devices. Nanoplasmonics is a rapidly developing field of research and technology that is based on the ability of small metal particles to interact strongly with light of wavelength significantly larger than their size. The development of nanoplasmonics has been closely associated with the application of colloid science to the controlled growth of metal nanocrystals in solution and to directing the self-assembly of such nanocrystals into organized arrays with enhanced collective properties. Engineering the morphology and the assembly of metal nanoparticles is a key step toward the fabrication of devices with great potential in detection and diagnosis as well as in a wide variety of other fields. In this Feature Article, we provide an overview of the recent work in our laboratory, which in our view somehow reflects the evolution of the field itself and provides guidelines for future research. 23614379 Glycosides from the bark of Machilus robusta. Six new glycosidic constituents (1-6), together with 10 known analogs, have been isolated from the bark of Machilus robusta. Structures of the new compounds, including the absolute configurations, were determined by spectroscopic and chemical methods as ( - )-nectandrin B-β-d-glucopyranoside (1), ( - )-(7R,7'R,8S,8'R)-4,4'-dihydroxy-3,3'-dimethoxy-7,7'-epoxylignan-4-O-β-d-glucopyranoside (2), ( - )-(7R,7'R,8S,8'R)-4,4'-dihydroxy-3,3'-dimethoxy-7,7'-epoxylignan-4'-O-β-d-glucopyranoside (3), ( - )-(8S,8'R)-4,4'-dihydroxy-3,3',5'-trimethoxylignan-4'-O-β-d-glucopyranoside (4), ( - )-(7R,8R)-syringylglycerol-8-O-β-d-glucopyranoside (5), and ( - )-3-hydroxy-2-methyl-4-pyrone-3-O-β-d-xylopyranosyl-(1 → 6)-O-β-d-glucopyranoside (6), respectively. 23627438 Sciadopitysin: active component from Taxus chinensis for anti-Alzheimer's disease. Five taxane diterpenoids derived from the 95% ethanol extract of Taxus chinensis were tested for the inhibitory activities on amyloid-beta (Aβ) peptide aggregation. Using thioflavin-T fluorescence assay, sciadopitysin was found to exhibit the most potency against Aβ aggregation and the formation of fibrils. Further cellular assay indicated that sciadopitysin increased the cell viability of SH-SY5Y cell and demonstrated neuroprotection against Aβ protein-induced insult in primary cortical neurons. According to the authors' best knowledge, this is the first report that sciadopitysin can inhibit the Aβ aggregation and reduce Aβ-induced toxicity in the primary cortical neurons. 22648529 An in vitro Study on the DNA Damaging Effects of Phytochemicals Partially Isolated from an Extract of Glinus lotoides. An extract of Glinus lotoides, a medicinal plant used in Africa and Asia for various therapeutic purposes, was recently shown to cause DNA damage in vitro. To further explore the potential genotoxicity of this plant, fractionation of the crude extract was performed using reverse phase solid-phase extraction and a stepwise gradient elution of methanol in water. Four fractions were collected and subsequently analysed for their DNA damaging effects in mouse lymphoma cells using an alkaline version of the comet assay. To identify potential genotoxic and non-genotoxic principles, each fraction was then subjected to liquid chromatography coupled to mass spectrometry, LC-MS/MS. 1D and 2D nuclear magnetic resonance analyses were used to confirm the identity of some saponins. Although fractions containing a mixture of flavonoids and oleanane-type saponins or oleanane-type saponins alone produced no DNA damage, those containing hopane-type saponins exhibited a pronounced DNA damaging effect without affecting the viability of the cells. To conclude, even if this study presents evidence that hopane-type of saponins are endowed with a DNA damaging ability, further studies are needed before individual saponins can be cited as a culprit for the previously reported genotoxicity of the crude extract of G. lotoides. Copyright © 2012 John Wiley & Sons, Ltd. 23395914 Site dependent intestinal absorption of darunavir and its interaction with ketoconazole. The expression of P-gp increases from proximal to distal parts of the small intestine, whereas for P450 enzymes the expression is reported to be highest in duodenum and jejunum, decreasing to more distal sites. To evaluate to what extent the regional differences in expression of P-gp and P450 enzymes affect the absorption of a dual substrate, we investigated the transport of darunavir across different small intestinal segments (duodenum, proximal jejunum and ileum). Moreover, the effect of ketoconazole on the intestinal absorption of darunavir was explored, since these drugs are commonly co-administered. Performing the rat in situ intestinal perfusion technique with mesenteric blood sampling, we found no significant differences in the transport of darunavir at the different intestinal segments. The involvement of P-gp in the absorption of darunavir was clearly shown by coperfusion of darunavir with the P-gp inhibitor zosuquidar. In presence of zosuquidar, a 2.2-, 4.2- and 5.7-fold increase in Papp values were measured for duodenum, proximal jejunum and ileum, respectively. Involvement of P450 mediated metabolism in the absorption of darunavir could not be demonstrated in this rat model. Upon studying the drug-drug interaction of darunavir with ketoconazole, data were indicative for an inhibitory effect of ketoconazole on P-gp as the main mechanism for the increased transport of darunavir across the small intestine. 23293000 Conformational dynamics of the human propeller telomeric DNA quadruplex on a microsecond time scale. The human telomeric DNA sequence with four repeats can fold into a parallel-stranded propeller-type topology. NMR structures solved under molecular crowding experiments correlate with the crystal structures found with crystal-packing interactions that are effectively equivalent to molecular crowding. This topology has been used for rationalization of ligand design and occurs experimentally in a number of complexes with a diversity of ligands, at least in the crystalline state. Although G-quartet stems have been well characterized, the interactions of the TTA loop with the G-quartets are much less defined. To better understand the conformational variability and structural dynamics of the propeller-type topology, we performed molecular dynamics simulations in explicit solvent up to 1.5 μs. The analysis provides a detailed atomistic account of the dynamic nature of the TTA loops highlighting their interactions with the G-quartets including formation of an A:A base pair, triad, pentad and hexad. The results present a threshold in quadruplex simulations, with regards to understanding the flexible nature of the sugar-phosphate backbone in formation of unusual architecture within the topology. Furthermore, this study stresses the importance of simulation time in sampling conformational space for this topology. 23578625 LC/MS analysis of proteolytic peptides in wheat extracts for determining the content of the allergen amylase/trypsin inhibitor CM3: Influence of growing area and variety. Food allergy from wheat is triggered by several protein classes, such as LTPs, ω5-gliadins and α-amylase/trypsin inhibitors. The latter proteins, belonging to the prolamin superfamily, are mostly involved in baker's asthma, a form of occupational allergy in which the sensitization occurs through the respiratory tract. α-Amylase/trypsin inhibitors were also found to be involved in wheat-related atopic dermatitis. In this work, the allergen Tri a 30 (the CM3 α-amylase/trypsin inhibitor) was quantified in durum wheat salt soluble extracts using a peptidomic approach. CM3 protein identification was confirmed by using LTQ-OrbiTrap analysis on peptides obtained from the enzymatically digested protein separated by gel electrophoresis. Then, marker peptides derived from the protein after enzymatic cleavage of the full wheat extracts were identified by LC-MS/MS. One of them was used as marker for quantitative determination on an UPLC/ESI-MS system by using its isotopically labelled analogue as internal standard, allowing to assess the protein content in the different samples. The CM3 allergenic proteins were found to greatly vary among different cultivation areas. 23106229 The velvet complex governs mycotoxin production and virulence of Fusarium oxysporum on plant and mammalian hosts. Fungal pathogens provoke devastating losses in agricultural production, contaminate food with mycotoxins and give rise to life-threatening infections in humans. The soil-borne ascomycete Fusarium oxysporum attacks over 100 different crops and can cause systemic fusariosis in immunocompromised individuals. Here we functionally characterized VeA, VelB, VelC and LaeA, four components of the velvet protein complex which regulates fungal development and secondary metabolism. Deletion of veA, velB and to a minor extent velC caused a derepression of conidiation as well as alterations in the shape and size of microconidia. VeA and LaeA were required for full virulence of F. oxysporum on tomato plants and on immunodepressed mice. A critical contribution of velvet consists in promoting chromatin accessibility and expression of the biosynthetic gene cluster for beauvericin, a depsipeptide mycotoxin that functions as a virulence determinant. These results reveal a conserved role of the velvet complex during fungal infection on plants and mammals. 23160527 Liver-specific disruption of the murine glucagon receptor produces α-cell hyperplasia: evidence for a circulating α-cell growth factor. Glucagon is a critical regulator of glucose homeostasis; however, mechanisms regulating glucagon action and α-cell function and number are incompletely understood. To elucidate the role of the hepatic glucagon receptor (Gcgr) in glucagon action, we generated mice with hepatocyte-specific deletion of the glucagon receptor. Gcgr(Hep)(-/-) mice exhibited reductions in fasting blood glucose and improvements in insulin sensitivity and glucose tolerance compared with wild-type controls, similar in magnitude to changes observed in Gcgr(-/-) mice. Despite preservation of islet Gcgr signaling, Gcgr(Hep)(-/-) mice developed hyperglucagonemia and α-cell hyperplasia. To investigate mechanisms by which signaling through the Gcgr regulates α-cell mass, wild-type islets were transplanted into Gcgr(-/-) or Gcgr(Hep)(-/-) mice. Wild-type islets beneath the renal capsule of Gcgr(-/-) or Gcgr(Hep)(-/-) mice exhibited an increased rate of α-cell proliferation and expansion of α-cell area, consistent with changes exhibited by endogenous α-cells in Gcgr(-/-) and Gcgr(Hep)(-/-) pancreata. These results suggest that a circulating factor generated after disruption of hepatic Gcgr signaling can increase α-cell proliferation independent of direct pancreatic input. Identification of novel factors regulating α-cell proliferation and mass may facilitate the generation and expansion of α-cells for transdifferentiation into β-cells and the treatment of diabetes. 23553905 An analysis of skeletal development in osteoblast- and chondrocyte-specific Runx2 knockout mice. Global gene deletion studies in mice and humans have established the pivotal role of runt related transcription factor-2 (Runx2) in both intramembranous and endochondral ossification processes during skeletogenesis. In this study, we for the first time generated mice carrying a conditional Runx2 allele with exon 4, which encodes the Runt domain, flanked by loxP sites. These mice were crossed with α1(I)-collagen-Cre or α1(II)-collagen-Cre transgenic mice to obtain osteoblast- or chondrocyte-specific Runx2 deficient mice, respectively. As seen in Runx2(-/-) mice, perinatal lethality was observed in α1(II)-Cre;Runx2(flox/flox) mice, but this was not the case in animals in which α1(I)-collagen-Cre was used to delete Runx2. When using double staining with Alizarin red for mineralized matrix and Alcian blue for cartilaginous matrix, we observed previously that mineralization was totally absent at embryonic day 15.5 throughout the body in Runx2(-/-) mice, but was found in areas undergoing intramembranous ossification such as skull and clavicles in α1(II)-Cre;Runx2(flox/flox) mice. In newborn α1(II)-Cre;Runx2(flox/flox) mice, mineralization impairment was restricted to skeletal areas undergoing endochondral ossification including long bones and vertebrae. In contrast, no apparent skeletal abnormalities were seen in mutant embryo, newborn, and 3- to 6-week old-mice in which Runx2 had been deleted with the α1(I)-collagen-Cre driver. These results suggest that Runx2 is absolutely required for endochondral ossification during embryonic and postnatal skeletogenesis, but that disrupting its expression in already committed osteoblasts as achieved here with the α1(I)-collagen-Cre driver does not affect overtly intramembranous and endochondral ossification. The Runx2 floxed allele established here is undoubtedly useful for investigating the role of Runx2 in particular cells. © 2013 American Society for Bone and Mineral Research. 23249525 Quinpirole and 8-OH-DPAT induce compulsive checking behavior in male rats by acting on different functional parts of an OCD neurocircuit. This study investigated whether the serotonin 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) can induce compulsive checking in a large open field, as does the dopamine D2/D3 receptor agonist quinpirole. To induce compulsive checking, male rats were exposed to eight injections of either 8-OH-DPAT (1 mg/kg), quinpirole (0.2 mg/kg), or saline. Subsequently, to assess cross-sensitization, rats received an acute challenge of 8-OH-DPAT or quinpirole. The results showed that treatment with 8-OH-DPAT induces compulsive checking and may have a stronger effect on this behavior compared with quinpirole. However, there was no cross-sensitization between 8-OH-DPAT and quinpirole on measures of compulsive checking and locomotion. Moreover, the spatial distribution of locomotor paths in 8-OH-DPAT animals was more confined and invariant than in quinpirole rats; their rate of locomotor sensitization was also faster than that in quinpirole animals. Thus, although 8-OH-DPAT and quinpirole can induce compulsive checking in a large open field, the results suggest that they do so differently. It is suggested that 8-OH-DPAT and quinpirole probably produce compulsive behavior by acting on different parts of a security motivation circuit underlying obsessive-compulsive disorder. Quinpirole may induce compulsive checking behavior by directly driving dopaminergic activity mediating the motivational drive to check. Conversely, 8-OH-DPAT may perpetuate the activated motivational state by inhibiting the serotonergic-negative feedback signals that normally deactivate the obsessive-compulsive disorder circuit. 23204443 Sphingosine 1-phosphate receptor 1 (S1P(1)) upregulation and amelioration of experimental autoimmune encephalomyelitis by an S1P(1) antagonist. Sphingosine 1-phosphate receptor 1 (S1P(1)) is a G protein-coupled receptor that is critical for proper lymphocyte development and recirculation. Agonists to S1P(1) are currently in use clinically for the treatment of multiple sclerosis, and these drugs may act on both S1P(1) expressed on lymphocytes and S1P(1) expressed within the central nervous system. Agonists to S1P(1) and deficiency in S1P(1) both cause lymphocyte sequestration in the lymph nodes. In the present study, we show that S1P(1) antagonism induces lymphocyte sequestration in the lymph nodes similar to that observed with S1P(1) agonists while upregulating S1P(1) on lymphocytes and endothelial cells. Additionally, we show that S1P(1) antagonism reverses experimental autoimmune encephalomyelitis in mice without acting on S1P(1) expressed within the central nervous system, demonstrating that lymphocyte sequestration via S1P(1) antagonism is sufficient to alleviate autoimmune pathology. 23570609 Design and evaluation of polyamidoamine dendrimer conjugate with PEG, α-cyclodextrin and lactose as a novel hepatocyte-selective gene carrier in vitro and in vivo. Abstract To develop a novel hepatocyte-selective gene carrier, we prepared polyamidoamine starburst dendrimer (generation 3, G3) conjugates with three functional molecules, i.e. α-cyclodextrin, polyethylene glycol (PEG, molecular weight = 2170) and lactose (PEG-LαCs), and evaluated gene delivery efficiency of these conjugates in vitro and in vivo. PEG-LαC (G3, degrees of substitution of the PEG moiety (DSP) 2.1) showed higher gene transfer activity than other PEG-LαCs (G3, DSP4.0, 6.2) in HepG2 cells, expressing asialoglycoprotein receptor, and the activity decreased in HeLa cells, non-expressing the receptor and in the presence of asialofetuin. High gene transfer activity of PEG-LαC (G3, DSP2.1) was retained even in the presence of 50% serum, although the activity of α-cyclodextrin/lactosylated dendrimer (G3) conjugate (Lac-α-CDE (G3)), which is lacking a PEG moiety, was severely decreased in the presence of 20% serum. PEG-LαC (G3, DSP2.1) provided negligible cytotoxicity up to a charge ratio of 50 (carrier/pDNA) in HepG2 cells and less acute organ toxicity. PEG-LαC (G3, DSP2.1) showed selective gene transfer activity to hepatic parenchymal cells rather than hepatic non-parenchymal cells. These results suggest that PEG-LαC (G3, DSP2.1) is useful as a hepatocyte-selective gene carrier in vitro and in vivo. 23614635 Safety concerns with the long-term management of osteoporosis. Introduction: Postmenopausal osteoporosis is a chronic disease that exerts a significant burden on both individuals and the community. Hence, there is a requirement for long-term treatment to be associated with a positive benefit-risk balance. Areas covered: In this descriptive review, the long-term safety of calcitonin, selective estrogen receptor modulators (SERMs), bisphosphonates, denosumab and strontium ranelate was reviewed based on randomized controlled trials of 3 years or longer supplemented by extension study data and data from large, observational studies. Expert opinion: Rare adverse events become apparent with all currently available treatments for osteoporosis with long-term therapy. Due to the rarity of these adverse events and to the worldwide burden of osteoporosis, the benefit-risk balance remains in favor of the beneficial effects of treatment on an outcome rather than the probability of an adverse effect. No single antiosteoporosis agent is appropriate for all patients. Treatment decisions should be made on an individual basis, taking into account the relative benefits and risks in different patient populations. 23402638 Iron(II)-catalyzed intramolecular aminohydroxylation of olefins with functionalized hydroxylamines. A diastereoselective aminohydroxylation of olefins with a functionalized hydroxylamine is catalyzed by new iron(II) complexes. This efficient intramolecular process readily affords synthetically useful amino alcohols with excellent selectivity (dr up to > 20:1). Asymmetric catalysis with chiral iron(II) complexes and preliminary mechanistic studies reveal an iron nitrenoid is a possible intermediate that can undergo either aminohydroxylation or aziridination, and the selectivity can be controlled by careful selection of counteranion/ligand combinations. 23117790 Orexin-A suppresses postischemic glucose intolerance and neuronal damage through hypothalamic brain-derived neurotrophic factor. Orexin-A (a glucose-sensing neuropeptide in the hypothalamus) and brain-derived neurotrophic factor (BDNF; a member of the neurotrophin family) play roles in many physiologic functions, including regulation of glucose metabolism. We previously showed that the development of postischemic glucose intolerance is one of the triggers of ischemic neuronal damage. The aim of this study was to determine whether there was an interaction between orexin-A and BDNF functions in the hypothalamus after cerebral ischemic stress. Male ddY mice were subjected to 2 hours of middle cerebral artery occlusion (MCAO). Neuronal damage was estimated by histologic and behavioral analyses. Expression of protein levels was analyzed by Western blot. Small interfering RNA directed BDNF, orexin-A, and SB334867 [N-(2-methyl-6-benzoxazolyl)-N'-1,5-naphthyridin-4-yl urea; a specific orexin-1 receptor antagonist] were administered directly into the hypothalamus. The level of hypothalamic orexin-A, detected by immunohistochemistry, was decreased on day 1 after MCAO. Intrahypothalamic administration of orexin-A (1 or 5 pmol/mouse) significantly and dose-dependently suppressed the development of postischemic glucose intolerance on day 1 and development of neuronal damage on day 3. The MCAO-induced decrease in insulin receptor levels in the liver and skeletal muscle on day 1 was recovered to control levels by orexin-A, and this effect of orexin-A was reversed by the administration of SB334867 as well as by hypothalamic BDNF knockdown. These results suggest that suppression of postischemic glucose intolerance by orexin-A assists in the prevention of cerebral ischemic neuronal damage. In addition, hypothalamic BDNF may play an important role in this effect of orexin-A. 23149908 QT dispersion in patients with acromegaly. Acromegaly is a rare condition caused by a pituitary adenoma that secretes growth hormone. The mortality rate is 72 % higher in patients with acromegaly than in the general population according to meta-analyses. Mortality analysis has shown as many as 60 % of acromegalic patients die due to cardiovascular disease. Sudden cardiac death may occur in patients with acromegaly and malignant ventricular arrhythmia may play an important role in this fatal complication; however, the precise mechanism is not fully known. QT dispersion (dQT) is an electrophysiological factor known to be associated with a tendency for ventricular arrhythmia and sudden cardiac death. This study aimed to evaluate dQT as an early predictor of ventricular tachyarrhythmia, as sudden cardiac death commonly occurs in acromegalic patients. This cross-sectional case-control study enrolled 20 patients (10 female and 10 male) with acromegaly and 20 healthy controls (11 female and 9 male) after exclusion criteria were applied. Each participant underwent 12-lead electrocardiography, including ≥3 QRS complexes, at a speed of 25 mm/s after a 15-min rest. In each participant, the QT interval (beginning of the Q wave to the end of the T wave) was corrected (QTc) for heart rate using Bazett's formula [Formula: see text] QTc dispersion (dQTc) (QTc max - QTc min) was also calculated. There was no significant difference in median dQTc between the acromegalic patients (0.79 s) and the controls (0.45 s) (p > 0.05). Active acromegalic patients (n = 14) were estimated to have a median dQTc of 0.82 s, after excluding from the analysis six patients that were under full biochemical control, and that had randomly obtained growth hormone levels <0.4 ng/mL, GH <1 ng/mL based on oral glucose tolerance test, and normal IGF-I for age and gender. A significant difference was noted in median dQTc between the active acromegalic patients and the controls (p = 0.015). The dQT in active acromegalic patients was longer than that in the control group, which indicates that patients with active acromegaly might have an elevated risk for ventricular arrhythmia. We think that a non-invasive, simple and inexpensive marker-measurement of dQT-as part of cardiac monitoring could be valuable for screening complications in acromegalic patients. 23343474 Chemisorbed monolayers of corannulene penta-thioethers on gold. Penta(tert-butylthio)corannulene and penta(4-dimethylaminophenylthio)corannulene form highly stable monolayers on gold surfaces, as indicated by X-ray photoelectron spectroscopy (XPS). Formation of these homogeneous monolayers involves multivalent coordination of the five sulfur atoms to gold with the peripheral alkyl or aryl substituents pointing away from the surface. No dissociation of C-S bonds upon binding could be observed at room temperature. Yet, the XPS experiments reveal strong chemical bonding between the thioether groups and gold. Temperature-dependent XPS study shows that the thermal stability of the monolayers is higher than the typical stability of self-assembled monolayers (SAMs) of thiolates on gold. 23561109 Research on the preparation of antioxidant peptides derived from egg white with assisting of high-intensity pulsed electric field. Egg white protein powder, one of the main egg products, was hydrolysed by Alcalase, Trypsin, and Pepsin respectively to prepare antioxidant peptides. All hydrolysates were assayed by determination of reducing power (RP) ability. Three kinds of hydrolysates were prepared under optimal enzymatic parameters that were obtained from the preliminary one-factor-at-a-time (OFAT) and response surface methodology (RSM) experiments. The results showed that the Alcalase hydrolysates exerted the best RP ability. Thereafter, the Alcalase hydrolysates were sequentially fractionated by ultra filtration membranes in cut-off molecular weight (MW) of 30, 10, and 1kDa, and tested their antioxidant activities in terms of RP ability, DPPH radical scavenging ability, ABTS radical scavenging ability, and FRAP assay. Effects of high intensity pulsed electric field treatment were further investigated on antioxidant peptides to improve their activities. The results showed that Alcalase hydrolysates possessed the strongest antioxidant ability compared with the other two hydrolysates, particularly for the Fraction-3 with MW <1kDa. After PEF treatment, this fraction showed a significant improvement of RP ability within 5h (P<0.05). 23411175 Interaction and digestibility of phaseolin/polyphenol in the common bean. The polyphenols and phaseolin interaction in common bean varieties was studied. Raw beans of three different colours were analysed: black (BRS Supremo), brown (BRS Pontal) and white (WAF-75). Based on the phaseolin digestibility in vitro and phaseolin-polyphenol complexation obtained by SDS-PAGE on a 10% polyacrylamide gel, it was observed that the polyphenols interfere with the digestibility of beans by decreasing the hydrolysis of phaseolin, especially in the darker ones. Furthermore it was possible to verify a difference in the electrophoretic pattern of phaseolin, indicating an interaction between phaseolin and polyphenols. 23118018 Role of 5-hydroxytryptamine 1B (5-HT1B) receptors in the regulation of ethanol intake in rodents. Evidence indicates that the serotonergic system is important in mediating dependence on and craving for alcohol. Among serotonin receptors, 5-hydroxytryptamine 1B (5-HT1B) receptors have been associated with drug abuse including alcohol. In this review, the neurocircuitry involving 5-HT1B receptors in central reward brain regions related to alcohol intake are discussed in detail. Emphasis has been placed on the pharmacological manipulations of 5-HT1B receptor-mediated alcohol intake. Furthermore, 5-HT1B auto- and hetero-receptors regulate alcohol intake through the regulatory mechanism involving release of 5-HT, gamma-aminobutyric acid (GABA), dopamine, and glutamate is evaluated. Thus, interactions between 5-HT1B receptors and these neurotransmitter systems are suggested to modulate alcohol-drinking behavior. This review on the role of 5-HT1B receptors in neurotransmitter release and consequent alcohol intake provides important information about the potential therapeutic role of 5-HT1B receptors for the treatment of alcohol dependence. 23459146 Effects of sodium fluoride on reproductive function in female rats. The aim of this study was to investigate the effects of sodium fluoride (NaF) on female reproductive function and examine the morphology of the ovaries and uteri of rats exposed to NaF. Eighty female Sprague-Dawley (SD) rats were divided randomly into four groups of 20: one control group and three NaF treated groups. The three NaF treated groups received 100, 150, and 200ppm, respectively, of NaF for 6months via their drinking water, while the control group (GC) received distilled water. The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), progesterone (P) and estradiol (E2) were measured using an enzyme-linked immunosorbent assay. Pathomorphological evaluation of the uteri and ovaries was conducted after staining with hematoxylin-eosin and immunohistochemistry. The rate of successful pregnancy in the NaF-treated groups declined in a dose-dependent manner. The concentration of reproductive hormones was significantly lower in the three NaF-treated groups, and the endometrium was damaged. The maturation of follicles was inhibited. In addition, the total number of follicles of all types was significantly lower in the NaF-treated groups. These results suggest that female reproductive function is inhibited by NaF and that exposure to NaF causes ovarian and uterine structural damage. NaF may thus significantly reduce the fertility of female rats. 23590689 High Level ab initio Calculations for ClFn(+) (n=1-6) Ions: Refining the Recoupled Pair Bonding Model. Based on detailed, high level ab initio calculations on a number of halogenated compounds of second row, late p-block elements, the SFn, ClFn, PFn, SCln, and SFnCl families, we found that a new type of bond - the recoupled pair bond - accounts for the ability of these elements to form hypervalent, or hypercoordinated, compounds. Hypervalent molecules are formed when it is energetically favorable for the electrons in a lone pair orbital to be recoupled, allowing each of the electrons to form chemical bonds with ligands. In this paper, we characterize the structures and energetics of the ground and low-lying excited states of the ClFn(+) (n=1-6) ions, using high level ab initio methods [MRCI, CCSD(T)/RCCSD(T)] with large correlation consistent basis sets. We computed a number of quantities, including ClFn(+) structures, bond dissociation energies and ClFn ionization energies, and compare our results with the available experimental data. Both the bond dissociation energies and ionization energies oscillate, variations that are readily explained using the recoupled pair bonding model. Comparisons are drawn between the ClFn(+) cations and their counterparts in the isoelectronic SFn series, which possess many similarities. We found two significant differences between the ClFn(+) and SFn series: (i) the bond dissociation energies of ClFn(+) are much weaker than those of the corresponding SFn species, and (ii) there is no stable (3)A2 state in ClF2(+) corresponding to the stable state found in SF2. Examination of the Mulliken populations at the HF/AVTZ level for ClFn(+) and SFn species predicts that the F atom in the axial (recoupled pair bonding) position is more highly charged than the F atom in the equatorial (covalent bonding) position; there is also less change transfer to the F atoms in ClFn(+) than in SFn. The positive charge on Cl(+) makes it more difficult for an F atom to attract electrons from Cl(+) than from S and correspondingly less favorable to recouple the electrons in the lone pair orbitals in the ClFn(+) species. 23587423 A small molecule inhibitor of fungal histone acetyltransferase Rtt109. The histone acetyltransferase Rtt109 is the sole enzyme responsible for acetylation of histone H3 lysine 56 (H3K56) in fungal organisms. Loss of Rtt109 renders fungal cells extremely sensitive to genotoxic agents, and prevents pathogenesis in several clinically important species. Here, via a high throughput chemical screen of >300,000 compounds, we discovered a chemical inhibitor of Rtt109 that does not inhibit other acetyltransferase enzymes. This compound inhibits Rtt109 regardless of which histone chaperone cofactor protein (Asf1 or Vps75) is present, and appears to inhibit Rtt109 via a tight-binding, uncompetitive mechanism. 23606301 Microfluidic Surface-Enhanced Raman Scattering Sensors Based on Nanopillar Forests Realized by an Oxygen-Plasma-Stripping-of-Photoresist Technique. A novel surface-enhanced Raman scattering (SERS) sensor is developed for real-time and highly repeatable detection of trace chemical and biological indicators. The sensor consists of a polydimethylsiloxane (PDMS) microchannel cap and a nanopillar forest-based open SERS-active substrate. The nanopillar forests are fabricated based on a new oxygen-plasma-stripping-of-photoresist technique. The enhancement factor (EF) of the SERS-active substrate reaches 6.06 × 10(6) , and the EF of the SERS sensor is about 4 times lower due to the influence of the PDMS cap. However, the sensor shows much higher measurement repeatability than the open substrate, and it reduces the sample preparation time from several hours to a few minutes, which makes the device more reliable and facile for trace chemical and biological analysis. 23560557 Takotsubo cardiomyopathy associated with thyrotoxicosis: A case report and review of the literature. Background: Takotsubo or stress-induced cardiomyopathy is a form of reversible cardiomyopathy, commonly associated with emotional or physical stress. Thyrotoxicosis has been identified as a rare cause of Takotsubo cardiomyopathy with only eleven cases reported in the literature. Here, we report a case of thyroid storm presenting with Takotsubo cardiomyopathy in the setting of Graves' disease. Patient Findings: A 71-year-old woman presented with abdominal pain, vomiting, confusion and history of weight loss. She was initially diagnosed and treated for diabetic ketoacidosis at another hospital and was transferred to our hospital one day after initial presentation due to concern for acute coronary syndrome. A diagnosis of Takotsubo cardiomyopathy was made on the basis of cardiac catheterization. At that time, she was diagnosed and treated for thyroid storm. Follow-up 7-weeks later, revealed improvement of her cardiac function and near-normalization of thyroid hormone levels. Summary: In this patient who presented with symptoms of congestive heart failure, acute coronary syndrome was initially considered, but the diagnosis of Takotsubo cardiomyopathy associated with thyroid storm was ultimately made based on cardiac catheterization and laboratory investigation. Conclusions: Thyrotoxicosis is associated with adverse disturbances in the cardiovascular system. Takotsubo cardiomyopathy could be a presenting manifestation of thyroid storm, perhaps related to excess catecholamine levels or sensitivity. 23122155 Antidepressant-like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L. The aim of this study was to investigate the antidepressant-like effect of fractions from Rosmarinus officinalis L.: ethyl acetate 1 and 2 (AcOEt1 and 2), hexane (HEX), ethanolic (ET), and essential oil-free (EOF) fractions, as well as essential oil, the isolated compounds carnosol and betulinic acid in the tail suspension test, a predictive test of antidepressant activity. Swiss mice were acutely administered by oral route (p.o.) with fractions, essential oil or isolated compounds, 60 min before the tail suspension test or open-field test. All of them produced a significant antidepressant-like effect: AcOEt1, ET, EOF fractions and essential oil (0.1-100mg/kg, p.o); HEX (0.1-10mg/kg, p.o) and AcOEt2 fraction (0.1-1mg/kg, p.o), carnosol (0.01-0.1mg/kg, p.o.) isolated from the HEX fraction and betulinic acid (10mg/kg, p.o.), isolated from the AcOEt1 and AcOEt2 fractions. No psychostimulant effect was shown in the open-field test, indicating that the effects in the tail suspension test are specific. This study suggests that carnosol and betulinic acid could be responsible for the anti-immobility effect of extracts from R. officinalis. 23102508 Enzyme kinetic and molecular docking studies for the inhibitions of miltirone on major human cytochrome P450 isozymes. Previous studies have shown that major tanshinones isolated from Danshen (Salvia miltiorrhiza) inhibited human and rat CYP450 enzymes-mediated metabolism of model probe substrates, with potential in causing herb-drug interactions. Miltirone, another abietane type-diterpene quinone isolated from Danshen, has been reported for its anti-oxidative, anxiolytic and anti-cancer effects. The aim of this study was to study the effect of miltirone on the metabolism of model probe substrates of CYP1A2, 2C9, 2D6 and 3A4 in pooled human liver microsomes. Miltirone showed moderate inhibition on CYP1A2 (IC(50)=1.73 μM) and CYP2C9 (IC(50)=8.61 μM), and weak inhibition on CYP2D6 (IC(50)=30.20 μM) and CYP3A4 (IC(50)=33.88 μM). Enzyme kinetic studies showed that miltirone competitively inhibited CYP2C9 (K(i)=1.48 μM), and displayed mixed type inhibitions on CYP1A2, CYP2D6 and CYP3A4 with K(i) values of 3.17 μM, 24.25 μM and 35.09 μM, respectively. Molecular docking study further confirmed the ligand-binding conformations of miltirone in the active sites of these human CYP450 isoforms, and provided some information on structure-activity relationships for the CYPs inhibition by tanshinones. Taken together, CYPs inhibitions of miltirone were weaker than dihydrotanshinone, but stronger than cryptotanshinone, tanshinone I and tanshinone IIA. 23376439 Aspiration toxicology of hydrocarbons and lamp oils studied by in vitro technology. Medical literature regularly reports on accidental poisoning in children after aspiration of combustibles such as lamp oils which usually contain hydrocarbons or rape methyl esters (RMEs). We aimed to analyze the toxic potential of alkanes and different combustible classes in vitro with regard to biologic responses and mechanisms mediating toxicity. Two different in vitro models were used, i.e. (i) a captive bubble surfactometer (CBS) to assess direct influence of combustibles on biophysical properties of surfactant film and (ii) cell cultures (BEAS-2B and R3/1 cells, primary macrophages, re-differentiated epithelia) closely mimicking the inner lung surface. Biological endpoints included cell viability, cytotoxicity and inflammatory mediator release. CBS measurements demonstrate that combustibles affect film dynamics, i.e. the surface tension/area characteristics during compression and expansion, in a dose and molecular chain length dependent manner. Cell culture results confirm the dose dependent toxicity. Generally, cytotoxicity and cytokine release are higher in short-chained alkanes and hydrocarbon-based combustibles than in long-chained substances, e.g. highest inducible cytotoxicity in BEAS-2B was for hexane 84.6%, decane 74% and hexadecane 30.8%. Effects of RME-based combustibles differed between the cell models. Our results confirm data from animal experiments and give new insights into the mechanisms underlying the adverse health effects observed. 23562245 Quantitative protein analysis using (13)C7-labeled iodoacetanilide and d5-labeled N-ethylmaleimide by nano liquid chromatography/nanoelectrospray ionization ion trap mass spectrometry. We have developed a methodology for quantitative analysis and concurrent identification of proteins by the modification of cysteine residues with a combination of iodoacetanilide (IAA, 1) and (13)C7-labeled iodoacetanilide ((13)C7-IAA, 2), or N-ethylmaleimide (NEM, 3) and d5-labeled N-ethylmaleimide (d5-NEM, 4), followed by mass spectrometric analysis using nano liquid chromatography/nanoelectrospray ionization ion trap mass spectrometry (nano LC/nano-ESI-IT-MS). The combinations of these stable isotope-labeled and unlabeled modifiers coupled with LC separation and ESI mass spectrometric analysis allow accurate quantitative analysis and identification of proteins, and therefore are expected to be a useful tool for proteomics research. 23540754 Biocompatible Polylactide-block-Polypeptide-block-Polylactide Nanocarrier. Polypeptides are successfully incorporated into poly(l-lactide) (PLLA) chains in a ring-opening polymerization (ROP) of l-lactide by using them as initiators. The resulting ABA triblock copolymers possess molecular weights up to 11000 g·mol(-1) and polydispersities as low as 1.13, indicating the living character of the polymerization process. In a nonaqueous emulsion, peptide-initiated polymerization of l-lactide leads to well-defined nanoparticles, consisting of PLLA-block-peptide-block-PLLA copolymer. These nanoparticles are easily loaded by dye-encapsulation and transferred into aqueous media without aggregation (average diameter of 100 nm) or significant dye leakage. Finally, internalization of PLLA-block-peptide-block-PLLA nanoparticles by HeLa cells is demonstrated by a combination of coherent anti-Stokes Raman spectroscopy (CARS) and fluorescence microscopy. This demonstrates the promise of their utilization as cargo delivery vehicles. 23207166 Birth defects after exposure to misoprostol in the first trimester of pregnancy: prospective follow-up study. Misoprostol during the first trimester of pregnancy is associated with a specific malformative pattern (Moebius sequence and limb defects) whose incidence remains unknown. Data originate mostly from illegal use for abortion and are mainly retrospective. The present prospective controlled study analyses outcomes of first trimester misoprostol exposures after medical prescriptions. Malformation rate was higher among 236 pregnancies exposed before 12 gestational weeks (4%) than in 255 controls (1.8%), although not statistically significant (OR=2.2 [95% CI=0.6-7.7]). Three malformations (2%) in the exposed group were consistent with the misoprostol malformative pattern. This is the largest prospective study on first trimester misoprostol exposure and the first one relying on prescriptions. A trend toward a doubling of the overall rate of malformations was observed and for the first time an estimation of the incidence of misoprostol specific spectrum is proposed (2%). Brainstem injuries including severe trismus might be added to this specific pattern. 23265526 The antioxidant activity of teas measured by the FRAP method adapted to the FIA system: optimising the conditions using the response surface methodology. This study proposes a FRAP assay adapted to FIA system with a merging zones configuration. The FIA system conditions were optimised with the response surface methodology using the central composite rotatable design. The optimisation parameters studied were: the carrier flow rate, the lengths of the sample and reagent loops, and reactor length. The conditions selected in accordance with the results were: carrier flow rate of 1.00 ml/min, length of the loops 18.2 cm and length of the reaction coil 210.1 cm. The detection and quantification limits were, respectively, 28.6 and 86.8 μmol/l Fe(2+), and the precision was 1.27%. The proposed method had an analytical frequency of 30 samples/h and about 95% less volume of FRAP reagent was consumed. The FRAP assay adapted to the FIA system under the optimised conditions was utilised to determine the antioxidant activity of tea samples. 23378200 Effects of baicalin on airway remodeling in asthmatic mice. Airway remodeling is an important characteristic of asthma, linking inflammation with airway hyperresponsiveness. Baicalin, a major active component, was isolated from Radix Scutellariae. Many studies show that baicalin has anti-inflammatory, anti-bacterial, and anti-allergic effects. Here we investigate the influence of baicalin on asthmatic airway remodeling and the mechanism underlining the anti-remodeling effect in vivo.Asthmatic airway remodeling mice model was established by ovalbumin exposure. Seventy female BALB/c mice were randomly assigned to seven experimental groups: blank, ovalbumin, hexadecadrol, control, and baicalin (25 mg/kg, 50 mg/kg, 100 mg/kg) groups. Pulmonary function was measured using a whole-body plethysmograph in conscious and unrestrained mice. The lung pathology was observed and measured. The production of cytokines in bronchoalveolar lavage fluid and serum was measured using enzyme-labeled immunosorbent assay kits, and the expression levels of transforming growth factor-β1 and vascular endothelial growth factor were detected by immunohistochemistry. The protein expression levels of transforming growth factor-β1, vascular endothelial growth factor, extracellular signal-regulated kinase, and p21ras were measured using Western blot. The results show that ovalbumin exposure significantly increased the expression of interleukin-13 in BALF and serum, and transforming growth factor-β1, vascular endothelial growth factor, extracellular signal-regulated kinase and p21ras expressions in the lungs. Baicalin attenuated the effects of ovalbumin significantly.It can be concluded that baicalin has significant anti-remodeling effect on ovalbumin-induced asthmatic airway remodeling mice model by decreasing expression of transforming growth factor-β1, interleukin-13, and vascular endothelial growth factor and inhibiting the activation of the extracellular signal-regulated kinase pathway. 23335220 Biotinylated phosphoproteins from kinase-catalyzed biotinylation are stable to phosphatases: implications for phosphoproteomics. Kinase-catalyzed protein phosphorylation is involved in a wide variety of cellular events. Development of methods to monitor phosphorylation is critical to understand cell biology. Our lab recently discovered kinase-catalyzed biotinylation, where ATP-biotin is utilized by kinases to label phosphopeptides or phosphoproteins with a biotin tag. To exploit kinase-catalyzed biotinylation for phosphoprotein purification and identification in a cellular context, the susceptibility of the biotin tag to phosphatases was characterized. We found that the phosphorylbiotin group on peptide and protein substrates was relatively insensitive to protein phosphatases. To understand how phosphatase stability would impact phosphoproteomics research applications, kinase-catalyzed biotinylation of cell lysates was performed in the presence of kinase or phosphatase inhibitors. We found that biotinylation with ATP-biotin was sensitive to inhibitors, although with variable effects compared to ATP phosphorylation. The results suggest that kinase-catalyzed biotinylation is well suited for phosphoproteomics studies, with particular utility towards monitoring low-abundance phosphoproteins or characterizing the influence of inhibitor drugs on protein phosphorylation. 23534442 Novel analgesic/anti-inflammatory agents: 1,5-diarylpyrrole nitrooxyalkyl ethers and related compounds as cyclooxygenase-2 inhibiting nitric oxide donors. A series of 3-substituted 1,5-diarylpyrroles bearing a nitrooxyalkyl side chain linked to different spacers were designed. New classes of pyrrole-derived nitrooxyalkyl inverse esters, carbonates, and ethers (7-10) as COX-2 selective inhibitors and NO donors were synthesized and are herein reported. By taking into account the metabolic conversion of nitrooxyalkyl ethers (9, 10) into corresponding alcohols, derivatives 17 and 18 were also studied. Nitrooxy derivatives showed NO-dependent vasorelaxing properties, while most of the compounds proved to be very potent and selective COX-2 inhibitors in in vitro experimental models. Further in vivo studies on compounds 9a,c and 17a highlighted good anti-inflammatory and antinociceptive activities. Compound 9c was able to inhibit glycosaminoglycan (GAG) release induced by interleukin-1β (IL-1β), showing cartilage protective properties. Finally, molecular modeling and (1)H- and (13)C-NMR studies performed on compounds 6c,d, 9c, and 10b allowed the right conformation of nitrooxyalkyl ester and ether side chain of these molecules within the COX-2 active site to be assessed. 23409765 Impact of quaternary structure dynamics on allosteric drug discovery. The morpheein model of allosteric regulation draws attention to proteins that can exist as an equilibrium of functionally distinct assemblies where: one subunit conformation assembles into one multimer; a different subunit conformation assembles into a different multimer; and the various multimers are in a dynamic equilibrium whose position can be modulated by ligands that bind to a multimer-specific ligand binding site. The case study of porphobilinogen synthase (PBGS) illustrates how such an equilibrium holds lessons for disease mechanisms, drug discovery, understanding drug side effects, and identifying proteins wherein drug discovery efforts might focus on quaternary structure dynamics. The morpheein model of allostery has been proposed as applicable for a wide assortment of disease-associated proteins (Selwood, T., Jaffe, E., (2012) Arch. Bioch. Biophys, 519:131-143). Herein we discuss quaternary structure dynamics aspects to drug discovery for the disease-associated putative morpheeins phenylalanine hydroxylase, HIV integrase, pyruvate kinase, and tumor necrosis factor α. Also highlighted is the quaternary structure equilibrium of transthyretin and successful drug discovery efforts focused on controlling its quaternary structure dynamics. 23574984 Antinociceptive Activity of Stephanolepis hispidus Skin Aqueous Extract Depends Partly on Opioid System Activation. Stephanolepis hispidus is one of the most common filefish species in Brazil. Its skin is traditionally used as a complementary treatment for inflammatory disorders. However, there are very few studies on chemical and pharmacological properties using the skin of this fish. This study was undertaken in order to investigate the effect of aqueous crude extract of S. hispidus skin (SAE) in different nociception models. Here, we report that intraperitoneal administration of SAE inhibited the abdominal constrictions induced by acetic acid in mice. In addition to the effect seen in the abdominal constriction model, SAE was also able to inhibit the hyperalgesia induced by carrageenan and prostaglandin E2 (PGE2) in mice. This potent antinociceptive effect was observed in the hot plate model too, but not in tail-flick test. Naloxone, an opioid receptor antagonist, was able to block the antinociceptive effect of SAE in the abdominal constriction and hot plate models. In addition, SAE did not present cytotoxic or genotoxic effect in human peripheral blood cells. Our results suggest that aqueous crude extract from S. hispidus skin has antinociceptive activity in close relationship with the partial activation of opioid receptors in the nervous system. Moreover, aqueous crude extract from S. hispidus skin does not present toxicity and is therefore endowed with the potential for pharmacological control of pain. 23011759 Carboxylesterases are uniquely expressed among tissues and regulated by nuclear hormone receptors in the mouse. Carboxylesterases (CES) are a well recognized, yet incompletely characterized family of proteins that catalyze neutral lipid hydrolysis. Some CES have well-defined roles in xenobiotic clearance, pharmacologic prodrug activation, and narcotic detoxification. In addition, emerging evidence suggests other CES may have roles in lipid metabolism. Humans have six CES genes, whereas mice have 20 Ces genes grouped into five isoenzyme classes. Perhaps due to the high sequence similarity shared by the mouse Ces genes, the tissue-specific distribution of expression for these enzymes has not been fully addressed. Therefore, we performed studies to provide a comprehensive tissue distribution analysis of mouse Ces mRNAs. These data demonstrated that while the mouse Ces family 1 is highly expressed in liver and family 2 in intestine, many Ces genes have a wide and unique tissue distribution defined by relative mRNA levels. Furthermore, evaluating Ces gene expression in response to pharmacologic activation of lipid- and xenobiotic-sensing nuclear hormone receptors showed differential regulation. Finally, specific shifts in Ces gene expression were seen in peritoneal macrophages following lipopolysaccharide treatment and in a steatotic liver model induced by high-fat feeding, two model systems relevant to disease. Overall these data show that each mouse Ces gene has its own distinctive tissue expression pattern and suggest that some CES may have tissue-specific roles in lipid metabolism and xenobiotic clearance. 23220562 Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation. Bleeding complications and delayed healing of gastric ulcer associated with use of clopidogrel is a common clinical concern; however, the underlying mechanisms remain to be determined. This study aimed to clarify whether clopidogrel could cause the damage of the human gastric epithelial cells and to further elucidate the mechanisms involved. After human gastric epithelial cell line GES-1 had been treated with clopidogrel (0.5-2.5 mM), the cell proliferation was examined by MTT assay, apoptosis was measured with DAPI staining and flow cytometry analysis, and the barrier function of the tight junctions (TJ) was evaluated by permeability measurement and transmission electron microscopy. Moreover, expression of the TJ proteins occludin and ZO-1 and the phosphorylation of the mitogen-activated protein kinases (MAPK) p38, ERK, and JNK were examined by western blot. In addition, three MAPK inhibitors specific to p38, ERK and JNK were used, respectively, to verify the signaling pathways responsible for regulating the expression of the TJ proteins being tested. Results showed that clopidogrel significantly increased dextran permeability, induced apoptosis, suppressed GES-1 cell viability, and reduced the expression of the TJ proteins (occludin and ZO-1), acting through p38 MAPK phosphorylation. Furthermore, these observed effects were partially abolished by SB-203580 (a p38 MAPK inhibitor), rather than by either U-0126 (an ERK inhibitor) or SP-600125 (a JNK inhibitor), suggesting that clopidogrel-induced disruption in the gastric epithelial cells is mediated by the p38 MAPK pathway. It is concluded that attenuated expression of the TJ proteins occludin and ZO-1 in human gastric epithelial cells could be involved in clopidogrel-induced gastric mucosal injury through activation of the p38 MAPK pathway. 23318226 ATP stimulates PGE(2)/cyclin D1-dependent VSMCs proliferation via STAT3 activation: role of PKCs-dependent NADPH oxidase/ROS generation. Vascular smooth muscle cells (VSMCs) that function as synthetic units play important roles in cardiovascular diseases. Extracellular nucleotides, such as ATP, have been shown to act via activation of P2 purinoceptors implicated in various inflammatory diseases, we hypothesized that extracellular nucleotides contribute to vascular diseases via up-regulation of inflammatory proteins, including cyclooxygenase-2 (COX-2) and cytosolic phospholipase A2 (cPLA2) in VSMCs. However, the mechanisms of ATP-induced cPLA2 and COX-2 expression and PGE2 synthesis remain largely unclear. We showed that pretreatment with the inhibitors of STAT3 (CBE), NADPH oxidase [diphenyleneiodonium chloride (DPI) or apocynin (APO)], ROS [N-acetyl-l-cysteine (NAC)], and PKC (Ro-318220, Gö6983, or Rottlerin) or transfection with siRNAs of STAT3 and p47(phox) markedly inhibited ATPγS-induced cPLA2 and COX-2 mRNA/protein expression and promoter activity and PGE2 secretion. ATPγS further stimulated PKC, p47(phox), and STAT3 translocation. Moreover, ATPγS-induced STAT3 phosphorylation and translocation was inhibited by pretreatment with the inhibitors of PKC, NADPH oxidase, and ROS. ATPγS enhanced NADPH oxidase activity and ROS generation in VSMCs, which were reduced by pretreatment with Ro-318220, Gö6983, or Rottlerin. Finally, we found that ATPγS significantly induced cyclin D1 expression and VSMCs proliferation, which were inhibited by pretreatment with NAC, APO, DPI, Ro-318220, Gö6983, Rottlerin, or CBE or transfection with siRNAs of COX-2 and cyclin D1. We also demonstrated that ATPγS induced cyclin D1 expression via a PGE2-dependent pathway. These results suggested that ATPγS-induced cPLA2/COX-2 expression and PGE2 secretion is mediated through a PKC/NADPH oxidase/ROS/STAT3-dependent pathway in VSMCs. 22733133 The p53 isoform, Δ133p53α, stimulates angiogenesis and tumour progression. The tumour suppressor p53, involved in DNA repair, cell cycle arrest and apoptosis, also inhibits blood vessel formation, that is, angiogenesis, a process strongly contributing to tumour development. The p53 gene expresses 12 different proteins (isoforms), including TAp53 (p53 (or p53α), p53β and p53γ) and Δ133p53 isoforms (Δ133p53α, Δ133p53β and Δ133p53γ). The Δ133p53α isoform was shown to modulate p53 transcriptional activity and is overexpressed in various human tumours. However, its role in tumour progression is still unexplored. In the present study, we examined the involvement of Δ133p53 isoforms in tumoural angiogenesis and tumour growth in the highly angiogenic human glioblastoma U87. Our data show that conditioned media from U87 cells depleted for Δ133p53 isoforms block endothelial cell migration and tubulogenesis without affecting endothelial cell proliferation in vitro. The Δ133p53 depletion in U2OS osteosarcoma cells resulted in a similar angiogenesis blockade. Furthermore, using conditioned media from U87 cells ectopically expressing each Δ133p53 isoform, we determined that Δ133p53α and Δ133p53γ but not Δ133p53β, stimulate angiogenesis. Our in vivo data using the chicken chorio-allantoic membrane and mice xenografts establish that angiogenesis and growth of glioblastoma U87 tumours are inhibited upon depletion of Δ133p53 isoforms. By TaqMan low-density array, we show that alteration of expression ratio of Δ133p53 and TAp53 isoforms differentially regulates angiogenic gene expression with Δ133p53 isoforms inducing pro-angiogenic gene expression and repressing anti-angiogenic gene expression. 23299191 Effects of asymmetric dimethylarginine on inflammatory cytokines (TNF-α, IL-6 and IL-10) in rats. This study is intended to examine the effects of administration of asymmetric dimethylarginine (ADMA) on the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10. A total of 30 Wistar adult albino rats were used. Group I was administrated (n = 10) with 1 mg/kg/day of ADMA, group II (n = 10) was administrated with 2 mg/kg/day of ADMA and the control group was administrated (n = 10) with 0.9% sodium chloride. ADMA was intraperitoneally administrated for 7 days. The serum levels of IL-6, TNF-α and IL-10 were measured. There was a significant decrease in the levels of TNF-α, IL-6 and IL-10 in group I compared with that of the control group (p < 0.001). There was also a significant decrease in the levels of IL-10 in group II compared with that of the control group (p < 0.05) but the increase was much more distinct in the levels of IL-6 and TNF-α (p < 0.001). When comparing the groups by the doses given, no difference between the levels of IL-6 and IL-10 in groups I and II (p > 0.05) was observed; the levels of TNF-α in group II were significantly lower than those of group I (p < 0.05). A significant decrease in the serum levels of inflammatory cytokines IL-6, TNF-α and IL-10, after administration of 1 mg/kg/day and 2 mg/kg/day of ADMA, indicates that ADMA has an effect on inflammation. Increase in ADMA levels in the rats shows that the effects of inflammatory cytokines were suppressed. 23463334 Formulation and pharmacokinetic evaluation of once-daily sustained-released system of nifedipine with solid dispersion and coating techniques. A novel sustained-release system was developed for poorly water-soluble drugs by applying solid dispersion (SD) technique to improve the solubility. The SD systems composed of polyvinyl pyrrolidone and stearic acid could not control the release of nifedipine. When the above SD granules were coated with ethylcellolulose (EC10, 45 and 100cp), the dissolution rate extended from 16 to 20 h. When the concentration of EC100cp was increased to 4-6 %, the sustained-release formulation F7 and F8 prepared with 4 % EC100cp and 6 % EC100cp, respectively, could control the drug release in a better manner, namely, they could control drug release in the initial hours with a high cumulative amount of drug at 24 h. The mechanism of drug release from F7 and F8 was diffusion coupled with erosion. When immediate-release capsules was orally administered to rabbits, its absorption was very rapid with a short elimination half-life, while a prolonged maintenance of the plasma drug level up to 24 h was obtained for F7 and F8. Furthermore, the oral bioavailability of F7 and F8 was significantly improved. The results suggested that this novel sustained-release system would be a promising system to improve the solubility and sustain the absorption of poorly water-soluble drugs. 23596972 Effect of moisture content, temperature and exposure time on the physical stability of chitosan powder and tablets. Abstract Context: Chitosan does not rank highly regarding its employment as tablet filler due to certain limitations. Undesirable properties that limit its utilization as excipient in solid dosage forms include its hydration propensity that negatively affects tablet stability, strength and disintegration. Objective: The objective of this study was to investigate the physical stability of chitosan powder, mixtures, granules and tablets under accelerated conditions such as elevated temperatures and humidity over different periods of time. Methods: Selected physico-chemical properties of pure chitosan powder, physical mixtures of chitosan with Kollidon® VA64 (BASF, Ludwigshafen, Germany), chitosan granules, as well as tablets were evaluated under conditions of elevated humidity and temperature. Results and discussion: The physical stability of chitosan tablets exhibited sensitivity towards varying exposure conditions. It was furthermore evident that the presence of moisture (sorbed water) had a marked influence on the physical stability of chitosan powder and tablets. It was evident that the presence of Kollidon® VA64 as well as the method of inclusion of this binder influenced the properties of chitosan tablets. The physical stability of chitosan powder deteriorated to a greater extent compared to that of the chitosan tablets, which were subjected to the same conditions. Conclusion: It is recommended that tablets containing chitosan should be stored at a temperature not exceeding 25 °C as well as at a relatively low humidity (<60%) to prevent deterioration of physical properties. Direct compression of chitosan granules which contained 5%w/w Kollidon® VA64 produced the best formulation in terms of physical stability at the different conditions. 23379723 Spiropyran polymeric microcapillary coatings for photodetection of solvent polarity. Fused silica microcapillaries were functionalized with spiropyran-polymer brushes using surface-initiated ring-opening metathesis polymerization. Based on the inherited spiropyran properties, the functionalized capillaries were successfully used to photoidentify solvents of different polarity when passing through the microcapillary in continuous flow. In the present study, six different solvents (toluene, tetrahydrofuran, acetone, acetonitrile, ethanol, and methanol) can be easily detected while passing through the modified microcapillary by simply irradiating a portion of it with UV light (365 nm). This converts the closed spiropyran moiety to the open merocyanine form, and as a consequence, the microcapillary gains a distinct color and spectral response depending on the polarity of the solvent. The rate of ring-opening of the spiropyran-polymer brushes coatings has been determined in situ in the presence of different solvents, showing that the coloration rate is also influenced by the solvent polarity and therefore can be used as an additional parameter for solvent sensing. 23579486 A New Strategy for Selective Targeting of Progesterone Receptor with Passive Antagonists. Currently available progesterone receptor (PR) antagonists, such as mifepristone (RU486), lack specificity and display partial agonist properties, leading to potential drawbacks in their clinical use. Recent X-ray crystallographic studies have identified key contacts involved in the binding of agonists and antagonists with PR opening the way for a new rational strategy for inactivating PR. We report here the synthesis and characterization of a novel class of PR antagonists designed from such studies. The lead molecule, the homosteroid APR19, displays in vivo endometrial antiprogesterone activity. APR19 inhibits progesterone-induced PR recruitment and transactivation from synthetic and endogenous gene promoters. Importantly, it exhibits high PR selectivity with respect to other steroid hormone receptors, and is devoid of any partial agonist activity on PR target gene transcription. Two-hybrid and immunostaining experiments reveal that APR19-bound PR is unable to interact with either transcriptional coactivators (SRC1, SCR2) or corepressors (NCoR, SMRT), in contrast to RU486-PR complexes. APR19 also inhibits agonist-induced phosphorylation of serine 294 regulating PR transcriptional activity and turnover kinetics. In-silico docking studies based on the crystal structure of the PR ligand-binding domain show that, in contrast to progesterone, APR19 does not establish stabilizing hydrogen bonds with the ligand binding cavity, resulting in an unstable ligand-receptor complex. Altogether, these properties highly distinguish APR19 from RU486 and likely its derivatives, suggesting that it belongs to a new class of pure antiprogestins which inactivate PR by a passive mechanism. These specific PR antagonists open new perspectives for long term hormonal therapy. 23532446 Transfer of highly porous nanoparticle layers to various substrates through mechanical compression. A new two-step layer transfer process is introduced that is capable of fabricating mechanically stabilized highly porous nanoparticle layers on various substrates. In a first step titanium dioxide nanoparticles were synthesized with Flame-Spray-Pyrolysis and accumulated on a filter paper in the gas phase. In a second step this highly porous filter cake is subsequently transferred to a final substrate via low pressure lamination at room temperature. This leads to mechanical restructuring and stabilization of the porous layer. Pore size analysis indicates homogenization of the layers through rearrangement of the aggregates inside the layers that increases with applied pressure. Additionally, the Young's moduli of the layers were quantified through Colloidal-Probe-Technique indentation measurements with an Atomic-Force-Microscope. The highest lamination pressure of 2.5 MPa resulted in triplication of the Young's modulus. The results show that our novel two-step layer transfer process leads to mechanically stabilized layers that preserve their high porosity. Through the decoupling of the high temperature nanoparticle synthesis and the final substrate the process also enables the possibility to apply temperature sensitive substrates such as polypropylene foil. 23274903 The suprachiasmatic nucleus controls circadian energy metabolism and hepatic insulin sensitivity. Disturbances in the circadian system are associated with the development of type 2 diabetes mellitus. Here, we studied the direct contribution of the suprachiasmatic nucleus (SCN), the central pacemaker in the circadian system, in the development of insulin resistance. Exclusive bilateral SCN lesions in male C57Bl/6J mice, as verified by immunochemistry, showed a small but significant increase in body weight (+17%), which was accounted for by an increase in fat mass. In contrast, mice with collateral damage to the ventromedial hypothalamus and paraventricular nucleus showed severe obesity and insulin resistance. Mice with exclusive SCN ablation revealed a loss of circadian rhythm in activity, oxygen consumption, and food intake. Hyperinsulinemic-euglycemic clamp analysis 8 weeks after lesioning showed that the glucose infusion rate was significantly lower in SCN lesioned mice compared with sham-operated mice (-63%). Although insulin potently inhibited endogenous glucose production (-84%), this was greatly reduced in SCN lesioned mice (-7%), indicating severe hepatic insulin resistance. Our data show that SCN malfunctioning plays an important role in the disturbance of energy balance and suggest that an absence of central clock activity, in a genetically intact animal, may lead to the development of insulin resistance. 23473804 Absence of correlation between oxysterol accumulation in lipid raft microdomains, calcium increase, and apoptosis induction on 158N murine oligodendrocytes. There is some evidence that oxidized derivatives of cholesterol, 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7βOHC), are increased in the plasma of patients with neurodegenerative diseases associated with demyelinization of the central nervous system (CNS). It was therefore of interest to investigate the effects of these oxysterols on oligodendrocytes, the myelin-forming cells in the CNS. To this end, 158N murine oligodendrocytes were treated with 7KC or 7βOHC inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving Mcl-1, and caspase-3 activation. In contrast, under treatment with 27-hydroxycholesterol (27OHC), no cell death was observed. When the cells were stained with Fura-2, no significant Ca(2+) rise was found with the different oxysterols, whereas strong signals were detected with ionomycin used as positive control. At concentrations which induced apoptosis, 7KC but not 7βOHC accumulated in lipid rafts. Although not cytotoxic, 27OHC was mainly detected in lipid rafts. It is noteworthy that α-tocopherol (but not ellagic acid and resveratrol) was able to counteract 7KC- and 7βOHC-induced apoptosis and to decrease the accumulation of 7KC and 27OHC in lipid rafts. Thus, in 158N cells, the ability of oxysterols to trigger a mode of cell death by apoptosis involving GSK-3 and caspase-3 activation is independent of the increase in the Ca(2+) level and of their accumulation in lipid raft microdomains. 23322559 New monoterpene lactones from Actaea cimicifuga. Three new monoterpene lactones, cimicifugolides A-C (1-3), along with a known one (4), were identified from the dried rhizome of Actaea cimicifuga L. that was used as traditional Chinese medicine for thousands of years with the Chinese common name of shengma. The structures of the new isolates were established using spectroscopic methods, including NMR, mass, UV, and IR spectra. The inhibition activity of compounds 1, 2, and 4 against pancreatic lipase was evaluated. 23426609 Prescription of antiepileptics and the risk of road traffic crash. Studies assessing the impact of epilepsy and its medication on the risk of road traffic crashes have shown inconsistent results. The aim in this study was to assess this risk using French databases. Data from three French national databases were extracted and matched: the national health care insurance database, police reports, and the national police database of injurious crashes. Only antiepileptics prescribed predominantly in epilepsy were studied (phenobarbital, phenytoin, ethosuximide, valproic acid, vigabatrin, tiagabin, levitiracetam, zonisamide, and lacosamide). A case-control analysis comparing responsible and non-responsible drivers and a case-crossover analysis were performed. Drivers (72 685) involved in an injurious crash in France between July 2005 and May 2008, were included. Drivers exposed to prescribed antiepileptic medicines (n = 251) had an increased risk of being responsible for a crash (OR 1.74 [1.29-2.34]). The association was also significant for the most severe epileptic patients (n = 99; OR = 2.20 [1.31-3.69]). Case-crossover analysis found no association between crash risk and treatment prescription. Patients with prescription of antiepileptic drugs should be cautioned about their potential risk of road traffic crash. This risk is however more likely to be related to seizures than to the effect of antiepileptic medicines. 23473801 Hinokitiol inhibits platelet activation ex vivo and thrombus formation in vivo. Hinokitiol is a tropolone-related bioactive compound that has been used in hair tonics, cosmetics, and food as an antimicrobial agent. Recently, hinokitiol has attracted considerable interest because of its anticancer activities. Platelet activation plays a crucial role in atherothrombotic processes. We examined the effects of hinokitiol treatment on platelet activation using human platelets. In the present study, hinokitiol (1 and 2μM) inhibited the collagen-induced aggregation of human platelets, but did not inhibit the activation of platelets by other agonists, including thrombin, arachidonic acid, and ADP. Hinokitiol inhibited the phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and Akt in collagen-activated human platelets, and significantly reduced intracellular calcium mobilization and hydroxyl radical (OH) formation. Hinokitiol also reduced the PKC activation and platelet aggregation stimulated by PDBu. In addition, hinokitiol significantly prolonged thrombogenesis in mice. Hinokitiol did not influence the binding of a fluorescent triflavin probe to the αIIbβ3 integrin on platelet membrane, and neither ODQ nor SQ22536 significantly reversed the hinokitiol-mediated inhibition of platelet aggregation. In conclusion, hinokitiol may inhibit platelet activation by inhibiting the PLCγ2-PKC cascade and hydroxyl radical formation, followed by suppressing the activation of MAPKs and Akt. Our study suggests that hinokitiol may represent a potential therapeutic agent for the prevention or treatment of thromboembolic disorders. 23338537 Intracameral cefuroxime: prophylaxis of postoperative endophthalmitis after cataract surgery. Results of the landmark European Society of Cataract and Refractive Surgeons trial and additional prospective and retrospective studies support the use of intracameral cefuroxime in the prophylaxis of endophthalmitis following cataract surgery. Prophylaxis with intracameral cefuroxime at the recommended dose appears to be well tolerated in patients undergoing cataract surgery. However, off-label use of intracameral cefuroxime usually requires a two-step dilution process with the potential for dilution errors, and there are also concerns regarding the risk of contamination. Aprokam® (intracameral cefuroxime) has been approved in the EU for the prophylaxis of postoperative endophthalmitis after cataract surgery. After reconstitution of Aprokam®, no further dilution is required and each vial is only indicated for single-patient use; this has the potential to reduce the risk of both dilution errors and contamination. 23091189 Pharmacokinetic mechanism involved in the prolonged high retention of laninamivir in mouse respiratory tissues after intranasal administration of its prodrug laninamivir octanoate. Laninamivir octanoate (LO) (Inavir; Daiichi Sankyo, Japan) is an ester prodrug of the neuraminidase inhibitor laninamivir. We previously reported that a prolonged high retention of laninamivir in mouse respiratory tissues was achieved by intranasal administration of LO. In this study, we evaluated intrapulmonary pharmacokinetics both in vivo and in vitro to investigate the potential mechanism involved in such a preferable retention. After intranasal administration of LO to mice (0.5 μmol/kg), the drug was distributed from the airway space into the lungs, and laninamivir remained in the lung at 24 hours postdose (2680 pmol/g), with a higher concentration than that in the epithelial lining fluid. The laninamivir was localized mainly on the epithelial cells of airway tracts, determined by microautoradiography using (14)C-labeled LO. In mouse airway epithelial cells, the cellular uptake and hydrolysis of LO were observed over incubation time without any apparent saturation at the highest concentration tested (1000 μM). Furthermore, after additional incubation in drug-free medium, the intracellular laninamivir was released very slowly into the medium with an estimate rate constant of 0.0707 h(-1), which was regarded as a rate-limiting step in the cellular retention. These results demonstrated that the prolonged high retention of laninamivir in the respiratory tissues was attributed to a consecutive series of three steps: uptake of LO into the airway epithelial cells, hydrolysis of LO into laninamivir by intracellular esterase(s), and limited efflux of the generated laninamivir due to its poor membrane permeability. This prodrug approach could be useful for lung-targeting drug delivery. 23427007 Meal conditions affect the absorption of supplemental vitamin D(3) but not the plasma 25-hydroxyvitamin D response to supplementation. It is sometimes assumed that dietary fat is required for vitamin D absorption, although the impact of different amounts of dietary fat on vitamin D absorption is not established. This study was conducted to determine whether the presence of a meal and the fat content of the meal influences vitamin D absorption or the 25-hydroxyvitamin D (25OHD) response to supplemental vitamin D(3) . Based on earlier studies in rats we postulated that absorption would be greatest in the low-fat meal group. Sixty two healthy older men and women were randomly assigned to one of three meal groups: no meal, high-fat meal or low-fat meal; each was given a monthly 50,000 IU vitamin D(3) supplement with the test breakfast meal (or after a fast for the no-meal group) and followed for 90 days. Plasma vitamin D(3) was measured by LC/MS before and 12 hrs after the first dose; plasma 25OHD was measured by radioimmunoassay at baseline and after 30 and 90 days. The mean 12-hr increments in vitamin D(3) , after adjusting for age and sex, were 200.9 nmol/L in the no-meal group, 207.4 nmol/L in the high-fat meal group, and 241.1 nmol/L in the low-fat meal group (P = 0.038), with the increase in the low-fat group being significantly greater than the increases in the other two groups. However, increments in 25OHD levels at 30 and 90 days didn't differ significantly in the three groups. We conclude that absorption was increased when a 50,000 IU dose of vitamin D was taken with a low-fat meal, compared with a high-fat meal and no meal, but that the greater absorption didn't result in higher plasma 25OHD levels in the low-fat meal group. © 2013 American Society for Bone and Mineral Research. 23562324 Genome-wide Analysis Reveals SR Protein Cooperation and Competition in Regulated Splicing. SR proteins are well-characterized RNA binding proteins that promote exon inclusion by binding to exonic splicing enhancers (ESEs). However, it has been unclear whether regulatory rules deduced on model genes apply generally to activities of SR proteins in the cell. Here, we report global analyses of two prototypical SR proteins, SRSF1 (SF2/ASF) and SRSF2 (SC35), using splicing-sensitive arrays and CLIP-seq on mouse embryo fibroblasts (MEFs). Unexpectedly, we find that these SR proteins promote both inclusion and skipping of exons in vivo, but their binding patterns do not explain such opposite responses. Further analyses reveal that loss of one SR protein is accompanied by coordinated loss or compensatory gain in the interaction of other SR proteins at the affected exons. Therefore, specific effects on regulated splicing by one SR protein actually depend on a complex set of relationships with multiple other SR proteins in mammalian genomes. 23143036 Cadmium(Cd)-induced oxidative stress down-regulates the gene expression of DNA mismatch recognition proteins MutS homolog 2 (MSH2) and MSH6 in zebrafish (Danio rerio) embryos. DNA mismatch repair (MMR) of simple base mismatches and small insertion-deletion loops in eukaryotes is initiated by the binding of the MutS homolog 2 (MSH2)-MSH6 heterodimer to mismatched DNA. Cadmium (Cd) is a genotoxic heavy metal that has been recognized as a human carcinogen. Oxidant stress and inhibition of DNA repair have been proposed as major factors underlying Cd genotoxicity. Our previous studies indicated the ability of Cd to disturb the gene expression of MSH6 in zebrafish (Danio rerio) embryos. This study was undertaken to explore if Cd-induced oxidative stress down-regulated MSH gene activities. Following the exposure of zebrafish embryos at 1 h post fertilization (hpf) to sublethal concentrations of Cd at 3-5 μM for 4 or 9 h, a parallel down-regulation of MSH2, MSH6 and Cu/Zn superoxide dismutase (Cu/Zn-SOD) gene expression was detected by real-time RT-PCR and the expression levels were 40-50% of control after a 9-h exposure. Cd exposure also induced oxidative stress, yet no inhibition of catalase gene activity was observed. Whole mount in situ hybridization revealed a wide distribution of msh6 mRNA in the head regions of 10 hpf embryos and pretreatment of embryos with antioxidants butylhydroxytoluene (BHT), d-mannitol or N-acetylcysteine (NAC) at 1-10 μM restored Cd-suppressed msh6 expression. QPCR confirmed the protective effects of antioxidants on Cd-suppressed msh2/msh6 mRNA production. Down-regulated MSH gene activities reaching about 50% of control were also induced in embryos exposed to paraquat, a reactive oxygen species (ROS)-generating herbicide, or hydrogen peroxide at 200 μM. Hence, Cd at sublethal levels down-regulates msh2/msh6 expression primarily via ROS as signaling molecules. The transcriptional activation of human msh6 is known to be fully dependent on the specificity factor 1 (Sp1). Cd failed to inhibit the DNA binding activity of zebrafish Sp1 unless at lethal concentrations based on band shift assay, therefore excluding the involvement of Sp1 inactivation in Cd-induced MSH gene inhibition in zebrafish embryos. 23481677 Helicusin E, Isochromophilone X and Isochromophilone XI: New Chloroazaphilones Produced by the Fungus Bartalinia robillardoides Strain LF550. Microbial studies of the Mediterranean sponge Tethya aurantium led to the isolation of the fungus Bartalinia robillardoides strain LF550. The strain produced a number of secondary metabolites belonging to the chloroazaphilones. This is the first report on the isolation of chloroazaphilones of a fungal strain belonging to the genus Bartalinia. Besides some known compounds (helicusin A (1) and deacetylsclerotiorin (2)), three new chloroazaphilones (helicusin E (3); isochromophilone X (4) and isochromophilone XI (5)) and one new pentaketide (bartanolide (6)) were isolated. The structure elucidations were based on spectroscopic analyses. All isolated compounds revealed different biological activity spectra against a test panel of four bacteria: three fungi; two tumor cell lines and two enzymes. 23322709 A unique palladium catalyst for efficient and selective alkoxycarbonylation of olefins with formates. Forget about CO! Carbonylations are among the most important homogeneously catalyzed reactions in the chemical industry, but typically require carbon monoxide. Instead, straightforward and efficient alkoxycarbonylations of olefins can proceed with alkyl formates in the presence of a specific palladium catalyst. Aromatic, terminal aliphatic, and internal olefins are carbonylated to give industrially important linear esters at low catalyst loadings. 23620199 Trastuzumab Emtansine: First Global Approval. Genentech and ImmunoGen are collaborating on the development of trastuzumab emtansine, a HER2 antibody-drug conjugate that comprises Genentech's trastuzumab antibody linked to ImmunoGen's anti-mitotic agent, mertansine (a maytansine derivative; also known as DM1). The conjugate combines two strategies: the anti-HER2 activity of trastuzumab, and the targeted intracellular delivery of mertansine, a tubulin polymerisation inhibitor which interferes with mitosis and promotes apoptosis. The linker in trastuzumab emtansine is a non-reducible thioether linker, N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC, designated MCC after conjugation). Trastuzumab emtansine (Kadcyla™) has been launched in the USA as second-line monotherapy for HER2-positive metastatic breast cancer, and has been filed for approval in the EU and Japan in this indication. Trastuzumab emtansine is in phase III development as first-line combination therapy or monotherapy for metastatic HER2-positive breast cancer, and as third-line monotherapy for metastatic HER2-positive breast cancer. Phase II development is underway for early-stage breast cancer and phase II/III development is underway in patients with HER2-positive gastric cancer. This article summarizes the milestones in the development of trastuzumab emtansine leading to this first approval for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. 23208609 Endocrine-disrupting effects of thioxanthone photoinitiators. Photoinitiators used in food packaging ink, such as 2-isopropylthioxanthone (2-ITX), have been shown to migrate into food and beverages. Recently, several studies indicated that 2-ITX might be an endocrine-disrupting chemical. In this work, the effects of 2-ITX, 4-isopropylthioxanthone (4-ITX), 2,4-diethylthio xanthone (2,4-diethyl-TX), 2-chlorothioxanthone (2-chloro-TX), and 1-chloro-4-propoxythioxanthone (1-chloro-4-propoxy-TX) on steroidogenesis and androgen and estrogen receptor-mediated transcription activation have been studied using human H295R adrenocarcinoma cells and yeast hormone bioassays, respectively. None of the compounds showed androgenic or estrogenic activities, but clear antiandrogenic and antiestrogenic activities were observed for 2-ITX, 4-ITX, and 2,4-diethyl-TX, whereas 2-chloro-TX showed only antiandrogenic activity. In an adapted version of the H295R steroidogenesis assay, using gas chromatography-tandem mass spectrometry analysis of H295R media, all five compounds increased levels of 17ß-estradiol and estrone. H295R cells incubated with 2-ITX also showed significantly reduced androgen and increased pregnenolone and progesterone levels. Expression of particular steroidogenic genes, including the one encoding for aromatase (CYP19A1), was significantly upregulated after incubation of H295R cells with 2-ITX, 4-ITX, and 2,4-diethyl-TX. In line with the increased CYP19A1 mRNA expression, 2-ITX increased catalytic activity of aromatase in H295R cells as measured by cognate aromatase assays. The results indicate that thioxanthone derivatives can act as potential endocrine disruptors both at the level of nuclear receptor signaling and steroid hormone production. 23470034 A new tetracyclic triterpenoid compound from Mastich. A new tetracyclic triterpenoid compound named as mastichinoic acid A (1) was isolated from Mastich. The structure was established as 3,7-dioxo-11β-hydroxy-5α-tirucalla-8,24(Z)-dien-26-oic acid by various spectroscopic techniques including MS, 1D, and 2D NMR and HRTOFMS. 23577042 Microrheology of highly crosslinked microtubule networks is dominated by force-induced crosslinker unbinding. We determine the time- and force-dependent viscoelastic responses of reconstituted networks of microtubules that have been strongly crosslinked by biotin-streptavidin bonds. To measure the microscale viscoelasticity of such networks, we use a magnetic tweezers device to apply localized forces. At short time scales, the networks respond nonlinearly to applied force, with stiffening at small forces, followed by a reduction in the stiffening response at high forces, which we attribute to the force-induced unbinding of crosslinks. At long time scales, force-induced bond unbinding leads to local network rearrangement and significant bead creep. Interestingly, the network retains its elastic modulus even under conditions of significant plastic flow, suggesting that crosslinker breakage is balanced by the formation of new bonds. To better understand this effect, we developed a finite element model of such a stiff filament network with labile crosslinkers obeying force-dependent Bell model unbinding dynamics. The coexistence of dissipation, due to bond breakage, and the elastic recovery of the network is possible because each filament has many crosslinkers. Recovery can occur as long as a sufficient number of the original crosslinkers are preserved under the loading period. When these remaining original crosslinkers are broken, plastic flow results. 23511610 Patterning of controllable surface wettability for printing techniques. Patterning of controllable surface wettability has attracted wide scientific attention due to its importance in both fundamental research and practical applications. In particular, it is crucial to form clear image areas and non-image areas in printing techniques based on wetting and dewetting. This review summarizes the recent research on and applications of patterning of controllable surface wettability for printing techniques, with a focus on the design and fabrication of the precise surface wettability patterning by enhancing the contrast of hydrophilicity and hydrophobicity, such as superhydrophilicity and superhydrophobicity. The selected topics mainly include patterned surface wettability for lithographic printing with different plate-making techniques, patterned surface wettability for microcontact printing with a patterned wetting stamp and special wettability mediated patterning microtransfer printing, patterned surface wettability for inkjet printing with controllable surface wettability of the substrate and printing head to ink, and patterned surface wettability by a combination of different printing techniques. A personal perspective on the future development and remaining challenges of this research is also briefly discussed. 23418859 Salidroside attenuates myocardial ischemia-reperfusion injury via PI3K/Akt signaling pathway. To investigate the cardioprotective effects of salidroside on myocardial ischemia-reperfusion injury (IRI) in rabbits and the underlying action mechanisms in PI3K/Akt signaling pathway, a rabbit ischemia/reperfusion model was created by ligating the left anterior descending coronary arterial branch for 30 min and by releasing the ligature to allow reperfusion for 120 min. Salidroside or salidroside+PI3K inhibitor (LY294002) was administered via intracoronary injections at the onset of reperfusion. Apoptosis of cardiomyocytes was assessed by terminal dUTP nick-end labeling assay, and the expression of apoptosis-related proteins was observed by immunohistochemistry. The expressions of total Akt and phosphorylated Akt (p-Akt) were detected by western blot analysis. The results showed that intracoronary injection of salidroside at the onset of reperfusion markedly reduced the apoptosis of cardiomyocytes, significantly increasing Bcl-2 and p-Akt proteins expressions and decreasing Bax and caspase-3 expressions in the hearts subjected to ischemia followed by 120-min reperfusion. However, the anti-apoptotic effect induced by salidroside was inhibited by LY294002, which blocked the activation of Akt. These results suggested that intracoronary administration of salidroside at the onset of reperfusion could significantly reduce the IRI-induced apoptosis of cardiomyocytes, and this protective mechanism seemed to be mediated by the PI3K-Akt signaling pathway. 23391484 In vitro toxicological characterization of perfluorinated carboxylic acids with different carbon chain lengths. Perfluorooctanoic acid (PFOA) is in use for the production of fluoropolymers (PFT). Due to its toxic properties it was proposed to replace the substance in its industrial applications by homologous compounds with shorter carbon chain length that were supposed to be less toxic compared to PFOA, however, the smaller PFOA homologs are poorly characterized so far. In this study we have conducted a comparative analysis of the toxicity of perfluorinated carboxylic acids (PFCA) with a carbon chain length ranging from four to twelve carbon atoms. By using the human hepatocarcinoma cell line HepG2 as an in vitro model for human hepatocytes we could show a positive correlation between the carbon chain length of the respective PFCA and its cytotoxicity. There was, however, no indication of an apoptotic mechanism for cytotoxicity. All PFCA under investigation were negative in two independent genotoxicity assays. As PFOA, being a well-known peroxisome proliferator, the other PFCA tested in this study were also shown to activate human peroxisome proliferator-activated receptor alpha (PPARα) with PFOA having the highest potential of PPARα activation. Moreover, the compounds showed weak potential to activate PPARγ and hardly activated PPARδ. Taken together, the in vitro study revealed that PFCA with a shorter carbon chain length seem to be less toxic than PFOA. 23599431 Induction of C-X-C Chemokine Receptor Type 7 (CXCR7) Switches Stromal Cell-Derived Factor-1 (SDF-1) Signaling and Phagocytic Activity in Macrophages Linked to Atherosclerosis. The discovery of CXCR7 as a new receptor for SDF-1 places many previously described SDF-1 functions attributed to CXCR4 in question, though whether CXCR7 acts as a signaling or decoy receptor has been in debate. It is known that CXCR7 is not expressed in normal blood leukocytes; however, the potential role of leukocyte CXCR7 in disease states has not been addressed. The aim of this study was to determine the expression and function of macrophage CXCR7 linked to atherosclerosis. Here, we show that CXCR7 was detected in macrophage-positive area of aortic atheroma of ApoE-null mice, but not in healthy aorta. During monocytes differentiation to macrophages, CXCR7 was up-regulated at mRNA and protein levels, with more expression in M1 than in M2 phenotype. In addition, CXCR7 induction was associated with a SDF-1 signaling switch from the pro-survival ERK and AKT pathways in monocytes to the pro-inflammatory JNK and p38 pathways in macrophages. The latter effect was mimicked by a CXCR7-selective agonist TC14012 and abolished by siRNA knockdown of CXCR7. Furthermore, CXCR7 activation increased macrophage phagocytic activity, which was suppressed by CXCR7 siRNA silencing or by inhibiting either the JNK or p38 pathways, but was not affected by blocking CXCR4. Finally, activation of CXCR7 by I-TAC showed a similar signaling and phagocytic activity in macrophages with no detectable CXCR3. We conclude that CXCR7 is induced during monocyte-to-macrophage differentiation, which is required for SDF-1 and I-TAC signaling to JNK and p38 pathways, leading to enhanced macrophage phagocytosis, thus possibly contributing to atherogenesis. 23297713 Topical wound-healing effects and phytochemical composition of heartwood essential oils of Juniperus virginiana L., Juniperus occidentalis Hook., and Juniperus ashei J. Buchholz. Ethnobotanical surveys indicated that in the traditional medicines worldwide, several Juniperus species are utilized as antihelmintic, diuretic, stimulant, antiseptic, carminative, stomachic, antirheumatic, antifungal, and for wound healing. In the present study, essential oils obtained from heartwood samples of Juniperus virginiana L., Juniperus occidentalis Hook. and Juniperus ashei J. Buchholz were evaluated for wound healing and anti-inflammatory activities by using in vivo experimental methods. The essential oils were obtained by the supercritical carbon dioxide extraction method. Linear incision and circular excision wound models were performed for the wound-healing activity assessment. The tissues were also evaluated for the hydroxyproline content as well as histopathologically. To evaluate the anti-inflammatory activity of the essential oils, the test used was an acetic acid-induced increase in capillary permeability. The essential oil of J. occidentalis showed the highest activity on the in vivo biological activity models. Additionaly, the oil of J. virginiana was found highly effective in the anti-inflammatory activity method. The experimental data demonstrated that essential oil of J. occidentalis displayed significant wound-healing and anti-inflammatory activities. 23517541 Comparative pharmacokinetics of N(ω)-hydroxy-nor-L-arginine, an arginase inhibitor, after single-dose intravenous, intraperitoneal and intratracheal administration to brown Norway rats. Abstract 1.  Rodent studies have documented that N(ω)-hydroxy-nor-L-arginine (nor-NOHA), an arginase inhibitor, has therapeutic potential in the treatment of cardiovascular and obstructive airway diseases. However, its bioavailability and pharmacokinetics have not been described so far. 2.  Anesthetized brown Norway rats were administered single doses of nor-NOHA (10, 30 or 90 mg/kg) intravenously (i.v.), intraperitonealy (i.p.) or via intratracheal (i.t.) instillation of aerosol. Plasma nor-NOHA was assayed using a validated HPLC method. 3.  Upon i.v. administration, the mean concentration showed a biphasic decline and its value dropped below 10% of the maximum after 20 min. The pharmacokinetics were linear with the total and inter-compartmental clearances of 33 and 17 mL/min/kg, central and peripheral volumes of distribution of 0.19 and 0.43 L/kg and terminal half-life of 30 min. 4.  The average absolute bioavailability of nor-NOHA after i.p. and i.t. delivery was 98% and 53%, respectively. The absorption from the airways was rate-limiting and its extent decreased with the dose. 5.  In conclusion, nor-NOHA is rapidly cleared from the plasma in concordance with the short time window of its in vivo inhibitory activity reported in the literature. I.t. instillation of aerosol for topical effects of nor-NOHA in the airways is characterized with significant systemic availability. 23289585 Infrared multiple photon dissociation action spectroscopy of deprotonated DNA mononucleotides: gas-phase conformations and energetics. The gas phase structures of the deprotonated 2'-deoxymononucleotides including 2'-deoxyadenosine-5'-monophosphate (dA5'p), 2'-deoxycytidine-5'-monophosphate (dC5'p), 2'-deoxyguanosine-5'-monophosphate (dG5'p), and thymidine-5'-monophosphate (T5'p) are examined via infrared multiple photon dissociation (IRMPD) action spectroscopy and theoretical electronic structure calculations. The measured IRMPD action spectra of all four deprotonated DNA mononucleotides exhibit unique spectral features in the region extending from ~600 to 1800 cm(-1) such that they can be readily differentiated from one another. The measured IRMPD action spectra are compared to the linear IR spectra calculated at the B3LYP/6-311+G(d,p) level of theory to determine the conformations of these species accessed in the experiments. On the basis of these comparisons and the computed energetic information, the most stable conformations of the deprotonated forms of dA5'p, dC5'p, and T5'p are conformers where the ribose moiety adopts a C3' endo conformation and the nucleobase is in an anti conformation. By contrast, the most stable conformations of the deprotonated form of dG5'p are conformers where the ribose adapts a C3' endo conformation and the nucleobase is in a syn conformation. In addition to the ground-state conformers, several stable low-energy excited conformers that differ slightly in the orientation of the phosphate ester moiety were also accessed in the experiments. 23327580 Pharmacogenomics as a risk mitigation strategy for chemotherapeutic cardiotoxicity. Damage to the heart can result from both traditional chemotherapeutic agents, such as doxorubicin, and newer 'targeted' therapies, such as trastuzumab. This chemotherapeutic cardiotoxicity is potentially life-threatening and necessitates limiting or discontinuing an otherwise-effective cancer treatment. Clinical strategies focus on surveillance rather than prevention, although there are no specific therapies for this highly morbid adverse effect. Current models for prospectively predicting risk of chemotherapeutic cardiotoxicity are limited. Cardiotoxicity can occur idiosyncratically in patients without obvious demographic risk factors, suggesting a genetically determined susceptibility, and candidate-gene studies have identified a limited number of variants that increase risk. In this commentary we indicate a need for more powerful means to identify risk prospectively, and suggest that broad pharmacogenomic approaches may be fruitful. 23639437 Cognitive Function During Nicotine Withdrawal: Implications for Nicotine Dependence Treatment. Nicotine withdrawal is associated with deficits in neurocognitive function including sustained attention, working memory, and response inhibition. Several convergent lines of evidence suggest that these deficits may represent a core dependence phenotype and a target for treatment development efforts. A better understanding of the mechanisms underlying withdrawal-related cognitive deficits may lead to improve nicotine dependence treatment. We begin with an overview of the neurocognitive effects of withdrawal in rodent and human models, followed by discussion of the neurobehavioral mechanisms that are thought to underlie these effects. We then review individual differences in withdrawal-related neurocognitive effects including genetics, gender, and psychiatric comorbidity. We conclude with a discussion of the implications of this research for developing improved therapies, both pharmacotherapy and behavioral treatments, that target cognitive symptoms of nicotine withdrawal. 23562636 Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound. Oncolytic viruses (OV) and ultrasound-enhanced drug delivery are powerful novel technologies. OV selectively self-amplify and kill cancer cells but their clinical use has been restricted by limited delivery from the bloodstream into the tumor. Ultrasound has been previously exploited for targeted release of OV in vivo, but its use to induce cavitation, microbubble oscillations, for enhanced OV tumor extravasation and delivery has not been previously reported. By identifying and optimizing the underlying physical mechanism, this work demonstrates that focused ultrasound significantly enhances the delivery and biodistribution of systemically administered OV co-injected with microbubbles. Up to a fiftyfold increase in tumor transgene expression was achieved, without any observable tissue damage. Ultrasound exposure parameters were optimized as a function of tumor reperfusion time to sustain inertial cavitation, a type of microbubble activity, throughout the exposure. Passive detection of acoustic emissions during treatment confirmed inertial cavitation as the mechanism responsible for enhanced delivery and enabled real-time monitoring of successful viral delivery. 23097024 Simulated microgravity exposure modulates the phenotype of cultured vascular smooth muscle cells. Evidence from ground-based animal studies using tail-suspended hindlimb unloaded rats model has clearly demonstrated that simulated microgravity-induced smooth muscle cell phenotype conversion, a characteristic vascular structural and functional remodeling, may be one of the key contributors to postspaceflight orthostatic intolerance. However, the rats model involves multiple collective effects of microgravity including cephalic fluid shift and postural muscle unloading on smooth muscle cells (SMCs). It cannot isolate a single factor from the collective ones and therefore is not ideal to study the effects of gravitational vector alteration alone on SMCs. To test the hypothesis that gravitational vector alteration per se might affect smooth muscle cell phenotype, a roller culture apparatus was employed to expose cultured rat aortic smooth muscle cells (RASMCs) to simulated microgravity. Cell proliferation, cell cycle distribution, apoptosis, migration, and nitric oxide production rates were measured and compared between the control and the simulated microgravity groups. Cell cytoskeleton reorganization induced by simulated microgravity was observed by confocal microscopy. Specific contractile and synthetic Gene expression at the mRNA level was quantified by reverse transcriptional polymerase chain reaction. It was observed that simulated microgravity suppressed RASMC proliferation and migration, enhanced cell apoptosis, stimulated NO release, and destroyed the original well-organized cytoskeleton. Moreover, at the mRNA level, long-time exposure (≥72 h) to simulated microgravity induced a contractile phenotype tendency by up-regulating smMHC expression. All these findings suggest that the phenotype modulation of vascular smooth muscle cells may be gravity dependent. 23624706 Enhanced lithium storage in Fe2O3-SnO2-C nanocomposite anode with a breathable structure. A novel nanocomposite architecture of a Fe2O3-SnO2-C anode, based on clusters of Fe2O3 and SnO2 nanoparticles dispersed along the conductive chains of Super P Li™ carbon black (Timcal Ltd.), is presented as a breathable structure in this paper for lithium-ion batteries. The synthesis of the nanocomposite is achieved by combining a molten salt precipitation process and a ball milling method for the first time. The crystalline structure, morphology, and electrochemical characterization of the synthesised product are investigated systematically. Electrochemical results demonstrate that the reversible capacity of the composite anode is 1110 mA h g(-1) at a current rate of 158 mA g(-1) with only 31% of initial irreversible capacity in the first cycle. A high reversible capacity of 502 mA h g(-1) (higher than the theoretical capacity of graphite, ∼372 mA h g(-1)) can be obtained at a high current rate of 3950 mA g(-1). The electrochemical performance is compared favourably with those of Fe2O3-SnO2 and Fe2O3-SnO2-C composite anodes for lithium-ion batteries reported in the literature. This work reports a promising method for the design and preparation of nanocomposite electrodes for lithium-ion batteries. 23609782 Drugs in Development for Relapsing Multiple Sclerosis. Drug development for multiple sclerosis (MS), as with any other neurological disease, faces numerous challenges, with many drugs failing at various stages of development. The disease-modifying therapies (DMTs) first introduced for MS are only moderately effective, but given the lack of competition, they have been widely accepted in clinical practice. Although safety and efficacy continue to be the two main metrics by which drugs will be judged, the newer agents in the market also face challenges of a more comparative nature-are they more efficacious than the currently available drugs on the market? Are they safer or better tolerated? Do they offer any practical advantages over current treatments? Fingolimod represented a milestone following its approval as an oral drug for MS in 2010, offering patients a far more convenient administration route. However, association with cardiovascular complications has led to a more cautious approach in its initial prescribing, now requiring cardiac monitoring for the first 6 h as well as subsequent monitoring of blood pressure and for macular oedema. Natalizumab, amongst licensed drugs, represents the current benchmark for efficacy. The risk of progressive multifocal leukoencephalopathy during natalizumab treatment is now more quantifiable. Other monoclonal antibodies are in various phases of development. Marketing authorisation for alemtuzumab has been filed, and whilst trial data suggest that its efficacy outperforms both licensed drugs and others in development, there is a significant risk of secondary autoimmunity. Its once-yearly administration, however, seems particularly advantageous. Rituximab is unlikely to be developed further as its license will expire, but ocrelizumab, another monoclonal antibody directly targeting B cells, is currently in phase 2 development and looks promising. Daclizumab is also moderately efficacious but may struggle to establish itself given its monthly subcutaneous dosing. There are new oral drugs in development, and it is likely that BG-12 will be licensed this year. This has been licensed for psoriasis so there are good safety data in humans that may also hold true in MS; however, its three times daily dosage will probably impact on patient compliance. Laquinimod has lower efficacy than BG-12 but appears safe and could find a place as a first-line agent. Teriflunomide has just been licensed by the US FDA and may challenge the current injectable first-line therapies as it has a similar efficacy but the advantage of being taken orally. However, risk of teratogenicity may caution against its use in some women of child-bearing potential. This review will examine drugs that have been recently approved as well as those that are in late phase 2 or 3 development as treatment for relapsing MS, highlighting their mechanism of action as well as the clinical trial and safety data before discussing their potential for success in an increasingly florid and complex DMT armamentarium. 22394118 Carbon sources and medium pH affects the growth of Withania somnifera (L.) Dunal adventitious roots and withanolide A production. This work deals with optimisation of adventitious root suspension culture of Withania somnifera (L.) Dunal (Solanaceae) for the production of biomass and withanolide A and we investigated the effect of carbon source and the initial medium pH on growth and production of withanolide A in adventitious root cultures of Withania somnifera. A 2% sucrose concentration was found to be best for both biomass (113.58 g L(-1) fresh weight (FW) and 11.33 g L(-1) dry weight (DW)) and secondary metabolite accumulation (8.93 mg g(-1) DW) in the tested range of concentration (1-8%). The biomass of adventitious roots was optimal when the initial medium pH was 5.8 (113.26 g L(-1) FW and 11.33 g L(-1) DW) but the withanolide A production was highest at the medium pH level of 5.5 (9.09 mg g(-1) DW). 23127601 Consumption of tomato products is associated with lower blood mercury levels in Inuit preschool children. Some evidence suggests that various diet components and nutrients, including vegetables, fruit and food-derived antioxidants, could mitigate contaminant exposure and/or adverse health effects of contaminants. To examine the effect of the consumption of tomato products on blood mercury levels in Inuit preschool children, 155 Inuit children (25.0±9.1months) were recruited from 2006-2008 in Nunavik childcare centers (northern Québec, Canada). Food frequency questionnaires were completed at home and at the childcare center, and total blood mercury concentration was measured by inductively coupled plasma-mass spectrometry. Multivariate regression analysis was performed after multiple imputation. The median blood concentration of mercury was 9.5nmol/L. Age, duration of breastfeeding, annual consumption frequency of seal meat, and monthly consumption frequency of tomato products were significant predictors of blood mercury levels, whereas annual consumption frequencies of beluga muktuk, walrus, Arctic char, and caribou meat were not. Each time a participant consumed tomato products during the month before the interview was associated with a 4.6% lower blood mercury level (p=0.0005). All other significant predictors in the model were positively associated with blood mercury levels. Further studies should explore interactions between consumption of healthy store-bought foods available in Arctic regions and contaminant exposure. 23584948 Vandetanib: opening a new treatment practice in advanced medullary thyroid carcinoma. Medullary thyroid cancer (MTC) is frequently diagnosed in a locally advanced or metastatic stage, and 10-year survival rates in these cases are below 20 %. Cytotoxic chemotherapy has no significant impact on overall or progression-free survival. Vandetanib (Caprelsa(®), AstraZeneca) is a once-daily oral tyrosine kinase inhibitor that selectively inhibits signalling mediated by growth-factor receptor tyrosine kinase RET (constitutively activated in roughly 60 % of all MTCs), vascular endothelial growth-factor receptors 2 and 3, and epidermal growth-factor receptors. It is the first systemic drug with demonstrated anti-tumor benefits in advanced MTC, and it has recently been approved for locally advanced or metastatic MTC by the United States Food and Drug Administration (April 2011) and the European Medicines Agency (February 2012). This review, starting from the phases II and III efficacy and safety data that led to these approvals, explores important issues related to dosing, patient selection, and strategies for managing the substantial risk of toxicity associated with the drug (including life-threatening cardiac events that are the subject of a black-box warning in the United States). All these issues still remain to be defined. Vandetanib is becoming a standard of care for symptomatic, progressive, metastatic MTCs, to be used selectively in those patients who are likely to benefit from it. 23410152 Insight into the medicinal chemistry of the endocannabinoid hydrolase inhibitors. Endocannabinoid hydrolases are nowadays increasingly considered as potential therapeutic targets for treating several pathological states. So far, numerous classes of endocannabinoid hydrolase inhibitors have been described. We herein review the medicinal chemistry of these inhibitors with a particular emphasis on the basis of their design, chemical structure, structure-activity relationships, and inhibition mechanisms. 23406429 Novel triaryl sulfonamide derivatives as selective cannabinoid receptor 2 inverse agonists and osteoclast inhibitors: discovery, optimization, and biological evaluation. Cannabinoid receptors have gained increasing attention as drug targets for developing potential therapeutic ligands. Here, we report the discovery and optimization of triaryl sulfonamides as a novel series possessing significant CB2 receptor affinity and selectivity. Four sets of triaryl ligands were designed and synthesized for further structural modifications and led to the identification of eight compounds as potent and selective CB2 inverse agonists with high binding affinity (CB2K(i) < 10 nM). Especially, compound 57 exhibited the strongest binding affinity on the CB2 receptor (CB2K(i) of 0.5 nM) and the best selectivity over the CB1 receptor (selectivity index of 2594). Importantly, 57 also showed potent inhibitory activity on osteoclast formation, and it was confirmed by a cell viability assay that the inhibition effects were not derived from the cytotoxicity. Finally, 3D QSAR studies confirmed our SAR findings that three bulky groups play an important role for CB2 receptor binding affinity. 23224942 Molecular vibrational spectroscopy characterization of epoxy graphene oxide from density functional calculations. To further understand the structure of graphene oxide, several structures of graphene oxide were systematically investigated using density functional theory (DFT). Our models consisted of a hexagonal in-plane structure of graphene with epoxy groups, and different oxidation levels. We found that different arrangements of these units yielded a range of vibrational spectra. Raman positions of the D and G bands depend sensitively on the local atomic configurations. Both structure energy and spectra computations indicate that the oxidation functional groups are energetically favorable to aggregate together and to be close to one another on the opposite side of graphene surface. 23109279 Enantioselective toxicity and bioaccumulation of fipronil in fathead minnows (Pimephales promelas) following water and sediment exposures. Fipronil is a widely used, broad-spectrum pesticide that is applied as an equal mixture of two enantiomers. As regulations on older pesticides become more stringent, production and application of fipronil is expected to grow, leading to increased inputs into aquatic environments and complex exposures to biota. To better understand the potential exposures introduced by fipronil contamination, we conducted subchronic toxicity tests with larval fathead minnows (Pimephales promelas) and waterborne fipronil and its enantiomers and exposed juvenile fathead minnows to fipronil-spiked sediment. Enantioselective toxicity was observed in fish after the 7-d subchronic exposure, with increased toxicity of the racemate and (+) enantiomer observed compared with the (-) enantiomer. Curiously, toxicities of the racemate and (+) enantiomer were not significantly different, even though the racemate contains 50% of the (+) enantiomer and 50% of the less toxic (-) enantiomer. During the sediment exposure, racemic fipronil in sediment was transformed primarily to fipronil sulfide, while exposed fish rapidly accumulated fipronil and/or fipronil sulfide and transformed the majority to fipronil sulfone. Using the results of the sediment-exposure experiment, the authors explored a mechanism that may contribute to the interesting trends in enantioselective toxicity observed during the waterborne exposures. In tandem, the aquatic toxicity experiment and the spiked sediment exposure demonstrate the potentially complex behavior of fipronil in sediment and fish. 23314757 Forming double layer-encapsulated quantum dots for bio-imaging and cell targeting. We report a simple and effective approach for the preparation of double layer-encapsulated quantum dots (DL-Qdots) composed of alkyl-capping ligands to interdigitate with hydrophobic, protective agents on the surface of AgInS(2)/ZnS quantum dots (Qdots), which allow phase transfer of hydrophobic Qdots from the organic phase into the aqueous phase. The alkyl-capping ligands consist of a hydrophobic, aliphatic chain and different functional terminal groups (e.g., carboxyl, amine, hydroxyl, and thiol groups) that can serve as reactive sites to chemically couple with other materials. The resulting DL-Qdots bearing various functional groups retain good fluorescence properties and show excellent solubility as well as stability over a range of pH in the aqueous phase. Cytotoxicity studies of DL-Qdots bearing carboxyl groups (DL-Qdots-COOH) were carried out against human cervical (HeLa) cancer cells to elicit no apparent toxicity even at high concentrations of 300 μg mL(-1) and 24 h of incubation. To demonstrate their potential biomedical application, DL-Qdots-COOH were further conjugated with folate for staining in HeLa, human liver carcinoma (HepG2), and human breast (MCF-7) cancer cells. Confocal imaging characterization revealed that folate-conjugated DL-Qdots could target most specifically and effectively HeLa cells via folate receptor-mediated targeted delivery compared to HepG2 and MCF-7 cells. The generality and simplicity of this newly developed strategy can possibly be extended to a large variety of hydrophobic Qdots and nanocrystals whose surface protective agents have a long aliphatic chain. 23432587 Aminophosphonate metal complexes of biomedical potential. Metals and their complexes with organic ligands have an important role in biochemical systems such as enzymatic catalysis, metal ion transfer across the cell membranes, treatment of malignancy, rheumatoid arthritis, ulcer and other types of diseases. Special attention is directed to metal complexes with ligands which are important in biological systems, as their incorporation into metallo-organic compounds offers much scope for design of potential metal-based agents that provide new opportunities in the medicinal chemistry. In view of this, derivatives of aminophosphonic acids, owing to their broad spectrum of biological activities and wide range of applications in the medicinal and agrochemical fields, are very attractive metal-ligand agents that might form biomedical important metal complexes. Thus, a number of aminophosphonate complexes of platinum group metals have been found to possess remarkable antitumor activity while complexes of some other transition and rare-earth metals like technetium, rhenium, samarium and gadolinium have been used either as therapeutic and diagnostic radiopharmaceuticals or as magnetic resonance imaging (MRI) contrast agents. In addition, the high phosphonate affinity towards bone and other calcified tissues may be utilized for the drug targeting based on synthesis of metal complexes linked to bioactive carrier systems, affording better modalities of attack to the site of pathology. In this review article, aminophosphonate metal-based compounds with potential biomedical applications are described. 23561113 Anticancer activity and mediation of apoptosis in human HL-60 leukaemia cells by edible sea cucumber (Holothuria edulis) extract. Sea cucumbers have been a dietary delicacy and important ingredient in Asian traditional medicinal over many centuries. In this study, edible sea cucumber Holothuria edulis was evaluated for its in vitro anticancer potential. An aqueous fraction of the edible sea cucumber (ESC-AQ) has been shown to deliver a strong cytotoxic effect against the human HL-60 leukaemia cell line. An induction effect of apoptotic body formation in response to ESC-AQ treatment was confirmed in HL-60 cells stained with Hoechst 33342 and confirmed via flow cytometry analysis. The up regulation of Bax and caspase-3 protein expression was observed while the expression of Bcl-xL protein was down regulated in ESC-AQ treated HL-60 cells. Due to the profound anticancer activity, ESC-AQ appears to be an economically important biomass fraction that can be exploited in numerous industrial applications as a source of functional ingredients. 23506073 Novel regulatory system nemRA-gloA for electrophile reduction in Escherichia coli K-12. Electrophilic compounds such as glyoxals, which are toxic due to their reactive carbonyl group, are generated in vivo through various pathways. In this study, we obtained evidence indicating that the nemRA operon, previously reported to encode a repressor and the N-ethylmaleimide reductase, respectively, is co-transcribed with the 3'-proximal gloA gene encoding glyoxalase I. The operon is not only involved in cytosolic detoxification but is also regulated by electrophiles such as quinones and glyoxals. A gel mobility shift assay revealed that purified NemR repressor bound to DNA was dissociated upon interaction with quinones and glyoxals, while their reduced forms were ineffective. The cysteines of NemR at 21 and 116 were essential in sensing electrophiles in vivo and in vitro. Reversible intermolecular disulphide bonds were observed with a reducing agent as well as with electrophiles. DNA binding affinity reduced by glyoxal was also increased with a reducing agent. The NemA reductase, an FMN-containing enzyme, exhibited catalytic activity toward various electrophiles including quinones, while GloA played a major role in glyoxal detoxification. Therefore, we propose that cells have a cytosolic system consisting of the nemRA-gloA operon for the reduction of electrophiles, especially quinones and glyoxals, to maintain an appropriate intracellular redox balance. 23386058 Vascular endothelial growth factor induces growth of uterine cervix and immune cell recruitment in mice. Knowledge of uterine cervical epithelial biology and factors that influence its events may be critical in understanding the process of cervical remodeling (CR). Here, we examine the impact of exogenous vascular endothelial growth factor (VEGF) on uterine cervical epithelial growth in mice (nonpregnant and pregnant) treated with VEGF agents (recombinant and inhibitor) using a variety of morphological and molecular techniques. Exogenous VEGF altered various uterine cervical epithelial cellular events, including marked induction of growth, edema, increase in inter-epithelial paracellular space, and recruitment of immune cells to the outer surface of epithelial cells (cervical lumen). We conclude that VEGF induces multiple alterations in the uterine cervical epithelial tissues that may play a role in local immune surveillance and uterine cervical growth during CR. 23241030 Anharmonic motion in experimental charge density investigations. In the charge density study of 9-diphenylthiophosphinoylanthracene the thermal motion of several atoms needed an anharmonic description via Gram-Charlier coefficients even for data collected at 15 K. As several data sets at different temperatures were measured, this anharmonic model could be proved to be superior to a disorder model. Refinements against theoretical data showed the resemblance of an anharmonic model and a disorder model with two positions very close to each other (~0.2 Å), whereas these two models could be clearly distinguished if the second position is 0.5 Å apart. The refined multipole parameters were distorted when the anharmonic motion was not properly refined. Therefore, this study reveals the importance of detecting and properly handling anharmonic motion. Unrefined anharmonic motion leads to typical shashlik-like residual density patterns. Therefore, careful analysis of the residual density and the derived probability density function after the refinement of the Gram-Charlier coefficients proved to be the most useful tools to indicate the presence of anharmonic motion. 23403395 Targeted co-delivery of docetaxel, cisplatin and herceptin by vitamin E TPGS-cisplatin prodrug nanoparticles for multimodality treatment of cancer. We developed a nanocarrier system of herceptin-conjugated nanoparticles of d-alpha-tocopheryl-co-poly(ethylene glycol) 1000 succinate (TPGS)-cisplatin prodrug (HTCP NPs) for targeted co-delivery of cisplatin, docetaxel and herceptin for multimodality treatment of breast cancer of high human epidermal growth factor receptor 2 (HER2) overexpression. Co-polymers poly(lactic acid)-TPGS (PLA-TPGS) and carboxyl group-terminated TPGS (TPGS-COOH) were also added in the polymeric matrix to stabilize the prodrug nanoparticles and to facilitate herceptin conjugation. The HTCP NPs of high, moderate and low docetaxel versus cisplatin ratio were prepared by the nanoprecipitation method, which showed a pH-sensitive release for both anticancer drugs. The therapeutic effects of HTCP NPs were evaluated in vitro and compared with Taxotere® and cisplatin. The HTCP NPs of high docetaxel versus cisplatin ratio were found to have better efficacy than those of moderate and low docetaxel versus cisplatin ratio. The targeting effects of the HTCP NPs were demonstrated by a much lower IC50 value of 0.0201+0.00780+0.1629μg/mL of docetaxel+cisplatin+herceptin for SK-BR-3 cells, which are of high HER2 overexpression, than that of 0.225+0.0875+1.827μg/mL for NIH3T3 cells, which are of low HER2 overexpression, after 24h incubation. The same design of TPGS prodrug nanoparticles can also be applied for targeted co-delivery of other hydrophilic and hydrophobic drugs. 23567041 Evidence for a new mechanism behind HIFU-triggered release from liposomes. A promising approach for local drug delivery is high-intensity focused ultrasound (HIFU)-triggered release of drugs from stimuli-responsive nanoparticles such as liposomes. The aim of this study was to investigate whether another release mechanism is involved with HIFU-triggered release from liposomes beside cavitation and temperature. Furthermore, it was studied whether this new release mechanism allows the release of lipophilic compounds. Therefore, both a lipophilic (Nile red) and a hydrophilic (fluorescein) compound were loaded into thermosensitive (TSL) or non-thermosensitive liposomes (NTSL) and the liposomes were subjected both to continuous wave- (CW) and pulsed wave (PW)-HIFU. The mean liposome size varied from 97 to 139nm with a polydispersity index (PDI)≤0.06 for the different formulations. The Tm of the phospholipid bilayer of the TSL was around 42°C. Approximately 80% of fluorescein was released within 15min from TSL at temperatures≥42°C. In contrast, no fluorescein release from NTSL and NR release from both TSL and NTSL was observed at temperatures up to 60°C. CW-HIFU exposure of TSL resulted in rapid temperature elevation up to 52°C and subsequently almost quantitative fluorescein release. Fluorescein release from NTSL was also substantial (~64% after 16min at 20W). Surprisingly, CW-HIFU exposure (20W for 16min) resulted in the release of NR from TSL (~66% of the loaded amount), and this was even higher from NTSL (~78%). PW-HIFU exposure did not result in temperatures above the Tm of TSL. However, nearly 85% of fluorescein was released from TSL after 32min at 20W of PW-HIFU exposure, whereas the release from NTSL was around 27%. Interestingly, NR release from NTSL was~30% after 2min PW-HIFU exposure and increased to~70% after 32min. Furthermore, addition of microbubbles to the liposomes prior to PW-HIFU exposure did not result in more release, which suggests that cavitation can be excluded as the main mechanism responsible for the triggered release of both a hydrophilic and a lipophilic model compound from liposomes. Dynamic light scattering analysis showed that the mean size and PDI of the liposomes did not significantly change after CW- and PW-HIFU exposure. Taken together, it is therefore concluded that neither temperature elevation nor inertial cavitation is essential for the release of both hydrophilic and lipophilic compounds from liposomes. It is assumed that the release originates from radiation force-induced acoustic streaming, causing the liposomes to collide at the walls of the exposure chamber leading to shear forces which in turn results in reversible liposome destabilization and release of both hydrophilic and lipophilic compounds. 23644195 In vitro biosynthesis, isolation, and identification of predominant metabolites of 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one (RVX-208). The structures of the two predominant metabolites (M4 and M5) of RVX-208, observed both in in vitro human and animal liver microsomal incubations, as well as in plasma from animal in vivo studies, were determined. A panel of biocatalytic systems was tested to identify biocatalysts suitable for milligram scale production of metabolite M4 from RVX-208. Rabbit liver S9 fraction was selected as the most suitable system, primarily based on pragmatic metrics such as catalyst cost and estimated yield of M4 (∼55%). Glucuronidation of RVX-208 catalyzed by rabbit liver S9 fraction was optimized to produce M4 in amounts sufficient for structural characterization. Structural studies using LC/MS/MS analysis and (1)H NMR spectroscopy showed the formation of a glycosidic bond between the primary hydroxyl group of RVX-208 and glucuronic acid. NMR results suggested that the glycosidic bond has the β-anomeric configuration. A synthetic sample of M4 confirmed the proposed structure. Metabolite M5, hypothesized to be the carboxylate of RVX-208, was prepared using human liver microsomes, purified by HPLC, and characterized by LC/MS/MS and (1)H NMR. The structure was confirmed by comparison to a synthetic sample. Both samples confirmed M5 as a product of oxidation of primary hydroxyl group of RVX-208 to carboxylic acid. 23279841 Protective action of ethanolic extract of Rosmarinus officinalis L. in gastric ulcer prevention induced by ethanol in rats. The pathology of a gastric ulcer is complex and multifactorial. Gastric ulcers affect many people around the world and its development is a result of the imbalance between aggressive and protective factors in the gastric mucosa. In this study, we evaluated the ethanolic extract of Rosmarinus officinalis L. (eeRo); this plant, more commonly known as rosemary, has attracted the interest of the scientific community due to its numerous pharmacological properties and their potential therapeutic applications. Here, we tested the preventive effects of eeRo against gastric ulcer induced by 70% ethanol in male Wistar rats. In addition, we aimed to clarify the mechanism involved in the preventive action of the eeRo in gastric ulcers. Based on the analysis of markers of oxidative damage and enzymatic antioxidant defense systems, the measurement of nitrite and nitrate levels and the assessment of the inflammatory response, the eeRo exhibited significant antioxidant, vasodilator and antiinflammatory properties. 23384967 Comparative analysis of human CYP3A4 and rat CYP3A1 induction and relevant gene expression by bisphenol A and diethylstilbestrol: implications for toxicity testing paradigms. Bisphenol A (BPA) and diethylstilbestrol (DES) are endocrine-disrupting chemicals that interact with the human pregnane X receptor (PXR). CYP3A4 enzyme is essential in the hydroxylation of steroid hormones and is regulated by PXR. In the present study, human and rat hepatoma cell lines were exposed to BPA and DES. Both BPA and DES (10-50μM) caused a significant activation of the CYP3A4 promoter via the PXR in the DPX2 human hepatoma cell line. No activation of rat PXR was seen. BPA and DES treated DPX2 cells demonstrated increased expression of CYP3A4 mRNA, and increased enzyme activity. In summary, BPA, in concentrations relevant to current safety levels of human exposure, activates the human PXR and demonstrates an increase in CYP3A4 mRNA expression and enzyme activity. BPA actions in this model system occur to a greater extent than DES. This study raises concerns regarding our current toxicity testing paradigms and species utilization. 23394480 Gate-modulated thermoelectric power factor of hole gas in Ge-Si core-shell nanowires. We experimentally studied the thermoelectric power factor of hole gas in individual Ge-Si core-shell nanowires with Ge core diameters ranging from 11 to 25 nm. The Ge cores are dopant-free, but the Fermi level in the cores is pinned by surface and defect states in the epitaxial Si shell thereby doping the cores into the degenerate regime. This doping mechanism avoids the high concentration of dopants usually encountered in bulk thermoelectric materials and provides a unique opportunity to enhance the carrier mobility with suppressed ionized impurity scattering. Moreover, the carrier concentration in small diameter nanowires has also been effectively modulated by field effect, allowing one to probe the electrical conductivity and thermopower within a wide range of carrier concentrations, which is crucial to understand the thermoelectric transport behavior. We found that the thermopower of nanowires with Ge core diameters down to 11 nm still follows the behavior of bulk Ge. As a result, the power factor is found to be closely correlated with the carrier mobility, which is higher than that of bulk Ge in one of the core-shell nanowires studied here. 23349501 Impaired local production of pro-resolving lipid mediators in obesity and 17-HDHA as a potential treatment for obesity-associated inflammation. Obesity-induced chronic low-grade inflammation originates from adipose tissue and is crucial for obesity-driven metabolic deterioration including insulin resistance and type 2 diabetes.Chronic inflammation may be a consequence of a failure to actively resolve inflammation,and could result from a lack of local specialized pro-resolving lipid mediators (SPM) such as resolvins and protectins, which derive from the n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We assessed obesity-induced changes of n-3-derived SPM in adipose tissue and effects of dietary EPA/DHA thereon.Moreover, we treated obese mice with SPM precursors and investigated effects on inflammation and metabolic dysregulation. Obesity significantly decreased DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA, resolvin D1 precursor) and protectin D1 levels in murine adipose tissue. Dietary EPA/DHA treatment restored endogenous biosynthesis of n-3 derived lipid mediators in obesity while attenuating adipose tissue inflammation and improving insulin sensitivity. Notably, 17-HDHA treatment reduced adipose tissue expression of inflammatory cytokines, increased adiponectin expression and improved glucose tolerance parallel to insulin sensitivity in obese mice. These findings indicate that impaired biosynthesis of certain SPM and SPM precursors including 17-HDHA and protectin D1 contributes to adipose tissue inflammation in obesity and suggest 17-HDHA as a novel treatment option for obesity-associated complications. 23094864 Tanshinone derivatives: a patent review (January 2006 - September 2012). INTRODUCTION: Tanshinone IIA (TSIIA), cryptotanshinone and tanshinone I are major bioactive constituents of Danshen, a Chinese herbal medicine. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of TSIIA and it is currently used for treating cardiovascular diseases in China. AREAS COVERED: The article presents a review of the anti-atherosclerosis, cardioprotective effects, neuroprotection and anti-tumor activities of TSIIA and a review of patents on tanshinone derivatives from January 2006 to September 2012. EXPERT OPINION: Mechanistic studies have discovered that TSIIA modulates ion channels, kinases, hormone receptors, apoptosis proteins, growth factors, cytokines, microRNA, tumor suppressor and many other targets, revealing an intricate biological network modulated by TSIIA. Many patents have attempted to overcome the low water solubility of TSIIA and tanshinone I by attaching a polar substituent or by a prodrug strategy. However, biological activities of these tanshinone derivatives need to be further evaluated. Given the extensive in vitro and in vivo biological activities of TSIIA, this compound is a promising candidate to be further developed as a novel therapeutics for treating atherosclerosis, cardiovascular diseases, neurodegenerative diseases and cancer. 23627443 Nanocarrier-based topical drug delivery for an antifungal drug. Abstract Objective: The conventional liposomal amphotericin B causes many unwanted side effects like blood disorder, nephrotoxicity, dose-dependent side effects, highly variable oral absorption and formulation-related instability. The objective of the present investigation was to develop cost-effective nanoemulsion as nanocarreir for enhanced and sustained delivery of amphotericin B into the skin. Methods and characterizations: Different oil-in-water nanoemulsions were developed by varying the composition of hydrophilic (Tween® 80) surfactants and co-surfactant by the spontaneous titration method. The developed formulation were characterized, optimized, evaluated and compared for the skin permeation with commercial formulation (fungisome 0.01% w/w). Optimized formulations loaded with amphotericin B were screened using varied concentrations of surfactants and co-surfactants as decided by the ternary phase diagram. Results and discussion: The maximum % transmittance obtained were 96.9 ± 1.0%, 95.9 ± 3.0% and 93.7 ± 1.2% for the optimized formulations F-I, F-III and F-VI, respectively. These optimized nanoemulsions were subjected to thermodynamic stability study to get the most stable nanoemulsions (F-I). The results of the particle size and zeta potential value were found to be 67.32 ± 0.8 nm and -3.7 ± 1.2 mV for the final optimized nanoemulsion F-I supporting transparency and stable nanoemulsion for better skin permeation. The steady state transdermal flux for the formulations was observed between 5.89 ± 2.06 and 18.02 ± 4.3 µg/cm(2)/h whereas the maximum enhancement ratio were found 1.85- and 3.0-fold higher than fungisome and drug solution, respectively, for F-I. The results of the skin deposition study suggests that 231.37 ± 3.6 µg/cm(2) drug deposited from optimized nanoemulsion F-I and 2.11-fold higher enhancement ratio as compared to fungisome. Optimized surfactants and co-surfactant combination-mediated transport of the drug through the skin was also tried and the results were shown to have facilitated drug permeation and skin perturbation (SEM). Conclusion: The combined results suggested that amphotericin B nanoemulsion could be a better option for localized topical drug delivery and have greater potential as an effective, efficient and safe approach. 23231457 Hydrogel-based scaffolds for enclosing encapsulated therapeutic cells. Cell encapsulation technology holds promise for the sustained and controlled delivery of different therapeutic proteins. Alginate-poly-L-lysine-alginate (APA) microcapsules represent one of the most widely studied alginate-polycation microcapsules. On the basis of this technology, two types of hydrogel-based scaffolds have been developed and analyzed with the aim of improving the retention and the retrieval of erythropoietin (Epo) secreting cell-loaded microcapsules in the tissue where they are implanted. Furthermore, these hydrogels may help to reduce the post-transplant inflammation and pericapsular fibrotic overgrowth typically observed around capsules. The hydrogel-based scaffolds could be administered as implantable forms (preformed scaffolds) or injectable forms (in situ formed scaffolds). The in vitro studies confirmed the correct adaptation of the enclosed cells to the scaffolds in terms of viability and protein expression. The posterior implantation of the cell-loaded capsules containing hydrogel-based scaffolds in mice revealed that the hematocrit levels were maintained up to 80% for at least 2 months. The histological analysis of the explanted microcapsules performed at that point showed that pericapsular overgrowth was reduced when cell-loaded microcapsules were enclosed in the hydrogels scaffolds. Incorporating microencapsulated cells within hydrogel-based scaffolds may help to improve their administration protocol and retention while reducing post-transplantation inflammation. 23325846 Isolation and identification of cell-specific microRNAs targeting a messenger RNA using a biotinylated anti-sense oligonucleotide capture affinity technique. MicroRNAs (miRNAs) are small non-coding RNAs that regulate expression by translational repression or messenger RNA (mRNA) degradation. Although numerous bioinformatic prediction models exist to identify miRNA-mRNA interactions, experimental validation of bona fide interactions can be difficult and laborious. Few methods can comprehensively identify miRNAs that target a single mRNA. We have developed an experimental approach to search for miRNAs targeting any mRNA using a capture affinity assay involving a biotinylated DNA anti-sense oligonucleotide. This method identifies miRNAs targeting the full length of the mRNA. The method was tested using three separate mRNA targets: alpha-1 antitrypsin (AAT) mRNA, interleukin-8 mRNA and secretory leucoprotease inhibitor mRNA. AAT mRNA-specific and total miRNAs from three different cell lines (monocytic THP-1, bronchial epithelial 16HBE14o- and liver HepG2 cells) were profiled, and validation studies revealed that AAT mRNA-specific miRNAs functionally target the AAT mRNA in a cell-specific manner, providing the first evidence of innate miRNAs selectively targeting and modulating AAT mRNA expression. Interleukin-8 and secretory leucoprotease inhibitor mRNAs and their cognate miRNAs were also successfully captured using this approach. This is a simple and an efficient method to potentially identify miRNAs targeting sequences within the full length of a given mRNA transcript. 23570394 Ultrafast Charge Transfer at Monolayer Graphene Surfaces with Varied Substrate Coupling. The charge transfer rates of a localized excited electron to graphene monolayers with variable substrate coupling have been investigated by the core hole clock method with adsorbed argon. Expressed as charge transfer times, we find strong variations between ∼3 fs (on graphene "valleys" on Ru(0001)) to ∼16 fs (quasi-free graphene on SiC, O/Ru(0001), or SiO2/Ru). The values for the "hills" on Gr/Ru and on Gr/Pt(111) are in between, with the ratio 1.7 between the charge transfer times measured on "hills" and "valleys" of Gr/Ru. We discuss the results for Gr on metals in terms of hybridized Ru-C orbitals, which change with the relative Gr-Ru alignment and distance. The charge transfer on the decoupled graphene layers must represent the intrinsic coupling to the graphene empty π* states. Its low rate may be influenced by processes retarding the spreading of charge after transfer. 23621493 Uncovering the Enzymes that Catalyze the Final Steps in Oxytetracycline Biosynthesis. Tetracyclines are a group of natural products sharing a linearly fused four-ring scaffold, which is essential for their broad-spectrum antibiotic activities. Formation of the key precursor anhydrotetracycline 3 during oxytetracycline 1 biosynthesis has been previously characterized. However, the enzymatic steps that transform 3 into 1, including the additional hydroxylation at C5 and the final C5a-C11a reduction, have remained elusive. Here we report two redox enzymes, OxyS and OxyR, are sufficient to convert 3 to 1. OxyS catalyzes two sequential hydroxylations at C6 and C5 positions of 3 with opposite stereochemistry, while OxyR catalyzes the C5a-C11a reduction using F420 as a cofactor to produce 1. The crystal structure of OxyS was obtained to provide insights into the tandem C6- and C5-hydroxylation steps. The substrate specificities of OxyS and OxyR were shown to influence the relative ratio of 1 and tetracycline 2. 23183183 Natriuretic peptides in developing medaka embryos: implications in cardiac development by loss-of-function studies. Cardiac natriuretic peptides (NPs), atrial NP (ANP) and B-type NP (BNP), and their receptor, guanylyl cyclase (GC)-A have attracted attention of many basic and clinical researchers because of their potent renal and cardiovascular actions. In this study, we used medaka, Oryzias latipes, as a model species to pursue the physiological functions of NPs because it is a suitable model for developmental analyses. Medaka has two ligands, BNP and C-type NP3 (CNP3) (but not ANP), that have greater affinity for the two O. latipes GC-A receptors (OLGC), OLGC7 and OLGC2, respectively. CNP3 is the ancestral molecule of cardiac NPs. Initially, we examined developmental expression of cardiac NP/receptor combinations, BNP/OLGC7 and CNP3/OLGC2, using quantitative real-time PCR and in situ hybridization. BNP and CNP3 mRNA increased at stages 25 (onset of ventricular formation) and 22 (appearance of heart anlage), respectively, whereas both receptor mRNAs increased at as early as stage 12. BNP/OLGC7 transcripts were found in arterial/ventricular tissues and CNP3/OLGC2 transcripts in venous/atrial tissues by in situ hybridization. Thus, BNP and CNP3 can act locally on cardiac myocytes in a paracrine/autocrine fashion. Double knockdown of BNP/OLGC7 genes impaired ventricular development by causing hypoplasia of ventricular myocytes as evidenced by reduced bromodeoxyuridine incorporation. CNP3 knockdown induced hypertrophy of atria and activated the renin-angiotensin system. Collectively, it appears that BNP is important for normal ventricular, whereas CNP3 is important for normal atrial development and performance, a role usually taken by ANP in other vertebrates. The current study provides new insights into the role of cardiac NPs in cardiac development in vertebrates. 22827445 Electrophoretic deposition of the thiophene-based copolymer and its composites with C60. Electrophoretic deposition is a useful and efficient technique to deposit conjugated polymers, if suitable suspension of the target polymer is obtained. Unfortunately, neither general theory nor universal procedure for the preparation of a suspension suitable for electrophoretic deposition has seemed to be established yet. Thus, accumulation of individual knowledge is still important in this area. Here, the preparation of suspensions of a thiophene-based polymer poly(3-octylthiophene-2,5-diyl-co-3-decyloxythiophene-2,5-diyl) (POT-co-DOT) and their application to the electrophoretic deposition have been reported. The suspensions of POT-co-DOT with various good/poor solvents ratios were easily obtained by mixing a toluene solution of the polymer and acetonitrile. The composition of the dispersion medium significantly affects the surface morphology of the film prepared by the electrophoretic deposition in the suspension. Composite films consisting of POT-co-DOT and C(60) have also been successfully prepared by electrophoretic deposition. Because the optical absorption peak at 333 nm in C(60) showed neither significant broadening nor a red shift, C(60) molecules were expected to be well-dispersed in the composite films. A photovoltaic device with a composite film prepared from a POT-co-DOT/C(60) = 2:1 suspension showed 10 times larger short-circuit current density and 5 times larger power conversion efficiency than a device with pure POT-co-DOT, although further work is required to improve the device performance. 23071294 ApoE derived from adipose tissue does not suppress atherosclerosis or correct hyperlipidemia in apoE knockout mice. The synthesis of apoE by adipocytes has profound effects on adipose tissue lipid flux and gene expression. Using adipose tissue transplantation from wild-type (WT) to apoE knockout (EKO) mice, we show that adipose tissue also contributes to circulating apoE. Different from circulating apoE produced by bone marrow transplantation (BMT), however, adipose tissue-derived apoE does not correct hyperlipidemia or suppress atherosclerosis. ApoE secreted by macrophages has a more acidic isoform distribution, and it increases binding of reconstituted VLDL particles to hepatocytes and fibroblasts more effectively than apoE secreted by adipocytes. The incremental binding can be entirely accounted for by binding to the LDL receptor. After BMT into EKO hosts, plasma cholesterol and macrophage-derived apoE are largely within IDL/LDL- and HDL-sized particles. After adipose tissue transplantation, most cholesterol and adipocyte apoE remain in VLDL. After BMT, circulating apoE no longer demonstrates predominance of acidic isoforms compared with that circulating after fat transplantation. In conclusion, fat transplantation provides circulating apoE levels similar to those provided by bone marrow transplantation, but it does not suppress hyperlipidemia or atherosclerosis. A potential mechanism contributing to this difference is differential binding to cell surface lipoprotein receptors. 23159106 Ethanol modulates the neurovascular coupling. Despite some evidence of the underlying molecular mechanisms the neuronal basis of ethanol-induced effects on the neurovascular coupling that forms the BOLD (blood oxygenation level dependent) signal is poorly understood. In a recent fMRI (functional magnetic resonance imaging) study monitoring ethanol-induced changes of the BOLD signal a reduction of the amplitude and a prolongation of the BOLD signal were observed. However, the BOLD signal is assumed to consist of a complex superposition of different underlying signals. To gain insight how ethanol influences stimulus efficacy, oxygen extraction, transit time and vessel-related parameters the fMRI time series from the sensori-motor and the visual cortex were analyzed using the balloon model. The results show a region-dependent decrease of the stimulus efficacy to trigger a post-stimulus neurovascular response as well as a prolongation of the transit time through the venous compartment. Oxygen extraction, feedback mechanisms and other vessel-related parameters were not affected. The results may be interpreted as follows: the overall mechanisms of the neurovascular coupling are still acting well at the moderate ethanol level of about 0.8‰ (in particular the vessel-related parts), but the potency to evoke a neurovascular response is already compromised most obviously in the supplementary motor area responsible for complex synchronizing and planning processes. 23199257 Ultrasensitive broadband probing of molecular vibrational modes with multifrequency optical antennas. Optical antennas represent an enabling technology for enhancing the detection of molecular vibrational signatures at low concentrations and probing the chemical composition of a sample in order to identify target molecules. However, efficiently detecting different vibrational modes to determine the presence (or the absence) of a molecular species requires a multispectral interrogation in a window of several micrometers, as many molecules present informative fingerprint spectra in the mid-infrared between 2.5 and 10 μm. As most nanoantennas exhibit a narrow-band response because of their dipolar nature, they are not suitable for such applications. Here, we propose the use of multifrequency optical antennas designed for operating with a bandwidth of several octaves. We demonstrate that surface-enhanced infrared absorption gains in the order of 10(5) can be easily obtained in a spectral window of 3 μm with attomolar concentrations of molecules, providing new opportunities for ultrasensitive broadband detection of molecular species via vibrational spectroscopy techniques. 23394469 Free energy of adsorption for a peptide at a liquid/solid interface via nonequilibrium molecular dynamics. Protein adsorption is of wide interest including in many technological applications such as tissue engineering, nanotechnology, biosensors, drug delivery, and vaccine production among others. Understanding the fundamentals of such technologies and their design would be greatly aided by an ability to efficiently predict the conformation of an adsorbed protein and its free energy of adsorption. In the study reported here, we show that this is possible when data obtained from nonequilibrium thermodynamic integration (NETI) combined with steered molecular dynamics (SMD) is subject to bootstrapping. For the met-enkephalin pentapeptide at a water-graphite interface, we were able to obtain accurate predictions for the location of the adsorbed peptide and its free energy of adsorption from around 50 and 80 SMD simulations, respectively. It was also shown that adsorption in this system is both energetically and entropically driven. The free energy of adsorption was also decomposed into that associated with formation of the cavity in the water near the graphite surface sufficient to accommodate the adsorbed peptide and that associated with insertion of the peptide into this cavity. This decomposition reveals that the former is modestly energetically and entropically unfavorable, whereas the latter is the opposite in both regards to a much greater extent. 23235158 First crystal structure of a fungal high-redox potential dye-decolorizing peroxidase: substrate interaction sites and long-range electron transfer. Dye-decolorizing peroxidases (DyPs) belong to the large group of heme peroxidases. They utilize hydrogen peroxide to catalyze oxidations of various organic compounds. AauDyPI from Auricularia auricula-judae (fungi) was crystallized, and its crystal structure was determined at 2.1 Å resolution. The mostly helical structure also shows a β-sheet motif typical for DyPs and Cld (chlorite dismutase)-related structures and includes the complete polypeptide chain. At the distal side of the heme molecule, a flexible aspartate residue (Asp-168) plays a key role in catalysis. It guides incoming hydrogen peroxide toward the heme iron and mediates proton rearrangement in the process of Compound I formation. Afterward, its side chain changes its conformation, now pointing toward the protein backbone. We propose an extended functionality of Asp-168, which acts like a gatekeeper by altering the width of the heme cavity access channel. Chemical modifications of potentially redox-active amino acids show that a tyrosine is involved in substrate interaction. Using spin-trapping experiments, a transient radical on the surface-exposed Tyr-337 was identified as the oxidation site for bulky substrates. A possible long-range electron transfer pathway from the surface of the enzyme to the redox cofactor (heme) is discussed. 23211525 Regulation of the human hydroxysteroid sulfotransferase (SULT2A1) by RORα and RORγ and its potential relevance to human liver diseases. The retinoid-related orphan receptors (RORs) were postulated to have functions in tissue development and circadian rhythm. In this study, we revealed a novel function of RORα (NR1F1) and RORγ (NR1F3) in regulating the human hydroxysteroid sulfotransferase (SULT2A1), a phase II conjugating enzyme known to sulfonate bile acids, hydroxysteroid dehydroepiandrosterone, and related androgens. A combination of promoter reporter gene assay and EMSA and chromatin immunoprecipitation (ChIP) assays showed that both RORα and RORγ transactivated the SULT2A1 gene promoter through their binding to a ROR response element found in the SULT2A1 gene promoter. Interestingly, this ROR response element overlaps with a previously reported constitutive androstane receptor response element on the same promoter. Down-regulation of RORα and/or RORγ by small interfering RNA inhibited the expression of endogenous SULT2A1. In primary human hepatocytes and human livers, we found a positive correlation between the expression of SULT2A1 and RORs, which further supported the regulation of SULT2A1 by RORs. We also found that the expression of RORα and RORγ was impaired in several liver disease conditions, such as steatosis/steatohepatitis, fibrosis, and hepatocellular carcinoma. The positive regulation of human SULT2A1 by RORs is opposite to the negative regulation of Sult2a1 by RORs in rodents. In summary, our results established SULT2A1 as a novel ROR target gene. The expression of RORs is a potential predictor for the expression of SULT2A1 as well as disease conditions. 23237482 Tuning the light emission from GaAs nanowires over 290 meV with uniaxial strain. Strain engineering has been used to increase the charge carrier mobility of complementary metal-oxide-semiconductor transistors as well as to boost and tune the performance of optoelectronic devices, enabling wavelength tuning, polarization selectivity and suppression of temperature drifts. Semiconducting nanowires benefit from enhanced mechanical properties, such as increased yield strength, that turn out to be beneficial to amplify strain effects. Here we use photoluminescence (PL) to study the effect of uniaxial stress on the electronic properties of GaAs/Al0.3Ga0.7As/GaAs core/shell nanowires. Both compressive and tensile mechanical stress were applied continuously and reversibly to the nanowire, resulting in a remarkable decrease of the bandgap of up to 296 meV at 3.5% of strain. Raman spectra were measured and analyzed to determine the axial strain in the nanowire and the Poisson ratio in the <111> direction. In both PL and Raman spectra, we observe fingerprints of symmetry breaking due to anisotropic deformation of the nanowire. The shifts observed in the PL and Raman spectra are well described by bulk deformation potentials for band structure and phonon energies. The fact that exceptionally high elastic strain can be applied to semiconducting nanowires makes them ideally suited for novel device applications that require a tuning of the band structure over a broad range. 23337523 Pharmacy benefit managers and their obligations during serious prescription drug shortages. Pharmacy benefit managers are connected to some 215 million Americans and to every prescribing physician and retail pharmacy in the United States. Many of them have their own large and sophisticated dispensing operations. These capabilities could be put to use when drug shortages threaten life. Indeed, these capabilities are such that they confer obligations on pharmacy benefit managers to address such shortages--not only on behalf of their clients but for society in general. 23553708 Impact of Sildenafil on Survival of Patients With Eisenmenger Syndrome. The favorable effects of short-term use of sildenafil on patients with Eisenmenger syndrome have been reported. We further studied the impact of long-term use of sildenafil on survival of these patients. In this study, the baseline data of patients newly diagnosed as Eisenmenger syndrome in our hospital between January 2005 and December 2009 were retrospectively collected. Patients were followed-up either by telephone contacts or during visits in our out-patient clinic. A total of 121 patients (68 patients in conventional group and 53 patients in sildenafil group) were finally included and 29 patients were re-evaluated after sildenafil therapy for 3-4 months. Compared with the baseline, a 6-minute walk distance, functional classes, plasma hemoglobin level, and hemodynamics were significantly improved after sildenafil treatment. During a median follow-up period of 35.8 months, 15 patients died (11 patients in conventional group). The 1- and 3-year survival rates in sildenafil group were 97.0% and 95.2%, significantly higher than 90.6% and 82.9% in conventional group P = .025). Multivariate analysis showed that sildenafil therapy, functional class and mean pulmonary arterial pressure were independently associated with survival. Therefore, long-term sildenafil therapy improved survival in patients with Eisenmenger syndrome. 23526144 Serum trace elements levels in preeclampsia and eclampsia: correlation with the pregnancy disorder. Preeclampsia and eclampsia are fatal medical complications of pregnancy accounting for 20-80 % of increased maternal death in developing countries. Their aetiologies are still under investigation. Serum trace elements have been suggested to be involved in the pathogenesis of preeclampsia. Aim of this study was to address the correlation of serum trace elements with preeclampsia and eclampsia. It was a comparative cross-sectional study conducted on conveniently recruited 44 preeclampsia, 33 eclampsia and 27 normotensive pregnant patients. Atomic absorption spectrometry was employed to analyse serum concentrations of Ca, Mg, Cu, Zn and Fe. Data were analysed by Student's t test, one-way analysis of variance and multinomial logistic and binary regression analyses. p < 0.05 was considered as a level of significance. In preeclampsia, the serum Ca and Mg were significantly lower than those in eclampsia, while Cu and Zn values were higher. Significant changes of Ca, Mg and Cu were noted among preeclampsia, eclampsia and pregnant control. Serum Ca and Mg indicated a positive association, and Cu gave a negative association in preeclampsia. Cu/Fe ratio was high in eclampsia. Significant correlations of Mg with Zn in eclampsia and Mg with Fe in preeclampsia and eclampsia were predicted. Significant changes in serum trace element levels were present in preeclampsia and eclampsia that may have a link with the pathogenesis of pregnancy disorder. 23643792 In vivo toxicological evaluation of polymeric nanocapsules after intradermal administration. Polymeric nanocarriers have shown great promise as delivery systems. An alternative strategy has been to explore new delivery routes, such as intradermal (i.d.) that can be used for vaccines and patch-based drug delivery. Despite their many advantages, there are few toxicity studies, especially in vivo. We report a safety assessment of biodegradable poly(-caprolactone) lipid-core nanocapsules (LNC) with a mean size of 245 ± 10 nm following single and repeated intradermal injections to Wistar rats. Suspensions were prepared by interfacial deposition of polymer. The animals (n = 6/group) received a single dose of saline solution (1.2 ml/kg) or LNC (7.2 × 10(12) LNC/kg), or repeated doses of two controls, saline solution or Tween 80 (0.9 ml/kg), or three different concentrations of LNC (1.8, 3.6, and 5.4 × 10(12) LNC/kg) for 28 consecutive days. Clinical and physiological signs and mortality were observed. Samples of urine, blood, and tissue were used to perform toxicological evaluation. There were no clinical signs of toxicity or mortality, but there was a slight decrease in the relative body weights in the Tween 80-treated group (p < 0.01) after repeated administration. No histopathological alterations were observed in tissues or significant changes in blood and urinary biomarkers for tissue damage. Mild alterations in white blood cells count with increases in granulocytes in the Tween-80 group (p < 0.05) were found. Genotoxicity was evaluated through the comet assay and no statistical difference was observed among the groups. Therefore, we conclude that, under the conditions of these experiments, biodegradable LNC did not present appreciable toxicity after 28 consecutive days of intradermal administration and is promising for its future application in vaccines and patch-based devices for enhancing the delivery of drugs. 23578690 Novel ROS-activated agents utilize a tethered amine to selectively target acute myeloid leukemia. This study explores the possible use of reactive oxygen-activated DNA modifying agents against acute myeloid leukemia (AML). A key amine on the lead agent was investigated via cytotoxicity assays and was found necessary for potency. The two best compounds were screened via the NCI-60 cell panel. These two compounds had potency between 200 and 800nM against many of the leukemia cancer cell types. Subsequent experiments explored activity against a transformed AML model that mimics the molecular signatures identified in primary AML patient samples. A lead compound had an IC50 of 760nM against this AML cell line as well as a therapeutic index of 7.7±3 between the transformed AML model cell line and non-cancerous human CD34+ blood stem/progenitor cells (UCB). The selectivity was much greater than the mainstays of AML treatment: doxorubicin and cytarabine. This manuscript demonstrates that this novel type of agent may be useful against AML. 23504247 Synthesis of new 1,3,4-benzotriazepin-5-one derivatives and their biological evaluation as antitumor agents. New derivatives of 1,3,4-benzotriazepin-5-one were designed and synthesized as structural analogues to the antitumor agents devazepide and asperlicin. An efficient and novel approach to the synthesis of 2-amino-1,3,4-benzotriazepin-5-one 2 was developed and its structure was confirmed. The newly synthesized derivatives were evaluated for their in vitro antitumor activity on 60 different cell lines. Compounds 8 and 9 displayed the most potent antitumor activity against several cell lines specifically ovarian cancer, renal cancer and prostate cancer, while compounds 5, 10 and 12 showed significant activities against UO-31 renal cancer cell line. 23139020 Determination of the dominant arachidonic acid cytochrome p450 monooxygenases in rat heart, lung, kidney, and liver: protein expression and metabolite kinetics. Cytochrome P450 (P450)-derived arachidonic acid (AA) metabolites serve pivotal physiological roles. Therefore, it is important to determine the dominant P450 AA monooxygenases in different organs. We investigated the P450 AA monooxygenases protein expression as well as regioselectivity, immunoinhibition, and kinetic profile of AA epoxygenation and hydroxylation in rat heart, lung, kidney, and liver. Thereafter, the predominant P450 epoxygenases and P450 hydroxylases in these organs were characterized. Microsomes from heart, lung, kidney, and liver were incubated with AA. The protein expression of CYP2B1/2, CYP2C11, CYP2C23, CYP2J3, CYP4A1/2/3, and CYP4Fs in the heart, lung, kidney, and liver were determined by Western blot analysis. The levels of AA metabolites were determined by liquid chromatography-electrospray ionization mass spectroscopy. This was followed by determination of regioselectivity, immunoinhibition effect, and the kinetic profile of AA metabolism. AA was metabolized to epoxyeicosatrienoic acids and 19- and 20-hydroxyeicosatetraenoic acid in the heart, lung, kidney, and liver but with varying metabolic activities and regioselectivity. Anti-P450 antibodies were found to differentially inhibit AA epoxygenation and hydroxylation in these organs. Our data suggest that the predominant epoxygenases are CYP2C11, CYP2B1, CYP2C23, and CYP2C11/CYP2C23 for the heart, lung, kidney, and liver, respectively. On the other hand, CYP4A1 is the major ω-hydroxylase in the heart and kidney; whereas CYP4A2 and/or CYP4F1/4 are probably the major hydroxlases in the lung and liver. These results provide important insights into the activities of P450 epoxygenases and P450 hydroxylases-mediated AA metabolism in different organs and their associated P450 protein levels. 23391162 Structure-Relaxivity Relationships of Serum Albumin Targeted MRI Probes Based on a Single Amino Acid Gd Complex. The Gd(III) complex of DO3A-N-α-aminopropionate, Gd(DOTAla), was used to generate a small library of putative MRI probes targeted to human serum albumin (HSA). Ten compounds were synthesized via multistep organic synthesis, and the corresponding Gd complexes were investigated for their affinity to HSA, lipophilicity, and relaxivity in the absence and presence of HSA. Negative charge and moderate lipophilicity correlate with increased HSA affinity and relaxivity. 23518599 Effects of rare-earth co-doping on the local structure of rare-earth phosphate glasses using high and low energy X-ray diffraction. Rare-earth co-doping in inorganic materials has a long-held tradition of facilitating highly desirable optoelectronic properties for their application to the laser industry. This study concentrates specifically on rare-earth phosphate glasses, (R2O3)x(R'2O3)y(P2O5)1-(x+y), where (R, R') denotes (Ce, Er) or (La, Nd) co-doping and the total rare-earth composition corresponds to a range between metaphosphate, RP3O9, and ultraphosphate, RP5O14. Thereupon, the effects of rare-earth co-doping on the local structure are assessed at the atomic level. Pair-distribution function analysis of high-energy X-ray diffraction data (Qmax = 28 Å(-1)) is employed to make this assessment. Results reveal a stark structural invariance to rare-earth co-doping which bears testament to the open-framework and rigid nature of these glasses. A range of desirable attributes of these glasses unfold from this finding; in particular, a structural simplicity that will enable facile molecular engineering of rare-earth phosphate glasses with 'dial-up' lasing properties. When considered together with other factors, this finding also demonstrates additional prospects for these co-doped rare-earth phosphate glasses in nuclear waste storage applications. This study also reveals, for the first time, the ability to distinguish between P-O and P[double bond, length as m-dash]O bonding in these rare-earth phosphate glasses from X-ray diffraction data in a fully quantitative manner. Complementary analysis of high-energy X-ray diffraction data on single rare-earth phosphate glasses of similar rare-earth composition to the co-doped materials is also presented in this context. In a technical sense, all high-energy X-ray diffraction data on these glasses are compared with analogous low-energy diffraction data; their salient differences reveal distinct advantages of high-energy X-ray diffraction data for the study of amorphous materials. 23228475 Cyprodinil as an activator of aryl hydrocarbon receptor. Cyprodinil is a pyrimidinamine fungicide, used worldwide by agriculture. It is used to protect fruit plants and vegetables from a wide range of pathogens. Benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are toxic environmental pollutants and are prototypes of aryl hydrocarbon receptor (AHR) ligands. Although the structure of cyprodinil distinctly differs from those of BaP and TCDD, our results show that cyprodinil induced nuclear translocation of the AHR, and induced the transcriptional activity of aryl hydrocarbon response element (AHRE). Cyprodinil induced the expression of cytochrome P450 (CYP) 1A1, a well-known AHR-targeted gene, in ovarian granulosa cells, HO23, and hepatoma cells, Hepa-1c1c7. Its induction did not appear in AHR signal-deficient cells, and was blocked by the AHR antagonist, CH-223191. Cyprodinil decreased AHR expression in HO23 cells, resulting in CYP1A1 expression decreasing after it peaked at 9h of treatment in HO23 cells. Dexamethasone is a synthetic agonist of glucocorticoids. Cyprodinil enhanced dexamethasone-induced gene expression, and conversely, its induction of CYP1A1 expression was decreased by dexamethasone in HO23 cells, indicating its induction of crosstalk between the AHR and glucocorticoid receptor and its role as a potential endocrine disrupter. In addition to BaP, TCDD, and an AHR agonist, β-NF, cyprodinil also phosphorylated extracellular signal-regulated kinase (ERK) in HO23 and Hepa-1c1c7 cells, indicating its deregulation of ERK activity. In summary, our results demonstrate that cyprodinil, similar to BaP, acts as an AHR activator, a potential endocrine disrupter, and an ERK disrupter. 22815248 Protective Effects of a Purified Saponin Mixture from Astragalus corniculatus Bieb., in vivo Hepatotoxicity Models. In this study, the in vivo effects of a purified saponin mixture (PSM), obtained from Astragalus corniculatus Bieb., were investigated using two in vivo hepatotoxicity models based on liver damage caused by paracetamol (PC) and carbon tetrachloride (CCl4 ). The effects of PSM were compared with silymarin. Male Wistar rats were challenged orally with 20% CCl4 or PC (2 g/kg) four days after being pre-treated with PSM (100 mg/kg) or silymarin (200 mg/kg). A significant decrease of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH) activities and glutathione (GSH) levels and an increase of malondialdehyde (MDA) quantity was observed after CCl4 and PC administration alone. PSM pre-treatment decreased serum transaminases and LDH activities and MDA levels and increased the levels of cell protector GSH. Biotransformation phase I enzymes were also assessed in both models. In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine-N-demethylase and aniline 4-hydroxylase activity and cytochrome P450, compared to the CCl4 only group. Neither silymarin nor PSM influenced PC biotransformation. Our results suggest that PSM, obtained from A. corniculatus, Bieb. showed in vivo hepatoprotective and antioxidant activities against CCl4 and PC-induced liver damage comparable to that of silymarin. Copyright © 2012 John Wiley & Sons, Ltd. 23010870 Nondestructive indices of mercury exposure in three species of turtles occupying different trophic niches downstream from a former chloralkali facility. Turtles are useful for studying bioaccumulative pollutants such as mercury (Hg) because they have long life spans and feed at trophic levels that result in high exposure to anthropogenic chemicals. We compared total Hg concentrations in blood and toenails of three species of turtles (Chelydra serpentina, Sternotherus odoratus, and Graptemys geographica) with different feeding ecologies from locations up- and downstream of a superfund site in Virginia, USA. Mercury concentrations in turtle tissues were low at the reference site (average ± 1SE: blood = 48 ± 6 ng g(-1); nail = 2,464 ± 339 ng g(-1) FW) but rose near the contamination source to concentrations among the highest ever reported in turtles [up to 1,800 ng g(-1) (blood) and 42,250 ng g(-1) (nail) FW]. Tissue concentrations remained elevated ~130 km downstream from the source compared to reference concentrations. Tissue Hg concentrations were higher for C. serpentina and S. odoratus than G. geographica, consistent with the feeding ecology and our stable isotope (δ(13)C and δ(15)N) analyses of these species. In addition, we suggest that toenails were a better indication of Hg exposure than blood, probably because this keratinized tissue represents integrated exposure over time. Our results demonstrate that downstream transport of Hg from point sources can persist over vast expanses of river thereby posing potential exposure risks to turtles, but relative exposure varies with trophic level. In addition, our study identifies turtle toenails as a simple, cost-efficient, and minimally invasive tissue for conservation-minded sampling of these long-lived vertebrates. 23318729 The in vitro and in vivo genotoxicity of isotretinoin assessed by cytokinesis blocked micronucleus assay and comet assay. Isotretinoin is a retinoic acid frequently used in monotherapy or combined with narrow-band ultraviolet B (NBUVB) irradiation to treat patients with acne and psoriasis vulgaris. As both diseases need frequent and/or prolonged therapeutic interventions, the study of the genotoxicity of retinoids becomes important. Our aim was to study the genotoxic effects of isotretinoin alone or combined with NBUVB. In vitro studies were performed in the absence of S9 metabolic activation using blood from five healthy volunteers, incubated 72 h with isotretinoin (1.2-20 μM) (i.e., at concentrations usually achieved in blood with therapeutic doses as well as at higher concentrations). In vivo studies were also performed using blood from two patients with acne and three patients with psoriasis vulgaris treated with isotretinoin in monotherapy (8 or 20mg/day) or combined with NBUVB (20mg isotretinoin/day+NBUVB). The genotoxic effect was evaluated by the cytokinesis-blocked micronucleus and the comet assays. Our studies showed that isotretinoin alone was not genotoxic when tested in human lymphocytes in vitro and in vivo. There was no clear genotoxic effect in psoriatic patients treated with isotretinoin and NBUVB. The in vitro studies showed that isotretinoin induced apoptosis and necrosis in human lymphocytes at higher doses. 23355493 Occupational exposure to anaesthetic gases and high-frequency audiometry. Objectives: Occupational exposure to anaestethic gases has been suggested to induce auditory damages. The aim of this study is to investigate high-frequency audiometric responses in subjects exposed to anaesthetic gases, in order to highlight the possible effects on auditory system. METHODS: The study was performed on a sample of 30 medical specialists of Messina University Anaesthesia and Intensive care. We have used tonal audiometry as well as high-frequency one. We have compared the responses with those obtained in a similar control group not exposed to anaesthetic gases. Results were compared statistically. Results: Results show a strong correlation (p = 0.000) between left and right ear responses to all the audiometric tests. The exposed and the control group run though the standard audiometry analysis plays different audiometric responses up only to higher frequencies (2000 HZ p = 0.009 and 4000 Hz p = 0.04); in high-frequency audiometry, as all other frequencies, the attention is drew to the fact that the sample groups distinguish themselves in a significantly statistic way (10,000 Hz p = 0.025, 12,000 Hz p = 0.008, 14,000 Hz p = 0.026, 16,000 Hz p = 0.08). The highest values are the ones related to exposed subjects both in standard (2000 Hz p = 0.01, 4000 Hz p = 0.02) and in high-frequency audiometry (10,000 Hz p = 0.011, 12,000 Hz p = 0.004, 14,000 Hz p = 0.012, 16,000 Hz p = 0.004). Conclusion: Results, even if preliminary and referred to a low-range sample, show an involvement of the anatomic structure responsible for the perception of high-frequency audiometric responses in subjects exposed to anaesthetic gases. 23296979 Anti-platelet Activity of Erythro-(7S,8R)-7-acetoxy-3,4,3`,5`-tetramethoxy-8-O-4`-neolignan from Myristica fragrans. Platelets play a critical role in pathogenesis of cardiovascular disorders and strokes. The inhibition of platelet function is beneficial for the treatment and prevention of these diseases. In this study, we investigated the anti-platelet activity of erythro-(7S,8R)-7-acetoxy-3,4,3`,5`-tetramethoxy-8-O-4`-neolignan (EATN), a neolignan isolated from Myristica fragrans, using human platelets. EATN preferentially inhibited thrombin- and platelet-activating factor (PAF)-induced platelet aggregation without affecting platelet damage in a concentration-dependent manner with IC(50) values of 3.2 ± 0.4 and 3.4 ± 0.3 μM, respectively. However, much higher concentrations of EATN were required to inhibit platelet aggregation induced by arachidonic acid. EATN also inhibited thrombin-induced serotonin and ATP release, and thromboxane B(2) formation in human platelets. Moreover, EATN caused an increase in cyclic AMP (cAMP) levels and attenuated intracellular Ca(2+) mobilization in thrombin-activated human platelets. Therefore, we conclude that the inhibitory mechanism of EATN on platelet aggregation may increase cAMP levels and subsequently inhibit intracellular Ca(2+) mobilization by interfering with a common signaling pathway rather than by directly inhibiting the binding of thrombin or PAF to their receptors. This is the first report of the anti-platelet activity of EATN isolated from M. fragrans. Copyright © 2013 John Wiley & Sons, Ltd. 23287728 Cloning and characterization of an antibacterial L-amino acid oxidase from Crotalus durissus cumanensis venom. An L-amino acid oxidase (LAAO) from Crotalus durissus cumanensis venom (CdcLAAO) was purified to homogeneity using a combination of size-exclusion and ion exchange chromatographies. CdcLAAO is a monomeric protein exhibiting an apparent molecular mass of 55 kDa and a calculated pI of 8. Its complete 498-amino-acid sequence was deduced through cDNA and protein sequencing. The enzyme oxidized L-Leu with K(m) and a V(Max) of 9.23 μM and 0.46 μM/min respectively, and exhibited Kcat and a Kcat/K(m) of 1.8 s(-1) and 195 mM(-1)s(-1). CdcLAAO inhibited in a dose-dependent manner the growth of Staphylococcus aureus and Acinetobacter baumannii. The inhibitory effect was more significant on S. aureus, with a Minimal Inhibitory Concentration (MIC) of 8 μg/mL and Minimal Bactericidal Concentration (MBC) of 16 μg/mL, than against A. baumannii, with a MIC of 16 μg/mL and MBC of 32 μg/mL. However, against Escherichia coli CdcLAAO did not show inhibitory capacity at the concentrations tested (2-128 μg/mL). CdcLAAO did not exhibit cytotoxic activity on the mouse myoblast cell line C(2)C(12) and on peripheral blood mononuclear cell (PBMC). 23542039 The in vitro cytotoxicity and genotoxicity of cigarette smoke particulate matter with reduced toxicant yields. Tobacco smoke contains more than 5600 constituents, of which approximately 150 are toxicants. This paper describes the activities in the Neutral Red uptake (NRU) assay, the Salmonella mutagenicity test (SAL), the mouse lymphoma mammalian cell mutation assay (MLA) and the in vitro micronucleus test (IVMNT) of Particulate Matter (PM) obtained from experimental cigarettes (ECs), designed to produce reduced levels of toxicants. The designs included tobacco substitute sheet (TSS) containing glycerol, which dilutes toxicants in smoke, or the incorporation of blend-treated (BT) tobacco to reduce the levels of nitrogenous toxicant precursors and some polyphenols. All samples were cytotoxic in the NRU, however TSS reduced PM cytotoxicity in this assay. All PMs were mutagenic in the SAL, MLA and IVMNT. Reductions in bacterial mutagenicity were observed in the SAL, for cigarettes with BT tobacco, compared with their respective controls. The quantitative changes in bacterial mutagenicity could be explained by analytical chemistry data on smoke generated from the ECs used in the study. These observations, and the absence of consistent qualitative differences in the activities of the experimental, control and reference cigarettes, suggest that reduced toxicity cigarettes, as measured by the tests described in this paper, may be developed without introducing any additional cytotoxic or genotoxic hazards, but the impact of this on human health risks remains unknown. 23212975 Poly(N-vinylpyrrolidone)-modified surfaces for biomedical applications. Poly(N-vinylpyrrolidone) (PVP), an important water soluble synthetic polymer, has many desirable properties including low toxicity, chemical stability, and good biocompatibility. Since PVP is hemocompatible and physiologically inactive, it has been used as a blood plasma substitute. Surface modification with PVP has been investigated extensively over the past few years as a means of preventing nonspecific protein adsorption. PVP may therefore be seen as a promising antifouling surface modifier comparable to poly(ethylene glycol) (PEG). In this review, various approaches for the design and preparation of PVP-modified surfaces are summarized and potential biomedical applications of these PVP-modified materials are indicated. Finally, some perspectives on future research on PVP for surface modification are discussed. 23043441 Grafting efficiency of synthetic polymers onto biomaterials: a comparative study of grafting-from versus grafting-to. In the present study, the two grafting techniques grafting-from - by activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) - and grafting-to - by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) - were systematically compared, employing cellulose as a substrate. In order to obtain a meaningful comparison, it is crucial that the graft lengths of the polymers that are grafted from and to the substrates are essentially identical. Herein, this was achieved by utilizing the free polymer formed in parallel to the grafting-from reaction as the polymer for the grafting-to reaction. Four graft lengths were investigated, and the molar masses of the four free polymers (21 ≤ M(n) ≤ 100 kDa; 1.07 ≤ Đ(M) ≤ 1.26), i.e. the polymers subsequently employed in the grafting-to reaction, were shown to be in the same range as the molar masses of the polymers grafted from the surface (23 ≤ M(n) ≤ 87 kDa; 1.08 ≤ Đ(M) ≤ 1.31). The molecular weights of the chains grafted from the surface were established after cleavage from the cellulose substrates via size exclusion chromatography (SEC). High-resolution Fourier transform infrared microscopy (FT-IRM) was employed as an efficient tool to study the spatial distribution of the polymer content on the grafted substrates. In addition, the functionalized substrates were analyzed by X-ray photoelectron spectroscopy (XPS), contact angle (CA) measurements, and field-emission scanning electron microscopy (FE-SEM). For cellulose substrates modified via the grafting-from approach, the content of polymer on the surfaces increased with increasing graft length, confirming the possibility to tailor not only the length of the polymer grafts but also the polymeric content on the surface. In comparison, for the grafting-to reaction, the grafted content could not be controlled by varying the length of the preformed polymer: the polymer content was essentially the same for the four graft lengths. Consequently, the obtained results, when employing cellulose as a substrate and under these conditions, suggest that the grafting-from approach is superior to the grafting-to technique with respect to controlling the distribution of the polymeric content on the surface. 23446276 Single-molecule chemical denaturation of riboswitches. To date, single-molecule RNA science has been developed almost exclusively around the effect of metal ions as folding promoters and stabilizers of the RNA structure. Here, we introduce a novel strategy that combines single-molecule Förster resonance energy transfer (FRET) and chemical denaturation to observe and manipulate RNA dynamics. We demonstrate that the competing interplay between metal ions and denaturant agents provides a platform to extract information that otherwise will remain hidden with current methods. Using the adenine-sensing riboswitch aptamer as a model, we provide strong evidence for a rate-limiting folding step of the aptamer domain being modulated through ligand binding, a feature that is important for regulation of the controlled gene. In the absence of ligand, the rate-determining step is dominated by the formation of long-range key tertiary contacts between peripheral stem-loop elements. In contrast, when the adenine ligand interacts with partially folded messenger RNAs, the aptamer requires specifically bound Mg(2+) ions, as those observed in the crystal structure, to progress further towards the native form. Moreover, despite that the ligand-free and ligand-bound states are indistinguishable by FRET, their different stability against urea-induced denaturation allowed us to discriminate them, even when they coexist within a single FRET trajectory; a feature not accessible by existing methods. 23122129 Differential sensitivity of D-galactose-binding lectins from fruits of dwarf elder (Sambucus ebulus L.) to a simulated gastric fluid. Some lectins from Sambucus spp. share amino acid sequences with the pollen Sam n1 allergen. The lectins ebulin f and SELfd from the early stages of growth were isolated and subjected to analysis by MALDI-TOF mass spectrometry, tryptic peptide fingerprinting, molecular characterization and pepsin digestibility. The molecular mass (33.214) and other structural features of the Sam n1 allergen fit best with a monomeric lectin like SELlm (Mr 34.2 kDa) found in shoots of dwarf elder. Ebulin f toxicity to mice was higher intraperitoneally than orally at the same dose (5mg/kg body weight). In contrast SELfd at the same dose lacks of apparent toxicity. Ebulin f, but not SELfd, undergoes extensive pepsin proteolysis, which could explain the differences in toxicity. The present study supports our hypothesis that the Sam n1 allergen could be a sequence-related monomeric lectin like SELlm present in shoots of Sambucus ebulus rather than ebulin. 23401602 Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice. The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat. Young male mice were fed three combinations of fatty acids at three doses (0.06%, 0.2%, and 0.6%, w/w) incorporated into AIN76 diets for 7 weeks. The types of fatty acids were linoleic acid (control), an equal mixture of trans-10, cis-12 (10,12) CLA plus linoleic acid, and an equal isomer mixture of 10,12 plus cis-9, trans-11 (9,11) CLA. Mice receiving the 0.2% and 0.6% dose of 10,12 CLA plus linoleic acid or the CLA isomer mixture had decreased white adipose tissue (WAT) and brown adipose tissue (BAT) mass and increased incorporation of CLA isomers in epididymal WAT and liver. Notably, in mice receiving 0.2% of both CLA treatments, the mRNA levels of genes associated with browning, including uncoupling protein 1 (UCP1), UCP1 protein levels, and cytochrome c oxidase activity, were increased in epididymal WAT. CLA-induced browning in WAT was accompanied by increases in mRNA levels of markers of inflammation. Muscle cytochrome c oxidase activity and BAT UCP1 protein levels were not affected by CLA treatment. These data suggest a linkage between decreased adiposity, browning in WAT, and low-grade inflammation due to consumption of 10,12 CLA. 23553560 Axitinib in metastatic renal cell carcinoma: results of a pharmacokinetic and pharmacodynamic analysis. Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, approved for second-line therapy for advanced renal cell carcinoma (RCC). Axitinib population pharmacokinetic and pharmacokinetic/pharmacodynamic relationships were evaluated. Using nonlinear mixed effects modeling with pooled data from 383 healthy volunteers, 181 patients with metastatic RCC, and 26 patients with other solid tumors in 17 trials, the disposition of axitinib was best described by a 2-compartment model with first-order absorption and a lag time, with estimated mean systemic clearance (CL) of 14.6 L/h and central volume of distribution (Vc ) of 47.3 L. Of 12 covariates tested, age over 60 years and Japanese ethnicity were associated with decreased CL, whereas Vc increased with body weight. However, the magnitude of predicted changes in exposure based on these covariates does not warrant dose adjustments. Multivariate Cox proportional hazard regression and logistic regression analyses showed that higher exposure and diastolic blood pressure were independently associated with longer progression-free and overall survivals and higher probability of partial response in metastatic RCC patients. These findings support axitinib dose titration to increase plasma exposure in patients who tolerate axitinib, and also demonstrate diastolic blood pressure as a potential marker of efficacy. 23609128 Dynamics and structural changes of small water clusters on ionization. Despite utmost importance in understanding water ionization process, reliable theoretical results of structural changes and molecular dynamics (MD) of water clusters on ionization have hardly been reported yet. Here, we investigate the water cations [(H2 O)n = 2-6 (+) ] with density functional theory (DFT), Möller-Plesset second-order perturbation theory (MP2), and coupled cluster theory with single, double, and perturbative triple excitations [CCSD(T)]. The complete basis set limits of interaction energies at the CCSD(T) level are reported, and the geometrical structures, electronic properties, and infrared spectra are investigated. The characteristics of structures and spectra of the water cluster cations reflect the formation of the hydronium cation moiety (H3 O(+) ) and the hydroxyl radical. Although most density functionals fail to predict reasonable energetics of the water cations, some functionals are found to be reliable, in reasonable agreement with high-level ab initio results. To understand the ionization process of water clusters, DFT- and MP2-based Born-Oppenheimer MD (BOMD) simulations are performed on ionization. On ionization, the water clusters tend to have an Eigen-like form with the hydronium cation instead of a Zundel-like form, based on reliable BOMD simulations. For the vertically ionized water hexamer, the relatively stable (H2 O)5 (+) (5sL4A) cluster tends to form with a detached water molecule (H2 O). © 2013 Wiley Periodicals, Inc. 23427850 Formation of a polymer surface with a gradient of pore size using a microfluidic chip. Here we demonstrate the generation of polymer monolithic surfaces possessing a gradient of pore and polymer globule sizes from ~0.1 to ~0.5 μm defined by the composition of two polymerization mixtures injected into a microfluidic chip. To generate the gradient, we used a PDMS microfluidic chip with a cascade micromixer with a subsequent reaction chamber for the formation of a continuous gradient film. The micromixer has zigzag channels of 400 × 680 μm(2) cross section and six cascades. The chip was used with a reversible bonding connection, realized by curing agent coating. After polymerization in the microfluidic chip the reversible bond was opened, resulting in a 450 μm thick polymer film possessing the pore size gradient. The gradient formation in the microfluidic reaction chamber was studied using microscopic laser-induced fluorescence (μLIF) and different model fluids. Formation of linear gradients was shown using the fluids of the same density by both diffusive mixing at flow rates of 0.001 mL/min and in a convective mixing regime at flow rates of 20 mL/min. By using different density fluids, formation of a two-dimensional wedge-like gradient controlled by the density difference and orientation of the microfluidic chip was observed. 23391631 The role of aryl hydrocarbon receptor signaling pathway in cardiotoxicity of acute lead intoxication in vivo and in vitro rat model. Lead (Pb(2+)) is a naturally occurring systemic toxicant heavy metal that affects several organs in the body including the kidneys, liver, and central nervous system. However, Pb(2+)-induced cardiotoxicity has never been investigated yet and the exact mechanism of Pb(2+) associated cardiotoxicity has not been studied. The current study was designed to investigate the potential effect of Pb(2+) to induce cardiotoxicity in vivo and in vitro rat model and to explore the molecular mechanisms and the role of aryl hydrocarbon receptor (AhR) and regulated gene, cytochrome P4501A1 (CYP1A1), in Pb(2+)-mediated cardiotoxicity. For these purposes, Wistar albino rats were treated with Pb(2+) (25, 50 and 100mg/kg, i.p.) for three days and the effects on physiological and histopathological parameters of cardiotoxicity were determined. At the in vitro level, rat cardiomyocyte H9c2 cell lines were incubated with increasing concentration of Pb(2+) (25, 50, and 100μM) and the expression of hypertrophic genes, α- and β-myosin heavy chain (α-MHC and β-MHC), brain Natriuretic Peptide (BNP), and CYP1A1 were determined at the mRNA and protein levels using real-time PCR and Western blot analysis, respectively. The results showed that Pb(2+) significantly induced cardiotoxicity and heart failure as evidenced by increase cardiac enzymes, lactate dehydrogenase and creatine kinase and changes in histopathology in vivo. In addition, Pb(2+) treatment induced β-MHC and BNP whereas inhibited α-MHC mRNA and protein levels in vivo in a dose-dependent manner. In contrast, at the in vitro level, Pb(2+) treatment induced both β-MHC and α-MHC mRNA levels in time- and dose-dependent manner. Importantly, these changes were accompanied with a proportional increase in the expression of CYP1A1 mRNA and protein expression levels, suggesting a role for the CYP1A1 in cardiotoxicity. The direct evidence for the involvement of CYP1A1 in the induction of cardiotoxicity by Pb(2+) was evidenced by the ability of AhR antagonist, resveratrol, to significantly inhibit the Pb(2+)-modulated effect on β-MHC and α-MHC mRNAs. It was concluded that acute lead exposure induced cardiotoxicity through AhR/CYP1A1-mediated mechanism. 23419783 Metformin and Sulfonylureas in Relation to Cancer Risk in Type II Diabetes Patients: A Meta-analysis using primary data of published studies. INTRODUCTION: Accumulating evidence suggests that patients with type 2 diabetes mellitus (T2DM) and hyperinsulinemia are at increased risk for developing malignancies. It remains to be fully elucidated whether use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affect cancer incidence in subjects with T2DM. MATERIAL & METHODS: We performed a meta-analysis using PubMed, of randomized control trials (RCTs), cohorts, and case-control studies published through July 2012 that assess effects of metformin and/or sulfonylurea sulfonylureas on cancer risk at any site, in subjects with T2DM. Fixed and random effects meta-analysis models were used, and the effect size was summarized as relative risk (RR) for RCTs/cohorts and as odds ratio (OR) for the case-control studies. RESULTS: Analysis of 24 metformin studies in subjects with T2DM showed that metformin use is associated with reduced risk for the development of cancer, in both cohort (RR=0.70 [95% CI=0.67-0.73]) and case-control studies (OR=0.90 [95% CI=0.84-0.98]), but this finding was not supported by RCTs (RR=1.01[95% CI=0.81-1.26]). Data from 18 sulfonylurea studies in subjects with T2DM showed that sulfonylurea use is associated with an increase in all-cancer risk, in cohort studies (RR=1.55 [95% CI=1.48 -1.63]), though data from RCTs (RR=1.17 [95% CI=0.95-1.45]) and case-control studies (OR=1.02 [95% CI=0.93-1.13]) failed to demonstrate a statistically significant effect. CONCLUSIONS: This analysis using pooled primary data demonstrates that metformin use reduces, while sulfonylurea use may be associated with an increased cancer risk in subjects with T2DM. These findings need to be confirmed in large-scale RCTs before they are translated into clinical practice. 22275383 Protective effect of honey against cigarette smoke induced-impaired sexual behavior and fertility of male rats. Cigarette smoking is associated with sexual dysfunction and impaired fertility in males. The aim of this study was to determine the potential protective effect of honey against the toxic effect of cigarette smoke (CS) on sexual behavior and fertility of male rats. Thirty-two adult Sprague-Dawley rats were randomly divided into four groups (8 rats/group) as control, honey (H), CS and H plus CS (H + CS) groups. Rats in control and CS groups received oral administration of distilled water daily while rats in H and H + CS groups received honey (1.2 g/kg body weight/day) by oral gavage. Rats in CS and H + CS groups were also exposed to CS for 8 min 3 times/day. From 10 to 13 weeks of treatment, each male rat was cohabited with 3 untreated female rats for sexual behavioral and reproductive performance studies. Honey significantly increased the percentages of rats achieving intromission and ejaculation as well as increased mating and fertility indexes of male rats exposed to CS. Thus, honey has a protective effect against CS-induced impaired sexual behavior and fertility in male rats. 23427056 Exendin-4, a GLP-1 receptor agonist, prevents osteopnia by promoting bone formation and suppressing bone resorption in aged ovariectomized rats. Osteoporosis mainly affects postmenopausal women and older men. Gastrointestinal hormones released after meal ingestion, such as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide (GLP)-2, have been shown to regulate bone turnover. However, whether GLP-1, another important gastrointestinal hormone, and its analogues also have anti-osteoporotic effects, especially in aged postmenopausal situation, is not confirmed yet. In the present study, we evaluated the effects of the GLP-1 receptor agonist exendin-4 on ovariectomy (OVX) induced osteoporosis in old rats. Twelve-month-old female Sprague-Dawley rats were subjected to OVX, and exendin-4 were administrated 4 weeks after the surgery and lasted for 16 weeks. Bone characters and related serum and gene biomarkers were analyzed. Sixteen weeks treatment of exendin-4 slowed down the body weight gain by decreasing fat mass and prevented the loss of bone mass in old OVX rats. Exendin-4 also enhanced the bone strength and prevented the deterioration of trabecular microarchitecture. Moreover, exendin-4 decreased urinary DPD/creatinine ratio and serum CTX-I and increased serum ALP, OC and P1NP levels, key biochemical markers of bone turnover. Interestingly, gene expression results further showed that exendin-4 not only inhibited bone resorption by increasing OPG/RANKL ratio, but also promoted bone formation by increasing the expressions of OC, Col1, Runx2, and ALP, which exhibited dual regulatory effects on bone turnover as compared with previous anti-osteoporotic agents. In conclusion, these findings demonstrated for the first time the anti-osteoporotic effects of exendin-4 in old OVX rats and that it might be a potential candidate for treatment of aged postmenopausal osteoporosis. © 2013 American Society for Bone and Mineral Research. 23474013 Intact inhibitory control processes in abstinent drug abusers (I): A functional neuroimaging study in former cocaine addicts. Neuroimaging studies in current cocaine dependent (CD) individuals consistently reveal cortical hypoactivity across regions of the response inhibition circuit (RIC). Dysregulation of this critical executive network is hypothesized to account for the lack of inhibitory control that is a hallmark of the addictive phenotype, and chronic abuse is believed to compound the issue. A crucial question is whether deficits in this circuit persist after drug cessation, and whether recovery of this system will be seen after extended periods of abstinence, a question with implications for treatment course and outcome. Utilizing functional magnetic resonance imaging (fMRI), we examined activation in nodes of the RIC in abstinent CD individuals (n = 27) and non-using controls (n = 45) while they performed a motor response inhibition task. In contrast to current users, these abstinent individuals, despite extended histories of chronic cocaine-abuse (average duration of use = 8.2 years), performed the task just as efficiently as non-users. In line with these behavioral findings, no evidence for between-group differences in activation of the RIC was found and instead, robust activations were apparent in both groups within the well-characterized nodes of the RIC. Similarly, our complementary Electroencephalography (EEG) investigation also showed an absence of behavioral and electrophysiological deficits in abstinent drug abusers. These results are consistent with an amelioration of neurobiological deficits in inhibitory circuitry following drug cessation, and could help explain how long-term abstinence is maintained. Finally, regression analyses revealed a significant association between level of activation in the right insula with inhibition success and increased abstinence duration in the CD cohort suggesting that this region may be integral to successful recovery from cocaine addiction. 23343324 Ordered nanoscale Archimedean tilings of a templated 3-miktoarm star terpolymer. The directed self-assembly of 3-miktoarm star terpolymer chains (polyisoprene-arm-polystyrene-arm-polyferrocenylethylmethylsilane (3 μ-ISF)) into 2D Archimedean tilings is described. A morphological change from (4.8(2)) to (6(3)) tiling is reported in the 3 μ-ISF thin film blended with PS homopolymer when a greater swelling of PI is achieved during the solvent annealing process. Highly oriented (4.8(2)) tilings were produced by templating the self-assembled three colored structures in blended thin films. The use of (4.8(2)) and (6(3)) tilings as nanolithographic masks to transfer square and triangular hole arrays into the substrate is also demonstrated. 23535870 Controlling potassium selectivity and proton blocking in a hybrid biological/solid-state polymer nanoporous membrane. Specific separations of protons and cations are usually performed by electromembrane processes, which require external electric energy. An easier process would be using a membrane able to separate both entities by passive diffusion. Presently, such synthetic nanoporous membranes do not exist. Here, we report the production of a robust hybrid biological/artificial solid-state membrane, which allows selective permeation of alkali metal cations without competing or concurrent permeation of protons. This membrane is simple to prepare and is based on the hydrophobic nature of the polymeric pore walls, and the confined gramicidin A molecules within. This work opens a new route for separation in the domain of nanobiofiltration, especially for tunable nanodevices based on differential ion conduction, with a fundamental understanding of the confinement mechanism. 23461650 Vibronic and Vibrational Coherences in Two-Dimensional Electronic Spectra of Supramolecular J-Aggregates. In J-aggregates of cyanine dyes, closely packed molecules form mesoscopic tubes with nanometer-diameter and micrometer-length. Their efficient energy transfer pathways make them suitable candidates for artificial light harvesting systems. This great potential calls for an in-depth spectroscopic analysis of the underlying energy deactivation network and coherence dynamics. We use two-dimensional electronic spectroscopy with sub-10 fs laser pulses in combination with two-dimensional decay-associated spectra analysis to describe the population flow within the aggregate. Based on the analysis of Fourier-transform amplitude maps, we distinguish between vibrational or vibronic coherence dynamics as the origin of pronounced oscillations in our two-dimensional electronic spectra. 23494106 Toxicological profiles of selected synthetic cannabinoids showing high binding affinities to the cannabinoid receptor subtype CB1. Products containing synthetic cannabinoids are consumed as a surrogate for marihuana due to their non-detectability with commonly used drug tests and their strong cannabimimetic effects. Because data concerning their toxicological properties are scarce, the cytotoxic, genotoxic, immunomodulatory, and hormonal activities of four naphthoylindole compounds (JWH-018, JWH-073, JWH-122 and JWH-210) and of one benzoylindole (AM-694) were studied in human cell lines and primary cells; tetrahydrocannabinol was included as the classical non-endogenous cannabinoid receptor ligand. All compounds induced damage to the cell membranes of buccal (TR146) and breast (MCF-7) derived cells at concentrations of ≥75-100 μM. No cytotoxic responses were seen in other assays which reflect mitochondrial damage, protein synthesis, and lysosomal activities. JWH-073 and JWH-122 induced DNA migration in buccal and liver cells (HepG2) in single cell gel electrophoresis assays, while JWH-210 was only in the latter cell line active. No estrogenic activities were detected in bone marrow cells (U2-OS), but all compounds caused anti-estrogenic effects at levels between 2.1 and 23.0 μM. Furthermore, no impact on cytokine release (i.e., on IL-10, IL-6, IL-12/23p40 and TNFα levels) was seen in LPS-stimulated human PBMCs, except with JWH-210 and JWH-122 which caused a decrease of TNFα and IL-12/23p40. All toxic effects were observed with concentrations higher than those expected in body fluids of users. Since genotoxic effects are in general linear over a wide concentration range and the exposure levels may be higher in epithelial cells or in serum, further experimental work is required to find out if DNA damage takes place in drug users. 23253856 Distinct functions of human RECQ helicases WRN and BLM in replication fork recovery and progression after hydroxyurea-induced stalling. Human WRN and BLM genes are members of the conserved RECQ helicase family. Mutations in these genes are associated with Werner and Bloom syndromes. WRN and BLM proteins are implicated in DNA replication, recombination, repair, telomere maintenance, and transcription. Using microfluidics-assisted display of DNA for replication track analysis (ma-RTA), we show that WRN and BLM contribute additively to normal replication fork progression, and non-additively, in a RAD51-dependent pathway, to resumption of replication after arrest by hydroxyurea (HU), a replication-stalling drug. WRN but not BLM is required to support fork progression after HU. Resumption of replication by forks may be necessary but is not sufficient for timely completion of the cell cycle after HU arrest, as depletion of WRN or BLM compromises fork recovery to a similar degree, but only BLM depletion leads to extensive delay of cell division after HU, as well as more pronounced chromatin bridging. Finally, we show that recovery from HU includes apparent removal of some of the DNA that was synthesized immediately after release from HU, a novel phenomenon that we refer to as nascent strand processing, NSP. 23519153 The early molecular processes underlying the neurological manifestations of an animal model of Wilson's disease. The Long-Evans Cinnamon (LEC) rat shows age-dependent hepatic manifestations that are similar to those of Wilson's disease (WD). The pathogenic process in the brain has, however, not been evaluated in detail due to the rarity of the neurological symptoms. However, copper accumulation is noted in LEC rat brain tissue from 24 weeks of age, which results in oxidative injuries. The current study investigated the gene expression profiles of LEC rat brains at 24 weeks of age in order to identify the important early molecular changes that underlie the development of neurological symptoms in WD. Biological ontology-based analysis revealed diverse altered expressions of the genes related to copper accumulation. Of particular interest, we found altered expression of genes connected to mitochondrial respiration (Sdhaf2 and Ndufb7), calcineurin-mediated cellular processes (Ppp3ca, Ppp3cb, and Camk2a), amyloid precursor protein (Anks1b and A2m) and alpha-synuclein (Snca). In addition to copper-related changes, compensatory upregulations of Cp and Hamp reflect iron-mediated neurotoxicity. Of note, reciprocal expression of Asmt and Bhmt is an important clue that altered S-adenosylhomocysteine metabolism underlies brain injury in WD, which is directly correlated to the decreased expression of S-adenosylhomocysteine hydrolase in hepatic tissue in LEC rats. In conclusion, our study indicates that diverse molecular changes, both variable and complex, underlie the development of neurological manifestations in WD. Copper-related injuries were found to be the principal pathogenic process, but Fe- or adenosylhomocysteine-related injuries were also implicated. Investigations using other animal models or accessible human samples will be required to confirm our observations. 23357976 Longer HSD11B2 CA-repeat in impaired glucose tolerance and type 2 diabetes. Type 2 11β-hydroxysteroid dehydrogenase encoded by the HSD11B2 gene converts cortisol to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. We investigated the association of HSD11B2 variant with glucose homeostasis. Subjects with normal glucose tolerance (n=585), impaired glucose tolerance (n=202) and type 2 diabetes (n=355) were genotyped for a highly polymorphic CA-repeat polymorphism in the first intron of HSD11B2. Allele and genotype frequencies differed between normal and impaired glucose tolerance (P = 0.0014 and 0.0407, respectively; 4DF) or type 2 diabetes (P = 0.0053 and 0.0078), with significant linear trends between the repeat length and the phenotype fraction. In normal subjects, total CA-repeat length was negatively correlated with fasting insulin and HOMA-β. Thus, subjects having more CA repeats are susceptible to developing abnormal glucose tolerance, whereas normal subjects carrying more CA repeats appeared to have frugal characteristics in insulin secretion. 23639741 Ultrasound-assisted extraction of Na and K from swine feed and its application in a digestibility assay: A green analytical procedure. The study is aimed to evaluate the efficiency of ultrasound-assisted extraction (UAE) as a simple strategy focused on sample preparation for metal determination in biological samples. The extraction of sodium and potassium extraction was carried out from swine feed followed by determination of the concentration of these metals by flame atomic emission spectrometry (FAES). The experiment was performed to cover the study of the variables influencing the extraction process and its optimal conditions (sample mass, particle size, acid concentration, sonication time and ultrasound power); the determination of these analytical characteristics and method validation using certified reference material; and the analysis of pre-starter diets. The optimal conditions established conditions were as follows: mass: 100mg, particle size:<60μm, acid concentration: 0.10molL(-1) HCl, sonication time: 50s and ultrasound power: 102W. The proposed method (UAE) was applied in digestibility assays of those nutrients present in different piglet pre-starter feeds and their results proved to be compatible with those obtained from mineralized samples (P<0.05). The ultrasound extraction method was demonstrated to be an excellent alternative for handless sampling and operational costs and the method also has the advantage of does not generating toxic residues that may negatively affect human health and contaminate the environment. 23583169 Beyond the Sympathetic Tone: The New Brown Fat Activators. If we could avoid the side effects associated with global sympathetic activation, activating brown adipose tissue to increase thermogenesis would be a safe way to lose weight. The discovery of adrenergic-independent brown fat activators opens the prospect of developing this alternative way to efficiently and safely induce negative energy balance. 23232941 Density functional theory study of the structure and vibrational modes of acrylonitrile adsorbed on Cu(100). We present a theoretical study of the structure and vibrations of acrylonitrile adsorbed on a Cu(100) metal surface. Simulations have been carried out by means of the density functional theory adopting periodic boundary conditions and including van der Waals dispersion forces. The two most stable structures (which are almost degenerate in energy) correspond to the molecule adsorbed parallel to the metal surface. In both geometries, the vinyl (C=C) and the cyano (C≡N) groups are the anchorage sites to the surface atoms. Low energy transition barriers allow fast isomerization between both structures. Molecular adsorption shifts some of their vibrational frequencies with respect to the gas phase, mainly the C=C and the C≡N stretching modes, in agreement with recent experimental measurements [Tornero et al., Phys. Chem. Chem. Phys., 2011, 13, 8475]. 23163430 Effective targeting of Aβ to macrophages by sonochemically prepared surface-modified protein microspheres. Imbalanced homeostasis and oligomerization of the amyloid-β (Aβ) peptide in the brain are hallmarks of Alzheimer's disease (AD). Microglia and macrophages play a critical role in the etiology of AD either by clearing Aβ from the brain or inducing inflammation. Recent evidence suggests that clearance of Aβ by microglia/macrophages via the phagocytic pathway is defective in AD, which can contribute to the accumulation of Aβ in the brain. We have recently demonstrated that protein microspheres modified at their surface with multiple copies of an Aβ-recognition motif can strongly bind Aβ, inhibit its aggregation, and directly reduce its toxicity by sequestering it from the medium. Here, we describe how microsphere-bound Aβ can stimulate microglial cells and be phagocytosed through a mechanism that is distinct from that of Aβ removal and, thus, contribute to the clearance of Aβ, even by defective microglial cells. The phagocytosis was most effective, with microspheres having a diameter of <1 μm. The introduction of polyethylene glycol to the surface of the microspheres changed the kinetics of the phagocytosis. Moreover, while aggregated Aβ induced a significant inflammatory response that was manifested by the release of TNF-α, the microsphere-bound Aβ dramatically reduced the amount of cytokine released from microglial cells. 23199984 Effects of chemical interesterification on the physicochemical, microstructural and thermal properties of palm stearin, palm kernel oil and soybean oil blends. Blends of palm stearin (PS), palm kernel oil (PKO) and soybean oil (SBO) at certain proportions were formulated using a mixture design based on simplex-lattice (Design Expert 8.0.4 Stat-Ease Inc., Minneapolis, 2010). All the 10 oil blends were subjected to chemical interesterification (CIE) using sodium methoxide as the catalyst. The solid fat content (SFC), triacylglycerol (TAG) composition, thermal properties (DSC), polymorphism and microstructural properties were studied. Palm-based trans-free table margarine containing ternary mixture of PS/PKO/SBO [49/20/31 (w/w)], was optimally formulated through analysis of multiple isosolid diagrams and was found to have quite similar SMP and SFC profile as compared to the commercial table margarine. This study has shown chemical interesterification are effective in modifying the physicochemical properties of palm stearin, palm kernel oil, soybean oil and their mixtures. 23376408 Developing advanced X-ray scattering methods combined with crystallography and computation. The extensive use of small angle X-ray scattering (SAXS) over the last few years is rapidly providing new insights into protein interactions, complex formation and conformational states in solution. This SAXS methodology allows for detailed biophysical quantification of samples of interest. Initial analyses provide a judgment of sample quality, revealing the potential presence of aggregation, the overall extent of folding or disorder, the radius of gyration, maximum particle dimensions and oligomerization state. Structural characterizations include ab initio approaches from SAXS data alone, and when combined with previously determined crystal/NMR, atomistic modeling can further enhance structural solutions and assess validity. This combination can provide definitions of architectures, spatial organizations of protein domains within a complex, including those not determined by crystallography or NMR, as well as defining key conformational states of a protein interaction. SAXS is not generally constrained by macromolecule size, and the rapid collection of data in a 96-well plate format provides methods to screen sample conditions. This includes screening for co-factors, substrates, differing protein or nucleotide partners or small molecule inhibitors, to more fully characterize the variations within assembly states and key conformational changes. Such analyses may be useful for screening constructs and conditions to determine those most likely to promote crystal growth of a complex under study. Moreover, these high throughput structural determinations can be leveraged to define how polymorphisms affect assembly formations and activities. This is in addition to potentially providing architectural characterizations of complexes and interactions for systems biology-based research, and distinctions in assemblies and interactions in comparative genomics. Thus, SAXS combined with crystallography/NMR and computation provides a unique set of tools that should be considered as being part of one's repertoire of biophysical analyses, when conducting characterizations of protein and other macromolecular interactions. 23376412 A review on indole alkaloids isolated from Uncaria rhynchophylla and their pharmacological studies. Uncaria rhynchophylla (Miq.) Jacks, Rubiaceae, is one of the original plants of the important Chinese crude drug, Gou-teng, mainly used for the treatment of convulsion, hypertension, epilepsy, eclampsia, and cerebral diseases. The pharmacological activities of this plant are related to the presence of active compounds predominantly indole alkaloids. In this article, we have reviewed some reports about the pharmacological activities of the main indole alkaloids isolated from U. rhynchophylla. This review paper will contribute to the studies on the chemistry, safety and quality control of medicinal preparations containing Uncaria species. 23146766 Physiologically based toxicokinetics of serum aflatoxin B1-lysine adduct in F344 rats. Aflatoxin B(1)-lysine adduct (AFB-Lys) is a reliable biomarker for aflatoxin exposure; however, a systematic toxicokinetic evaluation has not been reported. In this study, male F344 rats were orally exposed to single, or repeated, doses of AFB(1) and the toxicokinetics of serum AFB-Lys that followed treatments were investigated. A single-dose of AFB(1) increased serum AFB-Lys levels rapidly peaking at 4h, followed by first-order elimination, through which the half-life was estimated to be 2.31 days. A physiologically based pharmacokinetic model showed that approximately 3.00-3.90% and 1.12-1.98% of the administered AFB(1) doses were converted to serum AFB-Lys adducts at 2h and 24h post treatment, respectively. Repeated AFB(1) exposure at 5-25 μg/kg body weight linearly increased serum AFB-Lys levels for 5 weeks in animals, resulting in a 1-1.5 times higher AFB-Lys level overall. This indicates the potential of this adduct as a reliable biomarker for repeated low dose exposure. Higher dose exposure at 75 μg/kg increased the level of AFB-Lys to a maximum at 2 weeks, followed by a gradual decrease to near plateau level up to 5 weeks. In conclusion, this study systematically evaluated the toxicokinetics of serum AFB-Lys adduct in F344 rats using a physiologically based pharmacokinetic model and robust statistical modeling analysis and provided a firm and clear understanding of the toxicokinetics of this biomarker. 23561213 Diversity of (dihydro) hydroxycinnamic acid conjugates in Colombian potato tubers. In potato tuber, caffeic acid (the predominant hydroxycinnamic acid (HCA)), its conjugates (HCAcs; i.e. chlorogenic acid (ChA), crypto-ChA, and neo-ChA), and anthocyanin-linked HCAs have been extensively described in the literature. In contrast, only little information is available on the occurrence of other HCAcs and didydrohydroxycinnamic acid conjugates (DHCAcs). Fifteen Colombian potato cultivars were screened for these less commonly described conjugates by reversed-phase ultrahigh performance liquid chromatography coupled to a diode array detector and a heated electrospray ionisation mass spectrometer. A total of 62 HCAs/HCAcs/DHCAcs were found in extracts from peel and flesh. Among them, only twelve compounds were common to all cultivars in both peel and flesh. The less commonly described compounds accounted for 7.1-20.1% w/w of the total amount of HCAs/HCAcs/DHCAcs in whole tubers, highlighting their contribution to the total phenolic profile of potato tubers. Among all cultivars, the abundance (mg/100g DW whole tuber) of neo-ChA (0.8-7.4) ranged in similar quantities as the less commonly reported feruloyl octopamine (1.2-5.2), 5-O-feruloyl quinic acid (0.1-7.5), cis-ChA (1.1-2.2), caffeoyl putrescine (0.6-2.5), sinapoyl hexose (0.1-1.8), N(1),N(14)-bis-(dihydrocaffeoyl) spermine (0.2-1.7), N(1),N(10)-bis-(dihydrocaffeoyl) spermidine (1.1-2.6), and N(1),N(5),N(14)-tris-(dihydrocaffeoyl) spermine (trace - 11.1). 23396094 Polycationic nanoparticles synthesized using ARGET ATRP for drug delivery. This work provides a systemic comparison for ARGET ATRP and UV-initiated polycationic nanoparticles for drug delivery and a guide to deciding which type of polycationic nanoparticles have the best properties for specific applications. Polycationic nanoparticles were synthesized using a previously developed UV-initiated photoemulsion polymerization or a newly developed ARGET ATRP synthesis technique. The effect of the ratio of hydrophobic monomer in the feed was evaluated. Increasing the feed ratio of hydrophobic monomer was necessary to maintain biocompatibility and pH-responsive membrane disruptive characteristics when switching from the UV-initiated polymerization to ARGET ATRP. The resulting polycationic nanoparticles have utility as drug delivery carriers for hydrophobic drugs and/or nucleic acids. 22385272 Chemical composition and antibacterial activity of the essential oil from Mentha requienii Bentham. The chemical composition of essential oil obtained by hydrodistillation of the fresh aerial parts of Mentha requienii Bentham (Lamiaceae) collected on the Gennargentu Mountains (Sardinia, Italy) has been investigated by gas chromatography and gas chromatography-mass spectrometry. The main constituents that resulted were pulegone (78%), menthone (0.5%), isomenthone (18%), isopulegone (1.3%) and limonene (1.76%). In vitro antifungal activity is evaluated in order to identify new means that could be helpful in the prevention of contamination in indoor environments. 23497908 Wine bottle colour and oxidative spoilage: whole bottle light exposure experiments under controlled and uncontrolled temperature conditions. Exposure of a Chardonnay wine to light from a mercury vapour lamp under controlled temperature conditions showed that colour enhancement was dependent on bottle colour. The increase in colouration was Antique Green42 h, and less within-patient day-to-day variability in glucose-lowering effect than the long-acting insulin analogue insulin glargine. In clinical trials, insulin degludec achieved similar glycaemic control to that seen with insulin glargine in patients with type 1 or 2 diabetes, but with a lower risk of nocturnal hypoglycaemia. In addition, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes show the potential for adjusting the injection time, without compromising glycaemic control or safety. A 200 U/mL formulation of insulin degludec is also available for use in patients who require large volumes of basal insulin. Insulin degludec/insulin aspart was noninferior to the long-acting insulin analogue insulin detemir in patients with type 1 diabetes and has the potential to reduce the number of daily injections. Trial results also indicate that insulin degludec/insulin aspart may be an appropriate option for initiating insulin therapy in patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs. Subcutaneous insulin degludec was generally well tolerated in patients with type 1 or 2 diabetes. In conclusion, insulin degludec and insulin degludec/insulin aspart represent a useful advance in the treatment of type 1 or 2 diabetes. 23425601 Biotransformation of ursolic acid by Syncephalastrum racemosum CGMCC 3.2500 and anti-HCV activity. Microbial transformation of ursolic acid (UA, 3β-hydroxy-urs-12-en-28-oic acid, 1) by filamentous fungus Syncephalastrum racemosum CGMCC 3.2500 was conducted. Five metabolites 3β, 7β, 21β-trihydroxy-urs-12-en-28-oic acid (2); 3β, 21β-dihydroxy-urs-11-en-28-oic acid-13-lactone (3); 1β, 3β, 21β-trihydroxy-urs-12-en-28-oic acid (4); 3β, 7β, 21β-trihydroxy-urs-1-en-28-oic acid-13-lactone (5); and 21-oxo-1β, 3β-dihydroxy-urs-12-en-28-oic acid (6) were afforded. Elucidation of the structures of these metabolites was primarily based on 1D and 2D NMR and HR-MS data. Metabolite 2 was a new compound. In addition, the anti-HCV activity of compounds 1-6 was evaluated. 23402847 Nano bioresearch approach by microtechnology. To progress in basic science and drug development, convenient methodology for detecting specific biological molecules and their interaction in living organism is in high demand. After more than 20 years of increasing research efforts, micro and nanotechnologies are now mature to propose a new class of miniature devices and principles enabling compartmentalized bioassays. Among them, this review proposes various examples that include array of electro-active microwells for highly parallel single cell analysis, cost-effective nanofluidic for DNA separation, parallel enzymatic reaction in 100pL droplet and high-throughput platform for membrane proteins assays. The micro devices are presented with relevant experiments to foresee their future contribution to translational research and drug discovery. 23343193 The dynamic nature of the kinome. Recent advances in proteomics have facilitated the analysis of the kinome 'en masse'. What these studies have revealed is a surprisingly dynamic network of kinase responses to highly selective kinase inhibitors, thereby illustrating the complex biological responses to these small molecules. Moreover these studies have identified key transcription factors, such as c-Myc and FOXO (forkhead box O), that play pivotal roles in kinome reprogramming in cancer cells. Since many kinase inhibitors fail despite a high efficacy of blocking their intended targets, elucidating kinome changes at a more global level will be essential to understanding the mechanisms of kinase inhibitor pharmacology. The development of technologies to study the kinome, as well as examples of kinome resilience and reprogramming, will be discussed in the present review. 23214979 3-Amido pyrrolopyrazine JAK kinase inhibitors: development of a JAK3 vs JAK1 selective inhibitor and evaluation in cellular and in vivo models. The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties. Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1-dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2-dependent IL-6 stimulated pathway. 23459147 Ninety-day dietary toxicity study of apple polyphenol extracts in Crl: CD (SD) rats. To examine the safety of Dietary Applephenon® (AP) in feed, Crl: CD (SD) rats of each sex were divided into four groups and given diets containing AP at 0%, 1.25%, 2.5%, or 5.0% for 90days. All rats survived and toxic changes were not observed throughout the study. Body weight and food efficiency in the 5.0% AP group of both sexes were significantly decreased compared with that in controls. These changes were considered to be caused by the physiological effects of AP (including the inhibitory effects on pancreatic lipase activity). Slight hypertrophy in acinar cells in the parotid and submandibular glands appeared in the 2.5% and 5.0% groups. These were suggested not to be toxicological but physiologic adaptive responses to oral stimuli by the lower pH of AP-containing diets. In conclusion, dietary AP in feed, up to a maximum level of 5.0% for 90days, given to rats did not induce toxicological effects. 23146694 Bisphenol A inhibits proliferation and induces apoptosis in micromass cultures of rat embryonic midbrain cells through the JNK, CREB and p53 signaling pathways. Bisphenol A (BPA) has been widely used in the manufacture of polycarbonate plastic, water bottles and food containers. Previous studies have established that BPA could cause developmental toxicity by inhibiting the proliferation and differentiation of rat embryonic midbrain (MB) cells in vitro. However, the underlying mechanisms have not been well studied yet. In the current study, we examined the proliferation and differentiation of MB cells treated with 10(-12)-10(-4)M BPA and found that only 10(-4)M BPA inhibited proliferation and differentiation. Then, we investigated the cell cycle progression and apoptosis of MB cells; 10(-4)M BPA caused an explicit S phase and G2/M phase arrest in the cell cycle and increased the percentage of apoptotic cells. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) and cyclic-AMP response binding protein (CREB) and the expression of some apoptotic regulatory genes were investigated. BPA (10(-4)M) reduced the phosphorylation of C-Jun N-terminal kinase (JNK) and CREB, and increased the mRNA expression level of Bax and p53. Our findings demonstrated that BPA could cause developmental toxicity through anti-proliferation and pro-apoptosis in MB cells. Multiple signaling pathways, such as the JNK, CREB and p53-mitochondrial apoptosis pathways, participate in these effects. 23561188 Antibacterial activity-guided purification and identification of a novel C-20 oxygenated ent-kaurane from Rabdosia serra (MAXIM.) HARA. The objective of this work was to conduct an activity-guided isolation of antibacterial compounds from Rabdosia serra. The ethanol extracts of R. serra leaf and stem were partitioned sequentially into petroleum ether, ethyl acetate, butanol and water fractions, respectively. The ethanol extract of leaf evidenced broad-spectrum antibacterial activity against Gram-positive bacterial, including Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, and Listeria monocytogenes. The ethyl acetate fractions of leaf and stem exhibited strong inhibition against Gram-positive bacteria, and were then purified further. On the basis of antibacterial assay-guided purification, three phenolic compounds (rosmarinic acid, methyl rosmarinate and pedalitin) and four C-20 oxygenated ent-kauranes (effusanin E, lasiodin, rabdosichuanin D and a new compound namely effusanin F) were obtained, whose contents were determined by HPLC analysis. The broth microdilution method confirmed the important inhibition potential of C-20 oxygenated ent-kauranes with low minimum inhibitory concentration (MIC) values. Effusanin E, lasiodin and effusanin F could be useful for the development of new antibacterial agents. 22972179 Energy depletion of bovine mammary epithelial cells activates AMPK and suppresses protein synthesis through inhibition of mTORC1 signaling. The molecular mechanisms by which cellular energy status regulates global protein synthesis in mammary epithelial cells have not been characterized. The objective of this study was to examine the effect of AMP-activated protein kinase (AMPK) activation by 2-deoxyglucose on protein synthesis and the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in bovine mammary epithelial cells. Phosphorylation of AMPK at Thr172 increased by 1.4-fold within 5 min, and remained elevated throughout a 30-min time course, in response to 2-deoxyglucose. Global rates of protein synthesis declined by 78% of control values. The decline in protein synthesis was associated with repression of mTORC1 signaling, as indicated by reduced phosphorylation of ribosomal protein S6 kinase 1 and eIF4E binding protein-1 (4E-BP1). Phosphorylation of ER-stress marker eIF2α was also increased but only at 30 min of 2-deoxyglucose exposure. 2-Deoxyglucose increased phosphorylation of tuberous sclerosis complex 2 (TSC2) on AMPK consensus sites but did not change the amount of TSC1 bound to TSC2. Activation of AMPK did not result in changes in the amount of raptor bound to mTOR. The inhibitory effects of AMPK activation on mTORC1 signaling were associated with a marked increase in Ser792 phosphorylation on raptor. Collectively, the results suggest that activation of AMPK represses global protein synthesis in mammary epithelial cells through inhibition of mTORC1 signaling. 23111887 Two cases of acute dexmedetomidine withdrawal syndrome following prolonged infusion in the intensive care unit: Report of cases and review of the literature. Prolonged infusion of dexmedetomidine, an α(2)-adrenoreceptor agonist anesthetic used in the intensive care unit, produces a withdrawal syndrome of sympathetic over-activity, characterized by tachycardia, hypertension and agitation, but there is no recommended standard treatment for this syndrome. We describe two patients with a clinical diagnosis of acute dexmedetomidine withdrawal and its management with oral clonidine. We utilized the principle of managing acute drug withdrawal with longer acting medications. These two cases demonstrated the benefit of using oral, longer acting clonidine to manage acute withdrawal from shorter-acting, intravenous dexmedetomidine. 22820275 Atomoxetine modulates spontaneous and sensory-evoked discharge of locus coeruleus noradrenergic neurons. Atomoxetine (ATM) is a potent norepinephrine (NE) uptake inhibitor and increases both NE and dopamine synaptic levels in prefrontal cortex, where it is thought to exert its beneficial effects on attention and impulsivity. At the behavioral level, ATM has been shown to cause improvements on the measures of executive functions, such as response inhibition, working memory and attentional set shifting across different species. However, the exact mechanism of action for ATM's effects on cognition is still not clear. One possible target for the cognitive enhancing effects of ATM is the noradrenergic locus coeruleus (LC), the only source of NE to key forebrain areas such as cerebral cortex and hippocampus. Although it is known that ATM increases NE availability overall by blocking reuptake of NE, the effects of this agent on impulse activity of LC neurons have not been reported. Here, the effect of ATM (0.1-1 mg/kg, ip) on NE-LC neurons was investigated by recording extracellular activity of LC neurons in isoflurane-anesthetized rats. ATM caused a significant decrease of the tonic activity of LC single-units, although leaving intact the sensory-evoked excitatory component of LC phasic response. Moreover, the magnitude of the inhibitory component of LC response to paw stimulation was increased after 1 mg/kg of ATM and its duration was prolonged at 0.3 mg/kg. Together, these effects of ATM produced an increase in the phasic-to-tonic ratio of LC phasic response to sensory stimulation. ATM also modulated the average sensory-evoked local field potential (LFP) and spike-field coherence in LC depending on the dose tested. The lower dose (0.1 mg/kg) significantly decreased early positive and negative components of the sensory-evoked LFP response. Higher doses (0.3-1 mg/kg) initially increased and then decreased the amplitude of components of the evoked fields, whereas the spike-field coherence was enhanced by 1 mg/kg ATM across frequency bands. Finally, coherence between LC fields and EEG signals was generally increased by 1 mg/kg ATM, whereas 0.1 and 0.3 mg/kg respectively decreased and increased coherence values in specific frequency bands. Taken together these results suggest that ATM effects on LC neuronal activity are dose-dependent, with different doses affecting different aspects of LC firing. This modulation of activity of LC-NE neurons may play a role in the cognitive effects of ATM. This article is part of a Special Issue entitled 'Cognitive Enhancers'. 23328126 Omega-3 Fatty acids reduce adipose tissue macrophages in human subjects with insulin resistance. Fish oils (FOs) have anti-inflammatory effects and lower serum triglycerides. This study examined adipose and muscle inflammatory markers after treatment of humans with FOs and measured the effects of ω-3 fatty acids on adipocytes and macrophages in vitro. Insulin-resistant, nondiabetic subjects were treated with Omega-3-Acid Ethyl Esters (4 g/day) or placebo for 12 weeks. Plasma macrophage chemoattractant protein 1 (MCP-1) levels were reduced by FO, but the levels of other cytokines were unchanged. The adipose (but not muscle) of FO-treated subjects demonstrated a decrease in macrophages, a decrease in MCP-1, and an increase in capillaries, and subjects with the most macrophages demonstrated the greatest response to treatment. Adipose and muscle ω-3 fatty acid content increased after treatment; however, there was no change in insulin sensitivity or adiponectin. In vitro, M1-polarized macrophages expressed high levels of MCP-1. The addition of ω-3 fatty acids reduced MCP-1 expression with no effect on TNF-α. In addition, ω-3 fatty acids suppressed the upregulation of adipocyte MCP-1 that occurred when adipocytes were cocultured with macrophages. Thus, FO reduced adipose macrophages, increased capillaries, and reduced MCP-1 expression in insulin-resistant humans and in macrophages and adipocytes in vitro; however, there was no measureable effect on insulin sensitivity. 23473802 The insecticidal neurotoxin Aps III is an atypical knottin peptide that potently blocks insect voltage-gated sodium channels. One of the most potent insecticidal venom peptides described to date is Aps III from the venom of the trapdoor spider Apomastus schlingeri. Aps III is highly neurotoxic to lepidopteran crop pests, making it a promising candidate for bioinsecticide development. However, its disulfide-connectivity, three-dimensional structure, and mode of action have not been determined. Here we show that recombinant Aps III (rAps III) is an atypical knottin peptide; three of the disulfide bridges form a classical inhibitor cystine knot motif while the fourth disulfide acts as a molecular staple that restricts the flexibility of an unusually large β hairpin loop that often houses the pharmacophore in this class of toxins. We demonstrate that the irreversible paralysis induced in insects by rAps III results from a potent block of insect voltage-gated sodium channels. Channel block by rAps III is voltage-independent insofar as it occurs without significant alteration in the voltage-dependence of channel activation or steady-state inactivation. Thus, rAps III appears to be a pore blocker that plugs the outer vestibule of insect voltage-gated sodium channels. This mechanism of action contrasts strikingly with virtually all other sodium channel modulators isolated from spider venoms that act as gating modifiers by interacting with one or more of the four voltage-sensing domains of the channel. 23411184 Multi-class method for determination of veterinary drug residues and other contaminants in infant formula by ultra performance liquid chromatography-tandem mass spectrometry. A rapid, simple and generic analytical method which was able to simultaneously determine 220 undesirable chemical residues in infant formula had been developed. The method comprised of extraction with acetonitrile, clean-up by low temperature and water precipitation, and analysis by ultra performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS-MS) using multiple reaction monitoring (MRM) mode. Most fat materials in acetonitrile extract were eliminated by low temperature clean-up. The water precipitation, providing a necessary and supplementary cleanup, could avoid losses of hydrophobic analytes (avermectins, ionophores). Average recoveries for spiked infant formula were in the range from 57% to 147% with associated RSD values between 1% and 28%. For over 80% of the analytes, the recoveries were between 70% and 120% with RSD values in the range of 1-15%. The limits of quantification (LOQs) were from 0.01 to 5 μg/kg, which were usually sufficient to verify the compliance of products with legal tolerances. Application of this method in routine monitoring programs would imply a drastic reduction of both effort and time. 23402855 Anti-inflammatory activity of edible brown alga Saccharina japonica and its constituents pheophorbide a and pheophytin a in LPS-stimulated RAW 264.7 macrophage cells. Anti-inflammatory activity of Saccharina japonica and its active components was evaluated via in vitro inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression in RAW 264.7 murine macrophage cells. Since the methanolic extract of S. japonica showed strong anti-inflammatory activity, it was fractionated with several solvents. Among the fractions, the ethyl acetate fraction demonstrated the highest inhibition of LPS-induced NO production (IC50=25.32μg/mL), followed by the CH2Cl2 fraction (IC50=75.86μg/mL). Considering the yield and anti-inflammatory potential together, the CH2Cl2 fraction was selected for chromatographic separation to yield two active porphyrin derivatives, pheophorbide a and pheophytin a, together with an inactive fucoxanthin. In contrast to fucoxanthin, pheophorbide a and pheophytin a showed dose-dependent inhibition against LPS-induced NO production at nontoxic concentrations in RAW 264.7 cells. Both compounds also suppressed the expression of iNOS proteins, while they did not inhibit the COX-2 expression in LPS-stimulated macrophages. These results indicate that pheophorbide a and pheophytin a are two important candidates of S. japonica as anti-inflammatory agents which can inhibit the production of NO via inhibition of iNOS protein expression. Thus, these compounds hold great promise for use in the treatment of various inflammatory diseases. 23164615 Differential modulation of retinal ganglion cell light responses by orthosteric and allosteric metabotropic glutamate receptor 8 compounds. To investigate the role of mGluR8 in modulating the synaptic responses of retinal ganglion cells, we used a recently identified positive allosteric modulator of mGluR8, AZ12216052 (AZ) and the mGluR8-specific orthosteric agonist (S)-3,4-dicarboxyphenylglycine (DCPG). These agents were applied to whole-cell voltage-clamped ganglion cells from an isolated, superfused mouse retina preparation. DCPG reduced OFF-ganglion cell excitatory currents, whereas AZ enhanced the peak excitatory currents in ON-, OFF-, and ON-OFF-ganglion cells. The effects on ganglion cell inhibitory currents were more varied. The effects of the allosteric modulator were stronger for bright stimuli than for dim stimuli, consistent with receptor stimulation by endogenous glutamate being stronger during bright light stimulation and with mGluR8 receptors mainly being localized away from glutamate release sites, immuno-labeled with VGLUT1. The differential sensitivity of ganglion cell light responses to DCPG and AZ supports multiple sites where mGluR8 modulates the light responses of ganglion cells. 23603193 Anti-epileptogenic and antioxidant effect of Lavandula officinalis aerial part extract against pentylenetetrazol-induced kindling in male mice. ETHNOPHARMACOLOGICAL RELEVANCE: Repeated application of Lavandula officinalis (L. officinalis) has been recommended for a long time in Iranian traditional medicine for some of nervous disorders like epilepsy and dementia. However, there is no available report for the effect of chronic administration of Lavandula extract in development (acquisition) of epilepsy. Therefore, this study was designed to investigate the anti-epileptogenic and antioxidant activity of repeated administration of Lavandula officinalis extract on pentylenetetrazol (PTZ) kindling seizures in mice model. MATERIALS AND METHODS: Lavandula officinalis was tested for its ability (i) to suppress the seizure intensity and lethal effects of PTZ in kindled mice (anti-epileptogenic effect), (ii) to attenuate the PTZ-induced oxidative injury in the brain tissue (antioxidant effect) when given as a pretreatment prior to each PTZ injection during kindling development. Valproate (Val), a major antiepileptic drug, was also tested for comparison. RESULTS: Val and Lavandula officinalis extract showed anti-epileptogenic properties as they reduced seizure score of kindled mice and PTZ-induced mortality. In this regard, Lavandula officinalis was more effective than Val. Both Lavandula officinalis and Val suppressed brain nitric oxide (NO) level of kindled mice in comparison with the control and PTZ group. Meanwhile, Lavandula officinalis suppressed NO level more than Val and Lavandula officinalis also decreased brain MDA level relative to PTZ group. CONCLUSION: This is the first report to demonstrate NO suppressing and anti-epileptogenic effect of chronic administration of Lavandula officinalis extract on acquisition of epilepsy in PTZ kindling mice model. In this regard, Lavandula officinalis extract was more effective than Val, possibly and in part via brain NO suppression. 23090968 A-kinase-anchoring protein-Lbc anchors IκB kinase β to support interleukin-6-mediated cardiomyocyte hypertrophy. In response to stress, the heart undergoes a pathological remodeling process associated with hypertrophy and the reexpression of a fetal gene program that ultimately causes cardiac dysfunction and heart failure. In this study, we show that A-kinase-anchoring protein (AKAP)-Lbc and the inhibitor of NF-κB kinase subunit β (IKKβ) form a transduction complex in cardiomyocytes that controls the production of proinflammatory cytokines mediating cardiomyocyte hypertrophy. In particular, we can show that activation of IKKβ within the AKAP-Lbc complex promotes NF-κB-dependent production of interleukin-6 (IL-6), which in turn enhances fetal gene expression and cardiomyocyte growth. These findings provide a new mechanistic hypothesis explaining how hypertrophic signals are coordinated and conveyed to interleukin-mediated transcriptional reprogramming events in cardiomyocytes. 23360548 Toward large-scale energy harvesting by a nanoparticle-enhanced triboelectric nanogenerator. This article describes a simple, cost-effective, and scalable approach to fabricate a triboelectric nanogenerator (NG) with ultrahigh electric output. Triggered by commonly available ambient mechanical energy such as human footfalls, a NG with size smaller than a human palm can generate maximum short-circuit current of 2 mA, delivering instantaneous power output of 1.2 W to external load. The power output corresponds to an area power density of 313 W/m(2) and a volume power density of 54,268 W/m(3) at an open-circuit voltage of ~1200 V. An energy conversion efficiency of 14.9% has been achieved. The power was capable of instantaneously lighting up as many as 600 multicolor commercial LED bulbs. The record high power output for the NG is attributed to optimized structure, proper materials selection and nanoscale surface modification. This work demonstrated the practicability of using NG to harvest large-scale mechanical energy, such as footsteps, rolling wheels, wind power, and ocean waves. 23517565 N-Methyldihydroquinazolinone Derivatives of Retro-2 with Enhanced Efficacy against Shiga Toxin. The Retro-2 molecule protects cells against Shiga toxins by specifically blocking retrograde transport from early endosomes to the trans-Golgi network. A SAR study has been carried out to identify more potent compounds. Cyclization and modifications of Retro-2 led to a compound with roughly 100-fold improvement of the EC50 against Shiga toxin cytotoxicity measured in a cell protein synthesis assay. We also demonstrated that only one enantiomer of the dihydroquinazolinone reported herein is bioactive. 23496305 Obstructed Diffusion in Silica Colloidal Crystals. The hindered diffusion in silica colloidal crystals was studied experimentally, both by fluorescence recovery after photobleaching and by measurement of ionic conductivity. Particle size was varied to include 120, 220, 470, and 1300 nm, and the porosities were determined by flow measurements. For fluorescein, the results showed that the obstruction factor, which is the ratio of the diffusion coefficients inside the media and in open solution, is equal to the porosity within experimental error. For proteins, the same conclusion is made after correction for size exclusion of the pores. The obstruction factors for these media are 2-fold lower than those measured for chromatographic media, 60% higher than theoretical predictions, and equal to what is assumed for electrophoretic sieving in random fibers. 23170954 Getting in shape: controlling peptide bioactivity and bioavailability using conformational constraints. Chemical biologists commonly seek out correlations between the physicochemical properties of molecules and their behavior in biological systems. However, a new paradigm is emerging for peptides in which conformation is recognized as the primary determinant of bioactivity and bioavailability. This review highlights an emerging body of work that directly addresses how a peptide's conformation controls its biological effects, cell penetration, and intestinal absorption. Based on this work, the dream of mimicking the potency and bioavailability of natural product peptides is getting closer to reality. 23122066 Lipid components prepared from a freshwater Clam (Corbicula fluminea) extract ameliorate hypercholesterolaemia in rats fed high-cholesterol diet. To explore the hypocholesterolaemic components in the fat fraction of freshwater clam extract (FCE), we further fractionated the fat fraction by silica gel column chromatography into nine fat subfractions. In the present study, we used exogenous hypercholesterolaemic rats induced by feeding a high-cholesterol diet; the doses of the added fat subfractions were equivalent to those in 30% FCE. Two (FF1, FF2) out of the nine fat subfractions strongly reduced serum cholesterol levels in the rats fed a high-cholesterol diet. Both FF1 and FF2 up-regulated the hepatic gene expression of cholesterol 7α-hydroxylase, a rate-limiting enzyme of bile acid biosynthesis. Thin-layer chromatography showed that FF1 primarily contained sphingolipids, while FF2 mainly contained triacylglycerols and sterol esters. These results indicate that fractions containing sphingolipids, triacylglycerols, and sterol esters are possibly responsible for the hypocholesterolaemic action in a novel manner through the up-regulation of the hepatic biosynthesis of bile acids. 23397049 A prospective open-label trial of paliperidone monotherapy for the treatment of bipolar spectrum disorders in children and adolescents. RATIONALE: Treatment studies for the management of pediatric bipolar disorder are limited. OBJECTIVES: This study evaluates the safety and efficacy of paliperidone monotherapy as an acute treatment of mania and related symptoms in youth with bipolar spectrum disorders. METHODS: An 8-week, prospective, open-label paliperidone monotherapy trial to assess effectiveness and tolerability in treating pediatric bipolar spectrum and related disorders (depression, psychosis, attention-deficit/hyperactivity disorder [ADHD]). Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impression scale (CGI), Children's Depression Rating Scale-Revised (CDRS-R), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs, weight monitoring, and laboratory analysis. RESULTS: Fifteen youth with bipolar spectrum disorders (YMRS at entry: 32.8 ± 6.1) were enrolled in the study and 11 (73 %) completed the 8-week trial. The total daily dose of paliperidone at study endpoint was 3 mg in 12 subjects and 6 mg in three subjects. Treatment with paliperidone was associated with statistically significant levels of improvement in mean YMRS scores (-18.7 ± 13.9, p < 0.001) at endpoint. Paliperidone treatment also resulted in significant improvement in the severity of ADHD and psychotic symptoms. Although treatment with paliperidone was generally well tolerated and was not associated with clinically significant change in cardiovascular or metabolic parameters, increases in body weight (4.1 ± 5.5 lb) were substantial. CONCLUSIONS: Open-label paliperidone treatment appears to be beneficial in the treatment of bipolar spectrum disorders and associated conditions in youth. Future placebo-controlled studies are warranted to confirm these findings. 23499945 Complex genomic interactions in the dynamic regulation of transcription by the glucocorticoid receptor. The glucocorticoid receptor regulates transcriptional output through complex interactions with the genome. These events require continuous remodeling of chromatin, interactions of the glucocorticoid receptor with chaperones and other accessory factors, and recycling of the receptor by the proteasome. Therefore, the cohort of factors expressed in a particular cell type can determine the physiological outcome upon treatment with glucocorticoid hormones. In addition, circadian and ultradian cycling of hormones can also affect GR response. Here we will discuss revision of the classical static model of GR binding to response elements to incorporate recent findings from single cell and genome-wide analyses of GR regulation. We will highlight how these studies have changed our views on the dynamics of GR recruitment and its modulation of gene expression. 22926048 A bioactive probe of the oxidative pentose phosphate cycle: novel strategy to reverse radioresistance in glucose deprived human colon cancer cells. The specific effects of glucose deprivation on oxidative pentose phosphate cycle (OPPC) function, thiol homeostasis, protein function and cell survival remain unclear due to lack of a glucose-sensitive chemical probe. Using p53 wild type and mutant human colon cells, we determined the effects of hydroxyethyl disulfide (HEDS) on NADPH, GSH, GSSG, total glutathione, total non-protein and protein thiol levels, the function of the DNA repair protein Ku, and the susceptibility to radiation-induced free radicals under normal glucose or glucose-deprived conditions. HEDS is rapidly detoxified in normal glucose but triggered a p53-independent metabolic stress in glucose depleted state that caused loss of NADPH, protein and non-protein thiol homeostasis and Ku function, and enhanced sensitivity of both p53 wild type and mutant cells to radiation induced oxidative stress. Additionally, high concentration of HEDS alone induced cell death in p53 wild type cells without significant effect on p53 mutant cells. HEDS offers a useful tool to gain insights into how glucose metabolism affects OPPC dependent stress-induced cellular functions and injury, including in tumor cells, where our findings imply a novel therapeutic approach to target glucose deprived tumor. Our work introduces a novel probe to address cancer metabolism and ischemic pathology. 23614643 Dimerized Glycosaminoglycan Chains Increase FGF Signaling during Zebrafish Development. Proteoglycans (PGs) modulate numerous signaling pathways during development through binding of their glycosaminoglycan (GAG) side chains to various signaling molecules, including fibroblast growth factors (FGFs). A majority of PGs possess two or more GAG side chains, suggesting that GAG multivalency is imperative for biological functions in vivo. However, only a few studies have examined the biological significance of GAG multivalency. In this report, we utilized a library of bis- and tris-xylosides that produce two and three GAG chains on the same scaffold, respectively, thus mimicking PGs, to examine the importance of GAG valency and chain type in regulating FGF/FGFR interactions in vivo in zebrafish. A number of bis- and tris-xylosides, but not mono-xylosides, caused an elongation phenotype upon their injection into embryos. In situ hybridization showed that elongated embryos have elevated expression of the FGF target gene mkp3 but unchanged expression of reporters for other pathways, indicating that FGF/FGFR signaling was specifically hyperactivated. In support of this observation, elongation can be reversed by the tyrosine kinase inhibitor SU5402, mRNA for the FGFR antagonist sprouty4, or FGF8 morpholino. Endogenous GAGs seem to be unaffected after xyloside treatment, suggesting that this is a gain-of-function phenotype. Furthermore, expression of a multivalent but not a monovalent GAG containing syndecan-1 proteoglycan recapitulates the elongation phenotype observed with the bivalent xylosides. On the basis of these in vivo findings, we propose a new model for GAG/FGF/FGFR interactions in which dimerized GAG chains can activate FGF-mediated signal transduction pathways. 23194512 Podocarpane, isopimarane, and abietane diterpenoids from Isodon lophanthoides var. graciliflorus. Four new diterpenoids including two podocarpanes, graciliflorins A (1) and B (2), an isopimarane acetal, graciliflorin C (3), and a rearranged abietane, graciliflorin D (4) were isolated from the aerial parts of Isodon lophanthoides var. graciliflorus (Lamiaceae) along with podocarpa-8,11,13-triene-3α,13-diol (5) and micranthin B (6). Their structures were elucidated based on the spectroscopic data. The in vitro cytotoxicity of compounds 1-4 and 6 against human carcinoma A549, MCF-7, and HeLa cell lines were evaluated using the MTT colourimetric assay. Micranthin B (6) showed moderate activity against all the cells with IC(50) values of 16.29, 18.20, and 22.25 μM, while compounds 1-4 were inactive (IC(50)>50 μg/ml). 23183532 Intestinal luminal nitrogen metabolism: role of the gut microbiota and consequences for the host. Alimentary and endogenous proteins are mixed in the small intestinal lumen with the microbiota. Although experimental evidences suggest that the intestinal microbiota is able to incorporate and degrade some of the available amino acids, it appears that the microbiota is also able to synthesize amino acids raising the view that amino acid exchange between the microbiota and host can proceed in both directions. Although the net result of such exchanges remains to be determined, it is likely that a significant part of the amino acids recovered from the alimentary proteins are used by the microbiota. In the large intestine, where the density of bacteria is much higher than in the small intestine and the transit time much longer, the residual undigested luminal proteins and peptides can be degraded in amino acids by the microbiota. These amino acids cannot be absorbed to a significant extent by the colonic epithelium, but are precursors for the synthesis of numerous metabolic end products in reactions made by the microbiota. Among these products, some like short-chain fatty acids and organic acids are energy substrates for the colonic mucosa and several peripheral tissues while others like sulfide and ammonia can affect the energy metabolism of colonic epithelial cells. More work is needed to clarify the overall effects of the intestinal microbiota on nitrogenous compound metabolism and consequences on gut and more generally host health. 23479194 Antibacterial substances from Albizia myriophylla wood against cariogenic Streptococcus mutans. Albizia myriophylla has been used for long by Thai traditional healers as an important ingredient herb in Thai herbal formulas for caries. In this study, three flavonoids lupinifolin (6), 8-methoxy-7,3',4'-trihydroxyflavone (7), and 7,8,3',4'-tetrahydroxyflavone (8), a triterpenoid lupeol (3) as well as four sterols β-sitosterone (1), stigmasta-5,22-dien-3-one (2), β-sitosterol (4), and stigmasterol (5) were isolated from A. myriophylla wood. The antibacterial activity of these compounds against Streptococcus mutans ATCC 25175 was performed using broth microdilution method. All compounds exhibited antibacterial activity against S. mutans with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) ranging from 1-256 and 2-256 μg/ml, respectively. Among the isolated compounds, lupinifolin (6) was found to be the most potent with MIC and MBC of 1 and 2 μg/ml, respectively. Lupinifolin (6) also showed a strong activity against ten clinical isolates of S. mutans with MIC and MBC ranging from 0.25-2 and 0.5-8 μg/ml, respectively. These results reported the bioactive ingredients of A. myriophylla which support its ethnomedical claims as well. Lupinifolin (6) may have a potential to be a natural anticariogenic agent. 22728231 Transfer of a two-tiered keratinocyte assay: IL-18 production by NCTC2544 to determine the skin sensitizing capacity and epidermal equivalent assay to determine sensitizer potency. At present, the identification of potentially sensitizing chemicals is carried out using animal models. However, it is very important from ethical, safety and economic point of view to have biological markers to discriminate allergy and irritation events, and to be able to classify sensitizers according to their potency, without the use of animals. Within the Sens-it-iv EU Frame Programme 6 funded Integrated Project (LSHB-CT-2005-018681), a number of in vitro, human cell based assays were developed which, when optimized and used in an integrated testing strategy, may be able to distinguish sensitizers from non-sensitizers. This study describes two of these assays, which when used in a tiered strategy, may be able to identify contact sensitizers and also to quantify sensitizer potency. Tier 1 is the human keratinocyte NCTC2544 IL-18 assay and tier 2 is the Epidermal Equivalent potency assay. The aim of this study is to show the transferability of the two-tiered approach with training chemicals: 3 sensitizers (DNCB, resorcinol, pPD) and 1 non sensitizer (lactic acid) in tier 1 and 2 sensitizers with different potency in tier 2 (DNCB; extreme and resorcinol; moderate). The chemicals were tested in a non-coded fashion. Here we describe the transferability to naïve laboratories, the establishment of the standard operating procedure, critical points, acceptance criteria and project management. Both assays were successfully transferred to laboratories that had not performed the assays previously. The two tiered approach may offer an unique opportunity to provide an alternative method to the Local Lymph Node Assay (LLNA). These assays are both based on the use of human keratinocytes, which have been shown over the last two decades, to play a key role in all phases of skin sensitization. 23293950 Luminescence enhancement of pyrene/dispersant nanoarrays driven by the nanoscale spatial effect on mixing. This work presents a simple method to generate ordered chromophore/dispersant nanoarrays through a pore-filling process for a nanoporous polymer template to enhance chromophore luminescence. Fluorescence results combining with the morphological evolution examined by scanning probe microscopy reveal that the enhanced luminescence intensity reaches the maximum intensity as the nanopores of the template are completely filled by the chromophore/dispersant mixture. The variation is attributed to nanoscale spatial effect on the enhanced mixing efficiency of chromophore and dispersant, that is, the alleviation of self-quenching problem, as evidenced by the results of attenuated total reflection Fourier transform IR spectroscopy combining with grazing incident wide-angle X-ray diffraction. The enhanced luminescence of the chromophore/dispersant nanoarrays driven by the nanoscale spatial effect is highly promising for use in designing luminescent nanodevices. 23640471 Free volume in ionic liquids: a connection of experimentally accessible observables from PALS and PVT experiments with the molecular structure from XRD data. In the current work, free volume concepts, primarily applied to glass formers in the literature, were transferred to ionic liquids (ILs). A series of 1-butyl-3-methylimidazolium ([C4MIM](+)) based ILs was investigated by Positron Annihilation Lifetime Spectroscopy (PALS). The phase transition and dynamic properties of the ILs [C4MIM][X] with [X](-) = [Cl](-), [BF4](-), [PF6](-), [OTf](-), [NTf2](-) and [B(hfip)4](-) were reported recently (Yu et al., Phys. Chem. Chem. Phys., 2012, 14, 6856-6868). In this subsequent work, attention was paid to the connection of the free volume from PALS (here the mean hole volume, 〈vh〉) with the molecular structure, represented by volumes derived from X-ray diffraction (XRD) data. These were the scaled molecular volume Vm,scaled and the van der Waals volume Vvdw. Linear correlations of 〈vh〉 at the "knee" temperature (〈vh〉(Tk)) with Vm,scaled and Vvdw gave good results for the [C4MIM](+) series. Further relationships between volumes from XRD data with the occupied volume Vocc determined from PALS/PVT (Pressure Volume Temperature) measurements and from Sanchez-Lacombe Equation of State (SL-EOS) fits were elaborated (Vocc(SL-EOS) ≈ 1.63 Vvdw, R(2) = 0.981 and Vocc(SL-EOS) ≈ 1.12 Vm,scaled, R(2) = 0.980). Finally, the usability of Vm,scaled was justified in terms of the Cohen-Turnbull (CT) free volume theory. Empirical CT type plots of viscosity and electrical conductivity showed a systematic increase in the critical free volume with molecular size. Such correlations allow descriptions of IL properties with the easily accessible quantity Vm,scaled within the context of the free volume. 23479390 Peltogynoids and 2-Phenoxychromones from Peltophorum pterocarpum and Evaluation of Their Estrogenic Activity. Phytochemical investigation of the dichloromethane extract of the leaves of Peltophorum pterocarpum, a tropical ornamental tree, led to the isolation of twelve compounds (1-12). One new derivative of peltogynoid ophioglonin (1) and a new 2-phenoxychromone (2) with its 3'-O-β-D-glucoside derivative (3) are described here for the first time. In addition, nine flavonoid derivatives, including peltogynoid ophioglonin (4), were isolated for the first time from this plant. The structures were determined by spectroscopic and chemical methods. Evaluation of the estrogenic activities of 1, 2, and 4 using different model cell systems revealed that 4 was estrogenic and that 2 was largely inactive. Interestingly, 1 was unable to stimulate the proliferation of breast and endometrial cancer cells but exhibited substantial estrogen receptor α-mediated activation of gene expression. This observation indicates that 1 can be further evaluated for its cancer chemopreventive potential. 23608699 Effects of 17α-ethinylestradiol (EE2) on reproductive endocrine status in mummichog (Fundulus heteroclitus) under differing salinity and temperature conditions. Exposure to 17α-ethinylestradiol (EE2), a synthetic estrogen, has previously been shown to decrease reproductive endocrine status and egg production in northern mummichog (Fundulus heteroclitus macrolepidotus). The objective of this study was to evaluate if variations in salinity or temperature conditions of EE2-exposed mummichog modify the effect on whole organism reproductive endocrine status and gonadal steroidogenesis. Mummichog were exposed in vivo for 14 days to 0, 50 and 250ng/L EE2 in 0, 16 and 32ppt salinity at 18°C and to 0 and 250ng/L EE2 at 10, 18 and 26°C at 16ppt. There was a little overall effect of salinity on measured endpoints. In the salinity exposure, 250ng/L EE2-exposed females had significantly reduced 17β-estradiol (E2) levels. Increased temperature triggered gonadal growth in both sexes and increased plasma E2 and E2 production and decreased 11-KT (11-ketotestosterone) production. EE2 counteracted the effect of temperature by depressing gonadal growth in males. In both exposures, EE2 effects on testosterone (T) production were variable. The use of steroidogenic precursors (25-OH-cholesterol, and/or pregnenolone and/or testosterone) in the in vitro gonadal incubations indicated decreased E2 production in females and 11-KT production in males were predominately due to suppression of the terminal conversion step between T and E2 or 11-KT. Ovarian aromatase A (cyp19a) gene expression at 16ppt and 18°C was not affected by 250ng/L EE2 (the only treatment combinations tested). Overall, temperature is a factor regulating northern mummichog reproduction; EE2 overrides its effects and disrupts the terminal step of steroidogenesis. Our results should be considered in designing future estuarine fish bioassays and in understanding effects of estrogenic endocrine disruptors in estuaries. 23452219 Computational design and biosensor applications of small molecule-sensing allosteric ribozymes. Here I describe accurate and time-efficient computational methods for designing small molecule-sensing allosteric ribozymes that serve as logic gates with NOT or YES Boolean logic functions. Theophylline-sensing ribozymes are engineered to have a high cleavage rate of 1.3 min(-1) under physiologically relevant conditions. They are highly specific to theophylline and do not respond to caffeine, which differs in a single methyl group. These ribozymes are designed by fusing a theophylline aptamer with an extended version of the hammerhead ribozyme by modeling secondary structures. Purine-sensing ribozymes are designed by fusing the minimal version of the hammerhead ribozyme with bacterial guanine or adenine aptamers by modeling 3D interactions. I have developed high-throughput compatible arrays based on purine RNA sensors that can be used for antibacterial drug discovery. The ribozymes can be employed as molecular sensors in various applications, including exogenous control of gene expression, high-throughput screening arrays, and molecular computing. 23305294 Anomalous high ionic conductivity of nanoporous β-Li3PS4. Lithium-ion-conducting solid electrolytes hold promise for enabling high-energy battery chemistries and circumventing safety issues of conventional lithium batteries. Achieving the combination of high ionic conductivity and a broad electrochemical window in solid electrolytes is a grand challenge for the synthesis of battery materials. Herein we show an enhancement of the room-temperature lithium-ion conductivity by 3 orders of magnitude through the creation of nanostructured Li(3)PS(4). This material has a wide electrochemical window (5 V) and superior chemical stability against lithium metal. The nanoporous structure of Li(3)PS(4) reconciles two vital effects that enhance the ionic conductivity: (1) the reduction of the dimensions to a nanometer-sized framework stabilizes the high-conduction β phase that occurs at elevated temperatures, and (2) the high surface-to-bulk ratio of nanoporous β-Li(3)PS(4) promotes surface conduction. Manipulating the ionic conductivity of solid electrolytes has far-reaching implications for materials design and synthesis in a broad range of applications, including batteries, fuel cells, sensors, photovoltaic systems, and so forth. 23422263 Investigation of the cumulative body burden of estrogen-3,4-quinone in breast cancer patients and controls using albumin adducts as biomarkers. Both 17β-estradiol-2,3-quinone (E2-2,3-Q) and 17β-estradiol-3,4-quinone (E2-3,4-Q) are reactive metabolites of estrogen. Elevation of E2-3,4-Q to E2-2,3-Q ratio is thought to be an important indicator of estrogen-induced carcinogenesis. Our current study compared the cumulative body burden of these estrogen quinones in serum samples taken from Taiwanese women with breast cancer (n=152) vs healthy controls (n=75) by using albumin (Alb) adducts as biomarkers. Results clearly demonstrated the presence of cysteinyl adducts of E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb in all study population at levels ranging from 61.7-1330 to 66.6-1,590 pmol/g, respectively. Correlation coefficient between E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb was 0.610 for controls and 0.767 for breast cancer patients (p<0.001). We also noticed that in premenopausal subjects with body mass index (BMI) less than 27, background levels of E2-3,4-Q-2-S-Alb was inversely proportional to BMI with about 25% increase in E2-3,4-Q-2-S-Alb per 5 kg/m(2) decrease in BMI (p<0.001). In addition, we confirmed that mean levels of E2-3,4-Q-2-S-Alb in breast cancer patients were ∼5-fold greater than in those of controls (p<0.001). Overall, this evidence suggests that disparity in estrogen disposition and the subsequent elevation of cumulative body burden of E2-3,4-Q may play a role in the development of breast cancer. 23499664 Levomilnacipran (F2695), a norepinephrine-preferring SNRI: Profile in vitro and in models of depression and anxiety. Levomilnacipran (LVM; F2695) is the more active enantiomer of the serotonin/norepinephrine (5-HT/NE) reuptake inhibitor (SNRI) milnacipran and is currently under development for the treatment of major depressive disorder. LVM was benchmarked against two other SNRIs, duloxetine and venlafaxine, in biochemical, neurochemical and pharmacological assays. LVM exhibited high affinity for human NE (Ki = 92.2 nM) and 5-HT (11.2 nM) transporters, and potently inhibited NE (IC50 = 10.5 nM) and 5-HT (19.0 nM) reuptake (human transporter) in vitro. LVM had 2-fold greater potency for norepinephrine relative to serotonin reuptake inhibition (i.e. NE/5-HT potency ratio: 0.6) and 17 and 27 times higher selectivity for NE reuptake inhibition compared with venlafaxine and duloxetine, respectively. LVM did not exhibit affinity for 23 off-target receptors. LVM (i.p.) increased cortical extracellular levels of 5-HT, and NE (minimal effective doses: MEDs = 20 and 10 mg/kg, respectively). In anti-depressive/anti-stress models, i.p. LVM diminished immobility time in the mouse forced swim (MED = 20 mg/kg) and tail suspension (MED = 2.5 mg/kg) tests, and reduced shock-induced ultrasonic vocalizations in rats (MED = 5 mg/kg). Duloxetine and venlafaxine were less potent (MEDs ≥ 10 mg/kg). At doses active in these three therapeutically-relevant models, LVM (i.p.) did not significantly affect spontaneous locomotor activity. In summary, LVM is a potent, selective inhibitor of NE and 5-HT transporters with preferential activity at the former. It is efficacious in models of anti-depressive/anti-stress activity, with minimal potential for locomotor side effects. 23610086 Reactive Metabolite Trapping Studies on Imidazo- and 2-Methylimidazo[2,1-b]thiazole-based Inverse Agonists of the Ghrelin Receptor. The current study examined the bioactivation potential of ghrelin receptor inverse agonists, 1-(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(imidazo[2,1-b]thiazol-6-yl)ethanone (1) and 1-(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(2-methylimidazo[2,1-b]thiazol-6-yl)ethanone (2), containing a fused imidazo[2,1-b]thiazole motif in the core structure. Both compounds underwent oxidative metabolism in NADPH- and glutathione-supplemented human liver microsomes to yield glutathione conjugates, which was consistent with their bioactivation to reactive species. Mass spectral fragmentation and NMR analysis indicated that the site of attachment of the glutathionyl moiety in the thiol conjugates was on the thiazole ring within the bicycle. Two glutathione conjugates were discerned with the imidazo[2,1-b]thiazole derivative 1. One adduct was derived from the Michael addition of glutathione to a putative S-oxide metabolite of 1, whereas, the second adduct was formed via the reaction of a second glutathione molecule with the initial glutathione-S-oxide adduct. In the case of the 2-methylimidazo[2,1-b]thiazole analog 2, glutathione conjugation occurred via an oxidative desulfation mechanism, possibly involving thiazole ring epoxidation as the rate-limiting step. Additional insights into the mechanism were obtained via 18O exchange and trapping studies with potassium cyanide. The mechanistic insights into the bioactivation pathways of 1 and 2 allowed the deployment of a rational chemical intervention strategy that involved replacement of the thiazole ring with a 1,2,4-thiadiazole group to yield -(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)ethanone (3). These structural changes not only abrogated the bioactivation liability but also retained the attractive pharmacological attributes of the prototype agents. 23111883 Toxicity of cadmium and protective effect of bee honey, vitamins C and B complex. The present work aimed to study the toxic effect of cadmium (Cd) on rabbits' blood indices, as well as the therapeutic effect of the antioxidant agents, vitamins C and B complex and bee honey on Cd intoxicated rabbits. Cadmium chloride (CdCl2) was injected subcutaneously at a dose of 3 mg/kg of body weight. The results showed a significant increase in serum glucose, triglycerides, cholesterol, total protein, albumin, globulin, urea and creatinine, compared to the control group. In addition, CdCl2 intoxication increased the levels of uric acid, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin. Concerning haematological parameters, the more obvious changes were an increase in mean corpuscular volume and a decrease in white blood cells count, platelets, lymphocytes, heamatocrit, haemoglobin and red blood cells count. Treatment of CdCl2-intoxicated animals with vitamins C and B complex and bee honey showed a decrease in the harmful effects of Cd by restoring haematological and biochemical changes. Bee honey treatment was the most effective in providing recoveries in the altered blood parameters. 23178656 A novel recombinant fibrinogenase of Agkistrodon acutus venom protects against hyperacute rejection via degradation of complements. Hyperacute rejection (HAR) is a main barrier in xenotransplantation, which is mediated by the combination of natural antibody to the xenograft and complement activation. Current therapies have focus on the inhibition of complement by development of complement inhibitor and transgenic animal organ. Here, we investigated the effects of rFII, a recombinant fibrinogenase from Agkistrodon acutus venom, on complement and HAR. The degradation effect of rFII on complement was tested by SDS-PAGE, CH50 examination, ELISA Kit and cofocal immunofluorescence microscopy in vitro and in vivo. An ex-vivo rat-to-human perfusion model and a vivo guinea-pig-to-rat heat HAR model were used to determine the protection of rFII against HAR. Our investigation indicated that rFII could significantly degrade human C5, C6, and C9, decrease the activity of complement, and inhibit the MAC deposition on HUVECs membrane in vitro. In addition, serum levels of C1q, C3 and C4 in rat were gradually reduced after infusion of rFII. Importantly, in an ex vivo rat-to-human perfusion model, the survival of rat hearts perfused with human serum treated with rFII (83.36 ± 16.63 min) were significantly longer than that of hearts perfused with fresh human serum(15.94 ± 4.75 min). At the time of 15 minutes after perfusion, functions of hearts added with 50 ug/ml rFII sustained well with heart rates at 283 ± 65.32 beats/minute and LVDP at 13.70 ± 5.45 Kpa, while that of hearts perfused with fresh human serum were severely damaged by HAR with heart rates at 107.77 ± 40.31 beats/minute and LVDP at 1.01 ± 0.83 Kpa. We also found that rFII significantly decreased the levels of C1q, C3 and C4 in human fresh serum perfusate. In a vivo guinea-pig-to-rat heat HAR model, the survival of rat hearts treated with rFII were significantly longer than that of hearts perfused with normal saline; and relieved heart damage by complete activation. Our finding demonstrates the anti-complement property of rFII and its protection against HAR, indicating that rFII might be as a potential therapeutic agent for xenotransplantation. 23561103 Interlocking of β-carotene in beta-lactoglobulin aggregates produced under high pressure. Vitamin A deficiency is one of the major causes of mortality and morbidity in the developing World. This deficiency can be prevented by alimentary or pharmaceutical supplementation. However, both vitamin A oxidation and isomerization should be prevented, as these phenomenons result in loss of nutritional efficacy. The aim of this study was to investigate the effect of a food protein matrix, β-lactoglobulin (β-Lg) aggregates produced by high pressure (HP), on the stabilization of β-carotene during storage and gastro-duodenal digestion and therefore on its bioavailability. In vitro gastro-duodenal digestion of β-Lg aggregates entrapping β-carotene showed that up to 12% and 33% of total β-carotene was released after peptic and pancreatic digestion, respectively. Overall, our study showed that β-Lg aggregates are efficient for caging and stabilization of β-carotene during storage and digestion. Hence, it may be an interesting approach for the protection and the delivery of vitamin A. 23085266 Zymosan induces NADPH oxidase activation in human neutrophils by inducing the phosphorylation of p47phox and the activation of Rac2: involvement of protein tyrosine kinases, PI3Kinase, PKC, ERK1/2 and p38MAPkinase. Reactive oxygen species (ROS) production by the neutrophil NADPH oxidase plays a key role in host defense against pathogens, such as bacteria and fungi. Zymosan a cell-wall preparation from Saccharomyces cerevisiae is largely used to activate neutrophils in its opsonized form. In this study, we show that non-opsonized zymosan alone induced ROS production by human neutrophils. Zymosan-induced ROS production is higher than the formyl-methionyl-leucyl-phenylalanine (fMLF)- or the phorbol myristate acetate (PMA)-induced ROS production but is lower than the one induced by opsonized zymosan. Most of the zymosan-induced ROS production is intracellular. Interestingly, zymosan induced the phosphorylation of the NADPH oxidase cytosolic component p47phox on several sites which are Ser315, Ser328 and Ser345. Zymosan induced also the activation of the small G-protein Rac2. Phosphorylation of the p47phox as well as Rac2 activation were inhibited by genistein a broad range protein tyrosine kinase inhibitor and by wortmannin a PI3Kinase inhibitor. GF109203X a PKC inhibitor inhibited phosphorylation of p47phox on Ser315 and Ser328. SB203580 and UO126, inhibitors of p38MAPK and ERK1/2-pathway, respectively, inhibited phosphorylation of p47phox on Ser345. Zymosan-induced ROS production was completely inhibited by genistein and wortmannin and partially inhibited by SB203580, UO126 and GF109203X. These results show that zymosan alone is able to activate NADPH oxidase in human neutrophils via the phosphorylation of p47phox and Rac2 activation and that a protein tyrosine kinase, PI3Kinase, p38MAPK, ERK1/2 and PKC are involved in this process. These pathways could be potential pharmacological targets to treat zymosan- and S. cerevisiae-induced inflammation. 23527585 Does Dietary Copper Supplementation Enhance or Diminish PCB126 Toxicity in the Rodent Liver? Copper is essential for the function of the mitochondrial electron transport chain and several antioxidant proteins. However, in its free form copper can participate in Fenton-like reactions that produce reactive hydroxyl radicals. Aryl-hydrocarbon receptor (AhR) agonists, including the most potent polychlorinated biphenyl (PCB) congener, 3,3',4,4',5-pentachlorobiphenyl (PCB126), increase copper levels in rodent livers. This is accompanied by biochemical and toxic changes. To assess the involvement of copper in PCB toxicity, male Sprague-Dawley rats were fed an AIN-93G diet with differing dietary copper levels: low (2 ppm), adequate (6 ppm), and high (10 ppm). After three weeks, rats from each group were given a single ip injection of corn oil (control), 1, or 5 μmol/kg body weight PCB126. Two weeks following injections, biochemical and morphological markers of hepatic toxicity, trace metal status, and hepatic gene expression of metalloproteins were evaluated. Increasing dietary copper was associated with elevated tissue levels of copper and ceruloplasmin. In the livers of PCB126-treated rats, the hallmark signs of AhR activation were present, including increased cytochrome P450 and lipid levels and decreased glutathione. In addition, a doubling of hepatic copper levels was seen, and overall metal homeostasis was disturbed, resulting in decreased hepatic selenium, manganese, zinc, and iron. Expression of key metalloproteins was either decreased (cytochrome c oxidase), unchanged (ceruloplasmin and CuZnSOD), or increased (tyrosinase and metallothioneins 1 and 2) with exposure to PCB126. Increases in metallothionein may contribute/reflect the increased copper seen. Alterations in dietary copper did not amplify or abrogate the hepatic toxicity of PCB126. PCB126 toxicity, i.e., oxidative stress and steatosis, is clearly associated with disturbed metal homeostasis. Understanding the mechanisms of this disturbance may provide tools to prevent liver toxicity by other AhR agonists. 23212103 Clinical applications for microRNAs in cancer. The discovery that noncoding components of the genome, including microRNA (miRNA or miR), can contribute to the pathogenesis of cancer has led investigators to contemplate using these molecules to guide clinical decision making. Currently, miRNA signatures are being applied in human clinical trials and miRNA-directed therapy is under way, with miR-122 targeting in hepatitis C (HCV) being the most developed therapy thus far. miRNA-based targeting in cancer is not far behind, with several private companies developing therapeutics. We are recognizing the potential for miRNA biology to clarify both the molecular pathogenesis of cancer and the inherent complexities in translating its biology to clinics. An increased understanding of fundamental miRNA biology, improved bioinformatics, and directed in vivo targeting while minimizing off-target effects and toxicity will be required for successful translational application. Here, we provide an overview of miRNAs, with a focus on aspects of translating bench-based discoveries to the clinic. 23522833 Cu(OTf)2 catalyzed three component reaction: Efficient synthesis of spiro[indoline-3,4'-pyrano[3,2-b]pyran derivatives and their anticancer potency towards A549 human lung cancer cell lines. Cu(OTf)2 catalyzed efficient synthesis of spiropyrano[3,2-b]pyran-4(8H)-ones is accomplished via one-pot three component reaction between isatin, kojic acid and active methylenes. This synthetic protocol is operationally simple and affords product with good to excellent yields at a short reaction time. The synthesized compounds were evaluated for their tumor cell growth inhibitory activity against the human lung cancer cell line (A549) and found that 13 compounds exhibited moderate to good anticancer potency. Molecular docking studies were performed for all the synthesized compounds and the results showed that compound 4e showed greater affinity for anaplastic lymphoma kinase (ALK) receptor. 23458727 Design, synthesis, and biological evaluation of highly potent small molecule-peptide conjugates as new HIV-1 fusion inhibitors. The small molecule fusion inhibitors N-(4-carboxy-3-hydroxyphenyl)-2,5-dimethylpyrrole (NB-2) and N-(3-carboxy-4-hydroxyphenyl)-2,5-dimethylpyrrole (A12) target a hydrophobic pocket of HIV-1 gp41 and have moderate anti-HIV-1 activity. In this paper, we report the design, synthesis, and structure-activity relationship of a group of hybrid molecules in which the pocket-binding domain segment of the C34 peptide was replaced with NB-2 and A12 derivatives. In addition, the synergistic effect between the small molecule and peptide moieties was analyzed, and lead compounds with a novel scaffold were discovered. We found that either the nonpeptide or peptide part alone showed weak activity against HIV-1-mediated cell-cell fusion, but the conjugates properly generated a strong synergistic effect. Among them, conjugates Aoc-βAla-P26 and Noc-βAla-P26 exhibited a low nanomolar IC50 in the cell-cell fusion assay and effectively inhibited T20-sensitive and -resistant HIV-1 strains. Furthermore, the new molecules exhibited better stability against proteinase K digestion than T20 and C34. 23565753 Androgen receptor: past, present and future. Androgens and the androgen receptor have been the focus of prostate cancer research since the early 1940s, when Huggins and Hodges demonstrated that removal of androgens caused advanced prostate cancer to regress. Since that time, a large number of androgen deprivation therapies have been developed in an effort to cure this disease, but prostate cancer remains one of the leading causes of cancer death in males worldwide. This is due in part to the emergence of castration- recurrent prostate cancer in patients with advanced disease who have failed androgen deprivation therapy. The androgen receptor is still a major player in castration-recurrent disease, and though much has been discovered since the early work of Huggins and Hodges regarding how prostate cancer cells manage to avoid the effects of androgen deprivation, survival times for men with advanced prostate cancer have changed only modestly. Research is now directed toward delineating the mechanisms of action of the androgen receptor under castrate conditions, whether through amplification of the AR, mutation, expression of splice variants, use of alternate signaling pathways, aberrant expression and activation of coregulators, or intratumoral androgen biosynthesis. Genome-wide association studies are also adding to the wealth of knowledge surrounding the androgen receptor, and with this knowledge comes the ability to design new drug therapies directed toward eradication of this disease. 23488728 Gold nanoparticles on oxide-free silicon-molecule interface for single electron transport. Two different organic monolayers were prepared on silicon Si(111) and modified for attaching gold nanoparticles. The molecules are covalently bound to silicon and form very ordered monolayers sometimes improperly called self-assembled monolayers (SAM). They are designed to be electrically insulating and to have very few electrical interface states. By positioning the tip of an STM above a nanoparticle, a double barrier tunnel junction (DBTJ) is created, and Coulomb blockade is demonstrated at 40 K. This is the first time Coulomb blockade is observed with an organic monolayer on oxide-free silicon. This work focuses on the fabrication and initial electrical characterization of this double barrier tunnel junction. The organic layers were prepared by thermal hydrosilylation of two different alkene molecules with either a long carbon chain (C11) or a shorter one (C7), and both were modified to be amine-terminated. FTIR and XPS measurements confirm that the Si(111) substrate remains unoxidized during the whole chemical process. Colloidal gold nanoparticles were prepared using two methods: either with citrate molecules (Turkevich method) or with ascorbic acid as the surfactant. In both cases AFM and STM images show a well-controlled deposition on the grafted organic monolayer. I-V curves obtained by scanning tunneling spectroscopy (STS) are presented on 8 nm diameter nanoparticles and exhibit the well-known Coulomb staircases at low temperature. The curves are discussed as a function of the organic layer thickness and silicon substrate doping. 23567037 Hemolysin from Escherichia coli induces oxidative stress in blood. Hemolysin (HlyA) produced by some stains of Escherichia coli is considered to be an important virulence factor of those bacteria. On the other hand, reactive oxygen species (ROS) have been reported to be involved in the pathogenesis of different diseases via oxidative stress generation. The purpose of this study was to analyze the capacity of HlyA to induce oxidative stress in whole blood cultures (WBCs). To this end, ROS production, the damage induced in lipids and proteins, and the antioxidant defense system was evaluated in blood cultures exposed to low concentrations of HlyA. We found that HlyA increased the level of free radicals detected by chemiluminescence assay. Moreover, lipid peroxidation and protein damage was significantly increased in cultures treated with HlyA in comparation with those found in control cultures. On the other hand, a decrease in total antioxidant capacity of plasma and in the activity of superoxide dismutase (SOD) was observed in plasma from blood treated with HlyA. Collectively, our data demonstrate that low concentrations of E. coli hemolysin induced oxidative stress in WBCs with the induction of different oxidative damage biomarkers. 23427338 Surface-confined electroactive molecules for multistate charge storage information. Bi-stable molecular systems with potential for applications in binary memory devices are raising great interest for device miniaturization. Particular appealing are those systems that operate with electrical inputs since they are compatible with existing electronic technologies. The processing of higher memory densities in these devices could be accomplished by increasing the number of memory states in each cell, although this strategy has not been much explored yet. Here we highlight the recent advances devoted to the fabrication of charge-storage molecular surface-confined devices exhibiting multiple states. Mainly, this goal has been realized immobilizing a variety (or a combination) of electroactive molecules on a surface, although alternative approaches employing non-electroactive systems have also been described. Undoubtedly, the use of molecules with chemically tunable properties and nanoscale dimensions are raising great hopes for the devices of the future in which molecules can bring new perspectives such as multistability. 23159331 Perseverative behavior in rats with methamphetamine-induced neurotoxicity. Methamphetamine induces monoamine depletions thought to contribute to cognitive and behavioral dysfunctions. Previously, we reported that methamphetamine-induced neurotoxicity is associated with impaired formation of stimulus-response associations. Additionally, subjective observations suggested that behavioral flexibility might be affected. Thus, the present study examined whether methamphetamine neurotoxicity induces perseverative behavior. Rats were pretreated with (±)-methamphetamine (4 × 10 mg/kg, 2-hr intervals) or saline. Three weeks later, rats were trained to press a lever on one side of an operant chamber and then retrieve the reinforcer from a magazine on the opposite side until they reached criterion (>50 reinforcers/30-min). After four consecutive sessions performing the task at criterion, rats were sacrificed and brains removed for monoamine determinations. Methamphetamine-pretreated rats had ∼50% loss of striatal dopamine and prefrontal serotonin. Methamphetamine- and saline-pretreated rats were not different in the number of sessions required to reach criterion or in the total numbers of lever presses and/or head entries made across the four consecutive sessions at criterion-level performance. However, methamphetamine-pretreated rats earned fewer reinforcers, because they made extra lever-presses and head entries when they should have been retrieving the reinforcer or returning to the lever. Latencies for methamphetamine-pretreated rats to switch between the two behaviors also were significantly slower than latencies for controls. Interestingly, the degree of additional lever-presses negatively correlated with serotonin-transporter binding in the prefrontal cortex, even in saline-pretreated controls. These data suggest that methamphetamine-induced partial monoamine toxicity is associated with perseveration and that the degree of perseveration may depend on serotonin innervation of the frontal cortex. 23284082 Amide hydrolysis of a novel chemical series of microsomal prostaglandin E synthase-1 inhibitors induces kidney toxicity in the rat. A novel microsomal prostaglandin E synthase 1 (mPGES-1) inhibitor induced kidney injury at exposures representing less than 4 times the anticipated efficacious exposure in man during a 7-day toxicity study in rats. The findings consisted mainly of tubular lesions and the presence of crystalline material and increases in plasma urea and creatinine. In vitro and in vivo metabolic profiling generated a working hypothesis that a bis-sulfonamide metabolite (determined M1) formed by amide hydrolysis caused this toxicity. To test this hypothesis, rats were subjected to a 7-day study and were administered the suspected metabolite and two low-potency mPGES-1 inhibitor analogs, where amide hydrolysis was undetectable in rat hepatocyte experiments. The results suggested that compounds with a reduced propensity to undergo amide hydrolysis, thus having less ability to form M1, reduced the risk of inducing kidney toxicity. Rats treated with M1 alone showed no histopathologic change in the kidney, which was likely related to underexposure to M1. To circumvent rat kidney toxicity, we identified a potent mPGES-1 inhibitor with a low propensity for amide hydrolysis and superior rat pharmacokinetic properties. A subsequent 14-day rat toxicity study showed that this compound was associated with kidney toxicity at 42, but not 21, times the anticipated efficacious exposure in humans. In conclusion, by including metabolic profiling and exploratory rat toxicity studies, a new and active mPGES-1 inhibitor with improved margins to chemically induced kidney toxicity in rats has been identified. 23636303 Involvement of serotonin 5-HT3 receptors in the modulation of noradrenergic transmission by serotonin reuptake inhibitors: a microdialysis study in rat brain. RATIONALE: Selective serotonin reuptake inhibitors (SSRIs), in addition to being able to enhance serotonergic neurotransmission, are able to modulate other brain systems involved in depression. OBJECTIVES: This study evaluates the neurochemical effect of the SSRI citalopram on brain noradrenergic activity and the serotonin receptor involved in this effect. METHODS: Dual-probe microdialysis in the locus coeruleus (LC) and prefrontal cortex (PFC) was performed in freely awake rats. RESULTS: Systemic citalopram (10 mg/kg, i.p.) increased noradrenaline (NA) in the LC (E max = 141 ± 13 %) and simultaneously decreased NA in the PFC (Emax = -46 ± 7 %). In the local presence into the LC of the α2-adrenoceptor antagonist RS79948 (1 μM), systemic citalopram increased NA in the LC (Emax = 157 ± 25 %) and PFC (Emax = 175 ± 24 %). Local citalopram (0.1-100 μM) into the LC induced NA increase in the LC (Emax = 210 ± 25 %) and decrease in the PFC (Emax = -38 ± 9 %). Local LC citalopram effect was abolished by LC presence of the 5-HT3 receptor antagonist MDL72222 (1 μM) but not the 5-HT1/2 receptor antagonist methiothepin (1 μM). Systemic citalopram in the LC presence of MDL72222 did not modify NA in the LC but increased NA in the PFC (Emax = 158 ± 26 %). Local citalopram into the PFC enhanced NA (Emax = 376 ± 18 %) in the area, which was prevented by MDL72222. CONCLUSIONS: The SSRI citalopram modulates central noradrenergic neurotransmission by activation, through endogenous serotonin, of 5-HT3 receptors expressed in the somatodendritic (LC) and terminal (PFC) areas, which subsequently promote an enhancement of local NA. Therefore, 5-HT3 receptors and somatodendritic α2-adrenoceptors in the LC play an important role in the global effect of SSRIs. 23303281 Global CNS gene delivery and evasion of anti-AAV-neutralizing antibodies by intrathecal AAV administration in non-human primates. Injection of adeno-associated virus (AAV) into the cerebrospinal fluid (CSF) offers a means to achieve widespread transgene delivery to the central nervous system, where the doses can be readily translated from small to large animals. In contrast to studies with other serotypes (AAV2, AAV4 and AAV5) in rodents, we report that a naturally occurring capsid (AAV9) and rationally engineered capsid (AAV2.5) are able to achieve broad transduction throughout the brain and spinal cord parenchyma following a single injection into the CSF (via cisterna magna or lumbar cistern) in non-human primates (NHP). Using either vector at a dose of ∼2 × 10(12) vector genome (vg) per 3-6 kg animal, approximately 2% of the entire brain and spinal cord was transduced, covering all regions of the central nervous system (CNS). AAV9 in particular displayed efficient transduction of spinal cord motor neurons. The peripheral organ biodistribution was highly reduced compared with intravascular delivery, and the presence of circulating anti-AAV-neutralizing antibodies up to a 1:128 titer had no inhibitory effect on CNS gene transfer. Intra-CSF delivery effectively translates from rodents to NHPs, which provides encouragement for the use of this approach in humans to treat motor neuron and lysosomal storage diseases. 23423468 An investigation of the photophysical properties of minor groove bound and intercalated DAPI through quantum-mechanical and spectroscopic tools. The fluorescent probe 4',6-diamidino-2-phenylindole (DAPI) is a dye known to interact with polynucleotides in a non-univocal manner, both intercalation and minor groove binding modes being possible, and to specifically change its photophysical properties according to the different environments. To investigate this behavior, quantum-mechanical calculations using time-dependent density functional theory (TDDFT), coupled with polarizable continuum and/or atomistic models, were performed in combination with spectroscopic measurements of the probe in the different environments, ranging from a homogeneous solution to the minor groove or intercalation pockets of double stranded nucleic acids. According to our simulation, the electronic transition involves a displacement of the electron charge towards the external amidine groups and this feature makes the absorption energies very environment-sensitive while a much smaller sensitivity is seen in the fluorescence energies. Moreover, the calculations show that the DAPI molecule, when minor groove bound to the nucleic acid, presents both a reduced geometrical flexibility because of the rigid DNA pocket and a reduced polarization due to the very "apolar" microenvironment. All these effects can be used to better understand the observed enhancement of the fluorescence, which makes it an excellent marker for DNA. 23350730 Parathyroid and calcium metabolism disorders during pregnancy. Abstract Parathyroid disorders are not common among pregnant women, but harbor a significant morbidity and mortality potential if they remain unrecognized and untreated. The symptoms caused by abnormally low or high blood free calcium level are mostly non-specific in the initial stages, thus when recognized might pose a real danger. Here we will survey the alterations in calcium metabolism induced by pregnancy, and describe the clinical manifestations, diagnosis and treatment of parathyroid and other calcium metabolism disorders during pregnancy. The current literature on the impact of calcium and vitamin D deficiency during pregnancy will also be reviewed. 23402938 Biotransformation and toxicokinetics of the insect repellent IR3535® in male and female human subjects after dermal exposure. The absorption and excretion of the insect repellent IR3535(®) was studied in human subjects (five males and five females) after dermal application of approx. 3g of a formulation containing 20% IR3535(®), i.e. the amounts of IR3535(®) applied were between 1.94 and 3.4 mmol/person (418-731 mg/person). Blood and urinary concentrations of IR3535(®) and its only metabolite, IR3535(®)-free acid, were determined over time. In plasma, concentrations of the parent compound IR3535(®) were at or below the limit of quantification (0.037 μmol/L). IR3535(®)-free acid peaked in plasma samples 2-6h after dermal application. Cmax mean values were 5.7 μmol/L in males, 3.0 μmol/L in females and 4.2 μmol/L in all volunteers. Mean AUC values were 41.6, 24.5 and 33.9 μmolL(-1)h in males, females and all subjects, respectively. In urine samples from all human subjects, both IR3535(®) and IR3535(®)-free acid were detectable, however, only very small amounts of IR3535(®) were found. Concentrations of IR3535(®)-free acid were several thousand-fold higher than the parent compound and peaked at the first two sampling points (4h and 8h after dermal application). Overall, IR3535(®) and IR3535(®)-free acid excreted with urine over 48 h representing 13.3 ± 3.05% of the dose applied. Since IR3535(®) is rapidly and extensively metabolized, and IR3535(®)-free acid has a low molecular weight and high water solubility, it is expected that urinary excretion of IR3535(®)-free acid and IR3535(®) represents the total extent of absorption of IR3535(®) in humans. Based on the results of this study, the skin penetration rate of IR3535(®) is 13.3% in humans after dermal application. 23157637 Systematic review of the influence of antipsychotics on the blood oxygenation level-dependent signal of functional magnetic resonance imaging. Functional Magnetic Resonance Imaging (FMRI) is a non-invasive technique for brain mapping and mostly performed using changes of the blood-oxygen-level-dependent (BOLD)-signal. It has been widely used to investigate patients with schizophrenia. Most of the studies examine patients treated with antipsychotic drugs, although little is known about the effects of these drugs on the BOLDsignal. Here we examined studies of patients with schizophrenia treated with different antipsychotics to address the question whether and to what extent antipsychotic drugs in themselves produce BOLD-signal changes. We performed a PubMed-search for the period from 1999 until January 2012 with the search items "schizophrenia" and "Magnetic Resonance Imaging" and "Antipsychotic Agents; or "Magnetic Resonance Imaging" and "Antipsychotic Agents"; or "schizophrenia" and "Antipsychotic Agents" and "FMRI". We extracted articles that examined at least two patient groups with different treatments, or patients examined on different medications at different times and that provided information about drug effects. No common effect of antipsychotics on BOLD-signal was found. However, based on the results for different antipsychotics (haloperidol, olanzapine, quetiapine and risperidone) we found evidence that the affinity to the dopamine (DA) D(2)-receptor may influence BOLD-signal. 23215461 Recombinant human fibrinogen that produces thick fibrin fibers with increased wound adhesion and clot density. Human fibrinogen is a biomaterial used in surgical tissue sealants, scaffolding for tissue engineering, and wound healing. Here we report on the post-translational structure and functionality of recombinant human FI (rFI) made at commodity levels in the milk of transgenic dairy cows. Relative to plasma-derived fibrinogen (pdFI), rFI predominately contained a simplified, neutral carbohydrate structure and >4-fold higher levels of the γ'-chain transcriptional variant that has been reported to bind thrombin and Factor XIII. In spite of these differences, rFI and pdFI were kinetically similar with respect to the thrombin-catalyzed formation of protofibrils and Factor XIIIa-mediated formation of cross-linked fibrin polymer. However, electron microscopy showed rFI produced fibrin with much thicker fibers with less branching than pdFI. In vivo studies in a swine liver transection model showed that, relative to pdFI, rFI made a denser, more strongly wound-adherent fibrin clot that more rapidly established hemostasis. 23568455 Potent Inhibitors of Phosphatidylinositol 3 (PI3) Kinase that have Antiproliferative Activity Only When Delivered as Prodrug Forms. Prodrugs for PI3K: A series of substituted analogues of the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002 were prepared and found to potently inhibit the isolated enzyme but not MCF7 cell proliferation. Two tetrazolyl-substituted analogues were further derivatized as prodrugs resulting in restoration of cell-based activity. These data provide a conceptual model for development of tumor-targeting prodrug forms of cell-impermeable PI3K inhibitors. 23287538 Alcohol intoxications during adolescence increase motivation for alcohol in adult rats and induce neuroadaptations in the nucleus accumbens. Adolescent alcohol binge drinking constitutes a major vulnerability factor to develop alcoholism. However, mechanisms underlying this susceptibility remain unknown. We evaluated the effect of adolescent binge-like ethanol intoxication on vulnerability to alcohol abuse in Sprague-Dawley rats. To model binge-like ethanol intoxication, every 2 days, rats received an ethanol injection (3.0 g/kg) for 2 consecutive days across 14 days either from postnatal day 30 (PND30) to 43 (early adolescence) or from PND 45 to PND 58 (late adolescence). In young adult animals, we measured free ethanol consumption in the two-bottle choice paradigm, motivation for ethanol in the operant self-administration task and both ethanol's rewarding and aversive properties in the conditioned place preference (CPP) and taste aversion (CTA) paradigms. While intermittent ethanol intoxications (IEI) during late adolescence had no effect on free-choice 10% ethanol consumption, we found that IEI during early adolescence promoted free-choice 10% ethanol consumption, enhanced motivation for ethanol in the self-administration paradigm and induced a loss of both ethanol-induced CPP and CTA in young adults. No modification in either sucrose self-administration or amphetamine-induced CPP was observed. As the nucleus accumbens (Nac) is particularly involved in addictive behavior, we analyzed IEI-induced long-term neuroadaptations in the Nac using c-Fos immunohistochemistry and an array of neurotransmission-related genes. This vulnerability to ethanol abuse was associated with a lower c-Fos immunoreactivity in the Nac and enduring alterations of the expression of Penk and Slc6a4, 2 neurotransmission-related genes that have been shown to play critical roles in the behavioral effects of ethanol and alcoholism. 23085085 Histone deacetylase 3 is required for maintenance of bone mass during aging. Histone deacetylase 3 (Hdac3) is a nuclear enzyme that removes acetyl groups from lysine residues in histones and other proteins to epigenetically regulate gene expression. Hdac3 interacts with bone-related transcription factors and co-factors such as Runx2 and Zfp521, and thus is poised to play a key role in the skeletal system. To understand the role of Hdac3 in osteoblasts and osteocytes, Hdac3 conditional knockout (CKO) mice were created with the osteocalcin (OCN) promoter driving Cre expression. Hdac3 CKO(OCN) mice were of normal size and weight, but progressively lost trabecular and cortical bone mass with age. The Hdac3 CKO(OCN) mice exhibited reduced cortical bone mineralization and material properties and suffered frequent fractures. Bone resorption was lower, not higher, in the Hdac3 CKO(OCN) mice, suggesting that primary defects in osteoblasts caused the reduced bone mass. Indeed, reductions in bone formation were observed. Osteoblasts and osteocytes from Hdac3 CKO(OCN) mice showed increased DNA damage and reduced functional activity in vivo and in vitro. Thus, Hdac3 expression in osteoblasts and osteocytes is essential for bone maintenance during aging. 23546395 Antimutagenic and genoprotective effects of Saraca asoca bark extract. Aim of the study:Traditionally herbal formulations have been used effectively for the management of disorders that are now being accepted worldwide. Saraca asoca bark extract (SAE) finds use in traditional herbal medicine. In the present study, SAE were studied for their antioxidant, antimutagenic, and antigenotoxic properties. METHODS: SAE were evaluated for antimutagenic property in Salmonella strains (TA97a, TA98, TA100, and TA102), in the presence and absence of metabolic activation (S9). The SAE was also studied for antigenotoxic property against cyclophosphamide (CP) in Swiss albino male mice in vivo. The extract was analyzed using high-performance liquid chromatography (HPLC). RESULTS: The study reveals antimutagenic property of the bark extract in Salmonella strains in the presence and absence of metabolic activation (S9). The study reports antigenotoxic property of the bark extract against CP in vivo. Thiobarbituric acid reactive species assay on the bark extract revealed antioxidant property. HPLC revealed the presence of two peaks corresponding to gallic acid and (-)-epicatechin, respectively. CONCLUSION: The study clearly reveals the antimutagenic and antigenotoxic properties of SAE. 23186624 Effect of clonidine in mice injected with Tityus discrepans scorpion venom. A study was conducted to assess the effect of clonidine (α(2)-adrenoceptor selective agonist) on glycemia, serum and urine α-amylase, blood urea nitrogen (BUN), serum creatinine, white blood cell count, kidney histology and zymogen granule content in pancreatic acini, in mice under the effect of Tityus discrepans (Td) scorpion venom. BALB/c male mice (20 ± 2 g, n = 7-11) were intraperitoneally (ip) injected with a sublethal dose (1 μg/g) of Td venom, and were treated (ip) with 0.1 μg/g of clonidine (Catapresan(®)) or 0.9% NaCl 30 min after the venom injection, and then every 2 h. Six hours later, mice were anesthetized with diethylether and urine and blood samples were withdrawn by cystocentesis and cardiocentesis, respectively. Tissue samples were obtained and fixed immediately in buffered formalin (2%, pH 7.4) and then processed for stain H&E. Td venom did not cause hyperglycemia by itself. However, clonidine induced hyperglycemia, which was synergized by Td venom. Although the venom did not produce hyperamylasemia, clonidine significantly diminished serum α-amylase activity in envenomed mice. Td venom did not significantly increase urinary α-amylase activity, which was unaffected by clonidine. Morphometric analysis using microphotographs of pancreata from mice injected with Td venom showed a reduced zymogen granule content as judged by the acidophilic bidimensional area of acini. This effect was significantly reduced by clonidine. Kidney samples showed histological changes which were partially affected by the drug. Clonidine reduced the increase in BUN and serum creatinine concentration in envenomed mice. Td venom produced neutrophilia and lymphopenia, which were clonidine-resistant at the assayed dose. These results suggest that α(2)-adrenoceptor selective agonists would be able to reduce some scorpion venom-induced renal and pancreatic disturbances, possibly through the inhibition of neurotransmitter release from presynaptic cholinergic and noradrenergic terminals, as well as from adrenal medulla. 23320940 Determination of very rapid molecular rotation by using the central electron paramagnetic resonance line. Picosecond rotational correlation times of perdeuterated tempone (PDT) are found in alkane and aromatic liquids by directly using the spectral width of the central electron paramagnetic resonance line. This is done by mathematically eliminating the nonsecular spectral density from the spectral parameter equations, thereby removing the need to assume a particular form for it. This is preferable to fitting a constant correction factor to the spectral density, because such a factor does not fit well in the low picosecond range. The electron-nuclear spin dipolar interaction between the probe and solvent is shown to be negligible for the very rapid rotation of PDT in these liquids at the temperatures of the study. The rotational correlation times obtained with the proposed method generally agree to within experimental uncertainty with those determined by using the traditional parameters. Using the middle line width offers greater precision and smoother trends. Previous work with the central line width is discussed, and past discrepancies are explained as possibly resulting from residual inhomogeneous broadening. The rotational correlation time almost forms a common curve across all of the solvents when plotted with respect to isothermal compressibility, which shows the high dependence of rotation on liquid free volume. 23219979 Bioactive cis-stilbenoids from the tubers of Scirpus yagara. Two new cis-stilbenoids, sciryagarol I (1) and II (2) were isolated from the EtOAc extract of the tubers of Scirpus yagara, together with four known compounds. The structures of all compounds were determined by comprehensive analyses of their spectroscopic data and comparison with literature information. The compounds 3, 4 and 6 were isolated for the first time from this genus. Some compounds were tested for their cytotoxicity against human tumor cell lines and antimicrobial activity. Compounds 1-4 showed significant cytotoxicity against the Hela cell lines with IC(50) values ranging from 7.21 to 61.21μM. 1 and 2 exhibited some antimicrobial activity against Staphylococcus aureus and Candida albicans with uniform MICs of 79.3μl/ml for 2, and 152μl/ml for 1, respectively. 22864622 Aurora A kinase (AURKA) in normal and pathological cell division. Temporally and spatially controlled activation of the Aurora A kinase (AURKA) regulates centrosome maturation, entry into mitosis, formation and function of the bipolar spindle, and cytokinesis. Genetic amplification and mRNA and protein overexpression of Aurora A are common in many types of solid tumor, and associated with aneuploidy, supernumerary centrosomes, defective mitotic spindles, and resistance to apoptosis. These properties have led Aurora A to be considered a high-value target for development of cancer therapeutics, with multiple agents currently in early-phase clinical trials. More recently, identification of additional, non-mitotic functions and means of activation of Aurora A during interphase neurite elongation and ciliary resorption have significantly expanded our understanding of its function, and may offer insights into the clinical performance of Aurora A inhibitors. Here we review the mitotic and non-mitotic functions of Aurora A, discuss Aurora A regulation in the context of protein structural information, and evaluate progress in understanding and inhibiting Aurora A in cancer. 23073171 Effects of conjugated linoleic acid supplementation and exercise on post-heparin lipoprotein lipase, butyrylcholinesterase, blood lipid profile and glucose metabolism in young men. This study was designed to investigate the effects of conjugated linoleic acid (CLA) supplementation and endurance exercise training-induced changes on post-heparin lipoprotein lipase (PH-LPL) and butyrylcholinesterase (BChE) activities along with leptin, insulin and lipid levels in plasma by a randomized double blind experiment. Eighteen sedentary male volunteers were randomly divided into CLA and Placebo (PLC) supplementation groups. Both groups underwent daily supplementation of either 3g CLA or 3g placebo for 30days, respectively, and performed exercise on a bicycle ergometer 3 times per week for 30-40min at 50% VO2 peak workload. For plasma glucose, insulin and leptin levels and BChE activity fasting blood was used. For PH-LPL measurements, blood was collected 15min after 50IU/kg iv heparin injection. In all groups, there is a statistically significant decrease in BChE (p=0.03, p=0.02) and leptin (p=0.002), insulin and HOMA-IR levels (p=0.02). Exercise with or without CLA supplementation decreased insulin levels and increased insulin sensitivity. PH-LPL activity was increased significantly in both groups, displaying increased fatty acid mobilization. We conclude that though CLA supplementation and exercise can affect these parameters, CLA is not more effective than exercise alone. Hence, a prolonged supplementation regime may be more effective. Taken together in our small study group, our findings display that BChE is a potential marker for synthetic function of liver, fat metabolism, an obesity marker, a function long overlooked. 23532897 Impact of the Proline Residue on Ligand Binding of Neurotensin Receptor 2 (NTS2)-Selective Peptide-Peptoid Hybrids. To investigate the binding mode and structure-activity relationships (SARs) of selective neurotensin receptor 2 (NTS2) ligands, novel peptide-peptoid hybrids that simulate the function of the endogenous ligand were developed. Starting from our recently described NTS2 ligands of type 1, structural variants of type 2 and the metabolically stable analogues 3 a,b were developed. Replacement of the proline unit by a collection of structural surrogates and evaluation of the respective molecular probes for NTS2 affinity and selectivity indicated similar SARs as described for NT(8-13) derivatives bound to the subtype NTS1. Peptide-peptoid hybrids 2 d, 3 a,b showed substantial NTS2 binding affinity (Ki =8.1-16 nM) and 2400-8600-fold selectivity over NTS1. The thiazolidine derivative 3 b showed metabolic stability over 32 h in a serum degradation assay. In an inositol phosphate accumulation assay, the neurotensin mimetics 3 a and 3 b displayed an inhibition of constitutive activity exceeding 1.7-2.0 times the activity of NT(8-13). The fluorinated derivative 3 a could afford attractive opportunities to detect NTS2 by (19) F magnetic resonance imaging. 23537599 Oxidative stress and myocardial dysfunction in young rabbits after short term anabolic steroids administration. The present study focuses on the short term effects of repeated low level administration of turinabol and methanabol on cardiac function in young rabbits (4months-old). The experimental scheme consisted of two oral administration periods, lasting 1month each, interrupted by 1-month wash-out period. Serial echocardiographic evaluation at the end of all three experimental periods was performed in all animals. Oxidative stress markers have also been monitored at the end of each administration period. Treated animals originally showed significantly increased myocardial mass and systolic cardiac output, which normalized at the end of the wash out period. Re-administration led to increased cardiac output, at the cost though of a progressive myocardial mass reduction. A dose-dependent trend towards impaired longitudinal systolic, diastolic and global myocardial function was also observed. The adverse effects were more pronounced in the methanabol group. For both anabolic steroids studied, the low dose had no significant effects on oxidative stress markers monitored, while the high dose created a hostile oxidative environment. In conclusion, anabolic administration has been found to create a possible deleterious long term effect on the growth of the immature heart and should be strongly discouraged especially in young human subjects. 23170796 Minocycline mediated mitochondrial cytoprotection: premises for therapy of cerebrovascular and neurodegenerative diseases. In the last decades, emerging molecular targets for ischemic neuroprotection and regeneration have been postulated. This fact allowed that classical drugs with well established therapeutic applications might be used in cerebrovascular diseases as well as neurodegenerative diseases. Minocycline is a commonly used antibiotic of the tetracycline family (7-dimethylamino-6-dimethyl-6-deoxytetracycline) which reveals cytoprotective capability and potential use in treatment of different diseases. Here, we discuss the literature concerning minocycline. The available data indicate that the antibiotic has multi-faceted effects on cell functions and, consequently, a number of clinical properties that are useful and/or could be useful for treatment of different diseases including bacterial infections, cancer, autoimmune disorders, ischemia as well as neurodegenerative and psychiatric diseases. Thus, application of minocycline as a therapeutic agent is the subject of clinical trials for various diseases. It is also evident that minocycline-mediated cytoprotection, including neuroprotection, is an important aspect of its clinical application. Here, we have reviewed the basis of the minocycline activity as well as different studies indicating that minocycline can be used as potential therapeutic agent in both cerebrovascular and neurodegenerative diseases in human. 23492810 Developing Predictive Approaches to Characterize Adaptive Responses of the Reproductive Endocrine Axis to Aromatase Inhibition: I. Data Generation in a Small Fish Model. Adaptive or compensatory responses to chemical exposure can significantly influence in vivo concentration-duration-response relationships. This study provided data to support development of a computational dynamic model of the hypothalamic-pituitary-gonadal axis of a model vertebrate and its response to aromatase inhibitors as a class of endocrine active chemicals. Fathead minnows (Pimephales promelas) were either exposed to the aromatase inhibitor fadrozole (0.5 or 30 μg/l) continuously for 1, 8, 12, 16, 20, 24, or 28 days or exposed for 8 days and then held in control water (no fadrozole) for an additional 4, 8, 12, 16, or 20 days. The time course of effects on ovarian steroid production, circulating 17β-estradiol (E2) and vitellogenin (VTG) concentrations, and expression of steroidogenesis-related genes in the ovary was measured. Exposure to 30 μg fadrozole/l significantly reduced plasma E2 and VTG concentrations after just 1 day and those effects persisted throughout 28 days of exposure. In contrast, ex vivo E2 production was similar to that of controls on day 8-28 of exposure, whereas transcripts coding for aromatase and follicle-stimulating hormone receptor were elevated, suggesting a compensatory response. Following cessation of fadrozole exposure, ex vivo E2 and plasma E2 concentrations exceeded and then recovered to control levels, but plasma VTG concentrations did not, even after 20 days of depuration. Collectively these data provide several new insights into the nature and time course of adaptive responses to an aromatase inhibitor that support development of a computational model (see companion article). 23546867 Ionizing radiation-inducible microRNA miR-193a-3p induces apoptosis by directly targeting Mcl-1. The functions of microRNAs (miRNAs) as either oncogenes or tumor suppressors in regulating cancer-related events have been established. We analyzed the alterations in the miRNA expression profile of the glioma cell line U-251 caused by ionizing radiation (IR) by using an miRNA array and identified several miRNAs whose expression was significantly affected by IR. Among the IR-responsive miRNAs, we further examined the function of miR-193a-3p, which exhibited the most significant growth-inhibiting effect. miR-193a-3p was observed to induce apoptosis in both U-251 and HeLa cells. We also demonstrated that miR-193a-3p induces the accumulation of intracellular reactive oxygen species (ROS) and DNA damage as determined by the level of γH2AX and by performing the comet assay. The induction of both apoptosis and DNA damage by miR-193a-3p was blocked by antioxidant treatment, indicating the crucial role of ROS in the action of miR-193a-3p. Among the putative target proteins, the expression of Mcl-1, an anti-apoptotic Bcl-2 family member, decreased because of miR-193a-3p transfection. A reporter assay using a luciferase construct containing the 3'-untranslated region of Mcl-1 confirmed that Mcl-1 is a direct target of miR-193a-3p. Down-regulation of Mcl-1 by siRNA transfection closely mimicked the outcome of miR-193a-3p transfection showing increased ROS, DNA damage, cytochrome c release, and apoptosis. Ectopic expression of Mcl-1 suppressed the pro-apoptotic action of miR-193a-3p, suggesting that Mcl-1 depletion is critical for miR-193a-3p induced apoptosis. Collectively, our results suggest a novel function for miR-193a-3p and its potential application in cancer therapy. 23395717 Xestospongin C induces monocytic differentiation of HL60 cells through activation of the ERK pathway. Xestospongin C (XC), which is a group of macrocyclic bis-1-oxaquinolizidines, is a potent inhibitor of sarcoendoplasmic reticulum calcium transport ATPase and IP3 receptor. Nevertheless, very less information is available regarding whether XC induces AML differentiation. We investigated the potential role of XC in the differentiation of human leukemia HL60 cells and mechanisms underlying XC actin. XC treatment inhibited proliferation by inducing G1-phase cell cycle arrest in the HL60 cells. In addition, XC induced differentiation of HL60 cells into the CD14(+) monocytic lineage, which was indicated by morphological changes, nitroblue tetrazolium reduction assay, and expressions of CD11b and CD14 surface antigens. Our results also showed that XC promotes phagocytic activity and granularity in HL60 cells, suggesting that the cells are functionally activated. Furthermore, XC enhanced tumor necrosis factor (TNF)-α-mediated cytotoxic effect by increasing the numbers of TNF receptors. Moreover, we showed that XC activates extracellular signal-regulated kinase (ERK) pathway in the differentiation stages. Inhibition of ERK activation using PD98059 significantly decreased NBT+HL60 cells induced by XC treatment. Taken together, the results show that XC promotes monocytic differentiation of HL60 cells via ERK pathway activation, suggesting that XC could be a candidate for use as a differentiation-inducing agent for AML treatment. 23521360 New methylated flavonol glucosides from Fumana montana Pomel. Three new methylated flavonol glucosides: 3-methoxy-7-O-β-(6″-galloylgluco-pyranoside) quercetin (1), 3,4'-dimethoxy-7-O-β-(6″-galloyl-glucopyranoside) quercetin (2) and 3-methoxy-7-O-β-(6″-galloylgluco-pyranoside) kaempferol (3), in addition to six known flavonols, were isolated from the ethyl acetate extract of Fumana montana Pomel. Their structures were assigned by spectroscopic methods. 23398290 Retinoids and glucocorticoids target common genes in hippocampal HT22 cells. Vitamin A metabolite retinoic acid (RA) plays a major role in the aging adult brain plasticity. Conversely, chronic excess of glucocorticoids (GC) elicits some deleterious effects in the hippocampus. We questioned here the involvement of RA and GC in the expression of target proteins in hippocampal neurons. We investigated proteins involved either in the signaling pathways [RA receptor β (RARβ) and glucocorticoid receptor (GR)] or in neuron differentiation and plasticity [tissue transglutaminase 2 (tTG) and brain-derived neurotrophic factor (BDNF)] in a hippocampal cell line, HT22. We applied RA and/or dexamethasone (Dex) as activators of the pathways and investigated mRNA and protein expression of their receptors and of tTG and BDNF as well as tTG activity and BDNF secretion. Our results confirm the involvement of RA- and GC-dependent pathways and their interaction in our neuronal cell model. First, both pathways regulate the transcription and expression of own and reciprocal receptors: RA and Dex increased RARβ and decreased GR expressions. Second, Dex reduces the expression of tTG when associated with RA despite stimulating its expression when used alone. Importantly, when they are combined, RA counteracts the deleterious effect of glucocorticoids on BDNF regulation and thus may improve neuronal plasticity under stress conditions. In conclusion, GC and RA both interact through regulations of the two receptors, RARβ and GR. Furthermore, they both act, synergistically or oppositely, on other target proteins critical for neuronal plasticity, tTG and BDNF. 23501109 Synthesis and antibacterial evaluation of novel pleuromutilin derivatives. A series of novel pleuromutilin derivatives possessing thioether moiety has been synthesized via acylation reaction under mild conditions. Their in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae were tested by agar dilution method and Oxford cup assay. Among the 17 compounds screened, 14-O-[(4-methoxybenzamide-2- methylpropane-2-yl) thioacetate] mutilin 4i, 14-O-[(2-aminobenzamide-2-methylpropane-2-yl) thioacetate] mutilin 5a and 14-O-[(4-aminobenzamide-2-methylpropane-2-yl) thioacetate] mutilin 5c were resulted as most active antibacterial agents. 23246580 Effect of monospecific antibodies against baltergin in myotoxicity induced by Bothrops alternatus venom from northeast of Argentina. Role of metalloproteinases in muscle damage. Myotoxicity, one of the most relevant local manifestations in envenomation by Bothrops genus, may result from a direct action of myotoxins or be due to an indirect vascular degeneration and ischemia. Baltergin, a snake venom metalloproteinase (SVMP), isolated from Bothrops alternatus venom has been used to obtain monospecific IgG, in order to determine the relative role of toxin in myotoxicity induced by whole venom. Bothrops diporus venom, another medical relevant genus of the northeastern region of Argentina, was also studied. Anti-baltergin IgG was able to neutralize completely the hemorrhagic activity of B. alternatus venom at an antibodies:venom ratio of 30:1 (w:w). However, mice injected with B. diporus venom showed a small spot remaining even at the highest ratio of IgG:venom assayed (50:1; w:w). Specific antibodies were efficient to neutralize the myotoxicity of B. alternatus venom at ratio 30:1 (w:w) but did not neutralize the same effects in B. diporus venom. Anti-baltergin polyclonal antibodies were useful tools for revealing the central role of SVMPs in the development of myotoxicity of B. alternatus venom, as well as, helping to suggest indirectly presence of potent myotoxic phospholipases A2 (PLA2s) in B. diporus venom. 23416799 The production and characterization of anti-bothropic and anti-crotalic IgY antibodies in laying hens: a long term experiment. Ophidian accidents represent a great public health problem in developing countries. Recent studies have shown that antibodies produced in laying hens could be an alternative method for producing antivenin in mammals. In this study we analyzed the production of IgY antibodies in laying hens inoculated with snake venom from the Bothrops and Crotalus genera over a 360-day period. IgY antibodies present in the serum and egg yolks were analyzed according to avidity, antigen recognition pattern and efficiency in neutralizing the venom. The levels of anti-bothropic and anti-crotalic IgY antibodies increased significantly after the third immunization, and remained at these levels until the end of the experiment. Significantly high avidity levels were observed for anti-bothropic IgY antibodies on the 142nd day and for anti-crotalic antibodies on the 232nd day after the first immunization. Anti-bothropic IgY antibodies recognized antigens with molecular masses ranging from 25 kDa to 50 kDa, whereas anti-crotalic IgY antibodies mainly recognized antigens with molecular masses of 14 kDa and 30 kDa. An increase in the antigens recognized by the antivenins was observed during the experimental period. Samples of bothropic IgY antivenin antibodies presented an efficiency of 290 μl/3 DL50, a potency of 0.307 mg/ml and a specific activity of 0.230. Samples of anti-crotalic IgY antibodies presented an efficiency of 246 μl/4 DL50, a potency of 0.829 mg/ml and a specific activity of 0.271. These results show that the administration of successive doses of the venoms for more than 6 months results in an antivenin with higher avidity that is able to recognize a greater number of antigens present in the venoms. These characteristics indicate a more efficient and potent antivenin than what has been described in other studies. 23625272 Sequential Therapy Versus Standard Triple-Drug Therapy for Helicobacter pylori Eradication: a Systematic Review of Recent Evidence. BACKGROUND: Several alternative treatment regimens for Helicobacter pylori eradication have been proposed since the efficacy of standard triple therapy has declined over time, and sequential therapy is one of them. The purpose of this systematic review is to analyze and compare the efficacy, adverse effects and cost of sequential therapy with that of standard triple therapy for H. pylori infection. METHODS: MEDLINE, EMBASE, Google Scholar and Cochrane databases were used to retrieve all relevant articles published in the English language over the last 5 years (January 2008-October 2012). Eligibility criteria were randomized controlled trials (RCTs) comparing sequential and standard triple therapies in patients with documented H. pylori infection. Eligibility and quality of the trials were assessed independently by two reviewers, and the data regarding eradication rate, adverse effects and the cost of therapy were extracted. RESULTS: Of the 17 RCTs included in the analysis (Asia 13, Europe 3, Latin America, 1), 12 reported better eradication rates with the sequential therapy, four did not find a significant difference between the two treatment regimens, and one reported a better eradication rate with standard triple therapy. All except one RCT reported no significant difference in the incidence of adverse effects between standard triple therapy and sequential therapy. Sequential therapy was cheaper than standard triple therapy in all three RCTs where a cost analysis was performed. The limitations of the RCTs included in the systematic review were that the sequential therapy regimen and the duration of standard triple therapy were not uniform. Antibiotic susceptibility tests were performed in only three RCTs. CONCLUSIONS: While the majority of the RCTs have shown superior eradication rates with sequential therapy, the largest RCT from Latin America did not find a significant difference between the two treatment regimens. Sequential therapy has good efficacy; however, further trials other than those from Asia and Italy are required to assess its superiority over existing regimens before recommending sequential therapy as the first line of treatment for H. pylori infection. 23297023 Materiomics: an -omics approach to biomaterials research. The past fifty years have seen a surge in the use of materials for clinical application, but in order to understand and exploit their full potential, the scientific complexity at both sides of the interface--the material on the one hand and the living organism on the other hand--needs to be considered. Technologies such as combinatorial chemistry, recombinant DNA as well as computational multi-scale methods can generate libraries with a very large number of material properties whereas on the other side, the body will respond to them depending on the biological context. Typically, biological systems are investigated using both holistic and reductionist approaches such as whole genome expression profiling, systems biology and high throughput genetic or compound screening, as already seen, for example, in pharmacology and genetics. The field of biomaterials research is only beginning to develop and adopt these approaches, an effort which we refer to as "materiomics". In this review, we describe the current status of the field, and its past and future impact on the biomedical sciences. We outline how materiomics sets the stage for a transformative change in the approach to biomaterials research to enable the design of tailored and functional materials for a variety of properties in fields as diverse as tissue engineering, disease diagnosis and de novo materials design, by combining powerful computational modelling and screening with advanced experimental techniques. 23541767 The Decapping Scavenger Enzyme DCS-1 Controls MicroRNA Levels in Caenorhabditis elegans. In metazoans, microRNAs play a critical role in the posttranscriptional regulation of genes required for cell proliferation and differentiation. MicroRNAs themselves are regulated by a multitude of mechanisms influencing their transcription and posttranscriptional maturation. However, there is only sparse knowledge on pathways regulating the mature, functional form of microRNA. Here, we uncover the implication of the decapping scavenger protein DCS-1 in the control of microRNA turnover. In Caenorhabditis elegans, mutations in dcs-1 increase the levels of functional microRNAs. We demonstrate that DCS-1 interacts with the exonuclease XRN-1 to promote microRNA degradation in an independent manner from its known decapping scavenger activity, establishing two molecular functions for DCS-1. Our findings thus indicate that DCS-1 is part of a degradation complex that performs microRNA turnover in animals. 23401217 Mild oxidation of thiofunctional polymers to cytocompatible and stimuli-sensitive hydrogels and nanogels. Nanogels consist of three dimensionally cross-linked hydrophilic polymer chains and can thus be easily modified through functionalization of the polymeric building blocks, for example to yield stimuli-sensitive materials. For drug transport and intracellular release, redox-sensitive systems are especially of interest, as the intracellular space is reductive. In this study, parameters that allow preparation of nanogels with tunable size between 150 and 350 nm are systematically evaluated and identified. Most importantly, a new and mild oxidation catalyst, alloxan, is introduced for the preparation of the nanogels. This broadens the range of possible payloads to more-sensitive molecules. Particle stability, degradation in cytosolic conditions, and cytocompatibility in concentrations up to 10 mg · mL(-1) are demonstrated. 23574008 Photorheological Response of Aqueous Wormlike Micelles with Photocleavable Surfactant. Recently, we have reported a new cinnamic acid-type photocleavable surfactant, C4-C-N-PEG9 that experiences a photocleavage through UV-induced cyclization in aqueous solution, yielding a coumarin derivative (7-butoxy-2H-chromen-2-one) and an aminated polyoxyethylene compound. Here, we have studied the effects of C4-C-N-PEG9 on the photorheological behavior of viscoelastic wormlike micelles formed by aqueous mixture of nonionic surfactants, polyoxyethylene phytosterol ether (PhyEO20) and tetraoxyethylene dodecyl ether (C12EO4). The 4.9 wt % PhyEO20/H2O + 2.4 wt % C12EO4 solution forms wormlike micelles, and its viscosity is ∼10 Pa·s. We have found that the addition of C4-C-N-PEG9 into this viscous, non-Newtonian fluid system decreases the viscosity. Viscosity decreased in parallel to the C4-C-N-PEG9 concentration reaching ∼0.003 Pa·s at 2.5 wt % of C4-C-N-PEG9. However, viscosity of the C4-C-N-PEG9 incorporated system increased significantly (∼200 times at 1.5 wt % of C4-C-N-PEG9 system) upon UV irradiation. Small-Angle X-ray scattering studies have shown that addition of C4-C-N-PEG9 favors wormlike-to-sphere type transition in the micellar structure. However, UV irradiation in the C4-C-N-PEG9 incorporated system causes one-dimensional micellar growth. Since C4-C-N-PEG9 has relatively bigger headgroup size compared to the C12EO4, addition of C4-C-N-PEG9 into wormlike micelles reduces the critical packing parameter resulting in the formation of spherical aggregates. UV irradiation induced one-dimensional micellar growth is caused due to photocleavage of the C4-C-N-PEG9 into a less surface-active coumarin derivative and an aminated polyoxyethylene compound, as confirmed by UV-vis spectrometry and HPLC measurements. The hydrophobic coumarin derivative formed after cleavage of C4-C-N-PEG9 goes to the micellar core and is responsible for decreasing the viscosity. However, the hydrophilic aminated polyoxyethylene prefers to reside at the vicinity of headgroup of PhyEO20 reducing the interhead repulsion, increasing the critical packing parameter and the viscosity as well. 23194525 The nutritional supplement Active Hexose Correlated Compound (AHCC) has direct immunomodulatory actions on intestinal epithelial cells and macrophages involving TLR/MyD88 and NF-κB/MAPK activation. Active Hexose Correlated Compound (AHCC) is an immunostimulatory nutritional supplement. AHCC effects and mechanism of action on intestinal epithelial cells or monocytes are poorly described. AHCC was added to the culture medium of intestinal epithelial cells (IEC18 and HT29 cells) and monocytes (THP-1 cells) and assessed the secretion of proinflammatory cytokines by ELISA. Inhibitors of NFκB and MAPKs were used to study signal transduction pathways while TLR4 and MyD88 were silenced in IEC18 cells using shRNA. It was found that AHCC induced GROα and MCP1 secretion in IEC18 and IL-8 in HT29 cells. These effects depended on NFκB activation, and partly on MAPKs activation and on the presence of MyD88 and TLR4. In THP-1 cells AHCC evoked IL-8, IL-1β and TNF-α secretion. The induction of IL-8 depended on JNK and NFκB activation. Therefore, AHCC exerts immunostimulatory effects on intestinal epithelial cells and monocytes involving TLR4/MyD88 and NFκB/MAPK signal transduction pathways. 23297689 Chemical composition and antibacterial activities of the essential oils isolated from Juniperus thurifera L. var. Africana. This study describes the chemical composition and antibacterial activities of essential oils of Moroccan Juniperus thurifera L. var. Africana (Cupressaceae). The essential oil of dried leaves was isolated by hydrodistillation, vapohydrodistillation and microwaves. Sixty-four compounds in J. thurifera L. var. Africana oils were identified (79.9%, 92.4% and 98.4% of the oil, respectively). The most abundant compound in J. thurifera L. var. Africana oils is sabinene (38%, 36.2% and 39.4%). Antibacterial activities of J. thurifera essential oils was tested against bacteria Gram ( - ) and Gram (+). The oil is very active against all bacteria tested except Pseudomonas, which turned out to be very resistant. 23428155 Solubility-driven optimization of (pyridin-3-yl) benzoxazinyl-oxazolidinones leading to a promising antibacterial agent. The solubility-driven structural modification of (pyridin-3-yl) benzoxazinyl-oxazolidinones is described, which resulted in the development of a new series of benzoxazinyl-oxazolidinone analogues with high antibacterial activity against Gram-positive pathogens, including that against linezolid-resistant strains and low hERG inhibition. With regard to structure-activity relationship (SAR) trends among the various substituents on the pyridyl ring, relatively small and nonbasic substituents were preferable to sterically demanding or basic substituents. Oxazolidinone ring substitution on the pyridyl ring generated analogues with antibacterial activity superior to imidazolidinone ring. Solubility was enhanced by the incorporation of polar groups, especially when compounds were converted to their prodrugs. Among the prodrugs, compound 85 exhibited excellent solubility and a good pharmacokinetic profile. In a MRSA systemic infection model, compound 85 displayed an ED50 = 5.00 mg/kg, a potency that is 2-fold better than that of linezolid. 23442213 Osteogenesis of mesenchymal stem cells by nanoscale mechanotransduction. It is likely that mesenchymal stem cells will find use in many autologous regenerative therapies. However, our ability to control cell stem growth and differentiation is presently limited, and this is a major hurdle to the clinical use of these multipotent cells especially when considering the desire not to use soluble factors or complex media formulations in culture. Also, the large number of cells required to be clinically useful is currently a hurdle to using materials-based (stiffness, chemistry, nanotopography, etc.) culture substrates. Here we give a first demonstration of using nanoscale sinusoidal mechanotransductive protocols (10-14 nm displacements at 1 kHz frequency), "nanokicking", to promote osteoblastogenesis in human mesenchymal stem cell cultures. On the basis of application of the reverse piezo effect, we use interferometry to develop the optimal stem cell stimulation conditions, allowing delivery of nanoscale cues across the entire surface of the Petri dishes used. A combination of immunofluorescence, PCR, and microarray has then been used to demonstrate osteoblastogenesis, and the arrays implicate RhoA as central to osteoblastic differentiation in agreement with materials-based strategies. We validate this with pharmacological inhibition of RhoA kinase. It is easy to envisage such stimulation protocols being up-scaled to form large-scale osteoblast bioreactors as standard cell culture plates and incubators are used in the protocol. 23370795 Parallel buprenorphine phMRI responses in conscious rodents and healthy human subjects. Pharmacological magnetic resonance imaging (phMRI) is one method by which a drug's pharmacodynamic effects in the brain can be assessed. Although phMRI has been frequently used in preclinical and clinical settings, the extent to which a phMRI signature for a compound translates between rodents and humans has not been systematically examined. In the current investigation, we aimed to build on recent clinical work in which the functional response to 0.1 and 0.2 mg/70 kg i.v. buprenorphine (partial µ-opioid receptor agonist) was measured in healthy humans. Here, we measured the phMRI response to 0.04 and 0.1 mg/kg i.v. buprenorphine in conscious, naive rats to establish the parallelism of the phMRI signature of buprenorphine across species. PhMRI of 0.04 and 0.1 mg/kg i.v. buprenorphine yielded dose-dependent activation in a brain network composed of the somatosensory cortex, cingulate, insula, striatum, thalamus, periaqueductal gray, and cerebellum. Similar dose-dependent phMRI activation was observed in the human phMRI studies. These observations indicate an overall preservation of pharmacodynamic responses to buprenorphine between conscious, naive rodents and healthy human subjects, particularly in brain regions implicated in pain and analgesia. This investigation further demonstrates the usefulness of phMRI as a translational tool in neuroscience research that can provide mechanistic insight and guide dose selection in drug development. 23579182 Clinical and Subclinical Macrovascular Disease as Predictors of Cognitive Decline in Older Patients With Type 2 Diabetes: The Edinburgh Type 2 Diabetes Study. OBJECTIVEMacrovascular disease may contribute to increased risk of accelerated cognitive decline in patients with type 2 diabetes. We aimed to determine associations of measures of macrovascular disease with cognitive change in a cognitively healthy older population with type 2 diabetes.RESEARCH DESIGN AND METHODSEight-hundred thirty-one men and women (aged 60-75 years) attended two waves of the prospective Edinburgh Type 2 Diabetes Study (ET2DS). At baseline, clinical and subclinical macrovascular disease was measured, including cardiovascular event history, carotid intima-media thickness (cIMT), ankle brachial index (ABI), and serum N-terminal probrain natriuretic peptide (NT-proBNP). Seven neuropsychological tests were administered at baseline and after 4 years; scores were combined to a standardized general ability factor (g). Adjustment of follow-up g for baseline g assessed 4-year cognitive change. Adjustment for vocabulary (estimated premorbid ability) was used to estimate lifetime cognitive change.RESULTSMeasures of cognitive decline were significantly associated with stroke, NT-proBNP, ABI, and cIMT, but not with nonstroke vascular events. The association of stroke with increased estimated lifetime cognitive decline (standardized β, -0.12) and of subclinical markers with actual 4-year decline (standardized β, -0.12, 0.12, and -0.15 for NT-proBNP, ABI, and cIMT, respectively) reached the Bonferroni-adjusted level of statistical significance (P < 0.006). Results altered only slightly on adjustment for vascular risk factors.CONCLUSIONSStroke and subclinical markers of cardiac stress and generalized atherosclerosis are associated with cognitive decline in older patients with type 2 diabetes. Further investigation into the potential use of subclinical vascular disease markers in predicting cognitive decline is warranted. 23486538 Eliciting preferences for priority setting in genetic testing: a pilot study comparing best-worst scaling and discrete-choice experiments. Given the increasing number of genetic tests available, decisions have to be made on how to allocate limited health-care resources to them. Different criteria have been proposed to guide priority setting. However, their relative importance is unclear. Discrete-choice experiments (DCEs) and best-worst scaling experiments (BWSs) are methods used to identify and weight various criteria that influence orders of priority. This study tests whether these preference eliciting techniques can be used for prioritising genetic tests and compares the empirical findings resulting from these two approaches. Pilot DCE and BWS questionnaires were developed for the same criteria: prevalence, severity, clinical utility, alternatives to genetic testing available, infrastructure for testing and care established, and urgency of care. Interview-style experiments were carried out among different genetics professionals (mainly clinical geneticists, researchers and biologists). A total of 31 respondents completed the DCE and 26 completed the BWS experiment. Weights for the levels of the six attributes were estimated by conditional logit models. Although the results derived from the DCE and BWS experiments differed in detail, we found similar valuation patterns in the DCE and BWS experiments. The respondents attached greatest value to tests with high clinical utility (defined by the availability of treatments that reduce mortality and morbidity) and to testing for highly prevalent conditions. The findings from this study exemplify how decision makers can use quantitative preference eliciting methods to measure aggregated preferences in order to prioritise alternative clinical interventions. Further research is necessary to confirm the survey results.European Journal of Human Genetics advance online publication, 13 March 2013; doi:10.1038/ejhg.2013.36. 23561141 Chemical stability of astaxanthin nanodispersions in orange juice and skimmed milk as model food systems. Solubilising astaxanthin in nanodispersion systems is a promising approach to incorporate astaxanthin into water-based food formulations. In this research, the chemical stabilities of astaxanthin nanodispersions diluted in orange juice and skimmed milk as model food systems and in deionised water as a control were evaluated. The nanodispersions displayed significantly (p<0.05) better stability in food systems compared to the control. The effects of stabilisers and dilution factor were also studied. In skimmed milk and deionised water, the type of stabiliser had a significant effect (p<0.05) on astaxanthin degradation during storage. In vitro cellular uptake of astaxanthin from diluted astaxanthin nanodispersions in selected food systems was also evaluated. The cellular uptake of astaxanthin nanodispersions in skimmed milk was significantly higher (p<0.05) than that of astaxanthin nanodispersions in orange juice and deionised water. High in vitro cellular uptake of astaxanthin from the prepared astaxanthin nanodispersions can be achieved via incorporation into protein-based foods such as milk. 23016524 Molecular mechanism aspect of ER stress in Alzheimer's disease: current approaches and future strategies. Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by progressive loss of memory and cognitive impairment. Aggregation of amyloid-β (Aβ) peptides is the crucial factor in the onset of AD. The toxic Aβ peptides Aβ40 and Aβ42 are produced from the Aβ precursor protein (APP), a transmembrane protein which is folded and modified in endoplasmic reticulum (ER). ER is the main organelle for the synthesis and processing of nearly all proteins as well as the main cellular source of Ca2+. Under stress conditions, three main ER pathways including inositol-requiring enzyme 1, protein kinase RNA-like ER kinase, and activating transcription factor 6 become activated causing the accumulation of unfolded or misfolded proteins within ER lumen. These pathways manage the stress by regulating the expression of chaperones and enzymes involved in protein folding. Several studies have reported the dysfunction of these stress-sensing pathways in pathological conditions, including neurodegenerative diseases. Recent studies have proposed that neuronal death in AD arises from dysfunction of the ER. Here, we will review recent research findings on the interaction between ER and mitochondria, and its effect on apoptotic pathways. We further provide insights into studies which suggest the role of ER in animal and/or cellular models of AD. Therapeutic strategies that modulate ER could represent a promising approach for prevention or treatment of AD. 23465612 Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates. The structure-activity relationship of a series of dihydroisoquinoline BACE-1 inhibitors is described. Application of structure-based design to screening hit 1 yielded sub-micromolar inhibitors. Replacement of the carboxylic acid of 1 was guided by X-ray crystallography, which allowed the replacement of a key water-mediated hydrogen bond. This work culminated in compounds such as 31, which possess good BACE-1 potency, excellent permeability and a low P-gp efflux ratio. 23198810 Profluorogenic reductase substrate for rapid, selective, and sensitive visualization and detection of human cancer cells that overexpress NQO1. Achieving the vision of identifying and quantifying cancer-related events and targets for future personalized oncology is predicated on the existence of synthetically accessible and economically viable probe molecules fully able to report the presence of these events and targets in a rapid and highly selective and sensitive fashion. Delineated here are the design and evaluation of a newly synthesized turn-on probe whose intense fluorescent reporter signature is revealed only through probe activation by a specific intracellular enzyme present in tumor cells of multiple origins. Quenching of molecular probe fluorescence is achieved through unique photoinduced electron transfer between the naphthalimide dye reporter and a covalently attached, quinone-based enzyme substrate. Fluorescence of the reporter dye is turned on by rapid removal of the quinone quencher, an event that immediately occurs only after highly selective, two-electron reduction of the sterically and conformationally restricted quinone substrate by the cancer-associated human NAD(P)H:quinone oxidoreductase isozyme 1 (hNQO1). Successes of the approach include rapid differentiation of NQO1-expressing and -nonexpressing cancer cell lines via the unaided eye, flow cytometry, fluorescence imaging, and two-photon microscopy. The potential for use of the turn-on probe in longer-term cellular studies is indicated by its lack of influence on cell viability and its in vitro stability. 23473037 Identification of a SIRT1 mutation in a family with type 1 diabetes. Type 1 diabetes is caused by autoimmune-mediated β cell destruction leading to insulin deficiency. The histone deacetylase SIRT1 plays an essential role in modulating several age-related diseases. Here we describe a family carrying a mutation in the SIRT1 gene, in which all five affected members developed an autoimmune disorder: four developed type 1 diabetes, and one developed ulcerative colitis. Initially, a 26-year-old man was diagnosed with the typical features of type 1 diabetes, including lean body mass, autoantibodies, T cell reactivity to β cell antigens, and a rapid dependence on insulin. Direct and exome sequencing identified the presence of a T-to-C exchange in exon 1 of SIRT1, corresponding to a leucine-to-proline mutation at residue 107. Expression of SIRT1-L107P in insulin-producing cells resulted in overproduction of nitric oxide, cytokines, and chemokines. These observations identify a role for SIRT1 in human autoimmunity and unveil a monogenic form of type 1 diabetes. 23504923 Inhibitory Effect of Ketoconazole on the Pharmacokinetics of a Multireceptor Tyrosine Kinase Inhibitor BMS-690514 in Healthy Participants: Assessing the Mechanism of the Interaction With Physiologically-Based Pharmacokinetic Simulations. BMS-690514, a selective inhibitor of the ErbB and vascular endothelial growth factor receptors, has shown antitumor activity in early clinical development. The compound is metabolized by multiple enzymes, with CYP3A4 responsible for the largest fraction (34%) of metabolism. It is also a substrate of P-glycoprotein (P-gp) in vitro. To assess the effect of ketoconazole on BMS-690514 pharmacokinetics, 17 healthy volunteers received 200 mg BMS-690514 alone followed by 100 mg BMS-690514 with ketoconazole (400 mg once daily for 4 days). The AUC∞ of 100 mg BMS-690514 concomitantly administered with ketoconazole was similar to that of 200 mg BMS-690514 alone. The dose-normalized Cmax and AUC∞ of BMS-690514 from the 100-mg BMS-690514/400-mg ketoconazole treatment increased by 55% and 127%, respectively, relative to those from 200 mg BMS-690514 alone. Prediction of the drug-drug interaction (DDI) using a population-based simulator (Simcyp) indicated that, in addition to CYP3A4 inhibition, the inhibition of P-gp by ketoconazole in the intestine, liver, and kidneys must be invoked to fully account for the DDI observed. This finding suggests that the inhibition of P-gp by ketoconazole, along with its effect on CYP3A4, needs to be considered when designing a DDI study of ketoconazole with a victim drug that is a dual substrate. 23411194 Adhesive microbeads for the targeting delivery of anticaries agents of vegetable origin. The formulation of quinic acid, a food constituent demonstrating potential anticaries and antigingivitis properties, was investigated in an adhesive microparticulate delivery system with the goal of improving its effect by prolonging its residence time at the site of action. Alginate and chitosan were selected as mucoadhesive polymers. The microspheres were prepared by coacervation. Different types of alginates, polymers blends and crosslinking agent concentrations were considered and evaluated. The best results in terms of encapsulation efficiency, in vitro active agent release profile and in vitro adhesive properties, both to oral mucosa and to teeth surface, were obtained with a blend of Alginate Protanal LF200S: Alginate Protanal LF120LS 1:1.5 w/w, 0.1M CaCl(2), and chitosan coating, prepared by a one-step complex coacervation method. This microparticulate delivery system showed prolonged release of quinic acid, and could be used as an active component in chewing gums or mouthwashes for both caries and gingivitis prevention. 23183084 Progestin effects on expression of AKR1C1-AKR1C3, SRD5A1 and PGR in the Z-12 endometriotic epithelial cell line. Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity. This disease is associated with diminished protective effects of progesterone, which are usually explained by inadequate activation of progesterone receptors and also enhanced pre-receptor metabolism of progesterone. Endometriosis is often treated with progestins, which act as progesterone receptor agonists, although their exact mechanisms of action are not completely understood. The aim of the present study was to investigate how the progestins medroxyprogesterone acetate, dydrogesterone and dienogest, as well as progesterone, impact on the expression of genes of pre-receptor progesterone metabolism in Z-12 epithelial cell line, a model system of peritoneal endometriosis. Our data demonstrate that these progestins affect local pre-receptor metabolism to a different extent. The most favorable effects were seen for dydrogesterone and dienogest, where the first, dydrogesterone, significantly reduced SRD5A1, AKR1C2 and AKR1C3 expression, and additionally had a nonsignificant impact on progesterone receptor B (PR-B) protein levels. This might slow down the first step of pre-receptor metabolism, the conversion of progesterone to 5α-dihydroprogestrone by SRD5A1, and it might also affect further reduction of 3-keto and 20-keto groups catalyzed by AKR1C2 and AKR1C3. Similarly favorable effects were seen for dienogest, which promoted significant reduction of AKR1C1 and AKR1C2 expression and also showed no effect on PR-B protein levels. Different effects were seen for progesterone, which significantly decreased SRD5A1, PR-B and HSD17B2 protein levels. In contrast, treatment with medroxyprogesterone acetate resulted in increased AKR1C1 expression and decreased levels of PR-B, which might lead to enhanced progesterone metabolism and reduced signaling through progesterone receptors. Altogether, our data in this Z-12 cell model suggest that the beneficial effects of treatment with progestin observed in endometriosis patients might arise from decreased pre-receptor metabolism of the protective progesterone by the SRD5A1 and AKR1C enzymes. 22776039 GLP-1 receptor activated insulin secretion from pancreatic β-cells: mechanism and glucose dependence. The major goal in the treatment of type 2 diabetes mellitus is to control the hyperglycaemia characteristic of the disease. However, treatment with common therapies such as insulin or insulinotrophic sulphonylureas (SU), while effective in reducing hyperglycaemia, may impose a greater risk of hypoglycaemia, as neither therapy is self-regulated by ambient blood glucose concentrations. Hypoglycaemia has been associated with adverse physical and psychological outcomes and may contribute to negative cardiovascular events; hence minimization of hypoglycaemia risk is clinically advantageous. Stimulation of insulin secretion from pancreatic β-cells by glucagon-like peptide 1 receptor (GLP-1R) agonists is known to be glucose-dependent. GLP-1R agonists potentiate glucose-stimulated insulin secretion and have little or no activity on insulin secretion in the absence of elevated blood glucose concentrations. This 'glucose-regulated' activity of GLP-1R agonists makes them useful and potentially safer therapeutics for overall glucose control compared to non-regulated therapies; hyperglycaemia can be reduced with minimal hypoglycaemia. While the inherent mechanism of action of GLP-1R agonists mediates their glucose dependence, studies in rats suggest that SUs may uncouple this dependence. This hypothesis is supported by clinical studies showing that the majority of events of hypoglycaemia in patients treated with GLP-1R agonists occur in patients treated with a concomitant SU. This review aims to discuss the current understanding of the mechanisms by which GLP-1R signalling promotes insulin secretion from pancreatic β-cells via a glucose-dependent process. 23456681 Hierarchical porous surface for efficiently controlling microdroplets' self-removal. Superhydrophobic porous surfaces with hydrophilic polymers adsorbed in pores are designed to control the coalescing behavior of microdroplets as well as their quick self-removal. The combination of chemical composition and surface structure are greatly important in the design of new materials for heat exchange, antifogging, and anti-icing. 23161373 Ecological risk assessment in the context of global climate change. Changes to sources, stressors, habitats, and geographic ranges; toxicological effects; end points; and uncertainty estimation require significant changes in the implementation of ecological risk assessment (ERA). Because of the lack of analog systems and circumstances in historically studied sites, there is a likelihood of type III error. As a first step, the authors propose a decision key to aid managers and risk assessors in determining when and to what extent climate change should be incorporated. Next, when global climate change is an important factor, the authors recommend seven critical changes to ERA. First, develop conceptual cause-effect diagrams that consider relevant management decisions as well as appropriate spatial and temporal scales to include both direct and indirect effects of climate change and the stressor of management interest. Second, develop assessment end points that are expressed as ecosystem services. Third, evaluate multiple stressors and nonlinear responses-include the chemicals and the stressors related to climate change. Fourth, estimate how climate change will affect or modify management options as the impacts become manifest. Fifth, consider the direction and rate of change relative to management objectives, recognizing that both positive and negative outcomes can occur. Sixth, determine the major drivers of uncertainty, estimating and bounding stochastic uncertainty spatially, temporally, and progressively. Seventh, plan for adaptive management to account for changing environmental conditions and consequent changes to ecosystem services. Good communication is essential for making risk-related information understandable and useful for managers and stakeholders to implement a successful risk-assessment and decision-making process. 23407893 Imogolite-like nanotubes: structure, stability, electronic and mechanical properties of the phosphorous and arsenic derivatives. Imogolite is a single-walled aluminosilicate nanotube (NT) found in nature that can be easily synthesized, as well as its analogue aluminogermanate NT. Based on geometrical assumptions and pKa values, species such as H3PO4, H3PO3, H3AsO3, H3AsO4 could also be candidates to form imogolite-like structures. In the present work, we provide insights about the stability, electronic, structural and mechanical properties of possible imogolite like NTs by means of self-consistent charge density-functional tight-binding method (SCC-DFTB). Similarly to aluminogermanate, where the tetrahedral silicate groups are replaced by germanate, in this work tetrahedral silicate groups are substituted by phosphate, phosphite, arsenate and arsenite units in the imogolite structure. Detailed analysis is focused on structural properties, strain energy, band gap and Mulliken charges distribution. The calculated strain energy curves for all studied zigzag imogolite-like NTs present well-defined minima, which change as a consequence of composition variation. Moreover, the strain energy curves of armchair imogolite-like NTs also present minima, although in all cases less stable than zigzags by at least 2.2 meV per atom. The insulating NT behaviour changes after internal modification from silicate to phosphate, phosphite, arsenate and arsenite, as well as the charge distribution inside and outside the nanotubes. 23027804 Mechanisms in endocrinology. Role of emotional stress in the pathophysiology of Graves' disease. The role of stress in the pathophysiology of Graves' disease is suggested by several clinical observations, by recent advances in immunology and by better understanding of autoimmune diseases which provides new insights into potential effects of stress hormones on T helper cell imbalance involved in the pathogenesis of autoimmune diseases. Stress management should therefore be an important part of the treatment of Graves' disease, as stress reduction may improve the effect of therapy. However, this field still requires interventional data to support stress management in the treatment of Graves' disease. 23564646 ALLERGIC SKIN INFLAMMATION INDUCED BY CHEMICAL SENSITIZERS IS CONTROLLED BY THE TRANSCRIPTION FACTOR NRF2. Allergic contact dermatitis (ACD) is induced by low molecular weight electrophilic chemicals and metal ions. Chemical contact sensitizers trigger reactive oxygen species (ROS) production and provoke electrophilic stress leading to the accumulation of the transcription factor nuclear related factor 2 (Nrf2) in innate immune cell types. The objective of this work was to identify the role of Nrf2 in the regulation of ACD. We used the Local Lymph Node Assay (LLNA) and the Mouse Ear Swelling Test (MEST) to study the role of Nrf2 in both the sensitization and elicitation phase in nrf2 knock out (nrf2(-/-)) and wild type (nrf2(+/+)) mice. Five chemicals were used: two compounds known to react with cysteine residues, 2,4-dinitrochlorobenzene (DNCB) and cinnamaldehyde (CinA); one sensitizer known to exhibit mixed reactivity to cysteine and lysine residues, isophorone diisocyanate (IPDI); and one reacting specifically with lysine residues, trimellitic anhydride (TMA) and croton oil a well-known irritant. In the MEST assay, DNCB (1% and 2%) induced a significant increase in ear thickness in nrf2(-/-) as compared to nrf2(+/+) mice suggesting a role for Nrf2 in the control of the inflammatory process. When DNCB was used at 0.25% and 0.5% or when mice were treated with CinA, inflammation was found only in nrf2(-/-) mice. In the LLNA all chemical sensitizers induced an increase of lymphocyte proliferation in nrf2(-/-) compared to nrf2(+/+) mice for the same chemical concentration.These results reveal an important role for Nrf2 in controlling ACD and lymphocyte proliferation in response to sensitizers. 23316964 Matrix metalloproteinases as drug targets in preeclampsia. Preeclampsia is an important syndrome complicating pregnancy. While the pathogenesis of preeclampsia is not entirely known, poor placental perfusion leading to widespread maternal endothelial dysfunction is accepted as a major mechanism. It has been suggested that altered placental expression of matrix metalloproteinases (MMPs) may cause shallow cytotrophoblastic invasion and incomplete remodeling of the spiral arteries. MMPs are also thought to link placental ischemia to the cardiovascular alterations of preeclampsia. In fact, MMPs may promote vasoconstriction and surface receptors cleavage affecting the vasculature. Therefore, the overall goal of this review article is to provide an overview of the pathophisiology of preeclampsia, more specifically regarding the role of MMPs in the pathogenesis of preeclampsia and the potential of MMP inhibitors as therapeutic options. 23352910 Cell penetrating peptide tethered bi-ligand liposomes for delivery to brain in vivo: Biodistribution and transfection. Targeted nano-particulate systems hold extraordinary potential for delivery of therapeutics across blood brain barrier (BBB). In this work, we investigated the potential of novel bi-ligand (transferrin-poly-l-arginine) liposomal vector for delivery of desired gene to brain, in vivo. The in vivo evaluation of the delivery vectors is essential for clinical translation. We followed an innovative approach of combining transferrin receptor targeting with enhanced cell penetration to design liposomal vectors for improving the transport of molecules into brain. The biodistribution profile of 1, 1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine iodide(DiR)-labeled liposomes was evaluated in adult rats after single intravenous injection at dose of 15.2μmoles of phospholipids/kg body weight. We demonstrated that bi-ligand liposomes accumulated in rat brain at significantly (p<0.05) higher concentrations as compared to the single-ligand (transferrin) or plain liposomes. In addition, the bi-ligand liposomes resulted in increased expression of β-galactosidase(β-gal) plasmid in rat brain tissue in comparison to the single-ligand liposomes. Histological examination of the transfected tissues did not show any signs of tissue necrosis or inflammation. Hemolysis assay further authenticated the biocompatibility of bi-ligand liposomes in blood up to 600 nmoles of phospholipids/1.4×10(7) erythrocytes. The findings of this study provide important and detailed information regarding the distribution of bi-ligand liposomes in vivo and accentuate their ability to demonstrate improved brain penetration and transfection potential over single-ligand liposomes. 23475433 Electrophysiological study for comparing the effect of biological activity between type A botulinum toxins in rat gastrocnemius muscle. Background: New cosmetic applications and products based on the effects of botulinum toxin (BTX) treatment have stimulated demand for this class of natural compounds. This demand generates the need for appropriate standardized protocols to test and compare the effectiveness of new BTX preparations.Objectives: Based on the previously described electrophysiological methods, we measured and compared the inhibitory effects of two BTX type A (BTX-A) preparations on neuromuscular transmission through split-body test.Methods: The effectiveness was evaluated in terms of the compound muscle action potential (CMAP) and conduction velocity after BTX-A injection. We used a split-body method to compare two different BTX-As in the rat.Results: Based on the changes in the CMAP, the two different BTX-As induced paralytic effect on the rat tibialis anterior muscle. However, the two different BTX-A preparations did not differ significantly in effectiveness and did not induce a delay in conduction velocity.Conclusions: The new BTX-A preparation used in this electrophysiological study had similar effect compared with the previously marketed BTX-A.[AQ: Please approve the edits made to the sentence "The new BTX-A preparation…") We propose that a split-body electrophysiological protocol will be useful in establishing the comparative effectiveness of new BTX products. 23444783 Effects of insulin-like growth factor-1 on neurochemical phenotypes of cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate. Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays an important role in promoting axonal growth from dorsal root ganglion (DRG) neurons. The neuropeptide- and neurofilament (NF)-immunoreactive (IR) neurons are two major phenotypical classes in DRG. Whether IGF-1 affects neurochemical phenotypes of DRG neurons remains unknown. In the present study, primary cultured DRG neurons were used to determine the effects of IGF-1 on neurochemical phenotypes of the neurons with excitotoxicity induced by glutamate (Glu). DRG neurons were dissociated and cultured for 48 hours and then exposed to IGF-1 (20 nmol/L), Glu (0.2 mmol/L), Glu (0.2 mmol/L) plus IGF-1 (20 nmol/L) for additional 24 hours. The DRG neurons were continuously exposed to culture media as control. After that, all above cultured DRG neurons were processed for detecting mRNA levels of calcitonin gene-related peptide (CGRP) and neurofilament-200 (NF-200) by real time-PCR analysis. CGRP and NF-200 expression in situ was determined by fluorescent labeling technique. The results showed that CGRP mRNA, but not NF-200 mRNA, increased after IGF-1 administration in the absence or presence of Glu. IGF-1 could increase the percentage of CGRP-expressing neurons, but not NF-200-expressing neurons, in the absence or presence of Glu. The ability of IGF-1 on CGRP expression may play a role in neurogenic inflammation or nociception. 23409925 Multifunctional carboxymethyl cellulose-based magnetic nanovector as a theragnostic system for folate receptor targeted chemotherapy, imaging, and hyperthermia against cancer. A multifunctional biocompatible nanovector based on magnetic nanoparticle and carboxymethyl cellulose (CMC) was developed. The nanoparticles have been characterized using TEM, SEM, DLS, FT-IR spectra, VSM, and TGA studies. We found that the synthesized carboxymethyl cellulose magnetic nanoparticles (CMC MNPs) were spherical in shape with an average size of 150 nm having low aggregation and superparamagnetic properties. We found that the folate-tagged CMC MNPs were delivered to cancer cells by a folate-receptor-mediated endocytosis mechanism. 5-FU was encapsulated as a model drug for delivering cytotoxicity, and we could demonstrate the sustained release of 5-FU. It was also observed that the FITC-labeled CMC MNPs could effectively enter cells, and the fate of nanoparticles was tracked with Lysotracker. The CMC MNPs could induce significant cell death when an alternating magnetic field was applied. These results indicate that the multifunctional CMC MNPs possess a high drug loading efficiency and high biocompatibility and with low cell cytotoxicity and can be considered to be promising candidates for CMC-based targeted drug delivery, cellular imaging, and magnetic hyperthermia (MHT). 23584545 Synthesis and in vitro antiproliferative effect of novel quinoline-based potential anticancer agents. Several derivatives with a quinoline scaffold and a flexible, semi-flexible or rigid side chains at position 8 of the quinoline ring were synthesized and assessed for their in vitro activity versus the human colon cancer cell line HT29 and the human breast cancer cell line MDA-MB231. The HT29 cell line was more refractory to the cytotoxic activity of some compounds, meanwhile all the quinoline derivatives except one displayed high to moderate activity against MDA-MB231 with IC50 values ranging between 4.6 and 48.2 μM. The most active derivative in this study against both tested cell lines was the Schiff's base 4e with IC50 of 4.7 and 4.6 μM against HT29 and MDA-MB231, respectively. 23421737 Novel microbial transformation of desacetylcinobufagin by Fusarium avenaceum AS 3.4594. In this paper, the microbial transformation of desacetylcinobufagin (1) by Fusarium avenaceum AS 3.4594 was investigated, and four metabolites were isolated and characterized as 3-keton-desacetylcinobufagin (2), 3-epi-desacetylcinobufagin (3), bufadienolide A (4), and 15β,16α-dihydroxyl-17βH-bufalin (5), respectively. Among them, 4 and 5 are new compounds. The cytotoxicities of transformed products (2-5) against Hela cells were also investigated. 23343200 Physically-motivated force fields from symmetry-adapted perturbation theory. We present a general methodology for generating accurate and transferable ab initio force fields, employing the framework of symmetry adapted perturbation theory (SAPT). The resulting force fields are "physically-motivated" in that they contain separate, explicit terms to account for the various fundamental intermolecular interactions, such as exchange, electrostatics, induction, and dispersion, with each term parametrized to a corresponding term in the SAPT energy decomposition. Crucially, the resulting force fields are largely compatible with existing, standard simulation packages, requiring only minimal modifications. We present several novel parametrization techniques that yield robust, physically meaningful atomic parameters that are transferable between molecular environments. We demonstrate the accuracy and generality of our method by validating against experimental second virial coefficients for a variety of small molecules. We then show that the resulting atomic parameters can be combined using physically motivated ansatzes to accurately predict arbitrary heteromolecular interaction energies, with example applications including prediction of gas adsorption in functionalized metal-organic framework materials. 23336368 Separation and structure elucidation of a new homoflavanol derivative from Pteridium aquilinum (L.) Kuhn. A novel homoflavanol derivative (1) with an unprecedented skeleton, as well as two known flavonoids kaempferol (2) and quercetin (3), was isolated from the plant Pteridium aquilinum (L.) Kuhn, and the structure and relative stereochemistry of the new compound (1) were elucidated on the basis of spectroscopic data. 23549673 Long-term Effects of Perinatal Androgenization on Reproductive Parameters of Male Rat Offspring Androgenization and Male Rat Reproduction. It is known that during sex differentiation, fetal androgens are critical determinants of the male phenotype. Although testosterone is necessary for normal development of male sexual behavior, perinatal androgen treatment can result in disruption of normal male sexual reproduction. Pregnant Wistar rats were administered either corn oil (vehicle) or testosterone propionate at 0.2 mg/kg from gestational day 12 until the end of lactation and the reproductive function of male offspring was evaluated at 90 (adulthood) and 270 (middle age) days of age. Perinatal androgenization in the rat provoked a reduction in sperm production and reserves in adulthood that did not affect fertility and did not persist at more advanced ages, as shown by the results at post-natal day 270. If perinatal androgenization promotes similar effects in humans of reproductive age, the results of the present work can impact male reproduction health, given the less efficient spermatogenesis and lower sperm reserves in the human epididymis, compared to rodents. 22693035 Angiotensin-Converting Enzyme Inhibitory Activity and Antioxidant Properties of Nepeta crassifolia Boiss & Buhse and Nepeta binaludensis Jamzad. This article reports phytochemical and biological studies on Nepeta binaludensis and Nepeta crassifolia. Both species were investigated for their angiotensin-converting enzyme (ACE) inhibitory activity and antioxidant properties through three in vitro models [2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and ferric reducing antioxidant power (FRAP) assay]. Aerial parts were extracted with methanol and partitioned between water and subsequently n-hexane, ethyl acetate and n-butanol. N. binaludensis methanol extract exerted significantly higher reducing power (1.9 μM Fe(II)/g) than did the positive control butylhydroxytoluene (63.2 μM Fe(II)/g) in FRAP assay. The highest DPPH radical scavenging activity was found for N. crassifolia, with IC50 values of 9.6 and 12.1 µg/mL for ethyl acetate and n-butanol fractions, respectively. n-Butanol fraction of both species showed the highest ACE inhibitory activity, with IC50 values of 59.3 and 81.7 µg/mL for N. binaludensis and N. crassifolia, respectively. Phytochemical investigations resulted in the isolation of ursolic acid, oleanolic acid, apigenin, luteolin and ixoroside. Apigenin-7-O-glucoside, 8-hydroxycirsimaritin and cirsimaritin were furthermore identified in N. crassifolia ethyl acetate-soluble fraction. Nepetanudoside B was isolated from the n-butanol fraction of N. binaludensis. Copyright © 2012 John Wiley & Sons, Ltd. 23603059 Arsenic upregulates the expression of angiotensin II Type I receptor in mouse aortic endothelial cells. Although chronic arsenic exposure is a well-known risk for cardiovascular disease and has a strong correlation with hypertension, the molecular pathogenesis underlying arsenic exposure-induced hypertension remains poorly understood. To delineate the pathogenesis, we examined changes in the mRNA levels of 2 angiotensin II Type I receptor (AT1R) subtypes, AT1AR and AT1BR, in a mouse aortic endothelial cell line, END-D. Quantitative real-time PCR analysis revealed significant increases in the mRNA levels of 2 AT1R subtypes, AT1AR and AT1BR following sodium arsenite (SA) treatment. Flow cytometry analysis revealed that SA increases the generation of reactive oxygen species (ROS) in a dose-dependent manner. In addition, western blot analysis revealed that SA enhances the phosphorylations of c-Jun N-terminal kinases (JNK) and activated protein 1 (AP-1). These phosphorylations were inhibited by N-acetylcysteine (NAC), an anti-oxidant. Finally, SA-induced AT1R expression was found to be prevented both by NAC and specific JNK inhibitor, SP6001325, strongly indicating that AT1R upregulation is a result of the ROS-mediated activation of the JNK signaling pathway. Taken together, our results indicate that arsenic indeed upregulates the AT1R expression, thus highlighting a role of arsenic-induced aberrant AT1R signaling in the pathogenesis of hypertension. 23565574 Applicability of a Blood-Brain Barrier Specific Artificial Membrane Permeability Assay at the Early Stage of Natural Product-Based CNS Drug Discovery. While numerous natural products (NPs) possess activity on central nervous system (CNS) targets, there has been no analytical approach to effectively identify compounds with high brain penetration potential in complex mixtures at the early stage of drug discovery. To overcome this issue, the performance of an in vitro parallel artificial membrane permeability assay for the blood-brain barrier (PAMPA-BBB) for natural products and for plant extracts has been validated and characterized. It was found that the PAMPA-BBB assay preserves its predictive power in the case of natural products and provides high phytochemical selectivity, which enables its use as a unique filtering tool in terms of selecting brain-penetrable compounds from plant extracts. Moreover, the present study has demonstrated that simple modifications in the assay design allow the direct use of PAMPA-BBB filtered samples in a dereplication process, as performed by NMR and LC-MS. The applicability of this procedure was demonstrated using extracts prepared from Tanacetum parthenium, Vinca major, Salvia officinalis, and Corydalis cava, representing different types of chemical diversity and complexity. Thus, the proposed protocol represents a potentially valuable strategy in the NP-based CNS drug discovery environment with a high-throughput screening platform. 23561076 Blueberry estimated harvest from seven new cultivars: Fruit and anthocyanins. This study compares the yields, weights and anthocyanin contents of fruit from a group of seven new cultivars released from the New Zealand blueberry breeding programme and selected for the longest possible combined harvest season. The measured factors were primarily influenced by cultivar, and seasonal variations had relatively minor effects. The late-ripening cultivars 'Velluto Blue' and 'Centra Blue' had the highest fruit yields, anthocyanin contents and estimated total anthocyanin harvestable from a given area. 'Blue Moon' and 'Sky Blue' had the largest fruit sizes. The early-ripening cultivars 'Blue Bayou', 'Blue Moon' and 'Sunset Blue' had the lowest anthocyanin contents. The yield, fruit size and total anthocyanin content results obtained from any single year were highly correlated with the average of the three years, which makes pursuing the evaluation for these traits from a single year and at an early stage of plant development a practical proposition. 23563178 Myeloid cell RelA/p65 promotes lung cancer proliferation through Wnt/β-catenin signaling in murine and human tumor cells. Smoking is the most important risk factor for both lung cancer (LC) and chronic obstructive pulmonary disease. The aim of this study was to investigate the role of myeloid cell nuclear factor-κB in the regulation of tumor cell growth signaling. We subjected mice lacking myeloid RelA/p65 (rela(Δ-/-)) to a metastatic LC model. Cigarette smoke (CS) exposure significantly increased the proliferation of Lewis lung carcinoma cell tumors in wild-type mice. In CS-exposed rela(Δ-/-) mice, the tumor growth was largely inhibited. Transcriptome and pathway analysis of cancer tissue revealed a fundamental impact of myeloid cells on various growth signaling pathways, including the Wnt/β-catenin pathway. In conclusion, myeloid RelA/p65 is necessary to link smoke-induced inflammation with LC growth and has a role in the activation of Wnt/β-catenin signaling in tumor cells.Oncogene advance online publication, 8 April 2013; doi:10.1038/onc.2013.75. 23639423 Gene flow vs. pollution pressure: Genetic diversity of Mytilus galloprovincialis in eastern Adriatic. Environmental pollution may modify all the evolutionary processes involved in shaping the genetic patterns of exposed populations. In order to evaluate the pollution impact on the genetic diversity of Mediterranean mussel Mytilus galloprovincialis ten populations inhabiting differently polluted sites along the eastern Adriatic coast, from pristine bays to heavily trafficked harbours, were studied. Pollution pressure was assessed through an integrated study of biological effects and responses across different levels of biological organization. Eight microsatellite markers were analysed to assess genetic diversity of investigated populations. Both the principal component analysis (PCA) of the biomarker data set as well as the biomarker response index (BRI) confirmed substantial pollution pressure at the highly polluted sites, and very low pollution exposure at the three reference sites. Very shallow genetic differentiation was found in respect to maritime distances or pollution status, and this was attributed to a high gene flow among the populations. However, populations inhabiting polluted sites exhibited higher levels of genetic diversity and evolutionary mechanisms underlying this phenomenon are discussed. 23603380 Piperidine, pyridine alkaloid inhibition of fetal movement in a day 40 pregnant goat model. Inhibition of fetal movement is one mechanism behind the development of multiple congenital contracture-type defects in developing fetuses of humans and animals. We tested the alkaloids anabasine, lobeline, and myosmine for agonist actions, and sensitivity to alpha conotoxins EI and GI blockade at fetal muscle-type nicotinic acetylcholine receptors (nAChR) expressed by TE-671 cells. We also determined if the alkaloids decreased fetal movement in an IV dosed, day 40 pregnant goat model. In TE-671 cells, all three alkaloids elicited concentration-dependent changes in membrane potential sensing dye fluorescence. 1.0μM alpha conotoxin GI shifted the concentration-effect curves of anabasine and myosmine to the right, and decreased maximal responses. Neither of the conotoxins blocked the actions of lobeline in TE-671 cells. In the day 40 pregnant goats, 0.8mg/kg anabasine abolished fetal movement at 30 and 60min after dosing and fetal movement was reduced by lobeline and myosmine. The blockade of anabasine and myosmine actions in TE-671 cells by alpha conotoxin GI indicates that they are agonists at fetal muscle-type nAChR. All three alkaloids did significantly decrease fetal movement in the day 40 pregnant goat model suggesting a potential for these alkaloids to cause multiple congenital contracture-type defects in developing fetuses. 23612423 Gastroprotective mechanism of Bauhinia thonningii Schum. ETHNOPHARMACOLOGICAL RELEVANCE: Bauhinia thonningii Schum. (Cesalpiniaceae) is locally known as Tambarib and used to treat various diseases including gastric ulcer. AIM OF THE STUDY: The current study aims to evaluate the gastroprotecive mechanism(s) of methanolic (MEBT) and chloroform (CEBT) extracts of Bauhinia thonningii leaves on ethanol-induced gastric ulceration. MATERIALS AND METHODS: Gastric acidity, quantification and histochemistry of mucus, gross and microscopic examination, nitric oxide, lipid peroxidation, 2D gel electrophoresis, mass spectroscopy and biochemical tests were utilized to assess the mechanism(s) underlying the gastroprotective effects of MEBT and CEBT. Effect of these extracts into lipopolysaccharide/interferon-γ stimulated rodent cells were done in vitro. In vitro and in vivo toxicity studies were also conducted. Antioxidant activities of MEBT and CEBT were examined using DPPH, FRAP and ORAC assays. Phytochemical analyses of MEBT and CEBT were conducted using chemical and spectroscopic methods. RESULTS: Gross and histological features confirmed the anti-ulcerogenic properties of Bauhinia thonningii. Gastroprotective mechanism of MEBT was observed to be mediated through the modulation of PAS-reactive substances, MDA and proteomics biomarkers (creatine kinase, malate dehydrogenase, ATP synthase, actin and thioredoxin). MEBT and CEBT showed no significant in vitro and in vivo effects on nitric oxide. Methanolic extract (MEBT) showed superior gastroprotective effects, polyphenolic content and antioxidant activities compared to CEBT. The plant extracts showed no in vitro or in vivo toxicity. CONCLUSION: It could be concluded that MEBT possesses anti-ulcer activity, which could be attributed to the inhibition of ethanol-induced oxidative damage and the intervention in proteomic pathways but not the nitric oxide pathway. 23022398 NMDA receptor blockade impairs the muscarinic conversion of sub-threshold transient depression into long-lasting LTD in the hippocampus-prefrontal cortex pathway in vivo: correlation with gamma oscillations. Cholinergic fibers from the brainstem and basal forebrain innervate the medial prefrontal cortex (mPFC) modulating neuronal activity and synaptic plasticity responses to hippocampal inputs. Here, we investigated the muscarinic and glutamatergic modulation of long-term depression (LTD) in the intact projections from CA1 to mPFC in vivo. Cortical-evoked responses were recorded in urethane-anesthetized rats for 30 min during baseline and 4 h following LTD. In order to test the potentiating effects of pilocarpine (PILO), independent groups of rats received either a microinjection of PILO (40 nmol; i.c.v.) or vehicle, immediately before or 20 min after a sub-threshold LTD protocol (600 pulses, 1 Hz; LFS600). Other groups received either an infusion of the selective NMDA receptor antagonist (AP7; 10 nmol; intra-mPFC) or vehicle, 10 min prior to PILO preceding LFS600, or prior to a supra-threshold LTD protocol (900 pulses, 1 Hz; LFS900). Our results show that PILO converts a transient cortical depression induced by LFS600 into a robust LTD, stable for at least 4 h. When applied after LFS600, PILO does not change either mPFC basal neurotransmission or late LTD. Our data also indicate that NMDA receptor pre-activation is essential to the muscarinic enhancement of mPFC synaptic depression, since AP7 microinjection into the mPFC blocked the conversion of transient depression into long-lasting LTD produced by PILO. In addition, AP7 effectively blocked the long-lasting LTD induced by LFS900. Therefore, our findings suggest that the glutamatergic co-activation of prefrontal neurons is important for the effects of PILO on mPFC synaptic depression, which could play an important role in the control of executive and emotional functions. 23200778 Selective induction of glutathione S-transferases in round spermatids from the Brown-Norway rat by the chemotherapeutic regimen for testicular cancer. Chemotherapeutic drugs can affect DNA in male germ cells, thereby impacting on the integrity of the genome transmitted to offspring. Drug metabolizing enzymes can protect cells from xenobiotic insult. We analyzed the expression pattern of such enzymes in isolated round spermatids from rats exposed to drugs used to treat testicular cancer: bleomycin, etoposide, and cisplatin (BEP). The number of isozymes expressed and the overall relative expression values were highest for the glutathione S-transferases (GSTs). Moreover, BEP treatment significantly increased the expression of 8 GSTs and 3 aldehyde dehydrogenases. Increased expression of GST isozymes was confirmed by qRT-PCR and Western blot analysis. Although Gst genes can be targets for epigenetic modifications, promoter DNA methylation was not affected by BEP treatment. As GSTs are involved in drug resistance mechanisms, we hypothesize that BEP induction of GST expression may lead to the survival of damaged germ cells and the production of abnormal sperm. 23252848 Antiproliferative withanolides from Datura wrightii. A new withanolide, named withawrightolide (1), and four known withanolides (2-5) were isolated from the aerial parts of Datura wrightii. The structure of compound 1 was elucidated through 2D NMR and other spectroscopic techniques. In addition, the structure of withametelin L (2) was confirmed by X-ray crystallographic analysis. Using MTS viability assays, withanolides 1-5 showed antiproliferative activities against human glioblastoma (U251 and U87), head and neck squamous cell carcinoma (MDA-1986), and normal fetal lung fibroblast (MRC-5) cells with IC50 values in the range between 0.56 and 5.6 μM. 23537321 Spray drying method for large-scale and high-performance silicon negative electrodes in li-ion batteries. Nanostructured silicon electrodes have shown great potential as lithium ion battery anodes because they can address capacity fading mechanisms originating from large volume changes of silicon alloys while delivering extraordinarily large gravimetric capacities. Nonetheless, synthesis of well-defined silicon nanostructures in an industrially adaptable scale still remains as a challenge. Herein, we adopt an industrially established spray drying process to enable scalable synthesis of silicon-carbon composite particles in which silicon nanoparticles are embedded in porous carbon particles. The void space existing in the porous carbon accommodates the volume expansion of silicon and thus addresses the chronic fading mechanisms of silicon anodes. The composite electrodes exhibit excellent electrochemical performance, such as 1956 mAh/g at 0.05C rate and 91% capacity retention after 150 cycles. Moreover, the spray drying method requires only 2 s for the formation of each particle and allows a production capability of ∼10 g/h even with an ultrasonic-based lab-scale equipment. This investigation suggests that established industrial processes could be adaptable to the production of battery active materials that require sophisticated nanostructures as well as large quantity syntheses. 23381974 Graded doping for enhanced colloidal quantum dot photovoltaics. A novel approach to improving all-inorganic colloidal quantum dot (CQD) homojunction solar cells by engineering the doping spatial profile to produce a doping gradient within the n-type absorber is presented. The doping gradient greatly improves carrier collection and enhances the voltages attainable by the device, leading to a 1 power point power conversion efficiency (PCE) improvement over previous inorganic CQD solar cells. 23241354 Biomolecular Interactions of small-molecule inhibitors affecting the YopH protein tyrosine phosphatase. We have developed competitive and direct binding methods to examine small-molecule inhibitors of protein tyrosine phosphatase activity. Focusing on the Yersinia pestis outer protein H, a potent bacterial protein tyrosine phosphatase, we describe how an understanding of the kinetic interactions involving Yersinia pestis outer protein H, peptide substrates, and small-molecule inhibitors of protein tyrosine phosphatase activity can be beneficial for inhibitor screening, and we further translate these results into a microarray assay for high-throughput screening. 23429911 Molecular mechanism regulating 24-hour rhythm of dopamine d3 receptor expression in mouse ventral striatum. The dopamine D3 receptor (DRD3) in the ventral striatum is thought to influence motivation and motor functions. Although the expression of DRD3 in the ventral striatum has been shown to exhibit 24-hour variations, the mechanisms underlying the variation remain obscure. Here, we demonstrated that molecular components of the circadian clock act as regulators that control the 24-hour variation in the expression of DRD3. The transcription of DRD3 was enhanced by the retinoic acid-related orphan receptor α (RORα), and its activation was inhibited by the orphan receptor REV-ERBα, an endogenous antagonist of RORα. The serum or dexamethasone-induced oscillation in the expression of DRD3 in cells was abrogated by the downregulation or overexpression of REV-ERBα, suggesting that REV-ERBα functions as a regulator of DRD3 oscillations in the cellular autonomous clock. Chromatin immunoprecipitation assays of the DRD3 promoter indicated that the binding of the REV-ERBα protein to the DRD3 promoter increased in the early dark phase. DRD3 protein expression varied with higher levels during the dark phase. Moreover, the effects of the DRD3 agonist 7-hydroxy-N,N-dipropyl-2-aminotetralin (7-OH-DPAT)-induced locomotor hypoactivity were significantly increased when DRD3 proteins were abundant. These results suggest that RORα and REV-ERBα consist of a reciprocating mechanism wherein RORα upregulates the expression of DRD3, whereas REV-ERBα periodically suppresses the expression at the time of day when REV-ERBα is abundant. Our present findings revealed that a molecular link between the circadian clock and the function of DRD3 in the ventral striatum acts as a modulator of the pharmacological actions of DRD3 agonists/antagonists. 23117149 The relationship between bone marrow characteristics and the clinical prognosis of antithyroid drug-induced agranulocytosis. This study is aimed to explore the relationship between bone marrow characteristics and clinical prognosis of antithyroid drug (ATD) induced agranulocytosis. A retrospective study was conducted in the first affiliated hospital of the University of South China. A total of 33 hospitalized patients diagnosed with ATD-induced agranulocytosis were analyzed. The bone marrow characteristics were classified into two types. Type I was characterized by reduction or absence of granulocytic precursors and type II was recognized as hypercellular bone marrow with dysmaturity of granulocytic cells. Bone marrow of 20 cases (61%) were characterized with type I whereas 13 cases (39%) with type II. The median duration of neutrophil recovery and high-grade fever were 4.7 ± 1.0 days and 3.6 ± 2.5 days respectively for type II, compared to 8.0 ± 2.8 days and 8.6 ± 3.1 days for type I (p < 0.01 in both compared groups). However, there was no significant difference between the two types in terms of age, median duration of drug administration before the diagnosis of agranulocytosis, the amount of neutrophil count on admission and the total administration dose of granulocyte-colony stimulating factor (G-CSF) before bone marrow examination. Two cases of type I died of complications from infection. This study showed that the bone marrow characteristics of ATD-induced agranulocytosis could be classifed into two types. Also, the clinical prognosis was closely related to the bone marrow features. Type I is the dominant type which is usually associated with worse clinical prognosis compared to type II. 23219696 Do mollusks use vertebrate sex steroids as reproductive hormones? II. Critical review of the evidence that steroids have biological effects. In assessing the evidence as to whether vertebrate sex steroids (e.g. testosterone, estradiol, progesterone) have hormonal actions in mollusks, ca. 85% of research papers report at least one biological effect; and 18 out of 21 review papers (published between 1970 and 2012) express a positive view. However, just under half of the research studies can be rejected on the grounds that they did not actually test steroids, but compounds or mixtures that were only presumed to behave as steroids (or modulators of steroids) on the basis of their effects in vertebrates (e.g. Bisphenol-A, nonylphenol and sewage treatment effluents). Of the remaining 55 papers, some can be criticized for having no statistical analysis; some for using only a single dose of steroid; others for having irregular dose-response curves; 40 out of the 55 for not replicating the treatments; and 50 out of 55 for having no within-study repetition. Furthermore, most studies had very low effect sizes in comparison to fish-based bioassays for steroids (i.e. they had a very weak 'signal-to-noise' ratio). When these facts are combined with the fact that none of the studies were conducted with rigorous randomization or 'blinding' procedures (implying the possibility of 'operator bias') one must conclude that there is no indisputable bioassay evidence that vertebrate sex steroids have endocrinological or reproductive roles in mollusks. The only observation that has been independently validated is the ability of estradiol to trigger rapid (1-5 min) lysosomal membrane breakdown in hemocytes of Mytilus spp. This is a typical 'inflammatory' response, however, and is not proof that estradiol is a hormone - especially when taken in conjunction with the evidence (discussed in a previous review) that mollusks have neither the enzymes necessary to synthesize vertebrate steroids nor nuclear receptors with which to respond to them. 23391387 Horizontal gene transfer: linking sex and cell fate. Integrative conjugative elements (ICEs) enable horizontal gene transfer among bacteria. In Pseudomonas, only a phenotypically distinct subpopulation of ICE-bearing cells can mobilize ICE DNA to new hosts. Transfer competence is a terminal state; division is limited, and many cells lyse. 23457119 [18F]FDG-PET as an Imaging Biomarker to NMDA Receptor Antagonist-Induced Neurotoxicity. Positron emission tomography (PET) is an effective tool for noninvasive examination of the body and provides a range of functional information. PET imaging with [(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG) has been used to image alterations in glucose metabolism in brain or cancer tissue in the field of clinical diagnosis but not in the field of toxicology. A single dose of N-methyl-d-aspartate (NMDA) receptor antagonist induces neuronal cell degeneration/death in the rat retrosplenial/posterior cingulate (RS/PC) cortex region. These antagonists also increase local cerebral glucose utilization. Here, we examined the potential of [(18)F]FDG-PET as an imaging biomarker of neurotoxicity induced by an NMDA receptor antagonist, MK-801. Using [(18)F]FDG-PET, we determined that increased glucose utilization involved the neurotoxicity induced by MK-801. The accumulation of [(18)F]FDG was increased in the rat RS/PC cortex region showing neuronal cell degeneration/death and detected before the onset of neuronal cell death. This effect increased at a dose level at which neuronal cell degeneration recovered 24h after MK-801 administration. Scopolamine prevented the neurotoxicity and [(18)F]FDG accumulation induced by MK-801. Furthermore, in cynomolgus monkeys that showed no neuronal cell degeneration/death when treated with MK-801, we noted no differences in [(18)F]FDG accumulation between test and control subjects in any region of the brain. These findings suggest that [(18)F]FDG-PET, which is available for clinical trials, may be useful in generating a predictive imaging biomarker for detecting neurotoxicity against NMDA receptor antagonists with the same pharmacological activity as MK-801. 23249745 Antibiotics that bind to the A site of the large ribosomal subunit can induce mRNA translocation. In the absence of elongation factor EF-G, ribosomes undergo spontaneous, thermally driven fluctuation between the pre-translocation (classical) and intermediate (hybrid) states of translocation. These fluctuations do not result in productive mRNA translocation. Extending previous findings that the antibiotic sparsomycin induces translocation, we identify additional peptidyl transferase inhibitors that trigger productive mRNA translocation. We find that antibiotics that bind the peptidyl transferase A site induce mRNA translocation, whereas those that do not occupy the A site fail to induce translocation. Using single-molecule FRET, we show that translocation-inducing antibiotics do not accelerate intersubunit rotation, but act solely by converting the intrinsic, thermally driven dynamics of the ribosome into translocation. Our results support the idea that the ribosome is a Brownian ratchet machine, whose intrinsic dynamics can be rectified into unidirectional translocation by ligand binding. 23583454 Substituted methcathinones differ in transporter and receptor interactions. The use of synthetic methcathinones, components of "bath salts," is a world-wide health concern. These compounds, structurally similar to methamphetamine (METH) and 3,4-methylendioxymethamphetamine (MDMA), cause tachycardia, hallucinations and psychosis. We hypothesized that these potentially neurotoxic and abused compounds display differences in their transporter and receptor interactions as compared to amphetamine counterparts. 3,4-Methylenedioxypyrovalerone and naphyrone had high affinity for radioligand binding sites on recombinant human dopamine (hDAT), serotonin (hSERT) and norepinephrine (hNET) transporters, potently inhibited [(3)H]neurotransmitter uptake, and, like cocaine, did not induce transporter-mediated release. Butylone was a lower affinity uptake inhibitor. In contrast, 4-fluoromethcathinone, mephedrone and methylone had higher inhibitory potency at uptake compared to binding and generally induced release of preloaded [(3)H]neurotransmitter from hDAT, hSERT and hNET (highest potency at hNET), and thus are transporter substrates, similar to METH and MDMA. At hNET, 4-fluoromethcathinone was a more efficacious releaser than METH. These substituted methcathinones had low uptake inhibitory potency and low efficacy at inducing release via human vesicular monoamine transporters (hVMAT2). These compounds were low potency (1) h5-HT1A receptor partial agonists, (2) h5-HT2A receptor antagonists, (3) weak h5-HT2C receptor antagonists. This is the first report on aspects of substituted methcathinone efficacies at serotonin (5-HT) receptors and in superfusion release assays. Additionally, the drugs had no affinity for dopamine receptors, and high-nanomolar to mid-micromolar affinity for hSigma1 receptors. Thus, direct interactions with hVMAT2 and serotonin, dopamine, and hSigma1 receptors may not explain psychoactive effects. The primary mechanisms of action may be as inhibitors or substrates of DAT, SERT and NET. 23589624 Cell-free co-production of an orthogonal transfer RNA activates efficient site-specific non-natural amino acid incorporation. We describe a new cell-free protein synthesis (CFPS) method for site-specific incorporation of non-natural amino acids (nnAAs) into proteins in which the orthogonal tRNA (o-tRNA) and the modified protein (i.e. the protein containing the nnAA) are produced simultaneously. Using this method, 0.9-1.7 mg/ml of modified soluble super-folder green fluorescent protein (sfGFP) containing either p-azido-l-phenylalanine (pAzF) or p-propargyloxy-l-phenylalanine (pPaF) accumulated in the CFPS solutions; these yields correspond to 50-88% suppression efficiency. The o-tRNA can be transcribed either from a linearized plasmid or from a crude PCR product. Comparison of two different o-tRNAs suggests that the new platform is not limited by Ef-Tu recognition of the acylated o-tRNA at sufficiently high o-tRNA template concentrations. Analysis of nnAA incorporation across 12 different sites in sfGFP suggests that modified protein yields and suppression efficiencies (i.e. the position effect) do not correlate with any of the reported trends. Sites that were ineffectively suppressed with the original o-tRNA were better suppressed with an optimized o-tRNA (o-tRNA(opt)) that was evolved to be better recognized by Ef-Tu. This new platform can also be used to screen scissile ribozymes for improved catalysis. 23092237 Pump-Probe Microscopy: Spatially Resolved Carrier Dynamics in ZnO Rods and the Influence of Optical Cavity Resonator Modes. Femtosecond pump-probe microscopy is used to investigate the charge recombination dynamics at different points within a single needle-shaped ZnO rod. Recombination in the tips of the rod occurs through an excitonic or electron-hole plasma state, taking place on a picosecond time scale. Photoexcitation in the larger diameter sections of the interior exhibit dramatically slower recombination that occurs primarily through defects sites, i.e., trap mediated recombination. Transient absorption imaging shows that the spatial variation in the dynamics is also influenced by the cavity resonances supported within the hexagonal cross section of the rod. Finite element simulations suggest that these optical resonator modes produce qualitatively different intensity patterns in the two different locations. Near the end of the rod, the intensity pattern has significant standing-wave character, which leads to the creation of photoexcited carriers in the core of the structure. The larger diameter regions, on the other hand, exhibit intensity distributions in which the whispering gallery (WG) mode character dominates. At these locations, the photoexcited carriers are produced in subsurface depletion zone, where the internal fields separate the electrons and holes and lead to a greater degree of trap recombination on longer time scales. 23265296 Block copolymer modified surfaces for conjugation of biomacromolecules with control of quantity and activity. Polymer brush layers based on block copolymers of poly(oligo(ethylene glycol) methacrylate) (POEGMA) and poly(glycidyl methacrylate) (PGMA) were formed on silicon wafers by activators generated by electron transfer atom transfer radical polymerization (AGET ATRP). Different types of biomolecule can be conjugated to these brush layers by reaction of PGMA epoxide groups with amino groups in the biomolecule, while POEGMA, which resists nonspecific protein adsorption, provides an antifouling environment. Surfaces were characterized by water contact angle, ellipsometry, and Fourier transform infrared spectroscopy (FTIR) to confirm the modification reactions. Phase segregation of the copolymer blocks in the layers was observed by AFM. The effect of surface properties on protein conjugation was investigated using radiolabeling methods. It was shown that surfaces with POEGMA layers were protein resistant, while the quantity of protein conjugated to the diblock copolymer modified surfaces increased with increasing PGMA layer thickness. The activity of lysozyme conjugated on the surface could also be controlled by varying the thickness of the copolymer layer. When biotin was conjugated to the block copolymer grafts, the surface remained resistant to nonspecific protein adsorption but showed specific binding of avidin. These properties, that is, well-controlled quantity and activity of conjugated biomolecules and specificity of interaction with target biomolecules may be exploited for the improvement of signal-to-noise ratio in sensor applications. More generally, such surfaces may be useful as biological recognition elements of high specificity for functional biomaterials. 23619613 Soluble polysialylated NCAM: a novel player of the innate immune system in the lung. Posttranslational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is well studied in the nervous system and described as a dynamic modulator of plastic processes like precursor cell migration, axon fasciculation, and synaptic plasticity. Here, we describe a novel function of polysialylated NCAM (polySia-NCAM) in innate immunity of the lung. In mature lung tissue of healthy donors, polySia was exclusively attached to the transmembrane isoform NCAM-140 and located to intracellular compartments of epithelial cells. In patients with chronic obstructive pulmonary disease, however, increased polySia levels and processing of the NCAM carrier were observed. Processing of polysialylated NCAM was reproduced in a mouse model by bleomycin administration leading to an activation of the inflammasome and secretion of interleukin (IL)-1β. As shown in a cell culture model, polySia-NCAM-140 was kept in the late trans-Golgi apparatus of lung epithelial cells and stimulation by IL-1β or lipopolysaccharide induced metalloprotease-mediated ectodomain shedding, resulting in the secretion of soluble polySia-NCAM. Interestingly, polySia chains of secreted NCAM neutralized the cytotoxic activity of extracellular histones as well as DNA/histone-network-containing "neutrophil extracellular traps", which are formed during invasion of microorganisms. Thus, shedding of polySia-NCAM by lung epithelial cells may provide a host-protective mechanism to reduce tissue damage during inflammatory processes. 22989704 Efficacy of all-trans retinoid acid in preventing nickel induced cardiotoxicity in myocardial cells of rats. Nickel, a metal commonly found in battery plants and welding factories, has potential cardiotoxicity, while all-trans retinoid acid (atRA) can promote cardiovascular repair and myocardial recovery. The purpose of this study was to investigate whether atRA could prevent cardiotoxicity induced by nickel both in vitro and in vivo. In the study, a rat myocardial cell line (H9c2) exposed to different concentrations of nickel chloride (NiCl(2)) displayed apoptotic features accompanied by reactive oxygen species generation. In addition, NiCl(2) also caused obvious apoptosis and systolic dysfunction in primary myocardial cells. Treatment with atRA efficiently attenuated the cytotoxicities triggered by NiCl(2) as it significantly mitigated ROS generation and decreased MAP kinases activity in NiCl(2)-treated cardiomyocytes. Additionally, NiCl(2) exposure caused obvious arrhythmia in Sprague-Dawley rats with the maximum tolerance dose of NiCl(2) between 2 and 3mg/kg. A combinational intragastric administration of 40mg/kg atRA can partially reverse NiCl(2)-induced arrhythmia in rats. Our results suggested that atRA might have therapeutic potential in alleviating the adverse effects of nickel on the cardiovascular system. 22993237 Inference on population histories by approximating infinite alleles diffusion. Reconstruction of the past is an important task of evolutionary biology. It takes place at different points in a hierarchy of molecular variation, including genes, individuals, populations, and species. Statistical inference about population histories has recently received considerable attention, following the development of computational tools to provide tractable approaches to this very challenging problem. Here, we introduce a likelihood-based approach which generalizes a recently developed model for random fluctuations in allele frequencies based on an approximation to the neutral Wright-Fisher diffusion. Our new framework approximates the infinite alleles Wright-Fisher model and uses an implementation with an adaptive Markov chain Monte Carlo algorithm. The method is especially well suited to data sets harboring large population samples and relatively few loci for which other likelihood-based models are currently computationally intractable. Using our model, we reconstruct the global population history of a major human pathogen, Streptococcus pneumoniae. The results illustrate the potential to reach important biological insights to an evolutionary process by a population genetics approach, which can appropriately accommodate very large population samples. 23371303 Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination. Avibactam (formerly NXL104, AVE1330A) is a synthetic non-β-lactam, β-lactamase inhibitor that inhibits the activities of Ambler class A and C β-lactamases and some Ambler class D enzymes. This review summarizes the existing data published for ceftazidime-avibactam, including relevant chemistry, mechanisms of action and resistance, microbiology, pharmacokinetics, pharmacodynamics, and efficacy and safety data from animal and human trials. Although not a β-lactam, the chemical structure of avibactam closely resembles portions of the cephem bicyclic ring system, and avibactam has been shown to bond covalently to β-lactamases. Very little is known about the potential for avibactam to select for resistance. The addition of avibactam greatly (4-1024-fold minimum inhibitory concentration [MIC] reduction) improves the activity of ceftazidime versus most species of Enterobacteriaceae depending on the presence or absence of β-lactamase enzyme(s). Against Pseudomonas aeruginosa, the addition of avibactam also improves the activity of ceftazidime (~fourfold MIC reduction). Limited data suggest that the addition of avibactam does not improve the activity of ceftazidime versus Acinetobacter species or most anaerobic bacteria (exceptions: Bacteroides fragilis, Clostridium perfringens, Prevotella spp. and Porphyromonas spp.). The pharmacokinetics of avibactam follow a two-compartment model and do not appear to be altered by the co-administration of ceftazidime. The maximum plasma drug concentration (C(max)) and area under the plasma concentration-time curve (AUC) of avibactam increase linearly with doses ranging from 50 mg to 2,000 mg. The mean volume of distribution and half-life of 22 L (~0.3 L/kg) and ~2 hours, respectively, are similar to ceftazidime. Like ceftazidime, avibactam is primarily renally excreted, and clearance correlates with creatinine clearance. Pharmacodynamic data suggest that ceftazidime-avibactam is rapidly bactericidal versus β-lactamase-producing Gram-negative bacilli that are not inhibited by ceftazidime alone.Clinical trials to date have reported that ceftazidime-avibactam is as effective as standard carbapenem therapy in complicated intra-abdominal infection and complicated urinary tract infection, including infection caused by cephalosporin-resistant Gram-negative isolates. The safety and tolerability of ceftazidime-avibactam has been reported in three phase I pharmacokinetic studies and two phase II clinical studies. Ceftazidime-avibactam appears to be well tolerated in healthy subjects and hospitalized patients, with few serious drug-related treatment-emergent adverse events reported to date.In conclusion, avibactam serves to broaden the spectrum of ceftazidime versus ß-lactamase-producing Gram-negative bacilli. The exact roles for ceftazidime-avibactam will be defined by efficacy and safety data from further clinical trials. Potential future roles for ceftazidime-avibactam include the treatment of suspected or documented infections caused by resistant Gram-negative-bacilli producing extended-spectrum ß-lactamase (ESBL), Klebsiella pneumoniae carbapenemases (KPCs) and/or AmpC ß-lactamases. In addition, ceftazidime-avibactam may be used in combination (with metronidazole) for suspected polymicrobial infections. Finally, the increased activity of ceftazidime-avibactam versus P. aeruginosa may be of clinical benefit in patients with suspected or documented P. aeruginosa infections. 23327993 Thioredoxin-mimetic peptides (TXM) reverse auranofin induced apoptosis and restore insulin secretion in insulinoma cells. The thioredoxin reductase/thioredoxin system (TrxR/Trx1) plays a major role in protecting cells from oxidative stress. Disruption of the TrxR-Trx1 system keeps Trx1 in the oxidized state leading to cell death through activation of the ASK1-Trx1 apoptotic pathway. The potential mechanism and ability of tri- and tetra-oligopeptides derived from the canonical -CxxC- motif of the Trx1-active site to mimic and enhance Trx1 cellular activity was examined. The Trx mimetics peptides (TXM) protected insulinoma INS 832/13 cells from oxidative stress induced by selectively inhibiting TrxR with auranofin (AuF). TXM reversed the AuF-effects preventing apoptosis, and increasing cell-viability. The TXM peptides were effective in inhibiting AuF-induced MAPK, JNK and p38(MAPK) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation. The ability to form a disulfide-bridge-like conformation was estimated from molecular dynamics simulations. The TXM peptides restored insulin secretion and displayed Trx1 denitrosylase activity. Their potency was 10-100-fold higher than redox reagents like NAC, AD4, or ascorbic acid. Unable to reverse ERK1/2 phosphorylation, TXM-CB3 (NAc-Cys-Pro-Cys amide) appeared to function in part, through inhibiting ASK1-Trx dissociation. These highly effective anti-apoptotic effects of Trx1 mimetic peptides exhibited in INS 832/13 cells could become valuable in treating adverse oxidative-stress related disorders such as diabetes. 23561169 Carotenoids and tocopherols in yellow and red raspberries. The composition of carotenoids, chlorophyll derivatives and tocopherols in raspberries of different varieties, including yellow and red varieties, over different ripening stages has been studied. The profile of pigments in ripening raspberries changes drastically, with a dramatic decrease of β-carotene and chlorophyll derivatives, the xanthophyll lutein has also decreased but not to the same extent. In contrast esterified lutein increased and is present in ripe raspberries esterified with saturated fatty acids with C8-C16 chains. Ripe raspberries contain considerable amounts of free lutein, esterified lutein, and tocopherols (up to 20, 49 and 366mg/kg dry weight, respectively). The different samples analysed show different contents of carotenoids and tocopherols. Whether the differences arise from the variety or other factors such as the environmental conditions needs to be ascertained but isoprenoids should not be neglected when considering raspberry antioxidant and nutraceutical composition. 23264021 Molecular diversity of class 2 integrons in antibiotic-resistant gram-negative bacteria found in wastewater environments in China. The molecular architecture of class 2 integrons among gram-negative bacteria from wastewater environments was investigated in Jinan, China. Out of the 391 antibiotic-resistant bacteria found, 38 isolates harboring class 2 integrons encoding potentially transferrable genes that could confer antibiotic resistance were found. These isolates were classified into 19 REP-PCR types. These strains were identified using 16S rRNA gene sequencing and found to be as follows: Proteus mirabilis (16), Escherichia coli (7), Providencia spp. (7), Proteus spp. (2), P. vulgaris (3), Shigella sp. (1), Citrobacter freundii (1), and Acinetobacter sp. (1). Their class 2 integron cassette arrays were amplified and then either analyzed using PCR-RFLP or sequenced. The typical array dfrA1-sat2-aadA1 was detected in 27 isolates. Six atypical arrays were observed, including three kinds of novel arrangements (linF2(∆attC1)-dfrA1(∆attC2)-aadA1-orf441 or linF2(∆attC1)-dfrA1(∆attC2)-aadA1, dfrA1-catB2-sat2-aadA1, and estX(Vr)-sat2-aadA1) and a hybrid with the 3'CS of class 1 integrons (dfrA1-sat2-aadA1-qacH), and dfrA1-sat1. Twenty-four isolates were also found to carry class 1 integrons with 10 types of gene cassette arrays. Several non-integron-associated antibiotic resistance genes were found, and their transferability was investigated. Results showed that water sources in the Jinan region harbored a diverse community of both typical and atypical class 2 integrons, raising concerns about the overuse of antibiotics and their careless disposal into the environment. 23630043 Synthesis and Characterization of 5-(1,2,4-Triazol-3-yl)tetrazoles with various energetic functionalities. In this contribution the synthesis and full structural as well as spectroscopic characterization of three 5-(1,2,4-triazol-3-yl)tetrazoles along with selected energetic moieties like nitro, nitrimino, and azido groups are presented. The main goal is a comparative study on the influence of those variable energetic moieties on structural and energetic properties. A complete characterization including IR and Raman as well as multinuclear NMR spectroscopy of all compounds is presented. Additionally, X-ray crystallographic measurements were performed and reveal insights into structural characteristics as well as inter- and intramolecular interactions. The standard enthalpies of formation were calculated for all compounds at the CBS-4M level of theory and reveal high positive heats of formation for all compounds. The calculated detonation parameters (using the EXPLO5.05 program) are in the range of 8000 m s(-1) (8097 m s(-1) (5), 8020 m s(-1) (6), 7874 m s(-1) (7)). As expected, the measured impact and friction sensitivities as well as decomposition temperatures strongly depend on the energetic moiety at the triazole ring. The CC connection of a triazole ring with its opportunity to introduce a large variety of energetic moieties and a tetrazole ring, implying a large energy content, leads to the selective synthesis of primary and secondary explosives. 23353815 Involvement of the essential metal transporter Zip14 in hepatic Cd accumulation during inflammation. Upregulation of Zip14 contributes to hepatic zinc (Zn) and non-transferrin-bound iron (Fe) uptake during infection and inflammation. We investigated whether this essential metal transporter is also involved in hepatic cadmium (Cd) uptake under these conditions. An injection of lipopolysaccharide (LPS), turpentine oil (Tur) and n-hexane (Hex) resulted in an decrease in plasma Zn and Fe concentrations to 25-50% and an increase in hepatic concentrations of both metals to 150-200% of control mice. LPS significantly increased plasma interleukin (IL)-6 levels more rapidly than Tur or Hex. Tur or Hex significantly increased hepatic Zip14 mRNA expression and decreased ferroportin 1 mRNA expression following continuous increase of IL-6 level. Hepatic Cd and Zn concentrations increased significantly after repeated injections of Cd in Tur- or Hex-treated mice fed a control diet. Treatment with Tur or Hex additionally increased hepatic Cd accumulation in Zn-deficient mice, unlike in Fe-deficient mice. These results suggest that Zn transporters, such as Zip14, may be involved in hepatic Cd uptake during inflammation. 23556448 Association of a functional FAAH polymorphism with methamphetamine-induced symptoms and dependence in a Malaysian population. Aim: FAAH is a membrane enzyme that terminates the activity of a large class of endogenous signaling lipids. Recent studies suggest that the FAAH Pro129Thr polymorphism is a common mutation in the FAAH gene that is significantly associated with drug-addictive traits. This study investigated the association of the Pro129Thr polymorphism of the FAAH gene with methamphetamine dependence, methamphetamine-induced psychosis, manic episodes and panic disorder in a Malaysian population. Materials & methods: This polymorphism was genotyped in 232 male methamphetamine-dependent subjects and in 241 male controls of four different ethnicities: Malay, Chinese, Kadazan-Dusun and Bajau. Intergroup statistical analyses were performed by using the χ(2)-square test and Fisher's exact test, where necessary. In cases of multiple comparisons, the Bonferroni correction was performed. Results: Our results indicated that the FAAH Pro129Thr polymorphism showed a significant association with risk of methamphetamine dependence in the pooled subjects (odds ratio [OR]: 2.017; p < 0.001) and in the Malay (OR: 2.829; p < 0.001) and Chinese (OR: 3.685; p < 0.001) groups. We also found an association of this polymorphism with episodes of methamphetamine-induced mania in the Malay group (OR: 2.836; p = 0.035). However, there was no association between this polymorphism and age of onset of drug use or the occurrence of methamphetamine-induced psychosis or of panic disorder. Conclusion: Our findings suggest that the FAAH Pro129Thr polymorphism may contribute to methamphetamine dependence in the Malay and Chinese ethnic groups. Original submitted 4 October 2012; Revision submitted 1 February 2013. 23604140 Exploration of the Orthosteric/Allosteric Interface in Human M1 Muscarinic Receptors by Bitopic Fluorescent Ligands. Bitopic binding properties apply to a variety of muscarinic compounds that span and simultaneously bind to both the orthosteric and allosteric receptor sites. We provide evidence that fluorescent pirenzepine derivatives, with the M1 antagonist fused to the Bodipy [558/568] fluorophore via spacers of varying lengths, exhibit orthosteric/allosteric binding properties at muscarinic M1 receptors. This behaviour was inferred from a combination of functional, radioligand and FRET binding experiments, performed under equilibrium and kinetic conditions on EGFP-fused M1 receptors. Though displaying a common orthosteric component, the fluorescent compounds inherit bitopic properties from a linker-guided positioning of their Bodipy moiety within the M1 allosteric vestibule. Depending on linker length, the fluorophore is allowed to reach neighbouring allosteric domains, overlapping or not with the classical gallamine site, but distinct from the allosteric indocarbazolole 'WIN' site. Site-directed mutagenesis, as well as molecular modeling and ligand docking studies based on recently solved muscarinic receptor structures, further support the definition of two groups of Bodipy-pirenzepine derivatives exhibiting distinct allosteric binding poses. Thus, the linker may dictate pharmacological outcomes for bitopic molecules that are hardly predictable from the properties of individual orthosteric and allosteric building blocks. Our findings also demonstrate that the fusion of a fluorophore to an orthosteric ligand is not neutral as it may confer, unless carefully controlled, unexpected properties to the resultant fluorescent tracer. Altogether, this study illustrates the importance of a 'multifacette' experimental approach to unravel and validate bitopic ligand binding mechanisms. 23639069 Parent-only vs. parent-child (family-focused) approaches for weight loss in obese and overweight children: a systematic review and meta-analysis. Families are recommended as the agents of change for weight loss in overweight and obese children; family approaches are more effective than those that focus on the child alone. However, interventions that focus on parents alone have not been summarized. The objective of this review was to assess the effectiveness of interventions that compared a parent-only (PO) condition with a parent-child (PC) condition. Four trials using a similar between-group background approaches to overweight and obese children's weight loss met the inclusion criteria, but only one trial reported sufficient data for meta-analysis. Further information was obtained from authors. Meta-analysis showed no significant difference in z-BMI from baseline to end of treatment between the conditions (three trials) or to end of follow up (two trials). The trials were at risk of bias and no single trial was at lower risk of bias than others. There is an absence of high quality evidence regarding the effect of parent-only interventions for weight loss in children compared to parent-child interventions, but current evidence suggests the need for further investigation. 23034931 Interplay between protein carbonylation and nitrosylation in plants. ROS and reactive nitrogen species (RNS) are key regulators of redox homeostasis in living organisms including plants. As control of redox homeostasis plays a central function in plant biology, redox proteomics could help in characterizing the potential roles played by ROS/RNS-induced posttranslational modification in plant cells. In this review, we focus on two posttranslational modifications: protein carbonylation (a marker of protein oxidation) and protein S-nitrosylation, both of which having recently emerged as important regulatory mechanisms during numerous fundamental biological processes. Here, we describe the recent progress in proteomic analysis of carbonylated and nitrosylated proteins and highlight the achievements made in understanding the physiological basis of these oxy/nitro modifications in plants. In addition, we document the existence of a relationship between ROS-based carbonylation and RNS-based nitrosylation thus supporting the finding that crosstalk between cellular signaling stress pathways induced by ROS and RNS could be mediated by specific protein modifications. 23508961 Agonist-induced Down-regulation of Endogenous Protein Kinase C α through an Endolysosomal Mechanism. Protein kinase C (PKC) isozymes undergo down-regulation upon sustained stimulation. Previous studies have pointed to the existence of both proteasome-dependent and -independent pathways of PKCα processing. Here we demonstrate that these down-regulation pathways are engaged in different subcellular compartments; proteasomal degradation occurs mainly at the plasma membrane, whereas non-proteasomal processing occurs in the perinuclear region. Using cholesterol depletion, pharmacological inhibitors, RNA interference, and dominant-negative mutants, we define the mechanisms involved in perinuclear accumulation of PKCα and identify the non-proteasomal mechanism mediating its degradation. We show that intracellular accumulation of PKCα involves at least two clathrin-independent, cholesterol/lipid raft-mediated pathways that do not require ubiquitination of the protein; one is dynamin-dependent and likely involves caveolae, whereas the other is dynamin- and small GTPase-independent. Internalized PKCα traffics through endosomes and is delivered to the lysosome for degradation. Supportive evidence includes (a) detection of the enzyme in EEA1-positive early endosomes, Rab7-positive late endosomes/multivesicular bodies, and LAMP1-positive lysosomes and (b) inhibition of its down-regulation by lysosome-disrupting agents and leupeptin. Only limited dephosphorylation of PKCα occurs during trafficking, with fully mature enzyme being the main target for lysosomal degradation. These studies define a novel and widespread mechanism of desensitization of PKCα signaling that involves endocytic trafficking and lysosome-mediated degradation of the mature, fully phosphorylated protein. 23220646 Design and synthesis of novel benzoheterocyclic derivatives as human acrosin inhibitors by scaffold hopping. Human acrosin is an attracting target for the development of novel male contraceptives. Scaffold hopping was used to optimize the isoxazolecarbaldehyde human acrosin inhibitors and extend their structure-activity relationships. Four kinds of scaffolds, namely benzimidazole, benzothiazole, 3H-indazole, and 5-phenyl-1H-pyrazole, were designed and synthesized. Most of the synthesized compounds showed potent human acrosin inhibitory activity and their binding modes were investigated by molecular docking. The scaffold of the compounds was found to be important for the inhibitory activity. Several compounds were more active than the positive control TLCK, suggesting that they can serve as good starting points for the discovery of novel male contraceptive agents. 22705340 Potentiation of mGlu5 receptors with the novel enhancer, VU0360172, reduces spontaneous absence seizures in WAG/Rij rats. Absence epilepsy is generated by the cortico-thalamo-cortical network, which undergoes a finely tuned regulation by metabotropic glutamate (mGlu) receptors. We have shown previously that potentiation of mGlu1 receptors reduces spontaneous occurring spike and wave discharges (SWDs) in the WAG/Rij rat model of absence epilepsy, whereas activation of mGlu2/3 and mGlu4 receptors produces the opposite effect. Here, we have extended the study to mGlu5 receptors, which are known to be highly expressed within the cortico-thalamo-cortical network. We used presymptomatic and symptomatic WAG/Rij rats and aged-matched ACI rats. WAG/Rij rats showed a reduction in the mGlu5 receptor protein levels and in the mGlu5-receptor mediated stimulation of polyphosphoinositide hydrolysis in the ventrobasal thalamus, whereas the expression of mGlu5 receptors was increased in the somatosensory cortex. Interestingly, these changes preceded the onset of the epileptic phenotype, being already visible in pre-symptomatic WAG/Rij rats. SWDs in symptomatic WAG/Rij rats were not influenced by pharmacological blockade of mGlu5 receptors with MTEP (10 or 30 mg/kg, i.p.), but were significantly decreased by mGlu5 receptor potentiation with the novel enhancer, VU0360172 (3 or 10 mg/kg, s.c.), without affecting motor behaviour. The effect of VU0360172 was prevented by co-treatment with MTEP. These findings suggest that changes in mGlu5 receptors might lie at the core of the absence-seizure prone phenotype of WAG/Rij rats, and that mGlu5 receptor enhancers are potential candidates to the treatment of absence epilepsy. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. 23247824 Nicotinic receptors in addiction pathways. Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that consist of pentameric combinations of α and β subunits. These receptors are widely distributed throughout the brain and are highly expressed in addiction circuitry. The role of nAChRs in regulating neuronal activity and motivated behavior is complex and varies both in and among brain regions. The rich diversity of central nAChRs has hampered the characterization of their structure and function with use of classic pharmacological techniques. However, recent molecular approaches using null mutant mice with specific regional lentiviral re-expression, in combination with neuroanatomical and electrophysiological techniques, have allowed the elucidation of the influence of different nAChR types on neuronal circuit activity and behavior. This review will address the influence of nAChRs on limbic dopamine circuitry and the medial habenula-interpeduncular nucleus complex, which are critical mediators of reinforced behavior. Characterization of the mechanisms underlying regulation of addiction pathways by endogenous cholinergic transmission and by nicotine may lead to the identification of new therapeutic targets for treating tobacco dependence and other addictions. 23168293 Bone hemodynamic responses to changes in external pressure. Adequate blood supply and circulation to the bones is required to maintain a healthy skeleton. Inadequate blood perfusion is associated with numerous bone pathologies and a decrease in bone mineral density, yet bone hemodynamics remains poorly understood. This study aims to 1) quantify bone hemodynamic responses to changes in external pressure, and 2) identify the predominant mechanisms regulating bone hemodynamic responses to pressure changes. Photoplethysmography was used to measure bone and skin perfusion in response to changes in external pressure. Single-limb pressure chamber experiments were performed over a pressure range of -50 to +50mmHg. Bone perfusion is decreased at all negative pressures, and larger decrements in perfusion are observed at the more extreme pressure differences. At positive pressures we observed an initial increase in perfusion followed by activation of intramuscular pressure receptors at +30mmHg, which overrides the initial response and results in decreased perfusion at the highest positive pressure levels. The myogenic effect is observed and is shown to be the predominant control mechanism in bone over a wide range of pressure exposures. Greater understanding of these hemodynamic mechanisms may be important in developing new drugs and therapies to treat various bone disorders. 23386704 Serum levels of 25-hydroxyvitamin D and the CYP3A biomarker 4β-hydroxycholesterol in a high-dose vitamin D supplementation study. The primary aim was to study the relationship between individual serum levels of 25-hydroxyvitamin D and 4β-hydroxycholesterol, which is an endogenous biomarker of the drug-metabolizing CYP3A enzymes. In addition, the relationship between this biomarker and inflammation, measured as C-reactive protein (CRP), was investigated. Serum samples were used from a recently performed clinical trial in patients with antibody deficiency or increased susceptibility to respiratory tract infections that were randomized to either placebo or high-dose (4000 IU/day) vitamin D for 12 months. One hundred sixteen patients were included in the final analyses, and serum samples collected 6 months after study start were analyzed. At this time point, 25-hydroxyvitamin D levels were found to range between 10 and 284 nM. Individual levels of 25-hydroxyvitamin D as well as CRP were compared with 4β-hydroxycholesterol levels. In addition, all participants were genotyped for two polymorphisms (Taq1 and Foq1) in the vitamin D receptor gene. There was no significant correlation between individual serum levels of 25-hydroxyvitamin D and 4β-hydroxycholesterol. However, a moderate, but statistically significant, negative correlation between CRP and 4β-hydroxycholesterol levels was observed. This study in patients with highly variable serum levels of 25-hydroxyvitamin D could not reveal any relationship between vitamin D and 4β-hydroxycholesterol, an endogenous biomarker of CYP3A activity. However, the negative correlation between CRP and 4β-hydroxycholesterol supports earlier experimental results that inflammation may suppress hepatic CYP3A activity, a finding of potentially high clinical relevance that warrants further exploration. 23124677 Cadmium chelation by frustulins: a novel metal tolerance mechanism in Nitzschia palea (Kützing) W. Smith. The ubiquity of diatom distribution, species richness, short generation time, and specific sensitivity to several environmental stressors such as metals, make diatoms particularly useful for scientific studies. Anthropogenic activities have increased the concentration of metals in air, soil and water. Due to their toxicity and persistent character, the effects of metals on organisms have been extensively studied. In this work, the association of cadmium to different extracellular molecules of Nitzschia palea cells was investigated. Cells were grown in the absence and presence (0.2 mg l(-1)) of cadmium in Chu no. 10 medium. Extracellular polysaccharides were extracted, and subsamples were used for polysaccharide and Cd determination. The frustules were broken mechanically under liquid nitrogen and the intracellular and frustule fractions separated. Frustulins, a protein family found on the outmost frustule layer, constituting a protection coating to environmental stress, were extracted. In each fraction proteins were quantified by the BCA method and separated by gel electrophoresis (SDS-PAGE). Cadmium associated to each fraction was quantified by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis. Exposure of Nitzschia palea to cadmium decreased extracellular polysaccharides by 52.8 % and increased 6 times the amount of frustulins. Cadmium was mostly retained extracellularly: 85.4 % was bound to the frustulin fraction, and 11.1 % to polysaccharides. The ability of Nitzschia palea to increase the production of frustulins due to the presence of Cd, the extracellular location of this frustulin coating and the ability of these proteins to bind Cd, suggests a new cellular defense mechanism to metals unknown until now. 23225671 Enhanced nonenzymatic ligation of homopurine miniduplexes: support for greater base stacking in a pre-RNA world. The ancestors of RNA? There is a long-standing proposal that contemporary nucleic acids might have evolved from RNA-like polymers that utilized only purine-purine base pairs. Here we demonstrate the great advantage that increased nucleobase stacking area provides for nonenzymatic ligation. 23265544 Multi-targeted screening of botanicals in food supplements by liquid chromatography with tandem mass spectrometry. Safety, quality and composition assessments of food supplements based on botanical ingredients are of major concern, as they have usually not been through a rigorous testing process as required for the approval of therapeutic phytopreparations. Therefore, an efficient multi-targeted method was developed to screen selected botanicals of interest in herbal food supplements. Liquid chromatography coupled with a hybrid triple quadrupole linear ion trap was used for this purpose. Botanicals were characterised by means of appropriate biomarkers, which were unambiguously identified by mass spectrometry using an information dependent acquisition experiment which combined a multiple reaction monitoring survey with dependent enhanced product ion scans. During this procedure, product ion scans of targeted analytes were generated at three collision energies and compared with an in-house library of MS/MS spectra acquired from reference standards of all biomarkers. This generic method enables detection, identification and quantification of 98 biomarkers intended to characterise 79 selected plants. 23391632 The increased number of Leydig cells by di(2-ethylhexyl) phthalate comes from the differentiation of stem cells into Leydig cell lineage in the adult rat testis. The objective of the present study is to determine whether di(2-ethylhexyl) phthalate (DEHP) exposure at adulthood increases rat Leydig cell number and to investigate the possible mechanism. 90-day-old Long-Evans rats were randomly divided into 3 groups, and were gavaged with the corn oil (control) or 10 or 750mg/kg DEHP daily for 7 days, and then received an intraperitoneal injection of 75mg/kg ethane dimethanesulfonate (EDS) to eliminate Leydig cells. Serum testosterone concentrations were assessed by RIA, and the mRNA levels of Leydig cell genes were measured by qPCR. EDS eliminated all Leydig cells in the control testis on day 4 post-EDS, as judged by undetectable serum testosterone level and no 3β-hydroxysteroid dehydrogenase positive (3β-HSD(pos)) cells in the interstitium. However, in DEHP-treated groups, there were detectable serum testosterone concentrations and some oval-shaped 3β-HSD(pos) cells in the interstitium. These 3β-HSD(pos) cells were not stained by the antibody against 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), a marker for Leydig cells at a more advanced stage. The disappearance of mRNAs of Leydig cell biomarkers including Lhcgr, Cyp11a1, Cyp17a1, Insl3 and Hsd11b1 in the control testis was observed on day 4 post-EDS. However, there were detectable concentrations of Lhcgr, Cyp11a1 and Cyp17a1 mRNAs but undetectable concentrations of Insl3, Hsd17b3 and Hsd11b1 in the DEHP-treated testes, indicating that these 3β-HSD(pos) cells were newly formed progenitor Leydig cells. The mRNA level for nestin (Nes, biomarker for stem Leydig cells) was significantly increased in the control testis on day 4 post-EDS, but not in the DEHP treated testes, suggesting that these nestin positive stem cells were differentiated into progenitor Leydig cells in the DEHP-treated testes. The present study suggests that DEHP increases the differentiation of stem cells into progenitor Leydig cells. 23327112 Coumarins from roots of Clausena excavata. Two new coumarins, clauexcavatins A (1) and B (2), along with seven known ones (3-9), were isolated from the roots of Clausena excavata Burm. f. (Rutaceae). Their structures were elucidated on the basis of spectral data. 23471969 An Intracellular Domain Fragment of the p75 Neurotrophin Receptor (p75NTR) Enhances Tropomyosin Receptor Kinase A (TrkA) Receptor Function. Facilitation of nerve growth factor (NGF) signaling by the p75 neurotrophin receptor (p75(NTR)) is critical for neuronal survival and differentiation. However, the interaction between p75(NTR) and TrkA receptors required for this activity is not understood. Here, we report that a specific 29-amino acid peptide derived from the intracellular domain fragment of p75(NTR) interacts with and potentiates binding of NGF to TrkA-expressing cells, leading to increased neurite outgrowth in sympathetic neurons as a result of enhanced Erk1/2 and Akt signaling. An endogenous intracellular domain fragment of p75(NTR) (p75(ICD)) containing these 29 amino acids is produced by regulated proteolysis of the full-length receptor. We demonstrate that generation of this fragment is a requirement for p75(NTR) to facilitate TrkA signaling in neurons and propose that the juxtamembrane region of p75(ICD) acts to cause a conformational change within the extracellular domain of TrkA. This finding provides new insight into the mechanism by which p75(NTR) and TrkA interact to enhance neurotrophic signaling. 23483327 Transcriptional responses indicate attenuated oxidative stress in the springtail Folsomia candida exposed to mixtures of cadmium and phenanthrene. Since the 'omics revolution', the assessment of toxic chemical mixtures has incorporated approaches where phenotypic endpoints are connected to a mechanistic understanding of toxicity. In this study we determined the effect of binary mixtures of cadmium and phenanthrene on the reproduction of Folsomia candida and investigated the cellular mechanisms underlying this response. Mixture toxicity modeling showed an antagonistic deviation from concentration addition for reproduction effects of the mixtures. Subsequent transcriptional response analysis was done using five mixtures at the modeled 50 % effect level for reproduction. The transcription profiles of 86 high throughput RT-qPCR assays were studied by means of partial least squares regression analysis. The first and second principal components (PCs) were correlated with global responses to cadmium and phenanthrene, while correlations with the mixture treatments were found in the higher PCs. Specifically associated with the mixture treatments were a biotransformation phase II gene, four mitochondrial related genes and a gene involved in the biosynthesis of antioxidant selenoproteins. Membrane integrity related gene inductions were correlated with the single phenanthrene treatment but not with the mixtures. Immune and inflammatory response assays did not correlate with any of the mixtures. These results suggest moderated oxidative stress, a higher mitochondrial maintenance and less compromised membrane function in the mixture exposed samples compared to the separate cadmium or phenanthrene exposures. The antagonism found for inhibition of reproduction may partially originate from these differences. Mechanistic studies on mixture toxicity can ultimately aid risk assessment by defining relevant toxicity pathways in organisms exposed to real-world mixture exposures present in the field. 23473027 A new "immunological" role for adipocytes in obesity. Obesity-induced insulin resistance is associated with low-grade adipose tissue inflammation, but the mechanism driving this process remains unclear. In this issue of Cell Metabolism, a study by Deng et al. (2013) demonstrates a direct immunological role of adipocytes in instigating adipose inflammation via a MHCII-dependent process. 23377609 Preparation of novel monoclonal antibodies against chelated cadmium ions. The detection of cadmium ions using enzyme-linked immunosorbent assays (ELISA) has been reported by several research groups. Because cadmium ions are too small to stimulate the immune system, high molecular weight immunogens of cadmium are constructed using bifunctional chelators. At present, the most commonly used bifunctional chelator for the preparation of antigens for heavy metal ions is 1-(4-isothiocyanobenzyl) ethylenediamine N,N,N',N'-tetraacetic acid (ITCBE). However, the price of ITCBE is high. So we are interested in a cheaper bifunctional chelator, 1-(4-aminobenzyl) ethylenediamine N,N,N',N'-tetraacetic acid (aminobenzyl-EDTA). Here, cadmium ions were conjugated to carrier proteins using aminobenzyl-EDTA to make artificial antigens. Then, several mice were immunized with the antigen. And monoclonal antibodies (MAbs) against cadmium were produced. Spleen cells of immunized mice were fused with myeloma cells. The resulting hybridomas were screened using protein conjugates which were covalently bound to metal-free EDTA or cadmium. Three hybridoma cell lines (A3, E4 and B5) that produced MAbs with high selectivity and sensitivity were expanded for further study. Cross-reactivities with other metals were below 1 %. These antibodies were used to construct competitive ELISAs. The IC50 for A3 was 8.4 μg/l. The detection range and the lowest detection limit using the antibody A3 was 0.394-64.39 and 0.051 μg/l, respectively. Spike-recovery studies in tap water showed that the antibody A3 could be used for cadmium detection in drinking water. 23327668 Bioactive abietane and ent-kaurane diterpenoids from Isodon tenuifolius. Three new abietane diterpenoids, isoabietenins A-C (1-3), and 13 new ent-kauranoids, tenuifolins A-M (4-16), along with four known compounds (17-20), were isolated from the aerial parts of Isodon tenuifolius. The structures of the new metabolites were established on the basis of detailed spectroscopic analysis. The absolute configurations of 1, 15, and 16 were confirmed by single-crystal X-ray diffraction. Selected compounds were evaluated for their cytotoxicity against a small panel of human tumor cell lines, and some compounds showed inhibitory effects. Furthermore, several isolates exhibited inhibitory activity against nitric oxide production in LPS-activated RAW264.7 macrophages. 23609944 Fluorescent amino acids: modular building blocks for the assembly of new tools for chemical biology. Fluorescence spectroscopy is a powerful tool for probing complex biological processes. The ubiquity of peptide-protein and protein-protein interactions in these processes has made them important targets for fluorescence labeling, and to allow sensitive readout of information concerning location, interactions with other biomolecules, and macromolecular dynamics. This review describes recent advances in design, properties and applications in the area of fluorescent amino acids (FlAAs). The ability to site-selectively incorporate fluorescent amino acid building blocks into a protein or peptide of interest provides the advantage of closely retaining native function and appearance. The development of an array of fluorescent amino acids with a variety of properties, such as environment sensitivity, chelation-enhanced fluorescence, and profluorescence, has allowed researchers to gain insights into biological processes, including protein conformational changes, binding events, enzyme activities, and protein trafficking and localization. 23306171 A new spatane diterpenoid from the cultured soft coral Sinularia leptoclados. A new spatane diterpenoid, leptoclalin A (1), along with two previously reported known norcembranoid diterpenes (2 and 3), were isolated from a cultured soft coral Sinularia leptoclados. The structures were determined by extensive spectroscopic analyses and by comparison with the spectral data of related known compounds. Metabolite 1 is rarely found in spatane skeletons reported from soft corals. In addition, compound 1 exhibited weak cytotoxicity towards human tumor cell lines T-47 D and K-562. 22269904 Fish, contaminants and human health: quantifying and weighing benefits and risks. This paper describes a quantitative risk-benefit assessment of fish consumption. We compare the net health effect expressed in DALYs of two scenarios. The reference scenario is the current fish intake of the Dutch population, which is less than what is recommended by the health authorities. The alternative scenario describes the health effects if the population consumes 200g of fish per week, which is close to the recommendation. All health effects due to fish consumption for which there is convincing evidence are incorporated in the assessment. The QALIBRA software (www.qalibra.eu) is used to simulate the two scenarios. The results show there is a net benefit for the population if it consumes 200g of fish each week. 23237974 Lignans from Schisandra sphenathera Rehd. et Wils. and semisynthetic schisantherin A analogues: absolute configuration, and their estrogenic and anti-proliferative activity. A new dibenzocyclooctene-type lignan, named schisandrin A1 (1), together with nine known lignans (2-10), was isolated from the stems of Schisandra sphenathera. The structure of schisandrin A1, which contains a spirocyclic epoxy unit, was established by means of spectroscopic methods. The absolute configurations of schisandrin A1 (1) and schisantherin A (2) were determined by electronic circular dichroism (CD) and TDDFT calculations, with 2 further confirmed by X-ray crystallographic data. Ten new schisantherin A derivatives (11-20) and 6,7-secoschisantherol A (2b) were synthesized. In addition, natural lignans and semisynthetic schisantherin A derivatives showed the antiproliferative activity on four human cancer cell lines and Id1 (an inhibitor of DNA binding protein) and estrogenic potency. Compounds 5, 7, and 8 exhibited very potent estrogenic activity. 23625194 Lifestyle intervention and anti-obesity therapies in the polycystic ovary syndrome: impact on metabolism and fertility. Obesity is frequently present in patients with polycystic ovary syndrome (PCOS) and plays an important role in the pathogenesis of the metabolic, endocrine, and reproductive abnormalities associated with this syndrome. We aimed to summarize the effects of lifestyle changes and anti-obesity pharmacotherapy in patients with PCOS. We reviewed the literature regarding the effects of lifestyle changes and anti-obesity agents on the metabolic and endocrine abnormalities of PCOS. Lifestyle changes, including diet, exercise, and behavioral modification, appear to improve the metabolic and reproductive abnormalities of overweight and obese patients with PCOS. Therefore, lifestyle changes appear to represent the first-line management for all overweight and obese patients with PCOS. However, the optimal composition of diet and the optimal type of exercise in these patients are unknown. Anti-obesity agents that have been studied in PCOS include orlistat, sibutramine, and rimonabant. However, the latter two agents have been withdrawn from the market because of side effects. Long-term studies with orlistat in overweight and obese diabetic patients showed greater weight loss and metabolic and cardiovascular benefits than those achieved with lifestyle changes alone. However, there are limited data on the efficacy of orlistat in women with PCOS. In conclusion, lifestyle changes (diet, exercise and behavioral modification), particularly when combined with anti-obesity agents, exert beneficial effects on the endocrine abnormalities of obese patients with PCOS and improve metabolic parameters. 23359435 Crosslinking using rapid thermal processing for the fabrication of efficient solution-processed phosphorescent organic light-emitting diodes. Copolymers with a triscarbazole hole-transport group and an oxetane or benzocyclobutene crosslinkable group can be readily thermally crosslinked on timescales of 30 min or less, with rapid thermal processing (RTP) being highly effective for this purpose. Devices with RTP-crosslinked hole-transport layers and spin-coated emissive layers exhibit high external quantum efficiencies of up to 15%. 23178243 Evaluation of immunohistochemical markers to detect the genotoxic mode of action of fine and ultrafine dusts in rat lungs. Data on local genotoxicity after particle exposure are crucial to resolve mechanistic aspects such as the impact of chronic inflammation, types of DNA damage, and their role in lung carcinogenesis. We established immunohistochemical methods to quantify the DNA damage markers poly(ADP-ribose) (PAR), phosphorylated H2AX (γ-H2AX), 8-hydroxyguanosine (8-OH-dG), and 8-oxoguanine DNA glycosylase (OGG1) in paraffin-embedded tissue from particle-exposed rats. The study was based on lungs from a subchronic study that was part of an already published carcinogenicity study where rats had been intratracheally instilled with saline, quartz DQ12, amorphous silica (Aerosil(®) 150), or carbon black (Printex(®) 90) at monthly intervals for 3 months. Lung sections were stained immunohistochemically and markers were quantified in alveolar lining cells. Local genotoxicity was then correlated with already defined endpoints, i.e. mean inflammation score, bronchoalveolar lavage parameters, and carcinogenicity. Genotoxicity was most pronounced in quartz DQ12-treated rats, where all genotoxicity markers gave statistically significant positive results, indicating considerable genotoxic stress such as occurrence of DNA double-strand breaks (DSB), and oxidative damage with subsequent repair activity. Genotoxicity was less pronounced for Printex(®) 90, but significant increases in γ-H2AX- and 8-OH-dG-positive nuclei and OGG1-positive cytoplasm were nevertheless detected. In contrast, Aerosil(®) 150 significantly enhanced only 8-OH-dG-positive nuclei and oxidative damage-related repair activity (OGG1) in cytoplasm. In the present study, γ-H2AX was the most sensitive genotoxicity marker, differentiating best between the three types of particles. The mean number of 8-OH-dG-positive nuclei, however, correlated best with the mean inflammation score at the same time point. This methodological approach enables integration of local genotoxicity testing in subchronic inhalation studies and makes immunohistochemical detection, in particular of γ-H2AX and 8-hydroxyguanine, a very promising approach for local genotoxicity testing in lungs, with prognostic value for the long-term outcome of particle exposure. 23576355 Tirucallane Triterpenoids from the Stems of Brucea mollis. Three new tirucallane triterpenoids, brumollisols A-C (1-3, resp.), together with five known analogues, (23R,24S)-23,24,25-trihydroxytirucall-7-ene-3,6-dione (4), piscidinol A (5), 24-epipiscidinol A (6), 21α-methylmelianodiol (7), and 21β-methylmelianodiol (8), were isolated from an EtOH extract of the stems of Brucea mollis. Their structures were elucidated by means of spectroscopic methods including 1D- and 2D-NMR techniques and mass spectrometry. In the in vitro assays, compound 6 exhibited significant cytotoxic activity against A549 and BGC-823 cancer cells with IC50 values of 1.16 and 3.01 μM, respectively. At a concentration of 10 μM, compounds 1-5, 7, and 8 were found to inhibit NO production in mouse peritoneal macrophages with inhibitory ratios ranging from 39.8±7.7 to 68.2±4.5%. 23122077 Bacillus cereus AR156 induces resistance against Rhizopus rot through priming of defense responses in peach fruit. The biocontrol effects of Bacillus cereus AR156 on Rhizopus rot caused by Rhizopus stolonifer in postharvest peach fruit and the possible mechanisms were investigated. The results showed that fruit treated with B. cereus AR156 had significantly lower disease incidence and smaller lesion diameter than the control fruit did. B. cereus AR156 treatment remarkably enhanced activities of chitinase and β-1,3-glucanase, promoted accumulation of H(2)O(2), and improved total phenolic content and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity. Transcripts of four defense related genes were only significantly enhanced in fruit both treated with B. cereus AR156 and inoculated with R. stolonifer compared with those that were only treated with B. cereus AR156 or inoculated with R. stolonifer. These results suggest that B. cereus AR156 can effectively inhibit Rhizopus rot caused by R. stolonifer and enhance antioxidant activity in peach fruit through the priming of defense responses. 23123737 Involvement of the ANGPTs/Tie-2 system in ovarian hyperstimulation syndrome (OHSS). Ovarian hyperstimulation syndrome (OHSS) is a disorder associated with ovarian stimulation. OHSS features are ovarian enlargement with fluid shifting to the third space. Disturbances in the vasculature are considered the main changes that lead to OHSS. Our aim was to analyze the levels of angiopoietins 1 and 2 (ANGPT1 and 2) and their soluble and membrane receptors (s/mTie-2) in follicular fluid (FF) and in granulosa-lutein cells culture (GLCs) from women at risk of developing OHSS. We also evaluated the effect of ANGPT1 on endothelial cell migration. In ovaries from an OHSS rat model, we analyzed the protein concentration of ANGPTs, their mTie-2 receptor, and platelet-derived growth factor PDGF-B, -D and PDGFR-β. ANGPT1 levels were increased in both FF and GLCs from women at risk of OHSS. Incubation of these FF with an ANGPT1 neutralizing antibody decreased endothelial cell migration. In the ovaries of OHSS rat model, mTie-2 protein levels increased and PDGF-B and -D decreased. In summary, these results suggest that ANGPT1 could be another mediator in the development of OHSS. 23293962 Hepatocyte growth factor activator inhibitor type 2 (HAI-2) modulates hepcidin expression by inhibiting the cell surface protease matriptase-2. Matriptase-2, a recently identified cell surface protease, is the key enzyme of iron homoeostasis modulating the expression of the liver peptide hormone hepcidin. HAI (hepatocyte growth factor activator inhibitor) types 1 and 2 (HAI-1 and HAI-2 respectively) have been shown to inhibit the close homologue, i.e. matriptase. By co-expressing matriptase-2 and the inhibitor HAI-2 we have identified HAI-2 displaying high inhibitory potential against matriptase-2 at the cell surface as well as in conditioned medium. Accordingly, complex formation between matriptase-2 and HAI-2 was demonstrated by isolation of the complex via immobilizing either HAI-2 or matriptase-2 from lysates and conditioned medium of co-expressing cells. Furthermore, HAI-2 indirectly influences the expression of the hepcidin-encoding gene HAMP. The inhibitor abrogates the matriptase-2-mediated suppression of HAMP expression, presumably by inhibiting the supposed potential of matriptase-2 to cleave membrane-bound HJV (haemojuvelin). Taken together, the results of the present study have characterized HAI-2 as an inhibitor of matriptase-2 that modulates the synthesis of hepcidin and provides new insights into the regulatory mechanism of iron homoeostasis, with clinical importance for a treatment of iron overload diseases. 23643839 Activator or Inhibitor? GSK-3 as a new drug target. Glycogen synthase kinase-3 (GSK-3) is a cytoplasmic serine/threonine protein kinase that phosphorylates and inhibits glycogen synthase, thereby inhibiting glycogen synthesis from glucose. However, this serine/threonine kinase is now known to regulate numerous cellular processes through a number of signaling pathways important for cell proliferation, stem cell renewal, apoptosis and development. Because of these diverse roles, malfunction of this kinase is also known to be involved in the pathogenesis of human diseases, such as nervous system disorders, diabetes, bone formation, inflammation, cancer and heart failure. Therefore, GSK-3 is recognized as an attractive target for the development of new drugs. The present review summarizes the roles of GSK-3 in the insulin, Wnt/β-catenin and hedgehog signaling pathways including the regulation of their activities. The roles of GSK-3 in the development of human diseases within the context of its participation in various signaling pathways are also summarized. Finally, the possibility of new drug development targeting this kinase is discussed with recent information about inhibitors and activators of GSK-3. 23293094 Dietary exposure of mink (Mustela vison) to fish from the upper Hudson River, New York, USA: effects on reproduction and offspring growth and mortality. The effects of feeding farm-raised mink (Mustela vison) diets containing polychlorinated biphenyl (PCB)-contaminated fish from the upper Hudson River (New York, USA) on adult reproductive performance and kit growth and mortality were evaluated. Diets contained 2.5 to 20% Hudson River fish, providing 0.72 to 6.1 µg ∑PCBs/g feed (4.8-38 pg toxic equivalents [TEQWHO 2005 ]/g feed). The percentage of stillborn kits per litter was significantly increased by dietary concentrations of 4.5 µg ∑PCBs/g feed (28 pg TEQWHO 2005 /g feed) and greater. All offspring exposed to dietary concentrations of 4.5 and 6.1 µg ∑PCBs/g feed (28 and 38 pg TEQWHO 2005 /g feed) died by 10 weeks of age, and all offspring exposed to 1.5 and 2.8 µg ∑PCBs/g feed (10 and 18 pg TEQWHO 2005 /g feed) died by 31 weeks of age, leaving juveniles in the control and 0.72 µg ∑PCBs/g feed (0.41- and 4.8 pg TEQWHO 2005 /g feed) groups only. The dietary concentration predicted to result in 20% kit mortality (LC20) at six weeks of age was 0.34 µg ∑PCBs/g feed (2.6 pg TEQWHO 2005 /g feed). The corresponding maternal hepatic concentration was 0.80 µg ∑PCBs/g liver, wet weight (13 pg TEQWHO 2005 /g liver, wet wt). Mink residing in the upper Hudson River would be expected to consume species of fish that contain an average of 4.0 µg ∑PCBs/g tissue. Thus, a daily diet composed of less than 10% Hudson River fish could provide a dietary concentration of ∑PCBs that resulted in 20% kit mortality in the present study. 23333647 Viper venom induced inflammation with Montivipera xanthina (Gray, 1849) and the anti-snake venom activities of Artemisia absinthium L. in rat. The present study was conducted to explore the characterization of Montivipera xanthina crude venom partially by in vitro and in vivo and the anti-snake venom activities of Artemisia absinthium L. in comparison with carrageenan-induced acute inflammation model in rats. The LD50 value was estimated as 8.78 mg/kg within 24 h by different venom doses administrated intraperitoneally in mice. The IC50 value was 0.43 ± 0.18 μg/ml after 48 h treatment while the calculated value was 0.73 ± 0.10 μg/ml for the culture media totally refreshed after 2 h treatment with venom. Wistar rats were treated intraperitoneally with A. absinthium extract, 30 min before venom or carrageenan was injected subplantarly into the left hind paw. Intraperitoneal administration of 25 and 50 mg/kg extract was inhibited venom induced paw swelling at 0.5, 1, 2 and 3 h (p < 0.05) while 12.5, 25 and 50 mg/kg extract treatment was inhibited carrageenan-induced paw swelling at 2, 3, 4 and 5 h (p < 0.05). In conclusion, the in vivo toxicity and inflammatory actions and in vitro cytotoxic actions of crude M. xanthina venom were performed as a first report and inhibition of venom-induced inflammation by methanolic extract of A. absinthium was described. 23456735 Life-threatening hypoglycemia associated with intentional insulin ingestion. There are reports of insulin overdose by injection, yet little is known regarding the potential harms of intentional oral ingestion of insulin. In this report, we describe a case of massive insulin ingestion and ensuing hypoglycemia. To our knowledge, there are no previously published cases of hypoglycemia caused by intentional insulin ingestion. A 51-year-old man intentionally ingested three 10-ml vials (total of 3000 units) of various insulins: one vial each of insulin aspart, lispro, and glargine. Four symptomatic hypoglycemic episodes, with blood glucose levels of 48, 25, 34, and 40 mg/dl, occurred approximately 1, 3, 4, and 5 hours, respectively, after ingestion. The hypoglycemia could not be explained other than the ingestion of the insulins. The patient was admitted for observation, and euglycemia occurred within 24 hours without any additional hypoglycemic episodes. Hypoglycemia treatment is reviewed in this case report, and factors that may affect systemic response of orally ingested insulin, including gastrointestinal absorption and insulin sensitivity, are discussed. In addition, the findings of our case report may provide useful insight into the development of novel oral insulin products that are currently in research. Despite poor bioavailability (1%) when taken orally, insulin may produce symptomatic hypoglycemia with a massive ingestion. Vigilant blood glucose monitoring, supportive care with glucose replacement therapy, and admission to the hospital for observation may be required. 23164984 Placental concentrations of mercury, lead, cadmium, and arsenic and the risk of neural tube defects in a Chinese population. To examine whether in utero exposure to mercury (Hg), cadmium (Cd), lead (Pb) and arsenic (As) is associated with an elevated neural tube defects (NTDs) risk, placental concentrations of total Hg, Cd, Pb and As were measured with an inductively coupled plasma mass spectrometer (ICP-MS) in 36 anencephaly and 44 spina bifida cases as well as in 50 healthy controls. The median Hg concentration in the NTD cases (2.25 ng/g) was higher than that of the controls (1.16 ng/g). The odds ratio (OR) for an Hg concentration above the median was 8.80 (95% CI 3.80-20.36) for the NTD cases. NTD risks increased for the second and third high levels of the concentrations, with ORs of 2.70 (95% CI 1.13-6.43) and 18.20 (95% CI 5.45-60.73), respectively. Therefore, higher placental levels of Hg are associated with an elevated risk of NTDs. 23583437 Two new steroidal saponins from Selaginella uncinata (Desv.) Spring and their protective effect against anoxia. Four steroidal saponins were isolated from the anti-anoxic fraction of the 60% EtOH extract of Selaginella uncinata, including two new compounds, (3β, 7β, 12β, 25R)-spirost-5-ene-3, 7, 12-triol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-O-β-d-glucopyranoside (1), (2α, 3β, 12β, 25R)-spirost-5-ene-2, 3, 12-triol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-O-β-d-glucopyranoside (2) and two known compounds, (3β, 12β, 25R)-spirost-5-ene-3,12-diol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-O-β-d-glucopyranoside, (3), (1α, 3β, 25R)-spirost-5-ene-2-diol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl(1→4)]-O-β-d-glucopyranoside (4). The four compounds showed potent protective effect against anoxia in the anoxic PC12 cells assay, among which compounds 1 and 2 were the most active. To our knowledge, this is the first study to report the steroidal saponins in the plant S. uncinata and demonstrate their protective effect against anoxia in PC12 cell assay. 23419638 Pelargonidin activates the AhR and induces CYP1A1 in primary human hepatocytes and human cancer cell lines HepG2 and LS174T. We examined the effects of anthocyanidins (cyanidin, delphinidin, malvidin, peonidin, petunidin, pelargonidin) on the aryl hydrocarbon receptor (AhR)-CYP1A1 signaling pathway in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cells. AhR-dependent reporter gene expression in transfected HepG2 cells was increased by pelargonidin in a concentration-dependent manner at 24h. Similarly, pelargonidin induced the expression of CYP1A1 mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the most potent activator of AhR. CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme. Ligand binding analysis demonstrated that pelargonidin was a weak ligand of AhR. Enzyme kinetic analyses using human liver microsomes revealed inhibition of CYP1A1 activity by delphinidin (IC50 78 μM) and pelargonidin (IC50 33 μM). Overall, although most anthocyanidins had no effects on AhR-CYP1A1 signaling, pelargonidin can bind to and activate the AhR and AhR-dependent gene expression, and pelargonidin and delphinidin inhibit the CYP1A1 catalytic activity. 23121767 EGR1 is critical for gastrin-dependent upregulation of anion exchanger 2 in gastric cancer cells. The essential anion exchanger (AE) involved in bicarbonate secretion is AE2/SLC4A2, a membrane protein recognized to be relevant for the regulation of the intracellular pH in several cell types. Here we report that gastrin, a major gastrointestinal hormone, upregulates the expression of AE2 mRNA and protein in a cholecystokinin B receptor dependent manner in gastric cancer cells. The upregulated species of AE2 mRNA originates from the classical upstream promoter of the AE2 gene (here referred to as AE2a1) which provides the binding site for transcription factors early growth response 1 (EGR1) and SP1. EGR1 upregulated the AE2 expression that can be competitively inhibited by SP1 in co-transfection experiments. This competitive inhibition was avoided in cells because the SP1 expression was time-staggered to EGR1 in response to gastrin. Overexpression or knockdown of EGR1 consistently increased or decreased the expression of AE2. Our data linked a novel signal pathway involved in gastrin-stimulated AE2 expression. 23518155 A novel GIP-oxyntomodulin hybrid peptide acting through GIP, glucagon and GLP-1 receptors exhibits weight reducing and anti-diabetic properties. Oxyntomodulin (Oxm) is a 37-amino acid peptide linked to alleviation of obesity-diabetes through a dual mode of action mediated at both glucagon and GLP-1 receptors. GIP is the principle physiological regulator of postprandial insulin secretion. Therefore, the primary aim was to design a novel GIP-Oxm peptide incorporating the actions of GIP, GLP-1 and glucagon in a single molecule. The first 11 N-terminal residues of Oxm were substituted with the sequence of stable dA(2)GIP molecule to generate a novel GIP-Oxm peptide (dA(2)GIP-Oxm). dA(2)GIP-Oxm was resistant to DPP-IV and significantly stimulated in vitro insulin release. dA(2)GIP-Oxm stimulated cAMP production in GIP-R, glucagon-R and GLP-1-R transfected cells by up to 95%, 83% and 77% of that elicited by respective native ligands. Acute administration of dA(2)GIP-Oxm to HFF mice resulted in reduced plasma glucose (45% reduction) and increased insulin concentrations (1.7-fold increase). Furthermore, dA(2)GIP-Oxm lowered plasma glucose (42% reduction) and increased plasma insulin (1.6-fold increase) when administered to HFF mice four hours prior to a glucose load. Once-daily administration of dA(2)GIP-Oxm for 15 days in HFF mice lowered body weight (13% reduction), reduced plasma glucose (40% reduction) and increased plasma insulin (1.7-fold increase). Furthermore, glycemic responses were improved (38% reduction) and glucose-mediated plasma insulin concentrations enhanced (2-fold increase). These improvements in metabolic control were independent of changes in food intake and insulin sensitivity. dA(2)GIP-Oxm exerts positive beneficial actions on glucose homeostasis, beta-cell insulin secretion and body weight, mediated through GIP, glucagon and GLP-1 receptors. Such multiple-acting peptides may hold promise as novel therapies for obesity-diabetes. 23363335 Base-flipping propensities of unmethylated, hemimethylated, and fully methylated CpG sites. Methylation of C5 of cytosines at CpG dinucleotide sites of the DNA is one of the most important factors regulating the expression of genes. The interactions of these CpG sites with proteins are essential for recognition and catalysis and in many cases are characterized by the flipping of either of the cytosine bases out of the DNA helix. In this paper, we present results from molecular dynamics simulations indicating that methylation of CpG sites suppresses spontaneous extra-helical conformations of either of the two cytosines. Thus, cytosines in unmethylated sites flip out easier than in hemimethylated sites and the latter flip out easier than in fully methylated sites. The different propensities for base flipping is observed not only between the cytosines that differ in their methylation states but also between the cytosines on the complementary strand. From alchemical mutation calculations, we find that methylation of one of the cytosines increases the free energy of the extra-helical conformation by 10.3-16.5 kJ/mol and this increase is additive with respect to the second methylation. Potential of mean force calculations confirm these results and reveal that cytosines in unmethylated sites favor flipping via the major-groove pathway. We perform several analyses to correlate this behavior with structural changes induced by the different methylation states of the CpG site. However, we demonstrate that the driving force for these propensities is the change in the electronic distribution around the pyrimidine ring upon methylation. In particular, unmethylated cytosine interacts more favorably (primarily via electrostatic forces) with solvent water molecules than methylated cytosine. This is observed for, both, extra-helical cytosines and intra-helical cytosines in which the cytosine on the complementary strand flips out and water molecules enter the DNA double-helix and substitute the hydrogen bonds with the orphan guanine. On the basis of these results of spontaneous base flipping, we conjecture that the mechanism for base flipping observed in complexes between hemimethylated DNAs and proteins is not likely to be passive. 23183186 P21-activated protein kinase 1 (Pak1) mediates the cross talk between insulin and β-catenin on proglucagon gene expression and its ablation affects glucose homeostasis in male C57BL/6 mice. In gut endocrine L cells, the Wnt signaling pathway effector β-catenin (β-cat)/transcription factor 7-like 2 mediates the stimulatory effect of insulin on proglucagon (gcg) expression and glucagon-like peptide-1 (GLP-1) production. In several other cell lineages, insulin is able to stimulate p21-activated protein kinase 1 (Pak1). Here we determined the role of Pak1 in gcg expression and the effect of Pak1 deletion on glucose homeostasis. Insulin stimulated Pak1 activation through increasing its Thr423 phosphorylation in gut gcg-expressing cell lines, associated with increased gcg mRNA levels. This stimulation was attenuated by the Pak inhibitor 2,2'-dihydroxy-1,1'-dinaphthyldisulfide (IPA3) or dominant-negative Pak1. Both insulin and cAMP-promoting agents activated β-cat Ser675 phosphorylation, which was attenuated by IPA3 or protein kinase A inhibition, respectively. Gut gcg levels were reduced in male Pak1(-/-) mice, associated with impaired glucose tolerance after an ip or oral glucose challenge. These mice had lower circulating active GLP-1 levels after a glucose challenge as well as reduced distal ileum GLP-1 content after insulin treatment. Finally, the Pak1(-/-) mice exhibited reduced brainstem gcg level and abolished β-cat Ser675 phosphorylation in brain neurons after insulin treatment. We suggest that Pak1 mediates the cross talk between insulin and Wnt signaling pathways on gut and brain gcg expression, and its ablation impairs glucose homeostasis. 23265660 Superomniphobic surfaces for effective chemical shielding. Superomniphobic surfaces display contact angles >150° and low contact angle hysteresis with essentially all contacting liquids. In this work, we report surfaces that display superomniphobicity with a range of different non-Newtonian liquids, in addition to superomniphobicity with a wide range of Newtonian liquids. Our surfaces possess hierarchical scales of re-entrant texture that significantly reduce the solid-liquid contact area. Virtually all liquids including concentrated organic and inorganic acids, bases, and solvents, as well as viscoelastic polymer solutions, can easily roll off and bounce on our surfaces. Consequently, they serve as effective chemical shields against virtually all liquids--organic or inorganic, polar or nonpolar, Newtonian or non-Newtonian. 23644256 Ibuprofen plus Isosorbide Dinitrate treatment in the mdx mice ameliorates dystrophic heart structure. BACKGROUND: Co-administration of ibuprofen (IBU) and isosorbide dinitrate (ISDN) provides synergistic beneficial effects on dystrophic skeletal muscle. Whether this treatment has also cardioprotective effects in this disease was still unknown. Aims: to evaluate the effects of co-administration of IBU and ISDN (a) on left ventricular (LV) structure and function, and (b) on cardiac inflammatory response and fibrosis in mdx mice. METHODS: three groups of mice were studied: mdx mice treated with IBU (50mgkg(-1))+ISDN (30mgkg(-1)) administered daily in the diet, mdx mice that received standard diet without drugs and wild type aged-matched mice. Animals were analysed after 10-11 months of treatment. Structural and functional parameters were evaluated by echocardiography while histological analyses were performed to evaluate inflammatory response, collagen deposition, cardiomyocyte number and area. RESULTS: treatment for 10-11 months with IBU+ISDN preserved LV wall thickness and LV mass. Drug treatment also preserved the total number of cardiomyocytes in the LV and attenuated the increase in cardiomyocyte size, when compared to untreated mdx mice. Moreover, a trend towards a decreased number of inflammatory cells, a reduced LV myocardial interstitial fibrosis and an enhanced global LV function response to stress was observed in treated mdx mice. CONCLUSIONS: treatment for 10-11 months with IBU+ISDN is effective in preventing the alterations in LV morphology of mdx mice while not reaching statistical significance on LV function and cardiac inflammation. 23559436 Molecule-Induced Peroxide Homolysis. The homolytic cleavage of peroxide bonds, leading to the formation of free radicals, plays an important role in the (spontaneous) oxidation of a wide variety of hydrocarbons in the presence of oxygen. Such aerobic oxidations can be desired (e.g. for industrially applied autoxidations) or undesired (e.g. food deterioration). In this contribution we provide experimental and computational evidence for a molecule-induced homolytic dissociation mechanism between alkyl peroxide and compounds featuring weakly bonded H atoms such as (di)unsaturated hydrocarbons. 22906572 Chemicals inducing acute irritant contact dermatitis mobilize intracellular calcium in human keratinocytes. Intracellular Ca(2+) increase is a common feature of multiple cellular pathways associated with receptor and channel activation, mediator secretion and gene regulation. We investigated the possibility of using this Ca(2+) signal as a biomarker for a reaction to chemical irritants of normal human keratinocytes (NHK) in submerged primary cell culture. We tested 14 referenced chemical compounds classified as strong (seven), weak (four) or non- (three) irritants in acute irritant contact dermatitis. We found that the strong irritant compounds tested at 20-40 mM induced an intracellular Ca(2+) increase measurable by spectrofluorimetry in an automated test. Weak and non-irritant compounds however did not increase intracellular Ca(2+) concentration. We further investigated the mechanisms by which the amine heptylamine, classified as a R34 corrosive compound, increases intracellular Ca(2+). Heptylamine (20mM) induced an ATP release that persisted in the absence of intra- and extra-cellular Ca(2+). In addition, we found that this ATP activates NHK purinergic receptors that subsequently cause the increase in intracellular Ca(2+) from sarcoplasmic reticular stores. We conclude that measuring the intracellular Ca(2+) concentration in NHK is a suitable and easy way of determining any potential reaction to soluble chemical compounds. 23228043 Drug safety evaluation of defibrotide. INTRODUCTION: Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). Defibrotide (DF) has been shown in Phase II and III trials to improve complete response in patients with severe VOD (sVOD). None of the articles, to date, provide a comprehensive review of the safety of DF in VOD and/or a range of other conditions. AREAS COVERED: This article reviews current clinical findings on DF, primarily in terms of safety for use in treatment and prophylaxis of VOD, and relevant safety data for its use in other diseases. The literature review was conducted using a PubMed search with the fixed term 'defibrotide' in combination with ≥ 1 of 'safety', 'veno-occlusive disease' (with and without 'treatment', 'prevention'), 'oncology', 'myeloma', 'microangiopathy', 'anti-thrombotic' and 'peripheral vascular disorder'. Related articles from the EBMT and ASH conference websites were also included. EXPERT OPINION: DF was well tolerated in majority of the studies. The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD. 23485065 Conformation Guides Molecular Efficacy in Docking Screens of Activated β-2 Adrenergic G Protein Coupled Receptor. A prospective, large library virtual screen against an activated β2-adrenergic receptor (β2AR) structure returned potent agonists to the exclusion of inverse-agonists, providing the first complement to the previous virtual screening campaigns against inverse-agonist-bound G protein coupled receptor (GPCR) structures, which predicted only inverse-agonists. In addition, two hits recapitulated the signaling profile of the co-crystal ligand with respect to the G protein and arrestin mediated signaling. This functional fidelity has important implications in drug design, as the ability to predict ligands with predefined signaling properties is highly desirable. However, the agonist-bound state provides an uncertain template for modeling the activated conformation of other GPCRs, as a dopamine D2 receptor (DRD2) activated model templated on the activated β2AR structure returned few hits of only marginal potency. 23143666 Survivin in adrenocortical tumors - pathophysiological implications and therapeutic potential. Treatment options for adrenocortical carcinoma (ACC) are very limited. In other solid tumors, small vaccination trials targeting the anti-apoptotic molecule survivin suggested immunological and clinical benefit in selected patients. Therefore, we investigated whether survivin might be a suitable target for immunotherapy in ACC. Survivin mRNA and protein expression was assessed in adrenal tissue specimens [by real-time-PCR in 29 ACC, 24 adrenocortical adenomas (ACA) and 12 normal adrenal glands; by immunohistochemistry in 167 ACCs, 15 ACA, and 5 normal adrenal glands]. Expression was correlated with clinical outcome using Kaplan-Meier and Cox regression analyses. The anti-apoptotic role of survivin was investigated in the SW13 ACC cell line using survivin siRNA. The presence of spontaneous survivin specific T-cells in peripheral blood was assessed by FACS dextramere staining in 29 ACC patients in comparison to healthy controls. Survivin mRNA in ACC was significantly overexpressed when compared with ACA or normal adrenal glands. Immunohistochemistry confirmed survivin protein expression in 97% of the ACCs. In 83% of samples, staining was moderate or high and clinical outcome in this subgroup showed a trend towards poorer prognosis [hazard ratio for death 2.28 (95% CI 0.99-5.28); p=0.053]. Survivin knockdown in SW-13 cell significantly increased the rate of apoptosis. Finally, spontaneous survivin-reactive T cells were detectable in 3 of 29 ACC patients. In conclusion, our data suggest that survivin could play an important role in the anti-apoptotic mechanisms in ACC and provide first hints that targeting survivin might be an interesting new therapeutic approach in this rare disease. 23265903 Inhibition of the β-carbonic anhydrases from Mycobacterium tuberculosis with C-cinnamoyl glycosides: identification of the first inhibitor with anti-mycobacterial activity. A small series of C-cinnamoyl glycoside containing the phenol moiety was tested for the inhibition of the three Mycobacterium tuberculosis β-carbonic anhydrases (CAs, EC 4.2.1.1) with activities in the low micromolar range detected. The compounds were also tested for the inhibition of growth of M. tuberculosis H(37)Rv strain, leading to the identification of (E)-1-(2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl)-4-(3-hydroxyphenyl)but-3-en-2-one (1) as the first carbonic anhydrase inhibitor with anti-tubercular activity. 23177255 Design, synthesis and biological evaluation of glucose-containing scutellarein derivatives as neuroprotective agents based on metabolic mechanism of scutellarin in vivo. Based on metabolic mechanism of scutellarin in vivo that scutellarin could be hydrolyzed into scutellarein by β-glucuronide enzyme, some glucose-containing scutellarein derivatives were designed and synthesized through the introduction of glucose moiety at C-7 position of scutellarein via a glucosidic bond. Biological activity evaluation showed that these glucose-containing scutellarein derivatives exhibited potent DPPH radical scavenging activities. Furthermore, the improvement of physicochemical properties such as anticoagulant and neuroprotective activities alongside with the water solubility was achieved by introducing glucose. These findings suggest that the introduction of the glucose moiety to scutellarein wattants further development of this kind of compounds as neuroprotective agents. 23600626 Layer-by-Layer Polyelectrolyte Deposition: A Mechanism for Forming Biocomposite Materials. Complex coacervates prepared from poly(aspartic acid) (polyAsp) and poly-l-histidine (polyHis) were investigated as models of the metastable protein phases used in the formation of biological structures such as squid beak. When mixed, polyHis and polyAsp form coacervates whereas poly-l-glutamic acid (polyGlu) forms precipitates with polyHis. Layer-by-layer (LbL) structures of polyHis-polyAsp on gold substrates were compared with those of precipitate-forming polyHis-polyGlu by monitoring with iSPR and QCM-D. PolyHis-polyAsp LbL was found to be stiffer than polyHis-polyGlu LbL with most water evicted from the structure but with sufficient interfacial water remaining for molecular rearrangement to occur. This thin layer is believed to be fluid and like preformed coacervate films, capable of spreading over both hydrophilic ethylene glycol as well as hydrophobic monolayers. These results suggest that coacervate-forming polyelectrolytes deserve consideration for potential LbL applications and point to LbL as an important process by which biological materials form. 23414841 A novel concept of radiosynthesis of a (99m)Tc-labeled dimeric RGD peptide as a potential radiotracer for tumor imaging. Radiolabeled Arg-Gly-Asp (RGD) peptides are promising agents for non invasive imaging of αvβ3 expression in malignant tumors. The integrin αvβ3 binding affinity and consequent tumor uptake could be improved when a dimeric RGD peptide is used as the targeting moiety instead of a monomer. Towards this, a novel approach was envisaged to synthesize a (99m)Tc labeled dimeric RGD derivative using a RGD monomer and [(99m)TcN](+2) intermediate. The dithiocarbamate derivative of cyclic RGD peptide G3-c(RGDfK) (G3=Gly-Gly-Gly, f=Phe, K=Lys) was synthesized and radiolabeled with [(99m)TcN](+2) intermediate to form the (99m)TcN-[G3-c(RGDfK)]2 complex in high yield (∼98%). Biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors showed good tumor uptake [4.61±0.04% IA/g at 30min post-injection] with fast clearance of the activity from non-target organs/tissue. Scintigraphic imaging studies showed visible accumulation of activity in the tumor with appreciable target to background ratio. 23194552 In vitro antibacterial, cytotoxicity and haemolytic activities and phytochemical analysis of seagrasses from the Gulf of Mannar, South India. It is essential to study the phytochemical constituents and toxicological properties of seagrasses when considering their food applications. Aqueous methanolic extracts of six seagrasses were evaluated for their antibacterial, cytotoxic (brine shrimp leathality assay) and haemolytic activity. Thin layer chromatography (TLC) and phytochemical analysis were used to compare the phytochemical profiles of six seagrasses. Among the six seagrasses examined, Halodule pinifolia and Cymodocea rotundata showed predominant growth inhibitory activity against all the tested human pathogens. Cytotoxicity of seagrass extracts against nauplii of Artemia salina revealed that Syringodium isoetifolium exhibited lesser toxicity with LC(50) value of 699.096 μg/ml. Of all the seagrasses tested, H. pinifolia recorded the minimum haemolytic activity of 2.07±0.63% at 1000 μg/ml concentration. Phytochemical analysis showed the presence of common plant chemical constituents which varied with respect to species. The present findings suggest the possible pharmacological applications of selected seagrasses that can be used as food ingredients. 23538843 Transcriptional Analysis of Drought-Induced Genes in the Roots of a Tolerant Genotype of the Common Bean (Phaseolus vulgaris L.). In Brazil, common bean (Phaseolus vulgaris L.) productivity is severely affected by drought stress due to low technology cultivation systems. Our purpose was to identify differentially expressed genes in roots of a genotype tolerant to water deficit (BAT 477) when submitted to an interruption of irrigation during its development. A SSH library was constructed taking as "driver" the genotype Carioca 80SH (susceptible to drought). After clustering and data mining, 1572 valid reads were obtained, resulting in 1120 ESTs (expressed sequence tags). We found sequences for transcription factors, carbohydrates metabolism, proline-rich proteins, aquaporins, chaperones and ubiquitins, all of them organized according to their biological processes. Our suppressive subtractive hybridization (SSH) library was validated through RT-qPCR experiment by assessing the expression patterns of 10 selected genes in both genotypes under stressed and control conditions. Finally, the expression patterns of 31 ESTs, putatively related to drought responses, were analyzed in a time-course experiment. Our results confirmed that such genes are more expressed in the tolerant genotype during stress; however, they are not exclusive, since different levels of these transcripts were also detected in the susceptible genotype. In addition, we observed a fluctuation in gene regulation over time for both the genotypes, which seem to adopt and adapt different strategies in order to develop tolerance against this stress. 23503927 Impact of long-range van der Waals forces on chiral recognition in a Cinchona alkaloid chiral selector system. Singly-charged complexes of (8S,9R)-tert-butylcarbamoylquinine (tBuCQN), N-3,5-dinitrobenzoyl-(S,R)-leucine (DNB-S/R-leucine), and alkali metal counter ions (Li(+), Na(+), K(+)) were investigated by density-functional theory. It is shown that the cations prefer formation of an ionic pair with the carboxylate group of DNB-Leu over the formation of a cation-π interaction. The [tBuCQN·DNB-S/R-Leu·Na](+) complex is bound by a coulombic attraction, a hydrogen bond, a π-π interaction and van der Waals forces. The tBuCQN chiral selector preferentially complexes with the DNB-S-Leu enantiomer, because the favourable stereochemistry allows the stabilization of the complex by at least one binding mode more compared to the complex containing the DNB-R-Leu molecule. Weakening of the binding modes is observed using the lithium counter ion compared to the sodium one. The weakening is more pronounced in [tBuCQN·DNB-R-Leu·Li](+) than in [tBuCQN·DNB-S-Leu·Li](+). The exact opposite effect is observed using the potassium counter ion. Hence, the lithium counter ion enhances the enantioselectivity of tBuCQN while the potassium counter ion reduces the enantioselectivity of tBuCQN. 23383750 Understanding and Controlling Morphology Formation in Langmuir-Blodgett Block Copolymer Films Using PS-P4VP and PS-P4VP/PDP. This contribution offers a comprehensive understanding of the factors that govern the morphologies of Langmuir-Blodgett (LB) monolayers of amphiphilic diblock copolymers (BCs). This is achieved by a detailed investigation of a wide range of polystyrene-poly(4-vinyl pyridine) (PS-P4VP) block copolymers, in contrast to much more limited ranges in previous studies. Parameters that are varied include the block ratios (mainly for similar total molecular weights, occasionally other total molecular weights), the presence or not of 3-n-pentadecylphenol (PDP, usually equimolar with VP, with which it hydrogen bonds), the spreading solution concentration ("low" and "high"), and the LB technique (standard vs "solvent-assisted"). Our observations are compared with previously published results on other amphiphilic diblock copolymers, which had given rise to contradictory interpretations of morphology formation. Based on the accumulated results, we re-establish early literature conclusions that three main categories of LB block copolymer morphologies are obtained depending on the block ratio, termed planar, strand, and dot regimes. The block composition boundaries in terms of mol % block content are shown to be similar for all BCs having alkyl chain substituents on the hydrophilic block (such as PS-P4VP/PDP) and are shifted to higher values for BCs with no alkyl chain substituents (such as PS-P4VP). This is attributed to the higher surface area per repeat unit of the hydrophilic block monolayer on the water surface for the former, as supported by the onset and limiting areas of the Langmuir isotherms for the BCs in the dot regime. 2D phase diagrams are discussed in terms of relative effective surface areas of the two blocks. We identify and discuss how kinetic effects on morphology formation, which have been highlighted in more recent literature, are superposed on the compositional effects. The kinetic effects are shown to depend on the morphology regime, most strongly influencing the strand and, especially, planar regimes, where they give rise to a diversity of specific structures. Besides film dewetting mechanisms, which are different when occurring in structured versus unstructured films (the latter previously discussed in the literature), kinetic influences are discussed in terms of chain association dynamics leading to depletion effects that impact on growing aggregates. These depletion effects particularly manifest themselves in more dilute spreading solutions, with higher molecular weight polymers, and in composition regimes characterized by equilibrium degrees of aggregation that are effectively infinite. It is by understanding these various kinetic influences that the diversity of structures can be classified by the three main composition-dependent regimes. 23316965 Inhibition of matrix metalloproteinases (MMPs) as a potential strategy to ameliorate hypertension-induced cardiovascular alterations. A group of proteases, the matrix metalloproteinases (MMPs) are well known for their capacity to degrade extracellular matrix (ECM) proteins. Particularly MMP-2 and MMP-9 contribute to the degradation and reorganization of the ECM components and are involved in the pathophysiology of cardiovascular remodeling. Imbalanced MMP activity promotes vascular smooth muscle cells and migration and proliferation and endothelial dysfunction, thus resulting in increased cardiovascular stiffness and hypertrophy. Furthermore, MMP-2 cleaves non-ECM protein substrates including cellular receptors and intracellular proteins, thus causing cardiac and vascular dysfunction. It is now becoming clear that increased MMP activity promotes long-lasting cardiovascular structural and functional alterations in both experimental and clinical hypertension, and this alteration may contribute to sustained hypertension and its complications. Other pathogenic mechanisms including activation of the renin-angiotensin-aldosterone system and oxidative stress activate and upregulate MMPs. Therefore, MMP inhibition may prevent the deleterious consequences of hypertension to the cardiovascular system. This review article will focus on growing evidence supporting the relevance of MMPs in hypertension and the effects of MMP inhibitors. Particularly, the effects of doxycycline used as a non selective MMP inhibitor in experimental and clinical studies will be discussed. 23123331 Seventy-two-hour release formulation of the poorly soluble drug silybin based on porous silica nanoparticles: in vitro release kinetics and in vitro/in vivo correlations in beagle dogs. The objective of this study was to prepare a 72 h-release formulation of silybin (72 h-SLB) using a combination of solid dispersion, gel matrix and porous silica nanoparticles (PSNs) and to investigate the in vitro/in vivo correlations (IVIVCs). The results of scanning electron microscopy and N(2) adsorption demonstrated that empty PSNs possessed a spherical shape, a highly porous structure, a large specific surface area (385.89 ± 1.12 m(2)/g) and a small pore size (2.74 nm on average). The in vitro dissolution profiles of both 72 h-SLB and silybin-loaded PSNs in different concentrations (0.01, 0.06 and 0.08M) of Na(2)CO(3) solutions revealed that 0.06 M Na(2)CO(3) solution was the optimal medium in which silybin could be released from 72 h-SLB with first-order release kinetics and from PSNs with Higuchi kinetics. Furthermore, the IVIVCs of 72 h-SLB and silybin-loaded PSNs in beagle dogs were also established. Using 0.06 M Na(2)CO(3) solution as the in vitro dissolution medium, a good linear relationship could be achieved for both 72 h-SLB and silybin-loaded PSNs. The findings support the fact that the 72 h-SLB (consisting of solid dispersion, regular gel matrix and PSNs) together with Na(2)CO(3) solution as an in vitro dissolution medium can be developed into a promising formulation for poorly soluble drugs, which enjoys a good IVIVC. 23267837 Anti-tumor effects of peptide analogs targeting neuropeptide hormone receptors on mouse pheochromocytoma cells. Pheochromocytoma is a rare but potentially lethal chromaffin cell tumor with currently no effective treatment. Peptide hormone receptors are frequently overexpressed on endocrine tumor cells and can be specifically targeted by various anti-tumor peptide analogs. The present study carried out on mouse pheochromocytoma cells (MPCs) and a more aggressive mouse tumor tissue-derived (MTT) cell line revealed that these cells are characterized by pronounced expression of the somatostatin receptor 2 (sst2), growth hormone-releasing hormone (GHRH) receptor and the luteinizing hormone-releasing hormone (LHRH) receptor. We further demonstrated significant anti-tumor effects mediated by cytotoxic somatostatin analogs, AN-162 and AN-238, by LHRH antagonist, Cetrorelix, by the cytotoxic LHRH analog, AN-152, and by recently developed GHRH antagonist, MIA-602, on MPC and for AN-152 and MIA-602 on MTT cells. Studies of novel anti-tumor compounds on these mouse cell lines serve as an important basis for mouse models of metastatic pheochromocytoma, which we are currently establishing. 22301818 Screening of immunomodulatory activity of total and protein extracts of some Moroccan medicinal plants. Herbal and traditional medicines are being widely used in practice in many countries for their benefits of treating different ailments. A large number of plants in Morocco were used in folk medicine to treat immune-related disorders. The objective of this study is to evaluate the immunomodulatory activity of protein extracts (PEs) of 14 Moroccan medicinal plants. This activity was tested on the proliferation of immune cells. The prepared total and PEs of the plant samples were tested using MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide) assay on the splenocytes with or without stimulation by concanavalin-A (Con-A), a mitogenic agent used as positive control. The results of this study indicated different activity spectra. Three groups of activities were observed. The first group represented by Citrullus colocynthis, Urtica dioica, Elettaria cardamomum, Capparis spinosa and Piper cubeba showed a significant immunosuppressive activity. The second group that showed a significant immunostimulatory activity was represented by Aristolochia longa, Datura stramonium, Marrubium vulgare, Sinapis nigra, Delphynium staphysagria, Lepidium sativum, Ammi visnaga and Tetraclinis articulata. The rest of the plant extracts did not alter the proliferation induced by Con-A. This result was more important for the PE than for the total extract. In conclusion, this study revealed an interesting immunomodulating action of certain PEs, which could explain their traditional use. The results of this study may also have implications in therapeutic treatment of infections, such as prophylactic and adjuvant with cancer chemotherapy. 22771462 Postsynaptic mGluR mediated excitation of neurons in midbrain periaqueductal grey. Metabotropic glutamate (mGlu) receptors modulate pain from within the midbrain periaqueductal grey (PAG). In the present study, the postsynaptic mGlu receptor mediated effects on rat PAG neurons were examined using whole-cell patch-clamp recordings in brain slices. The selective group I agonist DHPG (10 μM) produced an inward current in all PAG neurons tested which was associated with a near parallel shift in the current-voltage relationship. By contrast, the group II and III mGlu receptor agonists DCG-IV (1 μM) and l-AP4 (3 μM) produced an outward current in only 10-20% of PAG neurons tested. The DHPG induced current was concentration dependent (EC(50) = 1.4 μM), was reduced by the mGlu1 antagonist CPCCOEt (100 μM), and was further reduced by CPCCOEt in combination with the mGlu5 antagonist MPEP (10 μM). The glutamate transport blocker TBOA (30 μM) also produced an inward current, however, this was largely abolished by CNQX (10 μM) plus AP5 (25 μM). Slow EPSCs were evoked following train, but not single shock stimulation, which were enhanced by TBOA (30 μM). The TBOA enhancement of slow EPSCs was abolished by MPEP plus CPCCOEt. These findings indicate that endogenously released glutamate, under conditions in which neurotransmitter spill-over is enhanced, activates group I mGlu receptors to produce excitatory currents within PAG. Thus, postsynaptic group I mGlu receptors have the potential to directly modulate the analgesic, behavioural and autonomic functions of the PAG. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. 23612419 Traditional and alternative natural therapeutic products used in the treatment of respiratory tract infectious diseases in the eastern Catalan Pyrenees (Iberian Peninsula). ETHNOPHARMACOLOGICAL RELEVANCE: Respiratory tract diseases, including mild troubles, such as the common cold, and also life-threatening ones such as bacterial pneumonia and lung cancer, are very important in terms of mortality, incidence, prevalence and costs. Classical medicine has undoubtedly addressed these illnesses, but the body of knowledge generated by alternative approaches, among which folk medicine plays an important role, is not at all negligible. AIMS OF THE STUDY: In this context, we performed an ethnobotanical study in a Catalan region of the eastern Pyrenees, northeast Iberian Peninsula, in order to assess the popular knowledge on useful plants. We present here the data concerning pharmaceutical uses of plants devoted to respiratory illnesses. METHODOLOGY: A total of 160 informants (94 women and 66 men, born between 1915 and 1988) were interviewed during 102 semi-structured interviews. Voucher specimens were collected, and then processed and deposited in the herbarium BCN. RESULTS: We collected information about 99 plant taxa (94 species - some of them with subspecies - of 85 genera belonging to 50 families) popularly employed to prevent or treat respiratory troubles. The degree of reliability of uses is high, as indicated for instance by an informant consensus factor of 0.83 and by high medicinal importance indexes for many taxa. In addition, we have recorded information on 14 animal and four mineral products also used against respiratory ailments, this constituting the first ethnopharmacological work in the Catalan linguistic area to report plant, animal and mineral remedies, and one of the very few in the Iberian Peninsula involving the study of ethnozoological medicines. CONCLUSIONS: The data collected show a high degree of consistency and indicate a remarkable persistence of folk knowledge on plant uses. The anticatarrhal, antitussive and for sore throat are the most valuable uses. This research could be the starting point for further research aiming to obtain products that may generalise the alternative medical uses here raised at a local level. Phytochemical and pharmacological studies on some of the plants quoted here - of which we could provide material to potentially interested researchers - would be useful first steps in this process. 23618900 Interlaboratory evaluation of a cow's milk allergy mouse model to assess the allergenicity of hydrolysed cow's milk based infant formulas. This study describes two phases of a multi-phase project aiming to validate a mouse model for cow's milk allergy to assess the potential allergenicity of hydrolysed cow's milk based infant formulas (claim support EC-directive 2006/141/E). The transferability and the discriminatory power of this model was evaluated in 4 research centers. Mice were sensitized by oral gavage with whey or extensively hydrolysed whey (eWH) using cholera toxin as an adjuvant. Whey-specific antibodies, mMCP-1 levels, anaphylactic shock symptoms, body temperature and the acute allergic skin response were determined upon whey challenge. In phases I and II, all 4 centers detected elevated levels of whey-specific IgE/IgG1 in whey sensitized animals. Elevated levels of mMCP-1, anaphylactic symptoms, body temperature drop and acute allergic skin response were scored upon whey challenge in 3 out of 4 research centers. In contrast, none of the evaluated parameters were elevated in eWH orally exposed groups. The cow's milk allergy mouse model is capable to distinguish the sensitizing capacity of complete or hydrolysed cow's milk protein. The model uses straightforward parameters relevant to food allergic responses and can be effectively transferred between different laboratories. We propose this mouse model as a new strategy for the screening of new hypoallergenic cow's milk formulas. 23007559 Developmental immunotoxicity of ethanol in an extended one-generation reproductive toxicity study. The susceptibility of developing immune system to chemical disruption warrants the assessment of immune parameters in reproductive and developmental testing protocols. In this study, a wide range of immune endpoints was included in an extended one-generation reproduction toxicity study (EOGRTS) design to determine the relative sensitivity of immune and developmental parameters to ethanol (EtOH), a well-known developmental toxicant with immunomodulatory properties. Adult Wistar rats were exposed to EtOH via drinking water (0, 1.5, 4, 6.5, 9, 11.5 and 14 % (w/v EtOH)) during premating, mating, gestation and lactation and continuation of exposure of the F(1) from weaning until killed. Immune assessments were performed at postnatal days (PNDs) 21, 42 and 70. Keyhole limpet hemocyanin (KLH)-specific immune responses were evaluated following subcutaneous immunizations on PNDs 21 and 35. EtOH exposure affected innate as well as adaptive immune responses. The most sensitive immune parameters included white blood cell subpopulations, ConA-stimulated splenocyte proliferation, LPS-induced NO and TNF-α production by adherent splenocytes and KLH-specific immune responses. Most parameters showed recovery after cessation of EtOH exposure after weaning in the 14 % exposure group. However, effects on LPS-induced NO and TNF-α production by adherent splenocytes and KLH-specific parameters persisted until PND 70. The results demonstrate the relative sensitivity to EtOH of especially functional immune parameters and confirm the added value of immune parameters in the EOGRTS. Furthermore, this study identified an expanded KLH-specific parameter set and LPS-induced NO and TNF-α production by adherent splenocytes as valuable parameters that can provide additional information on functional immune effects. 23395665 Facile one-pot synthesis of novel dispirooxindole-pyrrolidine derivatives and their antimicrobial and anticancer activity against A549 human lung adenocarcinoma cancer cell line. Novel dispirooxindole-pyrrolidine derivatives have been synthesized through 1,3-dipolar cycloaddition of an azomethine ylide generated from isatin and sarcosine with the dipolarophile 3-(1H-indol-3-yl)-3-oxo-2-(2-oxoindolin-3-ylidene)propanenitrile, and also spiro compound of acenaphthenequinone obtained by the same optimized reaction condition. Synthesized compounds were evaluated for their antimicrobial activity and all the compounds shown significant activity. Anticancer activity was evaluated against A549 human lung adenocarcinoma cancer cell lines. Compounds 7b, 7g, 7i and 7r exhibit very good anticancer activity 62.96%, 62.03%, 67.67% and 60.22%, respectively, at the dose of 200μg/mL and compound 7i shows IC50 value in 50μg/mL. 23565607 Predicting Transition Temperatures of Elastin-Like Polypeptide Fusion Proteins. Elastin-like polypeptides (ELPs) are thermally sensitive peptide polymers that undergo thermally triggered phase separation and this behavior is imparted to soluble proteins when they are fused to an ELP. The transition temperature of the ELP fusion protein is observed to be different than that of a free ELP, indicating that the surface properties of the fused protein modulate the thermal behavior of ELPs. Understanding this effect is important for the rational design of applications that exploit the phase transition behavior of ELP fusion proteins. We had previously developed a biophysical model that explained the effect of hydrophobic proteins on depressing the transition temperature of ELP fusion proteins relative to free ELP. Here, we extend the model to elucidate the effect of hydrophilic proteins on the thermal behavior of ELP fusion proteins. A linear correlation was found between overall residue composition of accessible protein surface weighted by a characteristic transition temperature for each residue and the difference in transition temperatures between the ELP protein fusion and the corresponding free ELP. In breaking down the contribution of residues to polar, nonpolar, and charged, the model revealed that charged residues are the most important parameter in altering the transition temperature of an ELP fusion relative to the free ELP. 23528251 Cross-talk between constitutive androstane receptor and hypoxia-inducible factor in the regulation of gene expression. Hypoxia inducible factor (HIF) and 5'-AMP-activated protein kinase are often activated under similar physiological conditions. Constitutive androstane receptor (CAR) translocates into the nucleus in accordance with 5'-AMP-activated protein kinase and thus confers transactivation. The aim of the present study was to investigate a possible link between CAR and HIFα. Phenobarbital (PB), a typical CAR activator, increased the gene expression of HIF-target genes in the livers of mice, including erythropoietin, heme oxygenase-1 and vascular endothelial growth factor-a. PB induced an accumulation of nuclear HIF-1α and an increase in the HIF-responsive element-mediated transactivation in HepG2 cells. Cobalt chloride, a typical HIF activator, induced the gene expression of CAR-target genes, including cyp2b9 and cyp2b10, an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver. Immunoprecipitation-immunoblot and chromatin immunoprecipitation analyses suggest that CAR binds to the PB-responsive enhancer module with HIF-1α in the liver of untreated mice and that the complex dissociates upon PB treatment. Taken together these results suggest that CAR and HIF-α interact and reciprocally modulate the functions of each other. 23279886 The significance of low substrate concentration measurements for mechanistic interpretation in cholinesterases. Cholinesterases do not follow the Michaelis-Menten kinetics. In the past, many reaction schemes were suggested to explain their complex interactions during the substrate turnover. Covalent catalysis was recognized very early and therefore, double intermediate traditional reaction scheme for the hydrolysis of good substrates at low concentrations was postulated. However, at intermediate and high substrate concentrations homotropic pseudocooperative effects take place in all cholinesterases, due to the nature of their buried active center. In this study, the significance and usefulness of experimental data obtained at low substrate concentrations, where only one substrate molecule accesses the active site at a time, are to be specified for the overall mechanistic evaluations. Indeed, different interpretations are expected when data are processed with equations derived from different reaction schemes. Consequently, the scheme with two substrate binding sites which comprises the structurally evidenced fully occupied active site as ultimate cause for substantially decreased cholinesterase activity at extremely high substrate concentrations is considered here. A special emphasis is put on butyrylcholinesterase, the enzyme with the largest active site among cholinesterases, where the pseudocooperative effects appear at much higher concentrations than in acetylcholinesterases. 23238611 Dietary intake of magnesium may modulate depression. Depressive symptoms are frequent in students and may lead to countless problems. Several hypotheses associate magnesium with depression because of the presence of this mineral in several enzymes, hormones, and neurotransmitters, which may play a key role in the pathological pathways of depression. The aim of this study was to assess whether magnesium intake could modulate depressive symptoms. A cross-sectional study was conducted on a convenience sample of 402 Iranian postgraduate students studying in Malaysia to assess the relationship between magnesium intake and depressive symptoms. The mean age of the participants was 32.54 ± 6.22 years. The results of the study demonstrated an inverse relationship between magnesium intake and depressive symptoms, which persisted even after adjustments for sex, age, body mass index, monthly expenses, close friends, living on campus, smoking (current and former), education, physical activity, and marital status. 23612487 Sphingosine-1-phosphate promotes the nuclear translocation of β-catenin and thereby induces osteoprotegerin gene expression in osteoblast-like cell lines. Sphingosine-1-phosphate (S1P) is a well-known signaling sphingolipid and bioactive lipid mediator. Recently, it was reported that S1P inhibits osteoclast differentiation and bone resorption. On the other hand, S1P effects on osteoblasts and bone formation are little known. In this study, we investigated the effects of S1P on osteoblasts, using two osteoblast-like cell lines, SaOS-2 and MC3T3-E1. S1P activated phosphatidylinositol 3-kinase (PI3K)/Akt signaling, leading to the inhibition of glycogen synthase kinase-3β and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells. The inhibitors of PI3K and Akt suppressed S1P-induced nuclear localization of β-catenin. We further investigated the effects of PI3K/Akt signaling on the Wnt/β-catenin signaling pathway, since β-catenin takes a central role in this signaling pathway. Both inhibitors for PI3K and Akt suppressed the nuclear localization of β-catenin and T-cell factor transcriptional activity induced by Wnt-3a. S1P increased the amount of osteoprotegerin at both mRNA and protein levels, and increased the activity of alkaline phosphatase, leading to the mineralization. These findings suggest that S1P activates the PI3K/Akt signaling pathway leading to the promotion of nuclear translocation of β-catenin in osteoblast-like cells, resulting in the upregulation of osteoptotegerin and osteoblast differentiation markers including alkaline phosphatase, probably relating to the inhibition of osteoclast formation and the mineralization, respectively. 23561183 High performance thin layer chromatography-densitometry: A step further for quality control of cranberry extracts. A method for selective quantitation of catechin, proanthocyanidin (PAC) A2 and PAC-B1 in American cranberry (Vaccinium macrocarpon) extracts using high performance thin layer chromatography (HPTLC)-densitometry is presented. Methylene chloride/ethyl acetate/formic acid (6:10:1, v/v) as the mobile phase and 1% vanillin hydrochloric solution as staining reagent were used. In these conditions, three standards considered as quality markers, catechin, PAC-A2 and PAC-B1, were well resolved allowing simultaneous quantitation on one plate. All standards were quantified in the range of 0.7-5μg with RSD of repeatability and intermediate precision not exceeding 5%. Catechin, PAC-A2 and PAC-B1 profiles of cranberry extracts were analysed regarding global PAC amounts obtained by BL-DMAC assay. It appears clearly that HPTLC-densitometry process provides additional information which, combined with BL-DMAC results, allows qualitative and quantitative control of cranberry extracts. Particularly, densitometric assay highlighted degradation of PACs in a 7day-extract, leading to high overestimation with BL-DMAC protocol. 23621857 Synthesis and Cytotoxic Evaluation of Acylated Brefeldin A Derivatives as Potential Anticancer Agents. Brefeldin A (BFA) has attracted considerable attention because of its potential function in cancer prevention. However, its therapeutic use is limited by its poor bioavailability. The modifications on BFA were difficult because of its low stability and selectivity toward two hydroxyl groups within the same molecule. In this study, we report the selective acylation of BFA under mild conditions and the preparation of a series of monoacylated and diacylated BFA derivatives. Their cytotoxicity, antitumor activity against TE-1 cell, and molecular properties of adsorption, distribution, metabolism, and elimination were evaluated. BFA 7-O-benzoate, BFA 4,7-O-dibenzoate, and BFA 7-O-biotin carboxylate showed the most potent cytotoxic activity, with GI50 values of 0.39, 0.46, and 0.50μM respectively. Molecular docking of these analogs revealed that the derivatives were well tolerated at the interface between ARF1 and its guanine nucleotide exchange factor ARNO. Our results may serve as a basis for the development of novel potential anti-cancer agents from BFA derivatives. This article is protected by copyright. All rights reserved. 23432912 Structural and mechanistic principles of intramembrane proteolysis--lessons from rhomboids. Intramembrane proteases cleave membrane proteins in their transmembrane helices to regulate a wide range of biological processes. They catalyse hydrolytic reactions within the hydrophobic environment of lipid membranes where water is normally excluded. How? Do the different classes of intramembrane proteases share any mechanistic principles? In this review these questions will be discussed in view of the crystal structures of prokaryotic members of the three known catalytic types of intramembrane proteases published over the past 7 years. Rhomboids, the intramembrane serine proteases that are the best understood family, will be the initial area of focus, and the principles that have arisen from a number of structural and biochemical studies will be considered. The site-2 metalloprotease and GXGD-type aspartyl protease structures will then be discussed, with parallels drawn and differences highlighted between these enzymes and the rhomboids. Despite the significant advances achieved so far, to obtain a detailed understanding of the mechanism of any intramembrane protease, high-resolution structural information on the substrate-enzyme complex is required. This remains a major challenge for the field. 23497876 Application of reduced graphene oxide and carbon nanotube modified electrodes for measuring the enzymatic activity of alcohol dehydrogenase. An electrochemical method was developed to measure the enzymatic activity of alcohol dehydrogenase (ADH) by monitoring the amount of reduced nicotinamide adenine dinucleotide (NADH) generated in the catalysed oxidation of ethanol by ADH. The concentration of NADH was determined by amperometric measurements, which recorded the oxidation current of NADH versus time on reduced graphene oxide and functionalised multi-walled carbon nanotube modified electrodes. The initial reaction rates and the apparent Michaelis constants of the enzymatic reaction were obtained in the absence and presence of Al(3+) and nanometre-sized tridecameric aluminium polycationic (nano-Al(13)) species. The results showed that Al(3+) and nano-Al(13) exhibited inhibitory effect on the enzymatic activity of ADH. Fluorescence and circular dichroism spectra indicated the inhibitory effect was likely caused by the conformational changes of ADH and/or NADH induced by Al(3+) and nano-Al(13). 23444256 Emtricitabine/tenofovir disoproxil fumarate: a review of its use in HIV-1 pre-exposure prophylaxis. The fixed-dose combination of emtricitabine (FTC) 200 mg and tenofovir disoproxil fumarate (TDF) 300 mg (Truvada(®)), administered orally once daily, is widely used as part of first-line regimens for the treatment of HIV-1 infection. Recently, once-daily administration of FTC/TDF was approved in the USA for pre-exposure prophylaxis in conjunction with safer sex practices to reduce the risk of sexually acquired HIV-1 in high-risk adults who are not infected. To date, results of four large, randomized, double-blind, placebo-controlled, multicentre trials with FTC/TDF as pre-exposure prophylaxis have been published. Three studies showed statistically significant reductions in the number of individuals with emergent HIV-1 infection when FTC/TDF was compared with placebo over the ≈1- to 2-year study periods. Efficacy (i.e. risk reduction relative to placebo) was 44 % in the iPrEx trial in men who have sex with men, 75 % in the Partners PrEP study in heterosexual HIV-1-serodiscordant couples and 62 % in the TDF2 trial in heterosexual men and women. The fourth study (FEM-PrEP) in heterosexual women did not show a statistically significant difference between FTC/TDF and placebo, although low adherence rates reported in this trial may have been a factor. No unexpected adverse events were reported in the trials. However, since pre-exposure prophylaxis involves long-term administration of drugs to healthy individuals, it is important to monitor the long-term safety of FTC/TDF (e.g. renal function, bone mineral density) in this setting. Other notable considerations include adherence, cost and the potential for development of drug resistance. Interim guidelines are available for prescribing FTC/TDF as pre-exposure prophylaxis. If used appropriately in selected high-risk individuals, pre-exposure prophylaxis with FTC/TDF represents an important additional strategy to reduce the spread of HIV-1 infection, which continues to be a significant global concern. 23220291 Toxicological analysis of limonene reaction products using an in vitro exposure system. Epidemiological investigations suggest a link between exposure to indoor air chemicals and adverse health effects. Consumer products contain reactive chemicals which can form secondary pollutants which may contribute to these effects. The reaction of limonene and ozone is a well characterized example of this type of indoor air chemistry. The studies described here characterize an in vitro model using an epithelial cell line (A549) or differentiated epithelial tissue (MucilAir™). The model is used to investigate adverse effects following exposure to combinations of limonene and ozone. In A549 cells, exposure to both the parent compounds and reaction products resulted in alterations in inflammatory cytokine production. A one hour exposure to limonene+ozone resulted in decreased proliferation when compared to cells exposed to limonene alone. Repeated dose exposures of limonene or limonene+ozone were conducted on MucilAir™ tissue. No change in proliferation was observed but increases in cytokine production were observed for both the parent compounds and reaction products. Factors such as exposure duration, chemical concentration, and sampling time point were identified to influence result outcome. These findings suggest that exposure to reaction products may produce more severe effects compared to the parent compound. 23240993 Porosity of pillared clays studied by hyperpolarized 129Xe NMR spectroscopy and Xe adsorption isotherms. The influence of the layer charge on the microstructure was studied for a series of three hybrid pillared interlayered clays based on the organic dication Me(2)DABCO(2+) and charge reduced synthetic fluorohectorites. To get a detailed picture of the local arrangements within the interlayer space, multinuclear solid-state NMR spectroscopy was performed in conjunction with high-resolution (129)Xe MAS NMR, temperature-dependent wide-line 1D and 2D (129)Xe NMR, and Ar/Ar(l) and Xe/Xe(l) physisorption measurements. The resulting layer charge (x) for the three samples are 0.48, 0.44, and 0.39 per formula unit (pfu). The samples exhibit BET equivalent surfaces between 150 and 220 m(2)/g and pore volumes which increase from 0.06 to 0.11 cm(3)/g while the layer charge reduces. 1D and 2D (1)H, (13)C, (19)F, and (29)Si MAS data reveal that the postsynthetic charge reduction induces regions with higher defect concentrations within the silicate layers. Although the pillars tend to avoid these defect-rich regions, a homogeneous and regular spacing of the Me(2)DABCO(2+) pillars is established. Both the Ar/Ar(l) physisorption and (129)Xe NMR measurements reveal comparable pore dimensions. The trend of the temperature-dependent wide-line (129)Xe spectra as well as the exchange in the EXSY spectra is typical for a narrow 2D pore system. (129)Xe high-resolution experiments allow for a detailed description of the microstructure. For x = 0.48 a bimodal distribution with pore diameters between 5.9 and 6.4 Å is observed. Reducing the layer charge leads to a more homogeneous pore structure with a mean diameter of 6.6 Å (x = 0.39). The adsorption enthalpies ΔH(ads) determined from the temperature-dependent (129)Xe chemical shift data fit well to the ones derived from the Xe/Xe(l) physisorption measurements in the high-pressure limit while the magnitude of ΔH(ads) in the low-pressure limit is significantly larger. Thus, the (129)Xe data are influenced by adsorbate-adsorbent as well as adsorbate-adsorbate interactions. 23517126 Growth Inhibition of Human Colon Carcinoma Cells by Sesquiterpenoids and Tetralones of Zygogynum calothyrsum. Bioassay-guided phytochemical investigation of Zygogynum calothyrsum using the human colon carcinoma cell lines COLO205 and KM12 led to the isolation of three new drimane-type sesquiterpenoids, 1β-p-hydroxy-E-cinnamoyldrimeninol (1), 1β-p-hydroxy-E-cinnamoyl-5α-hydroxydrimeninol (2), and methyl ether of 1β-p-hydroxy-E-cinnamoyl-12α-methoxydrimeninol (3). Also isolated was the known 1β-p-coumaroyloxypolygodial (4) together with two new tetralones, 3'-deoxyisozygolone A (5) and calothyrlone A (9), three known tetralones, isozygolone A (6), zygolone A (7), and 4'-O-methylzygolone A (8), and a known cinnamolide (10). Compounds 1, 7, and 8 demonstrated higher cytotoxicity against COLO205 (GI50 18, 17, and 11 μM, respectively) and KM12 (GI50 14, 14, and 17 μM, respectively) than the other compounds. 23292752 New oral anticoagulants: comparative pharmacology with vitamin K antagonists. New oral anticoagulants (OACs) that directly inhibit Factor Xa (FXa) or thrombin have been developed for the long-term prevention of thromboembolic disorders. These novel agents provide numerous benefits over older vitamin K antagonists (VKAs) due to major pharmacological differences. VKAs are economical and very well characterized, but have important limitations that can outweigh these advantages, such as slow onset of action, narrow therapeutic window and unpredictable anticoagulant effect. VKA-associated dietary precautions, monitoring and dosing adjustments to maintain international normalized ratio (INR) within therapeutic range, and bridging therapy, are inconvenient for patients, expensive, and may result in inappropriate use of VKA therapy. This may lead to increased bleeding risk or reduced anticoagulation and increased risk of thrombotic events. The new OACs have rapid onset of action, low potential for food and drug interactions, and predictable anticoagulant effect that removes the need for routine monitoring. FXa inhibitors, e.g. rivaroxaban and apixaban, are potent, oral direct inhibitors of prothrombinase-bound, clot-associated or free FXa. Both agents have a rapid onset of action, a wide therapeutic window, little or no interaction with food and other drugs, minimal inter-patient variability, and display similar pharmacokinetics in different patient populations. Since both are substrates, co-administration of rivaroxaban and apixaban with strong cytochrome P450 (CYP) 3A4 and permeability glycoprotein (P-gp) inhibitors and inducers can result in substantial changes in plasma concentrations due to altered clearance rates; consequently, their concomitant use is contraindicated and caution is required when used concomitantly with strong CYP3A4 and P-gp inducers. Although parenteral oral direct thrombin inhibitors (DTIs), such as argatroban and bivalirudin, have been on the market for years, DTIs such as dabigatran are novel synthetic thrombin antagonists. Dabigatran etexilate is a low-molecular-weight non-active pro-drug that is administered orally and converted rapidly to its active form, dabigatran--a potent, competitive and reversible DTI. Dabigatran has an advantage over the indirect thrombin inhibitors, unfractionated heparin and low-molecular-weight heparin, in that it inhibits free and fibrin-bound thrombin. The reversible binding of dabigatran may provide safer and more predictable anticoagulant treatment than seen with irreversible, non-covalent thrombin inhibitors, e.g. hirudin. Dabigatran shows a very low potential for drug-drug interactions. However, co-administration of dabigatran etexilate with other anticoagulants and antiplatelet agents can increase the bleeding risk. Although the new agents are pharmacologically better than VKAs--particularly in terms of fixed dosing, rapid onset of action, no INR monitoring and lower risk of drug interactions--there are some differences between them: the bioavailability of dabigatran is lower than rivaroxaban and apixaban, and so the dabigatran dosage required is higher; lower protein binding of dabigatran reduces the variability related to albuminaemia. The risk of metabolic drug-drug interactions also appears to differ between OACs: VKAs > rivaroxaban > apixaban > dabigatran. The convenience of the new OACs has translated into improvements in efficacy and safety as shown in phase III randomized trials. The new anticoagulants so far offer the greatest promise and opportunity for the replacement of VKAs. 23463898 Cyclic denaturation and renaturation of double-stranded DNA by redox-state switching of DNA intercalators. Hybridization of complementary nucleic acid strands is fundamental to nearly all molecular bioanalytical methods ranging from polymerase chain reaction and DNA biosensors to next generation sequencing. For nucleic acid amplification methods, controlled DNA denaturation and renaturation is particularly essential and achieved by cycling elevated temperatures. Although this is by far the most used technique, the management of rapid temperature changes requires bulky instrumentation and intense power supply. These factors so far precluded the development of true point-of-care tests for molecular diagnostics. To overcome this limitation we explored the possibility of using electrochemical means to control reversible DNA hybridization by using the electroactive intercalator daunomycin (DM). We show that redox-state switching of DM altered its properties from DNA binding to nonbinding, under otherwise constant conditions, and thus altered the thermodynamic stability of duplex DNA. The operational principle was demonstrated using complementary synthetic 20mer and 40mer DNA oligonucleotides. Absorbance-based melting curve analysis revealed significantly higher melting temperatures for DNA in the presence of oxidized compared to chemically reduced DM. This difference was exploited to drive cyclic electrochemically controlled denaturation and renaturation. Analysis with in situ UV-vis and circular dichroism spectroelectrochemistry, as two independent techniques, indicated that up to 80% of the DNA was reversibly hybridized. This remarkable demonstration of electrochemical control of five cycles of DNA denaturation and renaturation, under otherwise constant conditions, could have wide-ranging implications for the future development of miniaturized analytical systems for molecular diagnostics and beyond. 23313712 Interaction of polyhexamethylene biguanide hydrochloride (PHMB) with phosphatidylcholine containing o/w emulsion and consequences for microbicidal efficacy and cytotoxicity. Oil-in-water (o/w) emulsions containing egg yolk phosphatidylcholine (EPC) were combined with aqueous polyhexamethylene biguanide hydrochloride (PHMB). The PHMB concentration in the aqueous phase was estimated by filtration centrifugation experiments. In parallel, PHMB concentration was assessed utilizing cytotoxicity assays (neutral red) on cultured murine fibroblasts (L929 cells) and tests of bactericidal efficacy on either Pseudomonas aeruginosa or Staphylococcus aureus. Biological tests were performed in cell culture medium. Filtration centrifugation experiments demonstrated much higher aqueous PHMB concentrations than did the assays for biologically effective PHMB. Therefore, biological test systems should preferably be used to verify effective PHMB concentrations. Tests of microbicidal efficacy in which the same 0.05% PHMB o/w emulsion was re-used 8 times revealed a drug delivery system activated by the presence of test bacteria. 23293875 Clinal variation in colony breeding structure and level of inbreeding in the subterranean termites Reticulitermes flavipes and R. grassei. Social insects exhibit remarkable variation in their colony breeding structures, both within and among species. Ecological factors are believed to be important in shaping reproductive traits of social insect colonies, yet there is little information linking specific environmental variables with differences in breeding structure. Subterranean termites (Rhinotermitidae) show exceptional variation in colony breeding structure, differing in the number of reproductives and degree of inbreeding; colonies can be simple families headed by a single pair of monogamous reproductives (king and queen) or they can be extended families headed by multiple inbreeding neotenic reproductives (wingless individuals). Using microsatellite markers, we characterized colony breeding structure and levels of inbreeding in populations over large parts of the range of the subterranean termites Reticulitermes flavipes in the USA and R. grassei in Europe. Combining these new data with previous results on populations of both species, we found that latitude had a strong effect on the proportion of extended-family colonies in R. flavipes and on levels of inbreeding in both species. We examined the effect of several environmental variables that vary latitudinally; while the degree of inbreeding was greatest in cool, moist habitats in both species, seasonality affected the species differently. Inbreeding in R. flavipes was most strongly associated with climatic variables (mean annual temperature and seasonality), whereas nonclimatic variables, including the availability of wood substrate and soil composition, were important predictors of inbreeding in R. grassei. These results are the first showing that termite breeding structure is shaped by local environmental factors and that species can vary in their responses to these factors. 23072918 In vitro and in vivo approaches to study osteocyte biology. Osteocytes, the most abundant cell population of the bone lineage, have been a major focus in the bone research field in recent years. This population of cells that resides within mineralized matrix is now thought to be the mechanosensory cell in bone and plays major roles in the regulation of bone formation and resorption. Studies of osteocytes had been impaired by their location, resulting in numerous attempts to isolate primary osteocytes and to generate cell lines representative of the osteocytic phenotype. Progress has been achieved in recent years by utilizing in vivo genetic technology and generation of osteocyte directed transgenic and gene deficiency mouse models. We will provide an overview of the current in vitro and in vivo models utilized to study osteocyte biology. We discuss generation of osteocyte-like cell lines and isolation of primary osteocytes and summarize studies that have utilized these cellular models to understand the functional role of osteocytes. Approaches that attempt to selectively identify and isolate osteocytes using fluorescent protein reporters driven by regulatory elements of genes that are highly expressed in osteocytes will be discussed. In addition, recent in vivo studies utilizing overexpression or conditional deletion of various genes using dentin matrix protein (Dmp1) directed Cre recombinase are outlined. In conclusion, evaluation of the benefits and deficiencies of currently used cell lines/genetic models in understanding osteocyte biology underlines the current progress in this field. The future efforts will be directed towards developing novel in vitro and in vivo models that would additionally facilitate in understanding the multiple roles of osteocytes. This article is part of a Special Issue entitled "The Osteocyte". 23300056 Determination of key receptor-ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model. Interest in structure-based G-protein-coupled receptor (GPCR) ligand discovery is huge, given that almost 30 % of all approved drugs belong to this category of active compounds. The GPCR family includes the dopamine receptor subtype D2 (D2DR), but unfortunately--as is true of most GPCRs--no experimental structures are available for these receptors. In this publication, we present the molecular model of D2DR based on the previously published crystal structure of the dopamine D3 receptor (D3DR). A molecular modeling study using homology modeling and docking simulation provided a rational explanation for the behavior of the arylpiperazine ligand. The observed binding modes and receptor-ligand interactions provided us with fresh clues about how to optimize selectivity for D2DR receptors. 23137957 Dietary exposure to mycotoxins and health risk assessment in the second French total diet study. Mycotoxins are produced in plants by micro-fungi species, and naturally contaminated the food chain. In the second French total diet study (TDS), mycotoxins were analyzed in 577 food samples collected in mainland France to be representative of the population diet and prepared ((as consumed)). Highest mean concentrations were found in wheat and cereal-based products (bread, breakfast cereals, pasta, pastries, pizzas and savoury pastries…). Exposure of adult and child populations was assessed by combining national consumption data with analytical results, using lowerbound (LB) and upperbound (UB) assumptions for left-censorship management. Individual exposures were compared with available health-based guidance values (HBGV). Only the exposure to deoxynivalenol (DON) and its acetylated derivatives was found to significantly exceed the HBGV in LB in adults (0.5% [0.1; 0.8]) and children (5% [4; 6]). HBGV was exceeded in UB only for T-2 and HT-2 toxins by, respectively, 0.2% [0.02; 0.05] and 4% [3; 5] of adults, and 11% [9; 12] and 35% [32; 37] of children. Although the exposures assessed were generally lower than the previous French TDS, the results indicated a health concern for trichothecenes and a need to reduce dietary exposure as well as analytical limits. 23178949 Pocketed microneedles for rapid delivery of a liquid-state botulinum toxin A formulation into human skin. Botulinum toxin A (BT) is used therapeutically for the treatment of primary focal hyperhidrosis, a chronic debilitating condition characterised by over-activity of the eccrine sweat glands. Systemic toxicity concerns require BT to be administered by local injection, which in the case of hyperhidrosis means multiple painful intradermal injections by a skilled clinician at 6-monthly intervals. This study investigates the potential of a liquid-loaded pocketed microneedle device to deliver botulinum toxin A into the human dermis with the aim of reducing patient pain, improving therapeutic targeting and simplifying the administration procedure. Initially, β-galactosidase was employed as a detectable model for BT to (i) visualise liquid loading of the microneedles, (ii) determine residence time of a liquid formulation on the device and (iii) quantify loaded doses. An array of five stainless steel pocketed microneedles was shown to possess sufficient capacity to deliver therapeutic doses of the potent BT protein. Microneedle-mediated intradermal delivery of β-galactosidase and formaldehyde-inactivated botulinum toxoid revealed effective deposition and subsequent diffusion within the dermis. This study is the first to characterise pocketed microneedle delivery of a liquid formulation into human skin and illustrates the potential of such systems for the cutaneous administration of potent proteins such as BT. A clinically appropriate microneedle delivery system for BT could have a significant impact in both the medical and cosmetic industries. 23376780 Consumer and farmer safety evaluation of application of botanical pesticides in black pepper crop protection. This study presents a consumer and farmer safety evaluation on the use of four botanical pesticides in pepper berry crop protection. The pesticides evaluated include preparations from clove, tuba root, sweet flag and pyrethrum. Their safety evaluation was based on their active ingredients being eugenol, rotenone, β-asarone and pyrethrins, respectively. Botanical pesticides from Acorus calamus are of possible concern because of the genotoxic and carcinogenic ingredient β-asarone although estimated margins of exposure (MOE) for consumers indicate a low priority for risk management. For the other three botanical pesticides the margin of safety (MOS) between established acute reference doses and/or acceptable daily intake values and intake estimates for the consumer, resulting from their use as a botanical pesticide are not of safety concern, with the exception for levels of rotenone upon use of tuba root extracts on stored berries. Used levels of clove and pyrethrum as botanical pesticides in pepper berry crop production is not of safety concern for consumers or farmers, whereas for use of tuba root and sweet flag some risk factors were defined requiring further evaluation and/or risk management. It seems prudent to look for alternatives for use of sweet flag extracts containing β-asarone. 23355488 Polycyclic peptide therapeutics. Owing to their excellent binding properties, high stability, and low off-target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics. Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide. All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish-hunting coil snail in the case of ziconotide. Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets. For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches. More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display. In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures. Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed. Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases. 22991192 Human apolipoprotein E isoforms differentially affect bone mass and turnover in vivo. The primary role of apolipoprotein E (apoE) is to mediate the cellular uptake of lipoproteins. However, a new role for apoE as a regulator of bone metabolism in mice has recently been established. In contrast to mice, the human APOE gene is characterized by three common isoforms APOE ε2, ε3, and ε4 that result in different metabolic properties of the apoE isoforms, but it remains controversial whether the APOE polymorphism influences bone traits in humans. To clarify this, we investigated bone phenotypes of apoE knock-in (k.i.) mice, which express one human isoform each (apoE2 k.i., apoE3 k.i., apoE4 k.i.) in place of the mouse apoE. Analysis of 12-week-old female k.i. mice revealed increased levels of biochemical bone formation and resorption markers in apoE2 k.i. animals as compared to apoE3 k.i. and apoE4 k.i., with a reduced osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) ratio in apoE2 k.i., indicating increased turnover with prevailing resorption in apoE2 k.i. Accordingly, histomorphometric and micro-computed tomography (µCT) analyses demonstrated significantly lower trabecular bone mass in apoE2 than in apoE3 and apoE4 k.i. animals, which was reflected by a significant reduction of lumbar vertebrae maximum force resistance. Unlike trabecular bone, femoral cortical thickness, and stability was not differentially affected by the apoE isoforms. To extend these observations to the human situation, plasma from middle-aged healthy men homozygous for ε2/ε2, ε3/ε3, and ε4/ε4 (n = 21, n = 80, n = 55, respectively) was analyzed with regard to bone turnover markers. In analogy to apoE2 k.i. mice, a lower OPG/RANKL ratio was observed in the serum of ε2/ε2 carriers as compared to ε3/ε3 and ε4/ε4 individuals (p = 0.02 for ε2/ε2 versus ε4/ε4). In conclusion, the current data strongly underline the general importance of apoE as a regulator of bone metabolism and identifies the APOE ε2 allele as a potential genetic risk factor for low trabecular bone mass and vertebral fractures in humans. 23623419 Facile synthesis of new imidazo[1,2-a]pyridines carrying 1,2,3-triazoles via click chemistry and their antiepileptic studies. The present article reports the synthesis and anticonvulsant studies of new 2-arylimidazo[1,2-a]pyridines carrying suitably substituted 1,2,3-triazoles as well as their intermediates. The structures of newly synthesized compounds were confirmed by various spectroscopic techniques. The anticonvulsant study was carried out by MES and scPTZ screening methods, while their toxicity study was performed following Rotarod method. The active compounds showed enhanced seizure control in scPTZ method when compared with that of MES method. Compounds 3f, 4c, 4f, 5k, 5p and 5w carrying active pharmacophores exhibited complete protection against seizure and their results were comparable with standard drug diazepam. Majority of new compounds were found to be non-toxic, while few of them showed toxicity at 100mg/kg. The clogP values of target compounds are in the range of 3.5-5.3, which confirm their lipophilic nature. 23627834 Dual Stimuli-Responsive Poly(N-isopropylacrylamide)-b-poly(l-histidine) Chimeric Materials for the Controlled Delivery of Doxorubicin into Liver Carcinoma. A series of dual stimuli responsive synthetic polymer bioconjugate chimeric materials, poly(N-isopropylacrylamide)55-block-poly(l-histidine)n [p(NIPAM)55-b-p(His)n] (n = 50, 75, 100, 125), have been synthesized by employing reversible addition-fragmentation chain transfer polymerization of NIPAM, followed by ring-opening polymerization of α-amino acid N-carboxyanhydrides. The dual stimuli responsive properties of the resulting biocompatiable and membrenolytic p(NIPAM)55-b-p(His)n polymers are investigated for their use as a stimuli responsive drug carrier for tumor targeting. Highly uniform self-assembled micelles (∼55 nm) fabricated by p(NIPAM)55-b-p(His)n polymers display sharp thermal and pH responses in aqueous media. An anticancer drug, doxorubicin (Dox), is effectively encapsulated in the micelles and the controlled Dox release is investigated in different temperature and pH conditions. Antitumor effect of the released Dox is also assessed using the HepG2 human hepatocellular carcinoma cell lines. Dox molecules released from the [p(NIPAM)55-b-p(His)n] micelles remain biologically active and have stimuli responsive capability to kill cancer cells. The self-assembling ability of these hybrid materials into uniform micelles and their efficiency to encapsulate Dox makes them a promising drug carrier to cancer cells. The new chimeric materials thus display tunable properties that can make them useful for a molecular switching device and controlled drug delivery applications needing responses to temperature and pH for the improvement of cancer chemotherapy. 23408851 Quantitative analysis of TALE-DNA interactions suggests polarity effects. Transcription activator-like effectors (TALEs) have revolutionized the field of genome engineering. We present here a systematic assessment of TALE DNA recognition, using quantitative electrophoretic mobility shift assays and reporter gene activation assays. Within TALE proteins, tandem 34-amino acid repeats recognize one base pair each and direct sequence-specific DNA binding through repeat variable di-residues (RVDs). We found that RVD choice can affect affinity by four orders of magnitude, with the relative RVD contribution in the order NG > HD ∼ NN ≫ NI > NK. The NN repeat preferred the base G over A, whereas the NK repeat bound G with 10(3)-fold lower affinity. We compared AvrBs3, a naturally occurring TALE that recognizes its target using some atypical RVD-base combinations, with a designed TALE that precisely matches 'standard' RVDs with the target bases. This comparison revealed unexpected differences in sensitivity to substitutions of the invariant 5'-T. Another surprising observation was that base mismatches at the 5' end of the target site had more disruptive effects on affinity than those at the 3' end, particularly in designed TALEs. These results provide evidence that TALE-DNA recognition exhibits a hitherto un-described polarity effect, in which the N-terminal repeats contribute more to affinity than C-terminal ones. 23558236 Design, synthesis and cytotoxicity of cell death mechanism of rotundic acid derivatives. In the present investigation, 16 new rotundic acid (RA) derivatives modified at the C-3, C-23 and C-28 positions were synthesized. The cytotoxicities of the derivatives were evaluated against HeLa, A375, HepG2, SPC-A1 and NCI-H446 human tumor cell lines by MTT assay. Among these derivatives, compounds 4-7 exhibited stronger cell growth inhibitory than RA and compound 4 was found to be the best inhibition activity on five human tumor cell lines with IC50 <10μM. The apoptosis mechanism of compound 4 in HeLa cells was investigated by western blot analysis. The results indicated that compound 4 could induce apoptosis through increasing protein expression of cleaved caspase-3 and Bax, and decreasing protein expression of Bcl-2. In summary, the present work suggests that compound 4 might serve as an effective chemotherapeutic candidate. 23294326 Density of GM1 in nanoclusters is a critical factor in the formation of a spherical assembly of amyloid β-protein on synaptic plasma membranes. The deposition of amyloid β-protein (Aβ) is a pathological hallmark of Alzheimer's disease (AD). We previously found that the ganglioside-enriched microdomains (ganglioside clusters) in presynaptic neuronal membranes play a key role in the initiation of the Aβ assembly process. However, not all ganglioside clusters accelerate Aβ assembly. In the present study, we directly observed a spherical Aβ in an atomic force microscopic study on the morphology of a reconstituted lipid bilayer composed of lipids that were extracted from a detergent-resistant membrane microdomain (DRM) fraction of synaptosomes prepared from aged mouse brain. The Aβ assembly was generated on a distinctive GM1 domain, which was characterized as the Aβ-sensitive ganglioside nanocluster (ASIGN). By using an artificial GM1 cluster-binding peptide, ASIGN was found to have a high density of GM1; therefore, there would be a critical density of GM1 in nanoclusters to induce Aβ binding and assembly. These results suggest that ganglioside-bound Aβ (GAβ), which acts as an endogenous seed for Aβ fibril formation in AD brains, is generated on ASIGN on synaptosomal membranes. 23339678 Impact of ketorolac administration around ovarian stimulation on in vivo and in vitro fertilization and subsequent embryo development. Abstract We performed this study to investigate the effect of ketorolac (a non-steroidal anti-inflammatory drug) administration around ovarian stimulation on in vivo and in vitro fertilization process. Sixty-four female mice (ICR) were injected with ketorolac (0, 7.5, 15 and 30 µg/d) for 3 d starting from the day of eCG treatment. In experiment 1, 41 mice were triggered by hCG and then mated; two-cell embryos were obtained and in vitro development up to blastocyst was observed. In experiment 2, 23 mice were triggered by hCG and mature oocytes were collected; in vitro fertilization rate and subsequent embryo development up to blastocyst was recorded. In experiment 1, the blastocyst-forming rates per in vivo fertilized two-cell embryo showed an inverse relationship with a dosage of ketorolac (97.6%, 64.2%, 35.4% and 25.9%). In experiment 2, degenerated oocytes were frequently observed in a dose-dependent manner (4.3%, 22.9%, 22.4% and 75.0%). Lower fertilization rates were noted in all the three ketorolac-treating groups; blastocyst-forming rate was significantly lower in 30-µg-treating group when compared with the control group. Administration of ketorolac around ovarian stimulation significantly affects the development of in vivo fertilized embryo in a dose-dependent manner. High-dose ketorolac could result in a poor oocyte quality and decreased embryo developmental competence. 23461969 Theoretical Characterization of Galanin Receptor Type 3 (Gal3 ) and Its Interaction with Agonist (GALANIN) and Antagonists (SNAP 37889 and SNAP 398299): An In Silico Analysis. In this study, we report on modeling of galanin receptor type 3 and its interaction with agonist and antagonists using in silico methodologies. Comparative structural modeling of galanin receptor type 3 was based on multiple templates. With the availability of reported selective galanin receptor type 3 antagonists, docking was carried out into the predicted binding site. Similarly, galanin, a reported agonist, was also modeled and then docked into the receptor's active site. CoMFA models were developed using ligand-based (q(2)  = 0.537, r(2)  = 0.961, noc = 5), and receptor-guided (docked mode 1: q(2)  = 0.574, r(2)  = 0.946, noc = 5), (docked mode 2: q(2)  = 0.499, r(2)  = 0.954, noc = 5) alignment schemes. CoMFA contour analysis revealed that bulky substitution around the meta position of the phenyl ring, as well as optimal substitution (para) of the phenyl ring, could produce molecules with improved activity. We also found that Gln79, Ile82, Asp86, Trp88, His99, Ile102, Tyr103, Glu170, Pro174, Ala175, Asp185, Arg273, His277, and Tyr281 are crucial, and mutational studies on these residues could be helpful. The results obtained from this study can further be exploited for structure-based drug design and also help the researchers to identify novel antagonists targeting galanin receptor type 3. 23267857 CYP2C19*17 gain-of-function polymorphism is associated with peptic ulcer disease. Single-nucleotide polymorphisms (SNPs) in the CYP2C gene cluster have been extensively investigated as predisposing factors for nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcer disease (PUD) or upper gastrointestinal bleeding (UGIB). However, results have been inconclusive owing to different study designs, limited genotyping strategies, and small sample sizes. We investigated whether eight functional SNPs in the CYP2C family of genes--CYP2C8*3 (rs11572080 and rs10509681), CYP2C8*4, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, and CYP2C19*17--are associated with PUD in 1,239 Caucasian patients. Logistic regression analysis showed that only CYP2C19*17 was associated with PUD (odds ratio additive model: 1.47 (95% confidence interval (CI) 1.12 to 1.92); P = 0.005; R(2) 16%), but not UGIB, independent of NSAID use or Helicobacter pylori infection. PUD distribution varied (P = 0.024) according to CYP2C19*17 genotype: *1/*1, 490 (64.3%); *1/*17, 304 (71.7%); and *17/*17, 31 (73.8%). CYP2C19*17, a gain-of-function polymorphism, is associated with PUD irrespective of etiology. 23512754 Effect of the Potent Antiviral 1-Cinnamoyl-3,11-Dihydroxymeliacarpin on Cytokine Production by Murine Macrophages Stimulated with HSV-2. The limonoid 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM) isolated from leaf extracts of Melia azedarach L, has potent antiherpetic effect in epithelial cells. Since Meliacine, the partially purified extract source of CDM, has therapeutic effect on murine genital herpes, the potential use of CDM as microbicide against herpetic infections was studied here. To determine the cytotoxic effect of CDM, the MTT assay and acridine orange staining of living cells were performed. The antiherpetic action of CDM was measured by plaque reduction assay, and the immunomodulatory effect was determined by measuring the cytokine production using a bioassay and ELISA method. The results presented here showed that CDM inhibited Herpes Simplex Virus type 2 (HSV-2) multiplication in Vero cells but did not affect its replication in macrophages which were not permissive to HSV infection. In macrophages, levels of TNF-α, IFN-γ, NO, IL-6 and IL-10 were increased by CDM used alone or in combination with HSV-2. Besides, CDM not only synergized TNF-α production combined with IFN-γ, but also prolonged its expression in time. Results indicate that CDM inhibits HSV-2 multiplication in epithelial cells and also increases cytokine production in macrophages, both important actions to the clearance of infecting virus in the mouse vagina. Copyright © 2013 John Wiley & Sons, Ltd. 23576174 Sarmentosumols A to F, New Mono- and Dimeric Alkenylphenols from Piper sarmentosum. Two new mono- and four new dimeric alkenylphenols, namely sarmentosumols A to F (1-6), were isolated from the aerial parts of Piper sarmentosum. The structures of these compounds were determined through a detailed analysis of NMR and MS data. Their antimicrobial activity against Escherichia coli, Staphyloccocus aureus, and Candida albicans, and their cytotoxic activity against human myeloid leukemia (K562) and human lung adenocarcinoma (A549) cell lines were also evaluated. Except for sarmentosumol A (1), whose MIC on S. aureus was reported to be 7.0 µg/mL, none of the other newly discovered compounds exhibited antimicrobial property. The studied compounds did not possess any cytotoxic property. 23553632 The N- and C- termini of ZO-1 are surrounded by distinct proteins and functional protein networks. The proteins and functional protein networks of the tight junction remain incompletely defined. Among the currently known proteins are barrier forming proteins like occludin and the claudin family, scaffolding proteins like ZO-1, and some cytoskeletal, signaling and cell polarity proteins. To define a more complete list of proteins and infer their functional implications, we identified the proteins which are within molecular dimensions of ZO-1 by fusing biotin ligase to either its N- or C-terminus, expressing these fusion proteins in MDCK epithelial cells and purifying and identifying the resulting biotinylated proteins by mass spectrometry. Out of a predicted proteome of ≈ 9000 we identified more than 400 proteins tagged by biotin ligase fused to ZO-1, with both identical and distinct proteins near the N- and C- terminal ends. Those proximal to the N-terminus were enriched in transmembrane tight junction proteins and those proximal to the C-terminus were enriched in cytoskeletal proteins. We also identified many unexpected, but easily rationalized proteins. In addition, functional networks of interacting proteins were tagged, such as the basolateral but not apical polarity network. These results provide a rich inventory of proteins and potential novel insights into functions and protein networks that should catalyze further understanding of tight junction biology. Unexpectedly, the technique demonstrates high spatial resolution which could be generally applied to defining subcellular protein compartmentalization. 23370306 Eight New Diterpenoids and Two New Nor-Diterpenoids from the Stems of Croton cascarilloides. From the stems of Croton cascarilloides, eight new diterpenoids, named crotocascarins A-H (1-8), having a crotofolane skeleton were isolated along with two new nor-diterpenoids (9 and 10), named crotocascarins α and β, derived through rearrangement of the crotofolane skeleton. The structures of these compounds were elucidated by means of extensive one- and two-dimensional NMR spectroscopic analyses. The absolute structures of the diterpene moiety were determined by application of the circular dichroism (CD) rule for the γ-lactone ring. The relative structures of the two crotofolanes (1 and 2) and one rearranged compound (9) were confirmed by X-ray crystallographic analyses. Compounds 1, 2 and 9 possessed 2-methylbutyric acid in their molecules, the absolute configuration of which was found to be 2S by comparison of its HPLC behavior with that of an authentic sample. Therefore, the absolute structures of these crotocascarins (1, 2 and 9) were unambiguously determined. The absolute structures of crotofolanes are reported for the first time in this paper. 23562076 Improved Insulin Sensitivity despite Increased Visceral Adiposity in Mice Deficient for the Immune Cell Transcription Factor T-bet. Low-grade inflammation in fat is associated with insulin resistance, although the mechanisms are unclear. We report that mice deficient in the immune cell transcription factor T-bet have lower energy expenditure and increased visceral fat compared with wild-type mice, yet paradoxically are more insulin sensitive. This striking phenotype, present in young T-bet(-/-) mice, persisted with high-fat diet and increasing host age and was associated with altered immune cell numbers and cytokine secretion specifically in visceral adipose tissue. However, the favorable metabolic phenotype observed in T-bet-deficient hosts was lost in T-bet(-/-) mice also lacking adaptive immunity (T-bet(-/-)xRag2(-/-)), demonstrating that T-bet expression in the adaptive rather than the innate immune system impacts host glucose homeostasis. Indeed, adoptive transfer of T-bet-deficient, but not wild-type, CD4(+) T cells to Rag2(-/-) mice improved insulin sensitivity. Our results reveal a role for T-bet in metabolic physiology and obesity-associated insulin resistance. 23138972 Homogeneous palladium-catalyzed asymmetric hydrogenation. The transition metal catalyzed asymmetric hydrogenation of unsaturated compounds arguably presents one of the most attractive methods for the synthesis of chiral compounds. Over the last few decades, Pd has gradually grown up as a new and popular metal catalyst in homogeneous asymmetric hydrogenation the same as traditional Ru, Rh and Ir catalysts. Much progress has been successfully achieved in the asymmetric reduction of imines, enamines, olefins, ketones and heteroarenes. It was also found that palladium catalyzed asymmetric hydrogenation could be used as a key step in tandem reactions to quickly synthesize chiral compounds. This tutorial review intends to offer an overview of recent progress in homogeneous palladium catalyzed asymmetric hydrogenation and should serve as an inspiration for further advances in this area. 23282066 Evaluation of animal models for intestinal first-pass metabolism of drug candidates to be metabolized by CYP3A enzymes via in vivo and in vitro oxidation of midazolam and triazolam. Abstract 1. To search an appropriate evaluation methodology for the intestinal first-pass metabolism of new drug candidates, grapefruit juice (GFJ)- and vehicle (tap water)-pretreated mice or rats were orally administered midazolam (MDZ) or triazolam (TRZ), and blood levels of the parent compounds and their metabolites were measured by liquid chromatography/MS/MS. A significant effect of GFJ to elevate the blood levels was observed only for TRZ in mice. 2. In vitro experiments using mouse, rat and human intestinal and hepatic microsomal fractions demonstrated that GFJ suppressed the intestinal microsomal oxidation of MDZ and especially TRZ. Substrate inhibition by MDZ caused reduction in 1'-hydroxylation but not 4-hydroxylation in both intestinal and hepatic microsomal fractions. The kinetic profiles of MDZ oxidation and the substrate inhibition in mouse intestinal and hepatic microsomal fractions were very similar to those in human microsomes but were different from those in rat microsomes. Furthermore, MDZ caused mechanism-based inactivation of cytochrome P450 3A-dependent TRZ 1'-hydroxylation in mouse, rat and human intestinal microsomes with similar potencies. 3. These results are useful information in the analysis of data obtained in mouse and rat for the evaluation of first-pass effects of drug candidates to be metabolized by CYP3A enzymes. 23070981 Electric control of the giant Rashba effect in bulk GeTe. Relativistic effects, including the Rashba effect, are increasingly seen as key ingredients in spintronics. A link between Rashba physics and the field of ferroelectrics is established by predicting giant Rashba spin-splitting in bulk GeTe (see the Figure showing the band-structure as well as in-plane and out- of-plane spin polarization for a constant energy cut). 23371451 Increased human dermal microvascular endothelial cell survival induced by cysteamine. BACKGROUND: Cystinosis is an autosomal recessive disease caused by intralysosomal cystine accumulation, treated with cysteamine. Recently, new adverse effects of cysteamine were reported. Skin biopsies showed microvascular proliferation (angioendotheliomatosis). To examine the mechanism of angioendotheliomatosis associated with cysteamine toxicity, we examined the effect of cysteamine on human dermal microvascular endothelial cells (HDMVEC). METHODS: After cysteamine exposure (range 0-3.0 mM) during 24 h, cell viability was measured using water soluble tetrazolium salt-1 (WST-1) in both control HDMVEC and fibroblasts. Cell proliferation and apoptosis rate were measured in HDMVEC by bromodeoxyuridine (BrdU) incorporation and caspase 3 and caspase 7 activity, respectively. Intracellular glutathione (GSH) was measured in HDMVEC after cysteamine exposure of 0, 0.1 or 1.0 mM. Medium and cysteamine were refreshed every 6 h to mimic the in vivo situation. Next, cell viability in HDMVEC was measured after 24 h of GSH exposure (range 0-10.0 mM). RESULTS: HDMVEC viability and proliferation increased after cysteamine exposure 0.03-3.0 mM (p < 0.01) and 0.03-1.0 mM (p = 0.01) respectively; cell viability in fibroblasts was not affected by incubation with cysteamine. Apoptosis remained unaffected by incubation with 0-1.0 mM cysteamine, 3.0 mM caused increased apoptosis. Intracellular GSH was significantly increased after incubation with cysteamine 0.1 mM (p = 0.02) and 1.0 mM (p < 0.01). HDMVEC viability increased after exposure to GSH 1.0-5.0 mM (p < 0.01). CONCLUSION: Cysteamine concentrations, similar to those described in plasma of cystinosis patients, stimulate HDMVEC viability and proliferation and increase intracellular GSH content. We postulate that this mechanism might underlie angioendotheliomatosis induced by cysteamine. 23330847 Hydroxy-terminated conjugated polymer nanoparticles have near-unity bright fraction and reveal cholesterol-dependence of IGF1R nanodomains. Fluorescent nanoparticles have enabled many discoveries regarding how molecular machines function. Quantum dots have been the dominant class of fluorescent nanoparticles but suffer from blinking and from a substantial dark fraction--particles where the fluorescence is never seen--complicating any analysis of biological function. Nanoparticles composed of conjugated fluorescent polymers (Pdots) have recently been shown to have high brightness and no blinking. Here we develop a robust and efficient means to measure the dark fraction of Pdots, conjugating Atto dyes to the nanoparticles and testing fluorescence colocalization of dye and Pdot puncta. This established that the Pdots we generated had minimal dark fraction: ∼3%. The application of nanoparticles in biological environments is highly sensitive to surface functionalization. For Pdots we found that passivation with uncharged hydroxy-terminated polyethylene glycol caused a dramatic reduction in nonspecific cell binding and aggregation compared to a charged coating. Using carbonyl di-imidazole the hydroxy-Pdots were functionalized efficiently with streptavidin for high stability targeting, allowing specific labeling of mammalian cells. Type I insulin-like growth factor receptor (IGF1R) regulates cell survival and development, with roles in aging, heart disease, and cancer. We used hydroxy-Pdots to track the dynamics of IGF1R on a breast cancer cell-line, determining the diffusion characteristics and showing cholesterol-containing membrane nanodomains were important for receptor mobility at the plasma membrane. The near-unity bright fraction and low nonspecific binding of hydroxy-Pdots, combined with Pdot photostability and lack of blinking, provides many advantages for investigations at the single molecule level. 23036893 Effect of combining in vitro estrogenicity data with kinetic characteristics of estrogenic compounds on the in vivo predictive value. With the ultimate aim of increasing the utility of in vitro assays for toxicological risk assessment, a method was developed to calculate in vivo estrogenic potencies from in vitro estrogenic potencies of compounds by taking into account systemic availability. In vitro estrogenic potencies of three model compounds (bisphenol A, genistein, and 4-nonylphenol) relative to ethinylestradiol (EE2), determined with the estrogen receptor alpha (ERα) transcriptional activation assay using hER-HeLa-9903 cells, were taken from literature and used to calculate the EE2 equivalent (EE2EQ) effect doses in the predominantly ERα-dependent rat uterotrophic assay. Compound-specific differences in hepatic clearance relative to the reference compound EE2 were determined in vitro to examine whether in vivo estrogenic potencies reported in literature could be more accurately estimated. The EE2EQ doses allowed to predict in vivo uterotrophic responses within a factor of 6-25 and the inclusion of the hepatic clearance further improved the prediction with a factor 1.6-2.1 for especially genistein and bisphenol A. Yet, the model compounds still were less potent in vivo than predicted based on their EE2 equivalent estrogenic potency and hepatic clearance. For further improvement of the in vitro to in vivo predictive value of in vitro assays, the relevance of other kinetic characteristics should be studied, including binding to carrier proteins, oral bioavailability and the formation of estrogenic metabolites. 23404750 Computational studies identifying entry inhibitor scaffolds targeting the Phe43 cavity of HIV-1 gp120. Targeting protein-protein interactions, such as the HIV-1 gp120-CD4 interface, has become a cutting-edge approach in the current drug discovery scenario. Many small molecules have been developed so far as inhibitors of the interaction between CD4 and HIV-1 gp120. However, due to a variety of reasons such as solubility, drug toxicity and drug resistance, these inhibitors have failed to prove clinically useful. As such, the identification of novel compounds that bind to protein-protein interactions is still a research area of considerable interest. Here, a structure-based virtual screening approach was successfully applied with the aim of identifying novel HIV-1 entry inhibitors targeting the Phe43 pocket of HIV-1 gp120. Several compounds able to inhibit viral replication in cell culture were identified, with the best agent endowed with an EC(50) value of 0.9 μM. Inactivity of all the identified hits toward a mutant (Met475Ile) strain strongly suggests that they interact in the Phe43 cavity of gp120, as intended. Remarkably, all of these small molecules have a chemical scaffold unrelated to any known class of entry inhibitors reported thus far. Overall, our strategy led to the identification of four novel chemical scaffolds that inhibit HIV-1 replication through the destabilization of the HIV-1 gp120-CD4 interface. 22976834 Loss of HtrA2/Omi activity in non-neuronal tissues of adult mice causes premature aging. mnd2 mice die prematurely as a result of neurodegeneration 30-40 days after birth due to loss of the enzymatic activity of the mitochondrial quality control protease HtrA2/Omi. Here, we show that transgenic expression of human HtrA2/Omi in the central nervous system of mnd2 mice rescues them from neurodegeneration and prevents their premature death. Interestingly, adult transgenic mnd2 mice develop accelerated aging phenotypes, such as premature weight loss, hair loss, reduced fertility, curvature of the spine, heart enlargement, increased autophagy, and death by 12-17 months of age. These mice also have elevated levels of clonally expanded mitochondrial DNA (mtDNA) deletions in their tissues. Our results provide direct genetic evidence linking mitochondrial protein quality control to mtDNA deletions and aging in mammals. 23434641 New 2-benzylsulfanyl-nicotinic acid based 1,3,4-oxadiazoles: Their synthesis and biological evaluation. A novel series of 5-(2-benzylsulfanyl-pyridin-3-yl)-2-(substituted)-sulfanyl-1,3,4-oxadiazoles 6a-j were synthesized from key intermediate 5-(2-benzylsulfanyl-pyridin-3-yl)-3H-[1,3,4]oxadiazole-2-thione 5. Nucleophilic substitution reactions with different electrophiles (E+), such as haloacetate and haloalkyl groups, were performed to get target compounds 6a-j. Compounds were characterized by NMR, mass, IR spectra and C, H, N analyses. All compounds were evaluated for their antimicrobial and antimycobacterial activities; selected analogs were screened for their anticancer activity on 60 tumor cell lines at single dose 1.00(-5) M. Unfortunately, none of the compounds showed a significant antitumor activity on 60 human tumor cell lines. However, compounds 6g and 6f with benzothiazole moiety (12.5 and 25 μg/ml) showed promising activity against Escherichia coli compared to ampicillin; compounds 6d, 6j bearing triazole and morpholine, respectively, showed promising antitubercular activity (25 μg/ml) compared to rifampicin. 23138381 New results on formaldehyde: the 2nd International Formaldehyde Science Conference (Madrid, 19-20 April 2012). The toxicology and epidemiology of formaldehyde were discussed on the 2nd International Formaldehyde Science Conference in Madrid, 19-20 April 2012. It was noted that a substantial amount of new scientific data has appeared within the last years since the 1st conference in 2007. Progress has been made in characterisation of genotoxicity, toxicokinetics, formation of exogenous and endogenous DNA adducts, controlled human studies and epidemiology. Thus, new research results are now at hand to be incorporated into existing evaluations on formaldehyde by official bodies. 23314331 Copper induced upregulation of apoptosis related genes in zebrafish (Danio rerio) gill. Copper (Cu) is an essential micronutrient that, when present in high concentrations, becomes toxic to aquatic organisms. It is known that Cu toxicity may induce apoptotic cell death. However, the precise mechanism and the pathways that are activated, in fish, are still unclear. Thus, this study aimed to assess which apoptotic pathways are triggered by Cu, in zebrafish (Danio rerio) gill, the main target of waterborne pollutants. Fish where exposed to 12.5 and 100 μg/L of Cu during 6, 12, 24 and 48 h. Fish gills were collected to TUNEL assay and mRNA expression analysis of selected genes by real time PCR. An approach to different apoptosis pathways was done selecting p53, caspase-8, caspase-9 and apoptosis inducing factor (AIF) genes. The higher incidence of TUNEL-positive cells, in gill epithelia of the exposed fish, proved that Cu induced apoptosis. The results suggest that different apoptosis pathways are triggered by Cu at different time points of the exposure period, as the increase in transcripts was sequential, instead of simultaneous. Apoptosis seems to be initiated via intrinsic pathway (caspase-9), through p53 activation; then followed by the extrinsic pathway (caspase-8) and finally by the caspase-independent pathway (AIF). A possible model for Cu-induce apoptosis pathways is proposed. 22546616 The brain GABA-benzodiazepine receptor alpha-5 subtype in autism spectrum disorder: a pilot [(11)C]Ro15-4513 positron emission tomography study. GABA (gamma-amino-butyric-acid) is the primary inhibitory neurotransmitter in the human brain. It has been proposed that the symptoms of autism spectrum disorders (ASDs) are the result of deficient GABA neurotransmission, possibly including reduced expression of GABAA receptors. However, this hypothesis has not been directly tested in living adults with ASD. In this preliminary investigation, we used Positron Emission Tomography (PET) with the benzodiazepine receptor PET ligand [(11)C]Ro15-4513 to measure α1 and α5 subtypes of the GABAA receptor levels in the brain of three adult males with well-characterized high-functioning ASD compared with three healthy matched volunteers. We found significantly lower [(11)C]Ro15-4513 binding throughout the brain of participants with ASD (p < 0.0001) compared with controls. Planned region of interest analyses also revealed significant reductions in two limbic brain regions, namely the amygdala and nucleus accumbens bilaterally. Further analysis suggested that these results were driven by lower levels of the GABAA α5 subtype. These results provide initial evidence of a GABAA α5 deficit in ASD and support further investigations of the GABA system in this disorder. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. 23600800 CASK is a new intracellular modulator of P2X3 receptors. ATP-gated P2X3 receptors of sensory ganglion neurons are important transducers of painful stimuli and are modulated by extracellular algogenic substances, via changes in the receptor phosphorylation state. The present study investigated the role of calcium/calmodulin-dependent serine protein kinase CASK in interacting and controlling P2X3 receptor expression and function in mouse trigeminal ganglia. Most ganglion neurons in situ or in culture co-expressed P2X3 and CASK. CASK was immunoprecipitated with P2X3 receptors from trigeminal ganglia and from P2X3/CASK-cotransfected HEK cells. Recombinant P2X3/CASK expression in HEK cells increased serine phosphorylation of P2X3 receptors, typically associated with receptor upregulation. CASK deletion mutants also enhanced P2X3 subunit expression. After silencing CASK, cell surface P2X3 receptor expression was decreased, which is consistent with depressed P2X3 currents. The reduction of P2X3 expression levels was reversed by the proteasomal inhibitor MG-132. Moreover, neuronal CASK/P2X3 interaction was upregulated by NGF signaling and downregulated by P2X3 agonist-induced desensitization. These data suggest a novel interaction between CASK and P2X3 receptors with positive outcome for receptor stability and function. As CASK-mediated control of P2X3 receptors was dependent on the receptor activation state, CASK represents an intracellular gateway to regulate purinergic nociceptive signaling. This article is protected by copyright. All rights reserved. 23157635 Antipsychotic drug effects in schizophrenia: a review of longitudinal FMRI investigations and neural interpretations. The evidence that antipsychotics improve brain function and reduce symptoms in schizophrenia is unmistakable, but how antipsychotics change brain function is poorly understood, especially within neuronal systems. In this review, we investigated the hypothesized normalization of the functional magnetic resonance imaging (fMRI) blood oxygen level dependent signal in the context of antipsychotic treatment. First, we conducted a systematic PubMed search to identify eight fMRI investigations that met the following inclusion criteria: case-control, longitudinal design; pre- and post-treatment contrasts with a healthy comparison group; and antipsychotic-free or antipsychotic-naive patients with schizophrenia at the start of the investigation. We hypothesized that aberrant activation patterns or connectivity between patients with schizophrenia and healthy comparisons at the first imaging assessment would no longer be apparent or "normalize" at the second imaging assessment. The included studies differed by analysis method and fMRI task but demonstrated normalization of fMRI activation or connectivity during the treatment interval. Second, we reviewed putative mechanisms from animal studies that support normalization of the BOLD signal in schizophrenia. We provided several neuronal-based interpretations of these changes of the BOLD signal that may be attributable to long-term antipsychotic administration. 23401323 Hemifluorinated maltose-neopentyl glycol (HF-MNG) amphiphiles for membrane protein stabilisation. SOAP OPERA: Fluorinated amphiphile F4-MNG confers greater stability on Rhodobacter capsulatus superassembly relative to conventional detergents and nonfluorinated MNGs. Such amphiphiles are attractive as tools for membrane science because of their ease of preparation and structure variation. 23411219 An electrospray ionisation-mass spectrometry screening of triacylglycerols in developing cultivated and wild peanut kernels (Arachis hypogaea L.). The accumulation of triacylglycerols during the development of three varieties of peanuts was monitored in two Tunisian cultivated peanut (Trabelsia (AraT) and Chounfakhi (AraC)) and one wild Tunisian peanut (Arbi (AraA)). The presence of TAGs composed of rare fatty acid residues such as hexacosanoic acid (C(23:0)) and heneicosanoic acid (C(21:0)) among the triacylglycerols C(23:0) LL, C(23:0) OO and C(21:0) LL was noted. The major molecular species of triacylglycerol detected in the three peanut varieties were dioleoyl linoleoyl (OOL), 1,2,3-trioleyl (OOO), 1,2-dioleyl-3-palmitoyl (POO), 1,2-dilinoleoyl-3-oleyl (OLL) and 1-oleoyl-2-linoleoyl-3-linolenoyl (OLLn). The TAG composition and content were significantly different among the three peanut varieties. The three major TAGs were OOL (20.6%), OOO (15.6%) and OLLn (13.2%) in AraA; OOL (21.4%), OOO (20.1%) and POO (17.5%) in AraC and finally OLL (20.7%), OOO (19.8%) and OLL (17.7%) in AraT. 23008229 Bonding and electronic transport properties of fullerene and fullerene derivatives in break-junction geometries. Fullerenes are considered anchoring groups for molecular electronics due to a large contact area and their affinity for noble metals. The conductances of fullerene-terminated molecules, however, are found to be even lower than for thiol termination. The effects of weak molecule-metal coupling and symmetry breaking are studied by transport measurements of C(60) and functionalized C(60). The results demonstrate highy efficient contacts between Au and C(60), despite of deposition from solution. 23424012 Cytotoxic triterpenoid saponins from the stems of Gordonia longicarpa. Nine new triterpenoid saponins named longicarposides A-I (1-9), together with three known saponins (10-12), were isolated from the stems of Gordonia longicarpa. The structures of the saponins were elucidated by a combination of 1D and 2D NMR techniques, mass spectrometry, and chemical methods. They were characterized to be oleanane-type saponins with sugar moieties linked to C-3 of the aglycone. Cytotoxic activities of these saponins were evaluated against five human tumor cell lines (HCT-8, Bel-7402, BGC-823, A549, and A2780) by using the MTT in vitro assay. Compounds 5, 7, 8, 10, and 11 exhibited potent cytotoxic activity with IC50 values of 1.42-8.42 µM, while 6, 9, and 12 showed selective cytotoxic activity toward the tested cell lines. 23300227 A G protein-biased ligand at the μ-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine. The concept of ligand bias at G protein-coupled receptors broadens the possibilities for agonist activities and provides the opportunity to develop safer, more selective therapeutics. Morphine pharmacology in β-arrestin-2 knockout mice suggested that a ligand that promotes coupling of the μ-opioid receptor (MOR) to G proteins, but not β-arrestins, would result in higher analgesic efficacy, less gastrointestinal dysfunction, and less respiratory suppression than morphine. Here we report the discovery of TRV130 ([(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethyl})amine), a novel MOR G protein-biased ligand. In cell-based assays, TRV130 elicits robust G protein signaling, with potency and efficacy similar to morphine, but with far less β-arrestin recruitment and receptor internalization. In mice and rats, TRV130 is potently analgesic while causing less gastrointestinal dysfunction and respiratory suppression than morphine at equianalgesic doses. TRV130 successfully translates evidence that analgesic and adverse MOR signaling pathways are distinct into a biased ligand with differentiated pharmacology. These preclinical data suggest that TRV130 may be a safer and more tolerable therapeutic for treating severe pain. 22963619 A comparative study of two novel nanosized radiolabeled analogues of methionine for SPECT tumor imaging. It has been reported that most tumor cells show an increased uptake of variety of amino acids specially methionine when compared with normal cells and amino acid transport is generally increased in malignant transformation. Based on the evidences, two novel nanosized analogues of methionine (Anionic Linear Globular Dendrimer G(2), a biodigredabale anionic linear globular-Methionin, and DTPA-Methionine(1) conjugates) were synthesized and labeled with (99m)Tc and used in tumor imaging/ therapy in vitro and in vivo. The results showed marked tumor SPECT molecular imaging liabilities for both compounds but with a better performance by administration of (99m)Tc-Dendrimer G(2)-Methionin. The results also showed a good anticancer activity for 99mTc-DTPA-Methionine. Based on the present study (99m)Tc-Dendrimer G(2)-Methionin or 99mTc-DTPA-(Methionine)(1) have potentials to be used in tumor molecular imaging as well as cancer therapy in future. 23416192 Synthesis and pharmacological evaluation of some novel 2-(5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles. A series of novel 2-(5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles (6) were synthesized by condensing 3-(2-bromoacetyl)coumarins (4) with various 5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-thiocarboxamides (5), obtained by the reaction of thiosemicarbazide with trifluoromethyl-β-diketones. All the tested compounds displayed significant to moderate in vivo anti-inflammatory activity when compared to the standard drug indomethacin, and good broad spectrum in vitro antibacterial activity against three Gram-positive and four Gram-negative bacteria when compared with cefixime. 23246436 Integration-dependent bacteriophage immunity provides insights into the evolution of genetic switches. Genetic switches are critical components of developmental circuits. Because temperate bacteriophages are vastly abundant and greatly diverse, they are rich resources for understanding the mechanisms and evolution of switches and the molecular control of genetic circuitry. Here, we describe a new class of small, compact, and simple switches that use site-specific recombination as the key decision point. The phage attachment site attP is located within the phage repressor gene such that chromosomal integration results in removal of a C-terminal tag that destabilizes the virally encoded form of the repressor. Integration thus not only confers prophage stability but also is a requirement for lysogenic establishment. The variety of these self-contained integration-dependent immunity systems in different genomic contexts suggests that these represent ancestral states in switch evolution from which more-complex switches have evolved. They also provide a powerful toolkit for building synthetic biological circuits. 22455800 Synthesis of 4-hydroxy-3,4-dialkyl-2,6-diaryl-piperidine derivatives as potent antimicrobial agent. A series of 4-hydroxy-3,4-dialkyl-2,6-diaryl-piperidine (7-12) have been synthesised by reduction of 3-alkyl-2,6-diarylpiperidin-4-one using the Grignard reagent. Structural assignments and conformational analysis of the compounds were established based on the spectral studies. All the piperdin-4-ol derivatives (7-12) were assayed for antibacterial, antifungal and anthelmintic activities and they exhibited significant results. 22683935 Dendritic cell migration assay: a potential prediction model for identification of contact allergens. This manuscript describes methodology and a prediction model for the MUTZ-LC migration assay. The assay represents the physiological change in Langerhans cell (LC) behavior after exposure to a sensitizing chemical, resulting in LC migration from the epidermis to the dermis. MUTZ-LC are derived from the commercially available MUTZ-3 cell line. Upon exposure to a sensitizer MUTZ-LC migrate preferentially towards CXCL12 whereas upon exposure to a non-sensitizer MUTZ-LC migrate towards CCL5. A CXCL12/CCL5 ratio >1.10 in 2/3 independent experiments is indicative of a sensitizer, whereas a CXCL12/CCL5 ratio ≤1.10 is indicative of a non-sensitizer. At non cytotoxic chemical concentrations 9 sensitizers (2,4-dinitrochlorobenzene, paraphenylendiamine, cinnamaldehyde, isoeugenol, nickel-sulfate, tetramethylthiuram disulfide, eugenol, cinnamic-alcohol, ammonium-hexachloroplatinate) were distinguished from 4 non sensitizers (sodium lauryl sulfate, salicylic acid, phenol, octanoic acid). Critical points in assay performance are (i) MUTZ-3 passage number after thawing (p6-p40); (ii) cell viability (>80%); (iii) standard curve to optimize correlation of fluorescence with cell number; and (iv) optimization of the concentration of rhCXCL12 and rhCCL5 in transwell. The protocol has been tested in three European laboratories and results suggest that it may provide working conditions for performing the DC migration assay which is aimed at distinguishing sensitizers from non sensitizers. 23099337 Caffeine reduces cadmium accumulation in the organism and enhances the levels of antioxidant protein expression in the epididymis. The aim of this study was to investigate the effects of caffeine (20 mg/L) intake on cadmium (15 mg/L) accumulation in the rat blood, testes, epididymis and prostate as well as cadmium-induced changes to the antioxidant defense system of the epididymis. Caffeine reduced the cadmium concentration in all tissues analyzed. Meanwhile, cadmium reduced catalase activity and increased superoxide dismutase (SOD) activity in the epididymis. Caffeine increased SOD activity, catalase and glutathione tissue expression and sustains the cadmium's effect on catalase and GSP-Px activity. No differences in the expression of metallothionein and lipid peroxidation were observed among the different treatments in the epididymis. In conclusion, low doses of cadmium alter the antioxidant enzymatic profile of the epididymis, but not induced oxidative lipid damage. Caffeine intake reduces overall cadmium accumulation in the organism and enhances the levels of antioxidant protein expression in the epididymis, thus exerting a protective effect against this metal. 23432579 RNAi in Clinical Studies. RNA interference (RNAi) is an efficient process of posttranscriptional gene silencing. In recent years it has been developed into a new technology in biopharmaceutical fields of science. RNAi products include short interference RNA (siRNA) but also short hairpin RNA (shRNA), bifunctional short hairpin RNA (bi-shRNA) and microRNA (miRNA). They combine with homologous fragments of the mRNA and cause its degradation. It results in inhibition of protein synthesis, or in mutation in the gene encoding it. RNAi has been used in analysis of genomes and creation of new animal models to test drugs. From the pharmaceutical point of view, what is the most important is its therapeutic application. So far the basic and clinical research has been focused on the following targets: macular degeneration, cancer and antiviral therapy. But there are also reports on clinical trials in asthma, hypercholesterolemia and genetic diseases such as inherited skin disorders and amyloidosis. Among over 20 therapeutics that reached clinical trials, only few are still investigated. Another few are clinical candidates. The review focuses on RNAi products under clinical evaluation and their most promising new applications. 23239639 Synthesis of maleimide-functionalyzed HPMA-copolymers and in vitro characterization of the aRAGE- and human immunoglobulin (huIgG)-polymer conjugates. Herein the synthesis of antibody-polymer conjugates, with a quite narrow dispersity based on the polymer HPMA, are reported. These conjugates are synthesized by coupling antibodies to maleimide-functionalized poly(N-(2-hydroxypropyl)-methacrylamide) (poly-HPMA) copolymers derived through reversible addition-fragmentation chain transfer (RAFT) polymerization of pentafluorophenyl methacrylate via the intermediate step of an activated ester polymer. We develop a protocol that allows the attachment of two different model antibodies, monoclonal anti-RAGE (receptor for advanced glycation end-products) antibody, and polyclonal human immunoglobulin (huIgG). Modification of the antibody and conjugation is monitored by SDS-PAGE electrophoresis. Preserved affinity is demonstrated by Western Blott and cell-uptake analysis, for example, to cells of the immune system. 23452147 Autoprocessing mechanism of severe acute respiratory syndrome coronavirus 3C-like protease (SARS-CoV 3CL(pro) ) from its polyproteins. Like many other RNA viruses, severe acute respiratory syndrome coronavirus (SARS-CoV) produces polyproteins containing several non-structural proteins, which are then processed by the viral proteases. These proteases often exist within the polyproteins, and are excised by their own proteolytic activity ('autoprocessing'). It is important to investigate the autoprocessing mechanism of these proteases from the point of view of anti-SARS-CoV drug design. In this paper, we describe a new method for investigating the autoprocessing mechanism of the main protease (M(pro) ), which is also called the 3C-like protease (3CL(pro) ). Using our method, we measured the activities, under the same conditions, of the mature form and pro-forms with the N-terminal pro-sequence, the C-terminal pro-sequence or both pro-sequences, toward the pro-form with both N- and C-terminal pro-sequences. The data indicate that the pro-forms of the enzyme have proteolytic activity, and are stimulated by the same proteolytic activity. The stimulation occurs in two steps, with approximately eightfold stimulation by N-terminal cleavage, approximately fourfold stimulation by C-terminal cleavage, and 23-fold stimulation by the cleavage of both termini, compared to the pro-form with both the N- and C-terminal pro-sequences. Such cleavage mainly occurs in a trans manner; i.e. the pro-form dimer cleaves the monomeric form. The stimulation by N-terminal pro-sequence removal is due to the cis (intra-dimer and inter-protomer) effect of formation of the new N-terminus, whereas that by C-terminal cleavage is due to removal of its trans (inter-dimer) inhibitory effect. A numerical simulation of the maturation pathway is presented. 23434931 TCF7L2 Variation and Proliferative Diabetic Retinopathy. Proliferative diabetic retinopathy (PDR) is the most severe vision-threatening complication of diabetes. To investigated genetic association between TCF7L2 and PDR in Caucasian type 2 diabetes mellitus (T2DM) and its functional consequences, 383 T2DM patients with PDR (T2DM-PDR) and 756 T2DM patients without diabetic retinopathy (T2DM-no DR) were genotyped with rs7903146 in TCF7L2. We found that risk allele (T) frequency of rs7903146 was significantly higher in T2DM-PDR patients (allelic P = 2.52E-04). In lymphoblastoid cells induced to undergo endoplasmic reticulum (ER) stress by treatment of tunicamycin, higher fold change of TCF7L2 and VEGFA mRNA levels were observed in rs7903146-TT cells than that in rs7903146-CC cells (P = 0.02 for TCF7L2; P = 0.004 for VEGFA), suggesting ER stress plays a role in PDR pathogenesis. Silencing TCF7L2 resulted in decreased mRNA levels of both TCF7L2 and VEGFA (P < 0.001). Retinas of oxygen-induced retinopathy (OIR) mice (a model for PDR) had higher TCF7L2 and VEGFA mRNA levels than controls (P = 2.9E-04 for TCF7L2; P = 1.9E-07 for VEGFA). Together, our study showed that TCF7L2-rs7903146 is associated with PDR in Caucasian T2DM and suggested TCF7L2 promoted pathological retinal neovascularization via ER stress-dependent upregulation of VEGFA. 23638658 Three-Dimensional Self-Assembly of Chalcopyrite Copper Indium Diselenide Nanocrystals into Oriented Films. CuInSe2, which is one of the highest efficiency thin-film solar cell active layer materials, has been an attractive target for nanocrystal synthesis and manipulation. Here, we report unprecedented, simultaneous control of the synthesis and self-assembly behavior of CuInSe2 nanocrystals. These nanocrystals are solution-processable, monodisperse tetragonal bipyramids that exhibit photoconductivity and self-assemble into crystallographically oriented thin films. Structural characterization indicates that these nanocrystals are tetragonal phase, as is used in high-efficiency, second-generation, thin-film solar cells. Elemental analysis indicates that approximately 1:1:2 Cu/In/Se stoichiometry can be achieved, and that the elemental composition can be adjusted from copper-rich to indium-rich with reaction time. 23270993 Kynurenic acid as an antagonist of α7 nicotinic acetylcholine receptors in the brain: facts and challenges. Kynurenic acid (KYNA), a major tryptophan metabolite, is a glutamate receptor antagonist, which is also reported to inhibit α7 nicotinic acetylcholine receptors (α7nAChRs). Due to variations in experimental approaches, controversy has arisen regarding the ability of KYNA to directly influence α7nAChR function. Here we summarize current concepts of KYNA neurobiology and review evidence pertaining to the proposed role of KYNA as an endogenous modulator of α7nAChRs and synaptic transmission. As dysfunction of α7nAChRs plays a major role in the pathophysiology of central nervous system disorders, elucidation of KYNA's action on this receptor subtype has significant therapeutic implications. 23318425 DMAP1 is an essential regulator of ATM activity and function. The hereditary autosomal recessive disease ataxia telangiectasia (A-T) is caused by mutation in the DNA damage kinase ATM. ATM's main function is to orchestrate DNA repair, thereby maintaining genomic stability. ATM activity is increased in response to several stimuli, including ionising radiation (IR) and hypotonic stress. DNMT1-associated protein 1 (DMAP1) is a member of the TIP60-p400 histone acetyl transferase (HAT) complex, which acetylates histone H4 at lysine 16 (H4K16) to affect chromatin relaxation and modulate ATM activation. Here we demonstrate that DMAP1 is required for both modes of ATM activation. Knockdown of DMAP1 impaired IR-induced ATM activation and consequently resulted in radiosensitivity and impaired the G2/M checkpoint. Moreover, DMAP1 was also required for efficient ATM signalling in response to hypotonic stress. Overexpression of DMAP1 increased IR-induced ATM substrate phosphorylation, suggesting that DMAP1 function is rate limiting for ATM signalling. DMAP1 associated with TIP60-dependent HAT activity, and depletion of DMAP1 reduced H4K16 acetylation in response to DNA damage. Treatment with histone deacetylase inhibitors rescued IR-induced ATM signalling in Dmap1-depleted cells. These results suggest that DMAP1 is a critical regulator of ATM activity and function.Oncogene advance online publication, 14 January 2013; doi:10.1038/onc.2012.597. 23000451 Plants as a source of butyrylcholinesterase variants designed for enhanced cocaine hydrolase activity. Cocaine addiction affects millions of people with disastrous personal and social consequences. Cocaine is one of the most reinforcing of all drugs of abuse, and even those who undergo rehabilitation and experience long periods of abstinence have more than 80% chance of relapse. Yet there is no FDA-approved treatment to decrease the likelihood of relapse in rehabilitated addicts. Recent studies, however, have demonstrated a promising potential treatment option with the help of the serum enzyme butyrylcholinesterase (BChE), which is capable of breaking down naturally occurring (-)-cocaine before the drug can influence the reward centers of the brain or affect other areas of the body. This activity of wild-type (WT) BChE, however, is relatively low. This prompted the design of variants of BChE which exhibit significantly improved catalytic activity against (-)-cocaine. Plants are a promising means to produce large amounts of these cocaine hydrolase variants of BChE, cheaply, safely with no concerns regarding human pathogens and functionally equivalent to enzymes derived from other sources. Here, in expressing cocaine-hydrolyzing mutants of BChE in Nicotiana benthamiana using the MagnICON virus-assisted transient expression system, and in reporting their initial biochemical analysis, we provide proof-of-principle that plants can express engineered BChE proteins with desired properties. 23383746 Fluorescence (fluidity/hydration) and calorimetric studies of interactions of bile acid-drug conjugates with model membranes. We have studied the interactions of three bile acid-tamoxifen conjugates, lithocholic acid-tamoxifen (LA-Tam(1)-Am), deoxycholic acid-tamoxifen (DCA-Tam(2)-Am), and cholic acid-tamoxifen (CA-Tam(3)-Am), possessing 1-3 tamoxifen molecules having an amine headgroup with model DPPC membranes and compared with N-desmethylated tamoxifen (TamNHMe) using DPH based fluorescence anisotropy, Prodan based hydration, and differential scanning calorimetry studies. DPH based anisotropy studies showed that bile acid-tamoxifen conjugates increase membrane fluidity, which strongly depends on the number of tamoxifen molecules conjugated to bile acid and the percentage of doping of bile acid-tamoxifen conjugates in the DPPC membranes. The order of membrane fluidity of the coliposomes from bile acid-tamoxifen conjugates and DPPC lipids in gel phase was found to be CA-Tam(3)-Am > DCA-Tam(2)-Am > LA-Tam(1)-Am > TamNHMe. Incorporation of bile acid-tamoxifen conjugates showed an unusual complex behavior of membrane hydration, as evident from Prodan based hydration studies. Temperature dependent study showed incorporation of LA-Tam(1)-Am and DCA-Tam(2)-Am conjugates decreases membrane hydration with an increase in temperature up to the phase transition temperature (T(m)). Differential scanning calorimetry studies showed a decrease in phase transition temperature (T(m)) upon an increase in the percentage of doping of TamNHMe and CA-Tam(3)-Am, whereas LA-Tam(1)-Am and DCA-Tam(2)-Am do not cause a major change in the phase transition temperature (T(m)) of DPPC liposomes. These studies showed the differential behavior of bile acid-tamoxifen conjugates regulating the membrane fluidity, hydration, and phase transition of model membranes depending upon the percentage of doping and tamoxifen conjugation to bile acids. 23566899 Prediction of dose-hepatotoxic response in humans based on toxicokinetic/toxicodynamic modeling with or without in vivo data: A case study with acetaminophen. In the present legislations, the use of methods alternative to animal testing is explicitly encouraged, to use animal testing only 'as a last resort' or to ban it. The use of alternative methods to replace kinetics or repeated dose in vivo tests is a challenging issue. We propose here a strategy based on in vitro tests and QSAR (Quantitative Structure Activity Relationship) models to calibrate a dose-response model predicting hepatotoxicity. The dose response consists in calibrating and coupling a PBPK (physiologically-based pharmacokinetic) model with a toxicodynamic model for cell viability. We applied our strategy to acetaminophen and compared three different ways to calibrate the PBPK model: only with in vitro and in silico methods, using rat data or using all available data including data on humans. Some estimates of kinetic parameters differed substantially among the three calibration processes, but, at the end, the three models were quite comparable in terms of liver toxicity predictions and close to the usual range of human overdose. For the model based on alternative methods, the good adequation with the two other models resulted from an overestimated renal elimination rate which compensated for the underestimation of the metabolism rate. Our study points out that toxicokinetics/toxicodynamics approaches, based on alternative methods and modelling only, can predict in vivo liver toxicity with accuracy comparable to in vivo methods. 23572520 S-nitrosation of glutathione transferase P1-1 is controlled by the conformation of a dynamic active-site helix. S-nitrosation is a post-translational modification of protein cysteine residues which occurs in response to cellular oxidative stress. Although it is increasingly being linked to physiologically important processes, the molecular basis for protein regulation by this modification remains poorly understood. We used transient kinetic methods to determine a minimal mechanism for spontaneous GSNO-mediated transnitrosation of human glutathione transferase (GST) P1-1, a major detoxification enzyme and key regulator of cell proliferation. C47 of GSTP1-1 is S-nitrosated in two steps, with the chemical step limited by a pre-equilibrium between the open and closed conformations of helix α2 at the active site. C101, in contrast, is S-nitrosated in a single step but is subject to negative cooperativity due to steric hindrance at the dimer interface. Despite the presence of a GSNO binding site at the active site of GSTP1-1, isothermal titration calorimetry as well as nitrosation experiments using CysNO demonstrate that GSNO binding does not precede S-nitrosation of GSTP1-1. Kinetics experiments using the cellular reductant GSH show that C101-NO is substantially more resistant to denitrosation than C47-NO, suggesting a potential role for C101-NO in long term nitric oxide storage or transfer. These results constitute the first report of the molecular mechanism of spontaneous protein transnitrosation, providing insight into the post-translational control of GSTP1-1 as well as the process of protein transnitrosation in general. 23348409 Genotoxicity of dried Hoodia parviflora aerial parts. Hoodia parviflora is being developed commercially for use in weight loss food and dietary supplement products. Its effects are ascribed to a number of glycosides that have been shown to be present in plant extracts from several Hoodia species, the best known of which is H. gordonii. H. parviflora has been identified as an alternative to H. gordonii, and, as part of the process to develop H. parviflora, in vitro genotoxicity tests, as recommended by recent European Food Safety Authority guidance, were conducted on a dried powder preparation of H. parviflora aerial parts. The preparation was tested for reverse mutation at doses up to 5,000μg/plate in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, and in Escherichia coli WP2 uvrA TA, both in the presence and in the absence of an exogenous source of metabolic activation (rat liver S9). In addition, the dried powder was evaluated in an in vitro cytotoxicity chromosome aberration assay using human lymphocytes. Test conditions included both a 4 (up to 2500μg/mg) and 44-h exposure period (up to 1000μg/mg) and the incorporation of an exogenous source of metabolic activation (4-h exposure only). H. parviflora dried powder was non-genotoxic in both in vitro assays. 23404458 Composition and distribution of elements and ultrastructural topography of a human cardiac calculus. Trace elements (TEs) may contribute to the formation of calculi or stones or be involved in the aetiopathogenesis of stone diseases. The compositions and spatial distribution of elements from the inner nucleus to outer crust of the cardiac calculus were investigated by energy-dispersive X-ray fluorescence (EDXRF) spectrometer. The surface topograph, distribution map of elements, elemental and chemical compositions were also determined by environmental scanning electron microscope (ESEM)-energy-dispersive X-ray (EDX) analysis. Twenty-five elements were identifiable from 18 positions on the cardiac calculus by EDXRF spectrometer, in which the highest concentrations of toxic TEs (Ni, Pt, Hg, Sn, Pb, W, Au, Al, Si) and higher levels of essential TEs (Ca, Sr, Cr, P) were detected. A moderate positive Pearson's correlation between TEs concentrations of Mg, Ca or P and location differences from centre to periphery in the cardiac calculus was observed. A positive correlation was also found for Ca/Zn and Ca/Cu, indicating the gradual increase of calcium concentration from inner nucleus to outer crust of cardiac calculus. The drop-like nodules/crystals on the surface of petrous part of cardiac calculus were observed from ESEM analysis. ESEM-EDX analysis determined the calculus to be predominantly composed of calcium hydroxyapatite and cholesterol, as indicated by the petrous surface and drop-like nodules/crystals, respectively. This composition was confirmed using a portable Raman analyser. The spatial distribution analysis indicated a gradual increase in Mg, P and Ca concentrations from the inner nucleus to the outer crust of the cardiac calculus. The major chemical compositions of calcium hydroxyapatite and cholesterol were detected on this cardiac calculus. 23625160 The Acute and Chronic Effects of Monosodium L-Glutamate on Serum Iron and Total Iron-Binding Capacity in the Jugular Artery and Vein of Pigs. We analyzed the effects of acute and chronic oral administration of monosodium L-glutamate (MSG) on serum iron (Fe) levels and total iron-binding capacity (TIBC) in piglets. In the first experiment, 12 piglets were randomly assigned to two groups: one fed a standard diet (SD) and the other fed an SD containing MSG (10 g/kg). On day 30, serum, liver, kidney, and spleen samples were collected to determine the Fe levels. In the second experiment, six pigs were surgically fitted with a catheter in the jugular artery and vein to investigate the dynamic changes of serum Fe and TIBC. Blood samples were taken from each pig via the catheter every 30 min, for a period of 4 h. The results show that MSG increases Fe levels in the spleen (P < 0.05) and in serum obtained from the jugular artery (P < 0.01). In addition, TIBC in serum obtained from the jugular artery demonstrated an increasing trend in pigs fed the MSG diet; however, this trend was not observed in the jugular vein. In conclusion, MSG increases Fe retention by enhancing TIBC in serum. 23356859 Formulation and characterization of Brucea javanica oil microemulsion for improving safety. Abstract Objective: This study engaged in investigation of optimal formulation, characteristics analysis of Brucea javanica oil microemulsion (BJOM) in order to address safety concerns and make recommendations for improvements in BJOM safety during clinical use in vivo. Methods: Pseudo-ternary phase diagram techniques were used to determine the appropriate ratio of surfactant, cosurfactant and oil phases. Subsequent stability testing of BJOM was performed by dilution, centrifugation and accelerated stability testing. The results were expounded through additional assessment utilizing the classical thermostat method to establish the shelf life of the material. These results were utilized to evaluate the safety of BJOM by haemolytic, irritative and allergic testing in vitro. In addition, the cytotoxicity of BJOM was examined using the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), with particular emphasis given to potential uses in cancer treatment. Results: The most suitable method of preparation for BJOM was found to be a one to one ratio (K(m) 1:1) of Solutol HS15 surfactant matched with sorbitol cosurfactant in the ratio. The microemulsion droplets of BJOM possessed a spherical shape, uniform size and average diameter of 23.8 nm. The expiration date of BJOM was found to be 568 d. The safety study demonstrated no hemolysis activity at the experimental BJOM concentrations; however, mild hemolysis was observed at higher concentrations of Brucea javanica oil emulsion (BJOE), a common commercially available product. Irritation observed upon BJOM treatment can be primarily attributed to Brucea javanica oil (BJO) with little influence of BJOM excipients. In addition, BJOM caused no observed hypersensitivity or other visible allergic reactions in guinea pigs. The anticancer activity curves of BJOM and BJOE demonstrate that both BJOM and BJOE inhibit Hela cells, with BJOM demonstrating significantly more dramatic anticancer activity. Conclusion: An optimal formulation of BJOM superior to commercially available products and safe for medical application such as intravenous injection has been outlined along with its anticancer activity rating. 23432335 Montiporic acid D, a new polyacetylene carboxylic acid from scleractinian coral Montipora digitata. A new polyacetylene carboxylic acid named montiporic acid D (1) was isolated along with a known polyacetylene alcohol, (Z)-13,15-hexadecadien-2,4-diyn-1-ol (2) from scleractinian coral Montipora digitata. The structures of compounds were determined by analyses of NMR and MS spectra. 23220513 Methyleugenol hepatocellular cancer initiating effects in rat liver. Methyleugenol (MEG), a constituent of plants used in the human diet, is hepatocarcinogenic in rodents. In an experiment to elucidate its mode of action in rat liver, male F344 rats were administered MEG intragastrically at 3 doses per week for up to 16 weeks in an initiation phase, after which half the rats were fed 500 ppm phenobarbital (PB) in the diet to promote liver neoplasia and the other half were maintained on control diet for 24 weeks. At 8 and 16 week interim terminations, (32)P-nucleotide postlabeling assay revealed 3 adducts in livers of all MEG groups. The hepatocellular replicating fractions, measured by proliferating cell nuclear antigen immunohistochemistry, were doubled or more in all MEG groups. Hepatocellular altered foci, detected by glutathione S-transferase-placental type (π) immunohistochemistry, were present beginning with the high dose group at 8 weeks and extending to all MEG groups at 16 weeks. At the end of maintenance/promotion phase, the incidences, multiplicity and size of foci was similar between control and low dose groups, while those of mid and high dose groups were increased. Hepatocellular adenomas occurred in the mid and high dose groups, attaining higher multiplicity and size with PB. Thus, MEG had rapid initiating activity, reflecting the formation of DNA adducts and possibly cell proliferation. 23244521 Medicinal chemistry meets proteomics: fractionation of the human plasma proteome. Human plasma and its fractions/derivatives are frequently used materials in biomedicine as it contains thousands and thousands of proteins representing the majority of human proteome. Several important methods were developed in the past for the fractionation of this important biological fluid and its use for medicinal purposes. One of the greatest challenges is the very large dynamic range of plasma proteins ranging up to 10-12 orders of magnitude. Early attempts were mainly based on methods such as salting out or cold ethanol precipitation, as well as chromatography utilizing affinity, size exclusion, ion exchange and hydrophobic interaction techniques. More recently, fractionation applications started with the depletion of the high abundant plasma components, such as serum albumin and immunoglobulins, before isolating lower abundant proteins of interest. Plasma volumes were utilized from the milliliter scale for diagnostic applications to hundreds of liters for industrial scale plasma fractionation (e.g., medicinal product manufacturing). In this paper we review this important part of medicinal chemistry, highlighting the traditional methods along with some of their variations as well as the most significant recent achievements of the field. 23511125 Acetylcholinesterase inhibition reveals endogenous nicotinic modulation of glutamate inputs to CA1 stratum radiatum interneurons in hippocampal slices. The involvement of brain nicotinic acetylcholine receptors (nAChRs) in the neurotoxicological effects of soman, a potent acetylcholinesterase (AChE) inhibitor and a chemical warfare agent, is not clear. This is partly due to a poor understanding of the role of AChE in brain nAChR-mediated functions. To test the hypothesis that AChE inhibition builds sufficient acetylcholine (ACh) in the brain and facilitates nAChR-dependent glutamate transmission, we used whole-cell patch-clamp technique to record spontaneous glutamate excitatory postsynaptic currents (EPSCs) from CA1 stratum radiatum interneurons (SRI) in hippocampal slices. First, the frequency, amplitude and kinetics of EPSCs recorded from slices of control guinea pigs were compared to those recorded from slices of guinea pigs after a single injection of the irreversible AChE inhibitor soman (25.2μg/kg, s.c.). Second, EPSCs were recorded from rat hippocampal slices before and after their superfusion with the reversible AChE inhibitor donepezil (100nM). The frequency of EPSCs was significantly higher in slices taken from guinea pigs 24h but not 7 days after the soman injection than in slices from control animals. In 52% of the rat hippocampal slices tested, bath application of donepezil increased the frequency of EPSCs. Further, exposure to donepezil increased both burst-like and large-amplitude EPSCs, and increased the proportion of short (20-100ms) inter-event intervals. Donepezil's effects were suppressed significantly in presence of 10μM mecamylamine or 10nM methyllycaconitine. These results support the concept that AChE inhibition is able to recruit nAChR-dependent glutamate transmission in the hippocampus and such a mechanism can contribute to the acute neurotoxicological actions of soman. 23306790 Verrucarin A enhances TRAIL-induced apoptosis via NF-κB-mediated Fas overexpression. We investigated whether verrucarin A (VA) sensitizes HepG2 hepatoma cells to tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. We found that VA alone induces little apoptosis, but when combined with TRAIL (VA/TRAIL), it triggered significant apoptosis, causing little or no toxicity in normal mouse splenocytes. VA/TRAIL-induced cell death is involved in the loss of mitochondrial transmembrane potential and the consequent activation of caspases. Because nuclear factor (NF)-κB inhibition has been known as a critical target in TRAIL-mediated apoptosis, we also investigated the role of NF-κB in VA/TRAIL treatment. We found that VA upregulated the DNA binding activity of NF-κB, but that the antioxidants glutathione and N-acetyl-l-cysteine, as well as NF-κB inhibitor MG132, and mutant-IκB (m-IκB) transfection, significantly downregulated VA/TRAIL-induced cell death by inhibiting caspase-3 and NF-κB activities. Transfection of mutant-eIF2α also resulted in a decrease in VA/TRAIL-induced cell death by inhibiting of caspase-3, but not NF-κB activity. Although VA/TRAIL treatment led to an increase of DR5 expression, transfection of m-IκB had no influence on the DR5 expressional level. Finally, we showed that NF-κB-mediated Fas expression is critical to VA/TRAIL-induced apoptosis. Taken together, these results indicate that VA/TRAIL sensitizes HepG2 cells to apoptosis via NF-κB-mediated overexpression of Fas. 23621616 Highly Confined Tunable Mid-Infrared Plasmonics in Graphene Nanoresonators. Single-layer graphene has been shown to have intriguing prospects as a plasmonic material, as modes having plasmon wavelengths ∼20 times smaller than free space (λp ∼ λ0/20) have been observed in the 2-6 THz range, and active graphene plasmonic devices operating in that regime have been explored. However there is great interest in understanding the properties of graphene plasmons across the infrared spectrum, especially at energies exceeding the graphene optical phonon energy. We use infrared microscopy to observe the modes of tunable plasmonic graphene nanoresonator arrays as small as 15 nm. We map the wavevector-dependent dispersion relations for graphene plasmons at mid-infrared energies from measurements of resonant frequency changes with nanoresonator width. By tuning resonator width and charge density, we probe graphene plasmons with λp ≤ λ0/100 and plasmon resonances as high as 310 meV (2500 cm(-1)) for 15 nm nanoresonators. Electromagnetic calculations suggest that the confined plasmonic modes have a local density of optical states more than 10(6) larger than free space and thus could strongly increase light-matter interactions at infrared energies. 23335833 Comparison of contact angle hysteresis of different probe liquids on the same solid surface. Advancing and receding contact angles of water, formamide and diiodomethane were measured on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) layers deposited on three different solid supports-glass, mica and poly(methyl methacrylate). Up to five statistical monolayers were deposited on the surfaces by spreading DPPC solution. It was found that even on five statistical DPPC monolayers, the hysteresis of a given liquid depends on the kind of solid support. Also on the same solid support the contact angle hysteresis is different for each probe liquid used. The AFM images show that the heights of roughness of the DPPC films cannot be the primary cause of the observed hysteresis because the heights are too small to cause the observed hystereses. It is believed that the hysteresis is due to the liquid film present right behind the three-phase solid surface/liquid drop/gas (vapour) contact line and the presence of Derjaguin pressure. The value of contact angle hysteresis depends on both the solid surface and liquid properties as well as on intermolecular interactions between them. 23505146 Diverse effects of macromolecular crowding on the sequential glycan-processing pathway involved in glycoprotein quality control. Compared with in vitro conditions, the intracellular environment is highly crowded with biomolecules; this has numerous effects on protein functions, including enzymatic activity. We examined the effects of macromolecular crowding on glycan processing of N-glycoprotein in the endoplasmic reticulum as a model sequential metabolic pathway. Experiments with synthetic substrates of physiological glycan structure clearly showed that the first half of the pathway (glucose trimming) was accelerated, whereas the second (mannose trimming) was decelerated under molecular crowding conditions. Furthermore, calreticulin, a lectin-like molecular chaperone, bound more strongly to a glycan-processing intermediate under these conditions. This study demonstrates the diverse effects of molecular crowding on sequential enzymatic processing, and the importance of the effects of macromolecular crowding on in vitro assays for understanding sequential metabolic pathways. 23593923 Functional conservation and structural diversification of silk sericins in two moth species. Sericins are hydrophilic structural proteins produced by caterpillars in the middle section of silk glands and are layered over fibroin proteins secreted in the posterior section. In the process of spinning, fibroins form strong solid filaments, while sericins seal the pair of filaments into a single fiber and glue the fiber into a cocoon. Galleria mellonella and the previously examined Bombyx mori harbor three sericin genes that encode proteins containing long repetitive regions. Galleria sericin genes are similar to each other and the protein repeats are built from short and extremely serine-rich motifs, while Bombyx sericin genes are diversified and encode proteins with long and complex repeats. Developmental changes in sericin properties are controlled at the level of gene expression and splicing. In Galleria, MG-1 sericin is produced throughout larval life until the wandering stage, while the production of MG-2 and MG-3 reaches a peak during cocoon spinning. 23571415 Structure-based Identification of OATP1B1/3 Inhibitors. Several recent studies show that inhibition of the hepatic transport proteins organic-anion transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1 or 1B3-transfected CHO cells. At an equimolar substrate-inhibitor concentration of 10 μM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (min 50 % inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 μM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20 % of the dataset) with high specificity (86 %) and sensitivity (78 %). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 % and 74 % of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively. 23265501 Physical attributes and chemical composition of organic strawberry fruit (Fragaria x ananassa Duch, Cv. Albion) at six stages of ripening. Organic strawberry fruits (Cv. 'Albion') were harvested at six different ripening stages and evaluated for physical and chemical parameters. Biometrical characteristics and moisture content did not change significantly during ripening. Total soluble solids, pH and colour development increased while titratable acidity and fruit firmness decreased 14.7% and 91%, respectively. Fructose, glucose, and sucrose followed similar tendencies. Final contents of these sugars were 2323.4, 1988.5, and 1578.4 mg/100 g. Citric, malic, and ascorbic acids followed a descending, irregular, and increasing tendency during ripening, respectively. Final contents of these acids were 822.8, 245.8, and 78.1 mg/100 g. Total anthocyanins content (TAC) increased during ripening, while the opposite was observed for total phenolic content (TPC). TAC and TPC in ripe fruit were 56.4 mg/100g and 196 mg gallic acid equivalents (GAE)/100 g. Twenty eight phenolic compounds, mainly glycosides, were identified and quantified by HPLC-DAD-MS analysis. The concentration of these compounds was ripening dependent. 23259666 Dendrimer-based multivalent vancomycin nanoplatform for targeting the drug-resistant bacterial surface. Vancomycin represents the preferred ligand for bacteria-targeting nanosystems. However, it is inefficient for emerging vancomycin-resistant species because of its poor affinity to the reprogrammed cell wall structure. This study demonstrates the use of a multivalent strategy as an effective way for overcoming such an affinity limitation in bacteria targeting. We designed a series of fifth generation (G5) poly(amidoamine) (PAMAM) dendrimers tethered with vancomycin at the C-terminus at different valencies. We performed surface plasmon resonance (SPR) studies to determine their binding avidity to two cell wall models, each made with either a vancomycin-susceptible (D)-Ala-(D)-Ala or vancomycin-resistant (D)-Ala-(D)-Lac cell wall precursor. These conjugates showed remarkable enhancement in avidity in the cell wall models tested, including the vancomycin-resistant model, which had an increase in avidity of four to five orders of magnitude greater than free vancomycin. The tight adsorption of the conjugate to the model surface corresponded with its ability to bind vancomycin-susceptible Staphylococcus aureus bacterial cells in vitro as imaged by confocal fluorescent microscopy. This vancomycin platform was then used to fabricate the surface of iron oxide nanoparticles by coating them with the dendrimer conjugates, and the resulting dendrimer-covered magnetic nanoparticles were demonstrated to rapidly sequester bacterial cells. In summary, this article investigates the biophysical basis of the tight, multivalent association of dendrimer-based vancomycin conjugates to the bacterial cell wall, and proposes a potential new use of this nanoplatform in targeting Gram-positive bacteria. 23305807 Prophylactic effect of resveratrol against ethinylestradiol-induced liver cholestasis. Estrogens, and particularly glucuronides such as ethinylestradiol (EE), have been shown to cause cholestasis in animal studies, by reducing bile acid uptake by hepatocytes. The aim of the present article was to investigate anticholestatic activity of resveratrol (RES) against liver cholestasis induced by EE in adult female rats. The daily oral administration of the RES at a concentration of 25 mg/kg body weight for 15 days to rats treated with EE (100 μg/kg body weight for 5 days) resulted in a significant protection against EE-induced decrease in both serum cholesterol and bile acid levels as well as against an increase of serum bilirubin concentration. The treatment also resulted in a significant increase in hepatic superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase activities as well as hepatic protein-bound and nonprotein sulfhydryl groups. RES inhibited serum alkaline phosphatase, alanine aminotransferase, pi-glutathione-S-transferase, gamma-glutamyl transpeptidase, and alpha-glutathione-S-transferase activities, as well as reduced serum tumor necrosis factor-alpha, nitric oxide, and hepatic malondialdehyde as compared to EE-treated rats. The results clearly suggest that RES has a powerful prophylactic action in cholestasis induced by EE. Taken together, RES has potential as a preventive and therapeutic agent for cholestasis and deserves clinical trial in the near future as an adjuvant therapy in women treated with estrogen. 23334176 Antidepressant use and glycemic control. RATIONALE: Past research on the association of antidepressant medication use with glycemic control abnormalities has produced mixed results. OBJECTIVE: To examine the association of antidepressant use with glycemic control abnormalities and screen-positive diabetes in a representative population sample of US adults without a diagnosis of diabetes. METHODS: Using data from adult participants of the National Health and Nutrition Examination Survey (NHANES, 2005-2010), the association of antidepressant use with continuous measures of HbA1c, fasting blood sugar, 2-h oral glucose tolerance test, insulin sensitivity and screen-positive diabetes according to HbA1c, fasting blood sugar and 2-h oral glucose tolerance test were assessed. RESULTS: Antidepressant use was not associated with increased levels of HbA1c, fasting blood sugar, 2-h oral glucose tolerance test, reduced insulin sensitivity or increased prevalence of screen-positive diabetes. Results were mostly consistent across sociodemographic groups and across different lengths of exposure, different classes of antidepressants and levels of body mass index. CONCLUSIONS: In this representative population sample, antidepressant use was not associated with an increased risk of abnormalities in glycemic control or undetected diabetes. Positive findings from past research may be attributable to detection bias, in that individuals prescribed antidepressants may be more likely to be tested and diagnosed with diabetes. 23316966 Matrix metalloproteinases as drug targets in acute pulmonary embolism. Acute pulmonary embolism is a critical condition associated with increased mortality. Lung embolization causes acute pulmonary hypertension and right ventricle afterload. Global heart ischemia supervenes and may lead to severe shock and death. In this article, we reviewed current literature supporting the idea that abnormal matrix metalloproteinase (MMP) activity contributes to acute pulmonary embolism-induced hemodynamic changes. While low MMP levels are usually found in normal lung tissues, it is well known that inflammation and lung injury increase MMP expression and activity. This is probably due to recruitment and migration of inflammatory cells from the circulation to lung tissues. In addition, recent studies have shown increased MMP levels and activity in the right ventricle from animals with acute pulmonary embolism. Such increases in proteolytic activity were associated with increased cardiac troponin I in serum, suggesting a possible role for MMPs in cardiomyocyte injury during acute pulmonary embolism. These alterations have justified the use of doxycycline as an MMP inhibitor in acute pulmonary embolism. We review current evidence indicating that MMPs are targets in this critical condition. MMP inhibition apparently exerts antihypertensive effects and protects against cardiomyocyte injury caused by acute pulmonary embolism. 23375851 Chronic, low concentration exposure to pharmaceuticals impacts multiple organ systems in zebrafish. Pharmaceuticals are found in both receiving and drinking water due to their persistent release in waste-water effluents, raising concerns for environmental and human health. Chronic, aqueous exposure of zebrafish (Danio rerio) to environmentally relevant concentrations of acetaminophen (ACE), venlafaxaine (VEN) (10μgL(-1)), carbamazepine (CBZ) and gemfibrozil (GEM) (0.5 and 10μgL(-1)) decreased reproductive output. Atretic oocytes and altered ovarian histology were seen in female zebrafish exposed to CBZ and GEM, suggesting a direct effect on oocyte development that may account for the reduced fecundity. Apoptosis within the theca and granulosa cells was identified in exposed female zebrafish with atretic oocytes by TUNEL positive staining. The incidence of follicular apoptosis was nearly 2-fold higher in exposed females than the controls. All compounds significantly altered kidney proximal tubule morphology but there was no difference in the incidence of apoptotic cells within the kidney between control and exposed in either males or females. Liver histology was altered by ACE and GEM exposure. Parental exposure to pharmaceuticals did not increase developmental abnormalities, hatching success, or mortality in embryos. Yet, direct exposure of embryos to ACE increased developmental abnormalities and mortality; exposure to 0.5μgL(-1) of all pharmaceuticals increased mortality. CBZ decreased plasma 11-ketotestosterone concentrations in males and females. Overall, these data suggest that low concentration, chronic exposure of fish to pharmaceuticals impacts fish development as well as multiple organ systems in adult fish, leading to effects on reproduction and histology of liver and kidney. These results are significant in understanding the consequences of chronic, low concentration pharmaceutical exposure to fish and suggest that exposed populations are at risk of negative impacts to reproduction and health. 23481139 Nicotinic acid conjugates of nonsteroidal anti-inflammatory drugs (NSAID's) and their anti-inflammatory properties. A series of nicotinic acid conjugates with non-steroidal anti-inflammatory drugs (NSAID's) have been effectively synthesized using TBTU in high yield and purity. All the synthesized conjugates were evaluated for their in vitro anti-inflammatory activity. 23432064 Transient receptor potential channels and dermatological disorders. Transient receptor potential (TRP) cation channels are an emerging field of research in dermatology. Beyond their classical role in skin sensory perception, TRPs are involved in various cutaneous functions that include keratinocyte differentiation, apoptosis and melanocyte pigmentation. In addition, they have a role as pharmacological targets in many inflammatory skin diseases including psoriasis, chronic itch, hair disorders and skin cancers. Moreover, mutations in TRPs have recently been related to rare skin conditions such as Olmsted syndrome. This review will cover the role of TRPs in dermatologic conditions with special emphasis on itch and skin inflammatory diseases. 23295711 The interplay between environmental and genetic factors in Parkinson's disease susceptibility: The evidence for pesticides. Parkinson's disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuron loss in the substantia nigra. Several genetic and environmental factors have been implicated in the pathogenesis of PD. Single risk factors are likely to exert relatively minor effects, whereas their interaction may prove to be sufficient to cause PD. In the present review we summarize current knowledge from human genetic association studies regarding the interaction between gene polymorphisms and pesticide exposure in the risk of PD. A number of genetic association studies have investigated joint effects between genes and pesticides on PD risk. They have provided some evidence that genetic susceptibility either in metabolism, elimination and transport of pesticides or in the extent of mitochondrial dysfunction, oxidative stress and neuronal loss may predispose individuals to PD if they have been exposed to pesticides. These findings confirm the importance of considering pesticide-gene interactions in future studies in order to gain a better understanding of the pathogenic mechanisms of PD. 23610045 In Vitro Evaluation of Combined Sulfated Silk Fibroin Scaffolds for Vascular Cell Growth. A combined sulfated silk fibroin scaffold is fabricated by modifying a knitted silk scaffold with sulfated silk fibroin sponges. In vitro hemocompatibility evaluation reveals that the combined sulfated silk fibroin scaffolds reduce platelet adhesion and activation, and prolong the activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). The response of porcine endothelial cells (ECs) and smooth muscle cells (SMCs) on the scaffolds is studied to evaluate the cytocompatibility of the scaffolds. Vascular cells are seeded on the scaffolds and cultured for 2 weeks. The scaffolds demonstrate enhanced EC adhesion, proliferation, and maintenance of cellular functions. Moreover, the scaffolds inhibit SMC proliferation and induce expression of contractile SMC marker genes. 23161673 Identifying protein interaction subnetworks by a bagging Markov random field-based method. Identification of differentially expressed subnetworks from protein-protein interaction (PPI) networks has become increasingly important to our global understanding of the molecular mechanisms that drive cancer. Several methods have been proposed for PPI subnetwork identification, but the dependency among network member genes is not explicitly considered, leaving many important hub genes largely unidentified. We present a new method, based on a bagging Markov random field (BMRF) framework, to improve subnetwork identification for mechanistic studies of breast cancer. The method follows a maximum a posteriori principle to form a novel network score that explicitly considers pairwise gene interactions in PPI networks, and it searches for subnetworks with maximal network scores. To improve their robustness across data sets, a bagging scheme based on bootstrapping samples is implemented to statistically select high confidence subnetworks. We first compared the BMRF-based method with existing methods on simulation data to demonstrate its improved performance. We then applied our method to breast cancer data to identify PPI subnetworks associated with breast cancer progression and/or tamoxifen resistance. The experimental results show that not only an improved prediction performance can be achieved by the BMRF approach when tested on independent data sets, but biologically meaningful subnetworks can also be revealed that are relevant to breast cancer and tamoxifen resistance. 23558646 Supramolecular H-bonded porous networks at surfaces: exploiting primary and secondary interactions in a bi-component melamine-xanthine system. The control over the formation of a bi-component porous network was attained by the self-assembly at a solid-liquid interface by exploiting both primary and secondary non-covalent interactions between melamine and N(3)-alkylated xanthine modules. 23454345 Biodiversity of small molecules - a new perspective in screening set selection. How is the 'diversity' of a compound set defined and how is the most appropriate compound subset identified for assay when screening the entire HTS deck is not an option? A common approach has so far been to cover as much of the chemical space as possible by screening a chemically diverse set of compounds. We show that, rather than chemical diversity, the biologic diversity of a compound library is an essential requirement for hit identification. We describe a simple and efficient approach for the design of a HTS library based on compound-target diversity. Biodiverse compound subsets outperform chemically diverse libraries regarding hit rate and the total number of unique chemical scaffolds present among hits. Specifically, by screening ∼19% of a HTS collection, we expect to discover ∼50-80% of all desired bioactive compounds. 23477344 Binding Preference of Carbon Nanotube Over Proline-Rich Motif Ligand on SH3-Domain: A Comparison with Different Force Fields. With the widespread applications of nanomaterials such as carbon nanotubes, there is a growing concern on the biosafety of these engineered nanoparticles, in particular their interactions with proteins. In molecular simulations of nanoparticle-protein interactions, the choice of empirical parameters (force fields) plays a decisive role, and thus is of great importance and should be examined carefully before wider applications. Here we compare three commonly used force fields, CHARMM, OPLSAA, and AMBER in study of the competitive binding of a single wall carbon nanotube (SWCNT) with a native proline-rich motif (PRM) ligand on its target protein SH3 domain, a ubiquitous protein-protein interaction mediator involved in signaling and regulatory pathways. We find that the SWCNT displays a general preference over the PRM in binding with SH3 domain in all the three force fields examined, although the degree of preference can be somewhat different, with the AMBER force field showing the highest preference. The SWCNT prevents the ligand from reaching its native binding pocket by (i) occupying the binding pocket directly, and (ii) binding with the ligand itself and then being trapped together onto some off-sites. The π-π stacking interactions between the SWCNT and aromatic residues are found to play a significant role in its binding to the SH3 domain in all the three force fields. Further analyses show that even the SWCNT-ligand binding can also be relatively more stable than the native ligand-protein binding, indicating a serious potential disruption to the protein SH3 function. 23561198 Cultivating conditions effects on kefiran production by the mixed culture of lactic acid bacteria imbedded within kefir grains. The influence of fermentation temperature, agitation rate, and additions of carbon sources, nitrogen sources, vitamins and minerals on production of kefiran by kefir grains lactic acid bacteria was studied in a series of experiments. The main aim of the work was to increase the exopolysaccharide (EPS) production where customised milk was used as fermentation medium. It was proved that the controlling of culturing conditions and the modifying of fermentation medium conditions (i.e., carbon, nitrogen, mineral sources and vitamins) can dramatically enhance the production of the EPS. The temperature and agitation rate were critical for kefiran production during the 24h cultivation of grains; our optimised conditions being 25°C and 80rpm, respectively. In addition, when optimising the effects of additional nutrition, it was found that 5% (w/v) lactose, 0.1% (w/v) thiamine, and 0.1% (w/v) FeCl3 led to the maximal production of EPS. The results indicate that nutrients can be utilised to improve the production of EPS and that good kefir grains growth does not appear to be a determining factor for a high production yield of EPS. 23629516 In ovo effects of two organophosphate flame retardants, TCPP and TDCPP, on pipping success, development, mRNA expression and thyroid hormone levels in chicken embryos. Tris(1-chloro-2-propyl) phosphate (TCPP) and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) are organic flame retardants detected in the environment and biota for which toxicological data for avian species are limited. In this study, domestic chicken eggs were injected with TCPP or TDCPP (maximum dose = 51600 and 45000 ng/g egg, respectively) to determine dose-dependent effects on pipping success, development, hepatic messenger RNA (mRNA) expression levels of genes associated with xenobiotic metabolism and the thyroid hormone (TH) pathway, and TH levels following 20-22 days of incubation. Neither compound reduced pipping success; however, TCPP significantly delayed pipping at 9240 and 51600 ng/g and reduced tarsus length at 51600 ng/g. TDCPP exposure resulted in significant decreases in head plus bill length, embryo mass and gallbladder size at 45000 ng/g and reduced plasma free T4 levels at 7640 ng/g. Type I deiodinase, liver fatty-acid binding protein and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by TCPP, while TDCPP induced CYP3A37 and CYP2H1. Chemical analysis of egg contents at incubation days 0, 5, 11, 18, and 19 revealed that >92% of the injected TCPP or TDCPP concentration was detectable up to day 5; however, <1% was detected by day 19. The observed phenotypic responses to TCPP and TDCPP exposure may be associated with disruption of the TH-axis, which is critical for normal growth and development in birds. The effects of TDCPP on the gallbladder indicate that the disturbance of lipid metabolism is a likely target in its mechanism of toxicity. 23104432 Lung inflammatory effects, tumorigenesis, and emphysema development in a long-term inhalation study with cigarette mainstream smoke in mice. Cigarette smoking is the leading cause of lung cancer and chronic obstructive pulmonary disease, yet there is little mechanistic information available in the literature. To improve this, laboratory models for cigarette mainstream smoke (MS) inhalation-induced chronic disease development are needed. The current study investigated the effects of exposing male A/J mice to MS (6h/day, 5 days/week at 150 and 300 mg total particulate matter per cubic meter) for 2.5, 5, 10, and 18 months in selected combinations with postinhalation periods of 0, 4, 8, and 13 months. Histopathological examination of step-serial sections of the lungs revealed nodular hyperplasia of the alveolar epithelium and bronchioloalveolar adenoma and adenocarcinoma. At 18 months, lung tumors were found to be enhanced concentration dependently (up to threefold beyond sham exposure), irrespective of whether MS inhalation had been performed for the complete study duration or was interrupted after 5 or 10 months and followed by postinhalation periods. Morphometric analysis revealed an increase in the extent of emphysematous changes after 5 months of MS inhalation, which did not significantly change over the following 13 months of study duration, irrespective of whether MS exposure was continued or not. These changes were found to be accompanied by a complex pattern of transient and sustained pulmonary inflammatory changes that may contribute to the observed pathogeneses. Data from this study suggest that the A/J mouse model holds considerable promise as a relevant model for investigating smoking-related emphysema and adenocarcinoma development. 23495719 Simulating adsorptive expansion of zeolites: application to biomass-derived solutions in contact with silicalite. We have constructed and applied an algorithm to simulate the behavior of zeolite frameworks during liquid adsorption. We applied this approach to compute the adsorption isotherms of furfural-water and hydroxymethyl furfural (HMF)-water mixtures adsorbing in silicalite zeolite at 300 K for comparison with experimental data. We modeled these adsorption processes under two different statistical mechanical ensembles: the grand canonical (V-Nz-μg-T or GC) ensemble keeping volume fixed, and the P-Nz-μg-T (osmotic) ensemble allowing volume to fluctuate. To optimize accuracy and efficiency, we compared pure Monte Carlo (MC) sampling to hybrid MC-molecular dynamics (MD) simulations. For the external furfural-water and HMF-water phases, we assumed the ideal solution approximation and employed a combination of tabulated data and extended ensemble simulations for computing solvation free energies. We found that MC sampling in the V-Nz-μg-T ensemble (i.e., standard GCMC) does a poor job of reproducing both the Henry's law regime and the saturation loadings of these systems. Hybrid MC-MD sampling of the V-Nz-μg-T ensemble, which includes framework vibrations at fixed total volume, provides better results in the Henry's law region, but this approach still does not reproduce experimental saturation loadings. Pure MC sampling of the osmotic ensemble was found to approach experimental saturation loadings more closely, whereas hybrid MC-MD sampling of the osmotic ensemble quantitatively reproduces such loadings because the MC-MD approach naturally allows for locally anisotropic volume changes wherein some pores expand whereas others contract. 23548149 PFKFB3 activation in cancer cells by the p38/MK2 pathway in response to stress stimuli. PFK-2/FBPase-2 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase) catalyses the synthesis and degradation of Fru-2,6-P2 (fructose-2,6-bisphosphate), a key modulator of glycolysis and gluconeogenesis. The PFKFB3 gene is involved in cell proliferation owing to its role in carbohydrate metabolism. Here we analyze its mechanism of regulation as an immediately early gene controlled by stress stimuli that activate p38/MK2 pathway. We report that exposure of HeLa and T98G cells to different stress stimuli (NaCl, H2O2, UV radiation and anisomycin) leads to a rapid increase (15-30 minutes) in PFKFB3 mRNA levels. The use of specific inhibitors in combination with MK2-deficient cells implicate control by MK2 protein kinase. Transient transfection of HeLa cells with deleted gene promoter constructs allowed us to identify a Serum Response Element (SRE) to which Serum Response Factor (SRF) binds and thus transactivates PFKFB3 gene transcription. Direct Binding of phospho-SRF to the SRE sequence (-918 nt) was confirmed by ChIP (chromatin immunoprecipiation) assays. Moreover, PFKFB3 isoenzyme phosphorylation at Ser461 by MK2 increases PFK-2 activity. Together, the results suggest a multimodal mechanism of stress stimuli affecting PFKFB3 transcriptional regulation and kinase activation by protein phosphorylation, resulting in an increase in Fru-2,6-P2 concentration and stimulation of glycolysis in cancer cells. 23629055 Porphyrin sensitizers with π-extended pull units for dye-sensitized solar cells. New π-extended porphyrin dyes with long alkoxyl chains at the ortho positions of the meso-phenyls, and meta di-tert-butylphenyl-substituted porphyrins , and were synthesized for dye-sensitized solar cells, and their optical, electrochemical and photovoltaic properties were investigated and compared with those of and . The absorption spectra of showed a slight red shift of Soret bands and blue shift of Q bands as compared to the meta-substituted porphyrins due to the electron-donating effects of dioctyloxy substituents at the ortho-positions of the meso-phenyl rings. Replacement of the carboxyl with a cyanoacrylic acid as the anchoring group results in significant broadening and red shifts of the absorptions, which is due to the strong electronic coupling between the pull unit and the porphyrin ring facilitated by the C[triple bond, length as m-dash]C triple bond. The electrochemical studies and quantum-chemical calculations (DFT) indicated that the ortho alkoxy-substituted sensitizers exhibit lower oxidation potential, i.e. a higher HOMO energy level, and their HOMO-LUMO gaps are comparable to the meta-substituted analogues. The photovoltaic measurements confirmed that the ortho-octyloxy groups in the two meso-phenyls of and play a significant role in preventing dye aggregation thereby enhancing the corresponding short-circuit current density and open-circuit voltage. The power conversion efficiency (η) of is 8.04%, which is 11% higher than that of , whereas the efficiency of is 6.03%, which is 135% higher than that of . On the other hand, the poor performance of and is due to the floppy structural nature and limited molecular rigidity of the cyanoacrylic acid anchor. 23411191 Increase in antioxidant and anticancer effects of ginsenoside Re-lysine mixture by Maillard reaction. Ginsenosides are the main active components of Panax ginseng. Structural changes in diol type ginsenosides along with generation of Maillard reaction products (MRPs) are strongly associated with increased free radical-scavenging activities. Ginsenoside Re, one of the major triol type ginsenosides of P. ginseng, possesses a hydrophobic four-ring steroid-like structure with hydrophilic sugar moieties at carbons-3 and -20. The aim of the present study was to identify changes in the structure, antioxidant and anticancer effects of ginsenoside Re upon Maillard reaction. Ginsenoside Re was transformed into less-polar ginsenosides, namely Rg(2), Rg(6) and F(4) by heat-processing. Free radical-scavenging activity of the ginsenoside Re-lysine mixture increased upon heat processing. This improved free radical-scavenging activity mediated by antioxidant MRPs, which were generated through Maillard reaction of a glucosyl moiety separated from carbon-20 of ginsenoside Re and lysine. The increased anticancer effect of ginsenoside Re-lysine mixture upon heat processing was mainly derived from the generation of less-polar ginsenosides through the regulation of Bcl-2 and Bax, as well as caspase-dependent apoptotic pathway. These results reported here have shed significant new lights on the mechanism of increased antioxidant and anticancer effects of P. ginseng upon heat processing. 23344429 Synthetic cascades are enabled by combining biocatalysts with artificial metalloenzymes. Enzymatic catalysis and homogeneous catalysis offer complementary means to address synthetic challenges, both in chemistry and in biology. Despite its attractiveness, the implementation of concurrent cascade reactions that combine an organometallic catalyst with an enzyme has proven challenging because of the mutual inactivation of both catalysts. To address this, we show that incorporation of a d(6)-piano stool complex within a host protein affords an artificial transfer hydrogenase (ATHase) that is fully compatible with and complementary to natural enzymes, thus enabling efficient concurrent tandem catalysis. To illustrate the generality of the approach, the ATHase was combined with various NADH-, FAD- and haem-dependent enzymes, resulting in orthogonal redox cascades. Up to three enzymes were integrated in the cascade and combined with the ATHase with a view to achieving (i) a double stereoselective amine deracemization, (ii) a horseradish peroxidase-coupled readout of the transfer hydrogenase activity towards its genetic optimization, (iii) the formation of L-pipecolic acid from L-lysine and (iv) regeneration of NADH to promote a monooxygenase-catalysed oxyfunctionalization reaction. 22963367 Oriented electrophoretic deposition of GdOCl nanoplatelets. Electrophoretic deposition has emerged as a versatile and precisely tunable approach for the rapid deposition of conformal thin films of colloidal nanocrystals. The electrophoretic deposition of phosphor particles has assumed special significance in recent years as a commercially viable means toward the fabrication of large-area, ultrathin high-resolution emissive display screens. Here, we demonstrate that the anisotropic shape of colloidal ligand-passivated GdOCl nanoplatelets enables their assembly with remarkable substrate alignment and a high packing density upon electrophoretic deposition. GdOCl nanocrystals are promising candidates for phosphor applications given their low maximum phonon cutoff energy, robust chemical stability over prolonged periods of operation, and ability to promote efficacious phonon energy transfer to dopant ions. Potentiostatic deposition of GdOCl nanoplatelets from cyclohexane dispersions allows the deposition of individual nanoplatelets with their basal planes parallel to the electrode surface. Tuning the applied voltage and solution concentration allows control of film thickness, ranging up to several tens of micrometers. The high degree of particle alignment is attributed to anisotropic charge distribution and entrainment within electroosmotic flows established in the vicinity of the electrode surface. The oriented high-particle-density GdOCl nanoplatelet thin films are possible candidates for phosphor applications, which is illustrated by the green emission from a Tb-doped GdOCl thin film on indium tin oxide (ITO)-coated glass. 22548348 Tomentomimulol and mimulone B: Two new C-geranylated flavonoids from Paulownia tomentosa fruits. Two new discovered C-geranylated flavonoids tomentomimulol (1) and mimulone B (2) were isolated from the methanol extract of Paulownia tomentosa (Thunb). Steud. (Paulowniaceae) fruits by exhaustive chromatographic separation together with one known compound tanariflavanone D (3). The identification of compounds and structure elucidation was carried out using 1D and 2D NMR experiments, as well as mass spectroscopy, ultra-violet, infra red and CD experiments. 23617462 Competitive Adsorption of Di-hydroxy and Tri-hydroxy Bile Salts with Whey Protein and Casein in Oil-in-Water Emulsions. The competitive adsorption between whey protein concentrate (WPC) or sodium caseinate (SCN) and four bile salts, sodium cholate (NaC), dexocycholate (NaDC), taurocholate (NaTC) and glycodeoxycholate (NaGDC) has been studied in protein stabilized oil-in-water emulsions. The bile salts that contain a conjugated amino acid (NaTC and NaGDC) were considerably more efficient at displacing both WPC and SCN proteins from the emulsion droplet interface, even though they are known to have a lower hydrophobicity than NaC and NaDC. This is explained in terms of a steric resistance to adsorption from the conjugated amino acids in NaTC and NaGDC. This leads to them adopting an adsorbed conformation at the oil-water interface that penetrates less into the oil phase causing greater disruption of the adsorbed layer and hence leads to greater displacement of protein from the interface. Complementary computer simulations of the adsorption of the four bile salts at the decane-water interface support the hypothesis that the NaTC and NaGDC adopt flatter conformations that stick out further in to the aqueous phase, which arises from a lower free energy of adsorption. The adsorption isotherms for the four bile salts have also been measured. These have been found to have a form that fits closely the Langmuir-Freundlich isotherm. The results for NaC suggest that it adsorbs as individual molecules and forms a saturated monolayer over much of the concentration range used in the displacement experiments, since it is below its critical micelle concentration in this range. For the other three bile salts on the other hand, the primary adsorbing species appears to be the micelle form, since the surface coverage is above that of a saturated monolayer for much of the concentration range studied. 23142020 A soluble guanylate cyclase stimulator, BAY 41-8543, preserves right ventricular function in experimental pulmonary embolism. Pulmonary embolism (PE) increases pulmonary vascular resistance, causing right ventricular (RV) dysfunction, and poor clinical outcome. Present studies test if the soluble guanylate cyclase stimulator BAY 41-8543 reduces pulmonary vascular resistance and protects RV function. Experimental PE was induced in anesthetized, male Sprague-Dawley rats by infusing 25 μm polystyrene microspheres (1.95 million/100 g body wt, right jugular vein) producing moderate PE. Pulmonary artery vascular resistance, estimated as RVPSP/CO, increased 3-fold after 5 h of PE. Treatment with BAY 41-8543 (50 μg/kg, I.V.; given at the time of PE induction) normalized this index by reducing RVPSP and markedly increasing CO, via preservation of heart rate and stroke volume. Ex vivo RV heart function showed minimal changes at 5 h of PE, but decreased significantly after 18 h of PE, including peak systolic pressure (PSP, Control 39 ± 1 mmHg vs. 19 ± 3 PE), +dP/dt (1192 ± 93 mmHg/s vs. 444 ± 64) and -dP/dt (-576 ± 60 mmHg/s vs. -278 ± 40). BAY 41-8543 significantly improved all three indices of RV heart function (PSP 35 ± 3.5, +dP/dt 1129 ± 100, -dP/dt -568 ± 87). Experimental PE produced increased PVR and RV dysfunction, which were ameliorated by treatment with BAY 41-8543. Thus, there is vasodilator reserve in this model of experimental PE that can be exploited to reduce the stress upon the heart and preserve RV contractile function. 23307587 Improper Selection of a Pre-specified Primary Dose-Response Analysis Delays Regulatory Drug Approval. Dose-response analysis is one of the accepted efficacy endpoints to establish effectiveness. The purpose of this research was to inform selection of an appropriate pre-specified primary dose-response analysis to demonstrate drug efficacy in a registration trial. The power and the type I error rate of the placebo-corrected (i.e., simply adjusting the observed treatment value by subtracting the placebo mean) and the placebo-anchored (i.e., including the placebo data as dose 0 in the regression) slope analyses were assessed based on regulatory submission data for two antihypertensive drugs and simulated data from hypothetical clinical trials. In the simulated hypothetical trials, the impact of different dosing strategies (i.e., the fixed dose versus the weight-based per kilogram dose), sample size, and scenarios governing the drug exposure-response relationship (e.g., E max, ED 50 , and SD) was also evaluated. For each scenario, a total 300 replications were simulated. The placebo-anchored slope analysis is always more powerful to demonstrate effectiveness in all plausible scenarios. The difference between the placebo-anchored and the placebo-corrected analyses was maximum when the studied doses were too high. However, the dose-response analysis is not sensitive to the dosing strategies. Furthermore, the type I error rate of these two methods was also found to be comparable. The design of dose-response studies should carefully consider these results to justify the inclusion of placebo and the analysis method. The pharmaceutical industry and the regulatory agencies are equally responsible for using the appropriate methods of primary analysis and providing justification in the protocol. 22921987 Repair efficiency and PUVA therapeutic response variation in patients with vitiligo. Vitiligo is an acquired depigmentation disorder affecting 0.1% to >8.8% in Indian population. Psoralen and ultraviolet A radiation (PUVA) is a gold standard treatment for vitiligo, however, response is still empirical. In order to investigate whether drug response variation is influenced by the repair ability of PUVA treated vitiligo subjects, single cell gel electrophoresis (SCGE) for genotoxicity and serum malonaldehyde (MDA) for cytotoxicity were performed on 107 subjects (77 cases and 30 healthy controls) in South Indian population. In vitro repair ability was assessed by considering the residual damage. A significant difference was observed between the patients and controls with regard to their mean values of DNA damage and MDA levels (p<0.05). On categorization to fast and slow responders based on the time of response, patients exhibited a significant deviation in residual DNA damage, suggestive of variation with respect to DNA repair efficiency (p<0.05). This is the first study to our knowledge with respect to PUVA drug response variation in vitiligo in relation to DNA repair. Large systematic studies on DNA repair may help in a better understanding of the mechanisms involved in the PUVA drug response variation. 23122104 Novel angiotensin I-converting enzyme inhibitory peptides derived from soya milk. Inhibitors of angiotensin I-converting enzyme (ACE) are useful in treating hypertension, and many have been derived from food products, including soybeans. Using the industrial protease PROTIN SD-NY10, we developed a processed soya milk (PSM) with enhanced ACE inhibitory activity. The ACE inhibitory activity of PSM (IC(50)=0.26 μg/ml) was greater than that of regular soya milk (IC(50)=8.75 μg/ml). Eight novel ACE inhibitory peptides were purified from PSM by reversed-phase chromatography: FFYY (IC(50),1.9 μM), WHP (4.8 μM), FVP (10.1 μM), LHPGDAQR (10.3 μM), IAV (27.0 μM), VNP (32.5 μM), LEPP (100.1 μM), and WNPR (880.0 μM). The IC(50) values of these peptides are comparable to those reported for other ACE inhibitory peptides derived from wheat, chicken, bonito, wine, etc. Due to the relatively low IC(50) values of several peptides identified in this study, they may serve as ideal base components of food supplements for patients with hypertension. 23471539 Minireview: ubiquitination-regulated G protein-coupled receptor signaling and trafficking. G protein-coupled receptors (GPCRs) are the largest and most diverse superfamily of membrane proteins and mediate most cellular responses to hormones and neurotransmitters. Posttranslational modifications are considered the main regulators of all GPCRs. In addition to phosphorylation, glycosylation, and palmitoylation, increasing evidence as reviewed here reveals that ubiquitination also regulates the magnitude and temporospatial aspects of GPCR signaling. Posttranslational protein modification by ubiquitin is a key molecular mechanism governing proteins degradation. Ubiquitination mediates the covalent conjugation of ubiquitin, a highly conserved polypeptide of 76 amino acids, to protein substrates. This process is catalyzed by 3 enzymes acting in tandem: an E1, ubiquitin-activating enzyme; an E2, ubiquitin-carrying enzyme; and an E3, ubiquitin ligase. Ubiquitination is counteracted by deubiquitinating enzymes that deconjugate ubiquitin-modified proteins and rescue the substrate from proteasomal degradation. Although ubiquitination is known to target many GPCRs for lysosomal or proteasomal degradation, emerging findings define novel roles for the basal status of ubiquitination and for rapid deubiquitination and transubiquitination controlling cell surface expression and cellular responsiveness of some GPCRs. In this review, we highlight the classical and novel roles of ubiquitin in the regulation of GPCR function, signaling, and trafficking. 23225536 Combined toxicity of polycyclic aromatic hydrocarbons and heavy metals to biochemical and antioxidant responses of free and immobilized Selenastrum capricornutum. The aquatic environment often contains different groups of contaminants, but their combined toxicity on microalgae has seldom been reported. The present study compared the toxic effects of combined mixed polycyclic aromatic hydrocarbons (PAHs) and heavy metals on growth and antioxidant responses of free and immobilized microalga, Selenastrum capricornutum. Five PAHs-phenanthrene, fluorene, fluoranthene, pyrene, and benzo[a]pyrene-and four heavy metals at different concentrations-0.05 to 0.1 µg Cd(2+) ml(-1) , 0.05 to 1 µg Cu(2+) ml(-1) , 0.05 to 1 µg Zn(2+) ml(-1) , and 0.5 to 2.5 µg Ni(2+) ml(-1) -were examined. Results showed that the chlorophyll a content of free and immobilized S. capricornutum was not affected by PAHs but was significantly inhibited by heavy metals. Conversely, the antioxidant parameters, including the content of reduced glutathione (GSH) and the activities of superoxide dismutase and peroxidase, were significantly induced by both PAHs and metals. For the combined toxic effects of PAHs and heavy metals, cell growth and antioxidant responses varied with exposure time and contaminants and differed between free and immobilized cells. The effects of cocontaminants on the GSH content in free cells were mainly synergistic but changed to antagonistic in immobilized cells. The toxic effects of cocontamination on free cells were also more obvious than those on immobilized cells. These findings suggest that immobilization offers some protection to microalgal cells against toxic contaminants causing differences in the interaction and responses to combined toxicants between free and immobilized cells. Immobilized cells might be more suitable for treating wastewater containing toxic contaminants than free cells. 23505043 A Stochastic Simulator of Birth-Death Master Equations with Application to Phylodynamics. In this article, we present a versatile new software tool for the simulation and analysis of stochastic models of population phylodynamics and chemical kinetics. Models are specified via an expressive and human-readable XML format and can be used as the basis for generating either single population histories or large ensembles of such histories. Importantly, phylogenetic trees or networks can be generated alongside the histories they correspond to, enabling investigations into the interplay between genealogies and population dynamics. Summary statistics such as means and variances can be recorded in place of the full ensemble, allowing for a reduction in the amount of memory used-an important consideration for models including large numbers of individual subpopulations or demes. In the case of population size histories, the resulting simulation output is written to disk in the flexible JSON format, which is easily read into numerical analysis environments such as R for visualization or further processing. Simulated phylogenetic trees can be recorded using the standard Newick or NEXUS formats, with extensions to these formats used for non-tree-like inheritance relationships. 23602989 Presynaptic CaMKIIα modulates dopamine D3 receptor activation in striatonigral terminals of the rat brain in a Ca(2+) dependent manner. CaMKIIα is expressed at high density in the nucleus accumbens where it binds to postsynaptic D3 receptors inhibiting their effects. In striatonigral projections, activation of presynaptic D3 receptors potentiates D1 receptor-induced stimulation of cAMP production and GABA release. In this study we examined whether the presynaptic effects of D3 receptor stimulation in the substantia nigra reticulata (SNr) are modulated by Ca(2+) activation of CaMKIIα. In SNr synaptosomes two procedures that increase cytoplasmic Ca(2+), ionomycin and K(+)-depolarization, blocked the additional stimulation of cAMP accumulation produced by coactivating D3 and D1 dopamine receptors. The selective CaMKIIα inhibitor KN-62 reversed the blockade produced by ionomycin and K(+)-depolarization. Incubation in either Ca(2) -free solutions or with the selective Ca(2+) blocker nifedipine, also reversed the blocking effects of K(+)-depolarization. Immunoblot studies showed that K(+)-depolarization increased CaMKIIα phosphorylation in a KN-62 sensitive manner and promoted CaMKIIα binding to D3 receptors. In K(+)-depolarized tissues, D3 receptors potentiated D1 receptor-induced stimulation of [(3)H]GABA release only when CaMKIIα was blocked with KN-62. In the presence of this inhibitor, the selective D3 agonist PD 128,907 reduced the ED50 for the D1 agonist SKF 38393 from 56 to 4 nM. KN-62 also enhanced the effects of dopamine on depolarization induced [(3)H]GABA release. KN-62 changed ED50 for dopamine from 584 to 56 nM. KN-62 did not affect D1 and D4 receptor responses. These experiments show that in striatonigral projections, CaMKIIα inhibits the action of D3 receptors in a Ca(2+) dependent manner blocking their modulatory effects on GABA release. These findings suggest a mechanism through which the frequency of action potential discharge in presynaptic terminals regulates dopamine effects. 23578632 Antioxidant ability of fractionated apple peel phenolics to inhibit fish oil oxidation. Polyphenols isolated from frozen and dried apple peels were studied as potential natural antioxidants to stabilize omega-3 polyunsaturated fatty acid (ω3 PUFA) enriched fish oil. The ethanolic extracts of apple peels were fractionated by reversed phase chromatography using gradient elution of 20-100% aqueous ethanol. The collected fractions were analyzed by ultra pressure liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). The total phenolic content and antioxidant capacity of each fraction were evaluated by Folin-Ciocalteu (FC), ferric reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging assays. Inhibition of fish oil oxidation was studied using the thiobarbituric acid reactive substances (TBARS) assay. Polyphenols fractionated using frozen apple peel extract had significantly higher FC, FRAP and DPPH(·) scavenging values than those of dried apple peel (p<0.05). The flavonol-rich fractions inhibited fish oil oxidation by 40-62% at a total phenolic concentration of 200μg/ml. The fractionated polyphenols from both dried and frozen apple peel showed higher inhibition of lipid oxidation compared to α-tocopherol, butylated hydroxytoluene and crude apple peel extracts. 22724545 Cytotoxic constituents from the fungus Daldinia concentrica (Xylariaceae). Phytochemical study on the methanol extract of the fruit bodies of Vietnamese fungus Daldinia concentrica has led to the isolation and structural elucidation of three cytotoxic constituents, 6,8-dihydroxy-3-methyl-3,4-dihydroisocoumarin (1), (22R)-hydroxylanosta-7,9(11),24-trien-3-one (2) and ergosterol (3). Their structures were elucidated by 2D-NMR and FT-ICR-MS. All the three compounds showed moderate cytotoxicity against four cancer cells, KB (a human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-1 (human lung carcinoma) and HepG2 (hepatocellular carcinoma). In addition, the isocoumarin (1) inhibited the growth of Staphylococcus aureus with the IC50 value of 87.81 µg mL(-1). 23293001 ParseCNV integrative copy number variation association software with quality tracking. A number of copy number variation (CNV) calling algorithms exist; however, comprehensive software tools for CNV association studies are lacking. We describe ParseCNV, unique software that takes CNV calls and creates probe-based statistics for CNV occurrence in both case-control design and in family based studies addressing both de novo and inheritance events, which are then summarized based on CNV regions (CNVRs). CNVRs are defined in a dynamic manner to allow for a complex CNV overlap while maintaining precise association region. Using this approach, we avoid failure to converge and non-monotonic curve fitting weaknesses of programs, such as CNVtools and CNVassoc, and although Plink is easy to use, it only provides combined CNV state probe-based statistics, not state-specific CNVRs. Existing CNV association methods do not provide any quality tracking information to filter confident associations, a key issue which is fully addressed by ParseCNV. In addition, uncertainty in CNV calls underlying CNV associations is evaluated to verify significant results, including CNV overlap profiles, genomic context, number of probes supporting the CNV and single-probe intensities. When optimal quality control parameters are followed using ParseCNV, 90% of CNVs validate by polymerase chain reaction, an often problematic stage because of inadequate significant association review. ParseCNV is freely available at http://parsecnv.sourceforge.net. 22551786 Negative allosteric modulation of metabotropic glutamate receptor 5 results in broad spectrum activity relevant to treatment resistant depression. Evidence suggests that 30-50% of patients suffering from major depressive disorder (MDD) are classified as suffering from treatment resistant depression (TRD) as they have an inadequate response to standard antidepressants. A key feature of this patient population is the increased incidence of co-morbid symptoms like anxiety and pain. Recognizing that current standards of care are largely focused on monoaminergic mechanisms of action (MOAs), innovative approaches to drug discovery for TRD are targeting glutamate hyperfunction. Here we describe the in vitro and in vivo profile of GRN-529, a novel negative allosteric modulator (NAM) of metabotropic glutamate receptor 5 (mGluR5). In cell based pharmacology assays, GRN-529 is a high affinity (Ki 5.4 nM), potent (IC50 3.1 nM) and selective (>1000-fold selective vs mGluR1) mGluR5 NAM. Acute administration of GRN-529 (0.1-30 mg/kg p.o.) had dose-dependent efficacy across a therapeutically relevant battery of animal models, comprising depression (decreased immobility time in tail suspension and forced swim tests) and 2 of the co-morbid symptoms overrepresented in TRD, namely anxiety (attenuation of stress-induced hyperthermia, and increased punished crossings in the four plate test) and pain (reversal of hyperalgesia due to sciatic nerve ligation or inflammation). The potential side effect liability of GRN-529 was also assessed using preclinical models: GRN-529 had no effect on rat sexual behavior or motor co-ordination (rotarod), however it impaired cognition in mice (social odor recognition). Efficacy and side effects of GRN-529 were compared to standard of care agents (antidepressant, anxiolytic or analgesics) and the tool mGluR5 NAM, MTEP. To assess the relationship between target occupancy and efficacy, ex vivo receptor occupancy was measured in parallel with efficacy testing. This revealed a strong correlation between target engagement, exposure and efficacy across behavioral endpoints, which supports the potential translational value of PET imaging to dose selection in patients. Collectively this broad spectrum profile of efficacy of GRN-529 supports our hypothesis that negative allosteric modulation of mGluR5 could represent an innovative therapeutic approach to the treatment of TRD. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. 22975155 Mechanism of interaction of novel uncharged, centrally active reactivators with OP-hAChE conjugates. A library of more than 200 novel uncharged oxime reactivators was used to select and refine lead reactivators of human acetylcholinesterase (hAChE) covalently conjugated with sarin, cyclosarin, VX, paraoxon and tabun. N-substituted 2-hydroxyiminoacetamido alkylamines were identified as best reactivators and reactivation kinetics of the lead oximes, RS41A and RS194B, were analyzed in detail. Compared to reference pyridinium reactivators, 2PAM and MMB4, molecular recognition of RS41A reflected in its Kox constant was compromised by an order of magnitude on average for different OP-hAChE conjugates, without significant differences in the first order maximal phosphorylation rate constant k2. Systematic structural modifications of the RS41A lead resulted in several-fold improvement with reactivator, RS194B. Kinetic analysis indicated Kox reduction for RS194B as the main kinetic constant leading to efficient reactivation. Subtle structural modifications of RS194B were used to identify essential determinants for efficient reactivation. Computational molecular modeling of RS41A and RS194B interactions with VX inhibited hAChE, bound reversibly in Michaelis type complex and covalently in the pentacoordinate reaction intermediate suggests that the faster reactivation reaction is a consequence of a tighter RS194B interactions with hAChE peripheral site (PAS) residues, in particular with D74, resulting in lower interaction energies for formation of both the binding and reactivation states. Desirable in vitro reactivation properties of RS194B, when coupled with its in vivo pharmacokinetics and disposition in the body, reveal the potential of this oxime design as promising centrally and peripherally active antidotes for OP toxicity. 23134349 Silk fibroin/hyaluronic acid 3D matrices for cartilage tissue engineering. In spite of commercially available products, the complete and sustained repair of damaged articular cartilage still presents various challenges. Among biomaterials proposed for cartilage repair, silk fibroin (SF) has been recently proposed as a material template for porous scaffolds cultured with chondrocytes and investigated in static and dynamic conditions. In addition to fibroin-based constructs, literature has reported that the combination of hyaluronic acid (HA) with other scaffold materials can protect the chondral phenotype and the cells in vitro response to the scaffold. In this study, the effect of the addition of HA on the physical properties of SF sponges, with and without cross-linking with genipin, was investigated. Salt-leached scaffolds were characterized in terms of morphology and structural and physical properties, as well as mechanical performance. Un-cross-linked sponges resulted in the physical separation of highly hydrophilic HA from the SF, while cross-linking prevented this phenomenon, resulting in a homogeneous blend. The presence of HA also influenced fibroin crystallinity and tended to decrease the cross-linking degree of the scaffolds when compared to the pure SF material. 23434228 Synthesis and photochemical behavior of coumarin-caged cholesterol. The syntheses of three coumarin-caged cholesterols are reported that contain the 6-diethylaminocoumarin (DEACM), 6-bromo-7-hydroxycoumarin (BHC) and 6-bromo-7-methoxycoumarin (BMCM) photocleavable groups. Upon photolysis, the best caged derivative was found to be BHC-cholesterol whose quantum yield was determined to be 0.032 at 350 nm. 22995755 Crosslinked linear polyethylenimine enhances delivery of DNA to the cytoplasm. Crosslinked polyethylenimines (PEIs) have been frequently examined over the past decade since they can maintain the transfection efficiency of commercially available, 25k branched PEI, but exhibit less cytotoxicity. The argument is often made that the degradability of such polymers, generally synthesized with either disulfide or hydrolytically degradable crosslinkers, is critical to the high efficiency and low toxicity of the system. In this work, we present a crosslinked linear PEI (xLPEI) system in which either disulfide-responsive or non-degradable linkages are incorporated. As with previous systems, strong transfection efficiency in comparison with commercial standards was achieved with low cytotoxicity. However, these properties were shown to be present when either the degradable or non-degradable crosslinker was used. Uncomplexed polymer was demonstrated to be the critical factor determining transfection efficiency for these polymers, mediating efficient endosomal escape without signs of cell membrane damage. While several crosslinked PEI systems in the literature have demonstrated the effect of the disulfide moiety, this work demonstrates that disulfide-mediated unpackaging may not be as important as conventionally thought for some PEI systems. 23323854 Heterogeneous cationic liposomes modified with 3β-{N-[(N',N'-dimethylamino)ethyl]carbamoyl}cholesterol can induce partial conformational changes in messenger RNA and regulate translation in an Escherichia coli cell-free translation system. The effect of cationic liposomes (CLs) on messenger RNA(mRNA) conformation and translation was studied, focusing on membrane heterogeneity. CLs, composed of 1,2-dioleoyl-sn-glycerol-3-phosphocholine/1,2-dioleoyl-3-timethylammonium propane (DOPC/DOTAP) and DOPC/3β-{N-[(N',N'-dimethylamino)ethyl]carbamoyl}cholesterol (DOPC/DC-Ch), inhibited mRNA translation in an Escherichia coli cell-free translation system. Analysis of the membrane fluidity and polarity indicated a heterogeneous DOPC/DC-Ch (70/30) membrane, while other CLs exhibited homogeneous disordered membranes. mRNA adsorbed onto DOPC/DC-Ch liposomes showed translational activity, while DOPC/DOTAP liposomes inhibited mRNA translation in proportion to its adsorption onto membranes. Dehydration of DOPC/DOTAP (70/30) and DOPC/DC-Ch (70/30) was observed in the presence of mRNA but not in the case of zwitterionic DOPC liposomes, indicating that mRNA binds in regions between the phosphate [-PO(2)(-)-] and carbonyl [-C=O-] moieties of lipids. UV resonance Raman spectroscopy suggests that adenine, cytosine, and guanine interact with DOPC/DOTAP (70/30) and DOPC/DC-Ch (70/30) but not with DOPC. Circular dichroism indicates that DOPC/DOTAP (70/30) extensively denatured the mRNA. In contrast, heterogeneous DOPC/DC-Ch (70/30) induced partial conformational changes but maintained the translational activity of mRNA. 23317100 A Novel Marine Drug, SZ-685C, Induces Apoptosis of MMQ Pituitary Tumor Cells by Downregulating miR-200c. Objective: We found a novel marine drug, SZ-685C, that was isolated from the secondary metabolites of a mangrove endophytic fungus (No. 1403) collected from the South China Sea, which has been reported to inhibit the proliferation of certain tumor cells. However, its anticancer mechanism remains unknown. The aims of this study were to observe the effectiveness of SZ-685C on pituitary adenoma cells and determine the underlying mechanisms of action. Methods: A rat prolactinoma cell line, MMQ, was used in this study. A dose escalation of SZ-685C was performed on this cell line, and cell viability was assessed using an MTT assay. Hoechst 33342, Annexin V-FITC/PI, TUNEL staining and flow cytometry were used to evaluate the extent of apoptosis at each concentration of SZ-685C. The effect of SZ-685C on prolactin expression was also evaluated using RT-PCR and immunoblotting. Quantitative RT-PCR was used to detect the expression of miR-200c in SZ-685C-stimulated MMQ cells and pituitary adenoma tissues. This miRNA was then overexpressed in MMQ cells via transfection of a miR-200c mimic to identify the mechanism underling the anti-tumor effect of SZ-685C. Results: SZ-685C inhibited MMQ cell growth in a dose-dependent manner but showed little toxicity toward rat pituitary cells (RPCs). The IC50s of SZ-685C in MMQ cells and RPCs were 13.2 ± 1.3 mM and 49.1 ± 11.5 mM, respectively, which was statistically significant. Increasing numbers of apoptotic cells were observed in response to escalating concentrations of SZ-685C, and the expression level of prolactin (PRL) was inhibited. Nevertheless, the level of PRL mRNA was unchanged. Additionally, miR-200c was upregulated in MMQ cells compared with RPCs, and downregulation of miR- 200c was observed in SZ-685C-treated MMQ cells. Furthermore, the overexpression of miR-200c weakened the effect of SZ-685C-induced apoptosis of MMQ cells. Conclusions: Our results suggest that SZ-685C induces MMQ cell apoptosis in a miR-200c-dependent manner. Therefore, SZ-685C might be a useful alternative treatment for pituitary adenoma. 23160940 CB(1) receptor allosteric modulators display both agonist and signaling pathway specificity. We have previously identified allosteric modulators of the cannabinoid CB(1) receptor (Org 27569, PSNCBAM-1) that display a contradictory pharmacological profile: increasing the specific binding of the CB(1) receptor agonist [(3)H]CP55940 but producing a decrease in CB(1) receptor agonist efficacy. Here we investigated the effect one or both compounds in a broad range of signaling endpoints linked to CB(1) receptor activation. We assessed the effect of these compounds on CB(1) receptor agonist-induced [(35)S]GTPγS binding, inhibition, and stimulation of forskolin-stimulated cAMP production, phosphorylation of extracellular signal-regulated kinases (ERK), and β-arrestin recruitment. We also investigated the effect of these allosteric modulators on CB(1) agonist binding kinetics. Both compounds display ligand dependence, being significantly more potent as modulators of CP55940 signaling as compared with WIN55212 and having little effect on [(3)H]WIN55212 binding. Org 27569 displays biased antagonism whereby it inhibits: agonist-induced guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPγS) binding, simulation (Gα(s)-mediated), and inhibition (Gα(i)-mediated) of cAMP production and β-arrestin recruitment. In contrast, it acts as an enhancer of agonist-induced ERK phosphorylation. Alone, the compound can act also as an allosteric agonist, increasing cAMP production and ERK phosphorylation. We find that in both saturation and kinetic-binding experiments, the Org 27569 and PSNCBAM-1 appeared to influence only orthosteric ligand maximum occupancy rather than affinity. The data indicate that the allosteric modulators share a common mechanism whereby they increase available high-affinity CB(1) agonist binding sites. The receptor conformation stabilized by the allosterics appears to induce signaling and also selectively traffics orthosteric agonist signaling via the ERK phosphorylation pathway. 23608896 Three-dimensionally ordered macroporous Cu2O/Ni inverse opal electrodes for electrochemical supercapacitors. With an ordered polystyrene (PS) template-assisted electrochemical approach we synthesized three-dimensional ordered macroporous (3DOM) Cu2O/Ni inverse opals as electrodes for supercapacitors. The 3DOM Cu2O/Ni electrodes display superior kinetic performance, and satisfactory rate capability and cycling performance. 23525902 Chemical genetic analyses of quantitative changes in Cdk1 activity during the human cell cycle. Cyclin-dependent kinase 1 (Cdk1) controls cell proliferation and is inhibited by promising anticancer agents, but its mode of action and the consequences of its inhibition are incompletely understood. Cdk1 promotes S- and M-phases during the cell-cycle but also suppresses endoreduplication, which is associated with polyploidy and genome instability. The complexity of Cdk1 regulation has made it difficult to determine whether these different roles require different thresholds of kinase activity and whether the surge of activity as inhibitory phosphates are removed at mitotic onset is essential for cell proliferation. Here, we have used chemical genetics in a human cell line to address these issues. We rescued cells lethally depleted of endogenous Cdk1 with an exogenous Cdk1 conferring sensitivity to one ATP analogue inhibitor (1NMPP1) and resistance to another (RO3306). At no 1NMPP1 concentration was mitosis in rescued clones prevented without also inducing endoreduplication, suggesting that these two key roles for Cdk1 are not simply controlled by different Cdk1 activity thresholds. We also rescued RO3306-resistant clones using exogenous Cdk1 without inhibitory phosphorylation sites, indicating that the mitotic surge of Cdk1 activity is dispensable for cell proliferation. These results suggest that the basic mammalian cycle requires at least some qualitative changes in Cdk1 activity and that quantitative increases in activity need not be rapid. Furthermore, the viability of cells that are unable to undergo rapid Cdk1 activation, and the strong association between endoreduplication and impaired proliferation, may place restrictions on the therapeutic use of a Cdk1 inhibitors. 23497227 Synthesis and in vitro evaluation of N-Aryl pyrido-quinazolines derivatives as potent EGFR inhibitors. A series of pyrido-quinazolines have been synthesised, characterised and tested for their in vitro EGFR tyrosine kinase inhibitory activity. The compounds were prepared from Alkylideno/arylideno-bis-ureas. Their final structure of the compounds were elucidated on the basis of spectral studies (IR., 1H NMR, FT-IR and EI-MS). The cellular EGFR internalization response of selected compounds was evaluated using HeLa cells. Most of the synthesized compounds displayed potent EGFR-TK inhibitory activity and structurally halogenated derivatives had a pronounced effect in inhibiting EGFR internalization. © 2013 John Wiley & Sons A/S. 23218712 Discovery of a novel phenylethyl benzamide glucokinase activator for the treatment of type 2 diabetes mellitus. Novel benzamide derivatives were synthesized and tested at in vitro assay by measuring fold increase of glucokinase activity at 5.0 mM glucose concentration. Among the prepared compounds, YH-GKA was found to be an active glucokinase activator with EC(50) of 70 nM. YH-GKA showed similar glucose AUC reduction of 29.6% (50 mg/kg) in an OGTT study with C57BL/J6 mice compared to 29.9% for metformin (300 mg/kg). Acute treatment of the compound in C57BL/J6 and ob/ob mice elicited basal glucose lowering activity. In subchronic study with ob/ob mice, YH-GKA showed significant decrease in blood glucose levels and no adverse effects on serum lipids or body weight. In addition, YH-GKA exhibited high bioavailability and moderate elimination in preclinical species. 23092723 Lipophilic stinging nettle extracts possess potent anti-inflammatory activity, are not cytotoxic and may be superior to traditional tinctures for treating inflammatory disorders. Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate to weak anti-inflammatory activity, while the methanol and especially the water soluble extracts exhibited noticeable cytotoxicity. In contrast, the lipophilic dichloromethane extracts of the roots, stems and leaves exhibited potent anti-inflammatory effects greater than or equal to 1 with minimal cytotoxicity to RAW264.7 cells. Collectively these results suggest that using lipophilic extracts of stinging nettle may be more effective than traditional tinctures (water, methanol, ethanol) in clinical evaluations for the treatment of inflammatory disorders especially arthritis. A chemical investigation into the lipophilic extracts of stinging nettle to identify the bioactive compound(s) responsible for their observed anti-inflammatory activity is further warranted. 23325486 Binding site exploration of CCR5 using in silico methodologies: a 3D-QSAR approach. Chemokine receptor 5 (CCR5) is an important receptor used by human immunodeficiency virus type 1 (HIV-1) to gain viral entry into host cell. In this study, we used a combined approach of comparative modeling, molecular docking, and three dimensional quantitative structure activity relationship (3D-QSAR) analyses to elucidate detailed interaction of CCR5 with their inhibitors. Docking study of the most potent inhibitor from a series of compounds was done to derive the bioactive conformation. Parameters such as random selection, rational selection, different charges and grid spacing were utilized in the model development to check their performance on the model predictivity. Final comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were chosen based on the rational selection method, Gasteiger-Hückel charges and a grid spacing of 0.5 Å. Rational model for CoMFA (q(2) = 0.722, r(2) = 0.884, Q(2) = 0.669) and CoMSIA (q(2) = 0.712, r(2) = 0.825, Q(2) = 0.522) was obtained with good statistics. Mapping of contour maps onto CCR5 interface led us to better understand of the ligand-protein interaction. Docking analysis revealed that the Glu283 is crucial for interaction. Two new amino acid residues, Tyr89 and Thr167 were identified as important in ligand-protein interaction. No site directed mutagenesis studies on these residues have been reported. 22718275 Lipid biomarkers of oxidative stress in a genetic mouse model of Smith-Lemli-Opitz syndrome. 7-Dehydrocholesterol (7-DHC) accumulates in tissues and fluids of patients with Smith-Lemli-Opitz syndrome (SLOS), which is caused by mutations in the gene encoding 3β-hydroxysterol-Δ(7)-reductase (DHCR7). We recently reported that 7-DHC is the most reactive lipid molecule toward free radical oxidation (lipid peroxidation) and 14 oxysterols have been identified as products of oxidation of 7-DHC in solution. As the high oxidizability of 7-DHC may lead to systemic oxidative stress in SLOS patients, we report here lipid biomarkers of oxidative stress in a Dhcr7-KO mouse model of SLOS, including oxysterols, isoprostanes (IsoPs), and neuroprostanes (NeuroPs) that are formed from the oxidation of 7-DHC, arachidonic acid and docosahexaenoic acid, respectively. In addition to a previously described oxysterol, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), we provide evidence for the chemical structures of three new oxysterols in the brain and/or liver tissue of Dhcr7-KO mice, two of which were quantified. We find that levels of IsoPs and NeuroPs are also elevated in brain and/or liver tissues of Dhcr7-KO mice relative to matching WT mice. While IsoPs and NeuroPs have been established as a reliable measurement of lipid peroxidation and oxidative stress in vivo, we show that in this genetic SLOS mouse model, 7-DHC-derived oxysterols are present at much higher levels than IsoPs and NeuroPs and thus are better markers of lipid oxidation and related oxidative stress. 23385214 Water ice nanoparticles: size and temperature effects on the mid-infrared spectrum. Mid-infrared spectra have been measured for cubic ice (I(c)) nanoparticles (3-150 nm diameter) formed by rapid collisional cooling over a wide range of temperatures (5-209 K). Spectral diagnostics, such as the ratio of surface related dangling OH to interior H-bonded OH stretch bands, reveal the manner in which particle size depends on bath gas temperature and density, and on water molecule concentration. For particles smaller than 5 nm strained intermolecular bonds on the surface and subsurface cause the predominant OH stretch peak position to be dramatically blue shifted by up to 40 cm(-1). In the size regime of 8-200 nm the position of the OH stretch absorption band maximum is relatively unaffected by particle size and it is possible to measure the temperature dependence of the peak location without influences from the surface or scattering. The band maximum shifts in a linear fashion from 3218 cm(-1) at 30 K to 3253 cm(-1) at 209 K, which may assist with temperature profiling of ice particles in atmospheric clouds and extraterrestrial systems. Over the same temperature range the librational mode band shifts very little, from 870 to 860 cm(-1). In the water stretching and bending regions discrete spectral features associated with the surface or sub-surface layers have been detected in particles as large as 80 nm. 23479738 Multilevel regulation of 2-cys peroxiredoxin reaction cycle by s-nitrosylation. S-Nitrosothiols (SNOs), formed by nitric oxide (NO)-mediated S-nitrosylation, and hydrogen peroxide (H2O2), a prominent reactive oxygen species, are implicated in diverse physiological and pathological processes. Recent research has shown that the cellular action and metabolism of SNOs and H2O2 involve overlapping, thiol-based mechanisms, but how these reactive species may affect each other's fate and function is not well understood. In this study we investigated how NO/SNO may affect the redox cycle of mammalian peroxiredoxin-1 (Prx1), a representative of the 2-Cys Prxs, a group of thioredoxin (Trx)-dependent peroxidases. We found that, both in a cell-free system and in cells, NO/SNO donors such as S-nitrosocysteine and S-nitrosoglutathione readily induced the S-nitrosylation of Prx1, causing structural and functional alterations. In particular, nitrosylation promoted disulfide formation involving the pair of catalytic cysteines (Cys-52 and Cys-173) and disrupted the oligomeric structure of Prx1, leading to loss of peroxidase activity. A highly potent inhibition of the peroxidase catalytic reaction by NO/SNO was seen in assays employing the coupled Prx-Trx system. In this setting, S-nitrosocysteine (10 μm) effectively blocked the Trx-mediated regeneration of oxidized Prx1. This effect appeared to be due to both competition between S-nitrosocysteine and Prx1 for the Trx system and direct modulation by S-nitrosocysteine of Trx reductase activity. Our findings that NO/SNO target both Prx and Trx reductase may have implications for understanding the impact of nitrosylation on cellular redox homeostasis. 23194505 Temperature-dependent kinetics of grape seed phenolic compounds extraction: experiment and model. The kinetics of a batch solid-liquid extraction of total phenolic compounds (PC) from milled grape seed (Vitis vinifera L. cv. "Frankovka") using 50% ethanol at different extraction temperatures (25-80°C) was studied. The maximum yield of PC was 0.13 kg(GAE)/kg(db) after 200 min of extraction in agitated vessel at 80°C. A new model based on the assumptions of a first order kinetics mechanism for the solid-liquid extraction and a linear equilibrium at the solid-liquid interface was developed. The model involves the concept of broken and intact cells in order to describe two successive extraction periods: a very fast surface washing process followed by slow diffusion of phenolic compounds from grape seeds to the solvent. The proposed model is suited to fit experimental data and to simulate the extraction of phenolic compounds, which was confirmed by the correlation coefficient (r≥0.965), the root mean square error (RMSE≤0.003 kg(GAE)/kg(db)) and the mean relative deviation modulus (E≤2.149%). The temperature influenced both equilibrium partition coefficients of phenolic compounds and transport properties, which is manifested by a relatively high value of activation energy (23-24) kJ/mol and by values of effective diffusivity in seed particles. 23567045 Lactosylated gramicidin-based lipid nanoparticles (Lac-GLN) for targeted delivery of anti-miR-155 to hepatocellular carcinoma. Lactosylated gramicidin-containing lipid nanoparticles (Lac-GLN) were developed for delivery of anti-microRNA-155 (anti-miR-155) to hepatocellular carcinoma (HCC) cells. MiR-155 is an oncomiR frequently elevated in HCC. The Lac-GLN formulation contained N-lactobionyl-dioleoyl phosphatidylethanolamine (Lac-DOPE), a ligand for the asialoglycoprotein receptor (ASGR), and an antibiotic peptide gramicidin A. The nanoparticles exhibited a mean particle diameter of 73nm, zeta potential of +3.5mV, anti-miR encapsulation efficiency of 88%, and excellent colloidal stability at 4°C. Lac-GLN effectively delivered anti-miR-155 to HCC cells with a 16.1- and 4.1-fold up-regulation of miR-155 targets C/EBPβ and FOXP3 genes, respectively, and exhibited significant greater efficiency over Lipofectamine 2000. In mice, intravenous injection of Lac-GLN containing Cy3-anti-miR-155 led to preferential accumulation of the anti-miR-155 in hepatocytes. Intravenous administration of 1.5mg/kg anti-miR-155 loaded Lac-GLN resulted in up-regulation of C/EBPβ and FOXP3 by 6.9- and 2.2-fold, respectively. These results suggest potential application of Lac-GLN as a liver-specific delivery vehicle for anti-miR therapy. 23395783 γ-Oryzanol protects against acute cadmium-induced oxidative damage in mice testes. Cadmium is a non-essential heavy metal that is present at low levels mainly in food and water and also in cigar smoke. The present study evaluated the testicular damage caused by acute cadmium exposure and verified the protective role of γ-oryzanol (ORY). Mice were administrated with a single dose of 2.5mg/kg of CdCl2, and then treated with ORY (50mM in canola oil, 5mL/kg). Testes were removed after 24h and tested for lipid peroxidation (TBARS), protein carbonylation, DNA breakage, ascorbic acid, cadmium and non-proteic thiols contents, and for the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and δ-aminolevulic acid dehydratase (δ-ALA-D). Cadmium presented a significant alteration in all parameters, except GPx and CAT activities. Therapy reduced in a slight degree cadmium concentration in testes (around 23%). ORY restored SOD and GST activities as well as TBARS production to the control levels. Furthermore, ORY partially recovered δ-ALA-D activity inhibited by cadmium. This study provides the first evidence on the therapeutic properties of ORY in protecting against cadmium-induced testicular toxicity. 23456814 Effects of Urtica dioica on oxidative stress, proliferation and apoptosis after partial hepatectomy in rats. The present study was performed to investigate the effect of Urtica dioica (UD) on liver regeneration after partial hepatectomy (PH) in rats. A total of 24 male Sprague Dawley rats were divided into three groups: sham-operated, PH and PH + UD; each group contains eight animals. The rats in UD-treated groups were given UD oils (2 ml/kg/day) once a day orally for 7 days starting 3 days prior to hepatectomy operation. At day 7 after resection, liver samples were collected. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were estimated in liver homogenates. Moreover, histopathological examination, mitotic index (MI), proliferating cell nuclear antigen labeling, proliferation index (PI), transferase-mediated deoxyuridine triphosphate nick end-labeling assay, apoptotic index (AI) were evaluated at day 7 after hepatectomy. As a result, UD significantly increased MI and PI, significantly decreased AI and also attenuated hepatic vacuolar degeneration and sinusoidal congestion in PH rats. UD treatment significantly decreased the elevated tissue MDA level and increased the reduced SOD activity and GSH level in the tissues. These results suggest that UD pretreatment was beneficial for rat liver regeneration after partial hepatectomy. 23080379 Patterned assembly of quantum dots onto surfaces modified with click microcontact printing. The self-assembly of CdSe quantum dots (QDs) onto a patterned silica surface generated from surface microcontact click printing is presented. The mechanically robust self-assembly process produces patterns of QDs which remain steadfast, even as subsequent reactions are performed on the substrate, demonstrating the utility and ease of this self-assembly process. 23402341 Characterization of the acyl-adenylate linked metabolite of mefenamic Acid. Mefenamic acid, (MFA), a carboxylic acid-containing nonsteroidal anti-inflammatory drug (NSAID), is metabolized into the chemically reactive conjugates MFA-1-O-acyl-glucuronide (MFA-1-O-G) and MFA-S-acyl-CoA (MFA-CoA), which are both implicated in the formation of MFA-S-acyl-glutathione (MFA-GSH) conjugates, protein-adduct formation, and thus the potential toxicity of the drug. However, current studies suggest that an additional acyl-linked metabolite may be implicated in the formation of MFA-GSH. In the present study, we investigated the ability of MFA to become bioactivated into the acyl-linked metabolite, mefenamyl-adenylate (MFA-AMP). In vitro incubations in rat hepatocytes with MFA (100 μM), followed by LC-MS/MS analyses of extracts, led to the detection of MFA-AMP. In these incubations, the initial rate of MFA-AMP formation was rapid, leveling off at a maximum concentration of 90.1 nM (20 s), while MFA-GSH formation increased linearly, reaching a concentration of 1.7 μM after 60 min of incubation. In comparison, MFA-CoA was undetectable in incubation extracts until the 4 min time point, achieving a concentration of 45.6 nM at the 60 min time point, and MFA-1-O-G formation was linear, attaining a concentration of 42.2 μM after 60 min of incubation. In vitro incubation in buffer with the model nucleophile glutathione (GSH) under physiological conditions showed MFA-AMP to be reactive toward GSH, but 11-fold less reactive than MFA-CoA, while MFA-1-O-G exhibited little reactivity. However, in the presence of glutathione-S-transferase (GST), MFA-AMP mediated formation of MFA-GSH increased 6-fold, while MFA-CoA mediated formation of MFA-GSH only increased 1.4-fold. Collectively, in addition to the MFA-1-O-G, these results demonstrate that mefenamic acid does become bioactivated by acyl-CoA synthetase enzyme(s) in vitro in rat hepatocytes into the reactive transacylating derivatives MFA-AMP and MFA-CoA, both of which contribute to the transacylation of GSH and may be involved in the formation of protein adducts and potentially elicit an idiosyncratic toxicity. 22995849 Molecular phylogeny of North American Branchiobdellida (Annelida: Clitellata). Branchiobdellidans, or crayfish worms, are ectosymbiotic clitellate annelids associated primarily with freshwater crayfishes. The main objectives of our study were to infer a molecular phylogeny for the North American Branchiobdellida, examine its congruence with morphology-based hypotheses of relationships at the subfamily and genus level, and use our dataset to assess consistency of GenBank-archived branchiobdellidan sequences. We used nucleotide sequence data from two mtDNA genes (COI and 16S rDNA) and three nuclear genes (28S rDNA, 18S rDNA, and ITS1) to estimate phylogenetic relationships among 47 described and one undescribed species of Branchiobdellida. We recovered a monophyletic branchiobdellidan clade with generally short branch lengths, suggesting that a large portion of the taxon has likely undergone a recent and rapid radiation in North America. Results from our phylogenetic analyses indicate that current taxonomic groupings are largely unsupported by the molecular data. All four subfamilies are either paraphyletic or polyphyletic, and only three of seven sampled non-monotypic genera were monophyletic. We found a high rate (49%) of inconsistency in GenBank-archived sequences, over 70% of which can be attributed to field- or laboratory-based error. 23563205 Correlation between activation of PPARγ and resistin downregulation in a mouse adipocyte cell line by a series of thiazolidinediones. The present study shows significant correlations between the EC50 for PPARγ activation in a reporter gene cell line and resistin downregulation in mouse adipocytes, and between the IC50 for resistin downregulation and the already published minimum effective dose for antihyperglycemic activity in a mouse model. These correlations indicate that PPARγ mediated downregulation of resistin might promote insulin sensitivity and that downregulation of resistin in mouse adipocytes provides an adequate and possibly more direct bioassay for screening of newly developed antihyperglycemic compounds. Because of the higher throughput of the PPARγ the resistin downregulation assays seems most suitable to be used as a second tier in a tiered screening strategy. 23379686 Self-aggregation properties of ionic liquid 1,3-didecyl-2-methylimidazolium chloride in aqueous solution: from spheres to cylinders to bilayers. The self-aggregation behavior of the double-chained ionic liquid (IL) 1,3-didecyl-2-methylimidazolium chloride ([C10C10mim]Cl) in aqueous solution has been investigated with a number of different experimental techniques. Two cmc values (cmc1 and cmc2) are obtained from conductivity measurements. The fraction of neutralized charge on the micellar surface suggests that cmc1 corresponds to the formation of spherical micelles and cmc2 to the transition from spherical to cylindrical micelles. Data obtained from fluorescence spectroscopy (using pyrene and Nile red as chemical probes), fluorescence anisotropy (using rhodamine B as probe), and chemical shift (1)H NMR (in D2O) provide a picture that is also consistent with a sphere-to-cylinder transition. This structural change is further confirmed by diffusion-ordered NMR spectroscopy (DOSY), from the self-diffusion coefficients for surfactant unimer and aggregates. Furthermore, a third evolution from cylindrical micelles to bilayer aggregates is proposed from the analysis of diffusion coefficients at high surfactant concentration ([IL] > 0.2 M). Phase scanning experiments performed with polarized light microscopy clearly demonstrate the presence of a lamellar liquid crystalline phase at very high IL concentration, thus confirming the coexistence of bilayer structures with elongated micelles, found at lower concentration. Additionally, [C10C10mim]Cl micelles are proposed as novel reaction media, as evidenced by the solvolysis reaction of 4-methoxybenzenesulfonyl chloride (MBSC). 23266451 How cationic lipids transfer nucleic acids into cells and across cellular membranes: recent advances. Cationic lipid- and polymer-based nanodevices are considered appropriate alternatives for virus-based particles for delivery of nucleic acids, including genes and siRNA, into eukaryotic cells. Because of colloidal stability concerns and toxicity issues the potential in vivo application of these so-called non-viral systems, in particular cationic lipids, was met with considerable skepticism. However, in recent years, the development of novel ionizable cationic lipid formulations in conjunction with sophisticated procedures to carefully control the size of the nanoparticles has rapidly advanced options for a successful therapeutic application. Thus it would appear that cationic lipids have taken a prominent step ahead in their potential use as nanocarriers for siRNA delivery in gene silencing of target genes in a variety of diseases. Verification and improvement of delivery efficiency as well as screening of targeting ligands justify further work in revealing underlying mechanisms that are instrumental in efficient crossing of cellular barriers by cationic lipid-based nanocarriers. In this regard, triggering entry into specific pathways or modulating trafficking along such pathways, either by targeting of nanoparticles or by affecting specific cellular signaling pathways, may represent promising tools. Such options may involve, for example, facilitating nanoparticle transport across endothelial cells by transcytotic mechanisms, or improving delivery efficiency by affecting nanoparticle trafficking that avoids lysosomal delivery. Here, recent progress in the field of lipid-based nanocarriers is discussed, with a focus on mechanisms underlying their interactions with cells in vitro. Where appropriate, we will include mechanisms for polymer-based systems in our discussion. 23512927 Fluorescent Polymeric Micelles with Aggregation-Induced Emission Properties for Monitoring the Encapsulation of Doxorubicin. A new type of fluorescent polymeric micelles is developed by self-assembly from a series of amphiphilic block copolymers, poly(ethylene glycol)-b-poly[styrene-co-(2-(1,2,3,4,5-pentaphenyl-1H-silol-1-yloxy)ethyl methacrylate)] [PEG-b-P(S-co-PPSEMA)]. Their capability of loading doxorubicin (DOX) is investigated by monitoring the loading content, encapsulation efficiency, and photophysical properties of micelles. Förster resonance energy transfer from PPSEMA to DOX is observed in DOX-loaded micelles, which can serve as an indication of successful encapsulation of DOX in these micelles. The application of this new type of fluorescent polymeric micelles as a fluorescent probe and an anticancer drug carrier simultaneously is explored by studying the intracellular uptake of DOX-loaded micelles. 23571414 Therapeutic Cleavage of Anti-Aquaporin-4 Autoantibody in Neuromyelitis Optica by an Igg-Selective Proteinase. Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system caused by binding of pathogenic IgG autoantibodies (NMO-IgG) to astrocyte water channel aquaporin-4 (AQP4). Astrocyte damage and downstream inflammation require NMO-IgG effector function to initiate complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Here, we evaluated the potential therapeutic utility of the bacterial enzyme IdeS (IgG-degrading enzyme of Streptococcus pyogenes), which selectively cleaves IgG antibodies to yield Fc and F(ab')2 fragments. In AQP4-expressing cell cultures, IdeS treatment of monoclonal NMO-IgGs and NMO patient sera abolished CDC and ADCC, even when IdeS was added after NMO-IgG was bound to AQP4. Binding of NMO-IgG to AQP4 was similar to that of the NMO-F(ab')2 generated by IdeS cleavage. NMO-F(ab')2 competitively displaced pathogenic NMO-IgG, preventing cytotoxicity, and the Fc fragments generated by IdeS cleavage reduced CDC and ADCC. IdeS efficiently cleaved NMO-IgG in mice in vivo, and greatly reduced NMO lesions in mice administered NMO-IgG and human complement. IgG-selective cleavage by IdeS thus neutralizes NMO-IgG pathogenicity, and yields therapeutic F(ab')2 and Fc fragments. IdeS treatment, by therapeutic apheresis or direct administration, may be beneficial in NMO. 22961087 Loss of TDAG51 results in mature-onset obesity, hepatic steatosis, and insulin resistance by regulating lipogenesis. Regulation of energy metabolism is critical for the prevention of obesity, diabetes, and hepatic steatosis. Here, we report an important role for the pleckstrin homology-related domain family member, T-cell death-associated gene 51 (TDAG51), in the regulation of energy metabolism. TDAG51 expression was examined during adipocyte differentiation. Adipogenic potential of preadipocytes with knockdown or absence of TDAG51 was assessed. Weight gain, insulin sensitivity, metabolic rate, and liver lipid content were also compared between TDAG51-deficient (TDAG51(-/-)) and wild-type mice. In addition to its relatively high expression in liver, TDAG51 was also present in white adipose tissue (WAT). TDAG51 was downregulated during adipogenesis, and TDAG51(-/-) preadipocytes exhibited greater lipogenic potential. TDAG51(-/-) mice fed a chow diet exhibited greater body and WAT mass, had reduced energy expenditure, displayed mature-onset insulin resistance (IR), and were predisposed to hepatic steatosis. TDAG51(-/-) mice had increased hepatic triglycerides and SREBP-1 target gene expression. Furthermore, TDAG51 expression was inversely correlated with fatty liver in multiple mouse models of hepatic steatosis. Taken together, our findings suggest that TDAG51 is involved in energy homeostasis at least in part by regulating lipogenesis in liver and WAT, and hence, may constitute a novel therapeutic target for the treatment of obesity and IR. 23442151 Phenol formation in gamma radiolysis of aqueous benzene solution with sodium hypochlorite. Phenol formation by gamma radiolysis of an aqueous benzene solution containing sodium hypochlorite is reported. The phenol formation in a benzene solution containing sodium hypochlorite irradiated with (60)Co γ-rays is about six times higher than that without sodium hypochlorite. Ten micromolar sodium hypochlorite enhanced the formation of phenol up to a total dose of 6 Gy. Above 6 Gy in solutions containing sodium hypochlorite, the rate of phenol yield sharply decreased and was essentially the same as that without sodium hypochlorite. The yield of phenol with sodium hypochlorite is 0.89 μmol J(-1) and is larger than the sum of yield for the radicals and reactive oxygen species by water radiolysis such as •OH, e(-), H, H2, and H2O2. The formation of phenol with sodium hypochlorite was reduced by NaCl. Results suggest that the radiolytic formation of phenol in a benzene solution with sodium hypochlorite relates to the reaction process involving chlorine atoms. Sodium hypochlorite can be applied as a sensitizer for a benzene chemical dosimetry system. The lower limit of dose detection calculated from the detection limit of phenol and the G value of phenol was estimated to be 1 × 10(-3) Gy. 23194555 Adsorption kinetics, thermodynamics and isotherm of Hg(II) from aqueous solutions using buckwheat hulls from Jiaodong of China. The adsorption kinetics and adsorption isotherms of buckwheat hulls in the region of Jiaodong, China (BHJC) for Hg(II) were investigated. Results revealed that the adsorption kinetics of BHJC for Hg(II) were well described by a pseudo second-order reaction model, and the adsorption thermodynamic parameters ΔG, ΔH and ΔS were -5.83 kJ mol(-1)(35°C), 73.1, and 256 JK(-1) mol(-1), respectively. Moreover, Langmuir, Freundlich and Redlich-Peterson isotherm models were applied to analyse the experimental data and to predict the relevant isotherm parameters. The best interpretation for the experimental data was given by the Langmuir isotherm equation, and the maximum adsorption capacity for Hg(II) is 243.90 mg/g at 35°C. Furthermore, investigation of the adsorption selectivity showed that BHJC displayed strong affinity for mercury in the aqueous solutions and exhibited 100% selectivity for mercury in the presence of Zn(II) and Cd(II). 23410166 Multi-target compounds acting in the central nervous system designed from natural products. Modern medicinal chemistry has come to its bottleneck and is full of challenges, specially when facing with long-term central nervous system (CNS) disorders induced by several factors, such as Alzheimer's disease (AD) or Parkinson's disease (PD). In order to probe these challenges, multi-target directed ligands (MTDLs) design has been applied recently by medicinal scientists trying to get single compounds that can simultaneously modulate multiple targets. In addition, natural products have drawn the attention of drug developers again in recent years, as they have been used by human race for thousands of years and are full of diversity with their concomitant high potential to exhibit biological activities. We hereby review some of the research within the last few years focusing on multiple-target compounds acting in the CNS using natural products as lead resources. The target compounds obtained and described here represent bioactive hybrids either covalently connected or obtained by fusion of different bioactive moieties with at least one part derived from or representing directly natural products, along with some natural compounds themselves showing multiple pharmacological activities. We describe suitable ways to connect the drug components chemically, how to use the approach to enhance biological activity and selectivity, as well as potential drawbacks of the hybrid approach. This review will also show the rationale that these MTDLs are more than just the sum of their components but in many cases should be considered as new pharmacological entities in their own respect. 23137276 A novel matrix for the short-term storage of cells: utility in drug metabolism and drug transporter studies with rat, dog and human hepatocytes. 1. The SureTran™ matrix is a novel method facilitating short-term maintenance of fresh primary hepatocyte cellular function and offers the potential use of primary cells "as fresh" for several days post isolation. In the study presented, the maintenance of several key phase I and II drug metabolizing enzyme and drug transporter activities is demonstrated with rat and dog hepatocytes preserved for up to 7 days after cell isolation. 2. Intrinsic clearance values were determined for 60 new chemical entities using rat hepatocytes freshly isolated at AstraZeneca and rat hepatocytes prepared at the facilities of Abcellute Ltd (SureTran™ purveyors), stored and incubated 24 hours after isolation. A very good correspondence in the intrinsic clearance values underlines the utility of the cell maintenance matrix. 3. For human hepatocytes many of the enzyme activities assayed were well maintained for 7 days of storage but some declined to below 50% of initial values between day 4 and 7 of storage. Human OATP1B1 activity was only determined with one batch and declined to 51% of the initial test value by day 4 and further down to 35% by day 7. 23518321 Acetaminophen prevents oxidative burst and delays apoptosis in human neutrophils. Acetaminophen is a frequently prescribed over-the-counter drug to reduce fever and pain in the event of inflammatory process. As neutrophils are relevant cells in inflammatory processes, the putative interaction of acetaminophen with these cells, if present, would be of paramount importance. The present study was undertaken to evaluate the effect of acetaminophen in human neutrophils' oxidative burst and lifespan in vitro. The obtained results demonstrate that acetaminophen efficiently modulates neutrophils' oxidative burst in phorbol myristate acetate-activated neutrophils, in a concentration-dependent manner, at in vivo relevant concentrations. It was clearly demonstrated that acetaminophen is a strong scavenger of HOCl and H2O2, which probably contributed to the effect observed in neutrophils. Acetaminophen also induced the depletion of glutathione in stimulated neutrophils, suggesting its transformation into a reactive intermediate. Obtained results further revealed that acetaminophen affects programmed cell death of human neutrophils, resulting in a delay of previously stimulated neutrophils-mediated apoptosis. Overall, our data suggested that acetaminophen has considerable potential to be included in anti-inflammatory therapeutic strategies, by preventing biological damage induced by an excessive production of reactive species generated in activated neutrophils and by extending the lifespan of neutrophils, favoring the elimination of pathogens, thus contributing to tissue healing and resolution of inflammation. 23625912 Effects of aluminum chloride on some trace elements and erythrocyte osmotic fragility in rats. Aluminum (Al) is a nonessential, toxic element to which humans are constantly exposed as a result of an increase in industrialization and improving technology practices. The aim of the study was to investigate the effects of different durations and doses of Al exposure on serum and tissue element levels and erythrocyte osmotic fragility in rats. A total of 40 male Wistar Albino rats were divided into five groups: control, group I (3 weeks, 8 mg/kg), group II (6 weeks, 8 mg/kg), group III (3 weeks, 16 mg/kg), and group IV (6 weeks, 16 mg/kg). Al chloride (AlCl3) was injected intraperitoneally (i.p.) five times a week. At the end of the experimental period, levels of Al, iron (Fe), copper (Cu), and zinc (Zn) in serum, liver, and kidney tissues were measured using inductively coupled plasma optical emission spectrometry. Osmotic fragility was determined using a spectrophotometer. The results of the experiment indicate that Al induced a statistically significant increase in Al and Fe concentrations in liver and serum as well as in Cu in the kidney. The Fe concentration in serum and kidney tissues was significantly lower in all the groups. As a result of our study, it may be concluded that tissue Al accumulation may lead to an increase in osmotic fragility of erythrocytes and abnormal trace element levels. 23394432 Tailoring the lasing modes in semiconductor nanowire cavities using intrinsic self-absorption. Understanding the optical gain and mode-selection mechanisms in semiconductor nanowire (NW) lasers is key to the development of high-performance nanoscale oscillators, amplified semiconductor/plasmon lasers and single photon emitters, and so forth. Modification of semiconductor band structure/bandgap through electric field modulation, elemental doping, or alloying semiconductors has so far gained limited success in achieving output mode tunability of the NW laser. One stifling issue is the considerable optical losses induced in the NW cavities by these extrinsic methods that limit their applicability. Herein we demonstrate a new optical self-feedback mechanism based on the intrinsic self-absorption of the gain media to achieve low-loss, room-temperature NW lasing with a high degree of mode selectivity (over 30 nm). The cadmium sulfide (CdS) NW lasing wavelength is continuously tunable from 489 to 520 nm as the length of the NWs increases from 4 to 25 μm. Our straightforward approach is widely applicable in most semiconductor or semiconductor/plasmonic NW cavities. 22789395 Urinary excretion of parabens in pregnant Japanese women. Urinary excretion of free and total (free plus conjugated) forms of methyl, ethyl, n-propyl and n-butyl parabens (MP, EP, PP and BP, respectively) and their metabolite p-hydroxybenzoic acid were measured for 111 pregnant Japanese women. Frequent detection of parabens and their metabolite indicated that exposure takes place daily for pregnant Japanese women. The estrogenic potency of PP was 20 times higher than those of the other 3 parabens for the present subjects when both abundance in the urine and the relative estrogenic activity of each compound was considered. Detection of free parabens suggested dermal exposure, probably from their inclusion in personal care products. No statistical association was found between the anogenital index (birth weight-adjusted AGD) of male offspring and the concentrations of any parabens in the urine of the mothers suggesting that the parabens were not apparently estrogenically active at the exposure level of the present subjects. 22842550 Interaction of tumor cells with the immune system: implications for dendritic cell therapy and cancer progression. There is a continuous demand for preclinical modeling of the interaction of dendritic cells with the immune system and cancer cells. Recent progress in gene expression profiling with nucleic acid microarrays, in silico modeling and in vivo cell and animal approaches for non-clinical proof of safety and efficacy of these immunotherapies is summarized. Immunoinformatic approaches look promising to unfold this potential, although still unstable and difficult to interpret. Animal models have progressed a great deal in recent years, finally narrowing the gap from bench to bedside. However, translation to the clinic should be done with precaution. The most significant results concerning clinical benefit might come from detailed immunologic investigations made during well designed clinical trials of dendritic-cell-based therapies, which in general prove safe. 23324400 HOW GOOD IS THE LEVOTHYROXINE REPLACEMENT IN PRIMARY HYPOTHYROIDISM PATIENTS IN BRAZIL?- DATA OF A MULTICENTRE STUDY. Background : Studies done in every continent has shown that only around 50% of the patients subjected to thyroid hormone replacement have TSH in the normal range. However, until to date, there are no consistent data about Brazil. Objectives: To evaluate levothyroxine (LT4) replacement treatment in patients with primary hypothyroidism followed in referral centers in Brazil. Methods: Patients with primary hypothyroidism followed in referral centers (University Hospitals from Universidade Federal do Rio de Janeiro -UFRJ, Unicamp, Universidade Federal do Paraná - UFPR and Universidade Federal do Ceará-UFC) answered a questionnairethat inquired about clinical and biochemical conditions, social-economic status, life quality and clinicians' orientations as well as their understanding about the information given. Serum TSH was checked close to the interview. Results: 2292 consecutive patients met the inclusion criteria. Mean age 51.2 years and TSH values between 0.4 and 4.0 mUI/l were considered to be within the reference range. Among all patients taking thyroid medication, 42.7%% had an abnormal serum TSH (28.3% were undertreated and 14.4% were over treated). Approximately all patients (99%) took LT4 in the morning but less than 30 minutes before breakfast (85.4%). Regarding the clinicians´ orientations: 97.5% of the patients were instructed to take the medication daily, and 92.6% to take 30 minutes before breakfast (92.6%). However, only 52.1% were told that not to take LT4 along with other medication. Conclusions: Our study found that there was a significant number of patients taking thyroid hormones were not in the therapeutic range. Clinicians should, therefore, consider monitoring patients on thyroid replacement more frequently and being more precise on giving recommendations about the correct use of LT4. 23055453 Alternative copolymerization of a conjugated segment and a flexible segment and fabrication of a fluorescent sensing film for HCl in the vapor phase. A novel fluorescently active co-oligomer (P1) was designed and prepared by alternative co-polymerization of oligo(p-phenyleneethynylene) (OPE), possessing two cholesterol-containing side chains, and ethanediamine. A control co-oligomer (P2) possessing similar structure to P1 was also prepared, but in this case the OPE bears no side chains. P1 and P2 have been used for the fabrication of two fluorescent films, film 1 and film 2, respectively. Fluorescence studies demonstrated that the emission of film 1 is sensitive and selective to the presence of trace amounts of HCl in air. In contrast, film 2 shows no such response. The quenching has been attributed to the protonation of the imino groups within the oligomer chains, and the difference in the sensing behaviors of the two films was rationalized by supposing the existence of molecular channels in film 1. The proposed mechanism is supported by the results from additional experiments and theoretical calculations. Furthermore, the film as fabricated is robust, and thereby it is believed that film 1 has the potential to be developed into a new generation of sensitive and selective HCl sensor. 23609769 Altered visual perception in long-term ecstasy (MDMA) users. RATIONALE: The present study investigated the long-term consequences of ecstasy use on visual processes thought to reflect serotonergic functions in the occipital lobe. Evidence indicates that the main psychoactive ingredient in ecstasy (methylendioxymethamphetamine) causes long-term changes to the serotonin system in human users. Previous research has found that amphetamine-abstinent ecstasy users have disrupted visual processing in the occipital lobe which relies on serotonin, with researchers concluding that ecstasy broadens orientation tuning bandwidths. However, other processes may have accounted for these results. OBJECTIVES: The aim of the present research was to determine if amphetamine-abstinent ecstasy users have changes in occipital lobe functioning, as revealed by two studies: a masking study that directly measured the width of orientation tuning bandwidths and a contour integration task that measured the strength of long-range connections in the visual cortex of drug users compared to controls. METHOD: Participants were compared on the width of orientation tuning bandwidths (26 controls, 12 ecstasy users, 10 ecstasy + amphetamine users) and the strength of long-range connections (38 controls, 15 ecstasy user, 12 ecstasy + amphetamine users) in the occipital lobe. RESULTS: Amphetamine-abstinent ecstasy users had significantly broader orientation tuning bandwidths than controls and significantly lower contour detection thresholds (CDTs), indicating worse performance on the task, than both controls and ecstasy + amphetamine users. CONCLUSION: These results extend on previous research, which is consistent with the proposal that ecstasy may damage the serotonin system, resulting in behavioral changes on tests of visual perception processes which are thought to reflect serotonergic functions in the occipital lobe. 23161677 G4LDB: a database for discovering and studying G-quadruplex ligands. The G-quadruplex ligands database (G4LDB, http://www.g4ldb.org) provides a unique collection of reported G-quadruplex ligands to streamline ligand/drug discovery targeting G-quadruplexes. G-quadruplexes are guanine-rich nucleic acid sequences in human telomeres and gene promoter regions. There is a growing recognition for their profound roles in a wide spectrum of diseases, such as cancer, diabetes and cardiovascular disease. Ligands that affect the structure and activity of G-quadruplexes can shed light on the search for G-quadruplex-targeting drugs. Therefore, we built the G4LDB to (i) compile a data set covering various physical properties and 3D structure of G-quadruplex ligands; (ii) provide Web-based tools for G-quadruplex ligand design; and (iii) to facilitate the discovery of novel therapeutic and diagnostic agents targeting G-quadruplexes. G4LDB currently contains >800 G-quadruplex ligands with ∼4000 activity records, which, to our knowledge, is the most extensive collection of its kind. It offers a user friendly interface that can meet a variety of data inquiries from researchers. For example, ligands can be searched for by name, molecular properties, structures, ligand activities and so on. Building on the reported data, the database also provides an online ligand design module that can predict ligand binding affinity in real time. 23561134 Pesticide residues determination in Polish organic crops in 2007-2010 applying gas chromatography-tandem quadrupole mass spectrometry. A sensitive, accurate and reliable multiresidue method based on the application of gas chromatography-tandem quadrupole mass spectrometry (GC-QqQ-MS/MS) has been established for screening, identification and quantification of a large number of pesticide residues in produce. The method was accredited in compliance with PN-EN ISO/IEC 17025:2005 standard and it was operated under flexible scope as PB-11 method. The flexible scope of accreditation allowed for minor modifications and extension of the analytical scope while using the same analytical technique. During the years 2007-2010, the method was used for the purpose of verification of organic crop production by multiresidue analysis for the presence of pesticides. A total of 528 samples of differing matrices such as fruits, vegetables, cereals, plant leaves and other green parts were analysed, of which 4.4% samples contained pesticide residues above the threshold value of 0.01mg/kg. A total of 20 different pesticide residues were determined in the samples. 23525215 Two populations of glucocorticoid receptor-binding sites in the male rat hippocampal genome. In the present study, genomic binding sites of glucocorticoid receptors (GR) were identified in vivo in the rat hippocampus applying chromatin immunoprecipitation followed by next-generation sequencing. We identified 2470 significant GR-binding sites (GBS) and were able to confirm GR binding to a random selection of these GBS covering a wide range of P values. Analysis of the genomic distribution of the significant GBS revealed a high prevalence of intragenic GBS. Gene ontology clusters involved in neuronal plasticity and other essential neuronal processes were overrepresented among the genes harboring a GBS or located in the vicinity of a GBS. Male adrenalectomized rats were challenged with increasing doses of the GR agonist corticosterone (CORT) ranging from 3 to 3000 μg/kg, resulting in clear differences in the GR-binding profile to individual GBS. Two groups of GBS could be distinguished: a low-CORT group that displayed GR binding across the full range of CORT concentrations, and a second high-CORT group that displayed significant GR binding only after administering the highest concentration of CORT. All validated GBS, in both the low-CORT and high-CORT groups, displayed mineralocorticoid receptor binding, which remained relatively constant from 30 μg/kg CORT upward. Motif analysis revealed that almost all GBS contained a glucocorticoid response element resembling the consensus motif in literature. In addition, motifs corresponding with new potential GR-interacting proteins were identified, such as zinc finger and BTB domain containing 3 (Zbtb3) and CUP (CG11181 gene product from transcript CG11181-RB), which may be involved in GR-dependent transactivation and transrepression, respectively. In conclusion, our results highlight the existence of 2 populations of GBS in the rat hippocampal genome. 23220612 Profiling of oxidized lipid products of marine fish under acute oxidative stress. Free radical products including reactive oxygen species are potent to oxidize lipids and reliable measurements have been established mostly in human and rodent. To date, robust biomarkers were not used to assess the peroxidation in marine fish. The changes of oxidized lipid products from polyunsaturated fatty acids and cholesterol were assessed after exposure of H(2)O(2) to fish (medaka). Oxidized lipid products released by free radical reaction (F(2)-isoprostanes and metabolites, F(3)-isoprostanes, neuroprostanes, 7-ketocholesterol, 7β-hydroxycholesterol), by lipoxygenase enzymes (5(S)-, 8(S)-, 12(S)- and 15(S)-HETE, and resolvin D1) and by cytochrome P450 (9(S)-, 11(S)- and 20-HETE, and 27-hydroxycholestrol) were measured in fish muscle using LC/MS/MS. Arachidonate, docosahexaenoate, eicosapentaenoate and cholesterol levels, and antioxidant enzymes activity (catalase, SOD and gluthathione reductase) measurement were also determined. Activity of antioxidant enzymes especially catalase were elevated in presence of H(2)O(2) however longer exposure time suppressed the antioxidant activities. Arachidonate, docosahexaenoate, eicosapentaenoate and cholesterol levels were reduced in presence of H(2)O(2) and oxidized lipid products (isoprostanes, neuroprostanes 5(S)-HETE, 20-HETE, 7-ketocholesterol, 27-hydroxycholesterol and resolvin D1) were rapidly released in the fish muscle. This study validates oxidized lipid products, noticeably isoprostanes are measurable in marine fish muscle and should be considered when assessing oxidative stress especially due to exogenous factors. 23435948 Potent α-glucosidase and protein tyrosine phosphatase 1B inhibitors from Artemisia capillaris. As a part of our ongoing effort to identify anti-diabetic constituents from natural sources, we examined the inhibitory activity of the methanol extracts of 12 species of the genus Artemisia, against α-glucosidase and protein tyrosine phosphatase 1B (PTP1B). The methanol extracts of different species exhibited promising α-glucosidase and PTP1B inhibitory activities. Since the methanol extract of Artemisia capillaris exhibited the highest α-glucosidase inhibitory activity together with significant PTP1B inhibitory activity, it was selected for further investigation. Repeated column chromatography based on bioactivity guided fractionation yielded 10 coumarins (esculetin, esculin, scopolin, isoscopolin, daphnetin, umbelliferone, 7-methoxy coumarin, scoparone, scopoletin, 6-methoxy artemicapin C), 8 flavonoids (hyperoside, quercetin, isorhamnetin, cirsilineol, arcapillin, isorhamnetin 3-robinobioside, linarin, isorhamnetin 3-glucoiside), 6 phenolic compounds (1,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid methyl ester, 4,5-dicaffeoylquinic acid, 3-caffeoylquinic acid), and one chromone (capillarisin). Among these compounds, esculetin, scopoletin, quercetin, hyperoside, isorhamnetin, 3,5-dicaffeoylquinic acid methyl ester, 3,4-dicaffeoylquinic acid, and 1,5-dicaffeoylquinic acid exhibited potent α-glucosidase inhibitory activity when compared to the positive control acarbose. In addition, esculetin and 6-methoxy artemicapin C displayed PTP1B inhibitory activity. Interestingly, all isolated dicaffeoylquinic acids showed significant PTP1B inhibitory activity. Therefore, the results of the present study clearly demonstrate the potential of the A. capillaris extract to inhibit α-glucosidase and PTP1B. These inhibitory properties can be largely attributed to a combination of different chemical structures, including coumarins, flavonoids, and dicaffeoylquinic acids, which could be further explored to develop therapeutic or preventive agents for the treatment of diabetes. 23581295 Synthesis of diazenido-ligated vanadium nanoparticles. Metallic vanadium nanoparticles stabilized with 4-octylphenyldiazenido groups (particle size: 1.7 ± 0.2 nm) were synthesized via the reduction of VCl4 with superhydride (LiBHEt3) in the presence of 4-octylphenyldiazonium salt in an Ar-filled glovebox. The resulting particles were characterized using TEM, elemental analysis, and XPS measurements. The unusual reaction on the surface resulted in the passivation of V-N═N-Ar covalent bonds. 22983118 The neurotoxicity of hallucinogenic amphetamines in primary cultures of hippocampal neurons. 3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") and 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) are hallucinogenic amphetamines with addictive properties. The hippocampus is involved in learning and memory and seems particularly vulnerable to amphetamine's neurotoxicity. We evaluated the neurotoxicity of DOI and MDMA in primary neuronal cultures of hippocampus obtained from Wistar rat embryos (E-17 to E-19). Mature neurons after 10 days in culture were exposed for 24 or 48 h either to MDMA (100-800 μM) or DOI (10-100 μM). Both the lactate dehydrogenase (LDH) release and the tetrazolium-based (MTT) assays revealed a concentration- and time-dependent neuronal death and mitochondrial dysfunction after exposure to both drugs. Both drugs promoted a significant increase in caspase-8 and caspase-3 activities. At concentrations that produced similar levels of neuronal death, DOI promoted a higher increase in the activity of both caspases than MDMA. In the mitochondrial fraction of neurons exposed 24h to DOI or MDMA, we found a significant increase in the 67 kDa band of apoptosis inducing factor (AIF) by Western blot. Moreover, 24h exposure to DOI promoted an increase in cytochrome c in the cytoplasmatic fraction of neurons. Pre-treatment with an antibody raised against the 5-HT(2A)-receptor (an irreversible antagonist) greatly attenuated neuronal death promoted by 48 h exposure to DOI or MDMA. In conclusion, hallucinogenic amphetamines promoted programmed neuronal death involving both the mitochondria machinery and the extrinsic cell death key regulators. Death was dependent, at least in part, on the stimulation of the 5-HT(2A)-receptors. 22836659 Sclerostin antibody improves skeletal parameters in a Brtl/+ mouse model of osteogenesis imperfecta. Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by osteopenia and easy susceptibility to fracture. Symptoms are most prominent during childhood. Although antiresorptive bisphosphonates have been widely used to treat pediatric OI, controlled trials show improved vertebral parameters but equivocal effects on long-bone fracture rates. New treatments for OI are needed to increase bone mass throughout the skeleton. Sclerostin antibody (Scl-Ab) therapy is potently anabolic in the skeleton by stimulating osteoblasts via the canonical wnt signaling pathway, and may be beneficial for treating OI. In this study, Scl-Ab therapy was investigated in mice heterozygous for a typical OI-causing Gly→Cys substitution in col1a1. Two weeks of Scl-Ab successfully stimulated osteoblast bone formation in a knock-in model for moderately severe OI (Brtl/+) and in WT mice, leading to improved bone mass and reduced long-bone fragility. Image-guided nanoindentation revealed no alteration in local tissue mineralization dynamics with Scl-Ab. These results contrast with previous findings of antiresorptive efficacy in OI both in mechanism and potency of effects on fragility. In conclusion, short-term Scl-Ab was successfully anabolic in osteoblasts harboring a typical OI-causing collagen mutation and represents a potential new therapy to improve bone mass and reduce fractures in pediatric OI. 23137833 Influence of resveratrol on rheumatoid fibroblast-like synoviocytes analysed with gene chip transcription. Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that primarily attacks joints and is therefore a common cause of chronic disability and articular destruction. The hyperplastic growth of RA-fibroblast-like synoviocytes (FLSs) and their resistance against apoptosis are considered pathological hallmarks of RA. The natural antioxidant resveratrol is known for its antiproliferative and pro-apoptotic properties. This study investigated the effect of resveratrol on RA-FLS. RA-FLS were isolated from the synovium of 10 RA patients undergoing synovectomy or joint replacement surgery. RA-FLS were first stressed by pre-incubation with interleukin 1beta (IL-1β) and then treated with 100 μM resveratrol for 24h. In order to evaluate the influence of resveratrol on the transcription of genes, a Gene Chip Human Gene 1.0 ST Array was applied. In addition, the effect of dexamethasone on proliferation and apoptosis of RA-FLS was compared with that of resveratrol. Gene array analysis showed highly significant effects of resveratrol on the expression of genes involved in mitosis, cell cycle, chromosome segregation and apoptosis. qRT-PCR, caspase-3/7 and proliferation assays confirmed the results of gene array analysis. In comparison, dexamethasone showed little to no effect on reducing cell proliferation and apoptosis. Our in vitro findings point towards resveratrol as a promising new therapeutic approach for local intra-articular application against RA, and further clinical studies will be necessary. 23301853 Benzoquinones and terphenyl compounds as phosphodiesterase-4B inhibitors from a fungus of the order Chaetothyriales (MSX 47445). Three bioactive compounds were isolated from an organic extract of an ascomycete fungus of the order Chaetothyriales (MSX 47445) using bioactivity-directed fractionation as part of a search for anticancer leads from filamentous fungi. Of these, two were benzoquinones [betulinan A (1) and betulinan C (3)], and the third was a terphenyl compound, BTH-II0204-207:A (2). The structures were elucidated using a set of spectroscopic and spectrometric techniques; the structure of the new compound (3) was confirmed via single-crystal X-ray diffraction. Compounds 1-3 were evaluated for cytotoxicity against a human cancer cell panel, for antimicrobial activity against Staphylococcus aureus and Candida albicans, and for phosphodiesterase (PDE4B2) inhibitory activities. The putative binding mode of 1-3 with PDE4B2 was examined using a validated docking protocol, and the binding and enzyme inhibitory activities were correlated. 23515497 Evaluation of estrogenic effects of polychlorinated biphenyls and organochlorinated pesticides using immature rat uterotrophic assay. In this study, we investigated the effects of polychlorinated biphenyls (PCBs) and organochlorinated pesticides on the serum levels of luteinising hormone (LH), follicle stimulating hormone (FSH) and weights and histomorphometry of uterine tissue in immature female rats using uterotrophic assay. A total of 36 rats were randomly divided into six groups (n = 6 per group) as control, oestradiol (E2, 100 μg/kg), PCB 180, Aroclor 1221, endosulfan and mirex at 10 mg/kg dosage. After 3 days of injections (subcutaneous), animals were decapitated and blood samples were collected. Uteri were dissected, weighed out and then fixed in 10% formaldehyde. They were processed for histomorphometry. The serum levels of LH and FSH were determined by enzyme immunoassay.Uterine weight was significantly increased by E2 and reduced by mirex (p < 0.001 and p < 0.05, respectively). Total volume of uterus was significantly raised by E2, Aroclor 1221 and endosulfan compared with that of the control group (p < 0.01). The ratio of epithelium was significantly increased by E2, PCBs and pesticides (p < 0.01). The uterine cavity ratio was decreased by aroclor (p < 0.01), PCB 180 and mirex (p < 0.05). The serum levels of LH did not significantly differ among the groups but the levels of FSH were decreased by PCB 180 and endosulfan (p < 0.05 and p < 0.01, respectively). These findings suggest that PCB 180, Aroclor 1221 and endosulfan may be estrogenic in immature uterotrophic assay. 22956631 PPTOX III: environmental stressors in the developmental origins of disease--evidence and mechanisms. Fetal and early postnatal development constitutes the most vulnerable time period of human life in regard to adverse effects of environmental hazards. Subtle effects during development can lead to functional deficits and increased disease risk later in life. The hypothesis stating that environmental exposures leads to altered programming and, thereby, to increased susceptibility to disease or dysfunction later in life has garnered much support from both experimental and epidemiological studies. Similar observations have been made on the long-term impact of nutritional unbalance during early development. In an effort to bridge the fields of nutritional and environmental developmental toxicity, the Society of Toxicology sponsored this work. This report summarizes novel findings in developmental toxicity as reported by select invited experts and meeting attendees. Recommendations for the application and improvement of current and future research efforts are also presented. 22543584 Endoplasmic reticulum protein 29 regulates epithelial cell integrity during the mesenchymal-epithelial transition in breast cancer cells. The epithelial-mesenchymal transition (EMT) correlates with disruption of cell-cell adhesion, loss of cell polarity and development of epithelial cell malignancy. Identifying novel molecules that inhibit EMT has profound potential for developing mechanism-based therapeutics. We previously demonstrated that the endoplasmic reticulum protein 29 (ERp29) is a novel factor that can drive mesenchymal-epithelial transition (MET) and induce cell growth arrest in MDA-MB-231 cells. Here, we show that ERp29 is an important molecule in establishing epithelial cell integrity during the MET. We demonstrate that ERp29 regulates MET in a cell context-dependent manner. ERp29 overexpression induced a complete MET in mesenchymal MDA-MB-231 cells through downregulating the expression of transcriptional repressors (for example, Slug, Snai1, ZEB2 and Twist) of E-cadherin. In contrast, overexpression of ERp29 induces incomplete MET in basal-like BT549 cells in which the expression of EMT-related markers (for example, vimentin; cytokeratin 19 (CK19) and E-cadherin) and the transcriptional repressors of E-cadherin were not altered. However, ERp29 overexpression in both cell-types resulted in loss of filamentous stress fibers, formation of cortical actin and restoration of an epithelial phenotype. Mechanistic studies revealed that overexpression of ERp29 in both cell-types upregulated the expression of TJ proteins (zonula-occludens-1 (ZO-1) and occludin) and the core apical-basal polarity proteins (Par3 and Scribble) at the membrane to enhance cell-cell contact and cell polarization. Knockdown of ERp29 in the epithelial MCF-7 cells decreased the expression of these proteins, leading to the disruption of cell-cell adhesion. Taken together, ERp29 is a novel molecule that regulates MET and epithelial cell integrity in breast cancer cells. 23157640 Prostate cancer, miRNAs, metallothioneins and resistance to cytostatic drugs. MicroRNAs (miRNAs) translationally repressing their target messenger RNAs due to their gene-regulatory functions play an important but not unexpected role in a tumour development. More surprising are the findings that levels of various miRNAs are well correlated with presence of specific tumours and formation of metastases. Moreover, these small regulatory molecules play a role in the resistance of cancer cells to commonly used anti-cancer drugs, such as cisplatin, anthracyclines, and taxanes. In that respect, miRNAs become very attractive target for potential therapeutic interventions. Improvements in the sensitivity of miRNAs detection techniques led to discovery of circulating miRNAs which became very attractive non-invasive biomarker of cancer with a substantial predictive value. In this review, the authors focus on i) oncogenic and anti-tumour acting miRNAs, ii) function of miRNAs in tumour progression, iii) possible role of miRNAs in resistance to anticancer drugs, and iv) diagnostic potential of miRNAs for identification of cancer from circulating miRNAs with special emphasis on prostate cancer. Moreover, relationship between miRNAs and expression of metallothionein is discussed as a possible explanation of resistance against platinum based drugs. 23637306 Renal and hepatotoxic alterations in adult mice on inhalation of specific mixture of organic solvents. This study was aimed at investigating alterations in renal and hepatic toxicity induced by exposing to a combination of three solvents, namely, benzene, toluene and xylene in adult mice. The mice were divided into three groups (control, low-dose-treated (450 ppm) and high-dose (675 ppm) groups) using randomization methods. The treated groups were exposed to vapours of a mixture of benzene, toluene and xylene at doses of 450 and 675 ppm, for 6 h day(-1) for a short-term of 7-day exposure period. The study revealed that the solvent exposure resulted in an increase in the weight of liver and kidney as compared to the control. Biochemical analyses indicated a significant decline in the activities of superoxide dismutase and catalase in both the treated groups, with concomitant increase in lipid peroxidation. Liver aminotransferases (alanine aminotransferase and aspartate aminotransferase) were elevated with significant alterations in the levels of protein, creatinine and cholesterol in these tissues upon solvent exposure. Correlated with these changes, serum thyroid hormones T3 and T4 were also significantly altered. This study, therefore, demonstrates that inhalation of vapours from the solvent mixture resulted in significant dose-dependent biochemical and functional changes in the vital tissues (liver and kidney) studied. The study has specific relevance since humans are increasingly being exposed to such solvents due to increased industrial use in such combinations. 22475014 Glaucogenin E, a new C21 steroid from Cynanchum stauntonii. Glaucogenin E (1), a new C(21) steroid sapogenin, along with three known ones (2-4) were isolated from the rhizomes of Cynanchum stauntonii (Decne.) Schltr. ex Levl. Their structures were established mainly by the spectroscopic analysis, including 2D NMR. All the isolated compounds were evaluated for their cytotoxicity against human cancer cell lines HeLa, Bel-7402, SGC-7901 and BGC-823. 23266732 Effects of Yerba Mate tea (Ilex paraguariensis) on vascular endothelial function and liver lipoprotein receptor gene expression in hyperlipidemic rats. Yerba Mate tea (Mate), an infusion made from the leaves of the tree Ilex paraguariensis, is a widely consumed beverage in South America. This study was performed to investigate the effect of Mate tea on vascular endothelial dysfunction and liver lipoprotein receptor gene expression in hyperlipidemic rats, with the aim of gaining insight into its known lipid-lowering protective mechanisms. Sixty male Sprague-Dawley rats were randomly divided into five groups: a normal control group (NC), a high-fat diet group (HC), and three Mate tea-treated groups. In the NC group, rats were fed with standard diet while in the other groups the rats were fed a high-fat diet for 8weeks. In the Mate tea-treated groups, the rats were fed a high-fat diet supplemented with low, moderate or high concentrations of aqueous Mate tea extract for the final 4weeks. Compared to the HC group, aqueous Mate tea extract significantly reduced endothelin (ET) and thromboxane B(2) (TXB(2)) levels and increased nitric oxide (NO) and 6-keto prostaglandin F(1α) (6-keto-PGF(1α)) levels in the blood, reduced the pathological damage of vascular endothelial cells, decreased intercellular adhesion molecule-1 (ICAM-1) protein expression in the thoracic aorta, and upregulated mRNA expression of hepatic low density lipoprotein receptor (LDLR) and scavenger receptor B1 (SR-B1). These findings indicate that Mate tea administration might have a regulatory effect on blood fat and endothelial function in hyperlipidemia rats. The mechanism may involve protecting vascular endothelial cell function and upregulating the expression of LDLR and SR-B1 genes, thereby inhibiting the occurrence of atherosclerosis. 22975406 Emerging opportunities for allosteric modulation of G-protein coupled receptors. Their ubiquitous nature, wide cellular distribution and versatile molecular recognition and signalling help make G-protein binding receptors (GPCRs) the most important class of membrane proteins in clinical medicine, accounting for ∼40% of all current therapeutics. A large percentage of current drugs target the endogenous ligand binding (orthosteric) site, which are structurally and evolutionarily conserved, particularly among members of the same GPCR subfamily. With the recent advances in GPCR X-ray crystallography, new opportunities for developing novel subtype selective drugs have emerged. Given the increasing recognition that the extracellular surface conformation changes in response to ligand binding, it is likely that all GPCRs possess an allosteric site(s) capable of regulating GPCR signalling. Allosteric sites are less structurally conserved than their corresponding orthosteric site and thus provide new opportunities for the development of more selective drugs. Constitutive oligomerisation (dimerisation) identified in many of the GPCRs investigated, adds another dimension to the structural and functional complexity of GPCRs. In this review, we compare 60 crystal structures of nine GPCR subtypes (rhodopsin, ß₂-AR, ß₁-AR, A(2a)-AR, CXCR4, D₃R, H₁R, M₂R, M₃R) across four subfamilies of Class A GPCRs, and discuss mechanisms involved in receptor activation and potential allosteric binding sites across the highly variable extracellular surface of these GPCRs. This analysis has identified a new extracellular salt bridge (ESB-2) that might be exploited in the design of allosteric modulators. 23345132 Androgen synthesis in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. A hallmark of severe congenital adrenal hyperplasia due to 21-hydroxylase deficiency is pre- and postnatal virilization. The most characteristic biochemical abnormality is the elevation of 17α-hydroxyprogesterone, which is metabolized to the most potent androgen receptor agonist dihydrotestosterone. 17α-Hydroxyprogesterone can be metabolized to dihydrotestosterone via 4-androstenedione through the classical Δ4-pathway or via 17α-hydroxypregnenolone and dehydroepiandrosterone through the classical Δ5-pathway, as well as through an alternative route, called the 'backdoor pathway', that bypasses dehydroepiandrosterone, 4-androstenedione, and testosterone as intermediates. This review article will summarize recent advances in the understanding of the activities of androgen synthesis pathways in patients with 21-hydroxylase deficiency obtained by urinary steroid metabolomics based on gas chromatography-mass spectrometry. Compared with healthy controls, the relative activities of the backdoor and Δ4-pathways increase in patients with congenital adrenal hyperplasia during neonatal age and infancy, whereas the activity of the Δ5-pathway remains unchanged. Thereafter, the activity of the Δ5-pathway dominates, whereas a decreasing 5α-reductase activity leads to a diminished role of the backdoor pathway for androgenic steroid production. Beside the backdoor pathway, the Δ4-pathway seems to be responsible for increased androgen generation in patients with 21-hydroxylase deficiency before the onset of adrenarche, whereas the Δ5-pathway might contribute to the increased androgen formation in those patients only after the onset of adrenarche. 23562633 Therapeutic targeting of chitosan-PEG-folate-complexed oncolytic adenovirus for active and systemic cancer gene therapy. Adenovirus (Ad)-based cancer therapies have shown much promise. However, until now, Ad has only been delivered directly to primary tumors because the therapeutic efficacy of systemic delivery is limited by the immune response of the host, short blood circulation times, and non-specific liver uptake of Ad. In order to circumvent the issues regarding systemic delivery and to increase the safety and efficacy of Ad therapies, the surface of oncolytic Ad was coated with cationic polymer chitosan via ionic crosslinking (Ad/chitosan), after which polyethylene glycol (PEG) and/or folic acid (FA) was chemically conjugated onto the surface of Ad/chitosan, generating Ad/chitosan-FA, Ad/chitosan-PEG, and Ad/chitosan-PEG-FA nanocomplex. The FA-coordinated Ad nanocomplexes (Ad/chitosan-FA & Ad/chitosan-PEG-FA) elicited folate receptor (FR)-selective cancer cell killing efficacy. In vivo administration of Ad/chitosan-PEG or Ad/chitosan-PEG-FA into mice demonstrated that PEGylation greatly increased blood circulation time, resulting in 9.0-fold and 48.9-fold increases at 24h after injection compared with naked Ad, respectively. In addition, generation of Ad-specific neutralizing antibodies in mice treated with Ad/chitosan-PEG-FA was markedly decreased by 75.3% compared with naked Ad. The quantitative polymerase chain reaction assay results showed a 285.0-fold increase in tumor tissues and a 378-fold reduction of Ad/chitosan-PEG-FA in liver tissues compared with naked Ad. Bioluminescence imaging study further supported the enhanced tumor-to-liver ratio of Ad/chitosan-PEG-FA. Consequently, systemic delivery of Ad/chitosan-PEG-FA significantly inhibited the growth of FR-positive tumor, decreasing 52.8% compared to the naked Ad-treated group. Importantly, PEGylated oncolytic Ad nanocomplexes showed no elevation of both alanine transaminase and aspartate transaminase levels, demonstrating that systemically delivered Ad-related hepatic damage can be completely eliminated with PEG conjugation. In sum, these results demonstrate that conjugation of chitosan-PEG-FA to oncolytic Ad significantly improves antitumor efficacy and safety profiles, suggesting that Ad/chitosan-PEG-FA has potential as a therapeutic agent to target FR-positive cancer via systemic administration. 22891663 The major indole alkaloid N,β-D-glucopyranosyl vincosamide from leaves of Psychotria leiocarpa Cham. & Schltdl. is not an antifeedant but shows broad antioxidant activity. N,β-D-glucopyranosyl vincosamide (GPV), a major alkaloid of Psychotria leiocarpa, constitutes up to 2.5% of the dry weight in leaves. Alkaloid content was not elicited by mechanical wounding or jasmonate. At concentrations found in natural conditions or 2.5 fold higher, GPV did not inhibit herbivory in two unrelated generalist models (Helix aspersa and Spodoptera frugiperda) or in a specific interaction model (Heliconius erato fed with Passiflora suberosa). In situ staining assay showed quenching activity of hydrogen peroxide by GPV. Exposure of P. leiocarpa to acute UV-B stress did not change GPV or chlorophyll content, indicating high tolerance to this stress by the species. In vitro antioxidant tests against singlet oxygen, superoxide anions and hydroxyl radicals showed efficient quenching activity of the alkaloid. GPV was not effective as antifeedant, but it may act indirectly in P. leiocarpa protection against oxidative stress generated upon wounding, UV exposure and perhaps other environmental stresses. 23231967 Selective and potent adenosine A3 receptor antagonists by methoxyaryl substitution on the N-(2,6-diarylpyrimidin-4-yl)acetamide scaffold. The influence of diverse methoxyphenyl substitution patterns on the N-(2,6-diarylpyrimidin-4-yl)acetamide scaffold is herein explored in order to modulate the A(3) adenosine receptor antagonistic profile. As a result, novel ligands exhibiting excellent potency (K(i) on A(3) AR < 20 nM) and selectivity profiles (above 100-fold within the adenosine receptors family) are reported. Moreover, our joint theoretical and experimental approach allows the identification of novel pharmacophoric elements conferring A(3)AR selectivity, first established by a robust computational model and thereafter characterizing the most salient features of the structure-activity and structure-selectivity relationships in this series. 23146690 Synergistic anti-cancer effects of resveratrol and chemotherapeutic agent clofarabine against human malignant mesothelioma MSTO-211H cells. Dietary phytochemicals as adjuvants have been suggested to play important roles in enhancing chemotherapeutic potential owing to multitargeted chemopreventive properties and lack of substantial toxicity. Here, we investigated the efficacy of the combined treatment of various phytochemicals with the anticancer drug clofarabine in malignant mesothelioma MSTO-211H cells and normal mesothelial MeT-5A cells. The combined treatment of resveratrol and clofarabine produced a synergistic antiproliferative effect in MSTO-211H cells, but not in MeT-5A cells. In MSTO-211H cells, the nuclear accumulation of Sp1 and the levels of p-Akt, Sp1, c-Met, cyclin D1, and p21 were effectively decreased by the combined treatment of them. In combination with clofarabine, the ability of resveratrol to reduce the contents of Sp1 and its target gene products was also evident in a time- and dose-dependent experiment. The inhibition of phosphoinositide 3-kinase using Ly294002 augmented a decrease in the p21 level induced by their combination, but it showed no significant effects on expression of Sp1 and cyclin D1. Taken together, the data provide evidence that the synergistic antiproliferative effect of resveratrol and clofarabine is linked to the inhibition of Akt and Sp1 activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma. 23640282 Characterization of surface ligands on functionalized magnetic nanoparticles using laser desorption/ionization mass spectrometry (LDI-MS). Functionalized magnetic nanoparticles (MNPs) have been characterized by laser desorption/ionization mass spectrometry (LDI-MS). Quantitative information about surface ligand composition and structure for monolayer and mixed monolayer protected Fe3O4 and FePt NPs can be obtained rapidly with very little sample consumption. 23125002 Free energy simulation of helical transitions. An umbrella sampling method for the calculation of free energies for helical transitions is presented. The method biases structures toward helices of a desired radius and pitch. Although computationally complex, the method has negligible overhead in actual applications. To illustrate the method, calculations of the helical free energy landscape of several peptides are presented for both the CHARMM and the AMBER force fields. 23347875 Acute effects of hexabromocyclododecane on Leydig cell cyclic nucleotide signaling and steroidogenesis in vitro. Hexabromocyclododecane (HBCDD), an additive brominated flame retardant routinely added to various consumer products, was reported to have toxic effects upon biota, including endocrine disruption. In this study, the potential toxicity of HBCDD was tested in peripubertal rat Leydig cells in vitro during 6h exposure. HBCDD inhibited human chorionic gonadotropin- and forskolin-supported cAMP accumulation and steroidogenesis. It also inhibited basal cAMP production, but elevated basal steroidogenesis. The expression of several cAMP-dependent genes, including steroidogenic acute regulatory protein, cholesterol side chain cleavage enzyme, and 3β-hydroxysteroid dehydrogenase, was also inhibited by HBCDD treatment. Nevertheless, this was not accompanied by a decrease in steroidogenic acute regulatory protein expression, as documented by western blot analysis, and activity of steroidogenic enzymes, as documented by unaffected steroidogenesis in the presence of permeable 22(R)-hydroxycholesterol. However, HBCDD caused significant decrease in mitochondrial membrane potential in untreated and human chorionic gonadotropin-treated cells. This indicates that HBCDD acute toxicity in Leydig cells reflects changes in mitochondrial membrane potential-dependent cAMP production and basal and cAMP-regulated cholesterol transport. This in turn facilitates basal but inhibits cAMP-dependent steroidogenesis. Acute effects of HBCDD treatment on transcription are also indicative of its sustained effects on Leydig cell function. 22983831 Ectopic acromegaly due to growth hormone releasing hormone. Acromegaly secondary to extra-pituitary tumors secreting growth hormone releasing hormone (GHRH) is rarely encountered. We review the literature on ectopic acromegaly and present the index report of ectopic acromegaly secondary to GHRH secretion from a mediastinal paraganglioma. Clinical and pathological manifestations and therapeutic management of 99 patients with ectopic acromegaly are reviewed. Acromegaly secondary to ectopic GHRH secretion is usually caused by a neuroendocrine tumor in the lung and pancreas. We report an additional cause of ectopic acromegaly from a mediastinal paraganglioma. Diagnostic criteria of ectopic GHRH syndrome include biochemical and pathologic tumoral confirmation of GHRH secretion and expression. Management of ectopic acromegaly consists of surgical resection of the primary tumor and biochemical normalization, with possible adjuvant use of somatostatin analogs. The review demonstrates that there are several tumor types, including paragangliomas which may secrete GHRH, leading to acromegaly. Clinical and laboratory manifestations of the syndrome and challenges in diagnosis and management of these rarely encountered patients require early diagnosis and appropriate treatment to prevent long-term morbidity and mortality with ectopic acromegaly. 23288091 Therapeutic drug monitoring of antiepileptic drugs by use of saliva. Blood (serum/plasma) antiepileptic drug (AED) therapeutic drug monitoring (TDM) has proven to be an invaluable surrogate marker for individualizing and optimizing the drug management of patients with epilepsy. Since 1989, there has been an exponential increase in AEDs with 23 currently licensed for clinical use, and recently, there has been renewed and extensive interest in the use of saliva as an alternative matrix for AED TDM. The advantages of saliva include the fact that for many AEDs it reflects the free (pharmacologically active) concentration in serum; it is readily sampled, can be sampled repetitively, and sampling is noninvasive; does not require the expertise of a phlebotomist; and is preferred by many patients, particularly children and the elderly. For each AED, this review summarizes the key pharmacokinetic characteristics relevant to the practice of TDM, discusses the use of other biological matrices with particular emphasis on saliva and the evidence that saliva concentration reflects those in serum. Also discussed are the indications for salivary AED TDM, the key factors to consider when saliva sampling is to be undertaken, and finally, a practical protocol is described so as to enable AED TDM to be applied optimally and effectively in the clinical setting. Overall, there is compelling evidence that salivary TDM can be usefully applied so as to optimize the treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide. Salivary TDM of valproic acid is probably not helpful, whereas for clonazepam, eslicarbazepine acetate, felbamate, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin, the data are sparse or nonexistent. 23018143 The role of personalized medicine in identifying appropriate candidates for menopausal estrogen therapy. Menopausal estrogen therapy has a complex balance of benefits and risks and is no longer routinely recommended for the majority of women during or after the transition to menopause. Recent findings from the Women's Health Initiative (WHI) and other studies suggest that a woman's clinical and biological characteristics may modify her health outcomes on hormone therapy (HT) and that some women may be more appropriate candidates for therapy than others. An emerging body of evidence suggests that it may be possible to identify women who are more likely to have favorable outcomes and less likely to have adverse events on HT, as well as to tailor the optimal dose, formulation, and route of delivery of treatment, by the use of individual risk stratification and a personalized approach. Several clinical characteristics that have been proposed for this purpose include a woman's age, time since menopause, symptom severity, baseline vascular health, risk for breast cancer, biomarker levels, and genetic predisposition. The underlying rationale for personalized medicine, that each person has a unique biologic profile that can help to guide the choice of therapy, applies well to HT decision making and holds promise for improved treatment efficacy and safety. This report, which focuses on vascular health, reviews the evidence on the role of such markers in tailoring the use of hormone therapy to appropriate candidates, with the ultimate goal of developing a personalized risk:benefit prediction model that takes into account clinical and genetic factors, "patient-centered" outcomes including sense of well being and quality of life, and other variables. The proposed personalized approach to HT decision making has the potential to improve the quality of health care. 23374871 Synthesis, crystal structure and antibacterial activity of new highly functionalized ionic compounds based on the imidazole nucleus. Several new highly functionalized imidazolium derivatives were synthesized, via appropriate synthetic routes, using imidazole, 1-methylimidazole and 2-phenyl-1-methylimidazole as key intermediates. The antibacterial activity of the prepared compounds was evaluated against: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella thipymurium using disk-diffusion and MIC methods. Crystal X-ray structures are reported for six compounds. 23485450 Multifunctional pH-sensitive superparamagnetic iron-oxide nanocomposites for targeted drug delivery and MR imaging. A multifunctional pH-sensitive superparamagnetic iron-oxide (SPIO) nanocomposite system was developed for simultaneous tumor magnetic resonance imaging (MRI) and therapy. Small-size SPIO nanoparticles were chemically bonded with antitumor drug doxorubicin (DOX) and biocompatible poly(ethylene glycol) (PEG) through pH-sensitive acylhydrazone linkages, resulting in the formation of SPIO nanocomposites with magnetic targeting and pH-sensitive properties. These DOX-conjugated SPIO nanocomposites exhibited not only good stability in aqueous solution but also high saturation magnetizations. Under an acidic environment, the DOX was quickly released from the SPIO nanocomposites due to the cleavage of pH-sensitive acylhydrazone linkages. With the help of magnetic field, the DOX-conjugated SPIO nanocomposites showed high cellular uptake, indicating their magnetic targeting property. Comparing to free DOX, the DOX-conjugated SPIO nanocomposites showed better antitumor effect under magnetic field. At the same time, the relaxivity value of these SPIO nanocomposites was higher than 146s(-1)mM(-1) Fe, leading to ~4 times enhancement compared to that of free SPIO nanoparticles. As a negative contrast agent, these SPIO nanocomposites illustrated high resolution in MRI diagnosis of tumor-bearing mice. All of these results confirm that these pH-sensitive SPIO nanocomposites are promising hybrid materials for synergistic MRI diagnosis and tumor therapy. 23292797 Smoothened is a fully competent activator of the heterotrimeric G protein G(i). Smoothened (Smo) is a 7-transmembrane protein essential to the activation of Gli transcription factors (Gli) by hedgehog morphogens. The structure of Smo implies interactions with heterotrimeric G proteins, but the degree to which G proteins participate in the actions of hedgehogs remains controversial. We posit that the G(i) family of G proteins provides to hedgehogs the ability to expand well beyond the bounds of Gli. In this regard, we evaluate here the efficacy of Smo as it relates to the activation of G(i), by comparing Smo with the 5-hydroxytryptamine(1A) (5-HT(1A)) receptor, a quintessential G(i)-coupled receptor. We find that with use of [(35)S]guanosine 5'-(3-O-thio)triphosphate, first, with forms of G(i) endogenous to human embryonic kidney (HEK)-293 cells made to express epitope-tagged receptors and, second, with individual forms of Gα(i) fused to the C terminus of each receptor, Smo is equivalent to the 5-HT(1A) receptor in the assay as it relates to capacity to activate G(i). This finding is true regardless of subtype of G(i) (e.g., G(i2), G(o), and G(z)) tested. We also find that Smo endogenous to HEK-293 cells, ostensibly through inhibition of adenylyl cyclase, decreases intracellular levels of cAMP. The results indicate that Smo is a receptor that can engage not only Gli but also other more immediate effectors. 23313797 Neuroprotective effects of resveratrol on embryonic dorsal root ganglion neurons with neurotoxicity induced by ethanol. Studies have established that ethanol (EtOH) consumption results in damage to the peripheral nervous systems. Although the pathobiological mechanism is still unclear, oxidative stress is known to play an important role in EtOH-induced neurotoxicity. Because resveratrol (Res) is attracting increased attention due to its antioxidative properties, we investigated the neuroprotective efficacy of Res in ethanol-treated embryonic dorsal root ganglion (DRG) neurons in vitro. Organotypic DRG explants and a dispersed cell culture model were used to evaluate the effects of Res on EtOH-induced neurotoxicity. Res increased the number of extended nerve fibers and neurons that migrated from the DRG explants. Hoechst 33342 staining and terminal deoxynucleotidyl-transferase-mediated dUTP nick-end-labeling analysis showed that the EtOH-induced apoptosis was inhibited by Res. The effects of Res were blocked by the 5'-adenosine monophosphate-activated protein kinase inhibitor Compound C and the sirtuin 1 inhibitor nicotinamide. The elevation of oxidative/nitrosative stress, as measured by the amount of reactive oxygen species, malondialdehyde, nitrite, glutathione and superoxide dismutase activity, was also attenuated by Res. The data from the present study indicate that Res protects DRG neurons from EtOH-induced neurotoxicity. Res and its derivative may be effective for the treatment of diseases characterized by axonopathy and neuron loss induced by EtOH. 23561194 The impact of Ca(2+) combination with organic acids on green tea infusions. The effect of Ca(2+) in brewing water on the organic acid content, turbidity, and formation of tea cream and sediment in green tea infusions was studied. When the Ca(2+) concentration of the brewing water was >40mgL(-1), the green tea infusion became more turbid. The turbidity of the tea infusion was highly negatively correlated with the contents of oxalic acid (R=-0.89, p<0.01), quinic acid (R=-0.90, p<0.01) and tartaric acid (R=-0.82, p<0.01). Oxalic acid on its own interacted with Ca(2+) at low concentrations, whereas polyphenols and protein did not. In conclusion, Ca(2+) in brewing water influences the quality of a tea infusion by inducing tea cream and sediment formation from combination of Ca(2+) and organic acids, such as oxalic acid, quinic acid and tartaric acid. Ca(2+) and oxalate are the main metal ion and anion, respectively, involved in tea cream and sediment formation on tea infusion cooling or concentrating. 23590129 Understanding the thermodynamic micro-environment inside a pan coater using a data logging device. Abstract Objective: The objective of the current study was to establish the use of PyroButton data-logging device to monitor and quantify the thermodynamic environment (temperature and humidity) of a pan coating process. Material and methods: PyroButtons were placed (fixed) at various locations in a pan coater, including exhaust plenum, spray-gun bar, baffles and were also allowed to freely move with the tablet-bed. A full factorial design of experiments (DOE) study on three process parameters, exhaust temperature, pan speed and spray rate was conducted on a 24 inch pan coater, using a coating system and a core tablet combination expected to have a narrow process operating space. Results: It was shown that the PyroButtons can provide a detailed and useful signature of the coating process. PyroButton data showed that the tablet-bed temperature was always lower than exhaust temperature and that the difference was a function of the operating conditions such as spray rate. Similarly, the tablet-bed humidity was found to always be higher than exhaust humidity. Some of the DOE batches showed coating defects (logo-bridging). It was shown that the relative humidity (RH), as measured by the freely-moving PyroButtons in the tablet-bed, correlated well with the logo-bridging events. A critical RH value (30%) was established, above which logo-bridging was observed for the selected formulation. Conclusions: This study showed that PyroButtons can provide very meaningful micro-environmental data that can be correlated to coating defects, and can aid in establishing a process design space for a given coating and tablet formulation. 23391637 The venom of the fishing spider Dolomedes sulfurous contains various neurotoxins acting on voltage-activated ion channels in rat dorsal root ganglion neurons. Dolomedes sulfurous is a venomous spider distributed in the south of China and characterized with feeding on fish. The venom exhibits great diversity and contains hundreds of peptides as revealed by off-line RP-HPLC/MALDI-TOF-MS analysis. The venom peptides followed a triple-modal distribution, with 40.7% of peptides falling in the mass range of 1000-3000 Da, 25.6% peptides in the 7000-9000 Da range and 23.5% peptides in the 3000-5000 Da range. This distribution modal is rather different from these of peptides from other spider venoms analyzed. The venom could inhibit voltage-activated Na(+), K(+) and Ca(2+) channels in rat DRG neurons as revealed by voltage-clamp analysis. Significantly, the venom exhibited inhibitory effects on TTX-R Na(+) and T-type Ca(2+) currents, suggesting that there exist both channel antagonists which might be valuable tools for investigation of both channels and drug development. Additionally, intrathoracically injection of venom could cause serve neurotoxic effects on zebrafish and death at higher concentrations. The LD50 value was calculated to be 28.8 μg/g body weight. Our results indicated that the venom of D. sulfurous contain diverse neurotoxins which serve to capture prey. Intensive studies will be necessary to investigate the structures and functions of specific peptides of the venom in the future. 23543413 A Re-evaluation of the Role of hCTR1, the Human High Affinity Cu Transporter in Pt-Drug Entry into Human Cells. Cisplatin (cDDP) is an anti-cancer drug used in a number of malignancies including testicular, ovarian, cervical, bladder, lung, head, and neck cancers. Its use is limited by the development of resistance, often rationalized via effects on cellular uptake. It has been claimed that hCTR1, the human high affinity copper transporter, is the major entry pathway for cDDP and related drugs via a mechanism that mimics copper. This is an unexpected property of hCTR1, a highly selective copper (I) transporter. We compared the uptake rates of copper with cDDP (and several analogs) into HEK293 cells over-expressing wild-type or mutant hCTR1, mouse embryonic fibroblasts (mefs) that do or do not express CTR1, and human ovarian tumor cells, sensitive or resistant to cDDP. We have also compared the effects of extracellular copper, which causes regulatory endocytosis of hCTR1, to those of cDDP. We confirm the correlation between higher hCTR1 levels and higher Pt-drug uptake in tumor cells sensitive to the drug. However, we show that hCTR1 is not the major entry route of platinum-drugs and that the copper transporter is not internalized in response to extracellular drug. Our data suggest the major entry pathway for platinum-drugs is not saturable at relevant concentrations and not protein-mediated. Clinical trials have been initiated that depend upon regulating membrane levels of hCTR1. If reduced drug uptake is a major factor in resistance, hCTR1 is unlikely to be a productive target in attempts to enhance efficacy, although the proteins involved in copper homeostasis may play a role. 23411168 Development of the simple and sensitive method for lipoxygenase assay in AOT/isooctane reversed micelles. In this study, we investigated the possibility of reversed micelles, widely used as an enzyme reactor for lipases, for the determination of lipoxygenase activity. Although it is rapid and simple, reversed micelles have some limitations, such as interference by UV-absorbing materials and surfactant. Lipoxygenase activity in the reversed micelles was determined by reading the absorbance of the lipid hydroperoxidation product (conjugated diene) at 234 nm. Among surfactants and organic media, AOT and isooctane were most effective for the dioxygenation of linoleic acid in reversed micelles. The strong absorbance of AOT in the UV region is a major obstacle for the direct application of the AOT/isooctane reversed micelles to lipoxygenase activity determination. To prevent interference by AOT, we added an AOT removal step in the procedure for lipoxygenase activity determination in reversed micelles. The lipoxygenase activity was dependent on water content, and maximum activity was obtained at an R-value of 10. 23561161 Effect of calcium on the kinetics of free fatty acid release during in vitro lipid digestion in model emulsions. The effects of different calcium salts on in vitro lipid digestion were examined by determining the free fatty acids released from various oil-in-water emulsions. The kinetics of the total and individual free fatty acids released by lipolysis were monitored by the pH-stat method and gas chromatography, respectively. The rate and the extent of free fatty acid release increased with an increase in the added calcium concentration, but the increase was dependent on the emulsifying agent. The effect of calcium was diminished when the emulsion contained phosphate. Soluble calcium salts, such as calcium gluconate, calcium acetate and CaCl2, had greater effects on the rate and extent of free fatty acid release than did insoluble salts, such as CaO and CaSO4, suggesting that the ionic state of calcium plays a critical role in lipid digestion in emulsions. The addition of calcium did not alter the profiles of the individual free fatty acids released. This study provides useful information for food formulation with respect to lipid digestion. 23568429 Profiling glycosyltransferase activities by tritium imaging of glycan microarrays. High-throughput microarray technology has been combined with ultrasensitive and high-resolution tritium autoradiography to create a new platform for the quantitative detection of glycosyltransferase activity on glycan arrays. In addition, we show full compatibility with the use of fluorescently labeled lectins to help with the stereochemical assignment of newly formed glycoside linkages. 23167566 Telomere length and dynamics predict mortality in a wild longitudinal study. Explaining variation in life expectancy between individuals of the same age is fundamental to our understanding of population ecology and life history evolution. Variation in the length and rate of loss of the protective telomere chromosome caps has been linked to cellular lifespan. Yet, the extent to which telomere length and dynamics predict organismal lifespan in nature is still contentious. Using longitudinal samples taken from a closed population of Acrocephalus sechellensis (Seychelles warblers) studied for over 20 years, we describe the first study into life-long adult telomere dynamics (1-17 years) and their relationship to mortality under natural conditions (n = 204 individuals). We show that telomeres shorten with increasing age and body mass, and that shorter telomeres and greater rates of telomere shortening predicted future mortality. Our results provide the first clear and unambiguous evidence of a relationship between telomere length and mortality in the wild, and substantiate the prediction that telomere length and shortening rate can act as an indicator of biological age further to chronological age when exploring life history questions in natural conditions. 23545161 Acetaminophen reduces lipopolysaccharide-induced fever by inhibiting cyclooxygenase-2. Acetaminophen is one of the world's most commonly used drugs to treat fever and pain, yet its mechanism of action has remained unclear. Here we tested the hypothesis that acetaminophen blocks fever through inhibition of cyclooxygenase-2 (Cox-2), by monitoring lipopolysaccharide induced fever in mice with genetic manipulations of enzymes in the prostaglandin cascade. We exploited the fact that lowered levels of a specific enzyme make the system more sensitive to any further inhibition of the same enzyme. Mice were immune challenged by an intraperitoneal injection of bacterial wall lipopolysaccharide and their body temperature recorded by telemetry. We found that mice heterozygous for Cox-2, but not for microsomal prostaglandin E synthase-1 (mPGES-1), displayed attenuated fever, indicating a rate limiting role of Cox-2. We then titrated a dose of acetaminophen that did not inhibit the lipopolysaccharide-induced fever in wild-type mice. However, when the same dose of acetaminophen was given to Cox-2 heterozygous mice, the febrile response to lipopolysaccharide was strongly attenuated, resulting in an almost normalized temperature curve, whereas no difference was seen between wild-type and heterozygous mPGES-1 mice. Furthermore, the fever to intracerebrally injected prostaglandin E2 was unaffected by acetaminophen treatment. These findings reveal that acetaminophen, similar to aspirin and other non-steroidal anti-inflammatory drugs, is antipyretic by inhibiting cyclooxygenase-2, and not by inhibiting mPGES-1 or signaling cascades downstream of prostaglandin E2. 23359538 Tailor-Made Micro-Object Optical Sensor Based on Mesoporous Pellets for Visual Monitoring and Removal of Toxic Metal Ions from Aqueous Media. Methods for the continuous monitoring and removal of ultra-trace levels of toxic inorganic species (e.g., mercury, copper, and cadmium ions) from aqueous media such as drinking water and biological fluids are essential. In this paper, the design and engineering of a simple, pH-dependent, micro-object optical sensor is described based on mesoporous aluminosilica pellets with an adsorbed dressing receptor (a porphyrinic chelating ligand). This tailor-made optical sensor permits ultra-fast (≤ 60 s), specific, pH-dependent visualization and removal of Cu(2+) , Cd(2+) , and Hg(2+) at sub-picomolar concentrations (∼10(-11) mol dm(-3) ) from aqueous media, including drinking water and a suspension of red blood cells. The acidic active acid sites of the pellets consist of heteroatoms arranged around uniformly shaped pores in 3D nanoscale gyroidal mesostructures densely coated with the chelating ligand. The sensor can be used in batch mode, as well as in a flow-through system in which sampling, target ion recognition and removal, and analysis are integrated in a highly automated and efficient manner. Because the pellets exhibit long-term stability, reproducibility, and versatility over a number of analysis/regeneration cycles, they can be expected to be useful for the fabrication of inexpensive sensor devices for naked-eye detection of toxic pollutants. 23240655 High performance multilayer MoS2 transistors with scandium contacts. While there has been growing interest in two-dimensional (2-D) crystals other than graphene, evaluating their potential usefulness for electronic applications is still in its infancy due to the lack of a complete picture of their performance potential. The focus of this article is on contacts. We demonstrate that through a proper understanding and design of source/drain contacts and the right choice of number of MoS(2) layers the excellent intrinsic properties of this 2-D material can be harvested. Using scandium contacts on 10-nm-thick exfoliated MoS(2) flakes that are covered by a 15 nm Al(2)O(3) film, high effective mobilities of 700 cm(2)/(V s) are achieved at room temperature. This breakthrough is largely attributed to the fact that we succeeded in eliminating contact resistance effects that limited the device performance in the past unrecognized. In fact, the apparent linear dependence of current on drain voltage had mislead researchers to believe that a truly Ohmic contact had already been achieved, a misconception that we also elucidate in the present article. 23479407 First-Line Management of EGFR-Mutated Advanced Lung Adenocarcinoma: Recent Developments. Gefitinib and erlotinib are small-molecule reversible tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR). Objective responses have been observed frequently in patients with non-small cell lung cancer (NSCLC) harbouring activating EGFR mutations, the most common being deletions in exon 19 and the exon 21 L858R mutation. EGFR mutations are prevalent in female patients, those who have never smoked, those of Asian ethnicity and those who have adenocarcinoma histology. Given the efficacy of EGFR TKIs in advanced NSCLC in the salvage setting, and their favourable toxicity profile compared with conventional chemotherapy, there is considerable interest in evaluating their efficacy in the first-line treatment of advanced NSCLC. To date, there have been several phase II and phase III studies that have examined the efficacy of first-line single-agent EGFR TKIs in unselected, clinically selected or molecularly selected populations. Here we review and compare the differences in these phase III trials. Most phase III trials chose progression-free survival (PFS) rather than overall survival (OS) as their primary endpoint. PFS was prolonged but OS was not. The recent development of novel irreversible EGFR TKIs, such as afatinib and dacomitinib, is also reviewed. 23453986 Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals. The thyroid hormone (TH) system is involved in several important physiological processes, including regulation of energy metabolism, growth and differentiation, development and maintenance of brain function, thermo-regulation, osmo-regulation, and axis of regulation of other endocrine systems, sexual behaviour and fertility and cardiovascular function. Therefore, concern about TH disruption (THD) has resulted in strategies being developed to identify THD chemicals (THDCs). Information on potential of chemicals causing THD is typically derived from animal studies. For the majority of chemicals, however, this information is either limited or unavailable. It is also unlikely that animal experiments will be performed for all THD relevant chemicals in the near future for ethical, financial and practical reasons. In addition, typical animal experiments often do not provide information on the mechanism of action of THDC, making it harder to extrapolate results across species. Relevant effects may not be identified in animal studies when the effects are delayed, life stage specific, not assessed by the experimental paradigm (e.g., behaviour) or only occur when an organism has to adapt to environmental factors by modulating TH levels. Therefore, in vitro and in silico alternatives to identify THDC and quantify their potency are needed. THDC have many potential mechanisms of action, including altered hormone production, transport, metabolism, receptor activation and disruption of several feed-back mechanisms. In vitro assays are available for many of these endpoints, and the application of modern '-omics' technologies, applicable for in vivo studies can help to reveal relevant and possibly new endpoints for inclusion in a targeted THDC in vitro test battery. Within the framework of the ASAT initiative (Assuring Safety without Animal Testing), an international group consisting of experts in the areas of thyroid endocrinology, toxicology of endocrine disruption, neurotoxicology, high-throughput screening, computational biology, and regulatory affairs has reviewed the state of science for (1) known mechanisms for THD plus examples of THDC; (2) in vitro THD tests currently available or under development related to these mechanisms; and (3) in silico methods for estimating the blood levels of THDC. Based on this scientific review, the panel has recommended a battery of test methods to be able to classify chemicals as of less or high concern for further hazard and risk assessment for THD. In addition, research gaps and needs are identified to be able to optimize and validate the targeted THD in vitro test battery for a mechanism-based strategy for a decision to opt out or to proceed with further testing for THD. 22616559 The first total synthesis of apigenin 7-O-β-D-cellobiosyl-4'-O-β-D-glucopyranoside isolated from Salvia uliginosa. The first total synthesis of apigenin 7-O-β-D-cellobioside (5) and apigenin 7-O-β-D-cellobiosyl-4'-O-β-D-glucopyranoside (8), which were isolated from petals of Salvia patens and Salvia uliginosa, were achieved in four and six steps and 76% and 57%, respectively, overall yield, from naringenin (1). The total synthesis contained two-glycosylation, acetylation, oxidation, selective deacetylation and deprotection steps. Although this route contained six steps, the targeted compounds were obtained with higher yields and easier purifications than other synthetic methods. 23266674 Inhibition of constitutive aryl hydrocarbon receptor (AhR) signaling attenuates androgen independent signaling and growth in (C4-2) prostate cancer cells. The aryl hydrocarbon receptor is a member of the basic-helix-loop-helix family of transcription factors. AhR mediates the biochemical and toxic effects of a number of polyaromatic hydrocarbons such as 2,3,7,8,-tetrachloro-dibenzo-p-dioxin (TCDD). AhR is widely known for regulating the transcription of drug metabolizing enzymes involved in the xenobiotic metabolism of carcinogens and therapeutic agents, such as cytochrome P450-1B1 (CYP1B1). Additionally, AhR has also been reported to interact with multiple signaling pathways during prostate development. Here we investigate the effect of sustained AhR signaling on androgen receptor function in prostate cancer cells. Immunoblot analysis shows that AhR expression is increased in androgen independent (C4-2) prostate cancer cells when compared to androgen sensitive (LNCaP) cells. RT-PCR studies revealed constitutive AhR signaling in C4-2 cells without the ligand induced activation required in LNCaP cells. A reduction of AhR activity by short RNA mediated silencing in C4-2 cells reduced expression of both AhR and androgen responsive genes. The decrease in androgen responsive genes correlates to a decrease in phosphorylated androgen receptor and androgen receptor expression in the nucleus. Furthermore, the forced decrease in AhR expression resulted in a 50% decline in the growth rate of C4-2 cells. These data indicates that AhR is required to maintain hormone independent signaling and growth by the androgen receptor in C4-2 cells. Collectively, these data provide evidence of a direct role for AhR in androgen independent signaling and provides insight into the molecular mechanisms responsible for sustained androgen receptor signaling in hormone refractory prostate cancer. 23200006 Detection of trace metal in distilled alcoholic drinks. The presence of trace metal cadmium assay was investigated with a copper immobilized on a graphite carbon electrode (GPC), the modified property of which was determined with handheld voltammetric systems. Following the determination of the analytical stripping conditions of 0.45 V amplitude, 30 Hz frequency, -1.4 V initial potential, and 4.0 mV increment potential, only a 60-s experimental accumulation time was used. Using these conditions, the analytical detection limit approached the nano range. At this condition, the analytical application was performed on distilled alcoholic drinks for food manufacturing systems. This developed technique is faster and less costly than the common voltammetric and spectrophotometric methods. 23419593 Temporal relationship between aquaporin-4 and glial fibrillary acidic protein in cerebellum of neonate and adult rats administered a BBB disrupting spider venom. Two astrocyte markers, the glial water channel aquaporin-4 (AQP4) and the glial fibrillary acidic protein (GFAP), have been implicated in several physiological and pathological conditions in the central nervous system (CNS) as well as in blood-brain barrier breakdown (BBBb). By color segmentation the immunoreactivity of both proteins, we demonstrate that the expression of AQP4 and GFAP was increased in the cerebellum of neonate (14-day-old, P14) and adult (8-week-old) rats administered Phoneutria nigriventer spider venom (PNV) known to cause perivascular edema, BBBb and convulsion. In the cerebellum's gray matter, PNV produced a major response, especially in the granular layer. Parallel increases in AQP4 and GFAP expression occurred 24 h after envenomation in the white matter of P14 and in the molecular layer of adults, as well as in the granular layer 2 h after envenomation. In the Purkinje layer there was a tendency of increased AQP4, for both, neonates (5 h), and adults (2 and 24 h). Moreover, PNV also provoked nonparallel upregulation of both markers with prevalence of upregulation of AQP 4 for P14 rats, and GFAP for adults. The major expression of both proteins was in the gray matter. The data indicates a venom effect in water/electrolyte balance in the cerebellum and the participation of AQP4 in these effects. Age-related and time-related regional differences probably reflect specificity in AQP4 distribution in different astrocytic membrane domains as well as its participation in K(+) buffering and neural activity. This study is the first to associate astrocytic AQP4 expression and reactive gliosis in a model of BBB permeability promoted by P. nigriventer venom. Our data provide compelling evidence that AQP4 expression was increased in the cerebellum of rats administered PNV. 23624289 Opioids and their receptors: Are we there yet? Opioids have an important place in pharmacology. While their clinical use as analgesics is fundamental in medicine, their use is constrained by their side-effects and abuse potential. Pharmacologists have sought analgesics lacking side-effects and the abuse liability of the current agents. The identification of the opioid receptors in 1973 marked the beginning of our understanding of the molecular mechanisms of these agents. The isolation of the opioid peptides quickly followed, along with the classification of three families of opioid receptors. Clinicians have long been aware of subtle differences among the mu opioids that were not easily reconciled with a single receptor and selective antagonists implied two subdivisions of mu receptors. However, the cloning of the mu opioid receptor MOR-1 has led to the realization of the extensive complexity of the mu opioid receptor gene and its vast array of splice variants. Many of these splice variants are truncated and do not conform to the structure of traditional G-protein coupled receptors. Yet, evidence now shows that they are quite important and may prove valuable targets in the development of potent analgesics lacking the undesirable properties of current opioids. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue' 23548974 Visual evoked potentials in children prenatally exposed to methylmercury. Prenatal exposure to methylmercury can cause both neurobehavioral deficits and neurophysiological changes. However, evidence of neurotoxic effects within the visual nervous system is inconsistent, possibly due to incomplete statistical adjustment for beneficial nutritional factors. We evaluated the effect of prenatal methylmercury exposure on visual evoked potential (VEP) latencies in Faroese children with elevated prenatal methylmercury exposure. A cohort of 182 singleton term births was assembled in the Faroe Islands during 1994-1995. At age 7 years, VEP tracings were obtained from 139 cohort subjects after exclusion of subjects with abnormal vision conditions. We used multiple regression analysis to evaluate the association of mercury concentrations in cord blood and maternal hair at parturition with VEP latencies after adjustment for potential confounders that included the cord-serum phospholipid concentration of n-3 polyunsaturated fatty acids (PUFAs) and the duration of breastfeeding. Unadjusted correlations between mercury exposure and VEP latencies were equivocal. Multiple regression models showed that increased mercury concentrations, especially in maternal hair, were associated with delayed latencies for VEP peak N145. After covariate adjustment, a delay of 2.22ms (p=0.02) was seen for each doubling of the mercury concentration in maternal hair. In agreement with neuropsychological findings, the present study suggests that prenatal methylmercury exposure may have an adverse effect on VEP findings despite the absence of clinical toxicity to the visual system. However, this association was apparent only after adjustment for n-3 PUFA status. 23536271 β-Ionone arrests cell cycle of gastric carcinoma cancer cells by a MAPK pathway. β-Ionone is an end ring analog of β-carotenoid which has been shown to possess potent anti-proliferative activity both in vitro and in vivo. To investigate the possible inhibitory effects of β-ionone, we studied cell growth characteristics, DNA synthesis, cell cycle progression, as well as mitogen-activated protein kinases (MAPKs) pathways in the human gastric adenocarcinoma cancer cell line (SGC-7901). Our results show that cell growth and DNA synthesis were inhibited, and the cell cycle was arrested at the G0/G1 phase in a dose-dependent manner in cells treated with β-ionone (25, 50, 100 and 200 μmol/L) for 24 h. We found that the β-ionone significantly decreased the extracellular signal-regulated kinase protein expression and significantly increased the levels of p38 and Jun-amino-terminal kinase protein expression (P < 0.01). β-Ionone also inhibited cell cycle-related proteins of Cdk4, Cyclin B1, D1 and increased p27 protein expression in SGC-7901 cells. These results suggested that the cell cycle arrest observed may be regulated through a MAPK pathway by transcriptional down-regulation of cell cycle proteins. These results demonstrate potent ability of β-ionone to arrest cell cycle of SGC-7901 cells and decrease proliferation. 23576297 "Raisin Bun"-Like Nanocomposites of Palladium Clusters and Porphyrin for Superior Formic Acid Oxidation. A novel "raisin bun"-like nanocomposite, where Pd clusters are embedded in porphyrin matrix, is developed as a promising electrocatalyst. Thanks to the synergy between the Pd clusters and the porphyrin matrix, this composite exhibits a low oxidation potential, high mass activity and excellent stability toward electrochemical oxidation of formic acid, which opens new routes for the design of high-performance catalysts in fuel cells. 23381951 Pharmacogenetics of Allopurinol-Making an Old Drug Safer. Allopurinol is a drug that has been used for decades to lower serum urate levels in patients with gout or chronic renal failure and in cancer patients undergoing chemotherapy at risk of tumor lysis syndrome. Patients may develop cutaneous hypersensitivity reactions, ranging from mild rashes to potentially fatal severe cutaneous adverse reactions (SCARs) namely drug hypersensitivity syndrome, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Recent studies have demonstrated the association between human leukocyte antigen (HLA) B*58:01 allele and allopurinol-induced SCARs, which might explain ethnic differences in their incidences. Genotyping is now required before starting abacavir and carbamazepine so as to identify individuals susceptible to SJS. However, no genetic screening is advocated before commencement of allopurinol. The lack of availability of a rapid and inexpensive screening test for the HLA-B*58:01 allele is one of the obstacles to such screening. Development of a test that is quick, accurate, and cost-effective is warranted. 23378608 Apelin inhibits diet-induced obesity by enhancing lymphatic and blood vessel integrity. Angiogenesis is tightly associated with the outgrowth of adipose tissue, leading to obesity, which is a risk factor for type 2 diabetes and hypertension, mainly because expanding adipose tissue requires an increased nutrient supply from blood vessels. Therefore, induction of vessel abnormality by adipokines has been well studied, whereas how altered vascular function promotes obesity is relatively unexplored. Also, surviving Prox1 heterozygous mice showed abnormal lymphatic patterning and adult-onset obesity, indicating that accumulation of adipocytes could be closely linked with lymphatic function. Here we propose a new anti-obesity strategy based on enhancement of lymphatic and blood vessel integrity with apelin. Apelin-knockout mice given a high-fat diet showed an obese phenotype associated with abnormal lymphatic and blood vessel enlargement. Fatty acids present in the high-fat diet induced hyperpermeability of endothelial cells, causing adipocyte differentiation, whereas apelin promoted vascular stabilization. Moreover, treatment of high-fat-diet-fed apelin-knockout mice with a selective cyclooxygenase-2 inhibitor, celecoxib, improved vascular function, and also attenuated obesity. Finally, apelin transgenic mice showed decreased subcutaneous adipose tissue owing to inhibition of high-fat-diet-induced hyperpermeability of vessels. These results indicate that apelin inhibits high-fat-diet-induced obesity by enhancing vessel integrity. Apelin could serve as a therapeutic target for treating obesity and related diseases. 23204325 Mitogen-inducible gene 6 triggers apoptosis and exacerbates ER stress-induced β-cell death. The increased insulin secretory burden placed on pancreatic β-cells during obesity and insulin resistance can ultimately lead to β-cell dysfunction and death and the development of type 2 diabetes. Mitogen-inducible gene 6 (Mig6) is a cellular stress-responsive protein that can negatively regulate the duration and intensity of epidermal growth factor receptor signaling and has been classically viewed as a molecular brake for proliferation. In this study, we used Mig6 heterozygous knockout mice (Mig6(+/-)) to study the role of Mig6 in regulating β-cell proliferation and survival. Surprisingly, the proliferation rate of Mig6(+/-) pancreatic islets was lower than wild-type islets despite having comparable β-cell mass and glucose tolerance. We thus speculated that Mig6 regulates cellular death. Using adenoviral vectors to overexpress or knockdown Mig6, we found that caspase 3 activation during apoptosis was dependent on the level of Mig6. Interestingly, Mig6 expression was induced during endoplasmic reticulum (ER) stress, and its protein levels were maintained throughout ER stress. Using polyribosomal profiling, we identified that Mig6 protein translation was maintained, whereas the global protein translation was inhibited during ER stress. In addition, Mig6 overexpression exacerbated ER stress-induced caspase 3 activation in vitro. In conclusion, Mig6 is transcriptionally up-regulated and resistant to global translational inhibition during stressed conditions in β-cells and mediates apoptosis in the form of caspase 3 activation. The sustained production of Mig6 protein exacerbates ER stress-induced β-cell death. Thus, preventing the induction, translation, and/or function of Mig6 is warranted for increasing β-cell survival. 23557931 Impact of longitudinal exposure to mycophenolic acid on acute rejection in renal-transplant recipients using a joint modeling approach. This study aimed to investigate the association between longitudinal exposure to mycophenolic acid (MPA) and acute rejection (AR) risk in the first year after renal transplantation, and to propose MPA exposure targets conditionally to this association. A joint model, adjusted for monitoring strategy (fixed-dose versus concentration-controlled) and recipient age, was developed; it combined a mixed-effects model to describe the whole pattern of MPA exposure (i.e. area under the concentration-time curve (AUC)) and a survival model. MPA AUC thresholds were determined using time-dependent receiver-operating characteristics (ROC) curves. Data from 490 adult renal-transplant recipients, representative of the general population of adult renal-transplant patients (i.e. including patients considered at low immunological risk-enrolled in the OPERA trial as well as second renal transplant and patients co-treated by either cyclosporine or tacrolimus), were analyzed. A significant association was found between the longitudinal exposure to MPA (MPA AUCs=f(t)) and AR (p=0.0081), and validated by bootstrapping. A significant positive correlation was observed between time post-transplantation and ROC thresholds which increased in average from 35mgh/L in the first days to 41mgh/L beyond six months post-transplantation (p<0.001). Using a new modeling approach which recognizes the repeated measures in a same patient, this study supports the association between MPA exposure and AR. 23576286 In Vitro and In Vivo Enzyme-Mediated Biomineralization of Oligo(poly(ethylene glycol) Fumarate Hydrogels. The enzyme alkaline phosphatase (ALP) is added at different concentrations (i.e., 0, 2.5, and 10 mg · ml(-1) ) to oligo(poly(ethylene glycol)fumarate) (OPF) hydrogels. The scaffolds are either incubated in 10 mM calcium glycerophosphate (Ca-GP) solution for 2 weeks or implanted in a rat subcutaneous model for 4 weeks. Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and alizarin red staining show a strong ability to form minerals exclusively in ALP-containing hydrogels in vitro. Additionally, the calcium content increases with increasing ALP concentration. Similarly, only ALP-containing hydrogels induce mineralization in vivo. Specifically, small (≈5-20 µm) mineral deposits are observed at the periphery of the hydrogels near the dermis/scaffold interface using Von Kossa and alizarin red staining. 23628621 Quality of Care of People With Type 2 Diabetes in Eight European Countries: Findings from the Guideline Adherence to Enhance Care (GUIDANCE) study. OBJECTIVESWe sought to determine levels of adherence in eight European countries to recommendations for the management of type 2 diabetes and to investigate factors associated with key intermediate outcomes.RESEARCH DESIGN AND METHODSGUIDANCE was a cross-sectional study including retrospective data extraction from the medical records of people with type 2 diabetes recruited, using a shared protocol, from primary and specialist care sites in the following eight European countries: Belgium, France, Germany, Italy, Ireland, Sweden, the Netherlands, and the United Kingdom. The dataset for analysis comprised 7,597 cases. Proportions meeting process and outcome criteria were determined, including between-country variations. Logistic regression was used to investigate potential predictors of meeting targets for HbA1c, blood pressure, and LDL cholesterol.RESULTSIn the total sample, adherence to process recommendations was high for some measures, for example, HbA1c recorded in past 12 months in 97.6% of cases. Target achievement for intermediate outcome measures was lower, with only 53.6% having HbA1c <7%. Considerable between-country variation was identified for both processes and outcomes. The following characteristics were associated with an increased likelihood of meeting targets for all three measures considered (HbA1c, blood pressure, LDL cholesterol): shorter diagnosis of diabetes; having one or more macrovascular complications; lower BMI; being prescribed lipid-lowering medication; and no current antihypertensive prescribing.CONCLUSIONSCompared with earlier reports, we have suggested some encouraging positive trends in Europe in relation to meeting targets for the management of people with type 2 diabetes, but there is still scope for further improvement and greater between-country consistency. 23122086 Sustainable production of pectin from lime peel by high hydrostatic pressure treatment. The application of high hydrostatic pressure technology for enzymatic extraction of pectin was evaluated. Cellulase and xylanase under five different combinations (cellulase/xylanase: 50/0, 50/25, 50/50, 25/50, and 0/50 U/g lime peel) at ambient pressure, 100 and 200 MPa were used to extract pectin from dried lime peel. Extraction yield, galacturonic acid (GalA) content, average molecular weight (M(w,ave)), intrinsic viscosity [η](w), and degree of esterification (DE) were compared to those parameters obtained for pectins extracted using acid and aqueous processes. Pressure level, type and concentration of enzyme significantly (p<0.05) influenced yield and DE of pectin. Enzyme and high pressure extraction resulted in yields which were significantly (p<0.05) higher than those using acid and aqueous extraction. Although pressure-induced enzymatic treatment improves pectin yield, it does not have any significant effect on M(w,ave) and [η](w) of pectin extracts indicating the potential of high pressure treatment for enzymatic pectin production as a novel and sustainable process. 23595692 Pine Oil Effects on Chemical and Thermal Injury in Mice and Cultured Mouse Dorsal Root Ganglion Neurons. A commercial resin-based pine oil (PO) derived from Pinus palustris and Pinus elliottii was the major focus of this investigation. Extracts of pine resins, needles, and bark are folk medicines commonly used to treat skin ailments, including burns. The American Burn Association estimates that 500,000 people with burn injuries receive medical treatment each year; one-half of US burn victims are children, most with scald burns. This systematic study was initiated as follow-up to personal anecdotal evidence acquired over more than 10 years by MH Bhattacharyya regarding PO's efficacy for treating burns. The results demonstrate that PO counteracted dermal inflammation in both a mouse ear model of contact irritant-induced dermal inflammation and a second degree scald burn to the mouse paw. Furthermore, PO significantly counteracted the tactile allodynia and soft tissue injury caused by the scald burn. In mouse dorsal root ganglion neuronal cultures, PO added to the medium blocked adenosine triphosphate-activated, but not capsaicin-activated, pain pathways, demonstrating specificity. These results together support the hypothesis that a pine-oil-based treatment can be developed to provide effective in-home care for second degree burns. Copyright © 2013 John Wiley & Sons, Ltd. 23320385 Inhibitory effect of anthocyanidins on hepatic glutathione S-transferase, UDP-glucuronosyltransferase and carbonyl reductase activities in rat and human. Abstract 1. Anthocyanins and their aglycone anthocyanidins represent the most abundant flavonoids in human diet and popular constituents of various dietary supplements. The aim of this study was to evaluate inhibitory effect of four anthocyanidins (delphinidin, cyanidin, malvidin and pelargonidin) on three families of important drug-metabolizing enzymes: carbonyl reductases (CBRs), glutathione S-transferases (GSTs) and UDP-glucuronosyltransferases (UGT). 2. Human or rat hepatic subcellular fractions were incubated with or without pure anthocyanidins (100 µM) and the activities of CBR, GST and UGT were assayed using menadione, 1-chloro-2,4-dinitrobenzene and p-nitrophenol as substrates, respectively. For the most potent inhibitors, half maximal inhibitory concentrations (IC(50)) were determined and the inhibition kinetics study was performed. 3. Anthocyanidins inhibited weakly the activity of GST and moderately the activities of CBR and UGT. Cyanidin was the most potent inhibitor of human UGT with IC(50) = 69 µM (at 200 µM substrate concentration) and competitive type of action. Delphinidin acted as significant non-competitive inhibitor of human CBR with IC(50) = 16 µM (at substrate concentration 500 µM). The inhibitory potency of anthocyanidins differed in rat and human samples significantly. 4. Anthocyanidins are able to inhibit CBR and UGT in vitro. Possible interference of anthocyanidins (in high-dose dietary supplements) with simultaneously administered drugs, which are UGT or CBR substrates, should be checked. 23480279 Experimental and computational study of the interaction of novel colchicinoids with a recombinant human αI/βI-tubulin heterodimer. The binding free energies on human tubulin of selected colchicine and thiocolchicine compounds were determined. Two methods were used for the determination of binding free energies. One is based on theoretical prediction simulating the dissociation of the compound from tubulin using a series of molecular dynamics simulations. The other method involved a series of experiments that measured the affinity of the compound on a synthetically expressed and purified tubulin protein using a spectrofluorometric technique. © 2013 John Wiley & Sons A/S. 23357629 Design, synthesis, characterization and anti-inflammatory evaluation of novel pyrazole amalgamated flavones. A series of novel pyrazole amalgamated flavones has been designed and synthesized from 1-methyl-5-(2,4,6-trimethoxy-phenyl)-1H-pyrazole 6. The structures of regioisomers 6 and 7 were resolved by 2D (1)H-(1)H COSY, (1)H-(13)C HSQC and (1)H-(13)C HMBC experiments. The newly synthesized compounds were tested for their in vitro COX inhibition and in vivo carrageenan induced hind paw edema in rats and acetic acid induced vascular permeability in mice. Although the compounds have inhibitory profile against both COX-1 and COX-2, some of the compounds are found to be selective against COX-2, supported by inhibition of paw edema and vascular permeability. Docking studies were also carried out to determine the structural features which sway the anti-inflammatory activity of the tested compounds. The keto and phenolic -OH are major factors that are prominently involved in interaction with COX-2 active site. 23061635 Menthol--pharmacology of an important naturally medicinal "cool". Menthol, a natural product of the peppermint plant Mentha x piperita (Lamiaceae), is a monoterpene which is widely used as a natural product in cosmetics, a flavoring agent, and as an intermediate in the production of other compounds. Various extracts from peppermint contain menthol as a major active constituent and have been used for centuries as traditional medicines for a number of ailments including infections, insomnia, and irritable bowel syndrome as well as an insect repellent. Menthol's characteristic cooling sensation is due, in part, to the activation of sensory neurons generally termed transient receptor potential (TRP) channels, in particular transient receptor potential melastatin family member 8 (TRPM8) and transient receptor potential subfamily A, member 1 (TRPA1). Menthol acts upon TRPM8 receptors by rapidly increasing intracellular calcium and mobilizing calcium flux through the channels to induce cold response signals at the application site. Aside from its cold-inducing sensation capabilities, menthol exhibits cytotoxic effects in cancer cells, induces reduction in malignant cell growth, and engages in synergistic excitation of GABA receptors and sodium ion channels resulting in analgesia. Notwithstanding its plethora of benefits, menthol's coldsensitivity response mechanism has been shown to inhibit mucosal recognition of nicotine and cigarette toxins common in mentholated cigarette brands thus potentially leading to toxic effects. Menthol may prove a valuable lead structure for the synthesis of drugs that target multiple receptors involved with a number of pharmacological effects. 22977168 CTNNA3 (α-catenin) gene variants are associated with diisocyanate asthma: a replication study in a caucasian worker population. Recently, a genome-wide association study (GWAS) conducted in Korean subjects identified four CTNNA3 (alpha-T catenin) single nucleotide polymorphisms (SNPs) (rs10762058, rs7088181, rs1786929, and rs4378283) associated with diisocyanate-induced occupational asthma (DA). The CTNNA3 gene codes for a cadherin involved in formation of stretch-resistant cell-cell adhesions. We conducted a candidate gene association study to replicate these findings in Caucasian workers. Genotyping was performed on DNA using a 5' nuclease PCR assay collected from 410 diisocyanate-exposed and predominantly Canadian workers including 132 workers with DA confirmed by a specific inhalation challenge (DA+); 131 symptomatic workers in whom DA was excluded by a negative challenge (DA-); and 147 hexamethylene diisocyanate-exposed asymptomatic workers (AWs). As in the Korean study, highly linked CTNNA3 rs7088181 and rs10762058 SNPs (but not rs4378283 and rs1786929) were significantly associated with DA+ when compared with AWs but not in comparison with DA- workers (p ≤ 0.05). After adjusting for potentially confounding variables of age, smoking status, and duration of exposure, minor allele homozygotes of rs7088181 and rs10762058 SNPs were at increased risk for DA compared with AWs (OR = 9.05 [95% CI: 1.69, 48.54] and OR = 6.82 [95% CI: 1.65, 28.24], respectively). In conclusion, we replicated results from the only reported GWAS study of DA demonstrating an association between two closely linked CTNNA3 gene SNPs and DA. These findings lend further support to the clinical relevance of these genotypes in predicting susceptibility to DA and the potential importance of catenins in the disease process. 23311754 Cucumber-like V2O5/poly(3,4-ethylenedioxythiophene)&MnO2 nanowires with enhanced electrochemical cyclability. Inspired by the cucumber-like structure, by combining the in situ chemical oxidative polymerization with facile soaking process, we designed the heterostructured nanomaterial with PEDOT as the shell and MnO(2) nanoparticles as the protuberance and synthesized the novel cucumber-like MnO(2) nanoparticles enriched vanadium pentoxide/poly(3,4-ethylenedioxythiophene) (PEDOT) coaxial nanowires. This heterostructured nanomaterial exhibits enhanced electrochemical cycling performance with the decreases of capacity fading during 200 cycles from 0.557 to 0.173% over V(2)O(5) nanowires at the current density of 100 mA/g. This method is proven to be an effective technique for improving the electrochemical cycling performance and stability of nanowire electrodes especially at low rate for application in rechargeable lithium batteries. 23436555 Weak-field, multiple-cycle carrier envelope phase effects in laser excitation. Although the absolute or carrier envelope phase (CEP) of a laser pulse is usually assumed to be effective for ultrashort and/or ultrastrong pulses only, it is demonstrated that these limitations can eventually be removed. Therefore, the excitation of a model positively charged homonuclear diatomic molecule, in which four electronic states are coupled by the laser field, is studied. In an initial step, nuclear wave packets in two dissociative states are prepared. Upon reaching the fragment channel, a weak pulse interacts with the system and prepares CEP-dependent asymmetries associated with electron density localized on one or the other fragmentation product. 23354391 Safety evaluation of daidzein in laying hens: part II. Effects on calcium-related metabolism. Daidzein, an estrogen-like product, has become increasingly popular as a dietary supplement, particularly for postpeak-estrus animals seeking a safe natural alternative to play a role of estrogen. However, there is little available safety data of it for raisers and consumers. A subchronic laying hensafety study has been conducted to examine if the high-dose daidzein could affect calcium-related metabolism (eggshell quality and bone mineralization). Seven hundred and sixty-eight 56-week-old Hyline Brown were randomly assigned to 4 groups with 8 replicates of 24 birds each (192 laying hensper group) and 3weeks later fed diets supplemented with 0(control), 10, 50 and 100mg of daidzein/kg for 12week. Eggshell thickness, eggshell percentage, eggshell strength, eggshell Ca concentration was increased linearly with increasing dietary daidzein supplementation (P=0.001, P=0.007, P=0.002 and P=0.000, respectively). Serum Ca increased linearly with increasing dietarydaidzein supplementation (P=0.042), and serum P showed a significant quadratic response to dietarydaidzein supplementation (P=0.036). Bone ash and bone Ca were significantly influenced by dietarydaidzein supplementation (P<0.05). These findings indicate that daidzein hold no observed adverse effect on calcium metabolism, but also a safe and effective food additive for calcium metabolism in animals and humans. 23402971 RP TLC data in correlation studies with in silico pharmacokinetic properties of benzimidazole and benztriazole derivatives. Reversed-phase thin-layer chromatographic (RP TLC) retention constants for a newly designed series benzimidazole/benztriazole with expected biological activity were determined as parameters of their lipophilicity and this series was recognized as congeneric. Pharmacokinetic descriptors of the compounds investigated were calculated in silico with the use of the established drug design software. The bioactivity descriptors, which are assumed to predicted drug absorption, distribution, metabolism, elimination and toxicity (ADMETox) in humans, were correlated with retention constants and good statistical parameters were obtained. Multiple regression analysis which was introduced suggested that the absorption through different epithelial membranes (intestinal, blood-brain or erythrocyte membrane) and distribution process depend on retention constants (as measure of lipophilicty) and total polar surface area and molar weight/volume of the analyte. Finally, the compounds with halogen substituent (compounds A4/A7 and A5/A8 in Table 1), were suggested as the best drug candidates, because of their predicted proper pharmacokinetics and have been proposed for further biological tests. 23511022 Photosensitized protein damage by dimethoxyphosphorus(V) tetraphenylporphyrin. For the purpose of the basic study of photodynamic therapy, the activity of the water-soluble P(V)porphyrin, dimethoxyP(V)tetraphenylporphyrin chloride (DMP(V)TPP), on photosensitized protein damage was examined. The quantum yield of singlet oxygen generation by DMP(V)TPP (0.64) was comparable with that of typical porphyrin photosensitizers. Absorption spectrum measurement demonstrated the binding interaction between DMP(V)TPP and human serum albumin, a water-soluble protein. Photo-irradiated DMP(V)TPP damaged the amino acid residue of human serum albumin, resulting in the decrease of the fluorescence intensity from the tryptophan residue of human serum albumin. A singlet oxygen quencher, sodium azide, could not completely inhibit the damage of human serum albumin, suggesting that the electron transfer mechanism contributes to protein damage as does singlet oxygen generation. The decrease of the fluorescence lifetime of DMP(V)TPP by human serum albumin supported the electron transfer mechanism. The estimated contribution of the electron transfer mechanism is 0.64. These results suggest that the activity of DMP(V)TPP can be preserved under lower oxygen concentration condition such as tumor. 23411212 Vitamin D and 25-hydroxyvitamin D determination in meats by LC-IT-MS. This paper reports a method for the rapid, sensitive and simultaneous analysis of vitamin D (Vit D) and 25-hydroxyvitamin D (25OH-Vit D) in meats. Samples were saponified and underwent solid phase extraction with analysis by normal phase liquid chromatography (LC) with ion trap mass spectroscopy (IT-MS), using positive polarity atmospheric pressure chemical ionisation (APCI). Limits of detection (LOD) and quantification (LOQ) for Vit D and 25OH-Vit D were 0.03 and 0.05 μg/100g respectively. Deuterium labelled Vit D and 25OH-Vit D internal standards were added as surrogates prior to saponification, correcting for extraction inefficiencies and potential MS matrix enhancement or suppression effects. Recoveries using internal/surrogate standard correction ranged from 80% to 100% for all vitamers. Measurement uncertainty ranged from 6% to 15% for all vitamers in this method. This process required only 7.5 g of sample per extraction and a batch of 28 extractions could be completed in six hours. 23360412 Bioactivation of the nasal toxicant 2,6-dichlorobenzonitrile: an assessment of metabolic activity in human nasal mucosa and identification of indicators of exposure and potential toxicity. The herbicide 2,6-dichlorobenzonitrile (DCBN) is a potent nasal toxicant in rodents; however, it is not known whether DCBN causes similar nasal toxicity in humans. The tissue-selective toxicity of DCBN in mouse nasal mucosa is largely dependent on target tissue bioactivation by CYP2A5. The human orthologues of CYP2A5, CYP2A6 and CYP2A13, are both expressed in nasal mucosa and are capable of activating DCBN. In this study, we directly determined the ability of human nasal mucosa to bioactivate DCBN. We also tested the suitability of a glutathione conjugate of DCBN (GS-DCBN) or its derivatives as biomarkers of DCBN exposure and nasal toxicity in mouse models. We found that human fetal nasal mucosa microsomes catalyze the formation of GS-DCBN, with a Km value comparable to that of adult mouse nasal mucosa microsomes. The activity of the human nasal mucosa microsomes was inhibited by 8-methoxypsoralen, a known CYP2A inhibitor. GS-DCBN and its metabolites were detected in the nasal mucosa and nasal-wash fluid obtained from DCBN-treated mice, in amounts that increased with escalations in DCBN dose, and they were all still detectable at 24 h after a DCBN treatment (at 10 mg/kg). Further studies in Cyp2a5-null mice indicated that GS-DCBN and its metabolites in nasal-wash fluid were generated in the nasal mucosa, rather than in other organs. Thus, our data indicate for the first time that the human nasal mucosa is capable of bioactivating DCBN and that GS-DCBN and its metabolites in nasal-wash fluid may collectively serve as indicators of DCBN exposure and potential nasal toxicity in humans. 23392606 Large-scale and highly efficient synthesis of micro- and nano-fibers with controlled fiber morphology by centrifugal jet spinning for tissue regeneration. PLLA fibrous tissue scaffolds with controlled fiber nanoscale surface roughness are fabricated with a novel centrifugal jet spinning process. The centrifugal jet spinning technique is a highly efficient synthesis method for micron- to nano-sized fibers with a production rate up to 0.5 g min(-1). During the centrifugal jet spinning process, a polymer solution jet is stretched by the centrifugal force of a rotating chamber. By engineering the rheological properties of the polymer solution, solvent evaporation rate and centrifugal force that are applied on the solution jet, polyvinylpyrrolidone (PVP) and poly(l-lactic acid) (PLLA) composite fibers with various diameters are fabricated. Viscosity measurements of polymer solutions allowed us to determine critical polymer chain entanglement limits that allow the generation of continuous fiber as opposed to beads or beaded fibers. Above a critical concentration at which polymer chains are partially or fully entangled, lower polymer concentrations and higher centrifugal forces resulted in thinner fibers. Etching of PVP from the PLLA-PVP composite fibers doped with increasing PVP concentrations yielded PLLA fibers with increasing nano-scale surface roughness and porosity, which increased the fiber hydrophilicity dramatically. Scanning electron micrographs of the etched composite fibers suggest that PVP and PLLA were co-contiguously phase separated within the composite fibers during spinning and nano-scale roughness features were created after the partial etching of PVP. To study the tissue regeneration efficacy of the engineered PLLA fiber matrix, human dermal fibroblasts are used to simulate partial skin graft. Fibers with increased PLLA surface roughness and porosity demonstrated a trend towards higher cell attachment and proliferation. 23329180 Targeting RET to induce medullary thyroid cancer cell apoptosis: an antagonistic interplay between PI3K/Akt and p38MAPK/caspase-8 pathways. Mutations in REarranged during Transfection (RET) receptor tyrosine, followed by the oncogenic activation of RET kinase is responsible for the development of medullary thyroid carcinoma (MTC) that responds poorly to conventional chemotherapy. Targeting RET, therefore, might be useful in tailoring surveillance of MTC patients. Here we showed that theaflavins, the bioactive components of black tea, successfully induced apoptosis in human MTC cell line, TT, by inversely modulating two molecular pathways: (i) stalling PI3K/Akt/Bad pathway that resulted in mitochondrial transmembrane potential (MTP) loss, cytochrome-c release and activation of the executioner caspases-9 and -3, and (ii) upholding p38MAPK/caspase-8/caspase-3 pathway via inhibition of Ras/Raf/ERK. Over-expression of either constitutively active myristoylated-Akt-cDNA (Myr-Akt-cDNA) or dominant-negative-caspase-8-cDNA (Dn-caspase-8-cDNA) partially blocked theaflavin-induced apoptosis, while co-transfection of Myr-Akt-cDNA and Dn-caspase-8-cDNA completely eradicated the effect of theaflavins thereby negating the possibility of existence of other pathways. A search for the upstream signaling revealed that theaflavin-induced disruption of lipid raft caused interference in anchorage of RET in lipid raft that in turn stalled phosphorylation of Ras and PI3Kinase. In such anti-survival cellular micro-environment, pro-apoptotic signals were triggered to culminate into programmed death of MTC cell. These findings not only unveil a hitherto unexplained mechanism underlying theaflavin-induced MTC death, but also validate RET as a promising and potential target for MTC therapy. 23335034 Mineralization of phenanthrene sorbed on multiwalled carbon nanotubes. Carbon nanotubes have attracted attention around the world because of their high sorption capacity for hydrophobic organic compounds (HOCs); however, the bioavailability of HOCs sorbed on carbon nanotubes to bacteria is not well known. In the present study, (14) C-labeled and unlabeled phenanthrene was spiked onto four kinds of multiwalled carbon nanotubes (MWCNTs) and aged for 60 d, and the mineralization of phenanthrene sorbed on MWCNTs was studied. The mineralization efficiencies of phenanthrene sorbed on the four kinds of MWCNTs were 2.38, 8.84, 23.88, and 31.47%, respectively, after incubation for 35 d, which were positively correlated with the sum of fast and slow desorption fractions of phenanthrene (p < 0.05). The authors found that the mineralization efficiencies agreed well with the MWCNT properties; the increasing specific surface area and mesopore and micropore volume of MWCNTs caused a significant decrease in the mineralization efficiency of phenanthrene (p < 0.05). After incubation for 35 d, the density of bacteria had a significant positive correlation with both the desorption and the mineralization efficiencies. The authors inferred that, although MWCNTs might have toxic effects on the bacteria, the biodegrading ability of bacteria might not decrease significantly under the influence of MWCNTs with low surface area. 23181488 Conformational landscape of diisopropyl ketone: quantum chemical calculations validated by microwave spectroscopy. We report on the gas-phase structure of the most abundant conformer of diisopropyl ketone, (CH(3))(2)HC-CO-CH(CH(3))(2), as observed by molecular beam Fourier transform microwave spectroscopy. The gas-phase structures of five conformers of diisopropyl ketone were optimized using ab initio calculations at the MP2/6-311++G(d,p) level of theory. The natures of the stationary points were verified using harmonic frequency calculations. The only conformer observed in the supersonic jet possesses C(2) symmetry and appears as an enantiomeric pair. From the microwave spectrum, a set of three highly accurate rotational constants, five centrifugal distortion constants, and three sextic centrifugal distortion constants were determined. The structure of the observed conformer was optimized again at different levels of theory using the HF, MP2, and B3LYP methods. The theoretical constants of the C(2) conformer were subsequently validated using the experimental constants. To understand the transitions of one conformer to the others, the isopropyl groups were rotated against each other. The resulting two-dimensional potential energy surface shows nicely the symmetry of the conformational landscape and also indicates the enantiomeric pairs of the conformers. The barriers to internal rotation of the methyl groups were determined to be 1052 and 905 cm(-1) at the MP2/6-311++G(d,p) and the B3LYP/6-311++G(d,p) levels, respectively. In agreement with the theoretical predictions, no internal rotation patterns could be observed in the microwave spectrum. 23323691 Bioactive carboxylic acids from Lysimachia clethroides. Six new carboxylic acids (1-6), together with 11 known ones (7-17), were isolated from the aerial parts of Lysimachia clethroides. Their structures were elucidated on the basis of spectroscopic analysis and chemical evidence. Five new carboxylic acids (1 and 3-6) were evaluated for their in vitro inhibitory activity against aldose reductase. 23296950 Chrysin and Luteolin Attenuate Diabetes-Induced Impairment in Endothelial-Dependent Relaxation: Effect on Lipid Profile, AGEs and NO Generation. Chrysin and luteolin are two important plant flavonoids. In the present study, we hypothesized that they protect against deleterious vascular effects of diabetes. Diabetes was induced in rats by streptozotocin (STZ) injection, while chrysin and luteolin were administered two weeks after STZ administration for 6 weeks. Then, blood pressure (BP) and serum levels of glucose, advanced glycation end products (AGEs), triglycerides (TGs), total cholesterol and low density lipoprotein-cholesterol (LDL-C) were determined. Concentration response curves for KCl, phenylephrine (PE), acetylcholine (ACh) and ACh-induced NO generation were obtained in isolated aorta. Compared with control, diabetes increased diastolic and systolic BP, while chrysin and luteolin attenuated diastolic BP elevation without affecting the developed hyperglycemia. Diabetes increased contractile response of aorta to KCl, PE, decreased relaxation response to ACh, while chrysin and luteolin prevented the impaired response to ACh. In addition, diabetes was accompanied by elevated levels of TGs, total and LDL cholesterol, while both chrysin and luteolin prevented this dyslipidemia. Furthermore, chrysin decreased the elevated AGEs level in serum of diabetic animals, while luteolin abrogated the impaired NO generation in diabetic aorta. Collectively, chrysin and luteolin attenuate diabetes-evoked impairment in endothelial-dependent relaxation possibly via ameliorating detrimental changes in lipid profile, AGEs and NO generation. Copyright © 2013 John Wiley & Sons, Ltd. 22887768 Microfabricated nanotopological surfaces for study of adhesion-dependent cell mechanosensitivity. Cells exhibit high sensitivity and diverse responses to the intrinsic nanotopography of the extracellular matrix through their nanoscale cellular sensing machinery. A simple microfabrication method for precise control and spatial patterning of the local nanoroughness on glass surfaces by using photolithography and reactive ion etching is reported. It is demonstrated that local nanoroughness as a biophysical cue could regulate a diverse array of NIH/3T3 fibroblast behaviors, including cell morphology, adhesion, proliferation, migration, and cytoskeleton contractility. The capability to control and further predict cellular responses to nanoroughness might suggest novel methods for developing biomaterials mimicking nanotopographic structures in vivo for functional tissue engineering. 23409716 Transient receptor potential channels - emerging novel drug targets for the treatment of pain. In mammals several members of the Transient Receptor Potential channel family (TRPs), expressed mainly in the sensory neurons and skin keratinocytes, are implicated in relevant physiological functions, including thermosensation,nociception and vision. Since the TRPV1-4, TRPA1 and TRPM8 channels from this family play a pivotal role in both the detection and possibly modulation of painful stimuli, they are regarded as a very promising target of novel analgesic drugs. A few agents acting at TRPs, such as capsaicin or menthol, have a long history of their application as analgesics,whereas others (e.g. SB705498, JTS653, JNJ17203212, AP18, A967079, Chembridge-5861528 or PBMC) are currently being evaluated both in animals and in humans. In this review we discuss pain physiology, as well as the pharmacological properties of the TRPs involved in pain detection as potential critical peripheral analgesic targets. We present one of the most relevant strategies in the search for novel analgesic drugs, namely the TRP channels and their ligands, both agonists and antagonists as potential novel therapeutics for inflammatory and neuropathic pain syndromes. The safety profile of these agents, in particular their impact on thermosensation, is also discussed below. 23497867 AKT signalling and mitochondrial pathways are involved in mushroom polysaccharide-induced apoptosis and G1 or S phase arrest in human hepatoma cells. This study describes molecular mechanisms for inhibiting tumour cell proliferation using polysaccharides from medicinal mushrooms in human hepatoma cells. The results show that regarding cell cycle-related proteins, three types of polysaccharides significantly enhance the expression of p27(Kip) in HepG2 and Bel-7404 cells, while suppressing the activity of cyclin D1/CDK4 and/or cyclin E/CDK2. Considering apoptosis-related factors, the polysaccharides suppressed AKT activity through the inhibition of AKT phosphorylation at Thr(308) and/or Ser(473). The growth of HepG2 and Bel-7404 cells was suppressed by the up-regulation of a subunit of PI3K and phospho-PTEN, which are modulators of AKT activity. The polysaccharides also activated the mitochondria-mediated apoptosis pathway by stimulating the activation of Bcl-2 family proteins to release cytochrome c and Smac and cleave caspase-9 and caspase-3 in HepG2 and Bel-7404 cells. These factors have a potent effect on cell cycle arrest in G(1) and/or S phase and induce apoptosis in HepG2 and Bel-7404 cells. 23427088 In vivo overexpression of tissue-nonspecific alkaline phosphatase increases skeletal mineralization and affects the phosphorylation status of osteopontin. Functional ablation of tissue-nonspecific alkaline phosphatase (TNAP) (Alpl(-/-) mice) leads to hypophosphatasia, characterized by rickets/osteomalacia attributable to elevated levels of extracellular inorganic pyrophosphate, a potent mineralization inhibitor. Osteopontin (OPN) is also elevated in the plasma and skeleton of Alpl(-/-) mice. Phosphorylated OPN is known to inhibit mineralization, however, the phosphorylation status of the increased OPN found in Alpl(-/-) mice is unknown. Here, we generated a transgenic mouse line expressing human TNAP under control of an osteoblast-specific Col1a1 promoter (Col1a1-Tnap). The transgene is expressed in osteoblasts, periosteum, and cortical bones, and plasma levels of TNAP in mice expressing Col1a1-Tnap are 10-20 times higher than those of wild-type mice. The Col1a1-Tnap animals are healthy and exhibit increased bone mineralization by microCT analysis. Crossbreeding of Col1a1-Tnap transgenic mice to Alpl(-/-) mice rescues the lethal hypophosphatasia phenotype characteristic of this disease model. Osteoblasts from [Col1a1-Tnap] mice mineralize better than non-transgenic controls and osteoblasts from [Col1a1-Tnap(+/-) ; Alpl(-/-) ] mice are able to mineralize to the level of Alpl(+/-) heterozygous osteoblasts, while Alpl(-/-) osteoblasts show no mineralization. We found that the increased levels of OPN in bone tissue of Alpl(-/-) mice are comprised of phosphorylated forms of OPN while WT and [Col1a1-Tnap(+/-) ; Alpl(-/-) ] mice had both phosphorylated and dephosphorylated forms of OPN. OPN from [Col1a1-Tnap] osteoblasts were more phosphorylated than non-transgenic control cells. Titanium dioxide-liquid chromatography and tandem mass spectrometry analysis revealed that OPN peptides derived from Alpl(-/-) bone and osteoblasts yielded a higher proportion of phosphorylated peptides than samples from WT mice, and at least two phosphopeptides, p(S(174) FQVS(178) DEQY(182) PDAT(186) DEDLT(191) )SHMK and FRIp(S(299) HELES(304) S(305) S(306) S(307) )EVN, with one non-localized site each, appear to be preferred sites of TNAP action on OPN. Our data suggest that the pro-mineralization role of TNAP may be related not only to its accepted pyrophosphatase activity but also to its ability to modify the phosphorylation status of OPN. © 2013 American Society for Bone and Mineral Research. 23561138 Enzyme-assisted extraction of bioactive compounds from ginger (Zingiber officinale Roscoe). Ginger (Zingiber officinale R.) is a popular spice used in various foods and beverages. 6-Gingerol is the major bioactive constituent responsible for the antiinflammatory, antitumour and antioxidant activities of ginger. The effect of application of α-amylase, viscozyme, cellulase, protease and pectinase enzymes to ginger on the oleoresin yield and 6-gingerol content has been investigated. Pre-treatment of ginger with α-amylase or viscozyme followed by extraction with acetone afforded higher yield of oleoresin (20%±0.5) and gingerol (12.2%±0.4) compared to control (15%±0.6 oleoresin, 6.4%±0.4 gingerol). Extraction of ginger pre-treated with enzymes followed by extraction with ethanol provided higher yield of gingerol (6.2-6.3%) than the control (5.5%) with comparable yields of the oleoresin (31-32%). Also, ethanol extract of cellulase pre-treated ginger had the maximum polyphenol content (37.5mg/g). Apart from 6-gingerol, 6-paradol along with 6- and 8-methyl shogaols were the other important bio-active constituents in the oleoresin from cellulase-treated ginger. 23436266 Clinical risk factors for adverse events in allopurinol users. Allopurinol, one of the most commonly used uric acid-lowering agents, can cause serious adverse events. To investigate the risk factors for allopurinol-induced adverse events, the authors enrolled 94 patients who developed allopurinol-induced adverse events and 378 controls who were randomly chosen from 1934 patients who used allopurinol but did not develop any adverse events in this retrospective case control study. Univariate analysis showed that patients who developed allopurinol-induced adverse events had more chronic kidney disease (46% vs 30%, P = .005), more hypertension (42% vs 30%, P = .036), less tumor lysis syndrome (P = .030), higher cholesterol (P = .013), and lower aspartate aminotransferase (P = .002) and alanine aminotransferase levels (P = .033) and more commonly used angiotensin receptor blockers (27% vs 15%, P = .007), colchicines (16% vs 5%, P = .010), or statins (19% vs 8%, P = .002) than those who did not. In multiple logistic regression analysis, the use of colchicines (odds ratio, 3.11; 95% confidence interval, 1.28-7.58; P = .012) and statins (2.10; 1.03-4.25; P = .041) was an independent risk factor predicting adverse events in allopurinol users. In conclusion, patients who use colchicine or statins are at significant risk for developing allopurinol-induced adverse events. 23613012 HDL Cholesterol Subfractions and the Effect of Testosterone Replacement in Hypogonadism. Metabolic disorders and cardiovascular events are increased in hypogonadism. Serum HDL composition is a better cardiovascular predictor than the HDL counts. However, there is no information about the HDL subfractions in patients with hypogonadism. We designed a prospective study to investigate the HDL subfractions in treatment naïve subjects with hypogonadism and the effects of 2 different testosterone replacement regimens on the HDL subfractions. Seventy young male patients with congenital hypogonadotropic hypogonadism (CHH) and 70 age and BMI-matched healthy males were enrolled in the present study. The patients were assigned to receive intramuscular injections of testosterone esters 250 mg every 3 weeks and transdermal testosterone applications 50 mg daily. Biochemical investigations including HDL subfractions and insulin resistance were done. Patients with CHH had higher levels of insulin, HOMA-IR, WC, triglyceride, and diastolic blood pressure. Although, the HDL cholesterol concentrations were similar in both groups, hypogonadal patients had lower HDL2 and higher HDL3 levels. The total testosterone levels were independent determinants of the HDL2 subfractions. During the follow-up, a significant increase in the BMI and WC values and a significant decrease in the levels of total cholesterol, HDL cholesterol, and HDL3 were observed. No difference was present between the 2 treatment arms. These results show that patients with hypogonadism have unfavorable HDL compositions in addition to the other dysmetabolic features. However, testosterone replacement for about six months neither improves the metabolic problems nor the HDL composition. Mechanistic studies are warranted to better understand the cardiovascular effects of unfavorable HDL compositions in hypogonadism. 23194544 Determination of acrylamide in local and commercial cultivar of potatoes from biological farm. This paper reports the results of a preliminary study on the characterization of parameters influencing formation of acrylamide in fried potatoes, from biological cultivation. The formation of acrylamide was investigated in relation to frying in biological extra virgin olive oil and commercial seed oil. Three different cultivars (Rossa di Colfiorito, Quarantina bianca genovese and Kennebec) were chosen. Asparagine, glucose, fructose and sucrose concentrations were determined in potato slice before frying, while acrylamide content was analysed by LC-ESI-MS/MS in the slices fried in seed and extra virgin olive oil. The Kennebec cultivar showed differences in its potential for acrylamide formation, which was primarily related to its relatively high asparagine and reducing sugars contents, respect the other local cultivars (particulary Quarantina). Values of acrylamide below detection limit (LOD) were found in Quarantina bianca genovese cultivar samples fried in extra virgin olive oil and peanuts seed oil and higher in peanuts seed oil fried potatoes of Kennebec cultivar. 23001627 Levothyroxine replacement therapy with vitamin E supplementation prevents oxidative stress and cognitive deficit in experimental hypothyroidism. Hypothyroidism has a variety of adverse effects on cognitive function. The treatment of levothyroxine alone cannot restore cognitive defects of hypothyroid patients. Antioxidant vitamin E supplementation could be useful in disturbances which are associated with oxidative stress and could effectively slow the progression of Alzheimer disease. Thus, the purpose of this study was to evaluate oxidative stress status of the serum and hippocampus in hypothyroidism and to examine the effects of levothyroxine replacement therapy with vitamin E supplementation on cognitive deficit. Sprague-Dawley rats were randomly divided into five groups: control group, PTU group, PTU + Vit E group, PTU + L-T4 group, and PTU + L-T4 + Vit E group. Serum and hippocampus malondialdehyde (MDA) levels were determined using the thiobarbituric-acid reactive substances method. Serum and hippocampus superoxide dismutase (SOD) levels were determined by measuring its ability to inhibit the photoreduction of nitroblue tetrazolium. Learning and memory was assessed by Morris water maze test. In the present study, we found that the rats of PTU + Vit E group spent less time to find the platform on days 2, 3, 4, and 5 than the PTU group. Moreover, the rats of PTU + L-T4 + Vit E group spent less time to find the platform on days 4 and 5 than the PTU + L-T4 group. The time spent in the target quadrants was measured in the probe test and no difference was observed in all groups. Oxidative damage has been observed in the serum and hippocampus of hypothyroidism rat. SOD levels of serum and hippocampus tissue were significantly increased and MDA levels were significantly decreased in the PTU + Vit E and PTU + L-T4 + Vit E groups than the PTU and PTU + L-T4 groups. Therefore, these findings indicate that levothyroxine replacement therapy with vitamin E supplementation may ameliorate cognitive deficit in PTU-induced hypothyroidism through the decrease of oxidative stress status. 23609963 LIVER X RECEPTORS, NERVOUS SYSTEM AND LIPID METABOLISM. Lipids in the nervous system are represented by cholesterol and phospholipids as constituents of cell membranes and, in particular, of myelin. Therefore, lipids are finely regulated to guarantee physiological functions. In the central nervous system, cholesterol is locally synthesized due to the presence of the blood brain barrier. In the peripheral nervous system cholesterol is either uptaken by lipoproteins and/or produced by de novo biosynthesis. Defects in lipid homeostasis in these tissues lead to structural and functional changes that often result in different pathological conditions depending on the affected pathways (i.e. cholesterol biosynthesis, cholesterol efflux, fatty acid biosynthesis etc.). Alterations in cholesterol metabolism in the central nervous system are linked to several disorders such as Alzheimer's disease, Huntington disease, Parkinson disease, Multiple Sclerosis, Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and glioblastoma. In the peripheral nervous system changes in lipid metabolism are associated with the development of peripheral neuropathy that may be caused by metabolic disorders, injuries, therapeutics and autoimmune diseases. Transcription factors, such as the Liver X receptors (LXRs), regulate both cholesterol and fatty acid metabolism in several tissues including the nervous system. In the last few years several studies elucidated the biology of LXRs in nervous system due to the availability of knock-out mice and the development of synthetic ligands. Here, we review a survey of the literature focused on central and peripheral nervous system and in physiological and pathological settings with particular attention on the roles played by LXRs in both districts. 23525092 A 3D-RISM-SCF method with dual solvent boxes for a highly polarized system: application to 1,6-anhydrosugar formation reaction of phenyl α- and β-d-glucosides under basic conditions. One of the difficulties in application of the usual reference interaction site model self-consistent field (RISM-SCF) method to a highly polarized and bulky system arises from the approximate evaluation of electrostatic potential (ESP) with pure point charges. To improve this ESP evaluation, the ESP near a solute is directly calculated with a solute electronic wavefunction, that distant from a solute is approximately calculated with solute point charges, and they are connected with a switching function. To evaluate the fine solvation structure near the solute by incorporating the long-range solute-solvent Coulombic interaction with low computational cost, we introduced the dual solvent box protocol; one small box with the fine spacing is employed for the first and the second solvation shells and the other large box with the normal spacing is employed for long-range solute-solvent interaction. The levoglucosan formation from phenyl α- and β-d-glucosides under basic conditions is successfully inspected by this 3D-RISM-SCF method at the MP2 and SCS-MP2 levels, though the 1D-RISM-SCF could not be applied to this reaction due to the presence of highly polarized and bulky species. This 3D-RISM-SCF calculation reproduces the experimentally reported higher reactivity of the β-anomer. The 3D-RISM-SCF-calculated activation free energy for the β-anomer is closer to the experimental value than the PCM-calculated one. Interestingly, the solvation effect increases the difference in reactivity between these two anomers. The reason is successfully elucidated with 3D-RISM-SCF-calculated microscopic solvation structure and decomposition analysis of solute-solvent interaction. 23401066 Genetic loci that control the loss and regain of trabecular bone during unloading and reambulation. Changes in trabecular morphology during un- and re-loading are marked by large variations between individuals, implicating a strong genetic influence on the magnitude of the response. Here, we subjected more than 350 second-generation (BALBxC3H) 4mo old adult female mice to 3wk of hindlimb unloading followed by 3wk of reambulation to identify the quantitative trait loci (QTLs) that define an individual's propensity to either lose trabecular bone when weightbearing is removed or to gain trabecular bone when weightbearing is reintroduced. Longitudinal in vivo µCT scans demonstrated that individual mice lost between 15% and 71% in trabecular BV/TV in the distal femur during unloading (average: -43%). Changes in trabecular BV/TV during the 3wk reambulation period ranged from a continuation of bone loss (-18%) to large additions (56%) of tissue (average: +10%). During unloading, six QTLs accounted for 21% of the total variability in changes in BV/TV while one QTL accounted for 6% of the variability in changes in BV/TV during reambulation. QTLs were also identified for changes in trabecular architecture. Most of the QTLs defining morphologic changes during unloading or reambulation did not overlap with those QTLs identified at baseline, suggesting that these QTLs harbor genes that are specific for sensing changes in the levels of weightbearing. The lack of overlap in QTLs between unloading and reambulation also emphasizes that the genes modulating the trabecular response to unloading are distinct from those regulating tissue recovery during reloading. The identified QTLs contain the regulatory genes underlying the strong genetic regulation of trabecular bone's sensitivity to weightbearing and may help to identify individuals that are most susceptible to unloading induced bone loss and/or the least capable of recovering. © 2013 American Society for Bone and Mineral Research. 23400925 Bioaccumulation and biomagnification of mercury and selenium in the sarasota bay ecosystem. The bioaccumulation and biomagnification of Hg and Se were investigated in Sarasota Bay, Florida, USA, to characterize the Hg exposure risks to wild bottlenose dolphins in the bay. Concentrations of total mercury (THg), monomethylmercury (MMHg), and total selenium (TSe) were monitored in the bay, the latter of which might reduce Hg toxicity. The food web structure and dolphins' trophic level-specific consumption rates were evaluated using stable isotope ratios of carbon (δ(13) C) and nitrogen (δ(15) N). Regressions developed for Hg biomagnification in the food chain were log10 CTHg (nanograms per gram) = 0.27 × δ(15) N (‰) - 0.42, R(2)  = 0.87, for THg and log10 CMMHg  = 0.33 × δ(15) N (‰) - 1.0, R(2)  = 0.93, for MMHg. Unlike Hg, nearly constant TSe concentrations were observed at 248 ± 179 ng g(-1) in the food web, and the TSe-to-THg molar ratio was predicted by log10 (CTSe /CTHg ) = -0.10 × δ(15) N (‰) + 2.8, R(2)  = 0.60. The THg-uptake rates of Sarasota bottlenose dolphins are estimated to vary between 2.1 and 4.9 µg kg(-1) d(-1) ; however, the estimated TSe-uptake rates (15.1 µg kg(-1) d(-1) ) were higher than those for THg, and the Hg-exposure risks of the Sarasota Bay resident bottlenose dolphins are considered to be low. Approaches employed in the present study can be extended to other environments to characterize Hg contamination in aquatic systems and Hg exposure risks in top predators. Environ. Toxicol. Chem. 2013;32:1143-1152. © 2013 SETAC. 23609145 Inhibition of the Proton-Coupled Folate Transporter (PCFT-SLC46A1) by Bicarbonate and Other Anions. The proton-coupled folate transporter (PCFT) plays a key role in intestinal folate absorption and loss-of-function mutations in the gene encoding this transporter are the molecular basis for hereditary folate malabsorption. Using a stable transfectant with high expression of PCFT, physiological levels of bicarbonate produced potent and rapidly reversible inhibition of PCFT-mediated transport at neutral pH. Bisulfite and nitrite also inhibited PCFT function at neutral pH, whereas sulfate, nitrate and phosphate had no impact at all. At weakly acidic pH (6.5), bisulfite and nitrite exhibited much stronger inhibition of PCFT-mediated transport while sulfate and nitrate remained non-inhibitory. Inhibition by bisulfite and nitrite at pH 6.5 was associated with a marked decrease in the influx Vmax and collapse of the transmembrane proton gradient attributed to the diffusion of the protonated forms into these cells. Monocarboxylates such as pyruvate and acetate also collapsed the pH gradient and were also inhibitory, while citrate and glycine neither altered the proton gradient nor inhibited PCFT-mediated transport. These observations add another dimension to the unfavorable pH environment for PCFT function in systemic tissues, the presence of high concentrations of bicarbonate. 23411223 Geographical origin identification of Romanian wines by ICP-MS elemental analysis. Trace elemental analysis, besides its ability to determine stable isotopes ratios, represents a possible complementary tool useful to differentiate wines based on their regional origins. Wines and their provenance soils from two major wine producing areas in Southeast Romania ('Valea Calugareasca' and 'Murfatlar'), and also wine from the region of Moldova (Eastern Romania) were analyzed by inductively coupled plasma mass spectrometry (ICP-MS), and statistical data of elemental composition was used to differentiate these wines according to grape type and geographical origin. Moreover, this study gathers relevant elemental trace composition of wines produced in most important Romanian vineyards, thus offering a useful wine differentiation tool by their production district. The results show that the differentiation of Romanian wines according to their provenance is based on the following main elements: Ni, Ag, Cr, Sr, Zn, and Cu for Valea Calugareasca, Rb, Zn, and Mn for Murfatlar, and Pb, Co, and V for Moldova. 23567038 Internalization of Bacillus intermedius ribonuclease (BINASE) induces human alveolar adenocarcinoma cell death. Ribonuclease (RNase) treatment represents a novel mechanism based approach to anticancer therapy as an alternative to the DNA damaging drugs commonly used in clinical practice. Apart from their ribonucleolytic activity, cytotoxic effects have attracted a considerable attention to RNases because of their potential as selective agents for treatment of certain malignancies. Among these enzymes, Binase, an RNase from Bacillus intermedius, has shown promising results. Here, we have found that binase selectively attacked human A549 alveolar adenocarcinoma cells to trigger an apoptotic response, whereas normal lung epithelial cells LEK were not affected by the ribonuclease. The tumor transformation led to the modification of certain cellular characteristics causing cell sensitivity to binase. Although a general mode for RNases cytotoxicity includes their penetration into the cell, translocation to the cytosol and degradation of ribonucleic acid, many aspects of this process have not been fully elucidated. Our data revealed the following time-dependent changes induced by binase in A549 cells: (a) fast permanent internalization of the enzyme during the first hours of treatment; (b) temporary increase in cellular permeability for macromolecules during the 4-6 h of treatment; (c) apoptotic alterations in population after 24 h and (d) DNA fragmentation and cell death after 72 h of treatment with binase. Elucidation of these molecular strategies used by this promising toxin provides us essential information for the development of new anticancer drugs. 23019137 Reversal of dopamine D2 agonist-induced inhibition of ventral tegmental area neurons by Gq-linked neurotransmitters is dependent on protein kinase C, G protein-coupled receptor kinase, and dynamin. Dopaminergic neurons of the ventral tegmental area are important components of brain pathways related to addiction. Prolonged exposure of these neurons to moderate concentrations of dopamine (DA) decreases their sensitivity to inhibition by DA, a process called DA-inhibition reversal (DIR). DIR is mediated by phospholipase C and conventional subtype of protein kinase C (cPKC) through concurrent stimulation of D2 and D1-like DA receptors, or by D2 stimulation concurrent with activation of 5-HT(2) or neurotensin receptors. In the present study, we further characterized this phenomenon by use of extracellular recordings in brain slices to examine whether DIR is linked to G protein-coupled receptor kinase-2 (GRK2) or dynamin by assessing DIR in the presence of antagonists of these enzymes. DIR was blocked by β-ARK1 inhibitor, which inhibits GRK2, and by dynasore, which blocks dynamin. Reversal of inhibition by D2 agonist quinpirole was produced by serotonin (50 µM) and by neurotensin (5-10 nM). Serotonin-induced or neurotensin-induced reversal was blocked by β-ARK1 inhibitor, dynasore, or cPKC antagonist 5,6,7,13-tetrahydro-13-methyl-5-oxo-12H-indolo[2,3-a]pyrrolo[3,4c]carbazole-12-propanenitrile (Gö6976). This further characterization of DIR indicates that cPKC, GRK2, and dynamin play important roles in the desensitization of D2 receptors. As drugs of abuse produce persistent increases in DA concentration in the ventral tegmental area, reduction of D2 receptor sensitivity as a result of drug abuse may be a critical factor in the processes of addiction. 23220293 Brain monoamines and antidepressant-like responses in MRL/MpJ versus C57BL/6J mice. The MRL/MpJ mouse demonstrates enhanced wound healing and tissue regeneration and increased neurotrophic mobilization to chronic antidepressant drug treatments. This study compared brain monoamine systems between MRL/MpJ and C57BL/6J mice as a potential basis for strain differences after chronic antidepressant treatment. MRL/MpJ mice had significantly higher tissue levels of serotonin and dopamine in multiple brain regions. Microdialysis studies demonstrated that baseline levels of extracellular serotonin did not differ between strains. However, acute administration of the selective serotonin reuptake inhibitor citalopram produced an increase in extracellular serotonin in the ventral hippocampus of MRL/MpJ mice that was twice as large as achieved in C57BL/6J mice. The greater effects in MRL/MpJ mice on 5-HT levels were not maintained after local perfusion of citalopram, suggesting that mechanisms outside of the hippocampus were responsible for the greater effect of citalopram after systemic injection. The density of serotonin and norepinephrine transporters in the hippocampus was significantly higher in MRL/MpJ mice. In addition, the expression of 5-HT(1A) mRNA was lower in the hippocampus, 5-HT(1B) mRNA was higher in the hippocampus and brainstem and SERT mRNA was higher in the brain stem of MRL/MpJ mice. The exaggerated neurotransmitter release in MRL/MpJ mice was accompanied by reduced baseline immobility in the tail suspension test and a greater reduction of immobility produced by citalopram or the tricyclic antidepressant desipramine. These data suggest that differences in the response to acute and chronic antidepressant treatments between the two strains could be attributed to differences in serotonin or catecholamine transmission. 23432708 Ab initio MRCI+Q study on low-lying states of CS including spin-orbit coupling. Carbon monosulfide (CS), which plays an important role in a variety of research fields, has long received considerable interest. Due to its transient nature and large state density, the electronic states of CS have not been well understood, especially the interactions between different states. In this paper, we performed a detail ab initio study on the low-lying electronic states of CS by means of the internally contracted multireference configuration interaction method (including Davidson correction) with scalar relativistic correction using the Douglas-Kroll-Hess Hamiltonian. We focused on the spin-orbit coupling of the states via the state interaction method with the full Breit-Pauli Hamiltonian. The potential energy curves (PECs) of 18 Λ-S states correlated with the lowest dissociation limit of the CS molecule were calculated, as well as those of 50 Ω states generated from the Λ-S states. The spectroscopic constants of the bound states were obtained, which are in good agreement with previous available experimental and theoretical results. The state perturbations of the a(3)Π and A(1)Π states with other low-lying electronic states are discussed in detail, based on the calculated spin-orbit matrix as well as the PECs of the Ω states. Avoided crossing in the states of CS was indicated when spin-orbit coupling was taken into account. Finally, the allowed transition dipole moments as well as the lifetimes of the five lowest vibrational states of the A(1)Π1, A'(1)Σ(+)0(+) and a(3)Πi states were obtained. 23530552 Maternal adiposity as an independent risk factor for pre-eclampsia: a meta-analysis of prospective cohort studies. Studies investigating the association between maternal adiposity and risk of pre-eclampsia showed contradictory results. Therefore, we performed a meta-analysis of prospective cohort studies to estimate the effect of maternal adiposity on pre-eclampsia. We reviewed 1,286 abstracts and finally included 29 prospective cohort studies with 1,980,761 participants and 67,075 pre-eclampsia events. We pooled data with a random-effects model, and obtained risk estimates for five predetermined bodyweight groups: low, normal-weight (reference), overweight, obese and severely obese. In the cohort studies that unadjusted for pre-eclampsia risk factors, the pooled unadjusted relative risks (RR) with 95% confidence intervals (95%CI) for pre-eclampsia of overweight, obese and severely obese women were 1.58 (95% CI 1.44-1.72, P < 0.001), 2.68 (95% CI 2.39-3.01, P < 0.001) and 3.12 (95% CI 2.24-4.36, P < 0.001), respectively. In those cohorts that adjusted for pre-eclampsia risk factors, the pooled unadjusted RRs for pre-eclampsia of overweight, obese and severely obese women were 1.70 (95% CI 1.60-1.81, P < 0.001), 2.93 (95% CI 2.58-3.33, P < 0.001) and 4.14 (95% CI 3.61-4.75, P < 0.001), respectively. Sensitivity analysis showed maternal adiposity was associated with increased risk of pre-eclampsia in both nulliparous and multiparas women. In conclusion, overweight or obese pregnant women have a substantially increased risk of pre-eclampsia, and maternal adiposity is an independent risk factor of pre-eclampsia. 23642029 Semi-synthesis of radiolabeled amino acid and lipid brevetoxin metabolites and their blood elimination kinetics in C57BL/6 mice. Brevetoxin B (BTX-B), produced by dinoflagellates of the species Karenia, is a highly reactive molecule, due in part to an α,β-unsaturated aldehyde group at the terminal side chain, leading to the production of metabolites by reduction, oxidation, and conjugation. We have investigated in mice the blood elimination of three common bioactive brevetoxin metabolites found in shellfish, which have been semi-synthesized from BTX-B in radioactive forms. BTX-B was reduced at C42 to yield [3H] dihydro-BTX-B. [3H] S-desoxy-BTX-B2 (cysteine brevetoxin B) was semi-synthesized from BTX-B by conjugation of cysteine at the C50 olefinic group, then [3H] radiolabeled by C42 aldehyde reduction. [14C] N-palmitoyl-S-desoxy-BTX-B2 was prepared using S-desoxy-BTX-B2 as the starting material with addition of the [14C] radiolabeled fatty acid via the cysteine-amide linkage. The elimination of intravenously administered [3H] S-desoxy-BTX-B2, [14C] N-palmitoyl-S-desoxy-BTX-B2, or [3H] dihydro-BTX-B was measured in blood collected from C57BL/6 mice over a 48 hour period. Each brevetoxin metabolite tested exhibited biexponential elimination kinetics and fit a two-compartment model of elimination that was applied to generate toxicokinetic parameters. The rate of transfer between the central compartment (i.e., blood) and the peripheral compartment (e.g., tissue) for each brevetoxin differed substantially, with dihydro-BTX-B exchanging rapidly with the peripheral compartment, and S-desoxy-BTX-B2 eliminating rapidly from the central compartment and N-palmitoyl-S-desoxy-BTX-B2 eliminating slowly from the central compartment. Toxicokinetic parameters were analyzed in the context of the unique structure of each brevetoxin metabolite resulting from a reduction, amino acid conjugation, or fatty acid addition to BTX-B. 23401211 Inter- and intraspecific variation in mercury bioaccumulation by snakes inhabiting a contaminated river floodplain. Although mercury (Hg) is a well-studied contaminant, knowledge about Hg accumulation in snakes is limited. The authors evaluated Hg bioaccumulation within and among four snake species (northern watersnakes, Nerodia sipedon; queen snakes, Regina septemvittata; common garter snakes, Thamnophis sirtalis; and rat snakes, Elaphe obsoleta [Pantherophis alleghaniensis]) from a contaminated site on the South River (Waynesboro, VA, USA) and two nearby reference sites. Total Hg (THg) concentrations in northern watersnake tail tissue at the contaminated site ranged from 2.25 to 13.84 mg/kg dry weight (mean: 4.85 ± 0.29), or 11 to 19 times higher than reference sites. Blood THg concentrations (0.03-7.04 mg/kg wet wt; mean: 2.24 ± 0.42) were strongly correlated with tail concentrations and were the highest yet reported in a snake species. Within watersnakes, nitrogen stable isotope values indicated ontogenetic trophic shifts that correlated with THg bioaccumulation, suggesting that diet plays a substantial role in Hg exposure. Female watersnakes had higher mean THg concentrations (5.67 ± 0.46 mg/kg) than males (4.93 ± 0.49 mg/kg), but no significant differences between sexes were observed after correcting for body size. Interspecific comparisons identified differences in THg concentrations among snake species, with more aquatic species (watersnakes and queen snakes) accumulating higher mean concentrations (5.60 ± 0.40 and 4.59 ± 0.38 mg/kg in tail tissue, respectively) than the more terrestrial species, garter snakes and rat snakes (1.28 ± 0.32 and 0.26 ± 0.09 mg/kg, respectively). The results of the present study warrant further investigation of potential adverse effects and will aid in prioritizing conservation efforts. Environ. Toxicol. Chem. 2013;32:1178-1186. © 2013 SETAC. 23153512 Proposed model for in vitro interaction between fenitrothion and DNA, by using competitive fluorescence, (31)P NMR, (1)H NMR, FT-IR, CD and molecular modeling. In this work we proposed a model for in vitro interaction of fenitrothion (FEN) with calf thymus-DNA by combination of multispectroscopic and two dimensional molecular modeling (ONIOM) methods. The circular dichroism results showed that FEN changes the conformation of B-DNA and caused some changes to C-DNA form. The FT-IR results confirmed a partial intercalation between FEN and edges of all base pairs. The competitive fluorescence, using methylene blue as fluorescence probe, in the presence of increasing amounts of FEN, revealed that FEN is able to release the non-intercalated methylene blue from the DNA. The weak chemical shift and peak broadening of (1)H NMR spectrum of FEN in the presence of DNA confirmed a non-intercalation mode. The (31)P NMR showed that FEN interacts more with DNA via its -NO2 moiety. The ONIOM, based on the hybridization of QM/MM (DFT, 6.31++G (d,p)/UFF) methodology, was also performed by Gaussian 2003 package. The results revealed that the interaction is base sequence dependent, and FEN interacts more with AT base sequences. 23423972 Absorption, distribution, and biotransformation of hexahydro-1,3,5-trinitro-1,3,5-triazine in B6C3F1 mice (Mus musculus). Absorption, distribution, and biotransformation are 3 critical aspects affecting toxicant action in animals. In the present study, B6C3F1 mice (Mus musculus) were exposed for 28 d to contaminated feed that contained 1 of 5 different hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) concentrations: 0 mg/kg, 0.5 mg/kg, 5 mg/kg, 50 mg/kg, and 500 mg/kg. The authors quantified RDX and its reductive transformation products hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine (DNX), and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX) in the stomach, intestine, plasma, liver, and brain of these mice. Average RDX concentrations followed a dose-dependent pattern for all matrices tested. No controls had concentrations above limits of detection. Average RDX concentrations in tissues of exposed mice ranged from 11.1 ng/mL to 182 ng/mL, 25.6 ng/g to 3319 ng/g, 123 ng/g to 233 ng/g, 144 ng/g to 35 900 ng/g, and 51.1 ng/g to 2697 ng/g in the plasma, brain, liver, stomach, and intestine, respectively. A considerable amount of RDX was present in the brain, especially in the highest-exposure group. This is consistent with the widely observed central nervous system effects caused by γ-aminobutyric acid inhibition associated with RDX exposure. N-nitroso metabolites of RDX were also present in tested tissues in a dose-dependent pattern. Average MNX concentrations in the stomachs of mice exposed to RDX ranged from nondetectable in control exposures to 490 ng/g in the highest-exposure groups. In the brain, MNX accumulated at a maximum average concentration of 165.1 ng/g, suggesting the potential formation of MNX from RDX within the brain. At higher exposures, DNX and TNX were present in the stomach, plasma, and brain of mice. The presence of RDX metabolites at notable amounts in different tissues suggests that RDX can transform into its N-nitroso metabolites in vivo by an undefined mechanism. Environ Toxicol Chem 2013;32:1295-1303. © 2013 SETAC. 23450151 Highly luminescent water-soluble quaternary Zn-Ag-In-S quantum dots for tumor cell-targeted imaging. Exploring the synthesis and biomedical applications of biocompatible quantum dots (QDs) is currently one of the fastest growing fields of nanotechnology. Hence, in this work, we present a facile approach to produce water-soluble (cadmium-free) quaternary Zn-Ag-In-S (ZAIS) QDs. Their efficient photoluminescence (PL) emissions can be tuned widely in the range of 525-625 nm by controlling the size and composition of the QDs with the PL quantum yields (QYs) of 15-30%. These highly luminescent ZAIS QDs are less toxic due to the absence of highly toxic cadmium, and can be versatilely modified by a DHLA-PEG-based ligand. Importantly, after being modified by tumor cell-specific targeting ligands (e.g., folate and RGD peptide), the PEGylated quaternary QDs show potential applications in tumor cell imaging as a promising alternative for Cd-based QDs. 22841916 Chronic caffeine prevents changes in inhibitory avoidance memory and hippocampal BDNF immunocontent in middle-aged rats. Beneficial effects of caffeine on memory processes have been observed in animal models relevant to neurodegenerative diseases and aging, although the underlying mechanisms remain unknown. Because brain-derived neurotrophic factor (BDNF) is associated with memory formation and BDNF's actions are modulated by adenosine receptors, the molecular targets for the psychostimulant actions of caffeine, we here compare the effects of chronic caffeine (1 mg/mL drinking solution for 30 days) on short- and long term memory and on levels of hippocampal proBDNF, mature BDNF, TrkB and CREB in young (3 month old) and middle-aged (12 month old) rats. Caffeine treatment substantially reduced i) age-related impairments in the two types of memory in an inhibitory avoidance paradigm, and ii) parallel increases in hippocampal BDNF levels. In addition, chronic caffeine increased proBDNF and CREB concentrations, and decreased TrkB levels, in hippocampus regardless of age. These data provide new evidence in favor of the hypothesis that modifications in BDNF and related proteins in the hippocampus contribute to the pro-cognitive effects of caffeine on age-associated losses in memory encoding. This article is part of a Special Issue entitled 'Cognitive Enhancers'. 23297712 Composition and evaluation of the anti-inflammatory and anticancer activities of the essential oil from Annona sylvatica A. St.-Hil. The essential oil from the leaves of Annona sylvatica (EOAS) was extracted by hydrodistillation, and the analysis was performed by gas chromatography-mass spectrometry. The main compounds identified in the EOAS were sesquiterpenes, such as hinesol, z-caryophyllene, β-maaliene, γ-gurjunene, silphiperfol-5-en-3-ol, ledol, cubecol-1-epi, and muurola-3,5-diene. Oral administration of the EOAS (20 and 200 mg/kg) and subcutaneous injection of dexamethasone (0.5 mg/kg, reference drug) significantly inhibited carrageenan- and complete Freund's adjuvant-induced mouse paw edema. The anticancer activity the EOAS showed growth inhibitory activity on all cell lines when administered in a high concentration. The EOAS inhibited the growth of human cancer cell lines with GI(50) values in the range of 36.04-45.37 μg/mL on all of the cell lines tested. This work describes for the first time the anti-inflammatory and anticancer effects of the essential oil of A. sylvatica and its composition. Considering that drugs currently available for the treatment of inflammatory and cancer conditions show undesirable side-effects, the present results may have clinical relevance and open new possibilities for the development of novel anti-inflammatory and anticancer drugs. 23253127 Putative impact of RNA editing on drug discovery. Virtually all organisms use RNA editing as a powerful post-transcriptional mechanism to recode genomic information and to increase functional protein diversity. The enzymatic editing of pre-mRNA by ADARs and CDARs is known to change the functional properties of neuronal receptors and ion channels regulating cellular excitability. However, RNA editing is also an important mechanism for genes expressed outside the brain. The fact that RNA editing breaks the 'one gene encodes one protein' hypothesis is daunting for scientists and a probable drawback for drug development, as scientists might search for drugs targeting the 'wrong' protein. This possible difficulty for drug discovery and development became more evident from recent publications, describing that RNA editing events have profound impact on the pharmacology of some common drug targets. These recent studies highlight that RNA editing can cause massive discrepancies between the in vitro and in vivo pharmacology. Here, we review the putative impact of RNA editing on drug discovery, as RNA editing has to be considered before using high-throughput screens, rational drug design or choosing the right model organism for target validation. 23122165 Occurrence and sensory perception of Z-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid in rooibos (Aspalathus linearis). Z-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid (PPAG), a compound postulated to contribute to the taste and mouthfeel of fermented rooibos tea (Aspalathus linearis), was isolated from unfermented rooibos plant material. Its structure was unequivocally confirmed by LC-MS, -MS(2), FT-IR and NMR of the underivatised natural product, and optical rotation measurements of the hydrolysed sugar moiety. A similar compound, postulated to be E-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid, was also detected. Analysis of the leaves of a large number of rooibos plants (n=54), sampled at commercial plantations, showed that PPAG is not ubiquitously present in detectable quantities in the leaves of different plants. This leads to large variation in the fermented plant material, infusions and food-grade extracts. PPAG was shown to have a slightly bitter to astringent taste and a detection threshold of 0.4 mg/l in water. 23578652 Comparison of antioxidant activity of hydroethanolic fresh and aged garlic extracts and their effects on cerebral ischemia. Antioxidant properties and protective effect of aged garlic extract (AGE) and of 20% hydroethanolic fresh extracts from garlic clove (GCE) and skin (GSE) on cerebral ischemia were evaluated by administering extracts at the beginning of reperfusion in a rat model of stroke. All three extracts scavenged superoxide anion, peroxynitrite anion, and peroxyl radicals, but with different efficiencies; furthermore, GCE and GSE scavenged hydroxyl radicals and GSE scavenged singlet oxygen. These extracts significantly prevented reduction of neuronal nuclear antigen in the infarcted area, although no improvement in neurological function was observed. Importantly, GCE and GSE contained S-allylcystein, a compound associated with AGE's neuroprotective effect against damage induced by cerebral ischemia. Extracts decreased mRNA expression of NR1- and NR2B-NMDA-receptor subunits and prevented ischemia-induced reduction in mitochondrial potential and in ATP synthesis. These results indicate that antioxidants present in garlic extracts may regulate ROS concentrations during ischemia, favour pro-survival pathways, and attenuate mitochondrial dysfunction. 23179966 Serotonin-glutamate and serotonin-dopamine reciprocal interactions as putative molecular targets for novel antipsychotic treatments: from receptor heterodimers to postsynaptic scaffolding and effector proteins. The physical and functional interactions between serotonin-glutamate and serotonin-dopamine signaling have been suggested to be involved in psychosis pathophysiology and are supposed to be relevant for antipsychotic treatment. Type II metabotropic glutamate receptors (mGluRs) and serotonin 5-HT(2A) receptors have been reported to form heterodimers that modulate G-protein-mediated intracellular signaling differentially compared to mGluR2 and 5-HT(2A) homomers. Additionally, direct evidence has been provided that D(2) and 5-HT(2A) receptors form physical heterocomplexes which exert a functional cross-talk, as demonstrated by studies on hallucinogen-induced signaling. Moving from receptors to postsynaptic density (PSD) scenario, the scaffolding protein PSD-95 is known to interact with N-methyl-D-aspartate (NMDA), D(2) and 5-HT(2) receptors, regulating their activation state. Homer1a, the inducible member of the Homer family of PSD proteins that is implicated in glutamatergic signal transduction, is induced in striatum by antipsychotics with high dopamine receptor affinity and in the cortex by antipsychotics with mixed serotonergic/dopaminergic profile. Signaling molecules, such as Akt and glycogen-synthase-kinase-3 (GSK-3), could be involved in the mechanism of action of antipsychotics, targeting dopamine, serotonin, and glutamate neurotransmission. Altogether, these proteins stand at the crossroad of glutamate-dopamine-serotonin signaling pathways and may be considered as valuable molecular targets for current and new antipsychotics. The aim of this review is to provide a critical appraisal on serotonin-glutamate and serotonin-dopamine interplay to support the idea that next generation schizophrenia pharmacotherapy should not exclusively rely on receptor targeting strategies. 23154301 Sensory gating, Cannabinoids and Schizophrenia. Sensory gating, a mandatory process in early information processing, has been found to be defective in neuropsychiatric diseases such as schizophrenia. Understanding the neurobiology of sensory gating may provide insight into unravelling the neurobiology of information processing and to yet unanswered queries on the pathophysiology of disabling neuropsychiatric diseases. The endocannabinoid system has been linked to the pathophysiology of schizophrenia. Furthermore, cannabinoids disrupt sensory gating in animals and humans which supports the hypothesis that the disruption of sensory gating by alterations in the endocannabinoid system is a significant factor in the etiology of schizophrenia. Based on the above hypothesis this article reviews the sensory gating process in relation to the auditory conditioning-test paradigm with an emphasis on its association with the endocannabinoid system and schizophrenia. 23289872 Engagement of CF3 group in N-H···F-C hydrogen bond in the solution state: NMR spectroscopy and MD simulation studies. Unambiguous evidence for the engagement of CF(3) group in N-H···F-C hydrogen bond in a low polarity solvent, the first observation of its kind, is reported. The presence of such weak molecular interactions in the solution state is convincingly established by one and two-dimensional (1)H, (19)F, and natural abundant (15)N NMR spectroscopic studies. The strong and direct evidence is derived by the observation of through-space couplings, such as, (1h)J(FH), (1h)J(FN), and (2h)J(FF), where the spin polarization is transmitted through hydrogen bond. In an interesting example of a molecule containing two CF(3) groups getting simultaneously involved in hydrogen bond, where hydrogen bond mediated couplings are not reflected in the NMR spectrum, (19)F-(19)F NOESY experiment yielded confirmatory evidence. Significant deviations in the strengths of (1)J(NH), variable temperature, and the solvent induced perturbations yielded additional support. The NMR results are corroborated by both DFT calculations and MD simulations, where the quantitative information on different ways of involvement of fluorine in two and three centered hydrogen bonds, their percentage of occurrences, and geometries have been obtained. The hydrogen bond interaction energies have also been calculated. 23318905 Identification of benzofuran-3-yl(phenyl)methanones as novel SIRT1 inhibitors: binding mode, inhibitory mechanism and biological action. SIRT1 is a NAD(+)-dependent deacetylase. Here we described new SIRT1 inhibitors with the scaffold of benzofuran-3-yl(phenyl)methanone. The inhibitors were predicted to bind in C-pocket of SIRT1, forming hydrophobic interactions with Phe273, Phe312 and Ile347. Introducing hydroxyl to meta position of phenyl may form H-bond with Asn346. Indeed, (2,5-dihydroxyphenyl)(5-hydroxy-1-benzofuran-3-yl)methanone (16), an analogue with hydroxyls at ortho and meta positions, showed greater inhibition. The binding mode was validated by structural modifications and kinetic studies. Since C-pocket is the site where the nicotinamide moiety of NAD(+) binds and the hydrolysis takes place, binding of 16 in C-pocket would block the transformation of NAD(+) to productive conformation and hence inhibit the deacetylase activity. Consistently, 16 inhibited SIRT1 through up-regulating p53 acetylation on cellular level. 23316021 Gadolinium- and manganite-based contrast agents with fluorescent probes for both magnetic resonance and fluorescence imaging of pancreatic islets: a comparative study. Three magnetic resonance (MR)/fluorescence imaging probes were tested for visualization, cellular distribution, and survival of labeled pancreatic islets in vitro and following transplantation. As T(1) contrast agents (CAs), gadolinium(III) complexes linked to β-cyclodextrin (Gd-F-βCD) or bound to titanium dioxide (TiO2 @RhdGd) were tested. As a T(2) CA, perovskite manganite nanoparticles (LSMO@siF@si) were examined. Fluorescein or rhodamine was incorporated as a fluorescent marker in all probes. Islets labeled with gadolinium(III) CAs were visible as hyperintense spots on MR in vitro, but detection in vivo was inconclusive. Islets labeled with LSMO@siF@si CA were clearly visible as hypointense spots or areas on MR scans in vitro as well as in vivo. All CAs were detected inside the islet cells by fluorescence. Although the vitality and function of the labeled islets was not impaired by any of the tested CAs, results indicate that LSMO@siF@si CA is a superior marker for islet labeling, as it provides better contrast enhancement within a shorter scan time. 23617851 High-resolution transcriptional analysis of the regulatory influence of cell-to-cell signalling reveals novel genes that contribute to Xanthomonas phytopathogenesis. The bacterium Xanthomonas campestris is an economically important pathogen of many crop species and a model for the study of bacterial phytopathogenesis. In X. campestris, a regulatory system mediated by the signal molecule DSF controls virulence to plants. The synthesis and recognition of the DSF signal depends upon different Rpf proteins. DSF signal generation requires RpfF whereas signal perception and transduction depends upon a system comprising the sensor RpfC and regulator RpfG. Here we have addressed the action and role of Rpf/DSF signalling in phytopathogenesis by high-resolution transcriptional analysis coupled to functional genomics. We detected transcripts for many genes that were unidentified by previous computational analysis of the genome sequence. Novel transcribed regions included intergenic transcripts predicted as coding or non-coding as well as those that were antisense to coding sequences. In total, mutation of rpfF, rpfG and rpfC led to alteration in transcript levels (more than fourfold) of approximately 480 genes. The regulatory influence of RpfF and RpfC demonstrated considerable overlap. Contrary to expectation, the regulatory influence of RpfC and RpfG had limited overlap, indicating complexities of the Rpf signalling system. Importantly, functional analysis revealed over 160 new virulence factors within the group of Rpf-regulated genes. 23454829 Tissue Distribution and Identification of Radioactivity Components at Elimination Phase after Oral Administration of [14C]CS-1036, an α-Amylase Inhibitor, to Rats. (2R,3R,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-3-yl 4-O-(6-deoxy-β-D-glucopyranosyl)-α-D-glucopyranoside (CS-1036) is a potent inhibitor of pancreatic and salivary α-amylase. After oral administration of [(14)C]CS-1036 to rats, the radioactivity was still detectable up to 7-14 days after administration in various tissues, and its terminal phase in plasma could be explained neither by the exposure of CS-1036 nor its major metabolite M1. The slow elimination of radioactivity in various tissues was hypothesized to be caused by covalent binding to macromolecules or use for biogenic components. To assess the use for biogenic components, amino acid analysis of plasma proteins and lipid analysis of adipose tissue were conducted after repeated oral administration of [(14)C]CS-1036 by high-performance liquid chromatography and accelerated mass spectrometry and by thin layer chromatography and liquid chromatography/mass spectrometry, respectively. In amino acid analysis, glutamic acid, aspartic acid, alanine, and proline were identified as major radioactive amino acids, and radioactive nonessential amino acids occupied 76.0% of the radioactivity. In lipid analysis, a part of the radioactive lipids were identified as the fatty acids constituting the neutral lipids by lipase-hydrolysis. The radioactive fatty acids from neutral lipids were identified as palmitic acid, oleic acid, and 8,11,14-eicosatrienoic acid. Intestinal flora were involved in CS-1036 metabolism and are indicated to be involved in the production of small molecule metabolites, which are the sources for amino acids and fatty acids, from [(14)C]CS-1036. In conclusion, radioactivity derived from [(14)C]CS-1036 was incorporated as the constituents of amino acids of plasma proteins and fatty acids of neutral lipids. 23247040 Engineering polypeptide coatings to augment gene transduction and in vivo stability of adenoviruses. We sought to modify adenoviral (Ad) particles by incorporating the advantageous characteristics of non-viral gene delivery vehicles to complement the viral vectors. α-Amino acid-N-carboxyanhydride chemistry was used to synthesize homopolypeptides and diblock copolypeptides that possess well-defined secondary structures. Using cryo-electron and fluorescence microscopy, we showed that these polypeptides can coat the surfaces of Ad particles in a non-covalent manner to modify their transduction properties. The coated Ad particles were found to bind to and be internalized by cells. In contrast to reports using covalently PEGylated Ad particles, we found that our physically coated Ad hybrid complexes facilitate gene transfer both in vitro and in vivo. We showed that our polypeptide coating was able to shield the Ad particles from the neutralizing effect of antibodies and mitigate the binding of blood coagulation factor (Factor X) in vitro. The coating also reduced the antigenicity of Ad in immunocompetent mice. The biodistribution of the systemically administered hybrid complexes mirrored the behavior of both viral and non-viral vectors, exhibiting liver tropism as well as enhanced lung transduction. These data demonstrated that our non-covalent modification was able to alter Ad's interactions with cells and organs with retention of transduction efficiency. Advantages such as facile coating of the Ad vector, design flexibility and ease of attaching ligands to the polypeptides make this system potentially useful as a platform for adding functionalities to Ad to target cancer metastasis. 23473444 Engineered iron-oxide-based nanoparticles as enhanced t1 contrast agents for efficient tumor imaging. We report the design and synthesis of small-sized zwitterion-coated gadolinium-embedded iron oxide (GdIO) nanoparticles, which exhibit a strong T1 contrast effect for tumor imaging through enhanced permeation and retention effect and the ability to clear out of the body in living subjects. The combination of spin-canting effects and the collection of gadolinium species within small-sized GdIO nanoparticles led to a significantly enhanced T1 contrast effect. For example, GdIO nanoparticles with a diameter of ∼4.8 nm exhibited a high r1 relaxivity of 7.85 mM(-1)·S(-1) and a low r2/r1 ratio of 5.24. After being coated with zwitterionic dopamine sulfonate molecules, the 4.8 nm GdIO nanoparticles showed a steady hydrodynamic diameter (∼5.2 nm) in both PBS buffer and fetal bovine serum solution, indicating a low nonspecific protein absorption. This study provides a valuable strategy for the design of highly sensitive iron-oxide-based T1 contrast agents with relatively long circulation half-lives (∼50 min), efficient tumor passive targeting (SKOV3, human ovarian cancer xenograft tumor as a model), and the possibility of rapid renal clearance after tumor imaging. 22469981 In vivo and in vitro models for the therapeutic targeting of Wnt signaling using a Tet-OΔN89β-catenin system. Although significant progress has been made in understanding the importance of Wnt signaling in the initiation of colorectal cancer, less is known about responses that accompany the reversal of oncogenic Wnt signaling. The aim of this study was to analyze in vivo and in vitro responses to an 'ideal' Wnt pathway inhibitor as a model for the therapeutic targeting of the pathway. A tetracycline-inducible transgenic mouse model expressing truncated β-catenin (ΔN89β-catenin) that exhibited a strong intestinal hyperplasia was analyzed during the removal of oncogenic β-catenin expression both in 3D 'crypt culture' and in vivo. Oncogenic Wnt signaling was rapidly and completely reversed. The strongest inhibition of Wnt target gene expression occurred within 24 h of doxycycline removal at which time the target genes Ascl2, Axin2 and C-myc were downregulated to levels below that in the control intestine. In vitro, the small molecule Wnt inhibitor CCT036477 induced a response within 4 h of treatment. By 7 days following doxycycline withdrawal, gene expression, cell proliferation and tissue morphology were undistinguishable from control animals.In conclusion, these results demonstrate that the reversal of Wnt signaling by inhibitors should ideally be studied within hours of treatment. The reversible system described, involving medium throughput in vitro approaches and rapid in vivo responses, should allow the rapid advance of early stage compounds into efficacy models that are more usually considered later in the drug discovery pipeline. 23411236 Purification and characterisation of a novel chitinase from persimmon (Diospyros kaki) with antifungal activity. A novel chitinase from the persimmon fruit was isolated, purified and characterised in this report. The Diospyros kaki chitinase (DKC) was found to be a monomer with a molecular mass of 29 kDa. It exhibited optimal activity at pH 4.5 with broad pH stability from pH 4.0-9.0. It has an optimal temperature of 60°C and thermostable up to 60°C when incubated for 30 min. The internal peptide sequences of DKC showed similarity with other reported plant chitinases. It has the ability to hydrolyse colloidal chitin into chito-oligomers such as chitotriose, chitobiose and into its monomer N-acetylglucosamine. It can be used to degrade chitin waste into useful products such as chito-oligosacchaarides. DKC exhibited antifungal activity towards pathogenic fungus Trichoderma viride. Chitinases with antifungal property can be used as biocontrol agents replacing chemical fungicides. 23319591 Methylation of histone H3 on lysine 4 by the lysine methyltransferase SET1 protein is needed for normal clock gene expression. The circadian oscillator controls time-of-day gene expression by a network of interconnected feedback loops and is reset by light. The requisite for chromatin regulation in eukaryotic transcription necessitates temporal regulation of histone-modifying and chromatin-remodeling enzymes for proper clock function. CHD1 is known to bind H3K4me3 in mammalian cells, and Neurospora CHD1 is required for proper regulation of the frequency (frq) gene. Based on this, we examined a strain lacking SET1 to determine the role of H3K4 methylation in clock- and light-mediated frq regulation. Expression of frq was altered in strains lacking set1 under both circadian- and light-regulated gene expression. There is a delay in the phasing of H3K4me3 relative to the peak in frq expression. White Collar 2 (WC-2) association with the frq promoter persists longer in Δset1, suggesting a more permissible chromatin state. Surprisingly, SET1 is required for DNA methylation in the frq promoter, indicating a dependence on H3K4me for DNA methylation. The data support a model where SET1 is needed for proper regulation by modulating chromatin at frq. 23337388 Crowd computing: using competitive dynamics to develop and refine highly predictive models. A recent application of a crowd computing platform to develop highly predictive in silico models for use in the drug discovery process is described. The platform, Kaggle™, exploits a competitive dynamic that results in model optimization as the competition unfolds. Here, this dynamic is described in detail and compared with more-conventional modeling strategies. The complete and full structure of the underlying dataset is disclosed and some thoughts as to the broader utility of such 'gamification' approaches to the field of modeling are offered. 23081947 Chlorine-enhanced surface mobility of Au(100). Motivated by experimental studies of two-dimensional Ostwald ripening on Au(100) electrodes in chlorine-containing electrolytes, we have studied diffusion processes using density functional theory. We find that chlorine has a propensity to temporary form AuCl complexes, which diffuse significantly faster than gold adatoms. With and without chlorine, the lowest activation energy is found for the exchange mechanism. Chlorine furthermore reduces the activation energy for the detachment from kink sites. Kinetic Monte Carlo simulations were performed on the basis of extensive density functional theory calculations. The island-decay rate obtained from these Monte Carlo simulations, as well as the decay rate obtained from the theoretical activation energies and frequency factors when inserted into analytical solutions for Ostwald ripening, are in agreement with experimental island-decay rates in chlorine-containing electrolytes. 23266502 Carbamate insecticide methomyl confers cytotoxicity through DNA damage induction. Carbamate insecticide methomyl could induce genotoxic effects, including micronuclei, chromosome aberrations and sister-chromatid exchanges. However, methomyl induction of cytotoxicity through DNA damage is largely unknown. Here we identify cytotoxicity and potential genotoxicity of methomyl in vitro. We have employed alkaline comet assay, γH2AX foci formation and DNA ladder assay to detected DNA damage and apoptosis of Drosophila S2, HeLa and HEK293 cells. The alkaline comet assay was used to evaluate total DNA single strand breaks (SSBs) in the target cells exposed in vitro to sublethal concentrations of methomyl. As expected, methomyl induced significant concentration-dependent increases in DNA damage of target cells compared with the negative control, as measured by increases in tail length (μm), tail DNA (percentage of the comet tail) and tail moment (arbitrary units). In agreement with the comet assay data, the percentage of γH2AX positive reaction in HeLa cells also revealed methomyl caused DNA double strand breaks (DSBs) in a time-dependent manner. Moreover, methomyl induced a significant increase of apoptosis in Drosophila S2, HeLa and HEK293 cells in a concentration- and time-dependent manner, as determined by Urea PAGE DNA fragmentation analysis. In conclusion, methomyl is a strongly genotoxic agent that induces cell DNA damage and apoptosis in vitro at these sublethal concentrations. 23199028 Synthesis, biological evaluation, and molecular modeling of glycyrrhizin derivatives as potent high-mobility group box-1 inhibitors with anti-heart-failure activity in vivo. Novel glycyrrhizin (GL) derivatives were designed and synthesized by introducing various amine or amino acid residues into the carbohydrate chain and at C-30. Their inhibitory effects on high-mobility group box 1 (HMGB1) were evaluated using a cell-based lipopolysaccharide (LPS) induced tumor necrosis factor α (TNF-α) release study. Compounds 10, 12, 18-20, 23, and 24, which had substituents introduced at C-30, demonstrated moderate HMGB1 inhibition with ED₅₀ values ranging from 337 to 141 μM, which are values comparable to that of the leading GL compound (1) (ED₅₀ = 70 μM). Compounds 23 and 24 emerged as novel and interesting HMGB1 inhibitors. These compounds were able to extend the survival of mice with chronic heart failure (CHF) and acute heart failure (AHF), respectively. In addition, molecular modeling studies were performed to support the biological data. 23464357 Three-dimensional in situ photocurrent mapping for nanowire photovoltaics. Devices based upon semiconductor nanowires provide many well-known advantages for next-generation photovoltaics, however, limited experimental techniques exist to determine essential electrical parameters within these devices. We present a novel application of a technique based upon two-photon induced photocurrent that provides a submicrometer resolution, three-dimensional reconstruction of photovoltaic parameters. This tool is used to characterize two GaAs nanowire-based devices, revealing the detail of current generation and collection, providing a path toward achieving the promise of nanowire-based photovoltaic devices. 23552482 Comparing molecular photofragmentation dynamics in the gas and liquid phases. This article explores the extent to which insights gleaned from detailed studies of molecular photodissociations in the gas phase (i.e. under isolated molecule conditions) can inform our understanding of the corresponding photofragmentation processes in solution. Systems selected for comparison include a thiophenol (p-methylthiophenol), a thioanisole (p-methylthioanisole) and phenol, in vacuum and in cyclohexane solution. UV excitation in the gas phase results in RX-Y (X = O, S; Y = H, CH3) bond fission in all cases, but over timescales that vary by ∼4 orders of magnitude - all of which behaviours can be rationalised on the basis of the relevant bound and dissociative excited state potential energy surfaces (PESs) accessed by UV photoexcitation, and of the conical intersections that facilitate radiationless transfer between these PESs. Time-resolved UV pump-broadband UV/visible probe and/or UV pump-broadband IR probe studies of the corresponding systems in cyclohexane solution reveal additional processes that are unique to the condensed phase. Thus, for example, the data clearly reveal evidence of (i) vibrational relaxation of the photoexcited molecules prior to their dissociation and of the radical fragments formed upon X-Y bond fission, and (ii) geminate recombination of the RX and Y products (leading to reformation of the ground state parent and/or isomeric adducts). Nonetheless, the data also show that, in each case, the characteristics (and the timescale) of the initial bond fission process that occurs under isolated molecule conditions are barely changed by the presence of a weakly interacting solvent like cyclohexane. These condensed phase studies are then extended to an ether analogue of phenol (allyl phenyl ether), wherein UV photo-induced RO-allyl bond fission constitutes the first step of a photo-Claisen rearrangement. 23578642 C-Phycocyanin from Oscillatoria tenuis exhibited an antioxidant and in vitro antiproliferative activity through induction of apoptosis and G0/G1 cell cycle arrest. This study was undertaken to develop an efficient single step chromatographic method for purification of C-phycocyanin (CPC) from species of Oscillatoria tenuis. Purification of CPC involves a multistep treatment of the crude extract by precipitation with ammonium sulphate, followed by gel filtration chromatography. Pure CPC was finally obtained from O. tenuis with purity ratio (A620/A280) 4.88. SDS-PAGE of pure CPC yielded two bands corresponding to α and β subunits; the molecular weight of α subunit is 17.0kDa, whereas the molecular weight of β subunit is 19.5kDa. Fluorescence and phase contrast microscopy revealed characteristic apoptotic features like cell shrinkage, membrane blebbing, nuclear condensation and DNA fragmentation. CPC exhibited antioxidant and antiproliferative activity against human cancer cells through apoptosis; nuclear apoptosis induction was accompanied by G0/G1 phase arrest and DNA fragmentation. CPC is a natural pigment with potential as an anticancer agent. 23159712 Mucoadhesive multiparticulate patch for the intrabuccal controlled delivery of lidocaine. The aim of the present study was to prepare and evaluate patches for the controlled release of lidocaine in the oral cavity. Mucoadhesive buccal patches, containing 8 mg/cm(2) lidocaine base, were formulated and developed by solvent casting method technique, using a number of different bio-adhesive and film-forming semi-synthetic and synthetic polymers (Carbopol, Poloxamer, different type Methocel) and plasticizers (PEG 400, triethyl citrate); the patches were evaluated for bioadhesion, in vitro drug release and permeation using a modified Franz diffusion cell. A lidocaine/Compritol solid dispersion in the form of microspheres, embedded inside the patch, alone or together with free lidocaine, was also examined to prolong the drug release. The effects of the composition were evaluated considering a number of technological parameters and the release of the drug. All the formulations tested offer a variety of drug release mechanisms, obtaining a quick or delayed or prolonged anesthetic local activity with simple changes of the formulation parameters. 23355616 Effects of DNA methylation on nucleosome stability. Methylation of DNA at CpG dinucleotides represents one of the most important epigenetic mechanisms involved in the control of gene expression in vertebrate cells. In this report, we conducted nucleosome reconstitution experiments in conjunction with high-throughput sequencing on 572 KB of human DNA and 668 KB of mouse DNA that was unmethylated or methylated in order to investigate the effects of this epigenetic modification on the positioning and stability of nucleosomes. The results demonstrated that a subset of nucleosomes positioned by nucleotide sequence was sensitive to methylation where the modification increased the affinity of these sequences for the histone octamer. The features that distinguished these nucleosomes from the bulk of the methylation-insensitive nucleosomes were an increase in the frequency of CpG dinucleotides and a unique rotational orientation of CpGs such that their minor grooves tended to face toward the histones in the nucleosome rather than away. These methylation-sensitive nucleosomes were preferentially associated with exons as compared to introns while unmethylated CpG islands near transcription start sites became enriched in nucleosomes upon methylation. The results of this study suggest that the effects of DNA methylation on nucleosome stability in vitro can recapitulate what has been observed in the cell and provide a direct link between DNA methylation and the structure and function of chromatin. 23607578 Fast Vortex-Assisted Self-Assembly of Carbon Nanoparticles on Air-Water Interface. In this work a new self-assembly technique is presented, allowing the fast formation of carbon black thin films. It consists in the controlled addition of a stable carbon material's dispersion over the water surface, disturbed by a vortex. The vortex, although not essential for the film formation, was found to drastically improve film homogeneity. A physical chemical study concerning how several parameters could be used to tune film properties was also conducted. The self-assembled films, which can be picked up in any hydrophilic substrate, showed a good electrical conductivity and a high optical transparency. As an application example, films about 200 nm thick were employed as supercapacitor electrodes. 23265529 Optimization of gas chromatography-single quadrupole mass spectrometry conditions for multiresidue analysis of pesticides in grapes in compliance to EU-MRLs. A single quadrupole GC-MS method was optimized for multiresidue determination of 47 pesticides in grapes with limit of quantifications of each compound in compliance with the EU-MRL requirements. Sample preparation involved extraction of 10 g sample with 10 ml ethyl acetate (+10 g sodium sulphate) by homogenization at 15,000 rpm followed by centrifugation at 3000 rpm. The supernatant was cleaned by dispersive solid phase extraction with primary secondary amine and acidified with 0.1% formic acid. Residues were estimated in selected ion monitoring mode with programmable temperature vaporizer-large volume injection (8 μl). All the GC and MS parameters were thoroughly optimized to achieve satisfactory linearity (R(2)>0.99) within 0.01-0.25 mg kg(-1) with minimum matrix interferences. Recoveries at 0.01 and 0.02 mg kg(-1) were within 67-120% with associated precision RSD below 19%. The method was successfully applied for analysis of the real world samples for incurred residues. 22982302 A chemistry wiki to facilitate and enhance compound design in drug discovery. At AstraZeneca a focus on hypothesis-driven design and the formation of drug design teams has placed a greater emphasis on collaboration in the drug discovery process. We have created a novel software tool based on the principles of wikis and social networks to facilitate collaborative working, visual planning and incorporation of predictive science to improve design capability. Monitoring the design and make process via the tool enabled the identification of bottlenecks and delays. Solutions to these problems were implemented, reducing the time taken from the initial idea stage to the generation of the synthesised compound by more than 50%. 23174517 Usage patterns of personal care products: important factors for exposure assessment. Complete information regarding the use of personal care products (PCPs) by consumers is limited, but such information is crucial for realistic consumer exposure assessment. To fill this gap, a database was created with person-oriented information regarding usage patterns and circumstances of use for 32 different PCPs. Out of 2700 potential participants from the Netherlands, 516 men and women completed a digital questionnaire. The prevalence of use varied by gender, age, level of education and skin type. A high frequency of use was observed for some products (e.g. lip care products), while toothpaste, deodorant and day cream were generally used once or twice a day. The frequency of use for other PCPs varied over a wide range. The amounts of use varied largely between and within different product groups. Body lotion, sunscreen and after sun lotion were often applied on adjacent body parts. The majority of PCPs were applied in the morning, but some products, such as night cream and after sun, were predominantly applied in the evening or night. As expected, the participants used several PCPs simultaneously. The database yields important personalized exposure factors which can be used in aggregate consumer exposure assessment for substances that are components of PCPs. 23022069 Performance of urinary and gene expression biomarkers in detecting the nephrotoxic effects of melamine and cyanuric acid following diverse scenarios of co-exposure. Although standard nephrotoxicity assessments primarily detect impaired renal function, KIM-1, clusterin, NGAL, osteopontin and TIMP-1 were recently identified biomarkers proposed to indicate earlier perturbations in renal integrity. The recent adulteration of infant and pet food with melamine (MEL) and structurally-related compounds revealed that co-ingestion of MEL and cyanuric acid (CYA) could form melamine-cyanurate crystals which obstruct renal tubules and induce acute renal failure. This study concurrently evaluated the ability of multiplexed urinary biomarker immunoassays and biomarker gene expression analysis to detect nephrotoxicity in F344 rats co-administered 60ppm each of MEL and CYA in feed or via gavage for 28days. The biomarkers were also evaluated for the ability to differentiate the effects of the compounds when co-administered using diverse dosing schedules (i.e., consecutive vs. staggered gavage) and dosing matrixes (i.e., feed vs. gavage). Our results illustrate the ability of both methods to detect and differentiate the severity of adverse effects in the staggered and consecutive gavage groups at much lower doses than previously observed in animals co-exposed to the compounds in feed. We also demonstrate that these urinary biomarkers outperform traditional diagnostic methods and represent a powerful, non-invasive indicator of chemical-induced nephrotoxicity prior to the onset of renal dysfunction. 23292988 Electron doping by charge transfer at LaFeO3/Sm2CuO4 epitaxial interfaces. Using X-ray absorption spectroscopy and electron energy loss spectroscopy with atomic-scale spatial resolution, experimental evidence for charge transfer at the interface between the Mott insulators Sm2 CuO4 and LaFeO3 is obtained. As a consequence of the charge transfer, the Sm2 CuO4 is doped with electrons and thus epitaxial Sm2 CuO4 /LaFeO3 heterostructures become metallic. 23265843 Lucidone from Lindera erythrocarpa Makino fruits suppresses adipogenesis in 3T3-L1 cells and attenuates obesity and consequent metabolic disorders in high-fat diet C57BL/6 mice. Obesity is associated with an increased risk of development of numerous diseases including type 2 diabetes, hypertension, hyperlipidemia, and cardiovascular disease. In this study, we investigated the effects of lucidone in vitro on gene expression during adipogenesis in 3T3-L1 cells and in vivo on high-fat diet induced obesity in C57BL/6 mice. Lucidone at 40 μmol/L suppressed adipogenesis in 3T3-L1 cells by reducing transcription levels of adipogenic genes, including PPARγ, C/EBPα, LXR-α, LPL, aP2, GLUT4 and adiponectin. Five-week-old male C57BL/6 mice fed a high fat diet (60% energy from fat) supplemented with lucidone at a dosage of 1250 mg/kg of diet for 12 weeks had reduced body and liver weight, reduced epididymal and perirenal adipose tissue, decreased food efficiency (percentage of weight gain divided by food intake), and lowered plasma cholesterol, triglyceride, glucose, and insulin levels. Dissection of adipose tissue from lucidone-treated mice showed a reduction in the average fat-cell size and percentage of large adipocytes. These results provide evidence that dietary intake of lucidone alleviates high fat diet-induced obesity in C57BL/6 mice and reveals the potential of lucidone as a nutraceutical to prevent obesity and consequent metabolic disorders. 23450829 Hierarchically Structured Nanotubes for Highly Efficient Dye-Sensitized Solar Cells. Hierarchical TiO2 nanotube arrays grown on Ti foil are yielded by subjecting electrochemically anodized, vertically oriented TiO2 nanotube arrays to hydrothermal processing. The resulting DSSCs exhibit a significantly enhanced power conversion efficiency of 7.24%, which is a direct consequence of the synergy of higher dye loading, superior light-scattering ability, and fast electron transport. 23281613 Two new ent-3,4-seco-labdane diterpenoids from Callicarpa nudiflora. Two new ent-3,4-seco-labdane diterpenoids, methylcallicarpate (1) and callicarpic acid (2), were isolated from the leaves of Callicarpa nudiflora Hook et Arn. Their structures and relative configurations were established by analysis of spectroscopic data. Their absolute configurations were assigned by the application of the CD technique for the first time among the ent-3,4-seco-labdane-type diterpenes. 23542008 Steric Complementarity in the Decoding Center Is Important for tRNA Selection by the Ribosome. Accurate tRNA selection by the ribosome is essential for the synthesis of functional proteins. Previous structural studies indicated that the ribosome distinguishes between cognate and near-cognate tRNAs by monitoring the geometry of the codon-anticodon helix in the decoding center using the universally conserved 16S ribosomal RNA bases G530, A1492 and A1493. These bases form hydrogen bonds with the 2'-hydroxyl groups of the codon-anticodon helix, which are expected to be disrupted with a near-cognate codon-anticodon helix. However, a recent structural study showed that G530, A1492 and A1493 form hydrogen bonds in a manner identical with that of both cognate and near-cognate codon-anticodon helices. To understand how the ribosome discriminates between cognate and near-cognate tRNAs, we made 2'-deoxynucleotide and 2'-fluoro substituted mRNAs, which disrupt the hydrogen bonds between the A site codon and G530, A1492 and A1493. Our results show that multiple 2'-deoxynucleotide substitutions in the mRNA substantially inhibit tRNA selection, whereas multiple 2'-fluoro substitutions in the mRNA have only modest effects on tRNA selection. Furthermore, the miscoding antibiotics paromomycin and streptomycin rescue the defects in tRNA selection with the multiple 2'-deoxynucleotide substituted mRNA. These results suggest that steric complementarity in the decoding center is more important than the hydrogen bonds between the A site codon and G530, A1492 and A1493 for tRNA selection. 23466488 Oral l-glutamine increases active GLP-1 (7-36) amide secretion and improves glycemic control in stretpozotocin-nicotinamide induced diabetic rats. l-glutamine is a non-essential amino acid. It decreased blood sugar, stimulated insulin secretion in type 2 diabetic patients. The objective of the present investigation was to evaluate l-glutamine increases glucagon like peptide-1 (GLP-1) (7-36) amide secretion in streptozotocin-nicotinamide (STZ-NTM) induced diabetic Sprague Dawley rats. Molecular docking study was performed to elucidate the molecular basis for GLP-1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100mg/kg, i.p.) followed by 20min after administration of streptozotocin (55mg/kg, i.p.). The rats were divided into; I - nondiabetic, II - diabetic control, III - sitagliptin (5mg/kg, p.o.), IV -l-glutamine (250mg/kg, p.o.), V -l-glutamine (500mg/kg, p.o.) and VI -l-glutamine (1000mg/kg, p.o.). The l-glutamine and sitagliptin treatment was 8week. Plasma glucose was estimated every week. Body weight, food and water intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, mRNA expression of proglucagon GLP-1, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8week. In acute study, the rats were divided into I - glucose (2.5g/kg, p.o.), II - sitagliptin (5mg/kg, p.o.), III -l-glutamine (250mg/kg, p.o.), IV -l-glutamine (500mg/kg, p.o.) and V -l-glutamine (1000mg/kg, p.o.). Plasma glucose, active GLP-1 (7-36) amide concentration and insulin levels were measured after glucose loading. The docking data indicated that l-glutamine bind to the GLP-1 receptor. l-glutamine decreased plasma glucose, increased plasma and pancreatic insulin, increased plasma and colonic active GLP-1 (7-36) amide secretion as well as decreased oxidative stress in streptozotocin-nicotinamide induced diabetic rats. 22709945 Neonatal exposure to low dose corticosterone persistently modulates hippocampal mineralocorticoid receptor expression and improves locomotor/exploratory behaviour in a mouse model of Rett syndrome. Rett syndrome (RTT) is a pervasive neurodevelopmental disorder, primarily affecting girls. RTT causes a wide variety of debilitating symptoms and no cure currently exists. Mouse models bearing mutations in the Mecp2 gene recapitulate most physiological and behavioural RTT-related abnormalities. Stimulating neonatal environments (e.g. brief maternal separations or maternal low-dose corticosterone supplementation) reduce stress and fear responses at adulthood. The present study investigated whether impacting early in development the hypothalamic-pituitary-adrenal axis, by exposing Mecp2-308 mutant pups to a low dose of corticosterone (50 µg/ml, during the 1st week of life) may contrast RTT-related abnormalities in neuroendocrine regulation and behavioural adaptation at adulthood. In line with previous reports, when fully symptomatic, MeCP2-308 mice showed a reduction in the regular nocturnal hyperactivity in the home-cage and increased anxiety-like behaviours and plasma corticosterone (CORT) levels in response to restraint stress. An abnormal elevation in mRNA levels of mineralocorticoid receptors (MR) and BDNF gene was also evident in the hippocampus of fully symptomatic mutant mice. Neonatal CORT modulated MR gene expression and behavioural reactivity towards a novel object, also restoring wt-like levels of locomotor/exploratory behaviour in mutant mice. Enhanced sensitivity to the neonatal treatment (in terms of increase in GR and MR mRNA levels), was also evident in the hippocampus of MeCP2-308 mice compared to wt littermates. Present results corroborate the hypothesis that targeting the glucocorticoid system may prove valid in contrasting at least some of the RTT-related symptoms and provide evidence that pharmacological interventions during critical early time windows can persistently improve the behavioural phenotype of RTT mice. Current data also support the emerging role played by Mecp2 in mediating the epigenetic programming induced by early life events and indicate that, in the absence of functional MeCP2, programming of the central nervous system in response to early environmental stimuli is abnormally regulated. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. 23411340 Redox spectrophotometric method involving electrolytically generated manganese(III) sulphate with diphenylamine for the determination of ascorbic acid present in the samples of various fruits, commercial juices and sprouted food grains. A spectrophotometric method was developed for ascorbic acid present in various fruits, commercial fruit juices and sprouted food grains. The method involves the oxidation of ascorbic acid with excess manganese(III) following reduction of unreacted manganese(III) with diphenylamine or barium diphenylamine sulphonate forming a product λ(max) 570 nm the system 1 or 540 nm the system 2 and decrease in the colour intensity is proportional to the concentration of vitamin C with quantification range 0.3-3.0 μg ml(-1). The molar absorptivity and Sandell's sensitivity values of the system 1 and the system 2 were 1.829 × 10(4) and 1.813 × 10(4)mol(-1)cm(-1) and 0.0096 and 0.0097 μg cm(-2) respectively. The stoichiometry was 4:1 between manganese(III) and diphenylamine. The ascorbic acid contents of the same samples were determined separately following the procedures of the developed method as well as the reference method and the results were comparable. 23432058 TRP Channels as Targets for Therapeutic Intervention in Obesity: Focus on TRPV1 and TRPM5. The disease of obesity is one of the greatest healthcare challenges of our time. The increasing urgency for effective treatment is driving an intensive search for new targets for anti-obesity drug discovery. The TRP channel super family represents a class of proteins now recognized to serve many functions in physiology related to maintenance of health and the development of diseases. A few of these might offer new potential for therapeutic intervention in obesity. Among the TRP channels, TRPV1 appears most closely associated with body weight homeostasis through its influence on energy expenditure. TRPM5 has been thoroughly characterized as a critical component of taste signaling and recently has been implicated in insulin release. Because of its role in taste signaling, we argue that drugs designed to modulate TRPM5 could be useful in controlling energy consumption by impacting taste sensory signals. As drug targets for obesity, both TRPV1 and TRPM5 offer the advantage of operating in compartments that could limit drug distribution to the site of action. The potential for other TRP channels as anti-obesity drug targets also is discussed. 23323829 Design and application of anthracene derivative with aggregation-induced emission charateristics for visualization and monitoring of erythropoietin unfolding. Erythropoietin (EPO) is an attractive protein-unfolding/folding model because of its high degree of unfolding and folding reversibility and intermediate size. Due to its function for regulating red blood cell production by stimulating late erythroid precursor cells, EPO presents obvious values to biological research. A nonemissive anthracene derivative, that is 9,10-bis[4-(3-sulfonatopropoxyl)-styryl]anthracene sodium salt (BSPSA), with aggregation-induced emission (AIE) charateristics shows a novel phenomenon of AIE when EPO is added. The AIE biosensor for EPO shows the limit of detection is 1 × 10(-9) M. Utilizing the AIE feature of BSPSA, the unfolding process of EPO using guanidine hydrochloride is monitored, which indicates three steps for the folding structures of EPO to transform to random coil. Computational modeling suggests that the BSPSA luminogens prefer docking in the hydrophobic cavity in the EPO folding structures, and the assembly of BSPSA in this cavity makes the AIE available, making the monitoring of unfolding of EPO possible. 22468741 Plant proteins, minerals and trace elements of Eurycoma longifolia (Tongkat Ali). A water extraction method has been used to extract plant proteins from the roots of Eurycoma longifolia harvested from Perak and Pahang, Malaysia. On the basis of the spectroscopic Bradford assay, Tongkat Ali Perak and Pahang contained 0.3868 and 0.9573 mg mL(-1) of crude protein, respectively. The crude proteins were separated by one dimensional 15% sodium dodecyl sulphate polyacrylamide gel electrophoresis into two (49.8 and 5.5 kD) and four (49.8, 24.7, 21.1 and 5.5 kD) protein spots for Tongkat Ali Perak and Pahang, respectively. Isoleucine was present in the highest concentration significantly. Both plant samples showed differences in the mineral and trace element profiles, but the minerals calcium, magnesium and potassium were present in the highest concentration. The highly concerned toxic metals such as arsenic and lead were not detected. 23194524 Recovery and characterisation of coloured phenolic preparations from apple seeds. The aim of this study was to investigate whether complexly constituted phenolic extracts from apple seeds may be utilised for the recovery of natural coloured antioxidant preparations, which might serve as potential food or cosmetic ingredients. In a first step, the recovery of phenolic compounds was optimised by varying crucial extraction parameters. A single extraction step at 25°C using an acetone-water mixture (60:40, v/v) and a solid-to-solvent ratio of 1:8 (w/v) for 1 h was found to be appropriate to achieve both high phenolic yields and antioxidant activities. In a second step, differently produced apple seed extracts and a phloridzin model solution were enzymatically treated by mushroom polyphenol oxidase to investigate the rate of pigment synthesis. Depending on the extraction procedure applied, synthesis rates, pigment yields and colour properties significantly differed. Compared to the phloridzin model solution, extracts recovered from the seeds showed comparable and even better results, thus indicating such preparations to be a promising alternative to synthetic yellow dyes. 23325489 Identification and quantification of the sedative and anticonvulsant flavone glycoside from Chrysanthemum boreale. The flowers or leaves of Chrysanthemum boreale (Compositae) have been traditionally used as herb tea to reduce anxiety, insomnia, and stress. Sedative and anticonvulsant activities were evaluated in mice using pentobarbital-induced sleeping assay and pentylenetetrazole (PTZ)-induced convulsion assay. The flower extract exhibited more potent activities than the extracts of the leaves and stems, and chromatographic isolation yielded the five compounds acacetin, linarin, acacetin 7-O-β-D-glucopyranosyl-(1 → 2)[α-L-rhamnopyranosyl-(1 → 6)]-β-D-glucopyranoside, chlorogenic acid, and 3,5-di-O-caffeoylquinic acid. These compounds were simultaneously analyzed by HPLC, and the method was validated. The contents of linarin, which were shown to be most abundant in C. boreale, were observed in the order of leaf (11.93 mg/g) > flower (8.50 mg/g) > stem (5.60 mg/g). Linarin and its aglycone, acacetin, exhibited sedative and anticonvulsant activities in the present in vivo assays. It can be considered that linarin is one of the active compounds effective against anxiety, insomnia, and stress, with acacetin as its active moiety. 23503472 Associations of ABCB1, NFKB1, CYP3A, and NR1I2 polymorphisms with cyclosporine trough concentrations in Chinese renal transplant recipients. Aim:Cyclosporine requires close therapeutic drug monitoring because of its narrow therapeutic index and marked inter-individual pharmacokinetic variation. In this study, we investigated the associations of CYP3A4, CYP3A5, ABCB1, NFKB1, and NR1I2 polymorphisms with cyclosporine concentrations in Chinese renal transplant recipients in the early period after renal transplantation.Methods:A total of 101 renal transplant recipients receiving cyclosporine were genotyped for CYP3A4(*)1G, CYP3A5(*)3, ABCB1 C1236T, G2677T/A, C3435T, NFKB1 -94 ins/del ATTG, and NR1I2 polymorphisms. Cyclosporine whole blood levels were measured by a fluorescence polarization immunoassay. Trough concentrations of cyclosporine were determined for days 7-18 following transplantation.Results:The dose-adjusted trough concentration (C0) of cyclosporine in ABCB1 2677 TT carriers was significantly higher than that in GG carriers together with GT carriers [90.4±24.5 vs 67.8±26.8 (ng/mL)/(mg/kg), P=0.001]. ABCB1 3435 TT carriers had a significantly higher dose-adjusted C0 of cyclosporine than CC carriers together with CT carriers [92.0±24.0 vs 68.4±26.5 (ng/mL)/(mg/kg), P=0.002]. Carriers of the ABCB1 1236TT-2677TT-3435TT haplotype had a considerably higher CsA C0/D than carriers of other genotypes [97.2±21.8 vs 68.7±26.9 (ng/mL)/(mg/kg), P=0.001]. Among non-carriers of the ABCB1 2677 TT and 3435 TT genotypes, patients with the NFKB1 -94 ATTG ins/ins genotype had a significantly higher dose-adjusted C0 than those with the -94 ATTG del/del genotype [75.9±32.9 vs 55.1±15.1 (ng/mL)/(mg/kg), P=0.026].Conclusion:These results illustrate that the ABCB1 and NFKB1 genotypes are closely correlated with cyclosporine trough concentrations, suggesting that these SNPs are useful for determining the appropriate dose of cyclosporine. 23238657 Acute Macrovascular Dysfunction in Patients With Type 2 Diabetes Induced by Ingestion of Advanced Glycated β-Lactoglobulins. OBJECTIVE Recent evidence indicates that heat-enhanced food advanced glycation end products (AGEs) adversely affect vascular function. The aim of this study was to examine the acute effects of an oral load of heat-treated, AGE-modified β-lactoglobulins (AGE-BLG) compared with heat-treated, nonglycated BLG (C-BLG) on vascular function in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS In a double-blind, controlled, randomized, crossover study, 19 patients with T2DM received, on two different occasions, beverages containing either AGE-BLG or C-BLG. We measured macrovascular [brachial ultrasound of flow-mediated dilatation (FMD)] and microvascular (laser-Doppler measurements of reactive hyperemia in the hand) functions at baseline (T0), 90 (T90), and 180 (T180) min. RESULTS Following the AGE-BLG, FMD decreased at T90 by 80% from baseline and remained decreased by 42% at T180 (P < 0.05 vs. baseline, P < 0.05 vs. C-BLG at T90). By comparison, following C-BLG, FMD decreased by 27% at T90 and 51% at T180 (P < 0.05 vs. baseline at T180). A significant decrease in nitrite (T180) and nitrate (T90 and T180), as well as a significant increase in N(ε)-carboxymethyllisine, accompanied intake of AGE-BLG. There was no change in microvascular function caused by either beverage. CONCLUSIONS In patients with T2DM, acute oral administration of a single AGE-modified protein class significantly though transiently impaired macrovascular function in concert with decreased nitric oxide bioavailability. These AGE-related changes were independent of heat treatment. 23356907 Phthalocyanine-Peptide Conjugates: Receptor-Targeting Bifunctional Agents for Imaging and Photodynamic Therapy. The synthesis of a series of new zinc phthalocyanine-peptide conjugates targeting the gastrin-releasing peptide (GRP) and integrin receptors is reported. Two alternative synthetic methods based on Sonogashira cross-coupling of an iodinated zinc phthalocyanine with acetylenic bombesin or arginine-glycine-aspartic acid (RGD) derivatives, either in solution or on solid phase, are presented. The water-soluble conjugates were screened for their photodynamic efficacy against several cancer cell lines expressing different levels of GRP and integrin receptors, and their intracellular localization was evaluated via confocal fluorescence microscopy. Variations in photocytotoxicity between the conjugates correlate to differences in hydrophobicity as well as receptor-mediated cell uptake. In the case of the phthalocyanine-bombesin conjugate, competition experiments confirm the involvement of the GRP receptor in both the phototherapeutic activity as well as intracellular localization. These findings warrant further in vivo studies to evaluate the potential of this conjugate as photosensitizer for photodynamic therapy (PDT) of cancers overexpressing the GRP receptor. 23331669 Morphological, ecological and genetic aspects associated with endemism in the Fly Orchid group. The European genus Ophrys (Orchidaceae) is famous for its insect-like floral morphology, an adaptation for a pseudocopulatory pollination strategy involving Hymenoptera males. A large number of endemic Ophrys species have recently been described, especially within the Mediterranean Basin, which is one of the major species diversity hotspots. Subtle morphological variation and specific pollinator dependence are the two main perceptible criteria for describing numerous endemic taxa. However, the degree to which endemics differ genetically remains a challenging question. Additionally, knowledge regarding the factors underlying the emergence of such endemic entities is limited. To achieve new insights regarding speciation processes in Ophrys, we have investigated species boundaries in the Fly Orchid group (Ophrys insectifera sensu lato) by examining morphological, ecological and genetic evidence. Classically, authors have recognized one widespread taxon (O. insectifera) and two endemics (O. aymoninii from France and O. subinsectifera from Spain). Our research has identified clear morphological and ecological factors segregating among these taxa; however, genetic differences were more ambiguous. Insights from cpDNA sequencing and amplified fragment length polymorphisms genotyping indicated a recent diversification in the three extant Fly Orchid species, which may have been further obscured by active migration and admixture across the European continent. Our genetic results still indicate weak but noticeable phylogeographic clustering that partially correlates with the described species. Particularly, we report several isolated haplotypes and genetic clusters in central and southeastern Europe. With regard to the morphological, ecological and genetic aspects, we discuss the endemism status within the Fly Orchid group from evolutionary, taxonomical and conservation perspectives. 23198819 Bioinspired and highly oriented clay nanocomposites with a xyloglucan biopolymer matrix: extending the range of mechanical and barrier properties. The development of clay bionanocomposites requires processing routes with nanostructural control. Moreover, moisture durability is a concern with water-soluble biopolymers. Here, oriented bionanocomposite coatings with strong in-plane orientation of clay platelets are for the first time prepared by continuous water-based processing. Montmorillonite (MTM) and a "new" unmodified biological polymer (xyloglucan (XG)) are combined. The resulting nanocomposites are characterized by FE-SEM, TEM, and XRD. XG adsorption on MTM is measured by quartz crystal microbalance analysis. Mechanical and gas barrier properties are measured, also at high relative humidity. The reinforcement effects are modeled. XG dimensions in composites are estimated using atomistic simulations. The nanostructure shows highly oriented and intercalated clay platelets. The reinforcement efficiency and effects on barrier properties are remarkable and are likely to be due to highly oriented and well-dispersed MTM and strong XG-MTM interactions. Properties are well preserved in humid conditions and the reasons for this are discussed. 23493449 Development of N-Hydroxycinnamamide-Based Histone Deacetylase Inhibitors with Indole-Containing Cap Group. A novel series of histone deacetylase inhibitors combining N-hydroxycinnamamide bioactive fragment and indole bioactive fragment was designed and synthesized. Several compounds (17c, 17g, 17h, 17j and 17k) exhibited comparable even superior total HDACs inhibitory activity and in vitro antiproliferative activities relative to the approved drug SAHA. A representative compound 17a with moderate HDACs inhibition was progressed to isoform selectivity profile, western blot analysis and in vivo antitumor assay. Although HDACs isoform selectivity of 17a was similar to that of SAHA, our western blot results indicated that intracellular effects of 17a at 1 μM were class I selective. It was noteworthy that the effect on histone H4 acetylation of SAHA decreased with time while the effect on histone H4 acetylation of 17a maintained even increased. Most importantly, compound 17a exhibited promising in vivo antitumor activity in a U937 xenograft model. 23235435 Computational study of the spin-state energies and UV-Vis spectra of bis(1,4,7-triazacyclononane) complexes of some first-row transition metal cations. We report here computed spin-state energies and UV-Vis spectra for several transition metal complexes with a triazacyclononane ligand. Our results show that the spin ground-state is correctly obtained with either OPBE or SSB-D, except for the high-spin ground-state of the Co(ii) complex that was properly described only by SSB-D. The UV-Vis spectra from TD-DFT reproduce in general rather well the experimental spectra, but in cases of the Cr(iii) and Co(ii) complexes it clearly failed. Better results for the UV-Vis spectra have been obtained by using Ligand Field DFT. 23360232 Surface-modified HK:siRNA nanoplexes with enhanced pharmacokinetics and tumor growth inhibition. We characterized in this study the pharmacokinetics and antitumor efficacy of histidine-lysine (HK):siRNA nanoplexes modified with PEG and a cyclic RGD (cRGD) ligand targeting αvβ3 and αvβ5 integrins. With noninvasive imaging, systemically administered surface-modified HK:siRNA nanoplexes showed nearly 4-fold greater blood levels, 40% higher accumulation in tumor tissue, and 60% lower luciferase activity than unmodified HK:siRNA nanoplexes. We then determined whether the surface-modified HK:siRNA nanoplex carrier was more effective in reducing MDA-MB-435 tumor growth with an siRNA targeting Raf-1. Repeated systemic administration of the selected surface modified HK:siRNA nanoplexes targeting Raf-1 showed 35% greater inhibition of tumor growth than unmodified HK:siRNA nanoplexes and 60% greater inhibition of tumor growth than untreated mice. The improved blood pharmacokinetic results and tumor localization observed with the integrin-targeting surface modification of HK:siRNA nanoplexes correlated with greater tumor growth inhibition. This investigation reveals that through control of targeting ligand surface display in association with a steric PEG layer, modified HK: siRNA nanoplexes show promise to advance RNAi therapeutics in oncology and potentially other critical diseases. 23337202 Self-Assembly of Discrete Metal Complexes in Aqueous Solution via Block Copolypeptide Amphiphiles. The integration of discrete metal complexes has been attracting significant interest due to the potential of these materials for soft metal-metal interactions and supramolecular assembly. Additionally, block copolypeptide amphiphiles have been investigated concerning their capacity for self-assembly into structures such as nanoparticles, nanosheets and nanofibers. In this study, we combined these two concepts by investigating the self-assembly of discrete metal complexes in aqueous solution using block copolypeptides. Normally, discrete metal complexes such as [Au(CN)(2)]-, when molecularly dispersed in water, cannot interact with one another. Our results demonstrated, however, that the addition of block copolypeptide amphiphiles such as K(183)L(19) to [Au(CN)(2)]- solutions induced one-dimensional integration of the discrete metal complex, resulting in photoluminescence originating from multinuclear complexes with metal-metal interactions. Transmission electron microscopy (TEM) showed a fibrous nanostructure with lengths and widths of approximately 100 and 20 nm, respectively, which grew to form advanced nanoarchitectures, including those resembling the weave patterns of Waraji (traditional Japanese straw sandals). This concept of combining block copolypeptide amphiphiles with discrete coordination compounds allows the design of flexible and functional supramolecular coordination systems in water. 23644652 An associative capacitive network based on nanoscale complementary resistive switches for memory-intensive computing. We report on the implementation of an Associative Capacitive Network (ACN) based on the nondestructive capacitive readout of two Complementary Resistive Switches (2-CRSs). ACNs are capable of performing a fully parallel search for Hamming distances (i.e. similarity) between input and stored templates. Unlike conventional associative memories where charge retention is a key function and hence, they require frequent refresh cycles, in ACNs, information is retained in a nonvolatile resistive state and normal tasks are carried out through capacitive coupling between input and output nodes. Each device consists of two CRS cells and no selective element is needed, therefore, CMOS circuitry is only required in the periphery, for addressing and read-out. Highly parallel processing, nonvolatility, wide interconnectivity and low-energy consumption are significant advantages of ACNs over conventional and emerging associative memories. These characteristics make ACNs one of the promising candidates for applications in memory-intensive and cognitive computing, switches and routers as binary and ternary Content Addressable Memories (CAMs) and intelligent data processing. 23322347 Emerging mechanistic targets in lung injury induced by combustion-generated particles. The mechanism for biological effect following exposure to combustion-generated particles is incompletely defined. The identification of pathways regulating the acute toxicological effects of these particles provides specific targets for therapeutic manipulation in an attempt to impact disease following exposures. Transient receptor potential (TRP) cation channels were identified as "particle sensors" in that their activation was coupled with the initiation of protective responses limiting airway deposition and inflammatory responses, which promote degradation and clearance of the particles. TRPA1, V1, V4, and M8 have a capacity to mediate adverse effects after exposure to combustion-generated particulate matter (PM); relative contributions of each depend upon particle composition, dose, and deposition. Exposure of human bronchial epithelial cells to an organic extract of diesel exhaust particle was followed by TRPV4 mediating Ca(++) influx, increased RAS expression, mitogen-activated protein kinase signaling, and matrix metalloproteinase-1 activation. These novel pathways of biological effect can be targeted by compounds that specifically inhibit critical signaling reactions. In addition to TRPs and calcium biochemistry, humic-like substances (HLS) and cell/tissue iron equilibrium were identified as potential mechanistic targets in lung injury after particle exposure. In respiratory epithelial cells, iron sequestration by HLS in wood smoke particle (WSP) was associated with oxidant generation, cell signaling, transcription factor activation, and release of inflammatory mediators. Similar to WSP, cytotoxic insoluble nanosized spherical particles composed of HLS were isolated from cigarette smoke condensate. Therapies that promote bioelimination of HLS and prevent the disruption of iron homeostasis could function to reduce the harmful effects of combustion-generated PM exposure. 22420410 Structure elucidation of a new natural diketopiperazine from a Microbispora aerata strain isolated from Livingston Island, Antarctica. A new natural diketopiperazine (1) was obtained from the culture broth of Microbispora aerata strain imbas-11A, isolated from penguin excrements collected on the Antarctic Livingston Island. Compound 1 was purified consecutively by solvent extraction, silica gel column chromatography and preparative HPLC. The structure of the compound was elucidated by 1D and 2D NMR experiments and mass spectrometric investigations. The absolute configuration of compound 1 was determined by amino acid analysis and NOESY correlations. A low antiproliferative and cytotoxic effect of trans-cyclo-(D-tryptophanyl-L-tyrosyl) (1) was determined with L-929 mouse fibroblast cells, K-562 human leukemia cells and HeLa human cervix carcinoma. Trans-cyclo-(D-tryptophanyl-L-tyrosyl) (1) did not show antimicrobial activity at a concentration of 50 µg per disc against Bacillus subtilis, Staphylococcus aureus, Streptomyces viridochromogenes, Escherichia coli, Candida albicans and Mucor miehei. 23234855 Influence of carboxylic acid functionalities in ruthenium (II) polypyridyl complexes on DNA binding, cytotoxicity and antioxidant activity: synthesis, structure and in vitro anticancer activity. Four new Ru(II) complexes [RuHCl(bpy)(PPh(3))(CO)] (1), [RuHCl(bpy)(AsPh(3))(CO)] (2) (bpy = 2,2'-bipyridine), [RuCl(HL)(PPh(3))(2)(CO)] (3) and [RuCl(HL)(AsPh(3))(2)(CO)] (4) (HL = 2,2'-bipyridine-4,4'-dicarboxylic acid) were synthesized and characterized. X-ray diffraction was used to characterize 3 in solid state. The interactions of these complexes with DNA were explored by different techniques which revealed that the complexes could bind to CT-DNA through non-intercalation. The in vitro cytotoxic and antioxidant activities of the complexes validated against a panel of cancer cell lines and free radicals showed that 3 and 4 possess quite high anticancer and antioxidant activities over 1, 2 and standard drugs. An apparent dependence of biological activities on incorporation of COOH in bipyridine moiety was noticed: Inclusion of COOH caused significant differences in DNA binding, cytotoxicity and antioxidant activity. 23074173 The iron chelator, deferasirox, as a novel strategy for cancer treatment: oral activity against human lung tumor xenografts and molecular mechanism of action. Deferasirox is an orally effective iron (Fe) chelator currently used for the treatment of iron-overload disease and has been implemented as an alternative to the gold standard chelator, desferrioxamine (DFO). Earlier studies demonstrated that DFO exhibits anticancer activity due to its ability to deplete cancer cells of iron. In this investigation, we examined the in vitro and in vivo activity of deferasirox against cells from human solid tumors. To date, there have been no studies to investigate the effect of deferasirox on these types of tumors in vivo. Deferasirox demonstrated similar activity at inhibiting proliferation of DMS-53 lung carcinoma and SK-N-MC neuroepithelioma cell lines compared with DFO. Furthermore, deferasirox was generally similar or slightly more effective than DFO at mobilizing cellular (59)Fe and inhibiting iron uptake from human transferrin depending on the cell type. However, deferasirox potently inhibited DMS-53 xenograft growth in nude mice when given by oral gavage, with no marked alterations in normal tissue histology. To understand the antitumor activity of deferasirox, we investigated its effect on the expression of molecules that play key roles in metastasis, cell cycle control, and apoptosis. We demonstrated that deferasirox increased expression of the metastasis suppressor protein N-myc downstream-regulated gene 1 and upregulated the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) while decreasing cyclin D1 levels. Moreover, this agent increased the expression of apoptosis markers, including cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase 1. Collectively, we demonstrate that deferasirox is an orally effective antitumor agent against solid tumors. 22954532 Attenuated effect of tungsten carbide nanoparticles on voltage-gated sodium current of hippocampal CA1 pyramidal neurons. Nanomaterials and relevant products are now being widely used in the world, and their safety becomes a great concern for the general public. Tungsten carbide nanoparticles (nano-WC) are widely used in metallurgy, aeronautics and astronautics, however our knowledge regarding the influence of nano-WC on neurons is still lacking. The aim of this study was to investigate the impact of nano-WC on tetrodotoxin (TTX)-sensitive voltage-activated sodium current (I(Na)) of hippocampal CA1 pyramidal neurons. Results showed that acute exposure of nano-WC attenuated the peak amplitudes of I(Na) in a concentration-dependent manner. The minimal effective concentration was 10(-5)g/ml. The exposure of nano-WC significantly decreased current amplitudes of the current-voltage curves of I(Na) from -50 to+50 mV, shifted the steady-state activation and inactivation curves of I(Na) negatively and delayed the recovery of I(Na) from inactivation state. After exposure to nano-WC, the peak amplitudes, overshoots and the V-thresholds of action potentials (APs) were markedly reduced. These results suggested that exposure of nano-WC could influence some characteristics of APs evoked from the hippocampal CA1 neurons by modifying the kinetics of voltage-gated sodium channels (VGSCs). 23246865 Lead-induced neurodegenerative events and abnormal behaviors occur via ORXRergic/GABA(A)Rergic mechanisms in a marine teleost. The hindering effects of metals and in particular lead (Pb) are representing a growing threat to aquatic organisms such as fish. This observation derives from toxic concentrations of Pb accounting for altered neurophysiological activities of some interesting teleost models like Thalassoma pavo, a fish species highly known for its host-cleaning symbiosis. In this study, the nominal PbNO(3) concentration of 1.6 mg/L was capable of reducing feeding and resting bouts as early as 24 h of exposure while hyperactive swimming episodes were also detected. Such abnormal behaviors were tightly correlated to up-regulated orexin receptor (ORXR) mRNA expression levels in some brain areas such as the lateral thalamic nucleus (+213%) and the optic tectum (+90%) with respect to controls. Interestingly, these transcriptional effects seemed to be attenuated when Pb-exposed fish received either 100 ng/g of ORX-A (-70%) or 0.1 μg/g of γ-aminobutyric acid(A) receptor (GABA(A)R) agonist muscimol (MUS; -97%) compared to fish exposed to Pb alone. Moreover, a net neurodegenerative process of the different brain areas was reported after Pb exposure as displayed by their marked amino cupric silver stained cells while these cells were devoid of any staining reaction after treatment with MUS only. Conversely, addition of the GABA(A)R antagonist bicuculline (BIC; 1 μg/g) moderately (p<0.05) enhanced Pb-dependent behavioral and neurodegenerative actions. Overall, these first indications strongly point to altered ORXR/GABA(A)R interactions during neurotoxic events of a metal that by evoking harmful neurobiological dysfunctions may endanger the survival of commercially valuable fish with eventual repercussions on human health. 23339577 Redox-active π-conjugated organometallic monolayers: pronounced Coulomb blockade characteristic at room temperature. We report the electrical transport characteristics of a series of molecular wires, fc-C≡C-C6H4-SAc (fc = ferrocenyl; Ac = acetyl) and AcS-C6H4-C≡C-(fc)n-C≡C-C6H4-SAc (n = 2, 3), consisting of multiple redox-active ferrocenyl centers. The self-assembled monolayers of these molecular wires on Au surfaces were comprehensively characterized by electrochemistry and conductive atomic force microscopy techniques. Characterization of the wires revealed that electron transport is made extremely efficient by the organometallic redox states. There is a strong electronic coupling between ferrocenyl moieties, and superior electron-transport ability exists through these semirigid molecular wires. Standard rate constants for the electron transfer between the electrode and the ferrocenyl moieties were measured for the monolayers by a potential-step chronoamperometry technique. The electron conduction through the molecular wires was estimated using the monolayers as a bridge from the Au(111) metal surface to the gold tip of a conductive atomic force microscope (CAFM). Using the CAFM, Coulomb blockade behavior arising from the capacitive charging of the multinuclear redox-active molecules was observed at room temperature. The conductance switching was mediated by the presence of various ferrocenyl redox states and each current step corresponded to a specific redox state. 23436791 A combination strategy to inhibit Pim-1: synergism between noncompetitive and ATP-competitive inhibitors. Pim-1 is a serine/threonine kinase critically involved in the initiation and progression of various types of cancer, especially leukemia, lymphomas and solid tumors such as prostate, pancreas and colon, and is considered a potential drug target against these malignancies. In an effort to discover new potent Pim-1 inhibitors, a previously identified ATP-competitive indolyl-pyrrolone scaffold was expanded to derive structure-activity relationship data. A virtual screening campaign was also performed, which led to the discovery of additional ATP-competitive inhibitors as well as a series of 2-aminothiazole derivatives, which are noncompetitive with respect to both ATP and peptide substrate. This mechanism of action, which resembles allosteric inhibition, has not previously been characterized for Pim-1. Notably, further evaluation of the 2-aminothiazoles indicated a synergistic inhibitory effect in enzymatic assays when tested in combination with ATP-competitive inhibitors. A synergistic effect in the inhibition of cell proliferation by ATP-competitive and ATP-noncompetitive compounds was also observed in prostate cancer cell lines (PC3), where all Pim-1 inhibitors tested in showed synergism with the known anticancer agent, paclitaxel. These results further establish Pim-1 as a target in cancer therapy, and highlight the potential of these agents for use as adjuvant agents in the treatment of cancer diseases in which Pim-1 is associated with chemotherapeutic resistance. 23596359 Exploring the Energy Landscapes of Cyclic Tetrapeptides with Discrete Path Sampling. Cyclic tetrapeptides are an important class of biologically active molecules that exhibit interesting conformational dynamics, with slow interconversion of several different structures. We present calculations on their energy landscapes using discrete path sampling. In acyclic peptides and large cyclic peptides, isomers containing cis-peptide groups are much less stable than the all-trans isomers and separated from them by large barriers. Strain in small cyclic peptides causes the cis and trans isomers to be closer in energy and separated by much lower barriers. If d-amino acids or proline residues are introduced, isomers containing cis-peptides become more stable than the all-trans structures. We also show that changing the polarity of the solvent has a significant effect on the energy landscapes of cyclic tetrapeptides, causing changes in the orientations of the peptide groups and in the degree of intramolecular hydrogen bonding. 23610057 Resistance to aerobic exercise training causes metabolic dysfunction and reveals novel exercise-regulated signaling networks. Low aerobic exercise capacity is a risk factor for diabetes and strong predictor of mortality; yet some individuals are "exercise resistant", and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease-risk, we used selective breeding for 15 generation to develop rat models of low- and high-aerobic response to training. Before exercise training, rats selected as low- and high-responders had similar exercise capacities. However, after 8-wks of treadmill training low-responders failed to improve their exercise capacity, while high-responders improved by 54%. Remarkably, low-responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the "exercise resistant" phenotype segregates with disease risk. Low-responders had impaired exercise-induced angiogenes0is in muscle; however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low-responders. Low-responders had increased stress/inflammatory signaling and altered TGFβ signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease. 23380243 Epigenetics and pesticides. Pesticides, a wide class of environmental contaminants, may cause both acute and delayed health effects in exposed subjects. These effects can range from simple irritation of the skin and eyes to more severe effects such as affecting the nervous system, the reproductive system and cancer. The molecular mechanisms underlying such effects are still under investigation. Epigenetics is the study of heritable changes in gene expression that occur without a change in the DNA sequence. Several epigenetic mechanisms, including DNA methylation, histone modifications and microRNA expression, can be triggered by environmental factors. We review current evidences indicating that epigenetic modifications may mediate pesticide effects on human health. In vitro, animal, and human investigations have identified several classes of pesticides that modify epigenetic marks, including endocrine disruptors, persistent organic pollutants, arsenic, several herbicides and insecticides. Several investigations have examined the effects of environmental exposures and epigenetic markers, and identified toxicants that modify epigenetic states. These modifications are similar to the ones found in pathological tissue samples. In spite of the current limitations, available evidence supports the concept that epigenetics holds substantial potential for furthering our understanding of the molecular mechanisms of pesticides health effects, as well as for predicting health-related risks due to conditions of environmental exposure and individual susceptibility. 23023136 Resveratrol attenuates hepatotoxicity of rats exposed to arsenic trioxide. Arsenic trioxide (As(2)O(3)) is an environmental pollutant and potent toxicant to humans. However, it also shows substantial anti-cancer activity in individuals with acute promyelocytic leukemia (APL). Unfortunately, As(2)O(3)-treated leukemia patients suffer hepatotoxicity. Resveratrol has been demonstrated to have efficient antioxidant and antineoplastic activities. The study that how As(2)O(3) in combination with resveratrol affects hepatotoxicity and arsenic accumulation in the liver is lacking, and the present study tackles this question. Wistar rats were injected with 3mg/kg As(2)O(3) on alternate days; resveratrol (8mg/kg) was administered 1h before As(2)O(3). Rats were killed on the 8th day to determine histological liver damage, the antioxidant enzymes in serum, the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), and arsenic accumulation in the liver. In the resveratrol+As(2)O(3) group, activities of superoxide dismutase, catalase in serum and GSH/GSSG were significantly increased, histopathological effects were reduced, and arsenic accumulation markedly decreased in the liver, compared with the As(2)O(3)-treated group. Thus, resveratrol attenuated As(2)O(3)-induced hepatotoxicity by decreasing oxidative stress and arsenic accumulation in the liver. These data suggest that use of resveratrol as post-remission therapy of APL and adjunctive therapy in patients with chronic exposure to arsenic may decrease arsenic hepatotoxicity. 23600656 Brucine-loaded liposomes composed of HSPC and DPPC at different ratios: in vitro and in vivo evaluation. Abstract Objective: The objective of this study is to test the hypothesis that the phase transition temperature (Tm), the main property of liposomes, can be easily controlled by changing the molar ratio of hydrogenated soy phosphatidylcholine (HSPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphacholine (DPPC) after drug encapsulation. Materials and methods: Brucine, an antitumor alkaloid, was encapsulated into the liposomes with different HSPC/DPPC compositions. The Tms of the brucine-loaded liposomes (BLs) were determined by differential scanning calorimetry (DSC). Then the physicochemical properties and pharmacokinetics of the BLs with different HSPC/DPPC compositions were investigated and compared. Results: The results of DSC revealed that HSPC and DPPC can combine into one phase. The findings of molecular modeling study suggested that HSPC interacts with DPPC via electrostatic interaction. The molar ratio of HSPC/DPPC influenced the sizes of BLs but had little effect on the entrapment efficiency (EE). The stability of BLs was improved with the increase of the HSPC ratios, especially with the presence of plasma. Following i.v. administration, it was found that AUC values of BLs in vivo were directly related to the HSPC/DPPC ratios of BLs, namely the Tms of BLs. Discussion: The behavior of liposomes, especially in vivo pharmacokinetic behavior, can be controlled by the modification of Tm. Conclusion: The characterization of BLs in vitro and in vivo had demonstrated that the Tm could be flexibly modified for liposomes composed of both HSPC and DPPC. Using HSPC/DPPC composition may be an efficient strategy to control the Tm, thus control the in vivo pharmacokinetic behavio, of BLs. 23462212 Anti-secretory and cyto-protective effects of chebulinic acid isolated from the fruits of Terminalia chebula on gastric ulcers. In continuation of our drug discovery program on Indian medicinal plants, the gastro protective mechanism of chebulinic acid isolated from Terminalia chebula fruit was investigated. Chebulinic acid was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity of chebulinic acid was observed against CRU (62.9%), AS (55.3%), AL (80.67%) and PL (66.63%) induced ulcer models. The reference drug omeprazole (10mg/kg, p.o.) showed 77.73% protection against CRU, 58.30% against AS and 70.80% against PL model. Sucralfate, another reference drug (500mg/kg, p.o.) showed 65.67% protection in AL induced ulcer model. Chebulinic acid significantly reduced free acidity (48.82%), total acidity (38.29%) and upregulated mucin secretion by 59.75% respectively. Further, chebulinic acid significantly inhibited H(+) K(+)-ATPase activity in vitro with IC50 of 65.01μg/ml as compared to the IC50 value of omeprazole (30.24μg/ml) confirming its anti-secretory activity. 23038768 A calibrated human Y-chromosomal phylogeny based on resequencing. We have identified variants present in high-coverage complete sequences of 36 diverse human Y chromosomes from Africa, Europe, South Asia, East Asia, and the Americas, representing eight major haplogroups. After restricting our analysis to 8.97 Mb of the unique male-specific Y sequence, we identified 6662 high-confidence variants, including single-nucleotide polymorphisms (SNPs), multi-nucleotide polymorphisms (MNPs), and indels. We constructed phylogenetic trees using these variants, or subsets of them, and recapitulated the known structure of the tree. Assuming a male mutation rate of 1 × 10(-9) per base pair per year, the time depth of the tree (haplogroups A3-R) was ~101,000-115,000 yr, and the lineages found outside Africa dated to 57,000-74,000 yr, both as expected. In addition, we dated a striking Paleolithic male lineage expansion to 41,000-52,000 yr ago and the node representing the major European Y lineage, R1b, to 4000-13,000 yr ago, supporting a Neolithic origin for these modern European Y chromosomes. In all, we provide a nearly 10-fold increase in the number of Y markers with phylogenetic information, and novel historical insights derived from placing them on a calibrated phylogenetic tree. 23377617 Decreased zinc availability affects glutathione metabolism in neuronal cells and in the developing brain. A deficit in zinc (Zn) availability can increase cell oxidant production, affect the antioxidant defense system, and trigger oxidant-sensitive signals in neuronal cells. This work tested the hypothesis that a decreased Zn availability can affect glutathione (GSH) metabolism in the developing rat brain and in neuronal cells in culture, as well as the capacity of human neuroblastoma IMR-32 cells to upregulate GSH when challenged with dopamine (DA). GSH levels were low in the brain of gestation day 19 (GD19) fetuses from dams fed marginal Zn diets throughout gestation and in Zn-deficient IMR-32 cells. γ-Glutamylcysteine synthetase (GCL), the first enzyme in the GSH synthetic pathway, was altered by Zn deficiency (ZD). The protein and mRNA levels of the GCL modifier (GCLM) and catalytic (GCLC) subunits were lower in the Zn-deficient GD19 fetal brain and in IMR-32 cells compared with controls. The nuclear translocation of transcription factor nuclear factor (erythroid-derived 2)-like 2, which controls GCL transcription, was impaired by ZD. Posttranslationally, the caspase-3-dependent GCLC cleavage was high in Zn-deficient IMR-32 cells. Cells challenged with DA showed an increase in GCLM and GCLC protein and mRNA levels and a consequent increase in GSH concentration. Although Zn-deficient cells partially upregulated GCL subunits after exposure to DA, GSH content remained low. In summary, results show that a low Zn availability affects the GSH synthetic pathway in neuronal cells and fetal brain both at transcriptional and posttranslational levels. This can in part underlie the GSH depletion associated with ZD and the high sensitivity of Zn-deficient neurons to pro-oxidative stressors. 23108851 On the origin of chirality in nanoplasmonic gyroid metamaterials. Metallic single gyroids, a new class of self-assembled nanoplasmonic metamaterials, are analyzed on the basis of a tri-helical metamaterial model. The physical mechanisms underlying the chiral optical behavior of the nanoplasmonic single gyroid are identified and it is shown that the optical chirality in this metallic structure is primarily determined by structural chirality and the connectivity of helices along the main cubic axes. 23212787 Fast screening of authentic ginseng products by surface desorption atmospheric pressure chemical ionization mass spectrometry. Surface desorption atmospheric pressure chemical ionization mass spectrometry was developed as a rapid online detection technology for the chemical fingerprints of ginseng products without any sample pretreatment. More than 20 ginsenosides were detected in the ginseng tissue and identified by their tandem mass spectrometry. Data were well matched with their reference compounds. Herein, surface desorption atmospheric pressure chemical ionization mass spectrometry was first applied to study the nonvolatile compounds in ginseng. White and red ginseng have been successfully differentiated from their counterfeits using some ginsenosides as chemical markers. Ginsenoside can be used to differentiate between white ginseng, red ginseng, unboiled ginseng, and their counterfeits. Ginsenosides Ra1-3, Rb2-3, and Rc might be used to differentiate between white ginseng and boiled ginseng. Our result showed that surface desorption atmospheric pressure chemical ionization mass spectrometry not only could be used for fast screening authentic ginseng products but also might become a useful promising technique for the characterization of nonvolatile compounds in medicinal herbs to save researchers the laborious effort of sample pretreatment. 23561191 Hepatic biotransformation of alkylresorcinols is mediated via cytochrome P450 and β-oxidation: A proof of concept study. Alkylresorcinols (AR) are phenolic lipids present in the bran of some cereals. AR may serve as a biomarker for whole grain wheat and rye intake. While AR pharmacokinetics and two major metabolites have been reported, the metabolic pathways contributing to their relatively rapid elimination from the circulation remain to be speculative. In this study, we investigated if ω- and β-oxidation mediate catabolism of the AR homologue C19:0 to form 3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), using 3 in vitro platforms, human cytochrome P450 4F2 (CYP4F2), human liver S9, and HepG2 cells. One hydroxylated C19:0 metabolite was formed by CYP4F2 and one hydroxylated and one carboxylated C19:0 were tentatively identified after incubation of AR with S9. The formation of DHPPA was quantifiable when HepG2 cells were treated with C19:0 for 48h. Our results are consistent with a metabolic pathway by which AR are degraded to phenolic acids via CYP4F2-mediated ω-oxidation and subsequent β-oxidation. 23472738 Anion-Exchange Reactions on a Robust Phosphonium Photopolymer for the Controlled Deposition of Ionic Gold Nanoclusters. UV curing (photopolymerization) is ubiquitous in many facets of industry ranging from the application of paints, pigments, and barrier coatings all the way to fiber optic cable production. To date no reports have focused on polymerizable phosphonium salts under UV irradiation, and despite this dearth of examples, they potentially offer numerous substantial advantages to traditional UV formulation components. We have generated a highly novel coating based on UV-curable trialkylacryloylphosphonium salts that allow for the fast (seconds) and straightforward preparation of ion-exchange surfaces amenable to a roll-to-roll process. We have quantified the surface charges and exploited their accessibility by employing these surfaces in an anion exchange experiment by which [Au25L18](-) (L = SCH2CH2Ph) nanocrystals can be assembled into the solid state. This unprecedented application of such surfaces offers a paradigm shift in the emerging chemistry of Au25 research where the nanocrystals remain single and intact and where the integrity of the cluster and its solution photophysical properties are resilient in the solid state. The specific loading of [Au25L18](-) on the substrates has been determined and the completely reversible loading and unloading of intact nanocrystals to and from the surface has been established. In the solid state, the assembly has an incredible mechanical resiliency, where the surface remains undamaged even when subjected to repeated Scotch tests. 23289710 Mammalian Trit1 is a tRNA([Ser]Sec)-isopentenyl transferase required for full selenoprotein expression. Selenoproteins are proteins carrying the rare amino acid Sec (selenocysteine). Full expression of selenoproteins requires modification of tRNA([Ser]Sec), including N(6)-isopentenylation of base A(37). We show that Trit1 is a dimethylallyl:tRNA([Ser]Sec) transferase. Knockdown of Trit1 reduces expression of selenoproteins. Incubation of in vitro transcribed tRNA[Ser]Sec with recombinant Trit1 transfers [(14)C]dimethylallyl pyrophosphate to tRNA([Ser]Sec). 37A>G tRNA([Ser]Sec) is resistant to isopentenylation by Trit1. 23545108 Discovery of a novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors. A novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors were derived from a fragment-based approach using information from X-ray crystallographic analysis of NS5B-inhibitor complexes and iterative rounds of parallel synthesis. Structure-based drug design strategies led to the discovery of potent sub-micromolar inhibitors 11a-c and 12a-c from a weak-binding fragment-like structure 1 as a starting point. 23430761 Design and evaluation of ondansetron liquid suppository for the treatment of emesis. The thermosensitive-mucoadhesive ondansetron liquid suppository (tmOLS) was developed to enhance patient compliance and bioavailability in high-risk patients receiving highly emetogenic therapy and having difficulty in swallowing, The thermosensitive-mucoadhesive liquid suppository bases were formulated using poloxamers (P407 and P188) and hydroxypropylmethyl cellulose (HPMC). The physicochemical properties of the liquid suppository bases were characterized by their gelation temperature, mucoadhesive force, rheological properties, and in vitro release. Rectal mucosal damage following rectal administration of tmOLS in rats was assessed using microscopy. Pharmacokinetic analyses were performed to compare tmOLS administered via the rectal route to ondansetron solution administered orally. The liquid suppository base of tmOLS contained P407, P188, and HPMC in the ratio 18:20:0.8, was in the liquid state at room temperature, underwent gelation at body temperature. Area under the curve and half-life (t(1/2)) of ondansetron were significantly higher in the tmOLS-treated group, indicating that the formulation bypassed the first-pass metabolism and that it was released slowly from the tmOLS because of the formation of mucoadhesive gel state. Furthermore, the t(1/2) of tmOLS was two-fold that of the oral solution. Thus, tmOLS could be administered to patients who have difficulty in swallowing; however, adjustments in dosing interval may be needed. 23276627 Methylation damage to RNA induced in vivo in Escherichia coli is repaired by endogenous AlkB as part of the adaptive response. Cytotoxic 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) lesions induced in DNA and RNA in vitro and in pre-damaged DNA and RNA bacteriophages in vivo are repaired by the Escherichia coli (E. coli) protein AlkB and a human homolog, ALKBH3. However, it is not known whether endogenous RNA is repaired in vivo by repair proteins present at physiological concentrations. The concept of RNA repair as a biologically relevant process has therefore remained elusive. Here, we demonstrate AlkB-mediated repair of endogenous RNA in vivo by measuring differences in lesion-accumulation in two independent AlkB-proficient and deficient E. coli strains during exposure to methyl methanesulfonate (MMS). Repair was observed both in AlkB-overproducing strains and in the wild-type strains after AlkB induction. RNA repair appeared to be highest in RNA species below 200 nucleotides in size, mainly comprising tRNAs. Strikingly, at least 10-fold more lesions were repaired in RNA than in DNA. This may be a consequence of some 30-fold higher levels of aberrant methylation in RNA than in DNA after exposure to MMS. A high primary kinetic isotope effect (>10) was measured using a deuterated methylated RNA substrate, D3-1me(rA), demonstrating that it is the catalytic step, and not the search step that is rate-limiting. Our results demonstrate that RNA repair by AlkB takes place in endogenous RNA as part of an adaptive response in wild-type E. coli cells. 23470922 Water deficit and heat affect the tolerance to high illumination in hibiscus plants. This work studies the effects of water deficit and heat, as well as the involvement of chlororespiration and the ferredoxin-mediated cyclic pathway, on the tolerance of photosynthesis to high light intensity in Hibiscus rosa-sinensis plants. Drought and heat resulted in the down-regulation of photosynthetic linear electron transport in the leaves, although only a slight decrease in variable fluorescence (Fv)/maximal fluorescence (Fm) was observed, indicating that the chloroplast was protected by mechanisms that dissipate excess excitation energy to prevent damage to the photosynthetic apparatus. The incubation of leaves from unstressed plants under high light intensity resulted in an increase of the activity of electron donation by nicotinamide adenine dinucleotide phosphate (NADPH) and ferredoxin to plastoquinone, but no increase was observed in plants exposed to water deficit, suggesting that cyclic electron transport was stimulated by high light only in control plants. In contrast, the activities of the chlororespiration enzymes (NADH dehydrogenase (NDH) complex and plastid terminal oxidase (PTOX)) increased after incubation under high light intensity in leaves of the water deficit plants, but not in control plants, suggesting that chlororespiration was stimulated in stressed plants. The results indicate that the relative importance of chlororespiration and the cyclic electron pathway in the tolerance of photosynthesis to high illumination differs under stress conditions. When plants were not subjected to stress, the contribution of chlororespiration to photosynthetic electron flow regulation was not relevant, and another pathway, such as the ferredoxin-mediated cyclic pathway, was more important. However, when plants were subjected to water deficit and heat, chlororespiration was probably essential. 23307663 Fueling open-source drug discovery: 177 small-molecule leads against tuberculosis. With the aim of fuelling open-source, translational, early-stage drug discovery activities, the results of the recently completed antimycobacterial phenotypic screening campaign against Mycobacterium bovis BCG with hit confirmation in M. tuberculosis H37Rv were made publicly accessible. A set of 177 potent non-cytotoxic H37Rv hits was identified and will be made available to maximize the potential impact of the compounds toward a chemical genetics/proteomics exercise, while at the same time providing a plethora of potential starting points for new synthetic lead-generation activities. Two additional drug-discovery-relevant datasets are included: a) a drug-like property analysis reflecting the latest lead-like guidelines and b) an early lead-generation package of the most promising hits within the clusters identified. 23154582 Applications of asymmetric organocatalysis in medicinal chemistry. In the last decade, organocatalysis, the use of small chiral organic molecules as catalysts, has proven to be a valuable and attractive tool for the synthesis of enantiomerically enriched molecules. A number of organocatalysts and processes, such as one-pot, tandem, cascade or multicomponent reactions, have been reported to date. Furthermore, the many advantages of organocatalysis - robust, non-toxic, affordable, inert atmosphere, easy reaction manipulation, etc. - allow the preparation of bioactive compounds using simple and metal-free procedures, thus avoiding false positives in the biological evaluation. This mini-review focuses on medicinal chemistry programs that have synthesized biologically active compounds using one or more organocatalytic steps. In this respect, the potential of organocatalytic methods for enabling the chemical synthesis of important medicinal targets will be highlighted. 23603907 FOXO3 growth inhibition of colonic cells is dependent on intraepithelial lipid droplet density. Forkhead transcription factor FOXO3 plays a critical role in suppressing tumor growth, in part, by increasing cell cycle inhibitor p27kip1, and Foxo3 deficiency in mice results in marked colonic epithelial proliferation. Here, we show in Foxo3 deficient colonic epithelial cells a striking increase in intracytoplasmic lipid droplets (LDs), a dynamic organelle recently observed in human tumor tissue. While the regulation and function of LDs in non-adipocytes is unclear, we hypothesize that the anti-proliferative effect of FOXO3 was dependent on lowering LD density, thus decreasing fuel energy in both normal and colon cancer cells. In mouse colonic tumors, we found an increased expression of LD coat protein PLIN2 compared to normal colonic epithelial cells. Stimulation of LD density in human colon cancer cells led to PI3K dependent loss of FOXO3 and a decrease in the negative regulator of lipid metabolism Sirtuin6 (SIRT6). Foxo3 deficiency also led to a decrease in SIRT6, revealing the existence of the LD and FOXO3 feedback regulation in colonic cells. In parallel, LD dependent loss of FOXO3 led to its dissociation from the promoter and decreased expression of the cell cycle inhibitor p27kip1. Stimulation of LD density promoted proliferation in colon cancer cells, while silencing PLIN2 or overexpression of FOXO3 inhibited proliferation. Taken together, FOXO3 and LDs might serve as new targets for therapeutic intervention of colon cancer. 23590667 Few-Layer MoS2 with High Broadband Photogain and Fast Optical Switching for Use in Harsh Environments. Few-layered MoS2 as Schottky metal-semiconductor-metal photodetectors (MSM PDs) for use in harsh environments makes its debut as two-dimensional (2D) optoelectronics with high broadband gain (up to 13.3), high detectivity (up to ∼10(10) cm Hz(1/2)/W), fast photoresponse (rise time of ∼70 μs and fall time of ∼110 μs), and high thermal stability (at a working temperature of up to 200 °C). Ultrahigh responsivity (0.57 A/W) of few-layer MoS2 at 532 nm is due to the high optical absorption (∼10% despite being less than 2 nm in thickness) and a high photogain, which sets up a new record that was not achievable in 2D nanomaterials previously. This study opens avenues to develop 2D nanomaterial-based optoelectronics for harsh environments in imaging techniques and light-wave communications as well as in future memory storage and optoelectronic circuits. 23454148 Effect of protein malnutrition on the metabolism and toxicity of cisplatin, 5-fluorouracil and mitomycin C in rat stomach. This study investigated the effect of protein malnutrition on metabolism and toxicity of cisplatin (CP), 5-fluorouracil (FU) and mitomycin C (MMC) in rat stomach. Weanling male Wistar rats received a normal (24%) or low (2.5%) protein diet for 28days and were allocated into: normally-fed control, protein-malnourished control (PM), 3 normally-fed drug-treated groups and 3 protein-malnourished drug-treated groups (PM-CP, PM-FU and PM-MMC). Cisplatin and MMC were injected intraperitoneally (8mg/kg on day 26 and 1mg/kg/day for 7days, respectively). 5-Fluorouracil was given orally (50mg/kg/day for 5days). Compared with normally-fed counterparts, PM-CP rats exhibited higher glutathione S-transferase, aminopeptidase N and cysteine S-conjugate beta-lyase (CCBL) and lower gamma-glutamyltransferase activities, PM-FU rats exhibited decreased dihydropyrimidine dehydrogenase and cytochrome P450 1A1/2 activities and PM-MMC rats showed higher quinone reductase and depleted xanthine oxidase activities. Protein-malnourished drug-treated groups exhibited exacerbated gastrotoxicity, relative to normally-fed counterparts, manifested by lower mucus levels, higher permeability and histopathological deterioration, along with increased oxidative stress in PM-CP rats and exaggerated prostaglandin E2 production in PM-MMC rats. Conclusively, protein malnutrition alters CP, FU and MMC metabolism in rat stomach by enhancing CCBL pathway for CP activation, delaying FU elimination and activating two-electron reduction of MMC, potentiating their gastrotoxicity. 23639652 Synthetic chalcones and sulfonamides as new classes of Yersinia enterocolitica YopH tyrosine phosphatase inhibitors. YopH plays a relevant role in three pathogenic species of Yersinia. Due to its importance in the prevention of the inflammatory response of the host, this enzyme has become a valid target for the identification and development of new inhibitors. In this work, an in-house library of 283 synthetic compounds was assayed against recombinant YopH from Yersinia enterocolitica. From these, four chalcone derivatives and one sulfonamide were identified for the first time as competitive inhibitors of YopH with binding affinity in the low micromolar range. Molecular modeling investigations indicated that the new inhibitors showed similar binding modes, establishing polar and hydrophobic contacts with key residues of the YopH binding site. 23265542 Chemical composition, antimicrobial, cytotoxic and antioxidant activities of the essential oil of Artemisia indica Willd. Essential oil from the aerial parts of Artemisia indica was analysed by GC-FID and GC-MS. A total of 43 compounds representing 96.8% of the oil were identified and the major components were found to be artemisia ketone (42.1%), germacrene B (8.6%), borneol (6.1%) and cis-chrysanthenyl acetate (4.8%). Antimicrobial activity of the oil was evaluated against seven clinically significant bacterial and two fungal strains. The essential oil and its major constituents exhibited moderate to potent, broad-spectrum antibacterial and antifungal activities targeting both Gram-positive and Gram-negative bacteria. In vitro cytotoxicity evaluation against four human cancer cell lines THP-1 (leukemia), A-549 (lung), HEP-2 (liver) and Caco-2 (colon) showed that the essential oil exhibited concentration dependant growth inhibition in the 10-100 μg/ml dilution range, with IC(50) values of 10 μg/ml (THP-1), 25 μg/ml (A-549), 15.5 μg/ml (HEP-2) and 19.5 μg/ml (Caco-2). It was interesting to note that the essential oil also exhibited potent antioxidant activity. 23517546 All Zinc-Blende GaAs/(Ga,Mn)As Core-Shell Nanowires with Ferromagnetic Ordering. Combining self-catalyzed vapor-liquid-solid growth of GaAs nanowires and low-temperature molecular-beam epitaxy of (Ga,Mn)As, we successfully synthesized all zinc-blende (ZB) GaAs/(Ga,Mn)As core-shell nanowires on Si(111) substrates. The ZB GaAs nanowire cores are first fabricated at high temperature by utilizing the Ga droplets as the catalyst and controlling the triple phase line nucleation, then the (Ga,Mn)As shells are epitaxially grown on the side facets of the GaAs core at low temperature. The growth window for the pure phase GaAs/(Ga,Mn)As core-shell nanowires is found to be very narrow. Both high-resolution transmission electron microscopy and scanning electron microscopy observations confirm that all-ZB GaAs/(Ga,Mn)As core-shell nanowires with smooth side surface are obtained when the Mn concentration is not more than 2% and the growth temperature is 245 °C or below. Magnetic measurements with different applied field directions provide strong evidence for ferromagnetic ordering in the all-ZB GaAs/(Ga,Mn)As nanowires. The hybrid nanowires offer an attractive platform to explore spin transport and device concepts in fully epitaxial all-semiconductor nanospintronic structures. 23373613 Pulsed magnetic field improves the transport of iron oxide nanoparticles through cell barriers. Understanding how a magnetic field affects the interaction of magnetic nanoparticles (MNPs) with cells is fundamental to any potential downstream applications of MNPs as gene and drug delivery vehicles. Here, we present a quantitative analysis of how a pulsed magnetic field influences the manner in which MNPs interact with and penetrate across a cell monolayer. Relative to a constant magnetic field, the rate of MNP uptake and transport across cell monolayers was enhanced by a pulsed magnetic field. MNP transport across cells was significantly inhibited at low temperature under both constant and pulsed magnetic field conditions, consistent with an active mechanism (i.e., endocytosis) mediating MNP transport. Microscopic observations and biochemical analysis indicated that, in a constant magnetic field, transport of MNPs across the cells was inhibited due to the formation of large (>2 μm) magnetically induced MNP aggregates, which exceeded the size of endocytic vesicles. Thus, a pulsed magnetic field enhances the cellular uptake and transport of MNPs across cell barriers relative to a constant magnetic field by promoting accumulation while minimizing magnetically induced MNP aggregation at the cell surface. 23595057 Marine Nutraceuticals: Prospects and Perspectives. By Se-Kwon Kim, CRC Press, 2013; 464 Pages. Price £108.00, ISBN 978-1-4665-1351-8. The following paragraphs are reproduced from the publisher's website [1]. There is a great deal of consumer interest in natural bioactive substances due to their health benefits. Offering the potential to provide valuable nutraceuticals and functional food ingredients, marine-derived compounds are an abundant source of nutritionally and pharmacologically active agents, with both chemical diversity and complexity. Functional ingredients derived from marine algae, invertebrates, vertebrates, and microorganisms can help fill the need for novel bioactives to treat chronic conditions such as cancer, microbial infections, and inflammatory processes. 23600754 Microbiological transformation of the triterpene nigranoic acid by the freshwater fungus Dictyosporium heptasporum. The microbiological transformation of the triterpene nigranoic acid (3,4-secocycloarta-4(28),24(Z)-diene-3,26-dioic acid) (1) to 3,4-secocycloarta-4(28),17(20),24(Z)-triene-7β-hydroxy-16β,26-lactone-3-oic acid (2) and 3,4-secocycloarta-4(28),17(20)(Z),24(Z)-triene-7β-hydroxy-16β-methoxy-3,26-dioic acid (3) by the freshwater fungus Dictyosporium heptasporum YMF1.01213 has been demonstrated. The structures of the biotransformation products were determined by spectroscopic and MS analyses. Compound 2, characterized by the presence of a formed C-16/C-26 ester bridge, provided a novel nine-membered lactone ring structural skeleton for 3,4-secocycloartane triterpenoid derivatives. In addition, Compounds 1-3 exhibited weak anti-HIV activity in vitro. Compounds 2 and 3 were reported for the first time as natural product derivatives. 23122154 Characterisation of kiwifruit and asparagus enzyme extracts, and their activities toward meat proteins. Two plant enzyme extracts from kiwifruit and asparagus were evaluated for their ability to hydrolyse commercially available substrates and proteins present in both beef connective tissue and topside myofibrillar extracts. The results show significant differences in protease activity depending on the assay used. Protease assays with connective tissue and meat myofibrillar extracts provide a more realistic evaluation of the potential of the enzymes for application in meat tenderization. Overall, the kiwifruit protease extract was found to be more effective at hydrolysing myofibrillar and collagen proteins than the asparagus protease extract. The two protease extracts appeared to target meat myofibrillar and collagen proteins differently, suggesting the potential of a synergistic effect of these proteases in improving the tenderness of specific cuts of meat, based on their intrinsic protein composition. 23111753 Benchmarks for 0-0 transitions of aromatic organic molecules: DFT/B3LYP, ADC(2), CC2, SOS-CC2 and SCS-CC2 compared to high-resolution gas-phase data. In the present study a benchmark set of medium-sized and large aromatic organic molecules with 10-78 atoms is presented. For this test set 0-0 transition energies measured in supersonic jets are compared to those calculated with DFT and the B3LYP functional, ADC(2), CC2 and the spin-scaled CC2 variants SOS-CC2 and SCS-CC2. Geometries of the ground and excited states have been optimized with these methods in polarized triple zeta basis sets. Zero-point vibrational corrections have been calculated with the same methods and basis sets. In addition the energies have been corrected by single point calculations with a triple zeta basis augmented with diffuse functions, aug-cc-pVTZ. The deviations of the theoretical results from experimental electronic origins, which have all been measured in the gas phase with high-resolution techniques, were evaluated. The accuracy of SOS-CC2 is comparable to that of unscaled CC2, whereas ADC(2) has slightly larger errors. The lowest errors were found for SCS-CC2. All correlated wave function methods provide significantly better results than DFT with the B3LYP functional. The effects of the energy corrections from the augmented basis set and the method-consistent calculation of the zero-point vibrational corrections are small. With this benchmark set reliable reference data for 0-0 transition energies for larger organic chromophores are available that can be used to benchmark the accuracy of other quantum chemical methods such as new DFT functionals or semi-empirical methods for excitation energies and structures and thereby augments available benchmark sets augments present benchmark sets which include mainly smaller molecules. 22401597 9,10-seco-9,19-cyclolanostane triterpene from Salix caprea L. (goat willow). Chemical investigation of low polar solvent extract of Salix caprea through chromatographic techniques led to the isolation of new triterpene as 1α,3β,25-trihydroxy-9(11)-ene-16-one-9,10-seco-9,19-cyclolanostane (1) along with fatty alcohols. The structure of compound 1 was established by IR, HRESI/MS and NMR including 1D and 2D experiments. The compound 1 showed moderate in vitro antiplasmodial activity. 23103568 Estrogen receptor signaling as a target for novel breast cancer therapeutics. In breast cancer (BC) epithelial cells, the mitogenic action of estradiol is transduced through binding to two receptors, ERα and ERβ, which act as transcription factors. Anti-estrogens (AEs) and aromatase inhibitors (AIs) are used clinically to arrest the estrogen-dependent growth of BC. In the case of AE or AI resistance, Herceptin or lapatinib may be used to inhibit growth factors. Estrogen effects are mediated not only through nuclear ERs but also through cytoplasmic/membrane ERs and G-protein-coupled ERs. These estrogen-binding systems associate with various proteins that direct cell cycle signaling, proliferation and survival. The partners of nuclear ER include SRC1-3, HDACs and ERβ itself as well as newly identified proteins, such as E6-AP, LKB1, PELP1, PAX-2 and FOXA1. The partners of extra-nuclear ERα include PI3K and the tyrosine kinase Src. These various factors are all potential targets for therapeutic intervention. In addition, BC proliferation is enhanced by insulin and EGF, which stimulate signaling through the MAPK and PI3K/AKT pathways by activation of the IGF-1R and EGFR axes, respectively. These pathways are tightly interconnected with ER-activated signaling, and membrane ERα forms complexes with Src and PI3K. Chemokine-mediated signaling also modulates the estrogen response. Inhibiting these pathways with specific inhibitors or activating some of the pathways by gene manipulation may be therapeutically valuable for arresting BC cell cycle progression and for inducing apoptosis to antagonize hormone-resistance. Here, we review some newly identified putatively targetable ER partners and highlight the need to develop tumor-targeting drug carrier systems affecting both the tumor cells and the tumor environment. 23305110 Anomalous high mobility in LaAlO3/SrTiO3 nanowires. Nanoscale control of the metal-insulator transition at the interface between LaAlO(3) and SrTiO(3) provides a pathway for reconfigurable, oxide-based nanoelectronics. Four-terminal transport measurements of LaAlO(3)/SrTiO(3) nanowires at room temperature (T = 300 K) reveal an equivalent 2D Hall mobility greatly surpassing that of bulk SrTiO(3) and approaching that of n-type Si nanowires of comparable dimensions. This large enhancement of mobility is relevant for room-temperature device applications. 22694738 Differences in the structure of anthocyanins from the two amphibious plants, Lobelia cardinalis and Nesaea crassicaulis. The foliar anthocyanin profiles of two amphibious plants, Nesaea crassicaulis and Lobelia cardinalis were analysed for the first time. N. crassicaulis produced very simple anthocyanins, achieving the highest concentrations when grown submerged. In contrast, L. cardinalis produced leaves with a high content of very complex, acylated anthocyanins, especially when growing emergent. Anthocyanins were separated by high performance liquid chromatography. Nesaea crassicaulis anthocyanins were identified according to their fragment mass spectra and ultra-visible-violet spectral characteristics and 1D and 2D NMR spectra as -3,5-di-O-β-glucosides of delphinidin, cyanidin, petunidin, malvidin and peonidin as well as cyanidine and peonidin-3-O-β-glucoside. In L. cardinalis cyanidin-3-O-[6-O-(4-O-E-p-coumaroyl-O-α-rhamnopyranosyl)-β-glucopyrano]-5-O-β-glucopyranoside was the major anthocyanin and contributed more than 98% of total anthocyanin content. The remaining 2% was made up by cyanidin-3-O-[6-O-(4-O-E-caffeoyl-O-α-rhamnopyranosyl)-β-glucopyrano]-5-O-β-glucopyranoside and pelargonidin-3-O-[6-O-(4-O-E-p-coumaroyl-O-α-rhamnopyranosyl)-β-glucopyrano]-5-O-β-glucopyranoside. 23391442 Protective effects of protein transduction domain-metallothionein fusion proteins against hypoxia- and oxidative stress-induced apoptosis in an ischemia/reperfusion rat model. Ischemic heart diseases caused by insufficient oxygen supply to the cardiac muscle require pharmaceutical agents for the prevention of the progress and recurrence. Metallothionein (MT) has a potential as a protein therapeutic for the treatment of this disease due to its anti-oxidative effects under stressful conditions. In spite of its therapeutic potential, efficient delivery systems need to be developed to overcome limitations such as low transduction efficiency, instability and short half-life in the body. To enhance intra-cellular transduction efficiency, Tat sequence as a protein transduction domain (PTD) was fused with MT in a recombinant method. Anti-apoptotic and anti-oxidative effects of Tat-MT fusion protein were evaluated under hyperglycemia and hypoxia stress conditions in cultured H9c2 cells. Recovery of cardiac functions by anti-apoptotic and anti-fibrotic effects of Tat-MT was confirmed in an ischemia/reperfusion (I/R) rat myocardial infarction model. Tat-MT fusion protein effectively protected H9c2 cells under stressful conditions by reducing intracellular ROS production and inhibiting caspase-3 activation. Tat-MT fusion protein inhibited apoptosis, reduced fibrosis area and enhanced cardiac functions in I/R. Tat-MT fusion protein could be a promising therapeutic for the treatment of ischemic heart diseases. 23466228 [11C]olanzapine, radiosynthesis and lipophilicity of a new potential PET 5-HT2 and D2 receptor radioligand. Olanzapine and its precursor desmethyl-Olanzapine were synthesized from malononitrile, propionaldehyde, 1-fluoro-2-nitrobenzene, and substituted piperazine in 4, 4, 5, and 5 steps with 35%, 32%, 26%, and 32% overall chemical yield, respectively. [(11)C]Olanzapine was prepared from desmethyl-Olanzapine with [(11)C]CH3OTf through N-[(11)C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40-50% radiochemical yield based on [(11)C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB. The calculated LogP (CLogP) value of [(11)C]Olanzapine is 3.39. 23625905 Effect of chromium (VI) exposure on antioxidant defense status and trace element homeostasis in acute experiment in rat. Occupational exposure to hexavalent chromium (Cr(VI)) compounds is of concern in many Cr-related industries and their surrounding environment. Cr(VI) is a proven toxin and carcinogen. The Cr(VI) compounds are easily absorbed, can diffuse across cell membranes, and have strong oxidative potential. Despite intensive studies of Cr(VI) pro-oxidative effects, limited data exist on the influence of Cr(VI) on selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (GPx)-important components of antioxidant defense system. This study investigates the effect of Cr(VI) exposure on antioxidant defense status, with focus on these selenoenzymes, and on trace element homeostasis in an acute experiment in rat. Male Wistar rats (130-140g) were assigned to two groups of 8 animals: I. control; and II. Cr(VI) treated. The animals in Cr(VI) group were administered a single dose of K2Cr2O7 (20 mg /kg, intraperitoneally (ip)). The control group received saline solution. After 24 h, the animals were sacrificed and the liver and kidneys were examined for lipid peroxidation (LP; thiobarbituric acid reactive substances (TBARS) concentration), the level of reduced glutathione (GSH) and the activities of GPx-1, TrxR-1, and glutathione reductase (GR). Samples of tissues were also used to estimate Cr accumulation and alterations in zinc, copper, and iron levels. The acute Cr(VI) exposure caused an increase in both hepatic and renal LP (by 70%, p < 0.01 and by 15%, p < 0.05, respectively), increased hepatic GSH level and GPx-1 activity, and decreased renal GPx-1 activity. The activity of GR was not changed. A significant inhibitory effect of Cr(VI) was found on TrxR-1 activity in both the liver and the kidneys. The ability of Cr(VI) to cause TrxR inhibition could contribute to its cytotoxic effects. Further investigation of oxidative responses in different in vivo models may enable the development of strategies to protect against Cr(VI) oxidative damage. 23276135 Glyconanoparticles-an update. This review summarized the progress of glyconanoparticles in the aspects of types, synthesis, and applications for recent five years. A major challenge in the development of Au glyconanoparticles for the study of cellular interactions is to span the cellular membrane, which is used for the drug delivery. A majority of glyco-functionalized quantum dots have been utilized as fluorescent probes for biolabeling, imaging and biosensing. Recently, magnetic nanoparticles have been more frequently used in biomedical applications. The application of these new multivalent systems of glyconanoparticles is to mainly study carbohydrate-mediated interactions, which opens the new field in glycobiology. 23111684 Theoretical investigation of a novel high density cage compound 4,8,11,14,15-pentanitro-2,6,9,13-tetraoxa-4,8,11,14,15-pentaazaheptacyclo[5.5.1.1(3,11).1(5,9)] pentadecane. A novel polynitro cage compound 4,8,11,14,15-pentanitro-2,6,9,13-tetraoxa-4,8,11,14,15-pentaazaheptacyclo [5.5.1.1(3,11).1(5,9)]pentadecane(PNTOPAHP) has been designed and investigated at the DFT-B3LYP/6-31(d) level. Properties, such as electronic structure, IR spectrum, heat of formation, thermodynamic properties and crystal structure have been predicted. This compound is most likely to crystallize in C2/c space group, and the corresponding cell parameters are Z = 8, a = 29.78 Å, b = 6.42 Å, c = 32.69 Å, α = 90.00°, β = 151.05°, γ = 90.00° and ρ = 1.94 g/cm(3). In addition, the detonation velocity and pressure have also been calculated by the empirical Kamlet-Jacobs equation. As a result, the detonation velocity and pressure of this compound are 9.82 km/s, 44.67 GPa, respectively, a little higher than those of 4,10-dinitro-2,6,8,12-tetraoxa-4,10-diazaisowurtzitane(TEX, 9.28 km/s, 40.72 GPa). This compound has a comparable chemical stability to TEX, based on the N-NO(2) trigger bond length analysis. The bond dissociation energy ranges from 153.09 kJ mol(-1) to 186.04 kJ mol(-1), which indicates that this compound meets the thermal stability requirement as an exploitable HEDM. 23147005 Organization of the BcgI restriction-modification protein for the cleavage of eight phosphodiester bonds in DNA. Type IIB restriction-modification systems, such as BcgI, feature a single protein with both endonuclease and methyltransferase activities. Type IIB nucleases require two recognition sites and cut both strands on both sides of their unmodified sites. BcgI cuts all eight target phosphodiester bonds before dissociation. The BcgI protein contains A and B polypeptides in a 2:1 ratio: A has one catalytic centre for each activity; B recognizes the DNA. We show here that BcgI is organized as A(2)B protomers, with B at its centre, but that these protomers self-associate to assemblies containing several A(2)B units. Moreover, like the well known FokI nuclease, BcgI bound to its site has to recruit additional protomers before it can cut DNA. DNA-bound BcgI can alternatively be activated by excess A subunits, much like the activation of FokI by its catalytic domain. Eight A subunits, each with one centre for nuclease activity, are presumably needed to cut the eight bonds cleaved by BcgI. Its nuclease reaction may thus involve two A(2)B units, each bound to a recognition site, with two more A(2)B units bridging the complexes by protein-protein interactions between the nuclease domains. 23108214 Ameliorative effect of Drynaria quercifolia (L.) J. Sm., an ethnomedicinal plant, in arthritic animals. Drynaria quercifolia (L.) J. Sm., is an ethnomedicinal plant used widely in Tamil Nadu to treat arthritis. The present study was aimed to evaluate the traditional claim of D. quercifolia rhizome water extract in adjuvant induced arthritic animals. Anti-arthritic effect was studied by assessing the levels of lysosomal enzymes, protein bound carbohydrates, urinary degradative collagen and serum cytokines on control and adjuvant induced arthritis. The paw swelling and body weight were also analyzed. The levels of ROS and lysosomal enzymes in neutrophils of control and adjuvant induced animals were also estimated. D. quercifolia rhizome water extract at doses of 100 and 200mg/kg reduced the paw thickness and elevated the mean body weight of arthritic rats. The treatment with extract showed a significant reduction in the levels of plasma and liver lysosomal enzymes as well as protein bound carbohydrates and urinary degradative collagen levels. The treatment reduced the levels of ROS and lysosomal enzymes in neutrophils significantly. The significant reduction in the levels of serum pro-inflammatory cytokines (TNF-α and IL-1β) and the increment in the levels of anti-inflammatory cytokine (IL-10) were also observed by the treatment. The present study supports the traditional claim of using D. quercifolia to treat rheumatism. 23325050 Synthesis of bisindolylmethanes and their cytotoxicity properties. Polymer supported dichlorophosphate (PEG-OPOCl(2)) is an efficient green catalyst for the electrophilic substitution reaction of indole with aromatic aldehydes, in neat condition, to afford an excellent yield of bis(indolyl) methanes with short reaction time, at room temperature. The synthesized compounds and their anti-cancer activity are evaluated. 23376249 Synthesis and biological evaluation of 1,3,4-thiadiazole analogues as novel AChE and BuChE inhibitors. In this paper a series of new 1,3,4-thiadiazole derivatives has been designed, synthesized and evaluated as the acetyl- and butyrylcholinesterase inhibitors. Some analogues showed promising inhibition of both enzymes in vitro in the nM range. Generally, inhibitory potency of compounds was stronger against AChE than BuChE, and one of them was 1154-fold more active inhibiting AChE (IC50 = 0.17 μM) than BuChE. The kinetic studies showed that one of the most active analogues 8 (IC50 = 0.09 μM, AChE) acted as a non-competitive AChE inhibitor and was characterized by the high selectivity index (300). The other derivative (1) exhibited a mixed-type of AChE inhibition. Docking simulations enabled the detection of key binding interactions of the compounds with AChE and revealed that they occupied mainly the catalytic active site. The scoring function for the novel compounds was similar or higher than for the reference inhibitor. Additionally, based on Lipinski and other filters, the drug-likeness of compounds was assessed. They revealed that the compounds possess properties which can suggest the favourable pharmacokinetics in the human body after oral admission. 23415893 Targeted drug delivery to renal proximal tubule epithelial cells mediated by 2-glucosamine. In order to develop a novel kidney-targeted drug delivery system, we synthesized prednisolone carbamate-glucosamine conjugate (PCG) using 2-glucosamine as a ligand, and investigated its potential targeting efficacy. In vitro studies demonstrated that PCG could remarkably improve the uptake of drug by kidney cells. And the specific uptake of PCG could be largely reduced by the inhibitors of megalin receptor. More importantly, PCG showed an excellent kidney targeting property in vivo, and the concentration of the conjugate in the kidney was 8.1-fold higher than that of prednisolone group at 60 min after intravenous injection. Besides, PCG could significantly reverse the disease progression in renal ischemia-reperfusion (I/R) injury animal models. Furthermore, PCG presented no adverse effect on bone density while prednisolone resulted in severe osteoporosis. Thus, it indicated that 2-glucosamine could be a potential ligand for kidney-targeted delivery of prednisolone. 23517636 Testosterone exposure in childhood: discerning pathology from physiology. Introduction: Testosterone (T) drives normal male sexual development both in utero and at puberty. Aberrant T exposure manifests as virilization of a female fetus, contrasexual precocity in girls, and isosexual precocity in boys. Evidence of pathologic T exposure warrants a prompt evaluation. Areas covered: The authors introduce the topic of T exposure in children by reviewing its physiology in the fetus and during childhood and adolescence. Pathologic conditions leading to virilization of a female fetus as well as androgen-mediated gonadotropin-independent precocious puberty in both genders are then discussed. The authors finish by noting exogenous T exposure in children and adolescents, focusing specifically on secondary exposure to topical T preparations. Expert opinion: Contrasexual precocity in a girl or sexual precocity in a boy should prompt evaluation for causes of gonadotropin-independent pubertal changes. Initial biochemical evaluation includes a bone age, T, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S) and high sensitivity gonadotropin levels. The provider must query exposure to topical androgen-containing preparations as unintentional secondary exposure to topical T must be considered. Hyperandrogenism is temporally related to exposure of topical T and removal of exposure results in a marked decrease in serum T as well as resolution or stabilization of the signs and symptoms. 22983652 A DFT study on the initial stage of thermal degradation of Poly(methyl methacrylate)/carbon nanotube system. DFT calculations, with VWN exchange correlation functional and double numeric basis set, were used to evaluate the energies required for the scission reactions taking place in the initial stage of the thermal degradation of Poly(methyl methacrylate) (PMMA) in the presence of a carbon nanotube (CNT). Side group and main chain scissions were investigated. The results averaged from five configurations of pure PMMA (DP=5) were used as references and compared to the results obtained for the five same configurations of PMMA grafted on three carbon nanotubes of similar diameter (1.49 nm). The bond dissociation energies (BDE) of main chain scission evaluated for grafted PMMA was 4 % less endothermic than for pure PMMA. These results seemed independent of the tested chirality (11,11); (12,10) and (16,5) of the carbon nanotubes. Comparisons with the BDE of the weakest bonds due to intrinsic defaults (head to head and unsaturated end chain) were performed. 23301948 Spectral marker for Cα damage in beta peptides. The work in this article describes a spectral signature for the detection of a C(α) radical damaged peptide, which should enable the use of infrared spectroscopic methods to directly monitor oxidative events. Spectra for radical damaged peptides are computed with ab initio methods. The amide bands A, I, II, and III are analyzed for trends in the damage site. The spectral signature is found in a region (i.e., 1700-1620 cm(-1)) normally void of vibrational absorption bands from stable undamaged beta peptides. An analysis of the vibrational motions of the spectral signature is described. The uniqueness of the spectral signature is explored by an examination and comparison with C(α) monoradicals and polyradicals, as well as with other bioradicals that could act as spectral interferences. The identification of unique infrared spectral features for C(α) damage could have important implications in diagnostics for beta conformational peptides damaged by oxidative stress processes. 23172229 Cardiolipin-dependent reconstitution of respiratory supercomplexes from purified Saccharomyces cerevisiae complexes III and IV. Here, we report for the first time in vitro reconstitution of the respiratory supercomplexes from individual complexes III and IV. Complexes III and IV were purified from Saccharomyces cerevisiae mitochondria. Complex III contained eight molecules of cardiolipin, and complex IV contained two molecules of cardiolipin, as determined by electrospray ionization-mass spectrometry. Complex IV also contained Rcf1p. No supercomplexes were formed upon mixing of the purified complexes, and low amounts of the supercomplex trimer III(2)IV(1) were formed after reconstitution into proteoliposomes containing only phosphatidylcholine and phosphatidylethanolamine. Further addition of cardiolipin to the proteoliposome reconstitution mixture resulted in distinct formation of both the III(2)IV(1) supercomplex trimer and III(2)IV(2) supercomplex tetramer. No other anionic phospholipid was as effective as cardiolipin in supporting tetramer formation. Phospholipase treatment of complex IV prevented trimer formation in the absence of cardiolipin. Both trimer and tetramer formations were restored by cardiolipin. Analysis of the reconstituted tetramer by single particle electron microscopy confirmed native organization of individual complexes within the supercomplex. In conclusion, although some trimer formation occurred dependent only on tightly bound cardiolipin, tetramer formation required additional cardiolipin. This is consistent with the high cardiolipin content in the native tetramer. The dependence on cardiolipin for supercomplex formation suggests that changes in cardiolipin levels resulting from changes in physiological conditions may control the equilibrium between individual respiratory complexes and supercomplexes in vivo. 23523557 Antagonism of the transient receptor potential ankyrin 1 (TRPA1) attenuates hyperalgesia and urinary bladder overactivity in cyclophosphamide-induced haemorrhagic cystitis. The aim of this study was to investigate the involvement of the transient receptor potential ankyrin 1 (TRPA1) in haemorrhagic cystitis, the main side effect of cyclophosphamide-based chemotherapy. Hannover female rats received intraperitoneal (i.p.) injection of cyclophosphamide (three doses of 100mg/kg, every other day, in a total of five days). This treatment was followed by the treatment with TRPA1 antagonist HC 030031 (50mg/kg, p.o.). The threshold for hindpaw withdrawal or abdominal retraction to von Frey Hair and the locomotor activity were measured. The treatment with the TRPA1 antagonist HC 030031 significantly decreased mechanical hyperalgesia induced by cyclophosphamide without interfere with locomotor activity. Urodynamic parameters were performed by cystometry 24h after a single treatment with cyclophosphamide (200mg/kg, i.p.) in control and HC 030031 treated rats. Analyses of the urodynamic parameters showed that a single dose of cyclophosphamide was enough to significantly increase the number and amplitude of non-voiding contractions and to decrease the voided volume and voiding efficiency, without significantly altering basal, threshold or maximum pressure. The treatment with HC 030031 either before (100mg/kg, p.o.) or after (30mg/kg, i.v.) cyclophosphamide inhibited the non-voiding contractions but failed to counteract the loss in voiding efficiency. Our data demonstrates that nociceptive symptoms and urinary bladder overactivity caused by cyclophosphamide, in part, are dependent upon the activation of TRPA1. In this context, the antagonism of the receptor may be an alternative to minimise the urotoxic symptoms caused by this chemotherapeutic agent. 23588094 Characterization of volatiles and anti-ulcerogenic effect of Turkish sweetgum balsam (Styrax liquidus). ETHNOPHARMACOLOGICAL RELEVANCE: Sweetgum, Styrax liquidus (Turkish sweetgum) is a resinous exudate obtained from the wounded barks of Liquidambar orientalis Miller tree which belongs to Altingiaceae (Hamamelidaceae). The plant material has been used for the treatment of peptic ulcer symptoms in Turkish folk medicine since centuries. In order to evaluate the claimed activity, we studied the anti-ulcerogenic effect of Styrax liquidus by using an in vivo anti-ulcerogenic activity model and to determine the chemical composition of the balsam. MATERIALS AND METHODS: Anti-ulcerogenic effects of the balsam "Styrax liquidus" itself and its fractions obtained by successive solvent extractions with chloroform and n-butanol, were investigated against the ethanol-induced peptic ulcer model in rats. The chloroform extract demonstrated a statistically significant gastroprotective effect. In addition, the chemical characterization of the volatiles obtained by microdistillation technique from the balsam and the sub-extracts were analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS), respectively. RESULTS: Pharmacological experiments have clearly demonstrated that 150 and 300mg/kg doses of Styrax liquidus given orally to rats showed significant gastric protection. On GC-MS analysis of the resin, overall, 31 compounds representing 99.8% of the total oil were identified where styrene (81.9%), cinnamyl alcohol (6.9%) and α-pinene (3.5%) were identified as the major components. CONCLUSION: Present study confirmed the anti-ulcerogenic activity of the local ethnobotanical usage of Styrax liquidus in Turkey. 23558233 Systems analysis of genetic variation in MPTP neurotoxicity in mice. We analyzed genetic variation in severity of neuronal damage using the known dopaminergic neurotoxicant, MPTP, as a prototypical chemical denervation agent. Male mice from ten members of the BXD family of recombinant inbred strains received 12.5mg/kg MPTP s.c. (vs. saline) and 48h later brains were taken for multiple related biochemical analyses. Striatal dopamine (DA) and its metabolites, DOPAC and HVA, and serotonin and its metabolite, 5-HIAAA, were analyzed by HPLC. DA turnover was assessed using DOPAC/DA and HVA/DA ratios. Striatal tyrosine hydroxylase (TH), glial fibrilary acidic protein (GFAP), and iron content in ventral midbrain were quantified. All dopamine measures, as well as TH and GFAP, demonstrated wide, genotype-dependent differences in response to MPTP. Serotonin was largely unaffected. Principal components analysis (PC) on difference values, saline minus MPTP, for DA, DOPAC, HVA, and TH, yielded a dominant principal component. The PC trait residuals for each genotype were compared against complementary expression data for striatum of the same strains. Three transcripts representing Mtap2, Lancl 1, and Kansl1l were highly correlated with the PC, as was the difference score, MPTP minus saline for GFAP. This systems approach to the study of environmental neurotoxicants holds promise to define individual genetic differences that contribute to variability in susceptibility to risk factors for diseases such as Parkinson's disease. 23394218 Discovery of 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an orally bioavailable, potent inhibitor of Akt kinases. Wide-ranging exploration of analogues of an ATP-competitive pyrrolopyrimidine inhibitor of Akt led to the discovery of clinical candidate AZD5363, which showed increased potency, reduced hERG affinity, and higher selectivity against the closely related AGC kinase ROCK. This compound demonstrated good preclinical drug metabolism and pharmacokinetics (DMPK) properties and, after oral dosing, showed pharmacodynamic knockdown of phosphorylation of Akt and downstream biomarkers in vivo, and inhibition of tumor growth in a breast cancer xenograft model. 23200747 Interactions of neuropathy inducers and potentiators/promoters with soluble esterases. Organophosphorus compounds (OPs) cause neurotoxic disorders through interactions with well-known target esterases, such as acetylcholinesterase and neuropathy target esterase (NTE). However, the OPs can potentially interact with other esterases of unknown significance. Therefore, identifying, characterizing and elucidating the nature and functional significance of the OP-sensitive pool of esterases in the central and peripheral nervous systems need to be investigated. Kinetic models have been developed and applied by considering multi-enzymatic systems, inhibition, spontaneous reactivation, the chemical hydrolysis of the inhibitor and "ongoing inhibition" (inhibition during the substrate reaction time). These models have been applied to discriminate enzymatic components among the esterases in nerve tissues of adult chicken, this being the experimental model for delayed neuropathy and to identify different modes of interactions between OPs and soluble brain esterases. The covalent interaction with the substrate catalytic site has been demonstrated by time-progressive inhibition during ongoing inhibition. The interaction of sequential exposure to an esterase inhibitor has been tested in brain soluble fraction where exposure to one inhibitor at a non inhibitory concentration has been seen to modify sensitivity to further exposure to others. The effect has been suggested to be caused by interaction with sites other than the inhibition site at the substrate catalytic site. This kind of interaction among esterase inhibitors should be considered to study the potentiation/promotion phenomenon, which is observed when some esterase inhibitors enhance the severity of the OP induced neuropathy if they are dosed after a non neuropathic low dose of a neuropathy inducer. 23517621 Nitroxide TEMPO: A genotoxic and oxidative stress inducer in cultured cells. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) is a low molecular weight nitroxide and stable free radical. In this study, we investigated the cytotoxicity and genotoxicity of TEMPO in mammalian cells using the mouse lymphoma assay (MLA) and in vitro micronucleus assay. In the absence of metabolic activation (S9), 3mM TEMPO produced significant cytotoxicity and marginal mutagenicity in the MLA; in the presence of S9, treatment of mouse lymphoma cells with 1-2mM TEMPO resulted in dose-dependent decreases of the relative total growth and increases in mutant frequency. Treatment of TK6 human lymphoblastoid cells with 0.9-2.3mM TEMPO increased the frequency of both micronuclei (a marker for clastogenicity) and hypodiploid nuclei (a marker of aneugenicity) in a dose-dependent manner; greater responses were produced in the presence of S9. Within the dose range tested, TEMPO induced reactive oxygen species and decreased glutathione levels in mouse lymphoma cells. In addition, the majority of TEMPO-induced mutants had loss of heterozygosity at the Tk locus, with allele loss of ⩽34Mbp. These results indicate that TEMPO is mutagenic in the MLA and induces micronuclei and hypodiploid nuclei in TK6 cells. Oxidative stress may account for part of the genotoxicity induced by TEMPO in both cell lines. 23643730 Juglone, isolated from Juglans mandshurica Maxim, induces apoptosis via down-regulation of AR expression in human prostate cancer LNCaP cells. Juglone is a natural compound which has been isolated from Juglans mandshurica Maxim. Recent studies have shown that juglone had various pharmacological effects such as anti-viral, anti-bacterial and anti-cancer. However, its anti-cancer activity on human prostate cancer LNCaP cell has not been examined. Thus, the current study was designed to elucidate the molecular mechanism of apoptosis induced by juglone in androgen-sensitive prostate cancer LNCaP cells. MTT assay was performed to examine the anti-proliferative effect of juglone. Occurrence of apoptosis was detected by Hoechst 33342 staining and flow cytometry in LNCaP cells treated with juglone for 24h. The result shown that juglone inhibited the growth of LNCaP cells in a dose-dependent manner. Morphological changes of apoptotic body formation after juglone treatment were observed by Hoechst 33342 staining. This apoptotic induction was associated with loss of mitochondrial membrane potential, and caspase-3, -9 activation. Moreover, we found that juglone significantly inhibited the expression levels of androgen receptor (AR) and prostate-specific antigen (PSA) in a dose-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and/or without dihydrotestosterone (DHT). Take together, our results demonstrated that juglone might induce the apoptosis in LNCaP cell via down-regulation of AR expression. Therefore, our results indicated that juglone may be a potential candidate of drug for androgen-sensitive prostate cancer. 23452857 Encoding and transducing the synaptic or extrasynaptic origin of NMDA receptor signals to the nucleus. The activation of N-methyl-D-aspartate-receptors (NMDARs) in synapses provides plasticity and cell survival signals, whereas NMDARs residing in the neuronal membrane outside synapses trigger neurodegeneration. At present, it is unclear how these opposing signals are transduced to and discriminated by the nucleus. In this study, we demonstrate that Jacob is a protein messenger that encodes the origin of synaptic versus extrasynaptic NMDAR signals and delivers them to the nucleus. Exclusively synaptic, but not extrasynaptic, NMDAR activation induces phosphorylation of Jacob at serine-180 by ERK1/2. Long-distance trafficking of Jacob from synaptic, but not extrasynaptic, sites depends on ERK activity, and association with fragments of the intermediate filament α-internexin hinders dephosphorylation of the Jacob/ERK complex during nuclear transit. In the nucleus, the phosphorylation state of Jacob determines whether it induces cell death or promotes cell survival and enhances synaptic plasticity. 23305918 The first total synthesis and biological evaluation of marine natural products ma'edamines A and B. We have developed the first total syntheses of marine natural products ma'edamines A (18) and B (20). Structurally, they contain a pyrazine-2-(1H)-one core and were screened for antiproliferative activity on several cancer cell lines. Out of the six cell lines tested, ma'edamines A and B showed significant cytotoxicity against human colon cancer line COLO 205 (IC(50) 7.9 and 10.3 μM, respectively), breast cancer cell line MCF-7 (IC(50): 6.9 and 10.5 μM, respectively) and human lung adenocarcinoma cell line A549 (IC(50): 12.2 and 15.4 μM, respectively). The apoptotic effect of ma'edamines was confirmed by comet assay. Hence ma'edamines are likely to be useful as leads for development of a new class of anti-cancer agents. 23041243 Process analytical tools for monitoring, understanding, and control of pharmaceutical fluidized bed granulation: A review. Fluidized bed granulation is a widely applied wet granulation technique in the pharmaceutical industry to produce solid dosage forms. The process involves the spraying of a binder liquid onto fluidizing powder particles. As a result, the (wetted) particles collide with each other and form larger permanent aggregates (granules). After spraying the required amount of granulation liquid, the wet granules are rapidly dried in the fluid bed granulator. Since the FDA launched its Process Analytical Technology initiative (and even before), a wide range of analytical process sensors has been used for real-time monitoring and control of fluid bed granulation processes. By applying various data analysis techniques to the multitude of data collected from the process analyzers implemented in fluid bed granulators, a deeper understanding of the process has been achieved. This review gives an overview of the process analytical technologies used during fluid bed granulation to monitor and control the process. The fundamentals of the mechanisms contributing to wet granule growth and the characteristics of fluid bed granulation processing are briefly discussed. This is followed by a detailed overview of the in-line applied process analyzers, contributing to improved fluid bed granulation understanding, modeling, control, and endpoint detection. Analysis and modeling tools enabling the extraction of the relevant information from the complex data collected during granulation and the control of the process are highlighted. 23448861 Acute respiratory distress syndrome due to exposure to high-concentration mixture of ethenone and crotonaldehyde. INTRODUCTION: Acute inhalational exposure leads to rapidly progressive acute respiratory distress syndrome (ARDS). This report is the first one to present a patient with ARDS in relation to long-standing exposure to a high-concentration mixture of ethenone and crotonaldehyde. Case report: A male worker in a chemical plant was accidentally exposed to the mixture of high-concentrated ethenone and crotonaldehyde for 5 min in an open space and worked continuously in the polluted area for approximately 12 h. On admission, he was conscious with the following vital parameters: blood pressure, 151/91 mmHg; pulse rate, 107 beats/min; respiratory rate, 30 breaths/min; temperature, 37.6°C; oxygen saturation, 92% supported by mask saturation 10 L/min; arterial blood gases showed P/F oxygen ratio of less than 200. Physical examination disclosed decreased bilateral vesicular sounds. A chest computed tomography revealed bilateral nonsegmental ground-glass opacities. The patient was mechanically ventilated and treated with corticosteroid. The patient was discharged without any symptoms. CONCLUSION: Exposure to mixtures of ethenone and crotonaldehyde can cause severe pulmonary injury leading to delayed ARDS. 23557933 One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Numerous studies have shown that resveratrol (RES) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited. Furthermore, the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood. Therefore, the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells (PBMCs) associated to the one-year daily intake of a RES enriched (8mg) grape extract (GE-RES) in hypertensive male patients with type 2 diabetes mellitus (T2DM). We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs (miRs) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES. We also examined the changes in several serobiochemical variables, inflammatory and fibrinolytic markers. Our results showed that supplementation with GE or GE-RES did not affect body weight, blood pressure, glucose, HbA1c or lipids, beyond the values regulated by gold standard medication in these patients. We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels. The expression of the pro-inflammatory cytokines CCL3, IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in PBMCs from patients taking the GE-RES extract. Also, a group of miRs involved in the regulation of the inflammatory response: miR-21, miR-181b, miR-663, miR-30c2, miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months. Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients. 23500411 Synthesis of C17-OH-north unit of ritterazine G via "Red-Ox" modifications of hecogenin acetate. The C17-OH-north unit of ritterazine G was prepared in 13 steps from hecogenin acetate. This synthesis features a highly efficient and stereoselective introduction of the C17-OH via E-ring cleavage/F-ring formation, D-ring oxidation, and F-ring cleavage/E-ring formation. 23233456 In vitro transfection mediated by dendrigraft poly(L-lysines): the effect of structure and molecule size. Dendritic poly(L-lysines) (DGL) constitute promising nanomaterials applicable as a nonviral gene-delivery vector. In this study, we evaluate the transfection abilities of four DGL generations with special emphasis on the systematic description of the relationship of how generation (i.e., molecule size) affects the transfection efficacy. Using Hep2 cells, we demonstrated that the capability of unmodified DGL to deliver plasmid is of a magnitude lower than that of jetPEI. On the other hand, employing the Hep2 cell line stably transduced with eGFP, we observed that DGL G5 delivers the siRNA oligonucleotide with the same efficiency as Lipofectamine 2000. In further experiments, it was shown that DGL affords excellent ability to bind DNA, protect it against DNase I attack, and internalize it into cells. 23583929 Lesions of the dorsomedial striatum impair formation of attentional set in rats. Behavioural flexibility refers to the ability to rapidly adapt to novel situations and it has been suggested that the frontal lobe and basal ganglia are implicated in various components of adjusting to changes in environmental contingencies. Behavioural flexibility can be assessed using attentional set-shifting tasks, in which performance is impaired after damage to the prefrontal cortex. The present study explores the downstream contribution of the prefrontal projection zone in the dorsomedial striatum (DMS) to attentional set shifting. Rats were tested in two set-shifting tasks following quinolinic acid injections bilaterally into the DMS. When tested in a rodent version of the set-shifting task, rats with a DMS lesion displayed a greater number of errors during the reversal stages of the task than sham lesion controls but the nature of the errors did not differ between the two groups. Interestingly, when the rats were tested in a modified version of the set-shifting task, directly designed for measuring the formation of an attentional set, sham lesion controls displayed a pronounced shift-cost, evident of successful set-formation. In contrast, rats with DMS lesions failed to form an attentional set, showing no performance cost when a shift of attention was required. These results support previous reports of the importance of the DMS in behavioural flexibility but also suggest that this region is vital for the formation of set, possibly by extrapolating different perceptions into a unified representation of a dimension. 23526663 Recent Advances in Metal-Organic Framework-Based Mixed Matrix Membranes. Mixed matrix membranes (MMMs) combine easy processability and low cost of polymers with the high selectivity of nanoporous filler particles. These membranes represent an important avenue for enhancing the performance of polymeric membranes in gas separations. Recently, a new group of nanoporous materials called metal-organic frameworks (MOFs) have been used as filler particles in MMM applications, and significant improvements in gas selectivity and permeability have been reported for these MOF-based membranes. We discuss the recent developments in MOF-based MMMs by reviewing both the experimental studies and computational modeling methods that can accelerate selection of MOF/polymer combinations for high-performance gas separations. 23565822 Spatially Resolved Mapping of Oxygen Reduction/Evolution Reaction on Solid-Oxide Fuel Cell Cathodes with Sub-10 nm Resolution. Spatial localization of the oxygen reduction/evolution reactions on lanthanum strontium cobaltite (LSCO) surfaces with perovskite and layered perovskite structures is studied at the sub-10 nm level. Comparison between electrochemical strain microscopy (ESM) and structural imaging by scanning transmission electron microscopy (STEM) suggests that small-angle grain boundaries act as regions with enhanced electrochemical activity. The ESM activity is compared across a family of LSCO samples, demonstrating excellent agreement with macroscopic behaviors. This study potentially paves the way for deciphering the mechanisms of electrochemical activity of solids on the level of single extended structural defects such as grain boundaries and dislocations. 23589223 Fullerene Nanoarchitectonics: From Zero to Higher Dimensions. The strategic design of nanostructured materials, the properties of which could be controlled across different length scales and which, at the same time, could be used as building blocks for the construction of devices and functional systems into new technological platforms that are based on sustainable processes, is an important issue in bottom-up nanotechnology.Such strategic design has enabled the fabrication of materials by using convergent bottom-up and top-down strategies. Recent developments in the assembly of functional fullerene (C60 ) molecules, either in bulk or at interfaces, have allowed the production of shape-controlled nano-to-microsized objects that possess excellent optoelectronic properties, thus enabling the fabrication of optoelectronic devices. Because fullerene molecules can be regarded as an ideal zero-dimensional (0D) building units with attractive functions, the construction of higher-dimensional objects, that is, 1D, 2D, and 3D nanomaterials may realize important aspects of nanoarchitectonics. This Focus Review summarizes the recent developments in the production of nanostructured fullerenes and techniques for the elaboration of fullerene nanomaterials into hierarchic structures. 23432586 Immunophilins are Involved in the Altered Platelet Aggregation Observed in Patients with Type 2 Diabetes Mellitus. Platelet hyperaggregability might contribute to vascular complications associated with type 2 diabetes mellitus (DM2).Experimental evidence supports a direct link between altered Ca2+ entry and hyperaggregability in DM2 patients. Objectives: We aimed to investigate whether altered immunophilin expression and function are involved in the abnormal Ca2+ entry observed in platelets from DM2 patients. Results: Inhibition of immunophilins by tacrolimus (FK506) and sirolimus (rapamycin) reduced Ca2+ entry in platelets from healthy donors and DM2 patients. Similarly, immunophilin inhibitors reduced platelet degranulation in both healthy and DM2 subjects. Nevertheless, α-granule secretion reduction was greater than that observed for dense granules in platelets from DM2 patients. However, no difference was observed in the inhibition of secretion in platelets from healthy subjects. Additionally, altered expression of FK506 binding protein-52 (FKBP52) and coupling to Ca(2+) channels were found in platelets from DM2 patients compared to healthy subjects. Finally, reduction in platelet function from healthy subjects and DM2 patients in the presence of immunophilin antagonists was observed, being this dysfunction more evident in platelets from DM2 patients. Conclusions: We suggest that, among others, FKBP52 expression and function are altered in platelets from DM2 patients, contributing to the altered Ca(2+) entry and hyperaggregability in these cells. 22945693 Methylation levels of sodium-iodide symporter (NIS) promoter in benign and malignant thyroid tumors with reduced NIS expression. DNA methylation regulates gene expression. Aberrant methylation plays an important role in human tumorigenesis. We have previously detected reduced NIS mRNA expression in thyroid tumors as compared to non-tumor tissues. Thus, in this study we investigated whether the methylation of the CpG-island located in the NIS gene promoter was associated with reduced mRNA expression in thyroid tumors. Methylation levels of 30 pairs of samples from 10 benign and 20 malignant thyroid tumors (T) along with matched non-tumor (NT) areas were determined by semiquantitative methylation specific-PCR. NIS methylation was detected in all samples. Methylation levels and frequencies did not differ between the groups and were not associated with BRAF mutational status. Highest methylation levels and frequencies were detected in the 5' region of the CpG-island decreasing toward the 3' end. Intraindividual analysis (T versus NT) showed high tumor methylation levels in 40 % of the samples in the benign group and 30 % in the malignant group, associated with low NIS mRNA expression. No quantitative correlation was detected between methylation levels and mRNA expression in any the groups. The results of this study showed that methylation of NIS promoter is a very frequent event in both benign and malignant tumors as well as in their surrounding tissues, and characterized a non-homogeneous methylation pattern along the CpG island. Therefore, further investigations involving other sites that may be implicated in methylation regulation of NIS expression are warranted. 23050902 Ribavirin-induced intracellular GTP depletion activates transcription elongation in coagulation factor VII gene expression. Coagulation FVII (Factor VII) is a vitamin K-dependent glycoprotein synthesized in hepatocytes. It was reported previously that FVII gene (F7) expression was up-regulated by ribavirin treatment in hepatitis C virus-infected haemophilia patients; however, its precise mechanism is still unknown. In the present study, we investigated the molecular mechanism of ribavirin-induced up-regulation of F7 expression in HepG2 (human hepatoma cell line). We found that intracellular GTP depletion by ribavirin as well as other IMPDH (inosine-5'-monophosphate dehydrogenase) inhibitors, such as mycophenolic acid and 6-mercaptopurine, up-regulated F7 expression. FVII mRNA transcription was mainly enhanced by accelerated transcription elongation, which was mediated by the P-TEFb (positive-transcription elongation factor b) complex, rather than by promoter activation. Ribavirin unregulated ELL (eleven-nineteen lysine-rich leukaemia) 3 mRNA expression before F7 up-regulation. We observed that ribavirin enhanced ELL3 recruitment to F7, whereas knockdown of ELL3 diminished ribavirin-induced FVII mRNA up-regulation. Ribavirin also enhanced recruitment of CDK9 (cyclin-dependent kinase 9) and AFF4 to F7. These data suggest that ribavirin-induced intracellular GTP depletion recruits a super elongation complex containing P-TEFb, AFF4 and ELL3, to F7, and modulates FVII mRNA transcription elongation. Collectively, we have elucidated a basal mechanism for ribavirin-induced FVII mRNA up-regulation by acceleration of transcription elongation, which may be crucial in understanding its pleiotropic functions in vivo. 23548897 G-protein coupled receptor agonist BV8/prokineticin-2 and STAT3 form a feed-forward loop in both normal and malignant myeloid cells. An important role of Bv8 in mobilization of myeloid cells and myeloid cell-dependent angiogenesis has been established. Recently, it has also been shown that granulocyte colony stimulating factor (G-CSF)-induced Bv8 expression is Stat3 dependent in CD11b+Gr1+ myeloid cells. However, Bv8 downstream signaling pathway(s) intrinsic to myeloid cells crucial for angiogenesis, and potentially also for development of cancers of myeloid origin, remains largely unknown. Here we show that BV8 activates STAT3, which is critical for regulating genes important for both tumor cell proliferation/survival and tumor angiogenesis, in both normal and malignant myeloid cells. Further, BV8-induced STAT3 activation requires Janus activated kinase 2 (JAK2) activity as shown by both genetic and pharmacologic inhibition. Knocking down BV8 in human myeloid leukemia cells inhibits STAT3 activity and expression of STAT3-downstream angiogenic and pro-proliferation/survival genes, leading to a decrease in tumor cell viability. BV8 shRNA expressing leukemia cells exhibit reduced STAT3 activity and tumor growth in vivo. Taken together, we have delineated a signaling pathway downstream of BV8 that plays critical roles in both the tumor microenvironment and malignant myeloid cells for angiogenesis and tumor cell proliferation/survival. 23601709 Radiosynthesis and evaluation of [(11)C]EMPA as a potential PET tracer for orexin 2 receptors. EMPA is a selective antagonist of orexin 2 (OX2) receptors. Previous literature with [(3)H]-EMPA suggest that it may be used as an imaging agent for OX2 receptors; however, brain penetration is known to be modest. To evaluate the potential of EMPA as a PET radiotracer in non-human primate (as a step to imaging in man), we radiolabeled EMPA with carbon-11. Radiosynthesis of [(11)C]N-ethyl-2-(N-(6-methoxypyridin-3-yl)-2-methylphenylsulfonamido)-N-(pyridin-3-ylmethyl)acetamide ([(11)C]EMPA), and evaluation as a potential PET tracer for OX2 receptors is described. Synthesis of an appropriate non-radioactive O-desmethyl precursor was achieved from EMPA with sodium iodide and chlorotrimethylsilane. Selective O-methylation using [(11)C]CH3I in the presence of cesium carbonate in DMSO at room temp afforded [(11)C]EMPA in 1.5-2.5% yield (non-decay corrected relative to trapped [(11)C]CH3I at EOS) with ⩾95% chemical and radiochemical purities. The total synthesis time was 34-36min from EOB. Studies in rodent suggested that uptake in tissue was dominated by nonspecific binding. However, [(11)C]EMPA also showed poor uptake in both rats and baboon as measured with PET imaging. 23570992 Proteomic Analysis of Arsenic-Exposed Zebrafish (Danio rerio) Identifies Altered Expression in Proteins Involved in Fibrosis and Lipid Uptake in a Gender-Specific Manner. The zebrafish (Danio rerio) was used to investigate protein expression in the liver following arsenic exposure. Several disorders have been linked to arsenic exposure, including cancer, diabetes, and cardiovascular disease. The mechanisms of arsenic toxicity are poorly understood. Prior studies have described altered gene expression, inflammation, and mitogenic signaling in acute or chronic exposure models. A proteomic approach was employed to investigate arsenic-induced alteration in the zebrafish liver proteome following a 7-day exposure to 50 ppb sodium arsenite. Over 740 unique proteins were identified, with fewer than 2% showing differential expression. Molecular pathway analysis software identified lipid metabolism and transport as potential molecular targets. Immunoblots were used to confirm protein expression changes, whereas qPCR was employed to investigate gene expression changes. Overall, 25 proteins were differentially expressed in a gender-specific manner, 11 in males and 14 in females. Of these 25, a single protein, hydroxysteroid dehydrogenase like 2, showed decreased expression in both males and females following arsenic exposure. These findings indicate that protein expression is altered following arsenic exposure. The changes presented here seem to be most prevalent in lipid transport and metabolic pathways, suggesting a potential increase in fibrosis in males and decreased lipid accumulation and uptake in females. 23511786 Model-based drug development in oncology: what's next? Model-based estimates of tumor growth inhibition (TGI) metrics have the potential to enhance learning in early (phase II) clinical studies. They can be used as end points and biomarkers to predict treatment effect on clinical outcome measures-e.g., overall survival (OS)-and support phase II study design, end-of-phase II decisions, and phase III planning and execution. Efforts should be made to assess models in simulating independent studies with treatments of varying mechanisms of action. 23000507 Experimental tooth movement-induced osteoclast activation is regulated by sympathetic signaling. Experimental tooth movement (ETM) changes the distribution of sensory nerve fibers in periodontal ligament and the bone architecture through the stimulation of bone remodeling. As the sympathetic nervous system is involved in bone remodeling, we examined whether ETM is controlled by sympathetic signaling or not. In male mice, elastic rubber was inserted between upper left first molar (M1) and second molar (M2) for 3 or 5 days. Nerve fibers immunoreactive for not only sensory neuromarkers, such as calcitonin gene-related peptide (CGRP), but also sympathetic neuromarkers, such as tyrosine hydroxylase (TH) and neuropeptide Y (NPY) were increased in the periodontal ligament during ETM. To elucidate the effect of the sympathetic signal mediated by ETM, mice were intraperitoneally injected with a β-antagonist, propranolol (PRO: 20 μg/g/day), or a β-agonist, isoproterenol (ISO: 5 μg/g/day) from 7 days before ETM. PRO treatment suppressed the amount of tooth movement by 12.9% in 3-day ETM and by 32.2% in 5-day ETM compared with vehicle treatment. On the other hand, ISO treatment increased it. Furthermore, ETM remarkably increased the osteoclast number on the bone surface (alveolar socket) (Oc.N/BS) in all drug treatments. PRO treatment suppressed Oc.N/BS by 39.4% in 3-day ETM, while ISO treatment increased it by 32.1% in 3-day ETM compared with vehicle treatment. Chemical sympathectomy using 6-hydroxydopamine (6-OHDA: 250 μg/g) showed results similar to those for PRO treatment in terms of both the amount of tooth movement and osteoclast parameters. Our data showed that blockade of sympathetic signaling inhibited the tooth movement and osteoclast increase induced by ETM, and stimulation of sympathetic signaling accelerated these responses. These data suggest that the mechano-adaptive response induced by ETM is controlled by sympathetic signaling through osteoclast activation. 23225542 Multifunctional uniform core-shell Fe3O4@mSiO2 mesoporous nanoparticles for bimodal imaging and photothermal therapy. Multimodal imaging and simultaneous therapy is highly desirable because it can provide complementary information from each imaging modality for accurate diagnosis and, at the same time, afford an imaging-guided focused tumor therapy. In this study, indocyanine green (ICG), a near-infrared (NIR) imaging agent and perfect NIR light absorber for laser-mediated photothermal therapy, was successfully incorporated into superparamagnetic Fe(3)O(4)@mSiO(2) core-shell nanoparticles to combine the merit of NIR/magnetic resonance (MR) bimodal imaging properties with NIR photothermal therapy. The resultant nanoparticles were homogenously coated with poly(allylamine hydrochloride) (PAH) to make the surface of the composite nanoparticles positively charged, which would enhance cellular uptake driven by electrostatic interactions between the positive surface of the nanoparticles and the negative surface of the cancer cell. A high biocompatibility of the achieved nanoparticles was demonstrated by using a cell cytotoxicity assay. Moreover, confocal laser scanning microscopy (CLSM) observations indicated excellent NIR fluorescent imaging properties of the ICG-loaded nanoparticles. The relatively high r(2) value (171.6 mM(-1) s(-1)) of the nanoparticles implies its excellent capability as a contrast agent for MRI. More importantly, the ICG-loaded nanoparticles showed perfect NIR photothermal therapy properties, thus indicating their potential for simultaneous cancer diagnosis as highly effective NIR/MR bimodal imaging probes and for NIR photothermal therapy of cancerous cells. 23313448 cDNA cloning of a snake venom metalloproteinase from the eastern diamondback rattlesnake (Crotalus adamanteus), and the expression of its disintegrin domain with anti-platelet effects. A 5' truncated snake venom metalloproteinase was identified from a cDNA library constructed from venom glands of an eastern diamondback rattlesnake (Crotalus adamanteus). The 5'-rapid amplification of cDNA ends (RACE) was used to obtain the 1865 bp full-length cDNA sequence of a snake venom metalloproteinase (CamVMPII). CamVMPII encodes an open reading frame of 488 amino acids, which includes a signal peptide, a pro-domain, a metalloproteinase domain, a spacer, and an RGD-disintegrin domain. The predicted amino acid sequence of CamVMPII showed a 91%, 90%, 83%, and 82% sequence homology to the P-II class enzymes of C. adamanteus metalloproteinase 2, Crotalus atrox CaVMP-II, Gloydius halys agkistin, and Protobothrops jerdonii jerdonitin, respectively. Disintegrins are potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion. Therefore, the disintegrin domain (Cam-dis) of CamVMPII was amplified by PCR, cloned into a pET-43.1a vector, and expressed in Escherichia coli BL21. Affinity purified recombinantly modified Cam-dis (r-Cam-dis) with a yield of 8.5 mg/L culture medium was cleaved from the fusion tags by enterokinase cleavage. r-Cam-dis was further purified by two-step chromatography consisting of HiTrap™ Benzamidine FF column, followed by Talon Metal affinity column with a final yield of 1 mg/L culture. r-Cam-dis was able to inhibit all three processes of platelet thrombus formation including platelet adhesion with an estimated IC(50) of 1 nM, collagen- and ADP-induced platelet aggregation with the estimated IC(50)s of 18 and 6 nM, respectively, and platelet function on clot retraction. It is a potent anti-platelet inhibitor, which should be further investigated for drug discovery to treat stroke patients or patients with thrombotic disorders. 23643851 Methods for Detection and Analysis of Apoptosis Signalling in the C. elegans Germline. This review assesses current and emerging methods for the detection, and analysis of apoptosis in the C. elegans germline. The nematode worm C. elegans is highly tractable to genetic manipulation, making it an excellent model for elucidating mechanisms of apoptosis signalling in a multicellular setting. Here we profile the most efficacious fluorescent tools to visualize and quantify germline apoptosis. We focus specifically on the application of fluorescent markers to screen by RNAi for genes and pathways that regulate germline apoptosis under normal conditions or in response to genotoxic stress. We also present the limitations of these methods, and suggest complimentary techniques in order that researchers new to the field can comprehensively assess apoptosis phenotypes in the C. elegans germline. 23237828 Cycloheximide stimulates suppressor of cytokine signaling-3 gene expression in 3T3-L1 adipocytes via the extracellular signal-regulated kinase pathway. Suppressor of cytokine signaling (SOCS)-3 can act as a regulator of energy metabolism and cytokine signaling in fat cells. It is regulated by hormones and toxicological factors. However, the action of cycloheximide on expression of adipocyte SOCS-3 gene is unknown. Using 3T3-L1 adipocytes, we found that cycloheximide up-regulated SOCS-3 mRNA expression in dose- and time-dependent manners. Treatment with actinomycin D prevented cycloheximide-stimulated SOCS-3 mRNA expression, suggesting that the effect of cycloheximide requires new mRNA synthesis. While cycloheximide was shown to increase activities of MEK1 and JNK, signaling was demonstrated to be inhibited by pretreatment with either MEK1 inhibitors U0126 and PD98059, or with the JNK inhibitor SP600125. U0126 and PD98059, respectively, reduced cycloheximide-stimulated SOCS-3 mRNA expression, but SP600125 did not antagonize cycloheximide effect. Moreover, cycloheximide was observed to up-regulate expression of other SOCS family members, such as SOCS-1, -2, -4, -5, -6, -7, and cytokine-inducible SH2-containing protein (CIS)-1 mRNAs. Such effects varied with the dosage and duration of cycloheximide treatment. These results imply the functional MEK1/ERK-mediated pathway is necessary for the cycloheximide stimulation of SOCS-3 gene expression. 23517010 Nanofiber near-field light-matter interactions for enhanced detection of molecular level displacements and dynamics. We experimentally demonstrate that plasmonic nanoparticles embedded in the evanescent field of subwavelength optical waveguides (WGs) are highly sensitive to distances normal to the propagation of light, showing an ∼10× increase in spatial resolution compared to the optical field decay of the WG. The scattering cross-section of the Au nanoparticle is increased by the plasmon-dielectric coupling interaction when the nanoparticle is placed near the dielectric surface of the WG, and the decay of the scattering signal is enhanced, showing angstrom level distance sensitivity within 10 nm from the WG. Numerical studies with the finite-difference time-domain (FDTD) method correlate well with the experimental results. To demonstrate real-time monitoring of a single molecule stretching in the evanescent field, we linked individual single-stranded DNA molecules between the WG and plasmonic nanoparticles and pushed on the nanoparticles with fluidic forces. The simple design and ease of obtaining optical feedback on molecular displacements makes our approach ideal for new in situ force sensing devices, imaging technologies, and high-throughput molecular analysis. 23589476 Wired Enzyme Electrodes-A Retroperspective Story about an Exciting Time at University of Texas at Austin and Its Impact on My Scientific Career. The present paper features an exciting time in the late 1980s when I, as a visiting scientist, had the privilege to participate in the early and very exciting development of the in vivo redox-polymer-wired glucose sensor in Professor Adam Heller's laboratory at the Department of Chemical Engineering at University of Texas at Austin. This story is followed by an overview of the research my visit initiated at Uppsala University. In collaboration with Swedish colleagues, we explored a few of the many possibilities to form new biosensors by utilizing Prof. Heller's concept of cross-linked redox-polymer/redox-enzyme electrodes. 23639627 Doxorubicin induces protein ubiquitination and inhibits proteasome activity during cardiotoxicity. Anthracycline-induced cardiotoxicity is a clinically complex syndrome that leads to substantial morbidity and mortality for cancer survivors. Despite several years of research, the underlying molecular mechanisms remain largely undefined and thus effective therapies to manage this condition are currently non-existent. This study therefore aimed to determine the contribution of the ubiquitin-proteasome pathway (UPP) and endoplasmic reticulum (ER)-stress within this context. Cardiotoxicity was induced with the use of doxorubicin (DXR) in H9C2 rat cardiomyoblasts (3μM) for 24hrs, whereas the tumour-bearing GFP-LC3 mouse model was treated with a cumulative dose of 20mg/kg. Markers for proteasome-specific protein degradation were significantly upregulated in both models following DXR treatment, however proteasome activity was lost. Moreover, ER-stress as assessed by increased ER load was considerably augmented (in vitro) with modest binding of DXR with ER. These results suggest that DXR induces intrinsic activation of the UPP and ER stress which ultimately contributes to dysfunction of the myocardium during this phenomenon. 23616190 High-Throughput Analytical Model to Evaluate Materials for Temperature Swing Adsorption Processes. In order for any material to be considered in a post-combustion carbon capture technology, it must have high working capacities of CO2 from flue gas and be regenerable using as little energy as possible. Shown here is an easy to use method to calculate both working capacities and regeneration energies and thereby predict optimal desorption conditions for any material. 23479389 [6]-gingerol: a novel AT₁ antagonist for the treatment of cardiovascular disease. Considering the prevalence of cardiovascular disease in public health and the limited validated therapeutic options, this study aimed to find novel compounds targeting the angiotensin II type 1 receptor, accepted as a therapeutic target in cardiovascular disease. A small library consisting of 89 compounds from 39 Chinese herbs was profiled using a cell-based calcium mobilization assay which was developed and characterized for high-throughput screening. [6]-Gingerol derived from Zingiber officinale Roscoe (ginger) was identified as a novel angiotensin II type 1 receptor antagonist, with an IC50 value of 8.173 µM. The hit was further tested by a specificity assay indicating that it had no antagonistic effects on other evaluated GPCRs, such as endothelin receptors. The major ingredient of ginger, [6]-gingerol, could inhibit angiotensin II type 1 receptor activation, which partially clarified the mechanism of ginger regulating blood pressure and strengthening heart in the cardiovascular system. 23252481 Total synthesis and evaluation of vinblastine analogues containing systematic deep-seated modifications in the vindoline subunit ring system: core redesign. The total synthesis of a systematic series of vinblastine analogues that contain deep-seated structural modifications to the core ring system of the lower vindoline subunit is described. Complementary to the vindoline 6,5 DE ring system, compounds with 5,5, 6,6, and the reversed 5,6 membered DE ring systems were prepared. Both the natural cis and unnatural trans 6,6-membered ring systems proved accessible, with the latter representing a surprisingly effective class for analogue design. Following Fe(III)-promoted coupling with catharanthine and in situ oxidation to provide the corresponding vinblastine analogues, their evaluation provided unanticipated insights into how the structure of the vindoline subunit contributes to activity. Two potent analogues (81 and 44) possessing two different unprecedented modifications to the vindoline subunit core architecture were discovered that matched the potency of the comparison natural products and both lack the 6,7-double bond whose removal in vinblastine leads to a 100-fold drop in activity. 23539351 Antidiabetic attributes of desert and steppic plants: a review. The rapidly increasing incidence of diabetes mellitus is becoming a serious threat to mankind's health in all parts of the world. In fact, known cases reflect only part of the problem, as many diabetics, especially with type 2 diabetes, are unaware of their disease, which initially shows no definitive symptoms. Despite the great efforts invested in diabetes research, its prevalence continues to grow, while current medications do not cover all of the symptoms and complications of the disease. The present review highlights a plethora of studies focusing on the antidiabetic properties of desert and semidesert (steppic) plants, many of them being used for centuries in traditional medicine by Bedouins living in the arid zones of the Middle East and also by ethnic groups in other arid and semiarid parts of the world. The review concludes in summarizing the work done on the subject and also in pointing to the yet existing gaps in diabetes research of desert and steppic plants, and suggests directions for future exploration. 23526814 tert-Butylcarbamate-Containing Histone Deacetylase Inhibitors: Apoptosis Induction, Cytodifferentiation, and Antiproliferative Activities in Cancer Cells. Herein we report novel pyrrole- and benzene-based hydroxamates (8, 10) and 2'-aminoanilides (9, 11) bearing the tert-butylcarbamate group at the CAP moiety as histone deacetylase (HDAC) inhibitors. Compounds 8 b and 10 c selectively inhibited HDAC6 at the nanomolar level, whereas the other hydroxamates effected an increase in acetyl-α-tubulin levels in human acute myeloid leukemia U937 cells. In the same cell line, compounds 8 b and 10 c elicited 18.4 and 21.4 % apoptosis, respectively (SAHA: 16.9 %), and the pyrrole anilide 9 c displayed the highest cytodifferentiating effect (90.9 %). In tests against a wide range of various cancer cell lines to determine its antiproliferative effects, compound 10 c exhibited growth inhibition from sub-micromolar (neuroblastoma LAN-5 and SH-SY5Y cells, chronic myeloid leukemia K562 cells) to low-micromolar (lung H1299 and A549, colon HCT116 and HT29 cancer cells) concentrations. In HT29 cells, 10 c increased histone H3 acetylation, and decreased the colony-forming potential of the cancer cells by up to 60 %. 23529905 Mimicking Nanofibrous Hybrid Bone Substitute for Mesenchymal Stem Cells Differentiation into Osteogenesis. Mimicking hybrid extracellular matrix is one of the main challenges for bone tissue engineering (BTE). Biocompatible polycaprolactone/poly(α,β)-DL-aspartic acid/collagen nanofibrous scaffolds were fabricated by electrospinning and nanohydroxyapatite (n-HA) was deposited by calcium phosphate dipping method for BTE. Human mesenchymal stem cells (hMSCs) were cultured on these hybrid scaffolds to investigate the cell proliferation, osteogenic differentiation by alkaline phosphatase activity, mineralization, double immunofluorescent staining using CD90 and expression of osteocalcin. The present study indicated that the PCL/PAA/collagen/n-HA scaffolds promoted greater osteogenic differentiation of hMSCs, proving to be a potential hybrid scaffolds for BTE. 23411173 Nutritional and antinutritional evaluation of raw and processed Australian wattle (Acacia saligna) seeds. Raw and processed (soaked, soaked/boiled, roasted) wattle, Acacia saligna subspecies (subsp.) saligna, pruinescens, stolonifera and lindleyi, seeds were analysed for nutritional and antinutritional qualities. Whole wattle seeds mainly comprised proteins (27.6-32.6%) and carbohydrates (30.2-36.4%), which had approximately 12.0-14.0% fat and 13.0-15.0% crude fibre. Palmitic (9.6%), stearic (2.0%), oleic (20.0%) and linoleic (64.3%) acids were identified by gas chromatography (GC) analysis. Phenolic (∼0.2%), oxalate (2.2-3.4%) and saponin (2.6-3.0%) contents were fairly high; phytate content was low. All untreated samples contained a high level of trypsin inhibitor (2474.3-3271.4 trypsin inhibitor units per gramme (TIU/g) of flour) and low level of α-chymotrypsin inhibitor (120.4-150.6 CIU/g). Soaking overnight following with 2-min boiling led to a significant reduction of protease inhibitor activity. Roasting at 2 min or longer was sufficient to reduce both trypsin and α-chymotrypsin inhibitors to negligible values, also to reduce phytate, oxalate and saponin contents, simultaneously enhanced the nutritional values of wattle seeds. 23589329 Arsenic inhibits autophagic flux activating the Nrf2-Keap1 pathway in a p62-dependent manner. The Nrf2-Keap1 signaling pathway is a protective mechanism promoting cell survival. Activation of the Nrf2 pathway by natural compounds has been proven to be an effective strategy for chemoprevention. Interestingly, a cancer-promoting function of Nrf2 has been recently observed in many types of tumors due to deregulation of the Nrf2-Keap1 axis, which leads to constitutive activation of Nrf2. Here, we report a novel mechanism of Nrf2 activation by arsenic that is distinct from that of chemopreventive compounds. Arsenic deregulates the autophagic pathway through blockage of autophagic flux, resulting in accumulation of autophagosomes and sequestration of p62, Keap1, and LC3. Thus, arsenic activates Nrf2 through a non-canonical mechanism (p62-dependent), leading to a chronic, sustained activation of Nrf2. In contrast, activation of Nrf2 by sulforaphane and tert-butylhydroquinone depend upon Keap1-C151 and not p62 (the canonical mechanism). More importantly, SF and tBHQ do not have any effect on autophagy. In fact, SF and tBHQ alleviate arsenic-mediated deregulation of autophagy. Collectively, these findings provide evidence that arsenic causes prolonged activation of Nrf2 through autophagy dysfunction, possibly providing a similar scenario to constitutive activation of Nrf2 found in certain human cancers. This may represent a previously unrecognized mechanism underlying arsenic toxicity and carcinogenicity in humans. 23570913 Electromagnetic-pulse-induced activation of p38 MAPK pathway and disruption of blood-retinal barrier. The blood-retinal barrier (BRB) is critical for maintaining retina homeostasis and low permeability. In this study, we evaluated the effects of electromagnetic pulse (EMP) exposure on the permeability of BRB, alterations of tight junction (TJ) proteins of BRB and if any, involvement of mitogen-activated protein kinase (MAPK) pathway. Male Sprague-Dawley (SD) rats and RF/6A cells which were pretreated with or without MAPKs inhibitors were sham exposed or exposed to EMP at 200kV/m for 200 pulses. The alteration of BRB permeability was examined through fluorescence microscope and quantitatively assessed using Evans blue (EB) and endogenous albumin as tracers. The expressions of TJ proteins and some signaling molecules of MAPK pathway were measured by Western blots. The observations were that EMP exposure resulted in increased BRB permeability concurrent with the decreased expressions of occludin and claudin-5, which were correlated with the increased expressions of phospho-p38, phospho-JNK and phospho-ERK and could be blocked when pretreated with p38 MAPK inhibitor. Thus, the results suggested that the alterations of occludin and claudin-5 may play an important role in the disruption of TJs, which may lead to the transient breakdown of BRB after EMP exposure with the involvement of p38 MAPK pathway through phosphorylation of signaling molecules. 23509039 2-aminothiazoles with improved pharmacotherapeutic properties for treatment of prion disease. Recently, we described the aminothiazole lead (4-biphenyl-4-ylthiazol-2-yl)-(6-methylpyridin-2-yl)-amine (1), which exhibits many desirable properties, including excellent stability in liver microsomes, oral bioavailability of ∼40 %, and high exposure in the brains of mice. Despite its good pharmacokinetic properties, compound 1 exhibited only modest potency in mouse neuroblastoma cells overexpressing the disease-causing prion protein PrP(Sc) . Accordingly, we sought to identify analogues of 1 with improved antiprion potency in ScN2a-cl3 cells while retaining similar or superior properties. Herein we report the discovery of improved lead compounds such as (6-methylpyridin-2-yl)-[4-(4-pyridin-3-yl-phenyl)thiazol-2-yl]amine and cyclopropanecarboxylic acid (4-biphenylthiazol-2-yl)amide, which exhibit brain exposure/EC50 ratios at least tenfold greater than that of compound 1. 23174539 Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats. Pesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases. Previous studies investigated the effect of permethrin (PERM) administered at 34 mg/kg, a dose close to the no observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in rats. Despite the PERM dose did not elicited overt signs of toxicity (i.e. normal body weight gain curve), it was able to induce striatal neurodegeneration (dopamine and Nurr1 reduction, and lipid peroxidation increase). The present study was designed to characterize the cognitive deficits in the current animal model. When during late adulthood PERM treated rats were tested for spatial working memory performances in a T-maze-rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls. No differences between groups were found in anxiety-like state, locomotor activity, feeding behavior and spatial orientation task. Our findings showing a selective effect of PERM treatment on the T-maze task point to an involvement of frontal cortico-striatal circuitry rather than to a role for the hippocampus. The predominant disturbances concern the dopamine (DA) depletion in the striatum and, the serotonin (5-HT) and noradrenaline (NE) unbalance together with a hypometabolic state in the medial prefrontal cortex area. In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls. The concentration of the most representative marker for pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12 h after the last treatment was 41.50 μg/L and it was completely eliminated after 96 h. 23199999 Effect of red wines with different in vitro antioxidant activity on oxidative stress of high-fat diet rats. It is not known if there is a correlation between in vitro and in vivo antioxidant activity of wines. Thus, in the present study, rats were fed with a high-fat diet to induce inflammation and oxidative stress, and received supplementation (1.0 mL/day) containing water or three red wine samples characterised by high (41.1 mmol TE/L), medium (35.7 mmol TE/L) and low (14.4 mmol TE/L) in vitro antioxidant activity. A correlation was observed between in vitro antioxidant activity measured in the wines and in vivo antioxidant activity measured in plasma (r=+0.49, p=0.011). In liver, only the wine containing the highest in vitro antioxidant activity was able to reduce malondialdehyde concentration. Groups supplemented with wines containing lower in vitro antioxidant activity showed an increase in antioxidant enzyme activity. We concluded that the correlation between in vitro and in vivo antioxidant activity depends on the biomarker selected to evaluate the oxidative stress. 23364612 Green approach—multicomponent production of boron—containing hantzsch and biginelli esters. Multicomponent reactions are excellent methods that meet the requirements of green chemistry, by reducing the number of steps, and consequently reducing purification requirements. Accordingly, in this work, 11 novel hybrid-boron-containing molecules, namely eight 1,4-dihydropyridines and three 3,4-dihydropyrimidinones, derived from formylphenylboronic acids (ortho, meta and para), were obtained using a green approach, involving H-4CR and B-3CR practices, in the presence of ethanol, which is a green solvent, and using three comparatively different modes of activation (mantle heating, yield 3%-7% in 24 h, Infrared Radiation (IR) irradiation, yield 12%-17% in 12 h, and microwave irradiation, yield 18%-80%, requiring very low reaction times of 0.25-0.33 h). In addition, as a green-approach is offered, a convenient analysis, of the 12 green chemistry principles for the overall procedure was performed. Finally, since all the products are new, characterizations were carried out using common analytic procedures (1H, 11B, and 13C NMR, FAB+MS, HRMS, and IR). The accurate mass data of unexpected ions related to interactions between thioglycerol and the expected products, in the FAB+-mode, enabled unequivocal characterization of the target molecules. 23123188 Glaucoma therapy by extended release of timolol from nanoparticle loaded silicone-hydrogel contact lenses. Glaucoma is the second major cause of blindness in the world after cataract. Glaucoma management through eye drops that reduce the intraocular pressure (IOP) has major deficiencies including low patient compliance and low bioavailability. Extended wear contact lenses that deliver glaucoma drugs for extended periods could increase patient compliance, while also increasing the bioavailability. To develop extended wear contact lenses that can also provide extended glaucoma therapy, we disperse nanoparticles of PGT (propoxylated glyceryl triacylate) that contain a glaucoma drug timolol. The particles can also be loaded into prefabricated lenses by soaking the lenses in a solution of particles in ethanol. The particle loaded gels can release timolol in phosphate buffered saline (PBS) for about a month at room temperature. The most likely rate controlling mechanism is hydrolysis of the ester bond that links timolol to the PGT matrix, but other mechanisms such as water and drug diffusion, drug dissolution, drug-polymer chain cleavage, time-dependent drug permeability within the polymeric matrix, etc. may also be important. Nanoparticle incorporation in the silicone hydrogels results in reduction in ion and oxygen permeabilities, and an increase in modulus, and the impact on each of these properties is proportional to the particle loading. A gel with 5% particle loading can deliver timolol at therapeutic doses for about a month at room temperature, with a minimal impact on critical lens properties. Preliminary animal studies in Beagle dogs conducted with lenses in which particles are loaded by soaking the lenses in ethanol show a reduction in IOP. 23411307 Fatty acid composition of cooked chicken meat and chicken meat products as influenced by price range at retail. The primary objective was to determine fatty acid composition of skinless chicken breast and leg meat portions and chicken burgers and nuggets from the economy price range, standard price range (both conventional intensive rearing) and the organic range from four leading supermarkets. Few significant differences in the SFA, MUFA and PUFA composition of breast and leg meat portions were found among price ranges, and supermarket had no effect. No significant differences in fatty acid concentrations of economy and standard chicken burgers were found, whereas economy chicken nuggets had higher C16:1, C18:1 cis, C18:1 trans and C18:3 n-3 concentrations than had standard ones. Overall, processed chicken products had much higher fat contents and SFA than had whole meat. Long chain n-3 fatty acids had considerably lower concentrations in processed products than in whole meat. Overall there was no evidence that organic chicken breast or leg meat had a more favourable fatty acid composition than had meat from conventionally reared birds. 23023933 Development and evaluation of a mechanistic bioconcentration model for ionogenic organic chemicals in fish. A mechanistic mass balance bioconcentration model is developed and parameterized for ionogenic organic chemicals (IOCs) in fish and evaluated against a compilation of empirical bioconcentration factors (BCFs). The model is subsequently applied to a set of perfluoroalkyl acids. Key aspects of model development include revised methods to estimate the chemical absorption efficiency of IOCs at the respiratory surface (E(W) ) and the use of distribution ratios to characterize the overall sorption capacity of the organism. Membrane-water distribution ratios (D(MW) ) are used to characterize sorption to phospholipids instead of only considering the octanol-water distribution ratio (D(OW) ). Modeled BCFs are well correlated with the observations (e.g., r(2)  = 0.68 and 0.75 for organic acids and bases, respectively) and accurate to within a factor of three on average. Model prediction errors appear to be largely the result of uncertainties in the biotransformation rate constant (k(M) ) estimates and the generic approaches for estimating sorption capacity (e.g., D(MW) ). Model performance for the set of perfluoroalkyl acids considered is highly dependent on the input parameters describing hydrophobicity (i.e., log K(OW) of the neutral form). The model applications broadly support the hypothesis that phospholipids contribute substantially to the sorption capacity of fish, particularly for compounds that exhibit a high degree of ionization at biologically relevant pH. Additional empirical data on biotransformation and sorption to phospholipids and subsequent incorporation into property estimation approaches (e.g., k(M) , D(MW) ) are priorities with respect to improving model performance. 23220644 Optimization of 5-hydroxytryptamines as dual function inhibitors targeting phospholipase A2 and leukotriene A4 hydrolase. Dual function inhibitors targeting phospholipase A(2) (PLA(2)) and leukotriene A(4) hydrolase (LTA(4)H) may balance the arachidonic acid (AA) metabolic network and be used as new anti-inflammatory drugs. In previous study, we discovered multi-target drugs towards the AA metabolic network, among which a dual-target inhibitor (JMC08-4) for human nonpancreatic secretory phospholipase A(2) (hnps-PLA(2)) and human leukotriene A(4) hydrolase (LTA(4)H-h) was found. Based on the structure of compound JMC08-4, new dual-target inhibitors were designed assisted by molecular docking. In this report, a series of 5-hydroxytryptamine compounds were synthesized; and most of these title compounds showed more potent inhibitory activity than compound JMC08-4 in the in vitro bioassay against these two enzymes. The best one inhibited hnps-PLA(2) and LTA(4)H-h with IC(50) values of 9.2 ± 0.5 μM and 2.4 ± 1.4 μM, respectively. 23534827 Generalized structural description of calcium-sodium aluminosilicate hydrate gels: the cross-linked substituted tobermorite model. Structural models for the primary strength and durability-giving reaction product in modern cements, a calcium (alumino)silicate hydrate gel, have previously been based solely on non-cross-linked tobermorite structures. However, recent experimental studies of laboratory-synthesized and alkali-activated slag (AAS) binders have indicated that the calcium-sodium aluminosilicate hydrate [C-(N)-A-S-H] gel formed in these systems can be significantly cross-linked. Here, we propose a model that describes the C-(N)-A-S-H gel as a mixture of cross-linked and non-cross-linked tobermorite-based structures (the cross-linked substituted tobermorite model, CSTM), which can more appropriately describe the spectroscopic and density information available for this material. Analysis of the phase assemblage and Al coordination environments of AAS binders shows that it is not possible to fully account for the chemistry of AAS by use of the assumption that all of the tetrahedral Al is present in a tobermorite-type C-(N)-A-S-H gel, due to the structural constraints of the gel. Application of the CSTM can for the first time reconcile this information, indicating the presence of an additional activation product that contains highly connected four-coordinated silicate and aluminate species. The CSTM therefore provides a more advanced description of the chemistry and structure of calcium-sodium aluminosilicate gel structures than that previously established in the literature. 23149927 Longitudinal cystic fibrosis care. Cystic fibrosis is a complex disease entity that presents considerable lifelong challenges. Implementation of medical and surgical treatment options involves multisystem interventions to prevent and treat lung and gastrointestinal manifestations of cystic fibrosis and associated comorbidities. From birth through adulthood, cystic fibrosis care entails a longitudinal regimen aimed at achieving relief of disease symptoms and enhanced life expectancy. With increased knowledge of the molecular behavior of the cystic fibrosis transmembrane conductance regulator (CFTR) in health and disease, clinical practice has been enriched by the prospect of novel strategies, including mutation-specific drug and gene therapy targeting restoration of corrupted transepithelial ion transport. Emerging paradigms of comprehensive care increasingly enable personalized solutions to address the root cause of disease-transforming management options for individuals with cystic fibrosis. 23552830 Characterization and Expression of the Gene Encoding En-MAPK1, an Intestinal Cell Kinase (ICK)-like Kinase Activated by the Autocrine Pheromone-Signaling Loop in the Polar Ciliate, Euplotes nobilii. In the protozoan ciliate Euplotes, a transduction pathway resulting in a mitogenic cell growth response is activated by autocrine receptor binding of cell type-specific, water-borne signaling protein pheromones. In Euplotes raikovi, a marine species of temperate waters, this transduction pathway was previously shown to involve the phosphorylation of a nuclear protein kinase structurally similar to the intestinal-cell and male germ cell-associated kinases described in mammals. In E. nobilii, which is phylogenetically closely related to E. raikovi but inhabits Antarctic and Arctic waters, we have now characterized a gene encoding a structurally homologous kinase. The expression of this gene requires +1 translational frameshifting and a process of intron splicing for the production of the active protein, designated En-MAPK1, which contains amino acid substitutions of potential significance for cold-adaptation. 23583168 Mechanisms and Metabolic Implications of Regional Differences among Fat Depots. Fat distribution is closely linked to metabolic disease risk. Distribution varies with sex, genetic background, disease state, certain drugs and hormones, development, and aging. Preadipocyte replication and differentiation, developmental gene expression, susceptibility to apoptosis and cellular senescence, vascularity, inflammatory cell infiltration, and adipokine secretion vary among depots, as do fatty-acid handling and mechanisms of enlargement with positive-energy and loss with negative-energy balance. How interdepot differences in these molecular, cellular, and pathophysiological properties are related is incompletely understood. Whether fat redistribution causes metabolic disease or whether it is a marker of underlying processes that are primarily responsible is an open question. 23401262 Effects of Lepidium sativum, Nigella sativa and Trigonella foenum-graceum on Phenytoin Pharmacokinetics in Beagle Dogs. The present work was designed to evaluate the effect of some commonly used herbs viz. garden cress (Lepidium sativum), black seed (Nigella sativa) and fenugreek (Trigonella foenum-graceum) on the disposition of phenytoin after oral administration in a dog model. Phenytoin was given orally at a dose of 50 mg, and blood samples were obtained for the determination of drug's pharmacokinetic parameters. After a suitable washout period, animals were commenced on a specific herb treatment for one week. Garden cress treatment caused a modest increase in maximum observed concentration (C(max) ) and terminal half-life (T(1/2λ) ) of phenytoin with a reduction in clearance by 33%. The effect of black seed therapy was more drastic on drug elimination and to a lesser extent on its volume of distribution at steady state (V(ss) ) with a consequent reduction in systemic exposure measured by area under the curve (AUC(0-∞) ) by about 87%. The effect of fenugreek therapy resembled, albeit to a lesser extent, that of black seed with a significant reduction in AUC(0-∞) by ~72%. In addition, there was a 73% increase in V(ss) . Our findings suggest that the phenytoin disposition can be significantly altered by the concurrent consumption of tested herbal products. Copyright © 2013 John Wiley & Sons, Ltd. 23477419 Design, Synthesis, and Pharmacological Characterization of Novel Endomorphin-1 Analogues as Extremely Potent μ-Opioid Agonists. Recently we reported the synthesis and structure-activity study of endomorphin-1 (EM-1) analogues containing novel, unnatural α-methylene-β-aminopropanoic acids (Map). In the present study, we describe new EM-1 analogues containing Dmt(1), (R/S)-βPro(2), and (ph)Map(4)/(2-furyl)Map(4). All of the analogues showed a high affinity for the μ-opioid receptor (MOR) and increased stability in mouse brain homogenates. Of the new compounds, Dmt(1)-(R)-βPro(2)-Trp(3)-(2-furyl)Map(4) (analogue 12) displayed the highest affinity toward MOR, in the picomolar range (Ki(μ) = 3.72 pM). Forskolin-induced cAMP accumulation assays indicated that this analogue displayed an extremely high agonistic potency, in the subpicomolar range (EC50 = 0.0421 pM, Emax = 99.5%). This compound also displayed stronger in vivo antinociceptive activity after iv administration when compared to morphine in the tail-flick test, which indicates that this analogue was able to cross the blood-brain barrier. 22804459 Antioxidant activity of Buglossoides purpureocaerulea (L.) I.M. Johnst. extracts. Buglossoides purpureocaerulea is a little-known plant used in the folk tradition for the preparation of a decoction in Sud, Italy, where it is appreciated for its beneficial effects on liver diseases. These properties may be due to the presence of antioxidant compounds. This study presents the phenolic characterisation and the antioxidant activity (AA) of B. purpureocaerulea extracts obtained by decoction, ethanol infusion and ethanol and methanol macerations. Total phenols ranged between 69 and 100 mg g(-1 ) dry weight (DW). The main compounds were: rosmarinic acid, caffeic acid, lithospermic acid and salvianolic acid C. The extracts showed a good AA, particularly high for the decoction (142-283 µmol TE g(-1) DW; TE, Trolox equivalent) and ethanol maceration extract (214-364 µmol TE g(-1) DW) when determined by DPPH and ferric reducing antioxidant power test, respectively. 22923473 Liver glycogen loading dampens glycogen synthesis seen in response to either hyperinsulinemia or intraportal glucose infusion. The purpose of this study was to determine the effect of liver glycogen loading on net hepatic glycogen synthesis during hyperinsulinemia or hepatic portal vein glucose infusion in vivo. Liver glycogen levels were supercompensated (SCGly) in two groups (using intraportal fructose infusion) but not in two others (Gly) during hyperglycemic-normoinsulinemia. Following a 2-h control period during which fructose infusion was stopped, there was a 2-h experimental period in which the response to hyperglycemia plus either 4× basal insulin (INS) or portal vein glucose infusion (PoG) was measured. Increased hepatic glycogen reduced the percent of glucose taken up by the liver that was deposited in glycogen (74 ± 3 vs. 53 ± 5% in Gly+INS and SCGly+INS, respectively, and 72 ± 3 vs. 50 ± 6% in Gly+PoG and SCGly+PoG, respectively). The reduction in liver glycogen synthesis in SCGly+INS was accompanied by a decrease in both insulin signaling and an increase in AMPK activation, whereas only the latter was observed in SCGly+PoG. These data indicate that liver glycogen loading impairs glycogen synthesis regardless of the signal used to stimulate it. 23311296 Characterization of bundled and individual triple-walled carbon nanotubes by resonant Raman spectroscopy. The optical characterization of bundled and individual triple-walled carbon nanotubes was studied for the first time in detail by using resonant Raman spectroscopy. In our approach, the outer tube of a triple-walled carbon nanotube system protects the two inner tubes (or equivalently the inner double-walled carbon nanotube) from external environment interactions making them a partially isolated system. Following the spectral changes and line-widths of the radial breathing modes and G-band by performing laser energy dependent Raman spectroscopy, it is possible to extract important information as regards to the electronic and vibrational properties, tube diameters, wall-to-wall distances, radial breathing mode, and G-band resonance evolutions as well as high-curvature intertube interactions in isolated double- and triple-walled carbon nanotube systems. 22080034 Nanosilver effects on growth parameters in experimental aflatoxicosis in broiler chickens. Aflatoxicosis is a cause of economic losses in broiler production. In this study, the effect of one commercial nanocompound, Nanocid (Nano Nasb Pars Co., Iran) was evaluated in reduction of aflatoxin effects on the growth and performance indices in broiler chickens suffering from experimental aflatoxicosis. For this, a total of 300 one-day-old broiler chicks (Ross strain) were randomly divided into 4 groups with 3 replicates of 15 chicks in each separated pen during the 28-day experiment. Treatment groups including group A: chickens fed basal diet, group B: chickens fed 3 ppm productive aflatoxin in basal diet, group C: chickens fed basal diet plus 2500 ppm Nanocid, and group D: chickens fed 3 ppm productive aflatoxin and 2500 ppm Nanocid, in basal diet. Data on body weight, body weight gain (BWG), feed intake, and feed conversion ratio (FCR) were recorded at weekly intervals. Also cumulative data were assessed. Results showed, although supplement of Nanocid to conventional diet had no effect on performance but addition of Nanocid to diet containing 3 ppm aflatoxin increased significantly the cumulative BWG, cumulative feed consumption and decreased FCR in the last 2 weeks of experimental period. The improvement in these performance indices by supplement of Nanocid to diet containing aflatoxin showed the ability of Nanocid to diminish the inhibitory effects of aflatoxin. 23636886 Statistical optimization of a multivariate fermentation process for enhancing antibiotic activity of Streptomyces sp. CS392. Antibiotic activity against various gram positive bacteria including Staphylococcus aureus and Enterococcus was ascertained from a soil-isolated microbial strain Streptomyces sp. CS392. The antibiotic activity of the strain was maximized by using a dual-stage, multivariate statistical optimization framework based on the response surface methodology considering a lab-scale fermentation process. Multiple nutrient constituents of the fermentation broth were jointly optimized in the first stage, while the fermentation culture conditions were optimized in the subsequent stage. Based on the empirical models derived from the dual-stage statistical optimization framework, 39.79 % of cumulative enhancement in the antibiotic activity was obtained (analytically) at the concurrent optimal settings (Optimal nutrient composition for the first stage of optimization: 29.82 glucose, 7.6 peptone, 4.678 MgCl2 and 0.5005 g/l casamino acid; and optimal fermentation condition for the second stage of optimization: incubation period 47.55 h; incubation temperature 29.15 °C; and pH 8.36). The analytically depicted enhancement in the antibiotic activity was validated experimentally. 23044489 Ketamine combinations for the field treatment of soman-induced self-sustaining status epilepticus. Review of current data and perspectives. Organophosphorus nerve agents (NA), potent irreversible cholinesterase inhibitors, could induce severe seizures, status epilepticus (SE), seizure-related brain damage (SRBD) and lethality. Despite the lack of data in the case of NA, clinical evidences suggest that SE survivors could suffer from neurological/cognitive deficits and impairments such as spontaneous recurrent seizures (epilepsy) after a latent period of epileptogenesis. It is beyond doubt that an effective and quick management of the initial seizures and prevention of SRBD are critical to prevent these long-term consequences, explaining why most experimental data are focusing on the 5-40min post-exposure time frame. However, in field conditions, treatment may be delayed and with the exception of NMDA receptor antagonists, currently no drug provides protection (against lethality, seizures, SRBD and neurological consequences) when seizures are left unabated for one hour or more. Ketamine (KET) is the only NMDA antagonist licensed as an injectable drug in different countries and remains an anesthetic of choice in some difficult field conditions. In this short review paper, after a presentation of some of the key points of the pathophysiology of NA-induced SE and a quick survey of the potential therapeutic avenues in the context of delayed treatment of NA-induced SE, we will review the recent data we obtained showing that KET, in combination with atropine sulfate (AS), with or without a benzodiazepine, considerably reduces soman-induced neuroinflammation, provides neuroprotection, histologically and functionally, and also positively modify soman-induced changes in brain metabolism. Finally, we will also mention some results from safety studies including those bringing evidence that, at difference with MK-801, KET does not impair thermoregulation and even seems to reduce AS-induced heat stress. All in all, KET, in combination, appears a good candidate for the out-of-hospital treatment of severe NA-induced SE. 23296105 Inhalation of uranium nanoparticles: respiratory tract deposition and translocation to secondary target organs in rats. Uranium nanoparticles (<100 nm) can be released into the atmosphere during industrial stages of the nuclear fuel cycle and during remediation and decommissioning of nuclear facilities. Explosions and fires in nuclear reactors and the use of ammunition containing depleted uranium can also produce such aerosols. The risk of accidental inhalation of uranium nanoparticles by nuclear workers, military personnel or civilian populations must therefore be taken into account. In order to address this issue, the absorption rate of inhaled uranium nanoparticles needs to be characterised experimentally. For this purpose, rats were exposed to an aerosol containing 10⁷ particles of uranium per cm³ (CMD=38 nm) for 1h in a nose-only inhalation exposure system. Uranium concentrations deposited in the respiratory tract, blood, brain, skeleton and kidneys were determined by ICP-MS. Twenty-seven percent of the inhaled mass of uranium nanoparticles was deposited in the respiratory tract. One-fifth of UO₂ nanoparticles were rapidly cleared from lung (T(½)=2.4 h) and translocated to extrathoracic organs. However, the majority of the particles were cleared slowly (T(½)=141.5 d). Future long-term experimental studies concerning uranium nanoparticles should focus on the potential lung toxicity of the large fraction of particles cleared slowly from the respiratory tract after inhalation exposure. 23494233 Effects of nitric oxide synthase inhibition in the dorsolateral periaqueductal gray matter on ethanol withdrawal-induced anxiety-like behavior in rats. RATIONALE: Nitric oxide (NO)-mediated transmission in the dorsolateral periaqueductal gray matter (dlPAG) has been involved in the expression of anxiety-like behaviors. Ethanol withdrawal sensitizes the dlPAG and results in increased anxiety-like responses. OBJECTIVES: The objective of the study was to test the hypothesis that NO in the dlPAG is involved in the expression of ethanol withdrawal-induced anxiety. METHODS: Male Wistar rats were implanted with guide cannulae aimed at the dlPAG. The animals were forced to consume a liquid diet containing ethanol 6-8 % (v/v) for 15 days as their only source of diet. Six days after surgery and 24 h after ethanol discontinuation, the animals received microinjections of the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), nonselective nitric oxide synthase inhibitor N (G)-nitro-L-arginine methyl ester (L-NAME), selective neuronal nitric oxide synthase inhibitor 1-(2-[trifluoromethyl]phenyl) imidazole (TRIM), or selective inducible nitric oxide synthase (iNOS) inhibitor N-([3-(aminomethyl)phenyl]methyl) ethanimidamide dihydrochloride (1400W) into the dlPAG. Ten minutes later, the animals were tested in the light/dark box. RESULTS: Carboxy-PTIO (1 nmol), L-NAME (200 nmol), TRIM (20 nmol), and 1400W (0.3 and 1 nmol) decreased the anxiogenic-like effects of ethanol withdrawal in rats in the light/dark box test. The NO precursor L-arginine reversed the effects of L-NAME. CONCLUSIONS: NO production in the dlPAG may play a role in the modulation of ethanol withdrawal-induced anxiety-like behavior in rats. Furthermore, iNOS-mediated NO synthesis in the dlPAG is predominantly involved in the behavioral expression of anxiety-like behavior during ethanol withdrawal. 23590892 Docosahexaenoic acid (DHA) ameliorates paraquat-induced pulmonary fibrosis in rats possibly through up-regulation of Smad 7 and SnoN. Paraquat (PQ) poisoning has caused a large number of human fatalities due to the progressive and irreversible pulmonary fibrosis. Docosahexaenoic acid (DHA) is well-recognized as important modulators of multiple biological pathways that affect health and disease. A line of studies have shown that DHA supplementation is associated with the alleviation of some tissue fibrosis. In the current study, pulmonary fibrosis of rats was produced by a single oral dose of 50mg/kgbw PQ treatment. Daily 500mg/kgbw DHA supplementation was provided 7days before PQ treatment and lasted for consecutive 35days. DHA was found to ameliorate the pulmonary fibrotic alterations induced by PQ, which was evidenced by significant reduction of histological changes, hydroxyproline content and level of the transforming growth factor-β1 (TGF-β1) mRNA. Furthermore, the protein levels of Smad 7 and SnoN in the DHA supplemented rats were significantly increased compared with those in the rats of the PQ group. These results suggested that DHA ameliorated pulmonary fibrosis induced by PQ might be attributed to its enhancement of Smad 7 and SnoN expression. 23541646 Glycyrrhetinic acid and its analogs: A new class of antifilarial agents. Although a number of chemicals have been isolated from Glycyrrhiza glabra, only a few have been evaluated for their biological significance. As part of our drug discovery program for antifilarial agents from Indian medicinal plants, the roots of G. glabra were chemically investigated, which resulted in the isolation and characterization of an antifilarial agent, glycyrrhetinic acid (GA, 1a) effective against microfilariae (mf) in vitro (LC100: 12.5μM; IC50: 1.20μM), but was inactive against adult worms. Further, GA (1a) was converted into six analogs (2a-7a) and their antifilarial potential was evaluated by studying in vitro motility and MTT reduction assays employing mf and adult worms of Brugia malayi. The results showed that out of six GA analogs, the benzyl amide analog (6a) killed adults and mf at 25 and 50μM concentration, respectively, and inhibited 49% MTT reduction potential of the adult parasites. The IC50 values were found to be 8.8 and 2.2μM for adults and mf, respectively. The SI of the compound was >60. On the other hand the octylamide analog (7a) required much higher concentration to adversely affect the parasites. Finally, both active amide analogs (6a and 7a) were in vivo evaluated using B. malayi-jird model, which showed that analog 6a possesses promising macrofilaricidal activity at 100mg/kg, s.c. ×5days and around 40% of the treated animals showed calcified masses of worm fragments in peritoneal cavity of the animals. To the best of our knowledge this is the first ever report on the antifilarial potential of GA analogs. Further work on optimization of the antifilarial lead is under progress. 23627605 How Graphene Slides: Measurement and Theory of Strain-Dependent Frictional Forces between Graphene and SiO2. Strain, bending rigidity, and adhesion are interwoven in determining how graphene responds when pulled across a substrate. Using Raman spectroscopy of circular, graphene-sealed microchambers under variable external pressure, we demonstrate that graphene is not firmly anchored to the substrate when pulled. Instead, as the suspended graphene is pushed into the chamber under pressure, the supported graphene outside the microchamber is stretched and slides, pulling in an annulus. Analyzing Raman G band line scans with a continuum model extended to include sliding, we extract the pressure dependent sliding friction between the SiO2 substrate and mono-, bi-, and trilayer graphene. The sliding friction for trilayer graphene is directly proportional to the applied load, but the friction for monolayer and bilayer graphene is inversely proportional to the strain in the graphene, which is in violation of Amontons' law. We attribute this behavior to the high surface conformation enabled by the low bending rigidity and strong adhesion of few layer graphene. 22972396 Luminescent neutral platinum complexes bearing an asymmetric N(^) N(^) N ligand for high-performance solution-processed OLEDs. The synthesis and full characterization of new platinum complexes bearing a bulky asymmetric dianionic tridentate ligand is reported. The hindrance of the ligand prevents detrimental intermolecular interactions yielding to highly emitting species in both crystalline state and thin-film. Such properties prompted their successful use in solution-processed OLEDs, showing remarkable external quantum efficiency up to 5.6%. 23422872 Balancing societal needs and regulatory certainty: the case study of peramivir in Japan. Regulators must balance societal and medical requirements against the need for certainty about benefit and risk for new medicines. This is described in a case study of the expedited review and approval of peramivir, a novel neuraminidase inhibitor, in Japan in the context of the emergence of new strain of influenza in 2009. The case illustrates the importance of regulatory science and transparency in supporting such decision making. 23410171 Design of multifunctional compounds for cardiovascular disease: from natural scaffolds to "classical" multitarget approach. Cardiovascular disease represents the main cause of death worldwide. Novel therapies to reduce elevated blood pressure and treat resistant hypertension, to consequently reduce the associated cardiovascular risk factors, are still required. Among the different strategies commonly used in medicinal chemistry to develop new molecules, the synthesis of multitarget/hybrid compounds combining two or more pharmacophore groups targeting simultaneously selected factors involved in cardiovascular diseases, has gained increasing interest. This review will focus on the most recent literature on multifunctional cardiovascular drugs, paying particular attention on hybrid compounds bearing natural scaffolds, considering that compounds derived from medicinal extracts are generally appealing for the medicinal chemist as they often bear the so-called "privileged structures". Moreover, taking into account many excellent reviews dealing with multitarget cardiovascular drugs published in the last few years, mainly devoted to RAAS inhibition and/or NO donors hybrid drugs, herein the most significant results obtained and the benefits and limitations of these approaches will be highlighted. 23373965 Discovery of a potential anti-inflammatory agent: 3-oxo-29-noroleana-1,9(11),12-trien-2,20-dicarbonitrile. Fifteen novel derivatives of glycyrrhetinic acid (GA) were synthesized and evaluated for anti-inflammatory activities. It was found that the introduction of 1-en-3-one and 9(11),12-diene and 2,20-dinitrile functionalities into the scaffold of GA led to the discovery of potent compound 19 for inhibition of LPS-induced NO production. Furthermore, 19 effectively inhibited the protein and mRNA expression of inducible NO synthase (iNOS) and the mRNA expression of TNF-α, IL-6, and IL-1β in LPS-stimulated RAW 264.7 macrophages. Mechanistically, 19 exerted inhibitory effects on the activation of the three main MAPKs and phosphorylation and degradation of IκB-α, as well as the ratio of nuclear/cytosolic content of p65. Importantly, 19 significantly decreased the mortality rate in the mouse model of LPS-induced sepsis shock. It is noteworthy that inhibitory effect of 19 on NO production was not blocked by the glucocorticoid receptor antagonist mifepristone, indicating that it does not act through the glucocorticoid receptor. 23401470 From spots to beads-PTM-peptide bead arrays for the characterization of anti-histone antibodies. Antibodies that recognize PTMs of histones play a central role in epigenetic proteomic research. Modification-specific antibodies are employed in chromatin immunoprecipitation, for Western blotting and during the immunoprecipitation steps for MS-based global proteomic analyses. Knowledge about the antibodies' off-target binding is essential for the interpretation of experimental data. To address this challenge we developed a fast and cost efficient system for generating peptide bead arrays. We employed this method to establish a bead-based peptide array containing 384 peptides displaying phosphorylated, acetylated, methylated, and citrullinated N-terminal regions of histones H2A, H2B, H3 and H4 and controls. We profiled the binding of 40 PTM-specific antibodies important for epigenetic proteomic research. 23620256 Study of endothelial cell apoptosis using fluorescence resonance energy transfer (FRET) biosensor cell line with hemodynamic microfluidic chip system. To better understand how hyperglycemia induces endothelial cell dysfunction under the diabetic conditions, a hemodynamic microfluidic chip system was developed. The system combines a caspase-3-based fluorescence resonance energy transfer (FRET) biosensor cell line which can detect endothelial cell apoptosis in real-time, post-treatment effect and with a limited cell sample, by using a microfluidic chip which can mimic the physiological pulsatile flow profile in the blood vessel. The caspase-3-based FRET biosensor endothelial cell line (HUVEC-C3) can produce a FRET-based sensor protein capable of probing caspase-3 activation. When the endothelial cells undergo apoptosis, the color of the sensor cells changes from green to blue, thus sensing apoptosis. A double-labeling fluorescent technique (yo pro-1 and propidium iodide) was used to validate the findings revealed by the FRET-based caspase sensor. The results show high rates of apoptosis and necrosis of endothelial cells when high glucose concentration was applied in our hemodynamic microfluidic chip combined with an exhaustive pulsatile flow profile. The two apoptosis detection techniques (fluorescent method and FRET biosensor) are comparable; but FRET biosensor offers more advantages such as real-time observation and a convenient operating process to generate more accurate and reliable data. Furthermore, the activation of the FRET biosensor also confirms the endothelial cell apoptosis induced by the abnormal pulsatile shear stress and high glucose concentration is through caspase-3 pathway. A 12% apoptotic rate (nearly a 4-fold increase compared to the static condition) was observed when the endothelial cells were exposed to a high glucose concentration of 20 mM under 2 h exhaustive pulsatile shear stress of 30 dyne cm(-2) and followed with another 10 h normal pulsatile shear stress of 15 dyne cm(-2). Therefore, the most important finding of this study is to develop a novel endothelial cell apoptosis detection method, which combines the microfluidic chip system and FRET biosensor. This finding may provide new insight into how glucose causes endothelial cell dysfunction, which is the major cause of diabetes-derived complications. 23396223 Protein carbonylation in human endothelial cells exposed to cigarette smoke extract. Cigarette smoke is a significant independent risk factor for vascular diseases and is a leading cause of structural and functional alterations of the vascular endothelium. In this study, we show protein carbonylation in the human umbilical vein endothelial cell line (ECV-304) exposed to whole-phase cigarette smoke extract. The main carbonylated proteins, including cytoskeletal proteins, glycolytic enzymes, xenobiotic metabolizing and antioxidant enzymes, and endoplasmic reticulum proteins, were identified by means of two-dimensional electrophoresis and Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) mass spectrometry (redox proteomics). Morphological analyses by fluorescence microscopy evidenced alterations in the microtubule cytoskeleton, especially at longer exposure time to cigarette smoke extract. Morphological analyses by transmission electron microscopy showed vacuolisation of the cytoplasm, alteration of mitochondria ultrastructure, and some enlargement of the perinuclear space. The possible role played by protein carbonylation caused by reactive species contained in cigarette smoke in the cigarette smoke-induced endothelial injury is discussed. 23348152 Disubstituted diaryl diselenides as potential atheroprotective compounds: Involvement of TrxR and GPx-like systems. Oxidative modifications of low-density lipoproteins (LDLs) have a determinant role in atherogenesis and the study of agents that can modulate LDL oxidation is of pharmacological and therapeutic significance. Therefore, the aim of this study was to evaluate the antioxidant effect of the disubstituted diaryl diselenides, p-methoxyl-diphenyl diselenide (p-CH(3)O-C(6)H(4)Se)(2) (DM) and p-chloro-diphenyl diselenide (p-Cl-C(6)H(4)Se)(2) (DC), on Cu(2+)-induced LDL oxidation. Both compounds caused a dose-dependent inhibition of human serum and isolated LDL oxidation evidenced by the increasing of the lag phase of lipid peroxidation and decreased the lipid oxidation rate (V(max)). The protein moieties from isolated LDL were also protected from Cu(2+)-induced oxidation. Moreover, the disubstituted diaryl diselenides efficiently decreased the oxidized LDL (ox-LDL) induced foam cell formation in J774A.1 macrophage cells. Mechanistically, we have demonstrated that the antioxidant and antiatherogenic effects of DM and DC are related to formation of their selenol intermediates (RSeH) either by a direct reaction with endogenous thiols (GPx-like activity) or via their reduction by TrxR (using NADPH as electron donor). Considering the powerful effect of DM and DC against LDL-induced toxicity, they could be considered for developing of new therapeutic approaches to preventing and treating atherosclerosis and cardiovascular diseases. 23535320 Potent naphthoquinones against antimony-sensitive and -resistant Leishmania parasites: Synthesis of novel α- and nor-α-lapachone-based 1,2,3-triazoles by copper-catalyzed azide-alkyne cycloaddition. Continuing our screening program for novel anti-parasite compounds, we synthesized seven 1,4-naphthoquinones coupled to 1,2,3-triazoles, five nor-β-lapachone-based 1,2,3-triazoles and ten α-lapachone-based 1,2,3-triazoles. These and other naphthoquinonoid compounds were evaluated for their activity against promastigote forms of antimony-sensitive and -resistant strains of Leishmania infantum (syn. Leishmania chagasi) and Leishmania amazonensis. The toxicity of these compounds to mammalian cells was also examined. The substances were more potent than an antimonial drug, with IC50 values ranging from 1.0 to 50.7 μM. Nor-α-lapachone derivatives showed the highest antileishmanial activity, with selectivity indices in the range of 10-15. These compounds emerged as important leads for further investigation as antileishmanial agents. Additionally, one of these compounds exhibited cross-resistance in Sb-resistant Leishmania and could provide a molecular tool for investigating the multidrug resistance mechanisms in Leishmania parasites. 23357628 Design and synthesis of dimethylaminomethyl-substituted curcumin derivatives/analogues: potent antitumor and antioxidant activity, improved stability and aqueous solubility compared with curcumin. A series of dimethylaminomethyl-substituted curcumin derivatives/analogues were designed and synthesized. All compounds effectively inhibited HepG2, SGC-7901, A549 and HCT-116 tumor cell lines proliferation in MTT assay. Particularly, compounds 2a and 3d showed much better activity than curcumin against all of the four tumor cell lines. Antioxidant test revealed that these compounds had higher free radical scavenging activity than curcumin towards both DPPH and galvinoxyl radicals. Furthermore, the aqueous solubility and stability of the target compounds were also significantly improved compared with curcumin. 23259985 Bioreducible polymers as a determining factor for polyplex decomplexation rate and transfection. Polyplex formation (complexation) and gene release from the polyplexes (decomplexation) are major events in polymeric gene delivery; however, the effect of the decomplexation rate on transfection has been rarely investigated. This study employed mixed polymers of poly((L)-lysine) (PLL: MW ~7.4 kDa) and reducible PLL (RPLL) (MW ~6.7 kDa) to design decomplexation rate-controllable PLL(100-x)RPLL(x)/pDNA complexes (PRL(x) polyplexes). The transfection efficiency of a model gene (luciferase) in MCF7 and HEK293 cell lines increased with increasing x (RPLL content) in the PRL(x) polyplexes until peaking at x = 2.5 and 10, respectively, after which point transfection efficiency declined rapidly. In MCF7 cells, PRL(2.5) polyplex produced 3 or 223 times higher gene expression than PLL or RPLL polyplexes, respectively. Similarly, the transfection efficiency of PRL(10) polyplex-transfected HEK293 cells was 3.8 or 67 times higher than that of PLL or RPLL polyplexes, respectively. The transfection results were not apparently related to the particle size, surface charge, complexation/compactness, cellular uptake, or cytotoxicity of the tested polyplexes. However, the decomplexation rate varied by RPLL content in the polyplexes, which in turn influenced the gene transfection. The nuclear localization of pDNA delivered by PRL(x) polyplexes showed a similar trend to their transfection efficiencies. This study suggests that an optimum decomplexation rate may result in high nuclear localization of pDNA and transfection. Understanding in decomplexation and intracellular localization of pDNA may help develop more effective polyplexes. 23603381 Ellagic acid attenuates bleomycin and cyclophosphamide-induced pulmonary toxicity in Wistar rats. Use of bleomycin (BLM) and cyclophosphamide (CP) as chemotherapeutic drugs is associated with side effects including toxicity to respiratory system. Their co-administration may enhance lung toxicity which may subsequently progress to the lung fibrosis. Natural compounds have shown mitigating effects against toxicity of anticancer drugs. Ellagic acid (EA), a polyphenolic compound present in many fruits and nuts in addition to walnut has shown promising protective effect against toxicity of drugs and chemicals. We studied the ameliorative effect of EA on lung toxicity in rats exposed to CP (150mg/kgb.w., i.p.) and BLM (10U/kgb.w., i.t.). EA (15mg/kgb.w., p.o.×14days) treatment modulated enhanced hydroxyproline level, lipid peroxidation, myeloperoxidase activity, nitric oxide production and protein carbonyl formation in lungs of rats exposed to toxic anticancer drugs. There was a marked decrease in GSH content and activities of antioxidant enzymes as a result of BLM and CP treatment. Bronchoalveolar lavage fluid showed increased level of cytotoxicity markers in drug treated animals. Treatment with EA attenuated these changes. Histopathological findings also showed protective effects of EA. In conclusion, EA emerged as a natural protectant with an ability to protect lungs from onslaught of pulmonary toxicity of anticancer drugs. 23298322 Timed-release polymer nanoparticles. Triggered-release of encapsulated therapeutics from nanoparticles without remote or environmental triggers was demonstrated in this work. Disassembly of the polymer nanoparticles to unimers at precise times allowed the controlled release of oligo DNA. The polymers used in this study consisted of a hydrophilic block for stabilization and second thermoresponsive block for self-assembly and disassembly. At temperatures below the second block's LCST (i.e., below 37 °C for in vitro assays), the diblock copolymer was fully water-soluble, and when heated to 37 °C, the polymer self-assembled into a narrow size distribution of nanoparticles with an average diameter of approximately 25 nm. The thermoresponsive nature of the second block could be manipulated in situ by the self-catalyzed degradation of cationic 2-(dimethylamino)ethyl acrylate (DMAEA) units to negatively charged acrylic acid groups and when the amount of acid groups was sufficiently high to increase the LCST of the second block above 37 °C. The disassembly of the nanoparticles could be controlled from 10 to 70 h. The use of these nanoparticles as a combined therapy, in which one or more agents can be released in a predetermined way, has the potential to improve the personal point of care treatment of patients. 23581965 Enhanced Hematite Water Electrolysis Using a 3D Antimony-Doped Tin Oxide Electrode. We present herein an example of nanocrystalline antimony-doped tin oxide (nc-ATO) disordered macroporous "inverse opal" 3D electrodes as efficient charge-collecting support structures for the electrolysis of water using a hematite surface catalyst. The 3D macroporous structures were created via templating of polystyrene spheres, followed by infiltration of the desired precursor solution and annealing at high temperature. Using cyclic voltammetry and electrochemical impedance spectroscopy, it was determined that the use of this 3D transparent conducting oxide with a hematite surface catalyst allowed for a seven-fold increase in active surface area for water splitting with respect to its 2D planar counterpart. This ratio of surface areas was evaluated based on the presence of oxidized trap states on the hematite surface, as determined from the equivalent circuit analysis of the Nyquist plots. Furthermore, the presence of nc-ATO 2D and 3D "underlayer" structures with hematite deposited on top resulted in decreased charge transfer resistances and an increase in the number of available active surface sites at the semiconductor-liquid junction when compared to hematite films lacking any nc-ATO substructures. Finally, absorption, transmission and reflectance spectra of all of the tested films were measured, suggesting the feasibility of using 3D disordered structures in photoelectrochemical reactions, due to the high absorption of photons by the surface catalyst material and trapping of light within the structure. 23275113 Toward a detailed characterization of oil adsorbates as "solid liquids". Solid lipid formulation systems are used to overcome oral bioavailability problems of poorly water-soluble drugs. One promising process is the conversion of a liquid lipid system in a free flowing powder by use of adsorbing excipients. The aim of this study was the detailed characterization of solid-liquid interactions in oil adsorbed to Fujicalin® and Neusilin® which were manufactured by means of dual asymmetric centrifugation or conventional mortar/pestle blending. The adsorption strength of the excipients was investigated by Benchtop-NMR and ESR spectroscopy revealing the highest adsorption power for the Neusilin® products. The adsorbate production methods as well as the storage of the excipients impact their adsorption properties. Environmental scanning electron microscopy (ESEM) and confocal laser scanning microscopy (CLSM) show that dual asymmetric centrifugation leads to a smoothing of the particle surface, whereas the mortar/pestle blending results in an uneven surface and particle destruction. The oil distribution at the particles is inhomogeneous for both production methods. The micropolarity of the adsorbed oil was investigated by ESR spectroscopy and multispectral fluorescence imaging. The adsorbing process on Neusilin® leads to an increased micropolarity of the oil component. The release of the oil component in aqueous media could be verified by Benchtop-NMR and multispectral fluorescence imaging. 23567318 Gene Cloning, Expression and Characterization of a Novel Xylanase from the Marine Bacterium, Glaciecola mesophila KMM241. Marine xylanases are rather less studied compared to terrestrial xylanases. In this study, a new xylanase gene, xynB, was cloned from the marine bacterium, Glaciecola mesophila KMM241, and expressed in Escherichia coli. xynB encodes a multi-domain xylanase XynB of glycoside hydrolase (GH) family 8. The recombinant XynB comprises an N-terminal domain (NTD) with unknown function and a catalytic domain, which is structurally novel among the characterized xylanases of GH family 8. XynB has the highest identity (38%) to rXyn8 among the characterized xylanases. The recombinant XynB showed maximal activity at pH 6-7 and 35 °C. It is thermolabile and salt-tolerant. XynB is an endo-xylanase that demands at least five sugar moieties for effective cleavage and to hydrolyze xylohexaose and xylopentaose into xylotetraose, xylotriose and xylobiose. NTD was expressed in Escherichia coli to analyze its function. The recombinant NTD exhibited a high binding ability to insoluble xylan and avicel and little binding ability to chitosan and chitin. Since the NTD shows no obvious homology to any known carbohydrate-binding module (CBM) sequence in public databases, XynB may contain a new type of CBM. 23230131 Pharmacogenomics of gemcitabine metabolism: functional analysis of genetic variants in cytidine deaminase and deoxycytidine kinase. Gemcitabine (dFdC, 2',2'-difluorodeoxycytidine) is metabolized by cytidine deaminase (CDA) and deoxycytidine kinase (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear. Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates. All three CDA proteins showed similar K(m) and V(max) for Ara-C and dFdC deamination, except for CDA70Thr, which had a 2.5-fold lower K(m) and 6-fold lower V(max) for Ara-C deamination. All four DCK proteins yielded comparable metabolic activity for Ara-C and dFdC monophosphorylation, except for DCK24Val, which demonstrated an approximately 2-fold increase (P < 0.05) in the intrinsic clearance of dFdC monophosphorylation due to a 40% decrease in K(m) (P < 0.05). DCK did not significantly contribute to dFdU monophosphorylation. In conclusion, the Lys27Gln substitution does not significantly modulate CDA activity toward dFdC, and therefore would not contribute to interindividual variability in response to gemcitabine. The higher in vitro catalytic efficiency of DCK24Val toward dFdC monophosphorylation may be relevant to dFdC clinical response. The substrate-dependent alterations in activities of CDA70Thr and DCK24Val in vitro were observed for the first time, and demonstrate that the in vivo consequences of these genetic variations should not be extrapolated from one substrate of these enzymes to another. 23604721 Arginase II inhibitory activity of flavonoid compounds from Scutellaria indica. Arginase II has recently reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. In the course of screening plants used in natural medicines as arginase II inhibitory activity, a methanol extract of Scutellaria indica showed significant inhibitory effect. Further fractionation and repeated column chromatography led to the isolation of a new flavan-type (1), and seven known compounds (2-8). The chemical structures of isolated compounds were elucidated based on extensive 1D and 2D NMR spectroscopic data. The isolates 1-8 were investigated in vitro for their arginase II inhibitory activity using enzyme solution prepared from kidney of anesthetized C57BL/6 mice. Compounds 3 and 5 significantly inhibited arginase II activity with IC50 values of 25.1 and 11.6 μM, respectively, whereas the other compounds were apparently inactive. 23489135 Comparative antimalarial activities and ADME profiles of ozonides (1,2,4-trioxolanes) OZ277, OZ439, and their 1,2-dioxolane, 1,2,4-trioxane, and 1,2,4,5-tetraoxane isosteres. To ascertain the structure-activity relationship of the core 1,2,4-trioxolane substructure of dispiro ozonides OZ277 and OZ439, we compared the antimalarial activities and ADME profiles of the 1,2-dioxolane, 1,2,4-trioxane, and 1,2,4,5-tetraoxane isosteres. Consistent with previous data, both dioxolanes had very weak antimalarial properties. For the OZ277 series, the trioxane isostere had the best ADME profile, but its overall antimalarial efficacy was not superior to that of the trioxolane or tetraoxane isosteres. For the OZ439 series, there was a good correlation between the antimalarial efficacy and ADME profiles in the rank order trioxolane > trioxane > tetraoxane. As we have previously observed for OZ439 versus OZ277, the OZ439 series peroxides had superior exposure and efficacy in mice compared to the corresponding OZ277 series peroxides. 23142753 Dichlorodiphenyltrichloroethane (DDT), DDT metabolites and pregnancy outcomes. Organochlorine pesticides (OCPs) are persistent endocrine disruptors. OCPs cross the placenta; this prenatal exposure has been associated with adverse pregnancy outcomes. We investigated associations between prenatal exposure to OCPs and gestational age and birth weight in 600 infants born between 1960 and 1963. The primary OCP was 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), its primary metabolite, 1,1'-dichloro-2,2'-bis(p-chlorophenyl)ethylene (p,p'-DDE) and the contaminant, 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)-ethane (o,p'-DDT). Regression analysis indicated that for each natural log unit increase in p,p'-DDT, birth weight increased by 274 g (95% CI: 122, 425) when controlling for p,p'-DDE and o,p'-DDT. At a given level of p,p'-DDT exposure, o,p'-DDT and p,p'-DDE were associated with decreased birth weight. p,p'-DDE was negatively associated with length of gestation, controlling for p,p'-DDT and o,p'-DDT. These findings suggest opposing associations between exposure to p,p'-DDT and p,p'-DDE and birth weight. We did not find evidence to support mediation by maternal thyroid hormone status nor that the association differed by sex. 23327494 Anxiogenic-like effects of Uncaria tomentosa (Willd.) DC. aqueous extract in an elevated plus maze test in mice: a preliminary study. The purpose of this study was to examine the effect of orally administered Uncaria tomentosa aqueous extracts (UTE) (Willd. ex Roem. & Schult.) DC. (Rubiaceae) during 7, 15, 30 and 90 days of treatment on the expression of anxiety, as expressed in the elevated plus maze test in male Albino Swiss mice. UTE revealed an anxiogenic effect in relation to the control group at 15 and 30 days, but it was reversed after 90 days of administration, without affecting the locomotor activity or any deleterious effects on the overall performance of the animal, either for its ambulation, or clinical status, and body weight and organ weight/body weight from liver, lung and kidney were unaffected. These biphasic effects are usually indicative of heterogeneity in sites of action due to the presence of many alkaloids (speciophylline, uncarine F and uncarine E) and flavanols (catechin and epigallocatechin) identified and isolated from UTE. 23411178 Simultaneous determination of 2-naphthol and 1-hydroxypyrene in fish and shellfish contaminated with crude oil by gas chromatography-mass spectrometry. This paper describes a gas chromatography-mass spectrometric method of l-hydroxypyrene (1-HOP) and 2-naphthol (2-NAP) in fish and shellfish. Alkali hydrolysis method in this study was chosen and optimized to the reaction condition for 90 min at 90°C in a 2.0M KOH solution. For five independent determinations at 0.2 and 1.0 μg/kg, the coefficient of variation was less than 5.1%. This method was used to assess the long-term influence of spilled crude oil on marine ecosystems and analyze fifty-two shellfish samples taken in the near of the accident region of the Hebei Spirit oil spill. 2-NAP and 1-HOP were detected in the mean concentration range of 0.09-12.42 and 0.03-0.06 μg/kg, respectively. 2-NAP was detected in a high concentration range in shellfishes gathered in 2 months after the accident and it decreased rapidly to 6 months after that. The results showed that 2-NAP might be an important biomarker in biota contaminated with crude oil. 23179765 Natures of benzene-water and pyrrole-water interactions in the forms of σ and π types: theoretical studies from clusters to liquid mixture. A combined and sequential use of quantum mechanical (QM) calculations and classical molecular dynamics (MD) simulations was made to investigate the σ and π types of hydrogen bond (HB) in benzene-water and pyrrole-water as clusters and as their liquid mixture, respectively. This paper aims at analyzing similarities and differences of these HBs resulted from QM and MD on an equal footing. Based on the optimized geometry at ωb97xD/aug-cc-pVTZ level of theory, the nature and property of σ and π types of HBs are unveiled by means of atoms in molecules (AIM), natural bond orbital (NBO) and energy decomposition analysis (EDA). In light of the above findings, MD simulation with OPLS-AA and SPC model was applied to study the liquid mixture at different temperatures. The MD results further characterize the behavior and structural properties of σ and π types HBs, which are somewhat different but reasonable for the clusters by QM. Finally, we provide a reasonable explanation for the different solubility between benzene/water and pyrrole/water. 23303191 Hyaluronan synthase 1 (HAS1) requires higher cellular UDP-GlcNAc concentration than HAS2 and HAS3. Mammals have three homologous genes encoding proteins with hyaluronan synthase activity (Has1-3), all producing an identical polymer from UDP-N-acetylglucosamine and UDP-glucuronic acid. To compare the properties of these isoenzymes, COS-1 cells, with minor endogenous hyaluronan synthesis, were transfected with human Has1-3 isoenzymes. HAS1 was almost unable to secrete hyaluronan or form a hyaluronan coat, in contrast to HAS2 and HAS3. This failure of HAS1 to synthesize hyaluronan was compensated by increasing the cellular content of UDP-N-acetyl glucosamine by ∼10-fold with 1 mm glucosamine in the growth medium. Hyaluronan synthesis driven by HAS2 was less affected by glucosamine addition, and HAS3 was not affected at all. Glucose-free medium, leading to depletion of the UDP-sugars, markedly reduced hyaluronan synthesis by all HAS isoenzymes while raising its concentration from 5 to 25 mm had a moderate stimulatory effect. The results indicate that HAS1 is almost inactive in cells with low UDP-sugar supply, HAS2 activity increases with UDP-sugars, and HAS3 produces hyaluronan at high speed even with minimum substrate content. Transfected Has2 and particularly Has3 consumed enough UDP-sugars to reduce their content in COS-1 cells. Comparison of different human cell types revealed ∼50-fold differences in the content of UDP-N-acetylhexosamines and UDP-glucuronic acid, correlating with the expression level of Has1, suggesting cellular coordination between Has1 expression and the content of UDP-sugars. 23424213 Protective effect of the roots extract of Platycodon grandiflorum on bile duct ligation-induced hepatic fibrosis in rats. The aim of the present study was to evaluate the protective effect of aqueous extract from Platycodon grandiflorum (BC703) on bile duct ligation (BDL)-induced hepatic fibrosis in rats. BDL rats were divided into three groups, which orally received distilled water or BC703 (10 or 50 mg/kg/day) for consecutive 28 days. Antifibrotic effects of BC703 on BDL-induced hepatic fibrosis in rats were estimated by assessing serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), blood urea nitrogen (BUN), transforming growth factor-beta 1 (TGF-β1) and hepatic levels of malondialdehyde (MDA), glutathione (GSH), total superoxide dismutase (SOD) and nitric oxide (NO). The biochemical observations were supplemented by histopathological examination of liver samples stained with hematoxylin and eosin and Masson's trichrome stain. ALT, AST, TBIL and BUN were elevated in the group treated with BDL alone than in the sham-operated group. These elevations were significantly decreased by BC703 treatment. Hepatic GSH and SOD levels, depressed by BDL, were also increased in the BC703 group. In addition, increases in hepatic MDA and NO levels in the BDL-induced cholestasis were attenuated by BC703 treatment. Furthermore, BC703 treatment significantly reduced the serum level of fibrogenic cytokine, TGF-β1. Histopathological studies further substantiated the protective effect of BC703 on BDL-induced hepatic fibrosis in rat. BC703 may have beneficial effects not only on hepatic fibrosis by cholestasis but also on hepatic fibrosis development in patients with chronic hepatic disease. 23451983 Efficient Pro-survival/angiogenic miRNA Delivery by an MRI-Detectable Nanomaterial. Herein, we report the use of biodegradable nanoparticles (NPs) containing perfluoro-1,5-crown ether (PFCE), a fluorine-based compound (NP170-PFCE) with the capacity to track cells in vivo by magnetic ressonance imaging (MRI) and efficiently release miRNA. NP170-PFCE complexed with miRNAs accumulate whitin the cell's endolysosomal compartment and interact with higher frequency with argonaute2 (Ago2) and GW182 proteins, which are involved in the biological action of miRNAs, than commercial complexes formed by commercial reagents and miRNA, which in turn accumulate in the cell cytoplasm. The release of miRNA132 (miR132) from the NPs increased 3-fold the survival of endothelial cells (ECs) transplanted in vivo and 3.5-fold the blood perfusion in ischemic limbs relatively to control. 23249341 Interaction of OH radicals with Arizona Test Dust: uptake and products. Kinetics and products of the interaction of OH radicals with solid films of Arizona Test Dust (ATD) were studied using a low pressure flow reactor (0.5-3 Torr) combined with a modulated molecular beam mass spectrometer for monitoring of the gaseous species involved. The reactive uptake coefficient of OH was measured from the kinetics of OH consumption on Pyrex rods coated with ATD as a function of OH concentration ((0.4-5.2) × 10(12) molecules cm(-3)), relative humidity (RH = 0.03-25.9%), temperature (T = 275-320 K), and UV irradiance intensity (J(NO(2)) = 0-0.012 s(-1)). Deactivation of ATD surface upon exposure to OH was observed. The initial uptake coefficient was found to be independent of temperature and irradiation conditions and to decrease with relative humidity: γ(0) = 0.2/(1 + RH(0.36)) (calculated using geometric surface area, with 30% estimated conservative uncertainty). H(2)O(2) and H(2)O were observed in the gas phase as products of the OH reaction with ATD surface with yields of (10 ± 3) and (98 ± 25) %, respectively. 22936177 Human β-cell killing by autoreactive preproinsulin-specific CD8 T cells is predominantly granule-mediated with the potency dependent upon T-cell receptor avidity. The end-stage immunopathology of type 1 diabetes resulting in β-cell destruction appears to be strongly dominated by cytotoxic CD8 T lymphocytes (CD8 T cells). However, the mechanism of cytotoxicity used by autoreactive CD8 T cells in the human setting remains unknown. Using type 1 diabetes patient-derived preproinsulin-specific CD8 T-cell clones recognizing either an HLA-A2 (A*0201) or HLA-A24 (A*2402)-restricted epitope (peptide of preproinsulin [PPI](15-24), ALWGPDPAAA; or PPI(3-11), LWMRLLPLL), we assessed the use of conventional mediators of cytotoxicity in the destruction of human β-cells in vitro compared with virus-specific cytotoxic CD8 T-cell clones. We show that PPI-specific CD8 T-cell clones are mainly reliant upon cytotoxic degranulation for inducing β-cell death. Furthermore, we find that in comparison with virus-specific CD8 T cells, there are differences in the killing potency of PPI-specific CD8 T cells that are not due to cell-intrinsic differences, but rather are mediated by differences in strength of signaling by peptide-HLA ligands. The study highlights the regulation of β-cell killing as a potential point for therapeutic control, including the possibility of blocking autoreactive CD8 T-cell function without impacting upon general immune competence. 23341258 Toxic effects of environment-friendly antifoulant nonivamide on Phaeodactylum tricornutum. Nonivamide, a synthetic derivate of natural capsaicin, has an effective antifouling activity. However, the poor understanding of the toxicity mechanism limits the application of nonivamide in antifouling paints. The present study investigated the inhibitory effects and toxicity mechanism of nonivamide on Phaeodactylum tricornutum. Under a 1.5 × 10(5) cells/ml of initial algal density (IAD), the effective concentration causing 50% inhibition at 4- d (4 d-EC50) value of nonivamide was 5.1 mg/L. Reactive oxygen species (ROS) level was significantly increased in nonivamide-treated algae. Algal antioxidants, including catalases (CAT), peroxidases (POD), superoxide dismutases (SOD), and glutathione (GSH), were all stimulated by the ROS burst. The excessive ROS substances led to the loss of algal photosynthetic pigments and also damage to the integrity of the lipid membrane. Furthermore, ROS-related genes, including psbA, psbD, psaB, rbcL, nad1, and cob, were found to be suppressed in the chloroplasts and mitochondria of nonivamide-treated algae, and the concentration of cytoplasmic Ca(2+) , an important regulator of chloroplast and mitochondrion, was elevated. The present study demonstrates that nonivamide could cause peroxidative damages to P. tricornutum by inducing ROS overproduction, which may be initiated by the suppression of ROS-related genes in algal chloroplasts and mitochondria. 23625787 Risk Factors for Excessive Anticoagulation Among Hospitalized Adults Receiving Warfarin Therapy Using a Pharmacist-Managed Dosing Protocol. STUDY OBJECTIVE: To identify specific risk factors for excessive anticoagulation, defined as an international normalized ratio (INR) higher than 5, in hospitalized adults receiving warfarin therapy using a pharmacist-managed dosing protocol. DESIGN: Retrospective nested case-control study. SETTING: Large academic tertiary care medical center. PATIENTS: Hospitalized nonsurgical patients 18 years or older who received at least one dose of warfarin according to the pharmacist-managed protocol from January 1, 2009, to January 31, 2012, were included. Patients who experienced an INR higher than 5 were designated as case patients; those who received warfarin for at least as many days as the case patients but who did not experience an INR more than 5 were deemed control patients. Controls were matched to cases in a 2:1 ratio by age, sex, INR goal, and type of warfarin therapy (new start or continuation). MEASUREMENTS AND MAIN RESULTS: A total of 87 case patients were matched to 174 controls. Ten different hypothesized risk factors were examined. Two variables, severity of illness score (odds ratio [OR] 4.89, p<0.001) and poor nutritional status (OR 4.27, p<0.001), demonstrated strong independent associations with risk of excessive anticoagulation. Administration of interacting drugs that highly potentiate warfarin's effect (OR 2.26, p=0.011) and concurrent diarrheal illness (OR 4.75, p<0.001) also displayed a statistically significant risk for excessive anticoagulation. CONCLUSION: Even in a highly standardized system for warfarin dosing by a pharmacist-managed protocol, higher disease severity and poor nutritional status placed hospitalized patients at greater risk of experiencing excessive anticoagulation. In addition, administration of interacting drugs that highly potentiate warfarin's effect or the occurrence of diarrheal illness may predict increased risk. 23523546 Pharmacokinetic evaluation in mice of amorphous itraconazole-based dry powder formulations for inhalation with high bioavailability and extended lung retention. Three Itraconazole (ITZ) dry powders for inhalation (DPI) were prepared by spray-drying a mannitol solution in which the ITZ was in suspension (F1) or was in solution without (F2) or with phospholipid (PL) (F3). These powders were endotracheally insufflated in vivo at a single dose of 0.5mg/kg for pharmacokinetic profile (lung and plasma concentration) determination in ICR CD-1 mice. ITZ was crystalline in F1 and assumed to be amorphous in the F2 and F3 formulations. The amorphous nature of ITZ in F2 and F3 formulations allowed the in vitro formation of an ITZ supersaturated solution with a maximum solubility of 450±124ng/ml (F2) and 498±44ng/ml (F3), in contrast to formulation F1 (<10ng/ml). As a result of these higher solubilities, absorption into the systemic compartment after endotracheal administration was faster for formulations F2 and F3 (shorter tmax) and in larger quantities compared to the F1 formulation (plasmatic AUC0-24h of 182ngh/ml, 491.5ngh/ml and 376.8ngh/ml, and tmax of 60min, 30min and 5min for F1, F2 and F3, respectively). PL increased the systemic bioavailability of ITZ (determined by the AUCplasma to AUClung ratio) as a consequence of their wetting and absorption enhancement effect. ITZ lung concentrations after pulmonary administration remained higher than the targeted dose, based on the minimal inhibitory concentrations for Aspergillus Fumigatus (2μg/gwetlung), 24h post-administration for both F1 and F2 formulations. However, this was not the case for formulation F3, which exhibited a faster elimination rate from the lung, with an elimination half-life of 4.1h vs. 6.5h and 14.7h for F1 and F2, respectively. 23122089 Introduction and nutritional evaluation of germinated soy germ. Germinated soy germ (GSG) were developed and evaluated for their nutritional value. Separated soy germ was germinated at room temperature for 24h under running water. As germination progressed, the protein and fibre content of GSG increased slightly, while the lipid and carbon to nitrogen (C/N) ratio decreased; free amino acids including GABA increased considerably while free sugars decreased. Linoleic and linolenic acid were the most abundant unsaturated fatty acids in soy germ, and slight changes were observed in GSG. The tocopherol and isoflavone contents showed a rapid increase of 32.4% and 27.9%, respectively, during germination. The abundance of GABA, isoflavones and tocopherols demonstrates the high nutritional value of GSG and suggests that GSG can be utilised as a reasonable and effective source of healthy foods. 23265483 Review: on published data and methods for selenium in mushrooms. Selected data published on selenium in several species of mushrooms are outlined and discussed in light of performance of analytical methods employed. Data was shown to be either dubious or concentrations too high to be credible and valid in some data reported by authors. Examples of methods and specifically the measurement techniques of Se as reported by authors studying mushrooms are outlined. Also examples of valid and incorrect data on Se in a given mushroom species with data by two or more analytical methods are illustrated. Excessive values reported due to selection of improper method of determination of Se in mushrooms relate largely to improper use of flame atomic absorption spectroscopy (AAS) and inductively coupled plasma - atomic emission spectroscopy (ICP-AES). The biased analytical data published gave a false picture on the composition and nutritional value of mushrooms with respect to selenium. 23225638 Non-ionic dendronized multiamphiphilic polymers as nanocarriers for biomedical applications. A new class of non-ionic dendronized multiamphiphilic polymers is prepared from a biodegradable (AB)n-type diblock polymer synthesized from 2-azido-1,3-propanediol (azido glycerol) and polyethylene glycol (PEG)-600 diethylester using Novozym-435 (Candida antarctica lipase) as a biocatalyst, following a well-established biocatalytic route. These polymers are functionalized with dendritic polyglycerols (G1 and G2) and octadecyl chains in different functionalization levels via click chemistry to generate dendronized multiamphiphilic polymers. Surface tension measurements and dynamic light scattering studies reveal that all of the multiamphiphilic polymers spontaneously self-assemble in aqueous solution. Cryogenic transmission electron microscopy further proves the formation of multiamphiphiles towards monodisperse spherical micelles of about 7-9 nm in diameter. The evidence from UV-vis and fluorescence spectroscopy suggests the effective solubilization of hydrophobic guests like pyrene and 1-anilinonaphthalene-8-sulfonic acid within the hydrophobic core of the micelles. These results demonstrate the potential of these dendronized multiamphiphilic polymers for the development of prospective drug delivery systems for the solubilization of poorly water soluble drugs. 23123248 Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors. Carboxylesterases (CEs) are ubiquitously expressed proteins that are responsible for the detoxification of xenobiotics. They tend to be expressed in tissues likely to be exposed to such agents (e.g., lung and gut epithelia, liver) and can hydrolyze numerous agents, including many clinically used drugs. Due to the considerable structural similarity between cholinesterases (ChE) and CEs, we have assessed the ability of a series of ChE inhibitors to modulate the activity of the human liver (hCE1) and the human intestinal CE (hiCE) isoforms. We observed inhibition of hCE1 and hiCE by carbamate-containing small molecules, including those used for the treatment of Alzheimer's disease. For example, rivastigmine resulted in greater than 95% inhibition of hiCE that was irreversible under the conditions used. Hence, the administration of esterified drugs, in combination with these carbamates, may inadvertently result in decreased hydrolysis of the former, thereby limiting their efficacy. Therefore drug:drug interactions should be carefully evaluated in individuals receiving ChE inhibitors. 23356867 Solution structure, dynamics and binding studies of a family 11 carbohydrate-binding module from Clostridium thermocellum (CtCBM11). Non-catalytic cellulosomal CBMs (carbohydrate-binding modules) are responsible for increasing the catalytic efficiency of cellulosic enzymes by selectively putting the substrate (a wide range of poly- and oligo-saccharides) and enzyme into close contact. In the present study we carried out an atomistic rationalization of the molecular determinants of ligand specificity for a family 11 CBM from thermophilic Clostridium thermocellum [CtCBM11 (C. thermocellum CBM11)], based on a NMR and molecular modelling approach. We have determined the NMR solution structure of CtCBM11 at 25°C and 50°C and derived information on the residues of the protein that are involved in ligand recognition and on the influence of the length of the saccharide chain on binding. We obtained models of the CtCBM11-cellohexaose and CtCBM11-cellotetraose complexes by docking in accordance with the NMR experimental data. Specific ligand-protein CH-π and Van der Waals interactions were found to be determinant for the stability of the complexes and for defining specificity. Using the order parameters derived from backbone dynamics analysis in the presence and absence of ligand and at 25°C and 50°C, we determined that the protein's backbone conformational entropy is slightly positive. This data in combination with the negative binding entropy calculated from ITC (isothermal titration calorimetry) studies supports a selection mechanism where a rigid protein selects a defined oligosaccharide conformation. 23641685 Cavity Ringdown Spectroscopy of the Hydroxy-Methyl-Peroxy Radical. We report vibrational and electronic spectra of the hydroxyl-methyl-peroxy radical (HOCH2OO, or HMP), the primary product of the reaction of the hydroperoxy radical, HO2, and formaldehyde, HCHO. The ν1 vibrational (OH stretch) spectrum and the Ã-X electronic spectrum of HMP were detected by Infrared Cavity Ringdown Spectroscopy (IR-CRDS), and assignments were verified with density functional calculations. The HMP radical was generated in reactions of HCHO with HO2. Free radical reactions were initiated by pulsed laser photolysis (PLP) of Cl2 in the presence of HCHO and O2 in a flow reactor at 300-330 Torr and 295K. IR-CRDS spectra were measured in mid-IR and near-IR regions over the ranges 3525-3700 cm(-1) (ν1) and 7250-7800 cm(-1) (Ã-X) (respectively, at a delay time 100 µs after photolysis. The ν1 spectrum had an origin at 3622 cm(-1) and exhibited partially resolved P- and R-branch contours and a small Q branch. At these short delay times, spectral interference from HOOH and HCOOH was minimal, and could be subtracted. From B3LYP/6-31G+(d,p) calculations, we found that the anharmonic vibrational frequency and band contour predicted for the lowest energy conformer, HMP-A, The calculated anharmonic vibrational frequency and band contour computed using B3LYP/63-1G(d,p) level were in good agreement with the observed spectrum. In the near-IR, we observed four well spaced vibronic bands, each with partially resolved rotational contours. We assigned the apparent origin of the electronic spectrum of HMP at 7392 cm(-1) and two bands to the blue to a progression in ν15', the lowest torsional mode of the state (ν15'= 171 cm(-1)). The band furthest to the red was assigned as a hot band in ν15", leading to a ground state torsional frequency of (ν15"= 122 cm(-1)). We simulated the spectrum using second order vibrational perturbation theory (VPT2) with B3LYP/6-31+G(d,p) calculations at the minimum energy geometries of the HMP-A conformer on the X ̃ and A ̃ states. The predictions of the electronic origin frequency, torsional frequencies, anharmonicities and rotational band contours matched the observed spectrum. We investigated the torsional modes more explicitly by computing potential energy surfaces of HMP as a function of the two dihedral angles τOCOH and τOOCO. Wave functions and energy levels were calculated based on this potential surface; these results were used to calculate the Franck-Condon factors, which reproduced the vibronic band intensities in the observed electronic spectrum. The transitions that we observed all involved states with wave functions localized on the minimum energy conformer, HMP-A. Our calculations indicated that the observed near-IR spectrum was that of the minimum energy conformer HMP-A, but that this conformer is not the lowest energy conformer in the state, which remains unobserved. We estimated that the energy of this lowest conformer (HMP-B) of the à state to be T0 (Ã) ≈ 7200 cm(-1), based on the energy difference E0(HMP-B) - E0(HMP-A) on the à state computed at the B3LYP/6-31+G(d,p) level. 23299647 Gender differences in drug bioequivalence: time to rethink practices. Currently, bioequivalence (BE) studies are carried out exclusively in males, assuming that intrasubject variabilities are similar between the sexes. This article challenges this hypothesis on the basis of available evidence and urges that studies of BE of sufficient power be undertaken in women also for all generic drugs aimed at women. 23570514 Discovery of Thieno[3,2-d]pyrimidine-6-carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3. The sirtuins SIRT1, SIRT2, and SIRT3 are NAD(+) dependent deacetylases that are considered potential targets for metabolic, inflammatory, oncologic, and neurodegenerative disorders. Encoded library technology (ELT) was used to affinity screen a 1.2 million heterocycle enriched library of DNA encoded small molecules, which identified pan-inhibitors of SIRT1/2/3 with nanomolar potency (e.g., 11c: IC50 = 3.6, 2.7, and 4.0 nM for SIRT1, SIRT2, and SIRT3, respectively). Subsequent SAR studies to improve physiochemical properties identified the potent drug like analogues 28 and 31. Crystallographic studies of 11c, 28, and 31 bound in the SIRT3 active site revealed that the common carboxamide binds in the nicotinamide C-pocket and the aliphatic portions of the inhibitors extend through the substrate channel, explaining the observable SAR. These pan SIRT1/2/3 inhibitors, representing a novel chemotype, are significantly more potent than currently available inhibitors, which makes them valuable tools for sirtuin research. 23042808 Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. Community-based studies suggest that cannabis products that are high in Δ⁹-tetrahydrocannabinol (THC) but low in cannabidiol (CBD) are particularly hazardous for mental health. Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form, under controlled conditions. In a between-subjects design, we tested the hypothesis that pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment. Healthy participants were randomised to receive oral CBD 600 mg (n=22) or placebo (n=26), 210 min ahead of intravenous (IV) THC (1.5 mg). Post-THC, there were lower PANSS positive scores in the CBD group, but this did not reach statistical significance. However, clinically significant positive psychotic symptoms (defined a priori as increases ≥ 3 points) were less likely in the CBD group compared with the placebo group, odds ratio (OR)=0.22 (χ²=4.74, p<0.05). In agreement, post-THC paranoia, as rated with the State Social Paranoia Scale (SSPS), was less in the CBD group compared with the placebo group (t=2.28, p<0.05). Episodic memory, indexed by scores on the Hopkins Verbal Learning Task-revised (HVLT-R), was poorer, relative to baseline, in the placebo pre-treated group (-10.6 ± 18.9%) compared with the CBD group (-0.4% ± 9.7 %) (t=2.39, p<0.05). These findings support the idea that high-THC/low-CBD cannabis products are associated with increased risks for mental health. 23019274 Novel assays for detection of urinary KIM-1 in mouse models of kidney injury. Kidney injury molecule-1 (KIM-1) has been qualified by the Food and Drug Administration and European Medicines Agency as a urinary biomarker to monitor preclinical nephrotoxicity in rats and on a case-by-case basis for the translation of potentially nephrotoxic drugs into first-in human studies. Although mouse models are widely employed in preclinical studies, few urinary biomarker studies have been performed in mice due to limited urine availability and lack of sensitive assays. Here, we report the development and validation of two different assays for quantitative assessment of mouse urinary KIM-1 (uKIM-1) and compare the sensitivity of KIM-1 relative to other standard markers in ischemia reperfusion and aristolochic acid (AA)-induced kidney injury in mice. A sensitive, reproducible, and quantitative microbead-based KIM-1 ELISA was established, which requires only 10 μl urine for triplicate determination with an assay range of 12.21 pg/ml to 50 ng/ml. The second assay is a laminar flow dipstick assay, which has an assay range of 195 pg/ml to 50 ng/ml and provides quantitative assessment of KIM-1 in 15 min. uKIM-1 levels increased with increasing time of ischemia or time after AA administration. After only 10-min ischemia followed by 24-h reperfusion, uKIM-1 was significantly elevated by 13-fold, whereas serum creatinine (sCr), blood urea nitrogen, N-acetyl-β-glucosaminidase (NAG), and proteinuria levels did not change. After AA administration, uKIM-1 levels were significantly upregulated by greater than threefold within 12 h, whereas sCr and NAG levels were unchanged. Mouse KIM-1 was stable for multiple freeze-thaw cycles, for up to 5 days at room temperature and up to at least an year when stored at -80°C. 23066853 Back to the future: can physical models of passive membrane permeability help reduce drug candidate attrition and move us beyond QSPR? It is widely recognized that adsorption, distribution, metabolism, excretion, and toxicology liabilities kill the majority of drug candidates that progress to clinical trials. The development of computational models to predict small molecule membrane permeability is therefore of considerable scientific and public health interest. Empirical qualitative structure permeability relationship models of permeability have been a mainstay in industrial applications, but lack a deep understanding of the underlying biologic physics. Others and we have shown that implicit solvent models to predict passive permeability for small molecules exhibit mediocre predictive performance when validated across experimental test sets. Given the vast increase in computer power, more efficient parallelization schemes, and extension of current atomistic simulation codes to general use graphical processing units, the development and application of physical models based on all-atom simulations may now be feasible. Preliminary results from rigorous free energy calculations using all-atom simulations indicate that performance relative to implicit solvent models may be improved, but many outstanding questions remain. Here, we review the current state-of-the-art physical models for passive membrane permeability prediction and present a prospective look at promising new directions for all-atom approaches. 23613312 Design, synthesis, and biological evaluation of cyclopropyl analogues of stilbene with raloxifene side chain as subtype-selective ligands for estrogen receptor. We have designed the cyclopropane analog of stilbene as subtype-selective ligands for estrogen receptor based on the bioisosterism that cyclopropane could act as alkene bioisoster. Three cyclopropane analogs were prepared efficiently starting from 4-benzyloxybenzaldehyde, and evaluated for their binding to estrogen receptors ERα and ERβ. These cyclopropane analogs were also found to be full agonists in estrogen receptor-mediated gene transcription assay. Compared to the stilbene analogs such as tamoxifen and raloxifene, the three cyclopropane analogs showed lower binding affinity for estrogen receptor, but higher subtype selectivity for ERα. The structure-activity relationship revealed from this study might provide clues for improving subtype selectivity for ERα. 23344975 Differential gene expression and bioinformatics analysis of copper resistance gene afe_1073 in Acidithiobacillus ferrooxidans. Copper resistance of acidophilic bacteria is very significant in bioleaching of copper ore since high concentration of copper are harmful to the growth of organisms. Copper resistance gene afe_1073 was putatively considered to be involved in copper homeostasis in Acidithiobacillus ferrooxidans ATCC23270. In the present study, differential expression of afe_1073 in A. ferrooxidans strain DY26 and DC was assessed with quantitative reverse transcription polymerase chain reaction. The results showed the expression of afe_1073 in two strains increased with the increment of copper concentrations. The expression of DY26 was lower than that of DC at the same copper concentration although A. ferrooxidans strain DY26 possessed higher copper resistance than strain DC. In addition, bioinformatics analysis showed AFE_1073 was a typical transmembrane protein P1b1-ATPase, which could reduce the harm of Cu(+) by pumping it out from the cell. There were two mutation sites in AFE_1073 between DY26 and DC and one may change the hydrophobicity of AFE_1073, which could enhance the ability of DY26 to pump out Cu(+). Therefore, DY26 needed less gene expression of afe_1073 for resisting copper toxicity than that of DC at the same copper stress. Our study will be beneficial to understanding the copper resistance mechanism of A. ferrooxidans. 23540796 A Coffee Ring Biosensor for Rapid Protein Detection. We introduce a new biosensing platform for rapid protein detection that combines one of the simplest methods for biomolecular concentration, coffee ring formation, with a sensitive aptamer-based optical detection scheme. In this approach, aptamer beacons are utilized for signal transduction where a fluorescence signal is emitted in the presence of the target molecule. Signal amplification is achieved by concentrating aptamer-target complexes within liquid droplets, resulting in the formation of coffee ring "spots". Surfaces with various chemical coatings were utilized to investigate the correlation between surface hydrophobicity, concentration efficiency and signal amplification. Based on our results, we found that the increase in coffee ring diameter with larger droplet volumes is independent of surface hydrophobicity. Furthermore, we show that highly hydrophobic surfaces produce enhanced particle concentration, via coffee ring formation, resulting in signal intensities 6-fold greater than those on hydrophilic surfaces. To validate this biosensing platform for the detection of clinical samples, we detected α-thrombin in human serum and 4x diluted whole blood. Based on our results, coffee ring spots produced detection signals 40x larger than samples in liquid droplets. Additionally, this biosensor exhibits a lower limit of detection of 2 ng/mL (54 pM) in serum, and 4 ng/mL (105 pM) in blood. Based on its simplicity and high performance, this platform demonstrates immense potential as an inexpensive diagnostic tool for the detection of disease biomarkers, particularly for use in developing countries that lack the resources and facilities required for conventional biodetection practices. 22502647 New furostanol saponins from the rhizomes of Tupistra chinensis. Three new furostanol saponins (1-3), including a polyhydroxyl saponin, were isolated from the rhizomes of Tupistra chinensis. The structures of these compounds were identified by NMR, MS spectral data and chemical methods. 23350945 Investigation of the interaction of γ-Al2O3 with aqueous solutions of dimethyl methylphosphonate using infrared multiple internal reflection spectroscopy. The interaction of dilute solutions of dimethyl methylphosphonate (DMMP) in H(2)O with thin porous layers of γ-Al(2)O(3) has been studied under steady-state conditions using infrared multiple-internal-reflection spectroscopy. Upon the initial introduction of the DMMP solution to a previously H(2)O-saturated surface, DMMP diffuses into the porous layer and displaces weakly hydrogen-bonded H(2)O molecules. This is accompanied by hydrolysis of the γ-Al(2)O(3) to form Al(OH)(3) and/or AlO(OH). The P═O group of DMMP interacts predominantly with H(2)O and gives no clear indication of bonding to the oxide surface itself, from which it is inferred that the displacement of weakly adsorbed H(2)O results from the interaction of acidic Al-OH sites with the methoxy O atoms of DMMP. No hydrolysis of the DMMP, either in solution or in contact with the oxide, was detectable under the present conditions. The results have practical implications in the decontamination of materials following exposure to toxic reagents related to DMMP. 23471710 Severe hypoglycemia from helicobacter pylori triple-drug therapy and insulin detemir drug interaction. Two drugs commonly used in triple-drug therapy for treatment of a Helicobacter pylori infection, clarithromycin and omeprazole, have rarely been associated with hypoglycemia when given alone. No documented interactions between H. pylori treatment with clarithromycin, amoxicillin, and omeprazole and insulin detemir have been previously reported. This case report describes an 82-year-old man with drug-controlled type 2 diabetes who experienced severe hypoglycemia during treatment for a H. pylori infection in an outpatient setting. His diabetes treatment included 32 units of insulin detemir once/day at bedtime and insulin aspart, determined by carbohydrate intake, 3 times/day with meals. After 5 days of clarithromycin 500 mg twice/day, amoxicillin 500 mg twice/day, and omeprazole 20 mg twice/day for treatment of the H. pylori infection, the patient experienced hypoglycemia and self-discontinued clarithromycin. Insulin detemir was decreased to 15 units and hypoglycemia reoccurred. Insulin detemir was further decreased to 10 units without further symptoms of hypoglycemia for the remainder of the H. pylori treatment. Once treatment was completed, the patient was instructed to resume taking 32 units of insulin detemir once/day. His blood glucose concentration returned to a baseline value, and he denied experiencing further hypoglycemic episodes. Health care practitioners should be aware of this possible drug interaction and anticipate that insulin detemir dosage adjustments may be required during treatment of H. pylori infection to avoid significant adverse events. 23584427 Transcriptomic analysis of cultured whale skin cells exposed to hexavalent chromium [Cr(VI)]. Hexavalent chromium Cr(VI) is known to produce cytotoxic effects in humans and is a highly toxic environmental contaminant. Interestingly, it has been shown that free ranging sperm whales (Phyester macrocephalus) may have exceedingly high levels of Cr in their skin. Also, it has been demonstrated that skin cells from whales appear more resistant to both cytotoxicity and clastogenicity upon Cr exposure compared to human cells. However, the molecular genetic mechanisms employed in whale skin cells that might lead to Cr tolerance are unknown. In an effort to understand the underlying mechanisms of Cr(VI) tolerance and to illuminate global gene expression patterns modulated by Cr, we exposed whale skin cells in culture to varying levels of Cr(VI) (i.e., 0.0, 0.5, 1.0 and 5.0μg/cm(2)) followed by short read (100bp) next generation RNA sequencing (RNA-seq). RNA-seq reads from all exposures (≈280 million reads) were pooled to generate a de novo reference transcriptome assembly. The resulting whale reference assembly had 11K contigs and an N50 of 2954bp. Using the reads from each dose (0.0, 0.5, 1.0 and 5.0μg/cm(2)) we performed RNA-seq based gene expression analysis that identified 35 up-regulated genes and 19 down-regulated genes. The experimental results suggest that low dose exposure to Cr (1.0μg/cm(2)) serves to induce up-regulation of oxidative stress response genes, DNA repair genes and cell cycle regulator genes. However, at higher doses (5.0μg/cm(2)) the DNA repair genes appeared down-regulated while other genes that were induced suggest the initiation of cytotoxicity. The set of genes identified that show regulatory modulation at different Cr doses provide specific candidates for further studies aimed at determination of how whales exhibit resistance to Cr toxicity and what role(s) reactive oxygen species (ROS) may play in this process. 23586812 Development of a Selective Peptide Macrocycle Inhibitor of Coagulation Factor XII toward the Generation of a Safe Antithrombotic Therapy. Inhibition of coagulation factor XII (FXII) activity represents an attractive approach for the treatment and prevention of thrombotic diseases. The few existing FXII inhibitors suffer from low selectivity. Using phage display combined to rational design, we developed a potent inhibitor of FXII with more than 100-fold selectivity over related proteases. The highly selective peptide macrocycle is a promising candidate for the control of FXII activity in antithrombotic therapy and a valuable tool in hematology research. 23401303 Comparing sorption behavior of pyrethroids between formulated and natural sediments. Formulated sediments are recommended for use in toxicity tests to achieve standardized evaluations. However, the organic matter used in formulated sediments may differ qualitatively from that in natural sediments, which may lead to different chemical partition patterns and, hence, different toxicity effects. By deriving partition coefficients for organic carbon and dissolved organic carbon (KOC and KDOC , respectively) for eight pyrethroid insecticides from three formulated and five natural sediments, the authors characterized the differences between formulated and natural sediments in pesticide sorption. For all pyrethroids, the mean values of KOC and KDOC of formulated sediments were two to three, and three to 10 times smaller than those of natural sediments, respectively. The two formulated sediments containing α-cellulose or Manitoba peat showed significantly (p < 0.0001) smaller KOC and KDOC values than natural sediments based on statistical analyses, while the difference was not significant for the formulated sediment containing New Brunswick peat. The KOC values were closely correlated (p < 0.001) with soot carbon content, while the amount of carboxylic or phenolic functional groups may have affected KDOC . Therefore, the source and quality of organic matter are likely the most important factors in formulated sediments and must be standardized to provide consistency in sediment toxicity tests. Environ. Toxicol. Chem. 2013;32:1033-1039. © 2013 SETAC. 23544771 Symptomatic Amyloid Goiters: Report of 5 Cases. Background: Massive amyloid deposition in the thyroid to the point of goiter formation is rare. Here we describe the clinical presentation and outcomes of 5 patients with amyloid goiter (radiographically confirmed goiter in the context of tissue-proven thyroid amyloidosis) encountered in the past 23 years at our institution. Methods: Mayo Clinic archives were searched between 1987 and 2010 for diagnosis "thyroid amyloidosis," "amyloid deposits," "amyloid deposition," or "liquid chromatography consistent with amyloid." Inclusion criteria were symptomatic thyromegaly; tissue confirmation of thyroid enlarged by amyloid deposits; and radiologic confirmation of thyroid enlargement. Results: Five patients were identified who met all inclusion criteria. Amyloid goiter etiology included both primary and secondary amyloidosis, and the goiters ranged from 50 to 130 g each. Diagnosis was made by fine-needle aspiration biopsy with Congo red staining and, if needed, spectrophotometry. All 5 patients had histories of persistent hoarseness for several years prior to presentation with compressive symptoms referable to their enlarging thyroids, and all had some degree of thyroid dysfunction (both hypothyroidism and hyperthyroidism) by the end of our follow-up period, which ranged from 5 months to 13 years. Two patients underwent surgical intervention(s), 2 were managed conservatively, and in 1, the goiter shrank following systemic therapy for amyloidosis. Conclusions: Our clinical observations suggest slower goiter progression and a higher prevalence of thyroid dysfunction than previously thought. 23507565 Intact inhibitory control processes in abstinent drug abusers (II): A high-density electrical mapping study in former cocaine and heroin addicts. Response inhibition deficits are well-documented in drug users, and are related to the impulsive tendencies characteristic of the addictive phenotype. Addicts also show significant motivational issues that may accentuate these inhibitory deficits. We investigated the extent to which these inhibitory deficits are present in abstinence. Salience of the task stimuli was also manipulated on the premise that emotionally-valenced inputs might impact inhibitory efficacy by overcoming the blunted responses to everyday environmental inputs characteristic of this population. Participants performed response inhibition tasks consisting of both neutral and emotionally valenced stimuli while high-density event-related potentials (ERPs) were recorded. Electrophysiological responses (N2/P3 components) to successful inhibitions in abstinent abusers (N = 20) and non-using participants (N = 21) were compared. In contrast to previous work in current users, our abstinent cohort showed no detectable behavioral or electrophysiological differences in their inhibitory responses, and no differences on self-reports of impulsivity, despite their long histories of chronic use (mean = 10.3 years). The current findings are consistent with a recovery of inhibitory control processes as a function of abstinence. Abstinent former users, however, did show a reduced modulation, relative to controls, of their ERPs to valenced input while performing successful inhibitions, although contrary to our hypothesis, the use of valenced inputs had no impact on inhibitory performance. Reduced ERP modulation to emotionally valenced inputs may have implications for relapse in emotional contexts outside the treatment center. 23554029 Clinical Study to Assess the Efficacy and Safety of a Citrus Polyphenolic Extract of Red Orange, Grapefruit, and Orange (Sinetrol-XPur) on Weight Management and Metabolic Parameters in Healthy Overweight Individuals. The present study investigated the efficacy and safety effects of Sinetrol-XPur (polyphenolic citrus dry extract) in weight management; metabolic parameters; and inflammatory, glycemic and oxidative status. In a 12-week, randomized, double-blind, placebo-controlled trial, Sinetrol-XPur was given to overweight subjects twice daily with meals in the tested group (N = 47) versus a placebo group (N = 48). Waist and hip circumference and abdominal fat were decreased in the Sinetrol-XPur group as compared with the placebo group (p < 0.0001) (-5.71% vs -1.56% for waist, -4.71% vs -1.35% for hip and -9.73% vs -3.18% for fat). Inflammatory markers were reduced (C-reactive protein: -22.87% vs +61%; fibrinogen: -19.93% vs -1.61%, p < 0.01). Oxidative stress was lowered as seen by the reduction of malondialdehyde (-14.03% vs 2.76%) and the increase in superoxide dismutase and glutathione (17.38% vs 2.19% and 4.63% vs -2.36%, respectively, p < 0.01). No adverse effects were observed. Kidney, liver, and lipid panels remained unchanged. These results indicated that Sinetrol-XPur supplementation is a viable option for reducing abdominal fat, waist and hip circumference, and body weight and for improving inflammatory, glycemic, and oxidative status in healthy overweight individuals. Copyright © 2013 John Wiley & Sons, Ltd. 23357565 Protective effect of silymarin against ethanol-induced gastritis in rats: role of sulfhydryls, nitric oxide and gastric sensory afferents. Silymarin has been known to exert antioxidant, anti-carcinogenic and anti-inflammatory effects. In this study, we examined the effect of silymarin on gastritis in rats. Oral administration of silymarin dose-dependently decreased gastric lesions in ethanol-induced gastritis model. Silymarin also significantly suppressed the development of gastric lesions in aspirin- or water immersion-restraint stress-induced gastritis models. Further study demonstrated that the gastroprotective effect of silymarin was blocked by nitric oxide (NO) synthase inhibitor l-NAME, SH blocker N-ethylmaleimide or TRPV1 antagonist capsazepine in ethanol-induced gastritis model. In addition, ex vivo analysis revealed that ethanol-induced decrease in gastric mucus and non-protein sulfhydryl (NPSH) groups was significantly reversed by silymarin treatment and lipid peroxidation was also suppressed by silymarin in ethanol-induced gastritis model. Taken together, these results suggest that silymarin exerts gastroprotective effects and the gastroprotective effects of silymarin might be related to the protection of gastric mucosal NO and NP-SH and the modulation of capsaicin-sensitive gastric sensory afferents. 23422745 NER initiation factors, DDB2 and XPC, regulate UV radiation response by recruiting ATR and ATM kinases to DNA damage sites. ATR and ATM kinases are central to the checkpoint activation in response to DNA damage and replication stress. However, the nature of the signal, which initially activates these kinases in response to UV damage, is unclear. Here, we have shown that DDB2 and XPC, two early UV damage recognition factors, are required for the damage-specific ATR and ATM recruitment and phosphorylation. ATR and ATM physically interacted with XPC and promptly localized to the UV damage sites. ATR and ATM recruitment and their phosphorylation were negatively affected in cells defective in DDB2 or XPC functions. Consequently, the phosphorylation of ATR and ATM substrates, Chk1, Chk2, H2AX, and BRCA1 was significantly reduced or abrogated in mutant cells. Furthermore, UV exposure of cells defective in DDB2 or XPC resulted in a marked decrease in BRCA1 and Rad51 recruitment to the damage site. Conversely, ATR- and ATM-deficiency failed to affect the recruitment of DDB2 and XPC to the damage site, and therefore did not influence the NER efficiency. These findings demonstrate a novel function of DDB2 and XPC in maintaining a vital cross-talk with checkpoint proteins, and thereby coordinating subsequent repair and checkpoint activation. 23222689 Removal of valproic acid by plasmapheresis in a patient treated for multiple sclerosis. We present a case of a patient with multiple sclerosis who was treated with plasmapheresis and valproic acid. We used therapeutic drug monitoring to determine whether plasma concentrations of valproic acid were kept within the therapeutic window and to determine the amount of valproic acid that was removed by plasmapheresis. 23462213 A Chinese herb formula decreases the monocarboxylate transporter-mediated absorption of valproic acid in rats. Huang-Qin-Tang (HQT), a Chinese medicine prescription containing Scutellariae Radix (SR), Paeoniae Radix (PR), Glycyrrhizae Radix (GR) and JuJubae Fructus (JF), was used for the treatments of cold with symptoms of abdominalgia and diarrhea. Valproic acid (VPA) is an antiepileptic drug with narrow therapeutic window. This study investigated the effect of coadministration of HQT on the pharmacokinetics of VPA, a probe drug for monocarboxylate transporter (MCT). Rats were administered VPA alone (200.0mg/kg) and coadministered HQT (8.0g/kg) at 0.5h before VPA and 1.5h after VPA in crossover designs. In addition, the chronic effect of HQT was also evaluated by coadministration of the 7th dose at 0.5h before VPA. The serum concentration of VPA was determined by a fluorescence polarization immunoassay. The results showed that coadministration of HQT at 0.5h before VPA significantly decreased the AUC0-t and Cmax by 62% and 77%, respectively, whereas coadministration of HQT at 1.5h after VPA exerted no significant influence. When the 7th dose of HQT was given at 0.5h before VPA, the AUC0-t and Cmax of VPA were markedly decreased by 65% and 82%, respectively. Mechanism study revealed that the MCT-mediated uptake of fluorescein was inhibited by HQT and each component herbs. In conclusion, the MCT-mediated absorption of VPA was significantly decreased by concomitant administration of HQT. 23530019 Nicotine Kinetics in Zebra Finches in vivo and in vitro. Nicotine enhances cognitive performance, and in the zebra finch (Taeniopygia guttata), which is a well-established model of cognition, the effect of nicotine on song production has been reported. Nicotine and cotinine plasma levels were assessed in vivo after s.c. injection of 0.18 mg/kg nicotine, a dose that elicits changes in song production. The half-life of nicotine elimination was 33 min, and levels were undetectable by 4h. Average plasma nicotine over 2 hours was 32 ng/ml, similar to levels seen in human smokers and rat models of nicotine behavior. Nicotine brain levels were 30 and 14 ng/g at 1 and 2 h after treatment. To understand the potential for drug interactions and regulation of nicotine metabolism in zebra finches, we characterized in vitro nicotine metabolism and the hepatic enzyme involved. In humans, cytochrome P450 (CYP) 2A6 metabolizes nicotine to cotinine, and CYP2A-like activity and protein have been reported in some birds. Zebra finch liver microsomes metabolized nicotine and bupropion (CYP2B substrate) but not coumarin (CYP2A substrate). Nicotine was metabolized to cotinine with a Km of 96 μM and Vmax of 56 pmol/min/mg. Nicotine and bupropion metabolism were inhibited by C-8-xanthate (specific CYP2B inhibitor) but not CYP2A-specific inhibitors, and hepatic levels of CYP2B-like but not CYP2A-like proteins correlated with nicotine (r = 0.52, p = 0.04) and bupropion metabolism (r = 0.81, p < 0.001), suggesting CYP2B-mediation of nicotine metabolism as seen in rats. These results will facilitate further investigation of nicotine's effects in zebra finches. 23595419 Highly selective lithium recovery from brine using a λ-MnO2-Ag battery. The demand for lithium has greatly increased with the rapid development of rechargeable batteries. Currently, the main lithium resource is brine lakes, but the conventional lithium recovery process is time consuming, inefficient, and environmentally harmful. Rechargeable batteries have been recently used for lithium recovery, and consist of lithium iron phosphate as a cathode. These batteries feature promising selectivity between lithium and sodium, but they suffer from severe interference from coexisting magnesium ions, an essential component of brine, which has prompted further study. This study reports on a highly selective and energy-efficient lithium recovery system using a rechargeable battery that consists of a λ-MnO2 positive electrode and a chloride-capturing negative electrode. This system can be used to recover lithium from brine even in the presence of magnesium ions as well as other dissolved cations. In addition, lithium recovery from simulated brine is successfully demonstrated, consuming 1.0 W h per 1 mole of lithium recovered, using water similar to that from the artificial brine, which contains various cations (mole ratio: Na/Li ≈ 15.7, K/Li ≈ 2.2, Mg/Li ≈ 1.9). 23454011 Impact of co-administration of protonated nanostructured aluminum silicate (cholesterol absorption inhibitor) on the absorption of lipid soluble vitamins D3 and K1: An assessment of pharmacokinetic and in vitro intraluminal processing. Protonated nanostructured aluminum silicate (NSAS) is a protonated montmorillonite clay that was shown to be effective as an inhibitor of intestinal cholesterol absorption. The effect of NSAS on the intestinal absorption of nutrients is unknown. An in vitro lipolysis model was adapted to test the intraluminal processing of vitamin D3 and K1 in the presence of various amounts of NSAS. Additionally, vitamin absorption was assessed in male Sprague-Dawley rats randomized in the following treatment groups: IV administration of 0.1mg/kg vitamin D3 and 1mg/kg vitamin K1, and a single-dose gavage of 1mg/kg vitamin D3 and 5mg/kg of vitamin K1 in peanut oil with various doses of NSAS slurry, 2% NSAS-fortified diet, or 50mg/kg stigmastanol. The solubilized fraction of vitamin D3 in the lipolysis medium was reduced from 70% to 46% upon the addition of 120mg NSAS. In contrast, the solubilized fractions of vitamin K1 were not significantly affected. Although the NSAS-fortified diet did not significantly affect the absorbed fraction of both vitamins, NSAS slurry decreased the absorption of vitamin D3 as compared to the control. These results indicate that NSAS may be incorporated in diet to treat hypercholesterolemia; however, vitamin D3 monitoring may be required. 23605905 Ischemic stroke functional outcomes are independently associated with C-reactive protein concentrations and cognitive outcomes with triiodothyronine concentrations: a pilot study. Elevated concentrations of C-reactive protein (CRP) and decreased concentrations of triiodothyronine (T3) were shown to predict poor outcomes in patients with stroke. However, the prognostic value of CRP and T3 has not been studied simultaneously in relation to stroke functional and cognitive outcomes despite of close interaction between inflammatory markers and thyroid function. We evaluated the association of thyroid hormone and CRP concentrations with immediate outcomes after ischemic stroke. Eighty-eight ischemic stroke patients on admission to the stroke unit were evaluated for clinical stroke severity (Scandinavian stroke scale or SSS) and concentrations of thyroid-stimulating hormone, free thyroxin, free T3, and CRP. Functional outcome (modified Rankin scale) and cognitive outcome (Mini mental state examination) were evaluated at discharge. Greater ln CRP concentrations (r = -0.35, p = 0.001), but not thyroid hormone concentrations, correlated with score on the SSS. In univariate analyses lower free T3 concentrations and higher CRP concentrations were associated with poor functional and poor cognitive outcomes. After adjustment for clinical stroke severity, higher CRP concentrations (β = 0.18, p = 0.04) remained associated with worse functional outcome and lower free T3 concentrations with worse cognitive outcome (β = 0.23, p = 0.03). In sum, clinical stroke severity is associated with elevated CRP concentration. Higher CRP concentration is independently associated with worse functional outcomes and lower free T3 concentration with worse cognitive outcomes at discharge. T3 and CRP can be important biomarkers in patients with acute ischemic stroke. 23296902 Urinary chromium excretion in response to an insulin challenge is not a biomarker for chromium status. Over 50 years ago, chromium (Cr) was proposed to be an essential trace element; however, recent studies indicate that this status should be removed as the effects of Cr supplementation appear to be pharmacological rather than nutritional. The pharmacological basis for Cr's effects can explain the inability of investigators to discover a biomarker for Cr status. One potential biomarker has not been examined to date. Cr is known to be mobilized in the body in response to insulin (or insulin release in response to a glucose challenge), resulting in an increase in urinary Cr excretion. The magnitude of increase in urinary Cr loss as a function of dietary Cr intake was tested as a potential biomarker for Cr. Zucker lean rats housed in carefully controlled metal-free conditions were provided a series of purified diets containing variable Cr contents (from 16 μg/kg diet to 2,000 μg/kg) for 23 weeks. The 16 μg/kg diet contained less Cr than any diet examined to date. Urine samples were collected before and after insulin and glucose challenges (0, 2, 6, and 12 h postinjection). Urinary Cr levels were analyzed by the standard method of addition using graphite furnace atomic absorption. The rate of urinary Cr loss after a glucose or insulin challenge was found to not be dependent on the Cr content of the rats' diets. Blood iron levels of the rats were also measured to determine if the addition of Cr to the diet altered iron status. The Cr content of the diet was found to have no affect on blood iron levels. Overall, the study demonstrated that insulin-stimulated urinary Cr excretion cannot be used as a biomarker for Cr status. 23470280 Corticotropin releasing factor and catecholamines enhance glutamatergic neurotransmission in the lateral subdivision of the central amygdala. Glutamatergic neurotransmission in the central nucleus of the amygdala (CeA) plays an important role in many behaviors including anxiety, memory consolidation and cardiovascular responses. While these behaviors can be modulated by corticotropin releasing factor (CRF) and catecholamine signaling, the mechanism(s) by which these signals modify CeA glutamatergic neurotransmission remains unclear. Utilizing whole-cell patch-clamp electrophysiology recordings from neurons in the lateral subdivision of the CeA (CeAL), we show that CRF, dopamine (DA) and the β-adrenergic receptor agonist isoproterenol (ISO) all enhance the frequency of spontaneous excitatory postsynaptic currents (sEPSC) without altering sEPSC kinetics, suggesting they increase presynaptic glutamate release. The effect of CRF on sEPSCs was mediated by a combination of CRFR1 and CRFR2 receptors. While previous work from our lab suggests that CRFRs mediate the effect of catecholamines on excitatory transmission in other subregions of the extended amygdala, blockade of CRFRs in the CeAL failed to significantly alter effects of DA and ISO on glutamatergic transmission. These findings suggest that catecholamine and CRF enhancement of glutamatergic transmission onto CeAL neurons occurs via distinct mechanisms. While CRF increased spontaneous glutamate release in the CeAL, CRF caused no significant changes to optogenetically evoked glutamate release in this region. The dissociable effects of CRF on different types of glutamatergic neurotransmission suggest that CRF may specifically regulate spontaneous excitatory transmission. 23218716 Indoleamine 2,3-dioxygenase inhibitory activity of derivatives of marine alkaloid tsitsikammamine A. Tsitsikammamines are marine alkaloids whose structure is based on the pyrroloiminoquinone scaffold. These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial, antifungal and antimalarial activity. Indoleamine 2,3-dioxygenase (IDO1) is a well-established therapeutic target as an important factor in the tumor immune evasion mechanism. In this preliminary communication, we report the inhibitory activity of tsitsikammamine derivatives against IDO1. Tsitsikammamine A analogue 11b displays submicromolar potency in an enzymatic assay. A number of derivatives are also active in a cellular assay while showing little or no activity towards tryptophan 2,3-dioxygenase (TDO), a functionally related enzyme. This IDO1 inhibitory activity is rationalized by molecular modeling studies. An interest is thus established in this class of compounds as a potential source of lead compounds for the development of new pharmaceutically useful IDO1 inhibitors. 23395001 Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells. To provide a lifelong supply of blood cells, hematopoietic stem cells (HSCs) need to carefully balance both self-renewing cell divisions and quiescence. Although several regulators that control this mechanism have been identified, we demonstrate that the transcription factor PU.1 acts upstream of these regulators. So far, attempts to uncover PU.1's role in HSC biology have failed because of the technical limitations of complete loss-of-function models. With the use of hypomorphic mice with decreased PU.1 levels specifically in phenotypic HSCs, we found reduced HSC long-term repopulation potential that could be rescued completely by restoring PU.1 levels. PU.1 prevented excessive HSC division and exhaustion by controlling the transcription of multiple cell-cycle regulators. Levels of PU.1 were sustained through autoregulatory PU.1 binding to an upstream enhancer that formed an active looped chromosome architecture in HSCs. These results establish that PU.1 mediates chromosome looping and functions as a master regulator of HSC proliferation. 23223641 Micro-mesoporous materials obtained by zeolite recrystallization: synthesis, characterization and catalytic applications. The review covers the recent developments in the field of novel micro-mesoporous materials obtained by zeolite recrystallization. The materials are classified into three distinctly different groups depending on the degree of recrystallization: (i) coated mesoporous zeolites (RZEO-1); (ii) micro-mesoporous nanocomposites (RZEO-2); and (iii) mesoporous materials with zeolitic fragments in the walls (RZEO-3). The first part of the review is focused on the analysis of the synthetic strategies leading to different types of recrystallized materials. In the second part, a comprehensive view on their structure, texture and porosity in connection with acidic and diffusion properties is given. The last part is devoted to the catalytic applications of recrystallized materials. The advantages and disadvantages with respect to pure micro- and mesoporous molecular sieves and other hierarchical zeolites are critically analyzed and the future opportunities and perspectives are discussed. 23567314 Evaluation of perfluoroalkyl acid activity using primary mouse and human hepatocytes. While perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been studied at length, less is known about the biological activity of other perfluoroalkyl acids (PFAAs) detected in the environment. Using a transient transfection assay developed in COS-1 cells, our group has previously evaluated a variety of PFAAs for activity associated with activation of peroxisome proliferator-activated receptor alpha (PPARα). Here we use primary heptatocytes to further assess the biological activity of a similar group of PFAAs using custom designed Taqman Low Density Arrays. Primary mouse and human hepatoyctes were cultured for 48h in the presence of varying concentrations of 12 different PFAAs or Wy14,643, a known activator of PPARα. Total RNA was collected and the expression of 48 mouse or human genes evaluated. Gene selection was based on either in-house liver microarray data (mouse) or published data using primary hepatocytes (human). Gene expression in primary mouse hepatocytes was more restricted than expected. Genes typically regulated in whole tissue by PPARα agonists were not altered in mouse cells including Acox1, Me1, Acaa1a, Hmgcs1, and Slc27a1. Cyp2b10, a gene regulated by the constitutive androstane receptor and a transcript normally up-regulated by in vivo exposure to PFAAs, was also unchanged in cultured mouse hepatocytes. Cyp4a14, Ehhadh, Pdk4, Cpt1b, and Fabp1 were regulated as expected in mouse cells. A larger group of genes were differentially expressed in human primary hepatocytes, however, little consistency was observed across compounds with respect to which genes produced a significant dose response making the determination of relative biological activity difficult. This likely reflects weaker activation of PPARα in human versus rodent cells as well as variation among individual cell donors. Unlike mouse cells, CYP2B6 was up-regulated in human hepatocytes by a number of PFAAs as was PPARδ. Rankings were conducted on the limited dataset. In mouse hepatocytes, the pattern was similar to that previously observed in the COS-1 reporter cell assay. With the exception of PFHxA, longer chain PFAA carboxylates were the most active. The pattern was similar in human hepatocytes, although PFDA and PFOS showed higher activity than previously observed while PFOA showed somewhat less activity. These data reflect inherent challenges in using primary hepatocytes to predict toxicological response. 23339036 The Inhibitory Effects of the Standardized Extracts of Ginkgo biloba on Aromatase Activity in JEG-3 Human Choriocarcinoma Cells. Breast cancer is the most common cancer in women worldwide. There are many endocrine adjuvant therapies for breast cancer patients that are categorized according to their mechanisms. Among them, aromatase inhibitors (AIs) that block the synthesis of estrogens have proven superiority compared with tamoxifen and have replaced it as a first-line hormonal therapy. However, AIs also have limitations due to their side effects - increased rate of bone loss and musculoskeletal complaints. We therefore need new candidate AIs with fewer side effects. The extracts of Ginkgo biloba (EGb), which contain phytochemicals from the tree, had biphasic effects for estrogens and osteoporosis-inhibiting activities in our previous experiments. In this study, we explored the possibility of EGb as an AI and their mechanisms. Aromatase activities were inhibited by EGb both in JEG-3 cells and in recombinant CYP19 microsomes. The results of polymerase chain reaction for aromatase from a coding sequence and specific promoter sequences (exon I.a, exon I.c) in JEG-3 cells as well as the results of reporter gene assays showed that EGb dose-dependently decreased the aromatase gene expression. The decreased protein levels were demonstrated by Western blotting. From these results, we concluded that EGb could act as an AI at both the enzyme and transcriptional levels. Copyright © 2013 John Wiley & Sons, Ltd. 23019217 Mithramycin A inhibits myeloid cell leukemia-1 to induce apoptosis in oral squamous cell carcinomas and tumor xenograft through activation of Bax and oligomerization. In several human malignancies, overexpression of myeloid cell leukemia-1 (Mcl-1) confers resistance to induction of apoptosis; however, Mcl-1-mediated inhibition of apoptosis in oral squamous cell carcinoma (OSCC) is not fully understood and has been investigated in this study. The Mcl-1 promoter activators (TPA) and epidermal growth factor (EGF) enhanced neoplastic transformation of JB6 cells and this response was accompanied by enhanced expression of Mcl-1, and knockdown of Mcl-1 by RNA interference (RNAi) decreased JB6 cell transformation. In the same cell line, we also demonstrated that mithramycin A (Mith) decreased TPA-induced JB6 cell transformation and Mcl-1 expression. Mcl-1 was overexpressed in human oral tumors compared with normal oral mucosa and also in several OSCC cell lines including HN22 and HSC-4 cells. Treatment of these cells with Mith also decreased Mcl-1 expression and neoplastic cell transformation, and this was accompanied by induction of several markers of apoptosis. Knockdown of Mcl-1 by RNAi also induced apoptotic cell death. The downregulation of Mcl-1 by Mith and RNAi increased pro-apoptotic protein Bax, resulting in the Bax translocation into mitochondria and its oligomerization. Mith also suppressed tumor growth in vivo and induced apoptosis in tumor by also regulating expression of Mcl-1 and Bax proteins. These indicate a critical role for Mcl-1 in the growth and survival of OSCC and demonstrate that Mith may be a potential anticancer drug candidate for clinical treatment of OSCC. 22349814 Potential tumor-suppressive role of monoglyceride lipase in human colorectal cancer. Human monoglyceride lipase (MGL) is a recently identified lipase and very little is known about its regulation and function in cellular regulatory processes, particularly in context to human malignancy. In this study, we investigated the regulation and function of MGL in human cancer(s) and report that MGL expression was either absent or reduced in the majority of primary colorectal cancers. Immunohistochemical studies showed that reduction of MGL expression in the colorectal tumor tissues predominantly occurred in the cancerous epithelial cells. MGL was found to reside in the core surface of a cellular organelle named 'lipid body'. Furthermore, it was found to interact selectively with a number of phospholipids, including phosphatidic acid and phosphoinositol(3,4,5)P3, phosphoinositol(3,5)P2, phosphoinositol(3,4)P2 and several other phosphoinositides, and among all phosphoinositides analyzed, its interaction with PI(3,4,5)P3 was found to be the strongest. In addition, overexpression of MGL suppressed colony formation in tumor cell lines and knockdown of MGL resulted in increased Akt phosphorylation. Taken together, our results suggest that MGL plays a negative regulatory role in phosphatidylinositol-3 kinase/Akt signaling and tumor cell growth. 23374868 1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones as novel CCR1 antagonists. A novel series of CCR1 antagonists based on the 1-(4-phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanone scaffold was identified by screening a compound library utilizing CCR1-expressing human THP-1 cells. SAR studies led to the discovery of the highly potent and selective CCR1 antagonist 14 (CCR1 binding IC(50)=4 nM using [(125)I]-CCL3 as the chemokine ligand). Compound 14 displayed promising pharmacokinetic and toxicological profiles in preclinical species. 23085979 Aryl hydrocarbon receptor-mediated disruption of contact inhibition is associated with connexin43 downregulation and inhibition of gap junctional intercellular communication. The aryl hydrocarbon receptor (AhR) contributes to the control of cell-to-cell communication, cell adhesion, migration or proliferation. In the present study, we investigated the regulation of connexin43 (Cx43) and Cx43-mediated gap junctional intercellular communication (GJIC) during the AhR-dependent disruption of contact inhibition in non-tumorigenic liver epithelial cells. The contact inhibition of cell proliferation is a process restricting the cell division of confluent non-transformed cells, which is frequently abolished in cancer cells; however, the mechanisms contributing to its disruption are still only partially understood. Disruption of contact inhibition, which was induced by toxic AhR ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or polycyclic aromatic hydrocarbons in epithelial WB-F344 cells, reduced Cx43 protein levels, possibly via enhanced proteasomal degradation, significantly decreased the amount of gap junction plaques and downregulated GJIC, in an AhR-dependent manner. Although both intracellular and membrane Cx43 pools were markedly reduced in cells released from contact inhibition by TCDD, siRNA-mediated Cx43 knock-down was not sufficient to stimulate proliferation in contact-inhibited cells. Our data suggest that downregulation of Cx43/GJIC in non-transformed epithelial cells is an inherent part of disruption of contact inhibition, which occurs at the post-transcriptional level. This process runs in parallel with alterations of other forms of cell-to-cell communication, thus suggesting that toxic AhR agonists may simultaneously abrogate contact inhibition and reduce GJIC, two essential mechanisms linked to deregulation of cell-to-cell communication during tumor promotion and progression. 23307185 Protease-activated receptor (PAR) 1 and PAR4 differentially regulate factor V expression from human platelets. With the recent interest of protease-activated receptors (PAR) 1 and PAR4 as possible targets for the treatment of thrombotic disorders, we compared the efficacy of protease-activated receptor (PAR)1 and PAR4 in the generation of procoagulant phenotypes on platelet membranes. PAR4-activating peptide (AP)-stimulated platelets promoted thrombin generation in plasma up to 5 minutes earlier than PAR1-AP-stimulated platelets. PAR4-AP-mediated factor V (FV) association with the platelet surface was 1.6-fold greater than for PAR1-AP. Moreover, PAR4 stimulation resulted in a 3-fold greater release of microparticles, compared with PAR1 stimulation. More robust FV secretion and microparticle generation with PAR4-AP was attributable to stronger and more sustained phosphorylation of myosin light chain at serine 19 and threonine 18. Inhibition of Rho-kinase reduced PAR4-AP-mediated FV secretion and microparticle generation to PAR1-AP-mediated levels. Thrombin generation assays measuring prothrombinase complex activity demonstrated 1.5-fold higher peak thrombin levels on PAR4-AP-stimulated platelets, compared with PAR1-AP-stimulated platelets. Rho-kinase inhibition reduced PAR4-AP-mediated peak thrombin generation by 25% but had no significant effect on PAR1-AP-mediated thrombin generation. In conclusion, stimulation of PAR4 on platelets leads to faster and more robust thrombin generation, compared with PAR1 stimulation. The greater procoagulant potential is related to more efficient FV release from intracellular stores and microparticle production driven by stronger and more sustained myosin light chain phosphorylation. These data have implications about the role of PAR4 during hemostasis and are clinically relevant in light of recent efforts to develop PAR antagonists to treat thrombotic disorders. 23313962 Pharmacokinetics of temoporfin-loaded liposome formulations: correlation of liposome and temoporfin blood concentration. Liposomal formulations of the highly hydrophobic photosensitizer temoporfin were developed in order to overcome solubility-related problems associated with the current therapy scheme. We have incorporated temoporfin into liposomes of varying membrane composition, cholesterol content, and vesicle size. Specifically, two phosphatidyl oligoglycerols were compared to PEG2000-DSPE with respect to the ability to prolong circulation half life of the liposomal carrier. We measured the resulting pharmacokinetic profile of the liposomal carrier and the incorporated temoporfin in a rat model employing a radioactive lipid label and (14)C-temoporfin. The data for the removal of liposomes and temoporfin were analyzed in terms of classical pharmacokinetic theory assuming a two-compartment model. This model, however, does not allow in a straightforward manner to distinguish between temoporfin eliminated together with the liposomal carrier and temoporfin that is first transferred to other blood components (e. g. plasma proteins) before being eliminated from the blood. We therefore additionally analyzed the data based on two separate one-compartment models for the liposomes and temoporfin. The model yields the ratio of the rate constant of temoporfin elimination together with the liposomal carrier and the rate constant of temoporfin elimination following the transfer to e. g. plasma proteins. Our analysis using this model demonstrates that a fraction of temoporfin is released from the liposomes prior to being eliminated from the blood. In case of unmodified liposomes this temoporfin release was observed to increase with decreasing bilayer fluidity, indicating an accelerated temoporfin transfer from gel-phase liposomes to e. g. plasma proteins. Interestingly, liposomes carrying either one of the three investigated surface-modifying agents did not adhere to the tendencies observed for unmodified liposomes. Although surface-modified liposomes exhibited improved pharmacokinetic properties with regard to the liposomal carrier, an enhanced temoporfin loss and elimination from the PEGylated-liposomes was observed. This effect was more pronounced for PEGylated liposomes than for the two oligo-glycerols. Our combined experimental-theoretical approach for in vivo plasma re-distribution of liposomal drugs may help to optimize colloidal drug carrier systems. 23301246 Dye sensitised solar cells with nickel oxide photocathodes prepared via scalable microwave sintering. Photoactive NiO electrodes for cathodic dye-sensitised solar cells (p-DSCs) have been prepared with thicknesses ranging between 0.4 and 3.0 μm by spray-depositing pre-formed NiO nanoparticles on fluorine-doped tin oxide (FTO) coated glass substrates. The larger thicknesses were obtained in sequential sintering steps using a conventional furnace (CS) and a newly developed rapid discharge sintering (RDS) method. The latter procedure is employed for the first time for the preparation of p-DSCs. In particular, RDS represents a scalable procedure that is based on microwave-assisted plasma formation that allows the production in series of mesoporous NiO electrodes with large surface areas for p-type cell photocathodes. RDS possesses the unique feature of transmitting heat from the bulk of the system towards its outer interfaces with controlled confinement of the heating zone. The use of RDS results in a drastic reduction of processing times with respect to other deposition methods that involve heating/calcination steps with associated reduced costs in terms of energy. P1-dye sensitized NiO electrodes obtained via the RDS procedure have been tested in DSC devices and their performances have been analysed and compared with those of cathodic DSCs derived from CS-deposited samples. The largest conversion efficiencies (0.12%) and incident photon-to-current conversion efficiencies, IPCEs (50%), were obtained with sintered NiO electrodes having thicknesses of ~1.5-2.0 μm. In all the devices, the photogenerated holes in NiO live significantly longer (τ(h) ~ 1 s) than have previously been reported for P1-sensitized NiO photocathodes. In addition, P1-sensitised sintered electrodes give rise to relatively high photovoltages (up to 135 mV) when the triiodide-iodide redox couple is used. 23448860 Extremely low-frequency magnetic field induces manganese accumulation in brain, kidney and liver of rats. The aim of the present study was to determine the effects of extremely low-frequency magnetic field (ELF-MF) on accumulation of manganese (Mn) in the kidney, liver and brain of rats. A total of 40 rats were randomly divided into eight groups. Four control groups received 0, 3.75, 15 and 60 mg Mn per kg body weight orally every 2 days for 45 days, respectively. The remaining four groups received same concentrations of Mn and were also exposed to ELF-MF (1.5 mT; 50 Hz) for 4 h for 5 days a week during 45 days. Following the last exposure, kidney, liver and brain were taken from all rats and they were analyzed for Mn accumulation levels using an inductively coupled plasma-optical emission spectrometer. In result of the current study, we observed that Mn levels in brain, kidney and liver were higher in Mn groups than in control groups. Mn levels in brain, kidney and liver were also higher in Mn plus ELF-MF groups than in Mn groups. In conclusion, result of the current study showed that the ELF-MF induced manganese accumulation in kidney, liver and brain of rats. 23143620 Induction of skin sensitization is augmented in Nrf2-deficient mice. Several in vitro DNA microarray studies have shown the importance of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in skin sensitization. Nevertheless, the exact in vivo role of the Nrf2-Keap1 pathway during the induction of skin sensitization remains unknown. To study the function of Nrf2, a local lymph node assay was performed in wild-type and Nrf2-deficient mice using 2,4-dinitrochlorobenzene. The Nrf2-deficient mice show a more pronounced response, indicating that Nrf2 is involved in dampening the induction of skin sensitization. 23645249 Repression of mammary adipogenesis by genistein limits mammosphere formationof human MCF-7 cells. Mammary adipose tissue may contribute to breast cancer development and progression by altering neighboring epithelial cell behavior and phenotype through paracrine signaling. Dietary exposure to soy foods is associated with lower mammary tumor risk and reduced body weight and adiposity in humans and in rodent breast cancer models. Despite the suggested linkage between obesity and breast cancer, the local influence of bioactive dietary components on mammary adiposity for anti-tumor effects remains unknown. Herein, we report that post-weaning dietary exposure to soy protein isolate and its bioactive isoflavone genistein lowered mammary adiposity and increased mammary tumor suppressor PTEN and E-cadherin expression in female mice, relative to control casein diet. To ascertain genistein's role in mammary adipose deposition that may affect underlying epithelial cell phenotype, we evaluated genistein's effects on SV40-immortalized mouse mammary stromal fibroblast-like (MSF) cells during differentiation to adipocytes. MSF cultured in differentiation medium with 40 nM genistein showed reductions in mature adipocyte numbers, triglyceride accumulation, and PPARγ and fatty acid synthase transcript levels. Genistein inhibition of adipose differentiation was accompanied by increased estrogen receptor (ER)-β gene expression and was modestly recapitulated by ERβ selective agonist 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN). Reduction of ERβ expression by siRNA targeting increased PPARγ transcript levels and stromal fibroblast differentiation into mature adipocytes; the latter was reversed by genistein but not DPN. Conditioned medium from genistein-treated adipocytes diminished anchorage-independent mammosphere formation of human MCF-7 breast cancer cells. Our results suggest a mechanistic pathway to support direct regulation by genistein of mammary adiposity for breast cancer prevention. 22745189 The response to sulpiride in social anxiety disorder: D2 receptor function. Some previous studies have suggested that patients with social anxiety disorder (SAD) have a hypoactive central dopaminergic system. Supporting this there have been reports from neuroimaging studies of reduced striatal D2 receptor binding in subjects with SAD. The aim of this study was to investigate D2 receptor sensitivity in patients with SAD compared with a group of matched, healthy controls using a neuroendocrine challenge with the selective D2 antagonist, sulpiride. D2 receptor function was assessed in 23 subjects with generalized SAD and 23 matched, healthy controls using a challenge with 400 mg of a selective D2 antagonist, sulpiride in a randomized, placebo-controlled, crossover design. Response to sulpiride was measured by the change in prolactin level and changes in self-rated measures of social anxiety, mood and the ability to experience pleasure. There was no significant difference in prolactin response to sulpiride between the two groups. Sulpiride resulted in no effect in either the SAD or healthy control group on measures of social anxiety, mood or the ability to experience pleasure. Contrary to our hypothesis, in this study we found no evidence of reduced D2 receptor function in subjects with SAD compared with healthy controls. 23064749 Evolutionary dynamism of the primate LRRC37 gene family. Core duplicons in the human genome represent ancestral duplication modules shared by the majority of intrachromosomal duplication blocks within a given chromosome. These cores are associated with the emergence of novel gene families in the hominoid lineage, but their genomic organization and gene characterization among other primates are largely unknown. Here, we investigate the genomic organization and expression of the core duplicon on chromosome 17 that led to the expansion of LRRC37 during primate evolution. A comparison of the LRRC37 gene family organization in human, orangutan, macaque, marmoset, and lemur genomes shows the presence of both orthologous and species-specific gene copies in all primate lineages. Expression profiling in mouse, macaque, and human tissues reveals that the ancestral expression of LRRC37 was restricted to the testis. In the hominid lineage, the pattern of LRRC37 became increasingly ubiquitous, with significantly higher levels of expression in the cerebellum and thymus, and showed a remarkable diversity of alternative splice forms. Transfection studies in HeLa cells indicate that the human FLAG-tagged recombinant LRRC37 protein is secreted after cleavage of a transmembrane precursor and its overexpression can induce filipodia formation. 23562369 The pathological effects of Heminecrolysin, a dermonecrotic toxin from Hemiscorpius lepturus scorpion venom are mediated through its lysophospholipase D activity. We have previously identified Heminecrolysin, a sphingomyelinase D (SMaseD), as the major protein responsible for the main pathological effects observed following Hemiscorpius (H.) lepturus scorpion envenomation. We aimed herein to further investigate the kinetics and molecular mechanisms triggered by Heminecrolysin to initiate hematological disorders and inflammatory reaction. We show that Heminecrolysin highly hydrolyzes lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA) and choline, with a Vmax = 1481 ± 51 μmol/min/mg and a Km = 97 ± 16.78 μM, at a much lesser extend sphingomyelin but not phosphatidylcholine substrates. Its lysophospholipase D (lysoPLD) catalytic efficiency, up to three orders of magnitude higher, comparatively to spider's SMaseDs (newly referred as phospholipases D; PLDs), could explain its strong hemolytic capacity. Chelating agents such as EDTA, EGTA, and 1, 10-phenantroline blocked Heminecrolysin-induced LPC hydrolysis at 98, 48, and 70% respectively. Hemolysis blockade occurs only when the toxin is added to erythrocytes in the presence of serum, source of LPC and complement, indicating that the production of LPA and the presence of complement are mandatory for hemolysis. Moreover, we show that Heminecrolysin efficiently binds to erythrocyte's membrane and provokes phosphatidylserine (PS) translocation without cleavage of glycophorin A, suggesting that, unlike spider's PLDs, complement was activated only via the classical pathway. Interestingly, Heminecrolysin was found to induce PS exposure on human nucleated Jurkat T cells, to stimulate secretion of the pro-inflammatory (TNF-α, IL-6), and anti-inflammatory (IL-10) cytokines by human monocytes, and to provoke a disseminated intravascular coagulation on chick embryo chorioallantoic membrane model system. Taken together, our results indicate that Heminecrolysin evokes the major characteristic clinical features of H. lepturus envenomation by using mainly its lysoPLD, rather than its SMaseD's, activity. 23291118 Syntheses and evaluation of the antioxidant activity of novel methoxypsoralen derivatives. A series of 5- and 8-methoxypsoralen (MOP) analogs, suitable for structure-antioxidative/anti-inflammatory activity relationship studies, were synthesized using as key-reactions the selective monobromination of MOPs with N-bromosaccharin and either a Heck reaction or a Suzuki coupling or a Suzuki coupling followed by a Wittig reaction to install side-chains of the acrylate- or benzoate- or cinnamate-type, respectively. The 8-MOP analogs 19 and 24, incorporating at position 5 of the psoralen nucleus a butyl acrylate or a tert-butyl cinnamate moiety, were the most powerful inhibitors of soybean LOX and inhibited effectively lipid peroxidation. Analog 19 was a more potent anti-inflammatory agent than the reference compound indomethacin and of comparable cytocompatibility to 8-MOP whereas analog 24 was a weaker inhibitor of inflammation than indomethacin and significantly more cytotoxic than 8-MOP. The results of the biological tests are discussed in terms of structural characteristics. 23580652 A lipoprotein receptor cluster IV mutant preferentially binds amyloid-β and regulates its clearance from the mouse brain. Soluble low-density lipoprotein receptor-related protein-1 (sLRP1) binds ~ 70% of amyloid β-peptide (Aβ) in human plasma. In Alzheimer's disease (AD) and individuals with mild cognitive impairment converting to AD, plasma sLRP1 levels are reduced and sLRP1 is oxidized which results in diminished Aβ peripheral binding and higher levels of free Aβ in plasma. Experimental studies have shown that free circulating Aβ re-enters the brain and that sLRP1 and/or its recombinant wild-type cluster IV (WT-LRPIV) prevent Aβ from entering the brain. Treatment of Alzheimer's APPsw+/0 mice with WT-LRPIV has been shown to reduce brain Aβ pathology. In addition to Aβ, LRPIV binds multiple ligands. To enhance LRPIV binding for Aβ relative to other LRP1 ligands, we generated a library of LRPIV-derived fragments and full-length LRPIV variants with glycine (G) replacing aspartic acid (D) residues 3394, 3556 and 3674 in the calcium binding sites. Compared to WT-LRPIV, a lead LRPIV-D3674G mutant had 1.6-fold and 2.7-fold higher binding affinity for Aβ40 and Aβ42 in vitro, respectively, and a lower binding affinity for other LRP1 ligands, e.g., apoliporotein E2, E3 and E4 (1.3-1.8-fold), tissue plasminogen activator (2.7-fold), matrix metalloproteinase-9 (4.1-fold) and Factor Xa (3.8-fold). LRPIV-D3674G cleared mouse endogenous brain Aβ40 and Aβ42 25-27% better than WT-LRPIV. A 3-month subcutaneous treatment of APPsw+/0 mice with LRPIV-D3674G (40 μg/kg/day) reduced Aβ40 and Aβ42 levels in the hippocampus, cortex and cerebrospinal fluid by 60-80%, and improved cerebral blood flow responses and hippocampal function at 9 months of age. Thus, LRPIV-D3674G is an efficient new Aβ clearance therapy. 23115086 Effects of hypothermia on the disposition of morphine, midazolam, fentanyl, and propofol in intensive care unit patients. Therapeutic hypothermia (TH) may induce pharmacokinetic changes that may affect the level of sedation. We have compared the disposition of morphine, midazolam, fentanyl, and propofol in TH with normothermia in man. Fourteen patients treated with TH following cardiac arrest (33-34°C) were compared with eight matched critically ill patients (36-38°C). Continuous infusions of morphine and midazolam were stopped and replaced with infusions of fentanyl and propofol to describe elimination and start of infusion pharmacokinetics, respectively. Serial serum and urine samples were collected for 6-8 hours for validated quantification and subsequent pharmacokinetic analysis. During TH, morphine elimination half-life (t(1/2)) was significantly higher, while total clearance (CL(tot)) was significantly lower (median [semi-interquartile range (s-iqr)]): t(1/2), 266 (43) versus 168 (11) minutes, P < 0.01; CL(tot), 1201 (283) versus 1687 (200) ml/min, P < 0.01. No significant differences were seen for midazolam. CL(tot) of fentanyl and propofol was significantly lower in hypothermic patients [median (s-iqr)]: fentanyl, 726 (230) versus 1331 (678) ml/min, P < 0.05; propofol, 2046 (305) versus 2665 (223) ml/min, P < 0.05. Compared with the matched, normothermic intensive care unit patients, t(1/2) of morphine was significantly higher during TH. CL(tot) was lower during TH for morphine, fentanyl, and propofol but not for midazolam. Reducing the infusion rates of morphine, fentanyl, and propofol during TH is encouraged. 23394393 Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy. In the past decade, advances in pharmacogenetics and pharmacogenomics (PGx) have gradually unveiled the genetic basis of interindividual differences in drug responses. A large portion of these advances have been made in the field of anticancer therapy. Currently, the US FDA has updated the package inserts of approximately 30 anticancer agents to include PGx information. Given the complexity of this genetic information (e.g., tumor mutation and gene overexpression, chromosomal translocation and germline variations), as well as the variable level of scientific evidence, the FDA recommendation and potential action needed varies among drugs. In this review, we have highlighted some of these PGx discoveries for their scientific values and utility in improving therapeutic efficacy and reducing side effects. Furthermore, examples are also provided for the role of PGx in new anticancer drug development by revealing novel druggable targets. 23621358 GALACTOSYLATED MICELLES FOR A RIBAVIRIN PRODRUG TARGETING TO HEPATOCYTES. Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, i.e., ASGPR, were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of alpha,beta-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLA-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, i.e. RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver-targeted RBV tripalmitate-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometric size. By in vitro experiments, the specificity of RBV tripalmitate-loaded PHEA-EDA-PLA-GAL micelles toward HepG2 was demonstrated by using a competitive inhibition assay in the presence of free GAL. This finding raises hope in terms of future micelles-based liver-targeted drug delivery strategy for the hepatitis C treatment. 23347683 A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: synthesis and structure-activity relationships. A series of 3-(phenoxy-phenyl-methyl)-pyrrolidine analogues were discovered to be potent and balanced norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. Several of these compounds were identified to have suitable in vitro pharmacokinetic properties for an orally dosed and CNS-targeted drug. Compound 39b, in particular, was identified as a potent NET and SERT reuptake inhibitor (NSRI) with minimal off-target activity and demonstrated robust efficacy in the spinal nerve ligation model of pain behavior. 23432582 Bisacylimidoselenocarbamates Cause G2/M Arrest Associated with the Modulation of CDK1 and Chk2 in Human Breast Cancer MCF-7 Cells. Bisacylimidoselenocarbamate derivatives (BSC) are potent anticancer agents with a strong cytotoxic activity against different types of tumour cells. Based in phosphatidylserine exposure on the cell membranes we show that BSC treatment resulted in enhanced cell death in leukaemia CCRF-CEM cells. DNA fragmentation detection in breast adenocarcinoma MCF-7 cells showed that BSC triggered cell death is concentration and time dependent. We also show that two of these compounds, BSC 3g and 3n, cause cell-cycle arrest in the late G2/M in MCF-7 cells. Consistent with this, a reduction in CDK1 and CDK2 expression with no change in cyclin A an B1 was observed in this cell line. Activation of caspase-2 was also detected. However, the involvement of the caspase-dependent pathway in the process of cell death induced by either BSC 3g or 3n is discarded since cell death could not be prevented by pretreatment with the pancaspase inhibitor z-VAD-fmk. Moreover, since reduced levels of p21CIP1 and Chk2 proteins but no change in p53 levels could be detected in MCF-7 cells after BSC 3g or 3n treatment our results suggest that BSC treated cells die from lethal mitosis. 23455312 Cerebrovascular Dilation via Selective Targeting of the Cholane Steroid-Recognition Site in the BK Channel β1-Subunit by a Novel Nonsteroidal Agent. The Ca(2+)/voltage-gated K(+) large conductance (BK) channel β1 subunit is particularly abundant in vascular smooth muscle. By determining their phenotype, BK β1 allows the BK channels to reduce myogenic tone, facilitating vasodilation. The endogenous steroid lithocholic acid (LCA) dilates cerebral arteries via BK channel activation, which requires recognition by a BK β1 site that includes Thr169. Whether exogenous nonsteroidal agents can access this site to selectively activate β1-containing BK channels and evoke vasodilation remain unknown. We performed a chemical structure database similarity search using LCA as a template, along with a two-step reaction to generate sodium 3-hydroxyolean-12-en-30-oate (HENA). HENA activated the BK (cbv1 + β1) channels cloned from rat cerebral artery myocytes with a potency (EC50 = 53 μM) similar to and an efficacy (×2.5 potentiation) significantly greater than that of LCA. This HENA action was replicated on native channels in rat cerebral artery myocytes. HENA failed to activate the channels made of cbv1 + β2, β3, β4, or β1T169A, indicating that this drug selectively targets β1-containing BK channels via the BK β1 steroid-sensing site. HENA (3-45 μM) dilated the rat and C57BL/6 mouse pressurized cerebral arteries. Consistent with the electrophysiologic results, this effect was larger than that of LCA. HENA failed to dilate the arteries from the KCNMB1 knockout mouse, underscoring BK β1's role in HENA action. Finally, carotid artery-infusion of HENA (45 μM) dilated the pial cerebral arterioles via selective BK-channel targeting. In conclusion, we have identified for the first time a nonsteroidal agent that selectively activates β1-containing BK channels by targeting the steroid-sensing site in BK β1, rendering vasodilation. 23579487 Cellular insulin resistance disrupts leptin-mediated control of neuronal signaling and transcription. Central resistance to the actions of insulin and leptin is associated with the onset of obesity and type 2 diabetes mellitus (T2DM), whereas leptin and insulin signaling is essential for both glucose and energy homeostasis. Although it is known that leptin resistance can lead to attenuated insulin signaling, whether insulin resistance can lead to or exacerbate leptin resistance is unknown. To investigate the molecular events underlying crosstalk between these signaling pathways, immortalized hypothalamic neuronal models, rHypoE-19 and mHypoA-2/10, were utilized. Prolonged insulin exposure was used to induce cellular insulin resistance, and thereafter leptin-mediated regulation of signal transduction and gene expression was assessed. Leptin directly repressed agouti-related peptide (AgRP) mRNA levels, but induced urocortin-2 (UCN2), insulin receptor substrate-1 (IRS1), IRS2, and IR transcription, through leptin-mediated phosphatidylinositol-3-kinase (PI3K)/Akt activation. Neuronal insulin resistance, as assessed by attenuated Akt phosphorylation, blocked leptin-mediated signal transduction, and AgRP, UCN2, IRS1, IRS2 and IR synthesis. Insulin resistance caused a substantial decrease in IR protein levels, forkhead box protein 1 (FoxO1) phosphorylation, and an increase in suppressor of cytokine signaling 3 (SOCS3) protein levels. Cellular insulin resistance may cause or exacerbate neuronal leptin resistance, and by extension, obesity. It is essential to unravel the effects of neuronal insulin resistance given that both peripheral, as well as the less widely studied central insulin resistance, may contribute to the development of metabolic, reproductive and cardiovascular disorders. This study provides an improved understanding of the complex cellular crosstalk between insulin-leptin signal transduction that is disrupted during neuronal insulin resistance. 23564329 A large gap opening of graphene induced by the adsorption of CO on the Al-doped site. We investigated CO adsorption on the pristine, Stone-Wales (SW) defected, Al- and Si- doped graphenes by using density functional calculations in terms of geometric, energetic and electronic properties. It was found that CO molecule is weakly adsorbed on the pristine and SW defected graphenes and their electronic properties were slightly changed. The Al- and Si- doped graphenes show high reactivity toward CO, so calculated adoption energies are about -11.40 and -13.75 kcal mol(-1) in the most favorable states. It was found that, among all the structures, the electronic properties of Al-doped graphene are strongly sensitive to the presence of CO molecule. We demonstrate the existence of a large Eg opening of 0.87 eV in graphene which is induced by Al-doping and CO adsorption. 23089896 ATP binding cassette transporters in two distinct compartments of the skin contribute to transdermal absorption of a typical substrate. The role of two ATP binding cassette transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), in transdermal absorption of a typical common substrate was examined in vivo. Skin and plasma concentrations of rhodamine123 (Rho123) after dermal application were reduced in P-gp knockout (mdr1a/1b⁻/⁻) mice and were below the detection limit in P-gp and BCRP triple-knockout (mdr1a/1b/bcrp⁻/⁻) mice. Lower epidermal-to-hypodermal permeation of Rho123 in mdr1a/1b/bcrp⁻/⁻ mouse skin compared to the wild-type mouse skin was confirmed in an Ussing-type chamber experiment. The reduction in skin concentration after dermal application in mdr1a/1b/bcrp⁻/⁻ mice was greater in the dermis than in the epidermis, suggesting functional expressions of these transporters in two distinct skin compartments. Coadministration of the inhibitor itraconazole reduced the skin and plasma concentrations of Rho123 in the wild-type mice, but not in mdr1a/1b/bcrp⁻/⁻ mice, and a marked decrease of Rho123 concentration was seen in the dermis, demonstrating that the functional activities of these transporters can be modulated in vivo. On the other hand, the distribution of Rho123 after intravenous infusion was higher in mdr1a/1b/bcrp⁻/⁻ mice than in the wild-type mice. This supports the occurrence of vectorial transport from the skin into systemic circulation, and is consistent with the immunohistochemical localization of P-gp and BCRP in mouse dermal endothelial cells. BCRP was immunohistochemically identified in human epidermis and dermal endothelial cells. Thus, our findings show that ABC transporters in different compartments of the skin contribute to transdermal absorption of a typical substrate in vivo and can be modulated by a specific inhibitor. These findings have implications for transdermal drug delivery. 23339974 Ubiquitin - omics reveals novel networks and associations with human disease. Human neurodegenerative and infectious diseases and tumorigenesis are associated with alterations in ubiquitin pathways. Over 10% of the genome encode for genes that either bind or manipulate ubiquitin to affect a large proportion of biological processes. This has been the basis for the development of approaches allowing the enrichment of ubiquitinated proteins for comparisons using proteomics and mass spectrometry. Tools such as tagged tandem ubiquitin binding domains, chemically derivatized ubiquitin or anti-gly-gly-lys antibodies combined with mass spectrometry have contributed to surveys of poly-ubiquitinated proteins, poly-ubiquitin linkage diversity and protein ubiquitination sites and their relation to other posttranslational modifications at a proteome wide level, providing insights in to how dynamic alterations in ubiquitination and deubiquitination steps are associated with normal physiology and pathogenesis. 23411206 Simultaneous detection of multiple adulterants in dry milk using macro-scale Raman chemical imaging. The potential of Raman chemical imaging for simultaneously detecting multiple adulterants in milk powder was investigated. Potential chemical adulterants, including ammonium sulphate, dicyandiamide, melamine, and urea, were mixed together into skim dry milk in the concentration range of 0.1-5.0% for each adulterant. Using a 785-nm laser, a Raman imaging system acquired hyperspectral images in the wavenumber range of 102-2538 cm(-1) for a 25 × 25 mm(2) area of each mixture sample, with a spatial resolution of 0.25 mm. Self-modelling mixture analysis (SMA) was used to extract pure component spectra, by which the four types of the adulterants were identified at all concentration levels based on their spectral information divergence values to the reference spectra. Raman chemical images were created using the contribution images from SMA, and their use to effectively visualise identification and spatial distribution of the multiple adulterant particles in the dry milk was demonstrated. 23583556 Variation in the dorsal gradient distribution is a source for modified scaling of germ layers in Drosophila. Specification of germ layers along the dorsoventral axis by morphogenetic gradients is an ideal model to study scaling properties of gradients and cell fate changes during evolution. Classical anatomical studies in divergent insects (e.g., flies and grasshoppers) revealed that the neuroectodermal size is conserved and originates similar numbers of neuroblasts of homologous identity [1-3]. In contrast, mesodermal domains vary significantly in closely related Drosophila species [4]. To further investigate the underlying mechanisms of scaling of germ layers across Drosophila species, we quantified the Dorsal (Dl)/NF-κB gradient, the main morphogenetic gradient that initiates separation of the mesoderm, neuroectoderm, and ectoderm [5-7]. We discovered a variable range of Toll activation across species and found that Dl activates mesodermal genes at the same threshold levels in melanogaster sibling species. We also show that the Dl gradient distribution can be modulated by nuclear size and packing densities. We propose that variation in mesodermal size occurs at a fast evolutionary rate and is an important mechanism to define the ventral boundary of the neuroectoderm. 23122064 Thermal stability of yeast hydrolysate as a novel anti-obesity material. We examined the thermal stability of yeast hydrolysates before and after ultrafiltration (UF) in vitro, and the anti-obesity activity of yeast hydrolysates before and after heat treatment in vivo. Yeast hydrolysate after UF showed significantly higher thermal stability than before UF. Yeast hydrolysates before and after UF showed 3 and 4 thermal transition peaks in their thermograms, respectively, and the total thermal denaturation enthalpies of yeast hydrolysates before and after UF were 69.5 and 36.5 J/g, respectively. For the anti-obesity activity study, yeast hydrolysates before and after heating were administered ad libitum with water to 7-week-old male SD rats. The administration of yeast hydrolysate (YH-control; no heat treatment, YH-1; heat treatment at 140°C, and YH-2; heat treatment at 160°C) significantly increased mRNA expression of cocaine- and amphetamine-regulated transcript (CART) compared with control rats (saline administration). However, there was no significant difference between the heat-treated groups and YH-control and there was no significant difference in neuropeptide Y expression between the heat-treated groups and YH-control. These results suggest that yeast hydrolysate can be use an anti-obesity material after heat treatment. 23337600 ⁹⁹mTc-(Me)FGCDEVD, a potential tracer for apoptosis detection. (Me)FGC(Bz)DEVD was radiolabeled with technetium-99m in high yield. This tracer was preferentially accumulated in apoptotic cells in the in vitro studies. Tumor uptake occurred in vivo after cisplatin injection due to the apoptosis induction, which not observed in the untreated tumors. Therefore, (99m)Tc-(Me)FGCDEVD is a potential tracer for apoptosis detection. 23561157 Characterization of Hachi (Camelus dromedarius) fat extracted from the hump. In this work, the characteristics of fat from the hump of young camels (Hachi) were evaluated. The physicochemical properties of the fat were as follows: melting point, 45°C; saponification value, 202.3mg KOH/g oil; refractive index (60°C), 1.468; unsaponifiable matter, 1.37%; free fatty acids (as the percentage of oleic acid), 0.96%; and peroxide value, 3.37mequiv. O2/kg oil. High-resolution (1)H nuclear magnetic resonance ((1)H NMR) was used for the direct determination of the iodine value of Hachi fat (62.74g/100g oil). The Hachi fat was composed primarily of oleic acid (33.35%), followed by palmitic acid (26.16%), stearic acid (10.07%), palmitelaidic acid (9.56%) and myristic acid (8.83%). The thermal properties were assessed by thermogravimetry (TG) and derivative thermogravimetry (DTG). The results of the present analytical study showed that Hachi fat could be used in food products and as an important source of biological materials. 23570451 Coalescence of Repelling Colloidal Droplets: A Route to Monodisperse Populations. Populations of droplets or particles dispersed in a liquid may evolve through Brownian collisions, aggregation, and coalescence. We have found a set of conditions under which these populations evolve spontaneously toward a narrow size distribution. The experimental system consists of poly(methyl methacrylate) (PMMA) nanodroplets dispersed in a solvent (acetone) + nonsolvent (water) mixture. These droplets carry electrical charges, located on the ionic end groups of the macromolecules. We used time-resolved small angle X-ray scattering to determine their size distribution. We find that the droplets grow through coalescence events: the average radius ⟨R⟩ increases logarithmically with elapsed time while the relative width σR/⟨R⟩ of the distribution decreases as the inverse square root of ⟨R⟩. We interpret this evolution as resulting from coalescence events that are hindered by ionic repulsions between droplets. We generalize this evolution through a simulation of the Smoluchowski kinetic equation, with a kernel that takes into account the interactions between droplets. In the case of vanishing or attractive interactions, all droplet encounters lead to coalescence. The corresponding kernel leads to the well-known "self-preserving" particle distribution of the coalescence process, where σR/⟨R⟩ increases to a plateau value. However, for droplets that interact through long-range ionic repulsions, "large + small" droplet encounters are more successful at coalescence than "large + large" encounters. We show that the corresponding kernel leads to a particular scaling of the droplet-size distribution-known as the "second-scaling law" in the theory of critical phenomena, where σR/⟨R⟩ decreases as 1/√⟨R⟩ and becomes independent of the initial distribution. We argue that this scaling explains the narrow size distributions of colloidal dispersions that have been synthesized through aggregation processes. 23010867 Influence of pH, light cycle, and temperature on ecotoxicity of four sulfonylurea herbicides towards Lemna gibba. In chemical regulation, e.g. the EU Water Framework Directive, REACH, or the Pesticide Directive, standardized ecotoxicological tests are applied to evaluate and rank the hazard of compounds and for deriving environmental quality standards (EQS). Standardized test methods prescribe fixed testing conditions e.g. specific temperature, pH, light intensity etc. However, environmental conditions under which the organisms live are rarely identical to the standard conditions. Thus, the ecotoxicity of compounds found in standard test is not only a function of the compounds inherent physico-chemical properties but is also affected by test conditions. It is therefore important to study the effect of changes in test conditions in order to get reliable input ecotoxicity data for assessing the potential risk posed by a compound. The objective of this study was to investigate the implications of changing test conditions on the toxicity of four sulfonylurea herbicides (SUs). The toxicity of the four SUs towards Lemna gibba was investigated at three pH levels (6, 7.5 and 9), at two temperatures (15 and 24 °C) and two light regimes (continuous and 12:12 h light:dark cycle) The EC50 increased twofold to tenfold for the four SUs when pH was increased from 6 to 9. Decreasing the temperature from 24 to 15 °C or introducing a dark:light cycle did not cause any trends in changes in toxicity. The results show that test conditions can have an effect on the toxicity and this should be considered when the standard test results are used for derivation of EQS. 23069627 Cathepsin K knockout mitigates high-fat diet-induced cardiac hypertrophy and contractile dysfunction. The cysteine protease cathepsin K has been implicated in pathogenesis of cardiovascular disease. We hypothesized that ablation of cathepsin K protects against obesity-associated cardiac dysfunction. Wild-type mice fed a high-fat diet exhibited elevated heart weight, enlarged cardiomyocytes, increased left ventricular wall thickness, and decreased fractional shortening. All these changes were reconciled in cathepsin K knockout mice. Cathepsin K knockout partly reversed the impaired cardiomyocyte contractility and dysregulated calcium handling associated with high-fat diet. Additionally, cathepsin K knockout alleviated whole-body glucose intolerance and improved insulin-stimulated Akt phosphorylation in high-fat diet-fed mice. High-fat feeding increased the expression of cardiac hypertrophic proteins and apoptotic markers, which were inhibited by cathepsin K knockout. Furthermore, high-fat feeding resulted in cathepsin K release from lysosomes into the cytoplasm. In H9c2 myoblasts, silencing of cathepsin K inhibited palmitic acid-induced release of cytochrome c from mitochondria and expression of proapoptotic signaling molecules. Collectively, our data indicate that cathepsin K contributes to the development of obesity-associated cardiac hypertrophy and may represent a potential target for the treatment to obesity-associated cardiac anomalies. 23605046 Computational identification of functional introns: high positional conservation of introns that harbor RNA genes. An appreciable fraction of introns is thought to have some function, but there is no obvious way to predict which specific intron is likely to be functional. We hypothesize that functional introns experience a different selection regime than non-functional ones and will therefore show distinct evolutionary histories. In particular, we expect functional introns to be more resistant to loss, and that this would be reflected in high conservation of their position with respect to the coding sequence. To test this hypothesis, we focused on introns whose function comes about from microRNAs and snoRNAs that are embedded within their sequence. We built a data set of orthologous genes across 28 eukaryotic species, reconstructed the evolutionary histories of their introns and compared functional introns with the rest of the introns. We found that, indeed, the position of microRNA- and snoRNA-bearing introns is significantly more conserved. In addition, we found that both families of RNA genes settled within introns early during metazoan evolution. We identified several easily computable intronic properties that can be used to detect functional introns in general, thereby suggesting a new strategy to pinpoint non-coding cellular functions. 23142558 The 17-β-oestradiol inhibits osteoclast activity by increasing the cannabinoid CB2 receptor expression. Bone is a highly metabolically active tissue and its formation and resorption is at the base of bone remodelling. The critical importance of a balanced bone remodelling is demonstrated by human diseases, i.e. osteoporosis, in which a net increase in bone resorption is responsible of skeleton weakening and fracture risk. Oestrogens display anti-resorptive properties on bone metabolism. Indeed, the so-called post-menopausal osteoporosis occurs after interruption of gonad function and benefits from hormonal replacement treatment. Recently, an important role for the endocannabinoid system in the regulation of skeletal remodelling in human has also been shown. In particular, we showed that CB2 stimulation is able to reduce the number of human OCs in vitro. Here, we provide unprecedented evidence that 17-β-oestradiol administration inhibits activity and formation of human OCs in vitro, demonstrating that oestrogens are able to induce an increase of CB2 expression probably through the recruitment of a putative oestrogens responsive element in the CB2 encoding for gene. 23540585 Heart failure therapy in patients with coronary artery disease. Heart failure and coronary artery disease share many risk factors. Coronary artery disease often pre-dates the development of heart failure with reduced ejection fraction. A diagnosis of heart failure should be considered in any patient with a history of coronary artery disease who presents with breathlessness, ankle oedema or fatigue. Several therapies, such as renin-angiotensin antagonists and B blockers, have been proven to improve survival in patients with heart failure with reduced ejection fraction but evidence for effectiveness in heart failure with preserved ejection fraction is lacking. The management of heart failure and coronary artery disease overlaps considerably but can also be conflicting. Optimal risk factor management is key to preventing progression to heart failure in patients with coronary artery disease. 23197771 Upregulation of Mer receptor tyrosine kinase signaling attenuated lipopolysaccharide-induced lung inflammation. Mer receptor tyrosine kinase (Mer) signaling plays a central role in the intrinsic inhibition of the inflammatory response to Toll-like receptor activation. Previously, we found that lung Mer protein expression decreased after lipopolysaccharide (LPS) treatment due to enhanced Mer cleavage. The purpose of the present study was to examine whether pharmacologically restored membrane-bound Mer expression upregulates the Mer signaling pathways and suppresses lung inflammatory responses. Pretreatment with the ADAM17 (a disintegrin and metalloproteinase-17) inhibitor TAPI-0 (tumor necrosis factor alpha protease inhibitor-0) reduced LPS-induced production of soluble Mer protein in bronchoalveolar lavage (BAL) fluid, restored membrane-bound Mer expression, and increased Mer activation in alveolar macrophages and lungs after LPS treatment. TAPI-0 also enhanced Mer downstream signaling, including phosphorylation of protein kinase b, focal adhesion kinase, and signal transducer and activator of transcription 1. As expected from enhanced Mer signaling, TAPI-0 also augmented suppressor of cytokine signaling-1 and -3 mRNA and protein levels and inhibited nuclear factor κB activation at 4 and 24 hours after LPS treatment. TAPI-0 suppressed LPS-induced inflammatory cell accumulation, total protein level elevation in BAL fluid, and production of inflammatory mediators, including tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2. Additionally, the effects of TAPI-0 on the activation of Mer signaling and the production of inflammatory responses could be reversed by cotreatment with specific Mer-neutralizing antibody. Restored Mer protein expression by treatment with TAPI-0 efficiently prevents the inflammatory cascade during acute lung injury. 23580027 Female sexual dysfunction in women with thyroid disorders. Background. Few data exist on the prevalence of FSD in thyroid disorders. Aim. We evaluated FSD in women with thyroid diseases and in control age matched healthy women to investigate the relationship between sexual function, and thyroid hormones. Methods. One hundred and four women with thyroid diseases and 53 controls participated in the study. Eighteen with hyperthyroidism (Group1), 22 hypothyroidism (Group2), 45 Hashimoto's thyroiditis (Group3), 19 nodular goiter (Group4) underwent thyroid function evaluation and sonography. The Female Sexual Function Index (FSFI) assessed sexual function. Results. The prevalence of FSD was 46.1% in thyroid diseases and 20.7% in controls. Only in Group4, the prevalence (68.4 %) was significantly higher than in controls (P < 0.005). The mean total FSFI score were 20.1±7.1 in women with thyroid diseases and 25.6±4.7 in the controls (P<0.001). Compared with controls, there was a significant decrease of desire in Group2; desire, arousal and lubrication in Group3; desire, arousal, lubrication, orgasm and satisfaction in Group4. In thyroid diseases the prevalence of FSD was 53% and 42%, while in the controls was 55% and 20%, in menopausal and pre-menopausal groups, respectively. We found a significant inverse correlation between TSH and FSFI (r =-0.7, P= 0.01) in Group 4, which showed the lowest FSFI score (17.8±5.7) and the highest BMI (28.4±7.1 Kg/m2).Conclusions: Women with thyroid diseases present a higher prevalence of FSD than controls. Although our findings suggest a higher impairment of sexual function in Group4 and a role for TSH in FSD, further researches are needed. 23434322 Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives. Tet proteins oxidize 5-methylcytosine (mC) to generate 5-hydroxymethyl (hmC), 5-formyl (fC), and 5-carboxylcytosine (caC). The exact function of these oxidative cytosine bases remains elusive. We applied quantitative mass-spectrometry-based proteomics to identify readers for mC and hmC in mouse embryonic stem cells (mESC), neuronal progenitor cells (NPC), and adult mouse brain tissue. Readers for these modifications are only partially overlapping, and some readers, such as Rfx proteins, display strong specificity. Interactions are dynamic during differentiation, as for example evidenced by the mESC-specific binding of Klf4 to mC and the NPC-specific binding of Uhrf2 to hmC, suggesting specific biological roles for mC and hmC. Oxidized derivatives of mC recruit distinct transcription regulators as well as a large number of DNA repair proteins in mouse ES cells, implicating the DNA damage response as a major player in active DNA demethylation. 23588560 Population pharmacokinetic analysis of tacrolimus in the first year after pediatric liver transplantation. PURPOSES: Tacrolimus (TAC) is the most widely used immunosuppressant for the prevention of acute rejection after solid organ transplantation. Its pharmacokinetics (PK) show considerable variability, making TAC a good candidate for therapeutic drug monitoring (TDM). The principal aim of the study was to describe the PK of TAC in pediatric patients during the first year after transplantation. METHODS: Routine TDM trough levels of TAC were obtained from 42 pediatric liver allograft recipients during the first year after transplantation. A population PK model was developed using nonlinear mixed-effects modeling to describe TAC PK during this period and to explain the observed variability by means of patients' demographics, biochemical test results and physiological characteristics. RESULTS: The PK of TAC were best described by a two-compartment model with first-order elimination. Apparent volumes of the central compartment, intercomparmental clearance and maximum blood clearance estimates were 253 L, 115 L/day and 314 L/day, respectively. The absorption first-order rate and volume of peripheral compartment were fixed to 4.5 h(-1) and 100 L, respectively. While hematocrit levels, time after transplantation and bodyweight influenced TAC clearance, bodyweight was the only covariate retained on volume of distribution. CONCLUSIONS: We developed a TAC population PK model in pediatrics covering the first year after liver transplantation that may serve as a tool for TAC dose individualization as part of TDM. 23159729 Immunotoxic effects of oil sands-derived naphthenic acids to rainbow trout. Naphthenic acids are the major organic constituents in waters impacted by oil sands. To investigate their immunotoxicity, rainbow trout (Oncorhynchus mykiss) were injected with naphthenic acids extracted from aged oil sands tailings water. In two experiments, rainbow trout were injected intraperitoneally with 0, 10, or 100 mg/kg of naphthenic acids, and sampled after 5 or 21 d. Half of the fish from the 21 d exposure were co-exposed to inactivated Aeromonas salmonicida (A.s.) to induce an immune response. A positive control experiment was conducted using an intraperitoneal injection of 100 mg/kg of benzo[a]pyrene, a known immune suppressing compound. T-lymphocytes, B-lymphocytes, thrombocytes, and myeloid cells were counted in blood and lymphatic tissue using flow cytometry. In the 5d exposure, there was a reduction in blood leucocytes and spleen thrombocytes at the 100 mg/kg dose. However, at 21 d, leucocyte populations showed no effects of exposure with the exception that spleen thrombocyte populations increase at the 100 mg/kg dose. In the 21 d exposure, B- and T-lymphocytes in blood showed a significant Dose × A.s. interaction, indicating stimulated blood cell proliferation due to naphthenic acids alone as well as due to A.s. Naphthenic acid injections did not result in elevated bile fluorescent metabolites or elevated hepatic EROD activity. In contrast to naphthenic acids exposures, as similar dose of benzo[a]pyrene caused a significant decrease in B- and T-lymphocyte absolute counts in blood and relative B-lymphocyte counts in spleen. Results suggest that the naphthenic acids may act via a generally toxic mechanism rather than by specific toxic effects on immune cells. 23247010 Regulation of human carbonyl reductase 1 (CBR1, SDR21C1) gene by transcription factor Nrf2. Monomeric carbonyl reductase 1 (CBR1, SDR21C1) is a member of the short-chain dehydrogenase/reductase superfamily and is involved in the metabolism of anthracycline anti-cancer drugs, prostaglandins, and isatin, which is an endogenous inhibitor of monoamine oxidases. Additionally, cancer progression may be partly regulated by CBR1. In the present study, we screened more than 10 drugs for the induction of the human CBR1 gene to investigate its regulation. Of the drugs, butylated hydroxyanisole (BHA) was found to be an inducer. BHA induced the mRNA and protein expression of CBR1 in hepatoma HepG2 cells. In a luciferase reporter gene assay, the promoter region between -2062 bp and the transcription start site of CBR1 was also activated by BHA. The transcription factor Nrf2 is known to be activated by BHA. There are 2 anti-oxidant responsive elements (ARE) that are bound by Nrf2 in this region. Mutation analyses revealed that one of the AREs participates in the gene regulation of CBR1 by Nrf2. Electrophoretic mobility shift assay revealed that Nrf2 binds the site. Moreover, to determine whether the functional ARE of CBR1 is conserved with the promoter region of homologues in other species, the nucleotide sequences of the functional AREs of the Chcr1 and Chcr2 genes, which are the Chinese hamster homologues of CBR1, were determined. The region has 2 AREs, and these genes were also induced by the forced expression of Nrf2 (cotransfection of pNrf2) in the luciferase reporter gene assay. In conclusion, Nrf2 is a novel transcriptional regulator of CBR1 genes in humans and the Chinese hamster. Because the regulation of CBR1 appears to be important for diseases, the induction of CBR1 by Nrf2 may be a therapeutic target. 23201124 Substrates of IAP ubiquitin ligases identified with a designed orthogonal E3 ligase, the NEDDylator. Inhibitors of Apoptosis Protein (IAPs) are guardian ubiquitin ligases that keep classic proapoptotic proteins in check. Systematic identification of additional IAP substrates is challenged by the heterogeneity and sheer number of ubiquitinated proteins (>5,000). Here we report a powerful catalytic tagging tool, the NEDDylator, which fuses a NEDD8 E2-conjugating enzyme, Ubc12, to the ubiquitin ligase, XIAP or cIAP1. This permits transfer of the rare ubiquitin homolog NEDD8 to the ubiquitin E3 substrates, allowing them to be efficiently purified for LC-MS/MS identification. We have identified >50 potential IAP substrates of both cytosolic and mitochondrial origin that bear hallmark N-terminal IAP binding motifs. These substrates include the recently discovered protein phosphatase PGAM5, which we show is proteolytically processed, accumulates in cytosol during apoptosis, and sensitizes cells to death. These studies reveal mechanisms and antagonistic partners for specific IAPs, and provide a powerful technology for labeling binding partners in transient protein-protein complexes. 23484546 Influence of gas phase equilibria on the chemical vapor deposition of graphene. We have investigated the influence of gas phase chemistry on the chemical vapor deposition of graphene in a hot wall reactor. A new extended parameter space for graphene growth was defined through literature review and experimentation at low pressures (≥0.001 mbar). The deposited films were characterized by scanning electron microscopy, Raman spectroscopy, and dark field optical microscopy, with the latter showing promise as a rapid and nondestructive characterization technique for graphene films. The equilibrium gas compositions have been calculated across this parameter space. Correlations between the graphene films grown and prevalent species in the equilibrium gas phase revealed that deposition conditions associated with a high acetylene equilibrium concentration lead to good quality graphene deposition, and conditions that stabilize large hydrocarbon molecules in the gas phase result in films with multiple defects. The transition between lobed and hexagonal graphene islands was found to be linked to the concentration of the monatomic hydrogen radical, with low concentrations associated with hexagonal islands. 23456038 Unraveling a phosphorylation event in a folded protein by NMR spectroscopy: phosphorylation of the Pin1 WW domain by PKA. The Pin1 protein plays a critical role in the functional regulation of the hyperphosphorylated neuronal Tau protein in Alzheimer's disease and is by itself regulated by phosphorylation. We have used Nuclear Magnetic Resonance (NMR) spectroscopy to both identify the PKA phosphorylation site in the Pin1 WW domain and investigate the functional consequences of this phosphorylation. Detection and identification of phosphorylation on serine/threonine residues in a globular protein, while mostly occurring in solvent-exposed flexible loops, does not lead to chemical shift changes as obvious as in disordered proteins and hence does not necessarily shift the resonances outside the spectrum of the folded protein. Other complications were encountered to characterize the extent of the phosphorylation, as part of the (1)H,(15)N amide resonances around the phosphorylation site are specifically broadened in the unphosphorylated state. Despite these obstacles, NMR spectroscopy was an efficient tool to confirm phosphorylation on S16 of the WW domain and to quantify the level of phosphorylation. Based on this analytical characterization, we show that WW phosphorylation on S16 abolishes its binding capacity to a phosphorylated Tau peptide. A reduced conformational heterogeneity and flexibility of the phospho-binding loop upon S16 phosphorylation could account for part of the decreased affinity for its phosphorylated partner. Additionally, a structural model of the phospho-WW obtained by molecular dynamics simulation and energy minimization suggests that the phosphate moiety of phospho-S16 could compete with the phospho-substrate. 23585770 Glassy Interfacial Dynamics of Ni Nanoparticles: Part II Discrete Breathers as an Explanation of Two-Level Energy Fluctuations. Recent studies of the dynamics of diverse condensed amorphous materials have indicated significant heterogeneity in the local mobility and a progressive increase in collective particle motion upon cooling that takes the form of string-like particle rearrangements. In a previous paper (Part I), we examined the possibility that fluctuations in potential energy E and particle mobility μ associated with this 'dynamic heterogeneity' might offer information about the scale of collective motion in glassy materials based on molecular dynamics simulations of the glassy interfacial region of Ni nanoparticles (NPs) at elevated temperatures. We found that the noise exponent associated with fluctuations in the Debye-Waller factor, a mobility related quantity, was directly proportional to the scale of collective motion L under a broad range of conditions, but the noise exponent associated with E(t) fluctuations was seemingly unrelated to L. In the present work, we focus on this unanticipated difference between potential energy and mobility fluctuations by examining these quantities at an atomic scale. We find that the string atoms exhibit a jump-like motion between two well-separated bands of energy states and the rate at which these jumps occur seems to be consistent with the phenomenology of the 'slow-beta' relaxation process of glass-forming liquids. Concurrently with these local E(t) jumps, we also find 'quake-like' particle displacements having a power-law distribution in magnitude so that particle displacement fluctuations within the strings are strikingly different from local E(t) fluctuations. An analysis of these E(t) fluctuations suggests that we are dealing with 'discrete breather' excitations in which large energy fluctuations develop in arrays of non-linear oscillators by virtue of large anharmonicity in the interparticle interactions and discreteness effects associated with particle packing. We quantify string collective motions on a fast caging times scale (picoseconds) and explore the significance of these collective motions for understanding the Boson peak of glass-forming materials. 23439660 Induction of xenobiotic receptors, transporters, and drug metabolizing enzymes by oxycodone. Perturbations of the expression of transporters and drug-metabolizing enzymes (DMEs) by opioids can be the locus of deleterious drug-drug interactions (DDIs). Many transporters and DMEs are regulated by xenobiotic receptors [XRs; e.g., pregnane X receptor (PXR), constitutive androstane receptor (CAR), and Aryl hydrocarbon receptor (AhR)]; however, there is a paucity of information regarding the influence of opioids on XRs. The objective of this study was to determine the influence of oxycodone administration (15 mg/kg intraperitoneally twice daily for 8 days) on liver expression of XRs, transporters, and DMEs in rats. Microarray, quantitative real-time polymerase chain reaction and immunoblotting analyses were used to identify significantly regulated genes. Three XRs (e.g., PXR, CAR, and AhR), 27 transporters (e.g., ABCB1 and SLC22A8), and 19 DMEs (e.g., CYP2B2 and CYP3A1) were regulated (P < 0.05) with fold changes ranging from -46.3 to 17.1. Using MetaCore (computational platform), we identified a unique gene-network of transporters and DMEs assembled around PXR, CAR, and AhR. Therefore, a series of transactivation/translocation assays were conducted to determine whether the observed changes of transporters/DMEs are mediated by direct activation of PXR, CAR, or AhR by oxycodone or its major metabolites (noroxycodone and oxymorphone). Neither oxycodone nor its metabolites activated PXR, CAR, or AhR. Taken together, these findings identify a signature hepatic gene-network associated with repeated oxycodone administration in rats and demonstrate that oxycodone alters the expression of many transporters and DMEs (without direct activation of PXR, CAR, and AhR), which could lead to undesirable DDIs after coadministration of substrates of these transporters/DMEs with oxycodone. 23201055 Optimization of encapsulation of a synthetic long peptide in PLGA nanoparticles: low-burst release is crucial for efficient CD8(+) T cell activation. Overlapping synthetic long peptides (SLPs) hold great promise for immunotherapy of cancer. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are being developed as delivery systems to improve the potency of peptide-based therapeutic cancer vaccines. Our aim was to optimize PLGA NP for SLP delivery with respect to encapsulation and release, using OVA24, a 24-residue long synthetic antigenic peptide covering a CTL epitope of ovalbumin (SIINFEKL), as a model antigen. Peptide-loaded PLGA NPs were prepared by a double emulsion/solvent evaporation technique. Using standard conditions (acidic inner aqueous phase), we observed that either encapsulation was very low (1-30%), or burst release extremely high (>70%) upon resuspension of NP in physiological buffers. By adjusting formulation and process parameters, we uncovered that the pH of the first emulsion was critical to efficient encapsulation and controlled release. In particular, an alkaline inner aqueous phase resulted in circa 330 nm sized NP with approximately 40% encapsulation efficiency and low (<10%) burst release. These NP showed enhanced MHC class I restricted T cell activation in vitro when compared to high-burst releasing NP and soluble OVA24, proving that efficient entrapment of the antigen is crucial to induce a potent cellular immune response. 23422033 Resveratrol enhances exercise training responses in rats selectively bred for high running performance. High Capacity Runner (HCR) rats have been developed by divergent artificial selection for treadmill endurance running capacity to explore an aerobic biology-disease connection. The beneficial effects of resveratrol supplementation have been demonstrated in endurance running and the antioxidant capacity of resveratrol is also demonstrated. In this study we examine whether 12weeks of treadmill exercise training and/or resveratrol can enhance performance in HCR. Indeed, resveratrol increased aerobic performance and strength of upper limbs of these rats. Moreover, we have found that resveratrol activated the AMP-activated protein kinase, SIRT1, and mitochondrial transcription factor A (p<0.05). The changes in mitochondrial fission/fusion and Lon protease/HSP78 levels suggest that exercise training does not significantly induce damage of proteins. Moreover, neither exercise training nor resveratrol supplementation altered the content of protein carbonyls. Changes in the levels of forkhead transcription factor 1 and SIRT4 could suggest increased fat utilization and improved insulin sensitivity. These data indicate, that resveratrol supplementation enhances aerobic performance due to the activation of the AMPK-SIRT1-PGC-1α pathway. 23606318 Reversal of Oral Anticoagulation. Although the use of dabigatran and rivaroxaban are increasing, data on the reversal of their effects are limited. The lack of reliable monitoring methods and specific reversal agents renders treatment strategies empirical, and as a result, treatment consists mainly of supportive measures. Therefore, we performed a systematic search of the PubMed database to find studies and reviews pertaining to oral anticoagulation reversal strategies. This review discusses current anticoagulation reversal recommendations for the oral anticoagulants warfarin, dabigatran, and rivaroxaban for patients at a heightened risk of bleeding, actively bleeding, or those in need of preprocedural anticoagulation reversal. We highlight the literature that shaped these recommendations and provide directions for future research to address knowledge gaps. Although reliable recommendations are available for anticoagulation reversal in patients treated with warfarin, guidance on the reversal of dabigatran and rivaroxaban is varied and equivocal. Given the increasing use of the newer agents, focused research is needed to identify effective reversal strategies and develop and implement an accurate method (assay) to guide reversal of the newer agents. Determining patient-specific factors that influence the effectiveness of reversal treatments and comparing the effectiveness of various treatment strategies are pertinent areas for future anticoagulation reversal research. 23458895 Increased vulnerability to β-cell destruction and diabetes in mice lacking NAD(P)H:quinone oxidoreductase 1. NAD(P)H:quinone oxidoreductase 1 (NQO1) has been known to protect cells against stressors, including the diabetogenic reagent streptozotocin (STZ). The present study demonstrated that NQO1 deficiency resulted in increased pancreatic β-cell death induced by multiple low dose of STZ (MLDS) injections. NQO1 knockout (KO) mice showed hyperglycemia, body weight loss, impaired glucose clearance rate and a lower plasma insulin level after MLDS treatment. Moreover, β-cell mass and pancreatic insulin content were significantly lower in KO mice than in wild-type (WT) mice after MLDS treatment. Five days after the first STZ treatment, the islets of KO mice had substantially more TUNEL-positive β-cells than those of WT mice, but there was no difference in the regeneration of β-cells between KO mice and WT mice. At the same time, MLDS-treated KO mice showed significantly increased apoptotic markers in β-cells, including cleaved caspase 3, Smac/DIABLO and AIF (apoptosis inducing factor) in the cytoplasm. These results suggest that mice deficient in NQO1 are vulnerable to MLDS-induced β-cell destruction and diabetes, caused by increase of β-cell apoptosis in pancreas. 23609238 Prospective observational study of physical functioning, physical activity and time outdoors and the risk of hip fracture: A population based cohort study of 158 057 older adults in the 45 and Up Study. Low levels of physical activity or sun exposure and limitations to physical functioning (or disability) have been identified as possible risk factors for hip fracture. However, these factors are closely related and data on their independent and joint association with risk of hip fracture are limited. A total of 158 057 individuals aged ≥45 years sampled from the general population of New South Wales, Australia, from the prospective 45 and Up Study completed a baseline postal questionnaire in 2006-9 including data on physical activity (Active Australia questionnaire); sun exposure (usual time outdoors); and physical functioning (Medical Outcomes Score-Physical Functioning; scored 0-100). Incident first hip fractures were ascertained by linkage to administrative hospital data (n = 293; average follow-up 2.3 years). The Relative Risk (RR) of hip fracture was estimated using Cox proportional hazards. Poorer physical functioning, lower physical activity and less time outdoors were positively related to each other at baseline and individually associated with significantly increased hip fracture risk. However, physical activity and time outdoors were not significantly related to hip fracture risk after adjustment for baseline physical functioning or when analysis was restricted to those with no or mild baseline physical limitation. In contrast, physical functioning remained strongly related to hip fracture risk after adjustment for the other two factors; compared with the group without limitation (100) the RR of hip fracture among those with mild (75-95), moderate (50-70), severe (25-45) and greatest (0-20) level of physical limitation were 1.38 (95%CI 0.88-2.14), 2.14 (1.29-3.53), 3.87 (2.31-6.44), and 5.61 (3.33-9.42), respectively. The findings suggest that limitation in physical functioning, but not physical activity or time outdoors, is strongly related to hip fracture risk. The apparent increased risk of hip fracture previously described for low physical activity or sun exposure may be, at least in part, due to uncontrolled confounding. 23247298 Chirality recognition of the protonated serine dimer and octamer by infrared multiphoton dissociation spectroscopy. Infrared multiphoton dissociation (IRMPD) spectroscopy has been used to record IR signatures of chirality recognition in the protonated serine dimer and octamer in the 3200-3800 cm(-1) region. This is the first IRMPD study to investigate the heterochiral biomolecular system by utilizing the isotope-labelled species. Noticeable differences in the homo- versus heterochiral IRMPD spectra have been obtained experimentally for both the dimer and octamer. Different dissociation patterns have been noted not only between the homo- and heterochiral octamers, but also between the two -OH stretching vibrational bands of the same chirality species. Systematic theoretical searches have been carried out to identify the most stable conformers of both the homo- and heterochiral protonated serine dimer and octamer. The final geometry optimization and harmonic vibrational calculations have been performed at the MP2/6-311++G(d,p) level for the homo- and heterochiral protonated serine dimer and at the B3LYP/6-31G(d) level for the homo- and heterochiral protonated serine octamer. For the homo- and heterochiral dimer, good agreement between the experimental and theoretical spectra has been achieved and the major conformers have been identified. For the homo- and heterochiral octamer, the main IR features observed have been satisfactorily reproduced theoretically and the dominant conformers identified. More than one main conformer has been identified for the homochiral octamer. This conclusion has been further supported by the analysis of the wavelength specific dissociation products. 22906800 The AChE membrane-binding tail PRiMA is down-regulated in muscle and nerve of mice with muscular dystrophy by merosin deficiency. Since Duchenne muscular dystrophy was attributed to mutations in the dystrophin gene, more than 30 genes have been found to be causally related with muscular dystrophies, about half of them encoding proteins of the dystrophin-glycoprotein complex (DGC). Through laminin-2, the DGC bridges the muscle cytoskeleton and the extracellular matrix. Decreased levels of PRiMA-linked acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) have been observed in dystrophic muscle and nerve of dystrophin-deficient (mdx) and laminin-2 deficient (Lama2dy) mice. To help explain these observations, the relative content of AChE, BuChE and PRiMA mRNAs were compared in normal and Lama2dy mouse muscle and sciatic nerve. The 17-fold lower level of PRiMA mRNA in Lama2dy muscle explained the deficit in PRiMA-linked ChEs. This would increase acetylcholine availability and, eventually, the desensitization of nicotinic receptors. Abnormal development of the Schwann cells led to peripheral neuropathy in the Lama2dy mouse. Compared with normal nerve, dystrophic nerve displayed 4-fold less AChE-T mRNA, 3-fold more BuChE mRNA and 2.5-fold less PRiMA mRNA, which agreed with the lower AChE activity in dystrophic nerve, its increased BuChE activity and the specific drop in PRiMA-linked BuChE. The widely accepted role of glial cells as the source of BuChE, the observed dysmyelination of Lama2dy nerve and its increased BuChE activity support the idea that BuChE up-regulation is related with the aberrant differentiation of the Schwann cells. 23420697 Protein-specific force field derived from the fragment molecular orbital method can improve protein-ligand binding interactions. Accurate computational estimate of the protein-ligand binding affinity is of central importance in rational drug design. To improve accuracy of the molecular mechanics (MM) force field (FF) for protein-ligand simulations, we use a protein-specific FF derived by the fragment molecular orbital (FMO) method and by the restrained electrostatic potential (RESP) method. Applying this FMO-RESP method to two proteins, dodecin, and lysozyme, we found that protein-specific partial charges tend to differ more significantly from the standard AMBER charges for isolated charged atoms. We did not see the dependence of partial charges on the secondary structure. Computing the binding affinities of dodecin with five ligands by MM PBSA protocol with the FMO-RESP charge set as well as with the standard AMBER charges, we found that the former gives better correlation with experimental affinities than the latter. While, for lysozyme with five ligands, both charge sets gave similar and relatively accurate estimates of binding affinities. © 2013 Wiley Periodicals, Inc. 23371032 Resistance to conventional insecticides in Pakistani populations of Musca domestica L. (Diptera: Muscidae): a potential ectoparasite of dairy animals. The house fly, Musca domestica L., is an important hygienic pest of humans and dairy animals with the potential to develop resistance to most chemical classes of insecticides. Six adult house fly strains from dairy farms in Punjab, Pakistan were evaluated for resistance to selected insecticides from organochlorine, organophosphate, carbamate and pyrethroid classes. For a chlorocyclodiene and two organophosphates tested, the resistance ratios (RR) at LC50 were in the range of 5.60-22.02 fold for endosulfan, 7.66-23.24 fold for profenofos and 2.47-7.44 fold for chlorpyrifos. For two pyrethroids and one carbamate, the RR values at LC50 were 30.22-70.02 for cypermethrin, 5.73-18.31 for deltamethrin, and 4.39-15.50 for methomyl. This is the first report of resistance to different classes of insecticides in Pakistani dairy populations of house flies. Regular insecticide resistance monitoring programs on dairy farms are needed to prevent field control failures. Moreover, integrated approaches including the judicious use of insecticides are needed to delay the development of insecticide resistance in house flies. 23383710 Conjugation with betaine: a facile and effective approach to significant improvement of gene delivery properties of PEI. Herein, we developed a new gene delivery vector by grafting a betaine monomer (N,N-dimethyl(acrylamidopropyl)ammonium propane sulfonate, DMAAPS) onto 25 KDa polyethylenimine (PEI 25K) via the Michael addition reaction. The graft ratio for betaine on PEI polymer could be readily controlled, and in this study three PEI-betaine conjugates PEI-DMAAPS23%, PEI-DMAAPS55%, and PEI-DMAAPS95% were prepared with their graft ratios of 23, 55, and 95%, respectively. The PEI-betaine conjugates exhibited much lower protein adsorption and cytotoxicities compared with PEI 25K, and they also showed little or no hemolytic effect. Moreover, the PEI-betaine conjugates display satisfactory DNA condensation capability; and in the absence and presence of serum, PEI-DMAAPS23%/pEGFP and PEI-DMAAPS55%/pEGFP complexes exhibited remarkable gene transfection efficiencies determined by flow cytometry, which are in general several times higher than that of PEI 25K. With these favorable properties, the PEI-betaine conjugates hold great potential for use as efficient gene delivery vectors. This study suggests that the betaine monomer may serve as a biocompatible modifying agent and this facile strategy may provide a facile and effective way for constructing some other biocompatible materials. 23486187 Modeling distinct osteosarcoma subtypes in vivo using Cre:lox and lineage-restricted transgenic shRNA. Osteosarcoma is the most common primary cancer of bone and one that predominantly affects children and adolescents. Osteoblastic osteosarcoma represents the major subtype of this tumor, with approximately equal representation of fibroblastic and chondroblastic subtypes. We and others have previously described murine models of osteosarcoma based on osteoblast-restricted Cre:lox deletion of Trp53 (p53) and Rb1 (Rb), resulting in a phenotype most similar to fibroblastic osteosarcoma in humans. We now report a model of the most prevalent form of human osteosarcoma, the osteoblastic subtype. In contrast to other osteosarcoma models that have used Cre:lox mediated gene deletion, this model was generated through shRNA-based knockdown of p53. As is the case with the human disease the shRNA tumors most frequently present in the long bones and preferentially disseminate to the lungs; feature less consistently modeled using Cre:lox approaches. Our approach allowed direct comparison of the in vivo consequences of targeting the same genetic drivers using two different technologies, Cre:lox and shRNA. This demonstrated that the effects of Cre:lox and shRNA mediated knock-down are qualitatively different, at least in the context of osteosarcoma, and yielded distinct subtypes of osteosarcoma. Through the use of complementary genetic modification strategies we have established a model of the most common clinical subtype of osteosarcoma that was not previously represented and more fully recapitulated the clinical spectrum of this cancer. 23462505 Cooperative activation of gene expression by agonists and antagonists mediated by estrogen receptor heteroligand dimer complexes. Estrogen receptor (ER) antagonists are generally thought to inhibit estrogen action through competitive inhibition, resulting in receptor binding to antagonist rather than agonist. However, microarray analyses reveal a group of genes for which ER agonist and antagonist cooperatively regulate expression, suggesting additional models of combined agonist/antagonist action must exist. In conjunction with a chimeric reporter gene and two modified ERs, one [ERα(GSCKV)] with a mutation in the DNA-binding domain and the other (ERα-G521R) with a ligand-binding specificity mutation, we herein demonstrate that ER agonist and antagonist cooperatively activate gene expression through an ER heteroligand dimer complex (ER-HLD) consisting of one subunit of the receptor dimer bound to agonist and another occupied by antagonist. Coimmunoprecipitation experiments confirmed interaction between the agonist-bound and antagonist-bound receptors. This cooperative activation of gene expression was enhanced by steroid receptor coactivator 3 coactivator, and required each ligand-bound subunit of the dimer to bind to DNA, as well as both activation function 1 domains for maximal transcriptional activity. Ligand combinations able to induce ER-HLD transcriptional activity include the agonists 17β-estradiol or conjugated estrogens with the antagonists tamoxifen, raloxifene, bazedoxifene, or fulvestrant. Moreover, ER-HLD can activate transcription in the context of a natural promoter. Taken together, these findings broaden our understanding of the complex relationship between ER agonist and antagonist, and suggest a novel model by which cell and tissue selective effects of antiestrogens may be achieved. 23523142 Ginkgetin induces apoptosis via activation of caspase and inhibition of survival genes in PC-3 prostate cancer cells. Ginkgetin is a natural biflavonoid isolated from leaves of Ginkgo biloba L. Though it was known to have anti-inflammatory, anti-influenza virus, anti-fungal activity, osteoblast differentiation stimulating activity and neuro-protective effects, the underlying antitumor mechanism of ginkgetin still remains unclear. Thus, in the present study, anti-cancer mechanism of ginkgetin was elucidated in human prostate cancer PC-3 cells. Ginkgetin suppressed the viability of PC-3 cells in a concentration-dependent manner and also significantly increased the sub-G1 DNA contents of cell cycle in PC-3 cells. Ginkgetin activated caspase-3 and attenuated the expression of survival genes such as Bcl-2, Bcl-xL, survivin and Cyclin D1 at protein and mRNA levels. Consistently, pan-caspase inhibitor Z-DEVD-fmk blocked sub G1 accumulation and cleavages of PRAP and caspase 3 induced by ginkgetin in PC-3 cells. Overall, these findings suggest that ginkgetin induces apoptosis in PC-3 cells via activation of caspase 3 and inhibition of survival genes as a potent chemotherapeutic agent for prostate cancer treatment. 23601397 The Slovenian food composition database. The preliminary Slovenian food composition database was created in 2003, through the application of the Data management and Alimenta nutritional software. In the subsequent projects, data on the composition of meat and meat products of Slovenian origin were gathered from analyses, and low-quality data of the preliminary database were discarded. The first volume of the Slovenian food composition database was published in 2006, in both electronic and paper versions. When Slovenia joined the EuroFIR NoE, the LanguaL indexing system was adopted. The Optijed nutritional software was developed, and later upgraded to the OPEN platform. This platform serves as an electronic database that currently comprises 620 foods, and as the Slovenian node in the EuroFIR virtual information platform. With the assimilation of the data on the compositions of foods of plant origin obtained within the latest project, the Slovenian database provides a good source for food compositional values of consistent and compatible quality. 23261715 Modulation of activity and inhibitor sensitivity of rabbit aldose reductase-like protein (AKR1B19) by oxidized glutathione and SH-reagents. Rabbit aldo-keto reductase (AKR) 1B19 is an ortholog of human aldose reductase-like protein (ARLP), AKR1B10, showing 86% amino acid sequence identity. AKR1B19 exhibits the highest catalytic efficiency for 4-oxo-2-nonenal, a major product of lipid peroxidation, compared to known reductases of this aldehyde. In this study, we found that the reductase activity of AKR1B19 was activated to about 5-fold immediately after the addition of 10 μM SH-reagents (p-chloromercuriphenylsulfonic acid and p-chloromercuribenzoic acid) in the absence or presence of NADPH. In addition, a maximum of 3-fold activation of AKR1B19 was induced by incubation with glutathione disulfide (GSSG) for 1h. The activated enzyme was converted into the native enzyme by further incubation with dithiothreitol and glutathione. The activation was abolished by the C299S mutation of AKR1B19, and the glutathionylated Cys299 was identified by mass spectrometry analysis. The Cys299-modified enzyme displayed different kinetic alterations depending on substrates and inhibitors. In the reduction of 4-oxo-2-nonenal, the catalytic efficiency was increased. Thus, AKR1B10 may be modulated by cellular ratio of GSSG/glutathione and more efficiently act as a detoxifying enzyme for the cytotoxic aldehyde under oxidatively stressed conditions. Furthermore, such an activity alteration by GSSG was not detected in AKR1B10 and rat ARLPs, suggesting the presence of a GSSG-binding site near Cys299 in AKR1B19. 23404062 Synergistic effects between CA1 mu opioid and dopamine D1-like receptors in impaired passive avoidance performance induced by hepatic encephalopathy in mice. BACKGROUND AND AIM: Numerous investigations have indicated that hepatic encephalopathy (HE) alters the levels of various neurotransmitters. However, comprehensive data regarding the effects of CA1 opioidergic and dopaminergic (DAergic) systems on HE-induced amnesia are still lacking. METHODS: Following intra-dorsal hippocampal (CA1) injection of mu opioid and dopamine D1- and D2-like receptors antagonists in male mice, one-trial step-down and hole-board paradigms were used to assess memory and exploratory behaviors, respectively. RESULTS: Our data demonstrated that HE impairs memory 24 days after bile duct ligation (BDL). Furthermore, while the higher dose of DA D1-like receptor antagonist (SCH23390, 0.5 μg/mouse) induced amnesia and anxiogenic-like behaviors, mu receptor antagonist (naloxone: 0.0125, 0.025 and 0.05 μg/mouse) and DA D2-like receptor antagonist (sulpiride: 0.0625, 0.125 and 0.25 μg/mouse) by themselves, could not exert an effect on memory performance in passive avoidance task. On the other hand, pre-test injection of all drugs reversed the HE-induced amnesia 24 days after BDL, while having no effect on exploratory behaviors. Pre-test co-administration of the subthreshold dose SCH23390 (0.25 μg/mouse) and sulpiride (0.0625 μg/mouse) or naloxone (0.0125 μg/mouse) could likewise reverse the BDL-induced amnesia. However, when the subthreshold sulpiride plus naloxone were co-administered, BDL-induced amnesia was not blocked. CONCLUSIONS: Memory performance is impaired 24 days post BDL and CA1 mu opioid and DA D1-like receptors antagonist synergistic effects are likely involved in this phenomenon. 23306172 Antibacterial polyketides from the marine alga-derived endophitic Streptomyces sundarbansensis: a study on hydroxypyrone tautomerism. Polyketide 13 [=2-hydroxy-5-((6-hydroxy-4-oxo-4H-pyran-2-yl)methyl)-2- propylchroman-4-one] and three related known compounds 7, 9 and 11 were obtained and structurally characterized from Streptomyces sundarbansensis strain, an endophytic actinomycete isolated from the Algerian marine brown algae Fucus sp. Compound 13 was obtained as the major metabolite from optimized culture conditions, by using Agar state fermentation. Due to tautomeric equilibrium, 13 in CD(3)OD solution was able to incorporate five deuterium atoms, as deduced by NMR and ESI-MS/MS analysis. The 2-hydroxy-γ-pyrone form was established for these metabolites based on the comparison of their experimental IR spectra with the DFT calculated ones, for both the corresponding 4-hydroxy-α-pyrone and 2-hydroxy-γ-pyrone forms. During antibacterial evaluation, compound 13 stood out as the most active of the series, showing a selective activity against the gram positive pathogenic methicillin-resistant S. aureus (MRSA, MIC = 6 μΜ), with a bacteriostatic effect. 22885793 Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update. Heat shock proteins (HSP) are a subset of the molecular chaperones, best known for their rapid and abundant induction by stress. HSP genes are activated at the transcriptional level by heat shock transcription factor 1 (HSF1). During the progression of many types of cancer, this heat shock transcriptional regulon becomes co-opted by mechanisms that are currently unclear, although evidently triggered in the emerging tumor cell. Concerted activation of HSF1 and the accumulation of HSPs then participate in many of the traits that permit the malignant phenotype. Thus, cancers of many histologies exhibit activated HSF1 and increased HSP levels that may help to deter tumor suppression and evade therapy in the clinic. We review here the extensive work that has been carried out and is still in progress aimed at (1) understanding the oncogenic mechanisms by which HSP genes are switched on, (2) determining the roles of HSF1/HSP in malignant transformation and (3) discovering approaches to therapy based on disrupting the influence of the HSF1-controlled transcriptome in cancer. 23514247 Nonviral Gene Delivery to Neural Stem Cells with Minicircles by Microporation. The main purpose of this work was to evaluate the transfection of novel DNA vectors, minicircles (mC), on embryonic stem cell-derived neural stem cells (NSC). We demonstrated that by combining microporation with mC, 75% of NSC expressing a transgene is achieved without compromising cell survival, morphology, and differentiation potential. When comparing mC with their plasmid DNA (pDNA) counterparts, both gave rise to similar transfection levels but cells harboring mC showed 10% higher cell viability, maintaining 90% of survival at least for 10 days. Long-term analysis showed that NSC harbor a higher number of mC copies and consequently exhibit higher transgene expression when compared to their pDNA counterpart. Taken together, our results offer the first insights on the use of mC as a novel and safe strategy to genetically engineer NSC envisaging their use as biopharmaceuticals in clinical settings for the treatment of neurodegenerative or neurological diseases. 23522564 Addition of artificial salt bridge by Ile646Lys mutation in gp41 coiled-coil domain regulates 6-helical bundle formation. HIV entry is mediated by the envelope glycoproteins gp120 and gp41. The gp41 subunit contains several functional domains: the N-terminal heptad repeat (NHR) domains fold a triple stranded coiled-coil forming a meta-stable prefusion intermediate. C-terminal heptad repeat (CHR) subsequently folds onto the hydrophobic grooves of the NHR coiled-coil to form a stable 6-helix bundle, which juxtaposes the viral and cellular membranes for fusion. The C34 which has 34 amino acid residues is known as the core structure in CHR. A highly anti-HIV peptide inhibitor derived from C34 was designed. An artificial salt bridge was added in the 6-helical bundle by substitution of lysine for Ile646. With a cholesterol modification at C-terminal, the inhibitor containing I646K mutation represented higher anti-viral activity than C34-cholesterol combination without mutation. 23351096 Stimuli-Responsive Magnetic Nanomicelles as Multifunctional Heat and Cargo Delivery Vehicles. Hybrid nanoarchitectures are among the most promising nanotechnology-enabled materials for biomedical applications. Interfacing of nanoparticles with active materials gives rise to the structures with unique multiple functionality. Superparamagnetic iron oxide nanoparticles particles SPION are widely employed in the biology and in developing of advanced medical technologies. Polymeric micelles offer the advantage of multifunctional carriers which can serve as delivery vehicles carrying nanoparticles, hydrophobic chemotherapeutics and other functional materials and molecules. Stimuli-responsive polymers are especially attractive since their properties can be modulated in a controlled manner. Here we report on multifunctional thermo-responsive poly(N-isopropylacrylamide-co-acrylamide)-block-poly(ε-caprolactone) random block copolymer micelles as magnetic hyperthermia-mediated payload release and imaging agents. The combination of copolymers, nanoparticles and doxorubicin drug was tailored the way that the loaded micelles were cable to respond to magnetic heating at physiologically-relevant temperatures. A surface functionalization of the micelles with the integrin β4 antibody and consequent interfacing of the resulting nanobio hybrid with squamous head and neck carcinoma cells which is known to specifically over-express the A9 antigen resulted in concentration of the micelles on the surface of cells. No inherent cytotoxicity was detected for the magnetic micelles without external stimuli application. Furthermore, SPION-loaded micelles demonstrate significant MRI contrast enhancement abilities. 23423695 Type 2 Diabetes With Partial Lipodystrophy of the Limbs: A new lipodystrophy phenotype. OBJECIVELipodystrophies are categorized by the extent of fat loss (generalized vs. partial) and by inheritance (congenital vs. acquired). We examined whether a group of patients with partial lipodystrophy of the limbs (PLL), type 2 diabetes mellitus (T2DM), and an absence of a family history of lipodystrophy constitute a new clinical subtype.RESEARCH AND DESIGN METHODSTen women with T2DM and PLL were identified in academic diabetes clinics and were matched by age, sex, BMI, ethnicity, and diabetes status with 10 women with control T2DM without lipodystrophy. All patients were characterized by clinical evaluation and hyperinsulinemic clamp.RESULTSPatients with T2DM and PLL exhibited symmetrical loss of subcutaneous fat in forearms, or forearms plus calves, and acanthosis nigricans. Maximally stimulated glucose disposal rates were markedly reduced by 56% in the T2DM with PLL group compared with the control T2DM patients, whether normalized by body weight or surface area. Most PLL patients exhibited little or no insulin-mediated glucose uptake after subtraction of non-insulin-mediated glucose uptake. The T2DM with PLL group also had greater elevations in hepatic transaminases and triglycerides and earlier onset of diabetes compared with control T2DM.CONCLUSIONST2DM with PLL represents a previously unrecognized phenotype of lipodystrophy and of T2DM. These T2DM patients exhibit symmetrical lipodystrophy of the distal limbs, acanthosis nigricans, marked insulin resistance with little insulin-mediated glucose uptake, hypertriglyceridemia, and hepatic transaminase elevations, which are greater in severity than observed in patients with common T2DM. 23595055 Brominated Skeletal Components of the Marine Demosponges, Aplysina cavernicola and Ianthella basta: Analytical and Biochemical Investigations. Demosponges possess a skeleton made of a composite material with various organic constituents and/or siliceous spicules. Chitin is an integral part of the skeleton of different sponges of the order Verongida. Moreover, sponges of the order Verongida, such as Aplysina cavernicola or Ianthella basta, are well-known for the biosynthesis of brominated tyrosine derivates, characteristic bioactive natural products. It has been unknown so far whether these compounds are exclusively present in the cellular matrix or whether they may also be incorporated into the chitin-based skeletons. In the present study, we therefore examined the skeletons of A. cavernicola and I. basta with respect to the presence of bromotyrosine metabolites. The chitin-based-skeletons isolated from these sponges indeed contain significant amounts of brominated compounds, which are not easily extractable from the skeletons by common solvents, such as MeOH, as shown by HPLC analyses in combination with NMR and IR spectroscopic measurements. Quantitative potentiometric analyses confirm that the skeleton-associated bromine mainly withstands the MeOH-based extraction. This observation suggests that the respective, but yet unidentified, brominated compounds are strongly bound to the sponge skeletons, possibly by covalent bonding. Moreover, gene fragments of halogenases suggested to be responsible for the incorporation of bromine into organic molecules could be amplified from DNA isolated from sponge samples enriched for sponge-associated bacteria. 23578584 Significance of the transient receptor potential canonical 2 (TRPC2) channel in the regulation of rat thyroid FRTL-5 cell proliferation, migration, adhesion and invasion. Mammalian transient receptor potential (TRP) channels are involved in many physiologically important processes. Here, we have studied the significance of the TRPC2 channel in the regulation of rat thyroid FRTL-5 cell proliferation, migration, adhesion and invasion, using stable TRPC2 (shTRPC2) knock-down cells. In the shTRPC2 cells, proliferation was decreased due to a prolonged G1/S cell cycle phase. The tumor suppressor p53 and the cyclin-dependant kinase inhibitors p27 and p21 were upregulated. Cell invasion, adhesion and migration were also attenuated in shTRPC2 cells, probably due to decreased activity of both Rac and calpain, and a decreased secretion and activity of matrix metalloproteinase 2. The attenuated proliferation, migration, invasion and ATP-evoked calcium entry was mimicked by overexpressing a non-conducting, truncated TRPC2 (TRPC2-DN) in wild type cells, and was reversed by overexpression of TRPC2-GFP in shTRPC2 cells. In conclusion, TRPC2 is an important regulator of rat thyroid cell function. 23603636 Is autologous chondrocyte implantation (ACI) an adequate treatment option for repair of cartilage defects in paediatric patients? Cartilage lesions in the knee of juvenile patients require an effective repair to regain life-long functional activity of the joint. Autologous chondrocyte implantation (ACI) is discussed to be advantageous over other methods for cartilage repair regarding long-term outcome. ACI has successfully been applied in juvenile patients, although currently recommended for patients ≥18 years of age. Only few controlled clinical trials present evidence of efficacy and safety of ACI in adolescent patients. ACI products have to undergo the process of a marketing authorisation application, including the submission of a paediatric investigation plan (PIP). Data from prospective clinical studies or retrospective collection of long-term data in paediatric patients should be submitted for risk-benefit evaluation by the Paediatric Committee (PDCO). 23147416 Decreased pain responses of C-C chemokine receptor 5 knockout mice to chemical or inflammatory stimuli. Chemokines are small chemotactic cytokines that elicit many physiological and pathological effects through binding to their corresponding receptors. Recent studies have suggested that C-C chemokine receptor (CCR) 5 interacts with μ-opioid receptor and modifies a nociceptive reaction. We examined effects of CCR5 deficiency on pain responses by employing CCR5 knockout (KO) mice. We found that pain responses of CCR5 KO mice to chemical or inflammation stimuli were milder than those of CCR5 wild type (WT) mice. However, there was no remarkable change in thermal nociception. To prove the involvement of CCR5 deletion in lowered nociception, we examined pain reactions with CCR5 WT mice following treatment of a CCR5 antagonist (D-Ala(1)-peptide T-NH(2,) DAPTA). Chemical or inflammatory pain behavior was significantly relieved by intracerebroventricular infusion of the inhibitor. When we assessed expression level of μ-opioid receptor (MOR) in the periaqueductal gray where the receptors are critical for analgesic effects, immunoreactivity of MOR was significantly higher in CCR5 KO mice than WT mice without change in phosphorylation level of the receptor. Reduced nociceptive responses in CCR5 KO mice were moderated by administration of naloxone and d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), MOR antagonists. Our data indicate that CCR5 deficiency is related to up-regulation of MOR without an increase in the receptor desensitization which might result in increased analgesic effects against chemical or inflammatory stimuli. Alternatively, higher amount of opioid ligands in CCR5 mice might be linked to these results. Therefore, CCR5 appears to be a therapeutic target for treatment of pain related diseases such as inflammatory hyperalgesia. 23597099 2-Methoxyjuglone Induces Apoptosis in HepG2 Human Hepatocellular Carcinoma Cells and Exhibits in Vivo Antitumor Activity in a H22 Mouse Hepatocellular Carcinoma Model. In order to discover anticancer agents from natural sources, an ethanol-soluble extract of the root bark of Juglans cathayensis was investigated and showed cytotoxic effects against various human cancer cell lines. A subsequent phytochemical study on the EtOAc-soluble fraction determined 2-methoxyjuglone (1) as one of the main active constituents. Compound 1 was shown to be cytotoxic against HepG2 cells. Morphological features of apoptosis were observed in 1-treated HepG2 cells, including cell shrinkage, membrane blebbing, nuclear condensation, and apoptotic body formation. Cell cycle analysis with propidium iodide staining showed that 1 induced cell cycle arrest at the S phase in HepG2 cells. Flow cytometric analysis with annexin V and propidium iodide staining demonstrated that 1 induced HepG2 cell apoptotic events in a dose-dependent manner (0-8 μg/mL). Western blot analysis of apoptosis-related proteins revealed that 1 induces HepG2 cell apoptosis through mitochondrial cytochrome c-dependent activation of the caspase-9 and caspase-3 cascade pathway (intrinsic pathway). An in vivo experiment using tumor-bearing mice showed that treatment with 1 at 0.5 and 1.0 mg/kg per day decreased the tumor mass by 56% and 67%, respectively. 23627254 Thermostated Hamiltonian Dynamics with Log-Oscillators. With this work we present two new methods for the generation of thermostated, manifestly Hamiltonian dynamics and provide corresponding illustrations. The basis for this new class of thermostats are the peculiar thermodynamics as exhibited by logarithmic oscillators. These two schemes are best suited when applied to systems with a small number of degrees of freedom. 23055393 Enhanced light focusing in self-assembled optoplasmonic clusters with subwavelength dimensions. Compact metallo-dielectric hybrid clusters with subwavelength dimensions are fabricated by template guided self-assembly. Elastic and inelastic scattering spectroscopy and electromagnetic simulations reveal that hybrid clusters comprising TiO(2) nanoparticles on top of a cluster of strongly coupled gold nanoparticles harness synergistic electromagnetic interactions between the building blocks. This results in a boost of the peak electric field intensity and a redistribution of the field in the ambient medium. The complex phase landscape in the clusters features optical vortices that enhance the magnetic field. 23454133 Co-encapsulating nanostructured lipid carriers for transdermal application: From experimental design to the molecular detail. Co-encapsulation of drugs directed at commonly associated diseases provides a convenient means for administration, especially if transdermally delivered. In this work, a comprehensive study for the co-encapsulation of drugs with a differential lipophilicity, olanzapine and simvastatin, and their transdermal delivery in a formulation containing nanostructured lipid carriers (NLC) is presented. Focus is given to the evaluation of a strategy in which NLC and chemical permeation enhancers are combined. It comprises in vitro, in silico and cellular viability approaches. The optimization and rationalization of the systems are carried out using a two-step factorial design. It is shown that the external medium in the NLC dispersion strongly influences permeation. It is also seen that the use of NLC determines a synergistic effect with selected permeation enhancers, thus promoting marked flux enhancement ratios (48 and 21, respectively for olanzapine and simvastatin) relative to the drugs in solution. The developed formulations can be considered non-irritant. A correlation between enhancer positioning in a lipid bilayer, partially governed by a H-bonding phenomenon, and enhancement effect is suggested from molecular dynamics studies and experimental observations. 23255073 Low percentage of KRAS mutations revealed by locked nucleic acid polymerase chain reaction: implications for treatment of metastatic colorectal cancer. Metastatic colorectal cancer (mCRC) is frequently characterized by the presence of mutations of the KRAS oncogene, which are generally associated with a poor response to treatment with anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies. With the methods currently used, a case is classified as KRAS-mutated when approximately 20% of the cells bear an activating KRAS mutation. These considerations raise the question of whether cells with a mutated KRAS can be found in mCRC cases classified as KRAS wild-type when more sensitive methods are used. In addition, the issue arises of whether these mCRC cases with low proportion of KRAS-mutated cells could account at least in part for the therapeutic failure of anti-EGFR therapies that occur in 40-60% of cases classified as KRAS wild type. In this study, we compared the classical assays with a very sensitive test, a locked nucleic acid (LNA) polymerase chain reaction (PCR), capable of detecting KRAS-mutated alleles at extremely low frequency (detection sensitivity limit 0.25% mutated DNA/wild-type DNA). By analyzing a cohort of 213 mCRC patients for KRAS mutations, we found a 20.6% discordance between the sequencing/TheraScreen methods and the LNA-PCR. Indeed, 44 mCRC patients initially considered KRAS wild type were reclassified as KRAS mutated by using the LNA-PCR test. These patients were more numerous among individuals displaying a clinical failure to anti-EGFR therapies. Failure to respond to these biological treatments occurred even in the absence of mutations in other EGFR pathway components such as BRAF. 23581492 The stabilization effect of dielectric constant and acidic amino acids on arginine-arginine (arg-arg) pairings: database survey and computational studies. Database survey in this study revealed that about one-third of the protein structures deposited in the Protein Data Bank (PDB) contain arginine-arginine (Arg-Arg) pairing with a carbon···carbon (CZ···CZ) interaction distance less than 5 Å. All the Arg-Arg pairings were found to bury in a polar environment composed of acidic residues, water molecules, and strong polarizable or negatively charged moieties from binding site or bound ligand. Most of the Arg-Arg pairings are solvent exposed and 68.3% Arg-Arg pairings are stabilized by acidic residues, forming Arg-Arg-Asp/Glu clusters. Density functional theory (DFT) was then employed to study the effect of environment on the pairing structures. It was revealed that Arg-Arg pairings become thermodynamically stable (about -1 kcal/mol) as the dielectric constant increases to 46.8 (DMSO), in good agreement with the results of the PDB survey. DFT calculations also demonstrated that perpendicular Arg-Arg pairing structures are favorable in low dielectric constant environment, while in high dielectric constant environment parallel structures are favorable. Additionally, the acidic residues can stabilize the Arg-Arg pairing structures to a large degree. Energy decomposition analysis of Arg-Arg pairings and Arg-Arg-Asp/Glu clusters showed that both solvation and electrostatic energies contribute significantly to their stability. The results reported herein should be very helpful for understanding Arg-Arg pairing and its application in drug design. 23351139 Drug-induced nanocarrier assembly as a strategy for the cellular delivery of nucleotides and nucleotide analogues. The natural nucleotide adenosine triphosphate (ATP) and nucleotide analogues such as azidothymidine triphosphate (AZT-TP) display important pharmacological activities for the treatment of ischemia and HIV infections, respectively. Their clinical use is, however, limited mostly due to their hydrophilicity, which highly restricts their diffusion into the target cells. Few nanocarriers have been proposed to address the challenge of ATP/AZT-TP cellular delivery, but the loading efficiency, preparation complexity, and efficient cellular delivery remain important barriers to their development. In this study, we propose an original, straightforward and versatile design of nucleotide and nucleotide analogue nanocarriers based on the natural polysaccharide chitosan (CS). We show that the drugs ATP and AZT-TP can induce ionotropic gelation of CS, leading to CS/ATP and CS/AZT-TP nanoparticles with high drug entrapment efficiency and loading rate-up to 44%. Such nanocarriers release ATP and AZT-TP in physiological media and allow an efficient in vitro cellular delivery of these molecules down to the cell cytoplasm. 23602442 Discovery of diarylurea P2Y1 antagonists with improved aqueous solubility. Preclinical data suggests that P2Y1 antagonists, such as diarylurea compound 1, may provide antithrombotic efficacy similar to P2Y12 antagonists and may have the potential of providing reduced bleeding liabilities. This manuscript describes a series of diarylureas bearing solublizing amine side chains as potent P2Y1 antagonists. Among them, compounds 2l and 3h had improved aqueous solubility and maintained antiplatelet activity compared with compound 1. Compound 2l was moderately efficacious in both rat and rabbit thrombosis models and had a moderate prolongation of bleeding time in rats similar to that of compound 1. 23142212 Microbiota of male genital tract: impact on the health of man and his partner. This manuscript describes the male genital tract microbiota and the significance of it on the host's and his partner's health. Microbiota exists in male lower genital tract, mostly in urethra and coronal sulcus while high inter-subject variability exists. Differences appear between sexually transmitted disease positive and negative men as well as circumcised and uncircumcised men. Upper genital tract is generally germ-free, except in case of infections. Prostatitis patients have frequently abundant polymicrobial communities in their semen, expressed prostatic secretion and/or post-massage urine. Coryneform bacteria have ambivalent role in male urogenital tract being frequently commensals but sometimes associated with prostatitis and urethritis. Interactions between male and female genital tract microbiota are highly likely yet there are very scarce studies on the couples' genital tract microbiota. Increase of bacterial vaginosis-type microbiota and coliforms are the most typical findings in men while the adverse effect of male genital tract bacteria on in vitro fertilization and pregnancy outcome has also been indicated. 23321054 Further evidence for the sleep-promoting effects of 5-HT2A receptor antagonists and demonstration of synergistic effects with the hypnotic, zolpidem in rats. 5-Hydroxytryptamine (5-HT)2A antagonists are promising therapeutic agents for the treatment of sleep maintenance insomnias, but unlike hypnotics, they have limited effects on sleep initiation. This study evaluated the effects of several 5-HT2A antagonists (eplivanserin, volinanserin and AVE8488) alone and/or in combination with the short-acting hypnotic, zolpidem, on the rat sleep profile. A repeated-measures design was used in which rats were treated with eplivanserin (3 and 10 mg/kg, i.p. or p.o.), volinanserin (0.3-3 mg/kg, i.p.), AVE8488 (0.1-3 mg/kg, i.p.) and zolpidem (3 and 10 mg/kg, p.o.). In addition, animals received a combination of eplivanserin (3 mg/kg, p.o.) and zolpidem (3 mg/kg, p.o.). Electroencephalogram was analyzed for 6 h after administration. Eplivanserin did not modify wakefulness and non-rapid eye movement sleep (NREMS), while zolpidem (10 mg/kg po) induced a marked increase in NREMS duration. Volinanserin (1 and 3 mg/kg) and AVE8488 (0.3 mg/kg) similarly increased NREMS, while reducing wakefulness. Moreover, the 5-HT2A antagonists and, to a lesser extent, zolpidem, increased duration of NREMS episodes, while decreasing their frequency. When eplivanserin was co-administered with zolpidem, a synergistic effect was observed as the combination produced an increase in NREMS time and bouts duration. These findings confirm further that 5-HT2A antagonists promote the maintenance of sleep, and suggest that combining a 5-HT2A antagonist with a short-acting hypnotic may be a useful strategy for the treatment of insomnia. 23625969 MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma. MYCN is a master regulator controlling many processes necessary for tumor cell survival. Here, we unravel a microRNA network that causes tumor suppressive effects in MYCN-amplified neuroblastoma cells. In profiling studies, histone deacetylase (HDAC) inhibitor treatment most strongly induced miR-183. Enforced miR-183 expression triggered apoptosis, and inhibited anchorage-independent colony formation in vitro and xenograft growth in mice. Furthermore, the mechanism of miR-183 induction was found to contribute to the cell death phenotype induced by HDAC inhibitors. Experiments to identify the HDAC(s) involved in miR-183 transcriptional regulation showed that HDAC2 depletion induced miR-183. HDAC2 overexpression reduced miR-183 levels and counteracted the induction caused by HDAC2 depletion or HDAC inhibitor treatment. MYCN was found to recruit HDAC2 in the same complexes to the miR-183 promoter, and HDAC2 depletion enhanced promoter-associated histone H4 pan-acetylation, suggesting epigenetic changes preceded transcriptional activation. These data reveal miR-183 tumor suppressive properties in neuroblastoma that are jointly repressed by MYCN and HDAC2, and suggest a novel way to bypass MYCN function. 23435942 A review on cholinesterase inhibitors for Alzheimer's disease. Alzheimer's disease (AD), a progressive neurodegenerative disorder, is characterized by the deficits in the cholinergic system and deposition of beta amyloid (Aβ) in the form of neurofibrillary tangles and amyloid plaques. Since the cholinergic system plays an important role in the regulation of learning and memory processes, it has been targetted for the design of anti-Alzheimer's drugs. Cholinesterase inhibitors enhance cholinergic transmission directly by inhibiting the enzyme acetylcholinesterase (AChE) which hydrolyses acetylcholine. Furthermore, it has been also demonstrated that both acetylcholinesterase and butrylcholinesterase (BuChE) play an important role in Aβ-aggregation during the early stages of senile plaque formation. Therefore, AChE and BuChE inhibition have been documented as critical targets for the effective management of AD by an increase in the availability of acetylcholine in the brain regions and decrease in the Aβ deposition. This review discusses the different classes of cholinesterase inhibitors including tacrine, donepezil, rivastigmine, galantamine, xanthostigmine, para-aminobenzoic acid, coumarin, flavonoid, and pyrrolo-isoxazole analogues developed for the treatment of AD. 23281101 Butyltin(IV) benzoates: inhibition of thioredoxin reductase, tumor cell growth inhibition, and interactions with proteins. Thioredoxin reductase (TrxR) is overexpressed in cancer cells and is therefore a putative cancer target. Inhibition of this enzyme is considered an important strategy for the development of new chemotherapeutic agents with a specific mechanism of action. Organotin compounds have been described as experimental antitumor agents, yet their mechanism of action remains largely unknown. Based on the outcome of a virtual screening study, various di- and tri-n-butyltin(IV) carboxylates were synthesized, and their biological properties were evaluated. All synthesized compounds were able to inhibit TrxR selectively within the micromolar range and showed potent antitumor activity against HT-29 and MCF-7 cancer cell lines. Moreover, tin(IV) organometallics were found to strongly induce apoptosis in the BJAB lymphoma cell line. Mass spectrometry and atomic absorption spectroscopy experiments revealed metal binding to proteins, and efficient cellular uptake was observed using a di-n-butyltin(IV) complex as an example. 23497894 High pressure homogenization increases antioxidant capacity and short-chain fatty acid yield of polysaccharide from seeds of Plantago asiatica L. Physiological properties of homogenized and non-homogenized polysaccharide from the seeds of Plantago asiatica L., including antioxidant capacity and short-chain fatty acid (SCFA) production, were compared in this study. High pressure homogenization decreased particle size of the polysaccharide, and changed the surface topography from large flake-like structure to smaller porous chips. FT-IR showed that high pressure homogenization did not alter the primary structure of the polysaccharide. However, high pressure homogenization increased antioxidant capacity of the polysaccharide, evaluated by 4 antioxidant capacity assays (hydroxyl radical-scavenging, superoxide radical-scavenging, 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH)-scavenging and lipid peroxidation inhibition). Additionally, the production of total SCFA, propionic acid and n-butyric acid in ceca and colons of mice significantly increased after dieting supplementation with homogenized polysaccharide. These results showed that high pressure homogenization treatment could be a promising approach for the production of value-added polysaccharides in the food industry. 23546600 A 5' flanking region of Gonadotropin Regulated Testicular RNA Helicase (GRTH/DDX25) gene directs its cell specific androgen regulated gene expression in testicular germ cells. Gonadotropin Regulated Testicular RNA Helicase (GRTH/Ddx25) is a post-transcriptional regulator of genes that are essential for spermatid elongation and completion of spermatogenesis. It also prevents Leydig cells (LC) from gonadotropin overstimulation of androgen production. In transgenic (Tg) mice carrying deletions of the GRTH 5' flanking regions we previously demonstrated that the -1085 bp to ATG contains the elements for basal and androgen-induced LC specific expression. No expression in germ cells (GC) was found with sequences extended up to -3.6 Kb. To define regulatory regions of GRTH required for expression in GC, Tg mice were generated with 5' flanking sequence 6.4 Kb (6.4 Kb-Tg) and/or deletion using GFP as reporter gene in the present study. GFP was expressed in all lines. Immuno-histochemistry analysis showed that 6.4Kb-Tg directed GFP expression in both GC and LC. Deletion of the sequence -205 bp to -3.6 Kb (6.4Kb/del-Tg) directs GFP expression only in meiotic and haploid GCs. This indicated that the distal region -6.4 Kb/-3.6 Kb is required for GRTH cell specific expression in GC. Also, it inhibits the expression of GRTH in LC directed by the 205 bp promoter, an effect that is neutralized by the -3.6Kb/-205bp sequence. Flutamide treatment prevents GFP/GRTH expression in Tg lines demonstrating in vivo direct and indirect effects of endogenous androgen on GC and LC, respectively. Our studies have generated and characterized transgenic lines that can be utilized to define requirements for cell specific expression of the GRTH gene and to further advance our knowledge on the regulation of GRTH by androgen in germ cells. 23122092 Chemical and sensory effects of the freezing process on the aroma profile of black truffles (Tuber melanosporum). The aim of this work was to evaluate the effect of freezing black truffles (Tuber melanosporum) on their aroma both in sensory and chemical terms. The truffles were frozen at temperatures of -20 to -80°C. Descriptive and discriminative sensory and chemical analyses, based on headspace solid phase microextraction followed by gas chromatography-mass spectrometry analysis (HS-SPME-GC-MS), were carried out after 1, 20, 40 and 60 days. Fifteen compounds with high aromatic potential in truffles were determined. Their selective ion peak areas were calculated, summed and expressed as percentage of active odour compound, in order to monitor changes in odour profile. The aroma of frozen truffles differed significantly from the aroma of fresh truffles. Volatile composition data revealed that T. melanosporum aromatic profile is deeply modified as a consequence of a freezing process. These aromatic changes could explain the loss of freshness observed in all frozen truffles. Methional and some phenols were suggested as markers of freezing time. Interestingly, 1-octen-3-one appeared as a general marker of freezing process. 23512181 Extending the range of FRET-the Monte Carlo study of the antenna effect. The problem of extending the utilizable range of Förster resonance energy transfer (FRET) is of great current interest, due to the demand of conformation studies of larger biological structures at distances exceeding typical limiting distance of 100 Å. One of the ways to address this issue is the use of so-called antenna effect. In the present work, the influence of the antenna effect on the FRET efficiency is investigated by the Monte Carlo analysis. The previously published results Bojarski et al. (J Phys Chem B 115:10120-10125, 2011) indicate that using a simple model of donor linked with a protein labeled with multiple acceptors, significantly increases the transfer efficiency in comparison with donor-single acceptor system. The effect is stronger if the transition moments of acceptors are mutually parallel. In this work, to extend the scope of possible biological systems to be analyzed, different distributions of donor-acceptors distance are analyzed, as well as the size and shape of the attached molecule. 23411314 Valuable compounds in macroalgae extracts. Bioactive compounds present in ethanolic extracts from 18 macroalgae of the Portuguese coast were analysed by gas chromatography-mass spectrometry (GC-MS), leading to the characterization of 14 compounds: proline, phloroglucinol, mannitol, 8 fatty acids and 3 sterols. A dose-dependent response against enzymes with biological significance (α-glucosidase, acetylcholinesterase and butyrylcholinesterase) and free radicals (DPPH, nitric oxide, superoxide and hydroxyl) was found, Phaeophyta being the most promising group. A PCA analysis was performed and allowed the establishment of a correlation between the algae chemical composition and the biological activity. Cystoseira tamariscifolia (Hudson) Papenfuss, Cystoseira nodicaulis (Withering) M. Roberts, Cystoseira usneoides (Linnaeus) M. Roberts and Fucus spiralis Linnaeus are among the most active species, which is in accordance with their higher contents in phloroglucinol, mannitol, oleic, arachidonic and eicosapentaenoic acids, and fucosterol. The results point to the potential interest of the use of Phaeophyta species as food additives, due to their potent antiradical activities, and especially highlights the importance of F. spiralis in the food chain of Mediterranean countries. Moreover, the incorporation of the extracts of these species in food products, nutraceutical and pharmaceutical preparations for human health should also be instigated, since they can suppress hyperglycemia and inhibit cholinesterases. 23159666 Transferrin conjugation does not increase the efficiency of liposomal Foscan during in vitro photodynamic therapy of oesophageal cancer. Photodynamic therapy (PDT) is based on the delivery of photocytotoxic agents to a target tissue, followed by irradiation. In order to increase the efficiency of PDT in oesophageal cancer therapy, polyethylene glycol (PEG)-grafted, transferrin (Tf)-conjugated liposome formulations of 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (Foscan), a second-generation photosensitiser, were prepared. Expression of transferrin receptors (CD71) in the oesophageal cancer cell line, OE21, was confirmed by immunoblot and confocal laser scanning microscopy. The anti-proliferative effect of Foscan liposomes was evaluated and compared with plain formulations (i.e., without Tf) as well as with free drug. In addition, the intracellular accumulation was studied using high content analysis. Surprisingly, delivering Foscan by transferrin-conjugated PEG-liposomes to oesophageal cancer cells did not improve the photocytotoxicity or the intracellular accumulation of Foscan when compared to unmodified liposomes or indeed free photosensitiser. Tf-targeted drugs and drug delivery systems have shown improved the therapy of many cancers. Our study, however, did not corroborate these findings. If this is due to the tumour type, the choice of in vitro model or the delivery systems remains to be confirmed. 23368705 Anti-Müllerian hormone trend after laparoscopic surgery in women with ovarian endometrioma. Abstract Operative laparoscopy is the gold standard in the treatment of endometriotic ovarian cysts. Excisional surgery is the best technique to prevent recurrences and improve symptoms but it may result in ovarian reserve damage due to the removal of healthy ovarian cortex. The aim of this study was to investigate the extent of the ovarian reserve damage after stripping technique of unilateral endometriomas, by dosing the Anti-Müllerian Hormone (AMH). This prospective study was conducted at the Center of Minimally Invasive Pelvic Surgery of the Department of Health of Woman and Child, University of Padua, from October 2010 to June 2012. Twenty-five women underwent excision of monolateral endometriosis ovarian cyst by stripping without accessing a bipolar coagulation and performing an intracortical suture. The AMH serum levels were estimated in the early proliferative phase of the cycle, before surgery (time 0), 24 h after surgery (time 1), the first menstrual cycle after surgery (time 2) and the third menstrual cycle after surgery (time 3). We found a nonstatistically significant decreases in serum AMH levels after surgical excision of the cysts. Our results suggest that an appropriate surgical technique, without the use of the bipolar coagulation of ovarian border, does not determine a significant reduction of ovarian reserve. 23436544 Vemurafenib-associated pancreatitis: case report. Vemurafenib is a novel BRAF kinase inhibitor indicated in metastatic melanoma patients with V600E mutation. We report the first case of vemurafenib-associated pancreatitis. Two weeks after initiation of vemurafenib, a patient presented to the emergency department with severe epigastric pain and a serum lipase of 1544 units/L. Drug-induced pancreatitis was diagnosed on exclusion of all other potential causes. Vemurafenib was rechallenged at half the daily dose and the patient subsequently developed exacerbated symptoms of pancreatitis after two doses. The strong temporal relationship between drug exposure and toxicity, along with the positive results from a rechallenge study, strongly support a conclusion of causality. To our knowledge, this is the first report of vemurafenib-induced pancreatitis. 23591044 Melatonin and ethanol intake exert opposite effects on circulating estradiol and progesterone and differentially regulate sex steroid receptors in the ovaries, oviducts, and uteri of adult rats. Chronic ethanol intake is associated with sex hormone disturbances, and it is well known that melatonin plays a key role in regulating several reproductive processes. We report the effects of ethanol intake and melatonin treatment (at doses of 100μg/100gBW/day) on sex hormones and steroid receptors in the ovaries, oviducts and uteri of ethanol-preferring rats. After 150 days of treatment, animals were euthanized, and tissue samples were harvested to evaluate androgen, estrogen, progesterone and melatonin receptor subunits (AR, ER-α and ER-β, PRA, PRB and MT1R, respectively). Melatonin decreased estradiol (E2) and increased progesterone (P4) and 6-sulfatoxymelatonin (6-STM), while an ethanol-melatonin combination reduced both P4 and E2. Ovarian AR was not influenced by either treatment, and oviduct AR was reduced after ethanol-melatonin combination. Oviduct ER-α, ER-β and uterine ER-β were down-regulated by either ethanol or melatonin. Conversely, ovarian PRA and PRB were positively regulated by ethanol and ethanol-melatonin combination, whereas PRA was down-regulated in the uterus and oviduct after ethanol consumption. MT1R was increased in ovaries and uteri of melatonin-treated rats. Ethanol and melatonin exert opposite effects on E2 and P4, and they differentially regulate the expression of sex steroid receptors in female reproductive tissues. 23170794 Global cerebral ischemia: synaptic and cognitive dysfunction. Cardiopulmonary arrest is one of the leading causes of death and disability, primarily occurring in the aged population. Numerous global cerebral ischemia animal models induce neuronal damage similar to cardiac arrest. These global cerebral ischemia models range from vessel occlusion to total cessation of cardiac function, both of which have allowed for the investigation of this multifaceted disease and detection of numerous agents that are neuroprotective. Synapses endure a variety of alterations after global cerebral ischemia from the resulting excitotoxicity and have been a major target for neuroprotection; however, neuroprotective agents have proven unsuccessful in clinical trials, as neurological outcomes have not displayed significant improvements in patients. A majority of these neuroprotective agents have specific neuronal targets, where the success of future neuroprotective agents may depend on non-specific targets and numerous cognitive improvements. This review focuses on the different models of global cerebral ischemia, neuronal synaptic alterations, synaptic neuroprotection and behavioral tests that can be used to determine deficits in cognitive function after global cerebral ischemia. 23043137 Regulation of a viral proteinase by a peptide and DNA in one-dimensional space: II. adenovirus proteinase is activated in an unusual one-dimensional biochemical reaction. Late in an adenovirus infection, the viral proteinase (AVP) becomes activated to process virion precursor proteins used in virus assembly. AVP is activated by two cofactors, the viral DNA and pVIc, an 11-amino acid peptide originating from the C terminus of the precursor protein pVI. There is a conundrum in the activation of AVP in that AVP and pVI are sequence-independent DNA-binding proteins with nm equilibrium dissociation constants such that in the virus particle, they are predicted to be essentially irreversibly bound to the viral DNA. Here, we resolve that conundrum by showing that activation of AVP takes place on the one-dimensional contour of DNA. In vitro, pVI, a substrate, slides on DNA via one-dimensional diffusion, D(1) = 1.45 × 10(6) bp(2)/s, until it binds to AVP also on the same DNA molecule. AVP, partially activated by being bound to DNA, excises pVIc, which binds to the AVP molecule that cut it out. pVIc then forms a disulfide bond with AVP forming the fully active AVP-pVIc complex bound to DNA. In vivo, in heat-disrupted immature virus, AVP was also activated by pVI in DNA-dependent reactions. This activation mechanism illustrates a new paradigm for virion maturation and a new way, by sliding on DNA, for bimolecular complexes to form among proteins not involved in DNA metabolism. 23160092 Effects of the extracts and an active compound curcumenone isolated from Curcuma zedoaria rhizomes on alcohol-induced drunkenness in mice. The Curcuma zedoaria rhizome has been used traditionally to treat gastrointestinal diseases as an aromatic stomachic drug, and this is currently used to treat alcohol-induced loss of appetite and nausea in Japan. We examined the effects of various fractions and isolated compounds on alcohol-induced drunkenness and blood alcohol concentrations in mice. The 30% ethanol-extract (1000mg/kg) of C. zedoaria rhizome prevented drunkenness 60 and 120min after 40% alcohol administration. The n-hexane-soluble fraction (300mg/kg) and an isolated compound (3, 10 or 30mg/kg) prevented drunkenness at 30, 60 or 120min. The extract, n-hexane-soluble fraction and isolated compound reduced the elevation in blood alcohol concentrations 30 and 60min after 40% alcohol administration. The isolated compound (10 and 30mg/kg) enhanced liver ADH activity 30 and 60min after 40% alcohol administration. The compound was identified as curcumenone by a direct comparison of (1)H- and (13)C-NMR spectral data. In conclusion, the protective effect of the C. zedoaria extract on drunkenness might be due to an active substance, curcumenone, and decreases in the elevation of blood alcohol concentrations through increased liver alcohol dehydrogenase activity. 23231439 Discovery, synthesis, and structure-based optimization of a series of N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides (ML188) as potent noncovalent small molecule inhibitors of the severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL protease. A high-throughput screen of the NIH molecular libraries sample collection and subsequent optimization of a lead dipeptide-like series of severe acute respiratory syndrome (SARS) main protease (3CLpro) inhibitors led to the identification of probe compound ML188 (16-(R), (R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide, Pubchem CID: 46897844). Unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, 16-(R) is a noncovalent SARS-CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity. A multicomponent Ugi reaction was utilized to rapidly explore structure-activity relationships within S(1'), S(1), and S(2) enzyme binding pockets. The X-ray structure of SARS-CoV 3CLpro bound with 16-(R) was instrumental in guiding subsequent rounds of chemistry optimization. 16-(R) provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action. 23599433 HSP90 functions to stabilize and activate the testis-specific serine/threonine kinases, a family of kinases essential for male fertility. Spermiogenesis is characterized by a profound morphological differentiation of the haploid spermatid into spermatozoa. The testis-specific serine/threonine kinases (TSSKs) comprise a family of post-meiotic kinases expressed in spermatids, are critical to spermiogenesis and are required for male fertility in mammals. To explore the role of HSP90 in regulation of TSSKs, the stability and catalytic activity of epitope-tagged murine TSSKs were assessed in 293T and COS-7 cells. TSSK1, 2, 4, and 6 (SSTK) were all found to associate with HSP90 and pharmacological inhibition of HSP90 function using the highly specific drugs 17-AAG, SNX-5422, or NVP-AUY922 reduced TSSK protein levels in cells. The attenuation of HSP90 function abolished the catalytic activities of TSSK4 and 6, but did not significantly alter the specific activities of TSSK1 and 2. Inhibition of HSP90 resulted in increased TSSK ubiquitination and proteasomal degradation indicating that HSP90 acts to control ubiquitin-mediated catabolism of the TSSKs. To study HSP90 and TSSKs in germ cells a mouse primary spermatid culture model was developed and characterized. Using specific antibodies against murine TSSK2 and 6, it was demonstrated that HSP90 inhibition resulted in a marked decrease of the endogenous kinases in spermatids. Together, our findings demonstrate that HSP90 plays a broad and critical role in stabilization and activation of the TSSK family of protein kinases. 23059626 The effect of CCL3 and CCR1 in bone remodeling induced by mechanical loading during orthodontic tooth movement in mice. Bone remodeling is affected by mechanical loading and inflammatory mediators, including chemokines. The chemokine (C-C motif) ligand 3 (CCL3) is involved in bone remodeling by binding to C-C chemokine receptors 1 and 5 (CCR1 and CCR5) expressed on osteoclasts and osteoblasts. Our group has previously demonstrated that CCR5 down-regulates mechanical loading-induced bone resorption. Thus, the present study aimed to investigate the role of CCR1 and CCL3 in bone remodeling induced by mechanical loading during orthodontic tooth movement in mice. Our results showed that bone remodeling was significantly decreased in CCL3(-/-) and CCR1(-/-) mice and in animals treated with Met-RANTES (an antagonist of CCR5 and CCR1). mRNA levels of receptor activator of nuclear factor kappa-B (RANK), its ligand RANKL, tumor necrosis factor alpha (TNF-α) and RANKL/osteoprotegerin (OPG) ratio were diminished in the periodontium of CCL3(-/-) mice and in the group treated with Met-RANTES. Met-RANTES treatment also reduced the levels of cathepsin K and metalloproteinase 13 (MMP13). The expression of the osteoblast markers runt-related transcription factor 2 (RUNX2) and periostin was decreased, while osteocalcin (OCN) was augmented in CCL3(-/-) and Met-RANTES-treated mice. Altogether, these findings show that CCR1 is pivotal for bone remodeling induced by mechanical loading during orthodontic tooth movement and these actions depend, at least in part, on CCL3. 23480348 Polyallylamine functionalized palladium icosahedra: one-pot water-based synthesis and their superior electrocatalytic activity and ethanol tolerant ability in alkaline media. Polyallylamine (PAH) functionalized Pd icosahedra are synthesized through a simple, one-pot, seedless and hydrothermal growth method. Herein, PAH is used efficiently as a complex-forming agent, capping agent, and facet-selective agent. The strong interaction between PAH and Pd atom sharply changes the electronic structure of Pd atom in the Pd icosahedra. The protective function of PAH layers and enhanced antietching capability of Pd atom are responsible for the formation of the Pd icosahedra. Very importantly, the as-prepared PAH functionalized Pd icosahedra exhibit superior electrocatalytic activity and ethanol tolerant ability toward the oxygen reduction reaction (ORR) compared to the commercially available Pt black in alkaline media. At 0.95 V (vs RHE), the ORR specific kinetic current density at the Pd icosahedra is 4.48 times higher than that at commercial Pt black. The fact demonstrates the appropriate surface modification of the Pd nanoparticles by nonmetallic molecules can be regarded as an effective way to enhance the electrocatalytic activity toward the ORR. 23110522 Large-scale production of edge-selectively functionalized graphene nanoplatelets via ball milling and their use as metal-free electrocatalysts for oxygen reduction reaction. Edge-selectively functionalized graphene nanoplatelets (EFGnPs) with different functional groups were efficiently prepared simply by dry ball milling graphite in the presence of hydrogen, carbon dioxide, sulfur trioxide, or carbon dioxide/sulfur trioxide mixture. Upon exposure to air moisture, the resultant hydrogen- (HGnP), carboxylic acid- (CGnP), sulfonic acid- (SGnP), and carboxylic acid/sulfonic acid- (CSGnP) functionalized GnPs readily dispersed into various polar solvents, including neutral water. The resultant EFGnPs were then used as electrocatalysts for oxygen reduction reaction (ORR) in an alkaline electrolyte. It was found that the edge polar nature of the newly prepared EFGnPs without heteroatom doping into their basal plane played an important role in regulating the ORR efficiency with the electrocatalytic activity in the order of SGnP > CSGnP > CGnP > HGnP > pristine graphite. More importantly, the sulfur-containing SGnP and CSGnP were found to have a superior ORR performance to commercially available platinum-based electrocatalyst. 23322508 Copper tolerance and genetic diversity of Porcellionides sexfasciatus (ISOPODA) in a highly contaminated mine habitat. Organisms inhabiting metal-contaminated areas may develop metal tolerance, with either phenotypic adjustments or genetic changes (adaptation) or with both. In the present study, three populations of the terrestrial isopod Porcellionides sexfasciatus, collected at an abandoned mine area, were compared to assess the effects of metal contamination on tolerance to lethal and sublethal levels of copper, through comparison of survival, avoidance, and feeding. The effects of metal contamination on genetic diversity were considered using random amplified polymorphic DNA (RAPD) markers. No evidence of increased metal tolerance of the population inhabiting the contaminated site was found. There was no correlation between metal exposure and within-population genetic variance, but the three populations were clearly separated from each other. In conclusion, the populations of P. sexfasciatus in the mine landscape live rather isolated from each other and show no differential tolerance to Cu or indications of genetic erosion. Their phenotypic plasticity provides a means to survive despite exposure to extremely high metal concentrations in the soil. 23402211 Measuring in situ primary and competitive DNA hybridization activity on microspheres. Microspheres serve as convenient substrates for studying DNA activity on surfaces. Here, in addition to employing conventional sample preparation involving multiple wash and resuspension steps prior to flow cytometry measurements, we also directly sampled the reaction volume to acquire in situ measurements of primary and competitive hybridization events. Even in the absence of post hybridization wash steps, nonspecific binding events were negligible and thus allowed for direct, quantitative assessment of hybridization events as they occurred on colloidal surfaces. The in situ results indicate that primary duplex formation between immobilized probes and soluble targets on microsphere surfaces is less favorable than predicted by solution models. The kinetics of competitive displacement of primary hybridization partners by secondary targets measured in situ or post washing also deviate from expectations based on theoretical solution thermodynamics, but are consistent with predicted kinetic trends stemming from differences in either the toehold base length or branch migration. 23411252 A simple HPLC method for the comprehensive analysis of cis/trans (Z/E) geometrical isomers of carotenoids for nutritional studies. Geometrical isomers of carotenoids behave differently in aspects like stability towards oxidants, bioavailability, vitamin A activity and specificity for enzymes. The availability of HPLC methods for their detailed profiling is therefore advisable to expand our knowledge on their metabolism and biological role. In this paper the development of a methodology to determine the highest number of geometrical isomers of major carotenoids in humans (phytoene, phytofluene, lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene and lycopene) is described. To assess its usefulness with biological samples both postprandial human plasma and lung samples from ferrets were analysed. Up to 48 isomers of the main human carotenoids were separated in 62 min. This is to the best of our knowledge the report of the highest number of carotenoid geometrical isomers separated with a HPLC method. Twenty-six different carotenoid isomers were readily detected in the biological samples. 22669363 Enzyme replacement therapy for mucopolysaccharidosis VI: long-term cardiac effects of galsulfase (Naglazyme®) therapy. Characteristic cardiac valve abnormalities and left ventricular hypertrophy are present in untreated patients with mucopolysaccharidosis type VI (MPS VI). Cardiac ultrasound was performed to investigate these findings in subjects during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB, rhN-acetylgalactosamine 4-sulfatase, galsulfase, Naglazyme®). Studies were conducted in 54 subjects before ERT was begun and at specific intervals for up to 96 weeks of weekly infusions of rhASB at 1 mg/kg during phase 1/2, phase 2, and phase 3 trials of rhASB. At baseline, mitral and aortic valve obstruction was present and was significantly greater in those ≥12 years of age. Mild mitral and trace aortic regurgitation were present, the former being significantly greater in those <12 years. Left ventricular hypertrophy, with averaged z-scores ranging from 1.6-1.9 SD greater than normal, was present for ages both <12 and ≥12 years. After 96 weeks of ERT, ventricular septal hypertrophy regressed in those <12 years. For those ≥12 years, septal hypertrophy was unchanged, and aortic regurgitation increased statistically but not physiologically. Obstructive gradients across mitral and aortic valves remained unchanged. The results suggest that long-term ERT is effective in reducing intraventricular septal hypertrophy and preventing progression of cardiac valve abnormalities when administered to those <12 years of age. 23185990 Aminoacyl-tRNA Substrate and Enzyme Backbone Atoms Contribute to Translational Quality Control by YbaK. Amino acids are covalently attached to their corresponding transfer RNAs (tRNAs) by aminoacyl-tRNA synthetases. Proofreading mechanisms exist to ensure that high fidelity is maintained in this key step in protein synthesis. Prolyl-tRNA synthetase (ProRS) can misacylate cognate tRNA(Pro) with Ala and Cys. The cis-editing domain of ProRS (INS) hydrolyzes Ala-tRNA(Pro), whereas Cys-tRNA(Pro) is hydrolyzed by a single domain editing protein, YbaK, in trans. Previous studies have proposed a model of substrate-binding by bacterial YbaK and elucidated a substrate-assisted mechanism of catalysis. However, the microscopic steps in this mechanism have not been investigated. In this work, we carried out biochemical experiments together with a detailed hybrid quantum mechanics/molecular mechanics study to investigate the mechanism of catalysis by Escherichia coli YbaK. The results support a mechanism wherein cyclization of the substrate Cys results in cleavage of the Cys-tRNA ester bond. Protein side chains do not play a significant role in YbaK catalysis. Instead, protein backbone atoms play crucial roles in stabilizing the transition state, while the product is stabilized by the 2'-OH of the tRNA. 23464859 Utilizing the Unique Properties of Nanowire MOSFETs for RF Applications. Nanostructures have attracted a great deal of attention because of their potential usefulness for high density applications. More importantly, they offer excellent avenues for improved scaling beyond conventional approaches. Less attention has been paid to their intrinsic potential for distinct circuit applications. Here we discuss how a combination of 1-D transport, operation in the quantum capacitance limit, and ballistic transport can be utilized for certain RF applications. In particular this work explores how the above transport properties can provide a high degree of transconductance linearity at the device level. The article also discusses how device characteristics can be interpreted and analyzed in terms of device linearity if the above conditions are not ideally fulfilled. Using aggressively scaled silicon nanowire field-effect transistors as an example device in this work provides new insights toward the proper choice of channel material to improve linearity through the above-mentioned transport conditions. According to this study, a high degree of linearity occurs feasible while operating at low supply voltages making low-dimensional systems, and here in particular nanowires, an interesting candidate for portable RF applications. 23400748 An algorithm to detect adverse drug reactions in the neonatal intensive care unit. Critically ill newborns in neonatal intensive care units (NICUs) are at greater risk of developing adverse drug reactions (ADRs). Differentiation of ADRs from reactions associated with organ dysfunction/immaturity is difficult. Current ADR algorithm scoring was established arbitrarily without validation in infants. The study objective was to develop a valid and reliable algorithm to identify ADRs in the NICU. Algorithm development began with a 24-item questionnaire for data collection on 100 previously suspected ADRs. Five pediatric pharmacologists independently rated cases as definite, probable, possible, and unlikely ADRs. Consensus "gold standard" was reached via teleconference. Logistic regression and iterative C programs were used to derive the scoring system. For validation, 50 prospectively collected ADR cases were assessed by 3 clinicians using the new algorithm and the Naranjo algorithm. Weighted kappa and intraclass correlation coefficient (ICC) were used to compare validity and reliability of algorithms. The new algorithm consists of 13 items. Kappa and ICC of the new algorithm were 0.76 and 0.62 versus 0.31 and 0.43 for the Naranjo algorithm. The new algorithm developed using actual patient data is more valid and reliable than the Naranjo algorithm for identifying ADRs in the NICU population. Because of the relatively small and nonrandom samples, further refinement and additional testing are needed. 23526571 Discovery of a Series of Thiazole Derivatives as Novel Inhibitors of Metastatic Cancer Cell Migration and Invasion. Effective inhibitors of cancer cell migration and invasion can potentially lead to clinical applications as therapy to block tumor metastasis, the primary cause of death in cancer patients. To this end we have designed and synthesized a series of thiazole derivatives that showed potent efficacy against cell migration and invasion in metastatic cancer cells. The most effective compound, 5k, was found to have an IC50 value of 176 nM in the dose-dependent transwell migration assays in MDA-MB-231cells. At the dose of 10 μM, 5k also blocked about 80% of migration in HeLa and A549 cells and 60% of invasion of MDA-MB-231 cells. Importantly, the majority of the derivatives exhibited no apparent cytotoxicity in the clonogenic assays. The low to negligible inhibition of cell proliferation is a desirable property of these anti-migration derivatives because they hold promise of low toxicity to healthy cells as potential therapeutic agents. Mechanistic studies analyzing the actin cytoskeleton by microscopy demonstrate that compound 5k substantially reduced cellular f-actin, and prevented localization of fascin to actin-rich membrane protrusions. These results suggest that the anti-migration activity may result from impaired actin structures in protrusions that are necessary to drive migration. 23354072 Isolation and identification of β-hematin inhibitors from Flacourtia indica as promising antiplasmodial agents. An ethanolic extract (A001) of the leaves and twigs of Flacourtia indica (Burm.f.) Merr., was purified to give a new phenolic glycoside, 2-(2-benzoyl-β-D-glucopyranosyloxy)-7-(1α,2α,6α-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol (1) together with poliothrysoside (2), catechin-[5,6-e]-4β-(3,4-dihydroxyphenyl)dihydro-2(3H)-pyranone (3), 2-(6-benzoyl-β-D-glucopyranosyloxy)-7-(1α,2α,6α-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol (4), chrysoeriol-7-O-β-D-glucopyranoside (5), and mururin A (6). Compound 6 significantly inhibited the in vitro growth of both a chloroquine-sensitive (3D7) and a chloroquine-resistant (K1) strain of Plasmodium falciparum. It forms a complex with hematin and inhibits β-hematin formation, suggesting that this compound act on a heme polymerization target. 23202880 Observation of rates and products in the reaction of NO3 with submicron squalane and squalene aerosol. The reactive uptake coefficients γ, for nitrate radical, NO(3), on ∼100 nm diameter squalane and squalene aerosol were measured (1 atm pressure of N(2) and 293 K). For squalane, a branched alkane, γ(NO(3)) of 2.8 × 10(-3) was estimated. For squalene which contains 6 double bonds, γ(NO(3)) was found to be a function of degree of oxidation with an initial value of 0.18 ± 0.03 on fresh particles increasing to 0.82 ± 0.11 on average of over 3 NO(3) reactions per squalene molecule in the aerosol. Synchrotron VUV-ionization aerosol mass spectrometry was used to detect the particle phase oxidation products that include as many as 3 NO(3) subunits added to the squalene backbone. The fraction of squalene remaining in the aerosol follows first order kinetics under oxidation, even at very high oxidation equivalents, which suggests that the matrix remains a liquid upon oxidation. Our calculation indicates a much shorter chemical lifetime for squalene-like particle with respect to NO(3) than its atmospheric lifetime to deposition or wet removal. 23565754 Improved therapeutic targeting of the androgen receptor: rational drug design improves survival in castration-resistant prostate cancer. The growth and dependence of Prostate Cancer (PCa) on androgen stimulation led to the use of castration to reduce circulating levels of androgens and anti-androgens to directly target the androgen receptor (AR) ligand-binding domain (LBD). However, castration-resistant prostate cancer (CRPC) resistant to anti-androgens invariably develops and can be associated with AR genomic aberrations (mutations, amplification) and/or an increase in AR mRNA expression. Efforts to more effectively target the AR in CRPC led to the rational design of CYP17A1 inhibitors and more potent antiandrogens. The front-runner 2nd generation rationally-designed therapeutics targeting the AR, abiraterone and enzalutamide have been shown to improve survival and clinical outcome for CRPC patients. Several other CYP17A1 inhibitors and anti-androgens are in clinical and preclinical development. However, patients ultimately progress and current evidence suggests that this can occur through reactivation of AR signaling. Several ongoing programs aim to develop LBD independent therapeutic strategies that for example target the N terminus domain (NTD) of the AR or chaperone proteins. Rationally-designed approaches combining different strategies for targeting the AR or associated pathways also warrant clinical evaluation. 23628509 Cyclopenta[c]phenanthrenes - Chemistry and biological activity. Despite cyclopenta-fused polycyclic aromatic hydrocarbons (CP-PAHs) having been detected in the environment, the ability of these compounds to induce cellular and tissue responses remains poorly characterized. In this review, we look at the chemistry and biological activity of the cyclopenta[c]phenanthrenes (CP[c]Ph) as potential chemicals of concern in the process of risk assessment. The first part of the review deals with the environmental occurrence and chemistry of CP-PAHs, focusing on available methods of CP[c]Ph chemical synthesis. The most interesting structural feature of the CP[c]Ph is the presence of a pseudo fjord-region constructed by the cyclopentane ring. This compound can be treated either as a structurally similar one to B[c]Ph, or as a phenanthrene skeleton with an electrodonating alkyl substituent in the bay-region of the molecule. The second thread, providing available data on the adverse effects of CP[c]Ph compounds on cells and tissues of living organisms, mainly fish, improves our understanding of these possible environmental hazards. The data show that CP[c]Ph is less potent at inducing CYP1A gene expression in rainbow trout than benzo[a]pyrene (B[a]P), a well-known Ah-receptor agonist. Interestingly, the CP[c]Ph dependent up-regulation of CYP1A mRNA is positively correlated with the incidences of clastogenic changes in rainbow trout erythrocytes. CP[c]Ph has, comparably to B[a]P, a potential to repress expression of tumor suppressor p53, in the head kidney of rainbow trout. Furthermore, estrogen responsive genes in fish liver, ERα and VTG, are not induced by CP[c]Ph, suggesting that the compound has no endocrine disrupting potential. However, some CP[c]Phs show mutagenic activity when investigated in the Ames test, and exhibit genotoxic properties in in vitro micronucleus assay. The above characteristics suggest that CP-PAHs are chemicals of concern for which potential pathways of exposure should be further identified. 23317497 Recent progress in biological activities and synthetic methodologies of pyrroloquinoxalines. Pyrroloquinoxalines have proved to be a very attractive scaffold for medicinal chemist in the recent past. These compounds were extensively studied as bioactive compounds and many of them are known to be biologically and medicinally useful molecules, such as anti-HIV agents, antimalarial agents, antagonist agents, anticancer agents, and PARP-1 inhibitors. Additionally, pyrroloquinoxalines are also important intermediates for the construction of 5-HT3 receptor agonists. In this review the developments in biological activities and synthetic methodologies of pyrroloquinoxalines are discussed. 23400262 The importance of the TiO2/quantum dots interface in the recombination processes of quantum dot sensitized solar cells. Quantum dot sensitized solar cells (QDSSCs) present a promising technology for next generation photovoltaic cells, having exhibited a considerable leap in performance over the last few years. However, recombination processes occurring in parallel at the TiO(2)-QDs-electrolyte triple junction constitute one of the major limitations for further improvement of QDSSCs. Reaching higher conversion efficiencies necessitates gaining a better understanding of the mechanisms of charge recombination in these kinds of cells; this will essentially lead to the development of new solutions for inhibiting the described losses. In this study we have systematically examined the contribution of each interface formed at the triple junction to the recombination of the solar cell. We show that the recombination of electrons at the TiO(2)/QDs interface is as important as the recombination from TiO(2) and QDs to the electrolyte. By applying conformal MgO coating both above and below the QD surface, recombination rates were significantly reduced, and an improvement of more than 20% in cell efficiency was recorded. 23195329 Brain tumor immunotherapy: seeing the brain in the body. Brain tumor immunotherapy is often interpreted in terms of immune privilege and the blood-brain barrier (BBB), but a broader view is warranted. The delicate regulatory balance of the immune system is relevant at any site, as are the heterogeneity and plasticity of tumor growth. Criteria for tumor antigens, and often the antigens themselves, cut across tumor types. Here, this broader view, complemented by current understanding of privilege and the BBB, provides the context for review. Future success is likely to exploit simplified methods, used in combination; and similarities - more than differences - between the brain and other sites. 23631490 Green Tea Polyphenols Improve Bone Microarchitecture in High-Fat-Diet-Induced Obese Female Rats Through Suppressing Bone Formation and Erosion. Abstract This study evaluates the effects of green tea polyphenols (GTPs) on bone microarchitecture in high-fat-diet (HFD)-induced obese female rats. Thirty-six 3-month-old female rats were fed either a control diet or a HFD for 4 months. Animals in the control group continued on the control diet for another 4 months. Animals in the HFD group were divided into two groups, with 0.5 g/100 mL GTP (the HFD+GTP group) or without GTP (the HFD group) in drinking water, in addition to the HFD for another 4 months. Compared to the control group, the HFD group increased bone formation and erosion rates at the tibia, decreased trabecular volume and thickness, but had no impact on bone mineral density (BMD), trabecular number (Tb.N), and separation. Compared to the control group, the HFD+GTP group demonstrates a greater Tb.N at the proximal tibia, and a greater trabecular thickness at the femur and the lumbar vertebrae, but a smaller trabecular separation (Tb.Sp) and mineralizing surface at the proximal tibia, and a reduced endocortical mineral apposition rate (MAR) at the tibia shaft. Relative to the HFD group, the HFD+GTP group demonstrates (1) a higher BMD at the femur, a greater trabecular volume, thickness, and number at the proximal tibia, a larger cortical area and thickness at the tibial shaft, and a greater trabecular volume and thickness at the femur and the lumbar vertebrae, (2) a smaller Tb.Sp, MAR, bone formation rate, and eroded surface at the tibia. We concluded that GTP supplementation in drinking water improves bone microarchitecture in the HFD-induced obese female rats, possibly through suppressing bone turnover, resulting in a larger net bone volume. 23631499 Possible Therapeutic Uses of Salvia triloba and Piper nigrum in Alzheimer's Disease-Induced Rats. Abstract This study aimed to investigate the role of Salvia triloba L. and Piper nigrum extracts in ameliorating neuroinflammatory insults characteristic of Alzheimer's disease (AD) in an experimentally induced rat model. Adult male Sprague-Dawley rats were classified into Group 1 (n=10): normal healthy animals serving as the negative control group; Group 2 (n=60): the AD-induced group. After AD induction, animals in the AD-induced group were divided randomly and equally into 6 subgroups. The first subgroup served as AD control; the second one, which served as positive control, was treated orally with the conventional therapy for AD (rivastigmine) at a dose of 0.3 mg/kg body weight (b.w.) daily for 3 months. The third and fourth subgroups were, respectively, treated orally with the S. triloba extract at a dose of 750 and 375 mg/kg b.w. daily for 3 months. The fifth and sixth subgroups were, respectively, treated orally with the P. nigrum extract at a dose of 187.5 and 93.75 mg/kg b.w. daily for 3 months. Levels of brain acetylcholine (Ach), serum and brain acetylcholinesterase (AchE) activity, C-reactive protein (CRP), total nuclear factor kappa-B (NF-κB), and monocyte chemoattractant protein-1 (MCP-1) were estimated. The results showed that administration of AlCl3 resulted in a significant elevation in the levels of AchE activity, CRP, NF-κB, and MCP-1 accompanied with a significant depletion in the Ach level. Treatment of AD rats with each of the selected medicinal plant extracts caused marked improvement in the measured biochemical parameters. In conclusion, S. triloba and P. nigrum methanolic extracts have potent anti-inflammatory effects against neuroinflammation characterizing AD. 23093603 The Online Protein Processing Resource (TOPPR): a database and analysis platform for protein processing events. We here present The Online Protein Processing Resource (TOPPR; http://iomics.ugent.be/toppr/), an online database that contains thousands of published proteolytically processed sites in human and mouse proteins. These cleavage events were identified with COmbinded FRActional DIagonal Chromatography proteomics technologies, and the resulting database is provided with full data provenance. Indeed, TOPPR provides an interactive visual display of the actual fragmentation mass spectrum that led to each identification of a reported processed site, complete with fragment ion annotations and search engine scores. Apart from warehousing and disseminating these data in an intuitive manner, TOPPR also provides an online analysis platform, including methods to analyze protease specificity and substrate-centric analyses. Concretely, TOPPR supports three ways to retrieve data: (i) the retrieval of all substrates for one or more cellular stimuli or assays; (ii) a substrate search by UniProtKB/Swiss-Prot accession number, entry name or description; and (iii) a motif search that retrieves substrates matching a user-defined protease specificity profile. The analysis of the substrates is supported through the presence of a variety of annotations, including predicted secondary structure, known domains and experimentally obtained 3D structure where available. Across substrates, substrate orthologs and conserved sequence stretches can also be shown, with iceLogo visualization provided for the latter. 23109233 Modeling toxicity of binary metal mixtures (Cu(2+) -Ag(+) , Cu(2+) -Zn(2+) ) to lettuce, Lactuca sativa, with the biotic ligand model. The biotic ligand model (BLM) was applied to predict metal toxicity to lettuce, Lactuca sativa. Cu(2+) had the lowest median effective activity (EA50(M) ), compared with Ag(+) and Zn(2+) (EA50(Cu)  = 2.60 × 10(-8) M, EA50(Ag) = 1.34 × 10(-7)  M, EA50(Zn) = 1.06 × 10(-4)  M). At the 50% response level, the fraction of the total number of biotic ligands occupied by ions (f50(M) ) was lowest for Ag(+) among the metals (f50(Ag) = 0.22, f50(Cu) = 0.36, f50(Zn) = 0.42). Cu(2+) had the highest affinity for biotic ligands compared with Ag(+) and Zn(2+) , as shown by stability constants of the cation-biotic ligand binding, expressed as log K(MBL) (log K(CuBL) = 7.40, log K(AgBL) = 6.39, log K(ZnBL) = 4.00). Furthermore, the BLM was combined with the toxic equivalency factor approach in predicting toxicity of mixtures of Cu(2+) -Zn(2+) and Cu(2+) -Ag(+) . The fraction of biotic ligands occupied by ions was used to determine the relative toxic potency of metals and the toxic equivalency quotient (TEQ) of mixtures. This approach allowed for including interactions in estimating mixture toxicity and showed good predictive power (r(2) = 0.64-0.84). The TEQ at the 50% response level (TEQ50, Cu(2+) equivalents) for Cu(2+) -Zn(2+) mixtures was significantly lower than the value for Cu(2+) -Ag(+) mixtures. Joint toxicity depended on both TEQ and specific composition of the mixture. The present study supports the use of the accumulation of metal ions at the biotic ligands as a predictor of toxicity of single metals and mixtures. 23041228 Pim kinases in cancer: diagnostic, prognostic and treatment opportunities. PIM proteins belong to a family of ser/thr kinases composed of 3 members, PIM1, PIM2 and PIM3, with greatly overlapping functions. PIM kinases are mainly responsible for cell cycle regulation, antiapoptotic activity and the homing and migration of receptor tyrosine kinases mediated via the JAK/STAT pathway. PIM kinases have been found to be upregulated in many hematological malignancies and solid tumors. Although these kinases have been described as weak oncogenes, they are heavily targeted for anticancer drug discovery. The present review summarizes the discoveries made to date regarding PIM kinases as driving oncogenes in the process of tumorigenesis and their validation as drug targets. 23479193 Synthesis and in-silico studies of some diaryltriazole derivatives as potential cyclooxygenase inhibitors. The synthesis of several 4-phenyl-5-pyridin-4-yl-2,3-dihydro-3H-1,2,4-triazole-3-thiones possessing N-2 Mannich bases or S-alkyl substituents, is reported. Several of them exhibited a low nanomolar COX enzyme inhibition activity. Most of the compounds showed inhibition of edema was similar to that evoked by celocoxib in animal model. Molecular docking studies of the compounds into the binding sites of COX-1 and COX-2 allowed us to shed light on the binding mode of these novel COX inhibitors. 23373648 Recent advancements in small molecule inhibitors of insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase as anticancer agents. Advancements in understanding of the genetics, genomics, biochemistry and the pharmacology of cancer inhuman, have driven the current cancer chemotherapy to intently focus on development of target-based approaches rather than conventional approaches. From among the various targets identified, validated and inhibited at different hallmarks of cancer, protein tyrosine kinases (PTKs) have been exploited the most. Insulin receptors (IRs), insulin like growth factor receptors (IGF-1R) and their hybrid receptors belong to tyrosine kinase receptor (TKR) family, constitute a structural homology among them and generate a growth promoting IGF system on binding with either insulin, IGF-1 or IGF-2. The system induces the mitogenic effects through a torrent of cell signals produced as a result of cross talk with other growth promoting peptides and steroidal hormones, ultimately resulting in hijacking apoptosis and increasing cell proliferation and cell survival in cancer cells. Various strategies such as anti-IGF-1R antibodies, IGF-1 mimetic peptides, antisense strategies, IGF-1R specific peptide aptamers, targeted degradation of IGF-1R and expression of dominant negative IGF-1R mutants have been explored to inhibit the IGF-1R signaling. However, targeting IGF-1R with small molecules has gained considerable attention in last few years due to their ease of synthesis, ease of optimization of absorption,distribution, metabolism, excretion and toxicity (ADMET) parameters, oral route of administration, lesser side effects and cost effectiveness. The present review provides a broad overview and discusses the highlights on discoveries, SAR studies and binding interactions of small molecules with either IGF-1R active or allosteric sites reported till date. 23260352 Novel in vivo active anti-malarials based on a hydroxy-ethyl-amine scaffold. A novel series of anti-malarials, based on a hydroxy-ethyl-amine scaffold, initially identified as peptidomimetic protease inhibitors is described. Combination of the hydroxy-ethyl-amine anti-malarial phramacophore with the known Mannich base pharmacophore of amodiaquine (57) resulted in promising in vivo active novel derivatives. 23151612 A review of anti-inflammatory agents for symptoms of schizophrenia. Schizophrenia is a chronic debilitating mental disorder that affects about 1% of the US population. The pathophysiology and etiology remain unknown, thus new treatment targets have been challenging and few novel treatments with new mechanisms of action have come to market in the past few decades. Increasing attention has been paid to the role of inflammation in schizophrenia and new data suggests that decreasing inflammation and inflammatory biomarkers may play some role in schizophrenia treatment. This review summarizes the clinical trial literature regarding medications that possess anti-inflammatory properties that have been tested for schizophrenia symptoms and covers such medications as non-steroidal anti-inflammatory agents, such as the cyclo-oxygenase-2 (COX-2) inhibitors and aspirin, omega-3 fatty acids, neurosteroids and minocycline. Overall, there is accumulating evidence, albeit mostly adjunctive treatments, that agents working on inflammatory pathways have some benefits in people with schizophrenia. In the next few years the field will begin to see data on many treatments with anti-inflammatory properties that are currently under study. Hopefully advancements in understanding inflammation and effective treatments having anti-inflammatory properties may help revolutionize our understanding and provide new targets for prevention and treatment in schizophrenia. 23334979 Characterization of osteoblastic and osteolytic proteins in prostate cancer bone metastases. BACKGROUND: Approximately 90% of patients who die of Prostate Cancer (PCa) have bone metastases, which promote a spectrum of osteoblastic, osteolytic or mixed bone responses. Numerous secreted proteins have been reported to promote osteoblastic or osteolytic bone responses. We determined whether previously identified and/or novel proteins were associated with the osteoblastic or osteolytic response in clinical specimens of PCa bone metastases. METHODS: Gene expression was analyzed on 14 PCa metastases from 11 patients by microarray profiling and qRT-PCR, and protein expression was analyzed on 33 PCa metastases from 30 patients by immunohistochemistry on highly osteoblastic and highly osteolytic bone specimens. RESULTS: Transcript and protein levels of BMP-2, BMP-7, DKK-1, ET-1, and Sclerostin were not significantly different between osteoblastic and osteolytic metastases. However, levels of OPG, PGK1, and Substance P proteins were increased in osteoblastic samples. In addition, Emu1, MMP-12, and sFRP-1 were proteins identified with a novel role of being associated with either the osteoblastic or osteolytic bone response. CONCLUSIONS: This is the first detailed analysis of bone remodeling proteins in human specimens of PCa bone metastases. Three proteins not previously shown to be involved may have a role in the PCa bone response. Furthermore, our data suggests that the relative expression of numerous, rather than a single, bone remodeling proteins determine the bone response in PCa bone metastases. Prostate © 2013 Wiley Periodicals, Inc. 23523781 Pharmacokinetic, neurochemical, stereological and neuropathological studies on the potential effects of paraquat in the substantia nigra pars compacta and striatum of male C57BL/6J mice. The pharmacokinetics and neurotoxicity of paraquat dichloride (PQ) were assessed following once weekly administration to C57BL/6J male mice by intraperitoneal injection for 1, 2 or 3 weeks at doses of 10, 15 or 25mg/kg/week. Approximately 0.3% of the administered dose was taken up by the brain and was slowly eliminated, with a half-life of approximately 3 weeks. PQ did not alter the concentration of dopamine (DA), homovanillic acid (HVA) or 3,4-dihydroxyphenylacetic acid (DOPAC), or increase dopamine turnover in the striatum. There was inconsistent stereological evidence of a loss of DA neurons, as identified by chromogenic or fluorescent-tagged antibodies to tyrosine hydroxylase in the substantia nigra pars compacta (SNpc). There was no evidence that PQ induced neuronal degeneration in the SNpc or degenerating neuronal processes in the striatum, as indicated by the absence of uptake of silver stain or reduced immunolabeling of tyrosine-hydroxylase-positive (TH(+)) neurons. There was no evidence of apoptotic cell death, which was evaluated using TUNEL or caspase 3 assays. Microglia (IBA-1 immunoreactivity) and astrocytes (GFAP immunoreactivity) were not activated in PQ-treated mice 4, 8, 16, 24, 48, 96 or 168h after 1, 2 or 3 doses of PQ. In contrast, mice dosed with the positive control substance, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 10mg/kg/dose×4 doses, 2h apart), displayed significantly reduced DA and DOPAC concentrations and increased DA turnover in the striatum 7 days after dosing. The number of TH(+) neurons in the SNpc was reduced, and there were increased numbers of degenerating neurons and neuronal processes in the SNpc and striatum. MPTP-mediated cell death was not attributed to apoptosis. MPTP activated microglia and astrocytes within 4h of the last dose, reaching a peak within 48h. The microglial response ended by 96h in the SNpc, but the astrocytic response continued through 168h in the striatum. These results bring into question previous published stereological studies that report loss of TH(+) neurons in the SNpc of PQ-treated mice. This study also suggests that even if the reduction in TH(+) neurons reported by others occurs in PQ-treated mice, this apparent phenotypic change is unaccompanied by neuronal cell death or by modification of dopamine levels in the striatum. 23205571 Design, synthesis and structure-activity relationship of new arginine vasopressin analogues containing proline derivatives in position 2. In this study, we present the synthesis and pharmacological properties of new analogues of arginine vasopressin modified in the N-terminal part of the molecule with proline derivatives: indoline-2-carboxylic acid (Ica) and (2S,4R)-4-(naphthalene-2-ylmethyl)pyrrolidine-2-carboxylic acid. All the peptides were tested for pressor, antidiuretic and in vitro uterotonic activities. We also determined their binding affinity to the human oxytocin receptor. The Ica(2) substitution resulted in two moderately potent and selective antioxytocic agents: [Mpa(1), Ica(2), D-Arg(8)]VP and [Mpa(1),Ica(2),Val(4),D-Arg(8)]VP (pA(2) = 7.09 and 7.50, respectively). On the other hand, peptides modified with (2S,4R)-4-(naphthalene-2-ylmethyl)pyrrolidine-2-carboxylic acid, apart from their moderate antioxytocic activity, turned out to be weak antagonists of the pressor response to arginine vasopressin. The results of this study provide useful information about the structure-activity relationship of arginine vasopressin analogues and can help to design compounds with desired biological properties. 23360392 Elucidation of the Molecular Interaction between Cisplatin and Flavonol(s) and their Effect on DNA Binding. Combination therapy of cisplatin with flavonols is a promising treatment for increasing the efficacy of cisplatin when combating cancer. However, little is known about the molecular interactions between cisplatin and flavonols. The data herein helps to elucidate this interaction. Spectrophotometric data in the UV-visible range indicates that hydroxyl groups on the B-ring of flavonols are essential for reactivity with cisplatin. The use of a quartz crystal microbalance with dissipation monitoring approach clearly supports the critical role played by B-ring hydroxyls in their interactions with a cisplatin-bound double-stranded DNA surface; an increase in the number of hydroxyl groups on the B-ring of flavonols parallels the increase in their reaction rates with cisplatin and correlates well with their reported effects on leukemia cell apoptosis efficacy. This study underscores the importance of B-ring hydroxyls in cisplatin's toxicity and may be used to better understand and improve combination therapies of flavonols with cisplatin. 23544667 Self-Assembling Behavior of Cellulose Nanoparticles during Freeze-Drying: Effect of Suspension Concentration, Particle Size, Crystal Structure, and Surface Charge. Cellulose nanocrystals and cellulose nanofibers with I and II crystalline allomorphs (designated as CNC I, CNC II, CNF I, and CNF II) were isolated from bleached wood fibers by alkaline pretreatment and acid hydrolysis. The effects of concentration, particle size, surface charge, and crystal structure on the lyophilization-induced self-assembly of cellulose particles in aqueous suspensions were studied. Within the concentration range of 0.5 to 1.0 wt %, cellulose particles self-organized into lamellar structured foam composed of aligned membrane layers with widths between 0.5 and 3 μm. At 0.05 wt %, CNC I, CNF I, CNC II, and CNF II self-assembled into oriented ultrafine fibers with mean diameters of 0.57, 1.02, 1.50, and 1.00 μm, respectively. The size of self-assembled fibers became larger when more hydroxyl groups and fewer sulfates (weaker electrostatic repulsion) were on cellulose surfaces. Possible formation mechanism was inferred from ice growth and interaction between cellulose nanoparticles in liquid-crystalline suspensions. 23357434 Genetic risk factors for glucocorticoid-induced osteonecrosis: a meta-analysis. Glucocorticoid-induced osteonecrosis is a common and severe adverse event. We conducted a meta-analysis to investigate whether polymorphisms in target genes were associated with the risk of corticosteroid-induced osteonecrosis. Published literature from PubMed and EMBASE were searched for eligible publications. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a fixed- or random-effects model. There were 23 articles with 35 genes described the relationship between polymorphisms and glucocorticoid-induced osteonecrosis. Meta-analyses were carried out for those SNPs with three or more eligible studies, which included four SNPs located in three genes (PAI-1, MTHFR, ABCB1). The meta-analysis revealed that the PAI-1 4G allele was associated with an increased risk of osteonecrosis compared with the 5G allele (combined studies: OR=1.932, 95% CI=1.145-3.261). The OR for the 4G/4G vs. 5G/5G genotype of PAI-1 was 3.217 (95% CI 1.667-6.209 with combined studies), The relative risk of osteonecrosis was increased in the 4G allele vs. 5G/5G and 4G/4G genotype vs. 5G allele, with odds ratios of 2.304 (95% CI=1.235-4.299) and 2.307 (95% CI=1.527-3.485) in combined studies, respectively. The ABCB1 C3435T genotype distributions available confirmed that the C allele increased osteonecrosis risk compared with the T allele (OR 1.668, 95% CI=1.214-2.293) and TT genotype (OR 2.946, 95% CI=1.422-6.101). There was no evidence for significant association between MTHFR C677T and ABCB1 G2677T/A polymorphisms and risk of osteonecrosis. Results of this meta-analysis indicate that the PAI-1 4G/5G and ABCB1 C3435T polymorphisms may be risk factors for osteonecrosis. 23411306 Determination of seven synthetic dyes in animal feeds and meat by high performance liquid chromatography with diode array and tandem mass detectors. An efficient method was developed for the simultaneous determination of seven commonly used synthetic sulfonate dyes (Ponceau 4RC, Sunset yellow, Allura red, Azophloxine, Ponceau xylidine, Erythrosine and Orange II) in animal feed and meat using high performance liquid chromatography (HPLC-DAD) and tandem mass spectrometry (HPLC-MS/MS). Ethanol-ammonia-water (80:1:19, V/V/V) solution was used as extract solution, which can extract target species while reducing interference from the sample matrices. The recoveries of these 7 dyes in animal feed and chicken meat were between 71% and 97% with relative standard deviations less than 14.8%. HPLC-MS/MS was employed as a further means of confirmation to assure accuracy of the results. Limits of detection for these dyes were in the range of 0.02-21.83 ng mL(-1). The proposed method can be applied to confirmative screening of seven commonly used food colorants in feed and meat samples. 23287710 Dose dependent molecular effects of acrylamide and glycidamide in human cancer cell lines and human primary hepatocytes. Recently published studies suggest a weak positive correlation between increased dietary acrylamide intake and the increased risk of endometrial and ovarian cancer. However, risk assessment of acrylamide remains difficult because the carcinogenic mechanisms are still unknown and in particular the molecular effects of low level acrylamide exposure as seen by dietary intake are not well understood. Therefore, we analyzed in ovarian and endometrial cancer cell lines as well as in primary hepatocytes the expression of genes involved in cancer development and xenobiotic metabolism after high and low dose exposure (1-0.001mM) of acrylamide and its metabolite glycidamide. In conclusion our in vitro results demonstrate that exposure to high doses of glycidamide/acrylamide - exceeding the dietary exposure of the general population by far - can induce genes with growth promoting potential like the oncogene cMYC and genes involved in the MAPK pathway. However, low-dose exposure seems to activate primarily genes involved in the elimination of the toxicant. 23297755 Isolation and anti-HIV-1 activity of a new sesquiterpene lactone from Calocephalus brownii F. Muell. As part of our ongoing collaborative effort to discover potential anti-HIV-1 agents from plants, the CH(2)Cl(2) extract of Calocephalus brownii F. Muell. was phytochemically investigated, which resulted in the isolation of two sesquiterpene lactones of the cis-fused guaianolides type, one new identified as 1α-hydroxy-3βH-3α,4α-epoxy-4,10-dimethyl-5αH,7αH,8βH,10αH-guai-11(13)-ene-7,8-olide (1) and one known identified 1αH-4α-hydroxy-4,10-dimethyl-5αH,7αH,8βH,10αH-guai-11(13)-ene-7,8-olide (2). Their structures were elucidated on the bases of IR, UV, 1D-NMR, 2D-NMR, DIFNOE and high-resolution ESI-TOF-MS. The anti-HIV-1 activity was evaluated and revealed that STLs (1 and 2) caused a reduction for the viability of mock-infected MT-4 cells by CC(50) = 29.1 and 0.5 μg/mL, respectively, and caused 50% protection of MT-4 cells against HIV-1 induced cytopathogeneticy by EC(50) = 29.1 and 0.5 μg/mL, respectively, as compared with Efavirenz (EFV) as positive control that showed a CC(50) = 11.6 and EC(50) = 0.0006 μg/mL, using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide method. 23135548 Dioxin inhibits zebrafish epicardium and proepicardium development. Embryonic exposure to the environmental contaminant and aryl hydrocarbon receptor agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), disrupts cardiac development and function in fish, birds, and mammals. In zebrafish, the temporal window of sensitivity to the cardiotoxic effects of TCDD coincides with epicardium formation. We hypothesized that this TCDD-induced heart failure results from disruption of epicardial development. To determine whether embryonic TCDD exposure inhibits epicardium and proepicardium (PE) development in zebrafish, we used histology and fluorescence immunocytochemistry to examine the epicardium formation in fish exposed to TCDD. TCDD exposure prevented epicardium formation. Using live imaging and in situ hybridization, we found that TCDD exposure blocked the formation of the PE cluster. In situ hybridization experiments showed that TCDD exposure also prevented the expression of the PE marker tcf21 at the site where the PE normally forms. TCDD also inhibited expansion of the epicardial layer across the developing heart: Exposure after PE formation was completed prevented further expansion of the epicardium. However, TCDD exposure did not affect epicardial cells already present. Because TCDD blocks epicardium formation, but is not directly toxic to the epicardium once complete, we propose that inhibition of epicardium formation can account for the window of sensitivity to TCDD cardiotoxicity in developing zebrafish. Epicardium development is crucial to heart development. Loss of this layer during development may account for most if not all of the TCDD-induced cardiotoxicity in zebrafish. 23256510 Morphology-dependent trap formation in bulk heterojunction photodiodes. We show that local structural variation affects the rate of aging in nanostructured polymer solar cells by comparing time-resolved electrostatic force microscopy (trEFM) and conventional device measurements on model polymer blends. Specifically, we study photovoltaic devices made from 1:1 blends of the polyfluorene copolymers poly(9,9'-dioctylfluorene-co-bis-N,N'-(4-butylphenyl)-bis-N,N'-phenyl-1,4-phenylene-diamine) (PFB) and poly(9,9'-dioctylfluorene-co-benzothiadiazole) (F8BT). We photooxidize these films in situ using 365, 405, and 455 nm illumination under ambient conditions, with the wavelengths chosen to preferentially excite the different components. During photooxidation, we observe a faster loss of photocurrent generation from F8BT-rich domains, leaving the PFB-rich phases to show higher photoresponse even at wavelengths absorbed predominantly by F8BT. We propose that this effect is due to the more rapid degradation of PFB hole-transport pathways in the F8BT-rich regions, resulting in a loss of percolation pathways for hole transport in the F8BT-rich phase. 23594299 Automated actuation of nasal spray products: effect of hand-related variability on the in vitro performance of Flonase nasal spray. Abstract Objective: To determine if patient-related variability for adults and children recorded during hand spraying of Flonase with an instrumented nasal spray results in significant differences in spray weight, droplet size or spray pattern. Methods: Settings derived from adult and pediatric participants hand-spraying nasal sprays were implemented into force and velocity-controlled automated actuators. Spray weight, droplet size distribution and spray pattern tests were performed using iterations of actuation force (AF) and force rise, hold and fall times. Travel, actuation velocity and release velocity settings were also investigated. Results: The variability measured in adult-derived actuator settings did not result in any differences in spray weight, but pediatric participants spraying with low AF and/or compression velocity (CV) were predicted to receive a partial dose or no dose at all under some circumstances. Droplet size characteristics were sensitive to the hand-based variability, with actuation force, force rise time and CV hand-related settings all resulting in significant differences in the droplet size. Conclusions: This study demonstrated how variability in hand spraying by adults and pediatric patients could result in differences in nasal spray characteristics, thus demonstrating the importance of monitoring how the prospective patient groups are likely to use a nasal spray. 23401106 Modeling environmental and human health risks of veterinary medicinal products applied in pond aquaculture. A model called ERA-AQUA was developed to assess the risks posed by the use of veterinary medicinal products (VMPs) applied in aquaculture ponds for the targeted produce, surrounding aquatic ecosystems, consumers, and trade of the aquaculture produce. The model calculates risks by following a risk quotient approach, calculating predicted exposure concentrations (exposure assessment) and predicted no-effect concentrations (effect assessment) for the endpoint under study. The exposure assessment is performed by combining information on the environmental characteristics of the aquaculture pond, characteristics of the cultured species, aquaculture management practices, and physicochemical properties of the compound under study. The model predicts concentrations of VMPs in the pond water, pond sediment, cultured species, and watercourse receiving pond effluent discharges by mass balance equations. The effect assessment is performed by combining (eco)toxicological information and food safety threshold concentrations for the studied compound. In the present study, the scientific background, strengths, and limitations of the ERA-AQUA model are presented together with a sensitivity analysis and an example showing its potential applications. Environ. Toxicol. Chem. 2013;32:1196-1207. © 2013 SETAC. 23614368 Intestinal bacterial transformation - a nonnegligible part of Chinese medicine research. Intestinal bacteria play an essential part in the metabolism of the constituents of herbal drugs, and a lot of investigations have been done to unveil their functions and mechanisms in modification of these constituents and their effect. This review provides a progressive description of intestinal bacterial transformation with respect to properties, reactions, correlation with the effect of herbal drugs, research interests, and methodology. In addition, the problems encountered during the investigation are addressed and perspectives are proposed. 23111884 Estimation of BDNF gene polymorphism and predisposition to dependence development for selected psychoactive compounds: genetic aspects of addiction with the selected drugs, amphetamine, tetrahydrocannabinol and opiates. The etiology of drug addiction, a central nervous system (CNS) disease, is not fully known. This complex problem is believed to be connected with concurrently affecting genetic, psychological and environmental factors. The development of addiction is connected with CNS reinforcement system and dopaminergic neurotransmission. Molecular processes are postulated to be of universal character and allow to presume a similar mechanism of dependence for both ethanol and other substances. Therefore, elements of dopaminergic transmission become excellent candidates for the examination of genetic influence on the development of addiction. A relationship between alcoholic disease and the presence of TaqIA1 and DRD2 alleles permits to initiate another investigation of gene-coding DRD2 dopamine receptor. The latest results indicate the importance of brain-derived neurotrophic factor (BDNF) in the regulation of dopaminergic route. The purpose of this research was to reveal the relationship between the Val66Met BDNF gene polymorphism and dependence of psychoactive agent. The examinations were performed with the Local Research Ethics Committee approval and patient's consent. The study group consisted of 100 patients (88 men and 12 women) aged 18-52 years, qualified for research program according to the International Classification of Diseases, Tenth Revision (ICD-10) requirements, medical examination and detailed questionnaire. 23525330 State-Dependent Etomidate Occupancy of its Allosteric Agonist Sites Measured in a Cysteine-Substituted GABAA Receptor. A central axiom of ligand-receptor theory is that agonists bind more tightly to active than to inactive receptors. However, measuring agonist affinity in inactive receptors is confounded by concomitant activation. We identified a cysteine substituted mutant GABAA receptor with unique characteristics allowing determination of allosteric agonist site occupancy in both inactive and active receptors. Etomidate, the allosteric agonist, is an anesthetic that activates/modulates α1β2γ2L GABAA receptors via transmembrane sites near β2M286 residues in M3 domains. Voltage-clamp electrophysiology studies of α1β2M286Cγ2L receptors show that GABA is an efficacious agonist, and etomidate modulates GABA-activated activity, but direct etomidate agonism is absent. Quantitative analysis of mutant activity using an established Monod-Wyman-Changeux (MWC) allosteric model indicates that the intrinsic efficacy of etomidate, defined as its relative affinity for active vs. inactive receptors, is lower than in wild-type receptors. Para-chloromercuribenzene sulfonate (pCMBS) covalently modifies β2M286C sidechain sulfhydryls, irreversibly altering GABA-induced currents. Etomidate concentration-dependently reduces the apparent rate of β2M286C-pCMBS bond formation, tracked electrophysiologically. High etomidate concentrations completely protect the β2M286C suflhydryl from covalent modification, suggesting close steric interactions. The 50% protective etomidate concentration (PC50) is 14 μM in inactive receptors and 1.1 to 2.2 μM during GABA-activation, experimentally demonstrating that activated receptors bind etomidate more avidly than inactive receptors. The experimental PC50 values are remarkably close to, and therefore validate MWC model predictions for etomidate dissociation constants in both inactive and active receptors. Our results support MWC models as valid frameworks for understanding agonism, co-agonism, and modulation of ligand-gated ion channels. 22760156 Anion binding in water at lanthanide centres: from structure and selectivity to signalling and sensing. Reversible anion binding at lanthanide centres in aqueous media has emerged as an effective means of signalling and sensing the presence of selected anions. The constitution and configuration of a wide range of anion adducts has been defined by X-ray analyses and NMR methods, and both chelating and monodentate binding modes characterised. Variation of the lanthanide ion modulates charge density, and ligand modification allows alteration of both the peripheral electrostatic gradient and the local steric demand at the metal centre. Thus, selectivity for a target anion can be engineered, and the affinity constant modulated to target the desired concentration range. Changes in anion concentration can be monitored rapidly, accurately and with high spatial resolution using optical emission spectroscopy and microscopy, facilitating the measurement of anions such as bicarbonate, lactate, citrate and urate in a variety of bio-fluids. 23393209 Determinants of Maternal Triglycerides in Women With Gestational Diabetes Mellitus in the Metformin in Gestational Diabetes (MiG) Study. OBJECTIVEFactors associated with increasing maternal triglyceride concentrations in late pregnancy include gestational age, obesity, preeclampsia, and altered glucose metabolism. In a subgroup of women in the Metformin in Gestational Diabetes (MiG) trial, maternal plasma triglycerides increased more between enrollment (30 weeks) and 36 weeks in those treated with metformin compared with insulin. The aim of this study was to explain this finding by examining factors potentially related to triglycerides in these women.RESEARCH DESIGN AND METHODSOf the 733 women randomized to metformin or insulin in the MiG trial, 432 (219 metformin and 213 insulin) had fasting plasma triglycerides measured at enrollment and at 36 weeks. Factors associated with maternal triglycerides were assessed using general linear modeling.RESULTSMean plasma triglyceride concentrations were 2.43 (95% CI 2.35-2.51) mmol/L at enrollment. Triglycerides were higher at 36 weeks in women randomized to metformin (2.94 [2.80-3.08] mmol/L; +23.13% [18.72-27.53%]) than insulin (2.65 [2.54-2.77] mmol/L, P = 0.002; +14.36% [10.91-17.82%], P = 0.002). At 36 weeks, triglycerides were associated with HbA1c (P = 0.03), ethnicity (P = 0.001), and treatment allocation (P = 0.005). In insulin-treated women, 36-week triglycerides were associated with 36-week HbA1c (P = 0.02), and in metformin-treated women, they were related to ethnicity.CONCLUSIONSAt 36 weeks, maternal triglycerides were related to glucose control in women treated with insulin and ethnicity in women treated with metformin. Whether there are ethnicity-related dietary changes or differences in metformin response that alter the relationship between glucose control and triglycerides requires further study. 23500115 Characterization and skin permeation of ketoprofen loaded vesicular systems. PURPOSE: To determine the effect of elasticity on the skin permeation of ketoprofen from surfactant-based vesicular formulations and elastic liposomes. METHODS: Ketoprofen loaded surfactant-based vesicles and elastic liposomes were prepared by sonication. Citric buffer (at pH 3.0) was used as rehydration buffer. Characterization studies of the prepared liposomal formulations were performed by dynamic light scattering, extrusion, and (1)H and (31)P-nuclear magnetic resonance (NMR) spectroscopy. Ketoprofen transport studies across human skin were performed for all formulations. RESULTS: Stable ketoprofen loaded formulations were prepared. Addition of an edge activator, in the absence of the drug, increased the elasticity of the vesicles and liposomes. Ketoprofen loading reduced the elasticity of the liposomes and surfactant-based-vesicles. However, at saturation the elasticity was still higher than that in the absence of the edge activator and ketoprofen, except for ketoprofen loaded liposomes with Span 80. NMR studies revealed that the ketoprofen molecules were entrapped in a vesicle bilayer in all vesicular formulations, and that the ketoprofen molecules affected the phosphate mobility in the liposomal formulations. Ketoprofen transport studies across human skin clearly showed that the surfactant-based vesicular formulations were superior to the elastic liposomal formulations. CONCLUSION: Surfactant-based vesicles enhance ketoprofen transport across human skin, while no enhancement of ketoprofen was observed when loaded in elastic liposomes. 23424212 Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation. Hepatotoxicity is one of the major complications of methotrexate (MTX) therapy. This study was carried out to evaluate the possible protective effect of resveratrol (trans-3,5,4'-trihydroxystilbene, RVT) against MTX-induced hepatotoxicity. Rats were randomly divided into four groups as control, MTX treated (7 mg/kg/day, intraperitoneally (i.p.), once daily for 3 consecutive days), MTX + RVT treated (20 mg/kg/day, i.p.), and RVT treated. First dose of RVT was administrated 3 days before the MTX injection and continued for 3 days. Histopathology of liver was evaluated by light microscopy. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury. The levels of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation) and activities of hepatic antioxidant enzymes such as catalase (CAT) and glutathione-S-transferase (GST) were used to analyze the oxidative stress-mediated lipid peroxidation in liver sections. Our results showed that MTX administration significantly increased ALT, ASP, and ALP levels. TBARS, CAT, and GST levels were also markedly increased in liver after MTX administration. RVT treatment significantly prevented MTX-induced hepatotoxicity, as indicated by AST, ALT, and ALP levels and liver histopathology. Moreover, administration of RVT significantly decreased the elevated levels of TBARS and activities of CAT and GST in the liver compared to MTX-treated group. These results revealed that RVT may have a protective effect against MTX-induced hepatotoxicity by inhibiting oxidative stress-mediated lipid peroxidation. Consequently, RVT treatment might be a promising strategy against MTX-induced hepatotoxicity. 23576378 Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug-Resistant Bacteria. Five novel N-substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure-based approach. The in vitro antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA), gentamicin-resistant Enterococcus faecalis (GRE), methicillin-resistant Streptococcus pneumoniae (MRS), and vancomycin-resistant Enterococcus faecalis (VRE) were evaluated. One of the compounds, N-(6-phenylheptyl)demethylvancomycin (12 a), was found to exhibit more potent antibacterial activity than vancomycin and demethylvancomycin. Compound 12 a was also found to be ~18-fold more efficacious than vancomycin against MRSA; however, the two compounds were found to have similar efficacy against MRS. Furthermore, compound 12 a exhibited a favorable pharmacokinetic profile with a half-life of 5.11±0.52 h, which is longer than that of vancomycin (4.3±1.9 h). These results suggest that 12 a is a promising antibacterial drug candidate for further preclinical evaluation. 23261644 A comparative performance test of standard, medium- and high-throughput comet assays. A serious limitation of the conventional comet assay (single cell gel electrophoresis) is the restriction on the number of samples that can be processed in one experiment, imposed by the size of the electrophoresis platform. One approach to increasing throughput is to reduce the size of gels. We here compare the conventional system of two large gels on a microscope slide, with two recent developments, namely 12 minigels per slide, and a format with 96 minigels on GelBond® film. We used cells treated with X-rays or methylmethanesulphonate (MMS). The level of damage detected (% tail DNA) in X-irradiated or MMS-treated cells was not affected by the format used. Parallel experiments, using all three formats, were performed with MMS-treated cells in two independent laboratories; the difference in results between the two laboratories was of borderline significance. The potential problem of anomalous comets seen at the border of the gel, the so-called 'edge effects', has been addressed. A reliable, high throughput comet assay has applications in genotoxicity testing (particularly for in vivo studies with samples from different organs) as well as ecogenotoxicology and human biomonitoring, where the numbers of samples collected can be considerable. 23627806 Superparamagnetic Hollow Hybrid Nanogels as a Potential Guidable Vehicle System of Stimuli-Mediated MR Imaging and Multiple Cancer Therapeutics. Hollow hybrid nanogels were prepared first by co-assembly of the citric acid-coated superparamagnetic iron oxide nanoparticles (SPIONs) (44 wt%) with the graft copolymer (56 wt%) comprising acrylic acid and 2-methacryloylethyl acrylate units as the backbone and poly(ethylene glycol) and poly(N-isopropylacrylamide) as the grafts in aqueous phase of pH 3.0 into the hybrid vesicle structure, followed by in situ covalent stabilization via the photo-initiated polymerization of MEA residues within vesicles. The resultant hollow nanogels, though slightly swollen, satisfactorily retain the structural integrity while the medium pH being adjusted to 7.4. Confining SPION clusters to such a high level (44 wt%) within the pH-responsive thin gel layer remarkably enhances the transverse relaxivity (r2) and renders the MR imaging highly pH-tunable. For example, with the pH being adjusted from 4.0 to 7.4, the r2 value can be dramatically increased from 138.5 to 265.5 mM-1 s-1. The DOX-loaded hybrid nanogels also exhibit accelerated drug release in response to both pH reduction and temperature increase due to the substantial disruption of the interactions between drug molecules and copolymer components. With magnetic transport guidance toward the target and subsequent exposure to alternating magnetic field, this DOX-loaded nanogel system possessing combined capabilities of hyperthermia and stimuli-triggered drug release showed superior in vitro cytotoxicity against HeLa cells as compared to the case with only free drug or hyperthermia alone. This work demonstrates that the hollow inorganic/organic hybrid nanogels show great potential to serve as a multimodal theranostic vehicle functionalized with such desirable features as guidable delivery of stimuli-mediated diagnostic imaging and hyperthermia/chemotherapies. 23582779 Discovery of novel orally bioavailable GPR40 agonists. The GPR40 (FFA1) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency. A series of novel orally bioavailable GPR40 agonists was discovered. SAR study and structural optimization led to identification of compounds 28a and 30a as potent GPR40 agonists with superior physiochemical properties and robust in vivo efficacy in rhesus monkeys. 23379369 Synthesis, microwave spectrum, and conformational properties of 2-fluoroethyl azide (FCH2CH2N3). A novel synthesis producing neat 2-fluoroethyl azide (FCH2CH2N3) is described. A conformational analysis using microwave spectroscopy augmented by quantum chemical calculations at the CCSD(T)/cc-pVTZ, B3LYP/aug-cc-pVTZ, and B3LYP/cc-pVTZ levels of theory has been performed for this compound. The spectra of the ground vibrational state and two vibrationally excited states of one rotameric form were assigned. A large number of transitions was assigned, and very accurate values were obtained for the rotational and quartic centrifugal distortion constants. The identified conformer has synclinal orientations for the F-C-C-N and C-C-N-N chains of atoms bringing the fluorine atom and the azido group into close proximity. It is concluded from consideration of absolute intensities that this conformer is indeed the preferred form of the molecule in accord with the theoretical calculations. The experimental and CCSD(T) rotational constants are in very good agreement, whereas much larger discrepancies were seen for the experimental and B3LYP quartic centrifugal distortion constants. 23411220 Film forming ability of gelatins from splendid squid (Loligo formosana) skin bleached with hydrogen peroxide. Properties of gelatin films from splendid squid (Loligo formosana) skin bleached with hydrogen peroxide (H(2)O(2)) at various concentrations (0-8% w/v) were investigated. Tensile strength (TS) and water vapour permeability (WVP) of films decreased, but elongation at break (EAB) increased (p<0.05) as the concentration of H(2)O(2) increased. Among all films, that prepared from gelatin with 2% H(2)O(2) bleaching showed the lowest ΔE(∗)-value (total colour difference), which was concomitant with the highest L(∗)-value (lightness). Generally, higher concentration of H(2)O(2) resulted in increased b(∗)-value (yellowness) of resulting films. Electrophoretic study revealed that α-chains of gelatin in films became lowered with increasing H(2)O(2) concentrations used for bleaching. Thermogravimetric analysis indicated that heat susceptibility and weight loss of different films varied with H(2)O(2) concentrations. Rougher surface was obtained in gelatin films prepared from skin bleached with H(2)O(2) concentrations above 4%. Thus, the concentrations of H(2)O(2) used for bleaching of squid skin prior to gelatin extraction directly affected the properties of corresponding gelatin films. 23478800 Cucurbitacin I inhibits rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of janus tyrosine kinase 2 and p-rex1. The small GTPase Rac1 has been widely implicated in mammary tumorigenesis and metastasis. Previous studies established that stimulation of ErbB receptors in breast cancer cells activates Rac1 and enhances motility via the Rac-guanine nucleotide exchange factor P-Rex1. As the Janus tyrosine kinase 2 (Jak2)/signal transducer and activator of transcription 3 (Stat3) pathway has been shown to be functionally associated with ErbB receptors, we asked if this pathway could mediate P-Rex1/Rac1 activation in response to ErbB ligands. Here we found that the anticancer agent cucurbitacin I, a Jak2 inhibitor, reduced the activation of Rac1 and motility in response to the ErbB3 ligand heregulin in breast cancer cells. However, Rac1 activation was not affected by Jak2 or Stat3 RNA interference, suggesting that the effect of cucurbitacin I occurs through a Jak2-independent mechanism. Cucurbitacin I also failed to affect the activation of P-Rex1 by heregulin. Subsequent analysis revealed that cucurbitacin I strongly activates RhoA and the Rho effector Rho kinase (ROCK) in breast cancer cells and induces the formation of stress fibers. Interestingly, disruption of the RhoA-ROCK pathway prevented the inhibitory effect of cucurbitacin I on Rac1 activation by heregulin. Lastly, we found that RhoA activation by cucurbitacin I is mediated by reactive oxygen species (ROS). The ROS scavenger N-acetyl l-cysteine and the mitochondrial antioxidant Mito-TEMPO rescued the inhibitory effect of cucurbitacin I on Rac1 activation. In conclusion, these results indicate that ErbB-driven Rac1 activation in breast cancer cells proceeds independently of the Jak2 pathway. Moreover, they established that the inhibitory effect of cucurbitacin I on Rac1 activity involves the alteration of the balance between Rho and Rac. 23340858 Bandgap broadly tunable GaZnSeAs alloy nanowires. Composition-tunable semiconductor alloy nanowires are emerging as an important class of materials for the realization of high-performance laterally-arranged multiple bandgap (LAMB) solar cells. Here we report the first growth of GaZnSeAs quaternary alloy nanowires with composed elements between two different groups using a temperature/space-selective CVD route. Under laser excitation, these special quaternary alloy nanowires exhibit composition-related characteristic emissions, with peak wavelengths gradually tunable from 470 nm (2.64 eV) to 832 nm (1.49 eV), covering almost the entire visible spectrum. Surface photovoltage measurements further reveal that these alloy nanowires have tunable bandgaps along the length of the substrate, making them promising candidates for developing high-efficiency LAMB solar cells. These quaternary alloy nanowires represent a new advancement in material synthesis and would have potential applications in a variety of function-tunable and broadband-response optoelectronic devices. 23356964 Flavone tetraglycosides and benzyl alcohol glycosides from the Mongolian medicinal plant Dracocephalum ruyschiana. From an extract of the aerial parts of Dracocephalum ruyschiana, five new flavone tetraglycosides, five new benzyl alcohol glycosides, and 19 known compounds were isolated. The tetraglycosides contain a 7-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)]-β-d-glucopyranosyl moiety. The benzyl alcohol glycosides had acyl groups on their glycosyl or aglycone moieties. The compounds were tested for antioxidant activity using DPPH. Although the new compounds were not active, phenylpropanoylquinic acid derivatives were revealed as radical scavengers in D. ruyschiana. 23396441 Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes. Death domain-associated protein (Daxx) cooperates with X-linked α-thalassaemia retardation syndrome protein (ATRX), a putative member of the sucrose non-fermentable 2 family of ATP-dependent chromatin-remodelling proteins, acting as the core ATPase subunit in this complex, whereas Daxx is the targeting factor, leading to histone deacetylase recruitment, H3.3 deposition and transcriptional repression of cellular promoters. Despite recent findings on the fundamental importance of chromatin modification in host-cell gene regulation, it remains unclear whether adenovirus type 5 (Ad5) transcription is regulated by cellular chromatin remodelling to allow efficient virus gene expression. Here, we focus on the repressive role of the Daxx/ATRX complex during Ad5 replication, which depends on intact protein-protein interaction, as negative regulation could be relieved with a Daxx mutant that is unable to interact with ATRX. To ensure efficient viral replication, Ad5 E1B-55K protein inhibits Daxx and targets ATRX for proteasomal degradation in cooperation with early region 4 open reading frame protein 6 and cellular components of a cullin-dependent E3-ubiquitin ligase. Our studies illustrate the importance and diversity of viral factors antagonizing Daxx/ATRX-mediated repression of viral gene expression and shed new light on the modulation of cellular chromatin remodelling factors by Ad5. We show for the first time that cellular Daxx/ATRX chromatin remodelling complexes play essential roles in Ad gene expression and illustrate the importance of early viral proteins to counteract cellular chromatin remodelling. 23122135 Identification, characterisation, and quantification of phenolic compounds in the antioxidant activity-containing fraction from the seeds of Korean perilla (Perilla frutescens) cultivars. The present research was the first to investigate phenolic compound profiles and antioxidant properties in the seeds of various perilla (Perilla frutescens) cultivars. The 80% methanol extract (50 μg/ml) of this species showed potent antioxidant activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radicals. Phenolic compounds were characterised by nuclear magnetic resonance (NMR) spectroscopy, and ultra performance liquid chromatography with photodiode array detector and electrospray ionisation/mass (UPLC-PDA-ESI/MS) analysis. Nine compounds were elucidated as caffeic acid-3-O-glucoside (1), caffeic acid (2), luteolin-7-O-glucoside (3), apigenin-7-O-glucoside (4), rosmarinic acid-3-O-glucoside (5), rosmarinic acid (6), luteolin (7), apigenin (8), and chrysoeriol (9). The individual and total phenolic contents were remarkably different, especially rosmarinic acid-3-O-glucoside (5) and rosmarinic acid (6) which were the predominant compounds (>95%) in all perilla cultivars. Additionally, Yeupsil cultivar exhibited the highest phenolic content (5029.0 μg/g) and antioxidant activity, whereas the lowest was shown by Dasil (2138.7 μg/g). Therefore, these results suggest that antioxidant effects of perilla seeds are correlated with phenolic contents. 23508304 Multiple functional polymorphisms in the G6PC2 gene contribute to the association with higher fasting plasma glucose levels. AIMS/HYPOTHESIS: We previously identified the G6PC2 locus as a strong determinant of fasting plasma glucose (FPG) and showed that a common G6PC2 intronic single nucleotide polymorphism (SNP) (rs560887) and two common G6PC2 promoter SNPs (rs573225 and rs13431652) are highly associated with FPG. However, these promoter SNPs have complex effects on G6PC2 fusion gene expression, and our data suggested that only rs13431652 is a potentially causative SNP. Here we examine the effect of rs560887 on G6PC2 pre-mRNA splicing and the contribution of an additional common G6PC2 promoter SNP, rs2232316, to the association signal. METHODS: Minigene analyses were used to characterise the effect of rs560887 on G6PC2 pre-mRNA splicing. Fusion gene and gel retardation analyses characterised the effect of rs2232316 on G6PC2 promoter activity and transcription factor binding. The genetic association of rs2232316 with FPG variation was assessed using regression adjusted for age, sex and BMI in 4,220 Europeans with normal FPG. RESULTS: The rs560887-G allele was shown to enhance G6PC2 pre-mRNA splicing, whereas the rs2232316-A allele enhanced G6PC2 transcription by promoting Foxa2 binding. Genetic analyses provide evidence for association of the rs2232316-A allele with increased FPG (β = 0.04 mmol/l; p = 4.3 × 10(-3)) as part of the same signal as rs560887, rs573225 and rs13431652. CONCLUSIONS/INTERPRETATION: As with rs13431652, the in situ functional data with rs560887 and rs2232316 are in accord with the putative function of G6PC2 in pancreatic islets, and suggest that all three are potentially causative SNPs that contribute to the association between G6PC2 and FPG. 23617430 N3-substituted thymidine bioconjugates for cancer therapy and imaging. The compound class of 3-carboranyl thymidine analogues (3CTAs) are boron delivery agents for boron neutron capture therapy (BNCT), a binary treatment modality for cancer. Presumably, these compounds accumulate selectively in tumor cells via intracellular trapping, which is mediated by hTK1. Favorable in vivo biodistribution profiles of 3CTAs led to promising results in preclinical BNCT of rats with intracerebral brain tumors. This review presents an overview on the design, synthesis, and biological evaluation of first- and second-generation 3CTAs. Boronated nucleosides developed prior to 3CTAs for BNCT and non-boronated N3-substituted thymidine conjugates for other areas of cancer therapy and imaging are also described. In addition, basic features of carborane clusters, which are used as boron moieties in the design and synthesis of 3CTAs, and the biological and structural features of TK1-like enzymes, which are the molecular targets of 3CTAs, are discussed. 23542513 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via NF-κB suppression and Nrf-2-dependent heme oxygenase-1 induction. In this study, we found that 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone (5HHMF) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of inducible NO synthase (iNOS) in BV2 microglia. In addition, 5HHMF blocked LPS-induced phosphorylation of IκB, resulting in suppression of the nuclear translocation of nuclear factor-κB (NF-κB) subunits, namely p65 and p50, which are important molecules involved in the regulation of iNOS expression. Pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced iNOS expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF-κB activity. Thus, we found that 5HHMF enhances heme oxygenase-1 (HO-1) expression via nuclear factor-erythroid 2-related factor 2 (Nrf2) activation. In addition, cobalt protoporphyrin (CoPP), a specific HO-1 inducer, predominantly suppressed LPS-induced NO production. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, showed a partial suppressive effect of 5HHMF on LPS-induced NO production. Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity. Taken together, our findings indicate that 5HHMF suppresses NO production through modulation of iNOS, consequently suppressing NF-κB activity and induction of Nrf2-dependent HO-1 activity. 23567954 Polysulfones of new structural types as perspective antioxidant agents. A series of polysulfones of new structural types on the basis of azanorbornenes, 2,2-diallyl-1,1,3,3-tetraethylguanidiniumchloride and tris(diethylamino)diallylaminophosphonium salts were obtained by free radical polymerization reaction. Their antioxidant properties in lipid peroxidation induced by iron/ascorbate and in erythrocyte hemolysis by H2O2 were evaluated. The polysulfone of 2,2-diallyl-1,1,3,3-tetraethylguanidinium chloride showed protection of erythrocytes against hydrogen peroxide and thermal shock, protected epithelial cells against UV irradiation, was not toxic for erythrocytes, epithelial cells SPEV and 3T3 fibroblasts. The polysulfone of N-benzyl-2-azanorbornene-5 inhibited lipid peroxidation in liver homogenate, did not exhibit cytotoxicity in SPEV and 3T3 cells, protected these against UV irradiation. Both compounds had low bioavailability and may be recommended for further investigations as excipients to be externally applied. 23561131 Isolation of new monoterpene coumarins from Micromelum minutum leaves and their cytotoxic activity against Leishmania major and cancer cells. On the basis of a leishmanicidal assay-guided isolation, two new monoterpene coumarins, minutin A and minutin B, were purified from Micromelum minutum leaves together with four known coumarins, 8,4″-dihydroxy-3″,4″-dihydrocapnolactone-2',3'-diol, 8-hydroxyisocapnolactone-2',3'-diol, 8-hydroxy-3″,4″-dihydrocapnolactone-2',3'-diol, and clauslactone E. Among these compounds, minutin A, minutin B, 8-hydroxyisocapnolactone-2',3'-diol and clauslactone E showed a significant cytotoxic activity against Leishmania major with IC50 values of 26.2, 20.2, 12.1, and 9.8μM, respectively, while 8,4″-dihydroxy-3″4″-dihydrocapnolactone-2',3'-diol and 8-hydroxy-3″,4″-dihydrocapnolactone-2',3'-diol were not active. However, all these compounds exhibited some inhibitory activity against one or more lung adenocarcinoma (SBC3 and A549) and leukaemia (K562, and K562/ADM) cell lines. Amongst these, clauslactone E, minutin B and 8-hydroxyisocapnolactone-2',3'-diol possessed the strongest cytotoxic activity against SBC3, A549, K562, and K562/ADM cell lines, with IC50 values of 3.7, 10.4, 12.1, and 10.8μM for clauslactone E; 9.6, 17.5, 8.7 and 6.7μM for minutin B; 8.8, 10.1, 16.9, and 10.1μM for 8-hydroxyisocapnolactone-2',3'-diol, respectively. 23262279 High-throughput identification and characterization of novel, species-selective GPR35 agonists. Drugs targeting the orphan receptor GPR35 have potential therapeutic application in a number of disease areas, including inflammation, metabolic disorders, nociception, and cardiovascular disease. Currently available surrogate GPR35 agonists identified from pharmacologically relevant compound libraries have limited utility due to the likelihood of off-target effects in vitro and in vivo and the variable potency that such ligands exhibit across species. We sought to identify and characterize novel GPR35 agonists to facilitate studies aimed at defining the physiologic role of GPR35. PathHunter β-arrestin recruitment technology was validated as a human GPR35 screening assay, and a high-throughput screen of 100,000 diverse low molecular weight compounds was conducted. Confirmed GPR35 agonists from five distinct chemotypes were selected for detailed characterization using both β-arrestin recruitment and G protein-dependent assays and each of the human, mouse, and rat GPR35 orthologs. These studies identified 4-{(Z)-[(2Z)-2-(2-fluorobenzylidene)-4-oxo-1,3-thiazolidin-5-ylidene]methyl}benzoic acid (compound 1) as the highest potency full agonist of human GPR35 yet described. As with certain other GPR35 agonists, compound 1 was markedly selective for human GPR35, but displayed elements of signal bias between β-arrestin-2 and G protein-dependent assays. Compound 1 also displayed competitive behavior when assessed against the human GPR35 antagonist, ML-145 (2-hydroxy-4-[4-(5Z)-5-[(E)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]butanoylamino]benzoic acid). Of the other chemotypes studied, compounds 2 and 3 were selective for the human receptor, but compounds 4 and 5 demonstrated similar activity at human, rat, and mouse GPR35 orthologs. Further characterization of these compounds and related analogs is likely to facilitate a better understanding of GPR35 in health and disease. 22968133 Public support and consent preference for biomedical research and biobanking in Jordan. The success of any biobank depends on a number of factors including public's view of research and the extent to which it is willing to participate in research. As a prototype of surrounding countries, public interest in research and biobanking in addition to the influence and type of informed consent for biobanking were investigated in Jordan. Data were collected as part of a national survey of 3196 individuals representing the Jordanian population. The majority of respondents (88.6%) had a positive perception of the level of research in Jordan and they overwhelmingly (98.2%) agreed to the concept of investing as a country in research. When respondents were asked if the presence of an informed consent would influence their decision to participate in biobanking, more individuals (19.8%) considered having an informed consent mechanism as a positive factor than those who considered it to have negative connotations (13.1%). However, a substantial portion (65%) did not feel it affected their decision. The majority of survey participants (64%) expressed willingness to participate in biobanking and over 90% of them preferred an opt-in consent form whether general (75.2%) or specific for disease or treatment (16.9%). These results indicate a promising ground for research and biobanking in Jordan. Educational programs or mass awareness campaigns to promote participation in biobanking and increase awareness about informed consent and individual rights in research will benefit both the scientific community as well as the public. 23402860 A comparative study of the modulatory effects of (-)-cubebin on the mutagenicity/recombinogenicity induced by different chemical agents. (-)-Cubebin (CUB) is a lignan isolated from dry seeds of Piper cubeba. We aimed to assess its genotoxic potential and influence on chromosomal damage (frequency of micronuclei - MN) induced by doxorubicin (DXR) in V79 cells and by urethane (URE) in somatic Drosophila melanogaster cells. Our findings indicate an absence of a CUB-mediated genotoxic effect at the concentrations tested. The results also revealed that CUB significantly reduced the frequency of MN induced by DXR, with a mean reduction of 63.88%. In a previous study, our research group demonstrated an absence of CUB-mediated mutagenic effects through the wing Somatic Mutation and Recombination Test (SMART) in Drosophila. In the present study, we used the standard and high bioactivation versions of the SMART to estimate the antigenotoxic effects of CUB associated with URE. At lower concentrations, the recombination level decreased, but at the highest concentration, the recombination level increased. Our data and previous studies suggest that CUB may act as a free radical scavenger at low concentrations, a pro-oxidant at higher concentrations when it interacts with the enzymatic system that catalyzes the metabolic detoxification of DXR or URE, and/or an inducer of recombinational DNA repair. 23382013 Using conditional inference trees and random forests to predict the bioaccumulation potential of organic chemicals. The present study presents a data-oriented, tiered approach to assessing the bioaccumulation potential of chemicals according to the European chemicals regulation on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH). The authors compiled data for eight physicochemical descriptors (partition coefficients, degradation half-lives, polarity, and so forth) for a set of 713 organic chemicals for which experimental values of the bioconcentration factor (BCF) are available. The authors employed supervised machine learning methods (conditional inference trees and random forests) to derive relationships between the physicochemical descriptors and the BCF values. In a first tier, the authors established rules for classifying a chemical as bioaccumulative (B) or nonbioaccumulative (non-B). In a second tier, the authors developed a new tool for estimating numerical BCF values. For both cases the optimal set of relevant descriptors was determined; these are biotransformation half-life and octanol-water distribution coefficient (log D) for the classification rules and log D, biotransformation half-life, and topological polar surface area for the BCF estimation tool. The uncertainty of the BCF estimates obtained with the new estimation tool was quantified by comparing the estimated and experimental BCF values of the 713 chemicals. Comparison with existing BCF estimation methods indicates that the performance of this new BCF estimation tool is at least as high as that of existing methods. The authors recommend the present study's classification rules and BCF estimation tool for a consensus application in combination with existing BCF estimation methods. Environ Toxicol Chem 2013;32:1187-1195. © 2013 SETAC. 23361062 Understanding photosynthetic light-harvesting: a bottom up theoretical approach. We discuss a bottom up approach for modeling photosynthetic light-harvesting. Methods are reviewed for a full structure-based parameterization of the Hamiltonian of pigment-protein complexes (PPCs). These parameters comprise (i) the local transition energies of the pigments in their binding sites in the protein, the site energies; (ii) the couplings between optical transitions of the pigments, the excitonic couplings; and (iii) the spectral density characterizing the dynamic modulation of pigment transition energies and excitonic couplings by protein vibrations. Starting with quantum mechanics perturbation theory, we provide a microscopic foundation for the standard PPC Hamiltonian and relate the expressions obtained for its matrix elements to quantities that can be calculated with classical molecular mechanics/electrostatics approaches including the whole PPC in atomic detail and using charge and transition densities obtained with quantum chemical calculations on the isolated building blocks of the PPC. In the second part of this perspective, the Hamiltonian is utilized to describe the quantum dynamics of excitons. Situations are discussed that differ in the relative strength of excitonic and exciton-vibrational coupling. The predictive power of the approaches is demonstrated in application to different PPCs, and challenges for future work are outlined. 23474217 New plant sources of the anti-cancer alkaloid, camptothecine from the Icacinaceae taxa, India. In this study, the production of camptothecine and its derivatives, in thirteen species of the family Icacinaceae, namely, Apodytes dimidiata, Codiocarpus andamanicus, Gomphandra comosa, Gomphandra coriacea, Gomphandra polymorpha, Gomphandra tetrandra, Iodes cirrhosa, Iodes hookeriana, Miquelia dentata, Miquelia kleinii, Natsiatum herpeticum, Pyrenacantha volubilis and Sarcostigma kleinii is reported. Seeds of M. dentata were found to produce the highest content of camptothecine (1.0-1.4% by dry weight of seeds). Full scan LC-MS and ESI-MS/MS analysis of M. dentata revealed, besides camptothecine, a number of other derivatives, namely, 10-hydroxycamptothecine, 9-methoxycamptothecine, 20-deoxycamptothecine. Crude extract preparations of the seeds of M. dentata were effective against a breast cancer cell line (IC50=3.82μg/ml for MDA MB273 cell lines) and two ovarian cancer cell lines (IC50=2.8μg/ml for NCI/ADR-RES and 4.5μg/ml for SKOV). These results are the first reports of camptothecine and its derivatives in these species and offer rich alternative plant sources for the anticancer compound, camptothecine. 23142538 Effect of developmental dioxin exposure on methylation and expression of specific imprinted genes in mice. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disruptor affecting the reproductive system in humans. The aim of this study was to evaluate the effects of TCDD administered to pregnant mice at two different doses (2-10 ng/kg/day), on imprinted genes in the male offspring. The degree of methylation and the mRNA expression of Snrpn, Peg3 and Igf2r were analyzed in the sperm, skeletal muscle and liver. TCDD administration (10 ng/kg/day) decreased the sperm count in the male offspring. It did not affect methylation but increased mRNA expression of Snrpn, Peg3, Igf2r and Air ncRNA. In muscle and liver, TCDD (10 ng/kg/day) induced increases in methylation and decreases in mRNA expression of Igf2r. These results show that the robust effects of TCDD on the mRNA expression of Snrpn, Peg3 and Igf2r genes in the sperm and of Igf2r in the muscle and liver are unrelated to changes in methylation in their respective genes. 22546615 The metabotropic glutamate receptor 8 agonist (S)-3,4-DCPG reverses motor deficits in prolonged but not acute models of Parkinson's disease. Metabotropic glutamate receptors (mGlus) are 7 Transmembrane Spanning Receptors (7TMs) that are differentially expressed throughout the brain and modulate synaptic transmission at both excitatory and inhibitory synapses. Recently, mGlus have been implicated as therapeutic targets for many disorders of the central nervous system, including Parkinson's disease (PD). Previous studies have shown that nonselective agonists of group III mGlus have antiparkinsonian effects in several animal models of PD, suggesting that these receptors represent promising targets for treating the motor symptoms of PD. However, the relative contributions of different group III mGlu subtypes to these effects have not been fully elucidated. Here we report that intracerebroventricular (icv) administration of the mGlu(8)-selective agonist (S)-3,4-dicarboxyphenylglycine (DCPG [ 2.5, 10, or 30 nmol]) does not alleviate motor deficits caused by acute (2 h) treatment with haloperidol or reserpine. However, following prolonged pretreatment with haloperidol (three doses evenly spaced over 18-20 h) or reserpine (18-20 h), DCPG robustly reverses haloperidol-induced catalepsy and reserpine-induced akinesia. Furthermore, DCPG (10 nmol, icv) reverses the long-lasting catalepsy induced by 20 h pretreatment with the decanoate salt of haloperidol. Finally, icv administration of DCPG ameliorates forelimb use asymmetry caused by unilateral 6-hydroxydopamine lesion of substantia nigra dopamine neurons. These findings suggest that mGlu(8) may partially mediate the antiparkinsonian effects of group III mGlu agonists in animal models of PD in which dopamine depletion or blockade of D(2)-like dopamine receptors is prolonged and indicate that selective activation of mGlu(8) may represent a novel therapeutic strategy for alleviating the motor symptoms of PD. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. 23495769 Photoelectric energy conversion of plasmon-generated hot carriers in metal-insulator-semiconductor structures. Plasmonic excitation in metals has received great attention for light localization and control of light-matter interactions at the nanoscale with a plethora of applications in absorption enhancement, surface-enhanced Raman scattering, or biosensing. Electrically active plasmonic devices, which had remained underexplored, have recently become a growing field of interest. In this report we introduce a metal-insulator-semiconductor heterostructure for plasmo-electric energy conversion, a novel architecture to harvest hot-electrons derived from plasmonic excitations. We demonstrate external quantum efficiency (EQE) of 4% at 460 nm using a Ag nanostructured electrode and EQE of 1.3% at 550 nm employing a Au nanostructured electrode. The insulator interfacial layer has been found to play a crucial role in interface passivation, a requisite in photovoltaic applications to achieving both high open-circuit voltages (0.5 V) and fill-factors (0.5), but its introduction simultaneously modifies hot-electron injection and transport. We investigate the influence passivation has on these processes for different material configurations, and characterize different types of transport depending on the initial plasmon energy band, reporting power conversion efficiencies of 0.03% for nanopatterned silver electrodes. 23624419 Evaluation of the positive effects on insulin-resistance and β-cell measurements of vildagliptin in addition to metformin in type 2 diabetic patients. We evaluated the positive effects of vildagliptin in addition to metformin on glycemic control and β-cell function in type 2 diabetic patients. One hundred and seventy-one type 2 diabetic patients were instructed to add vildaglipin 50mg twice a day or placebo to metformin for 12 months. Body mass index (BMI), glycemic control, fasting plasma insulin (FPI), HOMA-IR, HOMA-β, fasting plasma proinsulin (FPPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), C-peptide, glucagon, vaspin, visfatin, and omentin-1 were evaluated. Before, and after 12 months since the addition of vildagliptin, patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation. Vildagliptin+metformin were more effective than placebo+metformin in reducing body weight and BMI, glycemic control, HOMA-IR, glucagon and insulin resistance measurements. Vildagliptin+metformin gave also a better increase of HOMA-β, and of all β-cell parameters after the clamp. We also recorded a significant correlation between M value increase and the decrease of vaspin, visfatin, and omentin-1 obtained with vildagliptin+metformin. Vildagliptin, in addition to metformin, proved to be effective in improving β-cell function and in reducing insulin resistance measurements. 23147376 Influence of experimental type 1 diabetes on the pulmonary effects of diesel exhaust particles in mice. Epidemiologically, exposure to particulate air pollution is associated with increases in morbidity and mortality, and diabetics are especially vulnerable to effects of particles. This study was carried out to determine the respiratory effect of diesel exhaust particles (DEP; 0.4mg/kg) on mice rendered diabetic by the injection of streptozotocin or vehicle (control). Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4mg/kg) or saline. 24h later, the measurement of airway reactivity to methacholine in vivo by a forced oscillation technique showed a significant and dose-dependent increase in airway resistance in non-diabetic mice exposed to DEP versus non-diabetic mice exposed to saline. Similarly, the airway resistance was significantly increased in diabetic mice exposed to DEP versus diabetic mice exposed to saline. Nevertheless, there was no difference in the airway resistance between diabetic and non-diabetic mice after i.t. administration of DEP. Following DEP administration there were neutrophil polymorphs infiltration of pulmonary interalveolar septae and the alveolar spaces with many macrophages containing DEP in both diabetic and non-diabetic mice. Interestingly, apoptotic cells were only found in the examined lung sections from diabetic mice exposed to DEP. Total proteins and albumin concentrations in bronchoalveolar lavage (BAL) fluid, markers for increase of epithelial permeability, were significantly increased in diabetic mice exposed to DEP compared to saline-treated diabetic and DEP-treated non diabetic mice. Superoxide dismutase activity and reduced glutathione concentration in BAL were significantly decreased in diabetic mice exposed to DEP compared to saline-treated diabetic and DEP-treated non diabetic mice. Moreover, tumor necrosis factor α (TNFα) concentrations were significantly increased in diabetic mice exposed to DEP compared to saline-treated diabetic and DEP-treated non diabetic mice. We conclude that, at the dose and time point investigated, DEP equally increased airway resistance and caused infiltration of inflammatory cells in the lung of both diabetic and non-diabetic mice. However, the occurrence of oxidative stress, the presence lung apoptotic cells and the increase of total proteins, albumin and TNFα in BAL fluid were only seen in DEP-exposed diabetic mice suggesting an increased respiratory susceptibility to particulate air pollution. 23534412 Antithrombotic activity of a newly synthesized coumarin derivative 3-(5-hydroxy-2,2-dimethyl-chroman-6-yl)-N-{2-[3-(5-hydroxy-2,2-dimethyl-chroman-6-yl)-propionylamino]-ethyl}-propionamide. Anti-platelet therapy is a useful strategy to prevent acute thromboembolic artery occlusions. This study was designed to assess the efficacy of seselin derivatives against murine pulmonary thromboembolism, bleeding time, platelet activation and thrombosis. Administration of C3 (16 mg/kg) offered 70% protection against collagen- and epinephrine-induced pulmonary thromboembolism and 30% protection against arachidonic acid-induced death in mice, without adversely affecting bleeding time. No significant difference was observed by C3 in ferric chloride-induced arterial thrombosis in rats. Significant reduction in thrombus weight was observed in arteriovenous shunt model. In rat PRP, C3 reduced ADP and collagen-induced platelet aggregation. In chronic hamster model of dyslipidemia, administration of C3 (16 mg/kg p.o. for 90 days) had no effect on plasma lipids, vasoreactivity and platelet adhesion. C3 fed hamsters showed reduced whole-blood aggregation response to ADP and collagen compared to HC-fed hamsters. In addition, C3 augmented thrombin time; however, time to occlusion was not increased. These results convincingly demonstrated that C3 is a novel molecule that reduces the risk of thrombosis and alleviates prothrombotic state associated with hyperlipidemia without any adverse effect on bleeding time. The high benefit/risk ratio of this compound makes it a suitable candidate for future valid studies. 23500335 Sex specific impact of perinatal bisphenol A (BPA) exposure over a range of orally administered doses on rat hypothalamic sexual differentiation. Bisphenol A (BPA) is a high volume production chemical used in polycarbonate plastics, epoxy resins, thermal paper receipts, and other household products. The neural effects of early life BPA exposure, particularly to low doses administered orally, remain unclear. Thus, to better characterize the dose range over which BPA alters sex specific neuroanatomy, we examined the impact of perinatal BPA exposure on two sexually dimorphic regions in the anterior hypothalamus, the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anterioventral periventricular (AVPV) nucleus. Both are sexually differentiated by estradiol and play a role in sex specific reproductive physiology and behavior. Long Evans rats were prenatally exposed to 10, 100, 1000, 10,000μg/kg bw/day BPA through daily, non-invasive oral administration of dosed-cookies to the dams. Offspring were reared to adulthood. Their brains were collected and immunolabeled for tyrosine hydroxylase (TH) in the AVPV and calbindin (CALB) in the SDN-POA. We observed decreased TH-ir cell numbers in the female AVPV across all exposure groups, an effect indicative of masculinization. In males, AVPV TH-ir cell numbers were significantly reduced in only the BPA 10 and BPA 10,000 groups. SDN-POA endpoints were unaltered in females but in males SDN-POA volume was significantly lower in all BPA exposure groups. CALB-ir was significantly lower in all but the BPA 1000 group. These effects are consistent with demasculinization. Collectively these data demonstrate that early life oral exposure to BPA at levels well below the current No Observed Adverse Effect Level (NOAEL) of 50mg/kg/day can alter sex specific hypothalamic morphology in the rat. 22583008 Fatty acid composition of the edible sea cucumber Athyonidium chilensis. The edible sea cucumber Athyonidium chilensis is a fishery resource of high commercial value in Chile, but no information on its lipid and fatty acid composition has been previously reported. Phospholipids were the major lipid contents of the ethanolic extracts of tubules, internal organs and body wall of A. chilensis. Saturated fatty acids predominated in tubule phospholipids (40.69%), while in internal organs and body wall phospholipids, the monounsaturated fatty acids were in higher amounts (41.99% and 37.94%, respectively). The main polyunsaturated fatty acids in phospholipids were C20 : 2ω-6, arachidonic (C20 : 4ω-6) and eicosapentaenoic (C20 : 5ω-3) acids. These results demonstrate for the first time that A. chilensis is a valuable food for human consumption in terms of fatty acids. 23566174 Conformational Plasticity of Hydrogen Bonded Bis-urea Supramolecular Polymers. We report a detailed structural investigation of supramolecular polymers formed by hydrogen bonded self-assembly of bis-urea monomers. The careful exploration of the energy landscape by molecular mechanics/molecular dynamics (MM/MD) simulations has allowed us to identify three distinct self-assembled structures of similar stabilities. These structures have been compared to X-ray crystal data. We observe that a slight change in the molecular structure can favor a particular structure over the others. Detailed analysis shows that hydrogen bonds stabilize all three structures to a similar extent. Therefore, it is the interactions among the lateral substituents, and with the filament environment, that are the decisive factors in the competition between the possible self-assembled structures. This study constitutes a clear reminder that the conformation of a supramolecular polymer is a sensitive function of the molecular structure and may significantly differ from the solid-state conformation of a model compound. 22991412 The role of adipokines in β-cell failure of type 2 diabetes. β-Cell failure coupled with insulin resistance is a key factor in the development of type 2 diabetes. Changes in circulating levels of adipokines, factors released from adipose tissue, form a significant link between excessive adiposity in obesity and both aforementioned factors. In this review, we consider the published evidence for the role of individual adipokines on the function, proliferation, death and failure of β-cells, focusing on those reported to have the most significant effects (leptin, adiponectin, tumour necrosis factor α, resistin, visfatin, dipeptidyl peptidase IV and apelin). It is apparent that some adipokines have beneficial effects whereas others have detrimental properties; the overall contribution to β-cell failure of changed concentrations of adipokines in the blood of obese pre-diabetic subjects will be highly dependent on the balance between these effects and the interactions between the adipokines, which act on the β-cell via a number of intersecting intracellular signalling pathways. We emphasise the importance, and comparative dearth, of studies into the combined effects of adipokines on β-cells. 23470418 Bioactivation of bisphenol A and its analogs (BPF, BPAF, BPZ and DMBPA) in human liver microsomes. Bisphenol A analogs are a class of chemicals known as diphenylmethanes, which contain two benzene rings separated by one central carbon atom, usually with a para-hydroxy group on both benzene rings. Bisphenol A (BPA) can induce an uterotrophic response in immature CD-1 mice and elicits estrogenic responses in many other experimental systems. Besides highlighting endocrine effects, a number of metabolic studies provide strong support for the idea that reactive species of BPA are formed in vitro and in vivo that can form covalent adducts with nucleophilic macromolecules and/or produce oxidative stress. We used a liquid chromatography with a triple quadrupole tandem mass spectrometry (LC-MS/MS) for the detection of metabolites and glutathione conjugates of BPA and its analogs (BPF, BPAF, BPZ and DMBPA) in human liver microsomes (HLM) or with recombinant CYP isozymes in the presence of NADPH and GSH as a trapping agent. We have confirmed that BPA and its structural analogs form hydroxylated metabolites and electrophilic species during bioactivation in HLM and CYP isozymes. These results provided important mechanistic insight into the metabolic fate of BPA structural analogs in vitro. 23500550 Current perspectives on parathyroid hormone (PTH) and PTH-related protein (PTHrP) as bone anabolic therapies. Osteoporosis is characterized by low bone mineral density and/or poor bone microarchitecture leading to an increased risk of fractures. The skeletal alterations in osteoporosis are a consequence of a relative deficit of bone formation compared to bone resorption. Osteoporosis therapies have mostly relied on antiresorptive drugs. An alternative therapeutic approach for osteoporosis is currently available, based on the intermittent administration of parathyroid hormone (PTH). Bone anabolism caused by PTH therapy is mainly accounted for by the ability of PTH to increase osteoblastogenesis and osteoblast survival. PTH and PTH-related protein (PTHrP)-an abundant local factor in bone- interact with the common PTH type 1 receptor with similar affinities in osteoblasts. Studies mainly in osteoporosis rodent models and limited data in postmenopausal women suggest that N-terminal PTHrP peptides might be considered a promising bone anabolic therapy. In addition, putative osteogenic actions of PTHrP might be ascribed not only to its N-terminal domain but also to its PTH-unrelated C-terminal region. In this review, we discuss the underlying cellular and molecular mechanisms of the anabolic actions of PTH and the similar potential of PTH-related protein (PTHrP) to increase bone mass and improve bone regeneration. 23639738 Enzyme-responsive surface erosion of poly(ethylene carbonate) for controlled drug release. Cholesterol esterase (CE) induced surface erosion of poly(ethylene carbonate) (PEC) and drug release from PEC under mild physiological environment was investigated. The degradation process was monitored by changes of mass and molecular weight (MW) and surface morphology of polymer films. During the whole period of degradation, MW of PEC was unchanged. Water uptake of the polymer was only 2.8 and 0.2% for PEC with the MW of 200 kDa (PEC200) and PEC with the MW of 41 kDa (PEC41), respectively. Degradation of less hydrophilic PEC41 with higher density was slower than that of PEC200. By this mechanism, CE-responsive drug in vitro release from PEC in situ forming depots (ISFD) was conducted successfully. As expected, less bovine serum albumin (BSA) was released from PEC41 compared with that of PEC200 in the same time period. In conclusion, this work enabled the in vitro drug release evaluation of existing PEC devices and implied a new candidate for the development of enzyme-responsive systems. 23578657 A calibrator plasmid for quantitative analysis of insect resistant maize (Yieldgard MON 810). Real-time PCR (RT-PCR) is the preferred method for the quantification of genetically modified organisms (GMOs) and implementation of labeling regulations. The precision, sensitivity, and reproducibility of RT-PCR data depend on the use of external calibrators. In this investigation, a dual target plasmid designated pRSETMON-02 comprising of MON 810 maize event specific and endogenous zein gene sequences in 1:1 ratio in tandem was constructed and validated. Commutability of plasmid DNA (pDNA) and genomic DNA (gDNA) calibrators for the quantification of MON 810 maize was assessed by employing a TaqMan RT-PCR targeting the P-35S and zein gene. Higher PCR efficiencies, good linearity and lower relative standard deviation (RSD) values were associated with pRSETMON-02 as opposed to gDNA calibrants. pDNA calibrants exhibited better performance characteristic in terms of closeness to the expected value of unknown samples than their genomic counterparts. Short term stability study of the pRSETMON-02 plasmid stored at different temperatures showed that pDNA is stable for 45days at -20, and 4°C. The results demonstrated that the developed dual target plasmid pRSETMON-02 is fit for the intended use of quantifying MON 810 maize and is a better alternative to conventional seed powder calibrants. 23411192 Effects of twin-screw extrusion on soluble dietary fibre and physicochemical properties of soybean residue. Extrusion cooking technology was applied for soluble dietary fibre extraction from soybean residue. Response surface methodology (RSM) was used to optimise the effects of extrusion parameters, namely extrusion temperature (90-130°C), feed moisture (25-35%) and screw speed (160-200 rpm) on the content of soluble dietary fibre. According to the regression coefficients significance of the quadratic polynomial model, the optimum extrusion parameters were as follows: extrusion temperature, 115°C; feed moisture, 31%; and screw speed, 180 rpm. Under these conditions, the soluble dietary fibre content of soybean residue could reach to 12.65% which increased 10.60% compared with the unextruded soybean residue. In addition, the dietary fibre in extrude soybean residue had higher water retention capacity, oil retention capacity and swelling capacity than those of dietary fibre in unextruded soybean residue. 23139351 The neuropathic diabetic foot ulcer microbiome is associated with clinical factors. Nonhealing diabetic foot ulcers (DFUs) are a common and costly complication of diabetes. Microbial burden, or "bioburden," is believed to underlie delayed healing, although little is known of those clinical factors that may influence microbial load, diversity, and/or pathogenicity. We profiled the microbiomes of neuropathic nonischemic DFUs without clinical evidence of infection in 52 individuals using high-throughput sequencing of the bacterial 16S ribosomal RNA gene. Comparatively, wound cultures, the standard diagnostic in the clinic, vastly underrepresent microbial load, microbial diversity, and the presence of potential pathogens. DFU microbiomes were heterogeneous, even in our tightly restricted study population, but partitioned into three clusters distinguished primarily by dominant bacteria and diversity. Ulcer depth was associated with ulcer cluster, positively correlated with abundance of anaerobic bacteria, and negatively correlated with abundance of Staphylococcus. Ulcer duration was positively correlated with bacterial diversity, species richness, and relative abundance of Proteobacteria, but was negatively correlated with relative abundance of Staphylococcus. Finally, poor glycemic control was associated with ulcer cluster, with poorest median glycemic control concentrating to Staphylococcus-rich and Streptococcus-rich ulcer clusters. Analyses of microbial community membership and structure may provide the most useful metrics in prospective studies to delineate problematic bioburden from benign colonization that can then be used to drive clinical treatment. 23511018 Evaluation of anti-HCV activity and SAR study of (+)-lycoricidine through targeting of host heat-stress cognate 70 (Hsc70). The anti hepatitis C virus (HCV) activity of (+)-lycoricidine (1) was evaluated for the first time in this letter, yielding an EC50 value of 0.55nmol/mL and an selection index (SI) value of 12.72. Further studies indicated that 1 induced this effect by down-regulating host heat-stress cognate 70 (Hsc70) expression. In addition, 20 derivatives were designed and synthesised to investigate the basic structure-activity relationship (SAR) of the title compound. Several of these derivatives exhibit a good inhibition of HCV, such as compound 3 (EC50=0.68nmol/mL, SI=33.86), compound 2d (EC50=15nmol/mL, SI=12) and compound 5 (EC50=33nmol/mL, SI >10.91). Meanwhile, the experimental data suggest that the modification of certain groups of (+)-lycoricidine can reduce the cytotoxicity of the compounds. 23371489 Mephedrone and methylenedioxypyrovalerone (MDPV), major constituents of "bath salts," produce opposite effects at the human dopamine transporter. RATIONALE: Psychoactive "bath salts" represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011. Two common ingredients of bath salts include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV). The mechanism of action of these synthetic cathinone analogs has not been well investigated. MATERIALS AND METHODS: Because cathinone and methcathinone are known to act as releasing agents at the human dopamine transporter (hDAT), mephedrone and MDPV were investigated at hDAT expressed in Xenopus oocytes. RESULTS: Whereas mephedrone was found to have the signature of a dopamine-releasing agent similar to methamphetamine or methcathinone, MDPV behaved as a cocaine-like reuptake inhibitor of dopamine. CONCLUSIONS: Mephedrone and MDPV produce opposite electrophysiological signatures through hDAT expressed in oocytes. Implications are that the combination (as found in bath salts) might produce effects similar to a combination of methamphetamine and cocaine. 23369537 Syntheses of lipophilic chalcones and their conformationally restricted analogues as antitubercular agents. Lipophilic chalcones and their conformationally restricted analogues were synthesized and evaluated for their antitubercular efficacy against Mycobacterium tuberculosis H37Rv strain. Compounds 16, 24, 25a and 25c were found to be active MIC at 60, 30, 3.5 and 7.5 μg-mL(-1). In vitro cytotoxicity of compounds 16, 24, 25a, 25c and 26 in non-cancerous human epithelial kidney cell line (HEK-293) showed that most active compound 25a was approximately 2.85 times selective towards tubercular versus healthy cells whereas compound 24 was found to be 16 times selective. 23275111 Drug release kinetics, cell uptake, and tumor toxicity of hybrid VVVVVVKK peptide-assembled polylactide nanoparticles. An exciting approach to tumor delivery is encapsulation of the drug in self-assembled polymer-peptide nanoparticles. The objective of this work was to synthesize a conjugate of low molecular weight polylactide (LMW PLA) and V6K2 peptide and investigate self-assembly, drug release kinetics, cell uptake and toxicity, drug pharmacokinetics, and tumor cell invasion with Doxorubicin (DOX) or paclitaxel (PTX). The results for PLA-V6K2 self-assembled NPs were compared with those of polyethylene glycol stabilized PLA (PLA-EG) NPs. The size of PLA-V6K2 and PLA-EG NPs was 100±20 and 130±50nm, respectively, with polydispersity index of 1.04 and 1.14. The encapsulation efficiency of DOX in PLA-V6K2 and PLA-EG NPs was 44±9% and 55±5%, respectively, and that of PTX was >90 for both NP types. The release of DOX and PTX from PLA-V6K2 was slower than that of PLA-EG, and the release rate was relatively constant with time. Based on molecular dynamic simulation, the less hydrophobic DOX was distributed in the lactide core as well as the peptide shell, while the hydrophobic PTX was localized mainly to the lactide core. PLA-V6K2 NPs had significantly higher cell uptake by 4T1 mouse breast carcinoma cells compared to PLA-EG NPs, which was attributed to the electrostatic interactions between the peptide and negatively charged moieties on the cell membrane. PLA-V6K2 NPs showed no toxicity to marrow stromal cells. DOX-loaded PLA-V6K2 NPs showed higher toxicity to 4T1 cells and the DNA damage response, and apoptosis was delayed compared to the free DOX. DOX or PTX encapsulated in PLA-V6K2 NPs significantly reduced invasion of 4T1 cells compared to those cells treated with the drug in PLA-EG NPs. Invasion of 4T1 cells treated with DOX in PLA-V6K2 and PLA-EG NPs was 5±1% and 30±5%, respectively, and that of PTX was 11±2% and 40±7%. The AUC of DOX in PLA-V6K2 NPs was 67% and 21% higher than those of free DOX and PLA-EG NPs, respectively. DOX-loaded PLA-V6K2 NPs injected in C3HeB/FeJ mice inoculated with MTCL syngeneic breast cancer cells displayed higher tumor toxicity than PLA-EG NPs and lower host toxicity than the free DOX. Cationic PLA-V6K2 NPs with higher tumor toxicity than the PLA-EG NPs are potentially useful in chemotherapy. 23046872 A cross-linked polymeric micellar delivery system for cisplatin(IV) complex. A polymeric cisplatin(IV) prodrug in the form of cross-linked micelles (M(Pt(IV)) was prepared by first constructing MPEG-b-PCL-b-PLL micelles and then attaching a cisplatin(IV) complex with two axial succinic moieties to the lysine residues of the carrier polymer in aqueous medium. The micelles obtained were characterized by TEM, DLS, and zeta potential measurement. Their in vitro release experiments were carried out at pH 7.4 and 5.0 or in the presence of 5mM sodium ascorbate (NaAsc). Results showed that the micelles were sensitive to both acidic hydrolysis and mild reducing agents; in the presence of 5mM NaAsc, cisplatin(II) was directly released and the released cisplatin(II) could chelate with nucleobases; the micelles displayed comparable cytotoxicities to cisplatin; and the micelles were much more efficiently internalized by the cells than cisplatin(II) and cisplatin(IV) counterparts. Moreover, in vivo study showed accumulation of more Pt species in the tumor site and lower systematic toxicity compared to free cisplatin(II) and cisplatin(IV). This polymeric prodrug of cisplatin is expected to be used more for future study and applications. 23594687 POST-SURGICAL THYROID ABLATION WITH LOW OR HIGH RADIOIODINE ACTIVITIES RESULTS IN SIMILAR OUTCOMES IN INTERMEDIATE RISK DIFFERENTIATED THYROID CANCER PATIENTS. BACKGROUND: In differentiated thyroid cancer (DTC) patients at intermediate risk of recurrences, no evidences are provided regarding the optimal radioactive iodine (RAI) activity to be administered for post-surgical thyroid ablation. METHODS: This study aimed to evaluate the impact of RAI activities on the outcome of 225 DTC patients classified as intermediate risk, treated with low (1110-1850 MBq) or high RAI activities (≥3700 MBq). RESULTS: Six-eighteen months after ablation remission was observed in 60.0% of patients treated with low and in 60% of those treated with high RAI activities, biochemical disease was found in 18.8% of patients treated with low and in 14.3% of patients treated with high RAI activities, metastatic disease was found in 21.2% of patients treated with low and in 25.7% of patients treated with high RAI activities (p=0.56). At the last follow-up (low activities, median 4.2 years: high activities median 6.9 years) remission was observed in 76.5% of patients treated with low and in 72.1% of patients treated with high RAI activities, persistent disease was observed in 18.8% of patients treated with low and in 23.5% of patients treated with high RAI activities, recurrent disease was 2.4% in patients treated with low and 2.1% in patients treated with high RAI activities, deaths occurred in 2.4% of patients treated with low and in 2.1% of patients treated with high RAI activities (p=0.87). CONCLUSION: our study provides the first evidence that in DTC patients at intermediate risk, high RAI activities at ablation have no major advantage over low activities. 23584886 Optimization of DDI Study Design: Comparison of Minimal PBPK Models on Prediction of CYP3A Inhibition by Ketoconazole. Ketoconazole is a potent CYP3A inhibitor used to assess the contribution of CYP3A to drug clearance and quantify the increase in drug exposure due to a strong inhibitor. Physiologically based pharmacokinetic (PBPK) models have been employed to evaluate dosing regimens resulting in maximal CYP3A inhibition by ketoconazole but have reached different conclusions. We compare two PBPK models of the ketoconazole-midazolam interaction, Model 1 (Chien et al., 2006) and Model 2 implemented in Simcyp (version 11) to predict 16 published dosing regimens. Using Model 2, 41% of the study point estimates of AUC ratio and 71% of the 90% confidence intervals were predicted within 1.5-fold of the observed but these increased to 82% and 100% respectively with Model 1. For midazolam, Model 2 predicted a maximal midazolam AUC ratio of 8 and a hepatic fraction metabolized by CYP3A of 0.97 whereas Model 1 predicted 17 and 0.90 respectively, which are more consistent with observed data. Based on Model 1, ketoconazole 400mg QD for at least 3 days and substrate administration within 2 hours is required for maximal CYP3A inhibition. Ketoconazole dosing regimens that employ 200 mg BID underestimate the systemic fraction metabolized by CYP3A (0.86 vs. 0.90) for midazolam. The systematic underprediction also applies to CYP3A substrates with high bioavailability and long half-lives. The superior predictive performance of Model 1 reflects the need for accumulation of ketoconazole at enzyme site and protracted inhibition. Model 2 is not recommended for inferring optimal study design and estimation of fraction metabolized by CYP3A. 23587660 Effect of Korean pear (Pyruspyrifolia cv. Shingo) juice on hangover severity following alcohol consumption. Korean pear has been used as a traditional prophylactic agent for alcohol hangover. However, its mechanism was not investigated in human yet. Therefore, we performed a randomized single blind crossover trial with 14 healthy young men to examine effects of Korean pear juice on alcohol hangover. All subjects consumed 540ml of spirits (alcohol conc. 20.1v/v%) after 30min from the intervention, i.e. placebo or Korean pear juice treatment. Blood and urine specimens were collected in time-courses (9 time-points for 15h after alcohol consumption). The total and average of hangover severity were alleviated to 16% and 21% by Korean pear juice at 15h after the alcohol consumption (ps<0.05). Particularly, 'trouble concentrating' was significantly improved by the pear juice treatment (p<0.05). Impaired memory, sensitivity to light and sound, and mean of hangover severity were significantly improved by Korean pear juice among the subjects with ALDH2*1/*1 or ALDH2*1/*2 genotypes (ps<0.05) but not in the subjects with ALDH2*2/*2 genotype. In addition, the pear juice treatment lowered levels of blood alcohol (p<0.01). Therefore, Korean pear juice may alleviate alcohol-hangover and its detoxification of alcohol seems to be modified by the genetic variation of ALDH2. 23295157 Anti-human VWF monoclonal antibody SZ-123 prevents arterial thrombus formation by inhibiting VWF-collagen and VWF-platelet interactions in Rhesus monkeys. The interactions between collagen, von Willebrand factor (VWF), and glycoprotein Ib (GPIb) are crucial for hemostasis and thrombosis. This axis represents a promising target for the development of new antithrombotic agents. In this study, we investigate the in vivo antithrombotic efficacy of an anti-VWF monoclonal antibody SZ-123 and its potential underlying mechanisms. Cyclic flow reductions (CFRs), an indicator of arterial thrombosis, were measured in the femoral artery of anesthetized Rhesus monkeys before and after intravenous administration of SZ-123. Ex vivo VWF binding to collagen, platelet agglutination, platelet count, and template bleeding time were used as measurements of antithrombotic activity. In addition, plasma VWF and SZ-123 levels, and VWF occupancy were measured by ELISA. Administration of 0.1, 0.3, and 0.6 mg/kg SZ-123 resulted in 45.3%, 78.2%, and 100% reductions in CFRs, respectively. When 0.3 and 0.6 mg/kg SZ-123 were administered, 100% of VWF was occupied by the antibody. Moreover, 100% ex vivo inhibition of VWF-collagen binding and 60-95% inhibition of platelet agglutination were observed from 15 min to 1 h. None of the doses resulted in significant prolongation of bleeding time. In vitro experiments revealed that SZ-123 not only blocks the collagen-VWF A3 interaction but also indirectly inhibits VWF A1 binding to GPIbα induced by ristocetin. Thus, we demonstrate that SZ-123 prevents in vivo arterial thrombus formation under high shear conditions by inhibiting VWF A3-collagen and VWF A1-platelet interactions and does not significantly prolong bleeding time. 23356946 Chemical synthesis and characterization of epicatechin glucuronides and sulfates: bioanalytical standards for epicatechin metabolite identification. The monoglucuronides and sulfates of epicatechin, 3'-O-methylepicatechin, and 4'-O-methylepicatechin, respectively, were synthesized as authentic bioanalytical standards. Reversed-phase HPLC methods capable of baseline separation of the glucuronides and sulfates have been developed. Both the epicatechin glucuronides and sulfates were stable in the solid state when stored under ambient conditions and in aqueous solution when stored refrigerated. These results should prove invaluable to the research community as analytical standards as well as in future studies of the biological and pharmacological effects of epicatechin in humans. 23174213 Osteopetrosis, osteopetrorickets and hypophosphatemic rickets differentially affect dentin and enamel mineralization. Osteopetrosis (OP) is an inherited disorder of defective bone resorption, which can be accompanied by impaired skeletal mineralization, a phenotype termed osteopetrorickets (OPR). Since individuals with dysfunctional osteoclasts often develop osteomyelitis of the jaw, we have analyzed, if dentin and enamel mineralization are differentially affected in OP and OPR. Therefore, we have applied non-decalcified histology and quantitative backscattered electron imaging (qBEI) to compare the dental phenotypes of Src(-/-), oc/oc and Hyp(-/0) mice, which serve as models for OP, OPR and hypophosphatemic rickets, respectively. While both, Src(-/-) and oc/oc mice, were characterized by defects of molar root formation, only oc/oc mice displayed a severe defect of dentin mineralization, similar to Hyp(-/0) mice. Most importantly, while enamel thickness was not affected in either mouse model, the calcium content within the enamel phase was significantly reduced in oc/oc, but not in Src(-/-) or Hyp(-/0) mice. Taken together, these data demonstrate that dentin and enamel mineralization are differentially affected in Src(-/-) and oc/oc mice. Moreover, since defects of dental mineralization may trigger premature tooth decay and thereby osteomyelitis of the jaw, they further underscore the importance of discriminating between OP and OPR in the respective individuals. 23424087 Air-plant exchange of brominated flame retardants at a rural site: Influencing factor, interspecies difference, and forest scavenging. Brominated flame retardants (BFRs) in eucalyptus leaves and pine needles from a rural site in southern China were measured to investigate the air-plant exchange. Mean concentrations of BFRs were higher in pine needles (79.8 ng/g dry wt) than in eucalyptus leaves (74.5 ng/g), whereas an inverse result was found for the leaf surface particles, with mean concentrations of 3490 ng/g and 5718 ng/g, respectively. For most of the BFRs, the correlations between their concentrations in plants and those in the vapor phase, atmospheric particles, leaf surface particles, and the environmental variables (temperature, wind speed, and relative humidity) at this site were in contrast to the results the authors observed at an electronic waste site previously, indicating that ambient air level plays a vital role in the relationships. The interspecies difference in the BFR profiles and the correlations above implied that pine needles likely have more advantages for uptake of BFRs from gaseous deposition than eucalyptus leaves, for which particle-bound deposition is more important. Like the electronic waste site, the leaf scavenging ratios of BFRs were also controlled by their octanol-air partition coefficient. It was estimated that approximately 154 kg of BFRs in the atmosphere are scavenged annually by forest in this region, which was 1.7 times larger than that via atmospheric deposition to nonforest ground. Environ Toxicol Chem 2013;32:1248-1253. © 2013 SETAC. 23159359 Challenges and recommendations for obtaining chemical structures of industry-provided repurposing candidates. There is an expanding amount of interest directed at the repurposing and repositioning of drugs, as well as how in silico methods can assist these endeavors. Recent repurposing project tendering calls by the National Center for Advancing Translational Sciences (USA) and the Medical Research Council (UK) have included compound information and pharmacological data. However, none of the internal company development code names were assigned to chemical structures in the official documentation. This not only abrogates in silico analysis to support repurposing but consequently necessitates data gathering and curation to assign structures. Here, we describe the approaches, results and major challenges associated with this. 23531533 Transgenerational, dynamic methylation of stomata genes in response to low relative humidity. Transgenerational inheritance of abiotic stress-induced epigenetic modifications in plants has potential adaptive significance and might condition the offspring to improve the response to the same stress, but this is at least partly dependent on the potency, penetrance and persistence of the transmitted epigenetic marks. We examined transgenerational inheritance of low Relative Humidity-induced DNA methylation for two gene loci in the stomatal developmental pathway in Arabidopsis thaliana and the abundance of associated short-interfering RNAs (siRNAs). Heritability of low humidity-induced methylation was more predictable and penetrative at one locus (SPEECHLESS, entropy ≤ 0.02; χ2 < 0.001) than the other (FAMA, entropy ≤ 0.17; χ2 ns). Methylation at SPEECHLESS correlated positively with the continued presence of local siRNAs (r2 = 0.87; p = 0.013) which, however, could be disrupted globally in the progeny under repeated stress. Transgenerational methylation and a parental low humidity-induced stomatal phenotype were heritable, but this was reversed in the progeny under repeated treatment in a previously unsuspected manner. 23259865 Synthesis and biological evaluation of indenoisoquinolines that inhibit both tyrosyl-DNA phosphodiesterase I (Tdp1) and topoisomerase I (Top1). Tyrosyl-DNA phosphodiesterase I (Tdp1) plays a key role in the repair of damaged DNA resulting from the topoisomerase I (Top1) inhibitor camptothecin and a variety of other DNA-damaging anticancer agents. This report documents the design, synthesis, and evaluation of new indenoisoquinolines that are dual inhibitors of both Tdp1 and Top1. Enzyme inhibitory data and cytotoxicity data from human cancer cell cultures were used to establish structure-activity relationships. The potencies of the indenoisoquinolines against Tdp1 ranged from 5 μM to 111 μM, which places the more active compounds among the most potent known inhibitors of this target. The cytotoxicity mean graph midpoints ranged from 0.02 to 2.34 μM. Dual Tdp1-Top1 inhibitors are of interest because the Top1 and Tdp1 inhibitory activities could theoretically work synergistically to create more effective anticancer agents. 23265546 Pattern recognition of peach cultivars (Prunus persica L.) from their volatile components. The volatile compounds of four peach cultivars (Prunus persica L.) were studied: Sudanell, San Lorenzo, Miraflores and Calanda (two clones, Calante and Jesca). 17-23 Samples of each cultivar with the same maturity level were analyzed, measuring color, firmness, and soluble solids content. The pulp was crushed and mixed with water prior to HS-SPME analysis, and GC-MS was used to determine the volatile compounds. Sixty-five compounds were identified using spectral library matching, Kovat's indices and, when available, pure standards. The main components were lactones and C6 compounds. From the distribution of these compounds, Principal Component Analysis led to the clustering of the samples according to their different cultivars. Finally, Canonical Component Analysis was used to create a classification function that identifies the origin of an unknown sample from its volatile composition. The results obtained will help to avoid fraud and protect the European Designation of Origin 'Melocotón de Calanda'. 23132751 Mechanical activation of CaO-based adsorbents for CO(2) capture. The reversible cycling of CaO adsorbents to CaCO(3) for high-temperature CO(2) capture is substantially improved by mechanical treatment. The mechanical milling intensity and conditions of grinding (e.g., wet vs. dry, planetary vs. vibratory milling) were determined to be the main factors that control the effectiveness of the mechanochemical synthesis to enhance the recycling stability of the sorbents prepared. In addition, MgO was used as an example of an inert binder to help mitigate CaCO(3) sintering. Wet planetary milling of MgO into CaCO(3) allowed efficient particle size reduction and the effective dispersion of MgO throughout the particles. Wet planetary milling yielded the most stable sorbents during 50 cycles of carbonation-calcination. 23379784 (Quasi-) 2D aggregation of polystyrene-b-dextran at the air-water interface. Polystyrene-b-dextran (PS-b-Dextran) copolymers can be used to prepare dextran brushes at solid surfaces, applying Langmuir-Blodgett deposition. When recording the interfacial pressure versus area isotherms of a PS-b-Dextran monolayer, time-dependent hysteresis was observed upon compression and expansion. We argue that this is due to (quasi-) 2D aggregation of the copolymer at the air-water surface, with three contributions. First, at large area per molecule, a zero surface pressure is measured; we ascribe this to self-assembly of block copolymers into surface micelles. At intermediate area we identify a second regime ("desorption regime") where aggregation into large patches occurs due to van der Waals attraction between PS blocks. At high surface pressure ("brush regime") we observe hysteretic behavior attributed to H-bonding between dextran chains. When compared to hysteresis of other amphiphilic diblock copolymers (also containing PS, e.g., polystyrene-b-poly(ethylene oxide)) a general criterion can be formulated concerning the extent of hysteresis: when the hydrophobic (PS) block is of equal size as (or bigger than) the hydrophilic block, the hysteresis is maximal. The (quasi-) 2D aggregation of PS-b-Dextran has significant implications for the preparation of dextran brushes at solid surfaces using Langmuir-Blodgett deposition. For each grafting density the monolayer needs to relax, up to several hours, prior to transfer. 23178279 Glucocorticoid receptor concentration and the ability to dimerize influence nuclear translocation and distribution. Glucocorticoid receptor (GR) concentrations and the ability of the GR to dimerize are factors which influence sensitivity to glucocorticoids. Upon glucocorticoid binding, the GR is actively transported into the nucleus, a crucial step in determining GR function. We examined the effects of GR concentration and the ability to dimerize on GR nuclear import, export and nuclear distribution using both live cell microscopy of GFP-tagged GR and immunofluorescence of untagged GR, with both wild type GR (GRwt) and dimerization deficient GR (GRdim). We found that the observed rate of GR nuclear import increases significantly at higher GR concentrations, at saturating concentrations of dexamethasone (10(-6) M) using GFP-tagged GR, while with untagged GR it is only discernable at sub-saturating ligand concentrations (10(-10)-10(-9) M). Loss of dimerization results in a slower observed rate of nuclear import (2.5- to 3.3-fold decrease for GFP-GRdim) as well as a decreased extent of GR nuclear localization (18-27% decrease for untagged GRdim). These results were linked to an increased rate of GR export at low GR concentrations (1.4- to 1.6-fold increase for untagged GR) and where GR dimerization is abrogated (1.5- to 1.7-fold increase for GFP-GRdim). Furthermore, GR dimerization was shown to be required for the appearance of discrete GC-dependent GR nuclear foci, the loss of which may explain the increased rate of GR export for the GRdim. The reduction in the observed rate of nuclear import and increased rate of nuclear export displayed at low GR concentrations and by the GRdim could explain the lowered glucocorticoid response under these conditions. 23607866 Π- Π Stacking Increases the Stability and Loading Capacity of Thermosensitive Polymeric Micelles for Chemotherapeutic Drugs. Thermosensitive amphiphilic block copolymers self-assemble into micelles above their lower critical solution temperature in water, however the micelles generally display mediocre physical stability. To stabilize such micelles and increase their loading capacity for chemotherapeutic drugs, block copolymers with novel aromatic monomers were synthesized by free radical polymerization of N-(2-benzoyloxypropyl methacrylamide (HPMAm-Bz) or the corresponding naphthoyl analogue (HPMAm-Nt), with N-(2-hydroxypropyl) methacrylamide monolactate, using a polyethylene glycol based macroinitiator. The critical micelle temperatures and critical micelle concentrations decreased with increasing the HPMAm-Bz/Nt content. The micelles of 30 to 50 nm were prepared by heating the polymer aqueous solutions from 0 to 50 oC and were colloidally stable for at least 48 h at pH 7.4 and 37 oC. Paclitaxel and docetaxel encapsulation was performed by mixing drug solutions in ethanol with polymer aqueous solutions and heating from 0 to 50 oC. The micelles had a drug loading capacity up to 34 weight % for docetaxel, which is amongst the highest loadings reported for polymeric micelles, with loaded micelle sizes ranging from 60 to 80 nm. The micelles without aromatic groups almost completely released loaded paclitaxel in 10 days, whereas the HPMAm-Bz/Nt containing micelles released 50% of the paclitaxel at the same time, which showed a better retention for the drug of the latter micelles. 1H solid-state NMR spectroscopy data are compatible with π-π stacking between aromatic groups. The empty micelles demonstrated good cytocompatibility, and paclitaxel loaded micelles showed high cytotoxicity to tumor cells. In conclusion, the π-π stacking effect introduced by aromatic groups increases the stability and loading capacity of polymeric micelles. 23143852 High-sensitivity real-time analysis of nanoparticle toxicity in green fluorescent protein-expressing zebrafish. Gold nanoparticles (AuNP) show great potential for diagnostic and therapeutic application in humans. A great number of studies have tested the cytotoxicity of AuNP using cell culture. There is, however, an urgent need to test AuNP in vertebrate animal models that interrogate biodistribution and complex biological traits like organ development, whole body metabolism, and cognitive function. The sheer number of different compounds precludes the use of small rodent model for initial screening. The extended fish embryo test (FET) is used here to bridge the gap between cell culture and small animal models. A study on the toxicity of ultrasmall AuNP in wild type and transgenic zebrafish is presented. FET faithfully reproduce all important findings of a previous study in HeLa cells and add new important information on teratogenicity and hepatotoxicity that could not be gained from studying cultured cells. 23341248 Silver nanoparticle toxicity effect on growth and cellular viability of the aquatic plant Lemna gibba. The toxicity effect of silver nanoparticles (AgNPs) on growth and cellular viability was investigated on the aquatic plant Lemna gibba exposed over 7 d to 0, 0.01, 0.1, 1, and 10 mg/L of AgNPs. Growth inhibition was demonstrated by a significant decrease of frond numbers dependent on AgNP concentration. Under these conditions, reduction in plant cellular viability was detected for 0.1, 1, and 10 mg/L of AgNPs within 7 d of AgNPs treatment. This effect was highly correlated with the production of intracellular reactive oxygen species (ROS). A significant increase of intracellular ROS formation was triggered by 1 and 10 mg/L of AgNP exposure. The induced oxidative stress was related to Ag accumulation within L. gibba plant cells and with the increasing concentration of AgNP exposure in the medium. The authors' results clearly suggested that AgNP suspension represented a potential source of toxicity for L. gibba plant cells. Due to the low release capacity of free soluble Ag from AgNP dissolution in the medium, it is most likely that the intracellular uptake of Ag was directly from AgNPs, triggering cellular oxidative stress that may be due to the release of free Ag inside plant cells. Therefore, the present study demonstrated that AgNP accumulation in an aquatic environment may represent a potential source of toxicity and a risk for the viability of duckweeds. 22258629 Toxic effects of chromium on tannery workers at Sialkot (Pakistan). Chromium is widely used in the leather industry, and tannery workers are under constant threat of adverse health effects due to its excessive exposure. Our objective was to find out the toxic effects of chromium on tannery workers at Sialkot, Pakistan. A total of 240 males consisting of 120 workers from tanneries at Sialkot and equal number of controls were included. Blood complete counts, high-sensitive C-reactive protein, malondialdehyde and routine biochemical tests were carried out by routine procedures. Chromium levels in blood (BCr) and urine were analyzed using graphite furnace atomic absorption spectrophotometer Perkin Elmer analyst-200. Results revealed that all the workers were male with average age of 33 years and 15 (13%) had skin rashes, 14 (12%) had chronic bronchitis, 10 (8%) had gastritis and 4 (3%) conjunctivitis. The tannery workers had significantly raised median (interquartile range) of BCr 569 (377-726) nmol/L as compared to 318 (245-397) nmol/L in the control (p < 0.001). Sixty-five (54%) workers had BCr levels above the upper limit set by Agency for Toxic Substance and Drug Registry. The urinary chromium excretion was significantly high in workers 131 (46-312) nmol/L as compared to 13 (3-26) nmol/L in controls (p < 0.01). The workers had hematological, hepatic and renal function impairment because of oxidative stress on body systems. It is concluded that about half of the workers had excessive exposure to chromium in the tanneries at Sialkot. They had significantly raised chromium levels in their biological fluids and adverse health effects due to enhanced oxidative stress and inflammatory changes. 23563922 Incidentally discovered thyroid nodules: frequency in an adult population during Doppler ultrasonographic evaluation of cervical vessels. In this study, the frequency of thyroid nodules was searched in a population of consecutive patients undergoing routine cervical Doppler evaluation with the use of high-end color Doppler ultrasound units equipped with new technologies that increase nodule conspicuity. Three hundred and fifteen subjects, who had been referred for Doppler ultrasonography of cervical vessel examination, were enrolled in the study. During the examinations, the presence or absence of thyroid nodules, if present, their number (as "single" or "multiple"), the longest diameter, and internal echo pattern of the largest nodule were noted. As a result, one hundred and sixty-one subjects (51 %) were shown to have at least one thyroid nodule. In this subgroup, 54 cases had single and 107 cases had multiple nodules. Incidental thyroid nodules were detected in similar ratios in both men and women (p = 0.34). The results of the study led to the conclusion that half of the elder adult population had at least one thyroid nodule. Use of ultrasound technologies with increasing resolution seems to help significantly in detecting and also evaluating smaller and previously unknown nodules. 22824787 Could maternal exposure to the antidepressants fluoxetine and St. John's Wort induce long-term reproductive effects on male rats? Based on the limited number of studies that have investigated the adverse effects of maternal treatment with antidepressants on the development of male descendents, this study was carried out in rat in order to evaluate if maternal exposure to fluoxetine (FLX) or St. John's Wort (SJW) could disrupt the development of male offspring. The dams were treated daily, by gavage, with 7.5 mg/kg of FLX or 100 mg/kg SJW during pregnancy and lactation. The reproductive and behavior parameters were analyzed in male pups. Results showed decreases in the weight of the full seminal vesicle and in the number of spermatozoa. Moreover, FLX-exposed pups presented reduced seminiferous epithelium height and diameter of seminiferous tubules. The present study shows that maternal exposure to FLX, but not SJW could interfere on reproductive parameters in adult male rats. 23570552 Retention and Release of Cinnamaldehyde from Wheat Protein Matrices. Cinnamaldehyde treatment of gliadin films provided a means of decreasing their solubility, increasing their molecular weight profile, and reducing their overall migration into food simulants as a consequence of the high degree of polymerization achieved. Despite losses incurred in the film manufacturing process, and the amount that remained covalently bonded with protein because of cross-linking, the addition of 1.5, 3, and 5% of cinnamaldehyde (g/100 g protein) to gliadins at pH 2 rendered 1.8, 4.8, and 11.0 mg cinnamaldehyde/g film, respectively, available to be released, and therefore to exert antimicrobial activity. Cinnamaldehyde diffusivity was largely dependent on environmental conditions, increasing from 0.49 × 10(-15) m(2)/s at 30% relative humidity (RH) to 13.1 × 10(-15) m(2)/s at 90% RH and 23 °C. This water sensitivity of films provides a mechanism with a noteworthy potential to retain the compound before its use, to trigger its release when needed, and to modulate the release rate according to the product humidity. 23194566 Comparison of sample preparation methods, validation of an UPLC-MS/MS procedure for the quantification of tetrodotoxin present in marine gastropods and analysis of pufferfish. Tetrodotoxin (TTX) is one of the most potent marine neurotoxins reported. The global distribution of this toxin is spreading with the European Atlantic coastline now being affected. Climate change and increasing pollution have been suggested as underlying causes for this. In the present study, two different sample preparation techniques were used to extract TTX from Trumpet shells and pufferfish samples. Both extraction procedures (accelerated solvent extraction (ASE) and a simple solvent extraction) were shown to provide good recoveries (80-92%). A UPLC-MS/MS method was developed for the analysis of TTX and validated following the guidelines contained in the Commission Decision 2002/657/EC for chemical contaminant analysis. The performance of this procedure was demonstrated to be fit for purpose. This study is the first report on the use of ASE as a mean for TTX extraction, the use of UPLC-MS/MS for TTX analysis, and the validation of this method for TTX in gastropods. 23506138 Interfacial rheology of asphaltenes at oil-water interfaces and interpretation of the equation of state. In an earlier study, (1) oil-water interfacial tension was measured by the pendant drop technique for a range of oil-phase asphaltene concentrations and viscosities. The interfacial tension was found to be related to the relative surface coverage during droplet expansion. The relationship was independent of aging time and bulk asphaltenes concentration, suggesting that cross-linking did not occur at the interface and that only asphaltene monomers were adsorbed. The present study extends this work to measurements of interfacial rheology with the same fluids. Dilatation moduli have been measured using the pulsating droplet technique at different frequencies, different concentrations (below and above CNAC), and different aging times. Care was taken to apply the technique in conditions where viscous and inertial effects are small. The elastic modulus increases with frequency and then plateaus to an asymptotic value. The asymptotic or instantaneous elasticity has been plotted against the interfacial tension, indicating the existence of a unique relationship, between them, independent of adsorption conditions. The relationship between interfacial tension and surface coverage is analyzed with a Langmuir equation of state. The equation of state also enabled the prediction of the observed relationship between the instantaneous elasticity and interfacial tension. The fit by a simple Langmuir equation of state (EOS) suggests minimal effects of aging and of nanoaggregates or gel formation at the interface. Only one parameter is involved in the fit, which is the surface excess coverage Γ∞ = 3.2 molecules/nm(2) (31.25 Å(2)/molecule). This value appears to agree with flat-on adsorption (2) of monomeric asphaltene structures consisting of aromatic cores composed of an average of six fused rings and supports the hypothesis that nanoaggregates do not adsorb on the interface. The observed interfacial effects of the adsorbed asphaltenes, correlated by the Langmuir EOS, are consistent with the asphaltene aggregation behavior in the bulk fluid expected from the Yen-Mullins model. (3, 4). 23435615 The (R)-omeprazole hydroxylation index reflects CYP2C19 activity in healthy Japanese volunteers. PURPOSE: Omeprazole has (R)- and (S)-enantiomers, which exhibit different pharmacokinetics (PK) among patients with cytochrome P450 (CYP) 2C19 genotype groups. The aim of this study was to investigate whether the 1-point, 4-h postdose (R)-omeprazole hydroxylation index (HI) of racemic omeprazole reflects the three CYP2C19 genotype groups in Japanese individuals. METHODS: Ninety healthy Japanese individuals were enrolled and classified into the three different CYP2C19 genotype groups: homozygous extensive metabolizers (hmEMs; n = 34), heterozygous EMs (htEMs; n = 44), and poor metabolizers (PMs; n = 12). Blood samples were drawn 4 h after the intake of an oral dose of omeprazole 40 mg, and plasma levels of omeprazole and its metabolites were analyzed by high-performance liquid chromatography (HPLC) using a chiral column. RESULTS: Mean plasma concentrations of (R)- and (S)-omeprazole in PMs were significantly higher than those in hmEMs and htEMs, and similar results were obtained in the case of omeprazole sulfone. Additionally, there was a significant difference in plasma concentrations of (R)-5-hydroxyomeprazole among CYP2C19 genotype groups, whereas no significant differences were observed in that of (S)-5-hydroxyomeprazole. Similarly, (R)-omeprazole HI in hmEMs, htEMs, and PMs were 5.6, 3.1, and 0.3, respectively, which were significantly different, but no significant difference was present in the (S)-omeprazole HI. CONCLUSION: Our findings demonstrate that (R)-omeprazole HI correlated better with CYP2C19 genotype groups than racemic-omeprazole HI, and these results may be useful for classification among patients in CYP2C19 genotype groups prior to omeprazole treatment. 23295224 Biocatalytic production of alpha-hydroxy ketones and vicinal diols by yeast and human aldo-keto reductases. The α-hydroxy ketones are used as building blocks for compounds of pharmaceutical interest (such as antidepressants, HIV-protease inhibitors and antitumorals). They can be obtained by the action of enzymes or whole cells on selected substrates, such as diketones. We have studied the enantiospecificities of several fungal (AKR3C1, AKR5F and AKR5G) and human (AKR1B1 and AKR1B10) aldo-keto reductases in the production of α-hydroxy ketones and diols from vicinal diketones. The reactions have been carried out with pure enzymes and with an NADPH-regenerating system consisting of glucose-6-phosphate and glucose-6-phosphate dehydrogenase. To ascertain the regio and stereoselectivity of the reduction reactions catalyzed by the AKRs, we have separated and characterized the reaction products by means of a gas chromatograph equipped with a chiral column and coupled to a mass spectrometer as a detector. According to the regioselectivity and stereoselectivity, the AKRs studied can be divided in two groups: one of them showed preference for the reduction of the proximal keto group, resulting in the S-enantiomer of the corresponding α-hydroxy ketones. The other group favored the reduction of the distal keto group and yielded the corresponding R-enantiomer. Three of the AKRs used (AKR1B1, AKR1B10 and AKR3C1) could produce 2,3-butanediol from acetoin. We have explored the structure/function relationships in the reactivity between several yeast and human AKRs and various diketones and acetoin. In addition, we have demonstrated the utility of these AKRs in the synthesis of selected α-hydroxy ketones and diols. 23494732 Ascorbigen Induces Dermal Papilla Cell Proliferation in Vitro, but Fails to Modulate Chemotherapy-Induced Alopecia in Vivo. Ascorbigen (ABG) is the predominant indole-derived compound from Brassica vegetables. In this study, we attempted to evaluate the effects of ABG on hair growth. To this end, we examined the proliferation of isolated human dermal papilla (DP) cells and keratinocytes after incubation in various concentrations (0-1.25 mM) of ABG. Furthermore, hair shaft regrowth was monitored in a mouse model of chemotherapy-induced alopecia (CIA), and hematoxylin and eosin staining was performed for histological analyses. We found that 1.25 mM ABG induced a 1.2-fold increase in the growth of DP cells, but not keratinocytes. However, ABG did not exert significant protective effects against CIA in the mouse model. These findings suggest that ABG may not be able to counteract CIA and that further investigation of the therapeutic potential of ABG in disease models is required. Copyright © 2013 John Wiley & Sons, Ltd. 22967722 Anti-obesity effects of glabridin-rich supercritical carbon dioxide extract of licorice in high-fat-fed obese mice. Licorice (Glycyrrhiza glabra Linne) is a well-known medicinal plant and glabridin is an isoflavan isolated from licorice. In this study, we investigated the anti-obesity effect of glabridin and glabridin-rich supercritical fluid extract of licorice (LSC). Glabridin effectively inhibited adipogenesis in 3T3-L1 cells. Moreover, LSC showed inhibitory effect on adipogenesis in a dose-dependent manner. The inhibitory effect of LSC resulted from inhibiting the induction of the transcriptional factors CCAAT enhancer binding protein alpha and peroxisome proliferator-activated receptor gamma. Then we fed mice with high-fat diet containing none, 0.1% and 0.25% LSC for 8weeks to explore the anti-obesity effect of LSC in vivo. LSC significantly reduced weight gain by high-fat diet in a dose-dependent manner. The reductions of the hypertrophy of white adipose tissue and of fat cell size were also observed. In the liver, LSC supplementation effectively inhibited high-fat diet-induced hepatic steatosis through downregulation of gluconeogenesis related phosphoenolpyruvate carboxykinase and glucose 6-phosphatase and upregulation of the β-oxidation related carnitine palmitoyltransferase 1. Taken together, our results suggest that glabridin and glabridin-rich licorice extract would be effective anti-obesity agents. 22798246 The influence of the genetic and non-genetic factors on bone mineral density and osteoporotic fractures in Chinese women. To investigate the effects of genetic and non-genetic factors on bone mineral densities (BMDs) and osteoporotic fractures. This was a cross-sectional study to investigate the relationships between 18 SNPs and non-genetic factors with BMDs and osteoporotic fractures in 1012 Chinese Han women. Five SNPs in genes GPR177, CTNNB1, MEF2C, SOX6, and TNFRSF11B were associated with L1-4 or total hip BMDs. rs11898505 in SPTBN1 gene was associated with osteoporotic fractures. Subjects carrying the largest number of risk alleles (highest 10 %) not only had lower BMD values as compared to those carrying the least number of risk alleles (lowest 10 %), they also had a higher risk of fracture [P = 0.002, OR = 2.252, 95 %CI (1.136, 4.463)]. Results from multivariate stepwise regression analysis revealed that age [P < 0.001, OR = 1.038, 95 % CI (1.018, 1.058)], number of falls in a year [P < 0.001, OR = 2.347, 95 % CI (1.459, 3.774)], the G risk allele in rs11898505 [P = 0.023, OR = 1.559, 95 % CI (1.062, 2.290)], and the L1-4 BMD [P = 0.017, OR = 0.286, 95 % CI (0.102, 0.798)] were associated with the occurrence of osteoporotic fractures. Genetic (rs11898505) and non-genetic factors (age, number of falls in a year and L1-4 BMD) could work in concert to contribute to the risk of osteoporotic fractures. 23474267 Continuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American Rattlesnake bite patients. BACKGROUND: In patients bitten by North American rattlesnakes and treated with Crotalidae Polyvalent Immune Fab (Ovine) (FabAV), late hematologic abnormalities-persistent, recurrent, or late, new onset of hypofibrinogenemia, prolonged PT/INR, prolonged PTT, and/or thrombocytopenia beyond 48 h post-envenomation-are common, difficult to manage, and may result in morbidity and mortality are common, difficult to manage, and may result in morbidity and mortality. The optimal management of late hematologic abnormalities, particularly the use of further treatment with antivenom, has not been well defined. The current FabAV treatment regimen is to give antivenom as a bolus dose over a one-hour period. We describe our experience using a continuous intravenous infusion of FabAV for late hematologic effects and/or associated bleeding complications in rattlesnake envenomation. METHODS: This is a retrospective, observational case series of patients envenomated by North American rattlesnakes at three medical centers managed with a continuous intravenous infusion of FabAV for late hematologic abnormalities and/or associated bleeding complications. Indications, dilution and infusion protocols, and duration of therapy were individualized. RESULTS: Five cases were identified between July 2010 and September 2011. All patients had profound late hematologic abnormalities and/or were associated with bleeding complications. Several patients had received repeat bolus infusions of FabAV, with or without human blood products, with either inadequate or only transient beneficial response. All patients were then managed with a continuous intravenous infusion of FabAV and all appeared to respond to the continuous intravenous infusion of FabAV, titrated to effect, with cessation of progression and, in most cases, improvement in hematologic abnormalities. Rates of infusion varied from 2 to 4 vials per 24 h (mean = 3.1 ± 0.4 vials/day). The termination of FabAV infusion was between day 6 and day 14 from the time of envenomation (mean = 10 ± 3 days), after which hematologic values were normalized or were normalizing in all patients and continued to do so. DISCUSSION: The use of FabAV as a continuous intravenous infusion, particularly after the acute phase of envenomation has passed, provides a continuous source of circulating antibodies to neutralize venom components reaching circulation from tissue stores and allows natural replenishment of hematologic factors such as platelets and/or fibrinogen. This method is an efficient use of FabAV, avoiding the wasteful excess of a bolus dose, may be more effective, eliminating the potential for destruction of hematologic factors when protective antivenom levels are lost between bolus FabAV doses, and appears to be safe. Further assessments of the stability and sterility of the product during infusion are needed. The need to continue hospitalization is the major drawback, but continued observation and inpatient care may be needed for other indications (e.g. bleeding) in this subset of patients. CONCLUSIONS: A continuous intravenous infusion of FabAV between 2 and 4 vials per day, titrated to effect, and continued for 6-14 days post-envenomation appeared to be associated with reversal of late hematologic effects of rattlesnake envenomation and, when combined with indicated human blood products, control of significant bleeding. Continuous intravenous infusion of FabAV may be safer, more efficacious, and more cost-effective than observation without FabAV treatment or as-needed bolus dosing in selected patients with late hematologic abnormalities. 23194504 Antioxidant activity and effective compounds of immature calamondin peel. The antioxidant activity and the flavonoids of mature and immature calamondin (Citrus mitis Blanco) peel were investigated. The hot water extract of immature calamondin peel exhibited the highest oxygen radical absorbance capacity (ORAC), reducing power, and superoxide scavenging effect. 3',5'-Di-C-β-glucopyranosylphloretin, naringin, hesperidin, nobiletin, and tangeretin are the five major flavonoids found in hot water extract with the levels of 6888±522, 2333±157, 1350±94, 165±13, and 8±4 mg/100 g dry basis, respectively. The contents of nobiletin and tangeretin increased after ripening. The hot water extract of immature calamondin peel was fractionated using a semi-preparative HPLC. Fraction VI showed the highest ORAC value (28.02±2.73 mmol Trolox equivalents (TE)/g fraction) and two compounds, naringin and hesperidin, were identified as the major active components attributed to the antioxidant activity. Fraction V contained 3',5'-di-C-β-glucopyranosylphloretin, which revealed low ORAC value with 7.43 mmol TE/g fraction. However, it might also contribute to antioxidant activity in immature calamondin peel due to its greatest quantity. 23329125 Differential sensitivity to pro-oxidant exposure in two populations of killifish (Fundulus heteroclitus). New Bedford Harbor (MA, U.S.A.; NBH) is a Superfund site inhabited by Atlantic killifish (Fundulus heteroclitus) with altered aryl hydrocarbon receptor (Ahr) signaling, leading to resistance to effects of polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The Ahr is a transcription factor that regulates gene expression of many Phase I and II detoxifying enzymes and interacts with Nrf2, a transcription factor that regulates the response to oxidative stress. This study tested the hypothesis that PCB-resistant killifish exhibit altered sensitivity to oxidative stress. Killifish F(1) embryos from NBH and a clean reference site (Scorton Creek, MA, U.S.A.; SC) were exposed to model pro-oxidant and Nrf2-activator, tert-butylhydroquinone (tBHQ). Embryos were exposed at specific embryonic developmental stages (5, 7, and 9 days post fertilization) and toxicity was assessed, using a deformity score, survival, heart rate, and gene expression to compare sensitivity between PCB -resistant and -sensitive (reference) populations. Acute exposure to tBHQ resulted in transient reduction in heart rate in NBH and SC F(1) embryos. However, embryos from NBH were more sensitive to tBHQ, with more frequent and severe deformities, including pericardial edema, tail deformities, small body size, and reduced pigment and erythrocytes. NBH embryos had lower basal expression of antioxidant genes catalase and glutathione-S-transferase alpha (gsta), and upon exposure to tBHQ, exhibited lower levels of expression of catalase, gsta, and superoxide dismutase compared to controls. This result suggests that adaptation to tolerate PCBs has altered the sensitivity of NBH fish to oxidative stress during embryonic development, demonstrating a cost of the PCB resistance adaptation. 23098805 Effects of menstrual cycle phase on cocaine self-administration in rhesus macaques. Epidemiological findings suggest that men and women vary in their pattern of cocaine use resulting in differences in cocaine dependence and relapse rates. Preclinical laboratory studies have demonstrated that female rodents are indeed more sensitive to cocaine's reinforcing effects than males, with estrous cycle stage as a key determinant of this effect. The current study sought to extend these findings to normally cycling female rhesus macaques, a species that shares a nearly identical menstrual cycle to humans. Dose-dependent intravenous cocaine self-administration (0.0125, 0.0250, and 0.0500 mg/kg/infusion) using a progressive-ratio schedule of reinforcement was determined across the menstrual cycle. The menstrual cycle was divided into 5 discrete phases - menses, follicular, periovulatory, luteal, and late luteal phases - verified by the onset of menses and plasma levels of estradiol and progesterone. Dependent variables including number of infusions self-administered per session, progressive ratio breakpoint, and cocaine intake were analyzed according to cocaine dose and menstrual cycle phase. Analysis of plasma hormone levels verified phase-dependent fluctuations of estradiol and progesterone, with estrogen levels peaking during the periovulatory phase, and progesterone peaking during the luteal phase. Progressive ratio breakpoint, infusions self-administered, and cocaine intake did not consistently vary based on menstrual cycle phase. These findings demonstrate that under the current experimental parameters, the reinforcing effects of cocaine did not vary across the menstrual cycle in a systematic fashion in normally cycling rhesus macaques. 23471156 Biomimetic metal oxides for the extraction of nanoparticles from water. Contamination of nanomaterials in the environment will pose significant health risks in the future. A viable purification method is necessary to address this problem. Here we report the synthesis and application of a series of metal oxides prepared using a biological template for the removal of nanoparticles from the aqueous environment. A simple synthesis of metal oxides such as ZnO, NiO, CuO, Co3O4 and CeO2 employing eggshell membrane (ESM) as a biotemplate is reported. The morphology of the metal oxide powders was characterized using electron microscopes and the lattice structure was established using X-ray diffraction methods. Extraction of nanoparticles from water was carried out to compare the efficiency of metal oxides. NiO showed good extraction efficiency in removing gold and silver nanoparticles from spiked water samples within an hour. Easy access and enhanced stability of metal oxides makes them interesting candidates for applications in industrial effluent treatments and water purifications. 23628455 High salt intake does not produce additional impairment in the coronary artery relaxation of spontaneously hypertensive aged rats. The effect of a salt-based diet on the coronary responsiveness in aged hypertensive rats (SHR) still unclear. We investigated the effects of high salt intake on the relaxation properties of coronary arteries of aged SHRs. Male SHR (32week-old) received drink water (SHR) or 1% NaCl solution (SHR-Salt) for 8weeks. Isolated coronary segments were subjected to concentration-response curves to acetylcholine (ACh) in the presence or absence of L-NAME (100μmol), enalaprilate (10μM), losartan (10μM), and spironolactone (100μM). Salt intake did not increase blood pressure in old SHRs, but caused ventricular hypertrophy. The endothelium-dependent relaxation in SHRs was lower than in Wistar rats. However, salt intake did not add further impairment. Both enalaprilate and losartan reduced the vasodilator response in coronary arteries from Wistar, but did not affect SHR-salt rats. Conversely, losartan attenuated the impaired ACh relaxation observed in SHR. Spironolactone reduced the relaxation induced by ACh in coronary arteries from Wistar rats but not in SHR. The renin-angiotensin-aldosterone system participates in the impaired coronary relaxation in aged SHR, but does not participate in deleterious effects under increased salt intake, indicating that age could differentiate the effects of high sodium intake in coronary arteries of SHR. 23435428 Activation of β-catenin/TCF targets following loss of the tumor suppressor SNF5. The SWI/SNF chromatin remodeling complex is a master regulator of developmental cell-fate decisions, although the key target pathways are poorly characterized. Here, we interrogated the contribution of the SWI/SNF subunit and tumor suppressor SNF5 to the regulation of developmental pathways using conditional mouse and cell culture models. We find that loss of SNF5 phenocopies β-catenin hyperactivation and that SNF5 is essential for regulating Wnt/β-catenin pathway target expression. These data provide insight into chromatin-based mechanisms that underlie developmental regulation and elucidate the emerging theme that mutation of this tumor suppressor complex can activate developmental pathways by uncoupling them from upstream control.Oncogene advance online publication, 25 February 2013; doi:10.1038/onc.2013.37. 23376997 Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: Synthesis and biological evaluation. Aggrecanases, in particular aggrecanase-2 (ADAMTS-5), are considered the principal proteases responsible for aggrecan degradation in osteoarthritis. For this reason, considerable effort has been put on the discovery and development of aggrecanase inhibitors able to slow down or halt the progression of osteoarthritis. We report herein the synthesis and biological evaluation of a series of arylsulfonamido-based hydroxamates as aggrecanase inhibitors. Compound 18 was found to have a nanomolar activity for ADAMTS-5, ADAMTS-4 and MMP-13 and high selectivity over MMP-1 and MMP-14. Furthermore, this compound proved to be effective in blocking ex vivo cartilage degradation without having effect on cell cytotoxicity. 23463609 Transparent stretchable single-walled carbon nanotube-polymer composite films with near-infrared fluorescence. We report transparent stretchable single-walled carbon nanotube-polymer composite films that emit pronounced Raman and near-infrared fluorescence with a fine spatial resolution. The independent modulation in Raman and fluorescence spectra is demonstrated in response to touch and temperature. The optical signal transduction of transparent stretchable optoelectronic films may enable a paradigm shift in touch-sensing devices eliminating electrical interconnects. 23400943 Neurogenetic disorders and treatment of associated seizures. Seizures are a frequent complication associated with several neurogenetic disorders. Antiepileptic medications remain the mainstay of treatment in these patients. We summarized the available data associated with various antiepileptic therapies used to treat patients with neurogenetic disorders who experienced recurrent seizures. A MEDLINE search was conducted to identify articles and abstracts describing the use of antiepileptic therapy for the treatment of various neurogenetic syndromes. Of all the neurogenetic syndromes, only autism spectrum disorders, Angelman syndrome, Rett syndrome, Dravet syndrome, and tuberous sclerosis complex were identified as having sufficient published information to evaluate therapy. Some efficacy trends were identified, including frequent successes with valproic acid with clonazepam for epilepsy with Angelman syndrome; valproic acid, stiripentol, and clobazam (triple combination therapy) for epilepsy with Dravet syndrome; and vigabatrin for infantile spasms associated with tuberous sclerosis complex. Due to a paucity of information regarding the mechanisms by which seizures are generated in the various disorders, approach to seizure control is primarily based on clinical experience and a limited amount of study data exploring patient outcomes. Although exposure of the developing brain to antiepileptic medications is of some concern, the control of epileptic activity is an important undertaking in these individuals, as the severity of eventual developmental delay often appears to correlate with the severity of seizures. As such, early aggressive therapy is warranted. 23122169 Abietane diterpenoids from Isodon lophanthoides var. graciliflorus and their cytotoxicity. Seven new (1-7) and three known (8-10) abietane diterpenoids were isolated from the methanolic extract of the aerial parts of Isodon lophanthoides var. graciliflorus (Lamiaceae), a folk Chinese medicine and an herb for functional beverages. They were identified as 16-acetoxylsugiol (1), graciliflorin E (2), graciliflorin F (3), 15-O-methylgraciliflorin F (4), 15-hydroxy-20-deoxocarnosol (5), 3β-hydroxysempervirol (6), 15-hydroxy-1-oxosalvibretol (7), abieta-8,11,13-triene-14,19-diol (8), 6,12,15-trihydroxy-5,8,11,13-abietatetraen-7-one (9), and 3α-hinokiol (10) based on the spectroscopic data including COSY (correlated spectroscopy), HMBC (heteronuclear multiple bond correlation), and HR-ESI-MS (high-resolution electrospray ionization mass spectrometry). All the compounds except 10 were obtained from I. lophanthoides for the first time. Compounds 1, 2, 5, 6, 8, and 9 exhibited in vitro cytotoxicity against A549 (human lung adenocarcinoma), MCF-7 (human breast adenocarcinoma), and HeLa (human cervical carcinoma) cell lines with the IC(50) values of 1.79-52.67 μM. 23353698 ABT-737 resistance in B-cells isolated from chronic lymphocytic leukemia patients and leukemia cell lines is overcome by the pleiotropic kinase inhibitor quercetin through Mcl-1 down-regulation. Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in adult population and despite numerous studies, it is considered an incurable disease. Since CLL is characterized by overexpression of pro-survival Bcl-2 family members, treatments with their antagonists, such as ABT-737, represent a promising new therapeutic strategy. ABT-737 is a BH3 mimetic agent which binds Bcl-2, Bcl-XL and Bcl-w with high affinity, while weakly interacts with Mcl-1 and Bfl-1. Previous studies demonstrated that quercetin, a flavonoid naturally present in food and beverages, was able to sensitize B-cells isolated from CLL patients to apoptosis when associated with death ligands or fludarabine, through a mechanism involving Mcl-1 down-regulation. Here, we report that the association between ABT-737 and quercetin synergistically induces apoptosis in B-cells and in five leukemic cell lines (Combination Index <1). Peripheral blood mononuclear cell from healthy donors were not affected by quercetin treatment. The molecular pathways triggered by quercetin have been investigated in HPB-ALL cells, characterized by the highest resistance to both ABT-737 and quercetin when applied as single molecules, but highly sensitivity to the co-treatment. In this cell line, quercetin down-regulated Mcl-1 through the inhibition of PI3K/Akt signaling pathway, leading to Mcl-1 instability. The same mechanism was confirmed in B-cells. These results may open new clinical perspectives based on a translational approach in CLL therapy. 23209189 Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21. Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻⁹). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D. 23292343 The evolution of RuBisCO stability at the thermal limit of photoautotrophy. A long-standing question in evolutionary biology is how organisms adapt to novel environments. In North American hot springs, diversification of a clade of the cyanobacterium Synechococcus into hotter environments has resulted in the unique innovation of a light-driven ecosystem at temperatures up to 74°C, and temperature adaptation of photosynthetic carbon fixation with the Calvin cycle contributed to this process. Here, we investigated the evolution of thermostability of the Calvin cycle enzyme ribulose-1, 5-bisphosphate carboxylase/oxygenase (RuBisCO) during Synechococcus divergence. Circular dichroism thermal scans revealed that the RuBisCO of the most thermotolerant Synechococcus lineage is more stable than those of other lineages or of resurrected ancestral enzymes. Using site-directed mutagenesis, we next identified four amino acid substitutions that together increased stability and activity of this enzyme at higher temperatures. These are clustered near critical subunit interfaces distant from the active site. Each of the four amino acids is also observed in a less thermostable Synechococcus RuBisCO, and the impact on stability of three of these appears to be epistatic. Recombination analyses that allow for recurrent mutation as well as patterns of synonymous variation surrounding these sites suggest that the evolution of a more thermostable RuBisCO may have involved homologous recombination. Our results provide insights on the molecular evolutionary processes that shape niche differentiation and ecosystem function. 23596325 In vivo hepatic lipid quantification using MRS at 7T in a mouse model of glycogen storage disease type 1a. The assessment of liver lipid content and composition is needed in preclinical research to investigate steatosis and steatosis-related disorders. The purpose of this study was to quantify in vivo hepatic fatty acid content and composition using a method based on short echo-time proton magnetic resonance spectroscopy at 7T. Mouse model of glycogen storage disease type 1a with inducible liver-specific deletion of the glucose-6-phosphatase gene (L-G6pc-/-) and control mice were fed a standard diet or a high fat/high sucrose diet (HF/HS) during 9 months. In control mice, hepatic lipid content was found significantly higher with HF/HS diet than with standard diet. As expected, hepatic lipid content was already elevated in L-G6pc-/- mice fed a standard diet compared to control mice. L-G6pc-/- mice rapidly developed steatosis which was not modified by HF/HS diet. On standard diet, estimated amplitudes from olefinic protons were found significantly higher in L-G6pc/- mice compared to that in control mice. L-G6pc-/- mice showed no noticeable polyunsaturation from diallylic protons. Total unsaturated fatty acid indexes measured by gas chromatography were in agreement with MRS measurements. These results showed the great potential of high magnetic field MRS to follow the diet impact and lipid alterations in mouse liver. 22740094 A pathogenetic link between non-alcoholic fatty liver disease and celiac disease. Non-alcoholic fatty liver disease (NAFLD) has recently been recognized as the leading cause of the abnormalities in the liver function tests in the Western countries. Celiac disease (CD) is a permanent immunological intolerance to gluten proteins in genetically predisposed individuals. CD has been reported in 4-13 % of the cases with steatohepatitis, although the pathogenesis of the liver steatosis in CD patients is unclear. Based on the literature data, it can be concluded that the inclusion of serological markers of CD should be a part of the general workup in the patients with steatosis when other causes of the liver disease are excluded and in the patients with NAFLD when metabolic risk factors are not evident. 23611508 Cross-Sectional Tracking of Particle Motion in Evaporating Drops: Flow Fields and Interfacial Accumulation. The lack of an effective technique for three-dimensional flow visualization has limited the experimental exploration of the "coffee ring effect" to the two dimensional, top-down viewpoint. In this report, high-speed, cross-sectional imaging of the flow fields was obtained by using optical coherence tomography to track particle motion in an evaporating colloidal water drop. This approach enables z-dimensional mapping of primary and secondary flow fields and changes in these fields over time. These sectional images show that 1μm diameter polystyrene particles have a highly non-uniform vertical distribution with particles accumulating at both the air-water interface and water-glass interface during drop evaporation. Particle density and relative humidity are shown to influence interfacial entrapment, which suggests that both sedimentation rate and evaporation rate affect the dynamic changes in the cross-sectional distribution of particles. Furthermore, entrapment at the air-water interface delays the time at which particles reach the ring structure. These results suggest that the organization of the ring structure can be controlled based on the ratio of different density particles in a colloidal solution. 23618624 Structure-activity relationships in aminosterol antibiotics: The effect of stereochemistry at the 7-OH group. Squalamine and three aminosterol analogs have been shown to inhibit bacterial cell growth and induce lysis of large unilamellar phospholipid vesicles. The analogs differ in the identity of the polyamine attached at C3 of the sterol, and the stereochemistry of a hydroxyl substituent at C7. Analogs with a tetraammonium spermine polyamine are somewhat more active than analogs with a shorter trisammonium spermidine polyamine, and analogs with an axial (α) hydroxyl substituent at C7 are more active than analogs with the corresponding equatorial (β) hydroxyl group. There is some variability noted; the 7β-OH spermine analog is the most active compound against Escherichia coli, but the least effective against Pseudomonas aeruginosa. Lytic activity correlates well with antimicrobial activity of the compounds, but the lytic activity varies with the phospholipid composition of the vesicles. 23351961 Inhibitory effects of curcumin on gastric cancer cells: A proteomic study of molecular targets. Curcumin, a natural anticancer agent, has been shown to inhibit cell growth in a number of tumor cell lines and animal models. We examined the inhibition of curcumin on cell viability and its induction of apoptosis using different gastric cancer cell lines (BGC-823, MKN-45 and SCG-7901). 3-(4,5-dimethyl-thiazol-2-yl)-2-5-diphenyltetrazolium-bromide (MTT) assay showed that curcumin inhibited cell growth in a dose- (1, 5, 10 and 30μM) and time- (24, 48, 72 and 96h) dependent manner; analysis of Annexin V binding showed that curcumin induced apoptosis at the dose of 10 and 30μM when the cells were treated for 24 and 48h. As cancers are caused by dysregulation of various proteins, we investigated target proteins associated with curcumin by two-dimensional gel electrophoresis (2-DE) and MALDI-TOF-TOF mass spectrometer. BGC-823cells were treated with 30μM curcumin for 24h and total protein was extracted for the 2-DE. In the first dimension of the 2-DE, protein samples (800μg) were applied to immobilized pH gradient (IPG) strips (24cm, pH 3-10, NL) and the isoelectric focusing (IEF) was performed using a step-wise voltage ramp; the second dimension was performed using 12.5% SDS-PAGE gel at 1W constant power per gel. In total, 75 proteins showed significant changes over 1.5-fold in curcumin-treated cells compared to control cells (Student's t-test, p<0.05). Among them, 33 proteins were upregulated and 42 proteins downregulated by curcumin as determined by spot densitometry. 52 proteins with significant mascot scores were identified and implicated in cancer development and progression. Their biological function included cell proliferation, cycle and apoptosis (20%), metabolism (16%), nucleic acid processing (15%), cytoskeleton organization and movement (11%), signal transduction (11%), protein folding, proteolysis and translation (20%), and immune response (2%). Furthermore, protein-protein interacting analysis demonstrated the interaction networks affected by curcumin in gastric cancer cells. These data provide some clues for explaining the anticancer mechanisms of curcumin and explore more potent molecular targets of the drug expected to be helpful for the development of new drugs. 23512337 Self-Assembled PAA-Based Nanoparticles as Potential Gene and Protein Delivery Systems. A series of nanoparticles is prepared via layer-by-layer assembly of oppositely charged, synthetic biocompatible polyamidoamine polymers as potential carriers. Particle size, surface charge and internal chain mobility are quantified as a function of the polymer type and number of layers. The effect of addition of surfactant is examined to simulate the effects of nanoparticle dissolution. The cyctotoxicity of these particles (in epithelia and murine cell lines) are orders of magnitude lower than polyethyleneimine controls. Stable nanoparticles may be prepared from mixtures of strongly, oppositely charged polymers, but less successfully from weakly charged polymers, and, given their acceptable toxicity characteristics, such modularly designed constructs show promise for drug and gene delivery. 22404642 Chemical constituents of Euphorbia hyberna L. (Euphorbiaceae). Chemical investigation of the aerial part and the roots of Euphorbia hyberna L. subs. hyberna. resulted in the isolation and identification of four triterpenoids (3β-O-octadecanoyllupeol (1), glut-5-en-3β-ol (2), 24-methylenecicloartan-3β-ol (3) and cicloart-23-ene-3β,25-diol (6)) along with the phenolic compounds ellagic acid (4) and 3,3'-di-O-methylellagic acid (7). Although these are all known compounds, this is the first report of their isolation from this plant. Their structures were elucidated on the basis of spectral methods, including 2D NMR experiences, and confirmed by comparing with the literature data. 23265892 Structure activity relationship studies of tricyclic bispyran sulfone γ-secretase inhibitors. An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (-)-1a (SCH 900229), a potent, PS1-selective γ-secretase inhibitor and clinical candidate for the treatment of Alzheimer's disease. Specifically, 4-CF(3) and 4-Br substituted arylsulfone analogs, (-)-1b and (-)-1c, are equipotent to compound (-)-1a. On the right hand side chain, linker size and terminal substituents of the pendant sulfone group are also investigated. 23442005 Density Functional Study of Organocatalytic Cross-Aldol Reactions between Two Aliphatic Aldehydes: Insight into Their Functional Differentiation and Origins of Chemo- and Stereoselectivities. The chemo-, diastereo-, and enantioselectivities in proline and axially chiral amino sulfonamide-catalyzed direct aldol reactions between two enolizable aldehydes with different electronic nature have been studied with the aid of density functional theory (DFT) method. The potential energy profiles for the enamine formation between each aliphatic aldehyde and the catalyst confirm that two subject catalysts can successfully differentiate between 3-methylbutanal as an enamine component and α-chloroaldehydes as a carbonyl component. Transition states associated with the stereochemistry-determining C-C bond-forming step with the enamine intermediate addition to the aldehyde acceptor for proline and chiral amino sulfonamide-promoted aldol reactions are reported. DFT calculations not only provide a good explanation for the formation of the sole cross-aldol product between two aliphatic aldehydes both bearing α-methylene protons but also well reproduce the opposite syn vs anti diastereoselectivities in the chiral amino sulfonamide and proline-catalyzed aldol reactions. 23047024 The cholinergic and non-cholinergic effects of organophosphates and oximes in cultured human myoblasts. Organophosphorus compounds (OPs) and oximes may interfere with other molecules than AChE in the living systems, affecting in this way various cellular processes and underlying mechanisms. These non-cholinergic effects may contribute to the clinical status in OP poisoning and therefore deserve equal scientific attention. Here, we investigated the effects of tabun and oxime K048 on the processes known to be involved in muscle response to the environmental factors, like IL-6 release and the regulation of the heat shock proteins (HSPs). While IL-6 stimulates muscle regeneration, which follows well known OP-induced myopathy, HSPs have cytoprotective effect against various stress factors including xenobiotics. All our experiments were carried out on cultured human myoblasts, as the precursors of muscle regeneration. We found unchanged AChE mRNA level after tabun/K048 treatment meaning that tabun and K048 did not interfere with the transcription or stability of this mRNA in the time period tested, even if AChE catalytic activity was significantly affected. On the other hand, after myoblast exposure to tabun, we observed significant changes in the protein levels of HSP 27 and in the secretion of IL-6. Namely, secretion of IL-6 decreased to 53% and the level of HSP 27 increased by 34% compared to the control level. Both effects were attenuated if myoblasts were pretreated with oxime K048, but not if they were treated with K048 after exposure to tabun. The molecular mechanism underlying these effects remains to be elucidated. However, it seems that these effects could be associated with OPs and oximes as a specific group of compounds rather than as a specific compound itself. Overall, the effects of OPs and oximes demonstrated here might play an important role in muscle regeneration which importantly determines the final outcome of OP myotoxicity. 23281069 Synthesis and biological evaluation of diaryl-substituted carboranes as inhibitors of hypoxia inducible factor (HIF)-1 transcriptional activity. Diaromatic-substituted ortho- and meta-carboranes were synthesized as mimics of manassantin A. Among the carboranes synthesized, compounds 1 and 2 showed significant inhibition of hypoxia-induced HIF-1 transcriptional activity, with IC(50) values of 3.2 and 2.2 μM, respectively. Compounds 1 and 2 similarly suppressed hypoxia-induced HIF-1α accumulation in a concentration-dependent manner without affecting the expression level of HIF-1α mRNA. The hypoxia-induced accumulation and translocation of HIF-1α into nuclei were not observed in HeLa cells treated with compounds 1 and 2 by immunofluorescence analysis, revealing that the inhibition of hypoxia-induced HIF-1 transcriptional activity is induced by compounds 1 and 2 through a degradation pathway of the HIF-1α protein under hypoxic conditions. 23323987 Two new diterpenoids from Excoecaria acerifolia. A new tigliane diterpenoid, acerifolin A (1), and a new isopimarane diterpenoid, acerifolin B (2), together with two known compounds, were isolated from Excoecaria acerifolia. Their structures were elucidated on the basis of their spectroscopic methods, including 1D and 2D NMR techniques. All of the compounds were evaluated for cytotoxicity against five human cancer cell lines with cisplantin as a positive control. 23497862 Morphology and structural properties of high-amylose rice starch residues hydrolysed by amyloglucosidase. High-amylose starches are attracting considerable attention because of their potential health benefits and industrial uses. Enzyme hydrolysis of starch is involved in many biological and industrial processes. In this paper, starches were isolated from high-amylose transgenic rice (TRS) and its wild type rice, Te-qing (TQ). The morphological and structural changes of starch residues following Aspergillus niger amyloglucosidase (AAG) hydrolysis were investigated. AAG hydrolysed TQ starch from the granule surface, and TRS starch from the granule interior. During AAG hydrolysis, the content of amorphous structure increased, the contents of ordered structure and single helix decreased, and gelatinisation enthalpy decreased in TQ and TRS starch residues. The A-type polymorph of TRS C-type starch was hydrolysed faster than the B-type polymorph. The short-range ordered structure and B-type polymorph in the peripheral region of the subgranule and the surrounding band of TRS starch increased the resistance of TRS starch to AAG hydrolysis. 23370776 Silencing of RB1 but not of RB2/P130 induces cellular senescence and impairs the differentiation potential of human mesenchymal stem cells. Stem cell senescence is considered deleterious because it may impair tissue renewal and function. On the other hand, senescence may arrest the uncontrolled growth of transformed stem cells and protect organisms from cancer. This double function of senescence is strictly linked to the activity of genes that the control cell cycle such as the retinoblastoma proteins RB1, RB2/P130, and P107. We took advantage of the RNA interference technique to analyze the role of these proteins in the biology of mesenchymal stem cells (MSC). Cells lacking RB1 were prone to DNA damage. They showed elevated levels of p53 and p21(cip1) and increased regulation of RB2/P130 and P107 expression. These cells gradually adopted a senescent phenotype with impairment of self-renewal properties. No significant modification of cell growth was observed as it occurs in other cell types or systems. In cells with silenced RB2/P130, we detected a reduction of DNA damage along with a higher proliferation rate, an increase in clonogenic ability, and the diminution of apoptosis and senescence. Cells with silenced RB2/P130 were cultivated for extended periods of time without adopting a transformed phenotype. Of note, acute lowering of P107 did not induce relevant changes in the in vitro behavior of MSC. We also analyzed cell commitment and the osteo-chondro-adipogenic differentiation process of clones derived by MSC cultures. In all clones obtained from cells with silenced retinoblastoma genes, we observed a reduction in the ability to differentiate compared with the control clones. In summary, our data show evidence that the silencing of the expression of RB1 or RB2/P130 is not compensated by other gene family members, and this profoundly affects MSC functions. 23440956 Graphene-Bonded and -Encapsulated Si Nanoparticles for Lithium Ion Battery Anodes. Silicon (Si) has been considered a very promising anode material for lithium ion batteries due to its high theoretical capacity. However, high-capacity Si nanoparticles usually suffer from low electronic conductivity, large volume change, and severe aggregation problems during lithiation and delithiation. In this paper, a unique nanostructured anode with Si nanoparticles bonded and wrapped by graphene is synthesized by a one-step aerosol spraying of surface-modified Si nanoparticles and graphene oxide suspension. The functional groups on the surface of Si nanoparticles (50-100 nm) not only react with graphene oxide and bind Si nanoparticles to the graphene oxide shell, but also prevent Si nanoparticles from aggregation, thus contributing to a uniform Si suspension. A homogeneous graphene-encapsulated Si nanoparticle morphology forms during the aerosol spraying process. The open-ended graphene shell with defects allows fast electrochemical lithiation/delithiation, and the void space inside the graphene shell accompanied by its strong mechanical strength can effectively accommodate the volume expansion of Si upon lithiation. The graphene shell provides good electronic conductivity for Si nanoparticles and prevents them from aggregating during charge/discharge cycles. The functionalized Si encapsulated by graphene sample exhibits a capacity of 2250 mAh g(-1) (based on the total mass of graphene and Si) at 0.1C and 1000 mAh g(-1) at 10C, and retains 85% of its initial capacity even after 120 charge/discharge cycles. The exceptional performance of graphene-encapsulated Si anodes combined with the scalable and one-step aerosol synthesis technique makes this material very promising for lithium ion batteries. 23071106 Potentiation of sulfonylurea action by an EPAC-selective cAMP analog in INS-1 cells: comparison of tolbutamide and gliclazide and a potential role for EPAC activation of a 2-APB-sensitive Ca2+ influx. Tolbutamide and gliclazide block the K(ATP) channel K(ir)6.2/Sur1, causing membrane depolarization and stimulating insulin secretion in pancreatic beta cells. We examined the ability of the EPAC-selective cAMP analog 8-pCPT-2'-O-Me-cAMP-AM to potentiate the action of these drugs and the mechanism that might account for it. Insulin secretion stimulated by both 200 μM tolbutamide and 20 μM gliclazide, concentrations that had equivalent effects on membrane potential, was inhibited by thapsigargin (1 μM) or the L-type Ca(2+) channel blocker nicardipine (2 μM) and was potentiated by 8-pCPT-2'-O-Me-cAMP-AM at concentrations ≥2 μM in INS-1 cells. Ca(2+) transients stimulated by either tolbutamide or gliclazide were inhibited by thapsigargin or nicardipine and were significantly potentiated by 8-pCPT-2'-O-Me-cAMP-AM at 5 μM but not 1 μM. Both tolbutamide and gliclazide stimulated phospholipase C activity; however, only gliclazide did so independently of its activity at K(ATP) channels, and this activity was partially inhibited by pertussis toxin. 8-pCPT-2'-O-Me-cAMP-AM alone (5 μM) did not stimulate insulin secretion, but did increase intracellular Ca(2+) concentration significantly, and this activity was inhibited by 25 μM 2-aminoethoxydiphenylborate (2-APB) or the removal of extracellular Ca(2+). 8-pCPT-2'-O-Me-cAMP-AM potentiation of insulin secretion stimulated by tolbutamide was markedly inhibited by 2-APB (25 μM) and enhanced by the PKC inhibitor bisindolylmaleimide I (1 μM). Our data demonstrate that the actions of both tolbutamide and gliclazide are strongly potentiated by 8-pCPT-2'-O-Me-cAMP-AM, that gliclazide can stimulate phospholipase C activity via a partially pertussis toxin-sensitive mechanism, and that 8-pCPT-2'-O-Me-cAMP-AM potentiation of tolbutamide action may involve activation of a 2-APB-sensitive Ca(2+) influx. 23422034 Antimicrobial, antiviral and antioxidant activities of "água-mel" from Portugal. "Água-mel" is a honey-based product produced in Portugal for ancient times. Several attributes have been reported to "água-mel" particularly in the alleviation of simple symptoms of upper respiratory tract. Samples of "água-mel" from diverse beekeepers from different regions of Portugal were studied in what concerns antimicrobial, antioxidant and antiviral properties. The amounts of phenol and brown pigment were also evaluated and correlated with the antioxidant activities. A great variability on the levels of these compounds was found among samples which were responsible for the variability detected also on the antioxidant activities, independent on the method used. Generally, antioxidant activity correlated better with brown pigments' amount than with phenols' content. The antimicrobial activity found for "água-mel" samples confirm the virtues reported by popular findings. In addition, this work also reveals the antiviral properties of "água-mel" evidenced by a decrease on the infectivity of the Qβ bacteriophage. 23519059 Tuning the electronic and photophysical properties of heteroleptic iridium(iii) phosphorescent emitters through ancillary ligand substitution: a theoretical perspective. The development and application of phosphorescent emitters in organic light-emitting diodes (OLEDs) have played a critical role in the push to commercialization of OLED-based display and lighting technologies. Here, we use density functional theory methods to study how modifying the ancillary ligand influences the electronic and photophysical properties of heteroleptic bis(4,6-difluorophenyl) pyridinato-N,C [dfppy] iridium(iii) complexes. We examine three families of bidentate ancillary ligands based on acetylacetonate, picolinate, and pyridylpyrazolate. It is found that the frontier molecular orbitals of the heteroleptic complexes can be substantially modulated both as a function of the bidentate ligand family and of the substitution patterns within a family. As a consequence, considerable control over the first absorption and phosphorescence emission transitions, both of which are dominated by one-electron transitions between the HOMO and LUMO, is obtained. Tuning the nature of the ancillary ligand, therefore, can be used to readily modulate the photophysical properties of the emitters, providing a powerful tool in the design of the emitter architecture. 22867274 Metabolic profiling of TRPV1 antagonists of the benzothiazole amide series: implications for in vitro genotoxicity assessment. In vitro metabolic profiling and in vitro genotoxicity assessment are important aspects of the drug discovery program as they eliminate harmful compounds from further development. In standard in vitro genotoxicity testing, induced rat liver S9 is used as an exogenous bio-activation system for detecting promutagens. In this study we show that rat liver S9 is an insufficient system regarding the conversion of TRPV1 antagonists of the benzothiazole amide series into relevant in vivo metabolites. Human and rat hepatocyte experiments demonstrated generation of an aryl amine metabolite that was subsequently N-acetylated. The hydrolyzed metabolites as well as the parent compound were also metabolized into glutathione (GSH) conjugates. Rat liver S9 exhibited a very low amide hydrolysis capacity and no formation of GSH conjugates when supplemented with NADPH and GSH. The discrepancy in metabolic capability between hepatocytes and rat liver S9 led to confounding results in in vitro genotoxicity assessment for this chemical class as judged by the results of Ames test, mouse lymphoma assay, SOS/umu test and Comet assay in rat hepatocytes. This study highlights the pivotal role that understanding the mechanism of metabolite formation has in interpreting as well as designing reliable and relevant in vitro genotoxicity experiments. 23538871 Sponge-Derived Kocuria and Micrococcus spp. as Sources of the New Thiazolyl Peptide Antibiotic Kocurin. Forty four marine actinomycetes of the family Microccocaceae isolated from sponges collected primarily in Florida Keys (USA) were selected from our strain collection to be studied as new sources for the production of bioactive natural products. A 16S rRNA gene based phylogenetic analysis showed that the strains are members of the genera Kocuria and Micrococcus. To assess their biosynthetic potential, the strains were PCR screened for the presence of secondary metabolite genes encoding nonribosomal synthetase (NRPS) and polyketide synthases (PKS). A small extract collection of 528 crude extracts generated from nutritional microfermentation arrays was tested for the production of bioactive secondary metabolites against clinically relevant strains (Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii and Candida albicans). Three independent isolates were shown to produce a new anti-MRSA bioactive compound that was identified as kocurin, a new member of the thiazolyl peptide family of antibiotics emphasizing the role of this family as a prolific resource for novel drugs. 23353026 Oxidative stress involvement in manganese-induced alpha-synuclein oligomerization in organotypic brain slice cultures. Overexposure to manganese (Mn) has been known to induce neuronal damage. However, little is known of the role that reactive oxygen species (ROS) play in protein aggregation resulting from Mn exposure. The current study investigated whether oxidative stress is involved in manganese-induced alpha-synuclein oligomerization in organotypic brain slices. After application of Mn (0-400μM) for 24h, there was a dose-dependent increase in average percentage of propidium iodide positive (PI(+)) nuclei in slices and levels of lactate dehydrogenase (LDH) in the culture medium. Moreover, the treatment with Mn resulted in a dose-dependent increase in neurocyte apoptosis, ROS level, and decrease in superoxide dismutase (SOD) activity. Mn also caused oxidative damage in cell lipid and protein. At the same time, the exposure of Mn leaded to significantly increase in the expression of alpha-synuclein mRNA and protein. Alpha-synuclein oligomerization occurred in Mn-treated slices, especially on membrane-bound form. It indicated that alpha-synuclein oligomers were more likely to combination cell membranes and resulting in membrane damage. Mn-induced neurocyte damage and alpha-synuclein oligomerization were also partially alleviated by the pretreatment with GSH and aggravated by H2O2 pretreatment. The findings revealed Mn might exert its neurotoxic effects by oxidative stress-mediated alpha-synuclein oligomerization in organotypic brain slices. 23359587 In vivo biological responses to silk proteins functionalized with bone sialoprotein. Recombinant 6mer + BSP protein, combining six repeats of the consensus sequence for Nephila clavipes dragline (6mer) and bone sialoprotein sequence (BSP), shows good support for cell viability and induces the nucleation of hydroxyapatite and tricalcium phosphate during osteoblast in vitro culture. The present study is conducted to characterize this bioengineered protein-based biomaterial further for in vivo behavior related to biocompatibility. 6mer + BSP protein films are implanted in subcutaneous pouches in the back of mice and responses are evaluated by flow cytometry and histology. The results show no major differences between the inflammatory responses induced by 6mer + BSP films and the responses observed for the controls. Thus, this new chimeric protein could represent an alternative for bone regeneration applications. 23455229 Capping-agent-free synthesis of substrate-supported porous icosahedral gold nanoparticles. We report a new capping-agent-free strategy for the synthesis of substrate-supported porous icosahedral Au nanoparticles (NPs) with rough naked surfaces, based on the crystallization from substrate-supported thin solution layers followed by solid-phase thermolysis. The plasmonic properties of icosahedral Au NPs have been studied using single particle dark-field scattering microscopy and spectroscopy. The two distinct localized surface plasmon resonance (LSPR) bands observed in the single particle dark-field spectra can be ascribed to the quadrupole resonance at ca. 425 nm and the size-dependent dipole resonance in the red region (645-708 nm). The unique rough naked surface, the facile synthesis, together with the ability to control the nanoparticle size and to vary the LSPR frequency in the red region, would make the substrate-supported porous icosahedral Au NPs promising on multiple levels in the applications of catalysis, ultrasensitive biosensors, and in surface-enhanced Raman scattering (SERS). 23376162 Sesquiterpenes from the rhizomes of Alpinia japonica and their inhibitory effects on nitric oxide production. A novel norsesquiterpene (1), three new bisabolenes sesquiterpenes (2-4), along with 7 known compounds (5-11), were isolated from the rhizomes of Alpinia japonica. The structures of the new compounds were elucidated by analysis of spectroscopic data. The absolute configuration of C-1 in 3 was deduced via the circular dichroism data of the in situ formed [Rh2(OCOCF3)4] complexes. Inhibitory effects of the isolates on nitric oxide production in lipopolysaccaride-activated RAW264.7 macrophages were evaluated. Compound 6 showed significant inhibitory activity with IC50 value of 5.3μΜ, and compounds 1, 3, 5 and 7-10 exhibited moderate inhibitory activities with IC50 values between 24.5 and 46.3μM. 23352430 Identification of early replicating fragile sites that contribute to genome instability. DNA double-strand breaks (DSBs) in B lymphocytes arise stochastically during replication or as a result of targeted DNA damage by activation-induced cytidine deaminase (AID). Here we identify recurrent, early replicating, and AID-independent DNA lesions, termed early replication fragile sites (ERFSs), by genome-wide localization of DNA repair proteins in B cells subjected to replication stress. ERFSs colocalize with highly expressed gene clusters and are enriched for repetitive elements and CpG dinucleotides. Although distinct from late-replicating common fragile sites (CFS), the stability of ERFSs and CFSs is similarly dependent on the replication-stress response kinase ATR. ERFSs break spontaneously during replication, but their fragility is increased by hydroxyurea, ATR inhibition, or deregulated c-Myc expression. Moreover, greater than 50% of recurrent amplifications/deletions in human diffuse large B cell lymphoma map to ERFSs. In summary, we have identified a source of spontaneous DNA lesions that drives instability at preferred genomic sites. 23470076 Cystatin C: an emerging biomarker in cardiovascular disease. Cystatin C (cys-C) is a small protein molecule (120 amino acid peptide chain, approximately 13kDa) produced by virtually all nucleated cells in the human body. It belongs to the family of papain-like cysteine proteases and its main biological role is the extracellular inhibition of cathepsins. It's near constant production rate, the fact that it is freely filtered from the glomerular membrane and then completely reabsorbed without being secreted from the proximal tubular cells, made it an almost perfect candidate for estimating renal function. The strong correlation between chronic kidney disease (CKD) and cardiovascular disease (CVD) along with the growing understanding of the role of cysteinyl cathepsins in the pathophysiology of CVD inspired researchers to explore the potential association of cys-C with CVD. Throughout the spectrum of CVD (peripheral arterial disease, stroke, abdominal aortic aneurysm, heart failure, coronary artery disease) adverse outcomes and risk stratification have been associated with high plasma levels of cys-C. The exact mechanisms behind the observed correlations have not been comprehensively clarified. Plausible links between high cys-C levels and poor cardiovascular outcome could be impaired renal function, atherogenesis and inflammatory mediators, remodeling of myocardial tissue and others (genetic factors, aging and social habits). The scope of the present article is to systematically review the current knowledge about cys-C biochemistry, metabolism, methods of detection and quantification and pathophysiological associations with different aspects of CVD. 23471218 Exendin-4 protects hypoxic islets from oxidative stress and improves islet transplantation outcome. Oxidative stress produced during pancreatic islet isolation leads to significant β-cell damage. Homeostatic cytokines secreted subsequently to islet transplantation damage β-cells by generating oxygen free radicals. In this study, exendin-4, a glucagon-like peptide-1 analog improved islet transplantation outcome by increasing the survival of diabetic recipient mice from 58% to 100%. We hypothesized that this beneficial effect was due to the ability of exendin-4 to reduce oxidative stress. Further experiments showed that it significantly reduced the apoptotic rate of cultured β-cells subjected to hypoxia or to IL-1β. Reduction of apoptotic events was confirmed in pancreatic islet grafts of exendin-4-treated mice. Exendin-4 enhanced Akt phosphorylation of β-cells and insulin released from them. It even augmented insulin secretion from islets cultivated at hypoxic conditions. Exposure to hypoxia led to a decrease in the activation of Akt, which was reversed when β-cells were pretreated with exendin-4. Moreover, exendin-4 increased the activity of redox enzymes in a hypoxia-treated β-cell line and reduced reactive oxygen species production in isolated pancreatic islets. Recovery from diabetes in mice transplanted with hypoxic islets was more efficient when they received exendin-4. In conclusion, exendin-4 rescued islets from oxidative stress caused by hypoxia or due to cytokine exposure. It improved the outcome of syngenic and xenogenic islet transplantation. 23274917 Determination of genotoxicity by the Comet assay applied to murine precision-cut lung slices. Precision-cut lung slices (PCLSs) are an organotypic lung model that is widely used in pharmacological, physiological, and toxicological studies. Genotoxicity testing, as a pivotal part of early risk assessment, is currently established in vivo in various organs including lung, brain, or liver, and in vitro in cell lines or primary cells. The aim of the present study was to provide the three-dimensional organ culture PCLS as a new ex vivo model for determination of genotoxicity using the Comet assay. Murine PCLS were exposed to increasing concentrations of ethyl methane sulfonate 'EMS' (0.03-0.4%) and formalin (0.5-5mM). Tissue was subsequently dissociated, and DNA single-strand breaks were quantified using the Comet assay. Number of viable dissociated lung cells was between 4×10(5) and 6.7×10(5)cells/slice. Even treatment with EMS did not induce toxicity compared to untreated tissue control. As expected, DNA single-strand breaks were increased dose-dependently and significantly after exposure to EMS. Here, tail length rose from 24μm to 75μm. In contrast, formalin resulted in a significant induction of DNA cross-links. The effects induced by EMS and formalin demonstrate the usefulness of PCLS as a new ex vivo lung model for genotoxicity testing in the early risk assessment of airborne substances in the future. 23541768 Two antagonistic clock-regulated histidine kinases time the activation of circadian gene expression. The cyanobacterial circadian pacemaker consists of a three-protein clock-KaiA, KaiB, and KaiC-that generates oscillations in the phosphorylation state of KaiC. Here we investigate how temporal information encoded in KaiC phosphorylation is transduced to RpaA, a transcription factor required for circadian gene expression. We show that phosphorylation of RpaA is regulated by two antagonistic histidine kinases, SasA and CikA, which are sequentially activated at distinct times by the Kai clock complex. SasA acts as a kinase toward RpaA, whereas CikA, previously implicated in clock input, acts as a phosphatase that dephosphorylates RpaA. CikA and SasA cooperate to generate an oscillation of RpaA activity that is distinct from that generated by either enzyme alone and offset from the rhythm of KaiC phosphorylation. Our observations reveal how circadian clocks can precisely control the timing of output pathways via the concerted action of two oppositely acting enzymes. 23530036 Discoidin Domain Receptor 1 is a novel modulator of megakaryocyte-collagen interactions. Growing evidence demonstrates that extracellular matrices (ECMs) regulate many aspects of megakaryocyte (MK) development; however, among the different ECM receptors, integrin alpha2beta1 and GPVI are the only collagen receptors studied in platelets and MKs. In this study, we demonstrate the expression of the novel collagen receptor Discoidin Domain Receptor 1 (DDR1) by human MKs at both mRNA and protein levels and provide evidence of DDR1 involvement in the regulation of MK motility on type I collagen through a mechanism based on the activity of SHP1 phosphatase and Syk tyrosine kinase. Specifically, we demonstrated that inhibition of DDR1 binding to type I collagen, preserving the engagement of the other collagen receptors, GPVI, alpha2beta1 and LAIR-1 determines a decrease in MK migration due to the reduction in SHP1 phosphatase activity and consequent increase in the phosphorylation level of its main substrate Syk. Consistently, inhibition of Syk activity restored MK migration on type I collagen. In conclusion, we report the expression and function of a novel collagen receptor on human MKs and we point out that increasing level of complexity is necessary to better understand MK-collagen interactions in the bone marrow environment. 23474320 Effects of metal burden and food avoidance on the transfer of metals from naturally contaminated prey to a marine predator Nassarius siquijorensis. Nassarid snails are important opportunistic scavengers widely found in marine intertidal shores and trophic transfer is a predominant source of metal accumulation in these species, thus there is a significant need to understand the controls of metal trophic transfer. In the present study, we took advantage of a severely contaminated estuary and collected two prey organisms (oysters Crassostrea angulata and barnacles Fistulobalanus albicostatus) with different contamination histories. These naturally contaminated prey were fed to a marine neogastropod Nassarius siquijorensis for a period of up to 7 weeks. We then investigated the influences of prey type, metal burden, and subcellular distribution in the prey on the metal accumulation, trophic transfer, and potential toxicity on N. siquijorensis. We demonstrated an obvious negative relationship between the trophic transfer and the metal concentration in prey or the metal dosage. N. siquijorensis exhibited food avoidance behavior to the Cu contaminated food, which effectively reduced the metal ingestion and resulted in a decrease of trophic transfer, as well as a potential toxic effect from dietary exposure. On the other hand, our results also implied the metal-specific impact of subcellular metal distribution in prey on the trophic transfer to N. siquijorensis. Our study suggested that metal burden and feeding avoidance should be considered in studying the trophic transfer of metals in marine benthic food chain. 23406166 A new O-prenylated flavonol from the roots of Sophora interrupta. A new O-prenylated flavonol, 3',4'-dimethoxy-7-(γ,γ-dimethylallyloxy)flavonol (1), together with three known compounds, 2'-hydroxy-3,4-dimethoxychalcone (2), biochanin A (3) and kaempferol-3-O-β-d-glucopyranoside (4), were isolated from the roots of Sophora interrupta Bedd. The structure of compound 1 was elucidated by extensive 1D and 2D NMR spectral studies. 23602986 Neuroactive effects of cotinine on the hippocampus: Behavioral and biochemical parameters. The present work evaluated the effects of nicotine (NIC), cotinine (COT), mecamylamine (MEC), methyllycaconitine (MLA) and dihydro-beta-eritroidine (DHβE) on memory extinction and the following biochemical parameters of the hippocampus: lipid peroxidation (LPO), antioxidant capacity (AC) and the phosphorylation of Extracellular-Signal-Regulated Kinase (ERK 1/2). Young male rats that were implanted bilaterally with cannulae were submitted to memory extinction tests sessions, and their hippocampi were dissected for biochemical assays. The extinction of fear memory was significantly improved by both nicotine and its metabolite. Cotinine significantly increased LPO, while nicotine significantly decreased it. Antioxidant capacity was increased by all treatments. Our results showed that cotinine, unlike nicotine, may increase oxidative stress in the hippocampus, but this increase depends upon the dose used and happens without causing corresponding impairments in cognitive function. Cotinine also increased the phosphorylation of ERK 1/2 in a similar fashion as nicotine. Considering these results, it is plausible to wonder to what extent nicotine-attributed effects are really due to the actions of this alkaloid and whether they could be due instead to cotinine or to cotinine-nicotine interactions within the brain. 23348499 Differential activation and modulation of the glucagon-like peptide-1 receptor by small molecule ligands. The glucagon-like peptide-1 receptor (GLP-1R) is a major therapeutic target for the treatment of type 2 diabetes due to its role in glucose homeostasis. Despite the availability of peptide-based GLP-1R drugs for treatment of this disease, there is great interest in developing small molecules that can be administered orally. The GLP-1R system is complex, with multiple endogenous and clinically used peptide ligands that exhibit different signaling biases at this receptor. This study revealed that small molecule ligands acting at this receptor are differentially biased to peptide ligands and also from each other with respect to the signaling pathways that they activate. Furthermore, allosteric small molecule ligands were also able to induce bias in signaling mediated by orthosteric ligands. This was dependent on both the orthosteric and allosteric ligand as no two allosteric-orthosteric ligand pairs could induce the same signaling profile. We highlight the need to profile compounds across multiple signaling pathways and in combination with multiple orthosteric ligands in systems such as the GLP-1R where more than one endogenous ligand exists. In the context of pleiotropical coupling of receptors and the interplay of multiple pathways leading to physiologic responses, profiling of small molecules in this manner may lead to a better understanding of the physiologic consequences of biased signaling at this receptor. This could enable the design and development of improved therapeutics that have the ability to fine-tune receptor signaling, leading to beneficial therapeutic outcomes while reducing side effect profiles. 23592429 Minireview: androgen metabolism in castration-resistant prostate cancer. The decades-old terminology of androgen independence has been replaced in recent years with castration-resistant prostate cancer. Biological and clinical evidence have together conspired to support the use of this revised terminology by demonstrating that in the vast majority of cases tumors are neither truly depleted of androgens, nor are they free of the requirement for androgens to sustain growth and progression. Abiraterone acetate, an androgen synthesis inhibitor, and enzalutamide, a potent androgen receptor antagonist, both exploit the continued requirement for androgens. A central question, given the therapeutic gains enabled by further suppression of the androgen axis with these newer agents, is whether there may be additional clinical benefit gained by moving the goal posts of androgen suppression even further. The answer lies in part with the mechanisms utilized by tumors that enable resistance to these therapies. The aims of this review were to give a broad outline of steroidogenesis in prostate cancer and to highlight recent developments in understanding resistance to hormonal therapies. 22736593 The Inhibitory Effect of 20(S)-Protopanaxatriol (ppt) Towards UGT1A1 and UGT2B7. Ginseng, a commonly used natural product, has been frequently reported to induce herb-drug interaction with many clinical drugs. The intestinal bacterial metabolites of ginsenosides have been widely regarded as the substance basis for ginseng-drug interactions. To date, little is known about the inhibitory effect of intestinal bacterial metabolites of ginsenosides towards UDP-glucuronosyltransferases (UGTs). In vitro investigation of the inhibition of 20(S)-protopanaxatriol (ppt) towards UGT1A1 and UGT2B7 was carried out. The results showed that ppt exhibited strong noncompetitive inhibition towards UGT1A1 and competitive inhibition towards UGT2B7. The inhibition kinetic parameters (Ki ) were calculated to be 8.8 and 2.2 μM for UGT1A1 and UGT2B7, respectively. Using the maximum plasma concentration of ppt, the alteration of area under the concentration-time curve was calculated to be 20% and 70% respectively for UGT1A1-mediated and UGT2B7-mediated metabolism. However, given that the varied contribution of these two UGT isoforms towards drug metabolism and the influence of herb complexity and individual difference, the explanation of these results should be paid more caution. Copyright © 2012 John Wiley & Sons, Ltd. 23454310 Light induced toxicity reduction of silver nanoparticles to Tetrahymena Pyriformis: Effect of particle size. As a result of the extensive application of silver nanoparticles (AgNPs), their potential hazards, once they are released into the natural environment, are of great concern to people. Since silver is very sensitive to light, the toxicity of AgNPs released into the natural environment will be inevitably affected by light. The aim of this study was to investigate the relationship between light, toxicity, and particle size of AgNPs and deduce the possible mechanism of any interaction. Our study revealed that there was negative correlation between the particle size and the toxicity: small AgNPs (5-10nm) had higher toxicity than large AgNPs (15-25nm) to Tetrahymena pyriformis (T. pyriformis) under dark condition. Comparing the size dependent AgNPs toxicity under dark and light conditions, the effect of light to size dependent AgNPs toxicity was ascertained. The results indicated that AgNPs toxicity was decreased by light and the most important discovery was that the change of size dependent AgNPs toxicity had significant difference under light irradiation. The decrease of small AgNPs toxicity induced by light was more notable than large AgNPs. The decreased level of cell toxicity for small AgNPs was 32±0.7%, whereas it was only 10.6±5.2% for large AgNPs kept 24h under light irradiation. The further investigation indicated that the above changes induced by light can be attributed to the decrease of released silver ions, particle growth and aggregation of AgNPs under light irradiation. The obtained results showed that the light irradiation can promote the rapid growth of small AgNPs and result in the obvious increase of particle size and serious aggregation. These phenomena would induce the decrease of silver ions released from small AgNPs, which is responsible for the remarkable decrease of toxicity for small AgNPs. 23270704 Apocynin and raisanberine alleviate intermittent hypoxia induced abnormal StAR and 3β-HSD and low testosterone by suppressing endoplasmic reticulum stress and activated p66Shc in rat testes. We hypothesized that hypoxia induced testicular damage is mediated by an activated NADPH oxidase (NOX), therefore, APO (apocynin) an inhibitor of NOX and raisanberine (RS), a calcium influx inhibitor were tested if they could attenuate hypoxic toxicity to the testis. Male Sprague-Dawley rats were exposed to hypoxia (10±0.5% O2) for 17d and intervened with APO and RS in the last 6d. Histological changes and expression of pro-inflammation factors were evaluated in vivo. Biomarkers in isolated Leydig cells incubated with H2O2 were also assayed in vitro. Hypoxic rats displayed lower serum testosterone and higher LH and FSH. Upregulation of p22/p47(phox), NOX2, MMP9, PERK and p66Shc was associated with downregulation of StAR, 3β-HSD and Cx43 in the hypoxia testis, revealed by Western blot and immunohistochemical assay, respectively. APO and RS at least partially normalize hypoxia caused male hypogonadism by suppressing ER stress, and p66Shc in testes. 23517028 Biophysical Fragment Screening of the β1-Adrenergic Receptor: Identification of High Affinity Arylpiperazine Leads Using Structure-Based Drug Design. Biophysical fragment screening of a thermostabilized β1-adrenergic receptor (β1AR) using surface plasmon resonance (SPR) enabled the identification of moderate affinity, high ligand efficiency (LE) arylpiperazine hits 7 and 8. Subsequent hit to lead follow-up confirmed the activity of the chemotype, and a structure-based design approach using protein-ligand crystal structures of the β1AR resulted in the identification of several fragments that bound with higher affinity, including indole 19 and quinoline 20. In the first example of GPCR crystallography with ligands derived from fragment screening, structures of the stabilized β1AR complexed with 19 and 20 were determined at resolutions of 2.8 and 2.7 Å, respectively. 23362105 Glycan sequence-dependent Nod2 activation investigated by using a chemically synthesized bacterial peptidoglycan fragment library. Nucleotide oligomerization domain-containing protein 2 (Nod2), an innate immune receptor, recognizes bacterial cell-wall peptidoglycan (PGN), the minimum ligand of which is muramyl dipeptide (MDP). Enzymatic digestion of PGN appears to be important for Nod2 recognition. PGN is degraded by muramidase or glucosamidase through a process that produces two types of glycan sequence; glycans containing GlcNAcβ(1→4)MurNAc or MurNAcβ(1→4)GlcNAc. In this report, a range of disaccharide or tetrasaccharide fragments of each sequence were chemically synthesized, and their activities in stimulating human Nod2 (hNod2) were investigated. The results reveal that hNod2 recognitions is dependent on the glycan sequence, as demonstrated by comparing the activities of glycans with the same peptide moieties. (MurNAcβ(1→4)GlcNAc)(2) -containing structures exhibited stronger activity than those containing (GlcNAcβ(1→4)MurNAc)(2) . The results suggest that differences in the enzymatic degradation process affect the host's immunomodulation process. 23180826 Versican 3'-untranslated region (3'-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity. This study was designed to explore the role of versican in the development of hepatocellular carcinoma (HCC). Ectopic expression of the versican 3'-untranslated region (3'-UTR) was studied as a competitive endogenous RNA for regulating miRNA functions. We used this approach to modulate the expression of versican and its related proteins in 3'-UTR transgenic mice and in the liver cancer cell line HepG2, stably transfected with the 3'-UTR or a control vector. We demonstrated that transgenic mice expressing the versican 3'-UTR developed HCC and increased expression of versican isoforms V0 and V1. HepG2 cells transfected with versican 3'-UTR displayed increased proliferation, survival, migration, invasion, colony formation, and enhanced endothelial cell growth, but decreased apoptosis. We found that versican 3'-UTR could bind to miRNAs miR-133a, miR-199a*, miR-144, and miR-431 and also interacted with CD34 and fibronectin. As a consequence, expression of versican, CD34, and fibronectin was up-regulated by ectopic transfection of the versican 3'-UTR, which was confirmed in HepG2 cells and in transgenic mice as compared with wild-type controls. Transfection with siRNAs targeting the versican 3'-UTR abolished the effects of the 3'-UTR. Taken together, these results demonstrate that versican V0 and V1 isoforms play important roles in HCC development and that versican mRNAs compete with endogenous RNAs in regulating miRNA functions. 23614815 Recycling factors for ribosome disassembly in the apicoplast and mitochondrion of Plasmodium falciparum. The reduced genomes of the apicoplast and mitochondrion of the malaria parasite Plasmodium falciparum are actively translated and antibiotic-mediated translation inhibition is detrimental to parasite survival. In order to understand recycling of organellar ribosomes, a critical step in protein translation, we identified ribosome recycling factors (RRF) encoded by the parasite nuclear genome. Targeting of PfRRF1 and PfRRF2 to the apicoplast and mitochondrion respectively was established by localization of leader sequence-GFP fusions. Unlike any RRF characterized thus far, PfRRF2 formed dimers with disulphide interaction(s) and additionally localized in the cytoplasm, thus suggesting adjunct functions for the factor. PfRRF1 carries a large 108-amino-acid insertion in the functionally critical hinge region between the head and tail domains of the protein, yet complemented Escherichia coli RRF in the LJ14frr(ts) mutant and disassembled surrogate E. coli 70S ribosomes in the presence of apicoplast-targeted EF-G. Recombinant PfRRF2 bound E. coli ribosomes and could split monosomes in the presence of the relevant mitochondrial EF-G but failed to complement the LJ14frr(ts) mutant. Although proteins comprising subunits of P. falciparum organellar ribosomes are predicted to differ from bacterial and mitoribosomal counterparts, our results indicate that the essential interactions required for recycling are conserved in parasite organelles. 23343595 Weight change by baseline BMI from three-year observational data: findings from the Worldwide Schizophrenia Outpatient Health Outcomes Database. The aim was to explore weight and body mass index (BMI) changes by baseline BMI in patients completing three years of monotherapy with various first- and second-generation antipsychotics in a large cohort in a post hoc analysis of three-year observational data. Data were analyzed by antipsychotic and three baseline BMI bands: underweight/normal weight (BMI <25 kg/m(2)), overweight (25-30 kg/m(2)) and obese (>30 kg/m(2)). Baseline BMI was associated with subsequent weight change irrespective of the antipsychotic given. Specifically, a smaller proportion of patients gained ≥7% baseline bodyweight, and a greater proportion of patients lost ≥7% baseline bodyweight with increasing baseline BMI. For olanzapine (the antipsychotic associated with highest mean weight gain in the total drug cohort), the percentage of patients gaining ≥7% baseline weight was 45% (95% CI: 43-48) in the underweight/normal weight BMI cohort and 20% (95% CI: 15-27) in the obese BMI cohort; 7% (95% CI: 6-8) of the underweight/normal cohort and 19% (95% CI: 13-27) of the obese cohort lost ≥7% baseline weight. BMI has an association with the likelihood of weight gain or loss and should be considered in analyses of antipsychotic weight change. 23639075 Two new cytotoxic iridoid esters from the rhizomes and roots of Patrinia heterophylla Bunge. Two new iridoid esters, named patriheterdoid B, C, have been isolated from the rhizomes and roots of Patrinia heterophylla Bunge. Their structures were elucidated by extensive spectroscopic technologies. Together with patriheterdoid B, C, two known analogues have been isolated and identified by means of mass spectrometry and (1)H and (13)C NMR spectrometry. These compounds showed cytotoxic activity against SGC-7901, PC3 cell lines. 23147475 First-principles simulation of the absorption bands of fluorenone in zeolite L. The absorption spectrum of fluorenone in zeolite L is calculated from first-principles simulations. The broadening of each band is obtained from the explicit treatment of the interactions between the chromophore and its environment in the statistical ensemble. The comparison between the simulated and measured spectra reveals the main factors affecting the spectrum of the chromophore in hydrated zeolite L. Whereas each distinguishable band is found to originate from a single electronic transition, the bandwidth is determined by the statistical nature of the environment of the fluorenone molecule. The K(+)···O=C motif is retained in all conformations. Although the interactions between K(+) and the fluorenone carbonyl group result in an average lengthening of the C[double bond, length as m-dash]O bond and in a redshift of the lowest energy absorption band compared to gas phase or non-polar solvents, the magnitude of this shift is noticeably smaller than the total shift. An important factor affecting the shape of the band is fluorenone's orientation, which is strongly affected by the presence of water. The effect of direct interactions between fluorenone and water is, however, negligible. 23362253 Physical interaction between MYCN oncogene and polycomb repressive complex 2 (PRC2) in neuroblastoma: functional and therapeutic implications. CLU (clusterin) is a tumor suppressor gene that we have previously shown to be negatively modulated by the MYCN proto-oncogene, but the mechanism of repression was unclear. Here, we show that MYCN inhibits the expression of CLU by direct interaction with the non-canonical E box sequence CACGCG in the 5'-flanking region. Binding of MYCN to the CLU gene induces bivalent epigenetic marks and recruitment of repressive proteins such as histone deacetylases and Polycomb members. MYCN physically binds in vitro and in vivo to EZH2, a component of the Polycomb repressive complex 2, required to repress CLU. Notably, EZH2 interacts with the Myc box domain 3, a segment of MYC known to be essential for its transforming effects. The expression of CLU can be restored in MYCN-amplified cells by epigenetic drugs with therapeutic results. Importantly, the anticancer effects of the drugs are ablated if CLU expression is blunted by RNA interference. Our study implies that MYC tumorigenesis can be effectively antagonized by epigenetic drugs that interfere with the recruitment of chromatin modifiers at repressive E boxes of tumor suppressor genes such as CLU. 23409952 Rotational dynamics of metal azide ion pairs in dimethylsulfoxide solutions. Azide ion is an excellent vibrational probe for studying ion-ion and ion-dipole interactions in solutions because its frequency is sensitively dependent on its local environments. When azide ion forms contact ion pairs with cations in dimethylsulfoxide (DMSO), free azide ion and contact ion pairs are spectrally well distinguished in FTIR spectra. Here, we investigated vibrational population relaxation, P(t), and orientational relaxation dynamics, r(t), of free azide ion and contact ion pairs (LiN3, NaN3, NH4N3, MgN3(+), and CaN3(+)) in DMSO by IR pump-probe spectroscopy. For metal azide ion pairs, the metal ion slowed down the vibrational relaxation of azide ion by acting like a thermal insulator. Biexponential behavior of r(t) was analyzed in the wobbling-in-a-cone model. The long time component of r(t) of free azide ion was found to be viscosity-dependent. The wobbling motion of azide ion within the frame of metal azide ion pairs was weakly dependent on the countercation. When the overall orientational relaxation of metal azide ion pairs was analyzed by the extended Debye-Stokes-Einstein equation, it was well described under stick or superstick boundary conditions due to a strong interaction between the metal ion and DMSO molecules. Our experimental results provide important insight in understanding the rotational dynamics of small ionic species in polar solvents when the size of the ionic species is smaller than or comparable to that of the solvent molecule. 23425604 Biomarkers of Exposure and Effect in Human Lymphoblastoid TK6 Cells Following [13C2]-Acetaldehyde Exposure. The dose-response relationship for biomarkers of exposure (N(2)-ethylidene-dG adducts) and effect (cell survival and micronucleus formation) was determined across 4.5 orders of magnitude (50nM-2mM) using [(13)C2]-acetaldehyde exposures to human lymphoblastoid TK6 cells for 12h. There was a clear increase in exogenous N (2)-ethylidene-dG formation at exposure concentrations ≥ 1µM, whereas the endogenous adducts remained nearly constant across all exposure concentrations, with an average of 3.0 adducts/10(7) dG. Exogenous adducts were lower than endogenous adducts at concentrations ≤ 10µM and were greater than endogenous adducts at concentrations ≥ 250µM. When the endogenous and exogenous adducts were summed together, statistically significant increases in total adduct formation over the endogenous background occurred at 50µM. Cell survival and micronucleus formation were monitored across the exposure range and statistically significant decreases in cell survival and increases in micronucleus formation occurred at ≥ 1000µM. This research supports the hypothesis that endogenously produced reactive species, including acetaldehyde, are always present and constitute the majority of the observed biological effects following very low exposures to exogenous acetaldehyde. These data can replace default assumptions of linear extrapolation to very low doses of exogenous acetaldehyde for risk prediction. 23539641 Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies. Full, persistent blockade of central neurokinin-1 (NK1) receptors may be a potential antidepressant mechanism. The selective NK1 antagonist orvepitant (GW823296) was used to test this hypothesis. A preliminary positron emission tomography study in eight male volunteers drove dose selection for two randomized six week studies in patients with major depressive disorder (MDD). Displacement of central [(11)C]GR205171 binding indicated that oral orvepitant doses of 30-60 mg/day provided >99% receptor occupancy for ≥24 h. Studies 733 and 833 randomized patients with MDD and 17-item Hamilton Depression Rating Scale (HAM-D)≥22 to double-blind treatment with orvepitant 30 mg/day, orvepitant 60 mg/day or placebo (1:1:1). Primary outcome measure was change from baseline in 17-item HAM-D total score at Week 6 analyzed using mixed models repeated measures. Study 733 (n=328) demonstrated efficacy on the primary endpoint (estimated drug-placebo differences of 30 mg: -2.41, 95% confidence interval (CI) (-4.50 to -0.31) p=0.0245; 60 mg: -2.86, 95% CI (-4.97 to -0.75) p=0.0082). Study 833 (n=345) did not show significance (estimated drug-placebo differences of 30 mg: -1.67, 95% CI (-3.73 to 0.39) p=0.1122; 60 mg: -0.76, 95% CI (-2.85 to 1.32) p=0.4713). The results support the hypothesis that full, long lasting blockade of central NK1 receptors may be an efficacious mechanism for the treatment of MDD. 23265533 Phase behaviour of oat β-glucan/sodium caseinate mixtures varying in molecular weight. The isothermal phase behaviour at 5 °C of mixtures of sodium caseinate and oat β-glucan isolates varying in molecular weight (MW) was investigated by means of phase diagram construction, rheometry, fluorescence microscopy and electrophoresis. Phase diagrams indicated that the compatibility of the β-glucan/sodium caseinate system increases as β-glucan MW decreases. Images of mixtures taken at various biopolymer concentrations revealed phase separated domains. Results also revealed that at the state of thermodynamic equilibrium, lower MW samples yielded considerable viscosity in the mixture. At equivalent hydrodynamic volume of β-glucan in the mixtures, samples varying in molecular weight exhibited similar flow behaviour. A deviation dependent on the protein concentration was observed for the high MW sample in the concentrated regime due to the size of β-glucan aggregates formed. Results demonstrate that by controlling the structural features of β-glucan in mixtures with sodium caseinate, informed manipulation of rheological properties in these systems can be achieved. 22841917 Cognitive enhancement by omega-3 fatty acids from child-hood to old age: findings from animal and clinical studies. Omega-(n)-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are major components of neuronal membranes and have a wide range of functions, from modulating synaptic plasticity and neurochemistry, to neuroimmune-modulation and neuroprotection. Thus, it is not surprising that n-3 PUFA are widely acknowledged to have cognitive-enhancing effects. Although clinical evidence is somewhat conflicting, probably in large part due to methodological issues, animal studies have consistently demonstrated that n-3 PUFA are indispensable for proper brain development, may enhance cognitive function in healthy, adult individuals and attenuate cognitive impairment in aging and age-related disorders, such as dementia. This review discusses and integrates up to date evidence from clinical and animal studies investigating the cognitive-enhancing effects of n-3 PUFA during development, child- and adult-hood, as well as old-age with associated neurodegenerative diseases, such as Alzheimer's disease. Furthermore, we cover the major underlying biochemical and neurophysiological mechanisms by which n-3 PUFA mediate these effects on cognition. This article is part of a Special Issue entitled 'Cognitive Enhancers'. 23535326 Novel and highly potent histamine H3 receptor ligands. Part 3: An alcohol function to improve the pharmacokinetic profile. Synthesis and biological evaluation of potent histamine H3 receptor antagonists incorporating a hydroxyl function are described. Compounds in this series exhibited nanomolar binding affinities for human receptor, illustrating a new possible component for the H3 pharmacophore. As demonstrated with compound BP1.4160 (cyclohexanol 19), the introduction of an alcohol function counter-intuitively allowed to reach high in vivo efficiency and favorable pharmacokinetic profile with reduced half-life. 23220588 Acrolein and chloroacetaldehyde: an examination of the cell and cell-free biomarkers of toxicity. Cyclophosphamide and ifosfamide are two commonly used DNA-alkylating agents in cancer chemotherapy that undergo biotransformation to several toxic and non-toxic metabolites, including acrolein and chloroacetaldehyde (CAA). Acrolein and CAA toxicities occur by several different mechanisms, including ROS formation and protein damage (oxidation), however, these pathways of toxicity and protecting agents used to prevent them have yet to be compared and ranked in a single study. This research focused on the molecular targets of acrolein and CAA toxicities and strategies to decrease toxicities. Hepatocyte viability (cytotoxicity) was assessed using Trypan blue uptake; formation of reactive oxygen species (ROS) and endogenous H2O2 were also assessed in the hepatocyte model. In cell-free models (bovine serum albumin and hepatic microsomes), protein carbonylation was the measurement of toxicity. The present study demonstrated that acrolein was a more potent toxin than CAA for freshly isolated rat hepatocytes, bovine serum albumin and rat hepatic microsomes. Acrolein protein carbonylation was dependent on its concentration; as acrolein concentration increased, protein carbonylation increased in a linear trend, whereas, CAA deviated from the trend and did not cause protein carbonylation at lower concentrations (<400 μM). Aldehyde dehydrogenase (ALDH) is a major pathway for detoxifying pathway for CAA in hepatocytes, as a 3-fold increase in cytotoxicity occurred when cells were incubated with cyanamide, an ALDH inhibitor. Inhibiting ALDH or depleting GSH in hepatocytes increased cytotoxicity by about 3-fold in acrolein-treated hepatocytes. The overall effectiveness of protecting agents to prevent or suppress acrolein or CAA toxicities in cell and cell-free models were ranked in order of most effective to least effective: reducing agents (sodium borohydride, sodium bisulfite)>thiol-containing compounds (N-acetylcysteine, cysteine, glutathione, 2-mercaptoethane sulfonate [MESNA], penicillamine)>carbonyl scavengers/amines (aminoguanidine, hydralazine, hydroxylamine)>antioxidants/ROS scavengers (ascorbic acid, Trolox; only utilized in hepatocyte system). An understanding of acrolein and CAA toxicities and the ability of protecting agents to protect against toxicities may help to establish or improve existing therapeutic interventions against the side effects associated with acrolein or CAA in cyclophosphamide or ifosfamide treatment. 23425339 Structure of iron ions in some acetone based electrolytes. X-ray absorption, Mössbauer, and Raman spectroscopy were combined to determine the local environment of iron ions in acetone based solutions of FeCl2. It is shown that part of the Fe(II) ions change their oxidation state, accompanied by symmetry change from octahedral Fe(H2O)6(2+) to tetrahedral [FeCl4](-) at large acetone concentrations. The ratio of Fe(II)/Fe(III) determined by Mössbauer spectroscopy agrees well with that determined by the X-ray absorption studies. Raman measurements confirm quantitative estimations of [FeCl4](-) species in acetone rich solutions. 23324437 Improved Postprandial Ghrelin Response by Nateglinide or Acarbose Therapy Contributes to Glucose Stability in Type 2 Diabetic Patients. Background: Recent studies highlight an important role of ghrelin in glucose homeostasis, while the association between ghrelin regulation and glucose fluctuation is unclear. Aim: We compared the effects of two postprandial hypoglycemic agents on ghrelin response and determined the contribution of ghrelin response to glucose stability in type 2 diabetic (T2DM) patients. Subjects and Methods: Forty newly-diagnosed T2DM patients were randomly allocated to receive Nateglinide or Acarbose for 4 weeks, with twenty BMI-matched normoglycemic subjects as controls. Mean glucose values and daily average glucose excursion were assessed using continuous glucose monitoring system. Serum ghrelin levels were determined by ELISA. Results: T2DM patients had similar fasting ghrelin levels (P = 0.546), while their postprandial ghrelin suppressions at 30 min and 120 min were reduced as compared to BMI-matched normoglycemic controls (P < 0.01). Both Nateglinide and Acarbose increased postprandial ghrelin suppression at 120 min and reduced ghrelin area under the curve (AUCGHRL) (P < 0.05), while only Nateglinide increased postprandial ghrelin suppression at 30 min (P < 0.01), which was positively correlated with the increased early-phase insulin secretion by 4 weeks of Nateglinide therapy (r = 0.48, P = 0.05). The decrease in AUCGHRL was positively correlated with the decrease in daily average glucose excursion and mean glucose values either by 4 weeks of Nateglinide or Acarbose therapy (P < 0.05). Conclusions: Both Natelinide and Acarbose increase postprandial ghrelin suppression. Improved ghrelin regulation is most likely to play a role in glucose stability in T2DM patients with Natelinide or Acarbose therapy. 23232333 Energetic constraints and parental care: is corticosterone indicative of energetic costs of incubation in a precocial bird? Suppression of the adrenocortical response (e.g., corticosterone release) to an acute stressor is a physiological adjustment thought to decrease the likelihood of avian parents abandoning their nests. However, some periods of parental care, like incubation, are energetically costly, thus corticosterone could increase during these stages to allow incubating parents to utilize energy reserves. Wood ducks (Aix sponsa) have ~30 day incubation periods and only the female incubates the eggs. We hypothesized that corticosterone would be important in regulating energy availability during incubation in this species. Because resources invested in reproduction increase with clutch size, we also hypothesized that clutch size would influence plasma corticosterone during incubation. We measured baseline and stress-induced corticosterone in incubating females during early and late stages of incubation. At both stages of incubation all hens had low baseline corticosterone levels. However, we found that stress-induced corticosterone was 105% greater late in incubation than early in incubation. We also detected a significant negative correlation between female body mass and stress-induced corticosterone late in incubation, but not during the early stages of incubation. Furthermore, we found a significant positive relationship between stress-induced corticosterone and clutch size. These lines of evidence support the hypothesis that incubation in wood ducks is energetically costly and corticosterone is important in supporting the energetic demands of incubating hens. Our findings suggest that corticosterone's role in supporting parental care behaviors are dynamic and are influenced by several factors and that there is a greater physiological cost associated with incubating larger clutches. 23296156 Role of immunoglobulin G fragment C receptor polymorphism-mediated antibody-dependant cellular cytotoxicity in colorectal cancer treated with cetuximab therapy. Antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via immunoglobulin G (IgG) fragment C receptors (FcRs), was proposed as a mechanism of cetuximab efficacy. Peripheral blood mononuclear cells (PBMCs) from 23 healthy donors and 13 patients with metastatic colorectal cancer (mCRC) treated with cetuximab were tested for FcγR polymorphisms and cetuximab-mediated ADCC. ADCC was measured by chromium-51 release on a epidermal growth factor receptor (EGFR)-positive human colon cancer cell line. Overall, 86 mCRC patients were genotyped for study purposes. PBMCs harbouring the FcγRIIIa 158 V/V genotype had a significantly higher cetuximab-mediated ADCC. No correlation was found between FcγR polymorphisms and response rate or time to progression after cetuximab-based therapy. Despite the in vitro analysis showing that the FcγRIIIa 158 V/V genotype is associated with higher ADCC, clinical data do not support a predictive role of FcγRIIIa polymorphisms in mCRC treated with cetuximab.The Pharmacogenomics Journal advance online publication, 8 January 2013; doi:10.1038/tpj.2012.54. 22963554 Development of New Drugs for COPD. Chronic obstructive pulmonary disease (COPD) is an increasing global health problem and cause of death. COPD is a chronic inflammatory disease predominantly affecting small airways and lung parenchyma that leads to progressive airway obstruction. However, current therapies fail to prevent either disease progression or mortality. The mainstay of current drug therapy is long-acting bronchodilators. Several once daily inhaled β2-agonists and muscarinic antagonists (and combinations) are now in development. No treatments effectively suppress chronic inflammation in COPD lungs. With better understanding of the inflammatory and destructive process in the pathophysiology of COPD, several new therapeutic targets have been identified. Several mediator antagonists or inhibitors tested in COPD have so far been disappointing, but CXCR2 antagonists that block pulmonary neutrophil and monocyte recruitment are more promising. Broad spectrum anti-inflammatory drugs may be more effective, and include inhibitors of the proinflammatory enzymes phosphodiesterase-4, p38 mitogen-activated protein kinase, Janus kinases, NF-κB kinase and PI3 kinase-γ and -δ, but side effects after oral administration are a major limitation so that in future inhaled delivery may be necessary. A new promising approach is reversal of corticosteroid resistance through increasing histone deacetylase-2 (HDAC2) activity. This might be achieved by existing treatments such as theophylline, nortriptyline and macrolides, or more selectively by PI3 kinase-δ inhibitors. Thus although there have been major advances in the development of long-acting bronchodilators for COPD, it has proved difficult to find anti-inflammatory treatments that are safe and effective. 23370180 Nonhuman primate models of polycystic ovary syndrome. With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment. Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming. Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T). Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction. 23541436 Anti-inflammatory effect of essential oil and its constituents from fingered citron (Citrus medica L. var. sarcodactylis) through blocking JNK, ERK and NF-κB signaling pathways in LPS-activated RAW 264.7 cells. We investigated the composition of essential oil from fingered citron (Citrus medica L. var. sarcodactylis) (FCEO) peels by GC-MS and its anti-inflammatory effects on lipopolysaccharide (LPS) - stimulated mouse macrophage (RAW 264.7) cells. Fifteen compounds, representing 98.97% of the essential oil, were tentatively identified; the main constituents were limonene (52.44%) and γ-terpinene (28.41%). FCEO significantly inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) by suppressing the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, respectively. Additionally, FCEO suppressed the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. FCEO attenuated LPS-induced nuclear factor-κB (NF-κB) activation via inhibition of inhibitor κB-α phosphorylation. Furthermore, FCEO blocked activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) but not that of p38 mitogen-activated protein kinase. These results indicate that FCEO inhibits LPS-stimulated inflammation by blocking the NF-κB, JNK, and ERK pathways in macrophages, and demonstrate that FCEO possesses anti-inflammatory properties. 23314045 Inhibition of protein glycation by urea and thiourea derivatives of glycine/proline conjugated benzisoxazole analogue - synthesis and structure-activity studies. Synthesis of a new series of urea/thiourea derivatives of Gly/Pro conjugated benzisoxazole has been reported. Structure of the compounds was characterized by physical and spectroscopical data and has been screened for their in vitro antiglycation activity. Several compounds showed promising activity with IC(50) < 5 μM compared to standard rutin (IC(50) = 41.9 μM). Further, it was found that compounds containing methoxy and bromine substituents have exerted highly potent activity. Thus, the title compounds represent novel class of potent antiglycating agents. 23413101 Population-based efficacy modeling of omalizumab in patients with severe allergic asthma inadequately controlled with standard therapy. Omalizumab, a recombinant humanized monoclonal antibody, is the first approved anti-immunoglobulin E (IgE) agent for the treatment of subjects with moderate to severe persistent allergic asthma that are inadequately controlled by the standard of care. The objective of this study was to quantitatively characterize relationships between serum free IgE and pulmonary function (as measured by forced expiratory volume in 1 s [FEV1]) as well as serum free IgE and airway inflammation (as measured by fractional exhaled nitric oxide [FeNO]) using population-based efficacy models. Data were collected from patients in the EXTRA trial who received omalizumab or placebo 150 to 375 mg subcutaneously every 2 or 4 weeks from week 0 to 48 with constant standard of care as background therapy. None of the covariates evaluated, including demographics, disease status, and baseline pharmacodynamic biomarkers, were significant in explaining the variability in the FEV1 or FeNO response to omalizumab. Results from the efficacy models further confirmed the current omalizumab dosing rationale based on the mean target free IgE level of 25 ng/ml and quantified the variability for the target. In addition, the resulting population models could be used to predict population FEV1 or FeNO response for omalizumab and/or other anti-IgE therapeutics for which PK-IgE models are constructed. 23344825 Heavy metals accumulation in crab and shrimps from Pulicat lake, north Chennai coastal region, southeast coast of India. The accumulation of heavy metals such as lead (Pb), iron (Fe), zinc (Zn), cadmium (Cd), and chromium (Cr) was examined in crab (Scylla serrata) and shrimps (Penaeus semisulcatus, Penaeus indicus, and Penaeus monodon) collected from Pulicat lake that receives effluents from industries located in north Chennai, southeast coast of India. The results showed limited difference between crab and prawns as well as significant variations between the organs. Pb is the highly accumulated metal in both crab and shrimps, except P. monodon. The highest metal concentration was mostly found in the liver followed by other organs. The concentration of metals in edible parts (muscle) was within the permissible level and safe for consumption. However, the results of the study clearly indicate the biomagnification of metals in Pulicat lake. 23202250 Nanoparticle toxicity in Daphnia magna reproduction studies: the importance of test design. The increasing use of titanium dioxide nanoparticles (nTiO(2)) inevitably results in their release into the environment, raising concerns about potential adverse effects in wildlife. By following standard test protocols, several studies investigated the ecotoxicity of nTiO(2) among others to Daphnia magna. These studies indicated a large variability - several orders of magnitude - in the response variables. However, other factors, like nanoparticle characteristics and test design, potentially triggering these differences, were largely ignored. Therefore, the present study assessed the chronic ecotoxicity of two nTiO(2) products with varying crystalline structure (A-100; P25) to D. magna. A semi-static and a flow-through exposure scenario were compared, ensuring that both contained environmentally relevant concentrations of dissolved organic carbon. Utilizing the semi-static test design, a concentration as low as 0.06 mg/L A-100 (∼330 nm) significantly reduced the reproduction of daphnia indicating environmental risk. In contrast, no implication in the number of released offspring was observed during the flow-through experiment with A-100 (∼140 nm). Likewise, P25 (∼130 nm) did not adversely affect reproduction irrespective of the test design utilized. Given the present study's results, the particle size, the product composition, i.e. the crystalline structure, and the accumulation of nTiO(2) at the bottom of the test vessel - the latter is relevant for a semi-static test design - may be suggested as factors potentially triggering differences in nTiO(2) toxicity to D. magna. Hence, these factors should be considered to improve environmental risk assessment of nanoparticles. 22750079 Predictors and mediators of add-on mirtazapine-induced cognitive enhancement in schizophrenia--a path model investigation. We aimed to evaluate predictors and mediators of enhancing effect of adjunctive mirtazapine on cognition in schizophrenia. Patients with difficult-to-treat schizophrenia received either mirtazapine (n = 19) or placebo (n = 18) in a double-blind fashion for six weeks. Mirtazapine outperformed placebo on the Block Design and Stroop Dots. In the present subsidiary study, factors underlying this difference were explored with Path Analysis. Add-on mirtazapine had an independent enhancing effect on the Block Design-measured visuo-spatial functioning. Further, this effect was mediated via changes in positive, depressive and parkinsonism symptoms, but not in negative symptoms. This effect was predicted by higher doses of FGAs, longer duration of illness and lower initial Block Design scores. Path Analysis model fit was good. Mirtazapine may have direct and indirect favorable effects on visuo-spatial functioning, but further research is needed. Path analysis may be a feasible statistical method for further research of neurocognition in psychopharmacological interventions in schizophrenia. This article is part of a Special Issue entitled 'Cognitive Enhancers'. 23383871 Robust array-based coregulator binding assay predicting ERα-agonist potency and generating binding profiles reflecting ligand structure. Testing chemicals for their endocrine-disrupting potential, including interference with estrogen receptor (ER) signaling, is an important aspect of chemical safety testing. Because of the practical drawbacks of animal testing, the development of in vitro alternatives for the uterotrophic assay and other in vivo (anti)estrogenicity tests has high priority. It was previously demonstrated that an in vitro assay that profiles ligand-induced binding of ERα to a microarray of coregulator-derived peptides might be a valuable candidate for a panel of in vitro assays aiming at an ultimate replacement of the uterotrophic assay. In the present study, the reproducibility and robustness of this coregulator binding assay was determined by measuring the binding profiles of 14 model compounds that are recommended by the Office of Prevention, Pesticides and Toxic Substances for testing laboratory proficiency in estrogen receptor transactivation assays. With a median coefficient of variation of 5.0% and excellent correlation (R(2) = 0.993) between duplicate measurements, the reproducibility of the ERα-coregulator binding assay was better than the reproducibility of other commonly used in vitro ER functional assays. In addition, the coregulator binding assay is correctly predicting the estrogenicity for 13 out of 14 compounds tested. When the potency of the ER-agonists to induce ERα-coregulator binding was compared to their ER binding affinity, their ranking was similar, and the correlation between the EC50 values was excellent (R(2) = 0.96), as was the correlation with their potency in a transactivation assay (R(2) = 0.94). Moreover, when the ERα-coregulator binding profiles were hierarchically clustered using Euclidian cluster distance, the structurally related compounds were found to cluster together, whereas the steroid test compounds having an aromatic A-ring were separated from those with a cyclohexene A-ring. We concluded that this assay is capable of distinguishing ERα agonists and antagonists and that it even reflects the structural similarity of ERα agonists, indicating a potential to achieve identification and classification of ERα endocrine disruptors with high fidelity. 23510192 Mechanism of One-Way Traffic of Hexameric Phi29 DNA Packaging Motor with Four Electropositive Relaying Layers Facilitating Antiparallel Revolution. The importance of nanomotors in nanotechnology is akin to that of mechanical engines to daily life. The AAA+ superfamily is a class of nanomotors performing various functions. Their hexagonal arrangement facilitates bottom-up assembly for stable structures. The bacteriophage phi29 DNA translocation motor contains three coaxial rings: a dodecamer channel, a hexameric ATPase ring, and a hexameric pRNA ring. The viral DNA packaging motor has been believed to be a rotational machine. However, we discovered a revolution mechanism without rotation. By analogy, the earth revolves around the sun while rotating on its own axis. One-way traffic of dsDNA translocation is facilitated by five factors: (1) ATPase changes its conformation to revolve dsDNA within a hexameric channel in one direction; (2) the 30° tilt of the channel subunits causes an antiparallel arrangement between two helices of dsDNA and channel wall to advance one-way translocation; (3) unidirectional flow property of the internal channel loops serves as a ratchet valve to prevent reversal; (4) 5'-3' single-direction movement of one DNA strand along the channel wall ensures single direction; and (5) four electropositive layers interact with one strand of the electronegative dsDNA phosphate backbone, resulting in four relaying transitional pauses during translocation. The discovery of a riding system along one strand provides a motion nanosystem for cargo transportation and a tool for studying force generation without coiling, friction, and torque. The revolution of dsDNA among 12 subunits offers a series of recognition sites on the DNA backbone to provide additional spatial variables for nucleotide discrimination for sensing applications. 23538839 Genetic diversity revealed by single nucleotide polymorphism markers in a worldwide germplasm collection of durum wheat. Evaluation of genetic diversity and genetic structure in crops has important implications for plant breeding programs and the conservation of genetic resources. Newly developed single nucleotide polymorphism (SNP) markers are effective in detecting genetic diversity. In the present study, a worldwide durum wheat collection consisting of 150 accessions was used. Genetic diversity and genetic structure were investigated using 946 polymorphic SNP markers covering the whole genome of tetraploid wheat. Genetic structure was greatly impacted by multiple factors, such as environmental conditions, breeding methods reflected by release periods of varieties, and gene flows via human activities. A loss of genetic diversity was observed from landraces and old cultivars to the modern cultivars released during periods of the Early Green Revolution, but an increase in cultivars released during the Post Green Revolution. Furthermore, a comparative analysis of genetic diversity among the 10 mega ecogeographical regions indicated that South America, North America, and Europe possessed the richest genetic variability, while the Middle East showed moderate levels of genetic diversity. 23115325 Hydrogen sulfide as an allosteric modulator of ATP-sensitive potassium channels in colonic inflammation. The ATP-sensitive potassium channel (K(ATP)) in mouse colonic smooth muscle cell is a complex containing a pore-forming subunit (Kir6.1) and a sulfonylurea receptor subunit (SUR2B). These channels contribute to the cellular excitability of smooth muscle cells and hence regulate the motility patterns in the colon. Whole-cell voltage-clamp techniques were used to study the alterations in K(ATP) channels in smooth muscle cells in experimental colitis. Colonic inflammation was induced in BALB/C mice after intracolonic administration of trinitrobenzene sulfonic acid. K(ATP) currents were measured at a holding potential of -60 mV in high K(+) external solution. The concentration response to levcromakalim (LEVC), a K(ATP) channel opener, was significantly shifted to the left in the inflamed smooth-muscle cells. Both the potency and maximal currents induced by LEVC were enhanced in inflammation. The EC(50) values in control were 6259 nM (n = 10) and 422 nM (n = 8) in inflamed colon, and the maximal currents were 9.9 ± 0.71 pA/pF (60 μM) in control and 39.7 ± 8.8 pA/pF (3 μM) after inflammation. As was seen with LEVC, the potency and efficacy of sodium hydrogen sulfide (NaHS) (10-1000 μM) on K(ATP) currents were significantly greater in inflamed colon compared with controls. In control cells, pretreatment with 100 µM NaHS shifted the EC(50) for LEV-induced currents from 2838 (n = 6) to 154 (n = 8) nM. Sulfhydration of sulfonylurea receptor 2B (SUR2B) was induced by NaHS and colonic inflammation. These data suggest that sulfhydration of SUR2B induces allosteric modulation of K(ATP) currents in colonic inflammation. 23363072 Homopolar dihydrogen bonding in alkali metal amidoboranes: crystal engineering of low-dimensional molecular materials. Hydrogen bonding is a predominant interaction in supramolecular chemistry. The absence of a conventional hydrogen bond donor in LiNMe(2)BH(3) and KNMe(2)BH(3) results in the formation of elaborate M···H-B polymeric arrays supported by heteropolar and homopolar H···H bonding, in a unique synergistic combination of unconventional intermolecular interactions. 23550656 Molecular Dynamics Simulations of CO2 Formation in Interstellar Ices. CO2 ice is one of the most abundant components in ice-coated interstellar ices besides H2O and CO, but the most favorable path to CO2 ice is still unclear. Molecular dynamics calculations on the ultraviolet photodissociation of different kinds of CO-H2O ice systems have been performed at 10 K in order to demonstrate that the reaction between CO and an OH molecule resulting from H2O photodissociation through the first excited state is a possible route to form CO2 ice. However, our calculations, which take into account different ice surface models, suggest that there is another product with a higher formation probability ((3.00 ± 0.07) × 10(-2)), which is the HOCO complex, whereas the formation of CO2 has a probability of only (3.6 ± 0.7) × 10(-4). The initial location of the CO is key to obtain reaction and form CO2: the CO needs to be located deep into the ice. The HOCO complex becomes trapped in the cold ice surface in the trans-HOCO minimum because it quickly loses its internal energy to the surrounding ice, preventing further reaction to H + CO2. Several laboratory experiments have been carried out recently, and they confirm that CO2 can also be formed through other, different routes. Here we compare our theoretical results with the data available from experiments studying the formation of CO2 through a similar pathway as ours, even though the initial conditions were not exactly the same. Our results also show that the HCO van der Waals complex can be formed through the interaction of CO with the H atom that is formed as a product of H2O photodissociation. Thus, the reaction of the H atom photofragment following H2O photodissociation with CO can be a possible route to form HCO ice. 23578636 Garnacha Tintorera-based sweet wines: Chromatic properties and global phenolic composition by means of UV-Vis spectrophotometry. Valdeorras (the N.W. corner of Spain) wants to promote the production and marketing of new sweet wines. The present work represents the first study on sweet wines manufactured with red grapes Vitis vinifera L. Garnacha Tintorera, a teinturier cultivar. Two different red sweet wines were elaborated: the first one was made with dried grapes; Vitis vinifera L. Garnacha Tintorera has excellent potential to produce wines from raisined grapes; the second one, a fortified sweet wine aged in oak barrels. Different red Garnacha Tintorera-based wines (a dry base wine, GBW; a naturally sweet wine, GNSW; and a fortified sweet wine, GFSW) were characterized. Chromatic characteristics and phenolic compounds were established by spectrophotometric methods in order to assess the technology of Garnacha Tintorera-based sweet wines. High molecular weight brown polymers, produced during the grape drying process and isolated from sweet wines by the dialysis process, were responsible for the brown colour of sweet wines. As a consequence, yellowness of sweet wines was also higher which was confirmed by colorimetric indexes. With respect to phenolic content, GFSW presented the lowest content because the maceration-alcoholic fermentation was stopped through the addition of alcohol before the diffusion of red pigments from skins to must was complete. GNSW presented the highest phenolic content due to the concentration effect resulting from evaporation of water from the grapes. Anthocyanins of sweet wines were polymerised in great extent. The percentage of polymerised tannins was sufficient to guarantee the aging process of sweet wines. 23127826 Structure-based design of flavone derivatives as c-myc oncogene down-regulators. Based on molecular docking analysis of complexes between flavone and the c-myc G-quadruplex, we designed and screened 30 flavone derivatives containing various side chains that could potentially form interactions with the G-quadruplex grooves. As a proof-of-concept, the highest-scoring flavone derivatives containing cationic pyridinium side chains were synthesized and their interactions with the c-myc G-quadruplex were examined using a PCR-stop assay. The stabilizing effects of the flavone derivatives were found to be selective towards the c-myc G-quadruplex over other biologically relevant G-quadruplex structures, such as the human telomeric sequence (HTS). The interaction between the most potent compound of the series and the c-myc G-quadruplex was examined in depth using UV-Vis titration, molecular modeling and CD spectroscopy. Our results suggest that in addition to stabilizing the c-myc G-quadruplex, the flavone derivatives were capable of inducing the formation of the G-quadruplex structure even in the absence of monovalent cations. The flavone derivatives were found to be potent inhibitors of c-myc promoters within the cellular environment and displayed promising cytotoxic behavior against human cancer cell lines. 22563917 Development of self-microemulsifying drug delivery system for oral bioavailability enhancement of berberine hydrochloride. The purpose of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral bioavailability of Berberine hydrochloride (BBH), an important bioactive compound from Chinese Medicines with poor water solubility. Pseudoternary phase diagrams were constructed using oil, surfactant and co-surfactant types to identify the efficient self-microemulsification region. SMEDDS was characterized by morphological observation, droplet size, zeta-potential determination, stability, in vitro release and in vivo bioavailability study. The optimal formulation with the best self-microemulsifying and solubilization ability consisted of 40% (w/w) of ethyl linoleate and oleic acid (2:1), 35% (w/w) Tween-80 and 25% (w/w) glycerol. The SMEDDS of BBH could exhibit good stability. In vitro release test showed a complete release of BBH from SMEDDS was in 5 h. In vivo results indicated that the peak plasma concentration (C(max)) and the area under the curve (AUC(0→12 h)) of SMEDDS of BBH were higher than the commercial tablet by 163.4% and 154.2%, respectively. The relative bioavailability of SMEDDS of BBH was enhanced about 2.42-fold compared with the commercial tablet in rats. The study confirmed that the SMEDDS formulation could be used as a possible alternative to traditional oral formulations of BBH to improve its bioavailability. 23584530 The histone demethylase Jmjd3 sequentially associates with the transcription factors Tbx3 and Eomes to drive endoderm differentiation. Stem cell differentiation depends on transcriptional activation driven by lineage-specific regulators as well as changes in chromatin organization. However, the coordination of these events is poorly understood. Here, we show that T-box proteins team up with chromatin modifying enzymes to drive the expression of the key lineage regulator, Eomes during endodermal differentiation of embryonic stem (ES) cells. The Eomes locus is maintained in a transcriptionally poised configuration in ES cells. During early differentiation steps, the ES cell factor Tbx3 associates with the histone demethylase Jmjd3 at the enhancer element of the Eomes locus to allow enhancer-promoter interactions. This spatial reorganization of the chromatin primes the cells to respond to Activin signalling, which promotes the binding of Jmjd3 and Eomes to its own bivalent promoter region to further stimulate Eomes expression in a positive feedback loop. In addition, Eomes activates a transcriptional network of core regulators of endodermal differentiation. Our results demonstrate that Jmjd3 sequentially associates with two T-box factors, Tbx3 and Eomes to drive stem cell differentiation towards the definitive endoderm lineage. 23261645 The effects of jaspamide on human cardiomyocyte function and cardiac ion channel activity. Jaspamide (jasplakinolide; NSC-613009) is a cyclodepsipeptide that has antitumor activity. A narrow margin of safety was observed between doses required for efficacy in mouse tumor models and doses that caused severe acute toxicity in rats and dogs. We explored the hypothesis that the observed toxicity was due to cardiotoxicity. Jaspamide was tested in a patch clamp assay to determine its effect on selected cardiac ion channels. Jaspamide (10 μM) inhibited Kv1.5 activity by 98.5%. Jaspamide also inhibited other channels including Cav1.2, Cav3.2, and HCN2; however, the Kv11.1 (hERG) channel was minimally affected. Using spontaneously contracting human cardiomyocytes derived from induced pluripotent stem cells, effects on cardiomyocyte contraction and viability were also examined. Jaspamide (30 nM to 30 μM) decreased cardiomyocyte cell indices and beat amplitude, putative measurements of cell viability and cardiac contractility, respectively. Concentration-dependent increases in rhythmic beating rate were noted at ≤ 6 h of treatment, followed by dose-dependent decreases after 6 and 72 h exposure. The toxic effects of jaspamide were compared with that of the known cardiotoxicant mitoxantrone, and confirmed by multiparameter fluorescence imaging analysis. These results support the hypothesis that the toxicity observed in rats and dogs is due to toxic effects of jaspamide on cardiomyocytes. 23352141 A bacterial source for mollusk pyrone polyketides. In the oceans, secondary metabolites often protect otherwise poorly defended invertebrates, such as shell-less mollusks, from predation. The origins of these metabolites are largely unknown, but many of them are thought to be made by symbiotic bacteria. In contrast, mollusks with thick shells and toxic venoms are thought to lack these secondary metabolites because of reduced defensive needs. Here, we show that heavily defended cone snails also occasionally contain abundant secondary metabolites, γ-pyrones known as nocapyrones, which are synthesized by symbiotic bacteria. The bacteria, Nocardiopsis alba CR167, are related to widespread actinomycetes that we propose to be casual symbionts of invertebrates on land and in the sea. The natural roles of nocapyrones are unknown, but they are active in neurological assays, revealing that mollusks with external shells are an overlooked source of secondary metabolite diversity. 23627597 Gold-Catalyzed Cycloisomerization of 1,6-Diyne Carbonates and Esters to 2,4a-Dihydro-1H-fluorenes. A synthetic method to prepare 2,4a-dihydro-1H-fluorenes efficiently from gold(I)-catalyzed 1,2-acyloxy migration/cyclopropenation/Nazarov cyclization of 1,6-diyne carbonates and esters is described. The suggested reaction pathway provides rare examples of [2,3]-sigmatropic rearrangement in this class of compounds as well as the involvement of an in situ formed cyclopropene intermediate in gold catalysis. Experimental and ONIOM(QM:QM') (our own n-layered integrated molecular orbital and molecular mechanics(quantum mechanics:quantum mechanics')) computational studies based on the proposed Au carbenoid species provide insight into this unique selectivity. 23160419 Nitrogen dioxide at the air-water interface: trapping, absorption, and solvation in the bulk and at the surface. The interaction of NO(2) with water surfaces in the troposphere is of major interest in atmospheric chemistry. We examined an initial step in this process, the uptake of NO(2) by water through the use of molecular dynamics simulations. An NO(2)-H(2)O intermolecular potential was obtained by fitting to high-level ab initio calculations. We determined the binding of NO(2)-H(2)O to be about two times stronger than that previously calculated. From scattering simulations of an NO(2) molecule interacting with a water slab we observed that the majority of the scattering events resulted in outcomes in which the NO(2) molecule became trapped at the surface or in the interior of the water slab. Typical surface-trapped/adsorbed and bulk-solvated/absorbed trajectories were analyzed to obtain radial distribution functions and the orientational propensity of NO(2) with respect to the water surface. We observed an affinity of the nitrogen atom for the oxygen in water, rather than hydrogen-bonding which was rare. The water solvation shell was less tight for the bulk-absorbed NO(2) than for the surface-adsorbed NO(2). Adsorbed NO(2) demonstrated a marked orientational preference, with the oxygens pointing into the vacuum. Such behavior is expected for a mildly hydrophobic and surfactant molecule like NO(2). Estimates based on our results suggest that at high NO(2) concentrations encountered, for example, in some sampling systems, adsorption and reaction of NO(2) at the surface may contribute to the formation of gas-phase HONO. 23620487 Inhibition of CYP2C19 and CYP3A4 by Omeprazole Metabolites and their Contribution to Drug-Drug Interactions. The aim of this study was to evaluate the contribution of metabolites to drug-drug interactions (DDI) using the inhibition of CYP2C19 and CYP3A4 by omeprazole and its metabolites as a model. Of the metabolites identified in vivo, 5-hydroxyomeprazole, 5'-O-desmethylomeprazole, omeprazole sulfone and carboxyomeprazole had an AUCm/AUCp ≥ 0.25 when either total or unbound concentrations were measured following a single 20 mg dose of omeprazole in a cocktail. All of the metabolites inhibited CYP2C19 and CYP3A4 reversibly. In addition omeprazole, omeprazole sulfone and 5'-O-desmethylomeprazole were mechanism-based inhibitors (MBI) of CYP2C19 while omeprazole and 5'-O-desmethylomeprazole were found to be MBIs of CYP3A4. Reversible [I]/Ki ratios and irreversible λ/kdeg ratios were used to evaluate whether characterization of the metabolites affected DDI risk assessment. Identifying omeprazole as an MBI of both CYP2C19 and CYP3A4 was the most important factor in DDI risk assessment. Consideration of reversible inhibition by omeprazole and its metabolites would not identify DDI risk with CYP3A4, and with CYP2C19 reversible inhibition values would only identify DDI risk if the metabolites are included in the assessment. Based on inactivation data, CYP2C19 and CYP3A4 inactivation by omeprazole would be sufficient to identify risk, but metabolites were predicted to contribute 30-63% to the in vivo hepatic interactions. Hence, consideration of metabolites may be important in quantitative predictions of in vivo DDIs. The results of this study show that while metabolites contribute to in vivo DDIs their relative abundance in circulation or logP values do not predict their contribution to in vivo DDI risk. 23430408 A toxicokinetic model for thiamethoxam in rats: implications for higher-tier risk assessment. Risk assessment for mammals is currently based on external exposure measurements, but effects of toxicants are better correlated with the systemically available dose than with the external administered dose. So for risk assessment of pesticides, toxicokinetics should be interpreted in the context of potential exposure in the field taking account of the timescale of exposure and individual patterns of feeding. Internal concentration is the net result of absorption, distribution, metabolism and excretion (ADME). We present a case study for thiamethoxam to show how data from ADME study on rats can be used to parameterize a body burden model which predicts body residue levels after exposures to LD50 dose either as a bolus or eaten at different feeding rates. Kinetic parameters were determined in male and female rats after an intravenous and oral administration of (14)C labelled by fitting one-compartment models to measured pesticide concentrations in blood for each individual separately. The concentration of thiamethoxam in blood over time correlated closely with concentrations in other tissues and so was considered representative of pesticide concentration in the whole body. Body burden model simulations showed that maximum body weight-normalized doses of thiamethoxam were lower if the same external dose was ingested normally than if it was force fed in a single bolus dose. This indicates lower risk to rats through dietary exposure than would be estimated from the bolus LD50. The importance of key questions that should be answered before using the body burden approach in risk assessment, data requirements and assumptions made in this study are discussed in detail. 23608613 Evaluation and modification of commercial dry powder inhalers for the aerosolization of a submicrometer excipient enhanced growth (EEG) formulation. The aim of this study was to evaluate and modify commercial dry powder inhalers (DPIs) for the aerosolization of a submicrometer excipient enhanced growth (EEG) formulation. The optimized device and formulation was then tested in a realistic in vitro mouth-throat - tracheobronchial (MT-TB) model. An optimized EEG submicrometer powder formulation, consisting of albuterol sulfate (drug), mannitol (hygroscopic excipient), l-leucine (dispersion enhancer) and poloxamer 188 (surfactant) in a ratio of 30:48:20:2 was prepared using a Büchi Nano spray dryer. The aerosolization performance of the EEG formulation was evaluated with five conventional DPIs: Aerolizer, Novolizer, HandiHaler, Exubera and Spiros. To improve powder dispersion, the HandiHaler was modified with novel mouth piece (MP) designs. The aerosol performance of each device was assessed using a next generation impactor (NGI) at airflow rates generating a pressure drop of 4kPa across the DPI. In silico and in vitro deposition and hygroscopic growth of formulations was studied using a MT-TB airway geometry model. Both HandiHaler and Aerolizer produced high emitted doses (EDs) together with a significant submicrometer aerosol fraction. A modified HandiHaler with a MP including a three-dimensional (3D) array of rods (HH-3D) produced a submicrometer particle fraction of 38.8% with a conventional fine particle fraction (%<5μm) of 97.3%. The mass median diameter (MMD) of the aerosol was reduced below 1μm using this HH-3D DPI. The aerosol generated from the modified HandiHaler increased to micrometer size (2.8μm) suitable for pulmonary deposition, when exposed to simulated respiratory conditions, with negligible mouth-throat (MT) deposition (2.6%). 23332762 Inactivation of BAD by IKK inhibits TNFα-induced apoptosis independently of NF-κB activation. The IκB kinase complex (IKK) is a key regulator of immune responses, inflammation, cell survival, and tumorigenesis. The prosurvival function of IKK centers on activation of the transcription factor NF-κB, whose target gene products inhibit caspases and prevent prolonged JNK activation. Here, we report that inactivation of the BH3-only protein BAD by IKK independently of NF-κB activation suppresses TNFα-induced apoptosis. TNFα-treated Ikkβ(-/-) mouse embryonic fibroblasts (MEFs) undergo apoptosis significantly faster than MEFs deficient in both RelA and cRel due to lack of inhibition of BAD by IKK. IKK phosphorylates BAD at serine-26 (Ser26) and primes it for inactivation. Elimination of Ser26 phosphorylation promotes BAD proapoptotic activity, thereby accelerating TNFα-induced apoptosis in cultured cells and increasing mortality in animals. Our results reveal that IKK inhibits TNFα-induced apoptosis through two distinct but cooperative mechanisms: activation of the survival factor NF-κB and inactivation of the proapoptotic BH3-only BAD protein. 23402647 Ionic liquid mediated synthesis and surface modification of multifunctional mesoporous Eu:GdF3 nanoparticles for biomedical applications. A procedure for the synthesis of multifunctional europium(III)-doped gadolinium(III) fluoride (Eu:GdF3) nanoparticles (~85 nm) with quasispherical shape by precipitation at 120 °C from diethylene glycol solutions containing lanthanide chlorides and an ionic liquid (1-Butyl, 2-methylimidazolium tetrafluoroborate) as fluoride source has been developed. These nanoparticles were polycrystalline and crystallized into a hexagonal structure, which is unusual for GdF3. They were also mesoporous (pore size = 3.5 Å), having a rather high BET surface area (75 m(2) g(-1)). The luminescent and magnetic (relaxivity) properties of the Eu:GdF3 nanoparticles have been also evaluated in order to assess their potentiality as "in vitro" optical biolabels and contrast agent for magnetic resonance imaging. Finally, a procedure for their functionalization with aspartic-dextran polymers is also reported. The functionalized Eu:GdF3 nanoparticles presented negligible toxicity for Vero cells, which make them suitable for biotecnological applications. 23591701 New testing procedures of a capacitive deionization reactor. Currently, according to conventional charge-discharge profiles, energy consumed in charging Capacitive Deionization (CDI) systems is always a function of different parameters (current used for charging, capacitance and current employed for discharging) making it difficult to separate the effect of these parameters on CDI performance and energy efficiency. Thus, energy efficiencies are strongly influenced by the current in the preceding charge or discharge stage of the process. We find consistently that this phenomenon, which to our knowledge has not been addressed in previous CDI communications, is much more intense when different currents are applied for each of the charging and discharging cycles. The investigation reported here provides a mechanistic analysis of the operational aspects of CDI and develops a new procedure that allows for a precise evaluation of performance and energy efficiency. Furthermore, the model developed here allows one to separate charge and discharge cycles, and therefore contributes to the possibility of defining an operational mode for real-world devices in which effective separation of deionization and regeneration steps needs to be implemented. This method of analysis could be useful not only for CDI but also for other electrochemical systems such as in secondary batteries and supercapacitors where charge and discharge are typically employed. 23494802 Curcuminoids Modulate Pro-Oxidant-Antioxidant Balance but not the Immune Response to Heat Shock Protein 27 and Oxidized LDL in Obese Individuals. Curcuminoids have potentially important functional qualities including anti-inflammatory and antioxidant properties. In this randomized double-blind placebo-controlled cross-over trial, the effects of a curcuminoid supplement on serum pro-oxidant-antioxidant balance (PAB) and antibody titres to Hsp27 (anti-Hsp27) and oxLDL (anti-oxLDL) were investigated. Thirty obese individuals were randomized to receive either curcuminoids (1 g/day) or placebo for a period of 30 days. After a wash-out period of 2 weeks, subjects were crossed over to the alternate regimen for another 30 days. Serum PAB along with anti-Hsp27 and anti-oxLDL titres was measured at the beginning and at the end of each study period. There was no significant carry-over effect for any of the assessed parameters. Curcuminoid supplementation was associated with a significant decrease in PAB (p = 0.044). However, no significant change was observed in serum concentrations of anti-Hsp27 or anti-oxLDL (p > 0.05). These findings suggest that oral curcuminoids supplementation (1g/day) is effective in reducing oxidative stress burden, though this needs to be validated in larger study populations. Copyright © 2013 John Wiley & Sons, Ltd. 23333908 Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies. The effectiveness of Hibiscus sabdariffa L. (HS) in the treatment of risk factors associated with cardiovascular disease is assessed in this review by taking a comprehensive approach to interpreting the randomized clinical trial (RCT) results in the context of the available ethnomedical, phytochemical, pharmacological, and safety and toxicity information. HS decoctions and infusions of calyxes, and on occasion leaves, are used in at least 10 countries worldwide in the treatment of hypertension and hyperlipidemia with no reported adverse events or side effects. HS extracts have a low degree of toxicity with a LD50 ranging from 2,000 to over 5,000mg/kg/day. There is no evidence of hepatic or renal toxicity as the result of HS extract consumption, except for possible adverse hepatic effects at high doses. There is evidence that HS acts as a diuretic, however in most cases the extract did not significantly influence electrolyte levels. Animal studies have consistently shown that consumption of HS extract reduces blood pressure in a dose dependent manner. In RCTs, the daily consumption of a tea or extract produced from HS calyxes significantly lowered systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults with pre to moderate essential hypertension and type 2 diabetes. In addition, HS tea was as effective at lowering blood pressure as the commonly used blood pressure medication Captropril, but less effective than Lisinopril. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides were lowered in the majority of normolipidemic, hyperlipidemic, and diabetic animal models, whereas high-density lipoprotein cholesterol (HDL-C) was generally not affected by the consumption of HS extract. Over half of the RCTs showed that daily consumption of HS tea or extracts had favorable influence on lipid profiles including reduced total cholesterol, LDL-C, triglycerides, as well as increased HDL-C. Anthocyanins found in abundance in HS calyxes are generally considered the phytochemicals responsible for the antihypertensive and hypocholesterolemic effects, however evidence has also been provided for the role of polyphenols and hibiscus acid. A number of potential mechanisms have been proposed to explain the hypotensive and anticholesterol effects, but the most common explanation is the antioxidant effects of the anthocyanins inhibition of LDL-C oxidation, which impedes atherosclerosis, an important cardiovascular risk factor. This comprehensive body of evidence suggests that extracts of HS are promising as a treatment of hypertension and hyperlipidemia, however more high quality animal and human studies informed by actual therapeutic practices are needed to provide recommendations for use that have the potential for widespread public health benefit. 23531107 Preventing Interfacial Recombination in Colloidal Quantum Dot Solar Cells by Doping the Metal Oxide. Recent research has pushed the efficiency of colloidal quantum dot solar cells toward a level that spurs commercial interest. Quantum dot/metal oxide bilayers form the most efficient colloidal quantum dot solar cells, and most studies have advanced the understanding of the quantum dot component. We study the interfacial recombination process in depleted heterojunction colloidal quantum dot (QD) solar cells formed with ZnO as the oxide by varying (i) the carrier concentration of the ZnO layer and (ii) the density of intragap recombination sites in the QD layer. We find that the open-circuit voltage and efficiency of PbS QD/ZnO devices can be improved by 50% upon doping of the ZnO with nitrogen to reduce its carrier concentration. In contrast, doping the ZnO did not change the performance of PbSe QD/ZnO solar cells. We use X-ray photoemission spectroscopy, ultraviolet photoemission spectroscopy, transient photovoltage decay measurements, transient absorption spectroscopy, and intensity-dependent photocurrent measurements to investigate the origin of this effect. We find a significant density of intragap states within the band gap of the PbS quantum dots. These states facilitate recombination at the PbS/ZnO interface, which can be suppressed by reducing the density of occupied states in the ZnO. For the PbSe QD/ZnO solar cells, where fewer intragap states are observed in the quantum dots, the interfacial recombination channel does not limit device performance. Our study sheds light on the mechanisms of interfacial recombination in colloidal quantum dot solar cells and emphasizes the influence of quantum dot intragap states and metal oxide properties on this loss pathway. 23000450 -116A and K BCHE gene variants associated with obesity and hypertriglyceridemia in adolescents from Southern Brazil. Butyrylcholinesterase (BChE) has been associated to body mass index (BMI), weight, cholesterol and triglyceride levels. -116A (rs1126680) and K (A539T, 1615A, rs1803274) BCHE gene variants had previously been associated to BChE activity, weight and BMI variance in adults. The present study examined -116A and K variants, BChE activity, anthropometric and biochemical variables associated with obesity in adolescents (120 obese and 150 non-obese from Curitiba, Brazil). Both -116A and K variants were found with significantly lower frequencies (p<0.05) in obese adolescents when compared with non-obese adolescents and with the general population. Mean BChE activity (KU/L) was significantly higher in obese adolescents when compared with non-obese adolescents and with the general population. Analyzing only the obese adolescents, it was found that carriers of the -116A variant showed lower BChE activity and higher triglyceride levels than homozygotes for the usual allele. Indeed, obese carriers of the -116A variant had triglyceride levels considered high according to reference values for serum triglycerides in Brazilian adolescents. These results show: (1) a protective effect of -116A and K variants on juvenile obesity risk, suggesting a role for the BCHE gene on juvenile onset obesity different from that observed on adult onset obesity and (2) an association of the -116A variant with hypertriglyceridemia in obese adolescents probably because of its effect on lowering BChE activity and consequently diminishing the enzyme capability of maintaining homeostasis on lipid metabolism during the metabolic stress caused by obesity. 23406277 Interactions of binuclear ruthenium(II) complexes with oligonucleotides in hydrogel matrix: enantioselective threading intercalation into GC context. A stretched poly(vinyl alcohol) (PVA) film provides a unique matrix that enables also short DNA oligonucleotide duplex to be oriented and studied by linear dichroism (LD). This matrix further allows controlling DNA secondary structure by proper hydration (A or B form), and such humid films could potentially also mimic the molecular crowding in cellular contexts. However, early attempts to study intercalators and groove binders for probing DNA in PVA failed due to competitive matrix binding. Here we report the successful orientation in PVA of DNA oligonucleotide duplex hairpins with thread-intercalated binuclear complex [μ-(11,11'-bidppz)(phen)4Ru2](4+), and how LD depends on oligonucleotide sequence and metal center chirality. Opposite enantiomers of the ruthenium complex, ΔΔ and ΛΛ, were investigated with respect to enantioselectivity toward GC stretches as long as 22 bp. LD, supported by emission kinetics, reveals that threading intercalation occurs only with ΔΔ whereas ΛΛ remains externally bound, probably in either or both of the grooves of the GC-DNA. Enantioselective binding properties of sterically rigid DNA probes such as the ruthenium complexes could find applications for targeting nucleic acids, e.g., to inhibit transcription in therapeutic context such as treatment of malaria or cancer. 23255284 Formation of RNA phosphodiester bond by histidine-containing dipeptides. A new scenario for prebiotic formation of nucleic acid oligomers is presented. Peptide catalysis is applied to achieve condensation of activated RNA monomers into short RNA chains. As catalysts, L-dipeptides containing a histidine residue, primarily Ser-His, were used. Reactions were carried out in self-organised environment, a water-ice eutectic phase, with low concentrations of reactants. Incubation periods up to 30 days resulted in the formation of short oligomers of RNA. During the oligomerisation, an active intermediate (dipeptide-mononucleotide) is produced, which is the reactive species. Details of the mechanism and kinetics, which were elucidated with a set of control experiments, further establish that the imidazole side chain of a histidine at the carboxyl end of the dipeptide plays a crucial role in the catalysis. These results suggest that this oligomerisation catalysis occurs by a transamination mechanism. Because peptides are much more likely products of spontaneous condensation than nucleotide chains, their potential as catalysts for the formation of RNA is interesting from the origin-of-life perspective. Finally, the formation of the dipeptide-mononucleotide intermediate and its significance for catalysis might also be viewed as the tell-tale signs of a new example of organocatalysis. 23471488 A randomised trial of enteric-coated nutrient pellets to stimulate gastrointestinal peptide release and lower glycaemia in type 2 diabetes. AIMS/HYPOTHESES: Glucagon-like peptide-1 (GLP-1), an important mediator of postprandial glycaemia, could potentially be stimulated by delivering small quantities of nutrient to a long length of distal gut. We aimed to determine whether enteric-coated pellets, releasing small amounts of lauric acid throughout the ileum and colon, could reduce glycaemic responses to meals in type 2 diabetes, associated with stimulation of GLP-1. METHODS: Eligible patients, who had type 2 diabetes controlled by diet or metformin, were each studied on two occasions in a hospital setting. After an overnight fast, patients consumed 5 g active pellets (47% lauric acid by weight) or placebo with breakfast (T = 0 min) and lunch (T = 240 min), in a crossover design with order randomised by the hospital pharmacy and allocation concealed by numbered containers. Patients and investigators making measurements were blinded to the intervention. Blood was sampled frequently for blood glucose (the primary outcome) and hormone assays. RESULTS: Eight patients were randomised (four to receive either intervention first), and all completed the study without adverse effects. Blood glucose was lower after breakfast (T = 0-240 min, area under the curve (AUC) 2,075 ± 368 vs 2,216 ± 163 mmol/l × min) and lunch (T = 240-480 min, AUC 1,916 ± 115 vs 2,088 ± 151 mmol/l × min) (p = 0.02 for each) after active pellets than after placebo. Plasma GLP-1 concentrations were higher after breakfast (p = 0.08) and lunch (p = 0.04) for active pellets. While there were no differences in insulin or glucose-dependent insulinotropic polypeptide concentrations, glucagon concentrations were higher after breakfast and lunch (p = 0.002 for each) for active pellets. CONCLUSIONS/INTERPRETATION: Delivering small amounts of nutrient to the ileum and colon can stimulate substantial endogenous GLP-1 release and attenuate postprandial glycaemia. This novel approach has therapeutic potential in type 2 diabetes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000600842. FUNDING: The study was funded by Meyer Nutriceuticals. 23261588 Short and long-term exposure of CNS cell lines to BPA-f a radiosensitizer for Boron Neutron Capture Therapy: safety dose evaluation by a battery of cytotoxicity tests. Despite the current clinical use of boronophenylalanine-fructose (BPA-f), as radiosensitizer, in BNCT application for brain tumors, still remains to be determined the safety dose of this agent. We evaluated the potential risk of primary BPA-f toxicity before neutronic irradiation at different concentrations (0-100μgBeq/ml) after short- and long-term exposure (4-48h and 7-10 days), using a battery of tests (i.e. MTT assay, calcein-AM/Propidium Iodide staining, clonogenic test) in CNS cell models (D384 and SH-SY5Y), and non-neuronal primary human fibroblasts (F26). MTT data showed: (i) no cytotoxic effects after short-term exposure (4h) to any of BPA-f concentrations tested in all cell models; (ii) dose- and time-dependent mitochondrial activity impairment in D384 and SH-SY5Y cells only (with 60% and 40% cell death in D384 and SH-SY5Y, respectively, after 48h exposure to BPA-f 100μgBeq/ml). By Calcein-AM/PI staining, BPA-f treatment was specific toward SH-SY5Y cells only: a dose-dependent cell density reduction was observed, with a more pronounced effect after 48h exposure (15-40% at doses ranging 20-100μgBeq/ml). Clonogenic data revealed dose-dependent decrease of cell proliferative capacity in all cell lines, still the SH-SY5Y cells were the most sensitive ones: the lowest dose (20μgBeq/ml) produced 90% cell decrease. These results indicate dose- and time-dependent cytotoxic effects of BPA-f, with CNS cells showing a lower tolerance compared to fibroblasts. Long-term exposure to BPA-f compromised the proliferative capacity regardless of cell model type (cell sensitivity being SH-SY5Y>D384>F26). In short-time exposure, BPA-f exhibits a safe dosage up to 40μgBeq/ml for the viability of CNS cell lines. 23172121 Elastic CNT-polyurethane nanocomposite: synthesis, performance and assessment of fragments released during use. Intended for use in high performance applications where electrical conductivity is required, we developed a CNT-TPU composite. Such a composite can be prepared by melt processing (extrusion) on an industrial scale. Due to the known hazard upon inhalation of CNTs, we assessed three degradation scenarios that may lead to the release of CNTs from the composite: normal use, machining and outdoor weathering. Unexpectedly, we find that the relative softness of the material actually enhances the embedding of CNTs also in its degradation fragments. A release of free CNTs was not detected under any condition using several detection methods. However, since machining may induce a high acute dose of human exposure, we assessed the cytotoxicity potential of released fragments in the in vitro model of precision-cut lung slices, and found no additional toxicity due to the presence of CNTs. At very low rates over years, weathering degrades the polymer matrix as expected for polyurethanes, thus exposing a network of entangled CNTs. In a preliminary risk assessment, we conclude that this material is safe for humans in professional and consumer use. 23153029 The progesterone positive feedback effect in women after ovariectomy. Various ovarian substances regulate the secretion of gonadotrophins during the menstrual cycle, but there are still several unclarified issues. The aim of this study was to investigate the positive feedback effect of progesterone during the immediate period following ovariectomy. Experiments were performed in 12 normally cycling women (aged 39-49 years). Following abdominal hysterectomy plus bilateral ovariectomy performed on cycle day 3 (day 0), the women received either estradiol via skin patches (days 0-7, n = 6, group 1) or estradiol as above plus vaginal progesterone (days 1-7, n = 6, group 2). Serum estradiol values increased similarly in the two groups. After the operation, serum progesterone levels decreased significantly in group 1, while in group 2 they remained stable becoming higher than in group 1 (p < 0.05). An LH and an FSH surge occurred in group 2 with the values after the peak returning to the pre-surge baseline. In contrast, in group 1 LH and FSH levels following an initial decrease, increased gradually until the end of the experiment. These results demonstrate that, despite a variable response to estrogens, the positive feedback effect of progesterone remained intact immediately after ovariectomy in women. It is suggested that it is the combining action of estradiol and progesterone that can ensure the expression of a positive feedback mechanism in women. 23400782 F1-ATPase of Escherichia coli: the ε- inhibited state forms after ATP hydrolysis, is distinct from the ADP-inhibited state, and responds dynamically to catalytic site ligands. F1-ATPase is the catalytic complex of rotary nanomotor ATP synthases. Bacterial ATP synthases can be autoinhibited by the C-terminal domain of subunit ε, which partially inserts into the enzyme's central rotor cavity to block functional subunit rotation. Using a kinetic, optical assay of F1·ε binding and dissociation, we show that formation of the extended, inhibitory conformation of ε (εX) initiates after ATP hydrolysis at the catalytic dwell step. Prehydrolysis conditions prevent formation of the εX state, and post-hydrolysis conditions stabilize it. We also show that ε inhibition and ADP inhibition are distinct, competing processes that can follow the catalytic dwell. We show that the N-terminal domain of ε is responsible for initial binding to F1 and provides most of the binding energy. Without the C-terminal domain, partial inhibition by the ε N-terminal domain is due to enhanced ADP inhibition. The rapid effects of catalytic site ligands on conformational changes of F1-bound ε suggest dynamic conformational and rotational mobility in F1 that is paused near the catalytic dwell position. 23288052 Molecular mechanisms of fibrosis-associated promotion of liver carcinogenesis. Hepatocellular carcinoma (HCC) mostly develops in patients with advanced fibrosis; however, the mechanisms of interaction between a genotoxic insult and fibrogenesis are not well understood. This study tested a hypothesis that fibrosis promotes HCC via a mechanism that involves activation of liver stem cells. First, B6C3F1 mice were administered diethylnitrosamine (DEN; single ip injection of 1mg/kg at 14 days of age). Second, carbon tetrachloride (CCl(4); 0.2ml/kg, 2/week ip starting at 8 weeks of age) was administered for 9 or 14 weeks to develop advanced liver fibrosis. In animals treated with DEN as neonates, presence of liver fibrosis led to more than doubling (to 100%) of the liver tumor incidence as early as 5 months of age. This effect was associated with activation of cells with progenitor features in noncancerous liver tissue, including markers of replicative senescence (p16), oncofetal transformation (Afp, H19, and Bex1), and increased "stemness" (Prom1 and Epcam). In contrast, the dose of DEN used did not modify the extent of liver inflammation, fibrogenesis, oxidative stress, proliferation, or apoptosis induced by subchronic CCl(4) administration. This study demonstrates the potential role of liver stem-like cells in the mechanisms of chemical-induced, fibrosis-promoted HCC. We posit that the combination of genotoxic and fibrogenic insults is a sensible approach to model liver carcinogenesis in experimental animals. These results may contribute to identification of cirrhotic patients predisposed to HCC by analyzing the expression of hepatic progenitor cell markers in the noncancerous liver tissue. 23337599 N-1, C-3 substituted indoles as 5-LOX inhibitors--in vitro enzyme immunoaasay, mass spectral and molecular docking investigations. Based upon the structures of some known 5-LOX inhibitors, a set of five compounds carrying appropriate substituents at N-1 and C-3 of indole were synthesized and investigated for 5-LOX inhibitory activities. Fifty percent inhibitory concn (IC(50)) of these compounds ranges from 0.6 to 5 μM and found to be comparable to that of clinically used 5-LOX inhibitor, zileuton. The compounds under present investigations exhibited appreciable interactions with 5-LOX as apparent from their association constants calculated from the mass spectral data. Compound 5a with a tosyl group at N-1 and pyrolidinyl-1,2-dione substituent at C-3 of indole, exhibiting IC(50) 0.6 μM and stoichiometry of 1:7 in the enzyme-compound complex was identified as highly potent 5-LOX inhibitor and seems to be suitable for further investigations. 23163508 Diversity patterns of uncultured Haptophytes unravelled by pyrosequencing in Naples Bay. Haptophytes are a key phylum of marine protists, including ~300 described morphospecies and 80 morphogenera. We used 454 pyrosequencing on large subunit ribosomal DNA (LSU rDNA) fragments to assess the diversity from size-fractioned plankton samples collected in the Bay of Naples. One group-specific primer set targeting the LSU rDNA D1/D2 region was designed to amplify Haptophyte sequences from nucleic acid extracts (total DNA or RNA) of two size fractions (0.8-3 or 3-20 μm) and two sampling depths [subsurface, at 1 m, or deep chlorophyll maximum (DCM) at 23 m]. 454 reads were identified using a database covering the entire Haptophyta diversity currently sequenced. Our data set revealed several hundreds of Haptophyte clusters. However, most of these clusters could not be linked to taxonomically known sequences: considering OTUs(97%) (clusters build at a sequence identity level of 97%) on our global data set, less than 1% of the reads clustered with sequences from cultures, and less than 12% clustered with reference sequences obtained previously from cloning and Sanger sequencing of environmental samples. Thus, we highlighted a large uncharacterized environmental genetic diversity, which clearly shows that currently cultivated species poorly reflect the actual diversity present in the natural environment. Haptophyte community appeared to be significantly structured according to the depth. The highest diversity and evenness were obtained in samples from the DCM, and samples from the large size fraction (3-20 μm) taken at the DCM shared a lower proportion of common OTUs(97%) with the other samples. Reads from the species Chrysoculter romboideus were notably found at the DCM, while they could be detected at the subsurface. The highest proportion of totally unknown OTUs(97%) was collected at the DCM in the smallest size fraction (0.8-3 μm). Overall, this study emphasized several technical and theoretical barriers inherent to the exploration of the large and largely unknown diversity of unicellular eukaryotes. 23428325 Plant development: brassinosteroids go out of bounds. Patterning in plants requires defining boundary domains that separate and organize the development of the neighboring organs. Two papers now show how the interplay between brassinosteroid phytohormones and frontier genes contributes to boundary formation in plants. 23527551 Using Supramolecular Binding Motifs To Provide Precise Control over the Ratio and Distribution of Species in Multiple Component Films Grafted on Surfaces: Demonstration Using Electrochemical Assembly from Aryl Diazonium Salts. Supramolecular interactions between two surface modification species are explored to control the ratio and distribution of these species on the resultant surface. A binary mixture of aryl diazonium salts bearing oppositely charged para-substituents (either -SO3(-) or -N(+)(Me)3), which also reduce at different potentials, has been examined on glassy carbon surfaces using cyclic voltammetry and X-ray photoelectron spectroscopy (XPS). Striking features were observed: (1) the two aryl diazonium salts in the mixed solution undergo reductive adsorption at the same potential which is distinctively less negative than the potential required for the reduction of either of the two aryl diazonium salts alone; (2) the surface ratio of the two phenyl derivatives is consistently 1:1 regardless of the ratio of the two aryl diazonium salts in the modification solutions. Homogeneous distribution of the two oppositely charged phenyl species on the modified surface has also been suggested by XPS survey spectra. Diffusion coefficient measurements by DOSY NMR and DFT based computation have indicated the association of the two aryl diazonium species in the solution, which has led to changes in the molecular orbital energies of the two species. This study highlights the potential of using intermolecular interactions to control the assembly of multicomponent thin layers. 23458385 Counterion condensation on heparin oligomers. The electropherogram of native heparin shows a broad distribution of mobilities μ, which truncates abruptly at a notably high μ = 4.7 × 10(-4) cm(2) V(-1) s(-1). This highly skewed mobility distribution is also found for the 20-saccharide chain, which shows from mass spectrometry a more uniform (symmetrical) with respect to sulfation level. Since a partially degraded heparin exhibits oligomer peaks with μ> 5 × 10(-4) cm(2) V(-1) s(-1) (appearing to escape the limitation of the mobility value for native heparin), we examined the electrophoretic behavior of chain-length monodisperse heparin oligomers. Their mobilities varied inversely with the logarithm of the contour length, L, for L from 3 to 10 nm and reached an asymptotic limit for L > 20 nm. The generality of this effect was indicated by similar behavior for oligomers of poly(styrene sulfonate). A recent theory of polyelectrolyte end effects (Manning, G. S. Macromolecules2008, 41, 6217-6227), in which chain termini exhibit reduced counterion condensation was found to quantitatively account for these results. A qualitative explanation for the anomalously high value of μ of native heparin, 10-20% higher than those seen for synthetic polyelectrolytes of higher linear charge density, is suggested on the basis of similar junction effects (Manning, G. S. Macromolecules2008, 41, 6217-6227), which reduce counterion condensation at the interfaces of regions of high and low sulfation. We suggest that these effects should be considered in models for the biofunctionality of the regulated high and low sulfation (NS/NA) domains of heparan sulfate. 23466444 Pro-inflammatory properties and neutrophil activation by Helicobacter pylori urease. The gastric pathogen Helicobacter pylori produces large amounts of urease, whose enzyme activity enables the bacterium to survive in the stomach. We have previously shown that ureases display enzyme-independent effects in mammalian models, most through lipoxygenases-mediated pathways. Here, we evaluated potential pro-inflammatory properties of H. pylori urease (HPU). Mouse paw edema and activation of human neutrophils were tested using a purified, cell-free, recombinant HPU. rHPU induced paw edema with intense neutrophil infiltration. In vitro 100 nM rHPU was chemotactic to human neutrophils, inducing production of reactive oxygen species. rHPU-activated neutrophils showed increased lifespan, with inhibition of apoptosis accompanied by alterations of Bcl-XL and Bad contents. These effects of rHPU persisted in the absence of enzyme activity. rHPU-induced paw edema, neutrophil chemotaxis and apoptosis inhibition reverted in the presence of the lipoxygenase inhibitors esculetin or AA861. Neutrophils exposed to rHPU showed increased content of lipoxygenase(s) and no alteration of cyclooxygenase(s). Altogether, our data indicate that HPU, besides allowing the bacterial survival in the stomach, could play an important role in the pathogenesis of the gastrointestinal inflammatory disease caused by H. pylori. 23643744 Repeated potentiation of the metabotropic glutamate receptor 5 and the alpha 7 nicotinic acetylcholine receptor modulates behavioural and GABAergic deficits induced by early postnatal phencyclidine (PCP) treatment. The underlying mechanism of the GABAergic deficits observed in schizophrenia has been proposed to involve NMDA receptor hypofunction. An emerging treatment strategy therefore aims at enhancing GABAergic signalling by increasing the excitatory transmission onto interneurons. We wanted to determine whether behavioural and GABAergic functional deficits induced by the NMDA receptor channel blocker, phencyclidine (PCP), could be reversed by repeated administration of two drugs known to enhance GABAergic transmission: the positive allosteric modulator (PAM) of the metabotropic glutamate receptor 5 (mGluR5), ADX47273, and the partial agonist of the α7 nicotinic acetylcholine receptor (α7 nAChR), SSR180711. Adolescent rats (4-5 weeks) subjected to PCP treatment during the second postnatal week displayed a consistent deficit in prepulse inhibition (PPI), which was reversed by a one week treatment with ADX47273 or SSR180711. We examined GABAergic transmission by whole cell patch-clamp recordings of miniature inhibitory postsynaptic currents (mIPSC) in pyramidal neurons in layer II/III of prefrontal cortex (PFC) and by activation of extrasynaptic δ-containing GABAA receptors by THIP. Following PCP treatment, pyramidal neurons displayed a reduced mIPSC frequency and up-regulation of extrasynaptic THIP-induced current. ADX47273 treatment restored this up-regulation of THIP-induced current. Finally, we showed that repeated treatment with ADX47273 and SSR180711 decreased the induction of spontaneous inhibitory current caused by acute and direct agonism of mGluR5s and α7 nAChRs in slices. These results show that repeated administration of ADX47273 or SSR180711 reverses certain behavioural and functional deficits induced by PCP, likely through down-regulation or desensitisation of mGluR5s and α7 nAChRs, respectively. 23537942 Anticancer activity of novel hybrid molecules containing 5-benzylidene thiazolidine-2,4-dione. Hybridization of two different bioactive molecules with different mechanism of action is one of the methods that are being adopted to treat cancer. Molecules bearing a thiazolidine-2,4-dione scaffold have been recognized as antineoplastic agents with a broad spectrum of activity against many cancer cell lines. In this manuscript we have described the synthesis and biological evaluation of two series of N-3-substituted-5-arylidene thiazolidine-2,4-diones, bearing the α-bromoacryloylamido moiety at the para- or meta-position on the phenyl of the arylidene portion. We have observed that selected compounds 5a, 5c and 5g suppress proliferation of human myeloid leukaemia HL-60 and U937 cells by triggering morphological changes and internucleosomal DNA fragmentation, which are well-known features of apoptosis. Finally, our results indicated that the investigated compounds induced apoptotic cell death through a mechanism that involved activation of multiple caspases and was also associated with the release of cytochrome c from the mitochondria. 23239601 Gold nanoparticles produced in situ mediate bioelectricity and hydrogen production in a microbial fuel cell by quantized capacitance charging. Oppan quantized style: By adding a gold precursor at its cathode, a microbial fuel cell (MFC) is demonstrated to form gold nanoparticles that can be used to simultaneously produce bioelectricity and hydrogen. By exploiting the quantized capacitance charging effect, the gold nanoparticles mediate the production of hydrogen without requiring an external power supply, while the MFC produces a stable power density. 23416409 Quantitative proteomic analysis reveals the mode-of-action for chronic mercury hepatotoxicity to marine medaka (Oryzias melastigma). Mercury (Hg) is a widespread persistent pollutant in aquatic ecosystems. We investigated the protein profiles of medaka (Oryzias melastigma) liver chronically exposed to different mercuric chloride (HgCl2) concentrations (1 or 10 μg/L) for 60 d using two-dimensional difference gel electrophoresis (2D-DIGE), as well as cell ultrastructure and Hg content analysis of the hepatic tissue. The results showed that Hg exposure significantly increased metal accumulation in the liver, and subsequently damaged liver ultrastructure. Comparison of the 2D-DIGE protein profiles of the exposed and control groups revealed that the abundance of 45 protein spots was remarkably altered in response to Hg treatment. The altered spots were subjected to matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry analysis, with the resultant identification of 33 spots. These proteins were mainly involved in cytoskeleton assembly, oxidative stress, and energy production. Among them, several proteins related to mitochondrial function (e.g. respiratory metabolism) were significantly altered in the treated hepatocytes, implying that this organelle might be the primary target for Hg attack in the cells. This study provided new insights into the molecular mechanisms and/or toxic pathways by which chronic Hg hepatotoxicity affects aquatic organisms, and also provided basic information for screening potential biomarkers for aquatic Hg monitoring. 23618921 Concurrent Regulation of the Transcription Factors Nrf2 and ATF4 Mediates the Enhancement of Glutathione Levels by the Flavonoid Fisetin. Glutathione (GSH) and GSH-associated metabolism provide the major line of defense for the protection of cells from various forms of toxic stress. GSH also plays a key role in regulating the intracellular redox environment. Thus, maintenance of GSH levels is developing into an important therapeutic objective for the treatment of a variety of diseases. Among the transcription factors that play critical roles in GSH metabolism are NF-E2-related factor 2 (Nrf2) and activating transcription factor 4 (ATF4). Thus, compounds that can upregulate these transcription factors may be particularly useful as treatment options through their effects on GSH metabolism. We previously showed that the flavonoid fisetin not only increases basal levels of GSH but also maintains GSH levels under oxidative stress conditions. However, the mechanisms underlying these effects have remained unknown until now. Here we show that fisetin rapidly increases the levels of both Nrf2 and ATF4 as well as Nrf2- and ATF4-dependent gene transcription via distinct mechanisms. Although fisetin greatly increases the stability of both Nrf2 and ATF4, only the effect on ATF4 is dependent on protein kinase activity. Using siRNA we found that ATF4, but not Nrf2, is important for fisetin's ability to increase GSH levels under basal conditions whereas both ATF4 and Nrf2 appear to cooperate to increase GSH levels under oxidative stress conditions. Based upon these results, we hypothesize that compounds able to increase GSH levels via multiple mechanisms, such as fisetin, will be particularly effective for maintaining GSH levels under a variety of different stresses. 23401355 Formation of nanostructured MnO/Co/solid-electrolyte interphase ternary composites as a durable anode material for lithium-ion batteries. Nanoporous MnO frameworks with highly dispersed Co nanoparticles were produced from MnCO3 precursors prepared in a gel matrix. The MnO frameworks that contain 20 mol% Co exhibited excellent cycle performance as an anode material for Li-ion batteries. The solid-electrolyte interphase (SEI) formed in the frameworks through the electrochemical reaction mediates the active materials, such as MnO, Mn, and Li2O, during the conversion reaction in the charge-discharge cycle. The Co nanoparticles and SEI provide the electron and Li-ion conductive networks, respectively. The ternary nanocomposites of the MnO framework, metallic Co nanoparticles, and embedded SEI are categorized as durable anode materials for Li-ion batteries. 22480291 RP-HPLC method for the simultaneous quantitation of boeravinone E and boeravinone B in Boerhaavia diffusa extract and its formulation. A high-performance liquid chromatography method was developed and validated for the simultaneous quantitation of two major rotenoids, boeravinone E and boeravinone B, in Boerhaavia diffusa extract and its formulation. Chromatographic separation was carried out on an Inertsil ODS-3 column by using gradient mobile phase containing 0.1% v/v orthophosphoric acid in water and acetonitrile. The detection was carried out at 276 nm. The method was validated for specificity, precision, accuracy and robustness. The linearity (r (2) = 0.9989 and 0.9991) was found to be in the range of 7.26-35.75 µg mL(-1) and 2.20-11.00 µg mL(-1) for boeravinone E and B, respectively. The percent recovery observed from the extract sample was 95.22-95.83. 23220295 Effects of adolescent social defeat on adult amphetamine-induced locomotion and corticoaccumbal dopamine release in male rats. Maturation of mesocorticolimbic dopamine systems occurs during adolescence, and exposure to social stress during this period results in behavioral dysfunction including substance abuse disorders. Adult male rats exposed to repeated social defeat in adolescence exhibit reduced basal dopamine tissue content in the medial prefrontal cortex, altered dopamine tissue content in corticoaccumbal dopamine regions following acute amphetamine, and increased amphetamine conditioned place preference following repeated amphetamine treatment. Such changes may reflect altered amphetamine-induced extracellular dopamine release in the corticoaccumbal regions. Therefore, we used in vivo microdialysis to measure extracellular dopamine simultaneously within the medial prefrontal cortex and nucleus accumbens core of previously defeated rats and controls, in response to either acute or repeated (7 daily injections) of amphetamine (1.0 mg/kg). Locomotion responses to acute/repeated amphetamine were also assessed the day prior to taking dopamine measurements. Adolescent defeat potentiated adult locomotion responses to acute amphetamine, which was negatively correlated with attenuated amphetamine-induced dopamine release in the medial prefrontal cortex, but there was no difference in amphetamine-induced accumbal dopamine release. However, both locomotion and corticoaccumbal dopamine responses to repeated amphetamine were equivalent between previously defeated rats and controls. These data suggest adolescent defeat enhances behavioral responses to initial amphetamine exposure as a function of diminished prefrontal cortex dopamine activity, which may be sufficient to promote subsequently enhanced seeking of drug-associated cues. Interestingly, repeated amphetamine treatment appears to normalize amphetamine-elicited locomotion and cortical dopamine responses observed in adult rats exposed to adolescent social defeat, providing implications for treating stress-induced dopamine dysfunction. 23215148 Lipid reassembly in asymmetric Langmuir-Blodgett/Langmuir-Schaeffer bilayers. Molecular-reorganization-induced morphology alteration in asymmetric substrate-supported lipid bilayers (SLBs) was directly visualized by means of atomic force microscopy (AFM) and total internal reflection fluorescence (TIRF) microscopy. SLB samples were fabricated on mica-on-glass and glass substrates by Langmuir-Blodgett (LB)/Langmuir-Schaeffer (LS) using binary lipid mixtures, namely, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and ternary mixtures DOPC/DPPC/1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS), labeled with 0.2 mol % Texas Red 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium salt (TR-DHPE) dye. Phase segregations were characterized by TIRF imaging, and DPPC-enriched domain structures were also observed. Interestingly for ∼40% (n = 6) of the samples with binary mixtures in the LB leaflet and a single component in the LS leaflet, that is, (DOPC/DPPC)(LB)+DOPC(LS), the contrast of the DPPC domains changed from the original dark (without dye) to bright (more TR dye partitioning) on TIRF images, returning to dark again. This contrast reverse was also correlated to AFM height images, where a DPPC-DPPC gel phase was spotted after the TIRF image contrast returned to dark. The rupture force mapping results measured on these binary mixture samples also confirmed unambiguously the formation of DPPC-DPPC gel domain components during the contrast change. The samples were tracked over 48 h to investigate the lipid molecule movements in both the DPPC domains and the DOPC fluid phase. The fluorescence contrast changes from bright to dark in SLBs indicate that the movement of dye molecules was independent of the movement of lipid molecules. In addition, correlated multimodal imaging using AFM, force mapping, and fluorescence provides a novel route to uncover the reorganization of lipid molecules at the solid-liquid interface, suggesting that the dynamics of dye molecules is highly structure dependent. 23436129 Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome. RATIONALE: Fragile X syndrome (FXS) is an inherited form of developmental disability and a single gene cause of autism. As a disorder with increasingly understood pathophysiology, FXS is a model form of developmental disability for targeted drug development efforts. Preclinical animal model findings have focused targeted drug treatment development in FXS on an imbalance between excessive glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission. METHODS: We conducted a prospective open-label 10-week trial of acamprosate in 12 youth aged 6-17 years (mean age: 11.9 years) with FXS. RESULTS: Acamprosate use (mean dose: 1,054 ± 422 mg/day) was associated with treatment response (defined by a Clinical Global Impressions Improvement (CGI-I) scale score of "very much improved" or "much improved") in nine of 12 (75 %) subjects. Improvement was noted in social behavior and inattention/hyperactivity using multiple standard behavioral outcome measures. No significant adverse effects or changes in vital signs, including weight or laboratory measures, occurred during treatment with acamprosate. Additionally, pre- and post-treatment blood biomarker analyses looking at brain-derived neurotrophic factor (BDNF) levels found a significant increase in BDNF with treatment. In our pilot sample, treatment response did not correlate with change in BDNF with treatment. CONCLUSIONS: Acamprosate was generally safe and well tolerated and was associated with a significant improvement in social behavior and a reduction in inattention/hyperactivity. The increase in BDNF that occurred with treatment may be a useful pharmacodynamic marker in future acamprosate studies. Given these findings, a double-blind, placebo-controlled study of acamprosate in youth with FXS is warranted. 22585450 Effects of Crataegus microphylla on vascular dysfunction in streptozotocin-induced diabetic rats. Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular disease. In this study, we aimed to investigate whether chronic in vivo treatment of Crataegus microphylla (CM) extract in diabetic rats induced with streptozotocin (STZ, intraperitoneal, 65 mg/kg) preserves vascular function and to evaluate whether the reduction of inducible nitric oxide synthase (iNOS), proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of action. Starting at 4 weeks of diabetes, CM extract (100 mg/kg) was administrated to diabetic rats for 4 weeks. In aortic rings, relaxation to acetylcholine and vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and plasma tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), total nitrite-nitrate, and malondialdehite levels were increased in diabetic rats compared with controls. Chronic CM treatment significantly corrected all the above abnormalities in diabetic rats. In comparison, pretreatment of the aorta of diabetic rats with N-[3(aminomethyl) benzyl]-acetamidine, dihydrochloride (10(-5)  M), a selective inhibitor of iNOS, produced a similar recovery in vascular reactivity. These results suggest that chronic in vivo treatment of CM preserves endothelium-dependent relaxation and vascular contraction in STZ-induced diabetes, possibly by reducing iNOS expression in the aorta and by decreasing plasma levels of TNF-α and IL-6 and by preventing lipid peroxidation. Copyright © 2012 John Wiley & Sons, Ltd. 22489960 Screening of ecotoxicological, qualitative and reproductive variables in male European sea bass Dicentrarchus labrax (L.) reared in three different fish farms: Facility location and typology. The aim of this study was to investigate the influence of both facility location and typology of fish farm on some ecotoxicological, qualitative and reproductive variables in European sea bass Dicentrarchus labrax L. Several variables were investigated: gonado-somatic index (GSI), liver-somatic index (LSI); 7-ethoxyresorufin-O-deethylase (EROD), benzo(a)pyrene monooxygenase and acetylcholinesterase activities; glutathione (GSH), testosterone, 17β-estradiol, total lipid, phospholipid (PL) and triglyceride contents. In addition, the histological sections of gonads were examined. Results suggest that LSI, EROD activity, GSI, GSH, PL, hormone levels and gonad morphology were influenced by different facility locations and typologies of fish farm. 23475901 Generation and characterization of fully human monoclonal antibodies against human orai1 for autoimmune disease. Calcium entry into T cells following antigen stimulation is crucial for nuclear factor of activated T cells (NFAT)-mediated T cell activation. The movement of calcium is mediated by calcium release-activated calcium (CRAC) channels. There are two key components of this channel: Orai1 is the pore-forming subunit located in the plasma membrane, and stromal interaction molecule 1 (STIM1) functions as a Ca(2+) sensor in the endoplasmic reticulum. A subset of human patients carry mutations in either STIM1 or Orai1 that affect protein function or expression, resulting in defective store-operated Ca(2+) influx and CRAC channel function, and impaired T cell activation. These patients suffer from a hereditary form of severe combined immune deficiency syndrome, highlighting the importance of the CRAC channel for T lymphocyte function in humans. Since autoreactive T cells play an important role in the development of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and organ transplantation, Orai1 becomes an attractive therapeutic target for ameliorating autoimmune disease. We developed a novel approach to inhibiting CRAC function by generating high-affinity fully human monoclonal antibodies to human Orai1. These antibodies inhibited ICRAC current, store-operated Ca(2+) influx, NFAT transcription, and cytokine release. These fully human antibodies to human Orai1 may represent a novel therapeutic approach for the treatment of autoimmunity. 22765022 Flavonoid constituents and biological screening of Astragalus bombycinus Boiss. Two new flavonoid compounds were isolated from Astragalus bombycinus Boiss. and identified as quercetin-3,7-di-O-β-glucopyranoside 4'-O-α-rhamnopyranoside and 5,2',4'-trihydroxy-flavone-8-C-α-arabinopyranoside-7-O-β-glucopyranoside. In addition, apigenin, apigenin-7-O-β-glucopyranoside, apigenin 7-O-gentobioside, luteolin, luteolin-7-O-β-glucopyranoside, quercetin-3,7-di-O-β-glucopyranoside, quercetin-3-O-β-glucopyranoside-7-O-α-rhamnopyranoside and daidzein were also isolated and identified. The structure elucidation of the isolated compounds was performed by chromatographic, chemical and spectroscopic methods. Antioxidant and cytotoxic activities were also determined for the four consecutive extracts of the plant. 23624358 Recent advances in delivery of drug-nucleic acid combinations for cancer treatment. Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. 23265488 Rhubarb inhibits hepatocellular carcinoma cell metastasis via GSK-3-β activation to enhance protein degradation and attenuate nuclear translocation of β-catenin. The aim of our study was to investigate the mechanisms by which rhubarb regulates β-catenin as well as metastasis of hepatocellular carcinomas. Our results revealed that rhubarb extract inhibited HA22T cell migration ability in wound healing, migration and invasion assays in a dose-dependent manner. Rhubarb also reduced β-catenin protein level, downregulated its downstream proteins, cyclin D, Tbx3 and c-Myc, and attenuated the expression of MMP9 and contactin-1 metastatic factors. Additionally, rhubarb inhibited β-catenin nuclear accumulation and induced its degradation via proteasome-mediated pathway. Furthermore, we found that rhubarb suppressed the p-ser(9) GSK-3-β protein level to inactivate Wnt signalling and reduce β-catenin protein level. Taken together; we found that rhubarb blocked the metastatic process of HA22T hepatocellular carcinoma cells mediated through GSK-3-β activation, and enhancement of protein degradation as well as reduction of the nuclear accumulation of β-catenin. 23303486 Synthetic strategies for the biotinylation of bioactive small molecules. Biotinylation, the functional appendage of a biotin moiety to a bioactive compound (including small molecules and biological macromolecules), represents a common technique for identification of the intracellular binding partners that underlie the foundation of observed biological activity. Introduction of an attachment tether to the framework of a compound of interest must be planned at an early stage of development, and many considerations apply: 1) region of attachment, so as not to impede the pharmacophore; 2) stability of the parent molecular architecture to biotinylation conditions; 3) regioselectivity for the chosen tethering location over other reactive functionalities; 4) toxicity of reagents if biotinylation is to be performed in vitro; and 5) overall ease of synthesis. This review is intended to serve as a guide for the selection of appropriate tethering modalities. Examples of the common techniques used to affix biotin, including amide bond formation, [3+2] cycloadditions through "click" chemistry, Staudinger ligation, and thioether formation will be discussed, along with analysis of the wider applications of synthetic methodology that have been applied toward the biotinylation of small molecules. 23464667 Liquiritigenin prevents Staphylococcus aureus-mediated lung cell injury via inhibiting the production of α-hemolysin. Staphylococcus aureus is a significant Gram-positive bacterium that is associated with a broad spectrum of diseases ranging from minor skin infections to lethal pneumonia, endocarditis, and toxinoses. α-Hemolysin is one of the most important exotoxins that contribute to the pathogenesis of S. aureus infections. Liquiritigenin is one of the most significant active components in licorice. In this study, hemolysis, western blot, and real-time reverse transcription-PCR assays were performed to investigate the impact of liquiritigenin on the production of S. aureus α-hemolysin. The results showed that low concentrations of liquiritigenin remarkably decreased S. aureus α-hemolysin production in a dose-dependent manner. Using live/dead cell staining and lactate dehydrogenase assays, we found that liquiritigenin could protect human lung cells (A549) from α-hemolysin-mediated injury. The data indicated that this compound could potentially be useful in developing drugs aiming at staphylococcal α-hemolysin. 23000251 Bioconversion of quercetin and rutin and the cytotoxicity activities of the transformed products. Quercetin and rutin are well-know flavonoids. In spite of this, the comprehension of their metabolism is still incomplete. In this work, the cytotoxic activity of quercetin and rutin and its metabolites produced by metabolism of filamentous fungi was investigated. Flavonoids metabolism was monitored by HPLC and LC-MS. Both flavonoids were extensively metabolized. Quercetin was converted into metabolite methylquercetin (2) and quercetin glucuronide (3) and rutin into metabolite rutin sulphate (5), methylrutin (6) and rutin glucuronide (7). Cytotoxic effects of rutin, quercetin and its metabolites were measured by MTT tetrazolium reduction test and the trypan blue exclusion assay on HL-60 leukemic cells. The results showed similar concentration-dependent cytotoxic effect for rutin and rutin sulphate (5), while no cytotoxic effect was detected with the metabolites 6 and 7. In relation to the quercetin and its metabolites the results showed that all compounds have a similar concentration-dependent inhibitory effect on HL-60 cells. These findings corroborate the literature, showing that bioconversion is a useful strategy for production of biological active metabolites. 23247504 Sophorolipids-functionalized iron oxide nanoparticles. Functional iron oxide nanoparticles (NP) have been synthesized in a one and a two-step method using a natural functional glycolipid belonging to the family of sophorolipids (SL). These compounds, whose open acidic form is highly suitable for nanoparticle stabilization, are readily obtained by a fermentation process of the yeast Candida bombicola (polymorph Starmerella bombicola) in large amounts. The final carbohydrate coated iron oxide nanoparticles represent interesting potentially biocompatible materials for biomedical applications. According to the synthesis strategy, magnetic properties can eventually be tuned, thus putting in evidence the direct effect of the glycolipid on the final material's structure (maghemite and ferrihydrite have been obtained here). A combination of FT-IR, Dynamic Light Scattering (DLS) and UV-Vis experiments shows that SL complex the nanoparticle surface via their accessible COOH group thus forming stable colloids, whose hydrodynamic diameter mostly varies between 10 nm and 30 nm, both in water and in KCl-containing (0.01 M and 2 M) solutions. The materials can stand multiple filtration steps (up to 10) at different extents, where the largest recorded average aggregate size is 100 nm. In general, materials synthesized at T = 80 °C display better stability and smaller size distribution than those obtained at room temperature. 22638814 Learning to forget: manipulating extinction and reconsolidation processes to treat addiction. Finding effective long-lasting treatments for drug addiction has been an elusive goal. Consequently, researchers are beginning to investigate novel treatment strategies including manipulations of drug-associated memories. When environmental stimuli (cues) become associated with drug use, they become powerful motivators of continued drug use and relapse after abstinence. Reducing the strength of these cue-drug memories could decrease the number of factors that induce craving and relapse to aid in the treatment of addiction. Enhancing the consolidation of extinction learning and/or disrupting cue-drug memory reconsolidation are two strategies that have been proposed to reduce the strength of cues in motivating drug-seeking and drug-taking behavior. Here, we review the latest basic and clinical research elucidating the mechanisms underlying consolidation of extinction and reconsolidation of cue-drug memories in the hopes of developing pharmacological tools that exploit these signaling systems to treat addiction. 23336729 Biomimetic polymer brushes containing tethered acetylcholine analogs for protein and hippocampal neuronal cell patterning. This paper describes a method to control neuronal cell adhesion and differentiation with both chemical and topographic cues by using a spatially defined polymer brush pattern. First, biomimetic methacrylate polymer brushes containing tethered neurotransmitter acetylcholine functionalities in the form of dimethylaminoethyl methacrylate or free hydroxyl-terminated poly(ethylene glycol) units were prepared using the "grown from" method through surface-initiated atom transfer radical polymerization reactions. The surface properties of the resulting brushes were thoroughly characterized with various techniques and hippocampal neuronal cell culture on the brush surfaces exhibit cell viability and differentiation comparable to, or even better than, those on commonly used poly-l-lysine coated glass coverslips. The polymer brushes were then patterned via UV photolithography techniques to provide specially designed surface features with different sizes (varying from 2 to 200 μm) and orientations (horizontal and vertical). Protein absorption experiments and hippocampal neuronal cell culture tests on the brush patterns showed that both protein and neurons can adhere to the patterns and therefore be guided by such patterns. These results also demonstrate that, because of their unique chemical composition and well-defined nature, the developed polymer brushes may find many potential applications in cell-material interactions studies and neural tissue engineering. 22619070 Tea tree oil-induced transcriptional alterations in Staphylococcus aureus. Tea tree oil (TTO) is a steam distillate of Melaleuca alternifolia that demonstrates broad-spectrum antibacterial activity. This study was designed to document how TTO challenge influences the Staphylococcus aureus transcriptome. Overall, bioinformatic analyses (S. aureus microarray meta-database) revealed that both ethanol and TTO induce related transcriptional alterations. TTO challenge led to the down-regulation of genes involved with energy-intensive transcription and translation, and altered the regulation of genes involved with heat shock (e.g. clpC, clpL, ctsR, dnaK, groES, groEL, grpE and hrcA) and cell wall metabolism (e.g. cwrA, isaA, sle1, vraSR and vraX). Inactivation of the heat shock gene dnaK or vraSR which encodes a two-component regulatory system that responds to peptidoglycan biosynthesis inhibition led to an increase in TTO susceptibility which demonstrates a protective role for these genes in the S. aureus TTO response. A gene (mmpL) encoding a putative resistance, nodulation and cell division efflux pump was also highly induced by TTO. The principal antimicrobial TTO terpene, terpinen-4-ol, altered ten genes in a transcriptional direction analogous to TTO. Collectively, this study provides additional insight into the response of a bacterial pathogen to the antimicrobial terpene mixture TTO. Copyright © 2012 John Wiley & Sons, Ltd. 23481281 Aphanamgrandiol A, a new triterpenoid with a unique carbon skeleton from Aphanamixis grandifolia. Aphanamgrandiol A (1), a novel triterpenoid with a bicyclo[3,2,1]octane ring skeleton produced by 2,3-ring opening and 2,6-ring closure, was isolated from the stems of Aphanamixis grandifolia. The structures were established on the basis of extensive spectroscopic methods, including 1D and 2D NMR techniques, and determined unambiguously by X-ray crystal diffraction. Aphanamgrandiol A showed moderate cytotoxicities against MCG-803, SKOV-3, HCT116 and HepG2 cell lines. 23480446 Self-Assembling Multidomain Peptide Fibers with Aromatic Cores. Self-assembling multidomain peptides have been shown to have desirable properties, such as the ability to form hydrogels that rapidly recover following shear-thinning and the potential to be tailored by amino acid selection to vary their elasticity and encapsulate and deliver proteins and cells. Here we describe the effects of substitution of aliphatic hydrophobic amino acids in the central domain of the peptide for the aromatic amino acids phenylalanine, tyrosine, and tryptophan. While the basic nanofibrous morphology is retained in all cases, selection of the particular core residues results in switching from antiparallel hydrogen bonding to parallel hydrogen bonding in addition to changes in nanofiber morphology and in hydrogel rheological properties. Peptide nanofiber assemblies are investigated by circular dichroism polarimetry, infrared spectroscopy, atomic force microscopy, transmission and scanning electron microscopy, oscillatory rheology, and molecular dynamics simulations. Results from this study will aid in designing next generation cell scaffolding materials. 23313176 Injectable nanomaterials for drug delivery: Carriers, targeting moieties, and therapeutics. Therapeutics such as nucleic acids, proteins/peptides, vaccines, anti-cancer, and other drugs have disadvantages of low bio-availability, rapid clearance, and high toxicity. Thus, there is a significant need for the development of efficient delivery methods and carriers. Injectable nanocarriers have received much attention due to their vast range of structures and ability to contain multiple functional groups, both within the bulk material and on the surface of the particles. Nanocarriers may be tailored to control drug release and/or increase selective cell targeting, cellular uptake, drug solubility, and circulation time, all of which lead to a more efficacious delivery and action of therapeutics. The focus of this review is injectable, targeted nanoparticle drug delivery carriers highlighting the diversity of nanoparticle materials and structures as well as highlighting current therapeutics and targeting moieties. Structures and materials discussed include liposomes, polymersomes, dendrimers, cyclodextrin-containing polymers (CDPs), carbon nanotubes (CNTs), and gold nanoparticles. Additionally, current clinical trial information and details such as trial phase, treatment, active drug, carrier sponsor, and clinical trial identifier for different materials and structures are presented and discussed. 23259773 Freeze fracture approach to directly visualize wetting transitions on nanopatterned superhydrophobic silicon surfaces: more than a proof of principle. Freeze fracturing is applied to make the wetting behavior of artificially nanopatterned Si surfaces directly visible. For this purpose, almost hexagonally arranged nanopillars of fixed areal density (127 μm(-2)) and diameters (35 nm) but varying heights (40-150 nm) were fabricated on silicon. Measurement of contact angles (CAs) including hysteresis allowed to distinguish between the Wenzel (W) and the Cassie-Baxter (CB) states with droplets completely wetting the pillars or residing on top of them, respectively. Providing additional depth contrast by evaporating the ice replica with thin carbon and (typically 3 nm) platinum layers under 45° allowed resolving 3D features of 5 nm within the ice replica. In this way, laterally sharp transitions from CB- to W-states could be revealed, indicating the formation of zero-curvature water surfaces even on the nanoscale. 23556453 Pharmacogenetics of opiates in clinical practice: the visible tip of the iceberg. Opioids are the cornerstone of analgesic therapy and are used as a substitution therapy for opiate addiction. Interindividual variability in response to opioids is a significant challenge in the management of pain and substitution. Therefore, treatment with opioids requires a careful individualization of dosage to achieve an appropriate balance of efficacy and adverse effects and, consequently, avoid toxicity, particularly respiratory depression, sedation and for some, cardiac ventricular fibrillations. Many studies have investigated the association between genetic factors and the variability of response to opioids. Variants in genes encoding proteins implied in opioid pharmacokinetics (absorption, distribution, metabolism, excretion and toxicity), together with those implied in opioids direct and indirect pharmacodynamics (genes of opioid receptors and monoaminergic systems), are the most studied. Many association studies have not been replicated. The purpose of this article is to summarize pharmacogenetic data associated with some opioids frequently encountered in managed care settings. 23286736 Delayed frost growth on jumping-drop superhydrophobic surfaces. Self-propelled jumping drops are continuously removed from a condensing superhydrophobic surface to enable a micrometric steady-state drop size. Here, we report that subcooled condensate on a chilled superhydrophobic surface are able to repeatedly jump off the surface before heterogeneous ice nucleation occurs. Frost still forms on the superhydrophobic surface due to ice nucleation at neighboring edge defects, which eventually spreads over the entire surface via an interdrop frost wave. The growth of this interdrop frost front is shown to be up to 3 times slower on the superhydrophobic surface compared to a control hydrophobic surface, due to the jumping-drop effect dynamically minimizing the average drop size and surface coverage of the condensate. A simple scaling model is developed to relate the success and speed of interdrop ice bridging to the drop size distribution. While other reports of condensation frosting on superhydrophobic surfaces have focused exclusively on liquid-solid ice nucleation for isolated drops, these findings reveal that the growth of frost is an interdrop phenomenon that is strongly coupled to the wettability and drop size distribution of the surface. A jumping-drop superhydrophobic condenser minimized frost formation relative to a conventional dropwise condenser in two respects: preventing heterogeneous ice nucleation by continuously removing subcooled condensate, and delaying frost growth by limiting the success of interdrop ice bridge formation. 23303710 The marine polyketide myriaporone 3/4 stalls translation by targeting the elongation phase. Myriaporone 3/4, a cytotoxic polyketide, has been reported as an inhibitor of eukaryotic protein synthesis. However, the mechanism by which it inhibits translation was unknown. Here we show that myriaporone 3/4 stalls protein synthesis in the elongation phase by inducing phosphorylation of eukaryotic elongation factor 2. The phosphorylation results from direct binding of myriaporone 3/4 to eukaryotic elongation factor 2 kinase. Our study also shows that myriaporone 3/4 in the nanomolar range inhibits in vitro tube formation by endothelial cells without being cytotoxic. In general, myriaporone 3/4 was at least 300 times less toxic to primary cells than to tumor cells. 23261676 (-) Epicatechin attenuates mitochondrial damage by enhancing mitochondrial multi-marker enzymes, adenosine triphosphate and lowering calcium in isoproterenol induced myocardial infarcted rats. Cardiac mitochondrial damage plays an important role in the pathology of myocardial infarction. The protective effects of (-) epicatechin on cardiac mitochondrial damage in isoproterenol induced myocardial infarction were evaluated in rats. Rats were pretreated with (-) epicatechin (20 mg/kg body weight) daily for a period of 21 days. After the pretreatment period, isoproterenol (100 mg/kg body weight) was injected subcutaneously into rats twice at an interval of 24 h to induce myocardial infarction. Isoproterenol induced myocardial infarcted rats showed a significant increase in the levels of cardiac diagnostic markers, heart mitochondrial lipid peroxidation, calcium, and a significant decrease in the activities/levels of heart mitochondrial glutathione peroxidase, glutathione reductase, reduced glutathione, isocitrate, succinate, malate, α-ketoglutarate and NADH-dehydrogenases, cytochrome-C-oxidase and adenosine triphosphate. (-) Epicatechin pretreatment showed significant protective effects on all the biochemical parameters evaluated. The in vitro study revealed the superoxide and hydroxyl radical scavenging activity of (-) epicatechin. The possible mechanisms for the beneficial effects of (-) epicatechin on cardiac mitochondria could be attributed to scavenging of free radicals, decreasing calcium, increasing multi-enzymes (antioxidant, tricarboxylic acid cycle and respiratory chain enzymes), reduced glutathione and adenosine triphosphate. Thus, (-) epicatechin attenuated mitochondrial damage in isoproterenol induced myocardial infarcted rats. 23619817 In Vitro Neo-cartilage Formation on a Three-Dimensional Composite Polymeric Cryogel Matrix. Limited blood supply and the avascular nature of articular cartilage restricts its self repair capacity, frequently leading to osteoarthritis. This work focuses on scaffolds for tissue repair from natural polymers, for example gelatin, chitosan, and agarose in the form of composite. A novel way of fabrication, known as cryogelation, is presented, in which matrices are synthesized at sub-zero temperature. Cell seeded scaffolds incubated under appropriate conditions result in the accumulation of matrix components on the surface of the gel in the form of neo-cartilage. Neo-cartilage exhibits similarity to native cartilage with respect to its physical, mechanical and biochemical properties. Based on the similarities of neo-cartilage to the native cartilage, it can provide a new approach for the treatment of localised joint injuries. 23644192 (99m)Tc-labeled dibenzylideneacetone derivatives as potential SPECT probes for in vivo imaging of β-amyloid plaque. Four (99m)Tc-labeled dibenzylideneacetone derivatives and corresponding rhenium complexes were successfully synthesized and biologically evaluated as potential imaging probes for Aβ plaques using SPECT. All rhenium complexes (5a-d) showed affinity for Aβ(1-42) aggregates (Ki = 13.6-120.9 nM), and selectively stained the Aβ plaques on brain sections of transgenic mice. Biodistribution in normal mice revealed that [(99m)Tc]5a-d exhibited moderate initial uptake (0.31%-0.49% ID/g at 2 min) and reasonable brain washout at 60 min post-injection. Although additional optimizations are still needed to facilitate it's penetration through BBB, the present results indicate that [(99m)Tc]5a may be a potential SPECT probe for imaging Aβ plaques in Alzheimer's brains. 23514378 The role of platelet/lymphocyte serotonin transporter in depression and beyond. A large amount of the data gathered in the last 50 years support the hypothesis that alterations of the serotonin (5-HT) neurotransmission play a crucial role in the pathophysiology of not only major depression (MD), but also of different neuropsychiatric disorders. Research in this field has been substantially promoted by the evidence that the reuptake protein (SERT), present in presynaptic neurons, is a key element in terminating the activity of the neurotransmitter in the synaptic cleft. For this reason, it was specifically targeted for the development of second-generation antidepressants, in particular of selective 5-HT reuptake inhibitors (SSRIs), with the aim of increasing the intrasynaptic 5-HT concentrations. Moreover, since a lot of studies showed that circulating platelets and, more recently, lymphocytes possess functional SERT proteins, they have been widely used as peripheral mirrors of the same structures located in the central nervous system. The presence of functional SERT in blood cells suggests strict relationships between the nervous and the immune system that need to be better clarified in MD, as well as the possibility of reciprocal modulation of the two systems by different drugs. This paper aims to review briefly the literature on the 5-HT hypothesis of depression with a major focus on the possible role of SERT in this disorder, while highlighting how recent data are more oriented on dimensional rather than nosological involvement of this structure in different conditions spanning from normality to pathology. 23623556 Octameric CENP-A Nucleosomes Are Present at Human Centromeres throughout the Cell Cycle. The presence of a single centromere on each chromosome that signals formation of a mitotic kinetochore is central to accurate chromosome segregation [1]. The histone H3 variant centromere protein-A (CENP-A) is critical for centromere identity and function; CENP-A chromatin acts as an epigenetic mark to direct both centromere and kinetochore assembly [2-4]. Interpreting the centromere epigenetic mark ensures propagation of a single centromere per chromosome to maintain ploidy. Thus, understanding the nature of CENP-A chromatin is crucial for all cell divisions. However, there are ongoing debates over the fundamental composition of centromeric chromatin. Here we show that natively assembled human CENP-A nucleosomes are octameric throughout the cell cycle. Using total internal reflection fluorescence (TIRF)-coupled photobleaching-assisted copy-number counting of single nucleosomes obtained from cultured cells, we find that the majority of CENP-A nucleosomes contain CENP-A dimers. In addition, we detect the presence of H2B and H4 in these nucleosomes. Surprisingly, CENP-A associated with the chaperone HJURP can exist as either monomer or dimer, indicating possible assembly intermediates. Thus, our findings indicate that octameric CENP-A nucleosomes mark the centromeric region to ensure proper epigenetic inheritance and kinetochore assembly. 23186623 Maturation-associated changes in the internal distribution of tetrodotoxin in the female goby Yongeichthys criniger. Maturation-associated changes in the internal distribution of tetrodotoxin (TTX) in the goby Yongeichthys criniger were investigated in 29 and 40 female specimens collected from Okinawa, Japan, from August 2008 to June 2009 (Group I), and from November 2009 to August 2010 (Group II), respectively. In Group I, based on changes in the gonadosomatic index (GSI) and histologic observation of the ovary, the period from October 2008 through January 2009 was estimated to be the 'previtelline-forming period', February through March 2009 the 'vitelline-forming period', April through June 2009 the 'spawning period', and August 2008 the 'end of spawning period' of the preceding year. The TTX content (mouse unit [MU] per gram tissue) of each Y. criniger tissue (skin, muscle, liver, and ovary) quantified by liquid chromatography/mass spectrometry (LC/MS) was generally high during the spawning period and continued to rise until the end of spawning period, especially in the ovary. Total TTX per individual increased considerably during the spawning period, most of which located in the ovary, indicating that Y. criniger obtains a high amount of TTX during the spawning period, and accumulates most of it in the ovary. In contrast, the TTX content of the skin was highest at the end of spawning period, and most of the total TTX located in the skin during this period as well as during the previtelline-forming period. In Group II, the maturation stage of the ovaries of all specimens was determined, and the specimens were grouped accordingly. In the perinucleolus stage, yolk vesicle stage, and yolk globule stage I, most of the TTX was localized in the skin, but the TTX in the ovary greatly increased as the maturation stage advanced from yolk globule stage I to yolk globule stage III. 23528109 Nanopore-spanning lipid bilayers on silicon nitride membranes that seal and selectively transport ions. We report the formation of POPC lipid bilayers that span 130 nm pores in a freestanding silicon nitride film supported on a silicon substrate. These solvent-free lipid membranes self-assemble on organosilane-treated Si3N4 via the fusion of 200 nm unilamellar vesicles. Membrane fluidity is verified by fluorescence recovery after photobleaching (FRAP), and membrane resistance in excess of 1 GΩ is demonstrated using electrical impedance spectroscopy (EIS). An array of 40 000 membranes maintained high impedance over 72 h, followed by rupture of most of the membranes by 82 h. Membrane incorporation of gramicidin, a model ion channel, resulted in increased membrane conductance. This membrane conductance was diminished when the gramicidin channels were blocked with CaCl2, indicating that the change in membrane conductance results from gramicidin-mediated ion transport. These very stable, biologically functional pore-spanning membranes open many possibilities for silicon-based ion-channel devices for applications such as biosensors and high-throughput drug screening. 23183669 Interactions of the intact FsrC membrane histidine kinase with the tricyclic peptide inhibitor siamycin I revealed through synchrotron radiation circular dichroism. The suitability of synchrotron radiation circular dichroism spectroscopy (SRCD) for studying interactions between the tricyclic peptide inhibitor siamycin I and the intact FsrC membrane sensor kinase in detergent micelles has been established. In the present study, tertiary structural changes demonstrate that inhibitor binding occurs at a different, non-overlapping site to the native ligand, GBAP. 23142699 Proto-oncogene PIM-1 is a novel estrogen receptor target associating with high grade breast tumors. We searched ERα cistromes of MCF-7 breast cancer cells for previously unrecognized ERα targets and identified proto-oncogene PIM-1 as a novel potential target gene. We show that the expression of PIM-1 is induced in response to estradiol in MCF-7 cells and that the induction is mediated by ERα-regulated enhancers located distally upstream from the gene. In keeping with the growth-promoting role of the PIM-1, depletion of the PIM-1 attenuated the proliferation of the MCF-7 cells, which was paralleled with up-regulation of cyclin-dependent protein kinase inhibitor CDKN1A and CDKN2B expression. Analysis of PIM-1 expression between invasive breast tumors and benign breast tissue samples showed that elevated PIM-1 expression is associated with malignancy and a higher tumor grade. In sum, identification of PIM-1 as an ERα target gene adds a novel potential mechanism by which estrogens can contribute to breast cancer cell proliferation and carcinogenesis. 23561079 Changes in selected parameters related to proteolysis during ageing of dry-cured pork loins inoculated with probiotics. The effect of inoculation with a probiotic strain, Lactobacillus casei ŁOCK 0900, on selected parameters related to proteolysis of dry-cured pork loins during ageing was studied. Moisture content decreased significantly (p<0.05) throughout ageing, accompanied by a progressive reduction in water activity. The total nitrogen (TN) content increased during ageing with no effect (p<0.05) of inoculation with L. casei on its level. The greatest increase in non-protein nitrogen (NPN) content during ageing occurred in an inoculated sample, corresponding with the more pronounced decrease in pH. The intensity of proteolysis, as assessed by proteolysis index (PI), remained statistically significantly (p<0.05) unchanged during examined ageing periods. Inoculation with a probiotic strain does not significantly affect the degree of proteolysis in examined meat products after 21 and 28days of ageing. 23369033 Left, right, or both? On the configuration of the phenanthroindolizidine alkaloid tylophorine from Tylophora indica. The alkaloid (-)-tylophorine was isolated from a sample of Tylophora indica, and the crude extract was analyzed by HPLC/MS(n) and chiral HPLC/MS. While the literature states that the naturally occurring form of this alkaloid is the R-enantiomer and that its S-antipode is usually not found in nature, we confirmed the hypothesis of Govindachari and Nagarajan that natural levorotatory tylophorine is indeed a nearly racemic mixture with a slight excess of the R-enantiomer. 23523906 Berberine attenuates bleomycin induced pulmonary toxicity and fibrosis via suppressing NF-κB dependant TGF-β activation: A biphasic experimental study. Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating and fatal lung disorder with high mortality rate. Unfortunately, to date the treatment for IPF remains unsatisfying and in severe cases lung transplantations are performed as a therapeutic measure. Thus, it becomes great interest to find novel agents to treat IPF. Berberine, a plant alkaloid known for its broad pharmacological activities remains a remedy against multiple diseases. This study was hypothesized to investigate the antifibrotic potential of berberine against bleomycin-induced lung injury and fibrosis, a tentative animal model. Male wistar rats were subjected to single intratracheal instillation of 2.5U/kg of bleomycin on day 0. Berberine treatments were either provided in preventive or therapeutic mode respectively. Berberine administration significantly ameliorated the bleomycin mediated histological alterations and reduced the inflammatory cell infiltrate in BALF. Berberine significantly blocked collagen accumulations with parallel reduction in the hydroxyproline level. The immunological sign of bleomycin stimulated mast cell deposition and histamine release were considerably reduced by berberine. Berberine enhanced the antioxidant status, through upregulating the redox sensing transcription factor nuclear factor E2-related factor 2 (Nrf2). Berberine inhibited the bleomycin mediated activation of inflammatory mediator nuclear factor kappa B (NF-κB) and suppressed its downstream target inducible nitric oxide synthase (iNOS). Strikingly, berberine exhibited target attenuation of tumor necrosis factor alpha (TNF-α) and key pro-fibrotic mediator, transforming growth factor beta 1 (TGF-β1). Taken together, this study reveals the beneficial effects of berberine against bleomycin mediated fibrotic challenge through activating Nrf2 and suppressing NF-κB dependent inflammatory and TGF-β1 mediated fibrotic events. 23441816 Ca(2+) -calmodulin interacts with DdCAD-1 and promotes DdCAD-1 transport by contractile vacuoles in Dictyostelium cells. The Ca(2+) -dependent cell-cell adhesion molecule DdCAD-1, encoded by the cadA gene of Dictyostelium discoideum, is synthesized at the onset of development as a soluble protein and then transported to the plasma membrane by contractile vacuoles. Calmodulin associates with contractile vacuoles in a Ca(2+) -dependent manner, and co-localizes with DdCAD-1 on the surface of contractile vacuoles. Bioinformatics analysis revealed multiple calmodulin-binding motifs in DdCAD-1. Co-immunoprecipitation and pull-down studies showed that only Ca(2+) -bound calmodulin was able to bind DdCAD-1. Structural integrity of DdCAD-1, but not the native conformation, was required for its interaction with calmodulin. To investigate the role of calmodulin in the import of DdCAD-1 into contractile vacuoles, an in vitro import assay consisting of contractile vacuoles derived from cadA(-) cells and recombinant proteins was employed. Prior stripping of the bound calmodulin from contractile vacuoles by EGTA impaired import of DdCAD-1, which was restored by addition of exogenous calmodulin. The calmodulin antagonists W-7 and compound 48/80 blocked the binding of calmodulin onto stripped contractile vacuoles, and inhibited the import of DdCAD-1. Together, the data show that calmodulin forms a complex with DdCAD-1 and promotes the docking and import of DdCAD-1 into contractile vacuoles. STRUCTURED DIGITAL ABSTRACT: CaM physically interacts with DdCAD-1 by pull down (View Interaction: 1, 2) DdCAD-1 binds to CaM by far western blotting (View interaction) DdCAD-1 physically interacts with CaM by anti bait coimmunoprecipitation (View interaction). 23416001 Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: the continued optimization of an MLPCN probe molecule. This Letter describes the further optimization of an MLPCN probe molecule (ML137) through the introduction of 5- and 6-membered spirocycles in place of the isatin ketone. Interestingly divergent structure-activity relationships, when compared to earlier M1 PAMs, are presented. These novel spirocycles possess improved efficacy relative to ML137, while also maintaining high selectivity for the human and rat muscarinic M1 receptor subtype. 23414433 Glial reactivity in resistance to methamphetamine-induced neurotoxicity. Neurotoxic regimens of methamphetamine (METH) result in reactive microglia and astrocytes in striatum. Prior data indicate that rats with partial dopamine (DA) loss resulting from prior exposure to METH are resistant to further decreases in striatal DA when re-exposed to METH 30 days later. Such resistant animals also do not show an activated microglia phenotype, suggesting a relation between microglial activation and METH-induced neurotoxicity. To date, the astrocyte response in such resistance has not been examined. Thus, this study examined glial-fibrillary acidic protein (GFAP) and CD11b protein expression in striata of animals administered saline or a neurotoxic regimen of METH on post-natal days 60 and/or 90 (Saline:Saline, Saline:METH, METH:Saline, METH:METH). Consistent with previous work, animals experiencing acute toxicity (Saline:METH) showed both activated microglia and astocytes, whereas those resistant to the acute toxicity (METH:METH) did not show activated microglia. Interestingly, GFAP expression remained elevated in rats exposed to METH at PND60 (METH:Saline), and was not elevated further in resistant rats treated for the second time with METH (METH:METH). These data suggest that astrocytes remain reactive up to 30 days post-METH exposure. In addition, these data indicate that astrocyte reactivity does not reflect acute, METH-induced DA terminal toxicity, whereas microglial reactivity does. 23127899 Epidemiology and clinical effects of hump-nosed pit viper (Genus: Hypnale) envenoming in Sri Lanka. Hump-nosed pit vipers of Genus Hypnale are the commonest cause of snake bite in Sri Lanka. Although there are many reports of local effects, coagulopathy and acute kidney injury, it remains unclear how frequent these clinical effects are and therefore the medical importance of this snake genus. The genus has been recently revised to include Hypnale hypnale from Sri Lanka and Western Ghats of Southern India, and the two endemic species to Sri Lanka, Hypnale zara and Hypnale nepa. This was a prospective hospital-based clinical study of definite Hypnale spp. bites from July 2008 to July 2010 in six Sri Lankan hospitals. There were 114 patients included and all snakes were correctly identified by hospital staff as Hypnale spp. Of these, 93 snakes were identified as H. hypnale by an expert, 16 as H. zara and five as H. nepa. Most bites occurred on the lower limbs in the daytime. There was no difference in the clinical effects between the three species. Pain and fang marks were present in all patients, 101 had local swelling and only 16 (14%) developed extensive local swelling that spread proximally and involved more than half of the bitten limb. Systemic symptoms occurred in 18 patients; four patients had an abnormal 20 min whole blood clotting test and one patient developed an acute kidney injury that required haemodialysis. All patients were discharged alive with a median length of stay of 2 days. This study confirms that hump-nosed viper bites cause only minor effects in most cases. Future studies need to undertake formal coagulation studies and identify important early indicators of renal impairment. 22607769 MicroRNA regulation of lipid metabolism. MicroRNAs are structural components of an epigenetic mechanism of post-transcriptional regulation of messenger RNA translation. Recently, there is significant interest in the application of microRNA as a blood-based biomarker of underlying physiologic conditions, and the therapeutic administration of microRNA inhibitors and mimics. The purpose of this review is to describe the current body of knowledge on microRNA regulation of genes involved in lipid metabolism, and to introduce the role of microRNA in development and progression of atherosclerosis. 23312946 Specific chlorination of isoquinolines by a fungal flavin-dependent halogenase. Rdc2 is the first flavin-dependent halogenase identified from fungi. Based on the reported structure of the bacterial halogenase CmlS, we have built a homology model for Rdc2. The model suggests an open substrate binding site that is capable of binding the natural substrate, monocillin II, and possibly other molecules such as 4-hydroxyisoquinoline (1) and 6-hydroxyisoquinoline (2). In vitro and in vivo halogenation experiments confirmed that 1 and 2 can be halogenated at the position ortho to the hydroxyl group, leading to the synthesis of the chlorinated isoquinolines 1a and 2a, respectively, which further expands the spectrum of identified substrates of Rdc2. This work revealed that Rdc2 is a useful biocatalyst for the synthesis of various halogenated compounds. 23038668 Simple photosystem II water oxidation centre analogues in visible light oxygen and H+ generation. Calcium manganese oxide nanoparticles for application in water oxidation are synthesized by combination with a carboxylated biopolymer stabilizing agent to form very simple but effective analogues of the photosynthetic PSII oxygen evolving complex. The relative efficiency of these materials for production of O(2) and protons under visible light-promoted reactions is evaluated and prolonged reaction lifetimes are observed. 23624810 Antiaggressive activity of central oxytocin in male rats. RATIONALE: A substantial body of research suggests that the neuropeptide oxytocin promotes social affiliative behaviors in a wide range of animals including humans. However, its antiaggressive action has not been unequivocally demonstrated in male laboratory rodents. OBJECTIVE: Our primary goal was to examine the putative serenic effect of oxytocin in a feral strain (wild type Groningen, WTG) of rats that generally show a much broader variation and higher levels of intermale aggression than commonly used laboratory strains of rats. METHODS: Resident animals were intracerebroventricularly (icv) administered with different doses of synthetic oxytocin and oxytocin receptor antagonist, alone and in combination, in order to manipulate brain oxytocin functioning and to assess their behavioral response to an intruder. RESULTS: Our data clearly demonstrate that acute icv administered oxytocin produces dose-dependent and receptor-selective changes in social behavior, reducing aggression and potentiating social exploration. These antiaggressive effects are stronger in the more offensive rats. On the other hand, administration of an oxytocin receptor antagonist tends to increase (nonsignificantly) aggression only in low-medium aggressive animals. CONCLUSIONS: These results suggest that transiently enhancing brain oxytocin function has potent antiaggressive effects, whereas its attenuation tends to enhance aggressiveness. In addition, a possible inverse relationship between trait aggression and endogenous oxytocinergic signaling is revealed. Overall, this study emphasizes the importance of brain oxytocinergic signaling for regulating intermale offensive aggression. This study supports the suggestion that oxytocin receptor agonists could clinically be useful for curbing heightened aggression seen in a range of neuropsychiatric disorders like antisocial personality disorder, autism, and addiction. 23451823 Cryptocapsinepoxide-Type Carotenoids from Red Mamey, Pouteria sapota. New carotenoids, cryptocapsin-5,6-epoxide, 3'-deoxycapsanthin-5,6-epoxide, and cryptocapsin-5,8-epoxides, have been isolated from the ripe fruits of red mamey (Pouteria sapota). Cryptocapsin-5,6-epoxide was prepared by partial synthesis via epoxidation of cryptocapsin, and the (5R,6S)- and (5S,6R)-stereoisomers were identified by HPLC-ECD analysis. Spectroscopic data of the natural (anti) and semisynthetic (syn) derivatives obtained by acid-catalyzed rearrangement of cryptocapsin-5,8-epoxide stereoisomers were compared for structural elucidation. Chiral HPLC separation of natural and semisynthetic samples of cryptocapsin-5,8-epoxides was performed, and HPLC-ECD analysis allowed configurational assignment of the separated stereoisomers. 23472709 H-H and Si-H Bond Addition to Fe≡NNR2 Intermediates Derived from N2. The synthesis and characterization of Fe-diphosphineborane complexes are described in the context of N2 functionalization chemistry. Iron aminoimides can be generated at room temperature under 1 atm N2 and are shown to react with E-H bonds from PhSiH3 and H2. The resulting products derive from delivery of the E fragment to Nα and the H atom to B. The flexibility and lability of the Fe-BPh interactions in these complexes engender this reactivity. 23332347 Therapy of obese patients with cardiovascular disease. Obesity has reached epidemic proportions and is a significant public health concern. Obesity is associated with increased diabetes, cardiovascular and kidney disease, and associated morbidity and mortality. Despite the increasing public health problem of obesity, there is a dearth of effective treatment options. Following the FDA mandated withdrawal of sibutramine, the treatment options for obesity were limited to orlistat as the only pharmacological treatment option for long-term management of obesity. Recently two new medications (Belviq and Qsymia) were approved by FDA for long-term management of obesity. Many other antiobesity drugs are under development. Bariatric surgery has been shown to be effective in the treatment of obesity and its comorbidities. The available data suggest that even modest weight loss improves diabetes and cardiovascular disease (CVD) risk factors. We summarize the treatment options for obesity and the efficacy of these options in ameliorating cardiovascular risk factors. We also focus on the recently approved antiobesity drugs. 23444773 Fanconi anemia pathway--the way of DNA interstrand cross-link repair. The study of rare genetic diseases usually inspires the research of cancer biology. Fanconi anemia (FA), is a rare cancer susceptibility syndrome with an incidence of only 1 per 350,000 births. FA is an autosomal recessive disease with three main features: chromosome instability, hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC), cisplatin and so on, and susceptible to a number of cancer types, mainly leukemia and squamous cell carcinomas of the head and neck or gynecologic system. DNA crosslinking agents may led to DNA cross-linking lesion, and Fanconi anemia pathway plays a key role in repairing its cross-linking. However, FA pathway is closely linked with carcinogenesis and tumor drug resistance. This paper mainly focuses on the FA pathway and its progress in cancer research. 23399639 Chemically diverse microtubule stabilizing agents initiate distinct mitotic defects and dysregulated expression of key mitotic kinases. Microtubule stabilizers are some of the most successful drugs used in the treatment of adult solid tumors and yet the molecular events responsible for their antimitotic actions are not well defined. The mitotic events initiated by three structurally and biologically diverse microtubule stabilizers; taccalonolide AJ, laulimalide/fijianolide B and paclitaxel were studied. These microtubule stabilizers cause the formation of aberrant, but structurally distinct mitotic spindles leading to the hypothesis that they differentially affect mitotic signaling. Each microtubule stabilizer initiated different patterns of expression of key mitotic signaling proteins. Taccalonolide AJ causes centrosome separation and disjunction failure to a much greater extent than paclitaxel or laulimalide, which is consistent with the distinct defects in expression and activation of Plk1 and Eg5 caused by each stabilizer. Localization studies revealed that TPX2 and Aurora A are associated with each spindle aster formed by each stabilizer. This suggests a common mechanism of aster formation. However, taccalonolide AJ also causes pericentrin accumulation on every spindle aster. The presence of pericentrin at every spindle aster initiated by taccalonolide AJ might facilitate the maintenance and stability of the highly focused asters formed by this stabilizer. Laulimalide and paclitaxel cause completely different patterns of expression and activation of these proteins, as well as phenotypically different spindle phenotypes. Delineating how diverse microtubule stabilizers affect mitotic signaling pathways could identify key proteins involved in modulating sensitivity and resistance to the antimitotic actions of these compounds. 23353658 In vitro permeability analysis, pharmacokinetic and brain distribution study in mice of imperatorin, isoimperatorin and cnidilin in Radix Angelicae Dahuricae. Coumarins are important constituents of Radix Angelicae Dahuricae, a well-known traditional Chinese medicine possess several known bioactivities with potentials in the treatment of central nervous system diseases. By using an HPLC-MS/MS method, we analyzed the in vivo plasma and brain pharmacokinetics of three ingredients of coumarins, including imperatorin, isoimperatorin and cnidilin in mice after oral administration of Dahuricae extract at doses of 800mg/kg. The biosamples were prepared using acetonitrile precipitation and the separation was achieved on an XDB-C18 column by gradient elution. The BBB permeability and P-gp-mediated efflux were further examined in Madin Canine kidney cells transfected with full length cDNA for human multidrug resistance gene1 (MDCKII-MDR1). Our results demonstrate that the method has excellent and satisfactory selectivity, sensitivity, linearity, precision, and accuracy for simultaneous determination of imperatorin, isoimperatorin and cnidilin. The pharmacokinetics parameters were determined by using noncompartmental analyses, including the AUC(0-t) in plasma (1695.22, 1326.45 and 636.98mg*h/L), the AUC(0-t) in brain (1812.35, 2125.17 and 1145.83ng*h/g) as well as the T1/2 in plasma (0.66, 0.82, 0.97h) and brain (0.96, 1.1, 0.99h) for imperatorin, isoimperatorin and cnidilin, respectively, suggesting that the three coumarins could easily pass through the BBB in vivo. In the in vitro model we observed high permeability of imperatorin and isoimperatorin with the P-gp-mediated efflux ratios of 0.53 and 0.06, as well as medium permeability of cnidilin with 0.82. All data suggest that these three coumarins have high BBB permeability and have pharmacokinetic potentials for the treatment of central nervous system diseases. 23456248 OsSNDP1, a Sec14-nodulin domain-containing protein, plays a critical role in root hair elongation in rice. Rice is cultivated in water-logged paddy lands. Thus, rice root hairs on the epidermal layers are exposed to a different redox status of nitrogen species, organic acids, and metal ions than root hairs growing in drained soil. To identify genes that play an important role in root hair growth, a forward genetics approach was used to screen for short-root-hair mutants. A short-root-hair mutant was identified and isolated by using map-based cloning and sequencing. The mutation arose from a single amino acid substitution of OsSNDP1 (Oryza sativa Sec14-nodulin domain protein), which shows high sequence homology with Arabidopsis COW1/AtSFH1 and encodes a phosphatidylinositol transfer protein (PITP). By performing complementation assays with Atsfh1 mutants, we demonstrated that OsSNDP1 is involved in growth of root hairs. Cryo-scanning electron microscopy was utilized to further characterize the effect of the Ossndp1 mutation on root hair morphology. Aberrant morphogenesis was detected in root hair elongation and maturation zones. Many root hairs were branched and showed irregular shapes due to bulged nodes. Many epidermal cells also produced dome-shaped root hairs, which indicated that root hair elongation ceased at an early stage. These studies showed that PITP-mediated phospholipid signaling and metabolism is critical for root hair elongation in rice. 23074035 Temperature controlled water/oil wettability of a surface fabricated by a block copolymer: application as a dual water/oil on-off switch. A temperature controlled dual water/oil on-off switch is achieved by using a PMMA-b-PNIPAAm block-copolymer coated mesh, determined by the conformational change of the PNIPAAm chain around the lower critical solution temperature (LCST) and also the cooperation between PNIPAAm and PMMA. Water can permeate through the BCP-coated mesh, and oil cannot below the LCST, whereas oil can and water cannot above the LCST. 23444782 Effects of a new sustained-release microsphere formulation of exenatide, DA-3091, on obese and non-alcoholic fatty liver disease mice. The aim of this study was to examine the effects of a new sustained-release (SR) microsphere formulation of exenatide, DA-3091, on body weight gain and hepatic injury in high fat diet (HFD)-induced obese mice and high sucrose diet (HSD)-induced non-alcoholic fatty liver disease (NAFLD) mice. Then, we determined whether DA-3091 has the potency as a drug for the treatment of metabolic disease. In obese mice, after 8-week treatment, the body weight gain was significantly more suppressed by both 1 mg/kg and 2 mg/kg of DA-3091, monthly subcutaneous administered, than by 10 mg/kg/day of sibutramin, a drug against obesity. In NAFLD mice, a significant reduction in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, representative markers of hepatic injury, was observed after biweekly subcutaneous administration of 1 mg/kg and 2 mg/kg of DA-3091 for 8 weeks. A significant reduction in hepatic lipid accumulation was observed in DA-3091 treated groups as well. Based on these results, it is demonstrated that DA-3091 has the potency as a drug for the treatment of metabolic disease. 23291264 Urinary chemokine (C-C motif) ligand 2 (monocyte chemotactic protein-1) as a tubular injury marker for early detection of cisplatin-induced nephrotoxicity. Because of the difficulty in detecting segment-specific response in the kidney, we investigated the molecular events underlying acute kidney injury in the proximal tubules of rats with cisplatin (cis-diamminedichloroplatinum II)-induced nephrotoxicity. Microarray analysis revealed that mRNA levels of several cytokines and chemokines, such as interleukin-1beta, chemokine (C-C motif) ligand (CCL) 2, CCL20, chemokine (C-X-C motif) ligand (CXCL) 1, and CXCL10 were significantly increased after cisplatin treatment in both isolated proximal tubules and whole kidney. Interestingly, tubular CCL2 mRNA levels increased soon after cisplatin administration, whereas CCL2 mRNA levels in whole kidney first decreased and then increased. Levels of both CCL2 and kidney injury molecule-1 (KIM-1) in the whole kidney increased after cisplatin administration. Immunofluorescence analysis revealed CCL2 changes in the proximal tubular cells initially and then in the medullary interstitium. Urinary CCL2 excretion significantly increased approximately 3-fold compared with controls the day after cisplatin administration (5mg/kg), when no changes were observed plasma creatinine and blood urea nitrogen levels. Urinary levels of KIM-1 also increased 3-fold after cisplatin administration. In addition, urinary CCL2 rather than KIM-1 increased in chronic renal failure rats after administration of low-dose cisplatin (2mg/kg), suggesting that urinary CCL2 was selective for cisplatin-induced nephrotoxicity in renal impairment. These results indicated that the increase in cytokine and chemokine expression in renal epithelial cells might be responsible for kidney deterioration in cisplatin-induced nephrotoxicity, and that urinary CCL2 is associated with tubular injury and serves as a sensitive and noninvasive marker for the early detection of cisplatin-induced tubular injury. 23617439 Praziquantel Derivatives with Anti-Schistosomal Activity: Aromatic ring Modification. A series of aromatic ring modified praziquantel (PZQ) derivatives were prepared and evaluated against juvenile and adult stage of Schistosoma japonicumin. Several analogues comparable in activity to the drug PZQ have been identified based on in vitro and in vivo japonuicum schistosomes worm viability assay. Structure and activity relationship of these PZQ aromatic ring modified compounds was revealed. Specifically, a compound in which a bromine has been introduced in the aromatic ring of praziquantel demonstrated close antischistosomal activity to praziquentel in vivo. This article is protected by copyright. All rights reserved. 23297817 CO oxidation on colloidal Au(0.80)Pd(0.20)-Fe(x)O(y) dumbbell nanocrystals. We report a colloidal synthesis of Au(0.80)Pd(0.20)-Fe(x)O(y) dumbbell nanocrystals (NCs) derived from Au(0.75)Pd(0.25) NCs by metal oxide overgrowth. We compared the catalytic activity of the two types of NCs in the CO oxidation reaction (CO + 1/2O(2) → CO(2)), after they had been dispersed on an alumina nanopowder support. In both cases, the surface active sites were identified by means of in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The enhanced catalytic performance of the dumbbell NCs (Au(0.80)Pd(0.20)-Fe(x)O(y)) catalyst over that of the initial Au(0.75)Pd(0.25) NCs could be correlated to the presence of the epitaxial connection between the Fe(x)O(y) and the Au(0.80)Pd(0.20) domains (as the main factor). Such connection should result in an electron flow from the metal oxide (Fe(x)O(y)) domain to the noble metal (Au(0.80)Pd(0.20)) domain and appears to influence favorably the nature and composition of the catalytically active surface sites of the dumbbells. Our experiments indicate indeed that, when the metal alloy domain is attached to the metal oxide domain (that is, in the dumbbell), surface Pd species are more active than in the case of the initial Au(0.75)Pd(0.25) NCs and also Au(δ-) sites are formed that were not present on the initial Au(0.75)Pd(0.25) NCs. 23583735 (1)H NMR-based metabonomics study on the toxicity alleviation effect of other traditional Chinese medicines in Niuhuang Jiedu tablet to realgar (As2S2). ETHNOPHARMACOLOGICAL RELEVANCE: Niuhuang Jiedu Tablet (NJT) is an effective prescription of traditional Chinese medicine (TCM) used in treating acute tonsillitis, pharyngitis, periodontitis and mouth ulcer. NJT is prepared from Xionghuang (Realgar, As2S2), Rengong Niuhuang (Bovis Calculus Artificialis), Bingpian (Borneolum Synthcticum), Shigao (Gypsum Fibrosum), Dahuang (Rhei Radix et Rhizoma), Huangqin (Scutellariae Radix), Jiegeng (Platycodonis Radix) and Gancao (Glycyrrhizae Radix et Rhizoma). In the prescription, significant level of realgar (As2S2) as a potentially toxic element is contained. AIM OF THE STUDY: In this study, (1)H NMR-based metabonomics approach has been used to investigate the toxicity of realgar (As2S2) after being counterbalanced by other TCMs in NJT. MATERIALS AND METHODS: Male Wistar rats were divided into five groups: control, group I (treated with Realgar), group II (treated with Realgar, Bovis Calculus Artificialis, Borneolum Synthcticum, Gypsum Fibrosum, Rhei Radix et Rhizoma, Scutellariae Radix, Platycodonis Radix and Glycyrrhizae Radix et Rhizoma), group III (treated with Realgar, Bovis Calculus Artificialis, Borneolum Synthcticum and Gypsum Fibrosum) and group IV (treated with Realgar, Rhei Radix et Rhizoma, Scutellariae Radix, Platycodonis Radix and Glycyrrhizae Radix et Rhizoma). Based on (1)H-NMR spectra of urine and serum from rats, PCA and PLS-DA were performed to identify different metabolic profiles. Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed. RESULTS: PLS-DA scores plots demonstrated that the cluster of group I was separated from that of control rats, while group II was located close to control rats, indicating that metabolic profiles of group II were restored toward those of control rats. The metabolic profiles of group III were similar to those of group I, while the metabolic profiles of group II were almost in line with those of group II. Statistics results were confirmed by the histopathological examination and biochemical assay. CONCLUSION: Our results indicated that it was more secure and much less toxic for counterbalanced realgar (As2S2) in NJT. The effective material bases of toxicity alleviation to realgar (As2S2) were Dahuang (Rhei Radix et Rhizoma), Huangqin (Scutellariae Radix), Jiegeng (Platycodonis Radix) and Gancao (Glycyrrhizae Radix et Rhizoma), which regulated energy metabolism, choline metabolism, amino acid metabolism and gut flora disorder affected by realgar (As2S2) exposure. 23389738 Hepatotumorigenicity of ethyl tertiary-butyl ether with 2-year inhalation exposure in F344 rats. Carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined with inhalation exposure using F344/DuCrlCrlj rats. Groups of 50 male and 50 female rats, 6 week old at commencement, were exposed to ETBE at 0, 500, 1,500 or 5,000 ppm (v/v) in whole-body inhalation chambers for 6 h/day, 5 days/week for 104 weeks. A significant increase in the incidence of hepatocellular adenomas was indicated in males exposed at 5,000 ppm, but not in females at any concentration. In addition, significantly increased incidences of eosinophilic and basophilic cell foci were observed in male rats at 5,000 ppm. Regarding non-neoplastic lesions, rat-specific changes were observed in kidney, with an increase in the severity of chronic progressive nephropathy in both sexes at 5,000 ppm. Increased incidences of urothelial hyperplasia of the pelvis were observed at 1,500 ppm and above, and mineral deposition was apparent in the renal papilla at 5,000 ppm in males. There were no treatment-related histopathological changes observed in any other organs or tissues in either sex. The present 2-year inhalation study demonstrated hepatotumorigenicity of ETBE in male, but not in female rats. 23225770 Biocompatible fibrous networks of cellulose nanofibres and collagen crosslinked using genipin: potential as artificial ligament/tendons. Bio-based fibrous nanocomposites of cellulose nanofibres and non-crosslinked/crosslinked collagen were prepared by in situ pH-induced fibrillation of collagen phase and sterilized using gamma rays at 25 KGy. Collagen phase is crosslinked using genipin, a bio-based crosslinker that introduces flexible crosslinks. Microscopy studies of the prepared materials showed nanostructured fibrous collagen and cellulose dispersed in collagen matrix. Mechanical performance of the sterilized nanocomposites was close to that of natural ligament and tendon, in simulated body conditions. Cytocompatibility studies indicated that these nanocomposites allowed human ligament cell and human endothelial cell adhesion, growth, and differentiation; which is eminently favourable to ligament tissue engineering. 23570269 Modular stitching to image single-molecule DNA transport. For study of time-dependent conformation, all previous single-molecule imaging studies of polymer transport involve fluorescence labeling uniformly along the chain, which suffers from limited resolution due to the diffraction limit. Here we demonstrate the concept of submolecular single-molecule imaging with DNA chains assembled from DNA fragments such that a chain is labeled at designated spots with covalently attached fluorescent dyes and the chain backbone with dyes of different color. High density of dyes ensures good signal-to-noise ratio to localize the designated spots in real time with nanometer precision and prevents significant photobleaching for long-time tracking purposes. To demonstrate usefulness of this approach, we image electrophoretic transport of λ-DNA through agarose gels. The unexpected pattern is observed that one end of each molecule tends to stretch out in the electric field while the other end remains quiescent for some time before it snaps forward and the stretch-recoil cycle repeats. These features are neither predicted by prevailing theories of electrophoresis mechanism nor detectable by conventional whole-chain labeling methods, which demonstrate pragmatically the usefulness of modular stitching to reveal internal chain dynamics of single molecules. 23511973 The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing. Despite progress in mechanistic understanding of the RNA interference (RNAi) pathways, the subcellular sites of RNA silencing remain under debate. Here we show that loading of lipid-transfected siRNAs and endogenous microRNAs (miRNA) into RISC (RNA-induced silencing complexes), encounter of the target mRNA, and Ago2-mediated mRNA slicing in mammalian cells are nucleated at the rough endoplasmic reticulum (rER). Although the major RNAi pathway proteins are found in most subcellular compartments, the miRNA- and siRNA-loaded Ago2 populations co-sediment almost exclusively with the rER membranes, together with the RISC loading complex (RLC) factors Dicer, TAR RNA binding protein (TRBP) and protein activator of the interferon-induced protein kinase (PACT). Fractionation and membrane co-immune precipitations further confirm that siRNA-loaded Ago2 physically associates with the cytosolic side of the rER membrane. Additionally, RLC-associated double-stranded siRNA, diagnostic of RISC loading, and RISC-mediated mRNA cleavage products exclusively co-sediment with rER. Finally, we identify TRBP and PACT as key factors anchoring RISC to ER membranes in an RNA-independent manner. Together, our findings demonstrate that the outer rER membrane is a central nucleation site of siRNA-mediated RNA silencing. 23553655 Treatment-, Patient-, and Disease-Related Factors and the Emergence of Adverse Events with Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia. Four breakpoint cluster region (BCR)-ABL1 tyrosine kinase inhibitors (TKIs) are currently available for the treatment of chronic myeloid leukemia (CML): imatinib, nilotinib, dasatinib, and bosutinib. Choosing the most appropriate TKI requires clinicians to consider a host of patient-, disease-, and treatment-related factors, not the least of which include the safety profiles of the agents. This review discusses the potential impact of treatment-, patient-, and disease-related characteristics on the emergence of adverse events during TKI therapy, with a focus on the underlying mechanisms believed to be responsible for a number of important adverse events associated with these agents and what implications they may have for treatment choice, particularly in the setting of first-line treatment. A literature search of the PubMed database was conducted to identify articles that described the molecular mechanisms of BCR-ABL1-mediated leukemic transformation, the efficacy and safety of imatinib, nilotinib, dasatinib, and bosutinib in patients with CML, the kinase-binding spectrum of each TKI, and evidence suggesting a link between the TKI-binding profile and adverse events. The pattern of adverse events associated with each agent is important when selecting treatment with a TKI. Clinical studies suggest that imatinib, nilotinib, dasatinib, and bosutinib have differing safety profiles, which are in part attributable to the specificity and selectivity of each agent. Although much basic research must be conducted to further illuminate the mechanisms responsible for TKI-related adverse events, on- and off-target effects are believed to be at least partly responsible for cardiovascular toxicity, myelosuppression, fluid retention, gastrointestinal toxicity, and dermatologic toxicity. Increased understanding of the factors that affect TKI-associated adverse events and long-term safety data will enable a more informed approach to the selection of therapy best suited to the individual needs of patients with CML. 23401244 EFFECT OF C60 FULLERENES ON THE ACCUMULATION OF WEATHERED p,p'-DDE BY PLANT AND EARTHWORM SPECIES UNDER SINGLE AND MULTISPECIES CONDITIONS. The use of engineered nanomaterials has increased dramatically in recent years, but an understanding of nanomaterial fate and effects in the environment is lacking. In particular, the interaction of nanomaterials with coexisting organic contaminants and the subsequent implications for sensitive biota is almost completely unknown. Here, the effect of C60 fullerenes on the accumulation of weathered dichlorodiphenyldichloroethylene (p,p'-DDE; DDT metabolite) by Cucurbita pepo (pumpkin) and Eisenia fetida (earthworm) was determined under single and multispecies conditions. The plants, in the presence or absence of earthworms, were grown in soil containing weathered DDE (200 ng/g) and 0 or 1,670 mg/kg C60 fullerenes. Plants and earthworms were added either simultaneously or sequentially (earthworms after plants). Neither DDE nor C60 had an impact on survival or biomass of plants and earthworms, although fullerenes significantly decreased (29.6-39.0%) the relative root mass. Under single or multispecies conditions, C60 had little impact on DDE bioaccumulation by either species. The DDE concentrations in non-fullerene-exposed shoots, roots, and earthworms were 181, 7,400, and 8,230 ng/g, respectively. On fullerene exposure, the DDE content was nonsignificantly lower at 163, 7280, and 7540 ng/g, respectively. In the presence of the earthworms, C60 significantly decreased the shoot DDE content (28.6%), but no impact on root concentrations was observed. Root DDE content was unaffected by the presence of fullerenes and decreased by 21.6 to 37.5% during coexposure with earthworms. Earthworm DDE content was decreased by plant presence. Earthworms added to soils after plant harvest accumulated more DDE but were unaffected by the C60 exposure. Additional work is necessary, but these findings suggest that fullerenes may have minimal impact on the bioaccumulation of weathered cocontaminants in soil. Environ. Toxicol. Chem. 2013;32:1117-1123. © 2013 SETAC. 22813628 Dose response analysis of monophthalates in the murine embryonic stem cell test assessed by cardiomyocyte differentiation and gene expression. The embryonic stem cell test (EST) is based on compound-induced inhibition of cardiomyocyte differentiation of pluripotent stem cells. We examined the use of transcriptomics to assess concentration-effect relationships and performed potency ranking within a chemical class. Three embryotoxic phthalate monoesters, monobutyl phthalate (MBuP), monobenzyl phthalate (MBzP) and mono-(2-ethylhexyl) phthalate (MEHP) and the non-embryotoxic monomethyl phthalate (MMP) were studied for their effects on gene expression. Effects on gene expression were observed at concentrations that did not inhibit cardiomyocyte differentiation or induce cytotoxicity. The embryotoxic phthalate monoesters altered the expression of 668 commonly expressed genes in a concentration-dependent fashion. The same potency ranking was observed for morphology and gene expression (MEHP>MBzP>MBuP>MMP). These results indicate that integrating transcriptomics provides a sensitive method to measure the dose-dependent effects of phthalate monoester exposure and enables potency ranking based on a common mode of action within a class of compounds. Transcriptomic approaches may improve the applicability of the EST, in terms of sensitivity and specificity. 23315496 Effect of the purinergic inhibitor oxidized ATP in a model of islet allograft rejection. The lymphocytic ionotropic purinergic P2X receptors (P2X1R-P2X7R, or P2XRs) sense ATP released during cell damage-activation, thus regulating T-cell activation. We aim to define the role of P2XRs during islet allograft rejection and to establish a novel anti-P2XRs strategy to achieve long-term islet allograft function. Our data demonstrate that P2X1R and P2X7R are induced in islet allograft-infiltrating cells, that only P2X7R is increasingly expressed during alloimmune response, and that P2X1R is augmented in both allogeneic and syngeneic transplantation. In vivo short-term P2X7R targeting (using periodate-oxidized ATP [oATP]) delays islet allograft rejection, reduces the frequency of Th1/Th17 cells, and induces hyporesponsiveness toward donor antigens. oATP-treated mice displayed preserved islet grafts with reduced Th1 transcripts. P2X7R targeting and rapamycin synergized in inducing long-term islet function in 80% of transplanted mice and resulted in reshaping of the recipient immune system. In vitro P2X7R targeting using oATP reduced T-cell activation and diminished Th1/Th17 cytokine production. Peripheral blood mononuclear cells obtained from long-term islet-transplanted patients showed an increased percentage of P2X7R(+)CD4(+) T cells compared with controls. The beneficial effects of oATP treatment revealed a role for the purinergic system in islet allograft rejection, and the targeting of P2X7R is a novel strategy to induce long-term islet allograft function. 23633219 Structure-Based DNA-Targeting Strategies with Small Molecule Ligands for Drug Discovery. Nucleic acids are the molecular targets of many clinical anticancer drugs. However, compared with proteins, nucleic acids have traditionally attracted much less attention as drug targets in structure-based drug design, partially because limited structural information of nucleic acids complexed with potential drugs is available. Over the past several years, enormous progresses in nucleic acid crystallization, heavy-atom derivatization, phasing, and structural biology have been made. Many complicated nucleic acid structures have been determined, providing new insights into the molecular functions and interactions of nucleic acids, especially DNAs complexed with small molecule ligands. Thus, opportunities have been created to further discover nucleic acid-targeting drugs for disease treatments. This review focuses on the structure studies of DNAs complexed with small molecule ligands for discovering lead compounds, drug candidates, and/or therapeutics. 23042730 Tumor necrosis factor-alpha potentiates the cytotoxicity of amiodarone in Hepa1c1c7 cells: roles of caspase activation and oxidative stress. Amiodarone (AMD), a class III antiarrhythmic drug, causes idiosyncratic hepatotoxicity in human patients. We demonstrated previously that tumor necrosis factor-alpha (TNF-α) plays an important role in a rat model of AMD-induced hepatotoxicity under inflammatory stress. In this study, we developed a model in vitro to study the roles of caspase activation and oxidative stress in TNF potentiation of AMD cytotoxicity. AMD caused cell death in Hepa1c1c7 cells, and TNF cotreatment potentiated its toxicity. Activation of caspases 9 and 3/7 was observed in AMD/TNF-cotreated cells, and caspase inhibitors provided minor protection from cytotoxicity. Intracellular reactive oxygen species (ROS) generation and lipid peroxidation were observed after treatment with AMD and were further elevated by TNF cotreatment. Adding water-soluble antioxidants (trolox, N-acetylcysteine, glutathione, or ascorbate) produced only minor attenuation of AMD/TNF-induced cytotoxicity and did not influence the effect of AMD alone. On the other hand, α-tocopherol (TOCO), which reduced lipid peroxidation and ROS generation, prevented AMD toxicity and caused pronounced reduction in cytotoxicity from AMD/TNF cotreatment. α-TOCO plus a pancaspase inhibitor completely abolished AMD/TNF-induced cytotoxicity. In summary, activation of caspases and oxidative stress were observed after AMD/TNF cotreatment, and caspase inhibitors and a lipid-soluble free-radical scavenger attenuated AMD/TNF-induced cytotoxicity. 23577701 New dipyranocoumarin from the leaves of Calophyllum apetalum Willd. A new dipyranocoumarin, α-hydroxytomentolide A (1) was isolated from the leaves of Calophyllum apetalum together with the known compounds friedelin (2), apetalactone (3), inophyllum C (4) and canophyllol (5). The structure of the new compound was established by spectroscopic studies which include (1)H NMR, (13)C NMR, NOESY, HetCOSY, COLOC experiments and single crystal X-ray diffraction analysis. 23606243 Hydrothermal Growth of TiO2 Nanorod Arrays and In Situ Conversion to Nanotube Arrays for Highly Efficient Quantum Dot-Sensitized Solar Cells. TiO2 nanorod (NR) and nanotube (NT) arrays grown on transparent conductive substrates are attractive electrode for solar cells. In this paper, TiO2 NR arrays are hydrothermally grown on FTO substrate, and are in situ converted into NT arrays by hydrothermally etching. The TiO2 NR arrays are reported as single crystalline, but the TiO2 NR arrays are demonstrated to be polycrystalline with a bundle of 2-5 nm single crystalline nanocolumns grown along [001] throughout the whole NR from bottom to top. TiO2 NRs can be converted to NTs by hydrothermal selective etching of the (001) core and remaining the inert sidewall of (110) face. A growth mechanism of the NR and NT arrays is proposed. Quantum dot-sensitized solar cells (QDSCs) are fabricated by coating CdSe QDs on to the TiO2 arrays. After conversion from NRs to NTs, more QDs can be filled in the NTs and the energy conversion efficiency of the QDSCs almost double. 23617279 Carbon Xerogel Microspheres and Monoliths from Resorcinol-Formaldehyde Mixtures with Varying Dilution Ratios: Preparation, Surface Characteristics, and Electrochemical Double-Layer Capacitances. Carbon xerogels in the form of microspheres and monoliths were obtained from the sol-gel polymerization of resorcinol and formaldehyde in the presence of potassium carbonate as catalyst, using water as solvent and two different molar dilution ratios. The objectives of this study were as follows: to investigate the effect of the dilution ratio, polymerization reaction time, and temperature on the rheological properties of the sols used to prepare the carbon xerogel microspheres and monoliths; and to determine the influence of their preparation methods and shapes on their surface characteristics and electrochemical double-layer (EDL) capacitance. An increase in the molar dilution ratio produced a decrease in the apparent activation energy of the sol-gel transition. Carbon xerogel microspheres were steam-activated at different burnoff percentages. The morphology, surface area, porosity, and surface chemistry of samples were determined. The main difference between the carbon xerogel microspheres and monoliths was that the latter are largely mesoporous. Better electrochemical behavior was shown by carbon xerogels in monolith than in microsphere form, but higher gravimetric and volumetric capacitances were found in activated carbon xerogel microspheres than in carbon xerogel monoliths. 23443408 In vivo evaluation of the interaction between titanium dioxide nanoparticle and rat liver DNA. Titanium dioxide nanoparticles (TiO2 NPs) are massively produced and widely used in daily life, which may pose potential risk to human health via uncharacterized interaction between DNAs. This research aims to examine the interaction between DNA and three types of TiO2 NPs of different sizes and crystallines. The interaction between TiO2 NPs and liver DNA molecules obtained from Sprague-Dawley rats was systematically evaluated in vivo using atomic force microscopy, transmission electron microscopy, various spectroscopic techniques and gel electrophoresis. We found that TiO2 NPs (diameter <25 nm and <100 nm) in anatase crystalline can covalently interact with liver DNA by either inserting itself in between DNA base pairs or binding to DNA nucleotide via P-O-Ti-O bond. Such interaction may not be NP size-dependent but may be crystalline phase-dependent, because such interaction did not occur in rutile crystal phase, in which the DNA damage was potentially caused by reactive oxygen species. 23480697 Predicting ligand binding modes from neural networks trained on protein-ligand interaction fingerprints. We herewith present a novel approach to predict protein-ligand binding modes from the single two-dimensional structure of the ligand. Known protein-ligand X-ray structures were converted into binary bit strings encoding protein-ligand interactions. An artificial neural network was then set up to first learn and then predict protein-ligand interaction fingerprints from simple ligand descriptors. Specific models were constructed for three targets (CDK2, p38-α, HSP90-α) and 146 ligands for which protein-ligand X-ray structures are available. These models were able to predict protein-ligand interaction fingerprints and to discriminate important features from minor interactions. Predicted interaction fingerprints were successfully used as descriptors to discriminate true ligands from decoys by virtual screening. In some but not all cases, the predicted interaction fingerprints furthermore enable to efficiently rerank cross-docking poses and prioritize the best possible docking solutions. 23459233 Comparative Analysis of the Symbiotic Efficiency of Medicago truncatula and Medicago sativa under Phosphorus Deficiency. Phosphorus (P)-deficiency is a major abiotic stress that limits legume growth in many types of soils. The relationship between Medicago and Sinorhizobium, is known to be affected by different environmental conditions. Recent reports have shown that, in combination with S. meliloti 2011, Medicago truncatula had a lower symbiotic efficiency than Medicago sativa. However, little is known about how Medicago-Sinorhizobium is affected by P-deficiency at the whole-plant level. The objective of the present study was to compare and characterize the symbiotic efficiency of N2 fixation of M. truncatula and M. sativa grown in sand under P-limitation. Under this condition, M. truncatula exhibited a significantly higher rate of N2 fixation. The specific activity of the nodules was much higher in M. truncatula in comparison to M. sativa, partially as a result of an increase in electron allocation to N2 versus H+. Although the main organic acid, succinate, exhibited a strong tendency to decrease under P-deficiency, the more efficient symbiotic ability observed in M. truncatula coincided with an apparent increase in the content of malate in its nodules. Our results indicate that the higher efficiency of the M. truncatula symbiotic system is related to the ability to increase malate content under limited P-conditions. 23497878 The influence of Goishi tea on adipocytokines in obese mice. This study investigated the influence of Goishi-tea on visceral fat weight in induced obese mice. Mice were divided into two main groups, normal and obesity. In obesity group, mice were fed with high-fat diet. Goishi-tea including its fractions (ethyl-acetate layer and water layer) was administrated in normal and obesity three sub-groups. Results showed no influence of Goishi-tea in normal group. However, visceral fat weight, size of adipose cell and cholesterol level were significantly decreased in obesity group fed Goishi-tea compared to control group. Moreover, adiponectin levels tended to increase and adipocytokines has significant values lower in obesity group fed Goishi-tea compared to control group. Interestingly, Goishi tea involved in the high-fat diet induced-obese mice can inhibit fat accumulation and maintain adiponectins without increasing tumor necrosis factor-alpha and interleukin-6. It would be beneficial for the prevention of metabolic syndrome and obesity-related disorder. 23545806 In Vitro Metabolism and Kinetics Studies on Methylone. Abuse of the stimulant designer drug methylone (methylenedioxymethcathinone) has been documented in most parts of the world. As with many of the new designer drugs that continuously appear in the illicit drug market, little is known about the pharmacokinetics of methylone. Using in vitro studies, CYP2D6 was determined to be the primary enzyme that metabolizes methylone, with minor contributions from CYP1A2, CYP2B6, and CYP2C19. The major metabolite was identified as dihydroxymethcathinone, and the minor metabolites were N-hydroxy-methylone, nor-methylone, and dihydro-methylone. Measuring the formation of the major metabolite, biphasic Michaelis-Menten kinetic parameters were determined: Vmax,1 = 0.046 ± 0.005 (S.E.) nmol/min/mg protein, Km,1 = 19.0 ± 4.2 μM, Vmax,2 = 0.22 ± 0.04 nmol/min/mg protein, and Km,2 = 1953 ± 761 μM; the low-capacity and high-affinity contribution was assigned to the activity of CYP2D6. Additionally, a time-dependent loss of CYP2D6 activity was observed when the enzyme was preincubated with methylone, reaching a maximum rate of inactivation at high methylone concentrations, indicating that methylone is a mechanism-based inhibitor of CYP2D6. The inactivation parameters were determined to be KI = 15.1 ± 3.4 (S.E) μM and kinact = 0.075 ± 0.005 min(-1). 23063002 Biomarkers in marine mussels, Mytilus galloprovincialis, exposed to environmentally relevant levels of the pesticides, chlorpyrifos and penoxsulam. The present study examines the influence of environmentally relevant concentrations of two pesticides, chlorpyrifos and penoxsulam on mussel physiological status. For this reason, lysosomal membrane stability (LMS), reactive oxygen species (ROS), DNA damage, protein carbonylation (PCC) and antioxidant capacity (TAC) in hemaolymph and hemocytes of the mussels was measured. Mussels were exposed to a range of concentrations of the pesticides chlorpyrifos and penoxsulam and the response of animals to the destabilization of lysosomal membrane in hemocytes (LMS) was studied. Subsequently, the half maximal effective concentration (EC50) for both pesticides was calculated. The animals were subsequently exposed for 0, 1, 3, 5, 7, 15 and 30 days to 10 times less concentration than EC50 of each pesticide (0.05 μg/l) and changes in LMS, ROS, DNA damage, protein carbonylation and antioxidant capacity of mussels was evaluated. Our results showed a significant change in the response of mussels for all parameters tested after 30 days exposure, in relation to the controls. The pesticides at the environmental concentrations used induced changes to the animal physiology through causing oxidative stress and lysosomal abnormalities and their usage in the agriculture demands great care. In addition, the results show that ROS, DNA damage, protein carbonylation and antioxidant capacity could constitute, after further investigation, reliable biomarkers for the evaluation of pollution or other environmental stressors. 23612708 Noncanonical NF-κB Activation by the Oncoprotein Tio Occurs Through a Nonconserved TRAF3-Binding Motif. Members of the nuclear factor κB (NF-κB) family of transcription factors regulate many cellular functions. Activation of NF-κB signaling is commonly classified as occurring through canonical or noncanonical pathways. Most NF-κB-inducing stimuli, including the viral oncoprotein Tio, lead to a concerted activation of both NF-κB pathways; however, extensive crosstalk at multiple levels between these signaling cascades restricts the ability to discriminate between the canonical and the noncanonical effects. We showed that noncanonical NF-κB activation by Tio depends on a distinct sequence motif that directly recruits tumor necrosis factor receptor-associated factor 3 (TRAF3). Through its TRAF3-binding motif, Tio triggered a ubiquitin-independent depletion of TRAF3 from the cytosol, which prevented TRAF3 from inhibiting signaling through the noncanonical NF-κB cascade. Furthermore, the Tio-TRAF3 interaction did not affect components of the canonical NF-κB signaling pathway or the expression of target genes; thus, Tio induced noncanonical NF-κB independently of crosstalk with the canonical pathway. Together, these data identify a distinct molecular mechanism of noncanonical NF-κB activation that should enable studies into the particular functions of this pathway. 23410168 Rationally designed multitarget anticancer agents. Balanced modulation of multiple targets is an attractive therapeutic strategy in treating complex diseases including cancer. Comparing with drugs combination, single molecule modulating desirable multiple targets has advantages in pharmacokinetic and pharmacodynamics. Different from previous reviews, we provided an overview of reported multitarget antitumor agents from the viewpoint of pharmacophores. These multitarget antitumor agents were designed by combination of pharmacophores or by high-throughput screening plus structural modification, which were exemplified by the privileged pharmacophore quinazoline and several other popular pharmacophores, including phenylaminopyrimidine, anthracycline and naphthalimide. Previous research demonstrated the importance of in-depth validation against multiple targets not only in cell-free system, but also in cancer cells. Furthermore, the multitarget compounds were also effective for resistance cell lines which highlighted their antitumor potency in the era of increasing drug resistance in cancer patients. 23210788 Green factories for biopharmaceuticals. Plants and plant cells have been used to produce many diverse and valuable recombinant proteins, including subunit vaccines, antibodies and antibody fragments, hormones, blood products, cytokines and enzymes. Different plant species and platforms have been explored as production hosts, each with unique properties in terms of production timescales, environmental containment, scalability, downstream processing strategy and overall costs. Whole plants are suitable for the economical and safe production of recombinant proteins on a large scale, providing unique advantages for pharmaceutical proteins that are required in large amounts and normally too expensive for conventional manufacturing processes. Seed-based systems have additional advantages because they exploit the natural storage properties of seeds to facilitate batch processing and distribution. The stabilizing effect of seeds after harvest allows recombinant subunit vaccines and antibodies to be delivered via the mucosal route as they are better able to withstand the harsh microenvironment when protected by the plant matrix. Although the differences between plant and human N-glycans were initially thought to limit the therapeutic potential of plant-derived glycoproteins, several such products have now been tested in the clinic and in some cases the presence of plant glycans has been turned into an advantage because they improve the performance of the protein or confer unique characteristics. In this review we discuss recent case studies of recombinant pharmaceuticals produced in plants to demonstrate the versatility and unique advantages of molecular farming and the bottlenecks that remain to be addressed. 23414252 Evidence of dynamical constraints imposed by water organization around a bio-hydrophobic interface. Molecular dynamics simulations and elastic neutron scattering experiments have been used to highlight how the structural organization of hydration water is able in some cases to locally constrain atomic movements at biologic interfaces. Using fully hydrated small peptides as models of protein interfaces, we show that the length of the side chains and the hydrophilic backbone have specific signatures. The dynamics of the side chain, which is part of biomolecules, have not only a crucial role in the whole flexibility as compared to the backbone, but also modify the values of transition temperatures. The analysis of the activation energies of methyl group dynamics suggests that the interaction between hydrophobic side chain and surrounding water plays an important role in the whole flexibility as well. We suggest that the progressive water cluster organization, around hydrophobic interfaces increases the activation energy and that a plateau regime is reached only when an extended hydrogen-bond network is established. The cluster size corresponds to a single layer of water molecules. 23373444 Metal-enzyme frameworks: role of metal ions in promoting enzyme self-assembly on α-zirconium(IV) phosphate nanoplates. Previously, an ion-coupled protein binding (ICPB) model was proposed to explain the thermodynamics of protein binding to negatively charged α-Zr(IV) phosphate (α-ZrP). This model is tested here using glucose oxidase (GO) and met-hemoglobin (Hb) and several cations (Zr(IV), Cr(III), Au(III), Al(III), Ca(II), Mg(II), Zn(II), Ni(II), Na(I), and H(I)). The binding constant of GO with α-ZrP was increased ∼380-fold by the addition of either 1 mM Zr(IV) or 1 mM Ca(II), and affinities followed the trend Zr(IV) ≃ Ca(II) > Cr(III) > Mg(II) ≫ H(I) > Na(I). Binding studies could not be conducted with Au(III), Al(III), Zn(II), Cu(II), and Ni(II), as these precipitated both proteins. Zr(IV) increased Hb binding constant to α-ZrP by 43-fold, and affinity enhancements followed the trend Zr(IV) > H(I) > Mg(II) > Na(I) > Ca(II) > Cr(III). Zeta potential studies clearly showed metal ion binding to α-ZrP and affinities followed the trend, Zr(IV) ≫ Cr(III) > Zn(II) > Ni(II) > Mg(II) > Ca(II) > Au(III) > Na(I) > H(I). Electron microscopy showed highly ordered structures of protein/metal/α-ZrP intercalates on micrometer length scales, and protein intercalation was also confirmed by powder X-ray diffraction. Specific activities of GO/Zr(IV)/α-ZrP and Hb/Zr(IV)/α-ZrP ternary complexes were 2.0 × 10(-3) and 6.5 × 10(-4) M(-1) s(-1), respectively. While activities of all GO/cation/α-ZrP samples were comparable, those of Hb/cation/α-ZrP followed the trend Mg(II) > Na(I) > H(I) > Cr(III) > Ca(II) ≃ Zr(IV). Metal ions enhanced protein binding by orders of magnitude, as predicted by the ICPB model, and binding enhancements depended on charge as well as the phosphophilicity/oxophilicity of the cation. 23535167 Methionine salvage and S-adenosylmethionine: essential links between sulfur, ethylene and polyamine biosynthesis. Both Met (methionine) and SAM (S-adenosylmethionine), the activated form of Met, participate in a number of essential metabolic pathways in plants. The subcellular compartmentalization of Met fluxes will be discussed in the present review with respect to regulation and communication with the sulfur assimilation pathway, the network of the aspartate-derived amino acids and the demand for production of SAM. SAM enters the ethylene, nicotianamine and polyamine biosynthetic pathways and provides the methyl group for the majority of methylation reactions required for plant growth and development. The multiple essential roles of SAM require regulation of its synthesis, recycling and distribution to sustain these different pathways. A particular focus of the present review will be on the function of recently identified genes of the Met salvage cycle or Yang cycle and the importance of the Met salvage cycle in the metabolism of MTA (5'-methylthioadenosine). MTA has the potential for product inhibition of ethylene, nicotianamine and polyamine biosynthesis which provides an additional link between these pathways. Interestingly, regulation of Met cycle genes was found to differ between plant species as shown for Arabidopsis thaliana and Oryza sativa. 23525118 Single-molecule surface-enhanced Raman spectroscopy: a perspective on the current status. This perspective presents an overview of single-molecule surface-enhanced Raman scattering (sm-SERS). Our overview is organized as a brief theoretical background, discussion of the factors that enhance SERS, various experimental preparations for inserting a single molecule in a hot spot, recent sm-SERS experiments, and a perspective. Although, there have been numerous review papers on sm-SERS, we mainly concentrated on the logical development of sm-SERS on the basis of the fundamental concepts and their physical significance, so that readers outside this field can understand the motivation and the underlying physics when describing current sm-SERS measurements. Indeed, understanding such current sm-SERS experiments conducted by representative groups would be very helpful for readers to answer for themselves the fundamental and practical questions surrounding sm-SERS: (1) what information can sm-SERS provide? (2) Which factors based on the SERS mechanism should be considered to significantly amplify the SERS signal? (3) What kinds of related microscopy techniques could be combined with sm-SERS to attain more meaningful results? (4) Which statistical approaches can be used and how they can be applied to properly analyze sm-SERS data? We hope that this review article can help readers answer these questions. 23620060 Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding. AIMS/HYPOTHESIS: While it is well known that diet-induced obesity causes insulin resistance, the precise mechanisms underpinning the initiation of insulin resistance are unclear. To determine factors that may cause insulin resistance, we have performed a detailed time-course study in mice fed a high-fat diet (HFD). METHODS: C57Bl/6 mice were fed chow or an HFD from 3 days to 16 weeks and glucose tolerance and tissue-specific insulin action were determined. Tissue lipid profiles were analysed by mass spectrometry and inflammatory markers were measured in adipose tissue, liver and skeletal muscle. RESULTS: Glucose intolerance developed within 3 days of the HFD and did not deteriorate further in the period to 12 weeks. Whole-body insulin resistance, measured by hyperinsulinaemic-euglycaemic clamp, was detected after 1 week of HFD and was due to hepatic insulin resistance. Adipose tissue was insulin resistant after 1 week, while skeletal muscle displayed insulin resistance at 3 weeks, coinciding with a defect in glucose disposal. Interestingly, no further deterioration in insulin sensitivity was observed in any tissue after this initial defect. Diacylglycerol content was increased in liver and muscle when insulin resistance first developed, while the onset of insulin resistance in adipose tissue was associated with increases in ceramide and sphingomyelin. Adipose tissue inflammation was only detected at 16 weeks of HFD and did not correlate with the induction of insulin resistance. CONCLUSIONS/INTERPRETATION: HFD-induced whole-body insulin resistance is initiated by impaired hepatic insulin action and exacerbated by skeletal muscle insulin resistance and is associated with the accumulation of specific bioactive lipid species. 23588796 Fluctuation analysis of an organic semiconductor-insulator interface. The space-charge region of an organic semiconductor (OS)-insulator interface is probed by analyzing the spontaneous, thermally driven drain current fluctuations of a field-effect transistor in which the OS forms the gate electrode. This so called "excess drain current noise" is the outcome of local fluctuations of the Fermi level, resulting from stochastic exchange of electrons between traps near the Fermi level. The power spectral density of this noise is characteristic of a Lorentzian process with a distribution of time constants, which is attributed to the disorder in the OS film. Furthermore, this disorder leads to local inhomogeneity of the work function in the film and a finite correlation length of the work function fluctuations. The measurement of work function noise is only possible within a correlation length of the OS-insulator interface. Through systematic variation of gate voltage, primary doping and secondary doping levels, the correlation length, disorder, and the trapping/de-trapping time constant are examined on polyaniline as a representative OS. A model is proposed for local work function variations and spontaneous charge-carrier fluctuations within polyaniline films with consequences for organic electronics using organic semiconductors. 23561093 Influence of air-drying temperature on drying kinetics, colour, firmness and biochemical characteristics of Atlantic salmon (Salmo salar L.) fillets. In this work the drying kinetics of Atlantic salmon (Salmo salar L.) fillets and the influence of air drying temperature on colour, firmness and biochemical characteristics were studied. Experiments were conducted at 40, 50 and 60°C. Effective moisture diffusivity increased with temperature from 1.08×10(-10) to 1.90×10(-10)m(2)s(-1). The colour difference, determined as ΔE values (from 9.3 to 19.3), as well as firmness (from 25 to 75Nmm(-1)) of dried samples increased with dehydration temperature. The lightness value L(∗) and yellowness value b(∗) indicated formation of browning products at higher drying temperatures, while redness value a(∗) showed dependence on astaxanthin value. Compared with fresh fish samples, palmitic acid and tocopherol content decreased in a 20% and 40%, respectively, with temperature. While eicosapentaenoic acid (EPA) content remained unchanged and docosahexaenoic acid (DHA) content changed slightly. Anisidine and thiobarbituric acid values indicated the formation of secondary lipid oxidation products, which is more relevant for longer drying time than for higher drying temperatures. 23229511 Aryl hydrocarbon receptor is a target of 17-Allylamino-17-demethoxygeldanamycin and enhances its anticancer activity in lung adenocarcinoma cells. We have demonstrated that aryl hydrocarbon receptor (AhR) is overexpressed in lung adenocarcinoma (AD). AhR is usually associated with heat shock protein 90 (Hsp90) in the cytoplasm. 17-Allylamino-17-demethoxygeldanamycin (17-AAG), an Hsp90 inhibitor, is currently under evaluation for its anticancer activity in clinical trials. Here we investigated whether AhR plays a role in 17-AAG-mediated anticancer activity by functioning as a downstream target or by modulating its anticancer efficacy. AhR expression in lung AD cells was modulated by siRNA interference or overexpression. Tumor growth was determined with colony formation in vitro or in vivo. Anticancer activity of 17-AAG was determined by measuring cell viability, cell cycle distribution, and expression of cell cycle regulators. Proteins and mRNA levels were examined by immunoblotting and the real-time reverse transcription-polymerase chain reaction, respectively. In this study, AhR overexpression positively modulated growth of lung AD cells, at least partially, via RelA-dependent mechanisms. Although treatment with 17-AAG reduced AhR levels and AhR-regulated gene expression in lung AD cells, AhR expression increased anticancer activity of 17-AAG. In addition, 17-AAG treatment reduced cell viability, CDK2, CDK4, cyclin E, cyclin D1, and phosphorylated Rb levels in AhR-expressing lung AD cells. NAD(P)H:quinone oxidoreductase (NQO1), which is regulated by AhR, was shown to increase anticancer activity of 17-AAG in cells. Knockdown of NQO1 expression attenuated the reduction of cell cycle regulators by 17-AAG treatment in AhR overexpressed cells. We demonstrated that AhR protein not only functions as a downstream target of 17-AAG, but also enhances anticancer activity of 17-AAG in lung AD cells. 23462194 In vitro evaluation of the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma. Anaplastic thyroid carcinoma (ATC) is a severe thyroid malignancy with poor prognosis, due to its early metastasis and unresponsiveness to both radiation and chemotherapy. Nevirapine, a non-nucleoside reverse transcriptase inhibitor, has been used as a re-differentiation agent to treat cancers in several human cancer models. So far, the effects of nevirapine on human thyroid anaplastic carcinoma cells have not been documented. The aim of this study was to evaluate the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma. Cell proliferation was determined by methly thiazolyl tetrazolium (MTT) assay. Cell apoptosis was analyzed by Hoechst 33258 staining. The mRNA expression of NIS and TSHR was determined by real-time quantitative reverse transcription-polymerase chain reaction (real time RT-PCR). Iodine uptake was determined by (125)I radioactivity assay. At all doses (100, 200, 350, 500μmol/L) tested, nevirapine significantly inhibited cell proliferation after 48h treatment. At high dose (500μmol/L), nevirapine significantly increased the percentage of apoptotic cells compared with control (P<0.01). At lower doses (200μmol/L and 350μmol/L), nevirapine did not induce cell apoptosis, but up-regulated NIS and THSR mRNA expression in a dose-dependent manner. In FRO cells pre-treated with nevirapine, the increase in NIS expression had no obvious effect on iodine uptake. These findings indicate that nevirapine has an anti-proliferative effect on FRO cells, which correlates with an induction of cell differentiation. 22310169 Seasonal variation in biomarkers in blue mussel (Mytilus edulis), Icelandic scallop (Chlamys islandica) and Atlantic cod (Gadus morhua): implications for environmental monitoring in the Barents Sea. In the Barents Sea, the limited data on biological relevant indicators and their responses to various anthropogenic stressors have hindered the development of a consistent scientific basis for selecting indicator species and developing practical procedures for environmental monitoring. Accordingly, the main aim of the present study was to develop a common set of baseline values for contaminants and biomarkers in three species, and to identify their strengths and limitations in monitoring of the Barents Sea. Blue mussel (Mytilus edulis), Icelandic scallop (Chlamys islandica) and Atlantic cod (Gadus morhua) were sampled from a north Norwegian fjord in March, June, September and December 2010. Digestive glands from the bivalve species and liver from Atlantic cod were analysed for biomarkers of oxidative stress (catalase [CAT], glutathione peroxidase [GPX], glutathione-S-transferase activities [GST], lipid peroxidation as thiobarbituric reactive substances [TBARS] and total oxyradical scavenging capacity [TOSC]), biotransformation (ethoxyresorufine-O-deethylase activity [EROD]) and general stress (lysosomal membrane stability [LMS]). Concentrations of polycyclic aromatic hydrocarbons (PAHs) and metals in the bivalves and PAH metabolites in fish bile were quantified. Finally, energy reserves (total lipids, proteins and carbohydrates) and electron transport system (ETS) activity in the digestive gland of the bivalves and liver of Atlantic cod provided background information for reproductive cycle and general physiological status of the organisms. Blue mussel and Icelandic scallop showed very similar trends in biological cycle, biomarker expression and seasonality. Biomarker baselines in Atlantic cod showed weaker seasonal variability. However, important biological events may have been undetected due to the large time intervals between sampling occasions. Physiological biomarkers such as energy reserves and ETS activity were recommended as complementary parameters to the commonly used stress biomarkers, as they provided valuable information on the physiological status of the studied organisms. Interpretation of the seasonality in oxidative stress biomarkers was in general difficult but TOSC and lipid peroxidation were preferred over the antioxidant enzyme activities. This study is the first reporting seasonal baseline in these three species in a sub-Arctic location. Overall, the Icelandic scallop was considered the most adequate organism for environmental monitoring in the Barents Sea due to the interpretability of the biomarker data as well as its abundance, ease to handle and wide distribution from the southern Barents Sea to Svalbard. 23416930 Autophagy in ageing and ageing-associated diseases. Autophagy is a cell self-digestion process via lysosomes that clears "cellular waste", including aberrantly modified proteins or protein aggregates and damaged organelles. Therefore, autophagy is considered a protein and organelle quality control mechanism that maintains normal cellular homeostasis. Dysfunctional autophagy has been observed in ageing tissues and several ageing-associated diseases. Lifespan of model organisms such as yeast, worms, flies, and mice can be extended through promoting autophagy, either by genetic manipulations such as over-expression of Sirtuin 1, or by administrations of rapamycin, resveratrol or spermidine. The evidence supports that autophagy may play an important role in delaying ageing or extending lifespan. In this review, we summarize the current knowledge about autophagy and its regulation, outline recent developments ie the genetic and pharmacological manipulations of autophagy that affects the lifespan, and discuss the role of autophagy in the ageing-related diseases. 23199983 Production of 1-lactulose and lactulose using commercial β-galactosidase from Kluyveromyces lactis in the presence of fructose. Production of 1-lactulose and lactulose using commercial β-galactosidase DSM Maxilact® 5000 in the presence of fructose was investigated. Experiments were performed at 40 °C and pH 7.5. Lactose starting concentration was constantly 250 g/l. A novel transgalactosylation product 1-lactulose was detected besides lactulose. Effects of fructose concentration, reaction time and enzyme concentration on transgalactosylation reactions were discussed. In all reactions, the yield ratio 1-lactulose:lactulose was close to 3:1 due to the regioselectivity of β-galactosidase. The maximum production of 1-lactulose and lactulose was approximately 22 and 8 g/l, respectively, when fructose concentration was increased to 100 g/l. Lactose hydrolysis was significantly retarded since fructose strongly attracted water molecules. Higher enzyme concentration can accelerate transgalactosylation reactions without affecting the maximum production of transgalactosylation products. Fructose was a more preferred galactosyl acceptor than lactose, since the synthesis of galactooligosacchairdes was found to be absolutely inhibited in the presence of fructose. 23523372 A Mammalian Pre-mRNA 5' End Capping Quality Control Mechanism and an Unexpected Link of Capping to Pre-mRNA Processing. Recently, we reported that two homologous yeast proteins, Rai1 and Dxo1, function in a quality control mechanism to clear cells of incompletely 5' end-capped messenger RNAs (mRNAs). Here, we report that their mammalian homolog, Dom3Z (referred to as DXO), possesses pyrophosphohydrolase, decapping, and 5'-to-3' exoribonuclease activities. Surprisingly, we found that DXO preferentially degrades defectively capped pre-mRNAs in cells. Additional studies show that incompletely capped pre-mRNAs are inefficiently spliced at all introns, a fact that contrasts with current understanding, and are also poorly cleaved for polyadenylation. Crystal structures of DXO in complex with substrate mimic and products at a resolution of up to 1.5Å provide elegant insights into the catalytic mechanism and molecular basis for their three apparently distinct activities. Our data reveal a pre-mRNA 5' end capping quality control mechanism in mammalian cells, indicating DXO as the central player for this mechanism, and demonstrate an unexpected intimate link between proper 5' end capping and subsequent pre-mRNA processing. 23335515 Scaffold effects on osteogenic differentiation of equine mesenchymal stem cells: an in vitro comparative study. The in vitro viability, osteogenic differentiation, and mineralization of four different equine mesenchymal stem cells (MSCs) from bone marrow, periosteum, muscle, and adipose tissue are compared, when they are cultured with different collagen-based scaffolds or with fibrin glue. The results indicate that bone marrow cells are the best source of MSCs for osteogenic differentiation, and that an electrochemically aggregated collagen gives the highest cell viability and best osteogenic differentiation among the four kinds of scaffolds studied. 22958332 Increased responses to the actions of fibroblast growth factor 21 on energy balance and body weight in a seasonal model of adiposity. The present study aimed to investigate the actions of fibroblast growth factor 21 (FGF21) on energy balance in a natural model of relative fatness, the Siberian hamster. Hamsters were studied under long days (LD) to promote weight gain, or short days to induce weight loss, and treated with rhFGF21 (3 mg/kg/day) via s.c. minipumps for 14 days. On days 7-9, detailed assessments of ingestive behaviour, metabolic gas exchange and locomotor activity were made. FGF21 caused substantial (P < 0.0001) weight loss in the fat LD state but not in the lean SD state: at the end of the study, FGF21-treated hamsters in LD lost 18% of body weight compared to vehicle controls, which is comparable to the natural body weight loss observed in SD. Epididymal fat pads, a correlate of total carcass fat content, were reduced by 19% in FGF21 treated hamsters in LD, whereas no difference was found in SD. Body weight loss in LD was associated with a reduction in food intake (P < 0.001) and a decreased respiratory exchange ratio (P < 0.001), indicating increased fat oxidation. Treatment with FGF21 maintained the normal nocturnal increase in oxygen consumption and carbon dioxide production into the early light phase in hamsters in LD, indicating increased energy expenditure, although locomotor activity was unaffected. These data suggest a greater efficacy of FGF21 in hamsters in LD compared to those in SD, which is consistent with both the peripheral and possibly central actions of FGF21 with respect to promoting a lean phenotype. The observed differences in FGF21 sensitivity may relate to day length-induced changes in adipose tissue mass. 23561158 A method for determining regioisomer abundances of polyunsaturated triacylglycerols in omega-3 enriched fish oils using reversed-phase liquid chromatography and triple-stage mass spectrometry. Reversed-phase high performance liquid chromatography (RP-HPLC), followed by post-column addition of lithium salts and electrospray ionisation triple-stage mass spectrometry (ESI-MS(3)) of lithiated TAG adducts, is shown to provide a useful method for the positional analysis of triacylglycerols (TAGs) in fish oils containing eicosapentaenoic (EPA, 20:5) and docosahexaenoic acids (DHA, 22:6). One prominent fragmentation pathway in the ESI-MS(3) of these adduct ions involves the loss of a fatty acid from the sn-1/3 position in the first step followed by the loss of an α,β-unsaturated fatty acid from the sn-2 position in the second. Regioisomeric TAGs of the type ABA and AAB produced abundant product ions - [ABA+Li-RACOOH-R'BCHCHCOOH](+) and [AAB+Li-RACOOH-R'ACHCHCOOH](+) - the relative intensities of which were dependent on the position of acyl substituents. Standard solutions of TAGs containing different ratios of the regioisomeric pairs MME/MEM, PPE/PEP, PPD/PDP, EEP/EPE and DDP/DPD (M=14:0, P=16:0, E=20:5, D=22:6) were analysed by ESI-MS(3) with a quadrupole linear ion trap instrument. Methodology developed on the standards was applied to quantifying the relative isomeric abundances of EPA and DHA in several fish oil samples. DHA was preferentially located at the sn-2 position in both DHA-containing TAGs studied, while EPA was either observed at near equal levels in all positions, or predominantly at the sn-1 and -3 positions in some cases. The analysis protocol allows for quantification of the designated regioisomers in one simple, rapid chromatographic procedure using a single column and has the advantage of specificity over other methods for the positional analysis of TAGs, since it eliminates interferences associated with co-eluting TAGs of the same molecular weight that yield isobaric diacylglycerol-like product ions. 23154127 Modulation of the cellular redox status by the Alternaria toxins alternariol and alternariol monomethyl ether. The mycotoxin alternariol (AOH) has been reported to possess genotoxic properties, inducing enhanced levels of DNA damage after only 1 h of incubation. In the present study we addressed the question whether the induction of oxidative stress might contribute to the genotoxic effects of AOH or its naturally occurring monomethylether (AME). In the dichlorofluorescein (DCF) assay, treatment of HT29 cells for 1 h enhanced the formation of dichlorofluorescein, indicative for ROS formation. The total glutathione (tGSH) was transiently decreased. In accordance with the results of the DCF assay, AOH and AME enhanced the proportion of the transcription factor Nrf2 in the nucleus. Concomitantly, the Nrf2/ARE-dependent genes γ-glutamylcysteine ligase (γ-GCL) and glutathione-S-transferase (GSTA1/2) showed enhanced transcript levels. After 24 h of incubation this effect was also reflected on the protein level by an increase of GST activity. However, in spite of the positive DCF assay and the activation of the redox-sensitive Nrf2/ARE-pathway, the level of oxidative DNA damage, measured in the comet assay by the addition of formamidopyrimidine-DNA-glycosylase (fpg) remained unaffected. Of note, after 3 h of incubation no significant DNA damaging potential of AOH and AME was detectable, indicating either inactivation of the compounds or enhanced DNA repair. In summary, the mycotoxins AOH and AME were found to modulate the redox balance of HT29 cells but without apparent negative effect on DNA integrity. 23603635 Non-peptidyl insulin mimetics as a potential antidiabetic agent. Insulin has an important role in the maintenance of blood sugar. It is the only available therapeutic agent for the treatment of type 1 diabetes mellitus and there is a dire need for an oral substitute. Different categories of compounds including mono and di substituted benzoquinones, vanadium based compounds and natural products have been reported to cause insulin-like effects either by increasing phosphorylation of insulin receptor (IR) or inhibiting the protein tyrosine phosphatases. This review summarizes the development of various insulin mimetics with special emphasis on their structure-activity relationships and various biological actions they produce. 23625745 Effectiveness of a Pharmacy Care Management Program for Veterans with Dyslipidemia. OBJECTIVE: To evaluate the effectiveness of a care management program provided by clinical pharmacists for veterans with dyslipidemia. DESIGN: Retrospective cohort design. SETTING: Two primary care clinics at a Veterans Affairs Medical Center. PATIENTS: An intervention (IT) cohort of 213 patients referred for management of dyslipidemia by clinical pharmacists and a control cohort of 219 patients with dyslipidemia receiving usual care (UC). METHODS: Data were obtained from electronic medical records regarding drug therapy, lipid levels, and patient characteristics. Using multivariable regression models to adjust for baseline characteristics, the primary analyses compared mean final measured values of low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides (TGs) among the IT and UC cohorts at the final follow-up visits. Secondary analyses compared the proportion of patients achieving National Cholesterol Education Program/Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP/ATPIII) concordant LDL goals and the time to achieve LDL goals between the two groups. RESULTS: Compared with the UC cohort, the adjusted difference in the mean final measured LDL for the IT cohort was -10.4 mg/dl (95% confidence interval [CI] -16.1 to -4.6, p < 0.001) and TC was -12.7 (95% CI -21.3 to -4.1, p=0.004). There were no significant differences in the adjusted mean final measured HDL or TGs between the two groups. The NCEP/ATPIII goal LDL was met in 80.3% of patients in the IT cohort and 65.3% of patients in the UC cohort (odds ratio [OR], 2.6; 95% CI 1.6-4.3, p<0.001). Time to achieve goal LDL was significantly shorter for the IT cohort compared with the UC cohort (risk ratio, 1.8; 95% CI 1.2-2.8, log-rank p=0.002). CONCLUSION: Veterans referred to a clinical pharmacist for treatment of dyslipidemia achieved significant reductions in TC and LDL. A greater proportion of patients achieved NCEP/ATPIII goal LDL, and the time to attainment of LDL goals was shorter in the pharmacist-managed cohort, supporting a continued role for pharmacy care management in the treatment of patients with dyslipidemia. 23068419 Methylparaben protects 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells and improved behavioral impairments in mouse model of Parkinson's disease. Parkinson's disease (PD) is a progressive neurodegenerative disorder of unknown etiology. Considerable evidence suggests that free radical formation and oxidative stress might play an important role in the pathogenesis of PD. In the present investigation we evaluated the therapeutic potential of methylparaben (MP) a well known pharmaceutical preservative against 6-hydroxydopamine (6-OHDA) neurotoxicity in SH-SY5Y cells and in a mouse model of PD. At nanomolar concentrations MP (0.01, 0.1 and 1 nM) significantly attenuated the 6-OHDA- and hydrogen peroxide-induced cytotoxicity in SH-SY5Y cells. The reactive oxygen species generated by 6-OHDA in SH-SY5Y cells was also inhibited by MP in a concentration dependent fashion. Further, intranigral damage induced by stereotaxically injecting 6-OHDA in mouse brain was significantly attenuated by MP treatment. MP (1, 10 or 50 μg/kg, i.p.) prevented apomorphine-induced rotational behavior and significantly improved motor deficits in 6-OHDA-lesioned mice. The cognitive impairments as evaluated by passive avoidance and Y-maze task in mice were also attenuated by MP concentration dependently. Immunohistochemical analysis of substantia nigra in MP treated mice showed significantly higher number of surviving tyrosine hydroxylase positive cells. Furthermore, MP also suppressed the lipid peroxidation products in 6-OHDA-lesioned mouse brain tissues. Considering the results obtained, the marked neuroprotection exhibited by MP might be attributed to its potent antioxidant property. In conclusion, this study reports the neuroprotective properties of MP in experimental models of PD for the first time and can be developed as a potential therapeutic agent. 23256445 Trigonelline ameliorates oxidative stress in type 2 diabetic Goto-Kakizaki rats. Previously, we showed that trigonelline (TRG) exerts antidiabetic effects in type 2 diabetic Goto-Kakizaki (GK) rats and also lowers blood and liver thiobarbituric acid reactive substances and urinary 8-hydroxydeoxyguanosine when compared with those levels in GK control rats without TRG. These results suggested that TRG also mitigates oxidative stress, which accelerates diabetes. In this study, the mechanisms of TRG prevention of oxidative stress were determined by measuring erythrocyte and liver antioxidant enzyme activities, and expressions of genes associated with reactive oxygen species production, and carbohydrate and lipid metabolisms by DNA microarray. Erythrocyte and liver glutathione peroxidase, and liver catalase activities in the GK rats fed with TRG were significantly lower than those of the GK control rats. TRG downregulated the gene expressions involved with NADPH oxidase and mitochondrial electron transfer system when compared with those of the GK control group. These results suggested that mitigation of diabetes by TRG is mediated by its ameliorating effects on oxidative stress. 23590882 Interacting Glutamate Receptor-Like Proteins in Phloem Regulate Lateral Root Initiation in Arabidopsis. Molecular, genetic, and electrophysiological evidence indicates that at least one of the plant Glu receptor-like molecules, GLR3.4, functions as an amino acid-gated Ca(2+) channel at the plasma membrane. The aspect of plant physiology, growth, or development to which GLR3.4 contributes is an open question. Protein localization studies performed here provide important information. In roots, GLR3.4 and the related GLR3.2 protein were present primarily in the phloem, especially in the vicinity of the sieve plates. GLR3.3 was expressed in most cells of the growing primary root but was not enriched in the phloem, including the sieve plate area. GLR3.2 and GLR3.4 physically interacted with each other better than with themselves as evidenced by a biophotonic assay performed in human embryonic kidney cells and Nicotiana benthamiana leaf cells. GLR3.3 interacted poorly with itself or the other two GLRs. Mutations in GLR3.2, GLR3.4, or GLR3.2 and GLR3.4 caused the same and equally severe phenotype, namely, a large overproduction and aberrant placement of lateral root primordia. Loss of GLR3.3 did not affect lateral root primordia. These results support the hypothesis that apoplastic amino acids acting through heteromeric GLR3.2/GLR3.4 channels affect lateral root development via Ca(2+) signaling in the phloem. 23208666 Poly(2-oxazoline)-derived contact biocides: contributions to the understanding of antimicrobial activity. A set of poly(2-oxazoline)-derived (co-)polymers was prepared by microwave-assisted polymerizations and acid-mediated hydrolysis and tested for antimicrobial activity in 50 × 50 × 2 mm PP compound plates containing 5 wt% of the polymers. Antimicrobial activity against gram-negative E. coli and P. aeruginosa as well as C. albicans depended only on the degree of hydrolysis, while antimicrobial activity against gram-positive S. aureus was only observed for hydrolyzed poly(2-nonyl-2-oxazoline)s. The surface energies of the compound plates compared to pure PP were hardly altered, and the compounds can be considered as alternatives for PP. The presence of the biocide additives at the surface of the PP compound plates could be shown by combined ATR-IR, zeta potential, and SEM-EDX measurements. Antimicrobial activity was maintained during double incubation as well as for lowered amounts of the biocide additive of 1% in PP compound plates. 23298810 Synthesis and biological evaluation of substituted benzoxazoles as inhibitors of mPGES-1: use of a conformation-based hypothesis to facilitate compound design. Microsomal prostaglandin E(2) synthase-1 (mPGES-1) is a novel therapeutic target for the treatment of inflammation and pain. In the preceding letter, we detailed the discovery of clinical candidate PF-04693627, a potent mPGES-1 inhibitor possessing a novel benzoxazole structure. While PF-04693627 was undergoing further preclinical profiling, we sought to identify a back-up mPGES-1 inhibitor that differentiated itself from PF-04693627. The design, synthesis, mPGES-1 activity and in vivo PK of a novel set of substituted benzoxazoles are described herein. Also described is a conformation-based hypothesis for mPGES-1 activity based on the preferred conformation of the cyclohexane ring within this class of inhibitors. 23640867 Facile Fluorescence-Based Detection of PAD4-Mediated Citrullination. The post-translational modifications of histone proteins are highly diverse and dynamic processes. It is becoming increasingly evident that modifying histone proteins can have a direct influence on both cellular homeostasis and disease states. Protein arginine deiminase 4 (PAD4) is an enzyme that converts peptidyl-arginine to citrulline. The overexpression of PAD4 has been found in numerous types of human cancer and autoimmune diseases. We report a new, facile, fluorescence-based assay for the detection of PAD4 activity that exploits the substrate specificity of trypsin to monitor the citrullination reaction carried out by PAD4 based on the fact that, upon citrullination, the positively charged arginine side chain is converted to the neutral citrulline. We show that the assay can be performed rapidly with readily available reagents and that it responds accordingly to a known PAD4 inhibitor. 23249747 Circular RNAs are abundant, conserved, and associated with ALU repeats. Circular RNAs composed of exonic sequence have been described in a small number of genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe of endogenous circular RNAs, we performed high-throughput sequencing (RNA-seq) of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease, RNase R. We identified >25,000 distinct RNA species in human fibroblasts that contained non-colinear exons (a "backsplice") and were reproducibly enriched by exonuclease degradation of linear RNA. These RNAs were validated as circular RNA (ecircRNA), rather than linear RNA, and were more stable than associated linear mRNAs in vivo. In some cases, the abundance of circular molecules exceeded that of associated linear mRNA by >10-fold. By conservative estimate, we identified ecircRNAs from 14.4% of actively transcribed genes in human fibroblasts. Application of this method to murine testis RNA identified 69 ecircRNAs in precisely orthologous locations to human circular RNAs. Of note, paralogous kinases HIPK2 and HIPK3 produce abundant ecircRNA from their second exon in both humans and mice. Though HIPK3 circular RNAs contain an AUG translation start, it and other ecircRNAs were not bound to ribosomes. Circular RNAs could be degraded by siRNAs and, therefore, may act as competing endogenous RNAs. Bioinformatic analysis revealed shared features of circularized exons, including long bordering introns that contained complementary ALU repeats. These data show that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression. 23494763 Assessment of Cytotoxic Properties of Safranal and Nanoliposomal Safranal in Various Cancer Cell Lines. Saffron (Crocus sativus) is a widely used food additive used for its color and taste. It has been reported that saffron possesses significant in vivo and in vitro anti-tumor activity. In the present study, anti-tumor effects of safranal, the major aromatic compound in saffron, and its liposomal form were investigated. The role of apoptosis has also been explored in this toxicity. HeLa, MCF7 and L929 cell lines were cultured and exposed to safranal (0.01-3 mM) or liposomal safranal (0.04-0.32 mM). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay was performed to assess cytotoxicity. Apoptosis was evaluated by staining cells with propidium iodide and quantifying sub-Gl peak by flow cytometry. MTT assay revealed a significant and concentration-dependent cytotoxic effect of safranal on HeLa and MCF7 cell lines. Liposomal safranal showed enhanced effect compared to the safranal solution, as compared by their IC50 concentrations. Flow cytometry results revealed induction of apoptosis by safranal. It might be concluded that safranal could be involved in saffron-induced cell death in HeLa and MCF7 cells. Liposome encapsulation improved anti-tumor effect of safranal. Safranal and particularly its liposomal form could be investigated as promising chemotherapeutic agents in cancer treatment. Copyright © 2013 John Wiley & Sons, Ltd. 23287389 Adult dose-dependent behavioral and cognitive disturbances after a single neonatal PFHxS dose. Perfluoroalkyl acids, including perfluorohexane sulfonate (PFHxS), are fluorinated organic compounds used as surfactants and water and stain repellents in carpets, paper, and textiles, with characteristics to bioaccumulate and biomagnify in the food chain. PFHxS is found in umbilical cord blood, human milk and child serum from all over the world. We have recently reported that neonatal exposure to certain perfluoroalkyl acids, PFOS and PFOA, can induce persistent aberrations in spontaneous behavior and also affect learning and memory functions in the adult animal. The present study indicates that a single exposure to PFHxS on postnatal day 10, during a vulnerable period of brain development can alter adult spontaneous behavior and cognitive function in both male and female mice, effects that are both dose-response related and long-lasting/irreversible. PFHxS affected the cholinergic system, manifested as altered nicotine-induced behavior in adult animals. This is also in agreement with earlier studies on neonatal exposure to PFOS and PFOA. The present findings show that PFHxS, a member of the perfluoroalkyl acid group, can act as a developmental neurotoxicant and affect the cholinergic system and cognitive function and the effects show similarities with effects earlier reported after neonatal exposure to other POPs, such as bisphenol A, PBDEs and PCBs. 22931186 Clinical pharmacology of etoposide in children undergoing autologous stem cell transplantation for various solid tumours. 1. The population pharmacokinetics of high-dose etoposide was studied in a group of young children and adolescents. 2. Twenty-six children and adolescent were administered high-dose etoposide as a continuous infusion over 24 h. Etoposide plasma concentration-time data was modelled using NONMEM® 7. The effect of age, weight, serum creatinine (SCr), and gender on pharmacokinetic parameters (CL and V(d)) were determined by a nonlinear mixed effect model. 3. The pharmacokinetics of etoposide based on BSA dosing was best described with a 1-compartment structural model which was parameterised in terms of clearance (CL) and volume of distribution (V(d)). An exponential error model was used to explain intersubject variability and a proportional error model was used to describe residual or intrapatient variability. The final model parameter estimates for the typical (normalised to 70 kg) values of CL and V(d) were 2.31 L/hr and 17.5 L, respectively. The CL and V(d) allometrically increased with weight with the power of 3/4 and 1, respectively. After accounting for weight dependence using the allometric scaling, age, serum creatinine, and gender did not have any influence on model parameters. 4. The results of this children and adolescent population pharmacokinetic study indicates that etoposide pharmacokinetics were influenced by body weight on an allometric basis. The pharmacokinetic parameters CL and V(d) increased with increasing weight similar to BSA. 23341175 A refined aquatic ecological risk assessment for a pyrethroid insecticide used for adult mosquito management. The use of pyrethroid insecticides has increased substantially throughout the world over the past few decades as the use of organophorous, carbamate, and organochlorine insecticides is being phased out. Pyrethroids are the most common class of insecticides for ultralow-volume (ULV) aerosol applications used to manage high densities of adult mosquitoes. Pyrethroids are highly toxic to nontarget organisms such as certain aquatic organisms, and there have been concerns about the effect of applications of ULV insecticides on these organisms. To address the uncertainties associated with the risks of ULV applications and the contradictory findings of other ecological risk assessments, the authors performed a probabilistic aquatic ecological risk assessment for permethrin using actual environmental deposition on surfaces to estimate permethrin concentrations in water. The present study is the first ecological risk assessment for pyrethroids to quantitatively integrate the reduction in bioavailability resulting from the presence of dissolved organic matter. As part of the risk assessment, the authors incorporated a species sensitivity distribution to take into account the differences in toxicity for different species. The 95th percentile estimated concentration would result in less than 0.0001% of the potentially affected fraction of species reaching the lethal concentration that kills 50% of a population. The results of the present study are supported by the weight of evidence that pyrethroids applied by ground-based ULV equipment will not result in deleterious effects on aquatic organisms. 23643737 1,4-Substituted 4-(1H)-pyridylene-hydrazone-type inhibitors of AChE, BuChE, and amyloid-β aggregation crossing the blood-brain barrier. Given the fundamentally multifactorial character of Alzheimer's disease (AD), addressing more than one target for disease modification or therapy is expected to be highly advantageous. Here, following the cholinergic hypothesis, we aimed to inhibit both acetyl- and butyrylcholinesterase (AChE and BuChE) in order to increase the concentration of acetylcholine in the synaptic cleft. In addition, the formation of the amyloid fibrils should be inhibited and already preformed fibrils should be destroyed. Based on a recently identified AChE inhibitor with a 1,4-substituted 4-(1H)-pyridylene-hydrazone skeleton, a substance library has been generated and tested for inhibition of AChE, BuChE, and fibril formation. Blood-brain barrier mobility was ensured by a transwell assay. Whereas the p-nitrosubstituted compound 18C shows an anti-AChE activity in the nanomolar range of concentration (IC50 = 90 nM), the bisnaphthyl substituted compound 20L was found to be the best overall inhibitor of AChE/BuChE and enhances the fibril destruction. 23481236 Modulation of cellular insulin signaling and PTP1B effects by lipid metabolites in skeletal muscle cells. Normal glucose regulation is achieved by having adequate insulin secretion and effective glucose uptake/disposal. Excess lipids in peripheral tissues - skeletal muscle, liver and adipose tissue - may attenuate insulin signaling through the protein kinase B (AKt) pathway and up-regulate protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signaling. We studied accumulation of lipid metabolites [triglycerides (TAGs), diglycerides (DAGs)] and ceramides in relation to insulin signaling and expression and phosphorylation of PTP1B by preincubating rat skeletal muscle cells (L6 myotubes) with three saturated and three unsaturated free fatty acids (FFAs) (200 μM). Cells were also evaluated in the presence of wortmannin, an inhibitor of phosphatidylinositol 3-kinases and thus AKt (0-100 nM). Unsaturated FFAs increased DAGs, TAGs and PTP1B expression significantly, but cells remained insulin sensitive as assessed by robust AKt and PTP1B phosphorylation at serine (Ser) 50, Ser 398 and tyrosine 152. Saturated palmitic and stearic acids increased ceramides, up-regulated PTP1B, and had AKt and PTP1B phosphorylation at Ser 50 impaired. We show a significant correlation between phosphorylation levels of AKt and of PTP1B at Ser 50 (R(2)=0.84, P<.05). The same was observed with increasing wortmannin dose (R(2)=0.73, P<.05). Only FFAs that increased ceramides caused impairment of AKt and PTP1B phosphorylation at Ser 50. PTP1B overexpression in the presence of excess lipids may not directly cause insulin resistance unless it is accompanied by decreased PTP1B phosphorylation. A clear relationship between PTP1B phosphorylation levels at Ser 50 and its negative effect on insulin signaling is shown. 23267855 The effect of novel promoter variants in MATE1 and MATE2 on the pharmacokinetics and pharmacodynamics of metformin. Interindividual variation in response to metformin, first-line therapy for type 2 diabetes, is substantial. Given that transporters are determinants of metformin pharmacokinetics, we examined the effects of promoter variants in both multidrug and toxin extrusion protein 1 (MATE1) (g.-66T → C, rs2252281) and MATE2 (g.-130G → A, rs12943590) on variation in metformin disposition and response. The pharmacokinetics and glucose-lowering effects of metformin were assessed in healthy volunteers (n = 57) receiving metformin. The renal and secretory clearances of metformin were higher (22% and 26%, respectively) in carriers of variant MATE2 who were also MATE1 reference (P < 0.05). Both MATE genotypes were associated with altered post-metformin glucose tolerance, with variant carriers of MATE1 and MATE2 having an enhanced (P < 0.01) and reduced (P < 0.05) response, respectively. Consistent with these results, patients with diabetes (n = 145) carrying the MATE1 variant showed enhanced metformin response. These findings suggest that promoter variants of MATE1 and MATE2 are important determinants of metformin disposition and response in healthy volunteers and diabetic patients. 23450806 Biological Design for Simultaneous Optical Transparency and Mechanical Robustness in the Shell of Placuna placenta. The flat circular-shaped shells from Placenta placenta demonstrate high optical transparency in the visible light range while still maintaining mechanical robustness. The optical and mechanical design of this mineralized material system in correlation to its multiscale structural and crystallographical features are discussed in detail through both experimental and theoretical approaches. 23248236 Inhibition of bacterial thioredoxin reductase: an antibiotic mechanism targeting bacteria lacking glutathione. Increasing antibiotic resistance makes the identification of new antibacterial principles an urgent task. The thioredoxin system including thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH plays critical roles in cellular DNA synthesis and defense against oxidative stress. Notably, TrxR is very different in structure and mechanism in mammals and bacteria. Ebselen [2-phenyl-1,2 benzisoselenazol-3(2H)-one], a well-known antioxidant and a substrate for mammalian TrxR and Trx, is rapidly bacteriocidal for methicillin-resistant Staphylococcus aureus by an unknown mechanism. We have discovered that ebselen is a competitive inhibitor of Escherichia coli TrxR with a Ki of 0.52 ± 0.13 μM, through reaction with the active site dithiol of the enzyme. Bacteria lacking glutathione (GSH) and glutaredoxin, in which TrxR and Trx are essential for DNA synthesis, were particularly sensitive to ebselen. In growth-inhibited E. coli strains, Trx1 and Trx2 were oxidized, demonstrating that electron transfer via thioredoxin was blocked. Ebselen and its sulfur analog ebsulfur were bactericidal for GSH-negative pathogens. Ebsulfur inhibited a clinically isolated Helicobacter pylori strain with a minimum inhibitory concentration value as low as 0.39 μg/ml. These results demonstrate that bacterial Trx and TrxR are viable antibacterial drug targets using benzisoselenazol and benzisothiazol derivates.-Lu, J., Vlamis-Gardikas, A., Kandasamy, K., Zhao, R., Gustafsson, T. N., Engstrand, L., Hoffner, S., Engman, L., Holmgren, A. Inhibition of bacterial thioredoxin reductase: an antibiotic mechanism targeting bacteria lacking glutathione. 23474441 Transcriptional cooperation between p53 and NF-κB p65 regulates microRNA-224 transcription in mouse ovarian granulosa cells. MicroRNAs (miRNAs) have been indicated to play key roles in ovarian follicular development. However, little is known about how the miRNA gene expression itself is regulated in the mammalian ovary. We previously reported that miR-224 is involved in TGF-β1-mediated follicular granulosa cell (GC) growth and estradiol (E2) production by targeting Smad4. Here, the transcriptional regulation of miR-224 expression in GCs was further investigated. Our results showed that both the tumor suppressor gene p53 and NF-κB p65 subunit suppressed the TGF-β1-induced increase in pri-miR-224 expression in GCs. ChIP assays demonstrated that TGF-β1 enhanced the binding of p53 and p65 to the proximal promoter region of GABAA receptor ε subunit (miR-224 host gene). p53 and p65 transcriptionally cooperated to inactivate the GABAA receptor ε subunit promoter. In addition, p53/p65 could up-regulate Smad4 expression by inhibiting its target miR-224 in GCs which contributed, at least partially, to the effects of miR-224 and Smad4 on GC proliferation and E2 release. Our results provide new data about the interplay between transcription factors involved in GC proliferation and function by cooperatively regulating miRNA expression. 23429231 Endothelial cell response to (co)polymer nanoparticles depending on the inflammatory environment and comonomer ratio. Endothelial cells lining the lumen of blood vessels serve as a physiological barrier controlling nanoparticle movement from the vasculature into the tissue. For exploring the effect of polymer hydrophilicity on nanoparticle interactions with human umbilical vein endothelial cells (HUVECs) in vitro, a series of monomodal poly[acrylonitrile-co-(N-vinylpyrrolidone)] model nanoparticles with increasing hydrophilicity as related to their increasing content (0-30mol.%) of N-vinylpyrrolidone (NVP) were synthesized by miniemulsion polymerization. Nanoparticles with a low NVP content were rapidly endocytized into all cells independent from the particle dose with toxic effects only observed at high particle concentrations, while only 10-30% of the cells incorporated particles with ⩾20mol.% NVP. Since pathologies are often related to inflammation, an inflammatory HUVEC culture condition with IL-1β stimulation has been introduced and suggested to be widely applied for studying nanocarriers, since cellular uptake in this assay was clearly increased for NVP contents ⩾20mol.%. Importantly, the secretion of functional biological mediators by HUVEC was not relevantly influenced by the nanoparticles for both homeostatic and inflammatory conditions. These findings may motivate concepts for nanocarriers specifically targeted to pathologic regions. Additionally, rapidly endocytized RhodaminB loaded particles with low NVP content may be explored for cell labeling and tracking. 23601393 Nutritional composition of minor indigenous fruits: Cheapest nutritional source for the rural people of Bangladesh. In line of the development of a food composition database for Bangladesh, 10 minor indigenous fruits were analysed for their nutrient composition comprising ascorbic acid, carotenoids and mineral values. Nutrient data obtained have been compared with published data reported in different literatures, book and United States Department of Agriculture-National Nutrient Database for Standard Reference. Ascorbic acid was highest in Wood apple and lowest in Roselle. Monkey jack contained the highest amount of carotenoids, zinc and copper. Content of calcium, magnesium and phosphorous were found highest in Antidesma velutinum. Potassium was the highest in Wood apple followed by in Moneky jack. It was noted that most of the minor fruits have much higher amount of ascorbic acid than the national fruit - Jack fruit ripe, the king fruit - Mango ripe of Bangladesh and exotic fruits - Apple and Grapes. The nutrient values of these minor fruits would make awareness among the people for their mass consumption for healthy life and to grow more minor fruit trees from extinction in order to maintain biodiversity. 23466231 Pregna-5,17(20)-dien-21-oyl amides affecting sterol and triglyceride biosynthesis in Hep G2 cells. Synthesis of series [17(20)Z]- and [17(20)E]-pregna-5,17(20)-dien-21-oyl amides, containing polar substituents in amide moiety, based on rearrangement of 17α-bromo-21-iodo-3β-acetoxypregn-5-en-20-one caused by amines, is presented. The titled compounds were evaluated for their potency to regulate sterol and triglyceride biosynthesis in human hepatoma Hep G2 cells in comparison with 25-hydroxycholesterol. Three [17(20)E]-pregna-5,17(20)-dien-21-oyl amides at a concentrations of 5 μM inhibited sterol biosynthesis and stimulated triglyceride biosynthesis; their regulatory potency was dependent on the structure of amide moiety; the isomeric [17(20)Z]-pregna-5,17(20)-dien-21-oyl amides were inactive. 23449223 A far-upstream (-70 kb) enhancer mediates Sox9 auto-regulation in somatic tissues during development and adult regeneration. SOX9 encodes a transcription factor that presides over the specification and differentiation of numerous progenitor and differentiated cell types, and although SOX9 haploinsufficiency and overexpression cause severe diseases in humans, including campomelic dysplasia, sex reversal and cancer, the mechanisms underlying SOX9 transcription remain largely unsolved. We identify here an evolutionarily conserved enhancer located 70-kb upstream of mouse Sox9 and call it SOM because it specifically activates a Sox9 promoter reporter in most Sox9-expressing somatic tissues in transgenic mice. Moreover, SOM-null fetuses and pups reduce Sox9 expression by 18-37% in the pancreas, lung, kidney, salivary gland, gut and liver. Weanlings exhibit half-size pancreatic islets and underproduce insulin and glucagon, and adults slowly recover from acute pancreatitis due to a 2-fold impairment in Sox9 upregulation. Molecular and genetic experiments reveal that Sox9 protein dimers bind to multiple recognition sites in the SOM sequence and are thereby both necessary and sufficient for enhancer activity. These findings thus uncover that Sox9 directly enhances its functions in somatic tissue development and adult regeneration through SOM-mediated positive auto-regulation. They provide thereby novel insights on molecular mechanisms controlling developmental and disease processes and suggest new strategies to improve disease treatments. 23485440 Effect of iontophoresis on the in vitro trans-scleral transport of three single stranded oligonucleotides. Oligonucleotides represent a subject of clinical interest due to their potential ability to treat several diseases, including those affecting the posterior segment of the eye. Unfortunately, therapeutic oligonucleotides are currently administered by means of highly invasive approaches, such as intravitreal injections. The aim of the present work was to study in vitro, across isolated bovine sclera, the effect of iontophoresis on the transport of three single stranded oligonucleotides (ssDNA), 12-, 24- and 36-mer, selected as reference compounds in view of a non-invasive drug delivery to the back of the eye. All the three sequences were able to cross bovine sclera in vitro without iontophoresis. When anodal iontophoresis was applied, no change in flux was observed, while in the presence of cathodal iontophoresis the permeability coefficients increased four-fold compared to passive conditions. This behavior can be ascribed to the electrorepulsive mechanism, due to the negative charge of the nucleic acid backbone. It was also observed that the molecular weights of the three sequences did not affect trans-scleral transport, neither in passive, nor in current assisted permeation. Furthermore, increasing the current intensity from 1.75mA to 3mA, no effect on the trans-scleral transport of the 24-mer was noticed. Although preliminary, the results demonstrate that cathodal iontophoresis enhances trans-scleral transport of single stranded oligonucleotides and suggest its use as a novel non-invasive approach for the treatment of diseases affecting the posterior segment of the eye. 23595510 Nuclear magnetic resonance study of ion adsorption on microporous carbide-derived carbon. A detailed understanding of ion adsorption within porous carbon is key to the design and improvement of electric double-layer capacitors, more commonly known as supercapacitors. In this work nuclear magnetic resonance (NMR) spectroscopy is used to study ion adsorption in porous carbide-derived carbons. These predominantly microporous materials have a tuneable pore size which enables a systematic study of the effect of pore size on ion adsorption. Multinuclear NMR experiments performed on the electrolyte anions and cations reveal two main environments inside the carbon. In-pore ions (observed at low frequencies) are adsorbed inside the pores, whilst ex-pore ions (observed at higher frequencies) are not adsorbed and are in large reservoirs of electrolyte between carbon particles. All our experiments were carried out in the absence of an applied electrical potential in order to assess the mechanisms related to ion adsorption without the contribution of electrosorption. Our results indicate similar adsorption behaviour for anions and cations. Furthermore, we probe the effect of sample orientation, which is shown to have a marked effect on the NMR spectra. Finally, we show that a (13)C →(1)H cross polarisation experiment enables magnetisation transfer from the carbon architecture to the adsorbed species, allowing selective observation of the adsorbed ions and confirming our spectral assignments. 22968089 Effects of metabotropic glutamate receptor ligands on male sexual behavior in rats. Metabotropic glutamate receptors (mGluRs), particularly mGluR2/3, mGluR5 and mGluR7, have received much attention in medication development for the treatment of drug addiction and other neuropsychiatric diseases. However, little is known as to whether mGluR ligands also alter natural sexual behavior, a possible unwanted effect when used in humans. In the present study, we used classical copulatory behaviors to evaluate the effects of LY379268 (a selective mGluR2/3 agonist), MPEP (a selective mGluR5 antagonist) and AMN082 (a selective mGluR7 agonist), on male sexual performance in rats. We found that systemic administration of LY379268 (1, 3 mg/kg, i.p.) had no effect, while MPEP (20 mg/kg, but not 10 mg/kg, i.p.) and AMN082 (10, 20 mg/kg, but not 3 mg/kg) produced a significant and dose-dependent reduction in both sex-seeking and sex-performance behaviors, manifested as an increase in mount or intromission latency and time required for ejaculation, and a reduction in mount or intromission frequency. This inhibition lasted for about 30-60 min. These findings suggest that compounds that target mGluR5 or mGluR7, but not mGluR2/3, may have short-term inhibitory effects on male sexual performance. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. 23540698 The Arabidopsis Nucleosome Remodeler DDM1 Allows DNA Methyltransferases to Access H1-Containing Heterochromatin. Nucleosome remodelers of the DDM1/Lsh family are required for DNA methylation of transposable elements, but the reason for this is unknown. How DDM1 interacts with other methylation pathways, such as small-RNA-directed DNA methylation (RdDM), which is thought to mediate plant asymmetric methylation through DRM enzymes, is also unclear. Here, we show that most asymmetric methylation is facilitated by DDM1 and mediated by the methyltransferase CMT2 separately from RdDM. We find that heterochromatic sequences preferentially require DDM1 for DNA methylation and that this preference depends on linker histone H1. RdDM is instead inhibited by heterochromatin and absolutely requires the nucleosome remodeler DRD1. Together, DDM1 and RdDM mediate nearly all transposon methylation and collaborate to repress transposition and regulate the methylation and expression of genes. Our results indicate that DDM1 provides DNA methyltransferases access to H1-containing heterochromatin to allow stable silencing of transposable elements in cooperation with the RdDM pathway. 23593960 Is Diacetyl a Respiratory Sensitizer? A Reconsideration Using QSAR, QMM, and Competition Experiments. Concerns have been raised that diacetyl (DA) might be a respiratory sensitizer based on its LUMO energy similar to that of the respiratory allergen toluene-2,4-diisocyanate (TDI) and results of a local lymph node assay (LLNA) that reported an EC3 of 1.9%. To better understand the concerns, we performed a systematic literature review and experimental competition reactions between DA and TDI. The experimental evidence demonstrates that DA is at least 400-fold less reactive than TDI. The literature review finds evidence that the EC3 for DA is actually >11%. We conclude that DA is unlikely to have significant respiratory sensitization potential. 23562074 The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders. Endocannabinoids and cannabinoid CB1 receptors are known to play a generalized role in energy homeostasis. However, clinical trials with the first generation of CB1 blockers, now discontinued due to psychiatric side effects, were originally designed to reduce food intake and body weight rather than the metabolic risk factors associated with obesity. In this review, we discuss how, in addition to promoting energy intake, endocannabinoids control lipid and glucose metabolism in several peripheral organs, particularly the liver and adipose tissue. Direct actions in skeletal muscle and pancreas are also emerging. This knowledge may help in the design of future therapies for the metabolic syndrome. 23032515 8-Hydroxycalamenene isolated from the rhizomes of Reynoutria elliptica exerts neuroprotective effects both in vitro and in vivo. Retinal ganglion cells (RGCs) death caused by oxidative stress is a common risk factor for glaucoma. In the present study, 8-hydroxycalamenene was isolated from the hexane fraction of Reynoutria elliptica. We showed that 8-hydroxycalamenene attenuated the cell death of transformed RGC-5 cells. This compound also produced a dose-dependent decrease in the expression of apoptotic proteins (cleaved PARP and caspase-3) induced by l-buthionine-(S,R)-sulfoximine (BSO) plus glutamate and stimulated glutathione and glutathione S-transferase activity. Moreover, the addition of 8-hydroxycalamenene to cell cultures restored the reduced mitochondrial membrane potential resulting from glutamate/BSO treatment. The presence of N-methyl-d-aspartate in the retina of rats affected the thickness of the inner plexiform layer (IPL) and increased the number of TUNEL-positive RGCs. However, 8-hydroxycalamenene protected against thinning of the IPL and reduced TUNEL-positive cells in the ganglion cell layer. Thus, 8-hydroxycalamenene isolated from R. elliptica exerts neuroprotective effects both in vitro and in vivo. 23030346 Direct measurement of coherency limits for strain relaxation in heteroepitaxial core/shell nanowires. The growth of heteroepitaxially strained semiconductors at the nanoscale enables tailoring of material properties for enhanced device performance. For core/shell nanowires (NWs), theoretical predictions of the coherency limits and the implications they carry remain uncertain without proper identification of the mechanisms by which strains relax. We present here for the Ge/Si core/shell NW system the first experimental measurement of critical shell thickness for strain relaxation in a semiconductor NW heterostructure and the identification of the relaxation mechanisms. Axial and tangential strain relief is initiated by the formation of periodic a/2 ⟨110⟩ perfect dislocations via nucleation and glide on {111} slip-planes. Glide of dislocation segments is directly confirmed by real-time in situ transmission electron microscope observations and by dislocation dynamics simulations. Further shell growth leads to roughening and grain formation which provides additional strain relief. As a consequence of core/shell strain sharing in NWs, a 16 nm radius Ge NW with a 3 nm Si shell is shown to accommodate 3% coherent strain at equilibrium, a factor of 3 increase over the 1 nm equilibrium critical thickness for planar Si/Ge heteroepitaxial growth. 23232150 Analysis and characterization of eight estradiol inducible genes and a strong promoter from the steroid degrading marine bacterial strain S19-1. Buttiauxella strain S19-1 is a new marine bacterium, isolated from the Baltic Sea, which can degrade steroids. In this report, a meta-genomic approach was used to isolate estradiol inducible genes from S19-1. SalI-fragments from the chromosomal DNA of S19-1 were ligated into plasmid pKEGFP2 bearing an EGFP gene as the reporter system. All resulting plasmids harboring SalI-fragments were transformed into Escherichia coli HB101 to measure the relative fluorescent units (RFU). E. coli cells showing higher RFU after estradiol induction than those without estradiol induction, were selected and the respective plasmids were sequenced. Sequences of 8 positive plasmids were analyzed and aligned by BLAST. Among the predicted genes we found similarities to the major facilitator superfamily, glycerol dehydratase activator, formate acetyltransferase activating enzyme, histidinol-phosphate/aromatic aminotransferase, ABC-transporter, transcriptional regulator nadR, lipoate-protein ligase A, and alcohol phosphatidyl-transferase. Interestingly, one of the E. coli cell clones (containing plasmid p302) showed up in green color by normal light microscopy, which indicated that a strong promoter was present in this plasmid. Sequencing and deletion-mutagenesis revealed that the putative promoter comprises a 108 bp DNA fragment within p302, from which the putative -10 and -35 regions are TTTGAT and TTGGTT, respectively. The promoter might be used to construct S19-1 mutants in which steroid degradation occurs at high levels. 23546879 Site-specific O-glycosylation on the MUC2 mucin inhibits cleavage by the Porphyromonas gingivalis secreted cysteine protease (RgpB). The colonic epithelial surface is protected by an inner mucus layer which the commensal microflora cannot penetrate. We previously demonstrated that Entamoeba histolytica (E.h.) secretes a protease capable of dissolving this layer that is required for parasite penetration. Here, we asked if there are bacteria that can secrete similar proteases. We screened bacterial culture supernatants for such activity using recombinant fragments of the MUC2 mucin, the major structural component and the only gel-forming mucin in the colonic mucus. MUC2 has two central heavily O-glycosylated mucin domains that are protease-resistant and has cysteine rich N- and C-termini responsible for polymerization. Culture supernatants of Porphyromonas gingivalis (P.g.), a bacterium that secretes proteases responsible for periodontitis, cleaved the MUC2-C terminal region, whereas the N-terminal region was unaffected. The active enzyme was isolated and identified as Arg-gingipain B (RgpB). Two cleavage sites were localized to IR↓TT and NR↓QA. IR↓TT cleavage will disrupt the MUC2 polymers. As this site has two potential O-glycosylation sites we tested whether recombinant GalNAc-transferases (GalNAc-Ts) could glycosylate a synthetic peptide covering the IRTT sequence. Only GalNAc-T3 was able to glycosylate the second Thr in IRTT, rendering the sequence resistant to cleavage by RgpB. Furthermore, when GalNAc-T3 was expressed in CHO-cells expressing the MUC2 C-terminal, the second threonine was glycosylated and the protein became resistant to RgpB cleavage. These findings suggest that bacteria can produce proteases capable of dissolving the inner protective mucus layer by specific cleavages in the MUC2 mucin and that this cleavage can be modulated by site-specific O-glycosylation. 23600865 Hydrodynamic Interactions between Two Equally Sized Spheres in Viscoelastic Fluids in Shear Flow. The effect of using a viscoelastic suspending medium on the in-plane hydrodynamic interaction between two equally sized spheres in shear flow is studied experimentally to understand flow-induced assembly behavior (i.e., string formation). A counterrotating device equipped with a Couette geometry is used together with quantitative videomicroscopy. To evaluate the effects of differences in rheological properties of the suspending media, fluids have been selected that highlight specific constitutive features. These include a reference Newtonian fluid (N), a constant-viscosity, high-elasticity Boger fluid (BF), a wormlike micellar surfactant solution with a single dominant relaxation time (WMS), and a broad spectrum shear-thinning elastic polymer solution (ST). As expected, the trajectories are symmetric in the Newtonian fluid. In the BF, the midpoints of the spheres are observed to remain in the same plane before and after the interaction, as in the Newtonian fluid, although the path lines are in this case no longer symmetric. Interactions in the ST and WMS are highly asymmetric. Two fundamentally different kinds of path lines are observed in the WMS and ST: reversing and open trajectories. The type of trajectory depends on the initial configuration of the spheres with respect to each other and on the shear rate. On the basis of the obtained results, shear-thinning of the viscosity seems to be the key rheological parameter that determines the overall nature of the interactions, rather than the relative magnitude of the normal stress differences. 23169614 How do the electrical properties of graphene change with its functionalization? Functionalization of graphene is essential to interface it with other moieties to expand the scope of its electrical/electronic applications. However, chemical functionalization and/or molecular interactions on graphene sensitively modulate its electrical properties. To evaluate and take advantage of the properties of functionalized graphene, it is important to understand how its electrical attributes (such as carrier scattering, carrier concentration, charge polarity, quantum-capacitance enhanced doping, energy levels, transport mechanisms, and orbital hybridization of energy-bands) are influenced by a change in carbon's structural conformation, hybridization state, chemical potential, local energy levels, and dopant/interface coupling induced via functionalization or molecular interactions. Here, a detailed and integrated model describes factors influencing these electrical characteristics of functionalized graphene (covalent bonds, adsorption, π-π bonds, and lattice incorporation). The electrical properties are governed via three mechanisms: (a) conversion of carbon's hybridized state, (b) dipole interactions enhanced via quantum capacitance, and (c) orbital hybridization with an interfacing molecule. A few graphenic materials are also identified where further studies are essential to understand the effect of their functionalization. 23260347 Synthesis and evaluation of diphenylphosphinic amides and diphenylphosphine oxides as inhibitors of Kv1.5. Diphenylphosphinic amides and diphenylphosphine oxides have been synthesized and tested as inhibitors of the Kv1.5 potassium ion channel as a possible treatment for atrial fibrillation. In vitro structure-activity relationships are discussed and several compounds with Kv1.5 IC(50) values of <0.5 μM were discovered. Selectivity over the ventricular IKs current was monitored and selective compounds were found. Results from a rabbit PD-model are included. 23540587 Interleukin-23: a promising therapeutic target in seronegative spondyloarthropathy. Particular therapeutic challenges are raised by the spondyloarthropathies which represent a key area of unmet medical need. Recent investigations have shown that these conditions are characterised both by altered responsiveness to interleukin(IL)-23 and expansion of IL-23 responsive cells as well as increased production of IL-23. The gut in particular has emerged as a key site of IL-23 production, and gut inflammation is known to be strongly clinically associated with these conditions. Moreover, HLA-B27, which is strongly associated with spondyloarthropathy, has also been shown to stimulate IL-23 production. The view is thus emerging that dysregulation of IL-23 biology is a unifying feature of spondyloarthropathy, suggesting that treatments targeting this cytokine are likely to be highly efficacious. 23319584 Comparison of orientation and rotational motion of skeletal muscle cross-bridges containing phosphorylated and dephosphorylated myosin regulatory light chain. Calcium binding to thin filaments is a major element controlling active force generation in striated muscles. Recent evidence suggests that processes other than Ca(2+) binding, such as phosphorylation of myosin regulatory light chain (RLC) also controls contraction of vertebrate striated muscle (Cooke, R. (2011) Biophys. Rev. 3, 33-45). Electron paramagnetic resonance (EPR) studies using nucleotide analog spin label probes showed that dephosphorylated myosin heads are highly ordered in the relaxed fibers and have very low ATPase activity. This ordered structure of myosin cross-bridges disappears with the phosphorylation of RLC (Stewart, M. (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 430-435). The slower ATPase activity in the dephosporylated moiety has been defined as a new super-relaxed state (SRX). It can be observed in both skeletal and cardiac muscle fibers (Hooijman, P., Stewart, M. A., and Cooke, R. (2011) Biophys. J. 100, 1969-1976). Given the importance of the finding that suggests a novel pathway of regulation of skeletal muscle, we aim to examine the effects of phosphorylation on cross-bridge orientation and rotational motion. We find that: (i) relaxed cross-bridges, but not active ones, are statistically better ordered in muscle where the RLC is dephosporylated compared with phosphorylated RLC; (ii) relaxed phosphorylated and dephosphorylated cross-bridges rotate equally slowly; and (iii) active phosphorylated cross-bridges rotate considerably faster than dephosphorylated ones during isometric contraction but the duty cycle remained the same, suggesting that both phosphorylated and dephosphorylated muscles develop the same isometric tension at full Ca(2+) saturation. A simple theory was developed to account for this fact. 23122097 GC/MS analysis of volatiles obtained by headspace solid-phase microextraction and simultaneous-distillation extraction from Rabdosia serra (MAXIM.) HARA leaf and stem. Volatiles in Rabdosia serra were investigated by headspace solid phase microextraction (HS-SPME) and simultaneous-distillation extraction (SDE). The HS-SPME technique was previously evaluated to optimise sampling conditions. A total of 56 and 48 compounds including alcohols, aldehydes, hydrocarbons, ketones, carboxylic acid, ester, and aromatics were identified in leaf and stem by optimised HS-SPME method (CAR/PDMS fibre; incubation time, 10 min; extraction temperature, 50°C; extraction time, 40 min), respectively. 1-Octen-3-ol and (2E)-hexenal had significant contribution to R. serra aroma. Cluster analysis indicated that leaf and stem exhibited different volatile diversity. Air drying was favourable for the retention of the volatiles, while freeze- and sun-drying led to the loss of volatiles. SDE method preferred to the analysis of compounds with low volatility including fatty acids and esters. HS-SPME was a useful technique for the analysis of readily volatile components for the characteristics of R. serra aroma. 23442197 Analysis and refactoring of the A-74528 biosynthetic pathway. A-74528 is a C30 polyketide natural product that functions as an inhibitor of 2',5'-oligoadenylate phosphodiesterase (2'-PDE), a key regulatory enzyme of the interferon pathway. Modulation of 2'-PDE represents a unique therapeutic approach for regulating viral infections. The gene cluster responsible for biosynthesis of A-74528 yields minute amounts of this natural product together with considerably larger quantities of a structurally dissimilar C30 cytotoxic agent, fredericamycin. Through construction and analysis of a series of knockout mutants, we identified the genes necessary for A-74528 biosynthesis. Remarkably, the formation of six stereocenters and the regiospecific formation of six rings in A-74528 appear to be catalyzed by only two tailoring enzymes, a cyclase and an oxygenase, in addition to the core polyketide synthase. The inferred pathway was genetically refactored in a heterologous host, Streptomyces coelicolor CH999, to produce 3 mg/L A-74528 in the absence of fredericamycin. 23553961 In Situ Study of CO Oxidation on HOPG-Supported Pt Nanoparticles. Catalyzed CO oxidation: A newly designed high-pressure flow cell is utilized to study CO oxidation on Pt nanoparticles in situ by simultaneous quadrupole mass spectrometry and high-pressure X-ray photoelectron spectroscopy. The spectroscopy data show that the active catalyst consists of metallic Pt with both chemisorbed O and patches/shell of surface oxides. 22956629 Differential mouse pulmonary dose and time course responses to titanium dioxide nanospheres and nanobelts. Three anatase titanium dioxide (TiO(2)) nanoparticles (NPs) were prepared; nanospheres (NSs), short nanobelts (NB1), and long nanobelts (NB2). These NPs were used to investigate the effect of NP shape and length on lung toxicity. Mice were exposed (0-30 µg per mouse) by pharyngeal aspiration and pulmonary toxicity was assessed over a 112-day time course. Whole lung lavage data indicated that NB1- and NB2-exposed mice, but not NS-exposed mice, had significant dose- and time-dependent pulmonary inflammation and damage. Histopathological analyses at 112 days postexposure determined no interstitial fibrosis in any NS-exposed mice, an increased incidence in 30 µg NB1-exposed mice, and significant interstitial fibrosis in 30 µg NB2-exposed mice. At 112 days postexposure, lung burden of NS was decreased by 96.4% and NB2 by 80.5% from initial deposition levels. At 112 days postexposure, enhanced dark field microscopy determined that alveolar macro- phages were the dominant deposition site, but a fraction of NB1 and NB2 was observed in the alveolar interstitial spaces. For the 30 µg exposure groups at 112 days postexposure, confocal micro- scopy and immunofluorescent staining demonstrated that retained NB2 but not NS were present in the interstitium subjacent to the terminal bronchiole near the normal location of the smallest lymphatic capillaries in the lung. These lymphatic capillaries play a critical role in particle clearance, and the accumulation of NB2, but not NS, suggests possible impaired lymphatic clearance by the high aspect ratio particles. In summary, our data indicate that TiO(2) NP shape alters pulmonary responses, with severity of responses being ranked as NS < NB1 < NB2. 23596084 Influence of the Molecular Structure of Surface-Attached Poly(N-alkyl Acrylamide) Coatings on the Interaction of Surfaces with Proteins, Cells and Blood Platelets. Blood protein adsorption and blood platelet adhesion onto surface-attached poly(alkylacrylamide) networks that exhibit small and systematic variations in chemical composition are investigated. The polymer coatings are generated by depositing a thin layer of benzophenone-group-containing copolymer onto a solid substrate, followed by photo crosslinking and simultaneous surface-attachment. The correlation of the swelling of the obtained surface-attached networks with the adsorption of blood proteins and cellular adhesion is studied. The swollen surface-attached layers are inert to blood proteins and platelet cells. These results suggest that the hydrogel-coated materials are promising candidates for the generation of hemocompatible surfaces. 23419139 In vivo drug interactions of the teratogen thalidomide with midazolam: heterotropic cooperativity of human cytochrome P450 in humanized TK-NOG mice. In vivo drug interactions of the teratogen thalidomide with the model cytochrome P450 (P450) 3A substrate midazolam were investigated in mice with humanized livers. The clearance of midazolam (administered intravenously, 10 mg kg(-1)) in chimeric mice was enhanced by orally co-administered thalidomide (100 mg kg(-1)). A larger area under the curve of the major metabolite 1'-hydroxymidazolam (1.7-fold) was obtained with thalidomide because of the heterotropic cooperativity of human P450 3A enzymes. A larger area under the curve of the minor metabolite 4-hydroxymidazolam (3.5-fold) was seen with daily pretreatment with thalidomide for 3 days, presumably because of human P450 3A induction. These results demonstrate that livers of humanized mice mediate drug interactions of thalidomide and suggest interactions of therapeutic agents during therapies with thalidomide. 23376119 p63 involvement in poly(ADP-ribose) polymerase 1 signaling of topoisomerase I-dependent DNA damage in carcinoma cells. Poly(ADP-ribose)polymerase 1 (PARP-1) inhibitors are thought as breakthrough for cancer treatment in solid tumors such as breast cancer through their effects on PARP's enzymatic activity. Our previous findings showed that the hydrophilic PARP inhibitor PJ34 enhances the sensitivity of p53 proficient MCF7 breast carcinoma cells to topotecan, a DNA Topoisomerase I (TOP 1) inhibitor. In the present study, we combine the classical TOP 1 poison camptothecin or its water-soluble derivative topotecan with PJ34 to investigate the potentiation of chemotherapeutic efficiency in MCF7 (p53(WT)), MDA-MB231 (p53(mut)) breast carcinoma cells and SCC022 (p53(null)) squamous carcinoma cells. We show that, following TPT-PJ34 combined treatment, MCF7 cells exhibit apoptotic death while MDA-MB231 and SCC022 cells are more resistant to these agents. Specifically, in MCF7, (i) PJ34 in combination with TPT causes a G2/M cell cycle arrest followed by massive apoptosis; (ii) PJ34 addition reverts TPT-dependent PARP-1 automodification and triggers caspase-dependent PARP-1 proteolysis; (iii) TPT, used as a single agent, stimulates p53 expression while in combination with PJ34 increases p53, TAp63α and TAp63γ protein levels with a concomitant reduction of MDM2 protein. The identification of p63 proteins as new players involved in the cancer cell response to TPT-PJ34 is relevant for a better understanding of the PARP1-dependent signaling of DNA damage. Furthermore, our data indicate that, in response to TPT-PJ34 combined chemotherapy, a functional cooperation between p53 and TAp63 proteins may occur and be essential to trigger apoptotic cell death. 23547584 Biological Active Analogues of the Opioid Peptide Biphalin: Mixed α/β(3)-Peptides. Natural residues of the dimeric opioid peptide Biphalin were replaced by the corresponding homo-β(3) amino acids. The derivative 1 containing hβ(3) Phe in place of Phe showed good μ- and δ-receptor affinities (Ki(δ) = 0.72 nM; Ki(μ) = 1.1 nM) and antinociceptive activity in vivo together with an increased enzymatic stability in human plasma. 23639717 Application of COSMO-RS as an Excipient Ranking Tool in Early Formulation Development. The low amounts of drug available in early discovery often results in limited information on the physico-chemical (solubility etc.) properties of a compound being obtained. As a result, predictive tools and miniaturised screens have been investigated to aid formulation development in early discovery. This study looks at the potential application of the quantum chemistry program, Conductor Screening Model for Real Solvents (COSMO-RS) to help with the selection of excipients for formulation development in early discovery. The excipient solubility predictions obtained from COSMO-RS were compared to experimentally obtained solubilities. The results showed that in general, COSMO-RS was able to help formulators with the selection of the most appropriate excipients to solubilise the model compound. 23627396 Antifungal Agents from Pseudallescheria boydii SNB-CN73 Isolated from a Nasutitermes sp. Termite. Defense mutualisms between social insects and microorganisms have been described in the literature. The present article describes the discovery of a Pseudallescheria boydii strain isolated from Nasutitermes sp. The microbial symbiont produces two antifungal metabolites: tyroscherin and N-methyltyroscherin, a compound not previously described in the literature. Methylation of tyroscherin has confirmed the structure of N-methyltyroscherin. Both compounds are effective antifungal agents with favorable selectivity indices for Candida albicans and Trichophyton rubrum. 23334322 Effects of vitamin B6 metabolism on oncogenesis, tumor progression and therapeutic responses. Pyridoxal-5'-phosphate (PLP), the bioactive form of vitamin B6, reportedly functions as a prosthetic group for >4% of classified enzymatic activities of the cell. It is therefore not surprising that alterations of vitamin B6 metabolism have been associated with multiple human diseases. As a striking example, mutations in the gene coding for antiquitin, an evolutionary old aldehyde dehydrogenase, result in pyridoxine-dependent seizures, owing to the accumulation of a metabolic intermediate that inactivates PLP. In addition, PLP is required for the catabolism of homocysteine by transsulfuration. Hence, reduced circulating levels of B6 vitamers (including PLP as well as its major precursor pyridoxine) are frequently paralleled by hyperhomocysteinemia, a condition that has been associated with an increased risk for multiple cardiovascular diseases. During the past 30 years, an intense wave of clinical investigation has attempted to dissect the putative links between vitamin B6 and cancer. Thus, high circulating levels of vitamin B6, as such or as they reflected reduced amounts of circulating homocysteine, have been associated with improved disease outcome in patients bearing a wide range of hematological and solid neoplasms. More recently, the proficiency of vitamin B6 metabolism has been shown to modulate the adaptive response of tumor cells to a plethora of physical and chemical stress conditions. Moreover, elevated levels of pyridoxal kinase (PDXK), the enzyme that converts pyridoxine and other vitamin B6 precursors into PLP, have been shown to constitute a good, therapy-independent prognostic marker in patients affected by non-small cell lung carcinoma (NSCLC). Here, we will discuss the clinical relevance of vitamin B6 metabolism as a prognostic factor in cancer patients.Oncogene advance online publication, 21 January 2013; doi:10.1038/onc.2012.623. 23289624 Distribution and seasonal variation in hypothalamic RF-amide peptides in a semi-desert rodent, the jerboa. The jerboa is a semi-desert rodent, in which reproductive activity depends on the seasons, being sexually active in the spring-summer. The present study aimed to determine whether the expression of two RF-amide peptides recently described to regulate gonadotrophin-releasing hormone neurone activity, kisspeptin (Kp) and RF-amide-related peptide (RFRP)-3, displays seasonal variation in jerboa. Kp and/or RFRP-3 immunoreactivity was investigated in the hypothalamus of jerboas captured in the field of the Middle Atlas mountain (Morocco), either in the spring or autumn. As in other rodents, the Kp-immunoreactive (-IR) neurones were found in the anteroventro-periventricular and arcuate nuclei. RFRP-3 neurones were noted within the dorso/ventromedial hypothalamus. A marked sexual dimorphism in the expression of Kp (but not RFRP-3) was observed. The number of Kp-IR neurones was nine-fold higher, and the density of Kp-IR fibres and terminal-like elements in the median eminence was two-fold higher in females than in males. Furthermore, a significant seasonal variation in peptide expression was obtained with an increase in both Kp- and RFRP-3-IR cell bodies in sexually active male jerboas captured in the spring compared to sexually inactive autumn animals. In the arcuate nucleus, the level of Kp-IR cells and fibres was significant higher during the sexually active period in the spring than during the autumnal sexual quiescence. Similarly, the number of RFRP-3-IR neurones in the ventro/dorsomedial hypothalamus was approximately three-fold higher in sexually active jerboa captured in the spring compared to sexually inactive autumn animals. Altogether, the present study reports the distribution of Kp and RFRP-3 neurones in the hypothalamus of a desert species and reveals a seasonal difference in their expression that correlates with sexual activity. These findings suggest that these two RF-amide peptides may act in concert to synchronise the gonadotrophic activity of jerboas with the seasons. 23432061 Possible Involvement of TRP Channels in Cardiac Hypertrophy and Arrhythmia. Over the past 20 years, studies of transient receptor potential (TRP) channels have significantly extended our knowledge regarding the molecular basis of Ca2+ signals in cardiac myocytes. The functional significance of cardiac TRP channels is likely connected to the alteration of membrane potential or Ca2+ entry into a noncontractile compartment, where gene expression responsible for various cardiac diseases is induced. This review highlights some aspects of TRP channels with anticipated roles in cardiac disease. Evidence suggests that (a) increased activities of TRPC1, TRPC3, or TRPC6 are involved in the development of cardiac hypertrophy, where these TRPC channels act as unique sensors for a wide range of hypertrophic stimuli, and (b) mutations in TRPM4 are now recognized as causes of human cardiac conduction disorders. Ultimately, TRP channels may become novel pharmacological targets in the treatment of human cardiac disease. 23306791 Polyethylene glycol-g-polyvinyl alcohol grafted copolymer: Reproductive toxicity study in Wistar rats. Polyethylene glycol-g-polyvinyl alcohol (PEG-PVA) grafted copolymer was administered by gavage to groups of 25 male and 25 female young Wistar rats at doses of 0 (vehicle control), 100, 300, or 1000mg/kg bw/day for one generation (F0). The study followed the treated F0 generation through mating, gestation, lactation, and weaning of the F1 generation. F1 animals were mated and followed to gestation day (GD) 15-17 at which time F2 implants were evaluated. There were no indications from the various clinical and gross pathological examinations that the oral administration of PEG-PVA grafted copolymer to the F0-parental rats produced any signs of general, reproductive, or developmental toxicity in the F0 or F1 animals or F2 implants. Based on the lack of any dose-related or biologically relevant effects on fertility, reproduction, development, and overall health of rats gavaged with PEG-PVA grafted copolymer and their progeny, the no-observed-adverse effect level (NOAEL) was determined to be the highest dose tested of 1000mg/kg bw/day. 23627717 Modeling of multiple equilibria in the self-aggregation of di-n-decyldimethylammonium chloride/octaethylene glycol monododecyl ether/cyclodextrin ternary systems. The surface tension equations of binary surfactant mixtures (di-n-decyldimethylammonium chloride and octaethylene glycol monododecyl ether) are established by combining the Szyszkowski equation of surfactant solutions, the ideal or nonideal mixing theory and the phase separation model. For surfactant mixtures, the surface tension at the air-water interface is calculated using nonideal theory due to synergism between the two adsorbed surfactant types. The incorporation of cyclodextrin complexation model to the surface tension equations gives a robust model for the description of the surface tension isotherms of binary, ternary and more complex systems involving numerous inclusion complexes. The surface tension data obtained experimentally shows excellent agreement with the theoretical model below and above the formation of micelles. The strong synergistic effect observed between the two surfactants is disrupted by the presence of CDs, leading to ideal behavior of ternary systems. Indeed, depending on the nature of the cyclodextrin (i.e. ,  or ) which allows a tuning of the cavity size, the binding constants with the surfactants are modified as well as the surface properties due to strong modification of equilibria involved in the ternary mixture. 23579962 VERY HIGH PREVALENCE OF ULTRASOUND THYROID SCAN ABNORMALITIES IN HEALTHY VOLUNTEERS IN MODENA, ITALY. Background: Italy is characterized by high prevalence of goiter. To date, only limited data about the prevalence of goiter in the Italian adult population are available. Aim. To investigate the prevalence of thyroid ultrasound abnormalities in adults unaware of any thyroid disease and evaluate the rate of differentiated thyroid cancer (DTC) obtained by this intervention. Methods. US thyroid scan was performed in adult volunteers recruited by advertisement in Modena, Italy. 135 women and 66 men (n= 201), unaware of any thyroid disease (mean age of 46 ± 10.7 years) underwent their first thyroid US scan. Results. US thyroid abnormalities were found in 101 subjects (50.3%): 91 nodular goiters (45.2%) and 13 US-thyroiditis (6.5%) associated with positive auto-antibodies in 11 of them. 17 subjects (18%) with nodules underwent US-FNAB with the following cytological class (C) outcome: 14 patients C2 (82 %), 1 patient C3 (6 %), 2 patients had C4 (12%), the latter received histological confirmation. Conclusions. The prevalence of thyroid abnormalities, is very high in subjects unaware of any thyroid disease. DTC was found in 1% of subjects and in 2% of those affected by nodular goiter. Compared to the detection rate of the well-established screening programs for breast (0.45%) and colorectal (0.27%) cancer, the prevalence of DTC seems to be much higher. Thyroid US screening could allow the detection of DTC in asymptomatic subjects and this diagnosis often includes DTC at an advanced stage. Thus, US screening not necessarily results in the over-diagnosis of clinically not relevant thyroid diseases. 23220617 Chemotherapy modulates the biological activity of breast cancer patients plasma: the protective properties of black chokeberry extract. In breast cancer patients (before and during anti-cancer therapy) oxidative/nitrative damage to various molecules is observed. Furthermore, anti-cancer treatments may also influence the hemostatic properties of blood platelets and plasma. The aim of our study was to assess the effect of oxidative/nitrative stress (estimated by measurements of the levels of carbonyl groups and 3-nitrotyrosine in proteins--ELISA and C-ELISA methods, respectively; lipid peroxidation and total antioxidant level--TAS) on the selected parameters of hemostatic activity of plasma (the process of fibrin polymerization and lysis) collected from breast cancer patients after surgery and after various phases of chemotherapy (doxorubicin and cyclophosphamide). Subsequently, we also evaluated the level of oxidative/nitrative stress and hemostatic activity in plasma from these patients in the presence of the commercial extract of Aronia melanocarpa (Aronox®) in vitro. Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy in Medical University of Lodz, Poland. We observed increased levels of biomarkers of oxidative/nitrative stress in plasma from patients with breast cancer (before or after surgery and after various phases of chemotherapy) in comparison to healthy group. Our further experiments demonstrated the hemostatic activity of plasma from the investigated patients differs from hemostatic properties of plasma obtained from healthy volunteers. We also recognize the existence of a relationship between oxidative stress (measured by the level of carbonyl groups) and changes of hemostasis in breast cancer patients after I and IV phases of chemotherapy. Moreover, the obtained results showed that the commercial extract from A. melanocarpa berries significantly reduced, in in vitro system, the oxidative/nitrative stress and hemostasis changes in plasma from breast cancer patients, after surgery and different phases of chemotherapy. Considering the data presented in this study, we suggest that the oxidative/nitrative stress in plasma obtained from breast cancer patients (not only before or after the surgery, but also after various phases of doxorubicin and cyclophosphamide chemotherapy) may induce changes of hemostatic activity, which may contribute to thrombosis in these patients. Our results also suggest that the commercial extract of A. melanocarpa may be regarded as a promising new source of bioactive antioxidant natural compounds for breast cancer patients. 23379362 Petroacetylene, a new polyacetylene from the marine sponge Petrosia solida that inhibits blastulation of starfish embryos. A new C(30) linear polyacetylene compound designated petroacetylene (1) has been isolated from the marine sponge Petrosia solida Hoshino 1981, collected off the coast of Amami-Oshima, Kagoshima Prefecture, Japan. The structure was elucidated on the basis of spectroscopic data and chemical means. Petroacetylene (1) inhibited blastulation of starfish embryos at a concentration of 3.1 μg mL(- 1) or greater. 23500772 Activation of ALDH2 with ethanol attenuates diabetes induced myocardial injury in rats. This study assessed changes in myocardial ALDH2 expression in the diabetic rat, in particular the diabetic rat pretreated with ALDH2 activator ethanol (EtOH). The rats were divided into six groups: control, EtOH control, diabetic rat at 4th week (DM4W), 8th week (DM8W), 12th week (DM12W) and EtOH+DM8W groups. Compared with control group, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels were increased in DM groups. HbA1c level in DM12W group was higher than in DM4W group, HbA1c level in EtOH+DM8W group was lower than in DM8W group. Compared with control group, there were no changes of LVDP, HR and ±dp/dtmax in DM4W group, but there were decreased in DM8W and DM12W groups, and increased in the EtOH+DM8W group. In DM groups, SOD activity, ALDH2 mRNA and protein levels were reduced, MDA content was increased compared with control group; which decreased further as diabetes progressed. Compared with DM8W group, SOD and ALDH2 in EtOH+DM8W group was increased, MDA was decreased. Our results indicated with the development of diabetes, myocardial ALDH2 expression was further decreased accompanying decreased ventricular function. However, activation of ALDH2 can decrease diabetes induced myocardial injury. ALDH2 may be one key endogenous cardiac protective factor in diabetic individuals. 23066821 Two new alkaloids from marine sponge Callyspongia sp. Two new alkaloids, callylactam A (1) and callyimine A (4), along with three known ones (2, 3 and 5), were isolated from the marine sponge Callyspongia sp. The structures were determined on the basis of NMR and MS analysis. 23027517 Light induced nanowire assembly: the electrostatic alignment of semiconductor nanowires into functional macroscopic yarns. The electrostatic alignment and directed assembly of semiconductor nanowires into macroscopic, centimeter-long yarns is demonstrated. Different morphologies can be produced, including longitudinally segmented/graded yarns or mixed composition fibers. Nanowire yarns display long range photoconductivities and open up exciting opportunities for potential use in future nanowire-based textiles or in solar photovoltaics. 23160934 Comparison of the structural characteristics of Cu(2+)-bound and unbound α-syn12 peptide obtained in simulations using different force fields. The effects of Cu(2+) binding and the utilization of different force fields when modeling the structural characteristics of α-syn12 peptide were investigated. To this end, we performed extensive temperature replica exchange molecular dynamics (T-REMD) simulations on Cu(2+)-bound and unbound α-syn12 peptide using the GROMOS 43A1, OPLS-AA, and AMBER03 force fields. Each replica was run for 300 ns. The structural characteristics of α-syn12 peptide were studied based on backbone dihedral angle distributions, free-energy surfaces obtained with different reaction coordinates, favored conformations, the formation of different Turn structures, and the solvent exposure of the hydrophobic residues. The findings show that AMBER03 prefers to sample helical structures for the unbound α-syn12 peptide and does not sample any β-hairpin structure for the Cu(2+)-bound α-syn12 peptide. In contrast, the central structure of the major conformational clusters for the Cu(2+)-bound and unbound α-syn12 peptide according to simulations performed using the GROMOS 43A1 and OPLS-AA force fields is a β-hairpin with Turn(9-6). Cu(2+) can also promote the formation of the β-hairpin and increase the solvent exposure of hydrophobic residues, which promotes the aggregation of α-syn12 peptide. This study can help us to understand the mechanisms through which Cu(2+) participates in the fibrillation of α-syn12 peptide at the atomic level, which in turn represents a step towards elucidating the nosogenesis of Parkinson's disease. 23624380 Inhibition of TGF-β1/Smad signal pathway is involved in the effect of Cordyceps sinensis against renal fibrosis in 5/6 nephrectomy rats. The present study aimed to investigate the effects of Cordyceps sinensis on renal fibrosis and its possible mechanisms. Sprague-Dawley rats were randomly divided into three groups: sham operation (SHAM) group, 5/6 subtotal nephrectomy (SNx) untreated group, and 5/6 subtotal nephrectomy treated with C. sinensis (2.0g/kgd) (CS) group. Rats were studied 12weeks after the surgery, and the CS group presented with significantly lower proteinuria, and better renal function compared with the SNx group (p<0.05). Pathological study showed that the glomerulosclerosis tubulointerstitial injury score was significantly reduced in the CS group compared with the SNx group. Furthermore, the mRNA expression of TGF-β1, Smad2 and Smad3 and the protein expression of TGF-β1, TβRI, TβRII and p-Smad2/3 were attenuated by the C. sinensis treatment. In constrast, the mRNA and protein expression of Smad7 was upregulated. Furthermore, the expression of α-SMA and FSP1 was also significantly attenuated, accompanied by the increasing expression of E-cadherin, suggesting the inhibition of the epithelial-mesenchymal transition (EMT). In conclusion: C. sinensis exerted its antifibrotic effect on the SNx rats through the inhibition of the TGF-β1/Smad pathway. 23261705 Stimulatory effect of insulin on theca-interstitial cell proliferation and cell cycle regulatory proteins through MTORC1 dependent pathway. The present study examined the effect of insulin-mediated activation of the mammalian target of rapamycin complex 1 (MTORC1) signaling network on the proliferation of primary culture of theca-interstitial (T-I) cells. Our results show that insulin treatment increased proliferation of the T-I cells through the MTORC1-dependent signaling pathway by increasing cell cycle regulatory proteins. Inhibition of ERK1/2 signaling caused partial reduction of insulin-induced phosphorylation of RPS6KB1 and RPS6 whereas inhibition of PI3-kinase signaling completely blocked the insulin response. Pharmacological inhibition of MTORC1 with rapamycin abrogated the insulin-induced phosphorylation of EIF4EBP1, RPS6KB1 and its downstream effector, RPS6. These results were further confirmed by demonstrating that knockdown of Mtor using siRNA reduced the insulin-stimulated MTORC1 signaling. Furthermore, insulin-stimulated T-I cell proliferation and the expression of cell cycle regulatory proteins CDK4, CCND3 and PCNA were also blocked by rapamycin. Taken together, the present studies show that insulin stimulates cell proliferation and cell cycle regulatory proteins in T-I cells via activation of the MTORC1 signaling pathway. 23178221 Highly regioselective glycosylation of xylosyl-containing taxanes by Enterobacter cloaceae. Three new diglycoside taxanes (4-6) containing an additional α-d-glucose unit were obtained via Enterobacter cloaceae-mediated, highly regioselective glycosylations at OH-4 of the xylosyl moieties in 7-xylosyl taxanes (1-3). Their structures were determined on the basis of extensive spectroscopic analysis and chemical reactivity. This is the first report of an enzymatic elongation of the saccharide chain in taxanes, and the glycosylation reaction is the first described example of a transformation effected by E. cloaceae. 23633563 LXR Mediates Enhanced Hepatic Gluconeogenic Gene Expression in Adult Male Rat MPR Offspring. Epidemiological studies demonstrate that the link between impaired fetal development and glucose intolerance in later life is exacerbated by postnatal catch-up growth. Maternal protein restriction (MPR) during pregnancy and lactation in the rat has been previously demonstrated to lead to impaired glucose tolerance in adulthood, however the effects of protein restoration during weaning on glucose homeostasis are largely unknown. Recent in vitro studies have identified that the Liver X Receptor-α (LXRα) maintains glucose homeostasis by inhibiting critical genes involved in gluconeogenesis including G6Pase, 11β-HSD1 and PEPCK. Therefore, we hypothesized MPR with postnatal catch-up growth would impair LXRα in vivo, which in turn would lead to augmented gluconeogenic LXRα-target gene expression and glucose intolerance. To examine this hypothesis, pregnant Wistar rats were fed a control (20%) protein diet (C) or a low (8%) protein diet during pregnancy and switched to a control diet at birth (LP). At four months, the LP offspring had impaired glucose tolerance. In additional, LP offspring had decreased LXRα expression, while hepatic expression of 11β-HSD1 and G6Pase were significantly higher. This was concomitant with decreased binding of LXRα to the putative LXRE on 11β-HSD1 and G6Pase. Finally, we demonstrated that the acetylation of Histone H3 [K9,14] surrounding the transcriptional start site of hepatic LXRα was decreased in LP offspring, suggesting MPR-induced epigenetic silencing of the LXRα promoter. In summary, our study demonstrates for the first time the important role of LXRα in mediating enhanced hepatic gluconeogenic gene expression and consequent glucose intolerance in adult MPR offspring. 23159894 Combining multiple autosomal introns for studying shallow phylogeny and taxonomy of Laurasiatherian mammals: Application to the tribe Bovini (Cetartiodactyla, Bovidae). Mitochondrial sequences are widely used for species identification and for studying phylogenetic relationships among closely related species or populations of the same species. However, many studies of mammals have shown that the maternal history of the mitochondrial genome can be discordant with the true evolutionary history of the taxa. In such cases, the analyses of multiple nuclear genes can be more powerful for deciphering interspecific relationships. Here, we designed primers for amplifying 13 new exon-primed intron-crossing (EPIC) autosomal loci for studying shallow phylogeny and taxonomy of Laurasiatherian mammals. Three criteria were used for the selection of the markers: gene orthology, a PCR product length between 600 and 1200 nucleotides, and different chromosomal locations in the bovine genome. Positive PCRs were obtained from different species representing the orders Carnivora, Cetartiodactyla, Chiroptera, Perissodactyla and Pholidota. The newly developed markers were analyzed in a phylogenetic study of the tribe Bovini (the group containing domestic and wild cattle, bison, yak, African buffalo, Asian buffalo, and saola) based on 17 taxa and 18 nuclear genes, representing a total alignment of 13,095 nucleotides. The phylogenetic results were compared to those obtained from analyses of the complete mitochondrial genome and Y chromosomal genes. Our analyses support a basal divergence of the saola (Pseudoryx) and a sister-group relationship between yak and bison. These results contrast with recent molecular studies but are in better agreement with morphology. The comparison of pairwise nucleotide distances shows that our nuDNA dataset provides a good signal for identifying taxonomic levels, such as species, genera, subtribes, tribes and subfamilies, whereas the mtDNA genome fails because of mtDNA introgression and higher levels of homoplasy. Accordingly, we conclude that the genus Bison should be regarded as a synonym of Bos, with the European bison relegated to a subspecies rank within Bos bison. We compared our molecular dating estimates to the fossil record in order to propose a biogeographic scenario for the evolution of Bovini during the Neogene. 23147715 Gamma-radiation induced formation of chromium oxide nanoparticles from dissolved dichromate. The formation of chromium oxide nanoparticles by gamma radiolysis of Cr(VI) (CrO(4)(2-) or Cr(2)O(7)(2-)) solutions was investigated as a function of pH and initial Cr(VI) concentration by measuring [Cr(VI)], the particle concentration ([Cr(III)(col)]) and [H(2)], and by characterizing the particles using TEM, Raman, FTIR and XPS. The results show that Cr(VI) is easily reduced to Cr(III) by a homogeneous aqueous reaction with ˙e(aq)(-), but, due to the stability of Cr(III) colloids, the growth of the Cr(OH)(3) particles is very slow. As the particles grow the interior of the particle dehydrates to form Cr(2)O(3) while the outer layer remains hydrated. When most of the Cr(VI) that is initially present in the solution is converted to Cr(OH)(3) further redox reactions of chromium species occur on the particle surfaces. The redox system reaches a pseudo-equilibrium state due to cyclic reactions of Cr(III) with ˙OH and H(2)O(2), and reactions of Cr(VI) with ˙e(aq)(-) and H(2)O(2). The size distribution of the particles that are formed is controlled by these solution-solid interface reactions. 22317823 Lethality, accumulation and toxicokinetics of aluminum in some tissues of male albino rats. In the present work, the lethality percentiles including median lethal doses (LD50), accumulation, distribution and toxicokinetics of aluminum in the liver, kidney, intestine, brain and serum of male albino rats, following a single oral administration were studied throughout 1, 3, 7, 14 and 28 days. The estimated LD50 at 24 h was 3.45 g Al/kg body weight (b.wt.). The utilized dose of Al was 1/50 LD50 (0.07 g Al/kg b.wt.). Aluminum residues, in Al-treated rats, were significantly decreased in response to the experimental periods and were negatively correlated with time. In addition, the hepatic, renal, intestinal, brain and serum Al contents were significantly higher than the corresponding controls at all experimental periods, except the brain that showed significant depletion when compared with its corresponding control after 28 days. Kinetically, the highest average of Al area under concentration - time curves (AUCtotal, μg/g day) and area under moment concentration - time curves (AUMCtotal, µg/g day(2)) recorded in the brain followed by kidney, serum, intestine and liver. The longest elimination half-life time (t 1/2, day) and the mean residence time (MRT, day) were recorded in the brain followed by the liver, kidney, serum and intestine. On the other hand, the slowest clearance rates (Cls, L/day) of Al, in order, were recorded in brain, kidney, serum, intestine and the liver. The elimination rate constant (Lz, day(-) (1)) of Al from the brain was less than that in the intestine and serum was less than that in the liver and kidney. The computed maximum concentrations (C max) of Al in the intestine > kidney > serum > brain > liver were recorded after 3, 3.8, 2.2, 5.4 and 3.8 days, respectively. The computed starting concentration (C 0, μg) of Al in serum was higher than its level in the intestine followed by the brain, kidney and liver. 23598904 Suppression of ZIP8 expression is a common feature of cadmium-resistant and manganese-resistant RBL-2H3 cells. Rat basophilic leukemia RBL-2H3 cells show markedly high sensitivity to both CdCl2 and MnCl2 compared with other rat cell lines, due to efficient accumulation of cadmium and manganese. To clarify the roles of metal transporters in hyperaccumulation of cadmium and manganese in RBL-2H3 cells, Cd-resistant and Mn-resistant cells were developed from RBL-2H3 cells by continuous exposure to CdCl2 and MnCl2, respectively. The established Cd-resistant (RBL-Cdr) and Mn-resistant (RBL-Mnr) cells exhibited about 20 times higher LC50 values of CdCl2 and MnCl2, respectively, than parental RBL-2H3 cells, and showed cross-resistance to each metal. The resistance to cadmium and manganese was primarily conferred by a marked decrease in the uptake of both metals. RBL-Cdr cells also showed cross-resistance to HgCl2 and AgNO3 probably due to enhanced expression of metallothionein. Among the possible transporters involved in the uptake of Cd(2+) and Mn(2+), the expression of ZIP8 (Zrt-, Irt-related protein 8), encoded by Slc39a8, showed a marked suppression in both RBL-Cdr and RBL-Mnr cells. These results suggest that ZIP8 plays a pivotal role in the transport and toxicity of Cd(2+) and Mn(2+) in RBL-2H3 cells. 23517093 Genomics-Guided Discovery of Thailanstatins A, B, and C As Pre-mRNA Splicing Inhibitors and Antiproliferative Agents from Burkholderia thailandensis MSMB43. Mining the genome sequence of Burkholderia thailandensis MSMB43 revealed a cryptic biosynthetic gene cluster resembling that of FR901464 (4), a prototype spliceosome inhibitor produced by Pseudomonas sp. No. 2663. Transcriptional analysis revealed a cultivation condition in which a regulatory gene of the cryptic gene cluster is adequately expressed. Consequently, three new compounds, named thailanstatins A (1), B (2), and C (3), were isolated from the fermentation broth of B. thailandensis MSMB43. Thailanstatins are proposed to be biosynthesized by a hybrid polyketide synthase-nonribosomal peptide synthetase pathway. They differ from 4 by lacking an unstable hydroxyl group and by having an extra carboxyl moiety; those differences endow thailanstatins with a significantly greater stability than 4 as tested in phosphate buffer at pH 7.4. In vitro assays showed that thailanstatins inhibit pre-mRNA splicing as potently as 4, with half-maximal inhibitory concentrations in the single to sub-μM range. Cell culture assays indicated that thailanstatins also possess potent antiproliferative activities in representative human cancer cell lines, with half-maximal growth inhibitory concentrations in the single nM range. This work provides new chemical entities for research and development and new structure-activity information for chemical optimization of related spliceosome inhibitors. 23561135 4-Methyl-7-hydroxycoumarin antifungal and antioxidant activity enhancement by substitution with thiosemicarbazide and thiazolidinone moieties. According to literature data, thiosemicarbazide and thiazolidinone moieties should enhance biological properties of coumarin. Antioxidant, metal-chelating and antifungal activities of all compounds were investigated and compared to the activity of the starting material, 7-hydroxy-4-methylcoumarin, and were proven to possess potent antioxidant and antifungal activity. In general, thiosemicarbazides showed higher scavenging activity towards DPPH and galvinoxyl radicals than did 4-thiazolidinones and some of them had the same or even better activity than had ascorbic acid itself, depending on the free radical used. In antifungal activity tests towards four foodborne mycotoxigenic fungi, Aspergillus flavus, Aspergillus ochraceus. Fusarium graminearum and Fusarium verticillioides, coumarin derivatives were proven to possess a very high activity in terms of growth inhibition, depending on the fungi investigated. In general, 4-thiazolidinones showed better antifungal activity than did thiosemicarbazides. F. graminearum was the most susceptible to the compounds investigated and F. verticillioides was proven to be the most resistant. Two compounds, both coumarinyl thiosemicarbazides, were found to possess both antifungal and antioxidant activity which could be useful for applications in medicine, food industry and agriculture. 23301701 Effects of water concentration on the structural and diffusion properties of imidazolium-based ionic liquid-water mixtures. We have used molecular dynamics simulations to study the properties of three ionic liquid (IL)-water systems: 1-butyl-3-methylimidazolium chloride ([bmim]Cl), 1-ethyl-3-methylimidazolium acetate ([emim][Ac]), and 1,3-dimethylimidazolium dimethylphosphate ([dmim][DMP]). We observe the transition of those mixtures from pure IL to aqueous solution by analyzing the changes in important bulk properties (density) and structural and bonding properties (radial distribution functions, water clustering, hydrogen bonding, and cationic stacking) as well as dynamical properties (diffusion coefficients) at 12 different concentration samplings of each mixture, ranging from 0.0 to 99.95 mol % water. Our simulations revealed across all of the different structural, bonding, and dynamical properties major structural changes consistent with a transition from IL-water mixture to aqueous solution in all three ILs at water concentrations around 75 mol %. Among the structural changes observed were rapid increase in the frequency of hydrogen bonds, both water-water and water-anion. Similarly, at these critical concentrations, the water clusters formed begin to span the entire simulation box, rather than existing as isolated networks of molecules. At the same time, there is a sudden decrease in cationic stacking at the transition point, followed by a rapid increase near 90 mol % water. Finally, the diffusion coefficients of individual cations and anions show a rapid transition from rates consistent with diffusion in IL's to rates consistent with diffusion in water beginning at 75 mol % water. The location of this transition is consistent, for [bmim]Cl and [dmim][DMP], with the water concentration limit above which the ILs are unable to dissolve cellulose. 23180692 Mitigating with macrophytes: submersed plants reduce the toxicity of pesticide-contaminated water to zooplankton. In ecotoxicology, appreciation is growing for the influence that ecological interactions have on the toxicity of contaminants, such as insecticides, to sensitive species. Most previous studies, however, have focused on factors that exacerbate insecticide effects on species, while factors that may mitigate these effects have been relatively ignored. In aquatic habitats, a small number of studies have shown that submersed macrophytes can remove some insecticides from the water column via sorption. Although examining sorption dynamics is important for understanding the environmental fate of insecticides, whether and to what extent macrophytes actually mitigate insecticide effects on aquatic species remains unknown. In the present study, the authors examined how much and how quickly several realistic densities of the macrophyte Elodea canadensis decreased the toxicity of the insecticide malathion to Daphnia magna, a keystone aquatic herbivore. To do this, the authors quantified Daphnia survival in outdoor test systems (0.95 L) exposed to a factorial combination of five Elodea densities crossed with five malathion concentrations. The authors discovered that malathion's lethality to Daphnia decreased with increasing Elodea density. Furthermore, the rate at which Elodea reduced malathion's toxicity in the water column increased with macrophyte density. These results provide strong evidence that submersed macrophytes can mitigate the ecological impacts of a popular insecticide and further support that ecological interactions can strongly influence contaminant environmental effects. 23305465 Meroterpenoid pigments from the basidiomycete Albatrellus ovinus. Eight grifolin derivatives, involving three new monomers, albatrelins A-C (1-3), three novel dimers (meroterpenoid pigments), albatrelins D-F (4-6), and two known ones, 6a,7,8,9,10,10a-hexahydro-3,6,9-trimethyl-6-(4-methyl-3-penten-1-yl)-1,9-epoxy-6H-dibenzo[b,d]pyran (7) and confluentin (8), were isolated from Albatrellus ovinus. Their structures were established by extensive spectroscopic analysis. The absolute configurations of compounds 2-4 were determined as 9R by comparing their optical rotations with data reported in the literature. Albatrelin F (6) was isolated as a pair of C-2' tautomers with a ratio of 1.3:1. Confluentin (8) showed weak cytotoxicity against four human tumor cell lines, HL-60, SMMC-7712, A-549, and MCF-7, in vitro. 22712581 Isolation, characterisation and biological evaluation of a phenoxazine, a natural dyestuff isolated from leaves of Peristrophe bivalvis. Peristrophe bivalvis (L.) Merr. (Acanthaceae) is a wild growing and cultivated plant used for dyeing of foods by the ethnic minorities of Vietnam. The major component of the colour aqueous extract (CAE) of its leaves was identified as peristrophine by spectral analysis, especially the 2D NMR spectra (HSQC, HMBC and NOESY). Considering the widespread utilisation of the decoction of this plant for food dyeing, we evaluated the acute oral toxicity of the CAE. Based on the results in an acute toxicity study in mice, the LD50 value of the CAE was determined as 9100 ± 290 mg kg(-1) body weight. Additionally, in vitro cytotoxic assay showed an inhibition of peristrophine against Hepatocellular carcinoma (HepG2, IC503.90 µg mL(-1)). CAE and peristrophine (1) have also been tested for their ability to affect the cell number of the OCI acute myeloid leukaemia cell line. CAE and peristrophine significantly decreased the OCI cell number at different concentrations and times of treatment. 23411185 Comparative analysis of nutritional compositions of transgenic high iron rice with its non-transgenic counterpart. Iron is an essential micronutrient for human nutrition and polished rice contains very low amount of iron. Rice with high iron content in seed endosperm has been developed by insertion of soybean ferritin gene under the control of the endosperm specific glutelin promoter into the genome of indica rice line IR68144. The nutritional composition of the brown and milled rice grain has been compared with that of the non-transgenic rice of the same variety. In this study, the nutritional components, as well as the anti-nutrient levels, were measured. Our studies established that apart from the increased level of iron and zinc in transgenic seeds, the nutritional quality of both the brown and milled rice grains from the transgenic line was substantially equivalent to that of the non-transgenic rice plants. The result clearly shows that the measured amounts of the nutritional components are well within the range of values reported for other commercial lines. 23528300 Design and synthesis of 2-substituted benzoxazoles as novel PTP1B inhibitors. A series of benzoxazole compounds containing oxamic acid were synthesized and screened for the PTP1B inhibition. Compound 31d showed best biochemical potency (Ki) of 6.7μM. Structure-activity relationship were explained with the help of molecular modeling approach. 23155201 The scintigraphic evaluation and genetic correlation of joint involvements in pediatric patients with familial Mediterranean fever. Purpose: We aimed to evaluate the articular involvements in pediatric patients with familial Mediterranean fever (FMF) with joint symptoms by bone scintigraphy and to correlate the involved joints with the gene mutations. Materials and methods: A total of 41 newly diagnosed patients in pediatric age group (28 girls and 13 boys; mean age 9.14 ± 2.91 years) with joint involvement symptoms were included in this study. Scintigraphic images were obtained at 5th min (blood pool or early phase) and starting at 3 h (late phase) after (after tracer injection) intravenous administration of technetium-99m (99mTc)-methylendiphosphonate (MDP). Genomic DNA was isolated from leukocytes using standard salting out procedure. The sequencing data were analyzed. Results: Of the 41 patients, arthritis was found in 21 (51.2%) patients. Of the 21 patients, there was single joint involvement in 15 (71.4%) patients and multiple joint involvement in six (28.6%) patients. The mean age of patients with joint involvement (8 ± 2.3 years) were considerably lower than the patients without joint involvement (10.35 ± 3.04 years), and this was statistically significant (p = 0.008). The most commonly involved joints were ankles and knees. Multiple joint involvements were most frequently observed in the M694V and M694I gene mutations (16.7%). Conclusions: We use and recommend the bone scintigraphy in patients with FMF to determine the presence and distribution of arthritis, since bone scintigraphy is inexpensive, noninvasive, easy-to-use, and also is more sensitive in the diagnosis and distribution of arthritis than conventional radiological methods and clinical examination. 23063593 Herbacetin induces apoptosis in HepG2 cells: Involvements of ROS and PI3K/Akt pathway. Herbacetin (HER) is a natural flavonoid compound that can be extracted from Ramose Scouring Rush Herb, and its biological and pharmacological activities lack of corresponding attention. In this study, the apoptotic effect of HER against the human hepatoma cell line (HepG2) was investigated. The results showed that HepG2 cells apoptosis occurred in a dose-dependent manner within 48h incubated with HER, which was confirmed by DNA fragmentation, nuclear shrinkage, and poly (ADP-ribose) polymerase (PARP) cleavage. HER at 25-100μM induced a mitochondria-dependent apoptotic pathway associated with Bcl-2/Bax ratio decrease, mitochondrial membrane potential (ΔΨ) collapse, cytochrome c release, and caspase-3 activation. Increasing expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) was also observed in HER-treated cells. Furthermore, the addition of a ROS inhibitor (N-Acetyl-l-cysteine, NAC) significantly attenuated the apoptosis induced by HER and also blocked the expression of PGC-1α protein. Additionally, HER effectively inhibited the phosphorylation of Akt and the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 increased the inhibition effect of HER on Akt phosphorylation. These findings provide evidences that HER induces HepG2 apoptosis in a ROS-mediated mitochondria-dependent manner that correlate with the inactivation of the PI3K/Akt pathway. 22975146 Alpha-asarone from Acorus gramineus alleviates epilepsy by modulating A-type GABA receptors. Alpha (α)-asarone is a major effective compound isolated from the Chinese medicinal herb Acorus gramineus, which is widely used in clinical practice as an antiepileptic drug; however, its mechanism of action remains unclear. In this study, we have characterized the action of α-asarone on the excitability of rat hippocampal neurons in culture and on the epileptic activity induced by pentylenetetrazole or kainate injection in vivo. Under cell-attached configuration, the firing rate of spontaneous spiking was inhibited by application of α-asarone, which was maintained in the Mg(2+)-free solution. Under whole-cell configuration, α-asarone induced inward currents in a concentration-dependent manner with an EC(50) of 248 ± 33 μM, which was inhibited by a GABA(A) receptor blocker picotoxin and a competitive GABA(A) receptor antagonist bicuculline but not a specific glycine receptor inhibitor strychnine. Measurement of tonic GABA currents and miniature spontaneous inhibitory postsynaptic currents indicated that α-asarone enhanced tonic GABAergic inhibition while left phasic GABAergic inhibition unaffected. In both pentylenetetrazole and kainate seizure models, α-asarone suppressed epileptic activity of mice by prolonging the latency to clonic and tonic seizures and reducing the mortality as well as the susceptibility to seizure in vivo presumably dependent on the activation of GABA(A) receptors. In summary, our results suggest that α-asarone inhibits the activity of hippocampal neurons and produces antiepileptic effect in central nervous system through enhancing tonic GABAergic inhibition. 23280101 Initiation of autophagy and apoptosis by sonodynamic therapy in murine leukemia L1210 cells. Sonodynamic therapy (SDT) has shown great potential in target cancer therapy, but it induced cell death modes has not been fully investigated. This study was to examine autophagic and apoptotic responses to protoporphyrin IX (PpIX) mediated SDT in murine leukemia L1210 cells. After SDT, the occurrence of autophagy was identified by morphological observation and biochemical analysis. Meanwhile, the mitochondria dependent apoptosis pathway was examined to participate in SDT induced cell death. The relationship between autophagy and apoptosis was further investigated by applying pharmacological inhibition studies, which indicated that impairment of autophagy enhanced the anti-tumor effect of SDT through induction of apoptosis and necrosis, while caspase inhibition did not affect autophagic vacuoles formation or protect SDT induced cytotoxicity. The findings supported that autophagic vacuoles formed upstream and independently from caspase-dependent cell death. Additionally, the possible mechanism of SDT-induced autophagy was evaluated by measurement of ROS (reactive oxygen species) formation. Result suggested ROS play important role in initiating autophagy, possibly through the sono-damaged mitochondria being enclosed by autophagic vacuoles. All together, these data indicate that autophagy may be cytoprotective in our experimental system, and point to an important insight into how autophagy inhibitors, in combination with SDT may contribute a regimen for cancer therapy. 23567999 Identification, structural and pharmacological characterization of τ-CnVA, a conopeptide that selectively interacts with somatostatin sst3 receptor. Conopeptides are a diverse array of small linear and reticulated peptides that interact with high potency and selectivity with a large diversity of receptors and ion channels. They are used by cone snails for prey capture or defense. Recent advances in venom gland transcriptomic and venom peptidomic/proteomic technologies combined with bioactivity screening approaches lead to the identification of new toxins with original pharmacological profiles. Here, from transcriptomic/proteomic analyses of the Conus consors cone snail, we identified a new conopeptide called τ-CnVA, which displays the typical cysteine framework V of the T1-conotoxin superfamily. This peptide was chemically synthesized and its three-dimensional structure was solved by NMR analysis and compared to that of TxVA belonging to the same family, revealing very few common structural features apart a common orientation of the intercysteine loop. Because of the lack of a clear biological function associated with the T-conotoxin family, τ-CnVA was screened against more than fifty different ion channels and receptors, highlighting its capacity to interact selectively with the somatostatine sst3 receptor. Pharmacological and functional studies show that τ-CnVA displays a micromolar (Ki of 1.5μM) antagonist property for the sst3 receptor, being currently the only known toxin to interact with this GPCR subfamily. 23580375 Solvent-induced delamination of a multifunctional two dimensional coordination polymer (adv. Mater. 15/2013). Unprecedented full delamination of a multifunctional 2D metal-organic framework (MOF) assisted only by solvent interaction is carried out on page 2141 by Félix Zamora, Salome Delgado, and co-workers. This observation is a direct consequence of the structure of the starting material, characterized by interlayer cavities that can be filled by the solvent molecules, producing delamination in a simple and reproducible way. 23345125 Conjugated oligoelectrolytes increase power generation in E. coli microbial fuel cells. A series of conjugated oligoelectrolytes with structural variations is used to stain E. coli. By taking advantage of a high-throughput screening platform that incorporates gold anodes, it is found that MFCs with COE-modified E. coli generate significantly higher power densities, relative to unmodified E. coli. These findings highlight the potential of using water-soluble molecules inspired by the work on organic semiconductors to improve electrode/microbe interfaces. 23219590 Mechanism of maprotiline-induced apoptosis: role of [Ca2+](i), ERK, JNK and caspase-3 signaling pathways. Antidepressants are generally used for treatment of various mood and anxiety disorders. Several studies have shown the anti-tumor and cytotoxic activities of some antidepressants, but the underlying mechanisms were unclear. Maprotiline is a tetracyclic antidepressant and possesses a highly selective norepinephrine reuptake ability. We found that maprotiline decreased cell viability in a concentration- and time-dependent manner in Neuro-2a cells. Maprotiline induced apoptosis and increased caspase-3 activation. The activation of caspase-3 by maprotiline appears to depend on the activation of JNK and the inactivation of ERK. Maprotiline also induced [Ca(2+)](i) increases which involved the mobilization of intracellular Ca(2+) stored in the endoplasmic reticulum. Pretreatment with BAPTA/AM, a Ca(2+) chelator, suppressed maprotiline-induced ERK phosphorylation, enhanced caspase-3 activation and increased maprotiline-induced apoptosis. In conclusion, maprotiline induced apoptosis in Neuro-2a cells through activation of JNK-associated caspase-3 pathways. Maprotiline also evoked an anti-apoptotic response that was both Ca(2+)- and ERK-dependent. 23639248 Bone Morphogenetic Protein-7 inhibits silica-induced pulmonary fibrosis in rats. Bone morphogenetic protein-7 (BMP-7) has been shown to inhibit liver and renal fibrosis in in vivo and in vitro studies. There is no study to investigate BMP-7's role in the development of pulmonary fibrosis induced by silica. In the current study, we used the rat model to explore the potential antifibrotic role of BMP-7 and its underlying mechanism in silica-induced pulmonary fibrosis. Sixty Wistar rats were randomly assigned into three groups. Control group received saline, silica group received silica and BMP-7 treated group received silica and BMP-7. BMP-7 was administered to silica-treated rats intraperitoneally at a dose of 300μg/kg/injection from day 8 to day 30 every other day. After the animals were sacrificed on day 15 and 30, hydroxyproline levels, the protein expressions of BMP/Smad and TGF-β/Smad signaling, and histopathology in lung tissues were analyzed. The hydroxyproline contents in BMP-7 treated groups were significantly lower than the silica groups (P<0.05). Histopathological results showed BMP-7 could reduce the progression of silica induced fibrosis. Furthermore, the expression of p-Smad1/5/8, a marker of BMP/Smad signaling, was significantly up-regulated in BMP-7 treated groups (P<0.05) compared with the silica groups. On the contrary, the expression of p-Smad2/3, a marker for TGF-β/Smad signaling, reduced significantly in BMP-7-treated groups compared with silica groups (P<0.05). In conclusion, the pulmonary fibrosis induced by silica in rats was significantly reduced with the therapeutic treatment of BMP-7. The antifibrotic effect of BMP-7 could be related to the activation of BMP/Smad signaling and inhibition of TGF-β/Smad pathways. 23506497 The heart in sepsis: from basic mechanisms to clinical management. Septic shock is characterized by circulatory compromise, microcirculatory alterations and mitochondrial damage, which all reduce cellular energy production. In order to reduce the risk of major cell death and a diminished likelihood of recovery, adaptive changes appear to be activated. As a result, cells and organs may survive in a non-functioning hibernation-like condition. Sepsis-induced cardiac dysfunction may represent an example of such functional shutdown. Sepsis-induced myocardial dysfunction is common, corresponds to the severity of sepsis, and is reversible in survivors. Its mechanisms include the attenuation of the adrenergic response at the cardiomyocyte level, alterations of intracellular calcium trafficking and blunted calcium sensitivity of contractile proteins. All these changes are mediated by cytokines. Treatment includes preload optimization with sufficient fluids. However, excessive volume loading is harmful. The first line vasopressor recommended at present is norepinephrine, while vasopressin can be started as a salvage therapy for those not responding to catecholamines. During early sepsis, cardiac output can be increased by dobutamine. While early administration of catecholamines might be necessary to restore adequate organ perfusion, prolonged administration might be harmful. Novel therapies for sepsis-induced cardiac dysfunction are discussed in this article. Cardiac inotropy can be increased by levosimendan, istaroxime or omecamtiv mecarbil without greatly increasing cellular oxygen demands. Heart rate reduction with ivabradine reduces myocardial oxygen expenditure and ameliorates diastolic filling. Beta-blockers additionally reduce local and systemic inflammation. Advances may also come from metabolic interventions such as pyruvate, succinate or high dose insulin substitutions. All these potentially advantageous concepts require rigorous testing before implementation in routine clinical practice. 23384387 Novel acylethanolamide derivatives that modulate body weight through enhancement of hypothalamic pro-opiomelanocortin (POMC) and/or decreased neuropeptide Y (NPY). Newly synthesized acylethanolamide derivatives oleoyl-L-valinolamide (1), oleoyl-D-valinolamide (2), elaidoyl-L-valinolamide (3), elaidoyl-D-valinolamide (4) stearoyl-L-valinolamide (5), and palmitoyl-L-valinolamide (6) were investigated in mice as antiobesity compounds. Compounds 1, 2, 5, 6 significantly decreased body weight by 6.57% following eight injections of 1 mg/kg i.p. during 39 days, while 3 and 4 showed no such activity. Receptor binding indicated that no compound activated CB1, CB2, PPARα, or TRPV1 receptors. Hypothalamic RT-PCR showed that mRNA expression of the anorexigenic genes POMC and CART was up-regulated by 1, 2, 5 and 1, 2, respectively, while that of the orexigenic genes NPY and CaMKK2 was down-regulated by the respective compounds 1, 5, 6 and 1, 2, 5. Oleoyl-L-valinolamide enhances anorectic pathways and lead to decreased glucose levels, enhanced locomotor activity, and improved cognition. Effects of oleoyl-L-valinolamide on weight were dose-dependent, and it could be given orally. 1, 2, 4, 5 down-regulated FAAH mRNA expression. 23552852 Effects of mixtures of azole fungicides in postimplantation rat whole-embryo cultures. The effect of mixtures of azole fungicides on development of postimplantation rat whole-embryos cultured in vitro has been tested. On the basis of bench mark dose (BMD) modeling of the in vitro effect in rat embryo, the potency of 7 azoles was determined and compared. Then, relative potency factors have been derived based on either the NOAEL or on the BMD curve. Alternatively, each compound was used as index compound (IC), and IC-equivalent concentrations have been calculated for each mixture. Expected effects of such IC-equivalent concentrations of the mixture were derived from the appropriate BMD curve. Test mixture includes the agrochemicals triadimefon and imazalil (MIX2) or triadimefon, imazalil, and the clinically used fluconazole (MIX3) at their previously determined no-effect concentration, corresponding to approximately a benchmark response of 5-10 %. Subsequently, we tested the effect of a mixture of the agrochemicals triadimefon, imazalil, triadimenol, cyproconazole, tebuconazole, and flusilazole (MIX6) at concentration levels derived from their established human acceptable daily intake. MIX6 was also added with fluconazole at concentration levels indicated as the minimum therapeutically effective plasmatic concentration (MIX7A) or ten times this level (MIX7B). Generally, the experimental response was higher than the estimated one, by a factor of 2-6. Our data suggest that it is in principle correct to assume that azoles act as teratogens via a common mode of action and therefore should be grouped together for risk assessment. The synergistic effect needs to be confirmed with more combinations of concentrations/compounds in vitro and with specific in vivo experiments. 23180158 Pocket-based drug design: exploring pocket space. The identification and application of druggable pockets of targets play a key role in in silico drug design, which is a fundamental step in structure-based drug design. Herein, some recent progresses and developments of the computational analysis of pockets have been covered. Also, the pockets at the protein-protein interfaces (PPI) have been considered to further explore the pocket space for drug discovery. We have presented two case studies targeting the kinetic pockets generated by normal mode analysis and molecular dynamics method, respectively, in which we focus upon incorporating the pocket flexibility into the two-dimensional virtual screening with both affinity and specificity. We applied the specificity and affinity (SPA) score to quantitatively estimate affinity and evaluate specificity using the intrinsic specificity ratio (ISR) as a quantitative criterion. In one of two cases, we also included some applications of pockets located at the dimer interfaces to emphasize the role of PPI in drug discovery. This review will attempt to summarize the current status of this pocket issue and will present some prospective avenues of further inquiry. 23178179 Inhibition of the thyroid hormone pathway in Xenopus laevis by 2-mercaptobenzothiazole. Determining the effects of chemicals on the thyroid system is an important aspect of evaluating chemical safety from an endocrine disrupter perspective. Since there are numerous chemicals to test and limited resources, prioritizing chemicals for subsequent in vivo testing is critical. 2-Mercaptobenzothiazole (MBT), a high production volume chemical, was tested and shown to inhibit thyroid peroxidase (TPO) enzyme activity in vitro, a key enzyme necessary for the synthesis of thyroid hormone. To determine the thyroid disrupting activity of MBT in vivo, Xenopus laevis larvae were exposed using 7- and 21-day protocols. The 7-day protocol used 18-357 μg/L MBT concentrations and evaluated: metamorphic development, thyroid histology, circulating T4, circulating thyroid stimulating hormone, thyroidal sodium-iodide symporter gene expression, and thyroidal T4, T3, and related iodo-amino acids. The 21-day protocol used 23-435 μg/L MBT concentrations and evaluated metamorphic development and thyroid histology. Both protocols demonstrated that MBT is a thyroid disrupting chemical at the lowest concentrations tested. These studies complement the in vitro study used to identify MBT as a high priority for in vivo testing, supporting the utility/predictive potential of a tiered approach to testing chemicals for TPO activity inhibition. The 7-day study, with more comprehensive, sensitive, and diagnostic endpoints, provides information at intermediate biological levels that enables linking various endpoints in a robust and integrated pathway for thyroid hormone disruption associated with TPO inhibition. 23395719 Identification of polyphenols and their metabolites in human urine after cranberry-syrup consumption. As the beneficial effects of American cranberry (Vaccinium macrocarpon) can be partly attributed to its phenolic composition, the evaluation of the physiological behaviour of this fraction is crucial. A rapid and sensitive method by ultra-performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) has been used to identify phenolic metabolites in human urine after a single dose of cranberry syrup. Prior to the analysis, metabolites were extracted using an optimised solid-phase extraction procedure. All possible metabolites were investigated based on retention time, accurate mass data and isotope and fragmentation patterns. Free coumaroyl hexose (isomer 1 and 2), dihydroxybenzoic acid, caffeoyl glucose, dihydroferulic acid 4-O-β-d-glucuronide, methoxyquercetin 3-O-galactoside, scopoletin, myricetin and quercetin, together with other 23 phase-I and phase-II metabolites, including various isomers, could be tentatively identified in the urine. Afterwards, the metabolites were simultaneously screened in the urine of different subjects at 0, 2, 4, and 6h after the ingestion of cranberry syrup by Target Analysis(TM) software. 23160089 Two new chromone glycosides from Drynaria fortunei. Two new chromone glycosides, drynachromoside A (1), drynachromoside B (2), along with three known flavanones, 5,7,3',5'-tetrahydroxy-flavanone (3), 5,7,3',5'-tetrahydroxy-flavanone-7-O-β-d-glucopyranoside (4), and 5,7,3',5'-tetrahydroxy-flavanone-7-O-neohesperidoside (5), were isolated from the dry rhizomes of Drynaria fortunei by means of bio-active screening. The two former compounds were elucidated on the basis of physico-chemical property and spectroscopic data. The osteoblastic proliferation activities of these flavonoids were evaluated by the method of MTT. The results showed that compound 1 exhibited the biochemical effects on the proliferation of MC3T3-E1 cells, while Compound 2 showed inhibitory effects against MC3T3-E1 cells. 23373530 Investigation of the conformational changes of a conducting polymer in gas sensor active layers by means of polarization-modulation infrared reflection absorption spectroscopy (PM-IRRAS). Polarization-Modulation Infrared Reflection Absorption Spectroscopy (PM-IRRAS) was employed to observe the changes in the molecular conformation of poly(2-phenyl-1,4-xylylene) (PPPX) films that occurred after exposure to organic solvent vapors. The PPPX films were supported on solid matrixes by casting, spin-coating, and Langmuir-Blodgett (LB) techniques. The results show that the polymer is sensitive to the solvent vapors, which affect some of the vibration dipole moments, as detected by PM-IRRAS. The sensitivity depends on the method employed to immobilize the polymer, with more significant changes in films formed using techniques that result in a less systematically organized conformation. This feature enables the use of surface vibration spectroscopy to detect organic solvent vapors and may be applied in an artificial nose. 23296102 Acrolein induces Alzheimer's disease-like pathologies in vitro and in vivo. The pathologic mechanisms of Alzheimer's disease (AD) have not been fully uncovered. Acrolein, a ubiquitous dietary pollutant and by-product of oxidative stress, can induce cytotoxicity in neurons, which might play an important role in the etiology of AD. Here, we examined the effects of Acrolein on the AD pathologies in vitro and in vivo. We found Acrolein induced HT22 cells death in concentration- and time-dependent manners. Interestingly, Acrolein increased proteins' levels of amyloid precursor protein (APP), β-secretase (BACE-1) and the amyloid β-peptide transporter receptor for advanced glycation end products, and decreased A-disintegrin and metalloprotease (ADAM) 10 levels. In vivo, chronic oral exposure to Acrolein (2.5 mg/kg/day by intragastric gavage for 8 weeks) induced mild cognitive declination and pyknosis/atrophy of hippocampal neurons. The activity of superoxide dismutase was down-regulated while the level of malondialdehyde was up-regulated in rat brain. Moreover, Acrolein resulted in activation of astrocytes, up-regulation of BACE-1 in cortex and down-regulation of ADAM-10 in hippocampus and cortex. Taken together, our findings suggest that exposure to Acrolein induces AD-like pathology in vitro and in vivo. Scavenging Acrolein might be beneficial for the therapy of AD. 23211364 AT1 receptor antagonism is proangiogenic in the brain: BDNF a novel mediator. Candesartan is an angiotensin II type 1 receptor blocker (ARB) that has been to shown to limit ischemic stroke and improve stroke outcome. In experimental stroke, candesartan induces a proangiogenic effect that is partly attributable to vascular endothelial growth factor. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that has been reported to have angiogenic effects and play an important role in recovery after stroke. The purpose of this investigation was to determine the role of BDNF in the proangiogenic effect of candesartan in the brain under hypertensive conditions. Accordingly, spontaneously hypertensive rats were treated with candesartan, and brain tissue samples were collected for quantification of BDNF expression. In addition, human cerebromicrovascular endothelial cells were treated with either low-dose (1 ƒM) or high-dose (1 µM) angiotensin II alone or in combination with candesartan (0.16 µM) to assess the effect of candesartan treatment and BDNF involvement in the behavior of endothelial cells. Candesartan significantly increased the expression of BDNF in the SHR (P < 0.05). In addition, candesartan reversed the antiangiogenic effect of the 1-µM dose of AngII (P = 0.0001). The observed effects of candesartan were ablated by neutralizing the effects of BDNF. Treatment with the AT2 antagonist PD-123319 significantly reduced tube-like formation in endothelial cells. AT2 stimulation induced the BDNF expression and migration (P < 0.05). In conclusion, candesartan exerts a proangiogenic effect on brain microvascular endothelial cells treated with angiotensin II. This response is attributable to increased BDNF expression and is mediated through stimulation of the AT2 receptor. 23177784 Rigid 5'-6-locked phenanthroline-derived nucleosides chelated to ruthenium and europium ions. We describe complexes of ruthenium and europium with rigid, 5'-6-locked 1,10-phenanthroline-containing nucleosides. Both nucleosides were synthesized from condensation of 5-amino-2'-deoxycytidine with the corresponding diketone. The ruthenium nucleoside displayed fluorescence characteristic of polypyridine ruthenium complexes with a maximum at 616 nm and a quantum yield of 0.011. Binding of europium to the 1,10-phenanthroline-2,9-diacid moiety of the lanthanide binding nucleoside showed formation of a 1:1 complex with emission at 570-630 nm, whose emission was enhanced by addition of two phenanthroline ligands. The lanthanide-binding nucleoside was incorporated into DNA oligonucleotides and shown to selectively bind one equivalent of europium ions. 22996932 Dual imaging and photoactivated nanoprobe for controlled cell tracking. A photoactivated nanoprobe for cell labeling and tracking is demonstrated. The nanoprobe enables all targeted cells to be imaged (at 680 nm) as well as specific cells to be photoactivated using 405 nm light. Photoactivated cells can then be tracked (at 525 nm) spatiotemporally in a separate channel over prolonged periods. 23583203 Hsp70 silencing with siRNA in nanocarriers enhances cancer cell death induced by the inhibitor of Hsp90. Inducers of heat shock protein 70 (Hsp70) commonly promote cancer cell viability whereas inhibitors of Hsp90 reduce it. The anticancer agent celastrol, interferes with signal transduction pathways involving these heat shock proteins. The objective of this in vitro study was to silence inducible Hsp70 and to promote celastrol-induced tumor cell death. Hsp70 siRNA loaded chitosan-TPP carriers were prepared by ionic gelation and characterized by photon correlation spectroscopy and asymmetric flow field-flow fractionation combined with dynamic light scattering. Viability of human leukemia and glioblastoma cells and Hsp70 silencing was determined following treatment with chitosan-TPP-Hsp70 siRNA particles. The results showed that silencing of Hsp70 by chitosan-TPP-Hsp70 siRNA treatment significantly reduced cell viability, and enhanced antiproliferative effects of celastrol in leukemia and glioblastoma cells. In glioblastoma spheroids, higher concentrations of celastrol and Hsp70 siRNA in chitosan-TPP nanocarriers were necessary to induce cell death. 23429184 Biochemical properties and comparative pharmacology of a coagulant from Deinagkistrodon acutus snake venom. A number of snake venom thrombin-like enzymes (TLEs) have already been characterized. Some TLEs play significant roles in vessel injury hemostasis. A novel TLE (Agacutase) was purified from Deinagkistrodon acutus snake venom by the means of Sephadex G-75, DEAE-Sepharose FF, and Sephadex G-25 column chromatography. Structural analysis indicated that Agacutase is a single-chain glycoprotein with a molecular mass of 31,084Da, isoelectric point of 4.38, optimal activity at 37°C and pH 6.6, sugar content of 7.6%. Its N-terminal 44 amino acid sequence was determined to be VIGGNECDTNEHRFLAAFFTSRPWIFQCAGTLIHEEWVLAAAHC, showing maximum identity of 80% with that of Dav-X protease. The Agacutase-induced clotting activity was not influenced by heparin, hirudin, or Dextran 40, but activated by Ca(2+) and inhibited by PMSF or lactose, which suggests that Agacutase is a serine protease and the coagulation activity is independent of Thrombin. Agacutase with arginine esterase activity specifically cleaves the α-chain of fibrinogen. Agacutase iv (0.03-0.12U/kg) shortened 16-68% of the rabbit blood clotting time. No significant influence was indicated on platelet, Factor II and XIII, or fibrinolytic system. It converts fibrinogen into the soluble fibrin that accelerates hemostasis at wound. Pharmacological comparison showed the hemostatic effect of Agacutase lasted 24h while Reptilase did 8h. Its maximum tolerated, abnormal toxicity, allergic, and hemorrhagin doses were 80U/kg, 1U, 2U, and 50U, respectively, whereas those of Reptilase or Agacutin were 35U/kg, 0.25U, 0.25U, and 0.2U, respectively. The results indicated that Agacutase may be a predominant coagulant. 23349500 β-Cell-Specific Protein Kinase A Activation Enhances the Efficiency of Glucose Control by Increasing Acute-Phase Insulin Secretion. Acute insulin secretion determines the efficiency of glucose clearance. Moreover, impaired acute insulin release is characteristic of reduced glucose control in the prediabetic state. Incretin hormones, which increase β-cell cAMP, restore acute-phase insulin secretion and improve glucose control. To determine the physiological role of the cAMP-dependent protein kinase (PKA), a mouse model was developed to increase PKA activity specifically in the pancreatic β-cells. In response to sustained hyperglycemia, PKA activity potentiated both acute and sustained insulin release. In contrast, a glucose bolus enhanced acute-phase insulin secretion alone. Acute-phase insulin secretion was increased 3.5-fold, reducing circulating glucose to 58% of levels in controls. Exendin-4 increased acute-phase insulin release to a similar degree as PKA activation. However, incretins did not augment the effects of PKA on acute-phase insulin secretion, consistent with incretins acting primarily via PKA to potentiate acute-phase insulin secretion. Intracellular calcium signaling was unaffected by PKA activation, suggesting that the effects of PKA on acute-phase insulin secretion are mediated by the phosphorylation of proteins involved in β-cell exocytosis. Thus, β-cell PKA activity transduces the cAMP signal to dramatically increase acute-phase insulin secretion, thereby enhancing the efficiency of insulin to control circulating glucose. 23246428 UPLC-Q-TOF/HSMS/MS(E)-based metabonomics for adenine-induced changes in metabolic profiles of rat faeces and intervention effects of ergosta-4,6,8(14),22-tetraen-3-one. Ergosta-4,6,8(14),22-tetraen-3-one (ergone), isolated from the medicinal fungus Polyporus umbellatus, has been proven to prevent the progression of renal injury and the subsequent renal fibrosis. Ultra performance liquid chromatography coupled with quadrupole time-of-flight high-sensitivity mass spectrometry and a novel mass spectrometry(Elevated Energy) (MS(E)) data collection technique was employed to investigate metabonomic characters of chronic renal failure (CRF) induced adenine and the protective effects of ergosta-4,6,8(14),22-tetraen-3-one (ergone). Coupled with blood biochemistry and kidney histopathology results, the significant difference in metabolic profiling between adenine-induced CRF group and ergone-treated CRF group by using pattern recognition analysis indicated that changes in global faecal metabolites were occurred. Seven endogenous metabolites were identified by using metabonomic method combined with multivariate data analysis, the accurate mass, isotopic pattern, MS(E) fragments information and MassLynx i-FIT algorithm. These biochemical changes in faecal metabolites are related to the perturbations of bile acid metabolism and phospholipid metabolism, which may be helpful to further understand the CRF and therapeutic mechanisms of ergone. This research proved that MS(E) can simultaneous acquire precursor ion information and fragment ion data at high and low collision energy in one analytical run, which facilitated the fast structural characterization of metabolites. 23640722 Structure-Activity Relationships of Quinoxaline-Based 5-HT3 A and 5-HT3 AB Receptor-Selective Ligands. Until recently, discriminating between homomeric 5-HT3 A and heteromeric 5-HT3 AB receptors was only possible with ligands that bind in the receptor pore. This study describes the first series of ligands that can discriminate between these receptor types at the level of the orthosteric binding site. During a recent fragment screen, 2-chloro-3-(4-methylpiperazin-1-yl)quinoxaline (VUF10166) was identified as a ligand that displays an 83-fold difference in [(3) H]granisetron binding affinity between 5-HT3 A and 5-HT3 AB receptors. Fragment hit exploration, initiated from VUF10166 and 3-(4-methylpiperazin-1-yl)quinoxalin-2-ol, resulted in a series of compounds with higher affinity at either 5-HT3 A or 5-HT3 AB receptors. These ligands reveal that a single atom is sufficient to change the selectivity profile of a compound. At the extremes of the new compounds were 2-amino-3-(4-methylpiperazin-1-yl)quinoxaline, which showed 11-fold selectivity for the 5-HT3 A receptor, and 2-(4-methylpiperazin-1-yl)quinoxaline, which showed an 8.3-fold selectivity for the 5-HT3 AB receptor. These compounds represent novel molecular tools for studying 5-HT3 receptor subtypes and could help elucidate their physiological roles. 23396116 Change in the transfer profile of orally administered tetrodotoxin to non-toxic cultured pufferfish Takifugu rubripes depending of its development stage. To investigate the effects of growth (organ development) on tetrodotoxin (TTX) dynamics in the pufferfish body, TTX-containing feed homogenate was administered to 6- and 15-month old non-toxic cultured specimens of the pufferfish Takifugu rubripes at a dose of 40 mouse units (MU) (8.8 μg)/20 g body weight by oral gavage. After 24 h, the specimens were killed and the skin tissues (dorsal and ventral), muscle, liver, digestive tract, and gonads were separated. TTX content (μg/g) in each tissue, determined by liquid chromatography/mass spectrometry, revealed that the TTX distribution profile, particularly the TTX content of the liver, greatly differed between the two ages; the TTX score of 15-month old fish (3.3 μg/g) was nearly 5-fold that of 6-month old fish (0.68 μg/g). The total remaining TTX amount per individual (relative amount to the given dose) was 31% in 6-month old fish, of which 71% was in the skin, and 84% in 15-month old fish, of which 83% was in the liver. The gonadosomatic index (GSI) and hepatosomatic index (HSI) scores, and histologic observations of the gonads and liver suggest that although there is little difference in maturation stage between these two ages, there are clear distinctions in the developmental stage of the liver. The results suggest that the TTX dynamics in T. rubripes are linked to the development of the liver, i.e., the TTX taken up into the pufferfish body via food organisms is eliminated or transferred mainly to the skin in young fish with an undeveloped liver, but as the fish grow and the liver continues to develop, most of the TTX is transferred to and accumulated in the liver. 23400795 Imposex effects on the veined rapa whelk (Rapana venosa) in Bohai Bay, China. Environmentally relevant concentrations of organotin compounds (OTs) may trigger sex changes in marine invertebrates and pose a threat to the marine ecosystem. In this study, we investigated organotin levels and the biological responses of wild veined rapa whelk (Rapana venosa) from Lüjuhe district (LJH), Dashentang district (DST), and Nanpaihe district (NPH) in Bohai Bay, China. We found that 11.11 and 22.95 % of the veined rapa whelks from DST and NPH exhibited imposex characteristics with a relative penis size index (RPSI) of 12.50 and 12.31, respectively. The RNA/DNA ratio was significantly lower in females from DST than those from LJH (p < 0.05), and a slight increase in DNA damage was observed in females and imposex individuals compared to males. Moreover, less genetic distance occurred between LJH and NPH (0.016) than between LJH and DST (0.028), although they belonged to the same regional population. OTs analysis showed that triphenyltin chloride concentrations (41.45 ng/g dried weight) were significantly higher than tributyltin concentrations (9.51 ng/g dried weight) in tissues (p < 0.05), but no significant differences were observed in sediments (p > 0.05). In conclusion, the occurrence of imposex individuals and biological responses of the wild veined rapa whelk from Bohai Bay suggest that the marine ecosystem might be at risk. 23373590 Stabilization of iron oxide nanoparticles in high sodium and calcium brine at high temperatures with adsorbed sulfonated copolymers. A series of sulfonated random and block copolymers were adsorbed on the surface of ~100 nm iron oxide (IO) nanoparticles (NPs) to provide colloidal stability in extremely concentrated brine composed of 8% wt NaCl + 2% wt CaCl2 (API brine; 1.4 M NaCl + 0.2 M CaCl2) at 90 °C. A combinatorial materials chemistry approach, which employed Ca(2+)-mediated adsorption of anionic acrylic acid-containing sulfonated polymers to preformed citrate-stabilized IO nanoclusters, enabled the investigation of a large number of polymer coatings. Initially a series of poly(2-methyl-2-acrylamidopropanesulfonate-co-acrylic acid) (poly(AMPS-co-AA)) (1:8 to 1:1 mol:mol), poly(styrenesulfonate-block-acrylic acid) (2.4:1 mol:mol), and poly(styrenesulfonate-alt-maleic acid) (3:1 mol:mol) copolymers were screened for solubility in API brine at 90 °C. The ratio of AMPS to AA groups was varied to balance the requirement of colloid dispersibility at high salinity (provided by AMPS) against the need for anchoring of the polymers to the iron oxide surface (via the AA). Steric stabilization of IO NPs coated with poly(AMPS-co-AA) (1:1 mol:mol) provided colloidal stability in API brine at room temperature and 90 °C for up to 1 month. The particles were characterized before and after coating at ambient and elevated temperatures by a variety of techniques including colloidal stability experiments, dynamic light scattering, zeta potential, and thermogravimetric analysis. 23085495 Changes in women's feelings about their romantic relationships across the ovulatory cycle. According to the dual mating hypothesis, women possess two overlapping suites of mate-choice mechanisms: one leading to preferences for sexually desirable men who have high-fitness genes and one leading to preferences for men who are able to invest in a woman and her children. Evidence increasingly demonstrates that women's preference for sexual desirability (but not investment attractiveness) increases when women are most fertile within the ovulatory cycle. Little is known, however, about the implications of these preference shifts for women's relationships with their long-term partners. Using luteinizing hormone tests to verify ovulation, across two studies (Samples 1 and 2), we found that women whose partners were relatively low in sexual desirability felt less close to their partner (Samples 1 and 2) and were more critical of their partner's faults (Sample 2) on high-fertility days of the cycle just prior to ovulation compared with low-fertility days of the cycle. Women whose partners were relatively high in sexual desirability felt closer to their partner (Sample 1) and more satisfied with their relationship (Sample 2) on high- than low-fertility days of the cycle. There were no such shifts in women's commitment to their relationship. Therefore, partner sexual desirability predicts women's high-fertility assessments of relationship quality but not their intentions to stay in their relationship, consistent with the dual mating hypothesis. These findings suggest that variations across the ovulation cycle in women's reproductive hormones play an important role in relationship dynamics. 23266737 Triterpenoid saponins from Clematis tangutica and their cardioprotective activities. Phytochemical investigation of the whole plants of Clematis tangutica led to the isolation of three new triterpenoid saponins (1-3), together with four known saponins (4-7). Their structures were determined by extensive spectral analysis and chemical evidences. Compounds 1-7 were evaluated for their cardioprotective activities in cardiomyocytes anoxia/reoxygenation (A/R) model. The results showed that those saponins exhibited cardioprotective effects by decreasing the levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). 23203920 Identification of LasR ligands through a virtual screening approach. With the widespread occurrence of bacterial resistance to antibiotics, the development of new strategies beyond conventional treatments is a pursuit taken by public health institutions worldwide. LasR, a transcription factor that controls quorum sensing in Pseudomonas aeruginosa, has emerged as an attractive therapeutic target for the next generation of antimicrobial agents. In the present study, a virtual screening workflow combining pharmacophore- and structure-based approaches was used to identify new LasR ligands. Five novel inducers and three inhibitors of LasR activity were validated experimentally by use of a cell-based assay. Interestingly, these compounds are molecularly distinct from the native signal molecule, N-3-oxododecanoyl-L-homoserine lactone (OHN), and may serve as lead structures for the design of new drugs. The binding modes of these compounds to the OHN binding site in LasR were predicted and used to identify the key interactions that contribute to the induction and inhibition of LasR activity. 23279844 Protection of the flavonoid fraction from Rosa laevigata Michx fruit against carbon tetrachloride-induced acute liver injury in mice. Protective effect of the total flavonoids (TFs) from Rosa laevigata Michx fruit against carbon tetrachloride (CCl4)-induced hepatotoxicity in mice was investigated. Pretreatment with TFs significantly decreased CCl4-induced elevation of serum aspartate transaminase (AST) and alanine transaminase (ALT) activities as well as the relative liver weight. Histopathological observation also revealed that TFs reduced the incidence of liver lesions and improved hepatocyte abnormality. Moreover, oral administration of TFs significantly enhanced antioxidant enzyme activities (superoxide dismutase, catalase and glutathione peroxidase), increased the content of glutathione and decreased the content of malondialdehyde. Further research indicated that TFs prevented the DNA fragmentation and mitochondrial ultrastructural alterations caused by CCl4 based on TUNEL and transmission electron microscopy (TEM) assays. Moreover, pretreatment with TFs down-regulated the protein expressions of CYP2E1, iNOS, NF-κB, Bak and Caspase-3. Quantitative Real-time PCR assay suggested that TFs markedly decreased the levels of TNF-α, Fas/FasL and Bax gene expressions, and increased the level of Bcl-2. This is the first time to report the significant hepatoprotective effect of TFs from R. laevigata Michx fruit against CCl4-induced liver injury in mice and the action should be through reducing oxidative stress and suppressing inflammation and apoptosis. 23190030 Phenolic compounds: the role of redox regulation in neurodegenerative disease and cancer. Much work has been carried out in the last two decades on the role of oxidative stress and antioxidants deficiency in the pathophysiology of civilization diseases. A considerable amount of chemical, biochemical, epidemiological and clinical evidence indicates that (poly)phenolic compounds widely distributed in the plant kingdom, exhibit a wide range effects on biomolecules. The beneficial effects on human health, many of phenolics have been described to their reactive oxygen (ROS) and nitrogen species (RNS) scavenging and antioxidant capacity. The consumption of vegetables, fruits and flavonoid-rich beverages has been reported to prevent against neurodegenerative diseases, cancer, and ageing. This paper reviews the recent data on (1) the role oxidative stress in the pathology of civilization diseases; (2) the protection against oxidative damage due to the toxicity of ROS/RNS; (3) the cellular and molecular interactions of the (poly)phenolic compounds relevant to the prevention of neurodegenerative diseases and cancer, and (4) the methods for assessing antioxidant capacity. 23611809 Human UGT2B10 in Drug N-glucuronidations: Substrate Screening and Comparison with UGT1A3 and UGT1A4. Recent observations revealed that human UDP-glucuronosyltransferase (UGT) 2B10 catalyzes N-glucuronidation of amine-containing compounds. Knowledge of the substrate specificity and clinical significance of UGT2B10 is still limited. The purpose of this study was to expand the knowledge of UGT2B10 substrates and to evaluate its significance in drug clearance. Using recombinant UGT2B10, we found that it catalyzes the N-glucuronidation of amitriptyline, imipramine, ketotifen, pizotifen, olanzapine, diphenhydramine, tamoxifen, ketoconazole and midazolam. These are drugs that were previously reported to be substrates for UGT1A4 or UGT1A3 and that contain in their structure either tertiary aliphatic amines, cyclic amines, or an imidazole group. UGT2B10 was inactive in the glucuronidation of desipramine, nortriptyline, carbamazepine and afloqualone. This group of drugs contains secondary or primary amines, and these results suggest that UGT2B10 preferably conjugates tertiary amines. This preference is partial because UGT2B10 did not conjugate the tertiary cyclic amine in trifluoperazine. Kinetic analyses revealed that the affinity and clearance of UGT2B10 for amitriptyline, imipramine, and diphenhydramine are significantly higher than the corresponding values of UGT1A4 and UGT1A3, although the Vmax values of UGT1A4 toward these drugs are considerably higher. These findings suggest that UGT2B10 plays a major role in the N-glucuronidation of these drugs at therapeutic concentrations. These results are also supported by inhibition studies with nicotine and hecogenin. In conclusion, this study expands the understanding of the substrate specificity of UGT2B10, highlighting its preference for tertiary amines with higher affinities and clearance values than those of UGT1A4 and UGT1A3. 23643748 Prosocial effects of oxytocin in two mouse models of autism spectrum disorders. Clinical evidence suggests that oxytocin treatment improves social deficits and repetitive behavior in autism spectrum disorders (ASDs). However, the neuropeptide has a short plasma half-life and poor ability to penetrate the blood-brain barrier. In order to facilitate the development of more bioavailable oxytocinergic compounds as therapeutics to treat core ASD symptoms, small animal models must be validated for preclinical screens. This study examined the preclinical utility of two inbred mouse strains, BALB/cByJ and C58/J, that exhibit phenotypes relevant to core ASD symptoms. Mice from both strains were intraperitoneally administered oxytocin, using either acute or sub-chronic regimens. Acute oxytocin did not increase sociability in BALB/cByJ; however, sub-chronic oxytocin had significant prosocial effects in both BALB/cByJ and C58/J. Increased sociability was observed 24 hours following the final oxytocin dose in BALB/cByJ, while prosocial effects of oxytocin emerged 1-2 weeks post-treatment in C58/J. Furthermore, acute oxytocin decreased motor stereotypy in C58/J and did not induce hypoactivity or anxiolytic-like effects in an open field test. This study demonstrates that oxytocin administration can attenuate social deficits and repetitive behavior in mouse models of ASD, dependent on dose regimen and genotype. These findings provide validation of the BALB/cByJ and C58/J models as useful platforms for screening novel drugs for intervention in ASDs and for elucidating the mechanisms contributing to the prosocial effects of oxytocin. 22951947 In vitro models for assessing the potential cardiovascular disease risk associated with cigarette smoking. Atherosclerotic cardiovascular disease is a prevalent human disorder and a significant cause of human morbidity and mortality. A number of risk factors may predispose an individual to developing atherosclerosis, and of these factors, cigarette smoking is strongly associated with the development of cardiovascular disease. Current thinking suggests that exposure to toxicants found in cigarette smoke may be responsible for this elevated disease likelihood, and this gives rise to the idea that reductions in the levels of some smoke toxicants may reduce the harm associated with cigarette smoking. To assess the disease risk of individuals who smoke cigarettes with altered toxicant levels, a weight-of-evidence approach is required examining both exposure and disease-related endpoints. A key element of such an assessment framework are data derived from the use of in vitro models of cardiovascular disease, which when considered alongside other forms of data (e.g. from clinical studies) may support evidence of potential reduced risk. Importantly, such models may also be used to provide mechanistic insight into the effects of smoking and of smoke toxicant exposure in cardiovascular disease development. In this review the use of in vitro models of cardiovascular disease and one of the contributory factors, oxidative stress, is discussed in the context of assessing the risk potential of both conventional and modified cigarettes. Practical issues concerning the use of these models for cardiovascular disease understanding and risk assessment are highlighted and areas of development necessary to enhance the power and predictive capacity of in vitro disease models in risk assessment are discussed. 23561072 Intake of mulberry 1-deoxynojirimycin prevents diet-induced obesity through increases in adiponectin in mice. In this study, the anti-obesity effect of 1-deoxynojirimycin (DNJ) was examined in the diet-induced obese mouse model. Mulberry DNJ was administered to the obese mice for 12weeks. As a result, DNJ decreased both the visceral fat weight and adipocyte size. To determine the influence of DNJ on lipid metabolism, lipid parameters of the plasma and the liver and the activities of several molecules related to lipid metabolism in the liver were measured. DNJ activated the β-oxidation system, suppressed lipid accumulation in the liver and reduced plasma triacylglycerol. Since it was thought that the factor activated in the β-oxidation system was adiponectin, plasma adiponectin levels were measured and it was shown that plasma adiponectin was increased with DNJ. Therefore, it was suggested that DNJ promoted an increase in plasma adiponectin and activated the β-oxidation system. Overall, it was shown that DNJ prevents diet-induced obesity through an increase in adiponectin. 23353733 A flexible approach to 1,4-di-substituted 2-aminoimidazoles that inhibit and disperse biofilms and potentiate the effects of β-lactams against multi-drug resistant bacteria. The pyrrole-imidazole alkaloids are a 2-aminoimidazoles containing family of natural products that possess anti-biofilm activity. A library of 1,4-di-substituted 2-aminoimidazole/triazoles (2-AITs) was synthesized, and its anti-biofilm activity as well as oxacillin resensitization efficacy toward methicillin resistant Staphylococcus aureus (MRSA) was investigated. These 2-AITs were found to inhibit biofilm formation by MRSA with low micromolar IC50 values. Additionally, the most active compound acted synergistically with oxacillin against MRSA lowering the minimum inhibitory concentration (MIC) 4-fold. 23385875 Mitochondrial DNA depletion syndromes: review and updates of genetic basis, manifestations, and therapeutic options. Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a genetically and clinically heterogeneous group of autosomal recessive disorders that are characterized by a severe reduction in mtDNA content leading to impaired energy production in affected tissues and organs. MDS are due to defects in mtDNA maintenance caused by mutations in nuclear genes that function in either mitochondrial nucleotide synthesis (TK2, SUCLA2, SUCLG1, RRM2B, DGUOK, and TYMP) or mtDNA replication (POLG and C10orf2). MDS are phenotypically heterogeneous and usually classified as myopathic, encephalomyopathic, hepatocerebral or neurogastrointestinal. Myopathic MDS, caused by mutations in TK2, usually present before the age of 2 years with hypotonia and muscle weakness. Encephalomyopathic MDS, caused by mutations in SUCLA2, SUCLG1, or RRM2B, typically present during infancy with hypotonia and pronounced neurological features. Hepatocerebral MDS, caused by mutations in DGUOK, MPV17, POLG, or C10orf2, commonly have an early-onset liver dysfunction and neurological involvement. Finally, TYMP mutations have been associated with mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease that typically presents before the age of 20 years with progressive gastrointestinal dysmotility and peripheral neuropathy. Overall, MDS are severe disorders with poor prognosis in the majority of affected individuals. No efficacious therapy is available for any of these disorders. Affected individuals should have a comprehensive evaluation to assess the degree of involvement of different systems. Treatment is directed mainly toward providing symptomatic management. Nutritional modulation and cofactor supplementation may be beneficial. Liver transplantation remains controversial. Finally, stem cell transplantation in MNGIE disease shows promising results. 23231350 Embryonic stem cell-based screen for small molecules: cluster analysis reveals four response patterns in developing neural cells. Neural differentiation of embryonic stem cells (ESC) is considered a promising model to perform in vitro testing for neuroactive and neurotoxic compounds. We studied the potential of a dual reporter murine ESC line to identify bioactive and/or toxic compounds. This line expressed firefly luciferase under the control of the neural cell-specific tubulin alpha promoter (TUBA1A), and renilla luciferase under the control of the ubiquitous translation elongation factor 1-alpha-1 (EEF1A1) promoter. During neural differentiation, TUBA1A activity increased, while EEF1A1 activity decreased. We first validated our test system using the known neurotoxin methyl mercury. This compound altered expression of both reporter genes, with ESC-derived neural precursors being affected at markedly lower concentrations than undifferentiated ESCs. Analysis of a library of 1040 bioactive compounds picked up 127 compounds with altered EEF1A1 and/or TUBA1A promoter activity, which were classified in 4 clusters. Cluster 1 (low EEF1A1 and TUBA1A) was the largest cluster, containing many cytostatic drugs, as well as known neurodevelopmental toxicants, psychotropic drugs and endocrine disruptors. Cluster 2 (high EEF1A1, stable TUBA1A) was limited to three sulfonamides. Cluster 3 (high EEF1A1 and TUBA1A) was small, but markedly enriched in neuroactive and neurotoxic compounds. Cluster 4 (stable EEF1A1, high TUBA1A) was heterogeneous, containing endocrine disruptors, neurotoxic and cytostatic drugs. The dual reporter gene assay described here might be a useful addition to in vitro drug testing panels. Our two-dimensional testing strategy provides information on complex response patterns, which could not be achieved by a single marker approach. 23041725 Sexually dimorphic transcriptomic responses in the teleostean hypothalamus: a case study with the organochlorine pesticide dieldrin. Organochlorine pesticides (OCPs) such as dieldrin are a persistent class of aquatic pollutants that cause adverse neurological and reproductive effects in vertebrates. In this study, female and male largemouth bass (Micropterus salmoides) (LMB) were exposed to 3mg dieldrin/kg feed in a 2 month feeding exposure (August-October) to (1) determine if the hypothalamic transcript responses to dieldrin were conserved between the sexes; (2) characterize cell signaling cascades underlying dieldrin neurotoxicity; and (3) determine whether or not co-feeding with 17β-estradiol (E(2)), a hormone with neuroprotective roles, mitigates responses in males to dieldrin. Despite also being a weak estrogen, dieldrin treatments did not elicit changes in reproductive endpoints (e.g. gonadosomatic index, vitellogenin, or plasma E(2)). Sub-network (SNEA) and gene set enrichment analysis (GSEA) revealed that neuro-hormone networks, neurotransmitter and nuclear receptor signaling, and the activin signaling network were altered by dieldrin exposure. Most striking was that the majority of cell pathways identified by the gene set enrichment were significantly increased in females while the majority of cell pathways were significantly decreased in males fed dieldrin. These data suggest that (1) there are sexually dimorphic responses in the teleost hypothalamus; (2) neurotransmitter systems are a target of dieldrin at the transcriptomics level; and (3) males co-fed dieldrin and E(2) had the fewest numbers of genes and cell pathways altered in the hypothalamus, suggesting that E(2) may mitigate the effects of dieldrin in the central nervous system. 23017393 Proteomic evaluation of myofibrillar carbonylation in chilled fish mince and its inhibition by catechin. The present study investigates the susceptibility of individual myofibrillar proteins from mackerel (Scomber scombrus) mince to undergo carbonylation reactions during chilled storage, and the antioxidant capacity of (+)-catechin to prevent oxidative processes of proteins. The carbonylation of each particular protein was quantified by combining the labelling of protein carbonyls by fluorescein-5-thiosemicarbazide (FTSC) with 1-D or 2-D gel electrophoresis. Alpha skeletal actin, glycogen phosphorylase, unnamed protein product (UNP) similar to enolase, pyruvate kinase, isoforms of creatine kinase, aldolase A and an isoform of glyceraldehyde 3-phosphate dehydrogenase (G3PDH) showed elevated oxidation in chilled non-supplemented mince. Myosin heavy chain (MHC) was not carbonylated in chilled muscle, but an extensive MHC degradation was observed in those samples. The supplementation of catechin reduced protein oxidation and lipid oxidation in a concentration-dependent manner: control>25>100≈200ppm. Therefore, the highest catechin concentrations (100 and 200ppm) exhibited the strongest antioxidant activity. Catechin (200ppm) reduced significantly carbonylation of protein spots identified as glycogen phosphorylase, pyruvate kinase muscle isozyme, isoforms of creatine kinase. Conversely, catechin was ineffective to inhibit the oxidation of actin and UNP similar to enolase. These results draw attention to the inefficiency of catechin to prevent actin oxidation, in contrast to the extremely high efficiency of catechin in inhibiting oxidation of lipids and other proteins. 23402636 Health benefits of blue-green algae: prevention of cardiovascular disease and nonalcoholic fatty liver disease. Blue-green algae (BGA) are among the most primitive life forms on earth and have been consumed as food or medicine by humans for centuries. BGA contain various bioactive components, such as phycocyanin, carotenoids, γ-linolenic acid, fibers, and plant sterols, which can promote optimal health in humans. Studies have demonstrated that several BGA species or their active components have plasma total cholesterol and triglyceride-lowering properties due to their modulation of intestinal cholesterol absorption and hepatic lipogenic gene expression. BGA can also reduce inflammation by inhibiting the nuclear factor κ B activity, consequently reducing the production of proinflammatory cytokines. Furthermore, BGA inhibit lipid peroxidation and have free radical scavenging activity, which can be beneficial for the protection against oxidative stress. The aforementioned effects of BGA can contribute to the prevention of metabolic and inflammatory diseases. This review provides an overview of the current knowledge of the health-promoting functions of BGA against cardiovascular disease and nonalcoholic fatty liver disease, which are major health threats in the developed countries. 23386468 Synthesis and biological evaluation of purine 2'-fluoro-2'-deoxyriboside ProTides as anti-influenza virus agents. 2'-Fluoro-2'-deoxyguanosine has been reported to have potent anti-influenza virus activity in vitro and in vivo. Herein we describe the synthesis and biological evaluation of 6-modified 2'-fluoro-2'-deoxyguanosine analogues and their corresponding phosphoramidate ProTides as potential anti-influenza virus agents. Whereas the parent nucleosides were devoid of antiviral activity in two different cellular assays, the 5'-O-naphthyl(methoxy-L-alaninyl) ProTide derivatives of 6-O-methyl-2'-fluoro-2'-deoxyguanosine, 6-O-ethyl-2'-fluoro-2'-deoxyguanosine, and 2'-deoxy-2'-fluoro-6-chloroguanosine, and the 5'-O-naphthyl(ethoxy-L-alaninyl) ProTide of 6-O-ethyl-2'-fluoro-2'-deoxyguanosine displayed antiviral EC(99) values of ~12 μM. The antiviral results are supported by metabolism studies. Rapid conversion into the L-alaninyl metabolite and then 6-modified 2'-fluoro-2'-deoxyguanosine 5'-monophosphate was observed in enzymatic assays with yeast carboxypeptidase Y or crude cell lysate. Evidence for efficient removal of the 6-substituent on the guanine part was provided by enzymatic studies with adenosine deaminase, and by molecular modeling of the nucleoside 5'-monophosphates in the catalytic site of a model of ADAL1, thus indicating the utility of the double prodrug concept. 23419814 The transdermal delivery of fentanyl. The fentanyl patch is one of the great commercial successes in transdermal drug delivery. The suitability of this molecule for delivery through skin had been identified in the 1970s, and subsequently, a number of transdermal formulations became available on the market. This article reviews the development of fentanyl patch technology with particular emphasis on the pharmacokinetics and disposition of the drug when delivered through the skin. The various patch designs are considered as well as the bioequivalence of the different designs. The influence of heat on fentanyl permeation is highlighted. Post-mortem redistribution of fentanyl is discussed in light of the reported discrepancies in serum levels reported in patients after death compared with therapeutic levels in living subjects. Finally, alternatives to patch technology are considered, and recent novel transdermal formulations are highlighted. 23386780 Apoptotic cell death in rat epididymis following epichlorohydrin treatment. Epichlorohydrin (ECH) is an antifertility agent that acts both as an epididymal toxicant and an agent capable of directly affecting sperm motility. This study identified the time course of apoptotic cell death in rat epididymides after ECH treatment. Rats were administrated with a single oral dose of ECH (50 mg/kg). ECH-induced apoptotic changes were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and its related mechanism was confirmed by Western blot analysis and colorimetric assay. The TUNEL assay showed that the number of apoptotic cells increased at 8 h, reached a maximum level at 12 h, and then decreased progressively. The Western blot analysis demonstrated no significant changes in proapoptotic Bcl-2-associated X (Bax) and anti-apoptotic Bcl-2 expression during the time course of the study. However, phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) and phospho-c-Jun amino-terminal kinase (p-JNK) expression increased at 8-24 h. Caspase-3 and caspase-8 activities also increased at 8-48 h and 12-48 h, respectively, in the same manner as p-p38 MAPK and p-JNK expression. These results indicate that ECH induced apoptotic changes in rat epididymides and that the apoptotic cell death may be related more to the MAPK pathway than to the mitochondrial pathway. 23314277 Biochemical and metabolic effects of a short-term exposure to nanoparticles of titanium silicate in tadpoles of Pelophylax perezi (Seoane). This study aimed to evaluate sublethal effects of a short-term exposure (96 h) to titanium silicate nanoparticles (TiSiO(4)-NP) on Pelophylax perezi tadpoles. Tadpoles were exposed to five concentrations of TiSiO(4)-NP (8.2, 10.2, 12.8, 16 and 20 mg/L) plus a control. Effect criteria were: mortality, cholinesterases, glutathione S-transferases, lactate dehydrogenase, and catalase activities, and alanine and lactate contents. Light scattering was used for physical characterization of TiSiO(4)-NP suspensions, revealing a high aggregation state of the NP, consistent with low z-potential values (<30 mV). Mortality among TiSiO(4)-NP treatments was <11%. Significant differences relatively to the control were observed at the biochemical level (for CAT and LDH) and in lactate and alanine contents, which may end-up in increased oxidative stress. Overall, some of the monitored endpoints suggest metabolic alterations in TiSiO(4)-NP exposed tadpoles, highlighting the potential of TiSiO(4)-NP long-term effects on these organisms. 23620266 Enantiomeric fraction determination of 2-arylpropionic acids in a package plant membrane bioreactor. Enantiomeric compositions of three 2-arylpropionic acid (2-APA) drugs, ibuprofen, naproxen, and ketoprofen, were monitored in a membrane bioreactor (MBR) treating municipal effluent in a small rural town in Australia. Specific enantiomers were determined as amide diastereomers using the chiral derivatizing reagent, (R)-1-phenylethylamine (PEA), followed by gas chromatography-tandem mass spectrometry (GC-MS/MS). The six individual enantiomers were quantified by isotope dilution and the enantiomeric fractions (EFs) were determined. Over four separate sampling events, ibuprofen EF ranged from 0.88 to 0.94 (median 0.93) in the influent and 0.38 to 0.40 (median 0.39) in the effluent. However, no significant change in ketoprofen EF was observed, with influent EFs of 0.56-0.60 (median 0.58) and effluent EFs 0.54-0.68 (median 0.56). This is the first report of enantiospecific analysis of ketoprofen in municipal wastewater and it is not yet clear why such different behavior was observed compared to ibuprofen. Naproxen EF was consistently measured at 0.99 in the influent and ranged from 0.86 to 0.94 (median 0.91) in the effluent. This study demonstrates that EF is a relatively stable parameter and does not fluctuate according to concentration or other short-term variables introduced by sampling limitations. The enantiospecific analysis of chiral chemicals presents a promising approach to elucidate a more thorough understanding of biological treatment processes and a potential tool for monitoring the performance of key biological pathways. Chirality 25:301-307, 2013. © 2013 Wiley Periodicals, Inc. 22678994 Mild Mitochondrial Depolarization is Involved in a Neuroprotective Mechanism of Citrus sunki Peel Extract. Mitochondrial membrane potential (∆Ψm ) contributes to determining a driving force for calcium to enter the mitochondria. It has been demonstrated that even a small mitochondrial depolarization is sufficient to prevent mitochondrial calcium overload and the subsequent apoptosis. Therefore, mild mitochondrial depolarization has been recently evaluated as a novel mechanism of neuroprotection via inhibiting neurotoxic mitochondrial calcium overload during neuronal insults. In the present study, using both real-time recording and flow cytometric analyses of ∆Ψm , we demonstrated that ethanolic peel extract of Citrus sunki Hort. ex Tanaka (CPE) and its active compounds are capable of inducing a mild mitochondrial depolarization. Polymethoxylated flavones such as nobiletin and tangeretin were found as the active compounds responsible for CPE effects on ∆Ψm . Neuronal viability was significantly increased in a dose-dependent manner by CPE treatment in H2 O2 -stimulated HT-22 cells as an in vitro neuronal insult model. CPE treatment significantly inhibited H2 O2 -induced apoptotic processes such as chromatin condensation, caspase 3 activation and anti-poly (ADP-ribose) polymerase (PARP) cleavage. CPE treatment significantly blocked mitochondrial calcium overload in H2 O2 -stimulated HT-22 neurons as indicated by rhod-2 acetoxymethyl ester. Taken together, our findings suggest that CPE and its active compounds may be considered as promising neuroprotective agents via inducing a mild mitochondrial depolarization. Copyright © 2012 John Wiley & Sons, Ltd. 23352650 Point-to-point ligand-receptor interactions across the subunit interface modulate the induction and stabilization of conformational states of alpha7 nAChR by benzylidene anabaseines. The homomeric α7 nicotinic acetylcholine receptor is a well-studied therapeutic target, though its characteristically rapid desensitization complicates the development of drugs with specific agonist effects. Moreover, some experimental compounds such as GTS-21 (2,4diMeOBA), a derivative of the α7-selective partial agonist benzylidene anabaseine (BA), produce a prolonged residual desensitization (RD) in which the receptor remains non-activatable long after the drug has been removed from extracellular solution. In contrast, the desensitization caused by GTS-21's dihydroxy metabolite (2,4diOHBA) is relatively short-lived. RD is hypothetically due to stable binding of the ligand to the receptor in its desensitized state. We can attribute the reduction in RD to a single BA hydroxyl group on the 4' benzylidene position. Computational prediction derived from homology modeling showed the serine36 (S36) residue of α7 as a reasonable candidate for point-to-point interaction between BA compounds and the receptor. Through evaluating the activity of BA and simple derivatives on wild-type and mutant α7 receptors, it was observed that the drug-receptor pairs which were capable of hydrogen bonding at residue 36 exhibited significantly less stable desensitization. Further experiments involving the type II positive allosteric modulator (PAM) PNU-120596 showed that the various BA compounds' preference to induce either a PAM-sensitive (D(s)) or PAM-insensitive (D(i)) desensitized state is concentration dependent and suggested that both states are destabilized by S36 H-bonding. These results indicate that the fine-tuning of agonists for specific interaction with S36 can facilitate the development of therapeutics with targeted effects on ion channel desensitization properties and conformational state stability. 23618528 Lactobacillus rhamnosus GG reduces hepatic TNFα production and inflammation in chronic alcohol-induced liver injury. The therapeutic effects of probiotic treatment in alcoholic liver disease (ALD) have been studied in both patients and experimental animal models. Although the precise mechanisms of the pathogenesis of ALD are not fully understood, gut-derived endotoxin has been postulated to play a crucial role in hepatic inflammation. Previous studies have demonstrated that probiotic therapy reduces circulating endotoxin derived from intestinal gram-negative bacteria in ALD. In this study, we investigated the effects of probiotics on hepatic tumor necrosis factor-α (TNFα) production and inflammation in response to chronic alcohol ingestion. Mice were fed Lieber DeCarli liquid diet containing 5% alcohol for 8weeks, and Lactobacillus rhamnosus GG (LGG) was supplemented in the last 2 weeks. Eight-week alcohol feeding caused a significant increase in hepatic inflammation as shown by histological assessment and hepatic tissue myeloperoxidase activity assay. Two weeks of LGG supplementation reduced hepatic inflammation and liver injury and markedly reduced TNFα expression. Alcohol feeding increased hepatic mRNA expression of Toll-like receptors (TLRs) and CYP2E1 and decreased nuclear factor erythroid 2-related factor 2 expression. LGG supplementation attenuated these changes. Using human peripheral blood monocytes-derived macrophages, we also demonstrated that incubation with ethanol primes both lipopolysaccharide- and flagellin-induced TNFα production, and LGG culture supernatant reduced this induction in a dose-dependent manner. In addition, LGG treatment also significantly decreased alcohol-induced phosphorylation of p38 MAP kinase. In conclusion, probiotic LGG treatment reduced alcohol-induced hepatic inflammation by attenuation of TNFα production via inhibition of TLR4- and TLR5-mediated endotoxin activation. 23600486 A Singlet Biradicaloid Zinc Compound and Its Nonradical Counterpart. Metal ions with radical centers in their coordination sphere are key participants in biological and catalytic processes. In the present study, we describe the synthesis of the cAAC:ZnCl2 adduct (1) using a cyclic alkylaminocarbene (cAAC) as donor ligand. Compound 1 was treated with 2 equiv of KC8 and LiB(sec-Bu)3H to yield a deep blue-colored dicarbene zinc compound (cAAC)2Zn (2) and the colorless hydrogenated zinc compound (cAACH)2Zn (3), respectively. Compounds 2 and 3 were well characterized by spectroscopic methods and single-crystal X-ray structural analysis. Density functional theory calculations were performed for 2 which indicate that this molecule possesses a singlet biradicaloid character. Moreover, we show the application of 2 in CO2 activation, which yields a zwitterionic cAAC·CO2 adduct. 22931212 Elucidation of the mechanism of ribose conjugation in a pyrazole-containing compound in rodent liver. 1. Here we report on the mechanism of ribose conjugation, through NADH as a cofactor, of a pyrazole-containing compound (PT). Incubation of PT in rat liver microsomes supplemented with NADP⁺/H, NAD⁺/H, and β-nicotinamide mononucleotide (NMN) resulted in complete conjugation to the adenine dinucleotide phosphate conjugate (ADP-C), adenine dinucleotide conjugate (AD-C), and 5-phosphoribose conjugate (Rib-C1), respectively. In hepatocytes, PT predominantly formed three ribose conjugates: Rib-C1, the ribose conjugate (Rib-C2), and the carboxylic acid of Rib-C2 (Rib-C3). 2. Phosphatase inhibitors were added to hepatocyte incubations. AD-C was detected in this reaction, which suggests that one of the major pathways for the formation of the ribose conjugates is through NAD⁺/H. When AD-C was incubated with phosphatase, Rib-C1 and Rib-C2 formed. 3. To understand the in vivo relevance of this metabolic pathway, rats were dosed with PT and Rib-C2 was found in the urine. 4. Structure-activity relationship shows that replacement of the distal thiazole group in the PT to a phenyl group abolishes this conjugation. Three amino acid residues in the active site preferentially interact with the sulfur atom in the thiazole of PT. 5. In summary, PT forms direct AD-C in hepatocytes, which is further hydrolyzed by phosphatase to give ribose conjugates. 23586441 Tuning the Emission Properties of Fluorescent Ligands by Changing pH: The Unusual Case of an Acridine-Containing Polyamine Macrocycle. Synthesis and characterization of a new macrocyclic compound, composed by a triethylentetraamine chain linking the 4 and 5 positions of an acridine moiety, are reported. The molecule, devised as a fluorescent chemosensor for anions, has revealed an intriguing pH-dependent spectroscopic behavior, whose features are the specific object of this article. Ligand protonation in aqueous solution has been analyzed by means of potentiometric, (1)H NMR, UV-vis, and fluorescence emission measurements. The molecule binds up to four protons in the pH range 2-11. Protonation takes place on the aliphatic tetraamine chain, while the acridine nitrogen does not participate to proton binding even at very low pH. Differently from acridine, the UV-vis spectra are almost unaffected by the pH. On the opposite, the emission spectra are strongly pH-dependent. In fact, at low pH values, the spectra show a blue-shifted emission, resembling that of unprotonated acridine, while at slightly acidic and alkaline pH the fluorescence features a red-shifted band similar to that of acridinium cation. This unusual behavior occurs in the mono-, bi-, and triprotonated forms of the compound and is interpreted as due to an excited state proton transfer from an aliphatic ammonium group adjacent to the acridine moiety to the acridine nitrogen. In the fully protonated state, this process is prevented owing to unfavorable molecular arrangements mainly determined by electrostatic repulsions. This interpretation is supported by quantum mechanical calculations as well as molecular dynamics simulations. 23057615 A new approach to counteract bacteria resistance: a comparative study between moxifloxacin and a new moxifloxacin derivative in different model systems of bacterial membrane. New drug design has been one of the major challenges to combat bacterial resistance over the past decade. Conventional antibiotics act by destroying bacterial cell wall or by blocking biosynthetic pathways necessary for its survival. Unfortunately, there has been a fast increase in multiresistance, to several conventional antibiotics, in clinical bacterial strains. Previous studies have shown that metalloantibiotics, ternary complexes of antibiotic-metal-phenanthroline, present an increased potential as antimicrobial agents. In this work moxifloxacin, a fourth-generation quinolone, with a broad spectrum of action, and its copper ternary complex (metalloantibiotic) have been study by fluorescence spectroscopy. Partition coefficients were determined and showed that while free moxifloxacin exhibits the same behaviour independently of the lipidic system tested, the metalloantibiotic presents higher partition to liposomes, in a lipid composition-dependent way. These significant differences in the interaction of the metalloantibiotic with model bacteria membranes point out for a putative change in its uptake mechanism with increased drug-lipid interaction potentiating metalloantibiotic influx. 23454054 Characteristics of indomethacin-saccharin (IMC-SAC) co-crystals prepared by an anti-solvent crystallization process. The creation of co-crystals of various insoluble drug substances has been extensively investigated as a promising approach to improve their pharmaceutical performance. In this study, co-crystal powders of indomethacin and saccharin (IMC-SAC) were prepared by an anti-solvent (water) addition and compared with co-crystals by evaporation method. No successful synthesis of a pharmaceutical co-crystal powder via an anti-solvent approach has been reported. Among solvents examined, methanol was practically the only one that resulted in the formation of highly pure IMC-SAC co-crystal powders by anti-solvent approach. The mechanism of a preferential formation of IMC-SAC co-crystal to IMC was explained with two aspects: phase solubility diagram and solution complexation concept. Accordingly, the anti-solvent approach can be considered as a competitive route for producing pharmaceutical co-crystal powders with acceptable properties. 23474645 Inverted CdSe/CdS/ZnS quantum dot light emitting devices with titanium dioxide as an electron-injection contact. We demonstrated the fabrication of inverted CdSe/CdS/ZnS quantum dot light emitting devices (QD-LEDs) using titanium dioxide (TiO2) as an electron-injection layer and investigated the operating mechanism by utilizing different hole-transport materials, 4,4-N,N-dicarbazole-biphenyl (CBP) and 4,4',4''-tris(carbazol-9-yl)-triphenylamine (TCTA). A more efficient device with CBP as the hole-transport layer (HTL) was obtained compared with the TCTA based device. The peak efficiency of 6.70 cd A(-1) for the CBP based device was found to be about 74.5% higher than the TCTA based device (3.84 cd A(-1)). The studies on the time-resolved photoluminescence spectra of the QD-HTL composite structures showed that the energy transfer (ET) efficiencies from the two HTLs to the QD layer were similar and the charge separation between QDs and HTLs could be neglected. The enhancement in the performance of the CBP based device was attributed to the more efficient hole-injection from CBP to QDs. 23532854 Structural and Functional Aspects of Hetero-oligomers Formed by the Small Heat-Shock Proteins αB crystallin and HSP27. Small heat shock proteins (sHSPs) exist as large polydisperse species in which there is constant dynamic subunit exchange between oligomeric and dissociated forms. Their primary role in vivo is to bind destabilized proteins and prevent their misfolding and aggregating. αB Crystallin (αB) and HSP27 are the two most widely distributed and most studied sHSPs in the human body. They are co-expressed in different tissues where they are known to associate with each other and form hetero-oligomeric complexes. This study aimed to determine how these two sHSPs interact to form hetero-oligomers in vitro and whether, by doing so, there is an increase in their chaperone activity and stability compared to their homo-oligomeric forms. Results demonstrate that HSP27 and αB form polydisperse hetero-oligomers in vitro which have an average molecular mass higher than each of the homo-oligomers and are more thermostable than αB, but less so than HSP27. The hetero-oligomer chaperone function was found to be equivalent to that of αB, with each being significantly better at preventing the amorphous aggregation of α-lactalbumin and the amyloid fibril formation of α-synuclein in comparison to HSP27. Using mass spectrometry to monitor subunit exchange over time it was found that HSP27 and αB exchange subunits 23% faster than the reported rate for HSP27/αA, and almost twice that of αA/αB. This represents the first quantitative evaluation of HSP27/αB subunit exchange and the results are discussed in the broader context of regulation of function and cellular proteostasis. 23153322 Salivary gland function 5 years after radioactive iodine ablation in patients with differentiated thyroid cancer: direct comparison of pre- and postablation scintigraphies and their relation to xerostomia symptoms. Background: Chronic sialadenitis is one of the most frequent chronic complications after radioactive iodine (RAI) therapy for thyroid cancer. To evaluate the long-term effects of RAI ablation on salivary gland function, we investigated scintigraphic changes in salivary glands by direct comparison of two salivary gland scintigraphies (SGSs) taken before and at 5 years after an RAI ablation. Methods: SGS was performed just before RAI ablation (pre-SGS) and ∼5 years after RAI ablation (F/U SGS) in 213 subjects who underwent thyroidectomy for thyroid cancer. The uptake score (U score) was graded, and the ejection fraction (EF) was quantified for the parotid and submandibular glands at pre-SGS and F/U SGS. Changes in salivary gland function were graded as mild, moderate, or severe according to the differences in U score and EF between the two SGSs. Xerostomia was assessed and compared with the SGS findings. Results: Worsening of the U score was observed in 182 of 852 salivary glands (total: 21.3%; mild: 4.2%, moderate: 7.4%, severe: 9.7%), and 47.4% of the patients had a worsening U score for at least one of four salivary glands. A decrease in EF was observed in 173 of 852 salivary glands (total: 20.3%; mild: 5.4%, moderate: 6.8%, severe: 8.1%), and 43.7% of the patients experienced a decrease in the EF of at least one of the four salivary glands. Bilateral parotid gland dysfunction was the most commonly observed condition. Thirty-five (16.4%) patients complained of xerostomia at 5 years after RAI ablation. Scintigraphic changes in salivary gland function and xerostomia were more common in patients receiving 5.55 GBq, compared with 3.7 GBq. Xerostomia was more common in patients with submandibular gland dysfunction than those with parotid gland dysfunction (68.8% vs. 33.3%, p<0.05). The number of dysfunctional salivary glands was correlated with xerostomia (p<0.01). Conclusion: About 20% of the salivary glands were dysfunctional on SGS 5 years after a single RAI ablation, especially in patients who received higher doses of RAI. While parotid glands are more susceptible to (131)I-related damage, xerostomia was more associated with submandibular gland dysfunction and the prevalence of dysfunctional salivary glands. 23170798 Neuroprotection & mechanism of ethanol in stroke and traumatic brain injury therapy: new prospects for an ancient drug. Effective efforts to screen for agents that protect against the devastating effects of stroke have not produced viable results thus far. As a result this article reviews the possible role of ethanol as a neuroprotective agent in stroke and traumatic brain injury (TBI). Previous studies have associated ethanol consumption with a decreased risk of ischemic stroke, suggesting a neuroprotective mechanism. The translation of this clinical knowledge into basic science research with the goal of new therapy for acute stroke patients remains in its initial stages. In a recent study involving rats, we have shown that ethanol administration, in the correct dose after stroke onset, protects against ischemia-induced brain injury. The purpose of this paper is to discuss ethanol's neuroprotective properties in stroke when consumed as a preconditioning agent, in TBI with a positive blood alcohol content, and finally in stroke treatment, with the goal of using post-ischemia ethanol (PIE) therapy to ameliorate brain damage in the future. 23603192 Reproductive toxicity of Campomanesia xanthocarpa (Berg.) in female Wistar rats. ETHNOPHARMACOLOGICAL RELEVANCE: There is no evidence in the literature that substantiates the safety of Campomanesia xanthocarpa (Berg.) use during pregnancy. MATERIALS AND METHODS: Thirty three female rats were randomly assigned to three groups. One group of animals received the Campomanesia xanthocarpa extract via gavage at a dose of 26.3mg/kg/day from 6 to 15 days of pregnancy (organogenic period, T1) and another group received the same extract throughout the gestational period (from the 1st to the 20th day of pregnancy, T2). Control groups received distilled water. Euthanasia was done on 20th day, when the liver, kidney, spleen ovaries, fetuses and their respective placentas were removed. Implantations, reabsorptions, live and dead fetuses were recorded. RESULTS AND CONCLUSIONS: Campomanesia xanthocarpa, in these experimental conditions, did not disturb the reproductive function of female rats and did not interrupt the progress of the embryofetal development. Moreover, our results provide further evidence that the Campomanesia xanthocarpa treatment reduces reabsorption sites, increases placenta weight and the number of live fetuses and may therefore have therapeutic applications. 23076840 Contamination, parasitism and condition of Anguilla anguilla in three Italian stocks. In conjunction with habitat loss and overfishing, pollution and parasitism are believed to be relevant causes of collapse of Anguilla, as these can affect eel swimming ability and the development of gonads and embryos. The present study investigated Persistent Organic Pollutant (POP) concentrations, infection levels of Anguillicoloides crassus, lipid content and gonad abnormalities in eels sampled in 2007-2008 in three Italian water bodies (Caprolace Lake, Lesina Lagoon and Tevere River) that vary in salinity, trophic condition, contamination level and fishing pressure. Our analysis revealed that low-to-moderate levels of contamination and parasitism were not associated with gonad abnormalities in Caprolace Lake and Lesina Lagoon. On the contrary, POP concentrations and abundances of swim bladder nematodes were remarkably high in eels from the heavily urbanized Tevere River and were associated with significant gonad and swim bladder alterations. Contamination and infestation levels were so high to potentially impair spawner successful migration and reproduction. POP concentrations in Tevere eels also exceeded levels considered safe for food consumption. Though marginally contaminated, eels from the oligotrophic Caprolace Lake were in critical health condition: their lipid reserve was so low as to be considered insufficient to sustain the energetic costs of the transoceanic migration. Lesina eel stock was the only one displaying relatively good quality but here spawner abundance is likely limited by overfishing. Our results suggest that multiple stressors may potentially affect eel reproductive success. More definitive studies are needed to assess whether health effects caused by these multiple stressors are additive, compensatory or synergistic. 22370645 Upregulation of CXCR4 is functionally crucial for maintenance of stemness in drug-resistant non-small cell lung cancer cells. The hypothesis of cancer stem cells has been proposed to explain the therapeutic failure in a variety of cancers including lung cancers. Previously, we demonstrated acquisition of epithelial-mesenchymal transition, a feature highly reminiscent of cancer stem-like cells, in gefitinib-resistant A549 cells (A549/GR). Here, we show that A549/GR cells contain a high proportion of CXCR4+ cells that are responsible for having high potential of self-renewal activity in vitro and tumorigenicity in vivo. A549/GR cells exhibited strong sphere-forming activity and high CXCR4 expression and SDF-1α secretion compared with parent cells. Pharmacological inhibition (AMD3100) and/or siRNA transfection targeting CXCR4 significantly suppressed sphere-forming activity in A549 and A549/GR cells, and in various non-small cell lung cancer (NSCLC) cell lines. A549/GR cells showed enhanced Akt, mTOR and STAT3 (Y705) phosphorylation. Pharmacological inhibition of phosphatidyl inositol 3-kinase or transfection with wild-type PTEN suppressed phosphorylation of Akt, mTOR and STAT3 (Y705), sphere formation, and CXCR4 expression in A549/GR cells, whereas mutant PTEN enhanced these events. Inhibition of STAT3 by WP1066 or siSTAT3 significantly suppressed the sphere formation, but not CXCR4 expression, indicating that STAT3 is a downstream effector of CXCR4-mediated signaling. FACS-sorted CXCR4+ A549/GR cells formed many large spheres, had self-renewal capacity, demonstrated radiation resistance in vitro and exhibited stronger tumorigenic potential in vivo than CXCR4- cells. Lentiviral-transduction of CXCR4 enhanced sphere formation and tumorigenicity in H460 and A549 cells, whereas introduction of siCXCR4 suppressed these activities in A549/GR cells. Our data indicate that CXCR4+ NSCLC cells are strong candidates for tumorigenic stem-like cancer cells that maintain stemness through a CXCR4-medated STAT3 pathway and provide a potential therapeutic target for eliminating these malignant cells in NSCLC. 23347422 Surface functionalization of a polymeric lipid bilayer for coupling a model biological membrane with molecules, cells, and microstructures. We describe a stable and functional model biological membrane based on a polymerized lipid bilayer with a chemically modified surface. A polymerized lipid bilayer was formed from a mixture of two diacetylene-containing phospholipids, 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DiynePC) and 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphoethanolamine (DiynePE). DiynePC formed a stable bilayer structure, whereas the ethanolamine headgroup of DiynePE enabled functional molecules to be grafted onto the membrane surface. Copolymerization of DiynePC and DiynePE resulted in a robust bilayer. Functionalization of the polymeric bilayer provided a route to a robust and biomimetic surface that can be linked with biomolecules, cells, and three-dimensional (3D) microstructures. Biotin and peptides were grafted onto the polymeric bilayer for attaching streptavidin and cultured mammalian cells by molecular recognition, respectively. Nonspecific adsorption of proteins and cells on polymeric bilayers was minimum. DiynePE was also used to attach a microstructure made of an elastomer (polydimethylsiloxan: PDMS) onto the membrane, forming a confined aqueous solution between the two surfaces. The microcompartment enabled us to assay the activity of a membrane-bound enzyme (cyochrome P450). Natural (fluid) lipid bilayers were incorporated together with membrane-bound proteins by lithographically polymerizing DiynePC/DiynePE bilayers. The hybrid membrane of functionalized polymeric bilayers and fluid bilayers offers a novel platform for a wide range of biomedical applications including biosensor, bioassay, cell culture, and cell-based assay. 23265904 Discovery of liver-targeted inhibitors of stearoyl-CoA desaturase (SCD1). Inhibitors based on a benzo-fused spirocyclic oxazepine scaffold were discovered for stearoyl-coenzyme A (CoA) desaturase 1 (SCD1) and subsequently optimized to potent compounds with favorable pharmacokinetic profiles and in vivo efficacy in reducing the desaturation index in a mouse model. Initial optimization revealed potency preferences for the oxazepine core and benzylic positions, while substituents on the piperidine portions were more tolerant and allowed for tuning of potency and PK properties. After preparation and testing of a range of functional groups on the piperidine nitrogen, three classes of analogs were identified with single digit nanomolar potency: glycine amides, heterocycle-linked amides, and thiazoles. Responding to concerns about target localization and potential mechanism-based side effects, an initial effort was also made to improve liver concentration in an available rat PK model. An advanced compound 17m with a 5-carboxy-2-thiazole substructure appended to the spirocyclic piperidine scaffold was developed which satisfied the in vitro and in vivo requirements for more detailed studies. 23281578 Glycofullerenes inhibit viral infection. Water-soluble glycofullerenes based on a hexakis-adduct of [60]fullerene with an octahedral addition pattern are very attractive compounds providing a spherical presentation of carbohydrates. These tools have been recently described and they have been used to interact with lectins in a multivalent manner. Here, we present the use of these glycofullerenes, including new members with 36 mannoses, as compounds able to inhibit a DC-SIGN-dependent cell infection by pseudotyped viral particles. The results obtained in these experiments demonstrate for the first time that these glycoconjugates are adequate to inhibit efficiently an infection process, and therefore, they can be considered as very promising and interesting tools to interfere in biological events where lectins such as DC-SIGN are involved. 23414802 Discovery of novel 2-hydroxydiarylamide derivatives as TMPRSS4 inhibitors. TMPRSS4 is a novel type II transmembrane serine protease that has been implicated in the invasion and metastasis of colon cancer cells. In this study, a novel series of 2-hydroxydiarylamide derivatives were synthesized and evaluated for inhibiting TMPRSS4 serine protease activity and suppressing cancer cell invasion. These derivatives demonstrated good inhibitory activity against TMPRSS4 serine protease, which correlated with the promising anti-invasive activity of colon cancer cells overexpressing TMPRSS4. 23313639 Design and synthesis of biaryl aryl stilbenes/ethylenes as antimicrotubule agents. Two new series of compounds E-2,3,4-trimethoxy-6-styrylbiphenyls and 2,3,4-trimethoxy-6-(1-phenylvinyl)biphenyls were designed, synthesized and evaluated for antitubulin activity. A common intermediate 4,5,6-trimethoxybiphenyl-2-carbaldehydes was employed to generate the two scaffolds. Majority of the analogs inhibited cell proliferation and those functionalized with 3,4-(1,3-dioxolane) and 3,4-difluoro groups were identified as effective inhibitors in both the series. Treatments with 19b, 19c, 22b and 22c arrested cells at G2/M phase, disrupted microtubule network, accumulated tubulin in the soluble fraction and manifested an increased expression of the G2/M marker, Cyclin B1. Molecular docking analysis demonstrated the interaction of these compounds at the colchicine binding site of tubulin. 23349494 Disruption of the cerebral white matter network is related to slowing of information processing speed in patients with type 2 diabetes. Patients with type 2 diabetes often show slowing of information processing. Disruptions in the brain white matter network, possibly secondary to vascular damage, may underlie these cognitive disturbances. The present study reconstructed the white matter network of 55 nondemented individuals with type 2 diabetes (mean age 71±4y) and 50 age-, sex- and education-matched controls using diffusion MRI based fiber tractography. Graph theoretical analysis was then applied to quantify the efficiency of these networks. Patients with type 2 diabetes showed alterations in local and global network properties compared to controls (p<0.05). These structural network abnormalities were related to slowing of information processing speed in patients. This relation was partly independent of cerebrovascular lesion load. This study shows that the approach of characterizing the brain as a network using diffusion MRI and graph theory can provide new insights into how abnormalities in the white matter affect cognitive function in patients with diabetes. 23583513 Optimization of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of HIV capsid assembly inhibitors 1: Addressing configurational instability through scaffold modification. The optimization of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of inhibitors of HIV-1 capsid assembly that possess a labile stereocenter at C3 is described. Quaternization of the C3 position of compound 1 in order to prevent racemization gave compound 2, which was inactive in our capsid disassembly assay. A likely explanation for this finding was revealed by in silico analysis predicting a dramatic increase in energy of the bioactive conformation upon quaternization of the C3 position. Replacement of the C3 of the diazepine ring with a nitrogen atom to give the 1,5-dihydro-benzo[f][1,3,5]triazepine-2,4-dione analog 4 was well tolerated. Introduction of a rigid spirocyclic system at the C3 position gave configurationally stable 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione analog 5, which was able to access the bioactive conformation without a severe energetic penalty and inhibit capsid assembly. Preliminary structure-activity relationships (SAR) and X-ray crystallographic data show that knowledge from the 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of inhibitors of HIV-1 capsid assembly can be transferred to these new scaffolds. 23356207 Quantitative purity-activity relationships of natural products: the case of anti-tuberculosis active triterpenes from Oplopanax horridus. The present study provides an extension of the previously developed concept of purity-activity relationships (PARs) and enables the quantitative evaluation of the effects of multiple minor components on the bioactivity of residually complex natural products. The anti-tuberculosis active triterpenes from the Alaskan ethnobotanical Oplopanax horridus were selected as a case for the development of the quantitative PAR (QPAR) concept. The residual complexity of the purified triterpenes was initially evaluated by 1D- and 2D-NMR and identified as a combination of structurally related and unrelated impurities. Using a biochemometric approach, the qHNMR purity and anti-TB activity of successive chromatographic fractions of O. horridus triterpenes were correlated by linear regression analysis to generate a mathematical QPAR model. The results demonstrate that impurities, such as widely occurring monoglycerides, can have a profound impact on the observed antimycobacterial activity of triterpene-enriched fractions. The QPAR concept is shown to be capable of providing a quantitative assessment in situations where residually complex constitution contributes toward the biological activity of natural products. 23159396 High resolution fluorescence microscopy evidence on the transport of immunoglobulins. Differences between mammalian IgG, F(ab')2 and avian IgY. We describe the subcellular localization of horse F(ab')(2) and IgG, and ostrich IgY labeled with fluorescein isothiocyanate (FITC) administered IV to mice. We used wide field high sensitivity fluorescence microscopy deblurred by 3-dimensional blind deconvolution of kidney, liver, lungs and brain sections. Sections were obtained from mice sacrificed 15 min, 1 or 5 h after receiving FITC-immunoproteins, counter-stained with DAPI (4',6'-diamidino-2-phenylindole) and Evans blue. FITC-IgG and its fractions are rapidly taken up and extravasated by vascular endothelium. FITC-IgG and FITC-F(ab')(2) appear to be quickly secreted by glomeruli endothelium and to be reabsorbed along all nephron segments. FITC-IgG and FITC-F(ab')(2) appeared 15 min after IV injection within bronchial, alveolar and bile duct epithelium. Hepatocytes were loaded with fluorescence after 15 min of administration. Fluorescence was absent from brain slices, except for the endothelium of some vessels in brain ventricles which appeared intensely fluorescent. Fluorescence appeared in intracellular vesicles which conferred the tissues a glowing foamy aspect for up to 5 h after inoculation. Arterial elastic layers were intensely green after horse FITC-Ig inoculation. Ostrich FITC-IgY behaved completely differently to horse Ig's; only 1 h after injection it was possible to observe small brightly green scarce vesicles in vascular endothelium of arteries, interstitial kidney capillaries between nephron tubules and were also scarce in glomeruli endothelium; FITC-IgY appeared only in hepatic sinusoids in the liver. No IgY was seen in bronchial and alveolar endothelium, in bile ducts or in hepatocytes. 23300338 The Akt DUBbed InAktive. Akt is a central node in the phosphoinositide-3 kinase-Akt-mammalian target of rapamycin pathway and is activated by a multistep process in response to growth factor stimulation. An additional layer of posttranslational modification has emerged as a new paradigm in the regulation of Akt. The identification of an E3 ligase for Lys(63)-linked ubiquitination of Akt has now been complemented with the discovery of the tumor suppressor cylindromatosis as a deubiquitinating enzyme (DUB) for Akt. Thus, like phosphorylation and dephosphorylation, cycles of ubiquitination and deubiquitination provide additional on-off switches that keep Akt activity in balance, and disturbances in this balance have pathological consequences. 23265282 Streamlined expressed protein ligation using split inteins. Chemically modified proteins are invaluable tools for studying the molecular details of biological processes, and they also hold great potential as new therapeutic agents. Several methods have been developed for the site-specific modification of proteins, one of the most widely used being expressed protein ligation (EPL) in which a recombinant α-thioester is ligated to an N-terminal Cys-containing peptide. Despite the widespread use of EPL, the generation and isolation of the required recombinant protein α-thioesters remain challenging. We describe here a new method for the preparation and purification of recombinant protein α-thioesters using engineered versions of naturally split DnaE inteins. This family of autoprocessing enzymes is closely related to the inteins currently used for protein α-thioester generation, but they feature faster kinetics and are split into two inactive polypeptides that need to associate to become active. Taking advantage of the strong affinity between the two split intein fragments, we devised a streamlined procedure for the purification and generation of protein α-thioesters from cell lysates and applied this strategy for the semisynthesis of a variety of proteins including an acetylated histone and a site-specifically modified monoclonal antibody. 23362239 Ca²⁺-dependent phosphorylation of Ca²⁺ cycling proteins generates robust rhythmic local Ca²⁺ releases in cardiac pacemaker cells. The spontaneous beating of the heart is governed by spontaneous firing of sinoatrial node cells, which generate action potentials due to spontaneous depolarization of the membrane potential, or diastolic depolarization. The spontaneous diastolic depolarization rate is determined by spontaneous local submembrane Ca²⁺ releases through ryanodine receptors (RyRs). We sought to identify specific mechanisms of intrinsic Ca²⁺ cycling by which sinoatrial node cells, but not ventricular myocytes, generate robust, rhythmic local Ca²⁺ releases. At similar physiological intracellular Ca²⁺ concentrations, local Ca²⁺ releases were large and rhythmic in permeabilized sinoatrial node cells but small and random in permeabilized ventricular myocytes. Furthermore, sinoatrial node cells spontaneously released more Ca²⁺ from the sarcoplasmic reticulum than did ventricular myocytes, despite comparable sarcoplasmic reticulum Ca²⁺ content in both cell types. This ability of sinoatrial node cells to generate larger and rhythmic local Ca²⁺ releases was associated with increased abundance of sarcoplasmic reticulum Ca²⁺-ATPase (SERCA), reduced abundance of the SERCA inhibitor phospholamban, and increased Ca²⁺-dependent phosphorylation of phospholamban and RyR. The increased phosphorylation of RyR in sinoatrial node cells may facilitate Ca²⁺ release from the sarcoplasmic reticulum, whereas Ca²⁺-dependent increase in phosphorylation of phospholamban relieves its inhibition of SERCA, augmenting the pumping rate of Ca²⁺ required to support robust, rhythmic local Ca²⁺ releases. The differences in Ca²⁺ cycling between sinoatrial node cells and ventricular myocytes provide insights into the regulation of intracellular Ca²⁺ cycling that drives the automaticity of sinoatrial node cells. 23219946 Progressive post-yield behavior of human cortical bone in shear. Bone fragility depends on its post-yield behavior since most energy dissipation in bone occurs during the post-yield deformation. Previous studies have investigated the progressive changes in the post-yield behavior of human cortical bone in tension and compression using a novel progressive loading scheme. However, little is known regarding the progressive changes in the post-yield behavior of bone in shear. The objective of this short study was to address this issue by testing bone specimens in an inclined double notch shear configuration using the progressive loading protocol. The results of this study indicated that the shear modulus of bone decreased with respect to the applied strain, but the rate of degradation was about 50% less than those previously observed in compression and tension tests. In addition, a quasi-linear relationship between the plastic and applied strains was observed in shear mode, which is similar to those previously reported in tension and compression tests. However, the viscous responses of bone (i.e. relaxation time constants and stress magnitude) demonstrated slight differences in shear compared with those observed in tension and compression tests. Nonetheless, the results of this study suggest that the intrinsic mechanism of plastic deformation of human cortical bone may be independent of loading modes. 23235742 Particle shape optimization by changing from an isotropic to an anisotropic nanostructure: preparation of highly active and stable supported Pt catalysts in microemulsions. We recently introduced a new method to synthesize an active and stable Pt catalyst, namely thermo-destabilization of microemulsions (see R. Y. Parapat, V. Parwoto, M. Schwarze, B. Zhang, D. S. Su and R. Schomäcker, J. Mater. Chem., 2012, 22 (23), 11605-11614). We are able to produce Pt nanocrystals with a small size (2.5 nm) of an isotropic structure i.e. truncated octahedral and deposit them well on support materials. Although we have obtained good results, the performance of the catalyst still needed to be improved and optimized. We followed the strategy to retain the small size but change the shape to an anisotropic structure of Pt nanocrystals which produces more active sites by means of a weaker reducing agent. We found that our catalysts are more active than those we reported before and even show the potential to be applied in a challenging reaction such as hydrogenation of levulinic acid. 22372916 Role of excipients in successful development of self-emulsifying/microemulsifying drug delivery system (SEDDS/SMEDDS). The oral delivery of hydrophobic drug presents a major challenge because of the low aqueous solubility of such compounds. Self-emulsifying/microemulsifying drug delivery system (SEDDS/SMEDDS), which are isotropic mixtures of oils, surfactants, solvents and co-solvents/surfactants, can be used for the design of formulations in order to improve the oral absorption of highly lipophilic drug compounds. The efficiency of oral absorption of said drug from such type of formulation depends on many formulation-related parameters, such as surfactant concentration, oil/surfactant ratio, polarity of the emulsion, droplet size and charge, all of which in essence determine the self-emulsification ability. Thus, only very specific pharmaceutical excipient combinations will lead to efficient self-emulsifying systems. With the growing interest in this field, there is an increasing need for guidelines in excipient selection to obtain effective delivery system with improved bioavailability. The aim of this review is to present the recent approaches in selecting the most appropriate lipid system(s); methods for its characterization and role of various excipients for improved delivery of dosage form. 23219325 Novel cinnoline-based inhibitors of LRRK2 kinase activity. Leucine rich repeat kinase 2 (LRRK2) has been implicated in the pathogenesis of Parkinson's disease (PD). Inhibition of LRRK2 kinase activity is a therapeutic approach that may lead to new treatments for PD. Herein we report the discovery of a series of cinnoline-3-carboxamides that are potent against both wild-type and mutant LRRK2 kinase activity in biochemical assays. These compounds are also shown to be potent inhibitors in a cellular assay and to have good to excellent CNS penetration. 23552843 Intracellular cleavable poly(2-dimethylaminoethyl methacrylate) functionalized mesoporous silica nanoparticles for efficient siRNA delivery in vitro and in vivo. A low cytotoxicity and high efficiency delivery system with the advantages of low cost and facile fabrication is needed for the application of small interfering RNA (siRNA) delivery both in vitro and in vivo. For these prerequisites, cationic polymer-mesoporous silica nanoparticles (ssCP-MSNs) were prepared by surface functionalized mesoporous silica nanoparticles with disulfide bond cross-linked poly(2-dimethylaminoethyl methacrylate) (PDMAEMA). In vitro and in vivo evaluations were performed. The synthesized ssCP-MSNs are 100-150 nm in diameter with a pore size of 10 nm and a positively charged surface with a high zeta potential of 27 mV. Consequently, the ssCP-MSNs showed an excellent binding capacity for siRNA, and an enhancement in the cell uptake and cytosolic availability of siRNA. Furthermore, the intracellular reducing cleavage of the disulfide bonds cross-linking the PDMAEMA segments led to intracellular cleavage of PDMAEMA from ssCP-MSNs, which facilitated the intracellular triggered release of siRNA. Therefore, promoted RNA interference was observed in HeLa-Luc cells, which was equal to that of Lipofectamine 2000. Significantly, compared to Lipofectamine 2000, the ssCP-MSNs were more biocompatible, with low cytotoxicity (even non-cytotoxicity) and promotion of cell proliferation to HeLa-Luc cells. The in vivo systemic distribution studies certified that ssCP-MSNs/siRNA could prolong the duration of siRNA in vivo, and that they accumulated in the adrenal gland, liver, lung, spleen, kidney, heart and thymus after intravenous injection. Encouragingly, with the ability to deliver siRNA to a tumor, ssCP-MSNs/siRNA showed a tumor suppression effect in the HeLa-Luc xenograft murine model after intravenous injection. Therefore, the ssCP-MSNs cationic polymer-mesoporous silica nanoparticles with low cytotoxicity are promising for siRNA delivery. 23280766 Comparing the effectiveness of chronic water column tests with the crustaceans Hyalella azteca (order: Amphipoda) and Ceriodaphnia dubia (order: Cladocera) in detecting toxicity of current-use insecticides. Standard U.S. Environmental Protection Agency laboratory tests are used to monitor water column toxicity in U.S. surface waters. The water flea Ceriodaphnia dubia is among the most sensitive test species for detecting insecticide toxicity in freshwater environments.Its usefulness is limited, however, when water conductivity exceeds 2,000 µS/cm (approximately 1 ppt salinity) and test effectiveness is insufficient. Water column toxicity tests using the euryhaline amphipod Hyalella azteca could complement C. dubia tests; however, standard chronic protocols do not exist. The present study compares the effectiveness of two water column toxicity tests in detecting the toxicity of two organophosphate (OP) and two pyrethroid insecticides: the short-term chronic C. dubia test, which measures mortality and fecundity, and a 10-d H. azteca test, which measures mortality and growth. Sensitivity was evaluated by comparing effect data, and end point variability was evaluated by comparing minimum significant differences. Tests were performed in synthetic water and filtered ambient water to quantify the influence of water matrix on effect concentrations. The H. azteca test detected pyrethroid toxicity far more effectively, while the C. dubia test was more sensitive to OPs. Among endpoints, H. azteca mortality was most robust. The results demonstrate that the H. azteca test is preferable when conductivity of water samples is 2,000 to 10,000 µS/cm or if contaminants of concern include pyrethroid insecticides. 23594789 Restoration of cardiac tissue thyroid hormone status in experimental hypothyroidism: a dose-response study in female rats. Thyroid hormones (THs) play a pivotal role in regulating cardiovascular homeostasis. To provide a better understanding of the coordinated processes that govern cardiac TH bioavailability, this study investigated the influence of serum and cardiac TH status on the expression of TH transporters and cytosolic binding proteins in the myocardium. In addition, we sought to determine if administration of T3 (instead of T4) improves the relationship between THs in serum and cardiac tissue, and cardiac function over a short-term treatment period. Adult female SD rats were made hypothyroid by seven weeks treatment with the anti-thyroid drug PTU (6-n-propyl-2-thiouracil). After establishing hypothyroidism, rats were assigned to one of five graded T3 (triiodothyronine) dosages plus PTU for a two week dose-response experiment. Untreated, age matched rats served as euthyroid controls. PTU was associated with depressed serum and cardiac tissue T3 and T4 levels, arteriolar atrophy, altered TH transporter and cytosolic TH binding protein expression, fetal gene re-expression, and cardiac dysfunction. Short-term administration of T3 led to a mismatch between serum and cardiac tissue TH levels. Normalization of serum T3 levels was not associated with restoration of cardiac tissue T3 levels or cardiac function. In fact, a 3 fold higher T3 dosage was necessary to normalize cardiac tissue T3 levels and cardiac function. Importantly, this study provides the first comprehensive data on the relationship between altered TH status (serum and cardiac tissue), cardiac function, and the coordinated in vivo changes in cardiac TH membrane transporters and cytosolic TH binding proteins in altered TH states. 23331178 Effect of headgroup on the physicochemical properties of phospholipid bilayers in electric fields: size matters. The effect of molecular structure on ensemble structure of phospholipid films has been investigated. Bilayers of dimyristoyl phosphatidylethanolamine (DMPE) were prepared on Au(111) electrodes using Langmuir-Blodgett and Langmuir-Schaeffer deposition. Capacitance and charge density measurements were used to investigate the adsorption behavior and barrier properties of the lipid bilayers. In situ polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) was employed to investigate the organization of the molecules within the bilayer. DMPE bilayers exhibit lower capacitance than bilayers formed from the related lipid, dimyristoyl phosphatidylcholine (DMPC). The infrared data show that these results can be explained by structural differences between the bilayers formed from each molecule. DMPE organizes into bilayers with hydrocarbon chains tilted at a smaller angle to the surface normal, which results in a thicker film. The hydrocarbon chains contain few conformational defects. Spectra in the carbonyl and phosphate stretching mode regions indicate low solvent content of DMPE films. Both of these effects combine to produce films with lower capacitance and enhanced barrier properties. The results are explained in terms of the differences in structure between the constituent molecules. 23535321 Heterocyclic bismuth carboxylates based on a diphenyl sulfone scaffold: Synthesis and antifungal activity against Saccharomycescerevisiae. A series of heterocyclic organobismuth(III) carboxylates 4 and 5 [RCO2Bi(C6H4-2-SO2C6H4-1'-)] derived from diphenyl sulfone was synthesized to determine the influence of the carboxylate ligand structure on the lipophilicity and antifungal activity against the yeast Saccharomyces cerevisiae. In contrast to the clear structure-activity relationship between the size of the inhibition zone and the value of ClogP for specific substitution on diphenyl sulfone scaffold 1 [ClBi(5-RC6H3-2-SO2C6H4-1'-)], scaffolds 4 and 5 showed similar inhibition activities irrespective of the ClogP value. This suggests that these molecules function inside the yeast cell by separating into the cationic heterocyclic bismuth scaffold and the anionic carboxylate moiety, and that the bismuth scaffold plays an important role in the inhibition activity. 23086035 PGC-1α improves glucose homeostasis in skeletal muscle in an activity-dependent manner. Metabolic disorders are a major burden for public health systems globally. Regular exercise improves metabolic health. Pharmacological targeting of exercise mediators might facilitate physical activity or amplify the effects of exercise. The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) largely mediates musculoskeletal adaptations to exercise, including lipid refueling, and thus constitutes such a putative target. Paradoxically, forced expression of PGC-1α in muscle promotes diet-induced insulin resistance in sedentary animals. We show that elevated PGC-1α in combination with exercise preferentially improves glucose homeostasis, increases Krebs cycle activity, and reduces the levels of acylcarnitines and sphingosine. Moreover, patterns of lipid partitioning are altered in favor of enhanced insulin sensitivity in response to combined PGC-1α and exercise. Our findings reveal how physical activity improves glucose homeostasis. Furthermore, our data suggest that the combination of elevated muscle PGC-1α and exercise constitutes a promising approach for the treatment of metabolic disorders. 23497879 Physicochemical characterisation of dietary fibre components and their ability to bind some process-induced mutagenic heterocyclic amines, Trp-P-1, Trp-P-2, AαC and MeAαC. The physicochemical properties of potato fibre, wheat bran and oat samples were investigated, along with their binding capability to heterocyclic amines (HCAs). Potato fibre displayed highest total dietary fibre content (71.8/100g dry weight basis, dwb), followed by wheat bran (57.2/100 g dwb) and oat sample 2 (53.0/100 g dwb). Oat samples 1, 3 and 4 displayed considerably lower dietary fibre content (20.5-28.8/100g, dwb). Oat samples 3 and 4 displayed highest soluble fibre content (70-83%), and oat sample 3 also displayed highest swelling and water retention capacity (WRC). Dietary fibre samples, except samples 3 and 4, displayed improved binding to HCAs as sample weight increased. The behaviour of wheat bran and potato fibre was similar to oat samples 1 and 2. Binding of MeAαC was comparatively greater than that of other HCAs. Dietary fibre fractions with high insoluble fibre and functional groups of HCAs may significantly contribute to the binding capacity. 23411283 Biguanide related compounds in traditional antidiabetic functional foods. Biguanides such as metformin are widely used worldwide for the treatment of type-2 diabetes. The identification of guanidine and related compounds in French lilac plant (Galega officinalis L.) led to the development of biguanides. Despite of their plant origin, biguanides have not been reported in plants. The objective of this study was to quantify biguanide related compounds (BRCs) in experimentally or clinically substantiated antidiabetic functional plant foods and potatoes. The corrected results of the Voges-Proskauer (V-P) assay suggest that the highest amounts of BRCs are present in green curry leaves (Murraya koenigii (L.) Sprengel) followed by fenugreek seeds (Trigonella foenum-graecum L.), green bitter gourd (Momordica charantia Descourt.), and potato (Solanum tuberosum L.). Whereas, garlic (Allium sativum L.), and sweet potato (Ipomea batatas (L.) Lam.) contain negligible amounts of BRCs. In addition, the possible biosynthetic routes of biguanide in these plant foods are discussed. 23619019 Cardioprotective effects of the YiQiFuMai injection and isolated compounds on attenuating chronic heart failure via NF-κB inactivation and cytokine suppression. ETHNOPHARMACOLOGICAL RELEVANCE: The YiQiFuMai injection (YQFM) is a traditional Chinese medicine for the treatment of chronic heart failure (CHF). The present study not only evaluated the cardioprotective effect and anti-inflammatory mechanism of the YQFM injection in an experimental model of CHF but also investigated its bioactive constituents in vitro. MATERIALS AND METHODS: The left anterior descending coronary artery (LAD) in rats was ligated to make an animal model of CHF. From this, electrocardiographic parameters and exterior signs of rat hearts were recorded. Additionally, the histopathology of heart tissues was examined, and parameters of inflammatory stress were measured. Experiments were performed over two months in LAD-ligation rats treated with YQFM or vehicle. Treatment with Captopril was used as a positive control, which has previously been shown to prevent CHF, and rats without LAD-ligation were used as a negative control. Furthermore, we screened and identified potential anti-inflammatory constituents by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) combined with NF-κB activity luciferase reporter assay systems. Further cytokine detection confirmed the anti-inflammatory effects of the potential NF-κB inhibitors from YQFM. RESULTS: The administration of YQFM significantly improved cardiac function and ameliorated the activity level of inflammatory mediators (such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1β) in CHF rats. Eight potential anti-inflammatory ingredients, ginsenosides Rb1, Rg1, Rf, Rh1, Rc, Rb2, Ro, and Rg3, were characterized and confirmed. Among these compounds, ginsenoside Ro was revealed as a new NF-κB inhibitor. CONCLUSION: The results suggested that NF-κB inactivation and cytokine suppression might be one of the main mechanisms of YQFM that caused ameliorative effects in CHF rats, and the major constituents of ginsenosides were identified playing a key role in the treatment of CHF. 23151381 Effect of Australian elapid venoms on blood coagulation: Australian Snakebite Project (ASP-17). Snake venoms contain toxins that activate the coagulation network and cause venom-induced consumption coagulopathy. A previously developed mathematical model of the coagulation network was refined and used to describe and predict the time course of changes in the coagulation factors following envenomation by Brown snake (Pseudonaja spp.), Tiger snake (Notechis scutatus), Rough-scaled snake (Tropidechis carinatus) and Hoplocephalus spp. (Stephens banded, Pale headed and Broad headed). Simulations of the time course of the change in coagulation factors were compared to data obtained from a large prospective study of Australian snake bites - the Australian Snakebite Project. The model predictions were also compared against data for partial and complete VICC obtained from the same study. The model simulations were used to understand the differences in consumption and recovery of clotting factors in partial versus complete VICC as well as among bites from different snake types. The model suggested that the venoms were absorbed almost instantaneously and provided a reasonable prediction of the observed concentration of clotting factors over time in patients bitten by Australian elapid snakes. The model predictions suggested a higher consumption of factors (fibrinogen, II and IX in particular) in patients with complete VICC compared to those with partial VICC. The model also predicted that snakes with "Xa-like" venoms may produce a less severe VICC than snakes with "Xa:Va-like" venoms. 23423353 Translational repression of thymidylate synthase by targeting its mRNA. Resistance to drugs targeting human thymidylate synthase (TS) poses a major challenge in the field of anti-cancer therapeutics. Overexpression of the TS protein has been implicated as one of the factors leading to the development of resistance. Therefore, repressing translation by targeting the TS mRNA could help to overcome this problem. In this study, we report that the compound Hoechst 33258 (HT) can reduce cellular TS protein levels without altering TS mRNA levels, suggesting that it modulates TS expression at the translation level. We have combined nuclear magnetic resonance, UV-visible and fluorescence spectroscopy methods with docking and molecular dynamics simulations to study the interaction of HT with a region in the TS mRNA. The interaction predominantly involves intercalation of HT at a CC mismatch in the region near the translational initiation site. Our results support the use of HT-like compounds to guide the design of therapeutic agents targeting TS mRNA. 23150491 Maternal and fetal exposure to bisphenol a is associated with alterations of thyroid function in pregnant ewes and their newborn lambs. The putative thyroid-disrupting properties of bisphenol A (BPA) highlight the need for an evaluation of fetal exposure and its consequence on the mother/newborn thyroid functions in models relevant to human. The goals of this study were to characterize in sheep a relevant model for human pregnancy and thyroid physiology, the internal exposures of the fetuses and their mothers to BPA and its main metabolite BPA-glucuronide (Gluc), and to determine to what extent it might be associated with thyroid disruption. Ewes were treated with BPA [5 mg/(kg · d) sc] or vehicle from d 28 until the end of pregnancy. Unconjugated BPA did not appear to accumulate in pregnant ewes, and its concentration was similar in the newborns and their mothers (0.13 ± 0.02 and 0.18 ± 0.03 nmol/ml in cord and maternal blood, respectively). In amniotic fluid and cord blood, BPA-Gluc concentrations were about 1300-fold higher than those of BPA. Total T(4) concentrations were decreased in BPA-treated pregnant ewes and in the cord and the jugular blood of their newborns (30% decrease). A similar difference was observed for free T(4) plasma concentrations in the jugular blood of the newborns. Our results show in a long-gestation species with a similar regulatory scheme of thyroid function as humans that BPA in utero exposure can be associated with hypothyroidism in the newborns. If such an effect were to be confirmed for a more relevant exposure scheme to BPA, this would constitute a major issue for BPA risk assessment. 23151000 Molecular modeling and simulation of membrane lipid-mediated effects on GPCRs. Functioning of G protein-coupled receptors (GPCRs) is tightly linked to the membrane environment, but a molecular level understanding of the modulation of GPCR by membrane lipids is not available. However, specific receptor-lipid interactions as well as unspecific effects mediated by the bulk properties of the membrane (thickness, curvature, etc.) have been proposed to be key regulators of GPCR modulation. In this review, we examine computational efforts made towards modeling and simulation of (i) the complex behavior of membrane lipids, (ii) membrane lipid-GPCR interactions as well as membrane lipid-mediated effects on GPCRs and (iii) GPCR oligomerization in a native-like membrane environment. We propose that, from the perspective of computational modeling, all three of these components need to be addressed in order to achieve a deeper understanding of GPCR functioning. Presently, we are able to simulate numerous lipid properties applying advanced computational techniques, although some barriers, such as the time-length of these simulations, need to be overcome. Implementing three-dimensional structures of GPCRs in such validated membrane systems can give novel insights in membrane-dependent receptor modulation and formation of higher order receptor complexes. Finally, more realistic GPCR-membrane models would provide a very useful tool in studying receptor behavior and its modulation by small drug-like ligands, a relevant issue for drug discovery. 23092877 GH improves spatial memory and reverses certain anabolic androgenic steroid-induced effects in intact rats. GH has previously been shown to promote cognitive functions in GH-deficient rodents. In this study we report the effects of GH on learning and memory in intact rats pretreated with the anabolic androgenic steroid nandrolone. Male Wistar rats received nandrolone decanoate (15 mg/kg) or peanut oil every third day for 3 weeks and were subsequently treated with recombinant human GH (1.0 IU/kg) or saline for 10 consecutive days. During the GH/saline treatment spatial learning and memory were tested in the Morris water maze (MWM). Also, plasma levels of IGF1 were assessed and the gene expression of the GH receptors (Ghr), Igf1 and Igf2, in hippocampus and frontal cortex was analyzed. The results demonstrated a significant positive effect of GH on memory functions and increased gene expression of Igf1 in the hippocampus was found in the animals treated with GH. In addition, GH was demonstrated to increase the body weight gain and was able to attenuate the reduced body weight seen in nandrolone-treated animals. In general, the rats treated with nandrolone alone did not exhibit any pronounced alteration in memory compared with controls in the MWM, and in many cases GH did not induce any alteration. Regarding target zone crossings, considered to be associated with spatial memory, the difference between GH- and steroid-treated animals was significant and administration of GH improved this parameter in the latter group. In conclusion, GH improves spatial memory in intact rats and can reverse certain effects induced by anabolic androgenic steroid. 23561199 A Rapid tool for the stability assessment of natural food colours. Natural food colours lack stability under a number of conditions such as pH variation, oxidation, hydration, heat treatment and, most importantly, exposure to daylight. Stability tests to assess shelf life of natural colours under light irradiation can be time consuming. Thus, an accelerated test carried out under high light intensity irradiation that can be related to normal daylight irradiation conditions is highly desirable. Samples of various natural colouring solutions were prepared in aqueous model matrices at a range of pH values to mimic the majority of food matrices, pasteurised and irradiated under normal D65 light (0.2W/m(2)) at 25°C, and in parallel under high light intensity irradiation (30W/m(2)) at 3 different temperatures (25, 35 and 45°C). Similarly to the already known Q10 parameters for temperature, acceleration factors QL for irradiation, were determined and used for the first time to obtain a link between colour degradation under normal and accelerated conditions. It was possible, using these acceleration factors, to greatly reduce the time required to predict and compare the shelf life stability for a series of natural colours in aqueous model systems. 23541637 Aldosterone-induced ENaC and basal Na(+)/K(+)-ATPase trafficking via protein kinase D1-phosphatidylinositol 4-kinaseIIIβ trans Golgi signalling in M1 cortical collecting duct cells. Aldosterone regulates Na(+) transport in the distal nephron through multiple mechanisms that include the transcriptional control of epithelial sodium channel (ENaC) and Na(+)/K(+)-ATPase subunits. Aldosterone also induces the rapid phosphorylation of Protein Kinase D1 (PKD1). PKD isoforms regulate protein trafficking, by the control of vesicle fission from the trans Golgi network (TGN) through activation of phosphatidylinositol 4-kinaseIIIβ (PI4KIIIβ). We report rapid ENaCγ translocation to the plasma membrane after 30min aldosterone treatment in polarized M1 cortical collecting duct cells, which was significantly impaired in PKD1 shRNA-mediated knockdown cells. In PKD1-deficient cells, the ouabain-sensitive current was significantly reduced and Na(+)/K(+)-ATPase α and β subunits showed aberrant localization. PKD1 and PI4KIIIβ localize to the TGN, and aldosterone induced an interaction between PKD1 and PI4KIIIβ following aldosterone treatment. This study reveals a novel mechanism for rapid regulation of ENaC and the Na(+)/K(+)-ATPase, via directed trafficking through PKD1-PI4KIIIβ signalling at the level of the TGN. 23472745 Bioactivity of tomato hybrid powder: antioxidant compounds and their biological activities. Abstract The antioxidant and cytotoxic activities and the polyphenolic and anthocyanin contents of tomato hybrid powders were studied. Tomato powders were obtained, starting from the fresh fruits that had undergone an industrial process of drying and pulverization at two different temperatures. Antioxidant activities were evaluated in different extracts by using spectrophotometric assays: 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid and N,N-dimethyl-p-phenylenediamine dihydrochloride cation radical inhibition for lipophilic and hydrophilic extracts, respectively, and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay for polyphenolic extracts. Moreover, polyphenolic and anthocyanin contents were also carried out to detect the presence of these bioactive compounds. The effect of cytotoxic activity in vitro of tomato hybrid powder extracts on T47D (human breast carcinoma) cells was also evaluated. Results showed good antioxidant activities in lipophilic, polyphenolic, and hydrophilic extracts of samples that were obtained at a lower temperature. Extracts of the sample obtained at a higher temperature presented moderate antioxidant activity, lower than the extracts of other samples, which was probably due to the loss of labile antioxidant compounds during the industrial process. Very interesting was the presence of anthocyanins in both samples, even if in traces, and also a moderate cytotoxicity of a lipophilic extract on T47D cells. Therefore, tomato hybrid powders, on the basis of their multifunctional properties, could have a biotechnological application in agri-food or cosmetic industries as an additive for improving nutritional and/or bioactive qualities of commercial products used in daily nutrition and cosmetics. 23420115 Psychopharmacology of theobromine in healthy volunteers. BACKGROUND: Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited. OBJECTIVES: We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. RESULTS: Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters. Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses, we also examined individual differences in the drug's effects in relation to genes related to their target receptors, but few associations were detected. CONCLUSIONS: This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative. 23477623 Comparison of the inhibitory effect against copper ion-induced oxidation in rat plasma after oral administration of salvianolic acid B and its decocted solutions. The effects of salvianolic acid B (Sal B) decoction on antioxidative activities were evaluated. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity, Fe(2+)-chelating activity, reducing power, and total phenolic content of the Sal B-decocted solutions did not change significantly after decoction in an aqueous solution. However, the formation of cholesteryl ester hydroperoxide (CE-OOH) in rat blood plasma containing the Sal B-decocted solutions was more effectively inhibited than that of plasma containing the Sal B solution, regardless of the decoction time. In addition, the accumulation of CE-OOH in rat plasma after oral administration of the Sal B-decocted solutions was more effectively suppressed than when the Sal B solution was administered, considering the lag time. It is likely that the decoction was partly responsible for the increased antioxidant activity in blood plasma. Therefore, the Sal B-decocted solution may contribute more to antioxidant defense in blood than a Sal B solution that is not decocted. 23315216 Transaldolase deficiency: report of 12 new cases and further delineation of the phenotype. PURPOSE: Transaldolase deficiency is a recently described inborn error of pentose phosphate pathway. We conducted this study to further delineate the associated phenotype. METHODS AND RESULTS: We report on 12 new cases representing six families with this metabolic defect that were observed over an 8 year span. None of these cases received the correct diagnosis initially because of significant overlap in the presenting symptoms (growth retardation, dysmorphic features, cutis laxa, congenital heart disease, hepatosplenomegaly, pancytopenia, and bleeding tendency) with a wide range of genetic disorders. However, the consanguineous nature of these families allowed us to pursue autozygome analysis, which highlighted TALDO as the likely candidate gene and sequencing confirmed segregation of a novel homozygous mutation with the disease in all the studied families. Biochemical analysis was also consistent with transaldolase deficiency. CONCLUSION: This study expands the clinical definition of transaldolase deficiency, and adds to its allelic heterogeneity. In addition, we emphasize the diagnostic challenge posed by this rare and pleiotropic metabolic disorder. 23448682 Synthetically tractable click hydrogels for three-dimensional cell culture formed using tetrazine-norbornene chemistry. The implementation of bio-orthogonal click chemistries is a topic of growing importance in the field of biomaterials, as it is enabling the development of increasingly complex hydrogel materials capable of providing dynamic, cell-instructive microenvironments. Here, we introduce the tetrazine-norbornene inverse electron demand Diels-Alder reaction as a new cross-linking chemistry for the formation of cell laden hydrogels. The fast reaction rate and irreversible nature of this click reaction allowed for hydrogel formation within minutes when a multifunctional PEG-tetrazine macromer was reacted with a dinorbornene peptide. In addition, the cytocompatibility of the polymerization led to high postencapsulation viability of human mesenchymal stem cells, and the specificity of the tetrazine-norbornene reaction was exploited for sequential modification of the network via thiol-ene photochemistry. These advantages, combined with the synthetic accessibility of the tetrazine molecule compared to other bio-orthogonal click reagents, make this cross-linking chemistry an interesting and powerful new tool for the development of cell-instructive hydrogels for tissue engineering applications. 23570328 Chemoselective metal-free aerobic alcohol oxidation in lignin. An efficient organocatalytic method for chemoselective aerobic oxidation of secondary benzylic alcohols within lignin model compounds has been identified. Extension to selective oxidation in natural lignins has also been demonstrated. The optimal catalyst system consists of 4-acetamido-TEMPO (5 mol %; TEMPO = 2,2,6,6-tetramethylpiperidine-N-oxyl) in combination with HNO3 and HCl (10 mol % each). Preliminary studies highlight the prospect of combining this method with a subsequent oxidation step to achieve C-C bond cleavage. 22674653 Formulas used by tibetan doctors at men-tsee-khang in India for the treatment of neuropsychiatric disorders and their correlation with pharmacological data. The aim of the present study was to identify formulas used at Men-Tsee-Khang (Tibetan Medical and Astrological Institute), India, for the treatment of neuropsychiatric disorders and to compare the Tibetan usage of particular ingredients with pharmacological data from the scientific database. Using ethnographic methods, five doctors were selected and interviewed. A correlation was observed between central nervous system disorders and rLung, one of the three humors in Tibetan medicine, which imbalance is the source of mental disorders, and ten multi-ingredient formulas used to treat the imbalance of this particular humor were identified. These formulas utilize 61 ingredients; among them were 48 plant species. Each formula treats several symptoms related to rLung imbalance, so the plants may have therapeutic uses distinct from those of the formulas in which they are included. Myristica fragrans, nutmeg, is contained in 100% of the formulas, and its seeds exhibit stimulant and depressant actions affecting the central nervous system. Preclinical and clinical data from the scientific literature indicate that all of the formulas include ingredients with neuropsychiatric action and corroborate the therapeutic use of 75.6% of the plants. These findings indicate a level of congruence between the therapeutic uses of particular plant species in Tibetan and Western medicines. Copyright © 2012 John Wiley & Sons, Ltd. 23577589 Flexibly timed once-daily dosing with degludec: a new ultra-long-acting basal insulin. Insulin treatment in type 1 and type 2 diabetes (T1D and T2D) is highly efficacious, but in practice, non-adherence and ineffective dose titration limit its effectiveness. Barriers to more effective insulin treatment are numerous, including hypoglycaemia, fear of hypoglycaemia and concern about weight gain. The regular treatment timing needed with conventional basal insulins [neutral protamine Hagedorn (NPH) insulin and the first-generation analogues glargine and detemir] may also make adherence to these treatments problematic for many patients. Indeed, surveys indicate that the rigidity of this schedule induces some patients with T1D and T2D to omit insulin doses. Degludec is a novel, ultra-long-acting basal insulin analogue that is as effective as insulin glargine, but significantly reduces patients' risk of nocturnal hypoglycaemia. Because of its peakless, extended and highly predictable glucose-lowering effect, once-daily dosing on a flexible schedule may be feasible with degludec. Studies testing this possibility suggest that degludec tolerates day-to-day variation in dose timing while maintaining full efficacy and low risk of nocturnal hypoglycaemia. Degludec would appear to be an appropriate choice for patients being considered for a basal analogue, and it may be particularly well suited to patients with unpredictable social or work schedules, those who travel frequently and those who find rigid scheduling of their insulin injections a burden or barrier to regular treatment. 23614571 Development of 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine analogues as potent N-methyl-D-aspartic acid receptor ligands. A series of 2'-substituted analogues of the selective NMDA receptor ligand (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine ((S)-CCG-IV) have been designed, synthesized and pharmacologically characterized. The design was based on a docking study hypothesizing that substituents in the 2'-position would protrude into a region where differences among the NMDA receptors GluN2 subunits exist. Various synthetic routes were explored, and two different routes provided a series of alkyl-substituted analogues. Pharmacological characterization disclosed that these compounds are NMDA receptor agonists and that potency decreases with increasing size of the alkyl groups. Variations in agonist activity are observed at recombinant NMDA receptor subtypes with increasing size of the alkyl-substituents and are developing differently depending on the GluN2 subunit. This study demonstrates that it is possible to introduce substituents in the 2'-position of (S)-CCG-IV while maintaining agonist activity and that variation among NMDA receptor subtypes may be achieved by probing this region of the receptor. 23567861 Evaluation of 7-O-galloyl-d-sedoheptulose, isolated from Corni Fructus, in the adipose tissue of type 2 diabetic db/db mice. The aim of the present study was to evaluate the beneficial effects of 7-O-galloyl-d-sedoheptulose (GS), isolated from Corni Fructus, using type 2 diabetic mice. GS was orally administered to db/db mice at doses of 20 and 100mg/kg body weight per day for 6weeks, and the effects of GS on biochemical factors in serum and adipose tissue were investigated. To define the underlying mechanism of these effects, protein expressions related to lipid metabolism, inflammation, fibrosis, and apoptosis, were measured. The results showed that levels of glucose, leptin, insulin, C-peptide, resistin, tumor necrosis factor-α, interleukin-6, triglycerides, total cholesterol, non-esterified fatty acids, high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol/low-density lipoprotein cholesterol, reactive oxygen species (ROS), and thiobarbituric acid-reactive substance (TBARS) in serum were down-regulated, while adiponectin was augmented by GS treatment. In addition, the elevated lipid, ROS, and TBARS contents in adipose tissue as well as serum levels in db/db mice were significantly decreased by the oral administration of GS. From protein analysis, the decreased expressions of peroxisome proliferator activated receptor (PPAR)α, PPARγ, and B-cell lymphoma 2 were up-regulated in the adipose tissue of db/db mice. The administration of GS significantly decreased sterol regulatory element binding protein-1, nuclear factor-kappa ?>Bp65, cyclooxygenase-2, inducible nitric oxide synthase, monocyte chemotactic protein-1, intracellular adhesion molecule-1, phosphor c-Jun N-terminal kinase, activator protein-1, transforming growth factor-β1, Bax, cytochrome c, and caspase-3 expressions. These results suggest that GS acts as a regulator of oxidative stress, inflammation, fibrosis, and apoptosis in the adipose tissue of db/db mice. 23578623 Volatile release and structural stability of β-lactoglobulin primary and multilayer emulsions under simulated oral conditions. The relationship between emulsion structure and the release of volatile organic compounds (VOCs) was investigated using a model mouth system under oral conditions (tongue mastication, artificial saliva, pH and salt). The VOCs were monitored on-line by proton transfer reaction mass spectrometry (PTR-MS). Two types of emulsion system were compared: primary and multilayer oil-in-water (P-O/W, M-O/W) emulsions consisting of soy oil coated by β-lactoglobulin and pectin layers. The P-O/W emulsions showed intensive flocculation at pH 5 and above 200mM NaCl where the electrostatic repulsive charge was at a minimum. Bridging and depletion flocculation were mostly observed for P-O/W emulsions containing artificial saliva with 1wt% mucin. The VOC release was found to increase when the emulsion droplets flocculated, thus changing the oil volume phase distribution. The adsorbed pectin layer stabilised the emulsion structure under conditions of short-time oral processing, and hindered the release of hydrophobic VOCs. 23351082 Contribution of lipids in honeybee (Apis mellifera) royal jelly to health. Honeybee (Apis mellifera) royal jelly (RJ) has a long history in human medicine because of its health-protecting properties. To develop a fundamental and comprehensive understanding of lipids in RJ, this article reviews the available literature on lipid compounds identified from RJ extracts and in vitro pharmacological effects of 10-hydroxy-2-decenoic acid in RJ and other closely related compounds, some of which are also identified as lipid compounds in RJ. Overall, the lipids in RJ are composed of mostly (aliphatic) fatty acids, almost all of which are present as free fatty acids and scarcely any as esters. Most fatty acids in RJ are medium-chain fatty acids, whether hydroxylated in terminal and/or internal positions, terminated with mono- or dicarboxylic acid groups, and saturated or monounsaturated at the 2-position. Besides these fatty acids, lipids in RJ contain sterols in minor amounts. Lipids in RJ are useful as preventive and supportive medicines with functionalities that include potential inhibitors of cancer growth, immune system modulators, alternative therapies for menopause, skin-aging protectors, neurogenesis inducers, and more. Taken together, the evidence suggests that health-protecting properties of RJ can be, in part, ascribed to actions of lipids in RJ. 23203870 EENdb: a database and knowledge base of ZFNs and TALENs for endonuclease engineering. We report here the construction of engineered endonuclease database (EENdb) (http://eendb.zfgenetics.org/), a searchable database and knowledge base for customizable engineered endonucleases (EENs), including zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). EENs are artificial nucleases designed to target and cleave specific DNA sequences. EENs have been shown to be a very useful genetic tool for targeted genome modification and have shown great potentials in the applications in basic research, clinical therapies and agricultural utilities, and they are specifically essential for reverse genetics research in species where no other gene targeting techniques are available. EENdb contains over 700 records of all the reported ZFNs and TALENs and related information, such as their target sequences, the peptide components [zinc finger protein-/transcription activator-like effector (TALE)-binding domains, FokI variants and linker peptide/framework], the efficiency and specificity of their activities. The database also lists EEN engineering tools and resources as well as information about forms and types of EENs, EEN screening and construction methods, detection methods for targeting efficiency and many other utilities. The aim of EENdb is to represent a central hub for EEN information and an integrated solution for EEN engineering. These studies may help to extract in-depth properties and common rules regarding ZFN or TALEN efficiency through comparison of the known ZFNs or TALENs. 23192981 The role of prolactin receptor in GH signaling in breast cancer cells. GH and prolactin (PRL) are structurally related hormones that exert important effects in disparate target tissues. Their receptors (GHR and PRLR) reside in the cytokine receptor superfamily and share signaling pathways. In humans, GH binds both GHR and PRLR, whereas PRL binds only PRLR. Both hormones and their receptors may be relevant in certain human and rodent cancers, including breast cancer. GH and PRL promote signaling in human T47D breast cancer cells that express both GHR and PRLR. Furthermore, GHR and PRLR associate in a fashion augmented acutely by GH, even though GH primarily activates PRLR, rather than GHR, in these cells. To better understand PRLR's impact, we examined the effects of PRLR knockdown on GHR availability and GH sensitivity in T47D cells. T47D-ShPRLR cells, in which PRLR expression was reduced by stable short hairpin RNA (shRNA) expression, were compared with T47D-SCR control cells. PRLR knockdown decreased the rate of GHR proteolytic turnover, yielding GHR protein increase and ensuing sensitization of these cells to GHR signaling events including phosphorylation of GHR, Janus kinase 2, and signal transducer and activator of transcription 5 (STAT5). Unlike in T47D-SCR cells, acute GH signaling in T47D-ShPRLR cells was not blocked by the PRLR antagonist G129R but was inhibited by the GHR-specific antagonist, anti-GHR(ext-mAb). Thus, GH's use of GHR rather than PRLR was manifested when PRLR was reduced. In contrast to acute effects, GH incubation for 2 h or longer yielded diminished STAT5 phosphorylation in T47D-ShPRLR cells compared with T47D-SCR, a finding perhaps explained by markedly greater GH-induced GHR down-regulation in cells with diminished PRLR. However, when stimulated with repeated 1-h pulses of GH separated by 3-h washout periods to more faithfully mimic physiological GH pulsatility, T47D-ShPRLR cells exhibited greater transactivation of a STAT5-responsive luciferase reporter than did T47D-SCR cells. Our data suggest that PRLR's presence meaningfully affects GHR use in breast cancer cells. 23200887 Resveratrol affects differently rat liver and brain mitochondrial bioenergetics and oxidative stress in vitro: investigation of the role of gender. Resveratrol (3,5,4'-trihydroxy-trans stilbene) is commonly recognized by its antioxidant properties. Despite its beneficial qualities, the toxic effects of this natural compound are still unknown. Since mitochondria are essential to support the energy-dependent regulation of several cell functions, the objective of this study was to evaluate resveratrol effects on rat brain and liver mitochondrial fractions from male and females regarding oxidative stress and bioenergetics. No basal differences were observed between mitochondrial fractions from males and females, except in liver mitochondria, the generation of H(2)O(2) by the respiratory chain is lower for female preparations. Resveratrol inhibited lipid peroxidation in preparations from both genders and organs. Furthermore, brain mitochondria in both gender groups appeared susceptible to resveratrol as seen by a decrease in state 3 respiration and alterations in mitochondrial membrane potential fluctuations during ADP phosphorylation. As opposed, liver mitochondria were less affected by resveratrol. Our data also demonstrates that resveratrol inhibits complex I activity in all mitochondrial preparations. The results suggest that brain mitochondria appear to be more susceptible to resveratrol effects, and gender appears to play a minor role. It remains to be determined if resveratrol effects on brain mitochondria contribute to deterioration of mitochondrial function or instead to mediate hormesis-mediated events. 22469988 miR-143 regulates hexokinase 2 expression in cancer cells. Tumor cells activate pathways that facilitate and stimulate glycolysis even in the presence of adequate levels of oxygen in order to satisfy their continuous need of molecules, such as nucleotides, ATP and fatty acids, necessary to support their rapid proliferation. Accordingly, a variety of human tumors are characterized by elevated expression levels of the hexokinase 2 isoform (HK2). Although different molecular mechanisms, including genetic and epigenetic mechanisms, have been suggested to account for the altered expression of HK2 in tumors, the potential role of microRNAs (miRNAs) in the regulation of HK2 expression has not been evaluated. Here, we report that miR-143 inhibits HK2 expression via a conserved miR-143 recognition motif located in the 3'-untranslated region (3'UTR) of HK2 mRNA. We demonstrate that miR143 inhibits HK2 expression both in primary keratinocytes and in head and neck squamous cell carcinoma (HNSCC)-derived cell lines. Importantly, we found that miR-143 inversely correlates with HK2 expression in HNSCC-derived cell lines and in primary tumors. We also report that the miRNA-dependent regulation of hexokinase expression is not limited to HK2 as miR-138 targets HK1 via a specific recognition motif located in its 3'UTR. All these data unveil a new miRNA-dependent mechanism of regulation of hexokinase expression potentially important in the regulation of glucose metabolism of cancer cells. 23121934 Synthesis and evaluation of a series of 3,4,5-trimethoxycinnamic acid derivatives as potential antinarcotic agents. A series of 3,4,5-trimethoxycinnamic acid derivatives was prepared and evaluated for antinarcotic effects on morphine dependence in mice and binding affinities on serotonergic receptors. The key synthetic strategies involve generation of ketones 6-7, esters 9-12 through condensation reaction, and amides 13-19 via coupling reaction using 1-hydroxybenzotriazole/ethyl(dimethylaminopropryl)carbodiimide system in high yield. We found that the naloxone-induced morphine withdrawal syndrome was significantly suppressed by new synthetic 3,4,5-trimethoxycinnamic acid derivatives (20 mg/kg/day). Most of 3,4,5-trimethoxycinnamic acid derivatives were found to have high affinity to 5-HT(1A) receptor. The naloxone-induced morphine withdrawal syndrome was attenuated by (+)8-OH-DPAT (0.1 mg/kg/day, i.p.), a 5-HT(1A) receptor agonist. In cortical neuronal cells, (+)8-OH-DPAT (1 μM) produced an elevation of the pERK 1/2 expression, and the elevated pERK levels were inhibited by WAY 100635, a 5-HT(1A) receptor-specific antagonist. Interestingly, the pERK levels were increased by the 3,4,5-trimethoxycinnamic acid derivatives and the derivatives-mediated changes in pERK levels were blocked by the WAY 100635. These results suggested that new synthetic 3,4,5-trimethoxycinnamic acid derivatives have a potential antinarcotic effect through acting as a 5-HT(1A) receptor agonist in mice. 23220004 Aldo-keto reductases in retinoid metabolism: search for substrate specificity and inhibitor selectivity. Biological activity of natural retinoids requires the oxidation of retinol to retinoic acid (RA) and its binding to specific nuclear receptors in target tissues. The first step of this pathway, the reversible oxidoreduction of retinol to retinaldehyde, is essential to control RA levels. The enzymes of retinol oxidation are NAD-dependent dehydrogenases of the cytosolic medium-chain (MDR) and the membrane-bound short-chain (SDR) dehydrogenases/reductases. Retinaldehyde reduction can be performed by SDR and aldo-keto reductases (AKR), while its oxidation to RA is carried out by aldehyde dehydrogenases (ALDH). In contrast to SDR, AKR and ALDH are cytosolic. A common property of these enzymes is that they only use free retinoid, but not retinoid bound to cellular retinol binding protein (CRBP). The relative contribution of each enzyme type in retinoid metabolism is discussed in terms of the different subcellular localization, topology of membrane-bound enzymes, kinetic constants, binding affinity of CRBP for retinol and retinaldehyde, and partition of retinoid pools between membranes and cytoplasm. The development of selective inhibitors for AKR enzymes 1B1 and 1B10, of clinical relevance in diabetes and cancer, granted the investigation of some structure-activity relationships. Kinetics with the 4-methyl derivatives of retinaldehyde isomers was performed to identify structural features for substrate specificity. Hydrophilic derivatives were better substrates than the more hydrophobic compounds. We also explored the inhibitory properties of some synthetic retinoids, known for binding to retinoic acid receptors (RAR) and retinoid X receptors (RXR). Consistent with its substrate specificity towards retinaldehyde, AKR1B10 was more effectively inhibited by synthetic retinoids than AKR1B1. A RARβ/γ agonist (UVI2008) inhibited AKR1B10 with the highest potency and selectivity, and docking simulations predicted that its carboxyl group binds to the anion-binding pocket. 23562634 Novel iontophoretic administration method for local therapy of breast cancer. Ductal drug therapy is a novel therapeutic approach for primary breast cancers, particularly those involving ductal carcinoma in situ lesions. Total or partial mastectomy with or without radiotherapy is the standard local therapy for primary breast cancer. Here, we propose a novel drug administration method for ductal drug therapy based on a drug delivery system (DDS) for primary breast cancer. This DDS was designed to deliver miproxifen phosphate (TAT-59), an antiestrogen drug, to ductal lesions via the milk duct, where carcinomas originate, more efficiently than systemic administration, using an iontophoretic technique applied to the nipple (IP administration). Autoradiography imaging confirmed that TAT-59 was directly delivered to the milk duct using IP administration. The plasma concentrations of TAT-59 and its active metabolite DP-TAT-59 were quite low with IP administration. The area under the curve value of DP-TAT-59 in the mammary tissue was approximately 3 times higher with IP administration than with oral administration, at a 6-fold lower dose, indicating higher availability of the drug delivered via DDS than via systemic administration. The low plasma concentrations would limit adverse effects to minor ones. These characteristics show that this DDS is suitable for the delivery of active DP-TAT-59 to ductal lesions. 23642965 Synthesis of 7-oxabicyclo[2.2.1]hept-5-en-2-yl derivatives and their screening for antimicrobial and antioxidant properties. Novel 7-oxabicyclo[2.2.1]hept-5-en-2-yl derivatives have been synthesized using boron trifluoride diethyl etherate catalyzed Diels-Alder reaction. This method presents considerable synthetic advantages in terms of high atom economy, mild reaction condition and good yields. The synthesized compounds have been screened for their antibacterial and antioxidant activities. 23250811 Curcumin improves TNBS-induced colitis in rats by inhibiting IL-27 expression via the TLR4/NF-κB signaling pathway. Curcumin is a widely used spice with anti-inflammatory and anticancer properties. It has been reported to have beneficial effects in experimental colitis. This study explored whether curcumin improves colonic inflammation in a rat colitis model through inhibition of the TLR4/NF-κB signaling pathway and IL-27 expression. After induction of colitis with 2,4,6-trinitrobenzene sulfonic acid, rats were intragastrically administered with curcumin or sulfasalazine daily for one week. Rat intestinal mucosa was collected for evaluation of the disease activity index, colonic mucosa damage index, and histological score. Myeloperoxidase activity was detected by immunohistochemistry, and mRNA and protein expression levels of TLR4, NF-κB, and IL-27 in colonic mucosa were detected by RT-PCR and Western blot. Compared with the untreated colitis group, the curcumin-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, NF-κB p65 protein, and IL-27 p28 protein (p < 0.05). TLR4 mRNA expression did not differ between groups. Disease activity index decreased more rapidly in the curcumin-treated group than in the sulfasalazine-treated group (p < 0.05). There was no significant difference in TLR4, NF-κB, and IL-27 mRNA and proteins between curcumin-treated and sulfasalazine-treated groups. Curcumin shows significant therapeutic effects on 2,4,6-trinitrobenzene sulfonic acid-induced colitis that are comparable to sulfasalazine. The anti-inflammatory actions of curcumin on colitis may involve inhibition of the TLR4/NF-κB signaling pathway and of IL-27 expression. 23558686 Disruption of Ttll5/Stamp gene (Tubulin tyrosine ligase-like protein 5/SRC-1 and TIF2 associated modulatory protein gene) in male mice causes sperm malformation and infertility. Tubulin tyrosine ligase-like family member 5 (TTLL5/STAMP) has multiple activities in cells. TTLL5 is one of 13 TTLLs, has polyglutamylation activity, augments the activity of p160 coactivators (SRC-1 and TIF2) in glucocorticoid receptor-regulated gene induction and repression, and displays steroid-independent growth activity with several cell types. To examine TTLL5/STAMP functions in whole animals, mice were prepared with an internal deletion that eliminated several activities of the Stamp gene. This mutation causes both reduced levels of STAMP mRNA and C-terminal truncation of STAMP protein. Homozygous targeted mutant (Stamptm/tm) mice appear normal except for marked decreases in male fertility associated with defects in progressive sperm motility. Abnormal axonemal structures with loss of tubulin doublets occur in most Stamptm/tm sperm tails in conjunction with substantial reduction in α-tubulin polyglutamylation, which closely correlates with the reduction in mutant STAMP mRNA. The axonemes in other structures appear unaffected. There is no obvious change in the organs for sperm development of wt vs. Stamptm/tm males despite the levels of wt STAMP mRNA in testes being 20-fold higher than in any other organ examined. This defect in male fertility is unrelated to other Ttll genes or 24 genes previously identified as important for sperm function. Thus, STAMP appears to participate in a unique, tissue-selective TTLL-mediated pathway for α-tubulin polyglutamylation that is required for sperm maturation and motility and may be relevant for male fertility. 23522182 Dose-ranging study with the glucokinase activator AZD1656 as monotherapy in Japanese patients with type 2 diabetes mellitus. AIM: To assess the glucose-lowering effects of monotherapy with the glucokinase activator AZD1656 in Japanese patients with type 2 diabetes mellitus. METHODS: This was a randomized, double-blind, placebo-controlled study performed in Japan (NCT01152385). Patients (n = 224) were randomized to AZD1656 (40-200, 20-140 or 10-80 mg titrated doses) or placebo. The primary variable was the placebo-corrected change from baseline to 4 months in glycated haemoglobin (HbA1c). Effects on fasting plasma glucose (FPG) and safety were also assessed. RESULTS: HbA1c was reduced numerically from baseline by 0.3-0.8% with AZD1656 and by 0.1% with placebo over the first 2 months of treatment, after which effects of AZD1656 started to decline. The changes from baseline to 4 months in HbA1c were not significant for the AZD1656 40-200 mg group versus placebo [mean (95% CI) placebo-corrected change: -0.22 (-0.65, 0.20)%; p = 0.30]. Formal significance testing was not carried out for the other two AZD1656 dose groups. A higher percentage of patients on AZD1656 achieved HbA1c ≤ 7% after 4 months versus placebo, but responder rates were low. Results for FPG reflected those for HbA1c. Cases of hypoglycaemia were rare with AZD1656 (one patient) and no safety concerns were raised. CONCLUSIONS: Although initially favourable plasma glucose reductions were observed, there was a loss of effect over time with sustained AZD1656 treatment. The study design did not allow an evaluation of the reasons for this lack of long-term efficacy. 23256446 Metabolic effects of honey in type 1 diabetes mellitus: a randomized crossover pilot study. The aim of this study was to evaluate the metabolic effects of 12-week honey consumption on patients suffering from type 1 diabetes mellitus (DM). This was a randomized crossover clinical trial done in the National Institute for Diabetes and Endocrinology, Cairo, Egypt. Twenty patients of both sexes aged 4-18 years with type 1 DM and HbA1C<10% participated in the study. They were randomized into two equal groups (intervention to control and control to intervention). The dietary intervention was 12-week honey consumption in a dose of 0.5 mL/kg body weight per day. The main outcome measures were serum glucose, lipids, and C-peptide, and anthropometric measurements. None of participants were lost in follow-up. The intervention resulted in significant decreases in subscapular skin fold thickness (SSFT; P=.002), fasting serum glucose (FSG; P=.001), total cholesterol (P=.0001), serum triglycerides (TG; P=.0001), and low-density lipoprotein (P=.0009), and significant increases in fasting C-peptide (FCP; P=.0004) and 2-h postprandial C-peptide (PCP; P=.002). As possible long-term effects of honey after its withdrawal, statistically significant reductions in midarm circumference (P=.000), triceps skin fold thickness (P=.006), SSFT (P=.003), FSG (P=.005), 2-h postprandial serum glucose (P=.000), TG (P=.003), and HbA1C (P=.043), and significant increases in FCP (P=.002) and PCP (P=.003) were observed. This small clinical trial suggests that long-term consumption of honey might have positive effects on the metabolic derangements of type 1 DM. 23523544 Lipidic spherulites: Formulation optimisation by paired optical and cryoelectron microscopy. Objective of this study was to assess the various steps leading to spherulite obtention by means of optical and cryoelectron microscopy. The formulation, resting and hydration steps were optimised. Green-based process and organic-based process were compared. It was found that spherulites could be obtained only when two key steps were followed: a prior resting phase of excipients and the shearing stress of the hydrated excipients. Moreover, the new formulation under study formed spherulites in the 100-200nm range, which is smaller than previously reported spherulites. Such laboratory scale optimised process led the integration of spherulites in a larger number of prospective studies. Indeed, we finally showed that the encapsulated payload of a hydrophobic compound, such as the anti-angiogenic agent fisetin, was increased to a much higher degree than with a liposomal encapsulation. 23410169 Recent developments in rationally designed multitarget antiprotozoan agents. Protozoan infections are the leading cause of morbidity and mortality among parasitic infections of humans, accounting for approximately 800 thousand mortalities and a loss of more than 30 million disability-adjusted life years annually. The major protozoan infections of humans, namely malaria, Chagas disease, human African trypanosomiasis, and leishmaniasis, are primarily centered in the tropics, with a reach into some subtropical regions of the world. Though globally massive in their impact, these diseases mostly afflict the least economically endowed and geographically marginalized populations in low-income countries. As such, there is no sufficient market incentive for industrial businessdriven antiprotozoal drug discovery due to poor marketing prospects and low returns on investment. Consequently, the pharmacopoeia for majority of these diseases, composed mainly of agents with poor efficacy and unsatisfactory safety profiles, has essentially remained unchanged for decades, creating a compelling need for more efficacious and better tolerated medicines. The policy makers and the scientific community are seeking effective ways to meet this need. So far, two approaches have emerged promising in this regard: combination chemotherapy and drug repositioning. Molecular hybridization has been cited as a potential third approach that could be used to deliver new antiprotozoal chemical entities. In this review article, recent applications of this novel strategy in antimalarial, antichagasic, antitrypanosomal, and antileishmanial drug discovery research and development over the last five years will be presented and discussed. 23576341 Synthesis and evaluation of biphenyl compounds as Kinesin spindle protein inhibitors. Kinesin spindle protein (KSP), an ATP-dependent motor protein, plays an essential role in bipolar spindle formation during the mitotic phase (M phase) of the normal cell cycle. KSP has emerged as a novel target for antimitotic anticancer drug development. In this work, we synthesized a range of new biphenyl compounds and investigated their properties in vitro as potential antimitotic agents targeting KSP expression. Antiproliferation (MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)) assays, combined with fluorescence-assisted cell sorting (FACS) and Western blot studies analyzing cell-cycle arrest confirmed the mechanism and potency of these biphenyl compounds in a range of human cancer cell lines. Structural variants revealed that functionalization of biphenyl compounds with bulky aliphatic or aromatic groups led to a loss of activity. However, replacement of the urea group with a thiourea led to an increase in antiproliferative activity in selected cell lines. Further studies using confocal fluorescence microscopy confirmed that the most potent biphenyl derivative identified thus far, compound 7, exerts its pharmacologic effect specifically in the M phase and induces monoaster formation. These studies confirm that chemical scope remains for improving the potency and treatment efficacy of antimitotic KSP inhibition in this class of biphenyl compounds. 23223405 Four-Year Change in Cardiorespiratory Fitness and Influence on Glycemic Control in Adults With Type 2 Diabetes in a Randomized Trial: The Look AHEAD Trial. OBJECTIVE To examine an intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) on 4-year change in fitness and physical activity (PA), and to examine the effect of change in fitness and PA, adjusting for potential confounders, on glycemic control in the Look AHEAD Trial. RESEARCH DESIGN AND METHODS Subjects were overweight/obese adults with type 2 diabetes mellitus (T2DM) with available fitness data at 4 years (n = 3,942).This clinical trial randomized subjects to DSE or ILI. DSE subjects received standard care plus information related to diet, PA, and social support three times per year. ILI subjects received weekly intervention contact for 6 months, which was reduced over the 4-year period, and were prescribed diet and PA. Measures included weight, fitness, PA, and HbA1c. RESULTS The difference in percent fitness change between ILI and DSE at 4 years was significant after adjustment for baseline fitness and change in weight (3.70 vs. 0.94%; P < 0.01). At 4 years, PA increased by 348 (1,562) kcal/week in ILI vs. 105 (1,309) kcal/week in DSE (P < 0.01). Fitness change at 4 years was inversely related to change in HbA1c after adjustment for clinical site, treatment, baseline HbA1c, prescribed diabetes medication, baseline fitness, and weight change (P < 0.01). Change in PA was not related to change in HbA1c. CONCLUSIONS A 4-year ILI increased fitness and PA in overweight/obese individuals with T2DM. Change in fitness was associated with improvements in glycemic control, which provides support for interventions to improve fitness in adults with T2DM. 23353699 c-Src-dependent MAPKs/AP-1 activation is involved in TNF-α-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells. TNF-α plays a critical mediator in the pathogenesis of chronic heart failure contributing to cardiac remodeling and peripheral vascular disturbances. The implication of TNF-α in inflammatory responses has been shown to be mediated through up-regulation of inflammatory genes, including matrix metalloproteinase-9 (MMP-9). However, the detailed mechanisms of TNF-α-induced MMP-9 expression are largely unclear in the heart cells. Here, we demonstrated that in rat embryonic-heart derived H9c2 cells, TNF-α could induce MMP-9 mRNA expression associated with an increase in the secretion of MMP-9, determined by real-time PCR, zymography, and promoter activity assays. TNF-α-mediated responses were attenuated by pretreatment with the inhibitor of c-Src (PP1), EGFR (AG1478), PDGFR (AG1296), PI3K (LY294002), Akt (SH-5), MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), or AP-1 (Tanshinone IIA) and transfection with siRNA of c-Src, EGFR, PDGFR, p110, Akt, or c-Jun. TNF-α stimulated c-Src, PDGFR, and EGFR phosphorylation, which were reduced by PP1. In addition, TNF-α-stimulated Akt phosphorylation was inhibited by PP1, AG1478, AG1296, or LY294002. We further demonstrated that TNF-α markedly stimulated p38 MAPK, p42/p44 MAPK, and JNK1/2 phosphorylation via a c-Src/EGFR, PDGFR/PI3K/Akt pathway. Finally, we showed that, in H9c2 cells, TNF-α-stimulated AP-1 promoter activity, c-Jun mRNA expression, and c-Jun phosphorylation were attenuated by PP1, AG1478, AG1296, LY294002, SB202190, SP600125, or U0126. These results suggested that TNF-α-induced MMP-9 expression is mediated through a c-Src/EGFR, PDGFR/PI3K/Akt/MAPKs/AP-1 cascade in H9c2 cells. Consequently, MMP-9 induction may contribute to cell migration and cardiovascular inflammation. 23026700 Cassia tora (Leguminosae) seed extract alleviates high-fat diet-induced nonalcoholic fatty liver. The aim of this study was to examine the effects of Cassia tora seeds on high-fat diet (HFD)-induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects. After being fed a HFD for two weeks, rats were orally dosed with Cassia seed ethanol extract (CSEE) (100, 200, or 300mg/kg) once daily for 8weeks. CSEE induced dose-dependent reductions in plasma lipid levels, as well as decreased the over hepatic lipid accumulation. Furthermore, CSEE treatment improved HFD-induced hepatic histological lesions. CSEE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase, up-regulated the gene expression of carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in the livers of HFD-fed rats. AMPK inhibition by compound C retarded CSEE-induced reduction in triglyceride accumulation in HepG2 cells stimulated by insulin. Our findings suggest that CSEE may regulate hepatic lipid homeostasis related with an AMPK-dependent signaling pathway. Targeting AMPK activation with CSEE may represent a promising approach for the prevention and treatment of obesity-related non-alcoholic fatty liver disease. 23380917 Perinatal phencyclidine administration decreases the density of cortical interneurons and increases the expression of neuregulin-1. RATIONALE: Perinatal phencyclidine (PCP) administration in rat blocks the N-methyl D-aspartate receptor (NMDAR) and causes symptoms reminiscent of schizophrenia in human. A growing body of evidence suggests that alterations in γ-aminobutyric acid (GABA) interneuron neurotransmission may be associated with schizophrenia. Neuregulin-1 (NRG-1) is a trophic factor important for neurodevelopment, synaptic plasticity, and wiring of GABA circuits. OBJECTIVES: The aim of this study was to determine the long-term effects of perinatal PCP administration on the projection and local circuit neurons and NRG-1 expression in the cortex and hippocampus. METHODS: Rats were treated on postnatal day 2 (P2), P6, P9, and P12 with either PCP (10 mg/kg) or saline. Morphological studies and determination of NRG-1 expression were performed at P70. RESULTS: We demonstrate reduced densities of principal neurons in the CA3 and dentate gyrus (DG) subregions of the hippocampus and a reduction of major interneuronal populations in all cortical and hippocampal regions studied in PCP-treated rats compared with controls. For the first time, we show the reduced density of reelin- and somatostatin-positive cells in the cortex and hippocampus of animals perinatally treated with PCP. Furthermore, an increase in the numbers of perisomatic inhibitory terminals around the principal cells was observed in the motor cortex and DG. We also show that perinatal PCP administration leads to an increased NRG-1 expression in the cortex and hippocampus. CONCLUSION: Taken together, our findings demonstrate that perinatal PCP administration increases NRG-1 expression and reduces the number of projecting and local circuit neurons, revealing complex consequences of NMDAR blockade. 23493571 Cytoplasmic-Nuclear Trafficking of G1/S Cell Cycle Molecules and Adult Human Beta Cell Replication: A Revised Model of Human Beta Cell G1/S Control. Harnessing control of human beta cell proliferation has proven frustratingly difficult. Most G1/S control molecules, generally presumed to be nuclear proteins in the human beta cell, are in fact constrained to the cytoplasm. Here, we asked whether G1/S molecules might traffic into and out of the cytoplasmic compartment in association with activation of cell cycle progression. Cdk6 and cyclin D3 were used to drive human beta cell proliferation, and promptly translocated into the nucleus in association with proliferation. In contrast, the cell cycle inhibitors p15, p18 and p19 did not alter their location, remaining cytoplasmic. Conversely, p16, p21, p27 all increased their nuclear frequency. In contrast once again, p57 decreased its nuclear frequency. While proliferating beta cells contained nuclear cyclin D3 and cdk6, proliferation generally did not occur in beta cells that contained nuclear cell cycle inhibitors, except p21. Dynamic cytoplasmic-nuclear trafficking of cdk6 was confirmed using GFP-tagged cdk6 and live-cell imaging. Thus, we provide novel working models describing the control of cell cycle progression in the human beta cell. In addition to known obstacles to beta cell proliferation, cytoplasmic-to-nuclear trafficking of G1/S molecules may represent both an obstacle, as well as a therapeutic opportunity, for human beta cell expansion. 22840229 A new cyclonerol derivative from a marine-derived fungus Ascotricha sp. ZJ-M-5. A new sesquiterpene, ascotrichic acid (1), was isolated from a marine-derived fungus Ascotricha sp., together with the other two known analogues, cyclonerodiol (2) and 10(Z)-cyclonerotriol (3). Its structure was established by spectroscopic methods (1D and 2D NMR, HR-ESI-MS). 23219778 Tartary buckwheat improves cognition and memory function in an in vivo amyloid-β-induced Alzheimer model. Protective effects of Tartary buckwheat (TB) and common buckwheat (CB) on amyloid beta (Aβ)-induced impairment of cognition and memory function were investigated in vivo in order to identify potential therapeutic agents against Alzheimer's disease (AD) and its associated progressive memory deficits, cognitive impairment, and personality changes. An in vivo mouse model of AD was created by injecting the brains of ICR mice with Aβ(25-35), a fragment of the full-length Aβ protein. Damage of mice recognition ability through following Aβ(25-35) brain injections was confirmed using the T-maze test, the object recognition test, and the Morris water maze test. Results of behavior tests in AD model showed that oral administration of the methanol (MeOH) extracts of TB and CB improved cognition and memory function following Aβ(25-35) injections. Furthermore, in groups receiving the MeOH extracts of TB and CB, lipid peroxidation was significantly inhibited, and nitric oxide levels in tissue, which are elevated by injection of Aβ(25-35), were also decrease. In particular, the MeOH extract of TB exerted a stronger protective activity than CB against Aβ(25-35)-induced memory and cognition impairment. The results indicate that TB may play a promising role in preventing or reversing memory and cognition loss associated with Aβ(25-35)-induced AD. 23220003 Glyoxal and methylglyoxal: autoxidation from dihydroxyacetone and polyphenol cytoprotective antioxidant mechanisms. Previously, this laboratory had shown that fructose and its downstream metabolites can be enzymatically metabolized to form glyoxal and methylglyoxal. Fructose metabolites, glycoaldehyde, glyceraldehyde and hydroxypyruvate have also been shown to be autoxidizable. In this study, however, fructose did not cause protein carbonylation itself and instead protected against apparent carbonylation by Fenton's reagent; fructose did not form significant levels of dicarbonyl compounds over a period of 6 days under standard conditions (37°C, pH 7.4). In contrast, dihydroxyacetone, a fructose metabolite, caused protein carbonylation and autoxidized to form dicarbonyls, which effects were further potentiated under oxidative stress conditions (Fenton's reaction). Natural polyphenols were tested for their ability to protect against glyoxal- and methylglyoxal-induced cytotoxicity, reactive oxygen species formation and improved mitochondrial membrane potential maintenance. The polyphenols investigated were gallic acid, methyl gallate, ethyl gallate, propyl gallate, rutin and curcumin. The polyphenols were assayed using primary and GSH-depleted hepatocytes. The polyphenols were also investigated for their rescuing ability and were found to provide greater hepatoprotection when toxins were pre-incubated for 30 min before adding the polyphenols. However, rutin was less protective when rescuing hepatocytes, perhaps, because rutin metabolites may scavenge reactive oxygen species more effectively than rutin itself. The longer the alkyl group attached to the gallate compound, the more cytoprotective the polyphenol was. However, the gallates with longer alkyl groups were less able to scavenge reactive oxygen species, and to maintain the mitochondrial membrane potential. 23536584 Efficacy and Safety of Lixisenatide Once-Daily Morning or Evening Injections in Type 2 Diabetes Inadequately Controlled on Metformin (GetGoal-M). OBJECTIVEExamine the efficacy and safety of lixisenatide (20 μg once daily, administered before the morning or evening meal) as add-on therapy in type 2 diabetes patients insufficiently controlled with metformin alone.RESEARCH DESIGN AND METHODSA 24-week, randomized, double-blind, placebo-controlled study in 680 patients with inadequately controlled type 2 diabetes (HbA1c 7-10% [53-86 mmol/mol]). Patients were randomized to lixisenatide morning (n = 255), lixisenatide evening (n = 255), placebo morning (n = 85), or placebo evening (n = 85) injections.RESULTSLixisenatide morning injection significantly reduced mean HbA1c versus combined placebo (mean change -0.9% [9.8 mmol/mol] vs. -0.4% [4.4 mmol/mol]; least squares [LS] mean difference vs. placebo -0.5% [5.5 mmol/mol], P < 0.0001). HbA1c was significantly reduced by lixisenatide evening injection (mean change -0.8% [8.7 mmol/mol] vs. -0.4% [4.4 mmol/mol]; LS mean difference -0.4% [4.4 mmol/mol], P < 0.0001). Lixisenatide morning injection significantly reduced 2-h postprandial glucose versus morning placebo (mean change -5.9 vs. -1.4 mmol/L; LS mean difference -4.5 mmol/L, P < 0.0001). LS mean difference in fasting plasma glucose was significant in both morning (-0.9 mmol/L, P < 0.0001) and evening (-0.6 mmol/L, P = 0.0046) groups versus placebo. Mean body weight decreased to a similar extent in all groups. Rates of adverse events were 69.4% in both lixisenatide groups and 60.0% in the placebo group. Rates for nausea and vomiting were 22.7 and 9.4% for lixisenatide morning and 21.2 and 13.3% for lixisenatide evening versus 7.6 and 2.9% for placebo, respectively. Symptomatic hypoglycemia occurred in 6, 13, and 1 patient for lixisenatide morning, evening, and placebo, respectively, with no severe episodes.CONCLUSIONSIn patients with type 2 diabetes inadequately controlled on metformin, lixisenatide 20 μg once daily administered in the morning or evening significantly improved glycemic control, with a pronounced postprandial effect, and was well tolerated. 23588477 Genome-Based Bacterial Vaccines: Current State and Future Outlook. Genome-based reverse vaccinology (RV) is a multi-step experimental strategy which starts from in silico analysis of whole genome sequences, from which vaccine candidates can be selected by using bioinformatic algorithms to identify putative protective antigens. In this review, we examine the current state of genome-based RV-engineered vaccines and future applications. The first product of genome-based RV is Bexsero(®), a vaccine developed for preventing Neisseria meningitidis serogroup B infection, and the strategy is currently being used for the development of new vaccines for other obdurate and emerging bacterial diseases. Improved sequencing technologies and the ongoing whole-genome sequence analyses of helminths, protozoa, and ectoparasites also currently serve as a basis for an RV strategy to produce new potential vaccines against eukaryotic pathogens. We also highlight an emerging approach-structure-based vaccinology-that exploits the information derived from the determined three-dimensional structures of vaccine candidates. Regardless, genome-based RV and other vaccine discovery platforms still depend on empirical experimental science to glean, from the hundreds of identified antigens from any one pathogen, those that should be combined to produce an effective vaccine. 23454648 Generation of intracellular reactive oxygen species and genotoxicity effect to exposure of nanosized polyamidoamine (PAMAM) dendrimers in PLHC-1 cells in vitro. Polyamidoamine (PAMAM) dendrimers have previously been demonstrated to elicit systematically variable cyto- and eco-toxic responses, promising as the basis for structure-activity relationships governing nanotoxicological responses. In this study, increased production of intracellular reactive oxygen species (ROS), genotoxicity and apoptosis due to in vitro exposure of fish hepatocellular carcinoma cells to dendrimer generations G4, G5 and G6 is demonstrated. A PAMAM dendrimer generation dependent increase in ROS and genotoxicity was observed, consistent with our previous studies. The toxicological responses correlate well with the nanoparticle surface chemistry, specifically, the number of surface amino groups per generation. Although ROS production initially increases approximately linearly, it saturates at higher doses. Notably, normalized to the molar dose of surface amino groups, the dose-dependent ROS production for different generations overlap exactly, indicating that the response is due to these functional units. The genotoxicity response is also well correlated to the number of surface amino groups and therefore generation of PAMAM dendrimers. The observed genotoxicity, related to DNA damage, is related to the generation and dose dependent production of intracellular ROS, at low levels. At the higher ROS levels, increased DNA damage is associated with the onset of necrosis. 23147377 Iron oxide particles modulate the ovalbumin-induced Th2 immune response in mice. This study was designed to investigate the modulatory effects of submicron and nanosized iron oxide (Fe(2)O(3)) particles on the ovalbumin (OVA)-induced immune Th2 response in BALB/c mice. Particles were intratracheally administered four times to mice before and during the OVA sensitization period. For each particle type, three different doses, namely 4×100, 4×250 or 4×500 μg/mouse, were used and for each dose, four groups of mice, i.e. group saline solution (1), OVA (2), particles (3), and OVA plus particles (4), were constituted. Mice exposed to OVA alone exhibited an allergic Th2-dominated response with a consistent increase in inflammatory scores, eosinophil numbers, specific IgE levels and IL-4 production. When the mice were exposed to OVA and to high and intermediate doses of iron oxide submicron- or nanoparticles, the OVA-induced allergic response was significantly inhibited, as evidenced by the decrease in eosinophil cell influx and specific IgE levels. However, the low dose (4×100 μg) of submicron particles had no significant effect on the OVA allergic response while the same dose of nanoparticles had an adjuvant effect on the Th2 response to OVA. In conclusion, these data demonstrate that the pulmonary immune response to OVA is a sensitive target for intratracheally instilled particles. Depending on the particle dose and size, the allergic response was suppressed or enhanced. 23542608 Pulmonary DWCNT exposure causes sustained local and low-level systemic inflammatory changes in mice. Carbon nanotubes (CNTs) represent promising vectors to facilitate cellular drug delivery and to overcome biological barriers, but some types may also elicit persistent pulmonary inflammation based on their fibre characteristics. Here, we show the pulmonary response to aqueous suspensions of block copolymer dispersed, double-walled carbon nanotubes (DWCNT, length 1-10μm) in mice by bronchoalveolar lavage (BAL) analysis, and BAL and blood cytokine and lung antioxidant profiling. The intratracheally instilled dose of 50μg DWCNT caused significant pulmonary inflammation that was not resolved during a 7-day observation period. Light microscopy investigation of the uptake of DWCNT agglomerates revealed no particle ingestion for granulocytes, but only for macrophages. Accumulating macrophage, multinucleated macrophage and lymphocyte numbers in the alveolar region further indicated ineffective resolution with chronification of the inflammation. The local inflammatory impairment of the lung was accompanied by pulmonary antioxidant depletion and haematological signs of systemic inflammation. While the observed inflammation during its acute phase was dominated by neutrophils and neutrophil recruiting cytokines, the contribution of macrophages and lymphocytes with related cytokines became more significant after day 3 of exposure. This study confirms that acute pulmonary toxicity can occur on exposure of high doses of DWCNT agglomerates and offers further insight for improved nanotube design parameters to avoid potential long-term toxicity. 23200005 Composition and distribution of the main active components in selenium-enriched fruit bodies of Cordyceps militaris link. Selenium-enriched Cordyceps militaris fruit bodies are industrially cultivated as functional food or medicinal food in China and southeast Asia. However, composition of selenium compounds and distribution of the main bioactive components are still unknown. In the selenium-enriched fruit bodies, the main soluble selenium compounds of low molecular weight were identified as SeMet (selenomethionine), and the main selenium compounds bound in proteins were identified as SeMet and SeCys (methylselenocysteine). Trace minerals as Se (selenium), Zn (zinc), Fe (iron) and the main active components as adenosine, cordycepin and carotenoids were mostly distributed in the terminal of fruit bodies, while P (phosphorus) and K (potassium) were evenly distributed in the fruit bodies. The results indicated that terminal of the fruit bodies should be the better materials for production of advanced functional food. So cultivation of relatively short and thick fruit bodies with bigger terminals deserves further research. 23460383 Thermoplastic Polyurethanes From Undecylenic Acid-Based Soft Segments: Structural Features and Release Properties. A set of thermoplastic polyurethanes is synthesized, combining undecylenic acid-derived telechelic diols as soft segments and 1,4-butanediol/4,4'-methylenebis(phenylisocyanate) as a hard segment (HS). These polymers are fully chemically and physically characterized by means of NMR and Fourier transform IR (FTIR) spectroscopy, size-exclusion chromatography (SEC), DSC, thermogravimetric analysis (TGA), tensile testing, and contact angle measurements. The obtained results reveal that both the molecular weight of the diol and the HS content greatly influence the physical and mechanical properties of these polymers. In addition, given the potential use of these materials for biomedical applications, hydrolytic degradation, their biocompatibility using a human fibroblast cell line, and performance as drug delivery carriers are evaluated. 23376354 Ion channel remodeling in vascular smooth muscle during hypertension: Implications for novel therapeutic approaches. Ion channels are multimeric, transmembrane proteins that selectively mediate ion flux across the plasma membrane in a variety of cells including vascular smooth muscle cells (VSMCs). The dynamic interplay of Ca(2+) and K(+) channels on the plasma membrane of VSMCs plays a pivotal role in modulating the vascular tone of small arteries and arterioles. The abnormally-elevated arterial tone observed in hypertension thus points to an aberrant expression and function of Ca(2+) and K(+) channels in the VSMCs. In this short review, we focus on the three well-studied ion channels in VSMCs, namely the L-type Ca(2+) (CaV1.2) channels, the voltage-gated K(+) (KV) channels, and the large-conductance Ca(2+)-activated K(+) (BK) channels. First, we provide a brief overview on the physiological role of vascular CaV1.2, KV and BK channels in regulating arterial tone. Second, we discuss the current understanding of the expression changes and regulation of CaV1.2, KV and BK channels in the vasculature during hypertension. Third, based on available proof-of-concept studies, we describe the potential therapeutic approaches targeting these vascular ion channels in order to restore blood pressure to normotensive levels. 23455995 Impacts of spinosad and λ-cyhalothrin on spider communities in cabbage fields in south Texas. Spiders are a principal arthropod group that preys on numerous pests of vegetables and other crops. In this study, we determined the effects of the two most commonly used insecticides, spinosad and λ-cyhalothrin, on diversity of spiders on cabbage in south Texas. In two seasons (fall 2008 and spring 2009), we collected a total of 588 spiders belonging to 53 species in 11 families from spinosad and λ-cyhalothrin-treated cabbages and the untreated control plants. A great majority of spiders were collected from the pitfall traps (554) where only a few (34) were collected from the blower/vacuum sampling. In the insecticide-treated plots, there were significantly fewer spider individuals, species and families than in untreated fields. Spinosad had significantly less effect on spiders in total individuals, number of species and families than λ-cyhalothrin. The effects of the two insecticides were further demonstrated by the Shannon-Weiner index (H') and the hierarchical richness index (HRI). Spider diversity in the spinosad-treated plots were not significantly different from that in the untreated fields but were greater than those in λ-cyhalothrin-treated plots in both seasons when measured by H' values. In contrast, the H' values of spider's diversity in the λ-cyhalothrin-treated plots were significantly lower than spinosad-treated and untreated plots. High values of HRI for spider richness in the spinosad-treated plots suggested that spinosad had less effect on spiders than λ-cyhalothrin. We concluded that spinosad was more compatible with spiders on cabbage compared to λ-cyhalothrin and that this information should be used when developing insecticide resistance management strategies. 23419007 Incorporation of rapid thermodynamic data in fragment-based drug discovery. Fragment-based drug discovery (FBDD) has enjoyed increasing popularity in recent years. We introduce SITE (single-injection thermal extinction), a novel thermodynamic methodology that selects high-quality hits early in FBDD. SITE is a fast calorimetric competitive assay suitable for automation that captures the essence of isothermal titration calorimetry but using significantly fewer resources. We describe the principles of SITE and identify a novel family of fragment inhibitors of the enzyme ketosteroid isomerase displaying high values of enthalpic efficiency. 23328252 Benzophenone-1 stimulated the growth of BG-1 ovarian cancer cells by cell cycle regulation via an estrogen receptor alpha-mediated signaling pathway in cellular and xenograft mouse models. 2,4-Dihydroxybenzophenone (benzophenone-1; BP-1) is an UV stabilizer primarily used to prevent polymer degradation and deterioration in quality due to UV irradiation. Recently, BP-1 has been reported to bioaccumulate in human bodies by absorption through the skin and has the potential to induce health problems including endocrine disruption. In the present study, we examined the xenoestrogenic effect of BP-1 on BG-1 human ovarian cancer cells expressing estrogen receptors (ERs) and relevant xenografted animal models in comparison with 17-β estradiol (E2). In in vitro cell viability assay, BP-1 (10(-8)-10(-5)M) significantly increased BG-1 cell growth the way E2 did. The mechanism underlying the BG-1 cell proliferation was proved to be related with the up-regulation of cyclin D1, a cell cycle progressor, by E2 or BP-1. Both BP-1 and E2 induced cell growth and up-regulation of cyclin D1 were reversed by co-treatment with ICI 182,780, an ER antagonist, suggesting that BP-1 may mediate the cancer cell proliferation via an ER-dependent pathway like E2. On the other hand, the expression of p21, a regulator of cell cycle progression at G1 phase, was not altered by BP-1 though it was down-regulated by E2. In xenograft mouse models transplanted with BG-1 cells, BP-1 or E2 treatment significantly increased the tumor mass formation compared to a vehicle (corn oil) within 8 weeks. In histopathological analysis, the tumor sections of E2 or BP-1 group displayed extensive cell formations with high density and disordered arrangement, which were supported by the increased number of BrdUrd positive nuclei and the over-expression of cyclin D1 protein. Taken together, these results suggest that BP-1 is an endocrine disrupting chemical (EDC) that exerts xenoestrogenic effects by stimulating the proliferation of BG-1 ovarian cancer via ER signaling pathway associated with cell cycle as did E2. 23266722 Non-melanoma skin cancer in mouse and man. As a frontier organ, skin is exposed to different environmental and/or occupational chemicals which cause cutaneous cancers in experimental animals. In mice, 7,12-dimethylbenz[a]anthrancene (DMBA) and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) are frequently used as skin model tumor initiator and promoter, respectively. The sequential administration of DMBA and TPA leads to the appearance of a large number of benign papillomas, of which some convert later into invasive squamous cell carcinomas (SCC). At the molecular level, initiation of carcinogenesis in mouse skin consists in the mutational activation of the Ha-ras oncoprotein. HA-RAS mutations are rare in human SCC, but HA-RAS-mutated tumors appear in melanoma patients treated with B-raf inhibitors, indicating that initiated, HA-RAS-mutated stem cells also reside in human skin. Similarly, UV-induced human SCC show footprint mutations in the tumor suppressor gene TP53 which are also observed in UV-induced mouse SCC. Strong species differences exist with respect to phorbol ester-mediated tumor promotion. While certain mouse strains are very susceptible, other rodent species are much less sensitive. Likewise, humans appear to be much more resistant to phorbol ester-mediated skin toxicity. Papilloma formation as a result of a chemical insult is uncommon in men, questioning the relevance of this preneoplastic lesion for humans. However, skin tumorigenesis in the experimental situation and in humans appears to follow common molecular mechanisms, even though there are species differences in the morphological correlates to the preneoplastic state. Therefore, we recommend not simply labeling them as irrelevant for human risk assessment. 22799569 Flavonoids and antioxidant activity of flowers of Mexican Crataegus spp. Flavonoids and antioxidant activity of extracts of flowers from some Mexican accessions of Crataegus were studied using six accessions with the purpose of contributing to the knowledge of the nutraceutical properties of the accessions of the Germplasm Bank of the Universidad Autonoma Chapingo. Flavonoids were identified by HPLC-MS. Among the flavonoids, the quercetin 3-O-glucoside (3), quercetin 3-O-rhamnoside (4), quercetin 3-O-rhamnosyl-(1 → 6)-glucoside (2) and quercetin 3-O-rhamnosyl-(1 → 2)-[rhamnosyl-(1 → 6)]-glucoside (1) were assigned. Flavonoid content and radical scavenging activity explain some of the medicinal properties attributed to flowers of Mexican hawthorns. 23628674 Effects of Traditional Chinese Medicine Wuzhi Capsule on Pharmacokinetics of Tacrolimus in Rats. Wuzhi capsule (WZC) is a preparation of an ethanol herbal extract of Schisandra sphenanthera(Nan-Wuweizi), with its main active ingredients including schisandrin, schisandrol B, schisantherin A, schisanhenol and deoxyshisandrin. WZC and tacrolimus are often co-administered for the treatment of drug-induced hepatitis in organ transplant recipients in China. Recently, it was reported that WZC could significantly increase the blood concentration of tacrolimus. The purpose of this study was to investigate whether and how WZC affects the pharmacokinetics of tacrolimus in rats. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to determine the plasma concentration of tacrolimus. The results showed that WZC increased the mean plasma concentration of tacrolimus. Compared with administration of tacrolimus alone (Cmax, 18.87±10.29 ng/mL; AUC0&→t, 40.98±37.07), a single intragastric administered dose of WZC increased, the pharmacokinetic parameters of tacrolimus (Cmax, 59.42±30.32 ng/mL; AUC0→t, 239.71±28.86) by five folds in rat plasma. After pretreatment with WZC for 12 days, there were still significant increases in AUC0→t (from 40.98±37.07 to 89.21±26.39 h ng/mL; p < 0.05) and Cmax (from 18.87±10.29 to 43.16±10.61 ng/mL; p < 0.05) of tacrolimus compared with oral of tacrolimus alone, suggesting that WZC increased the exposure of tacrolimus by one or more mechanisms. The increase in tacolimus Cmax by WZC was dose dependent. The effect of WZC on Tacrolimus AUC0→t also increased with dose with a maximal effect observed at 450 mg/kg (825.34 ng h/mL). No further increases in tacolimus AUC0→t were observed at WZC dose above 450 mg/kg. It is suggested that due to the effect of WZC on the pharmacokinetics of tacrolimus, the herb-drug interaction between WZC and tacrolimus should be taken into considered in clinical practice. 23214714 Mechanism of homogeneous reduction of CO2 by pyridine: proton relay in aqueous solvent and aromatic stabilization. We employ quantum chemical calculations to investigate the mechanism of homogeneous CO(2) reduction by pyridine (Py) in the Py/p-GaP system. We find that CO(2) reduction by Py commences with PyCOOH(0) formation where: (a) protonated Py (PyH(+)) is reduced to PyH(0), (b) PyH(0) then reduces CO(2) by one electron transfer (ET) via nucleophilic attack by its N lone pair on the C of CO(2), and finally (c) proton transfer (PT) from PyH(0) to CO(2) produces PyCOOH(0). The predicted enthalpic barrier for this proton-coupled ET (PCET) reaction is 45.7 kcal/mol for direct PT from PyH(0) to CO(2). However, when PT is mediated by one to three water molecules acting as a proton relay, the barrier decreases to 29.5, 20.4, and 18.5 kcal/mol, respectively. The water proton relay reduces strain in the transition state (TS) and facilitates more complete ET. For PT mediated by a three water molecule proton relay, adding water molecules to explicitly solvate the core reaction system reduces the barrier to 13.6-16.5 kcal/mol, depending on the number and configuration of the solvating waters. This agrees with the experimentally determined barrier of 16.5 ± 2.4 kcal/mol. We calculate a pK(a) for PyH(0) of 31 indicating that PT preceding ET is highly unfavorable. Moreover, we demonstrate that ET precedes PT in PyCOOH(0) formation, confirming PyH(0)'s pK(a) as irrelevant for predicting PT from PyH(0) to CO(2). Furthermore, we calculate adiabatic electron affinities in aqueous solvent for CO(2), Py, and Py·CO(2) of 47.4, 37.9, and 66.3 kcal/mol respectively, indicating that the anionic complex PyCOO(-) stabilizes the anionic radicals CO(2)(-) and Py(-) to facilitate low barrier ET. As the reduction of CO(2) proceeds through ET and then PT, the pyridine ring becomes aromatic, and thus Py catalyzes CO(2) reduction by stabilizing the PCET TS and the PyCOOH(0) product through aromatic resonance stabilization. Our results suggest that Py catalyzes the homogeneous reductions of formic acid and formaldehyde en route to formation of CH(3)OH through a series of one-electron reductions analogous to the PCET reduction of CO(2) examined here, where the electrode only acts to reduce PyH(+) to PyH(0). 23157442 Micro/nanostructured hyaluronic acid matrices with tuned swelling and drug release properties. Hyaluronic acid (HA) hydrogels were structured in the form of porous monoliths by means of the ice-segregation-induced self-assembly (ISISA) method coupled with freeze-drying. Physical and chemical parameters were explored in order to fine-tune the microstructure and the incidence on both swelling and dissolution behavior in aqueous media. Gentamicin-loaded HA matrices with tuned drug release properties were also prepared; their inherent properties and behavior in solution are discussed in the framework of thermal analysis and scanning electron microscopy inspection. 22640571 Syntheses and antibacterial activity of Schiff bases from 16-isopropyl-5, 9-dimethyltetracyclo [10.2.2.0(1, 10).0(4, 9)] hexadec-15-ene-5, 14-dicarboxylic acid. 16-Isopropyl-5, 9-dimethyltetracyclo [10.2.2.0(1, 10).0(4, 9)] hexadec-15-ene-5, 14-dicarboxylic acid (1b) was prepared from rosin through a Diels-Alder addition reaction. Then, a group of Schiff bases derived from 1b was synthesised. Their structures were characterised by IR,(1)H-NMR, MS and elemental analysis. The antibacterial activities of these newly synthesised Schiff bases were also investigated. The results show that these compounds possess antibacterial activities against Staphylococcus aureus and Escherichia coli. Among them, compounds 5a, 5b and 5c, exhibit remarkable antibacterial activity against E. coli. 23288103 A new hematite photoanode doping strategy for solar water splitting: oxygen vacancy generation. The enhancement of the electrical conductivity by doping is important in hematite (α-Fe(2)O(3)) photoanodes for efficient solar water oxidation. However, in spite of many successful demonstrations using extrinsic dopants, such as Sn, Ti, and Si, the achieved photocurrent is still lower than the practical requirement. There is still lack of our understanding of how intrinsic oxygen defects can change the photocurrent and interact with the extrinsic dopants. In this study, we systematically investigate the interplay of oxygen vacancies and extrinsic Sn dopants in the context of photoanodic properties. As a result, we demonstrate that the controlled generation of oxygen vacancies can activate the photoactivity of pure hematite remarkably and further enhance the Sn doping effects synergistically. Furthermore, the correlated behavior of oxygen vacancies and Sn dopants is closely linked to the variation of electrical conductance and results in the optimum concentration region to show the high photocurrent and low onset voltage. 23117208 Impact of Charcot neuroarthropathy on metatarsal bone mineral density and geometric strength indices. Charcot neuroarthropathy (CN), an inflammatory condition characterized by rapid and progressive destruction of pedal bones and joints, often leads to deformity and ulceration in individuals with diabetes mellitus (DM) and peripheral neuropathy (PN). Repetitive, unperceived joint trauma may trigger initial CN damage, causing a proinflammatory cascade that can result in osteolysis and contribute to subsequent neuropathic fracture. We aimed to characterize osteolytic changes related to development and progression of CN by measuring bone mineral density (BMD) and geometric strength indices using volumetric quantitative computed tomography. Twenty individuals with DM+PN were compared to twenty age-, sex-, and race-matched individuals with DM+PN and acute CN. We hypothesized that individuals with acute CN would have decreased BMD and decreased total area, cortical area, minimum section modulus, and cortical thickness in the diaphysis of the second and fifth metatarsals. Results showed BMD was lower in both involved and uninvolved feet of CN participants compared to DM+PN participants, with greater reductions in involved CN feet compared to uninvolved CN feet. There was a non-significant increase in total area and cortical area in the CN metatarsals, which helps explain the finding of similar minimum section modulus in DM+PN and CN subjects despite the CN group's significantly lower BMD. Larger cortical area and section modulus are typically considered signs of greater bone strength due to higher resistance to compressive and bending loads, respectively. In CN metatarsals, however, these findings may reflect periosteal woven bone apposition, i.e., a hypertrophic response to injury rather than increased fracture resistance. Future research using these techniques will aid further understanding of the inflammation-mediated bony changes associated with development and progression of CN and other diseases. 23010363 Proteins with an alpha/beta hydrolase fold: Relationships between subfamilies in an ever-growing superfamily. Alpha/beta hydrolases function as hydrolases, lyases, transferases, hormone precursors or transporters, chaperones or routers of other proteins. The amount of structural and functional available data related to this protein superfamily expands exponentially, as does the number of proteins classified as alpha/beta hydrolases despite poor sequence similarity and lack of experimental data. However the superfamily can be rationally divided according to sequence or structural homologies, leading to subfamilies of proteins with potentially similar functions. Since the discovery of proteins homologous to cholinesterases but devoid of enzymatic activity (e.g., the neuroligins), divergent functions have been ascribed to members of other subfamilies (e.g., lipases, dipeptidylaminopeptidase IV, etc.). To study the potentially moonlighting properties of alpha/beta hydrolases, the ESTHER database (for ESTerase and alpha/beta Hydrolase Enzymes and Relatives; http://bioweb.ensam.inra.fr/esther), which collects, organizes and disseminates structural and functional information related to alpha/beta hydrolases, has been updated with new tools and the web server interface has been upgraded. A new Overall Table along with a new Tree based on HMM models has been included to tentatively group subfamilies. These tools provide starting points for phylogenetic studies aimed at pinpointing the origin of duplications leading to paralogous genes (e.g., acetylcholinesterase versus butyrylcholinesterase, or neuroligin versus carboxylesterase). Another of our goals is to implement new tools to distinguish catalytically active enzymes from non-catalytic proteins in poorly studied or annotated subfamilies. 23523780 Differential responses to ω-agatoxin IVA in murine frontal cortex and spinal cord derived neuronal networks. ω-Agatoxin-IVA is a well known P/Q-type Ca(2+) channel blocker and has been shown to affect presynaptic Ca(2+) currents as well postsynaptic potentials. P/Q-type voltage gated Ca(2+) channels play a vital role in presynaptic neurotransmitter release and thus play a role in action potential generation. Monitoring spontaneous activity of neuronal networks on microelectrode arrays (MEAs) provides an important tool for examining this neurotoxin. Changes in extracellular action potentials are readily observed and are dependent on synaptic function. Given the efficacy of murine frontal cortex and spinal cord networks to detect neuroactive substances, we investigated the effects of ω-agatoxin on spontaneous action potential firing within these networks. We found that networks derived from spinal cord are more sensitive to the toxin than those from frontal cortex; a concentration of only 10nM produced statistically significant effects on activity from spinal cord networks whereas 50nM was required to alter activity in frontal cortex networks. Furthermore, the effects of the toxin on frontal cortex are more complex as unit specific responses were observed. These manifested as either a decrease or increase in action potential firing rate which could be statistically separated as unique clusters. Administration of bicuculline, a GABAA inhibitor, isolated a single response to ω-agatoxin, which was characterized by a reduction in network activity. These data support the notion that the two clusters detected with ω-agatoxin exposure represent differential responses from excitatory and inhibitory neuronal populations. 22993196 Hepatic ATGL knockdown uncouples glucose intolerance from liver TAG accumulation. Adipose triglyceride lipase (ATGL) is the predominant triacylglycerol (TAG) hydrolase in mammals; however, the tissue-specific effects of ATGL outside of adipose tissue have not been well characterized. Hence, we tested the contribution of hepatic ATGL on mediating glucose tolerance and insulin action. Glucose or insulin tolerance tests and insulin signaling were performed in C57BL/6 mice administered control (nongene specific shRNA) or Atgl shRNA adenoviruses. Glucose and lipid metabolism assays were conducted in primary hepatocytes isolated from mice transduced with control or Atgl shRNA adenoviruses. Knocking down hepatic ATGL completely abrogated the increase in serum insulin following either 1 or 12 wk of feeding a high-fat (HF) diet despite higher hepatic TAG content. Glucose tolerance tests demonstrated that ATGL knockdown normalized glucose tolerance in HF-diet-fed mice. The observed improvements in glucose tolerance were present despite unaltered hepatic insulin signaling and increased liver TAG. Mice with suppressed hepatic ATGL had reduced hepatic glucose production in vivo, and hepatocytes isolated from Atgl shRNA-treated mice displayed a 26% decrease in glucose production and a 38% increase in glucose oxidation compared to control cells. Taken together, these data suggest that hepatic ATGL knockdown enhances glucose tolerance by increasing hepatic glucose utilization and uncouples impairments in insulin action from hepatic TAG accumulation. 23614492 Terpenoids from the Chinese liverwort Plagiochila pulcherrima and their cytotoxic effects. Three new pimarane-type diterpenoids, 7β,11α-dihydroxypimara-8(14),15-diene (1), 1β,11α-dihydroxypimara-8(14),15-diene (2), and 11α-hydroxypimara-8(14),15-diene (3), five 2,3-secoaromadendrane-type sesquiterpenoids, including a new one, ethyoxyplagiochiline A2 (4), and three known fusicoccane-type diterpenoids were isolated from the Chinese liverwort Plagiochila pulcherrima. Their structures were established on the basis of extensive spectroscopic analysis. Compounds 6 and 7 exhibited moderate inhibitory activity on the proliferation of human cancer cell lines Hela, A172, and H460. Moreover, the cytotoxicity of compound 6 to Hela cells was related to apoptotis as confirmed by DAPI nuclear staining and flow cytometry. 23463333 Determination of robenidine residues in chicken muscle by high performance liquid chromatography with ultraviolet detection. A simple, robust and reliable method for the determination of residual robenidine in chicken muscle using high performance liquid chromatography with ultraviolet (UV) detection was developed and validated according to the Codex Alimentarius Commission guidelines. Chicken muscle was extracted by acetonitrile/formic acid (98:2, v/v) and defatted with hexane. Analytes were isocratically separated on a Luna C18 column (4.6 × 150 mm, 5 μm) using 70 % methanol in water containing 0.1 % trifluoroacetic acid at a flow rate of 1.0 mL/min at 30 °C. UV detection was performed at 312 nm. The method was validated by assessing performance parameters including selectivity, linearity, limit of quantification (LOQ), precision, accuracy, recovery, stability and robustness. A calibration curve that was constructed over 0.05-0.5 μg/g showed correlation coefficients of more than 0.999. The intra- and inter-day precisions (as coefficient of variation) were 1.45-3.32 and 2.63-4.99 %, respectively. The intra- and inter-day accuracies were 99.4-105.3 and 98.3-101.6 %, respectively. The recoveries were in the range of 76.6-81.8 % and the LOQ was 0.05 μg/g. The developed method showed suitable performance for the determination of robenidine residues in chicken muscle. 23600887 Two novel furostanol saponins from the tubers of Ophiopogon japonicus. Phytochemical investigation of the fresh tubers of Ophiopogon japonicus led to the isolation of two new furostanol saponins (1 and 2) together with two known steroidal saponins (3 and 4). Comprehensive spectroscopic analysis allowed the chemical structures of two new compounds to be elucidated as (25R)-26-O-[β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranosyl]-5-ene-furost-1β,3β,22α,26-tetraol-3-O-α-l-rhamnopyranosyl-(1 → 2)-[β-d-xylopyranosyl-(1 → 4)]-β-d-glucopyranoside (1, ophiopogonin P) and (25R)-26-O-[β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyl]-5-ene-furost-1β,3β,22α,26-tetraol-3-O-α-l-rhamnopyranosyl-(1 → 2)-[β-d-xylopyranosyl-(1 → 4)]-β-d-glucopyranoside (2, ophiopogonin Q). Furostanol saponins with the disaccharide chain linked at C-26 hydroxy group of the aglycone have been rarely reported from natural sources. 23421743 Dorsamin-A's, Glycerolipids Carrying a Dehydrophenylalanine Ester Moiety from the Seed-Eating Larvae of the Bruchid Beetle Bruchidius dorsalis. Using a TLC autographic assay for radical-scavenging activity with the ABTS radical, the presence of lipophilic antioxidants in the larvae of the wild bruchid seed beetle Bruchidius dorsalis was detected. Assay-guided fractionation of the CHCl(3)-soluble fraction of the larvae resulted in the isolation of new glycerolipids, designated dorsamin-A763, -A737, -A765, -A739, and -A767, comprising 1,2-diacyl-sn-glycero-3-dehydrophenylalanine ester structural units. The ABTS radical scavenging activity of the dorsamin-A's was comparable with or stronger than that of Trolox. 23572409 Pomalidomide: first global approval. Pomalidomide (Pomalyst(®)) is a small molecule analogue of thalidomide under development with Celgene Corporation for the oral treatment of haematological and connective tissue diseases. Pomalidomide has been approved in the USA and is awaiting approval in the EU for use with low-dose dexamethasone for the treatment of relapsed and refractory multiple myeloma that has progressed following at least two prior therapies, including lenalidomide and bortezomib. The efficacy and safety of pomalidomide as monotherapy in patients with relapsed and refractory multiple myeloma has also been evaluated in a phase III trial. The agent is in phase III clinical development for the treatment of myelofibrosis and in phase II development for systemic sclerosis. Pomalidomide is also being investigated in patients with amyloidosis, prostate cancer, small cell lung cancer, pancreatic cancer, graft-versus-host disease, and Waldenstrom's macroglobulinaemia. This article summarizes the milestones in the development of pomalidomide leading to this first global approval for relapsed and refractory multiple myeloma. 23131208 Is poor research the cause of the declining productivity of the pharmaceutical industry? An industry in need of a paradigm shift. For the past 20 years target-based drug discovery has been the main research paradigm used by the pharmaceutical industry and billions of dollars have been invested into this approach. However, recent industry data strongly indicate that the target-based approach is not an effective drug discovery paradigm and is likely to be the cause of the productivity crisis the industry is experiencing. However, from a theoretical and scientific perspective the target-based approach appears sound, so why is it not more successful? The purpose of this paper is first to analyse the real-life implementation of the target-based approach to identify possible reasons for the high failure rate and second to suggest changes to the drug discovery approach, which can improve productivity. 23503588 The exoribonuclease Dis3L2 defines a novel eukaryotic RNA degradation pathway. The final step of cytoplasmic mRNA degradation proceeds in either a 5'-3' direction catalysed by Xrn1 or in a 3'-5' direction catalysed by the exosome. Dis3/Rrp44, an RNase II family protein, is the catalytic subunit of the exosome. In humans, there are three paralogues of this enzyme: DIS3, DIS3L, and DIS3L2. In this work, we identified a novel Schizosaccharomyces pombe exonuclease belonging to the conserved family of human DIS3L2 and plant SOV. Dis3L2 does not interact with the exosome components and localizes in the cytoplasm and in cytoplasmic foci, which are docked to P-bodies. Deletion of dis3l2(+) is synthetically lethal with xrn1Δ, while deletion of dis3l2(+) in an lsm1Δ background results in the accumulation of transcripts and slower mRNA degradation rates. Accumulated transcripts show enhanced uridylation and in vitro Dis3L2 displays a preference for uridylated substrates. Altogether, our results suggest that in S. pombe, and possibly in most other eukaryotes, Dis3L2 is an important factor in mRNA degradation. Therefore, this novel 3'-5' RNA decay pathway represents an alternative to degradation by Xrn1 and the exosome. 23214415 Design of mixed PEO/PAA brushes with switchable properties toward protein adsorption. Adsorption of proteins at interfaces is an ubiquitous phenomenon of prime importance. Layers of poly(ethylene oxide) (PEO) are widely used to repel proteins. Conversely, proteins were shown to adsorb deeply into brushes of poly(acrylic acid) (PAA), and their subsequent partial release could be triggered by a change of pH and/or ionic strength (I). Mixed brushes of these polymers are thus promising candidates to tune protein adsorption onto new smart surfaces. In this work, the synthesis of such mixed brushes was performed based on a "grafting to" approach, the two polymers being either grafted sequentially or simultaneously. Detailed characterization of the obtained brushes using static water contact angle measurements, X-ray photoelectron spectroscopy, electrochemical impedance spectroscopy, and polarization-modulation reflection-absorption infrared spectroscopy is presented. While sequential grafting of the two polymers for different reactions times did not give rise to a broad range of composition of mixed brushes, simultaneous grafting of the polymers from solutions with different compositions allows for the synthesis of a range of mixed brushes (mass fraction of PEO in the mixed brushes from 0.35 to 0.65). A key example is then chosen to illustrate the switchable behavior of a selected mixed PEO/PAA brush toward albumin adsorption. The adsorption behavior was monitored with a quartz crystal microbalance. The mixed brush could adsorb high amounts of albumin, but 86% of the adsorbed protein could then be desorbed upon pH and I change. The obtained properties are thus a combination of the ones of PEO and PAA, and a highly switchable behavior is observed toward protein adsorption. 23380477 Autophagy takes place in mutated p53 neuroblastoma cells in response to hypoxia mimetic CoCl(2). Solid tumors like neuroblastoma exhibit hypoxic areas, which can lead both to cell death or aggressiveness increase. Hypoxia is a known stress able to induce stabilization of p53, implicated in cell fate regulation. Recently, p53 appeared to be involved in autophagy in an opposite manner, depending on its location: when nuclear, it enhanced transcription of pro-autophagic genes whereas when cytoplasmic, it inhibited the autophagic process. Today, we used cobalt chloride, a hypoxia mimetic that inhibits proteasomal HIF-1 degradation and generates reactive oxygen species (ROS). We focused on CoCl2-induced cell death in a DNA-binding mutated p53 neuroblastoma cell line (SKNBE(2c)). An autophagic signaling was evidenced by an increase of Beclin-1, ATG 5-12, and LC3-II expression whereas the p53(mut) presence decreased with CoCl2 time exposure. Activation of the pathway seemed to protect cells from ROS production and, at least in part, from death. The autophagic inhibitors activated the apoptotic signaling and the death was enhanced. To delineate the eventual implication of the p53(mut) in the autophagic process in response to hypoxia, we monitored signaling in p53(WT)SHSY5Y cells, after either shRNA-p53 down-regulation or transcriptional activity inhibition by pifithrin alpha. We did not detect autophagy neither with p53(wt) nor when p53 was lacking whereas such a response was effective with a mutated or inactivated p53. To conclude, mutated p53 in neuroblastoma cells could be linked with the switch between apoptotic response and cell death by autophagy in response to hypoxic mimetic stress. 23488987 Enzymatic Conversion of 6-Nitroquinoline to the Fluorophore 6-Aminoquinoline Selectively under Hypoxic Conditions. There is substantial interest in small molecules that can be used to detect or kill the hypoxic (low oxygen) cells found in solid tumors. Nitroaryl moieties are useful components in the design of hypoxia-selective imaging agents and prodrugs because one-electron reductases can convert the nitroaryl group to nitroso, hydroxylamino, and amino metabolites selectively under low oxygen conditions. Here, we describe the in vitro, cell free metabolism of a pro-fluorescent substrate, 6-nitroquinoline (1) under both aerobic and hypoxic conditions. Both LC-MS and fluorescence spectroscopic analyses provided evidence that the one-electron reducing enzyme system, xanthine/xanthine oxidase, converted the nonfluorescent parent compound 1 to the known fluorophore 6-aminoquinoline (2) selectively under hypoxic conditions. The presumed intermediate in this reduction process, 6-hydroxylaminoquinoline (6), is fluorescent and can be efficiently converted by xanthine/xanthine oxidase to 2 only under hypoxic conditions. This finding provides evidence for multiple oxygen-sensitive steps in the enzymatic conversion of nitroaryl compounds to the corresponding amino derivatives. In a side reaction that is separate from the bioreductive metabolism of 1, xanthine oxidase converted 1 to 6-nitroquinolin-2(1H)-one (5). These studies may enable the use of 1 as a fluorescent substrate for the detection and profiling of one-electron reductases in cell culture or biopsy samples. In addition, the compound may find use as a fluorogenic probe for the detection of hypoxia in tumor models. The occurrence of side products such as 5 in the enzymatic bioreduction of 1 underscores the importance of metabolite identification in the characterization of hypoxia-selective probes and drugs that employ nitroaryl units as oxygen sensors. 23394318 Antidepressant abietane diterpenoids from Chinese eaglewood. Ten new abietane diterpenoids, aquilarabietic acids A-J (1-10), and a new podocarpane diterpenoid, aquilarabietic acid K (11), were isolated from the petroleum ether and ethanol extracts of Chinese eaglewood. Among them, 3, 9, and 10 are artifacts. Their structures were established on the basis of data from extensive spectroscopic and X-ray diffraction analyses. Bioassay results indicated that 1 at 10 μM demonstrated remarkable antidepressant activity in vitro by inhibiting norepinephrine reuptake in rat brain synaptosomes by 81.4% and with an IC(50) value of 9.1 × 10(-7) M. 23055539 Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. Angiotensin IV (AngIV: VYIHPF)-related peptides have long been recognized as procognitive agents with potential as antidementia therapeutics. Their development as useful therapeutics, however, has been limited by physiochemical properties that make them susceptible to metabolic degradation and impermeable to gut and blood-brain barriers. A previous study demonstrated that the core structural information required to impart the procognitive activity of the AngIV analog, norleucine(1)-angiotensin IV, resides in its three N-terminal amino acids, Nle-Tyr-Ile. The goal of this project was to chemically modify this tripeptide in such a way to enhance its metabolic stability and barrier permeability to produce a drug candidate with potential clinical utility. Initial results demonstrated that several N- and C-terminal modifications lead to dramatically improved stability while maintaining the capability to reverse scopolamine-induced deficits in Morris water maze performance and augment hippocampal synaptogenesis. Subsequent chemical modifications, which were designed to increase hydrophobicity and decrease hydrogen bonding, yielded an orally active, blood-barrier permeant, metabolically stabilized analog, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide (dihexa), that exhibits excellent antidementia activity in the scopolamine and aged rat models and marked synaptogenic activity. These data suggest that dihexa may have therapeutic potential as a treatment of disorders, such as Alzheimer's disease, where augmented synaptic connectivity may be beneficial. 23265498 Development and validation of a real-time PCR method for the simultaneous detection of black mustard (Brassica nigra) and brown mustard (Brassica juncea) in food. The paper presents a real-time PCR method allowing the simultaneous detection of traces of black mustard (Brassica nigra) and brown mustard (Brassica juncea) in food. The primers and the probe target the B. nigra partial RT gene for reverse transcriptase from gypsy-like retroelement 13G42-26. The real-time PCR method does not show any cross-reactivity with other Brassicaceae species with the exception of white mustard. Low cross-reactivities with cinnamon, cumin, fenugreek, ginger, rye and turmeric can be ignored because in common mustard containing foodstuffs these biological species are present in very low amounts. By analysing serially diluted DNA extracts from black and brown mustard, the DNA of both mustard species could be detected down to 0.1 pg. With 10 ng DNA per PCR tube the real-time PCR method allows the detection of 5 ppm black and brown mustard in brewed sausages. 23325046 Stable Isolation of Phycocyanin from Spirulina platensis Associated with High-Pressure Extraction Process. A method for stably purifying a functional dye, phycocyanin from Spirulina platensis was developed by a hexane extraction process combined with high pressure. This was necessary because this dye is known to be very unstable during normal extraction processes. The purification yield of this method was estimated as 10.2%, whose value is 3%-5% higher than is the case from another conventional separation method using phosphate buffer. The isolated phycocyanin from this process also showed the highest purity of 0.909 based on absorbance of 2.104 at 280 nm and 1.912 at 620 nm. Two subunits of phycocyanin namely α-phycocyanin (18.4 kDa) and β-phycocyanin (21.3 kDa) were found to remain from the original mixtures after being extracted, based on SDS-PAGE analysis, clearly demonstrating that this process can stably extract phycocyanin and is not affected by extraction solvent, temperature, etc. The stability of the extracted phycocyanin was also confirmed by comparing its DPPH (α,α-diphenyl-β-picrylhydrazyl) scavenging activity, showing 83% removal of oxygen free radicals. This activity was about 15% higher than that of commercially available standard phycocyanin, which implies that the combined extraction method can yield relatively intact chromoprotein through absence of degradation. The results were achieved because the low temperature and high pressure extraction effectively disrupted the cell membrane of Spirulina platensis and degraded less the polypeptide subunits of phycocyanin (which is a temperature/pH-sensitive chromoprotein) as well as increasing the extraction yield. 23461617 Mechanisms Underlying the Varied Mammary Carcinogenicity of the Environmental Pollutant 6-Nitrochrysene and Its Metabolites (-)-[R,R]- and (+)-[S,S]-1,2-Dihydroxy-1,2-dihydro-6-nitrochrysene in the Rat. The mechanisms that can account for the remarkable mammary carcinogenicity of the environmental pollutant 6-nitrochrysene (6-NC) in the rat remain elusive. In our previous studies, we identified several 6-NC-derived DNA adducts in the rat mammary gland; one major adduct was derived from (±)-trans-1,2-dihydroxy-1,2-dihydro-6-nitrochrysene (1,2-DHD-6-NC). In the present study, we resolved the racemic (±)-1,2-DHD-6-NC into (-)-[R,R]- and (+)-[S,S]-1,2-DHD-6-NC and compared their in vivo mutagenicity and carcinogenicity in the mammary glands of female transgenic (BigBlue F344 × Sprague-Dawley)F1 rats harboring lacI/cII and Sprague-Dawley rats, respectively. Both [R,R]- and [S,S]-isomers exerted similar mutagenicity and carcinogenicity but were less potent than 6-NC. Additional in vivo and in vitro studies were then performed to explore possible mechanisms that can explain the higher potency of 6-NC than 1,2-DHD-6-NC. Using ELISA, we found that neither 6-NC nor 1,2-DHD-6-NC increased the levels of several inflammatory cytokines in plasma obtained from rats 24 h after treatment. In MCF-7 cells, as determined by immunoblotting, the effects of 6-NC and 1,2-DHD-6-NC on protein expression (p53, Akt, p38, JNK, c-myc, bcl-2, PCNA, and ERβ) were comparable; however, the expressions of AhR and ERα proteins were decreased by 6-NC but not 1,2-DHD-6-NC. The expression of both receptors was decreased in mammary tissues of rats treated with 6-NC. Our findings suggest that the differential effects of 6-NC and 1,2-DHD-6-NC on AhR and ERα could potentially account for the higher carcinogenicity of 6-NC in the rat mammary gland. 23256474 Fit-for-purpose bioanalytical cross-validation for LC-MS/MS assays in clinical studies. The paradigm shift of globalized research and conducting clinical studies at different geographic locations worldwide to access broader patient populations has resulted in increased need of correlating bioanalytical results generated in multiple laboratories, often across national borders. Cross-validations of bioanalytical methods are often implemented to assure the equivalency of the bioanalytical results is demonstrated. Regulatory agencies, such as the US FDA and European Medicines Agency, have included the requirement of cross-validations in their respective bioanalytical validation guidance and guidelines. While those documents provide high-level expectations, the detailed implementation is at the discretion of each individual organization. At Bristol-Myers Squibb, we practice a fit-for-purpose approach for conducting cross-validations for small-molecule bioanalytical methods using LC-MS/MS. A step-by-step proposal on the overall strategy, procedures and technical details for conducting a successful cross-validation is presented herein. A case study utilizing the proposed cross-validation approach to rule out method variability as the potential cause for high variance observed in PK studies is also presented. 22981668 Orphan drugs: the regulatory environment. The definition of a rare disease is not universal and depends on the legislation and policies adopted by each region or country. The main objective of this article is to describe and discuss the legal framework and the regulatory environment of orphan drugs worldwide. Some reflections and discussions on the need for specific orphan drug legislation or policies are described at length. Furthermore, some aspects of the history of each region in respect of the orphan drug legislation evolution are outlined. This article describes and compares the orphan drug legislation or policies of the following countries or regions: United Sates of America (US), European Union (EU), Japan, Australia, Singapore, Taiwan and Canada. The incentives described in the orphan drug legislations or policies, the criteria for designation of orphan status and the authorisation process of an orphan drug are also described and compared. The legislations and policies are to some extent similar but not the same. It is important to understand the main differences among all available legislative systems to improve the international collaboration in the field of orphan drugs and rare diseases. 23640872 The Distorted Tropane of Scopoline. The structural isomerization of scopine into scopoline (oscine) has been observed in a supersonic jet expansion using microwave spectroscopy. The rotational spectrum evidences a single structure in the gas phase, providing a first description of the (three-ring) structurally distorted tropane in scopoline. The absence of rotational signatures of any scopine conformation suggests a practically quantitative isomerization at the vaporization temperatures of the experiment (ca. 90 °C). The determined rotational parameters of scopoline reveal the structural consequences of the intramolecular cyclation of scopine, which breaks the original epoxy group and creates a new ether bridge and a 7β-hydroxytropane configuration. The hydroxy group further stabilizes the molecule by an OH⋅⋅⋅N intramolecular hydrogen bond, which, in turn, forces the N-methyl group to the less stable axial form. Supporting ab initio (MP2) and DFT (B3LYP, M06-2X) calculations are included. 23394309 Parameterization of Reactive Force Field: Dynamics of the [Nb6O19Hx]((8-x)-) Lindqvist Polyoxoanion in Bulk Water. We present results on parameterization of reactive force field [van Duin, A. C. T.; Dasgupta, S.; Lorant, F.; Goddard, W. A. ReaxFF: A Reactive Force Field for Hydrocarbons. J. Phys. Chem. A2001, 105, 9396-9409] for investigating the properties of the [Nb6O19Hx]((8-x)-) Lindqvist polyoxoanion, x = 0-8, in water. Force-field parameters were fitted to an extensive data set consisting of structures and energetics obtained at the Perdew-Burke-Ernzerhof density functional level of theory. These parameters can reasonably describe pure water structure as well as water with an excess of H(+) and OH(-) ions. Molecular dynamics simulations were performed on [Nb6O19Hx]((8-x)-), x = 0-8, submerged in bulk water at 298 K. Analysis of the MD trajectories showed facile H atom transfer between the protonated polyoxoanion core and bulk water. The number of oxygen sites labeled with an H atom was found to vary depending on the pH of the solution. Detailed analysis shows that the total number of protons at bridging (terminal), η-O (μ2-O), sites ranges from 3(1) at pH 7, to 2(0) at pH 11, to 1(0) at pH 15. These findings closely reflect available experimental measurements. 23597793 Discovery, synthesis and in combo studies of a tetrazole analogue of clofibric acid as a potent hypoglycemic agent. A tetrazole isosteric analogue of clofibric acid (1) was prepared using a short synthetic route and was characterized by elemental analysis, NMR ((1)H, (13)C) spectroscopy, and single-crystal X-ray diffraction. The in vitro inhibitory activity of 1 against 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) was evaluated, showing a moderate inhibitory enzyme activity (51.17% of inhibition at 10μM), being more active than clofibrate and clofibric acid. The antidiabetic activity of compound 1 was determined at 50mg/Kg single dose using a non insulin dependent diabetes mellitus rat model. The results indicated a significant decrease of plasma glucose levels, during the 7h post-administration. Additionally, we performed a molecular docking of 1 into the ligand binding pocket of one subunit of human 11β-HSD1. In this model, compound 1 binds into the catalytic site of 11β-HSD1 in two different orientations. Both of them, show important short contacts with the catalytic residues Ser 170, Tyr 183, Asp 259 and also with the nicotinamide ring of NADP(+). 23281937 Structural studies of mixed glass former 0.35Na2O + 0.65[xB2O3 + (1 - x)P2O5] glasses by Raman and 11B and 31P magic angle spinning nuclear magnetic resonance spectroscopies. The mixed glass former (MGF) effect (MGFE) is defined as a nonlinear and nonadditive change in the ionic conductivity with changing glass former composition at constant modifier composition. In this study, sodium borophosphate 0.35Na(2)O + 0.65[xB(2)O(3) + (1 - x)P(2)O(5)], 0 ≤ x ≤ 1, glasses which have been shown to exhibit a positive MGFE have been prepared and examined using Raman and (11)B and (31)P magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopies. Through examination of the short-range order (SRO) structures found in the ternary glasses, it was determined that the minority glass former, B for 0.1 ≤ x ≤ 0.7 and P for 0.7 ≤ x ≤ 0.9, is "overmodified" and contains more Na(+) ions than would be expected from simple linear mixing of the binary sodium borate, x = 1, and sodium phosphate, x = 0, glasses, respectively. Changes in the intermediate range order (IRO) structures were suggested by changes in the NMR spectral chemical shifts and Raman spectra wavenumber shifts over the full composition range x in the Raman and MAS NMR spectra. The changes observed in the chemical shifts of (31)P MAS NMR spectra with x are found to be too large to be caused solely by changing sodium modification of the phosphate SRO structural groups, and this indicates that internetwork bonding between phosphorus and boron through bridging oxygens (BOs), P-O-B, must be a major contributor to the IRO structure of these glasses. While not fully developed, a first-order thermodynamic analysis based upon the Gibbs free energies of formation of the various SRO structural units in this system has been developed and can be used to account for the preferential formation of tetrahedral boron groups, B(4), by the reaction of B(3) with P(2) groups to form B(4) and P(3) groups, respectively, where the superscript denotes the number of BOs on these units, in these glasses. This preference for B(4) units appears to be a predominate cause of the changing modifier to glass former ratio with composition x in these ternary MGF glasses and appears to be associated with the large negative value of the Gibbs free energy of formation of this group. 23286240 Antiproliferative and antiplasmodial dimeric phloroglucinols from Mallotus oppositifolius from the Madagascar Dry Forest (1). Bioassay-guided fractionation of an ethanol extract of the leaves and inflorescence of Mallotus oppositifolius collected in Madagascar led to the isolation of the two new bioactive dimeric phloroglucinols mallotojaponins B (1) and C (2), together with the known mallotophenone (3). The structures of the new compounds were determined on the basis of spectroscopic evidence, including their 1D- and 2D-NMR spectra, mass spectrometry, and an X-ray crystal structure. Compounds 1 and 2 showed potent antimalarial activity against chloroquine-resistant Plasmodium falciparum, with IC50 values of 0.75 ± 0.30 and 0.14 ± 0.04 μM, while 3 was inactive in this assay. Compounds 1-3 also displayed strong antiproliferative activity against the A2780 human ovarian cancer cell line (IC50 1.10 ± 0.05, 1.3 ± 0.1 and 6.3 ± 0.4 μM, respectively). 23243660 Gas-phase dissociative electron attachment to flavonoids and possible similarities to their metabolic pathways. The gas-phase empty-level structures and formation of anion states via resonance attachment of low-energy electrons to the flavonoids naringenin (III), quercetin (IV) and myricetin (V) and the smaller reference molecules chromone (I) and flavone (II) are investigated experimentally for the first time. Dissociative electron attachment spectroscopy (DEAS) is used to measure the fragment anion currents generated through dissociative decay channels of the molecular anions of compounds I–V, detected with a mass filter as a function of the incident electron energy in the 0–14 eV energy range. Due to the insufficient volatility of flavonoids III–V, the energies of vertical electron attachment associated with temporary occupation of the lower-lying virtual orbitals are measured with electron transmission spectroscopy (ETS) only in the smaller reference molecules I and II. The experimental findings are interpreted with the support of appropriate density functional theory calculations with the B3LYP functional. The experimental vertical electron attachment energies measured in the ET spectra of I and II are compared with the orbital energies of the neutral molecules scaled using an empirically calibrated linear equation. The vertical and adiabatic electron affinities are evaluated at the B3LYP/6-31+G(d) level as the anion/neutral total energy difference. The latter theoretical method is also used for evaluation of the most stable conformers of the neutral molecules, O–H bond dissociation energies and thermodynamic energy thresholds for production of the anion fragments observed in the DEA spectra. A possible role played by loss of an H(2) molecule from the parent molecular anion in vivo in the mitochondrial respiratory chain is briefly discussed. 23246701 The protective role of curcumin on perfluorooctane sulfonate-induced genotoxicity: single cell gel electrophoresis and micronucleus test. Perfluorooctane sulfonate (PFOS) is a man-made fluorosurfactant and global pollutant. PFOS a persistent and bioaccumulative compound, is widely distributed in humans and wildlife. Therefore, it was added to Annex B of the Stockholm Convention on Persistent Organic Pollutants in May 2009. Curcumin is a natural polyphenolic compound abundant in the rhizome of the perennial herb turmeric. It is commonly used as a dietary spice and coloring agent in cooking and anecdotally as an herb in traditional Asian medicine. In this study, male rats were treated with three different PFOS doses (0.6, 1.25 and 2.5 mg/kg) and one dose of curcumin, from Curcuma longa (80 mg/kg) and combined three doses of PFOS with 80 mg/kg dose of curcumin by gavage for 30 days at 48 h intervals. Here, we evaluated the DNA damage via single cell gel electrophoresis or comet assay and micronucleus test in bone marrow in vivo. PFOS induced micronucleus frequency and decreased the ratio of polychromatic erythrocyte to normochromatic erythrocyte in bone marrow. Using the alkaline comet assay, we showed that all doses of the PFOS strongly induced DNA damage in rat bone marrow and curcumin prevented the formation of DNA damage induced by PFOS. 23356985 Inactivation of Lrp5 in osteocytes reduces young's modulus and responsiveness to the mechanical loading. Low-density-lipoprotein receptor-related protein 5 (Lrp5) is a co-receptor in Wnt signaling, which plays a critical role in development and maintenance of bone. Osteoporosis-pseudoglioma syndrome, for instance, arises from loss-of-function mutations in Lrp5, and global deletion of Lrp5 in mice results in significantly lower bone mineral density. Since osteocytes are proposed to act as a mechanosensor in the bone, we addressed a question whether a conditional loss-of-function mutation of Lrp5 selective to osteocytes (Dmp1-Cre;Lrp5(f/f)) would alter responses to ulna loading. Loading was applied to the right ulna for 3 min (360 cycles at 2Hz) at a peak force of 2.65 N for 3 consecutive days, and the contralateral ulna was used as a non-loaded control. Young's modulus was determined using a midshaft section of the femur. The results showed that compared to age-matched littermate controls, mice lacking Lrp5 in osteocytes exhibited smaller skeletal size with reduced bone mineral density and content. Compared to controls, Lrp5 deletion in osteocytes also led to a 4.6-fold reduction in Young's modulus. In response to ulna loading, mineralizing surface, mineral apposition rate, and bone formation rate were diminished in mice lacking Lrp5 in osteocytes by 52%, 85%, and 69%, respectively. Collectively, the results support the notion that the loss-of-function mutation of Lrp5 in osteocytes causes suppression of mechanoresponsiveness and reduces bone mass and Young's modulus. In summary, Lrp5-mediated Wnt signaling significantly contributes to maintenance of mechanical properties and bone mass. 23409719 Photoactive analogs of farnesyl diphosphate and related isoprenoids: design and applications in studies of medicinally important isoprenoid- utilizing enzymes. Farnesyl diphosphate (FPP) is an important metabolic intermediate in the biosynthesis of a variety of molecules including sesquiterpenes and the side chains of a number of cofactors. FPP is also the source of isoprenoid side chains found attached to proteins. Enzymes that employ FPP as a substrate are of interest because they are involved in the semisynthesis of drugs as well as targets for drug design. Photoactive analogs of FPP have been useful for identifying enzymes that use this molecule as a substrate. A variety of photocrosslinking groups have been employed to prepare FPP analogs for use in such experiments including aryl azides, diazotrifluoropropionates and benzophenones. In this review, the design of these probes is described along with an examination of how they have been used in crosslinking experiments. 23453831 Induction of apoptosis in human pancreatic MiaPaCa-2 cells through the loss of mitochondrial membrane potential (ΔΨm) by Gentiana kurroo root extract. The objective of the current study was to evaluate the methanolic root extract of Gentiana kurroo for antioxidant and antiproliferative activities as well as to study the effect of the extract on the induction of apoptosis in human pancreatic cancer cell line (Miapaca-2). The extract exerted significant antioxidant activity as verified by DPPH, hydroxyl radical, lipid peroxidation and protective oxidative DNA damage assays. The results were comparable to standard antioxidants like α-tocopherol, catechin and BHT used in such experiments. Antioxidant potential of G. kurroo may be attributed to the presence of high phenolic and flavonoid content (73±1.02 and 46±2.05mg/g extract respectively). The anti-proliferative property of Gentiana kurroo root extract was determined by sulphorhodamine B (SRB) assay against Human colon cancer cell line (HCT-116), Lung carcinoma cell line (A-549), Pancreatic cancer cell line (Miapaca-2), Lung cancer cell line (HOP-62) and acute monocytic leukaemia cell line (THP-1). G. kurroo root extract inhibited cancer cell growth depending upon the cell line used and in a dose dependent manner. The extract induced cell cycle arrest in Miapaca-2 cells at G0/G1 phase of the cell cycle. The population of apoptotic cells increased from 11.4% in case of control to 49.6% at 100μg/ml of G. kurroo root extract. The extract also induced a remarkable decrease in mitochondrial membrane potential (ΔΨm) leading to apoptosis of cancer cells used. The main chemical constituents identified by the liquid chromatography-tandem mass spectrometry (LC-ESI-MSMS) were found to be iridoid glucosides (iridoids and secoiridoids), xanthones and flavonoids. Iridoid glucosides are the bitter principles of Gentiana species. Loganic acid, Sweroside, Swertiamarin, Gentiopicroside, Gentisin, Isogentisin, Gentioside, Norswertianolin, Swertianolin, 4″-O-β-d-glucosyl-6'-O-(4-O-β-d-glucosylcaffeoyl)-linearoside and Swertisin were the principal compounds present in the methanol root extract of G. kurroo. 23427063 Nanoscale poling of polymer films. Spots of second harmonic generation (SHG) are produced from nanopatterned sub-micrometer areas of nonlinear polymer media. Information is written by using a biased-AFM tip, a highly nonlinear polymer (poly(methyl metha-acrylate)-co-Disperse Red 1), and a novel "floating-tip nanolithography" (FTN) technique. Dipoles are oriented and aligned at the nanoscale under the biased-AFM tip, resulting in SHG production. The information is storable over weeks. 23641017 Associations of TSH within the reference range with future blood pressure and lipid concentrations. 11-year follow-up of the HUNT Study. Objective In cross-sectional studies, TSH levels within the reference range have been positively associated with blood pressure and adverse serum lipid levels. In a prospective study, we aimed to find out if differences in TSH within the reference range are associated with future levels of blood pressure and lipids.Design Prospective population-based study.Methods Among 9709 women and 4644 men without previous thyroid disease who had a baseline TSH of 0.45-4.5 mU/l, we studied the associations of baseline TSH with blood pressure and lipid levels at follow-up 11 years later.Results Higher TSH at baseline was associated with higher systolic (P=0.002 in women) and diastolic (P=0.03 in women) blood pressure, non-HDL cholesterol (P=0.01 in men), and triglycerides (P=0.008 in men), and lower HDL cholesterol (P<0.001 in women and men) at follow-up, but the associations were very modest and not consistent between sexes. Among people who remained free of thyroid disease, changes in TSH during follow-up were associated with concomitant changes in systolic and diastolic blood pressure, non-HDL cholesterol, and triglyceride levels (all P<0.001), with similar results for women and men. Thus, blood pressure and lipid levels increased among people with increase in TSH, and decreased among people with a decrease in TSH, compared to people with no change in TSH.Conclusions High TSH levels within the reference range may be associated with modestly higher future levels of blood pressure and adverse serum lipids. TSH may co-vary with blood pressure and lipid levels among people with apparently normal thyroid function. 22468693 Phytochemical analysis of Gymnema sylvestre and evaluation of its antimicrobial activity. Gymnema sylvestre (CS 149), known to be a rich source of saponins and other valuable phytochemicals, has been analysed for antimicrobial activity. The chloroform extracts of aerial and root parts of G. sylvestre exhibited higher antimicrobial activity as compared to diethyl ether and acetone. The root extracts of chloroform have shown competitive minimum inhibitory concentration and minimum bactericidal concentration values in the range of 0.04-1.28 mg mL(-1) and 0.08-2.56 mg/mL, respectively, towards the pathogens. The GC-MS analysis of chloroform extracts has shown the presence of compounds like eicosane, oleic acid, stigmasterol and vitamin E. 23327686 Long-loop G-quadruplexes are misfolded population minorities with fast transition kinetics in human telomeric sequences. Single-stranded guanine (G)-rich sequences at the 3' end of human telomeres provide ample opportunities for physiologically relevant structures, such as G-quadruplexes, to form and interconvert. Population equilibrium in this long sequence is expected to be intricate and beyond the resolution of ensemble-average techniques, such as circular dichroism, NMR, or X-ray crystallography. By combining a force-jump method at the single-molecular level and a statistical population deconvolution at the sub-nanometer resolution, we reveal a complex population network with unprecedented transition dynamics in human telomeric sequences that contain four to eight TTAGGG repeats. Our kinetic data firmly establish that G-triplexes are intermediates to G-quadruplexes while long-loop G-quadruplexes are misfolded population minorities whose formation and disassembly are faster than G-triplexes or regular G-quadruplexes. The existence of misfolded DNA supports the emerging view that structural and kinetic complexities of DNA can rival those of RNA or proteins. While G-quadruplexes are the most prevalent species in all the sequences studied, the abundance of a misfolded G-quadruplex in a particular telomeric sequence decreases with an increase in the loop length or the number of long-loops in the structure. These population patterns support the prediction that in the full-length 3' overhang of human telomeres, G-quadruplexes with shortest TTA loops would be the most dominant species, which justifies the modeling role of regular G-quadruplexes in the investigation of telomeric structures. 23455513 Glycosylation of conotoxins. Conotoxins are small peptides present in the venom of cone snails. The snail uses this venom to paralyze and capture prey. The constituent conopeptides display a high level of chemical diversity and are of particular interest for scientists as tools employed in neurological studies and for drug development, because they target with exquisite specificity membrane receptors, transporters, and various ion channels in the nervous system. However, these peptides are known to contain a high frequency and variability of post-translational modifications-including sometimes O-glycosylation-which are of importance for biological activity. The potential application of specific conotoxins as neuropharmalogical agents and chemical probes requires a full characterization of the relevant peptides, including the structure of the carbohydrate part. In this review, the currently existing knowledge of O-glycosylation of conotoxins is described. 23234537 Hybrid carbon nanotube networks as efficient hole extraction layers for organic photovoltaics. Transparent, highly percolated networks of regioregular poly(3-hexylthiophene) (rr-P3HT)-wrapped semiconducting single-walled carbon nanotubes (s-SWNTs) are deposited, and the charge transfer processes of these nanohybrids are studied using spectroscopic and electrical measurements. The data disclose hole doping of s-SWNTs by the polymer, challenging the prevalent electron-doping hypothesis. Through controlled fabrication, high- to low-density nanohybrid networks are achieved, with low-density hybrid carbon nanotube networks tested as hole transport layers (HTLs) for bulk heterojunction (BHJ) organic photovoltaics (OPV). OPVs incorporating these rr-P3HT/s-SWNT networks as the HTL demonstrate the best large area (70 mm(2)) carbon nanotube incorporated organic solar cells to date with a power conversion efficiency of 7.6%. This signifies the strong capability of nanohybrids as an efficient hole extraction layer, and we believe that dense nanohybrid networks have the potential to replace expensive and material scarce inorganic transparent electrodes in large area electronics toward the realization of low-cost flexible electronics. 23313621 Vasorelaxant effects of 1-nitro-2-phenylethane, the main constituent of the essential oil of Aniba canelilla, in superior mesenteric arteries from spontaneously hypertensive rats. The present study investigated the mechanisms underlying the vasorelaxant effects of the essential oil of Aniba canelilla (EOAC) and its main constituent 1-nitro-2-phenylethane (NP) in isolated superior mesenteric artery from spontaneously hypertensive rats (SHRs). At 0.1-1000 μg/mL, EOAC and NP relaxed SMA preparations pre-contracted with 75 mMKCl with IC(50) (geometric mean [95% confidence interval]) values of 294.19 [158.20-94.64] and 501.27 [378.60-624.00] μg/mL, respectively); or with phenylephrine (PHE) (IC(50)s=11.07 [6.40-15.68] and 7.91 [4.08-11.74) μg/mL, respectively). All these effects were reversible and remained unaltered by vascular endothelium removal. In preparations maintained under Ca(2+)-free conditions, EOAC and NP (both at 600 μg/mL) reduced the PHE-, but not the caffeine-induced contraction. In Ca(2+)-free and high K(+) (75 mM) medium, the contractions produced by CaCl(2) or BaCl(2) were reduced or even abolished by EOAC and NP at 100 and 600 μg/mL, respectively. EOAC and NP (both at 10-1000 μg/mL) also relaxed the contraction evoked by phorbol dibutyrate (IC(50)=52.66 [10.82-94.64] and 39.13 [31.55-46.72] μg/mL, respectively). It is concluded that NP has a myogenic endothelium-independent vasorelaxant effects and appears to be the active principle of the EOAC. Vasorelaxant effect induced by both EOAC and NP is preferential to receptor-activated pathways and it appears to occur intracellularly more than a superficial action restricted to the membrane environment such as a simple blocking activity on a given receptor or ion channel. 23250541 Comparison of tissue metal concentrations in Zucker lean, Zucker obese, and Zucker diabetic fatty rats and the effects of chromium supplementation on tissue metal concentrations. Diabetes results in several metabolic changes, including alterations in the transport, distribution, excretion, and accumulation of metals. While changes have been examined in several rat models of insulin resistance and diabetes, the metal ion concentrations in the tissues of Zucker lean, Zucker obese (an insulin resistance and early stage diabetes model), and Zucker diabetic fatty (ZDF, a type 2 diabetes model) have not previously been examined in detail. The concentration of Cu, Zn, Fe, Mg, and Ca were examined in the liver, kidney, heart and spleen, and Cr concentration in the liver and kidney of these rats were examined. Zucker obese rats have a reduction in the concentration of Cu, Zn, Fe, Mg in the liver compared to ZDF and/or lean Zucker rats, presumably as a result of the increased fat content of the liver of the obese rats. ZDF rats have increased concentrations of kidney Cu compared to the lean rats, while kidney Ca concentrations are increased in the Zucker obese rats. Spleen Fe concentrations are decreased in Zucker obese rats compared to the lean rats. No effects on metal concentrations in the heart were observed between the lean, obese, and ZDF rats, and no effects on Cr concentrations were identified. Cr(III) complexes have previously been shown to have beneficial effects on the signs of insulin resistance in Zucker obese and ZDF rats. The effects of daily gavage administration of chromium picolinate ([Cr(pic)(3)]) (1 mg Cr/kg body mass), CrCl(3) (1 mg Cr/kg body mass), and Cr3 ([Cr(3)O(propionate)(6)(H(2)O)(3)](+)) (33 μg and 1 mg Cr/kg body mass) on metal concentrations in these tissues were examined. Treatment with CrCl(3) and Cr3, but not [Cr(pic)(3)], at 1 mg Cr/kg resulted in a statistically significant accumulation of Cr in the kidney of lean and obese but not ZDF rats but resulted in lowering the elevated levels of kidney Cu in ZDF rats, suggesting a beneficial effect on this symptom of type 2 diabetes. 23330613 Polyamine production is downstream and upstream of oncogenic PI3K signalling and contributes to tumour cell growth. PI3K (phosphoinositide 3-kinase) signalling pathways regulate a large array of cell biological functions in normal and cancer cells. In the present study we investigated the involvement of PI3K in modulating small molecule metabolism. A LC (liquid chromatography)-MS screen in colorectal cancer cell lines isogenic for oncogenic PIK3CA mutations revealed an association between PI3K activation and the levels of polyamine pathway metabolites, including 5-methylthioadenosine, putrescine and spermidine. Pharmacological inhibition confirmed that the PI3K pathway controls polyamine production. Despite inducing a decrease in PKB (protein kinase B)/Akt phosphorylation, spermidine promoted cell survival and opposed the anti-proliferative effects of PI3K inhibitors. Conversely, polyamine depletion by an ornithine decarboxylase inhibitor enhanced PKB/Akt phosphorylation, but suppressed cell survival. These results suggest that spermidine mediates cell proliferation and survival downstream of PI3K/Akt and indicate that these two biochemical pathways control each other's activities, highlighting a mechanism by which small molecule metabolism feeds back to regulate kinase signalling. Consistent with this feedback loop having a functional role in these cell models, pharmacological inhibitors of PI3K and ornithine decarboxylase potentiated each other in inhibiting tumour growth in a xenograft model. The results of the present study support the notion that the modulation of spermidine concentrations may be a previously unrecognized mechanism by which PI3K sustains chronic proliferation of cancer cells. 23353626 MRI-detectable pH nanosensors incorporated into hydrogels for in vivo sensing of transplanted-cell viability. Biocompatible nanomaterials and hydrogels have become an important tool for improving cell-based therapies by promoting cell survival and protecting cell transplants from immune rejection. Although their potential benefit has been widely evaluated, at present it is not possible to determine, in vivo, if and how long cells remain viable following their administration without the use of a reporter gene. Here, we report a pH-nanosensor-based magnetic resonance imaging (MRI) technique that can monitor cell death in vivo non-invasively. We demonstrate that specific MRI parameters that change on cell death of microencapsulated hepatocytes are associated with the measured bioluminescence imaging radiance. Moreover, the readout from this pH-sensitive nanosensor can be directly co-registered with high-resolution anatomical images. All of the components of these nanosensors are clinical grade and hence this approach should be a translatable and universal modification of hydrogels. 23279943 Potential prevention and treatment of maifanite for Alzheimer's disease based on behavior test, oxidative stress assay, and trace element analysis in hippocampus of Aβ(₂₅₋₃₅)-induced AD rats. This study aimed to assess whether maifanite can improve the learning and memory, and antioxidant abilities of Alzheimer's disease (AD) rats. The 70 rats were divided into seven groups: [A] normal control group, [B] AD model group, [C] sham group, [D] positive control group (donepezil), [E] low-dose maifanite group, [F] middle-dose maifanite group, [G] high-dose maifanite group. For [B], [D], [E], [F], and [G] groups, Aβ(25-35) ventricle injection was carried out, then respective medicine were administered once a day for 60 consecutive days. The step-down and step-through test were used to measure learning and memory ability. The hippocampus levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were assayed. The hippocampus contents of Al, Fe, Cu, Zn, Se, and Mn were analyzed by inductively coupled plasma-atomic emission spectrometer. Maifanite decreased the acquisition errors and the retention errors while prolonging the step-down latency, and decreased the number of electric shocks while prolonging the first latency of AD rats. Aβ(25-35) ventricle injection initiated the decrease of SOD and GSH-Px activities and the increase of MDA content, and triggered the rise of Al, Fe, and Cu levels and the decline of Mn, Zn, and Se levels. The SOD and GSH-Px activities were enhanced followed by reduced MDA level, and the levels of Mn, Zn, and Se increased accompanied by Al, Fe, and Cu decreased in the maifanite treat groups. Maifanite could improve the learning and memory, and the antioxidant abilities of AD rats. Maifanite had the potential prevention and treatment for AD. 23500061 Anti-apoptotic cardioprotective effects of SHP-1 gene silencing against ischemia-reperfusion injury: Use of deoxycholic acid-modified low molecular weight polyethyleneimine as a cardiac siRNA-carrier. The cardiomyocyte apoptosis plays a critical role in the development of myocardial injury after ischemia and reperfusion. Thus, alteration of the major apoptosis-regulatory factors during myocardial ischemia-reperfusion is expected to have favorable cardioprotective effects. Herein, we report ischemic-reperfused myocardial infarction (MI) repair with siRNA against Src homology region 2 domain-containing tyrosine phosphatase-1 (SHP-1), which is known as a key factor involved in regulating the progress of apoptosis in many cell types. A low molecular weight polyethyleneimine modified with deoxycholic acid (PEI1.8-DA)-based delivery strategy was suggested for the cardiac application of SHP-1 siRNA to overcome the poor gene delivery efficiency to myocardium due to the highly charged structures of the compact cardiac muscles. The PEI1.8-DA conjugates formed stable nanocomplexes with SHP-1 siRNA via electrostatic and hydrophobic interactions. The PEI1.8-DA/SHP-1 siRNA polyplexes effectively silenced SHP-1 gene expression in cardiomyocytes, leading to a significant inhibition of cardiomyocyte apoptosis under hypoxia. In comparison to conventional gene carriers, relatively large amounts of siRNA molecules remained after treatment with the PEI1.8-DA/SHP-1 siRNA polyplexes. Cardiac administration of the PEI1.8-DA/SHP-1 siRNA polyplexes resulted in substantial improvement in SHP-1 gene silencing, which can be explained by the enhancement of cardiac delivery efficiency of the PEI1.8-DA conjugates. In addition, in vivo treatment with the PEI1.8-DA/SHP-1 siRNA polyplexes induced a highly significant reduction in myocardial apoptosis and infarct size in rat MI models. These results demonstrate that the PEI1.8-DA/SHP-1 siRNA polyplex formulation is a useful system for efficient gene delivery into the compact myocardium that provides a fundamental advantage in treating ischemic-reperfused MI. 23466461 Occurrence of fumonisins in organic and conventional cereal-based products commercialized in France, Germany and Spain. A fast and effective method for quantitative determination of fumonisins B1 and B2 (FB1 and FB2) in different cereal-based products was developed. Fumonisins were extracted combining a solid liquid extraction (SLE) pre-treatment and immunoaffinity columns (IACs), which were applied for an effective clean-up. Consecutively, high pressure liquid chromatography (HPLC) coupled to hybrid triple quadrupole-linear ion trap mass spectrometer (QTrap®) was used for the separation, detection and quantification of targeted mycotoxins. The analytical method showed acceptable recoveries ranged from 89.7% to 99.1%, as well as a relative standard deviation (%, RSD) lower than 12%. A total of 1250 samples from France, Germany and Spain were analysed. The incidence of fumonisin B1 and B2 in organic samples were 11.4% and 11.3%, respectively. By contrast, the occurrence of conventional samples was 3.6% of FB1 and 3.5% of FB2. The highest values were obtained in Spanish samples of flour, as an example toasted corn, called gofio that was contaminated with 1201.7 and 1010.5μgkg(-1) of FB1 and FB2, respectively. 23583882 Prior oral exposure to environmental immunosuppressive chemicals methoxychlor, parathion, or piperonyl butoxide aggravates allergic airway inflammation in NC/Nga mice. BACKGROUND: Immunosuppressive environmental chemicals may increase the potency of allergens and thereby play a role in the development of respiratory tract allergies, such as allergic rhinitis and asthma. OBJECTIVES: We investigated the association between environmental immunosuppressive chemicals and the allergic airway inflammation development. METHODS: We used a mouse model of ovalbumin (OVA)-induced allergic airway inflammation. NC/Nga mice were exposed orally to pesticides parathion (an organophosphate compound) or methoxychlor (an organochlorine compound), or to an insecticide synergist piperonyl butoxide, prior to OVA intraperitoneal sensitization and inhalation challenge. We assessed serum IgE levels, B-cell counts, cytokine production, IgE production in hilar lymph nodes, eosinophil counts, chemokine levels in bronchoalveolar lavage fluid, and cytokine gene expression in the lung. RESULTS: Exposure to environmental immunosuppressive chemicals markedly increased serum IgE - IgE-positive B-cells, IgE and cytokines in lymph nodes - eosinophils and chemokines in BALF - IL-10a and IL-17 in the lung. CONCLUSIONS: Allergic airway inflammation can be aggravated by prior exposure to immunosuppressive environmental chemicals. 23427074 Dechlorane plus monoadducts in a lake ontario (Canada) food web and biotransformation by lake trout (Salvelinus namaycush) liver microsomes. Compounds related to the high-production-volume flame retardant Dechlorane Plus (DP) were measured in a Lake Ontario food web located downstream of a DP manufacturing plant. These compounds, 1,3- and 1,5-DP-monoadducts (DPMA), are positional isomers and are thought to arise from the incomplete reaction of DP or impurities in the DP starting material during its manufacture. The 1,3-DPMA isomer was measured (0.12-199 ng g(-1) lipid wt) in all trophic levels, whereas 1,5-DPMA was measured only sporadically in the food web and was not detectable in the apex predator, lake trout (Salvelinus namaycush). Concentrations of DPMA isomers when detected in Lake Ontario biota were greater than that of total DP for all trophic levels. The prevalence of 1,3-DPMA in the food web, and especially in lake trout, may be due to obstruction of the existing carbon double bond to enzyme attack, rendering it less readily metabolized. To examine this hypothesis, biotransformation kinetic experiments using in vitro lake trout liver microsomal exposures were performed. Zero-order depletion rate constants for 1,3- and 1,5-DPMA were 92.2 and 134.6 pmole h(-1) , respectively, with corresponding half-lives of 2.03 ± 0.14 h (1,3-DPMA) and 1.39 ± 0.09 h (1,5-DPMA). Furthermore, the 1,5-isomer was depleted to a greater extent than 1,3-DPMA. Specific biotransformation products were not identified. These data support the hypothesis that 1,5-DPMA is more readily metabolized than 1,3-DPMA by lake trout. The present study also shows that the concentrations of these isomers, which the authors speculate might be unintended impurities or byproducts in some technical DP formulations, exceed that of the intended product in biota. Environ Toxicol Chem 2013;32:1376-1381. © 2013 SETAC. 23142804 Longitudinal in vivo imaging of bone formation and resorption using fluorescence molecular tomography. Bone research often focuses on anatomical imaging of the bone microstructure, but in order to gain better understanding in how bone remodeling is modulated through interventions also bone formation and resorption processes should be investigated. With this in mind, the purpose of this study was to establish a longitudinal in vivo imaging approach of bone formation and resorption using fluorescence molecular tomography (FMT). In this study the reproducibility, accuracy and sensitivity of FMT for bone imaging were assessed by performing longitudinal measurements with FMT and comparing it to in vivo micro-computed tomography on a set of control mice, and mice in which load-adaptation was induced in the sixth caudal vertebra. The precision error for FMT measurements, expressed as coefficient of variation, was smaller than 16%, indicating acceptable reproducibility. A correlation was found between bone resorption measured with FMT and bone resorption rate measured with in vivo micro-computed tomography only over the first 14days (R=0.81, p<0.01), but not between bone formation measured with FMT and bone formation rate measured with in vivo micro-CT. Bone formation measured by FMT was 89-109% greater (p<0.05) for mice subjected to mechanical loading than control mice. Bone resorption was 5-8% lower, but did not reach a significant difference between groups, indicating moderate sensitivity for FMT. In conclusion, in vivo FMT in mouse tail bones is feasible but needs to be optimized for monitoring load adaptation in living mice. 23274768 Effects of zinc on epithelial barrier properties and viability in a human and a porcine intestinal cell culture model. Zinc is an essential trace element with a variety of physiological and biochemical functions. Piglets are commonly supplemented, during the weaning period, with doses of zinc above dietary requirements with positive effects on health and performance that might be attributed to anti-secretory and barrier-enhancing effects in the intestine. For a better understanding of these observations increasing zinc sulfate (ZnSO4; 0-200μM) concentrations were used in an in vitro culture model of porcine (IPEC-J2) and human (Caco-2) intestinal epithelial cells and effects on barrier function, viability, and the mRNA expression of one selected heat shock protein (Hsp) were assessed. When treated apically with zinc sulfate, the transepithelial electrical resistance (TEER) did not change significantly. In contrast, cell viability measured by lactate dehydrogenase (LDH) leakage, by ATP and by WST-1 conversion in postconfluent IPEC-J2 monolayers was affected after a 24-h treatment with 200μM ZnSO4. Caco-2 cells were more resistant to Zn. ZnSO4 did not induce any effect on viability, except when it was used at the highest concentration (200μM), and only in preconfluent cells. Furthermore, ZnSO4 induced Hsp70 mRNA expression at 200μM and was more pronounced in preconfluent cells. The observed dose-related effects of zinc are cell-line specific and depended on the differentiation status of the cells. The IPEC-J2 cell line appears to be a suitable in vitro model to characterize specific effects on porcine intestinal cells. 23340334 A new bioassay for the ecotoxicological testing of VOCs on groundwater invertebrates and the effects of toluene on Niphargus inopinatus. A protocol was developed for testing the ecotoxicological effects of volatile organic compounds (VOCs) on groundwater invertebrates. Test substance volatility was addressed in a "closed from start to analysis"-design. Since manifestation of toxic effects may be delayed in 'slower metabolizing' organisms such as groundwater fauna, a time-independent (TI-) approach was adopted. Toluene was used as a model substance and its toxicity to the groundwater amphipod Niphargus inopinatus was assessed as an example. The method evaluation process considered various methodological issues such as partitioning of the toxicant between the water and the gas phase (Henry equilibrium), the possible depletion of oxygen in closed test vials, as well as microbial biodegradation of the test substance. For N. inopinatus, an LC50,14 days of 46.6mgL(-1) toluene was obtained. The ultimate LC50 value was estimated at 23.3mgL(-1) toluene. No oxygen depletion occurred in the test vials and Henry equilibrium was found to be established after 6h. The new test system proposed now awaits broad practical application. 23299834 Spatial modeling for refining and predicting surface potential mapping with enhanced resolution. Quantitatively mapping surface properties with nanometer or even subnanometer resolutions is critical for advanced scanning probe microscopy (SPM) characterization. However, the characterization performance often suffers from noises and artifacts due to instrumentation or environmental limitations. In this paper, we proposed a novel statistical approach with bivariate spatial modeling to efficiently refine and predict surface property mapping. Scanning Kelvin probe microscopy (SKPM) was selected as a representative example to test our proposed method on lateral nanowire assemblies. We revealed that the proposed method can effectively retrieve the artifact-free surface potential distribution by automatically identifying topological artifacts from surface potential maps. Furthermore, the statistical model built upon low spatial resolution was successfully used to predict the potential values from higher-resolution topography data. Compared to conventional regression model, our model is able to predict the surface potential distribution from less raw data but yields much higher accuracy. Through this means, the spatial resolution of SKPM surface potential maps can be significantly improved. This statistics-enabled predictive method opens a new route toward high-precision and high-resolution SPM characterizations without the enhancement of instrumentation capabilities. 23225366 Cytotoxic cycloartane triterpenes of the traditional Chinese medicine "shengma" (Cimicifuga dahurica). Twelve new 9,19-cycloartane triterpenes (1-12), together with fourteen known compounds (13-26), were isolated from the roots of Cimicifuga dahurica. Their structures were determined by application of spectroscopic analyses and chemical methods. Biological evaluation of the compounds against human HL-60, SMMC-7721, A549, MCF-7, and SW-480 cell lines indicated that cimigenol-type glycosides (1-3, 19, and 20) showed broad-spectrum and moderate cytotoxicities, with IC50 values ranging from 4.2 to 14.5 µM. Meanwhile, cimigenol-type aglycones (6-8, 15, 16, and 18) exhibited broad-spectrum and week cytotoxicities, having IC50 values around 20 µM. In addition, the key points of the structure-activity relationships of aglycones with a cimigenol skeleton were discussed. 23401084 Desired professional development pathways for clinical pharmacists. The 2012 American College of Clinical Pharmacy (ACCP) Certification Affairs Committee was charged with developing guidelines for the desired professional development pathways for clinical pharmacists. This document summarizes recommendations for postgraduate education and training for graduates of U.S. schools and colleges of pharmacy and describes the preferred pathways for achieving, demonstrating, and maintaining competence as clinical pharmacists. After initial licensure within the state or jurisdiction in which the pharmacist intends to practice, completion of an accredited PGY1 pharmacy residency is recommended to further develop the knowledge and skills needed to optimize medication therapy outcomes. An accredited PGY2 pharmacy residency should be completed if a pharmacist wishes to seek employment in a specific therapeutic area or practice setting, if such a residency exists. Clinical pharmacists intending to conduct advanced research that is competitive for federal funding are encouraged to complete a fellowship or graduate education. Initial certification by the Board of Pharmacy Specialties (BPS) or other appropriate sponsoring organizations should be completed in the desired primary therapeutic area or practice setting within 2 years after accepting a position within the desired specific therapeutic area or practice setting. Clinical pharmacists subsequently will need to meet the requirements to maintain pharmacist licensure and board certification. Traineeships, practice-based activities, and certificate programs can be used to obtain additional knowledge and skills that support professional growth. Pharmacists are strongly encouraged to adopt a lifelong, systematic process for professional development and work with ACCP and other professional organizations to facilitate the development and implementation of innovative strategies to assess core practice competencies. 23417717 Estimating population-level HC5 for copper using a species sensitivity distribution approach. Estimation of population-level benchmark concentrations for protecting aquatic organisms from chemicals is important for value-relevant ecological risk assessments. By employing a species sensitivity distribution (SSD) approach, the authors aimed to derive the population-level hazardous concentration for 5% of species (PHC5) for copper. Based on available information on copper toxicity and population models, the authors estimated population threshold concentrations at which the population size is stable (that is, 0 net population growth) for 13 freshwater species (3 algal, 6 invertebrate, and 4 fish species). The PHC5 for copper was then estimated (6.8 µg/L; 95% confidence interval [CI], 1.8-13.6 µg/L), by fitting a log-normal distribution to the population threshold concentrations obtained. The close overlap between the present study's estimate of the PHC5 and a field-derived threshold concentration suggests that the population-level SSD approach provides a reasonable level of protection for species richness in the natural environment. By contrast, and counterintuitively, the authors' estimate was comparable with the individual-level HC5 reported in the European Union risk assessment. Although the present study cannot determine the underlying reasons for the similar figures, the result provides an indication that the margin between individual-level and population-level benchmarks derived from SSD approaches can be very small. The results therefore suggest that attention is needed to achieve population-level protection using an individual-level SSD approach. Environ Toxicol Chem 2013;32:1396-1402. © 2013 SETAC. 23132843 Synthesis and evaluation of 3,4-dihydropyrimidin-2(1H)-ones as sodium iodide symporter inhibitors. The sodium iodide symporter (NIS) is responsible for the accumulation of iodide in the thyroid gland. This transport process is involved in numerous thyroid dysfunctions and is the basis for human contamination in the case of exposure to radioactive iodine species. 4-Aryl-3,4-dihydropyrimidin-2(1H)-ones were recently discovered by high-throughput screening as the first NIS inhibitors. Described herein are the synthesis and evaluation of 115 derivatives with structural modifications at five key positions on the pyrimidone core. This study provides extensive structure-activity relationships for this new class of inhibitors that will serve as a basis for further development of compounds with in vivo efficacy and adequate pharmacokinetic properties. In addition, the SAR investigation provided a more potent compound, which exhibits an IC(50) value of 3.2 nM in a rat thyroid cell line (FRTL5). 23202585 The ATPase domain of ISWI is an autonomous nucleosome remodeling machine. ISWI slides nucleosomes along DNA, enabling the structural changes of chromatin required for the regulated use of eukaryotic genomes. Prominent mechanistic models imply cooperation of the ISWI ATPase domain with a C-terminal DNA-binding function residing in the HAND-SANT-SLIDE (HSS) domain. Contrary to these models, we show by quantitative biochemical means that all fundamental aspects of nucleosome remodeling are contained within the compact ATPase module of Drosophila ISWI. This domain can independently associate with DNA and nucleosomes, which in turn activate ATP turnover by inducing a conformational change in the enzyme, and it can autonomously reposition nucleosomes. The role of the HSS domain is to increase the affinity and specificity for nucleosomes. Nucleosome-remodeling enzymes may thus have evolved directly from ancestral helicase-type motors, and peripheral domains have furnished regulatory capabilities that bias the remodeling reaction toward different structural outcomes. 23353816 Differential toxicity and gene expression in Caco-2 cells exposed to arsenic species. Inorganic arsenic [As(V)+As(III)] and its metabolites, especially the trivalent forms [monomethylarsonous acid, MMA(III), and dimethylarsinous acid, DMA(III)], are considered the forms of arsenic with the highest degree of toxicity, linked to certain types of cancer and other pathologies. The gastrointestinal mucosa is exposed to these forms of arsenic, but it is not known what toxic effect these species may have on it. The aim of the present work was to evaluate the toxicity and some mechanisms of action of inorganic arsenic and its metabolites [monomethylarsonic acid, MMA(V), dimethylarsinic acid, DMA(V), MMA(III) and DMA(III)] in intestinal epithelial cells, using the Caco-2 human cell line as a model. The results show that the pentavalent forms do not produce toxic effects on the intestinal monolayer, but the trivalent species have a different degree of toxicity. As(III) induces death mainly by necrosis, whereas only apoptotic cells are detected after exposure to MMA(III), and for DMA(III) the percentages of apoptosis and necrosis are similar. The three forms produce reactive oxygen species, accompanied by a reduction in intracellular GSH and lipid peroxidation, the latter being especially notable in the dimethylated form. They also alter the enzyme activity of glutathione peroxidase and catalase and induce expression of stress proteins and metallothioneins. The results indicate that the trivalent forms of arsenic can affect cell viability of intestinal cells by mechanisms related to the induction of oxidative stress. Further studies are needed to evaluate how the effects observed in this study affect the structure and functionality of the intestinal epithelium. 23274352 Growth inhibition in early life-stage tests predicts full life-cycle toxicity effects of lead in the freshwater pulmonate snail, Lymnaea stagnalis. The freshwater pulmonate snail, Lymnaea stagnalis, is the most sensitive freshwater organism tested to date for several metals (Co, Cu, Pb, Ni) based on 28 d early life-stage (ELS) tests in which growth was the most sensitive endpoint. The United States Environmental Protection Agency (USEPA) has expressed concern that growth in 28 d ELS tests with mollusks may overpredict toxicity because of the potential for recovery in a full life-cycle (LC) test. Consequently, the USEPA only accepts the survival endpoint for these tests in establishing water quality criteria (WQC). To address this concern, the current study aimed to test the sensitivity of L. stagnalis to Pb in a 56 d full LC test evaluating survival, growth, reproductive and embryonic growth endpoints and compare the estimated effect levels to those established using the 28 d ELS test design. The most sensitive endpoints in this study were 28 d growth and 56 d egg mass production, both with a NOEC of <1.0 μg L(-1) and a LOEC of 1.0 μg L(-1), showing that the ELS growth endpoint is predictive of the 56 d reproduction endpoint. Snails exposed to 1.0 and 2.7 μg L(-1) Pb showed full and partial recovery from growth inhibition between 28 and 56 d. While this recovery supports the USEPA's concern about the 28 d growth endpoint; considering the reproductive lifespan of L. stagnalis and the recovery dose-response, we conclude that the 28 d growth endpoint will be within a factor of 3 of full LC endpoints. This is consistent with the level of precision previously determined for fish ELS tests, which the USEPA accepts for WQC derivation, and suggests that tests using 28 d ELS growth endpoint for L. stagnalis may be acceptable for inclusion in WQC derivation. 23355467 Role of fat body lipogenesis in protection against the effects of caloric overload in Drosophila. The Drosophila fat body is a liver- and adipose-like tissue that stores fat and serves as a detoxifying and immune responsive organ. We have previously shown that a high sugar diet leads to elevated hemolymph glucose and systemic insulin resistance in developing larvae and adults. Here, we used stable isotope tracer feeding to demonstrate that rearing larvae on high sugar diets impaired the synthesis of esterified fatty acids from dietary glucose. Fat body lipid profiling revealed changes in both carbon chain length and degree of unsaturation of fatty acid substituents, particularly in stored triglycerides. We tested the role of the fat body in larval tolerance of caloric excess. Our experiments demonstrated that lipogenesis was necessary for animals to tolerate high sugar feeding as tissue-specific loss of orthologs of carbohydrate response element-binding protein or stearoyl-CoA desaturase 1 resulted in lethality on high sugar diets. By contrast, increasing the fat content of the fat body by knockdown of king-tubby was associated with reduced hyperglycemia and improved growth and tolerance of high sugar diets. Our work supports a critical role for the fat body and the Drosophila carbohydrate response element-binding protein ortholog in metabolic homeostasis in Drosophila. 23110976 The conjoint influence of home enriched environment and lead exposure on children's cognition and behaviour in a Mexican lead smelter community. A range of studies has been conducted on the detrimental effects of lead in mining and smelting communities. The neurocognitive and behavioural health effects of lead on children are well known. This research characterized the conjoint influence of lead exposure and home enriched environment on neurocognitive function and behaviour for first-grade children living in a Mexican lead smelter community. Structural equation models were used for this analysis with latent outcome variables, Cognition and Behaviour, constructed based on a battery of assessments administered to the first-grade children, their parents, and teachers. Structural equation modelling was used to describe complex relationships of exposure and health outcomes in a manner that permitted partition of both direct and indirect effects of the factors being measured. Home Environment (a latent variable constructed from information on mother's education and support of school work and extracurricular activities), and child blood lead concentration each had a main significant effect on cognition and behaviour. However, there were no statistically significant moderation relationships between lead and Home Environment on these latent outcomes. Home Environment had a significant indirect mediation effect between lead and both Cognition and Behaviour (p-value<0.001). The mediation model had a good fit with Root Mean Square Error of Approximation <0.0001 and a Weighted Root Mean Square Residual of 0.895. These results were highly significant and suggest that Home Environment has a moderate mediation effect with respect to lead effects on Behaviour (β=0.305) and a lower mediation effect on Cognition (β=0.184). The extent of home enrichment in this study was most highly related to the mother's support of schoolwork and slightly less by the mother's support of extracurricular activities or mother's education. Further research may be able to develop approaches to support families to make changes within their home and child rearing practices, or advocate for different approaches to support their child's behaviour to reduce the impact of lead exposure on children's cognitive and behavioural outcomes. 23427137 A liquid crystalline phase with uniform tilt, local polar order and capability of symmetry breaking. A new liquid crystalline (LC) phase with uniform tilt, local polar order and capability of symmetry breaking is found for a bent-core mesogen combining a 4-cyanoresorcinol unit with two azobenzene wings. The combination of local polar order and long range synclinic tilt in this SmCs PR phase leads, under special conditions, to macroscopic domains with opposite chirality, though the molecules themselves are achiral. 23524228 Cosmetics Europe multi-laboratory pre-validation of the SkinEthic™ reconstituted human corneal epithelium test method for the prediction of eye irritation. Cosmetics Europe, The Personal Care Association, known as Colipa before 2012, conducted a program of technology transfer and assessment of Within/Between Laboratory (WLV/BLV) reproducibility of the SkinEthic™ Reconstituted Human Corneal Epithelium (HCE) as one of two human reconstructed tissue eye irritation test methods. The SkinEthic™ HCE test method involves two exposure time treatment procedures - one for short time exposure (10min - SE) and the other for long time exposure (60min - LE) of tissues to test substance. This paper describes pre-validation studies of the SkinEthic™ HCE test method (SE and LE protocols) as well as the Eye Peptide Reactivity Assay (EPRA). In the SE WLV study, 30 substances were evaluated. A consistent outcome with respect to viability measurement across all runs was observed with all substances showing an SD of less than 18%. In the LE WLV study, 44 out of 45 substances were consistently classified. These data demonstrated a high level of reproducibility within laboratory for both the SE and LE treatment procedures. For the LE BLV, 19 out of 20 substances were consistently classified between the three laboratories, again demonstrating a high level of reproducibility between laboratories. The results for EPRA WLV and BLV studies demonstrated that all substances analysed were categorised similarly and that the method is reproducible. The SkinEthic™ HCE test method entered into the experimental phase of a formal ECVAM validation program in 2010. 23604819 Synthesis, cytotoxicity and QSAR study of N-tosyl-1,2,3,4-tetrahydroisoquinoline derivatives. 1-Substituted-N-tosyl-1,2,3,4-tetrahydroisoquinoline analogs (4a-4l) were synthesized using the modified Pictet-Spengler reaction and evaluated for cytotoxicity. All tetrahydroisoquinolines displayed cytotoxicity against MOLT-3 cell lines, except for p-methoxy analog 4d. Interestingly, the o-hydroxy derivative 4k was shown to be the most potent cytotoxic against HuCCA-1, A-549 and MOLT-3 cell lines. The lowest IC50 value of 1.23 μM was observed for MOLT-3 cells. Trimethoxy analog 4f exerted the most potent activity against HepG2 with an IC50 of 22.70 μM, which is lower than the reference drug, etoposide. QSAR studies showed that total symmetry index (Gu), 3D-MoRSE (Mor31v and Mor32u) and 3D Petitjean index (PJI3) were the most important descriptors accounting for the observed cytotoxicities. The most potent cytotoxic compound (4k) against MOLT-3 had the highest Gu value, correspondingly the inactive p-methoxy analog (4d) had the lowest Gu value. On the other hand, the highest molecular mass compound (4f) was shown to be the most potent cytotoxic against HepG2 cells. The studies disclose that tetrahydroisoquinolines 4f and 4k are potentially interesting lead pharmacophores that should be further explored. The QSAR models provided insights into the physicochemical properties of the investigated compounds. 23580257 Anti-asthmatic Effects of Baicalin in a Mouse Model of Allergic Asthma. The aim of the study was to investigate the anti-asthmatic effects of baicalin (BA) and the possible mechanisms. Asthma model was established by ovalbumin (OVA) intraperitoneal injection. A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg/kg), and BA (10 mg/kg, 20 mg/kg, 40 mg/kg). Airway resistance (RI) and lung compliance (Cdyn) were measured, histological studies were evaluated by the hematoxylin and eosin staining, Th1/Th2, OVA-specific serum, and BALF IgE levels and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay, and Th17 cells was evaluated by flow cytometry (FCM). Our study demonstrated that BA inhibited OVA-induced increases in RI and eosinophil count; interleukin (IL)-4, IL-17A levels, and Cdyn were recovered and increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that BA substantially inhibited OVA-induced eosinophilia in lung tissue and airway tissue. FCM studies demonstrated that BA substantially inhibited Th17 cells. These findings suggest that BA may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma. Copyright © 2013 John Wiley & Sons, Ltd. 23256609 First-principles prediction of the effects of temperature and solvent selection on the dimerization of benzoic acid. We introduce a procedure of quantum chemical calculations (B3P86/6-31G**) to study carboxylic acid dimerization and its correlation with temperature and properties of the solvent. Benzoic acid is chosen as a model system for studying dimerization via hydrogen bonding. Organic solvents are simulated using the self-consistent reaction field (SCRF) method with the polarized continuum model (PCM). The cyclic dimer is the most stable structure both in gas phase and solution. Dimer mono- and dihydrates could be found in the gas phase if acid molecules are in contact with water vapor. However, the formation of these hydrated conformers is very limited and cyclic dimer is the principal conformer to coexist with monomer acid in solution. Solvation of the cyclic dimer is more favorable compared to other complexes, partially due to the diminishing of hydrogen bonding capability and annihilation of dipole moments. Solvents have a strong effect on inducing dimer dissociation and this dependence is more pronounced at low dielectric constants. By accounting for selected terms in the total free energy of solvation, the solvation entropy could be incorporated to predict the dimer behavior at elevated temperatures. The temperature dependence of benzoic acid dimerization obtained by this technique is in good agreement with available experimental measurements, in which a tendency of dimer to dissociate is observed with increased temperatures. In addition, dimer breakup is more sensitive to temperature in low dielectric environments rather than in solvents with a higher dielectric constant. 23376110 Synthesis of novel 16-spiro steroids: Spiro-7'-(aryl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazolo-trans-androsterone hybrid heterocycles. The 1,3-dipolar cycloaddition of azomethine ylide derived in situ from the reaction of acenaphthylene-1,2-dione and 1,3-thiazolane-4-carboxylic acid to various exocyclic dipolarophiles synthesized from trans-androsterone and trans-dehydroandrosterone afforded a library of novel spiro[5'.2″]acenaphthylene-1″-one-spiro[16.6']-(7'-aryl)-tetrahydro-1H-pyrrolo [1,2-c][1,3]thiazolo-trans-androsterone/dehydroandrosterone hybrid heterocycles respectively. These reactions proceeded stereo-specifically affording a single isomer of the 16-spiro steroids in excellent yields. 23434226 Identification and characterization of small molecule inhibitors of signal transducer and activator of transcription 3 (STAT3) signaling pathway by virtual screening. Inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling pathway has been considered a novel therapeutic strategy to treat human cancers that harbor aberrantly-active STAT3. In this study, a series of small molecules were identified as novel inhibitors of STAT3 signaling pathway through virtual screening. A tricyclic scaffold containing compound, 6, was identified as an inhibitor of IL-6/STAT3 signaling with an IC50 of 26.68 μM. In addition, this compound inhibited Tyr705 phosphorylation of STAT3 and had no obvious effect on upstream tyrosine kinases. Thus, compound 6 is a potential lead structure and valuable for further drug development. 23623843 Protective effects of Keemun black tea polysaccharides on acute carbon tetrachloride-caused oxidative hepatotoxicity in mice. This study was designed to investigate chemical characterization of the water-soluble polysaccharides extracted from Keemun black tea (KBTP), and their antioxidant and hepatoprotective effects against CCl4-induced oxidative damage in mice. HPLC analysis revealed that KBTP is the typical acidic heteropolysaccharides and consisted of nine monosaccharides. Furthermore, KBTP showed highly ferric-reducing antioxidant power and scavenging effects against DPPH, OH and O2(-) in vitro. Administration of KBTP (200, 400 and 800mg/kgbw) in mice ahead of CCl4 injection could observably antagonize the CCl4-induced increases in serum ALT, AST, TG and TC, and the hepatic MDA and 8-iso-PGF2a levels, respectively. Mice with KBTP pretreatment displayed a better profile of hepatosomatic index and the improved GSH and SOD activities in comparison with CCl4-intoxicated mice. These biochemical results were further supported with liver histopathological assessment, revealing that KBTP has an observable prevention of liver damage induced by CCl4 in mice. 23454052 The effect of formulation on the penetration of coated and uncoated zinc oxide nanoparticles into the viable epidermis of human skin in vivo. The use of nanoparticulate zinc oxide (ZnO-NP) in sunscreens and other cosmetic products has raised public health concerns. The two key issues are the extent of exposure to ZnO-NP and the likely hazard after the application of ZnO-NP in sunscreen and cosmetic products to humans in vivo. Our aims were to assess exposure by the extent of ZnO-NP penetration into the viable epidermis and hazard by changes in the viable epidermal redox state for a number of topical products. Of particular interest is the role of the particle coating, formulation used, and the presence of any enhancers. Multiphoton tomography with fluorescence lifetime imaging microscopy (MPT-FLIM) was used to simultaneously observe ZnO-NP penetration and potential metabolic changes within the viable epidermis of human volunteers after topical application of various ZnO-NP products. Coated and uncoated ZnO-NP remained in the superficial layers of the SC and in the skin furrows. We observed limited penetration of coated ZnO-NP dispersed in a water-in-oil emulsion formulation, which was predominantly localized adjacent to the skin furrow. However, the presence of ZnO-NP in the viable epidermis did not alter the metabolic state or morphology of the cells. In summary, our data suggest that some limited penetration of coated and uncoated ZnO-NP may occur into viable stratum granulosum epidermis adjacent to furrows, but that the extent is not sufficient to affect the redox state of those viable cells. 23378820 Electrochemical Removal Of Selenate From Aqueous Solutions. Removal of selenate from solution is investigated in batch electrochemical systems using reactive iron anodes and copper plate cathode in a bicarbonate medium. Iron anodes produce ferrous hydroxide, which is a major factor in the removal of selenate from solution. Iron anodes also generate a significant decrease in the oxidation-reduction potential (ORP) of the solution because it prevents generation of oxygen gas at the anode by electrolysis. The removal rates varied from 45.1 to 97.4%, depending on current density and selenate concentration. The transformation of selenate by the process is modeled based on a heterogeneous reaction coupled with electrochemical generation of ferrous and hydroxide. The rates are optimized at lower initial concentrations, higher electrical currents, and the presence of anions. Presence of dissolved oxygen does not cause any significant effects the removal of selenate. 23195954 Serine protease activity of calnuc: regulation by Zn2+ and G proteins. The functions of calnuc, a novel Ca(2+)-binding protein with multiple structural domains and diverse interacting partners, are yet unknown. We demonstrate unknown facets of calnuc, which is a serine protease in which Ser-378 of GXSXG motif, Asp-328 of DTG motif, and His-339 form the "catalytic triad," locating the enzyme active site in the C-terminal region. Analogous to the active site of Zn(2+) carboxypeptidases, calnuc has two high affinity (K(d) ∼ 20 nm), well conserved Zn(2+)-binding sites near its N terminus, although it is inactive as a peptidase. Zn(2+) binding allosterically and negatively regulates the serine protease activity of calnuc, inhibition being caused by an "open to close" change in its conformation not seen upon Ca(2+) binding. Most strikingly, interaction with G protein α subunit completely inhibits the enzymatic activity of calnuc. We thus illustrate that G proteins and Zn(2+) act as two "keys" that control enzymatic activity of calnuc, arresting it in "locked" state. Calnuc, therefore, exists dynamically in two different forms, (i) as a Ca(2+)-binding protein in Zn(2+)-bound form and (ii) as a protease in Zn(2+)-free form, commissioning it to perform multiple functions. 23545348 Species differences in the neuromuscular activity of post-synaptic neurotoxins from two Australian black snakes (Pseudechis porphyriacus and Pseudechis colletti). Bites by Australian black snakes (Pseudechis spp.) do not cause neurotoxicity in human envenoming. This is unusual as in vitro neurotoxicity has been reported for all Pseudechis spp. venoms. The present study aimed to identify, isolate and characterise neurotoxins from the venoms of Pseudechis porphyriacus and Pseudechis colletti to elucidate the reason for the lack of neurotoxicity in humans. α-Elapitoxin-Ppr1 and α-elapitoxin-Pc1 were isolated from P. porphyriacus and P. colletti, respectively, using reverse-phase high performance liquid chromatography. Each toxin consisted of 62 amino acids with molecular weights of 6746.5Da and 6759.6Da, respectively. α-Elapitoxin-Ppr1 and α-elapitoxin-Pc1 caused concentration-dependent (0.1-0.3μM) inhibition of indirect twitches in the chick biventer cervicis nerve-muscle preparation. Both toxins inhibited contractile responses to exogenous ACh and CCh, but not KCl, suggesting a post-synaptic mode of action at the nicotinic acetylcholine receptor (nAChR). CCh concentration-response curves obtained in the presence or absence of α-elapitoxin-Ppr1 or α-elapitoxin-Pc1 indicated pA2 values of 6.97±0.03 and 7.04±0.07, respectively. Neither α-elapitoxin-Ppr1 (0.1μM) nor α-elapitoxin-Pc1 (0.1μM) had a significant effect on the electrically-induced twitches of the rat isolated phrenic nerve-diaphragm preparation. When the venom with the toxin removed (10μg/ml) was added to both the rat and chick preparations, the inhibition was significantly less than that caused by the intact whole venoms (10μg/ml). The current study shows that α-elapitoxin-Ppr1 and α-elapitoxin-Pc1 act as pseudo-irreversible antagonists at the nAChR of the skeletal neuromuscular junction and that the avian preparation is more sensitive to the neurotoxic effects of these toxins than the mammalian preparation. 23474357 Assessing vehicle effects on skin absorption using artificial membrane assays. A vast number of variations in drug/vehicle combinations may come into contact with skin. Evaluating the effect of potential drug, vehicle and skin interactions for all possible combinations is a daunting task. A practical solution is a rapid screening technique amenable to high throughput approaches (e.g. 96-well plates). In this study, three artificial membranes (isopropyl myristate (IPM), certramides and Strat-M™) were evaluated for their ability to predict the skin permeability of caffeine, cortisone, diclofenac sodium, mannitol, salicylic acid and testosterone applied in propylene glycol, water and ethanol as unsaturated and saturated concentrations. Resultant absorption data was compared to porcine skin diffusion cell data. The correlations (r(2)) between membrane and diffusion cell data from saturated and unsaturated concentrations were 0.38, 0.47 and 0.56 for the Strat-M™, certramide and IPM membranes, respectively. This relationship improved when only saturated concentrations were evaluated (r(2)=0.60, 0.63 and 0.66 for the Strat-M™, certramide and IPM membranes, respectively). A correlation between membrane retention and the amount remaining in skin had r(2) values of 0.73 (Strat-M™), 0.67 (certramides), and 0.67 (IPM). Quantitative structure-permeability relationship models for each membrane identified different physicochemical factors influencing the absorption process. Although further investigations exploring complex topical formulations are required, these results suggest potential use as an initial screening approach to assist in narrowing the selection of formulations to be evaluated with a more biologically intact model, thereby assisting in the development of new topical formulations. 23554215 The electronic origin of unusually large (n) JFN coupling constants in some fluoroximes. SOPPA(CCSD) calculations show that the FC term is the most important contribution to the through-space transmission of JFN coupling constants for the fluoroximes studied in this work. Because of the well-known behavior of FC term, a new rationalization for the experimental (TS) JFN SSCC is presented. It is mainly based on the overlap matrix (Sij ) between fluorine and nitrogen lone pairs obtained from NBO analyses. An expression is proposed to take into account the influence of the electronic density (Dij ) between coupled nuclei as well as the s% character at the site of the coupling nuclei of bonds and non-bonding electron pairs involved in Dij . In using this approach, a linear correlation between (TS) JFN versus Dij is obtained. The most important aspect of this rationalization is related to the facility for understanding the behavior of some unusual experimental coupling constants. It is shown that, at least in this case, the electronic origin of the so-called through-space coupling is transmitted through to the overlap of orbitals on the coupled atoms, suggesting that, at least for these compounds, instead of through-space coupling, it should better be dubbed as 'through overlapping orbital coupling'. Copyright © 2013 John Wiley & Sons, Ltd. 23526674 Acute Kidney Injury During Vancomycin Therapy in Critically Ill Children. STUDY OBJECTIVE: To determine the rate, risk factors, and outcome of vancomycin-associated acute kidney injury (AKI) in critically ill children. DESIGN: Retrospective cohort study. SETTING: Tertiary care children's hospital. PATIENTS: We reviewed the charts of children admitted to the pediatric intensive care unit during a 2-year period who were treated with vancomycin. Courses of vancomycin interrupted by 3 days or more were counted separately. Patients were excluded if they received vancomycin treatment for fewer than 3 days, had preexisting renal failure, or had incomplete serum creatinine (Scr ) data. MEASUREMENTS AND MAIN RESULTS: Demographic and laboratory data; vancomycin dose, duration, and concentrations; and concurrent use of nephrotoxic drugs were recorded. Acute kidney injury was defined as a decrease in estimated glomerular filtration rate of 50% or more from the beginning of vancomycin therapy. Descriptive statistics, step-wise logistic regression, and repeated measures ANOVA were used to analyze the data. A total of 284 patients were included, for a total of 391 courses of vancomycin (272 children and 119 infants). The mean duration of vancomycin therapy was 6.9 ± 4.5 days. Forty nine (17.2%) patients developed AKI during 61 (15.6%) courses. Elevated Scr concentrations returned to baseline after stopping vancomycin in 53 (87%) courses. Mortality was higher in children who developed AKI (p<0.001; Fisher's exact test). Administration of nephrotoxic drugs (odds ratio 2.23, Confidence Interval 1.27-3.93) and presence of high blood urea nitrogen (BUN):Scr ratio before vancomycin therapy (p<0.05) were associated with AKI. The BUN and Scr concentrations significantly increased during vancomycin therapy and decreased after vancomycin was discontinued (p<0.05). CONCLUSIONS: In critically ill children, the development of reversible AKI during vancomycin therapy is associated with administration of nephrotoxic drugs and an elevated BUN: Scr ratio. 23010362 Functional and structural interaction of (-)-reboxetine with the human α4β2 nicotinic acetylcholine receptor. The interaction of the selective norepinephrine reuptake inhibitor (-)-reboxetine with the human α4β2 nicotinic acetylcholine receptor (nAChR) in different conformational states was studied by several functional and structural approaches. Patch-clamp and Ca(2+)-influx results indicate that (-)-reboxetine does not activate hα4β2 nAChRs via interaction with the orthosteric sites, but inhibits agonist-induced hα4β2 activation by a noncompetitive mechanism. Consistently, the results from the electrophysiology-based functional approach suggest that (-)-reboxetine may act via open channel block; therefore, it is capable of producing a use-dependent type of inhibition of the hα4β2 nAChR function. We tested whether (-)-reboxetine binds to the luminal [(3)H]imipramine site. The results indicate that, although (-)-reboxetine binds with low affinity to this site, it discriminates between the resting and desensitized hα4β2 nAChR ion channels. Patch-clamp results also indicate that (-)-reboxetine progressively inhibits the hα4β2 nAChR with two-fold higher potency at the end of one-second application of agonist, compared with the peak current. The molecular docking studies show that (-)-reboxetine blocks the ion channel at the level of the imipramine locus, between M2 rings 6' and 14'. In addition, we found a (-)-reboxetine conformer that docks in the helix bundle of the α4 subunit, near the middle region. According to molecular dynamics simulations, (-)-reboxetine binding is stable for both sites, albeit less stable than imipramine. The interaction of these drugs with the helix bundle might alter allostericaly the functionality of the channel. In conclusion, the clinical action of (-)-reboxetine may be produced (at least partially) by its inhibitory action on hα4β2 nAChRs. 22533550 Microwave-assisted synthesis of N-isobutyl-4,5-epoxy-2(E)-decenamide. A new and efficient synthesis of a naturally occurring amide alkaloid, N-isobutyl-4,5-epoxy-2(E)-decenamide isolated from the roots of Piper nigrum has been described involving a total of nine steps. Octanal and 2-bromoacetic acid have been used as the starting materials. 23063069 Parental exposure to natural mixtures of POPs reduced embryo production and altered gene transcription in zebrafish embryos. Determination of toxicity of complex mixtures has been proposed to be one of the most important challenges for modern toxicology. In this study we performed genome wide transcriptome profiling to assess potential toxicant induced changes in gene regulation in zebrafish embryos following parental exposure to two natural mixtures of persistent organic pollutants (POPs). The mixtures used were extracted from burbot (Lota lota) liver originating from two lakes (Lake Mjøsa and Lake Losna) belonging to the same freshwater system in Norway. The dominating groups of contaminants were polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane metabolites (DDTs). Because both mixtures used in the present study induced similar effects, it is likely that the same toxicants are involved. The Mjøsa mixture contains high levels of PBDEs while this group of pollutants is low in the Losna mixture. However, both mixtures contain substantial concentrations of PCB and DDT suggesting these contaminants as the predominant contributors to the toxicity observed. The observed effects included phenotypic traits, like embryo production and survival, and gene transcription changes corresponding with disease and biological functions such as cancer, reproductive system disease, cardiovascular disease, lipid and protein metabolism, small molecule biochemistry and cell cycle. The changes in gene transcription included genes regulated by HNF4A, insulin, LH, FSH and NF-κB which are known to be central regulators of endocrine signaling, metabolism, metabolic homeostasis, immune functions, cancer development and reproduction. The results suggest that relative low concentrations of the natural mixtures of POPs used in the present study might pose a threat to wild freshwater fish living in the lakes from which the POPs mixtures originated. 23131797 Large, chemically diverse dataset of logP measurements for benchmarking studies. Lipophilicity is a crucial parameter in drug development since it impacts both ADME properties and target affinity of drug candidates. In early drug discovery stage, accurate tools for logP prediction are highly desired. Many calculation methods were developed to aid pharmaceutical scientists in drug research; however almost all suffer from insufficient accuracy and variation of performance in several regions of the chemical space associated with new chemical entities. The low predictive power of existing software packages can be explained by limited availability and/or variable quality of experimental logP values associated with training set used, which stem from various protocols and poorly cover chemical space. In this study, a dataset of 1000 diverse test compounds out of 4.5 million was generated; logP values of 759 purchasable compounds (46% non-ionizable, 30% basic, 17% acidic, 0.5% zwitterionic and 6.5% ampholytes) from this selected set were experimentally determined by UHPLC followed by UV detection or MS detection when necessary. Finally, a data collection of 707 validated logP values ranging from 0.30 to 7.50 is now available for benchmarking of existing and development of new approaches to predict octanol/water partition coefficients of chemical compounds. 23237590 Slip flow through colloidal crystals of varying particle diameter. Slip flow of water through silica colloidal crystals was investigated experimentally for eight different particle diameters, which have hydraulic channel radii ranging from 15 to 800 nm. The particle surfaces were silylated to be low in energy, with a water contact angle of 83°, as determined for a silylated flat surface. Flow rates through centimeter lengths of colloidal crystal were measured using a commercial liquid chromatograph for accurate comparisons of water and toluene flow rates using pressure gradients as high as 10(10) Pa/m. Toluene exhibited no-slip Hagen-Poiseuille flow for all hydraulic channel radii. For water, the slip flow enhancement as a function of hydraulic channel radius was described well by the expected slip flow correction for Hagen-Poiseuille flow, and the data revealed a constant slip length of 63 ± 3 nm. A flow enhancement of 20 ± 2 was observed for the smallest hydraulic channel radius of 15 nm. The amount of slip flow was found to be independent of shear rate over a range of fluid velocities from 0.7 to 5.8 mm/s. The results support the applicability of the slip flow correction for channel radii as small as 15 nm. The work demonstrates that packed beds of submicrometer particles enable slip flow to be employed for high-volume flow rates. 23299194 Protective effect of Lygodium flexuosum (family: Lygodiaceae) against excision, incision and dead space wounds models in experimental rats. Ethnopharmacological relevance: Lygodium flexuosum (Linn) Sw. is a climbing fern, and it is the sole genus in the family Lygodiaceae. It commonly grows epiphytically on moss covered tree trunks and branches as lithophytes on shady boulders along with moss. It has been reported as a traditional folkloric medicine for a variety of ailments particularly useful for carbuncles, inflammation, ulcer, various respiratory diseases, general disorders, muscle sprains and acts as panacea for wounds. However, there are no scientific reports on wound healing activity of the plant L. flexuosum (Linn) Sw.Aim of the study: To explore the protective effect of L. flexuosum against excision, incision and dead space wounds models in experimental rats. METHODS: Wistar albino rats of either sex weighing between 180 and 220 g were topically treated with extract formulated in ointment using simple ointment BP as base. Ointments, 4% and 5% (w/w), were applied once daily in excision wound model. L. flexuosum ethanolic extract was given orally at a dose of 100, 200 and 400 mg/kg in incision and dead space wound healing models. Rats of standard groups were treated with 0.2% nitrofurazone ointment topically. The percentage wound contraction, epithelization time in excision wound model; breaking strength in incision wound model and wet and dry granulation weight, hydroxyproline content were measured. RESULTS: Topical application of L. flexuosum in excision wound model increased the percentage of wound contraction, and the epithelization time was decreased. In the incision wound model, the breaking strength of wounds increased and in dead space model the weight of dry and wet granuloma of wounds and hydroxyproline was increased. Conclusively, the data of present study indicated that the leaf extract of L. flexuosum accelerated wound healing in rats and thus supports its traditional use. 23219469 Direct transmembrane interaction between actin and the pore-competent, cholesterol-dependent cytolysin pneumolysin. The eukaryotic actin cytoskeleton is an evolutionarily well-established pathogen target, as a large number of bacterial factors disturb its dynamics to alter the function of the host cells. These pathogenic factors modulate or mimic actin effector proteins or they modify actin directly, leading to an imbalance of the precisely regulated actin turnover. Here, we show that the pore-forming, cholesterol-dependent cytolysin pneumolysin (PLY), a major neurotoxin of Streptococcus pneumoniae, has the capacity to bind actin directly and to enhance actin polymerisation in vitro. In cells, the toxin co-localised with F-actin shortly after exposure, and this direct interaction was verified by Förster resonance energy transfer. PLY was capable of exerting its effect on actin through the lipid bilayer of giant unilamellar vesicles, but only when its pore competence was preserved. The dissociation constant of G-actin binding to PLY in a biochemical environment was 170-190 nM, which is indicative of a high-affinity interaction, comparable to the affinity of other intracellular actin-binding factors. Our results demonstrate the first example of a direct interaction of a pore-forming toxin with cytoskeletal components, suggesting that the cross talk between pore-forming cytolysins and cells is more complex than previously thought. 23518924 An Essential Role for Insulin and IGF1 Receptors in Regulating Sertoli Cell Proliferation, Testis Size, and FSH Action in Mice. Testis size and sperm production are directly correlated to the total number of adult Sertoli cells (SCs). Although the establishment of an adequate number of SCs is crucial for future male fertility, the identification and characterization of the factors regulating SC survival, proliferation, and maturation remain incomplete. To investigate whether the IGF system is required for germ cell (GC) and SC development and function, we inactivated the insulin receptor (Insr), the IGF1 receptor (Igf1r), or both receptors specifically in the GC lineage or in SCs. Whereas ablation of insulin/IGF signaling appears dispensable for GCs and spermatogenesis, adult testes of mice lacking both Insr and Igf1r in SCs (SC-Insr;Igf1r) displayed a 75% reduction in testis size and daily sperm production as a result of a reduced proliferation rate of immature SCs during the late fetal and early neonatal testicular period. In addition, in vivo analyses revealed that FSH requires the insulin/IGF signaling pathway to mediate its proliferative effects on immature SCs. Collectively, these results emphasize the essential role played by growth factors of the insulin family in regulating the final number of SCs, testis size, and daily sperm output. They also indicate that the insulin/IGF signaling pathway is required for FSH-mediated SC proliferation. 22561337 Sex, stroke, and inflammation: the potential for estrogen-mediated immunoprotection in stroke. Stroke is the third leading cause of death and the primary cause of disability in the developed world. Experimental and clinical data indicate that stroke is a sexually dimorphic disease, with males demonstrating an enhanced intrinsic sensitivity to ischemic damage throughout most of their lifespan. The neuroprotective role of estrogen in the female brain is well established, however, estrogen exposure can also be deleterious, especially in older women. The mechanisms for this remain unclear. Our current understanding is based on studies examining estrogen as it relates to neuronal injury, yet cerebral ischemia also induces a robust sterile inflammatory response involving local and systemic immune cells. Despite the potent anti-inflammatory effects of estrogen, few studies have investigated the contribution of estrogen to sex differences in the inflammatory response to stroke. This review examines the potential role for estrogen-mediated immunoprotection in ischemic injury. 23543460 Radioiodide induces apoptosis in human thyroid tissue in culture. Radioiodide ((131)I) is routinely used for the treatment of toxic adenoma, Graves' disease, and for ablation of thyroid remnant after thyroidectomy in patients with thyroid cancer. The toxic effects of ionizing radiations on living cells can be mediated by a necrotic and/or apoptotic process. The involvement of apoptosis in radiation-induced cell death in the thyrocytes has been questioned. The knowledge of the mechanisms that underlie the thyrocyte death in response to radiations can help to achieve a successful treatment with the lowest (131)I dose. We developed a method to study the effects of (131)I in human thyroid tissue in culture, by which we demonstrated that (131)I induces thyroid cell apoptosis. Human thyroid tissues of about 1 mm(3) were cultured in vitro and cell viability was determined up to 3 weeks by the MTT assay. Radioiodide added to the culture medium was actively taken up by the tissues. The occurrence of apoptosis in the thyrocytes was assessed by measuring the production of a caspase-cleavage fragment of cytokeratin 18 (M30) by an enzyme-linked immunoassay. Neither variation of cell number nor spontaneous apoptosis was revealed after 1 week of culture. (131)I added to the culture medium induced a dose-dependent and a time-dependent generation of M30 fragment. The apoptotic process was confirmed by the generation of caspase-3 and PARP cleavage products. These results demonstrate that (131)I induces apoptosis in human thyrocytes. Human thyroid tissue cultures may be useful to investigate the cell death pathways induced by (131)I. 22732441 What should we do about student use of cognitive enhancers? An analysis of current evidence. This article reviews current data on the use of cognition enhancers as study aids in the student population. It identifies gaps and uncertainties in the knowledge required to make a balanced assessment of the need for some form of regulation. The review highlights the weak evidence on the prevalence of use of such drugs, especially outside the US, and the ambiguous evidence for their efficacy in a healthy population. Risks are well documented for the commonly used drugs, but poorly appreciated by users. These include not only the side-effects of the drugs themselves, but risks associated with on-line purchase, which offers no guarantees of authenticity and which for some drugs is illegal. The case for urgent action to regulate use is often linked to the belief that new and more effective drugs are likely to appear in the near future. The evidence for this is weak. However, drugs are not the only possible route to neuroenhancement and action is needed to collect more data on the impact of existing drugs, as well as new technologies, in order to guide society in making a proportionate response to the issue. This article is part of a Special Issue entitled 'Cognitive Enhancers'. 23220002 Neuropathy target esterase (NTE): overview and future. Neuropathy target esterase (NTE) was discovered by M.K. Johnson in his quest for the entity responsible for the striking and mysterious paralysis brought about by certain organophosphorus (OP) esters. His pioneering work on OP neuropathy led to the view that the biochemical lesion consisted of NTE that had undergone OP inhibition and aging. Indeed, nonaging NTE inhibitors failed to produce disease but protected against neuropathy from subsequently administered aging inhibitors. Thus, inhibition of NTE activity was not the culprit; rather, formation of an abnormal protein was the agent of the disorder. More recently, however, Paul Glynn and colleagues showed that whereas conventional knockout of the NTE gene was embryonic lethal, conditional knockout of central nervous system NTE produced neurodegeneration, suggesting to these authors that the absence of NTE rather than its presence in some altered form caused disease. We now know that NTE is the 6th member of a 9-protein family called patatin-like phospholipase domain-containing proteins, PNPLA1-9. Mutations in the catalytic domain of NTE (PNPLA6) are associated with a slowly developing disease akin to OP neuropathy and hereditary spastic paraplegia called NTE-related motor neuron disorder (NTE-MND). Furthermore, the NTE protein from affected individuals has altered enzymological characteristics. Moreover, closely related PNPLA7 is regulated by insulin and glucose. These seemingly disparate findings are not necessarily mutually exclusive, but we need to reconcile recent genetic findings with the historical body of toxicological data indicating that inhibition and aging of NTE are both necessary in order to produce neuropathy from exposure to certain OP compounds. Solving this mystery will be satisfying in itself, but it is also an enterprise likely to pay dividends by enhancing our understanding of the physiological and pathogenic roles of the PNPLA family of proteins in neurological health and disease, including a potential role for NTE in diabetic neuropathy. 23318445 Evidence of mitochondrial dysfunction and impaired ROS detoxifying machinery in Fanconi Anemia cells. Fanconi Anemia (FA) is a rare genetic disorder associated with a bone-marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents. Majority of the 15 FA genes and encoded proteins characterized so far are integrated into DNA repair pathways, however, other important functions cannot be excluded. FA cells are sensitive to oxidants, and accumulation of oxidized proteins has been characterized for several FA subgroups. Clinical phenotypes of both FA and other closely related diseases suggest altered functions of mitochondria, organelles responsible for cellular energetic metabolism, and also serving as an important producer and the most susceptible target from reactive oxidative species (ROS). In this study, we have shown that elevated level of mitochondrial ROS in FA cells is in parallel with the decrease of mitochondrial membrane potential, the decrease of ATP production, impaired oxygen uptake and pathological changes in the morphology of mitochondria. This is accompanied by inactivation of enzymes that are essential for the energy production (F1F0ATPase and cytochrome C oxidase) and detoxification of ROS (superoxide dismutase, SOD1). In turn, overexpression of SOD1 could rescue oxygen consumption rate in FA-deficient cells. Importantly, the depletion of mitochondria improved survival rate of mitomycin C treated FA cells suggesting that hypersensitivity of FA cells to chemotherapeutic drugs could be in part due to the mitochondria-mediated oxidative stress. On the basis of our results, we propose that deficiency in FA genes lead to disabling mitochondrial ROS-scavenging machinery further affecting mitochondrial functions and suppressing cell respiration.Oncogene advance online publication, 14 January 2013; doi:10.1038/onc.2012.583. 23452855 Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm. Period determination in the mammalian circadian clock involves the turnover rate of the repressors CRY and PER. We show that CRY ubiquitination engages two competing E3 ligase complexes that either lengthen or shorten circadian period in mice. Cloning of a short-period circadian mutant, Past-time, revealed a glycine to glutamate missense mutation in Fbxl21, an F-box protein gene that is a paralog of Fbxl3 that targets the CRY proteins for degradation. While loss of function of FBXL3 leads to period lengthening, mutation of Fbxl21 causes period shortening. FBXL21 forms an SCF E3 ligase complex that slowly degrades CRY in the cytoplasm but antagonizes the stronger E3 ligase activity of FBXL3 in the nucleus. FBXL21 plays a dual role: protecting CRY from FBXL3 degradation in the nucleus and promoting CRY degradation within the cytoplasm. Thus, the balance and cellular compartmentalization of competing E3 ligases for CRY determine circadian period of the clock in mammals. 23085435 Nitrogen-containing bisphosphonates induce apoptosis of hematopoietic tumor cells via inhibition of Ras signaling pathways and Bim-mediated activation of the intrinsic apoptotic pathway. Nitrogen-containing bisphosphonates (N-BPs) induce apoptosis in tumor cells by inhibiting the prenylation of small G-proteins. However, the details of the apoptosis-inducing mechanism remain obscure. The present study showed that the induction of apoptosis by N-BPs in hematopoietic tumor cells is mediated by mitochondrial apoptotic signaling pathways, which are activated by the suppression of geranylgeranyl pyrophosphate (GGPP) biosynthesis. Furthermore, N-BPs decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and mTOR via suppression of Ras prenylation and enhanced Bim expression. The present results indicated that N-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways. The accumulation of N-BPs in bones suggests that they may act more effectively on tumors that have spread to bones or on Ras-variable tumors. This is the first study to show that the specific molecular pathways of N-BP-induced apoptosis. 23432009 Chemistry and theranostic applications of radiolabeled nanoparticles for cardiovascular, oncological, and pulmonary research. Labeling nanoparticles with radionuclides has been widely used to form multifunctional and multivalency agents for various biomedical applications. A variety of nanostructures including inorganic, organic and lipid nanoparticles have been labeled with positron or gamma emitting radioisotopes through versatile radiochemistry in a number of disease models to track their in vivo fate, image biomarkers, and monitor treatment response. This review briefly summarizes the recent applications of nanoparticles labeled with radionuclides for oncological, cardiovascular, and pulmonary theranostics. 23615074 Tea and human health: The dark shadows. Tea is one of the most popularly consumed beverage. Depending on the manufacturing process, different varieties of tea can be produced. The antioxidative and antimutagenic potential of tea in cardiovascular diseases, cancer and obesity have long been studied. These therapeutic and nutritional benefits of tea can be attributed to the presence of flavanoids. However, these flavanoids also have certain detrimental effects on human health when their consumption exceeds certain limits. The toxicity of these flavanoids can be attributed to the formation of reactive oxygen species in the body which causes damage to the DNA, lipid membranes etc. The aim of this review is to summarize briefly, the less studied evidences of various forms of toxicity associated with tea and its harmful effects on human health. 23584418 The influence of thermal degradation on the electrodeposition of aluminium from an air- and water-stable ionic liquid. Aluminium electrodeposition is demonstrated from a thermally degraded ionic liquid solution. NMR and voltammetric analyses established that Al(3+) reduction was remarkably similar to that in non-degraded IL solutions suggesting that the electroactive metal-containing species was unaffected by heat treatment. Electron microscopy revealed a significant grain refinement of the deposited metal. 23627685 Understanding Morphology-Controlled Synthesis of Zinc Nanoparticles and Their Characteristics of Hydrolysis Reaction. Two-step thermochemical water-splitting cycle based on a Zn/ZnO redox pair is considered as a potential route for carbon-free production of hydrogen because the first hydrolysis step of the cycle highly depends on the method of preparation and the resultant particle characteristics, such as size, morphology, surface state, and initial oxide content. Here, employing a conventional evaporation and condensation method, we successfully produce three types of Zn nanoparticles ranging from nanorods, mesoporous nanorods with nanospheres on their surfaces, and fully sintered nanocrystals. The achievement in morphology control is realized simply by changing the injection position of the quenching gas. We found that the resultant hydrolysis kinetics is highly dependent on the morphology and porosity of the Zn nanoparticles. Finally, a series of simple mathematical modeling is made in an effort to understand the formation mechanism of Zn nanoparticles. 23235151 Mast cells produce novel shorter forms of perlecan that contain functional endorepellin: a role in angiogenesis and wound healing. Mast cells are derived from hematopoietic progenitors that are known to migrate to and reside within connective and mucosal tissues, where they differentiate and respond to various stimuli by releasing pro-inflammatory mediators, including histamine, growth factors, and proteases. This study demonstrated that primary human mast cells as well as the rat and human mast cell lines, RBL-2H3 and HMC-1, produce the heparan sulfate proteoglycan, perlecan, with a molecular mass of 640 kDa as well as smaller molecular mass species of 300 and 130 kDa. Utilizing domain-specific antibodies coupled with N-terminal sequencing, it was confirmed that both forms contained the C-terminal module of the protein core known as endorepellin, which were generated by mast cell-derived proteases. Domain-specific RT-PCR experiments demonstrated that transcripts corresponding to domains I and V, including endorepellin, were present; however, mRNA transcripts corresponding to regions of domain III were not present, suggesting that these cells were capable of producing spliced forms of the protein core. Fractions from mast cell cultures that were enriched for these fragments were shown to bind endothelial cells via the α(2)β(1) integrin and stimulate the migration of cells in "scratch assays," both activities of which were inhibited by incubation with either anti-endorepellin or anti-perlecan antibodies. This study shows for the first time that mast cells secrete and process the extracellular proteoglycan perlecan into fragments containing the endorepellin C-terminal region that regulate angiogenesis and matrix turnover, which are both key events in wound healing. 23608129 Multiple origins for Hound's tongues (Cynoglossum L.) and Navel seeds (Omphalodes Mill.) - The phylogeny of the borage family (Boraginaceae s.str.). Recent studies all indicated that both the affinities and subdivision of Boraginaceae s.str. are unsatisfactorily resolved. Major open issues are the placement and affinities of Boraginaceae s.str. in Boraginales and the major clades of the family, with especially the large tribes Cynoglosseae and Eritrichieae repeatedly retrieved as non-monophyletic groups, and the doubtful monophyly of several larger genera, especially Cynoglossum and Omphalodes. The present study addresses and solves these questions using two plastid markers (trnL-trnF, rps16) on the basis of a sampling including 16 outgroup taxa and 172 ingroup species from 65 genera. The phylogeny shows high statistical support for most nodes on the backbone and on the individual clades. Boraginaceae s.str. are sister to African Wellstediaceae, Wellstediaceae-Boraginaceae s.str. is sister to African Codonaceae. Echiochileae are retrieved as sister to the remainder of Boraginaceae s.str., which, in turn, fall into two major clades, the Boragineae-Lithospermeae (in a well-supported sister relationship) and the Cynoglosseae s.l. (including Eritrichieae). Cynoglosseae s.l. is highly resolved, with Trichodesmeae (incl. Microcaryum, Lasiocaryum) as sister to the remainder of the group. Eritrichieae s.str. (Eritrichium, Hackelia, Lappula) are resolved on a poorly supported polytomy together with the Omphalodes-clade (incl. Myosotidium, Cynoglossum p.p.), and the Mertensia-clade (incl. O. scorpioides, Asperugo). The Myosotideae (Myosotis, Trigonotis, Pseudomertensia) are retrieved in a well-supported sister-relationship to the core-Cynoglosseae, the latter comprising all other genera sampled. Cynoglossum is retrieved as highly para- and polyphyletic, with a large range of generic segregates embedded in Cynoglossum, but other species of Cynoglossum are sister to Microula or to the American "Eritrichieae" (Cryptantha and allied genera). Representatives of the genus Cynoglossum in its current definition are segregated onto six independent lineages, members of Omphalodes onto three independent lineages. At least 11 of the genera here sampled are deeply nested in other genera. The data show that individual details of nutlet morphology (e.g., winged margins, glochidia) are highly homoplasious. Conversely, a complex of nutlet characters (e.g., characters of the gynobase and cicatrix together with nutlet orientation and sculpturing) tends to circumscribe natural units. Geographical distribution of major clades suggests that the family originated in Africa and western Asia and radiated to eastern Eurasia, with several independent dispersal events into Australia and the New World. 23161424 Topoisomerase I inhibitor evodiamine acts as an antibacterial agent against drug-resistant Klebsiella pneumoniae. Topoisomerase inhibitors have been developed in a variety of clinical applications. We investigated the inhibitory effect of evodiamine on E. coli topoisomerase I, which may lead to an anti-bacterial effect. Evodiamine inhibits the supercoiled plasmid DNA relaxation that is catalyzed by E. coli topoisomerase I, and computer-aided docking has shown that the Arg161 and Asp551 residues of topoisomerase I interact with evodiamine. We investigated the bactericidal effect of evodiamine against multidrug-resistant Klebsiella pneumoniae. Evodiamine showed a significantly lower minimal inhibitory concentration value (MIC 128 µg/mL) compared with antibiotics (>512 µg/mL) against the clinical isolate of K. pneumoniae. The results suggested that evodiamine is a potential agent against drug-resistant bacteria. 23288049 Toxicity of the flame-retardant BDE-49 on brain mitochondria and neuronal progenitor striatal cells enhanced by a PTEN-deficient background. Polybrominated diphenyl ethers (PBDEs) represent an important group of flame retardants extensively used, tonnage of which in the environment has been steadily increasing over the past 25 years. PBDEs or metabolites can induce neurotoxicity and mitochondrial dysfunction (MD) through a variety of mechanisms. Recently, PBDEs with < 5 Br substitutions (i.e., 2,2',4,4'-tetrabromodiphenyl ether [BDE-47] and 2,2',4,5'-tetrabromodiphenyl ether [BDE-49]) have gained interest because of their high bioaccumulation. In particular, congeners such as BDE-49 arise as one of the most biologically active, with concentrations typically lower than those observed for BDE-47 in biological tissues; however, its potential to cause MD at biologically relevant concentrations is unknown. To this end, the effect of BDE-49 was studied in brain mitochondria and neuronal progenitor striatal cells (NPC). BDE-49 uncoupled mitochondria at concentrations < 0.1 nM, whereas at > 1 nM, it inhibited the electron transport at Complex V (mixed type inhibition; IC(50) = 6 nM) and Complex IV (noncompetitive inhibition; IC(50) = 40 nM). These concentrations are easily achieved in plasma concentrations considering that BDE-49 (this study, 400-fold) and other PBDEs accumulate 1-3 orders of magnitude in the cells, particularly in mitochondria and microsomes. Similar effects were observed in NPC and exacerbated with PTEN (negative modulator of the PI3K/Akt pathway) deficiency, background associated with autism-like behavior, schizophrenia, and epilepsy. PBDE-mediated MD per se or enhanced by a background that confers susceptibility to this exposure may have profound implications in the energy balance of brain. 23238425 Possible presence of hydrophilic SO3H nanoclusters on the surface of dry ultrathin Nafion® films: a positron annihilation study. Solutions of Nafion® with an ion exchange capacity (IEC) of 0.91 meq g(-1), which are on the verge of the formation of SO(3)H nanoclusters, were spin coated on silicon (Si), glassy carbon (GC) and platinum/silicon (Pt/Si) substrates to form films of up to 256 nm thickness. Nanostructure of the films was studied using Doppler broadening of annihilation radiation (DBAR), positron annihilation lifetime (PAL), X-ray photoelectron spectroscopy (XPS), an atomic force microscope (AFM) and contact angle measurements. Contact angles as low as 10 degrees indicate that the surface of dry ultrathin Nafion® films on Si is highly hydrophilic. XPS data of 10 nm thick, ultrathin film on Si show that oxygen concentration is enhanced and the SO(3)H group concentration, in other words, IEC on the surface is much higher than other films. The S parameter measured by DBAR of an ultrathin Nafion® film on Si is much higher than that of the films on the other substrates. We consider that a large number of hydrophilic, reversed micelle like SO(3)H groups are on the surface of the ultrathin Nafion® film on Si but not on the surface of other films. Positrons implanted into the film are trapped by the SO(3)H clusters, annihilating with the electrons of oxygen and exhibit the high S parameter. The SO(3)H concentration on the surface of thin Nafion® films on GC and Pt/Si substrates may not be so high as the threshold for the formation of a large number of SO(3)H clusters. Positrons implanted into the films annihilate mostly with fluorine atoms, resulting in a low S parameter. The film-substrate interaction plays an essential role in nanostructuring of Nafion® thin films, which may also be the case for Nafion® on the catalysts of polymer electrolyte fuel cells. 23541949 The effects of RFRP-3, the mammalian ortholog of GnIH, on the female pig reproductive axis in vitro. RFamide-related peptide-3 (RFRP-3) has been proposed as a key inhibitory regulator of mammalian reproduction. To further determine the potential mechanisms and sites of action of RFRP-3, we systematically investigated the direct effect of RFRP-3 on the female pig reproductive axis in vitro. Initially, we confirmed that G protein-coupled receptor 147 (GPR147) was distributed in isolated hypothalamic, anterior pituitary and ovarian granulosa cells, suggesting that RFRP-3 could act on these cells in vitro. Subsequently, the direct effects of RFRP-3 on hormone and steroid secretion, the synthesis of subunit genes and the expression of proteins related to proliferation in the hypothalamus, pituitary and ovary were evaluated. Our results demonstrate that different doses of RFRP-3 inhibited the release and synthesis of gonadotrophin releasing hormone, gonadotrophin and steroid hormones and impacted the relative gene expression of KISS1 and GnRHR and the protein expression of cyclin B1, PCNA and ERK 1/2. 23578643 Effect of 5-hydroxymethylfurfural derived from processed Cornus officinalis on the prevention of high glucose-induced oxidative stress in human umbilical vein endothelial cells and its mechanism. The aim of this study was to investigate the protective effect of 5-HMF on human umbilical vein endothelial cells (HUVECs) injured by high glucose in vitro, and the mechanism underlying this process. Our results demonstrated that high glucose-induced oxidative stress in HUVECs was mainly mediated through activation of reactive oxygen species (ROS), Jun N-kinase 2/3 (JNK2/3) and plasma interleukin-8 (IL-8), and inactivation of phosphorylated protein kinase B (P-Akt). Treatment of HUVECs with media containing high glucose (4.5%) in the presence of 5-HMF (100, 200 and 400μM) resulted in significant inhibition of high glucose-induced oxidative stress and expression of JNK1 and JNK2/3. Furthermore, 5-HMF rapidly inhibited high glucose-induced activation of IL-8, a downstream activator of P-Akt. Diabetes mellitus can cause a wide variety of vascular complications and high glucose can induce vascular endothelial cell apoptosis. Free radicals are formed disproportionately in diabetes by glucose oxidation. The finding of this study highlights the pharmacological application of 5-HMF for preventing cardiovascular and diabetes mellitus diseases, and provides the theoretical basis for further development of a Cornus officinalis agent for diabetes-associated vascular diseases. 22751286 Dietary flaxseed oil supplementation ameliorates the effect of cisplatin on brush border membrane enzymes and antioxidant system in rat intestine. Cisplatin (CP; cis-diamminedichloroplatinum II) is a drug widely used against different types of solid tumors. Patients receiving CP, however, experience very profound and long lasting gastrointestinal symptoms. Recently, ω-3 polyunsaturated fatty acid-enriched flaxseed/flaxseed oil (FXO) has shown numerous health benefits. The present study was undertaken to investigate whether FXO can prevent CP-induced adverse biochemical changes in the small intestine of rats. A single intraperitoneal dose of CP (6 mg/kg body weight) was administered to male Wistar rats fed with control diet (CP group) and FXO diet (CPFXO group). Administration of CP led to a significant decline in the specific activities of brush border membrane enzymes both in the mucosal homogenates and in the isolated membrane vesicles. Lipid peroxidation and total sulfhydryl groups were altered upon CP treatment, indicating the generation of oxidative stress. The activities of SOD, catalase and glutathione peroxidase also decreased in CP-treated rats. In contrast, dietary supplementation of FXO prior to and following CP treatment significantly attenuated the CP-induced changes in all these parameters. FXO feeding markedly enhanced resistance to CP-elicited adverse gastrointestinal effects. The results suggest that FXO owing to its intrinsic biochemical/antioxidant properties is an effective agent in reducing the adverse effects of CP on intestine. 23424207 Rutin- and Selenium-attenuated cadmium-induced testicular pathophysiology in rats. Cadmium (Cd) is known to cause oxidative damage in the testes of rats. The aim of this study was to investigate the protective role of rutin (RUT, 30 mg/kg) and selenium (Se, 0.15 ppm) alone or in combination against Cd (200 ppm)-induced lipid peroxidation, steroidogenesis and changes in antioxidant defence system in the rat testes. The obtained results showed that Cd increased lipid peroxidation and abnormal sperm count and decreased plasma testosterone, lactate dehydrogenase, acid phosphatase, alkaline phosphatase and testicular steroidogenic enzymes: 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD activities as well as epididymal sperm counts and motility, while RUT and Se treatment reversed this change to control values. Acute intoxication with Cd was also followed by significantly decreased activity of the antioxidant defence system (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione (GSH), and glutathione-S-transferase (GST)). Treatment with RUT and Se reversed Cd-induced alterations of antioxidant defence system and significantly prevented Cd-induced testes damage and depletion of plasma and testicular Se levels. RUT and Se appear not to have more profound effects than their separate effects against Cd-induced testicular toxicity, although Se was more potent than RUT in the recovery of testosterone levels. These results suggest that both RUT and Se do not have synergistic role against Cd-induced testicular injury. 23122060 A novel mechanism for the promotion of quercetin glycoside absorption by megalo α-1,6-glucosaccharide in the rat small intestine. The presence of an α-1,6-glucosaccharide enhances absorption of water-soluble quercetin glycosides, a mixture of quercetin-3-O-β-d-glucoside (Q3G, 31.8%), mono (23.3%), di (20.3%) and more d-glucose adducts with α-1,4-linkage to a d-glucose moiety of Q3G, in a ligated small intestinal loop of anesthetized rats. We prepared α-1,6-glucosaccharides with different degrees of polymerization (DP) enzymatically and separated them into a megalo-isomaltosaccharide-containing fraction (M-IM, average DP=11.0) and an oligo-isomaltosaccharide-containing fraction (O-IM, average DP=3.6). Luminal injection of either saccharide fraction promoted the absorption of total quercetin-derivatives from the small intestinal segment and this effect was greater for M-IM than O-IM addition. M-IM also increased Q3G, but not the quercetin aglycone, concentration in the water-phase of the luminal contents more strongly than O-IM. The enhancement of Q3G solubilization in the luminal contents may be responsible for the increases in the quercetin glucoside absorption promoted by α-1,6-glucosaccharides, especially that by M-IM. These results suggest that the ingestion of α-1,6-glucosaccharides promotes Q3G bioavailability. 22998180 SiC-CNT composite prepared by electrophoretic codeposition and the polymer infiltration and pyrolysis process. The paper reports on the successful anodic codeposition of submicrometer SiC powder and multiwalled carbon nanotubes from aqueous suspensions to form SiC-CNT composites. On the basis of the comprehensive analysis of the aqueous suspensions with different pHs, solids contents, and CNT contents, optimal conditions for deposition were determined. Besides having the necessary high absolute value of the ζ-potential, the suspensions that resulted in firm deposits were characterized by limited conductivity (<1 mS/cm). Lowering of suspension conductivity was achieved either by dilution of the suspension or by dialysis of the as-received CNT suspension with high intrinsic conductivity. Selected SiC-CNT deposits were further densified by use of the polymer infiltration and pyrolysis process. 23357312 Paeonol suppresses oxidized low-density lipoprotein induced endothelial cell apoptosis via activation of LOX-1/p38MAPK/NF-κB pathway. Paeonol is an active compound isolated from traditional Chinese medicine, and has been shown to have anti-atherosclerosis, anti-inflammatory, antioxidant effects. The present investigation was undertaken to determine the suppression effects of paeonol on oxidized low-density lipoprotein (ox-LDL) induced endothelial cell line HUVEC apoptosis and to uncover some of the underlying mechanisms of these effects. Cell viability and lactate dehydrogenase (LDH) were measured to evaluate the cell injuries. Apoptosis was evaluated by Hoechst 33342 staining and flow cytometry. Intracellular reactive oxygen species (ROS) generation was detected by 2',7'-dichlorofluorescein diacetate (DCFH-DA). Real-time PCR was used to confirm the expression of LOX-1 mRNA. Western blotting was used to evaluate the protein expression of LOX-1 and Bcl-2, as well as caspase-3 cleavage, p38-mitogen-activated protein kinase (p38MAPK) phosphorylation. NF-κB nuclear translocation was detected by Western blotting and immunofluorescence. Caspase-3 activity was measured using a colorimetric protease assay kit. The results showed that ox-LDL significantly decreased cell viability and increased the LDH release, as well as the apoptotic rate (P<0.01). Pre-treatment of paeonol resulted in remarkable increase of cell viability, decrease of LDH release and cell apoptosis in a concentration-dependent manner. Besides, ox-LDL caused the up-regulation of LOX-1, the down-regulation of Bcl-2, the phosphorylation of p38MAPK, the translocation of NF-κB and the activation of caspase-3. Paeonol pre-treatment reversed these effects introduced by ox-LDL. Moreover, paeonol also showed its inhibition effects on ox-LDL induced ROS overproduction. These results indicate the preventive effects of paeonol on ox-LDL induced endothelial cell apoptosis. The effects might, at least partly, be obtained via inhibition of LOX-1-ROS- p38MAPK-NF-κB signaling pathway. 23511383 Effectiveness of in-patient rehabilitation in obesity-related orthopedic conditions. Background: The aim of the present paper is to provide initial evidence that in-patient multidisciplinary rehabilitation is effective in minimizing the obesity-related disability and enhancing functional capacities in obese patients with motor disability. Subjects: 464 obese patients with orthopedic conditions admitted to our Rehabilitation Unit for multidisciplinary rehabilitation were enrolled in this study. Methods: At admission and discharge (after 4 weeks), the following outcome measures were computed: body weight (BW; Kg), body mass index (BMI; Kg/m2), Functional Independence Measure (FIM) motor and cognitive, Obesity-related disability test (TSD-OC), Visual Analogue Score (VAS) for functioning, Timed-Up-Go (TUG). Intensive rehabilitation addressed to obese patients with orthopedic conditions and motor difficulties consisted of a 4-week and 3-hour daily multidisciplinary program covering nutritional, motor and psychological aspects. Results: All of the outcomes measured, except the FIM cognitive score, improved significantly after in-patient rehabilitation. The obesity-specific disability scale appears sensitive to changes among groups with different grades of disability and the percentage of change does not differ among groups. Younger obese individuals generally showed to benefit more from rehabilitation interventions than the older ones. Conclusions: In-patient rehabilitation interventions appear effective in reducing both mild and severe disabilities related to obesity with orthopedic co-morbidities. This paper provides initial evidence that in-patient multidisciplinary intensive rehabilitation is effective in minimizing the obesity-related disability and initial support to the indications of the Italian Ministry of Health for such rehabilitation pathway. The disability grading could help the decision making of allocating patients to appropriate rehabilitation settings. 23237546 Light-triggered biocatalysis using thermophilic enzyme-gold nanoparticle complexes. The use of plasmonic nanoparticle complexes for biomedical applications such as imaging, gene therapy, and cancer treatment is a rapidly emerging field expected to significantly improve conventional medical practices. In contrast, the use of these types of nanoparticles to noninvasively trigger biochemical pathways has been largely unexplored. Here we report the light-induced activation of the thermophilic enzyme Aeropyrum pernix glucokinase, a key enzyme for the decomposition of glucose via the glycolysis pathway, increasing its rate of reaction 60% with light by conjugating the enzyme onto Au nanorods. The observed increase in enzyme activity corresponded to a local temperature increase within a calcium alginate encapsulate of ~20 °C when compared to the bulk medium maintained at standard, nonthermophilic temperatures. The encapsulated nanocomplexes were reusable and stable for several days, making them potentially useful in industrial applications. This approach could significantly improve how biochemical pathways are controlled for in vitro and, quite possibly, in vivo use. 23378626 Absorption, elimination, and metabolism of CS-1036, a novel α-amylase inhibitor in rats and monkeys, and the relationship between gastrointestinal distribution and suppression of glucose absorption. The absorption, metabolism, and excretion of (2R,3R,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-3-yl 4-O-(6-deoxy-β-d-glucopyranosyl)-α-d-glucopyranoside (CS-1036), a novel and potent pancreatic and salivary α-amylase inhibitor, were evaluated in F344/DuCrlCrlj rats and cynomolgus monkeys. The total body clearance and volume of distribution of CS-1036 were low (2.67-3.44 ml/min/kg and 0.218-0.237 l/kg for rats and 2.25-2.84 ml/min/kg and 0.217-0.271 l/kg for monkeys). After intravenous administration of [(14)C]CS-1036 to rats and monkeys, radioactivity was mainly excreted into urine (77.2% for rats and 81.1% for monkeys). After oral administration, most of the radioactivity was recovered from feces (80.28% for rats and 88.13% for monkeys) with a low oral bioavailability (1.73-2.44% for rats and 0.983-1.20% for monkeys). In rats, intestinal secretion is suggested to be involved in the fecal excretion as a minor component because fecal excretion after intravenous administration was observed (15.66%) and biliary excretion was almost negligible. Although intestinal flora was involved in CS-1036 metabolism, CS-1036 was the main component in feces (70.3% for rats and 48.7% for monkeys) and in the intestinal contents (33-68% for rats up to 2 hours after the dose) after oral administration. In Zucker diabetic fatty rats, CS-1036 showed a suppressive effect on plasma glucose elevation after starch loading with a 50% effective dose at 0.015 mg/kg. In summary, CS-1036 showed optimal pharmacokinetic profiles: low oral absorption and favorable stability in gastrointestinal lumen, resulting in suppression of postprandial hyperglycemia by α-amylase inhibition. 23316913 Improved quantum efficiency of highly efficient perovskite BaSnO₃-based dye-sensitized solar cells. Ternary oxides are potential candidates as an electron-transporting material that can replace TiO₂ in dye-sensitized solar cells (DSSCs), as their electronic/optical properties can be easily controlled by manipulating the composition and/or by doping. Here, we report a new highly efficient DSSC using perovskite BaSnO₃ (BSO) nanoparticles. In addition, the effects of a TiCl₄ treatment on the physical, chemical, and photovoltaic properties of the BSO-based DSSCs are investigated. The TiCl₄ treatment was found to form an ultrathin TiO₂ layer on the BSO surface, the thickness of which increases with the treatment time. The formation of the TiO₂ shell layer improved the charge-collection efficiency by enhancing the charge transport and suppressing the charge recombination. It was also found that the TiCl₄ treatment significantly reduces the amount of surface OH species, resulting in reduced dye adsorption and reduced light-harvesting efficiency. The trade-off effect between the charge-collection and light-harvesting efficiencies resulted in the highest quantum efficiency (i.e., short-circuit photocurrent density), leading to the highest conversion efficiency of 5.5% after a TiCl₄ treatment of 3 min (cf. 4.5% for bare BSO). The conversion efficiency could be increased further to 6.2% by increasing the thickness of the BSO film, which is one of the highest efficiencies from non-TiO₂-based DSSCs. 23280620 Evidence of impaired health in yellow perch (Perca flavescens) from a biological mercury hotspot in northeastern North America. Few studies have investigated the effects of mercury (Hg) on wild fish from remote areas, even though these fish can have high total Hg concentrations. In Kejimkujik National Park and National Historic Site (KNPNHS), Nova Scotia, Canada, concentrations of total Hg in many yellow perch (Perca flavescens) currently exceed the estimated threshold level for adverse effects in fish (0.2 µg Hg g(-1) (wet wt), whole body). To determine whether Hg exposure is adversely affecting the general health of these fish, the authors collected male and female perch in the fall of 2009 and 2010 from 12 lakes within KNPNHS. The health endpoints condition, liver somatic index (LSI), and macrophage aggregates (MAs; indicators of oxidative stress and tissue damage) in the liver, kidney, and spleen were examined, and in female perch were compared between lakes and related to Hg concentrations measured in the muscle and liver tissue. No negative relationships between fish condition or LSI and Hg were found. However, within the liver, kidney, and spleen tissues of females, the relative area occupied by MAs was positively related to both muscle and liver Hg concentrations, indicating the health of these perch was adversely affected at the cellular level. These findings raise concerns for the health of these perch as well as for other wild fish populations known to have similarly elevated Hg concentrations. 23438500 Quantitative analysis of the coverage density of Br- ions on Pd{100} facets and its role in controlling the shape of Pd nanocrystals. We report an approach based on a combination of inductively coupled plasma mass spectrometry and X-ray photoelectron spectroscopy for quantitative analysis of the role played by Br(-) ions in the synthesis of Pd nanocrystals. The Br(-) ions were found to adsorb onto Pd{100} facets selectively with a coverage density of ca. 0.8 ion per surface Pd atom. The chemisorbed Br(-) ions could be removed via desorption at an elevated temperature under reductive conditions. They could also be gradually released from the surface when Pd cubic seeds grew into cuboctahedrons and then octahedrons. On the basis of the coverage density information, we were able to estimate the minimum concentration of Br(-) ions needed for the formation of Pd nanocubes with a specific size. If the concentration of Br(-) ions was below this minimum value, not all of the {100} facets could be stabilized by the capping agent, leading to the formation of nanocubes with truncated corners. The quantitative analysis developed in this study is potentially extendable to other systems involving chemisorbed capping agents. 23371760 Resin acid conversion with CYP105A1: an enzyme with potential for the production of pharmaceutically relevant diterpenoids. Cytochrome P450s are very versatile enzymes with great potential for biotechnological applications because of their ability to oxidize unactivated CH bonds. CYP105A1 from Streptomyces griseolus was first described as a herbicide-inducible sulfonylurea hydroxylase, but it is also able to convert other substrates such as vitamin D(3) . To extend the substrate pool of this interesting enzyme further, we screened a small diterpenoid compound library and were able to show the conversion of several resin acids. Binding of abietic acid, dehydroabietic acid, and isopimaric acid to the active site was assayed, and V(max) and K(m) values were calculated. The products were analyzed by NMR spectroscopy and identified as 15-hydroxyabietic acid, 15-hydroxydehydroabietic acid, and 15,16-epoxyisopimaric acid. As the observed products are difficult to obtain by chemical synthesis, CYP105A1 has proved to be a promising candidate for biotechnological applications that combine bioconversion and chemical synthesis to obtain functionalized resin acids. 23194526 Garlic oil attenuates the cardiac apoptosis in hamster-fed with hypercholesterol diet. Hypercholesterolemia is a well established risk factor for cardiac cell apoptosis. The purpose of this study is to evaluate the effects of garlic oil on cardiac apoptosis induced by a hypercholesterol diet. Twenty-four male Golden-Syrian hamsters at 3 months of age were randomly divided into three groups, control, cholesterol and garlic oil groups received a chow diet, chow diet with 2% cholesterol, and chow diet with 2% cholesterol and 1% garlic oil for 8 weeks, respectively. The TUNEL-positive apoptotic cells, and several apoptotic proteins were significantly induced in the excised left ventricle in cholesterol group, whereas significant reduction was observed in cholesterol plus garlic oil group. The IGFI receptor dependent survival pathway was inhibited in cholesterol group whereas it was obviously reversed in cholesterol plus garlic oil group. Our results suggest that administration of garlic oil shows protective effects on cardiac apoptosis in rats with high cholesterol intake. 23461821 Facile synthesis of silver nanoparticles stabilized by cationic polynorbornenes and their catalytic activity in 4-nitrophenol reduction. We report the facile one-pot single-phase syntheses of silver nanoparticles stabilized by norbornene type cationic polymers. Silver nanoparticles (AgNPs) stabilized by polyguanidino oxanorbornenes (PG) at 5 and 25 kDa and polyamino oxanorbornenes (PA) at 3 and 15 kDa have been synthesized by the reduction of silver ions with NaBH4 in aqueous solutions at ambient temperature. The four different silver nanoparticles have been characterized by UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and transmission electron microscopy (TEM) for their particle size distributions. Interestingly, PG stabilizes the silver nanoparticles better than PA as evident from our spectroscopic data. Furthermore, the AgNP-PG-5K (5K = 5 kDa) was found to serve as an effective catalyst for the reduction of 4-nitrophenol to 4-aminophenol in the presence of NaBH4. The reduction has a pseudo-first-order rate constant of 5.50 × 10(-3) s(-1) and an activity parameter of 1375 s(-1) g(-1), which is significantly higher than other systems reported in the literature. 23485417 Hieranoid: Hierarchical Orthology Inference. An accurate inference of orthologs is essential in many research fields such as comparative genomics, molecular evolution, and genome annotation. Existing methods for genome-scale orthology inference are mostly based on all-versus-all similarity searches that scale quadratically with the number of species. This limits their application to the increasing number of available large-scale datasets. Here, we present Hieranoid, a new orthology inference method using a hierarchical approach. Hieranoid performs pairwise orthology analysis using InParanoid at each node in a guide tree as it progresses from its leaves to the root. This concept reduces the total runtime complexity from a quadratic to a linear function of the number of species. The tree hierarchy provides a natural structure in multi-species ortholog groups, and the aggregation of multiple sequences allows for multiple alignment similarity searching techniques, which can yield more accurate ortholog groups. Using the recently published orthobench benchmark, Hieranoid showed the overall best performance. Our progressive approach presents a new way to infer orthologs that combines efficient graph-based methodology with aspects of compute-intensive tree-based methods. The linear scaling with the number of species is a major advantage for large-scale applications and makes Hieranoid well suited to cope with vast amounts of sequenced genomes in the future. Hieranoid is an open source and can be downloaded at Hieranoid.sbc.su.se. 23343117 Mechanism for different fluorescence response of a coumarin-amide-dipicolylamine linkage to Zn(II) and Cd(II) in water. A coumarin-amide-dipicolylamine linkage (L) was synthesized and used as a fluorescent receptor for metal cations in water. The receptor dissolved in water with neutral pH shows almost no fluorescence due to the photoinduced electron transfer (PET) from the amide and amine nitrogens to the excited state coumarin moiety. Coordination of Zn(2+) or Cd(2+) with L creates strong fluorescence at 437 or 386 nm, respectively, due to the suppression of PET. In contrast, other metal cations scarcely show fluorescence enhancement. IR, NMR, and potentiometric analysis revealed that both Zn(2+) and Cd(2+) are coordinated with two pyridine N, amine N, and amide O; however, the Zn(2+) center is also coordinated with a hydroxide anion (OH(-)). The structure difference for Zn and Cd complexes results in longer- and shorter-wavelength fluorescence. Ab initio calculations revealed that π electrons on the excited state Cd complex are delocalized over the molecules and the Cd complex shows shorter-wavelength emission. In contrast, π electrons of OH(-)-coordinated Zn complex are localized on the coumarin moiety. This increases the electron density of coumarin moiety and shows longer-wavelength fluorescence. 23580402 Age-Related Macular Degeneration. Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. 23245516 Overcoming acquired resistance to kinase inhibition: the cases of EGFR, ALK and BRAF. In the past decade, several kinase inhibitors have been approved based on their clinical benefit for cancer patients. Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms. This review will focus on the cases of acquired resistance to EGFR and ALK inhibitors for non-small cell lung cancer patients and BRAF inhibitors for melanoma patients. I will overview the main causes of acquired resistance, and explore the chemical scaffolds as well as combination of drugs, used to tackle these major causes of resistance. 23368777 Eukaryotic initiation factor 5A dephosphorylation is required for translational arrest in stationary phase cells. The protein known as eIF5A (eukaryotic initiation factor 5A) has an elusive role in translation. It has a unique and essential hypusine modification at a conserved lysine residue in most eukaryotes. In addition, this protein is modified by phosphorylation with unknown functions. In the present study we show that a phosphorylated state of eIF5A predominates in exponentially growing Trypanosoma cruzi cells, and extensive dephosphorylation occurs in cells in stationary phase. Phosphorylation occurs mainly at Ser(2), as shown in yeast eIF5A. In addition, a novel phosphorylation site was identified at Tyr(21). In exponential cells, T. cruzi eIF5A is partially associated with polysomes, compatible with a proposed function as an elongation factor, and becomes relatively enriched in polysomal fractions in stationary phase. Overexpression of the wild-type eIF5A, or eIF5A with Ser(2) replaced by an aspartate residue, but not by alanine, increases the rate of cell proliferation and protein synthesis. However, the presence of an aspartate residue instead of Ser(2) is toxic for cells reaching the stationary phase, which show a less-pronounced protein synthesis arrest and a decreased amount of eIF5A in dense fractions of sucrose gradients. We conclude that eIF5A phosphorylation and dephosphorylation cycles regulate translation according to the growth conditions. 23632032 Species tree reconstruction of a poorly resolved clade of salamanders (Ambystomatidae) using multiple nuclear loci. The analysis of diverse data sets can yield different phylogenetic estimates that challenge systematists to explain the source of discordance. The mole salamanders (family Ambystomatidae) are a classic example of this phylogenetic conflict. Previous attempts to resolve the ambystomatid species tree using allozymic, morphological, and mitochondrial sequence data have yielded different estimates, making it unclear which data source best approximates ambystomatid phylogeny and which ones yield phylogenetically inaccurate reconstructions. To shed light on this conflict, we present the first multi-locus DNA sequence-based phylogenetic study of the Ambystomatidae. We utilized a range of analyses, including coalescent-based methods of species-tree estimation that account for incomplete lineage sorting within a locus and concordance-based methods that estimate the number of sampled loci that support a particular clade. We repeated these analyses with the removal of individual loci to determine if any a locus has a disproportionate effect on our phylogenetic results. Collectively, these results robustly resolved many deep and relatively shallow clades within Ambystoma, including the placement of A. gracile and A. talpoideum as the sister clade to a clade containing all remaining ambystomatids, and the placement of A. maculatum as the sister lineage to all remaining ambystomatids excluding A. gracile and A. talpoideum. Both Bayesian coalescent and concordance methods produced similar results, highlighting strongly supported branches in the species tree. Furthermore, coalescent-based analyses that excluded loci produced overlapping species-tree posterior distributions, suggesting that no particular locus - including mtDNA - disproportionately contributed to our species-tree estimates. Overall, our phylogenetic estimates have greater similarity with previous allozyme and mitochondrial sequence-based phylogenetic estimates. However, intermediate depths of divergence in the ambystomatid species tree remain unresolved, potentially highlighting a region of rapid species radiation or a hard polytomy, and which limits our ability to comment on previous morphologically-based taxonomic groups. 23585274 Accurate detection of differential RNA processing. Deep transcriptome sequencing (RNA-Seq) has become a vital tool for studying the state of cells in the context of varying environments, genotypes and other factors. RNA-Seq profiling data enable identification of novel isoforms, quantification of known isoforms and detection of changes in transcriptional or RNA-processing activity. Existing approaches to detect differential isoform abundance between samples either require a complete isoform annotation or fall short in providing statistically robust and calibrated significance estimates. Here, we propose a suite of statistical tests to address these open needs: a parametric test that uses known isoform annotations to detect changes in relative isoform abundance and a non-parametric test that detects differential read coverages and can be applied when isoform annotations are not available. Both methods account for the discrete nature of read counts and the inherent biological variability. We demonstrate that these tests compare favorably to previous methods, both in terms of accuracy and statistical calibrations. We use these techniques to analyze RNA-Seq libraries from Arabidopsis thaliana and Drosophila melanogaster. The identified differential RNA processing events were consistent with RT-qPCR measurements and previous studies. The proposed toolkit is available from http://bioweb.me/rdiff and enables in-depth analyses of transcriptomes, with or without available isoform annotation. 23601389 Development of a regional food composition table for West Africa. Knowledge of the nutrient content of foods is fundamental for virtually all nutrition-related projects, programmes and policies. Low quality compositional data may lead to inappropriate policies and funds spent unnecessarily. Existing food composition tables (FCT) for most West African countries date back to 1960 and 1970 and contain in general few foods and components without documentation. As a result of the recommendations by the Economic Community of West African States (ECOWAS) Nutrition forum and other high level meetings, FAO/INFOODS, WAHO/ECOWAS and Bioversity International developed the West African FCT. It contains 472 foods and 28 components. Emphasis was given to include data on food biodiversity by incorporating cultivars/varieties and underutilized foods. The West African FCT enables users to address diet-related health problems, strengthen local development, enhance trade and promote biodiversity. In addition it contributes to poverty alleviation in both rural and urban areas. The FCT needs to be updated regularly and it is the most recent example of INFOODS for regional food composition activities. 23387865 NMR solution structure study of the representative component hydroxysafflor yellow A and other quinochalcone C-glycosides from Carthamus tinctorius. Hydroxysafflor yellow A (HSYA), a representative component of Carthamus tinctorius, has attracted much attention because of its remarkable cardiovascular activities. Its structure was originally reported in 1993 and has been widely cited to date. In our experiments, its solution structure was studied using NMR techniques in different solvents, including DMSO-d(6), pyridine-d(5), and CD(3)OH. The results indicate that the structure of HSYA is different than the previously described 1b, with 3-enol-1,7-diketo form. The structure has two keto-enol tautomers (2a and 2b), and 2a, with the 1-enol-3,7-diketo form, is the preferred tautomer. On the basis of this finding, other published quinochalcone C-glycoside structures were revised. Furthermore, a trend in the (13)C NMR data of the (E)-olefinic carbons of quinochalcone C-glycosides is summarized, and a hypothesis is proposed for the relationship between the features of the molecular structure and the preferred keto-enol tautomer. 23353058 Occurrence of copper acclimation in the least killifish Heterandria formosa, and associated biochemical and physiological mechanisms. We investigated the occurrence of copper acclimation in the least killifish, Heterandria formosa using both lethal and sublethal endpoints. We also investigated potential mechanisms underlying the observed acclimation. To assess the occurrence of acclimation, fish were exposed to either a background Cu level or to 15 μg/L Cu for seven days and subsequently exposed to a lethal Cu level (150 μg/L Cu). During the latter exposure, fish were monitored for survival till all fish had died, and (during the first 8h of this exposure) for changes in whole-body Na levels and lipid peroxidation (LPO). During the high-level Cu exposure, fish pre-exposed to copper had a significantly longer time-to-death than did the control fish. Similarly, neither whole-body Na nor LPO changed in the Cu-pre-exposed fish during the 8h of the exposure to 150 μg/L Cu - while both decreased significantly in the control fish. Thus, acclimation was evident for both time-to-death and the sublethal endpoints. These results also indicate that Cu toxicity may involve both Na loss and LPO, and that Cu-acclimation may be brought about by prevention of these effects. Our follow-up study on potential mechanisms underlying this copper acclimation used a similar pre-exposure/exposure design. Fish were subsampled at the end of the 7-day acclimation period - just before the commencement of high-level Cu exposure (T), after 4h of this Cu exposure (T), and again after 8h of this Cu exposure (T). Whole-body Cu accumulation, Na/K-ATPase activity, metallothionein levels, and catalase activity were quantified for these time points. While Cu levels were higher in the Cu-pre-exposed fish than in the control fish at T, net Cu accumulation was faster in the control fish than in the Cu-pre-exposed fish during the subsequent high-level Cu exposure. Consequently, changes in Cu accumulation dynamics may play a role in the resistance. Metallothionein induction may also play a role in the observed acclimation, as Cu-acclimated fish had a significantly higher metallothionein concentration compared to the control fish. There was no evidence of involvement of Na/K-ATPase in the acclimation, as the activity of this enzyme remained lower in the pre-exposed fish than in the control fish throughout both Cu exposure periods. There was limited evidence that a reduced loss of catalase activity plays a role in the acclimation; catalase activity did not differ after the pre-exposure period but was significantly higher in Cu-acclimated fish than in the control fish at T. 23265429 Electrodeposition of crystalline GaAs on liquid gallium electrodes in aqueous electrolytes. Crystalline GaAs (c-GaAs) has been prepared directly through electroreduction of As(2)O(3) dissolved in an alkaline aqueous solution at a liquid gallium (Ga(l)) electrode at modest temperatures (T ≥ 80 °C). Ga(l) pool electrodes yielded consistent electrochemical behavior, affording repetitive measurements that illustrated the interdependences of applied potential, concentration of dissolved As(2)O(3), and electrodeposition temperature on the quality of the resultant c-GaAs(s). Raman spectra indicated the composition of the resultant film was strongly dependent on both the electrodeposition temperature and dissolved concentration of As(2)O(3) but not to the applied bias. For electrodepositions performed either at room temperature or with high (≥0.01 M) concentrations of dissolved As(2)O(3), Raman spectra of the electrodeposited films were consistent with amorphous As(s). X-ray diffractograms of As(s) films collected after thermal annealing indicated metallurgical alloying occurred only at temperatures in excess of 200 °C. Optical images and Raman spectra separately showed the composition of the as-electrodeposited film in dilute (≤0.001 M) solutions of dissolved As(2)O(3)(aq) was pure c-GaAs(s) at much lower temperatures than 200 °C. Diffractograms and transmission electron microscopy performed on as-prepared films confirmed the identity of c-GaAs(s). The collective results thus provide the first clear demonstration of an electrochemical liquid-liquid-solid (ec-LLS) process involving a liquid metal that serves simultaneously as an electrode, a solvent/medium for crystal growth, and a coreactant for the synthesis of a polycrystalline semiconductor. The presented data serve as impetus for the further development of the ec-LLS process as a controllable, simple, and direct route for technologically important optoelectronic materials such as c-GaAs(s). 23219161 DNA polymerase POLQ and cellular defense against DNA damage. In mammalian cells, POLQ (pol θ) is an unusual specialized DNA polymerase whose in vivo function is under active investigation. POLQ has been implicated by different experiments to play a role in resistance to ionizing radiation and defense against genomic instability, in base excision repair, and in immunological diversification. The protein is formed by an N-terminal helicase-like domain, a C-terminal DNA polymerase domain, and a large central domain that spans between the two. This arrangement is also found in the Drosophila Mus308 protein, which functions in resistance to DNA interstrand crosslinking agents. Homologs of POLQ and Mus308 are found in multicellular eukaryotes, including plants, but a comparison of phenotypes suggests that not all of these genes are functional orthologs. Flies defective in Mus308 are sensitive to DNA interstrand crosslinking agents, while mammalian cells defective in POLQ are primarily sensitive to DNA double-strand breaking agents. Cells from Polq(-/-) mice are hypersensitive to radiation and peripheral blood cells display increased spontaneous and ionizing radiation-induced levels of micronuclei (a hallmark of gross chromosomal aberrations), though mice apparently develop normally. Loss of POLQ in human and mouse cells causes sensitivity to ionizing radiation and other double strand breaking agents and increased DNA damage signaling. Retrospective studies of clinical samples show that higher levels of POLQ gene expression in breast and colorectal cancer are correlated with poorer outcomes for patients. A clear understanding of the mechanism of action and physiologic function of POLQ in the cell is likely to bear clinical relevance. 23122145 Comparison of the affinity and selectivity of insoluble fibres and commercial proteins for wine proanthocyanidins. The fining action of commercial proteins and insoluble fibres for wine proanthocyanidin (PA) were compared. Fibres were prepared from fresh apple and grape sources, and their corresponding pomaces. PA removal by fibre was via adsorption, and required a higher dose to achieve a fining effect comparable with proteins. A principal component analysis data model revealed that PA molecular mass was significant in defining the fining response, and reflected changes in the proportion of the dominant terminal PA subunits catechin and epicatechin, but not epicatechin-3-O-gallate. For PA extension subunits, changes in epigallocatechin were inversely correlated with epicatechin and epicatechin-3-O-gallate. Generally, the application of proteins and fibres reduced PA molecular mass. Selectivity for PAs by subunit composition was variable between treatments, but differences were minor. This work demonstrates the potential use of fibres as an alternative to proteins in winemaking. Benefits, and possible limitations of such an approach are discussed. 22430207 Minor cell-death defects but reduced tumor latency in mice lacking the BH3-only proteins Bad and Bmf. Proapoptotic Bcl-2 family members of the Bcl-2 homology (BH)3-only subgroup are critical for the establishment and maintenance of tissue homeostasis and can mediate apoptotic cell death in response to developmental cues or exogenously induced forms of cell stress. On the basis of the biochemical experiments as well as genetic studies in mice, the BH3-only proteins Bad and Bmf have been implicated in different proapoptotic events such as those triggered by glucose- or trophic factor-deprivation, glucocorticoids, or histone deacetylase inhibition, as well as suppression of B-cell lymphomagenesis upon aberrant expression of c-Myc. To address possible redundancies in cell death regulation and tumor suppression, we generated compound mutant mice lacking both genes. Our studies revealed lack of redundancy in most paradigms of lymphocyte apoptosis tested in tissue culture. Only spontaneous cell death of thymocytes kept in low glucose or that of pre-B cells deprived of cytokines was significantly delayed when both genes were lacking. Of note, despite these minor apoptosis defects we observed compromised lymphocyte homeostasis in vivo that affected mainly the B-cell lineage. Long-term follow-up revealed significantly reduced latency to spontaneous tumor formation in aged mice when both genes were lacking. Together our study suggests that Bad and Bmf co-regulate lymphocyte homeostasis and limit spontaneous transformation by mechanisms that may not exclusively be linked to the induction of lymphocyte apoptosis. 23535186 Scoparone attenuates d-galactosamine/lipopolysaccharide-induced fulminant hepatic failure through inhibition of toll-like receptor 4 signaling in mice. The purpose of this study was to investigate the protective effects and molecular mechanisms of scoparone on d-galactosamine (d-GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure (FHF) in mice. FHF was induced in mice by intraperitoneal injection of d-GalN (800mg/kg)/LPS (40μg/kg). Mice were treated intraperitoneally with scoparone 1h before d-GalN/LPS treatment. Treatment with d-GalN/LPS markedly increased mortality, serum aminotransferase activity, and tolllike receptor 4 (TLR4) protein expression, and these increases were attenuated by scoparone. Treatment with d-GalN/LPS markedly increased myeloid differentiation primary response gene 88 protein expression, phosphorylation of p38, extracellular signal-regulated kinase and c-Jun N-terminal kinase, nuclear protein expression of nuclear factor κB and phosphorylated c-Jun, and levels of serum tumor necrosis factor-α and interleukin-6 and these increases were attenuated by scoparone. In addition, increased levels of toll-receptor-associated activator of interferon protein expression, phosphorylation of interferon (IFN) regulatory factor 3, and serum IFN-β level in d-GalN/LPS-treated mice were attenuated by scoparone. Our results suggest that scoparone attenuates d-GalN/LPSinduced liver damage by inhibition of the TLR-mediated inflammatory pathway. 23464789 Selective Reduction of PHA Biopolyesters and Their Synthetic Analogues to Corresponding PHA Oligodiols Proved by Structural Studies. A highly selective method is described for controlling the degradation of polyhydroxyalkanoates, PHA, via a reduction reaction that uses lithium borohydride. Using this method, oligo(hydroxyalkanoate)diols derived from a poly(3-hydroxybutyrate-co-4-hydroxybutyrate) biopolyester [poly(3HB-co-4HB)] and from synthetic atactic poly[(R,S)-3-hydroxybutyrate] (a-PHB) were obtained. The structural characterization of the oligo(hydroxyalkanoate)diols was conducted using NMR and ESI-mass spectrometry analyses, which confirmed that oligomers that were terminated by two hydroxyl end groups were formed. The reduction of the ester groups occurred in a statistical way regardless of the chemical structure of the comonomer units or of the microstructure of the polyester chain. The presented method can be used to synthesize various PHA oligodiols that are potentially useful in the further synthesis of tailor-made biodegradable materials. 23579427 Acute alcohol effects on subtypes of impulsivity and the role of alcohol-outcome expectancies. RATIONALE: It is well established that alcohol acutely impairs the ability to inhibit a pre-potent response (motor impulsivity), but its effects on cognitive impulsivity, including temporal (delayed gratification) and reflection (decision making) impulsivity, are not clear. An important factor contributing to the effects of alcohol is cognitive expectancies of alcohol-related outcomes. OBJECTIVES: The current study investigated the effect of alcohol, and alcohol outcome expectancies, on subtypes of impulsivity. METHODS: Impulsivity was tested using the Stop Signal, the Single Key Impulsivity and the Information Sampling Task for motor, temporal and reflection impulsivity, respectively. Participants (n = 48) received placebo, a low (0.4 g/kg) or high dose (0.8 g/kg) of alcohol, before completing the impulsivity measures. RESULTS: Motor impulsivity was affected by alcohol dose; participants receiving a high dose displayed reduced inhibitory control. Reflection impulsivity was affected by cognitive alcohol expectancies, but not by alcohol condition; participants expecting greater cognitive and behavioural impairment by alcohol exhibited low impulsivity. Temporal impulsivity was not affected by either alcohol dose or outcome expectancies. CONCLUSIONS: These data suggest that the effects of alcohol on the subtypes of impulsivity are dissociable. Motor impulsivity is sensitive to the pharmacological effects of alcohol, whereas the reflection subtype is affected by cognitive alcohol expectancies. The findings have implications for the understanding of impulsive behaviour under the influence of alcohol. 23499614 Phylogeny and phylogeography of Mantophryne (Anura: Microhylidae) reveals cryptic diversity in New Guinea. New Guinea is one of five high biodiversity wilderness areas, and frog diversity is exceptionally large, with more than 400 species described to date. The microhylid frog genus Mantophryne is endemic to New Guinea and consists of four species, three of which have narrow geographic distributions and a fourth, M. lateralis, with a broad range that spans the eastern half of the island. Here, we sequence 104 Mantophryne samples for three mitochondrial and three nuclear loci to reconstruct the first phylogeny of the genus and to examine spatial patterns of diversity within M. lateralis. Results indicate that the wide-ranging M. lateralis is composed of at least nine geographically separated and well-supported lineages that represent putative species. Biogeographic analysis suggests that Mantophryne evolved on the eastern Papuan peninsula with subsequent dispersal westward, as well as overwater dispersal events to the Louisiade and D'Entrecasteaux archipelagos. 23368510 Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin. AIM: Assess the pharmacodynamics of lixisenatide once daily (QD) versus liraglutide QD in type 2 diabetes insufficiently controlled on metformin. METHODS: In this 28-day, randomized, open-label, parallel-group, multicentre study (NCT01175473), patients (mean HbA1c 7.3%) received subcutaneous lixisenatide QD (10 µg weeks 1-2, then 20 µg; n = 77) or liraglutide QD (0.6 mg week 1, 1.2 mg week 2, then 1.8 mg; n = 71) 30 min before breakfast. Primary endpoint was change in postprandial plasma glucose (PPG) exposure from baseline to day 28 during a breakfast test meal. RESULTS: Lixisenatide reduced PPG significantly more than liraglutide [mean change in AUC(0) (:30-4:30h) : -12.6 vs. -4.0 h/mmol/l, respectively; p < 0.0001 (0:30 h = start of meal)]. Change in maximum PPG excursion was -3.9 mmol/l vs. -1.4 mmol/l, respectively (p < 0.0001). More lixisenatide-treated patients achieved 2-h PPG <7.8 mmol/l (69% vs. 29%). Changes in fasting plasma glucose were greater with liraglutide (-0.3 vs. -1.3 mmol/l, p < 0.0001). Lixisenatide provided greater decreases in postprandial glucagon (p < 0.05), insulin (p < 0.0001) and C-peptide (p < 0.0001). Mean HbA1c decreased in both treatment groups (from 7.2% to 6.9% with lixisenatide vs. 7.4% to 6.9% with liraglutide) as did body weight (-1.6 kg vs. -2.4 kg, respectively). Overall incidence of adverse events was lower with lixisenatide (55%) versus liraglutide (65%), with no serious events or hypoglycaemia reported. CONCLUSIONS: Once daily prebreakfast lixisenatide provided a significantly greater reduction in PPG (AUC) during a morning test meal versus prebreakfast liraglutide. Lixisenatide provided significant decreases in postprandial insulin, C-peptide (vs. an increase with liraglutide) and glucagon, and better gastrointestinal tolerability than liraglutide. 23576306 Carboxylate-Assisted Formation of Alkylcarbonate Species from CO2 and Tetramethylammonium Salts with a β-Amino Acid Anion. Tetramethylammonium-based molten salts bearing a β-amino acid anion (TMAAs) are synthesized through Michael addition reactions of amines with methyl acrylate followed by hydrolysis and subsequent neutralization by using aqueous tetramethylammonium hydroxide. The CO2 capture performances of the TMAAs are evaluated and are shown to interact with CO2 in a 1:1 mode in both water and alcohol. FTIR and (13) C NMR spectroscopic studies on the interactions of TMAAs with CO2 indicate that the type of CO2 adduct varies with the solvent used. When water is used as the solvent, a bicarbonate species is produced, whereas hydroxyethylcarbonate and methylcarbonate species are generated in ethylene glycol and methanol, respectively. Computational calculations show that the carboxylate groups of TMAAs contribute towards the formation and stabilization of 1:1 CO2 adducts through hydrogen bonding interactions with the hydrogen atoms of the amino groups. 23052192 Hard-metal (WC-Co) particles trigger a signaling cascade involving p38 MAPK, HIF-1α, HMOX1, and p53 activation in human PBMC. Hard-metals are made of tungsten carbide (WC) and metallic cobalt (Co) particles and are important industrial materials produced for their extreme hardness and high wear resistance properties. While occupational exposure to metallic Co alone is apparently not associated with an increased risk of cancer, the WC-Co particle mixture was shown to increase the risk of lung cancer in exposed workers. We have previously shown that WC-Co specifically induces a burst of reactive oxygen species (ROS) and in vitro mutagenic/apoptogenic effects in human peripheral blood mononucleated cells (PBMC) used as a validated experimental model. In the present study, PBMCs were treated during a short period (15 min) to focus on the very rapid ROS burst induced by WC-Co. We investigated by microarray the response to WC-Co versus Co(2+) ions (CoCl(2)) after 15 min exposure and found that the oxidative stress response HMOX1 gene was highly expressed in WC-Co-treated samples. This result was confirmed by qRT-PCR, and western blotting was carried out to analyze translational and post-translational regulation of genes belonging to the HMOX1 pathway. We show here that WC-Co, and metallic Co particles although with slower kinetics, but not CoCl(2) or WC alone, induced a temporally ordered cascade of events. This cascade implies p38/MAP kinase activation, HIF-1α stabilization, HMOX1 transcriptional activation, and ATM-independent p53 stabilization. These events, and in particular HIF-1α stabilization, could contribute to the carcinogenic activity of WC-Co dusts. 23495151 A cellular automata model of proton hopping down a channel. Proton hopping is the process where a H-atom on a hydronium ion forms a H-bond with the O-atom of a neighboring H(2)O molecule. There is then an exchange of bonding forces when that covalent bond of the H-atom in the hydronium ion changes to a H-bond, and the previous H-bond changes to a covalent bond with the neighboring O-atom. The neighboring molecule now becomes a hydronium (H(3)O(+)) ion. This process repeats itself very rapidly among neighboring hydronium and H(2)O molecules. There is a flow of protonic character through bulk H(2)O, referred to as proton hopping. This process carries information through living systems where H(2)O is present. A cellular automata model of proton hopping down a channel has been created and studied. Variations in the rate of proton entry into the channel and the effects of the polar character of the channel walls was studied using the model. The behavior of the models corresponds to experimental results. 23455592 Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin/orphanin FQ limiting its ability to reduce binge eating in female rats. RATIONALE: Nociceptin/orphanin FQ (N/OFQ) is a functional antagonist of corticotrophin-releasing factor, the main mediator of the stress response. Stress represents a key determinant of binge eating (BE) for highly palatable food (HPF). OBJECTIVES: In relation to the antistress properties of N/OFQ, we evaluated its effect on BE. After the observation that episodes of food restriction increase the sensitivity to its hyperphagic effects, the function of NOP receptor and N/OFQ was investigated after cycles of food restrictions. MATERIALS AND METHODS: In BE experiments, four groups were used: rats fed normally and not stressed or stressed, rats exposed to cycles of restriction/refeeding and then stressed, or not stressed. In the other experiments, two groups were used: rats exposed or not to food restriction. RESULTS: Only restricted and stressed rats exhibited BE for HPF (containing chocolate cream). Intracerebroventricular injections of N/OFQ of 0.5 nmol/rat significantly reduced BE. N/OFQ 1 nmol/rat did not reduce BE but significantly increased HPF intake following food restrictions. Cycles of food restriction increased animals' sensitivity to the hyperphagic effect of N/OFQ for HPF. In situ hybridization studies following food restrictions showed decreased ppN/OFQ mRNA expression in the bed nucleus of the stria terminalis and increased expression of ppN/OFQ and NOP receptor mRNA in the ventral tegmental area and in the ventromedial hypothalamus, respectively. CONCLUSIONS: These findings indicate that N/OFQ slightly reduces BE at low doses, while higher doses increase HPF intake, due to increased sensitivity to its hyperphagic effect following a history of caloric restrictions. 23376245 Inhibition of protein tyrosine phosphatases in spinal dorsal horn attenuated inflammatory pain by repressing Src signaling. Tyrosine phosphorylation of N-methyl-d-aspartate (NMDA) subtype glutamate receptors by Src-family protein tyrosine kinases (SFKs) plays a critical role in spinal sensitization. Besides SFKs, the tyrosine phosphorylation levels of proteins are also determined by protein tyrosine phosphatases (PTPs). However, whether PTPs are involved in spinal nociceptive processing is largely unknown. The present study found that intrathecal application of broad-spectrum PTPs inhibitors orthovanadate or Bpv (phen) generated little effects on the paw withdrawal thresholds of intact rats to Von Frey filament stimuli. Although the basal nociceptive responses didn't require the involvement of PTPs, the mechanical allodynia evoked by intrathecal injection of NMDA was greatly attenuated by orthovanadate and Bpv (phen), suggesting that PTPs activity, once stimulated by NMDA receptors, became essential for spinal sensitization. Biochemical analysis demonstrated that PTPs functioned to activate SFKs member Src and promote Src interaction with NR2B subunit-containing NMDA receptors (NR2B receptors). As a result, PTPs inhibition largely suppressed Src-mediated NR2B phosphorylation at Tyr1472 and reduced the synaptic concentration of NR2B receptors in spinal dorsal horn of NMDA-treated rats. Importantly, intraplantar injection of Complete Freund's Adjuvant (CFA) naturally activated spinal PTPs to initiate Src signaling, because PTPs inhibition significantly repressed Src activity, reduced Src phosphorylation of NR2B, decreased NR2B synaptic accumulation and eventually ameliorated inflammatory pain. These data indicated an important role played by spinal PTPs in inducing Src-dependent NR2B receptor hyperfunction and suggested that PTPs inhibition might represent an effective strategy for the treatment of inflammatory pain. 23123254 Assessing protection against OP pesticides and nerve agents provided by wild-type HuPON1 purified from Trichoplusia ni larvae or induced via adenoviral infection. Human paraoxonase-1 (HuPON1) has been proposed as a catalytic bioscavenger of organophosphorus (OP) pesticides and nerve agents. We assessed the potential of this enzyme to protect against OP poisoning using two different paradigms. First, recombinant HuPON1 purified from cabbage loopers (iPON1; Trichoplusia ni) was administered to guinea pigs, followed by exposure to at least 2times the median lethal dose (LD50) of the OP nerve agents tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF), or chlorpyrifos oxon, the toxic metabolite of the OP pesticide chlorpyrifos. In the second model, mice were infected with an adenovirus that induced expression of HuPON1 and then exposed to sequential doses of GD, VX, or (as reported previously) diazoxon, the toxic metabolite of the OP pesticide diazinon. In both animal models, the exogenously added HuPON1 protected animals against otherwise lethal doses of the OP pesticides but not against the nerve agents. Together, the results support prior modeling and in vitro activity data which suggest that wild-type HuPON1 does not have sufficient catalytic activity to provide in vivo protection against nerve agents. 23473681 Degradation of MAC13243 and studies of the interaction of resulting thiourea compounds with the lipoprotein targeting chaperone LolA. The discovery of novel small molecules that function as antibacterial agents or cellular probes of biology is hindered by our limited understanding of bacterial physiology and our ability to assign mechanism of action. We previously employed a chemical genomic strategy to identify a novel small molecule, MAC13243, as a likely inhibitor of the bacterial lipoprotein targeting chaperone, LolA. Here, we report on the degradation of MAC13243 into the active species, S-(4-chlorobenzyl)isothiourea. Analogs of this compound (e.g., A22) have previously been characterized as inhibitors of the bacterial actin-like protein, MreB. Herein, we demonstrate that the antibacterial activity of MAC13243 and the thiourea compounds are similar; these activities are suppressed or sensitized in response to increases or decreases of LolA copy number, respectively. We provide STD NMR data which confirms a physical interaction between LolA and the thiourea degradation product of MAC13243, with a Kd of ~150 μM. Taken together, we conclude that the thiourea series of compounds share a similar cellular mechanism that includes interaction with LolA in addition to the well-characterized target MreB. 23139413 Long range effect of mutations on specific conformational changes in the extracellular loop 2 of angiotensin II type 1 receptor. The topology of the second extracellular loop (ECL2) and its interaction with ligands is unique in each G protein-coupled receptor. When the orthosteric ligand pocket located in the transmembrane (TM) domain is occupied, ligand-specific conformational changes occur in the ECL2. In more than 90% of G protein-coupled receptors, ECL2 is tethered to the third TM helix via a disulfide bond. Therefore, understanding the extent to which the TM domain and ECL2 conformations are coupled is useful. To investigate this, we examined conformational changes in ECL2 of the angiotensin II type 1 receptor (AT1R) by introducing mutations in distant sites that alter the activation state equilibrium of the AT1R. Differential accessibility of reporter cysteines introduced at four conformation-sensitive sites in ECL2 of these mutants was measured. Binding of the agonist angiotensin II (AngII) and inverse agonist losartan in wild-type AT1R changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific "lid" conformations of ECL2. Without agonist stimulation, the ECL2 in the gain of function mutant N111G assumed a lid conformation similar to AngII-bound wild-type AT1R. In the presence of inverse agonists, the conformation of ECL2 in the N111G mutant was similar to the inactive state of wild-type AT1R. In contrast, AngII did not induce a lid conformation in ECL2 in the loss of function D281A mutant, which is consistent with the reduced AngII binding affinity in this mutant. However, a lid conformation was induced by [Sar(1),Gln(2),Ile(8)] AngII, a specific analog that binds to the D281A mutant with better affinity than AngII. These results provide evidence for the emerging paradigm of domain coupling facilitated by long range interactions at distant sites on the same receptor. 23546525 Azidoacetylene - interpretation of gas phase infrared spectra based on high-level vibrational configuration interaction calculations. Azidoacetylene is a highly explosive substance, which has been synthesized and characterized for the first time quite recently [Banert et al., Angew. Chem., Int. Ed., 2012, 51, 7515]. As outlined in this work, the vibrational spectrum of azidoacetylene is dominated by strong couplings. For that reason, we have studied the vibrational spectrum of the title compound by gas phase measurements and high-level vibrational structure calculations beyond the harmonic approximation. Based on the interplay of theory and experiment, we were able to identify all fundamentals, strong Fermi resonances and intense overtones, which contribute to the spectrum. 23591777 Hepatoprotective effect of methylsulfonylmethane against carbon tetrachloride-induced acute liver injury in rats. This study evaluated the effect of methylsulfonylmethane (MSM) on carbon tetrachloride (CCl4)-induced acute liver injury in rats. A single injection of CCl4 (2 ml/kg, i.p.) increased serum aminotransferases (ALT and AST) activities. In addition, CCl4 treatment led to elevation of hepatic malondialdehyde (MDA) content as well as decrease in superoxide dismutase (SOD) and catalase (CAT) activities. Furthermore, cytochrome P450 2E1 (CYP2E1) content was suppressed while proinflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels increased in liver tissue after CCl4 administration. We showed that acute CCl4-induced damage was accompanied by a rise in Bax/Bcl2 ratio indicating apoptosis. Pre-treatment with MSM (400 mg/kg) inhibited the increases of serum ALT and AST activities, decreased hepatic MDA, TNF-α, IL-6 and Bax/Bcl2 ratio compared to CCl4 treated group. On the other hand, MSM raised SOD and CAT activities as well as CYP2E1 level in liver tissues. The present study shows that MSM possesses a hepatoprotective effect against CCl4-induced liver injury in rats. This protective effect might be through its antioxidant, anti-inflammatory and antiapoptotic properties. 23012257 DCPIB, the proposed selective blocker of volume-regulated anion channels, inhibits several glutamate transport pathways in glial cells. 4-(2-Butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid (DCPIB) was identified as the selective blocker of volume-regulated anion channels (VRAC). VRAC are permeable to small inorganic and organic anions, including the excitatory neurotransmitter glutamate. In recent years DCPIB has been increasingly used for probing the physiologic and pathologic roles of VRAC and was found to potently suppress pathologic glutamate release in cerebral ischemia. Because ischemic glutamate release can be mediated by a plethora of mechanisms, in this study we explored the selectivity of DCPIB toward the majority of previously identified glutamate transporters and permeability pathways. l-[(3)H]glutamate, d-[(3)H]aspartate, and l-[(14)C]cystine were used to trace amino acid release and uptake. We found that in addition to its well-characterized effect on VRAC, DCPIB potently inhibited glutamate release via connexin hemichannels and glutamate uptake via the glutamate transporter GLT-1 in rat glial cells. In contrast, DCPIB had no direct effect on vesicular glutamate release from rat brain synaptosomes or the cystine/glutamate exchange in astrocytes. The compound did not affect the astrocytic glutamate transporter GLAST, nor did it block glutamate release via the P2X(7)/pannexin permeability pathway. The ability of DCPIB to directly block connexin hemichannels was confirmed using a gene-specific siRNA knockdown approach. Overall, our data demonstrate that DCPIB influences several glutamate transport pathways and that its effects on VRAC in vivo should be verified using additional pharmacological controls. 23477451 Isocoumarin Derivatives and Benzofurans from a Sponge-Derived Penicillium sp. Fungus. Ten new fungal metabolites, including three hydroisocoumarins, penicimarins A-C (1-3), three isocoumarins, penicimarins D-F (6-8), and four benzofurans, penicifurans A-D (11-14), together with four known isocoumarin derivatives (4, 5, 9, 10), were obtained from the sponge-derived fungus Penicillium sp. MWZ14-4, collected from the South China Sea. Their planar structures and relative configurations were elucidated by detailed analysis of spectroscopic data and by comparison with related known compounds. The absolute configurations of 1-4 were assigned by the modified Mosher's method and TDDFT ECD calculations together with comparison of their CD spectra. Compound 1 represents a rare naturally occurring isocoumarin derivative with 4-substitution, but no substituent at the 3-position. These compounds were evaluated for antibacterial activities and cytotoxic activities in vitro. Among them, penicifuran A (11) exhibited inhibitory activity against Staphylococcus albus with an MIC value of 3.13 μM. 23386599 The role of human carboxylesterases in drug metabolism: have we overlooked their importance? Carboxylesterases are a multigene family of mammalian enzymes widely distributed throughout the body that catalyze the hydrolysis of esters, amides, thioesters, and carbamates. In humans, two carboxylesterases, hCE1 and hCE2, are important mediators of drug metabolism. Both are expressed in the liver, but hCE1 greatly exceeds hCE2. In the intestine, only hCE2 is present and highly expressed. The most common drug substrates of these enzymes are ester prodrugs specifically designed to enhance oral bioavailability by hydrolysis to the active carboxylic acid after absorption from the gastrointestinal tract. Carboxylesterases also play an important role in the hydrolysis of some drugs to inactive metabolites. It has been widely believed that drugs undergoing hydrolysis by hCE1 and hCE2 are not subject to clinically significant alterations in their disposition, but evidence exists that genetic polymorphisms, drug-drug interactions, drug-disease interactions and other factors are important determinants of the variability in the therapeutic response to carboxylesterase-substrate drugs. The implications for drug therapy are far-reaching, as substrate drugs include numerous examples from widely prescribed therapeutic classes. Representative drugs include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antiplatelet drugs, statins, antivirals, and central nervous system agents. As research interest increases in the carboxylesterases, evidence is accumulating of their important role in drug metabolism and, therefore, the outcomes of pharmacotherapy. 23411189 Determination of ethylenediaminetetraacetic acid in foods by reversed-phase high-performance liquid chromatography. A convenient HPLC method for the quantitative determination of EDTA in foods was developed. EDTA in food samples was easily extracted with water by ultrasonication. After converting to Fe(III) complex in the presence of Fe(III) ions, EDTA was separated on a reversed-phase C30 column and detected with ultraviolet detection (260 nm). Citrate and malate, which are present in many foods, also formed Fe(III) complexes but they did not interfere the chromatographic detection of EDTA. The method allowed determination of EDTA in foods at concentrations as low as 0.01 mmol/kg. Good recoveries (95.2-101%) were obtained by the standard addition method on four samples with high repeatability (RSD, 0.8-3.4%). The method was successfully applied to the analysis of EDTA in carbonated drinks, jellies, canned beans, canned corn and food supplements. 23411239 Development of apple certified reference material for quantification of organophosphorus and pyrethroid pesticides. An apple certified reference material for the analysis of pesticide residues was issued by the National Metrology Institute of Japan. Organophosphorus and pyrethroid pesticides were sprayed on apples, and these were used as raw materials of certified reference material. The harvested apples were cut into small pieces, freeze-dried, pulverized, sieved, placed into 200 brown glass bottles (3g each), and sterilized by γ-irradiation. Stability and homogeneity assessment was performed, and the relative uncertainties due to instability (for an expiry date of 32 months) and inhomogeneity were 10.3-25.0% and 4.0-6.8%, respectively. The characterization was carried out using multiple analytical methods to ensure the reliability of analytical results; the values of target pesticides were obtained by isotope dilution mass spectrometry. Certified values were 2.28 ± 0.82 mg/kg for diazinon, 3.14 ± 0.79 mg/kg for fenitrothion, 1.55 ± 0.81 mg/kg for cypermethrin, and 2.81 ± 0.70 mg/kg for permethrin. 23583775 Unraveling Hidden Regulatory Sites in Structurally Homologous Metalloproteases. Monitoring enzymatic activity in vivo of individual homologous enzymes such as the matrix metalloproteinases (MMPs) by antagonist molecules is highly desired for defining physiological and pathophysiological pathways. However, the rational design of antagonists targeting enzyme catalytic moieties specific to one of the homologous enzymes often appears to be an extremely difficult task. This is mainly due to the high structural homology at the enzyme active sites shared by members of the protein family. Accordingly, controlling enzymatic activity via alternative allosteric sites has become an attractive proposition for drug design targeting individual homologous enzymes. Yet, the challenge remains to identify such regulatory alternative sites that are often hidden and scattered over different locations on the protein's surface. We have designed branched amphiphilic molecules exhibiting specific inhibitory activity towards individual members of the MMP family. These amphiphilic isomers share the same chemical nature, providing versatile nonspecific binding reactivity that allows to probe hidden regulatory residues on a given protein surface. Using the advantage provided by amphiphilic ligands, here we explore a new approach for determining hidden regulatory sites. This approach includes diverse experimental analysis, such as structural spectroscopic analyses, NMR, and protein crystallography combined with computational prediction of effector binding sites. We demonstrate how our approach works by analyzing members of the MMP family that possess a unique set of such sites. Our work provides a proof of principle for using ligand effectors to unravel hidden regulatory sites specific to members of the structurally homologous MMP family. This approach may be exploited for the design of novel molecular effectors and therapeutic agents affecting protein catalytic function via interactions with structure-specific regulatory sites. 23322164 Carnitine palmitoyltransferase 2 and carnitine/acylcarnitine translocase are involved in the mitochondrial synthesis and export of acylcarnitines. Acylcarnitines are commonly used in the diagnosis of mitochondrial fatty acid β-oxidation disorders (mFAODs). It is generally assumed that this plasma acylcarnitine profile reflects the mitochondrial accumulation of acyl-CoAs. The identity of the enzymes and the mitochondrial and plasmalemmal transporters involved in the synthesis and export of these metabolites have remained undefined. We used lentiviral shRNA to knock down the expression of medium-chain acyl-CoA dehydrogenase (MCAD) in control and carnitine palmitoyltransferase 2 (CPT2)-, carnitine/acylcarnitine translocase (CACT)-, and plasmalemmal carnitine transporter (OCTN2)-deficient human fibroblasts. These cell lines, including mock-transduced controls, were loaded with decanoic acid and carnitine, followed by the measurement of the acylcarnitine profile in the extracellular medium. In control fibroblasts, MCAD knockdown markedly increased the production of octanoylcarnitine (3-fold, P<0.01). OCTN2-deficient cell lines also showed extracellular accumulation of octanoylcarnitine (2.8-fold, P<0.01), suggesting that the cellular export of acylcarnitines does not depend on OCTN2. In contrast, in CPT2- and CACT-deficient cells, the accumulation of octanoylcarnitine in the medium did not significantly increase in the MCAD knockdown. Similar results were obtained using pharmacological inhibition of CPT2 in fibroblasts from MCAD-deficient individuals. This shows that CPT2 and CACT are crucial for mitochondrial acylcarnitine formation and export to the extracellular fluids in mFAOD.-Violante, S., IJlst, L., te Brinke, H., Tavares de Almeida, I., Wanders, R. J. A., Ventura, F. V., Houten, S. M. Carnitine palmitoyltransferase 2 and carnitine/acylcarnitine translocase are involved in the mitochondrial synthesis and export of acylcarnitines. 23266501 In vitro anti-inflammatory effect of apigenin in the Helicobacter pylori-infected gastric adenocarcinoma cells. Infection with Helicobacter pylori causes extensive gastric epithelial cell inflammation which may progress to atrophic gastritis, intestinal metaplasia, and even gastric adenocarcinoma. Apigenin (4',5,7-trihydroxyflavone) is widely distributed in fruits and vegetables, and is a well-known antiinflammatory supplement with low cytotoxicity. In this study, we investigated the anti-inflammatory effects of apigenin in H. pylori-infected MKN45 cells, for which IκBα, cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), reactive oxygen species (ROS), interleukin-8 (IL-8), IL-6, IL-1β, and mucin-2 (MUC-2) expressions were examined. Apigenin treatments (9.3-74 μM) significantly increased the IκBα expression, and thus inhibited nuclear factor kappa B (NF-κB) activation, and the inflammatory factor (COX-2, ICAM-1, ROS, IL-6, and IL-8) expressions decreased. The ROS levels decreased partially based on the intrinsic scavenging property of apigenin. In summary, apigenin treatments effectively inhibited NF-κB activation and the related inflammatory factor expressions, as well as increased MUC-2 expression in the H. pylori-infected MKN45 cells. The compound shows great potential as a candidate agent for the inhibition of H. pylori-induced extensive gastric epithelial cell inflammation. 23489301 Cardiovascular safety of the dipetidyl peptidase-4 inhibitor alogliptin in type 2 diabetes mellitus(†) AIM: As there have been concerns that some classes or agents for the treatment of type 2 diabetes may increase CV risk, we evaluated the cardiovascular profile of the dipeptidyl peptidase-4 inhibitor alogliptin. METHODS: We evaluated the incidence of CV events in patients treated with alogliptin, placebo or comparator antihyperglycaemic drugs in the clinical trial database for alogliptin using the composite major adverse cardiovascular event (MACE) endpoints of CV death, non-fatal myocardial infarction and non-fatal stroke. RESULTS: The pooled analysis included 4168 patients exposed to alogliptin 12.5 and 25 mg daily for 2023 patient-years compared to 691 patients treated with placebo for 263 patient-years and 1169 patients treated with other antidiabetic agents (metformin, sulfonylureas and thiazolidinediones) for 703 patient-years. CV events were adjudicated by an expert endpoint committee blinded to treatment allocation. The incidence rates of the combined MACE were not significantly different between patients treated with alogliptin and comparator therapies (hazard ratio=0.635, 95% confidence interval, 0.0, 1.41). Additionally, other types of serious CV events were not significantly different between patients treated with alogliptin and comparator therapies. CONCLUSION: These analyses have not shown a signal of increased CV risk with alogliptin in patients with type 2 diabetes. Future results from the adequately powered EXAMINE trial will definitively assess the CV safety profile of aloglipin in patients with type 2 diabetes mellitus. 23410105 Toward a physically based quantitative modeling of impact sensitivities. Among the subsequent steps leading from impact to explosive decomposition in nitro compounds, the ability of early exothermic reactions to trigger the decomposition of neighboring molecules before the released energy has dissipated away is assumed to be critical. The rate of this process is roughly estimated using as inputs the energy content and the dissociation energy of the weakest X-NO2 bonds. While the sensitivity index thus obtained was previously shown to exhibit striking correlations with gap test pressures, its correlation with drop weight impact test data is poorer. Nevertheless, considering four different subsets of molecules depending on the environment of the most labile nitro groups, straightforward regressions against this sensitivity index yield a practical method to estimate impact sensitivity, whose combination of fair performance and generality is provided by no alternative approach, except purely empirical models based on extensive parametrization. 23135892 Protein-size molecularly imprinted polymer nanogels as synthetic antibodies, by localized polymerization with multi-initiators. A new approach is proposed for the synthesis of molecularly imprinted polymers (MIPs) (synthetic antibodies) as soluble nanogels with sizes close to the size of real antibodies. To imprint a molecular memory in particles consisting of only a few polymer chains, an initiator carrying multiple iniferter moieties is used. This allows for the simultaneous initiation of several polymer chains, and yields molecularly imprinted nanogels (17 nm, molecular weight (MW) = 97 kDa) with good affinity and selectivity for the target. 23343325 Effective optical Faraday rotations of semiconductor EuS nanocrystals with paramagnetic transition-metal ions. Novel EuS nanocrystals containing paramagnetic Mn(II), Co(II), or Fe(II) ions have been reported as advanced semiconductor materials with effective optical rotation under a magnetic field, Faraday rotation. EuS nanocrystals with transition-metal ions, EuS:M nanocrystals, were prepared by the reduction of the Eu(III) dithiocarbamate complex tetraphenylphosphonium tetrakis(diethyldithiocarbamate)europium(III) with transition-metal complexes at 300 °C. The EuS:M nanocrystals thus prepared were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), inductively coupled plasma atomic emission spectroanalysis (ICP-AES), and a superconducting quantum interference device (SQUID) magnetometer. Enhanced Faraday rotations of the EuS:M nanocrystals were observed around 550 nm, and their enhanced spin polarization was estimated using electron paramagnetic resonance (EPR) measurements. In this report, the magneto-optical relationship between the Faraday rotation efficiency and spin polarization is discussed. 23597047 2012 Philip S. Portoghese Medicinal Chemistry Lectureship: Structure-Based Approaches to Ligands for G Protein-Coupled Adenosine and P2Y Receptors, From Small Molecules to Nanoconjugates. Adenosine receptor (ARs) and P2Y receptors (P2YRs) that respond to extracellular nucleosides/tides are associated with new directions for therapeutics. The X-ray structures of the A2AAR complexes with agonists and antagonists are examined in relationship to the G protein-coupled receptor (GPCR) superfamily and applied to drug discovery. Much of the data on AR ligand structure from early SAR studies, now is explainable from the A2AAR X-ray crystallography. The ligand-receptor interactions in related GPCR complexes can be identified by means of modeling approaches, e.g. molecular docking. Thus, molecular recognition in binding and activation processes has been studied effectively using homology modeling and applied to ligand design. Virtual screening has yielded new nonnucleoside AR antagonists, and existing ligands have been improved with knowledge of the receptor interactions. New agonists are being explored for CNS and peripheral therapeutics based on in vivo activity, such as chronic neuropathic pain. Ligands for receptors more distantly related to the X-ray template, i.e. P2YRs, have been introduced and are mainly used as pharmacological tools for elucidating the physiological role of extracellular nucleotides. Other ligand tools for drug discovery include fluorescent probes, radioactive probes, multivalent probes, and functionalized nanoparticles. 23505344 A computational study of water and CO migration sites and channels inside myoglobin. Pathways are computed for transport of H2O and CO in myoglobin (Mb), using the single sweep and zero-temperature string methods in a fully atomistic, explicitly solvated model system. Our predictions of sites and barriers in the pathways for CO transport agree with previous studies. For H2O, we predict a binding site in the distal pocket (DP), in agreement with crystallographic observations, and another one close to Leu 29 which explains the importance of this residue in controlling the pocket's hydrophobicity, as well as disordered minima in the largely apolar xenon cavities. In particular, H2O can occupy and transition among the xenon cavities, Xe4, Xe2, and Xe3. Our results support the hypothesis that the thermodynamically most favorable entry/exit portal for H2O is the so-called histidine gate (HG), the same as for CO. This result, along with the observation of water occupation of both DP and apolar Xe cavities, suggest that water and small gas molecules like CO compete for access to the protein interior, and therefore models of gas molecule transport within proteins should also explicitly consider water transport. 23474688 Nitrogen doped holey graphene as an efficient metal-free multifunctional electrochemical catalyst for hydrazine oxidation and oxygen reduction. Electrocatalysts for anode or cathode reactions are at the heart of electrochemical energy conversion and storage devices. Molecular design of carbon based nanomaterials may create the next generation electrochemical catalysts for broad applications. Herein, we present the synthesis of a three-dimensional (3D) nanostructure with a large surface area (784 m(2) g(-1)) composed of nitrogen doped (up to 8.6 at.%) holey graphene. The holey structure of graphene sheets (~25% of surface area is attributed to pores) engenders more exposed catalytic active edge sites. Nitrogen doping further improves catalytic activity, while the formation of the 3D porous nanostructure significantly reduces graphene nanosheet stacking and facilitates the diffusion of reactants/electrolytes. The three factors work together, leading to superb electrochemical catalytic activities for both hydrazine oxidation (its current generation ability is comparable to that of 10 wt% Pt-C catalyst) and oxygen reduction (its limiting current is comparable to that of 20 wt% Pt-C catalyst) with four-electron transfer processes and excellent durability. 23078542 Cell loss and autophagy in the extra-adrenal chromaffin organ of Zuckerkandl are regulated by glucocorticoid signalling. Neuroendocrine chromaffin cells exist in both intra- and extra-adrenal locations; the organ of Zuckerkandl (OZ) constitutes the largest accumulation of extra-adrenal chromaffin tissue in mammals. The OZ disappears postnatally by modes that are still enigmatic but can be maintained by treatment with glucocorticoids (GC). Whether the response to GC reflects a pharmacological or a physiological role of GC has not been clarified. Using mice with a conditional deletion of the GC-receptor (GR) gene restricted to cells expressing the dopamine β-hydroxylase (DBH) gene [GR(fl/fl) ; DBHCre abbreviated (GR(DBHCre) )], we now present the first evidence for a physiological role of GC signalling in the postnatal maintenance of the OZ: postnatal losses of OZ chromaffin cells in GR(DBHCre) mice are doubled compared to wild-type littermates. We find that postnatal cell loss in the OZ starts at birth and is accompanied by autophagy. Electron microscopy reveals autophagic vacuoles and autophagolysosomes in chromaffin cells. Autophagy in OZ extra-adrenal chromaffin cells is confirmed by showing accumulation of p62 protein, which occurs, when autophagy is blocked by deleting the Atg5 gene (Atg5(DBHCre) mice). Cathepsin-D, a lysosomal marker, is expressed in cells that surround chromaffin cells and are positive for the macrophage marker BM8. Macrophages are relatively more abundant in mice lacking the GR, indicating more robust elimination of degenerating chromaffin cells in GR(DBHCre) mice than in wild-type littermates. In summary, our results indicate that extra-adrenal chromaffin cells in the OZ show signs of autophagy, which accompany their postnatal numerical decline, a process that is controlled by GR signalling. 23042954 Efficacy of the GluK1/AMPA receptor antagonist LY293558 against seizures and neuropathology in a soman-exposure model without pretreatment and its pharmacokinetics after intramuscular administration. Control of brain seizures after exposure to nerve agents is imperative for the prevention of brain damage and death. Animal models of nerve agent exposure make use of pretreatments, or medication administered within 1 minute after exposure, in order to prevent rapid death from peripheral toxic effects and respiratory failure, which then allows the testing of anticonvulsant compounds. However, in a real-case scenario of an unexpected attack with nerve agents, pretreatment would not be possible, and medical assistance may not be available immediately. To determine if control of seizures and survival are still possible without pretreatment or immediate pharmacologic intervention, we studied the anticonvulsant efficacy of the GluK1 (GluR5)/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid (LY293558) in rats that did not receive any treatment until 20 minutes after exposure to the nerve agent soman. We injected LY293558 intramuscularly, as this would be the most likely route of administration to humans. LY293558 (15 mg/kg), injected along with atropine and the oxime HI-6 at 20 minutes after soman exposure, stopped seizures and increased survival rate from 64% to 100%. LY293558 also prevented neuronal loss in the amygdala and hippocampus, and reduced neurodegeneration in a number of brain regions studied 7 days after soman exposure. Analysis of the LY293558 pharmacokinetics after intramuscular administration showed that this compound readily crosses the blood-brain barrier. There was good correspondence between the time course of seizure suppression by LY293558 and the brain levels of the compound. 23277104 Identification and expression of multiple CYP1-like and CYP3-like genes in the bivalve mollusk Mytilus edulis. Various sequencing projects over the last several years have aided the discovery of previously uncharacterized invertebrate sequences, including new cytochrome P450 genes (CYPs). Here we present data on the identification and characterization of two CYP1-like and three CYP3-like genes from the bivalve mollusk Mytilus edulis, and assess their potential as biomarkers based on their responses to several known vertebrate aryl hydrocarbon receptor (AHR) agonists. Quantitative real-time PCR was used to measure CYP transcript levels in digestive gland, labial palps, adductor muscle, gill, foot, and different regions of the mantle. Levels of both CYP1-like genes were highest in digestive gland, whereas labial palps had the highest expression levels of the three CYP3-like genes followed by digestive gland and outer margin of the mantle. Mussels were exposed by injection to the AHR agonists, β-naphthoflavone (BNF; 25 μg g(-1)), 3,3',4,4',5-polychlorinated biphenyl (PCB126; 2 μg g(-1)), or 6-formylindolo[3,2-b]carbazole (FICZ; 0.1 μg g(-1)), or to Aroclor 1254 (a mixture of PCBs; 50 μg g(-1)) for 24 h, followed by CYP expression analysis. There was no statistically significant change in expression of either of the CYP1-like genes after exposure to the various AHR agonists. The CYP3-like-1 gene was significantly up-regulated by BNF in gill tissues and the CYP3-like-2 gene was up-regulated in digestive gland by PCB126 and in gill tissue by BNF. These results suggest that distinct mechanisms of CYP gene activation could be present in M. edulis, although the importance of the CYP1-like and CYP3-like genes for xenobiotic and endogenous lipids biotransformation requires additional investigation. 23387851 Sigma receptor modulators: a patent review. Introduction: Sigma receptors are involved in several central nervous system (CNS) disorders, including mood disorders (depression and anxiety), psychosis, schizophrenia, movement disorders (i.e., Parkinson's disease) and memory deficits (i.e., Alzheimer's disease). Recently, the involvement of sigma receptors in neuropathic pain and cancer has also been observed. Areas covered: This review aims at highlighting the research advancements published in the patent literature between 1986 and 2012, dividing patents according to both their time frame and applicants. The review especially focuses on the development of sigma receptor modulators and their application over the years with respect to CNS diseases, neuropathic pain and neurodegenerative pathologies. The literature was sought through Espacenet, Orbit, ISI Web and PubMed databases. Expert opinion: In recent years, considerable progress in the knowledge of the biology and pharmacology of sigma receptors has encouraged research on the potential benefits of sigma modulators in a wide range of pathologies. So far, only few potent agonists and antagonists of sigma receptors are in clinical trial for acute and chronic neurodegenerative diseases (SA4503 and ANAVEX 2-73) or neuropathic pain (E-52862). 23602516 Cisplatin-induced cell death in Saccharomyces cerevisiae is programmed and rescued by proteasome inhibition. Cisplatin is a highly effective chemotherapeutic drug used in the treatment of several tumors. It is a DNA-damaging agent that induces apoptosis of rapidly proliferating cells, an important factor underlying its therapeutic efficacy. Unfortunately, cellular resistance occurs often. A large fraction of tumor cells harbor mutations in p53, contributing to defects in apoptotic pathways and drug resistance. However, cisplatin-induced apoptosis can also occur in p53 deficient cells; thus, elucidation of the molecular mechanism involved will potentially yield new strategies to eliminate tumors that have defects in the p53 pathway. Most of the studies in this field have been conducted in cultured mammalian cells, not amenable to systematic genetic manipulation. Therefore, we aimed to establish a simplified model devoid of a p53 ortholog to study cisplatin-induced programmed cell death (PCD), using the yeast Saccharomyces cerevisiae. Our results indicate cisplatin induces an active form of cell death in yeast, as this process was partially dependent on de novo protein synthesis and did not lead to loss of membrane integrity. Cisplatin also increased DNA condensation and fragmentation/degradation, but no significant mitochondrial dysfunction other than partial fragmentation. Co-incubation with the proteasome inhibitor MG132 increased resistance to cisplatin and, accordingly, yeast strains deficient in proteasome activity were more resistant to cisplatin than wild-type strains. Proteasome inhibitors can sensitize tumor cells to cisplatin, but protect others from cisplatin-induced cell death. Our results indicate inhibition of the proteasome protects budding yeast from cisplatin-induced cell death and validate yeast as a model to study the role of the proteasome in cisplatin-induced PCD. Elucidation of this mechanism will aid in the development of new strategies to increase the efficacy of chemotherapy. 23317163 Cellular signaling crosstalk between multiple receptors for investigation of pathophysiology in multifactorial diseases--what is clinically-relevant crosstalk? Recently, genomics and proteomics have been utilized as advanced tools for investigation of cellular signaling pathways and molecular interactions, and elucidated promiscuous networks composed of numerous interactions among pathways. However, some of these interactions are considered to be simply contributing to background 'noise' and others are as 'crosstalk' biologically-relevant to cellular physiology, leading to synergy effects more than additive responses in an entire organism. Effort is now required to determine which interactions truly contribute to final physiological output. A receptor is the prime example of connectors among the networks. It functions, not simply as a signaling gateway, but also as an active trader by forming inter-receptor dimers. Furthermore, various receptors can modulate the function of the other receptors by input to common intracellular signaling pathways, establishing functional crosstalk among networks. Our findings by combined analyses of gene polymorphisms of two separate genes present evidences that such is the case with human body in a clinical setting: 1) an integrated effect of epidermal growth factor receptor (EGFR) and protease activated receptor-1 (PAR-1) on susceptibility to airway hyperresponsiveness (AHR), and 2) a crosstalk effect between muscarinic acetylcholine receptor (mAChRs) and β(2) adrenoceptor (β(2)AR) on bronchodilatory response to anticholinergic agents in patients with COPD. These results indicate that these interactions are unlikely to be 'noise' but functionally-relevant 'crosstalk' in a human body. This review attempts to highlight the clinically-relevant 'crosstalk' paradigm in a human body which provides us a novel insight necessary to investigate pathophysiology in common multifactorial diseases and to develop new drugs. 23422733 Co-extrusion as manufacturing technique for multilayer mini-matrices with dual drug release. The aim of this work was to develop by means of co-extrusion a multilayered dosage form characterized by a dual release profile of the same drug. Co-extrudates consisted of two concentric polymer matrices: a core having a lipophilic character and a coat with a hydrophilic character. Diclofenac sodium (DS) was incorporated as model drug in both layers. Several polymers were screened on the basis of their processability via hot melt extrusion (HME) and in vitro drug release. Polymer combinations with suitable properties (i.e., similar extrusion temperature, appropriate drug release profile) were processed via co-extrusion. (Co-) extruded samples were characterized in terms of solid state (XRD, SEM), in vitro drug release, core/coat adhesion, and bioavailability. Based on the polymer screening, two polymer combinations were selected for co-extrusion: ethylcellulose (core) combined with Soluplus® (coat) and polycaprolactone (core) with PEO (coat). These combinations were successfully co-extruded. XRD revealed that DS remained crystalline during extrusion in ethylcellulose, Soluplus®, polycaprolactone, and PEO. The polycaprolactone/PEO combination could be processed at a lower temperature (70°C), vs. 140°C for ethylcellulose/Soluplus®. The maximum drug load in core and coat depended on the extrusion temperature and the die dimensions, while adhesion between core and coat was mainly determined by the drug load and by the extrusion temperature. In vitro drug release from the co-extruded formulations was reflected in the in vivo behavior: formulations with a higher DS content in the coat (i.e., faster drug release) resulted in higher Cmax and higher AUC values. Co-extrusion is a viable method to produce in a single step a multilayer dosage form with dual drug release. 22288603 Allelopathic activity studies of Mikania scandens. Preliminary investigation of a number of plant extracts for allelopathic activity using seed germination inhibition bioassay showed a promising activity of the water extract of the aerial parts of Mikania scandens. Activity-guided fractionation of the M. scandens extract led to the isolation of the highly allelopathic active compound mikanolide, with minimum inhibitory concentration of 0.083 µM mL(-1). As M. scandens is a highly abundant invasive plant in Sri Lanka and other South Asian countries, this plant could be developed as an environment friendly natural herbicide, either in crude form as shredded plant material or as pure mikanolide, which is the major constituent (∼0.02%) in the plant. 23592568 Design, Synthesis and Biological Evaluation of Trimethine Cyanine Dyes as Fluorescent Probes for the Detection of Tau Fibrils in Alzheimer's Disease Brain and Olfactory Epithelium. Shedding light on grey matter: Fluorescent trimethine cyanines were evaluated as imaging probes for neurofibrillary tangles in post-mortem brain sections of Alzheimer's disease patients. These probes bind to neurofibrillary tangles with high contrast and selectivity over amyloid β plaques. 23017388 SB365, Pulsatilla saponin D suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT/mTOR signalling pathway. Pulsatilla koreana has been used as a traditional medicine for the treatment of several diseases. The purpose of this study was to determine if SB365, Pulsatilla saponin D isolated from the root of P. koreana inhibits the progression of colon cancer. We found that SB365 strongly suppressed the growth and proliferation of colon cancer cells and induced their apoptosis. Also, SB365 showed anti-angiogenic activity by decreasing the expression of HIF-1α and VEGF. These results were confirmed by an in vivo study showing that SB365 significantly inhibited tumor growth by the induction of apoptosis and inhibition of angiogenesis with stronger anticancer activity than 5-FU. When further examined for its anticancer mechanism, SB365 effectively suppressed the AKT/mTOR pathway both in vitro and in vivo. Taken together, our study demonstrated that SB365 inhibits the AKT/mTOR pathway, leading to the suppression of tumor growth and angiogenesis together with induction of apoptosis. Therefore, SB365 is a good candidate as a natural product for use in the treatment of colon cancer. 23371763 Anisotropically Luminescent Hydrogels Containing Magnetically-Aligned MWCNTs-Eu(III) Hybrids. The anisotropic emission properties of an Eu(III)-MWCNTs-based nanocomposite PNIPAAm hydrogel is induced upon application of a 10 T magnetic field, the latter dictating the alignment of the carbon nanotubes. This structuration creates directional highways for light to be preferentially absorbed, giving rise to orientation-dependent light emission intensity. Thermal control of the transparency of the aqueous matrix also allowed a stimulus-induced switching of the materials' emission properties. 23568508 Rhenium Complexes with Visible-Light-Induced Anticancer Activity. Shedding light on the matter: Rhenium(I) indolato complexes with highly potent visible-light-triggered antiproliferative activity (complex 1: EC50 light=0.1 μM vs EC50 dark=100 μM) in 2D- and 3D-organized cancer cells are reported and can be traced back to an efficient generation of singlet oxygen, causing rapid morphological changes and an induction of apoptosis. 23597071 Fabrication of Quantum Dot Microarrays Using Electron Beam Lithography for Applications in Analyte Sensing and Cellular Dynamics. Quantum dot (QD) based micro-/nanopatterned arrays are of broad interest in applications ranging from electronics, photonics, to sensor devices for biomedical purposes. Here, we report on a rapid, physico-chemically mild approach to generate high fidelity micropattern arrays of prefunctionalized water-soluble quantum dots using electron beam lithography. We show that such patterns retain their fluorescence and bioaffinity upon electron beam lithography and, based on the streptavidin-biotin interaction, allow for detection of proteins, colloidal gold nanoparticles and magnetic microparticles. Furthermore, we demonstrate the applicability of QD based microarray patterns differing in their shape (circles, squares, grid-like), size (from 1 to 10 μm) and pitch distance to study the adhesion, spreading and migration of human blood derived neutrophils. Using live cell confocal fluorescence microscopy, we show that pattern geometry and pitch distance influence the adhesion, spreading and migratory behavior of neutrophils. Research reported in this work paves the way for producing QD microarrays with multiplexed functionalities relevant for applications in analyte sensing and cellular dynamics. 23098818 The catalytic competence of cytochrome P450 in the synthesis of serotonin from 5-methoxytryptamine in the brain: an in vitro study. Brain serotonin has been implicated in the pathophysiology of a wide spectrum of psychiatric disorders, as well as in the mechanism of action of psychotropic drugs. The aim of present study was to identify rat cytochrome P450 (CYP) isoforms which can catalyze the O-demethylation of 5-methoxytryptamine to serotonin, and to find out whether that alternative pathway of serotonin synthesis may take place in the brain. The study was conducted on cDNA-expressed CYPs (rat CYP1A1/2, 2A1/2, 2B1, 2C6/11/13, 2D1/2/4/18, 2E1, 3A2 and human CYP2D6), on rat brain and liver microsomes and on human liver microsomes (the wild-type CYP2D6 or the allelic variant 2D6*4*4). Of the rat CYP isoforms studied, CYP2D isoforms were the most efficient in catalyzing the O-demethylation of 5-methoxytryptamine to serotonin, but they were less effective than the human isoform CYP2D6. Microsomes from different brain regions were capable of metabolizing 5-methoxytryptamine to serotonin. The reaction was inhibited by the specific CYP2D inhibitors quinine and fluoxetine. Human liver microsomes of the wild-type CYP2D6 metabolized 5-methoxytryptamine to serotonin more effectively than did the defective CYP2D6*4*4 ones. The obtained results indicate that rat brain CYP2D isoforms catalyze the formation of serotonin from 5-methoxytryptamine, and that the deficit or genetic defect of CYP2D may affect serotonin metabolism in the brain. The results are discussed in the context of their possible physiological and pharmacological significance in vivo. 23531217 Study on medicinal chemistry of k203 in wistar rats and beagle dogs. K203 is an experimental bis-pyridinium mono-aldoxime type cholinesterase reactivator of potential use in organophosphate/ organophosphonate poisoning. Pharmacokinetics of K203 were examined in Wistar rats and beagle dogs using ion-pair HPLC. Serum and cerebrospinal fluid concentrations of K203 were determined using ion-pair reversedphase chromatography on octadecyl silica column. HPLC with ultraviolet detection was used for determination of serum concentration of K203 higher than 0.1 μg/mL while its low concentrations in cerebrospinal fluid required electrochemical detection (0.015 through 4 μg/mL range). In rats the serum levels of K203 followed zero order pharmacokinetics from 15 to 120 minutes post administration. Zero order pharmacokinetics was also observed in beagle dogs after low dose (15 μmol/kg) of K203 administration. High dose administration (250 μmol/kg) led to subsequent hindered elimination from both cerebrospinal fluid and serum. 23601387 The influence of latitude on the concentration of vitamin D3 and 25-hydroxy-vitamin D3 in Australian red meat. There is little information on the vitamin D content of Australian red meat or on the possible influence of latitude on this content. To determine the content of vitamin D3 and 25-hydroxy-vitamin D3 (25OHD3), lamb and beef were analysed from 34° S with LC-IT-MS. To investigate the possible influence of latitude on vitamin D in meat, the lean meat and fat from five cuts of beef were analysed from 17° S and 41° S. Lamb contained 0.10μg vitamin D3/100g and 0.20μg 25OHD3/100g lean meat, while beef contained 0.12μg vitamin D3 and 0.27μg 25OHD3/100g (lean meat). Latitude had no effect on the vitamin D3 (P=0.21) or 25OHD3 (P=0.29) content of lean beef, but fat from cattle in the 17° S latitude group contained significantly higher (P<0.01) concentrations of vitamin D3 than fat from the 41° S group of cattle. 23140132 The effects of green tea consumption and resistance training on body composition and resting metabolic rate in overweight or obese women. Green tea has been shown to have thermogenic and antiobesity properties. Therefore, it is important to investigate its effect on weight loss in humans, especially in women. We investigated the effects of green tea consumption combined with resistance training on the body composition and the resting metabolic rate (RMR) in women who were overweight or obese (grade I). After 4 weeks on an adaptive diet, 36 women were divided into four groups (group 1 green tea; group 2 placebo; group 3 green tea plus resistance training; group 4 placebo plus resistance training). The study was double-blinded and placebo-controlled. The RMR and body composition were ascertained for each volunteer, blood tests were performed, and subjects in groups 3 and 4 were tested for their one repetition maximum. Each subject followed the protocol and continued the diet for eight additional weeks, and periodic evaluations were administered. The mean RMR of group 1 decreased significantly and was accompanied by weight loss, maintenance of lean body mass, and decreases in both waist circumference and body mass index. Group 2 showed no variations in anthropometric or blood variables and significantly decreased their mean RMR. Group 3 showed significant increases in RMR, lean body mass, and muscle strength, and significant decreases in body fat, triglycerides, and waist circumference as compared to group 4. Green tea combined with resistance training its potential is increased with decreasing body fat, waist circumference, and triacylglyceride levels and by increasing lean body mass and muscle strength. 22592975 Investigation into the genotoxicity of water extracts from hypoxis species and a commercially available hypoxis preparation. We performed an in vitro evaluation of the genotoxic potential of water extracts from four Hypoxis species (Hypoxis hemerocallidea, H. colchicifolia, H. rigidula, H. acuminata) and a commercial preparation thereof using the neutral red uptake (NRU) assay, the alkaline comet assay and the cytome assay in human hepatoma HepG2 cells. The relative cytotoxicity of these samples was established by determining their NI50 values (50% inhibition of NRU), and these results were used for dose-finding in genotoxicity tests. None of the tested extracts were identified as genotoxic in both the alkaline comet assay and cytome assay. Copyright © 2012 John Wiley & Sons, Ltd. 23264615 Cortisol and interferon tau regulation of endometrial function and conceptus development in female sheep. During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and cortisol via hydroxysteroid (11-β) dehydrogenase 1 (HSD11B1). Ovarian progesterone induces and PG and IFNT stimulates endometrial HSD11B1 expression and keto-reductase activity as well as many epithelial genes that govern trophectoderm proliferation, migration, and attachment during elongation. The primary aim of these studies was to test the hypothesis that HSD11B1-derived cortisol has a biological role in endometrial function and conceptus development during early pregnancy in sheep. In study 1, cyclic ewes received vehicle, cortisol, PF 915275 (PF; a selective inhibitor of HSD11B1), cortisol and PF, meloxicam (a selective inhibitor of PTGS2), cortisol and meloxicam, recombinant ovine IFNT, or IFNT and PF into the uterus from day 10 to day14 after estrus. Cortisol and IFNT stimulated endometrial HSD11B1 expression and activity, increased endometrial PTGS2 activity and the amount of PG in the uterine lumen, and up-regulated many conceptus elongation-related genes in the endometrium. Some effects of cortisol and IFNT were mediated by PTGS2-derived PG. In study 2, bred ewes received PF 915275 or recombinant ovine IFNT and into the uterus from day 10 to day 14 after mating. Inhibition of HSD11B1 activity in utero prevented conceptus elongation, whereas IFNT rescued conceptus elongation in PF-infused ewes. These results suggest that HSD11B1-derived cortisol mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep. 23323746 Chemistry, chemoecology, and bioactivity of the South China Sea opisthobranch molluscs and their dietary organisms. Opisthobranchs are slow-moving, brightly colored, and shell-less slug. Interestingly, these naked molluscs appear to be free of predation causing great interests to biologists, chemists, and pharmacologists as well. It is well documented that their ability to escape predation is realized by utilizing chemical substances as defensive allomones. Due to their extraordinary capacity to produce a variety of chemical defensive molecules and in particular, some of which exhibited promising pharmacological activities, opisthobranch molluscs became the hotspot of research subject in the recent years. The authors and co-workers have systematically investigated the possible diet relationship between the South China Sea opisthobranch molluscs and their related prey organisms, including sponges, corals, and algae in the last decade. A series of interesting results have been obtained concerning the chemistry and chemoecology of the studied marine organisms. The present review focuses on recent development dealing with chemistry, chemoecology, and bioactivity of the South China Sea opisthobranch molluscs and their dietary organisms. Some selected representative examples are described in detail. 23085330 Solid dispersions for preparation of phototoxic supersaturated solutions for antimicrobial photodynamic therapy (aPDT): Studies on curcumin and curcuminoides L. Curcumin is under investigation as a potential photosensitizer (PS) in antimicrobial photodynamic therapy (aPDT). The therapeutic potential of curcumin as a PS is limited by its low aqueous solubility, susceptibility to hydrolytic and photolytic degradation, and limited phototoxicity toward Gram negative (G-) bacteria. Supersaturated solutions of curcumin have demonstrated high phototoxicity toward several species of Gram positive (G+) bacteria as well as the G-Escherichia (E) coli. Thus, solid dispersions that can form supersaturated solutions of curcumin upon hydration may be beneficial in aPDT. In the present study, solid dispersions of curcumin have been prepared through lyophilization of concentrated solutions obtained from dissolution of hydroxypropyl-β-cyclodextrin (HPβCD)-curcumin co-precipitates. Hydroxypropyl methylcellulose (HPMC) was added to curcumin solutions prior to lyophilization. The resulting lyophilizates were porous, amorphous and hydrated and dissolved rapidly in contact with a model physiological salt solution. The detected drug load of the lyophilizates was in the range 0.5-1.0% (w/w) and was dependent on the selected ratio between HPβCD and curcumin in the co-precipitate. The lyophilizate with the highest drug load could easily be dissolved in aqueous medium to form curcumin solutions of relevant concentrations for aPDT (i.e., 10μM). Selected solutions of the curcumin solid dispersions showed a pronounced decrease in curcumin concentration up to 90% after storage for 168h, which indicated that supersaturated curcumin solutions were initially formed upon dissolution of the lyophilizates. Both freshly prepared and 2days old solutions of one selected curcumin lyophilizate induced significant inactivation of E. coli (∼1% bacterial survival) after exposure to a light dose of only 5J/cm(2). 23453039 Involvement of regucalcin in lipid metabolism and diabetes. Regucalcin (RGN/SMP30) was originally discovered in 1978 as a unique calcium-binding protein that does not contain the EF-hand motif of calcium-binding domain. The regucalcin gene (rgn) is localized on the X chromosome and is identified in over 15 species consisting the regucalcin family. Regucalcin has been shown to play a multifunctional role in cell regulation; maintaining of intracellular calcium homeostasis and suppressing of signal transduction, translational protein synthesis, nuclear deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis, proliferation, and apoptosis in many cell types. Moreover, regucalcin may play a pathophysiological role in metabolic disorder. The expression of regucalcin is stimulated through the action of insulin in liver cells in vitro and in vivo and it is decreased in the liver of rats with type I diabetes induced by streptozotocin administration in vivo. Overexpression of endogenous regucalcin stimulates glucose utilization and lipid production in liver cells with glucose supplementation in vitro. Regucalcin reveals insulin resistance in liver cells. Deficiency of regucalcin induces an impairment of glucose tolerance and lipid accumulation in the liver of mice in vivo. Overexpression of endogenous regucalcin has been shown to decrease triglyceride, total cholesterol and glycogen contents in the liver of rats, inducing hyperlipidemia. Leptin and adiponectin mRNA expressions in the liver tissues are decreased in regucalcin transgenic rats. Decrease in hepatic regucalcin is associated with the development and progression of nonalcoholic fatty liver disease and fibrosis in human patients. Regucalcin may be a key molecule in lipid metabolic disorder and diabetes. 23453068 Discovery of 4-alkylamino-7-aryl-3-cyanoquinoline LRRK2 kinase inhibitors. Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with familial Parkinson's disease (PD). The kinase activity of this complex protein is increased by pathogenic mutations. Inhibition of LRRK2 kinase activity has therefore emerged as a promising approach for the treatment of PD. Herein we report our findings on a series of 4-alkylamino-7-aryl-3-cyanoquinolines that exhibit kinase inhibitory activity against both wild type and G2019S mutant LRRK2. Activity was determined in both biochemical and cellular assays. Compound 14 was further evaluated in an in vivo pharmacodynamic study and found to significantly inhibit Ser935 phosphorylation after oral dosing. 23435356 Tryptophan hydroxylase-2: An emerging therapeutic target for stress disorders. Serotonin (5-HT) has been long recognized to modulate the stress response, and dysfunction of 5-HT has been implicated in numerous stress disorders. Accordingly, the 5-HT system has been targeted for the treatment of stress disorders. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in 5-HT synthesis, and the recent identification of a second, neuron-specific TPH isoform (TPH2) opened up a new area of research. With a decade of extensive investigation, it is now recognized that: (1) TPH2 exhibits a highly flexible gene expression that is modulated by an increasing number of internal and external environmental factors including the biological clock, stressors, endogenous hormones, and antidepressant therapies; and (2) genetically determined TPH2 activity is linked to a growing body of stress-related neuronal correlates and behavioral traits. These findings reveal an active role of TPH2 in the stress response and provide new insights into the long recognized but not yet fully understood 5-HT-stress interaction. As a major modulator of 5-HT neurotransmission and the stress response, TPH2 is of both pathophysiological and pharmacological significance, and is emerging as a new therapeutic target for the treatment of stress disorders. Given that numerous antidepressant therapies influence TPH2 gene expression, TPH2 is already inadvertently targeted for the treatment of stress disorders. With increased understanding of the regulation of TPH2 activity we can now purposely utilize TPH2 as a target to develop new or optimize current therapies, which are expected to greatly improve the prevention and treatment of a wide variety of stress disorders. 23212970 Bio-based biodegradable and biocompatible hyperbranched polyurethane: a scaffold for tissue engineering. Hyperbranched polyurethanes are synthesized using TDI, PCL diol, butanediol, and pentaerythritol (1-5 wt%) as the B(4) reactant with and without the monoglyceride of sunflower oil. The biodegradation, physico-mechanical, and thermal properties are found to be tailored by varying the percentage weight of the branching unit. An MTT/hemolytic assay and subcutaneous implantation in Wistar rats followed by cytokine/ALP assay and histopathology studies confirm a better biocompatibility of HBPU with MG than without MG. HBPU supports the proliferation of dermatocytes with no toxic effect in major organs, in addition the in vitro degraded products are non-toxic. Cell adherence and proliferation endorse the bio-based HBPU as a prospective scaffold material in the niche of tissue engineering. 23443957 Microfluidic oxygen imaging using integrated optical sensor layers and a color camera. In this work we present a high resolution oxygen imaging approach, which can be used to study 2D oxygen distribution inside microfluidic environments. The presented setup comprises a fabrication process of microfluidic chips with integrated luminescent sensing films combined with referenced oxygen imaging applying a color CCD-camera. Enhancement of the sensor performance was achieved by applying the principle of light harvesting. This principle enabled ratiometric imaging employing the red and the green channel of a color CCD-camera. The oxygen sensitive emission of platinum(ii)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorphenyl)-porphyrin (PtTFPP) was detected by the red channel, while the emission of a reference dye was detected by the green channel. This measurement setup allowed for accurate real-time 2D oxygen imaging with superior quality compared to intensity imaging. The sensor films were subsequently used to measure the respiratory activity of human cell cultures (HeLa carcinoma cells and normal human dermal fibroblasts) in a microfluidic system. The sensor setup is well suited for different applications from spatially and temporally resolving oxygen concentration inside microfluidic channels to parallelization of oxygen measurements and paves the way to novel cell based assays, e.g. in tissue engineering, tumor biology and hypoxia reperfusion phenomena. 23312281 Vascular complications of diabetes: mechanisms of injury and protective factors. In patients with diabetes, atherosclerosis is the main reason for impaired life expectancy, and diabetic nephropathy and retinopathy are the largest contributors to end-stage renal disease and blindness, respectively. An improved therapeutic approach to combat diabetic vascular complications might include blocking mechanisms of injury as well as promoting protective or regenerating factors, for example by enhancing the action of insulin-regulated genes in endothelial cells, promoting gene programs leading to induction of antioxidant or anti-inflammatory factors, or improving the sensitivity to vascular cell survival factors. Such strategies could help prevent complications despite suboptimal metabolic control. 23559221 Glucose and memory: The influence of drink, expectancy, and beliefs. RATIONALE: An increasing number of studies suggest that glucose can enhance aspects of memory and the central methodology is the use of the glucose-placebo design. One critical issue therefore is separating the pharmacological effects of glucose from the expectancies created by consuming a drink that might contain glucose. OBJECTIVE: A modified balanced placebo design examined the role that expectancy and belief about the drink consumed has on the pharmacological changes observed following glucose consumption. METHOD: Ninety-three participants, allocated according to a drink (glucose, placebo) × message (told glucose, told nothing, told placebo) unrelated design, were administered tasks assessing immediate and delayed verbal free recall, spatial recognition and semantic verification. Each task has some evidence for hippocampus involvement, and variations in task difficulty were used to assess the idea that glucose effects are sensitive to task difficulty. RESULTS: While the messages biased drink judgements in the expected direction, judgements of drink content were at chance and glucose only enhanced delayed free recall. The subtle effects of the messages did not modify the glucose enhancement. However, believing glucose had been consumed showed an independent improvement in delayed free recall. There was no evidence that task complexity enhanced the glucose effect. CONCLUSIONS: The findings indicate that expectancy effects are unlikely to be confused with glucose enhancements, but beliefs about consuming glucose can augment performance on delayed free recall. The discussion considers the hippocampus and complexity hypotheses of glucose's mode of action and proposes the routine collection of drink beliefs in future studies. 23155004 Inferring population histories using genome-wide allele frequency data. The recent development of high-throughput genotyping technologies has revolutionized the collection of data in a wide range of both model and nonmodel species. These data generally contain huge amounts of information about the demographic history of populations. In this study, we introduce a new method to estimate divergence times on a diffusion time scale from large single-nucleotide polymorphism (SNP) data sets, conditionally on a population history that is represented as a tree. We further assume that all the observed polymorphisms originate from the most ancestral (root) population; that is, we neglect mutations that occur after the split of the most ancestral population. This method relies on a hierarchical Bayesian model, based on Kimura's time-dependent diffusion approximation of genetic drift. We implemented a Metropolis-Hastings within Gibbs sampler to estimate the posterior distribution of the parameters of interest in this model, which we refer to as the Kimura model. Evaluating the Kimura model on simulated population histories, we found that it provides accurate estimates of divergence time. Assessing model fit using the deviance information criterion (DIC) proved efficient for retrieving the correct tree topology among a set of competing histories. We show that this procedure is robust to low-to-moderate gene flow, as well as to ascertainment bias, providing that the most distantly related populations are represented in the discovery panel. As an illustrative example, we finally analyzed published human data consisting in genotypes for 452,198 SNPs from individuals belonging to four populations worldwide. Our results suggest that the Kimura model may be helpful to characterize the demographic history of differentiated populations, using genome-wide allele frequency data. 23122108 Maple polyphenols, ginnalins A-C, induce S- and G2/M-cell cycle arrest in colon and breast cancer cells mediated by decreasing cyclins A and D1 levels. Polyphenols are bioactive compounds found in plant foods. Ginnalins A-C are polyphenols present in the sap and other parts of the sugar and red maple species which are used to produce maple syrup. Here we evaluated the antiproliferative effects of ginnalins A-C on colon (HCT-116) and breast (MCF-7) tumourigenic and non-tumourigenic colon (CCD-18Co) cells and investigated whether these effects were mediated through cell cycle arrest and/or apoptosis. Ginnalins A-C were twofold more effective against the tumourigenic than non-tumourigenic cells. Among the polyphenols, ginnalin A (84%, HCT-116; 49%, MCF-7) was more effective than ginnalins B and C (50%, HCT-116; 30%, MCF-7) at 50 μM concentrations. Ginnalin A did not induce apoptosis of the cancer cells but arrested cell cycle (in the S- and G(2)/M-phases) and decreased cyclins A and D1 protein levels. These results suggest that maple polyphenols may have potential cancer chemopreventive effects mediated through cell cycle arrest. 23472803 Directing cluster formation of au nanoparticles from colloidal solution. Discrete clusters of closely spaced Au nanoparticles can be utilized in devices from photovoltaics to molecular sensors because of the formation of strong local electromagnetic field enhancements when illuminated near their plasmon resonance. In this study, scalable, chemical self-organization methods are shown to produce Au nanoparticle clusters with uniform nanometer interparticle spacing. The performance of two different methods, namely electrophoresis and diffusion, for driving the attachment of Au nanoparticles using a chemical cross-linker on chemically patterned domains of polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) thin films are evaluated. Significantly, electrophoresis is found to produce similar surface coverage as diffusion in 1/6th of the processing time with an ∼2-fold increase in the number of Au nanoparticles forming clusters. Furthermore, average interparticle spacing within Au nanoparticle clusters was found to decrease from 2-7 nm for diffusion deposition to approximately 1-2 nm for electrophoresis deposition, and the latter method exhibited better uniformity with most clusters appearing to have about 1 nm spacing between nanoparticles. The advantage of such fabrication capability is supported by calculations of local electric field enhancements using electromagnetic full-wave simulations from which we can estimate surface-enhanced Raman scattering (SERS) enhancements. In particular, full-wave results show that the maximum SERS enhancement, as estimated here as the fourth power of the local electric field, increases by a factor of 100 when the gap goes from 2 to 1 nm, reaching values as large as 10(10), strengthening the usage of electrophoresis versus diffusion for the development of molecular sensors. 23526157 Blood Flow of the Acral Finger Arterioles in Patients With Type 2 Diabetes by Quality Doppler Profiles. Patients with diabetes mellitus exhibit peripheral arterioles lesions that is associated with reduced blood flow. Here, we intended to assess the acral arterioles lesion in patients with type 2 diabetes based on the rate of blood flow by multigate spectral Doppler ultrasonography. Fifty-two patients with type 2 DM were divided into two groups. Group 1 included 13 men and 12 women with an average age of 60.60 ± 14.03 years and a duration of type 2 diabetes for 2.44 ± 1.50 years. Group 2 included 17 men and 11 women with an average age of 64.25 ± 10.84 years and type 2 diabetes for 12.57 ± 6.26 years. Age-matched control subjects (n = 52) were recruited (30 men and 22 woman, mean age of 61.19 ± 10.38 years). A multigate spectral Doppler algorithm was applied to the acral finger of the thumb of the right hand to test the arteriole diameter and hemodynamic parameters, including diameter of the acral finger arterioles (D), area of the blood flow profile of the acral finger arterioles (A max) and hemodynamic parameters. Patients with diabetes exhibited a significant reduction in the arteriole diameter (1.63 ± 0.18 and 1.57 ± 0.22 mm, respectively, P < 0.001 for both) compared to control subjects (2.09 ± 0.17 mm). A max were significantly reduced in patients with diabetes (61.35 ± 10.66 mm(2)/s for group 1 and 46.50 ± 6.59 mm(2)/s for group 2, P < 0.001 for both) compared to that in control subjects (77.93 ± 12.37 mm(2)/s). Furthermore, a significant difference in Amax was found between group 1 and group 2 (P < 0.001). The vascular resistance index (RI) was significantly higher in both patient groups 0.58 ± 0.06 for group 1 (P < 0.001) and 0.64 ± 0.07 for group 2 (P < 0.001) than that in control subjects (0.48 ± 0.04). The RI value of the acral finger arterioles differed significantly between group 1 and group 2 (P < 0.01). Diabetic patients exhibited a weak blood flow in the acral finger arterioles. The multigate spectral Doppler technology can be used to test blood flow in the acral finger arterioles and provide hemodynamic data for systematic analyses of the peripheral arteriole lesions in diabetes. 23256442 Dandelion leaf extract protects against liver injury induced by methionine- and choline-deficient diet in mice. We investigated the hepatoprotective effects of the extract of dandelion leaves (EDL) on a murine model of methionine- and choline-deficient (MCD) diet-induced nonalcoholic steatohepatitis (NASH). C57BL/6 mice were fed for 4 weeks with one of the following diets: control diet (Cont), MCD diet (MCD), MCD diet supplemented with EDL at 200 mg/kg body weight·daily (MCD+D200), and MCD diet supplemented with EDL at 500 mg/kg body weight·daily (MCD+D500). Hepatic function was assessed by evaluating the following parameters: liver histology; plasma levels of alanine aminotransferase (ALT), triglyceride (TG), malondialdehyde (MDA), and reduced glutathione (GSH); expression levels of TNF-α and IL-6; and levels of caspase-3 and pJNK/JNK protein. Histopathological evaluations revealed that addition of EDL to the MCD diet dampens the severity of the clinical signs of NASH. Moreover, EDL led to a significant decrease in the serum levels of ALT, hepatic TG, and MDA, and in the expression levels of TNF-α, and IL-6; on the contrary, the levels of reduced GSH increased. At the post-transcriptional level, EDL significantly decreased the activation of procaspase-3 to active caspase-3, and the phosphorylation of JNK. These results suggest that the beneficial effects of EDL on NASH are mainly due to its antioxidant and anti-inflammatory activities. 23535516 Modulation of the JAK/ERK/STAT signaling in melanocortin-induced inhibition of local and systemic responses to myocardial ischemia/reperfusion. The janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers and activators of transcription (STAT) pathways have been shown to play a cardioprotective role. We previously gave evidence that melanocortins afford cardioprotection in conditions of myocardial ischemia/reperfusion. Here we aimed to investigate the influence of melanocortins on the JAK/ERK/STAT signaling in cardiac and systemic responses to prolonged myocardial ischemia/reperfusion. Ischemia was produced in rats by ligature of the left anterior descending coronary artery for 30min. At the end of the 2-h reperfusion, western blot analysis of the cardioprotective transcription factors pJAK2, pERK1/2, pTyr-STAT3 and pSer-STAT3, the inflammatory mediator tumor necrosis factor-α (TNF-α), the pro-apoptotic factors BAX and c-jun N-terminal kinases (pJNK), the anti-apoptotic protein Bcl-XL, as well as of the cardioprotective enzyme heme oxygenase-1 (HO-1), was performed in the left ventricle and spleen. Intravenous treatment, during coronary artery occlusion, with the melanocortin analogs [Nle(4), D-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) and adrenocorticotropic hormone 1-24 [ACTH-(1-24)], induced a left ventricle up-regulation of pJAK2, pERK1/2 and pTyr-STAT3 (JAK-dependent), and a reduction in pJNK and TNF-α levels; these effects of NDP-α-MSH and ACTH-(1-24) were associated with over-expression of the pro-survival proteins HO-1 and Bcl-XL, and marked decrease of the myocardial infarct size. Melanocortin treatment did not affect left ventricle pSer-STAT3 (ERK1/2-dependent) and BAX levels. In the spleen, NDP-α-MSH and ACTH-(1-24) induced similar effects on the expression of the above transcription factors/proteins, except for pERK1/2 (down-regulated) and HO-1 (unaffected). Blockade of JAK and ERK pathways with AG490 and U0126, respectively, abrogated the myocardial infarct size reduction by NDP-α-MSH. These results indicate that melanocortins inhibit local and systemic inflammatory and apoptotic cascades triggered by prolonged myocardial ischemia/reperfusion, with consequent reduction in myocardium infarct size, seemingly via activation of the JAK/STAT signaling and with modulation of an ERK (STAT unrelated) signaling pathway. 22911509 Superhydrophobic graphene foams. The static and dynamic wetting properties of a 3D graphene foam network are reported. The foam is synthesized using template-directed chemical vapor deposition and contains pores several hundred micrometers in dimension while the walls of the foam comprise few-layer graphene sheets that are coated with Teflon. Water contact angle measurements reveal that the foam is superhydrophobic with an advancing contact angle of ∼163 degrees while the receding contact angle is ∼143 degrees. The extremely water repellent nature of the foam is also confirmed when impacting water droplets are able to completely rebound from the surface. Such superhydrophobic graphene foams show potential in a variety of applications ranging from anti-sticking and self-cleaning to anti-corrosion and low-friction coatings. 23562707 CYP-450 isoenzymes catalyze the generation of hazardous aromatic amines after reaction with the azo dye Sudan III. This work describes the mutagenic response of Sudan III, an adulterant food dye, using Salmonella typhimurium assay and the generation of hazardous aromatic amines after different oxidation methods of this azo dye. For that, we used metabolic activation by S9, catalytic oxidation by ironporphyrin and electrochemistry oxidation in order to simulate endogenous oxidation conditions. The oxidation reactions promoted discoloration from 65% to 95% of Sudan III at 1×10(-4)molL(-1) and generation of 7.6×10(-7)molL(-1) to 0.31×10(-4)molL(-1) of aniline, o-anisidine, 2-methoxi-5-methylaniline, 4-aminobiphenyl, 4,4'-oxydianiline; 4,4'-diaminodiphenylmethane and 2,6-dimethylaniline. The results were confirmed by LC-MS-MS experiments. We also correlate the mutagenic effects of Sudan III using S. typhimurium with the strain TA1535 in the presence of exogenous metabolic activation (S9) with the metabolization products of this compound. Our findings clearly indicate that aromatic amines are formed due to oxidative reactions that can be promoted by hepatic cells, after the ingestion of Sudan III. Considering that, the use of azo compounds as food dyestuffs should be carefully controlled. 23614831 Influence of different polymers on crystallization tendency and dissolution behavior of cilnidipine in solid dispersions. Abstract Context: Cilnidipine (CN) is a novel dihydropyridine calcium antagonist that is practically insoluble in aqueous media and exhibits a low oral bioavailability or limited clinical efficacy. Objective: This study investigated the effects of three commercial and chemically diverse polymers - PVP, PVP/VA and Soluplus - on crystallization tendency and in vitro dissolution profiles of CN in order to determine an optimum carrier for composing the preferred solid dispersion (SD) of CN. Methods: All these co-evaporated systems were characterized up to 3 months by thermoanalytical (DSC), crystallographic (POM, PXRD), microscopic (SEM) and spectroscopic (FTIR) techniques. Results: The results showed that the polymers could be sorted by their effects of inhibiting CN crystallization in the ascending order: Soluplus, PVP/VA, PVP. The sequence was in accordance with that of the strength of drug-polymer hydrogen bonds revealed by FTIR spectra. It could be ascribed to relative hydrogen-bonding acceptor strengths of N-vinylpyrrolidone moiety in the polymer molecules. On the other hand, all the SDs showed enhanced dissolution profiles compared to pure CN alone. On their effects of enhancing CN dissolution, the polymers could be sorted in the descending order: Soluplus, PVP, PVP/VA. Conclusions: It implied that the dissolution behavior of CN could bear a close relationship to both hydration capacity and hydrogen-bonding interaction tendency of moieties of the polymers. It might suggest an optimal formulation for CN comprising both PVP and Soluplus. 23389039 Differential mRNA expression levels of human histone-modifying enzymes in normal karyotype B cell pediatric acute lymphoblastic leukemia. Histone modification enzymes regulate gene expression by altering the accessibility of promoters to transcription factors. We sought to determine whether the genes encoding histone modification enzymes are dysregulated in pediatric acute lymphoblastic leukemia (ALL). A real-time PCR array was designed, tested and used to profile the expression of 85 genes encoding histone modification enzymes in bone marrow mononuclear cells from 30 pediatric ALL patients and 20 normal controls. The expression profile of histone-modifying genes was significantly different between normal karyotype B cell pediatric ALL and normal controls. Eleven genes were upregulated in pediatric ALL, including the histone deacetylases HDAC2 and PAK1, and seven genes were downregulated, including PRMT2 and the putative tumor suppressor EP300. Future studies will seek to determine whether these genes serve as biomarkers of pediatric ALL. Ingenuity Pathway Analysis revealed that Gene Expression and Organ Morphology was the highest rated network, with 13 focus molecules (significance score = 35). Ingenuity Pathway Analysis also indicated that curcumin and miR-34 are upstream regulators of histone-modifying enzymes; future studies will seek to validate these results and examine the role of curcumin and miR-34 in leukemia. This study provides new clues into the molecular mechanisms of pediatric ALL. 23515582 Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH-expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation. RATIONALE: Selective rapid eye movement sleep (REMS) deprivation using the platform-on-water ("flower pot") method causes sleep rebound with increased REMS, decreased REMS latency, and activation of the melanin-concentrating hormone (MCH) expressing neurons in the hypothalamus. MCH is implicated in the pathomechanism of depression regarding its influence on mood, feeding behavior, and REMS. OBJECTIVES: We investigated the effects of the most selective serotonin reuptake inhibitor escitalopram on sleep rebound following REMS deprivation and, in parallel, on the activation of MCH-containing neurons. METHODS: Escitalopram or vehicle (10 mg/kg, intraperitoneally) was administered to REMS-deprived (72 h) or home cage male Wistar rats. During the 3-h-long "rebound sleep", electroencephalography was recorded, followed by an MCH/Fos double immunohistochemistry. RESULTS: During REMS rebound, the time spent in REMS and the number of MCH/Fos double-labeled neurons in the lateral hypothalamus increased markedly, and REMS latency showed a significant decrease. All these effects of REMS deprivation were significantly attenuated by escitalopram treatment. Besides the REMS-suppressing effects, escitalopram caused an increase in amount of and decrease in latency of slow wave sleep during the rebound. CONCLUSIONS: These results show that despite the high REMS pressure caused by REMS deprivation procedure, escitalopram has the ability to suppress REMS rebound, as well as to diminish the activation of MCH-containing neurons, in parallel. Escitalopram caused a shift from REMS to slow wave sleep during the rebound. Furthermore, these data point to the potential connection between the serotonergic system and MCH in sleep regulation, which can be relevant in depression and in other mood disorders. 23531119 Low-temperature NMR studies on the geometry of base pairs involving 5-substituted uracil derivatives. Uridine (U) imino proton chemical shifts, measured in the slow hydrogen-bond exchange regime at low temperatures in a freonic solution, show that electron-withdrawing 5-bromo and 5-fluoro substituents on the uracil base strengthen NHN hydrogen bonds in (X)U·A base pairs formed by the free nucleosides. Whereas the halogens do not alter the preferential formation of Watson-Crick geometries, self-associates of the halouracils point to a more favorable engagement of the 2-carbonyl as proton acceptor in the cyclic hydrogen bonds, suggesting increased formation of reverse geometries and wobble base pairs with guanine when compared to the thymine base. Employing (15)N-labeled 5-bromouridine, no noticeable population of minor enol tautomers is found in the freonic mixture at 113 K. 23303198 Antihypertensive and metabolic effects of high-dose olmesartan and telmisartan in type 2 diabetes patients with hypertension. We performed a crossover study in hypertensive patients with type 2 diabetes to compare olmesartan (40 mg/day) with telmisartan (80 mg/day) in terms of their antihypertensive and metabolic effects. The subjects were 36 patients (20 men and 16 women) with type 2 diabetes who did not achieve a blood pressure <130/80 mmHg following treatment with olmesartan at 40 mg/day or telmisartan at 80 mg/day for 8 weeks or more. The primary endpoint was the blood pressure reduction rate, while the secondary endpoints were BMI, parameters of glucose metabolism, HMW-adiponectin, hs-CRP and lipids metabolism. All parameters were measured in Weeks 0, 12, and 24. Treatments were switched in Week 0, and Week 12 and the following results were obtained. There were 1) no significant differences in baseline characteristics; 2) no significant difference of the blood pressure reduction rate; 3) significant reductions of HbA1c (NGSP), FPG and HOMA-IR in olmesartan group; 4) a significant increase of HDL-C in olmesartan group; 5) a decrease of hs-CRP and a increase of HMW-adiponectin in olmesartan group; and 6) a positive correlation between the percent changes of HOMA-IR and hs-CRP in olmesartan group. In conclusion, there was no difference of the blood pressure reduction achieved at the highest dose in olmesartan group and telmisartan group. But improvement of glycemic control and insulin resistance was only observed in olmesartan group. Because there was a correlation between the percent changes of HOMA-IR and hs-CRP, these effects of olmesartan might be mediated by an anti-inflammatory action. 23017417 Pre-bottling use of dehydrated waste grape skins to improve colour, phenolic and aroma composition of red wines. Different dehydrated waste grape skins from the juice industry were added into aged and young red wines as an innovative way of compensating for colour loss before bottling. After addition of grape skins, colour intensity of wines increased a mean 11% and a maximum of 31% with predominance of the red component. Total polyphenols mean increase was 10% with a maximum value of 20%. Analysis of low molecular weight phenolic compounds by HPLC-DAD showed a significant (p<0.05) content increase of the bioactive compounds gallic acid, (+)-catechin, (-)-epicatechin, and (E)-resveratrol. Anthocyanins content also increased at an average of 50mg/l. The volatile profile of wines analysed by SBSE-GC-MS was only moderately influenced by the treatments. Mixtures of dehydrated waste grape skins were useful to improve the colour and polyphenol profile of red wines, considering them a useful tool for correcting colour loss before bottling. 23544715 Abdominal adiposity through adipocyte secretion products, a risk factor for endometrial cancer. Abstract Background and aim: The adipose cell has been considered an inert cell from a secretory point of view. Studies over the past years have confirmed the capacity of the adipocyte to synthesize many substances including: adiponectin, leptin, which integrate multiple metabolic and endocrine signals. In the context of endometrial cancer, abdominal obesity as a risk factor is associated with a chronic inflammatory process, confirmed by the increase of inflammatory markers. The study aimed to identify a correlation between abdominal obesity, plasma adipokine levels and endometrial cancer. Material and method: Two groups of patients were included in the study: group I - 44 patients diagnosed with endometrial cancer, group II - 44 patients without gynecological pathology or inflammatory disorders. After the performance of clinical examination and anthropometric measurements, abdominal fat was determined by dual X-ray absorptiometry and plasma adiponectin and leptin levels were measured. Results: A significantly higher abdominal fat and leptin value was found in the group of patients in with endometrial cancer (p < 0.0001), while the plasma adiponectin level was significantly lower, compared to the control group (p < 0.0001). Abdominal fat was in a negative linear correlation with the plasma adiponectin level and in a positive linear correlation with the plasma leptin level. Conclusions: The measurement of adiponectin and leptin levels associated with the determination of abdominal adipose tissue can be a useful predictor factor for endometrial cancer. 23407410 Visualizing RNA base-pairing probabilities with RNAbow diagrams. There are many effective ways to represent a minimum free energy RNA secondary structure that make it easy to locate its helices and loops. It is a greater challenge to visualize the thermal average probabilities of all folds in a partition function sum; dot plot representations are often puzzling. Therefore, we introduce the RNAbows visualization tool for RNA base pair probabilities. RNAbows represent base pair probabilities with line thickness and shading, yielding intuitive diagrams. RNAbows aid in disentangling incompatible structures, allow comparisons between clusters of folds, highlight differences between wild-type and mutant folds, and are also rather beautiful. 23161731 Laminar silk scaffolds for aligned tissue fabrication. 3D-biomaterial scaffolds with aligned architecture are of vital importance in tissue regeneration. A generic method is demonstrated to produce aligned biomaterial scaffolds using the physics of directional ice freezing. Homogeneously aligned 3D silk scaffolds with high porosity and alignment are prepared. The method can be adapted to a wide range of polymers and is devoid of any chemical reactions, thus avoiding potential complications associated with by-products. Mechanical properties and cellular responses with chondrocytes and bone-marrow-derived hMSCs are studied, assessing survival, proliferation, and differentiation. In vivo tests suggest biocompatibility of the matrices for future tissue engineering applications, specifically in areas where high cellular alignment is needed. 23228469 From a cytotoxic agent to the discovery of a novel antimalarial agent. A novel cytotoxin 3,5-bis(4-chlorobenzylidene)-1-[4-{2-(4-morpholinyl)ethoxy}phenyl-carbonyl]-4-piperidone hydrochloride 2 demonstrated potent antimalarial properties with IC(50) values of 0.60 and 1.97 μM against the drug sensitive D6 strain and the C235 drug-resistant strain of Plasmodium falciparum. This compound concentrates in red blood cells, lowers glutathione concentrations in erythrocytes and permeates across CACO-2 cells. These data reveal 2 to be a promising lead compound in the quest for novel antimalarial agents. 23392568 Maternal exposure to mercury chloride during pregnancy and lactation affects the immunity and social behavior of offspring. Developmental HgCl2 exposures of F1 offspring (H-2(q/s)) from unsociable SJL/J (H-2(s)) dams with high susceptibility to Hg-induced autoimmunity (SFvF1) and from highly sociable FVB/NJ (FVB; H-2(q)) dams with lower susceptibility to Hg-induced autoimmunity (FvSF1) were investigated. Hg exposure increased the serum IgG levels of all offspring at postnatal day 21 (pnd21) and of SJL/J dams but not of FVB dams. Serum IgG anti-brain antibody (Ab) levels of pnd21 SFvF1 offspring and SJL dams were higher than those of the FvSF1 offspring and FVB dams, but Hg only increased the titers of the FVB dams and their offspring. Hg significantly elevated the presence of IgG in all brain regions of the pnd21 SFvF1 offspring, and the SFvF1 offspring had greater amounts of IgG in the brain than the FvSF1 offspring, which had Hg-induced increases in only two brain regions. Cytokine levels were elevated in the brain regions of Hg-treated pnd21 SFvF1 but not of FvSF1 offspring, and SFvF1 females had more brain regions expressing cytokines than the males. At pnd70, the serum IgG, serum antibrain Abs, amounts of brain IgG, and brain cytokine levels of all of the Hg-treated offspring were equivalent to those of their appropriate controls, suggesting that developmental Hg exposure did not induce chronic immunological effects. However, the social behaviors of Hg-exposed SFvF1 offspring at pnd70 were significantly impaired, and SFvF1 females displayed greater decline in social behaviors than males, suggesting that the higher neuroinflammation of SFvF1 females earlier in life is associated with the altered behavior. Thus, developmental Hg exposure induces long-lasting effects on social behavior of offspring, which is dependent on sex and genetics and the induction of neuroinflammation. 23317450 Mechanism of copper(I)/TEMPO-catalyzed aerobic alcohol oxidation. Homogeneous Cu/TEMPO catalyst systems (TEMPO = 2,2,6,6-tetramethylpiperidine-N-oxyl) have emerged as some of the most versatile and practical catalysts for aerobic alcohol oxidation. Recently, we disclosed a (bpy)Cu(I)/TEMPO/NMI catalyst system (NMI = N-methylimidazole) that exhibits fast rates and high selectivities, even with unactivated aliphatic alcohols. Here, we present a mechanistic investigation of this catalyst system, in which we compare the reactivity of benzylic and aliphatic alcohols. This work includes analysis of catalytic rates by gas-uptake and in situ IR kinetic methods and characterization of the catalyst speciation during the reaction by EPR and UV-visible spectroscopic methods. The data support a two-stage catalytic mechanism consisting of (1) "catalyst oxidation" in which Cu(I) and TEMPO-H are oxidized by O(2) via a binuclear Cu(2)O(2) intermediate and (2) "substrate oxidation" mediated by Cu(II) and the nitroxyl radical of TEMPO via a Cu(II)-alkoxide intermediate. Catalytic rate laws, kinetic isotope effects, and spectroscopic data show that reactions of benzylic and aliphatic alcohols have different turnover-limiting steps. Catalyst oxidation by O(2) is turnover limiting with benzylic alcohols, while numerous steps contribute to the turnover rate in the oxidation of aliphatic alcohols. 23584090 Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions. Colon cancer is a clinically diverse disease. This heterogeneity makes it difficult to determine which patients will benefit most from adjuvant therapy and impedes the development of new targeted agents. More insight into the biological diversity of colon cancers, especially in relation to clinical features, is therefore needed. We demonstrate, using an unsupervised classification strategy involving over 1,100 individuals with colon cancer, that three main molecularly distinct subtypes can be recognized. Two subtypes have been previously identified and are well characterized (chromosomal-instable and microsatellite-instable cancers). The third subtype is largely microsatellite stable and contains relatively more CpG island methylator phenotype-positive carcinomas but cannot be identified on the basis of characteristic mutations. We provide evidence that this subtype relates to sessile-serrated adenomas, which show highly similar gene expression profiles, including upregulation of genes involved in matrix remodeling and epithelial-mesenchymal transition. The identification of this subtype is crucial, as it has a very unfavorable prognosis and, moreover, is refractory to epidermal growth factor receptor-targeted therapy. 23529793 RANKL subcellular trafficking and regulatory mechanisms in osteocytes. The receptor activator of the NF-κB ligand (RANKL) is the central player in the regulation of osteoclastogenesis and the quantity of RANKL presented to osteoclast precursors is an important factor determining the magnitude of osteoclast formation. Since osteoblastic cells are thought to be a major source of RANKL, the regulatory mechanisms of RANKL subcellular trafficking have been studied in osteoblastic cells. However, recent reports showed that osteocytes are a major source of RANKL presentation to osteoclast precursors, prompting a need to reinvestigate RANKL subcellular trafficking in osteocytes. Investigation of molecular mechanisms in detail needs well-designed in vitro experimental systems. Thus, we developed a novel co-culture system of osteoclast precursors and osteocytes embedded in collagen gel. Experiments using this model revealed that osteocytic RANKL is provided as a membrane-bound form to osteoclast precursors through osteocyte dendritic processes and that the contribution of soluble RANKL to the osteoclastogenesis supported by osteocytes is minor. Moreover, the regulation of RANKL subcellular trafficking, such as OPG-mediated transport of newly synthesized RANKL molecules to lysosomal storage compartments, and the release of RANKL to the cell surface upon stimulation with RANK, are confirmed to be functional in osteocytes. These results provide a novel understanding of the regulation of osteoclastogenesis. © 2013 American Society for Bone and Mineral Research. 23205763 Magnetic nanoclusters exhibiting protein-activated near-infrared fluorescence. Composite nanoclusters with chemical, magnetic, and biofunctionality offer broad opportunities for targeted cellular imaging. A key challenge is to load a high degree of targeting, imaging, and therapeutic functionality onto stable metal-oxide nanoparticles. Here we report a route for producing magnetic nanoclusters (MNCs) with alkyne surface functionality that can be utilized as multimodal imaging probes. We form MNCs composed of magnetic Fe(3)O(4) nanoparticles and poly(acrylic acid-co-propargyl acrylate) by the co-precipitation of iron salts in the presence of copolymer stabilizers. The MNCs were surface-modified with near-infrared (NIR) emitting fluorophore used in photodynamic therapy, an azide-modified indocyanine green. The fluorophores engaged and complexed with bovine serum albumin, forming an extended coverage of serum proteins on the MNCs. These proteins isolated indocyanine green fluorophores from the aqueous environment and induced an effective "turn-on" of NIR emission. 23454297 Caffeic acid treatment alters the extracellular adenine nucleotide hydrolysis in platelets and lymphocytes of adult rats. This study evaluated the effects of caffeic acid on ectonucleotidase activities such as NTPDase (nucleoside triphosphate diphosphohydrolase), Ecto-NPP (nucleotide pyrophosphatase/phosphodiesterase), 5'-nucleotidase and adenosine deaminase (ADA) in platelets and lymphocytes of rats, as well as in the profile of platelet aggregation. Animals were divided into five groups: I (control); II (oil); III (caffeic acid 10mg/kg); IV (caffeic acid 50mg/kg); and V (caffeic acid 100mg/kg). Animals were treated with caffeic acid diluted in oil for 30days. In platelets, caffeic acid decreased the ATP hydrolysis and increased ADP hydrolysis in groups III, IV and V when compared to control (P<0.05). The 5'-nucleotidase activity was decreased, while E-NPP and ADA activities were increased in platelets of rats of groups III, IV and V (P<0.05). Caffeic acid reduced significantly the platelet aggregation in the animals of groups III, IV and V in relation to group I (P<0.05). In lymphocytes, the NTPDase and ADA activities were increased in all groups treated with caffeic acid when compared to control (P<0.05). These findings demonstrated that the enzymes were altered in tissues by caffeic acid and this compound decreased the platelet aggregation suggesting that caffeic acid should be considered a potentially therapeutic agent in disorders related to the purinergic system. 23614827 Two new compounds from Schisandra glaucescens. One new lignan (7S,8R,7'R,8'R)-7-(3,4-methylenedioxyphenyl)-8,8'-dimethyl-8'-hydroxyl-7'-methoxyl-7'-(3',4'-methylenedioxyphenyl)-tetrahydrofuran (1), one new sesquiterpene 2-hydroxy-11,12-dehydrocalamenene (2), one new natural product erythro-1-(3,4-dimethoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane (3), and two known lignans (+)-anwulignan(erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane) (4) and ( - )-zuonin-A (5) were isolated from the stems of Schisandra glaucescens Diels. Their structures were elucidated by spectroscopic methods. The cytotoxicity of compounds 1 and 2 was assayed. 23132743 Ligand-dependent actions of the vitamin D receptor are required for activation of TGF-β signaling during the inflammatory response to cutaneous injury. The vitamin D receptor (VDR) has both 1,25-dihydroxyvitamin D-dependent and -independent actions in the epidermis. Ligand-dependent actions of the VDR have been shown to promote keratinocyte differentiation and to regulate formation of the epidermal barrier. In contrast, the actions of the VDR that regulate postmorphogenic hair cycling do not require 1,25-dihydroxyvitamin D. The VDR also has immunomodulatory actions that are dependent on its ligand, 1,25-dihydroxyvitamin D. To determine whether the ligand-dependent or -independent actions of the VDR regulate the inflammatory response to cutaneous injury, studies were performed in control, VDR knockout, and vitamin D-deficient mice. These investigations demonstrate that absence of receptor or ligand impairs the dermal response to cutaneous injury. Although neutrophil recruitment is not affected, the absence of VDR signaling leads to defects in macrophage recruitment and granulation tissue formation. Studies performed to identify the molecular basis for this phenotype demonstrate that absence of the VDR, or its ligand, impairs TGF-β signaling in the dermis, characterized by decreased expression of monocyte chemotactic protein-1 and reduced phosphorylation of phosphorylated Smad-3 as well as attenuated phosphorylated Smad-3 phosphorylation in response to TGF-β in primary dermal fibroblasts lacking the VDR. Thus, these data demonstrate that the liganded VDR interacts with the TGF-β signaling pathway to promote the normal inflammatory response to cutaneous injury. 23639537 Design, synthesis and biological evaluation of indeno[1,2-d]thiazole derivatives as potent histone deacetylase inhibitors. Novel indeno[1,2-d]thiazole hydroxamic acids were designed, synthesized, and evaluated for histone deacetylases (HDACs) inhibition and antiproliferative activities on tumor cell lines. Most of the tested compounds exhibited HDAC inhibition and antiproliferative activity against both MCF7 and HCT116 cells with GI50 values in the sub-micromolar range. Among them, compound 6o showed good inhibitory activity against pan-HDAC with IC50 value of 0.14μM and significant growth inhibition on MCF7 and HCT116 cells with GI50 values of 0.869 and 0.535μM, respectively. 23449205 Lasiodiplodin analogues from the endophytic fungus Sarocladium kiliense. A new 12-membered ring lactone, (3S),(6R)-6-hydroxylasiodiplodin (1), with two known analogues, (3R)-lasiodiplodin (2), and (3R),(5S)-5-hydroxylasiodiplodin (3) were isolated from the EtOH extracts of normal Apriona germari (Hope)-associated fungus Sarocladium kiliense grown in rice medium. The structures of compounds 1-3 were elucidated by a combination of spectroscopic data interpretation, single-crystal X-ray diffraction analysis, and modified Mosher's method. 23325373 Can you enhance executive control without glucose? The effects of fructose on problem solving. The consumption of glucose can enhance executive control by increasing blood glucose and providing energy for brain processes. However, a glucose mouth rinse also positively affects executive control in the absence of an effect on blood glucose. This observation suggests that glucose can enhance executive control via another mechanism, perhaps by increasing cortical activation in motivational reward pathways. This hypothesis was examined in the current study by having participants consume fructose, glucose or a placebo 10 minutes before solving word anagrams. Fructose was used because it does not affect blood glucose levels, inhibits cortical responding, and cannot entrain a taste preference post-ingestion. The latter evidences that fructose differs from glucose in its ability to elicit activation in motivational reward pathways. It was observed that consuming fructose and glucose resulted in the resolution of more anagrams than the placebo. These results suggest that at least some of the effects of glucose and fructose on problem solving operate through a common peripheral mechanism that is independent of motivational reward pathways. 23387796 Isolation and characterization of unusual hydrazides from Streptomyces sp. impact of the cultivation support and extraction procedure. Three novel hydrazides, geralcins C-E (1-3), were isolated from Streptomyces sp. LMA-545, together with MH-031 and geralcins A and B. This unusual family of compounds was isolated from liquid-state and agar-supported fermentation using Amberlite XAD-16 solid-phase extraction during the cultivation step. The use of such neutral resin during the cultivation step allowed the specific adsorption of microbial secondary metabolites, avoiding any contamination of the crude extracts by the constituents of the culture medium. The trapped compounds were eluted from the resin with methanol, and their structures elucidated using (1)H, (13)C, and (15)N NMR spectroscopic analysis and high-resolution mass spectrometry. Molecular modeling calculations were applied in order to support structural attributions. No antimicrobial, cytotoxic, or DnaG-inhibition activities were detected for geralcins D and E. Geralcin C has no antimicrobial activity but exhibited an IC(50) of 0.8 μM against KB and HCT116 cancer cell lines. Furthermore, geralcin C inhibited the E. coli DnaG primase, a Gram-negative antimicrobial target, with an IC(50) of 0.7 mM. 23562910 Loss of FMR2 further emphasizes the link between deregulation of immediate early response genes FOS and JUN and intellectual disability. Loss of FMR2 causes Fragile X E (FRAXE) site-associated intellectual disability (ID). FMR2 regulates transcription, promotes alternative splicing with preference for G-quartet structure harbouring exons and is localized to the nuclear speckles. In primary skin fibroblasts from FRAXE patients (n = 8), we found a significant reduction in the number, but a significant increase in the size, of nuclear speckles, when compared with the controls (n = 4). Since nuclear speckles are enriched with factors involved in pre-mRNA processing, we explored the consequence of these defects and the loss of FMR2 on the transcriptome. We performed whole genome expression profiling using total RNA extracted from these cell lines and found 27 genes significantly deregulated by at least 2-fold at P < 0.05 in the patients. Among these genes, FOS was significantly upregulated and was further investigated due to its established role in neuronal cell function. We showed that (i) 30% depletion of Fmr2 in mouse primary cortical neurons led to a 2-fold increase in Fos expression, (ii) overexpression of FMR2 significantly decreased FOS promoter activity in luciferase assays, and (iii) as FOS promoter contains a serum response element, we found that not FOS, but JUN, which encodes for a protein that forms a transcriptional activator complex with FOS, was significantly upregulated in the patients' cell lines upon mitogen stimulation. These results suggest that FMR2 is an upstream regulator of FOS and JUN, and further link deregulation of the immediate early response genes to the pathology of ID- and FRAXE-associated ID in particular. 23525167 NMR characterisation of dynamics in solvates and desolvates of formoterol fumarate. Solid-state NMR is used to characterise dynamics in the ethanol solvate of the pharmaceutical material formoterol fumarate and its associated desolvate. Jump rates and activation barriers for dynamic processes such as phenyl ring rotation and methyl group rotational diffusion are derived from 1D-EXSY and (13)C spin-lattice relaxation times respectively. (2)H and (13)C spin-lattice relaxation times measured under magic-angle spinning conditions are used to show that the fumarate ion in the desolvate is undergoing small-amplitude motion on a frequency scale of 100s of MHz at ambient temperature with an activation parameter of about 32 kJ mol(-1). Exact calculations of relaxation times under MAS provide a simple and robust means to test motional models in cases where relaxation rate maxima are observed, including for systems where the crystal structure of the material is unknown. 23329065 Effects of dopamine D2 agonist quinpirole on neuronal activity of anterior cingulate cortex and striatum in rats. RATIONALE: The influence of acute D2 agonist quinpirole on locomotor activity has been effectively characterized. However, few studies have addressed the dynamic changes in neuronal activity of the anterior cingulate cortex (ACC) and striatum (STR), two crucial regions for cognitive and motor functions, after quinpirole administration. OBJECTIVE: This study was conducted in order to acquire detailed information on the evoked activity of the neurons in the ACC and STR after acute quinpirole administration. METHODS: Multichannel electrophysiological recording was used for tracking neuronal activity in the ACC and STR of urethane-anesthetized rats after administration of saline or 0.05 or 0.5 mg/kg quinpirole. RESULTS: In contrast to the responses to saline, quinpirole dose-dependently increased the ratio of neurons, the activity of which was inhibited in the ACC and STR. By examining the ensemble neuronal activities of inhibition-responded neurons, there was no significant activity difference among the "treatments" (saline and low- and high-dose quinpirole), the "periods" (the duration of 0-15 and 16-45 min after i.v. injection), and the interaction between "treatments" and "periods." Regarding activation-responded neurons, however, there was a significant "periods" difference in both ACC and STR, and the activity of 16-45 min was significantly higher than the activity of 0-15 min after high-dose quinpirole administration in ACC (p < 0.05) and STR (p < 0.001). CONCLUSION: Dose-dependent ACC and STR neuronal responses to quinpirole may offer a possible mechanism for understanding the locomotor responses to quinpirole in behaving rats. The late excitatory effect of high-dose quinpirole in the STR further suggests that this region would be critical for the activation of locomotor activity. 23632086 The Prevalence, Maintenance and Relevance of GPCR Oligomerization. Over the past decade ideas and experimental support for the hypothesis that G protein-coupled receptors may exist as dimeric or oligomeric complexes moved initially from heresy to orthodoxy, to the current situation in which the capacity of such receptors to interact is generally accepted but the prevalence, maintenance and relevance of such interactions to both pharmacology and function remain unclear. A vast body of data obtained following transfection of cultured cells is still to be translated to native systems and, even where this has been attempted, results often remain controversial and contradictory. This review will consider approaches that are currently being applied, why these might be challenging to interpret and suggest means to overcome these limitations. 23636446 A glucocorticoid education group meeting: an effective strategy for improving self-management to prevent adrenal crisis. OBJECTIVE: To assess self-management in patients receiving glucocorticoid replacement therapy for primary or secondary adrenal failure before and 6 months after a glucocorticoid education group meeting. METHODS: All patients with primary or secondary adrenal insufficiency, treated at the department of Medicine, Division of Endocrinology were invited by their endocrinologist to participate in a three-hour glucocorticoid education group meeting, consisting of a lecture about the disease and glucocorticoid doses adjustments in case of stress , followed by an instruction how to inject hydrocortisone intramusculary. Finally, all participants could practice the intramuscular injection and discuss their experience with (imminent) adrenal crises with other patients and the health care providers. Two weeks before the meeting and 6 months after the meeting, patients were asked to fill out a questionnaire about how they would act in 6 different conditions (e.g. febrile illness or vomiting). RESULTS: Of the 405 patients who were invited, 246 patients (61%) participated. At baseline the response by the participants on the questionnaire was 100% (N=246) and at follow-up 74% (N=183). At follow-up, significantly more participants (p=<0.005) gave the correct answers how to act in the different situations (e.g. self administration of a glucocorticoid injection and phone contact in case of vomiting/diarrhoea without fever). Moreover, the use of self-management tools, such as having a 'medicine passport (travel document with information about disease and medication) (p=0.007) or SOS medallion (p=0.0007)' increased. CONCLUSION: A glucocorticoid education group meeting for patients with adrenal failure seems helpful to improve self-management and proper use of stress-related glucocorticoid dose adjustment. 23453303 Protective effects of propolis on female rats' histopathological, biochemical and genotoxic changes during LPS induced endotoxemia. In recent years, propolis has been the object of extensive research for its antibacterial, antioxidant, anti-inflammatory, and antitumoral activities. This study aims to determine the hepatoprotective efficiency of propolis on experimental endotoxemia in rats. In the current study, fifty adult Sprague Dawley rats (weighing 200-300g) were randomly divided into five groups of ten rats each. Normal saline solution was administered to the rats in the control group, while in the second group LPS (30mg/kg), in the third group propolis (250mg/kg), in the fourth group first propolis and then LPS (30mg/kg), and in the fifth group, first LPS (30mg/kg) and then propolis were given. Six hours after the application, biochemical (MDA levels) and histopathological changes as well as global DNA methylation analysis in the liver tissue samples were determined, while in the blood tissue samples Genomic Template Stability (GTS, %) was evaluated using RAPD-PCR profiles. The results demonstrated that the administration of propolis could have a protective effect against changes of both genomic stability values and methylation profiles, and it minimized the increase in MDA and tissue damage caused by LPS. In conclusion, the application of propolis prior to LPS-induced endotoxemia has shown to reduce hepatic damage. 23237939 Inhibition of homologous recombination by hyperthermia shunts early double strand break repair to non-homologous end-joining. In S and G2 phase mammalian cells DNA double strand breaks (DSBs) can potentially be repaired by homologous recombination (HR) or non-homologous end-joining (NHEJ). Results of several studies suggest that these two mechanistically distinct repair pathways can compete for DNA ends. Because HR and NHEJ differ with respect to error susceptibility, generation of chromosome rearrangements, which are potentially carcinogenic products of DSB repair, may depend on the pathway choice. To investigate this hypothesis, the influence of HR and NHEJ inhibition on the frequencies of chromosome aberrations in G2 phase cells was investigated. SW-1573 and RKO cells were treated with mild (41 °C) hyperthermia in order to disable HR and/or NU7441/cisplatin to inactivate NHEJ and frequencies of chromosomal fragments (resulting from unrepaired DSBs) and translocations (products of erroneous DSB rejoining) were studied using premature chromosome condensation (PCC) combined with fluorescence in situ hybridization (FISH). It is shown here that temporary inhibition of HR by hyperthermia results in increased frequency of ionizing-radiation (IR)-induced chromosomal translocations and that this effect is abrogated by NU7441- or cisplatin-mediated inhibition of NHEJ. The results suggest that in the absence of HR, DSB repair is shifted to the error-prone NHEJ pathway resulting in increased frequencies of chromosomal rearrangements. These results might be of consequence for clinical cancer treatment approaches that aim at inhibition of one or more DSB repair pathways. 23537575 Design of pH responsive clickable prodrugs applied to histone deacetylase inhibitors: A new strategy for anticancer therapy. The aim of this study was to develop clickable prodrugs bearing a tunable pH responsive linker designed for acidic pH-mediated release of histone deacetylase inhibitors. HDACi are an important class of molecules belonging to the epigenetic modulators used for innovative cancer strategies. The behavior of these prodrugs was determined by a bioluminescence resonance energy transfer assay in living tumor cells. This work demonstrated that this innovative type of clickable prodrugs entered cancer cells and showed restored anti proliferative properties attributed to the effective release of the HDAC inhibitors. A correlation between kinetic studies, dose responses, and biological activities was obtained, making such clickable prodrugs good candidates for new strategies in epigenetic-oriented anticancer therapies. 23161664 Hypoxia-response element (HRE)-directed transcriptional regulation of the rat lysyl oxidase gene in response to cobalt and cadmium. Lysyl oxidase (LO) catalyzes crosslink of collagen, elastin, and histone H1, stabilizing the extracellular matrix and cell nucleus. This enzyme displays dual functions for tumorigenesis, i.e., as a tumor suppressor inactivating the ras oncogene and as a tumor promoter enhancing malignant cell metastasis. To elucidate LO transcriptional regulation, we have cloned the 804 base pair region upstream of the translation start site (ATG) of the rat LO gene with the maximal promoter activity. Computer analysis indicated that at least four hypoxia-response element (HRE) consensuses (5'-ACGTG-3') exist in the cloned LO promoter. Treatment of rat lung fibroblasts (RFL6) with CoCl2 (Co, 10-100 μM), a chemical hypoxia reagent, enhanced LO mRNA expression and promoter activities. Overexpression of LO was associated with upregulation of hypoxia-inducible factor (HIF)-1α at mRNA levels in cobalt (Co)-treated cells. Thus, LO is a hypoxia-responsive gene. Dominant negative-HIF-1α inhibited LO promoter activities stimulated by Co. Electrophoretic mobility shift, oligonucleotide competition, and in vitro translated HIF-1α binding assays indicated that only one HRE mapped at -387/-383 relative to ATG was functionally active among four consensuses. Site-directed mutation of this HRE significantly diminished the Co-induced and LO promoter-directed expression of the reporter gene. Cadmium (Cd), an inducer of reactive oxygen species, inhibited HIF-1α mRNA expression and HIF-1α binding to the LO gene in Co-treated cells as revealed by RT-PCR and ChIP assays, respectively. Thus, modulation of the HRE activity by Co and Cd plays a critical role in LO gene transactivation. 23612242 Transcriptional and catalytic responses of antioxidant and biotransformation pathways in mussels, Mytilus galloprovincialis, exposed to chemical mixtures. Antioxidant and biotransformation pathways are widely studied in marine organisms exposed to environmental stressors. However, mechanisms of responses and links between different intracellular levels are not always easy to elucidate and conflicting results are frequently observed between molecular and enzymatic data. In this study, transcriptional and catalytic responses of antioxidant and biotransformation parameters were analyzed after a 4-week exposure of a marine invertebrate, Mytilus galloprovincialis, to chemical mixtures from low polluted and highly polluted sediments. A significant, dose-dependent bioaccumulation was observed for polycyclic aromatic hydrocarbons, especially low molecular weight compounds. Among antioxidant defences, catalase and glutathione peroxidases did not exhibit variations in enzymatic activity, while the corresponding gene transcriptions were up- and down-regulated, respectively; unchanged mRNA levels of superoxide dismutase confirmed the non-synchronous pathways of variations for such antioxidants. Biotransformation responses also revealed inconsistent trends between transcriptional and catalytic variations of glutathione S-transferases, and a significant increase in mRNA levels for cytochrome P450 3A1. The overall results indicated that transcriptional responses might be sensitive but do not necessarily correspond to functional changes, being more useful as "exposure" rather than "effect" biomarkers. Data on gene transcription and catalytic activities should be carefully interpreted when assessing the impact of chemical pollutants and additional studies are needed on modulation of post-transcriptional mechanisms by environmental stressors. 23545999 Isolation of Five New Flavonoids from Melicope triphylla. Five new flavonoids, 5,8-dihydroxy-3,7-dimethoxy-3',4'-methylenedioxyflavone (1), 7-hydroxy-3,5-dimethoxy-3',4'-methylenedioxyflavone (2), 7-(2,3-dihydroxy-3-methylbutoxy)-3,5-dimethoxy-3',4'-methylenedioxyflavone (3), 7-(2,3-dihydroxy-3-methylbutoxy)-3,3',4',5-tetramethoxyflavone (4), and 7-(2,3-dihydroxy-3-methylbutoxy)-3,3',4',5,8-pentamethoxyflavone (5), were isolated from the leaves of Melicope triphylla. In addition, six known flavonoids were detected: 3,4',5-trihydroxy-3',7,8-trimethoxyflavone (6), 5,7-dihydroxy-3-methoxy-3',4'-methylenedioxyflavone (7), 4',5,7-trihydroxy-3,3'-dimethoxyflavone (8), 4',7-dihydroxy-3,3',5,8-tetramethoxyflavone (9), 4',7-dihydroxy-3,3',5-trimethoxyflavone (10), and 4',5,7-trihydroxy-3,3',8-trimethoxyflavone (11). The new compound structures were determined by spectroscopic methods. Compounds 1-5 did not exhibit any ichthyotoxic activity against Japanese killifish (medaka in Japanese) (Oryzias latipes var.) at 10 ppm. 23474899 Synthesis, in vitro antitumor evaluation and DNA-binding study of novel tetrahydroquinolines and some derived tricyclic and tetracyclic ring systems. The synthesis of some new tetrahydroquinolines, tetrahydropyrimido[4,5-b]quinolines, and tetrahydropentaazacyclopenta[a]anthracenes structurally related to some DNA intercalators is described. Fifteen compounds were evaluated for their antitumor activity by the National Cancer Institute (NCI), in vitro disease oriented antitumor screening. The most active tricyclic pyrimido[4,5-b]quinolines 3b, 6b, 7b and 8b were further subjected to DNA-binding investigation in an attempt to rationalize their activity. Compound 8b proved to be the most active member in this study as evidenced from its remarkable growth inhibitory potential against some individual cell lines, and its broad spectrum of antitumor activity (GI50, TGI and LC50 values 46.9, 85.3 and 97.4, respectively), together with a good DNA-binding affinity. 23268656 On-chip thin film Zernike phase plate for in-focus transmission electron microscopy imaging of organic materials. Transmission electron microscopy (TEM) is a powerful tool for imaging nanostructures, yet its capability is limited with respect to the imaging of organic materials because of the intrinsic low contrast problem. TEM phase plates have been in development for decades, yet a reliable phase plate technique has not been available because the performance of TEM phase plates deteriorates too quickly. Such an obstacle prohibits in-focus TEM phase imaging to be routinely achievable, thus limiting the technique being used in practical applications. Here we present an on-chip thin film Zernike phase plate which can effectively release charging and allow reliable in-focus TEM images of organic materials with enhanced contrast to be routinely obtained. With this stable system, we were able to characterize many polymer solar cell specimens and consequently identified and verified the existence of an unexpected nanoparticle phase. Furthermore, we were also able to observe the fine structures of an Escherichia coli specimen, without staining, using this on-chip thin film phase plate. Our system, which can be installed on a commercial TEM, opens up exciting possibilities for TEM to characterize organic materials. 22903169 Human and cattle ergotism since 1900: Symptoms, outbreaks, and regulations. Ergotism in humans and cattle are caused by several species of Claviceps that infect rye and other cereal grains. Symptoms in humans vary greatly and are generally classified as convulsive, gangrenous, or gastrointestinal (enteric). Cattle are particularly susceptible to both gangrenous and hyperthermic ergotism (also called summer syndrome). The prevalence of ergotism has decreased as knowledge of the fungus has increased, mainly through implementation of regulations and advances in milling procedures. However, outbreaks in humans have recently occurred in lower socioeconomic populations of Ethiopia (1977 and 2001) and India (1975) with devastating results. Prominent outbreaks in cattle have occurred in Australia (1987), the United States (1996), South Africa (1996-1997), and Brazil (1999) and, as opposed to human cases, they do not appear to be bound by economic development. This review provides a detailed summary of all major ergot epidemics since 1900 in both humans and cattle. Special attention is devoted to the ergotism symptoms and to the regulations surrounding the control of ergot in the food supply. 23574534 A Facile Integration of Zero- (I-III-VI Quantum Dots) and One- (Single SnO2 Nanowire) Dimensional Nanomaterials: Fabrication of a Nanocomposite Photodetector with Ultrahigh Gain and Wide Spectral Response. Via the integration of nanocomposites comprising I-III-VI semiconductor quantum dots (QDs) decorated onto a single SnO2 nanowire (NW), we successfully fabricate an ultrahigh-sensitivity and wide spectral-response photodetector. Under the illumination of He-Cd laser (325 nm) with the photon energy larger than the band gap of SnO2 nanowire, remarkably, an ultrahigh photocurrent gain up to 2.5 × 10(5) has been achieved, and an enhancement factor can reach up to 700% (cf. bare SnO2 NW) as light illumination onto the wire with an excitation intensity of 15 W/m(2). Also, a high gain value up to 1.3 × 10(5) is attained with the excited photon energy (488 nm) smaller than the band gap of SnO2 nanowire. Several key factors contribute to ultrahigh photocurrent gain and wide spectral response. First, the decorated quantum dot processes an inherent nature of a large absorption coefficient above its band gap. Furthermore, the single SnO2 nanowire provides an excellent conduction path for the photogenerated carriers as well as bears a large surface-to-volume ratio so that the coupling strength with quantum dots can be greatly enhanced. Most importantly, the spatial separation of photogenerated electrons and holes can be easily achieved due to the charge transfer arising from a type II band alignment between QDs and SnO2 NW. This work thus demonstrates a new approach in which by selectively decorating suitable QDs the photocurrent gain of SnO2 NWs can be greatly enhanced and extended to a wide spectral range of photoresponse previously inaccessible, providing a very useful guideline to create cheap, nontoxic, and highly efficient photodetectors. 23151250 Stabilizing the pro-apoptotic BimBH3 helix (BimSAHB) does not necessarily enhance affinity or biological activity. An attractive approach for developing therapeutic peptides is to enhance binding to their targets by stabilizing their α-helical conformation, for example, stabilized BimBH3 peptides (BimSAHB) designed to induce apoptosis. Unexpectedly, we found that such modified peptides have reduced affinity for their targets, the pro-survival Bcl-2 proteins. We attribute this loss in affinity to disruption of a network of stabilizing intramolecular interactions present in the bound state of the native peptide. Altering this network may compromise binding affinity, as in the case of the BimBH3 stapled peptide studied here. Moreover, cells exposed to these peptides do not readily undergo apoptosis, strongly indicating that BimSAHB is not inherently cell permeable. 23193260 Clone DB: an integrated NCBI resource for clone-associated data. The National Center for Biotechnology Information (NCBI) Clone DB (http://www.ncbi.nlm.nih.gov/clone/) is an integrated resource providing information about and facilitating access to clones, which serve as valuable research reagents in many fields, including genome sequencing and variation analysis. Clone DB represents an expansion and replacement of the former NCBI Clone Registry and has records for genomic and cell-based libraries and clones representing more than 100 different eukaryotic taxa. Records provide details of library construction, associated sequences, map positions and information about resource distribution. Clone DB is indexed in the NCBI Entrez system and can be queried by fields that include organism, clone name, gene name and sequence identifier. Whenever possible, genomic clones are mapped to reference assemblies and their map positions provided in clone records. Clones mapping to specific genomic regions can also be searched for using the NCBI Clone Finder tool, which accepts queries based on sequence coordinates or features such as gene or transcript names. Clone DB makes reports of library, clone and placement data on its FTP site available for download. With Clone DB, users now have available to them a centralized resource that provides them with the tools they will need to make use of these important research reagents. 23164613 The serotonin receptor 7 promotes neurite outgrowth via ERK and Cdk5 signaling pathways. Serotonergic neurotransmission is mediated by at least 14 subtypes of 5-HT receptors. Among these, the CNS serotonin receptor 7 (5-HTR7) is involved in diverse physiological processes. Here we show that treatment of murine striatal and cortical neuronal cultures with 5-HTR7 agonists (8-OH-DPAT and LP-211) significantly enhances neurite outgrowth. This effect is abolished by the selective 5-HTR7 antagonist SB-269970, by the ERK inhibitor U0126, by the cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine, as well as by cycloheximide, an inhibitor of protein synthesis. These data indicate that 5-HTR7 activation stimulates extensive neurite elongation in CNS primary cultures, subserved by ERK and Cdk5 activation, and de novo protein synthesis. Two-dimensional (2D) gel electrophoresis coupled to Western blot analyses reveals both qualitative and quantitative expression changes in selected cytoskeletal proteins, following treatment of striatal primary cultures with LP-211. In particular, the 34 kDa isoform of MAP1B is selectively expressed in stimulated cultures, consistent with a role of this protein in tubulin polymerization and neurite elongation. In summary, our results show that agonist-dependent activation of the endogenous 5-HTR7 in CNS neuronal primary cultures stimulates ERK- and Cdk5-dependent neurite outgrowth, sustained by modifications of cytoskeletal proteins. These data support the hypothesis that the 5-HTR7 might play a crucial role in shaping neuronal morphology and behaviorally relevant neuronal networks, paving the way to new approaches able to modulate CNS connectivity. 23411213 Simultaneous determination of aflatoxin B(1) and ochratoxin A in licorice roots and fritillary bulbs by solid-phase extraction coupled with high-performance liquid chromatography-tandem mass spectrometry. An effective method was developed for screening licorice roots and fritillary bulbs for contamination by aflatoxin B(1) and ochratoxin A using high-performance liquid chromatography connected to tandem mass spectrometry (HPLC-MS/MS). The samples were pre-concentrated and purified using solid-phase extraction, which provided satisfactory results. The separation was performed on a Waters Xbridge(TM) C18 column with a linear gradient of acetonitrile - water containing 5mM ammonium acetate. The MS spectrum was acquired in positive mode with both single quadrupole (Q1) and multiple reaction monitoring (MRM). The optimised method offered a good linear correlation (r(2)>0.9967), excellent precision (RSD<2.83%) and acceptable recovery (from 92.78 to 105.37%). The limits of detection (LOD) and the limits of quantification (LOQ) were less than 0.024 μg/kg and 0.095 μg/kg, respectively. The validated method was successfully applied to the rapid screening for AFB(1) and OTA in licorice roots and fritillary bulbs. 22918066 An unusual cause of factitious arthritis. Septic arthritis and toxic synovitis are clinical conditions that can develop in association with various causes and involve symptoms such as pain, swelling, redness, sensitivity and restricted movement in the joint. A 42-year-old male presented to the emergency department with severe joint pain and nausea after injecting a 1-cc mixture of turpentine oil, eucalyptus oil, mint oil and thyme oil, which he purchased from an alternative medicine store, into his right knee with a syringe because of chronic knee pain. Ballottement and sensitivity were present at physical examination. Knee puncture yielded 60 cc of cloudy fluid. There was no growth in the material obtained. Improvement was observed following subsequent arthroscopic washing of the joint space and IV antibiotherapy, and the patient was discharged on day 21 of hospitalization with oral antibiotic and analgesic therapy. Intra-articular injection of foreign bodies into the knee joint space for therapeutic purposes, as in this case report, is a very rare occurrence, but may lead to potentially complicated arthritis. 23411199 Quantification by UHPLC of total individual polyphenols in fruit juices. The present work proposes a new UHPLC-PDA-fluorescence method able to identify and quantify the main polyphenols present in commercial fruit juices in a 28-min chromatogram. The proposed method improve the IFU method No. 71 used to evaluate anthocyanins profiles of fruit juices. Fruit juices of strawberry, American cranberry, bilberry, sour cherry, black grape, orange, and apple, were analysed identifying 70 of their main polyphenols (23 anthocyanins, 15 flavonols, 6 hydroxybenzoic acids, 14 hydroxycinnamic acids, 4 flavanones, 2 dihydrochalcones, 4 flavan-3-ols and 2 stilbenes). One standard polyphenol of each group was used to calculate individual polyphenol concentration presents in a juice. Total amount of polyphenols in a fruit juice was estimated as total individual polyphenols (TIP). A good correlation (r(2)=0.966) was observed between calculated TIP, and total polyphenols (TP) determined by the well-known colorimetric Folin-Ciocalteu method. In this work, the higher TIP value corresponded to bilberry juice (607.324 mg/100mL fruit juice) and the lower to orange juice (32.638 mg/100mL fruit juice). This method is useful for authentication analyses and for labelling total polyphenols contents of commercial fruit juices. 22917637 Catalytic activities of a cocaine hydrolase engineered from human butyrylcholinesterase against (+)- and (-)-cocaine. It can be argued that an ideal anti-cocaine medication would be one that accelerates cocaine metabolism producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway, i.e., hydrolysis catalyzed by butyrylcholinesterase (BChE) in plasma. However, wild-type BChE has a low catalytic efficiency against naturally occurring (-)-cocaine. Interestingly, wild-type BChE has a much higher catalytic activity against unnatural (+)-cocaine. According to available positron emission tomography (PET) imaging analysis using [(11)C](-)-cocaine and [(11)C](+)-cocaine tracers in human subjects, only [(11)C](-)-cocaine was observed in the brain, whereas no significant [(11)C](+)-cocaine signal was observed in the brain. The available PET data imply that an effective therapeutic enzyme for treatment of cocaine abuse could be an exogenous cocaine-metabolizing enzyme with a catalytic activity against (-)-cocaine comparable to that of wild-type BChE against (+)-cocaine. Our recently designed A199S/F227A/S287G/A328 W/Y332G mutant of human BChE has a considerably improved catalytic efficiency against (-)-cocaine and has been proven active in vivo. In the present study, we have characterized the catalytic activities of wild-type BChE and the A199S/F227A/S287G/A328 W/Y332G mutant against both (+)- and (-)-cocaine at the same time under the same experimental conditions. Based on the obtained kinetic data, the A199S/F227A/S287G/A328 W/Y332G mutant has a similarly high catalytic efficiency (kcat/KM) against (+)- and (-)-cocaine, and indeed has a catalytic efficiency (kcat/KM=1.84×10(9)M(-1)min(-1)) against (-)-cocaine comparable to that (kcat/KM=1.37×10(9)M(-1)min(-1)) of wild-type BChE against (+)-cocaine. Thus, the mutant may be used to effectively prevent (-)-cocaine from entering brain and producing physiological effects in the enzyme-based treatment of cocaine abuse. 23371055 In obese postmenopausal women, bone microarchitecture and strength are not commensurate to greater body weight. The OFELY study. Obesity is associated with higher areal bone density (aBMD) but its protective effect on the risk of fracture is controversial. We aimed to analyse bone microarchitecture and biomechanical properties in obese (OB) postmenopausal French women compared with normal weight (NW) women. A matched case-control study from the OFELY cohort was conducted in 63 OB women (BMI>30, mean age69±8 years) age-matched with 126 NW women (19DON>ZEA>FB1. At cytotoxic doses of individual mycotoxins, all mixtures gave reduced cell viability compared to control. At noncytotoxic concentrations of individual mycotoxins, all mixtures were cytotoxic with DON-NIV, DON-ZEA, DON-NIV-FB1, DON-ZEA-FB1, NIV-ZEA-FB1 and all four mixed causing the greatest loss of cell viability. The latter observation in particular raises concerns over safety margins based on single toxin species, and suggests that the effects of multiple complex mixtures need to be better understood to assess health risks. 23623795 The effect of freeze-drying parameters and formulation composition on IgG stability during drying. The objective of this study was to explore the effects of freeze-drying parameters and formulation composition on polyclonal IgG stability during processing. Samples were freeze-dried with different primary drying pressures and secondary drying heating rates. After drying, changes in IgG in vitro binding activity, monomer recovery, average particle size, and polydispersity were studied from the rehydrated lyophilizates. Significant trends were not observed in binding activities or monomer recoveries, but increases in particle size and polydispersity were observed when using lower primary drying pressure. This effect could no longer be observed when sodium phosphate buffer was removed from the formulation. Altering the secondary drying heating rates did not result in any measurable changes in protein stability. 23570470 Disclosure of individual pharmacogenomic results in research projects: when and what kind of information to return to research participants. In the growing field of genomics, the utility of returning certain research results to participants has become a highly debated issue. Existing guidelines are not explicit as to the kind of genomic information that should be returned to research participants. Moreover, very few current recommendations and articles in the literature address the return of pharmacogenomic results. Although genetics and pharmacogenomics have many similarities, the circumstances in which disclosure could have a benefit for the participants are different. This review aims to describe the conditions in which disclosure of pharmacogenomic results is appropriate. 23151610 One hundred years of helicene chemistry. Part 2: stereoselective syntheses and chiral separations of carbohelicenes. Carbohelicenes generally incorporate a helical, distorted, conjugated, polyaromatic system with ortho-fused benzenoid rings, which is a fundamental molecular characteristic of this class of compounds. They have been described as "molecules in distress" due to their distortion. The generation of a chiral helicity in helicenes was observed because of a severe intramolecular steric strain. Helicity is a molecular necessity in the higher series of carbohelicenes, when at some point, a helical pitch occurs when a second coil is formed. The most interesting properties resulting from such molecular distortion are the very high chiroptical and circular dichroism values. For instance, the resolution of some helicene racemates by "hand picking" of a few homochiral single enantiomeric crystals allowed for a measurement of their optical rotation. Due to that intrinsic chirality spanned over a large polyaromatic template, preliminary results clearly established the efficiency of carbohelicenes to induce asymmetry and chirality in organic synthesis and in supramolecular chemistry. Additionally, they have some potential uses in several fields: materials science, nanoscience, chemical biology and supramolecular chemistry. It has encouraged many attempts to develop new asymmetric syntheses of carbohelicenes, as well as some chiral separations of enantiomers and diastereoisomers. This review is thus dedicated to carbohelicene chirality. It gathered a substantial collection of data, and a comprehensive review on the preparations of enantioenriched helicenes, either from an asymmetric synthesis or from a chiral separation. Utilizations of non-racemic helicenes and their applications will be treated in the following review (Part 3), and will not be the subject of this manuscript. 23311695 Time-resolved single molecule fluorescence spectroscopy of an α-chymotrypsin catalyzed reaction. Single molecule fluorescence spectroscopy offers great potential for studying enzyme kinetics. A number of fluorescence reporter systems allow for monitoring the sequence of individual reaction events with a confocal microscope. When using a time-correlated single photon counting (TCSPC) detection scheme, additional information about the fluorescence lifetimes of the fluorophores can be obtained. We have applied a TCSPC detection scheme for studying the kinetics of α-chymotrypsin hydrolyzing a double-substituted rhodamine 110-based fluorogenic substrate in a two-step reaction. On the basis of the lifetime information, it was possible to discriminate the intermediate and the final product. At the high substrate concentration used, only the formation of the intermediate was observed. No rebinding of the intermediate followed by rhodamine 110 formation occurred at these high concentrations. We have further found no alterations in the fluorescence lifetime of this intermediate that would indicate changes in the local environment of the fluorophore originating from strong interactions with the enzyme. Our results clearly show the power of using lifetime-resolved measurements for investigating enzymatic reactions at the single molecule level. 23547706 Oxadiazole-isopropylamides as potent and non-covalent proteasome inhibitors. Abstract Screening of the 50,000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited CT-L activity (IC50 0.60 μM) with little effects on the other 2 major proteasome proteolytic activities, T-L and PGPH-L. LC/MS-MS and dialysis show that 1 is a non-covalent and rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI-1840) with CT-L activity (IC50 27 nM). Detailed SAR studies indicate that the amide moiety and the 2 phenyl rings are sensitive toward modifications. Hydrophobic residues, such as propyl or butyl, in the para-position (not ortho or meta) of the A-ring and a meta-pyridyl group as B-ring significantly improve activity. Compound 11ad (IC50 0.37 µM) is more potent than 1 (IC50 3.5 µM) at inhibiting CT-L activity in intact MDA-MB-468 human breast cancer cells and inhibiting their survival. The activity of 11ad warrants further pre-clinical investigation of this class as non-covalent proteasome inhibitors. 23602891 Pregnancy Outcome following in utero Exposure to Hydroxychloroquine: A prospective comparative observational study. OBJECTIVE: To evaluate pregnancy safety of hydroxychloroquine (HCQ) for rheumatologic diseases. DESIGN: Prospective comparative observational study done at the Israeli teratology information service between 1998 and 2006. RESULTS: 114 HCQ-exposed pregnancies (98.2% in the first trimester, T1) were followed-up and compared with 455 pregnancies of women counseled for non-teratogenic exposure. The difference in the rate of congenital anomalies was not statistically significant [7/97 (7.2%) vs. 15/440 (3.4%), p=0.094]. The analysis was repeated among those exposed in T1 excluding genetic or cytogenetic anomalies or congenital infections [5/95 (5.3%) vs. 14/440 (3.2%), p=0.355]. There were no cases of neonatal lupus erythematosus. The gestational age at delivery was earlier, rate of preterm delivery higher, and birth weight lower, in the HCQ group. CONCLUSION: The present study suggests that HCQ treatment in pregnancy is not a major human teratogen. The earlier gestational age and lower birth weight might be associated with maternal disease. 23103426 Mitochondrial electron transfer chain complexes inhibition by different organochalcogens. Mitochondrial dysfunction plays a pivotal role in the cell toxicology and death decision. The aim of the present study was to investigate the effect of three organocompounds (ebselen [Ebs], diphenyl diselenide [(PhSe)(2)] and diphenyl ditelluride [(PhTe)(2)]) on mitochondrial complexes (I, II, I-III, II-III and IV) activity from rat liver and kidney to determine their potential role as molecular targets of organochalcogens. All studied organochalcogens caused a statistically significant inhibition of the mitochondrial complex I activity. Ebs and (PhTe)(2) caused a statistically significant inhibition of the mitochondrial complex II activity in both hepatic and renal membranes. Hepatic mitochondrial complex II activity was practically unchanged by (PhSe)(2), whereas it significantly inhibited renal complex II activity. Mitochondrial complex IV activity was practically unchanged by the organochalcogens. Furthermore, organochalcogens inhibited the mitochondrial respiration supported by complex I or complex II substrates. The inhibitory effect of Ebs, (PhSe)(2) and (PhTe)(2) on mitochondrial complex I was prevented by NADH, but it was not prevented by catalase (CAT) and/or superoxide dismutase (SOD). Additionally, the organochalcogens-induced inhibition of complex I and II was completely reversed by reduced glutathione (GSH). In conclusion, Ebs, (PhSe)(2) and (PhTe)(2) were more effective inhibitors of renal and hepatic mitochondrial complex I than complex II, whereas complexes III and IV were little modified by these compounds. Taking into account the presented results, we suggest that organochalcogen-induced mitochondrial complexes I and II inhibition can be mediated by their thiol oxidation activity, i.e., Ebs, (PhSe)(2) and (PhTe)(2) can oxidize critical thiol groups from mitochondrial complexes I and II. So, mitochondrial dysfunction can be considered an important factor in the toxicity of Ebs, (PhSe)(2) and (PhTe)(2). 22548364 A new cyclododeca[d]oxazole derivative from Streptomyces spp. CIBYL1. A novel secondary metabolite, N-trans-cinnamoyl 2-amino-3a,4,5,6,7,8,9,10,11,12,13,13a-dodecahydrocyclododeca[d]oxazole (1), was isolated from Streptomyces spp. CIBYL1, along with five known compounds, pimprinine (2), (3R,4S,5R,6R)-3,4,5,6-tetrahydro-4-hydroxy-3,5,6-trimethyl-2H-pyran-2-one (3), indolyl-3-carboxylic acid (4), 2-phenylacetamide (5) and di(1H-pyrrol-2-yl)methanone (6). The structures of these metabolites were elucidated on the basis of extensive analysis of spectroscopic data, including OR, IR, HRMS, 1D and 2D NMR data and chemical derivation. 23416650 Single and 90-day repeated oral dose toxicity studies of fermented Rhus verniciflua stem bark extract in Sprague-Dawley rats. Fermented Rhus verniciflua stem bark (FRVSB) extract, an urushiol-free extract of Rhus verniciflua Stokes (RVS) fermented with Fomitella fraxinea, has various biological activities. The present study was carried out to investigate the potential toxicity of the FRVSB extract following single and repeated oral administration to Sprague-Dawley rats. In the single dose toxicity study, the FRVSB extract was administered orally to male and female rats at single doses of 0, 2500, 5000, and 10,000mg/kg. No animals died and no toxic changes were observed in clinical signs, body weight, and necropsy findings during the 15-day period following administration. In the repeated dose toxicity study, the FRVSB extract was administered orally to male and female rats for 90days at doses of 0, 556, 1667, and 5000mg/kg/day. There were no treatment-related adverse effects in clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at any dose tested. The approximate lethal dose of the FRVSB extract was >10,000mg/kg in both genders, the oral no-observed-adverse-effect level of the FRVSB extract was >5000mg/kg/day in both genders, and no target organs were identified. 23401472 Epigenetic Regulation Is a Crucial Factor in the Repression of UGT1A1 Expression in the Human Kidney. Human UDP-glucuronosyltransferase (UGT) 1A1 catalyzes the metabolism of numerous clinically and pharmacologically important compounds such as bilirubin and SN-38. UGT1A1 is predominantly expressed in the liver and intestine, but not in the kidney. The purpose of this study was to uncover the mechanism of the tissue-specific expression of UGT1A1, focusing on its epigenetic regulation. Bisulfite sequence analysis revealed that the CpG-rich region near the UGT1A1 promoter (-85 to +40) was hypermethylated (83%) in the kidney, whereas it was hypomethylated (37%) in the liver. A chromatin immunoprecipitation assay demonstrated that histone H3 near the promoter was hypoacetylated in the kidney but was hyperacetylated in the liver; this hyperacetylation was accompanied by the recruitment of HNF1α to the promoter. The UGT1A1 promoter in human kidney-derived HK-2 cells that do not express UGT1A1 was fully methylated, but was relatively unmethylated in human liver-derived HuH-7 cells that express UGT1A1. Treatment with 5-aza-2'-deoxycytidine (5-Aza-dC), an inhibitor of DNA methylation, resulted in an increase of UGT1A1 mRNA expression in both cell types, but the increase was much larger in HK-2 cells than in HuH-7 cells. The transfection of an HNF1α expression plasmid into the HK-2 cells resulted in an increase of UGT1A1 mRNA only in the presence of 5-Aza-dC. In summary, we found that DNA hypermethylation along with histone hypoacetylation interferes with the binding of HNF1α, resulting in the defective expression of UGT1A1 in the human kidney. Thus, epigenetic regulation is a crucial determinant of tissue-specific expression of UGT1A1. 23214423 Anisotropy of chemical bonding in semifluorinated graphite C2F revealed with angle-resolved X-ray absorption spectroscopy. Highly oriented pyrolytic graphite characterized by a low misorientation of crystallites is fluorinated using a gaseous mixture of BrF(3) with Br(2) at room temperature. The golden-colored product, easily delaminating into micrometer-size transparent flakes, is an intercalation compound where Br(2) molecules are hosted between fluorinated graphene layers of approximate C(2)F composition. To unravel the chemical bonding in semifluorinated graphite, we apply angle-resolved near-edge X-ray absorption fine structure (NEXAFS) spectroscopy and quantum-chemical modeling. The strong angular dependence of the CK and FK edge NEXAFS spectra on the incident radiation indicates that room-temperature-produced graphite fluoride is a highly anisotropic material, where half of the carbon atoms are covalently bonded with fluorine, while the rest of the carbon atoms preserve π electrons. Comparison of the experimental CK edge spectrum with theoretical spectra plotted for C(2)F models reveals that fluorine atoms are more likely to form chains. This conclusion agrees with the atomic force microscopy observation of a chain-like pattern on the surface of graphite fluoride layers. 23553595 Aerosol particle size does not predict pharmacokinetic determined lung dose in children. In vitro measures of aerosol particles size, such as the fine particle mass, play a pivotal role for approval of inhaled anti-asthmatic drugs. However, the validity as a measure of dose to the lungs in children lacks evidence. In this study we investigated for the first time the association between an in vivo estimate of lung dose of inhaled drug in children and the corresponding particle size segments assessed ex vivo. Lung dose of fluticasone propionate after inhalation from a dry powder inhaler (Diskus®) was studied in 23 children aged 4-7 and 12-15 years with mild asthma. Six-hour pharmacokinetics was assessed after single inhalation. The corresponding emitted mass of drug in segments of aerosol particle size was assessed ex vivo by replicating the inhalation flows recorded by transducers built into the Diskus® inhaler and re-playing them in a breathing simulator. There was no correlation between any inhaled particle size segment and lung dose assessed by pharmacokinetics and adjusted for age and body size. Measures of particles size segments were not related to lung dose in children. Until further evidence is provided it may be warranted to emphasize pharmacokinetic or pharmacodynamic assessments of drug delivery to the lung. 23411334 Redox properties of catechins and enriched green tea extracts effectively preserve L-5-methyltetrahydrofolate: assessment using cyclic voltammetry analysis. A cyclic voltammetry (CV) study was performed in pH 5.5 Britton-Robinson buffer at room temperature to study the stability of 1mM l-5-methyltetrahydrofolate (l-5-MTHF) in combination with epigallocatechin-gallate-enriched extract (EGCGe) and epigallocatechin-enriched extract (EGCe). The combination of l-5-MTHF with enriched catechin extracts provided enhanced stability of l-5-MTHF over a period of 12h under ambient air conditions at pH 5.5. CV experiments showed that increasing the concentrations of EGCGe or EGCe extracts from 80 to 400mg/L produced a decrease in the second oxidation peak of l-5-MTHF. Thus, we calculated that l-5-MTHF remained at nearly 90% when in the presence of enriched tea extracts, compared to 74% without the tea antioxidants. The catechins responsible for this preservation were EGCG and C, confirmed by LC-MS. Compared to covalent link only low interaction (hydrogen bonds) between the different catechins present in the tea extract would stabilise l-5-MTHF. Rather, it was hypothesised that EGCGe and EGCe were effective agents to preserve l-5-MTHF, through a mechanism that also involved the redox potential of catechins to maintain l-5-MTHF in its reduced form. 23422226 Lanostane-type triterpenoid and steroid from the stem bark of Klainedoxa gabonensis. A new lanostane triterpenoid, 2-hydroxy-24-methylenelanostan-1,8-dien-3-one named klainedoxalanostenone (1) with one new steroid, 6-O-acyl-β-d-glucosyl-β-sitosterol named klainedoxasterol (2) together with ten known compounds including six triterpenoids (3-8), two steroids (9, 10) and two tanins (11, 12) were isolated from the stem bark of Klainedoxa gabonensis. To the best of our knowledge, this is the first report of lanostane-type triterpenoids from this genus. Their structures were determined by extensive analysis of spectroscopic data (1D and 2D NMR, MS) and by comparison with literature data. The xanthine oxidase inhibitory activity of nine compounds (1-6, 8, 10 and 11) were evaluated. Compound 5 showed a good xanthine oxidase inhibitory activity; the other tested compounds were moderately active. 23391485 Effect of low dose Bisphenol A on the early differentiation of human embryonic stem cells into mammary epithelial cells. It has been previously reported that Bisphenol A (BPA) can disturb the development of mammary structure and increase the risk of breast cancer in experimental animals. In this study, an in vitro model of human embryonic stem cell (hESC) differentiation into mammary epithelial cells was applied to investigate the effect of low dose BPA on the early stages of mammogenesis. A newly established hESC line was directionally differentiated into mammary epithelial cells by a well-established three-dimensional (3D) culture system. The differentiated mammary epithelial cells were characterized by immunofluorescence and western blotting assay, and were called induced differentiated mammary epithelial cells (iDMECs) based on these data. The hESCs were treated with low doses of BPA range 10(-9)-10(-6)M during the differentiation process, with DMSO as the solvent control and 17-β-estrodiol (E2) as the estrogen-positive control. Our results showed that low dose BPA and E2 could influence the mammosphere area of iDMECs and upregulate the expression level of Oct4 and Nanog proteins, while only BPA could downregulate the expression of E-cadherin protein. Taken together, this study provides some insights into the effects of low dose BPA on the early differentiation stage of mammary epithelial cells and suggests an easier canceration status of iDMECs under the effect of low dose BPA during its early differentiation stage. 23411082 Complexation of Hypocrellin A with Al3+ in water solution and the photodynamic therapy study. The complex of Hypocrellin A with Al(3+) is prepared in water solution by a facile method. The water-solubility and stability of complexes are improved. Irradiation of Al(3+)-HA complex results in higher efficient generation of singlet oxygen ((1)O2) and photocleavage ability to CT DNA than HA. In vitro studies have illustrated that the Al(3+)-HA complex has anti-cancer activity. 22080035 The influence of the intensity of smoking and years of work in the metallurgy on pro-oxidant/antioxidant balance in the blood of smelters. The aim of this study was to investigate the effect of cigarette smoking and occupational exposure to heavy metals on the degree of pro-oxidant/antioxidant imbalance in smelters. The investigations were performed on the blood and urine of 400 subjects: 300 male copper smelters and 100 nonexposed male subjects. Biological material was divided into three groups: nonsmokers, those who smoked less than 20 cigarettes a day and those who smoked more than 20 cigarettes a day. The results showed a significant increase in the concentration of lead, cadmium and arsenic in the blood and urine of smelters, while smoking more than 20 cigarettes a day caused a further increase in the concentration of these metals. The level of malondialdehyde was approximately twofold higher in the plasma of the smelters compared to the control group. We have observed a disturbance in the level of antioxidants in erythrocyte lysate manifested by an increase in metallothionein and glutathione concentrations as well as superoxide dismutase and glutathione peroxidase activities and the decrease in glutathione S-transferase activity. Cigarette smoking, years of work in metallurgy and age of smelters were additional factors significantly affecting the pro-oxidant/antioxidant balance. 23298612 Advancements in the field of intravaginal siRNA delivery. The vaginal tract is a suitable site for the administration of both local and systemic acting drugs. There are numerous vaginal products on the market such as those approved for contraception, treatment of yeast infection, hormonal replacement therapy, and feminine hygiene. Despite the potential in drug delivery, the vagina is a complex and dynamic organ that requires greater understanding. The recent discovery that injections of double stranded RNA (dsRNA) in Caenorhabditis elegans (C. elegans) results in potent gene specific silencing, was a major scientific revolution. This phenomenon known as RNA interference (RNAi), is believed to protect host genome against invasion by mobile genetic elements such as transposons and viruses. Gene silencing or RNAi has opened new potential opportunities to study the function of a gene in an organism. Furthermore, its therapeutic potential is being investigated in the field of sexually transmitted infections such as human immunodeficiency virus (HIV) and other diseases such as age-related macular degeneration (AMD), diabetes, hypercholesterolemia, respiratory disease, and cancer. This review will focus on the therapeutic potential of siRNA for the treatment and/or prevention of infectious diseases such as HIV, HPV, and HSV within the vaginal tract. Specifically, formulation design parameters to improve siRNA stability and therapeutic efficacy in the vaginal tract will be discussed along with challenges, advancements, and future directions of the field. 23535288 Aberrant activation of M phase proteins by cell proliferation-evoking carcinogens after 28-day administration in rats. We have previously reported that hepatocarcinogens increase liver cells expressing p21(Cip1), a G1 checkpoint protein and M phase proteins after 28-day treatment in rats. This study aimed to identify early prediction markers of carcinogens available in many target organs after 28-day treatment in rats. Immunohistochemical analysis was performed on Ki-67, p21(Cip1) and M phase proteins [nuclear Cdc2, phospho-Histone H3 (p-Histone H3), Aurora B and heterochromatin protein 1α (HP1α)] with carcinogens targeting different organs. Carcinogens targeting thyroid (sulfadimethoxine; SDM), urinary bladder (phenylethyl isothiocyanate), forestomach (butylated hydroxyanisole; BHA), glandular stomach (catechol; CC), and colon (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and chenodeoxycholic acid) were examined using a non-carcinogenic toxicant (caprolactam) and carcinogens targeting other organs as negative controls. All carcinogens increased Ki-67(+), nuclear Cdc2(+), p-Histone H3(+) or Aurora B(+) carcinogenic target cells, except for both colon carcinogens, which did not increase cell proliferation. On the other hand, p21(Cip1+) cells increased with SDM and CC. HP1α responded only to BHA. Results revealed carcinogens evoking cell proliferation concurrently induced cell cycle arrest at M phase or showing chromosomal instability reflecting aberration in cell cycle regulation, irrespective of target organs, after 28-day treatment. Therefore, M phase proteins may be early prediction markers of carcinogens evoking cell proliferation in many target organs. 23261528 Inhibition of Th1/Th17 responses via suppression of STAT1 and STAT3 activation contributes to the amelioration of murine experimental colitis by a natural flavonoid glucoside icariin. Inflammatory bowel disease (IBD) is a chronic inflammatory disorder in the intestine which involves overproduction of pro-inflammatory cytokines and excessive functions of inflammatory cells. However, current treatments for IBD may have potential adverse effects including steroid dependence, infections and lymphoma. Therefore new therapies or drug candidates for the treatment of IBD are desperately needed. In the present study we found that icariin, a major bioactive compound from plants in Epimedium family, exerted protective effect on intestinal inflammation in mice induced by dextran sulfate sodium. Oral administration of icariin significantly attenuated the disease progression and alleviated the pathological changes of colitis. It also inhibited the production of pro-inflammatory cytokines and expression of p-p65, p-STAT1 and p-STAT3 in colon tissues. Further study showed that icariin dose-dependently inhibited the proliferation and activation of T lymphocytes, and suppressed pro-inflammatory cytokine levels of activated T cells. Moreover, icariin treatment inhibited the phosphorylations of STAT1 and STAT3 in CD4(+) T cells, which were the crucial transcription factors for Th1 and Th17 respectively. Taken together, these results indicate that icariin is a potential therapeutic agent for IBD. 23628508 Aspidin BB, a phloroglucinol derivative, induces cell cycle arrest and apoptosis in human ovarian HO-8910 cells. Aspidin BB, an effective phloroglucinol derivative from Dryopteris fragrans (L.) Schott, has been previously reported to exert high biological activities. In this study, we analyzed the underlying mechanisms of aspidin BB on human ovarian cancer cell line, HO-8910. Aspidin BB significantly inhibited HO-8910 cell proliferation in a dose- and time-dependent manner. The IC50 values were 15.02, 25.79 and 68.81μM after 72, 48 and 24h treatment, respectively. Meanwhile, aspidin BB markedly induced apoptosis evidenced by characteristic apoptotic morphological changes, nuclear DNA fragmentation, annexin V-FITC/propidium iodide (PI) double staining and S peak. Western blot analysis showed that aspidin BB suppressed Bcl-2 expression and enhanced Bax expression to desintegrate the outer mitochondrial membrane, then caused cytochrome c release which led to the activation of effector caspase-3, and further cleaved the poly ADP-ribose polymerase (PARP) in the nucleus, finally induced cell apoptosis. Furthermore, aspidin BB provoked S phase arrest in HO-8910 cells with up-regulation of pRb, E2F1, CDK2, cyclin E and cyclin A proteins. Taken together, these findings support the conclusion that aspidin BB exhibits cytotoxicity towards human ovarian cancer HO-8910 cells through induction of apoptosis via mitochondrial pathway and arresting cell cycle progression in S phase. 23255471 Tungsten carbide nanoparticles as efficient cocatalysts for photocatalytic overall water splitting. Tungsten carbide exhibits platinum-like behavior, which makes it an interesting potential substitute for noble metals in catalytic applications. Tungsten carbide nanocrystals (≈5 nm) are directly synthesized through the reaction of tungsten precursors with mesoporous graphitic C(3)N(4) (mpg-C(3)N(4)) as the reactive template in a flow of inert gas at high temperatures. Systematic experiments that vary the precursor compositions and temperatures used in the synthesis selectively generate different compositions and structures for the final nanocarbide (W(2)C or WC) products. Electrochemical measurements demonstrate that the WC phase with a high surface area exhibits both high activity and stability in hydrogen evolution over a wide pH range. The WC sample also shows excellent hydrogen oxidation activity, whereas its activity in oxygen reduction is poor. These tungsten carbides are successful cocatalysts for overall water splitting and give H(2) and O(2) in a stoichiometric ratio from H(2)O decomposition when supported on a Na-doped SrTiO(3) photocatalyst. Herein, we present tungsten carbide (on a small scale) as a promising and durable catalyst substitute for platinum and other scarce noble-metal catalysts in catalytic reaction systems used for renewable energy generation. 23418960 Preparation and characterization of progesterone dispersions using supercritical carbon dioxide. Abstract Context: Supercritical fluid methods offer an alternative to conventional mixing methods, particularly for heat sensitive drugs and where an organic solvent is undesirable. Objective: To design, develop and construct a unit for the particles from a gas-saturated suspension/solution (PGSS) method and form endogenous progesterone (PGN) dispersion systems using SC-CO(2). Materials and methods: The PGN dispersions were manufactured using three selected excipients: polyethylene glycol (PEG) 400/4000 (50:50), Gelucire 44/14 and D-α-tocopheryl PEG 1000 succinate (TPGS). Semisolid dispersions of PGN prepared by PGSS method were compared to the conventional methods; comelting (CM), cosolvent (CS) and physical mixing (PM). The dispersion systems made were characterized by Raman and Fourier transform infrared (FTIR) spectroscopies, X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), PGN recovery, uniformity and in vitro dissolution, analyzed by high-performance liquid chromatography (HPLC). Results: Raman spectra revealed no changes in the crystalline structure of PGN treated with SC-CO(2) compared to that of untreated PGN. XRPD and FTIR showed the presence of peaks and bands for PGN confirming that PGN has been incorporated well with each individual excipient. All PGN dispersions prepared by the PGSS method resulted in the improvement of PGN dissolution rates compared to that prepared by the conventional methods and untreated PGN after 60 min (p value < 0.05). Conclusion: The novel PGN dispersions prepared by the PGSS method offer the great potential to enhance PGN dissolution rate, reduce preparation time and form stable crystalline dispersion systems over those prepared by conventional methods. 23537315 Hydrocarbon-soluble nanocatalysts with no bulk phase: coplanar, two-coordinate arrays of the base metals. A structurally unique class of hydrocarbon-soluble, ancillary-ligand-free, tetrametallic Co(I) and Ni(I) clusters is reported. The highly unsaturated complexes are supported by simple, sterically bulky phosphoranimide ligands, one per metal. The electron-rich nitrogen centers are strongly bridging but sterically limited to bimetallic interactions. The hydrocarbon-soluble clusters consist of four coplanar metal centers, mutually bridged by single nitrogen atoms. Each metal center is monovalent, rigorously linear, and two-coordinate. The clusters are in essence two-dimensional atomic-scale "molecular squares," a structural motif adapted from supramolecular chemistry. Both clusters exhibit high solution-phase magnetic susceptibility at room temperature, suggesting the potential for applications in molecular electronics. Designed to be catalyst precursors, both clusters exhibit high activity for catalytic hydrogenation of unsaturated hydrocarbons at low pressure and temperature. 23386600 Recommendations for meeting the pediatric patient's need for a clinical pharmacist: a joint opinion of the Pediatrics Practice and Research Network of the American College of Clinical Pharmacy and the Pediatric Pharmacy Advocacy Group. Children warrant access to care from clinical pharmacists trained in pediatrics. The American College of Clinical Pharmacy Pediatrics Practice and Research Network (ACCP Pediatrics PRN) released an opinion paper in 2005 with recommendations for improving the quality and quantity of pediatric pharmacy education in colleges of pharmacy, residency programs, and fellowships. Although progress has been made in increasing the availability of pediatric residencies, there is still much to be done to meet the direct care needs of pediatric patients. The purpose of this joint opinion paper is to outline strategies and recommendations for expanding the quality and capacity of pediatric clinical pharmacy practitioners by elevating the minimum expectations for pharmacists entering pediatric practice, standardizing pediatric pharmacy education, expanding the current number of pediatric clinical pharmacists, and creating an infrastructure for development of pediatric clinical pharmacists and clinical scientists. These recommendations may be used to provide both a conceptual framework and action items for schools of pharmacy, health care systems, and policymakers to work together to increase the quality and quantity of pediatric training, practice, and research initiatives. 23432095 Development of potent and selective indomethacin analogues for the inhibition of AKR1C3 (Type 5 17β-hydroxysteroid dehydrogenase/prostaglandin F synthase) in castrate-resistant prostate cancer. Castrate-resistant prostate cancer (CRPC) is a fatal, metastatic form of prostate cancer. CRPC is characterized by reactivation of the androgen axis due to changes in androgen receptor signaling and/or adaptive intratumoral androgen biosynthesis. AKR1C3 is upregulated in CRPC where it catalyzes the formation of potent androgens. This makes AKR1C3 a target for the treatment of CRPC. AKR1C3 inhibitors should not inhibit AKR1C1/AKR1C2, which inactivate 5α-dihydrotestosterone. Indomethacin, used to inhibit cyclooxygenase, also inhibits AKR1C3 and displays selectivity over AKR1C1/AKR1C2. Parallel synthetic strategies were used to generate libraries of indomethacin analogues, which exhibit reduced cyclooxygenase inhibitory activity but retain AKR1C3 inhibitory potency and selectivity. The lead compounds inhibited AKR1C3 with nanomolar potency, displayed >100-fold selectivity over AKR1C1/AKR1C2, and blocked testosterone formation in LNCaP-AKR1C3 cells. The AKR1C3·NADP(+)·2'-des-methyl-indomethacin crystal structure was determined, and it revealed a unique inhibitor binding mode. The compounds reported are promising agents for the development of therapeutics for CRPC. 23201439 New modified β-cyclodextrin derivatives as detoxifying agents of chemical warfare agents (I). Synthesis and preliminary screening: evaluation of the detoxification using a half-quantitative enzymatic assay. Current treatments of organophosphorus nerve agents poisoning are imperfect, and more efficient medical countermeasures need to be developed. Chemical scavengers based on β-cyclodextrin displayed promising results, but further investigations have to be performed to evaluate the possibility of application of substituted cyclodextrins as potential detoxification agents. Herein, five new cyclodextrins scavengers were synthesized. New optimal conditions for regioselectively monosubstitution of β-cyclodextrin at O-2 position were then studied to access to key intermediates. After these optimizations, a new series of three permethylated derivatives was developed, and two compounds bearing an α-nucleophilic group via a three carbon atoms linker were prepared. The ability of these five scavengers to detoxify nerve agents (cyclosarin, soman, tabun and VX) was evaluated by a semi-quantitative biological assay. All the modified cyclodextrins significantly decreased the inhibitory effect of chemical warfare G agents on acetylcholinesterase activity. For this purpose, we showed that the specific interactions between the organophosphorus compound and the oligosaccharidic moiety of the scavenger played a pivotal role in the detoxification process. 23474319 In vitro interceptive and reparative effects of myo-inositol against copper-induced oxidative damage and antioxidant system disturbance in primary cultured fish enterocytes. Copper (Cu) is essential for normal cellular processes in most eukaryotic organisms but is toxic in excess. Our previous study reported that a nutrient antioxidant, myo-inositol (MI), can protect fish from Cu-induced oxidative injury; however, the mechanisms involved are not fully understood. Therefore, the present study aimed to analyze potential pathways. First, to investigate the hypothesis that MI protects enterocytes against Cu toxicity via the intercept pathway, enterocytes were treated with different concentrations of MI (0-75mg/L medium) in the presence of 6mg/L of Cu for 24h (Experiment 1). Next, we investigated the potential reparative role of MI after a Cu challenge (Experiment 2). The results of Experiment 1 indicated that cells exposed to Cu alone for 24h exhibited increases in lactate dehydrogenase release (LDH), malondialdehyde (MDA) formation and protein oxidation (P<0.05). Notably, a dose-dependent inhibitory effect on LDH release was observed with all doses of MI. Moreover, co-treatment with MI completely inhibited Cu-induced protein carbonyl (PC) formation. However, Cu-induced lipid peroxidation was not altered by MI co-treatment. Additionally, Cu exposure suppressed total-superoxide dismutase (T-SOD), CuZnSOD and catalase (CAT) activities, and these changes were completely blocked by co-treatment with sufficient MI concentrations. In contrast, cells exposed to Cu exhibited adaptive increases in reduced glutathione (GSH) content and the activities of anti-hydroxyl radical (AHR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR). Interestingly, the Cu-stimulated increases in these antioxidants were blocked by co-treatment with sufficient MI concentrations. The results of Experiment 2 indicated that cell injury (LDH release), lipid peroxidation (MDA formation) and protein oxidation induced by Cu were reversed by subsequent MI treatment. Meanwhile, Cu-induced decreases in alkaline phosphatase (AKP), anti-superoxide anion (ASA), T-SOD and CuZnSOD activities were completely restored by subsequent MI treatment, while the reduced CAT activity was partially restored. However, MI rescues partially restored the adaptive increase in GPx activity induced by Cu, whereas the adaptive increase in reduced GSH content was completely reversed by 75mg/L of MI. However, subsequent MI treatments did not alter the induction of GST activity by Cu. In conclusion, we demonstrated for the first time that MI not only protected enterocytes from Cu-induced oxidative damage but also increased the repair activity in primary enterocytes after challenge with Cu. Moreover, MI-mediated increases in antioxidant enzyme activities contributed to lipid and protein oxidant repair. 23146838 Influence of ovarian and non-ovarian estrogens on weight gain in response to disruption of sweet taste--calorie relations in female rats. Regulation of energy balance in female rats is known to differ along a number of dimensions compared to male rats. Previous work from our lab has demonstrated that in female rats fed dietary supplements containing high-intensity sweeteners that may disrupt a predictive relation between sweet tastes and calories, excess weight gain is demonstrated only when females are also fed a diet high in fat and sugar, and is evidenced primarily in animals already prone to gain excess weight. In contrast, male rats show excess weight gain when fed saccharin-sweetened yogurt supplements when fed both standard chow diets and diets high in fat and sugar, and regardless of their proneness to excess weight gain. The goal of the present experiments was to determine whether ovarian, or other sources of estrogens, contributes to the resistance to excess weight gain in female rats fed standard chow diets along with dietary supplements sweetened with yogurt. Results of the first experiment indicated that when the ovaries were removed surgically in adult female rats, patterns of weight gain were similar in animals fed saccharin-sweetened compared to glucose-sweetened yogurt supplements. In the second experiment, when the ovaries were surgically removed in adult female rats, and local production of estrogens was suppressed with the aromatase inhibitor anastrozole, females fed the saccharin-sweetened yogurt consumed more energy and gained more weight than females fed the glucose-sweetened yogurt. However, when the ovaries were surgically removed prior to the onset of puberty (at 24-25 days of age), females given saccharin-sweetened yogurt along with vehicle gained excess weight. In contrast, weight gain was similar in those given saccharin-sweetened and glucose-sweetened yogurt along with anastrozole. The results suggest that behavioral differences between males and females in response to disruption of sweet→calorie relations may result from differences in patterns of local estrogen production. These differences may be established developmentally during the pubertal period in females. 22997060 Comparison of emetic potencies of the 8-ketotrichothecenes deoxynivalenol, 15-acetyldeoxynivalenol, 3-acetyldeoxynivalenol, fusarenon X, and nivalenol. Although the acute toxic effects of trichothecene mycotoxin deoxynivalenol (DON or vomitoxin), a known cause of human food poisoning, have been well characterized in several animal species, much less is known about closely related 8-ketotrichothecenes that similarly occur in cereal grains colonized by toxigenic fusaria. To address this, we compared potencies of DON, 15-acetyldeoxynivalenol (15-ADON), 3-acetyldeoxynivalenol (3-ADON), fusarenon X (FX), and nivalenol (NIV) in the mink emesis model following intraperitoneal (ip) and oral administration. All five congeners dose-dependently induced emesis by both administration methods. With increasing doses, there were marked decreases in latency to emesis with corresponding increases in emesis duration and number of emetic events. The effective doses resulting in emetic events in 50% of the animals for ip exposure to DON, 15-ADON, 3-ADON, FX, and NIV were 80, 170, 180, 70, and 60 µg/kg bw, respectively, and for oral exposure, they were 30, 40, 290, 30, and 250 µg/kg bw, respectively. The emetic potency of DON determined here was comparable to that reported in analogous studies conducted in pigs and dogs, suggesting that the mink is a suitable small animal model for investigating acute trichothecene toxicity. The use of a mouse pica model, based on the consumption of kaolin, was also evaluated as a possible surrogate for studying emesis but was found unsuitable. From a public health perspective, comparative emetic potency data derived from small animal models such as the mink should be useful for establishing toxic equivalency factors for DON and other trichothecenes. 23574014 Dual-Purpose Polymer Labels for Fluorescent and Mass Cytometric Affinity Bioassays. We describe the synthesis and characterization of a family of poly(N-alkylacrylamide) polymers carrying 2-6 fluorescent dye molecules, ∼70 pendant DTPA (diethylenetriaminepentaacetic acid) groups, and an orthogonal maleimide end-group for covalent attachment to an antibody (Ab). These dual-purpose labels were designed for use in multiplexed immunoassays based on both mass cytometry and fluorescent flow cytometry. A challenge in the polymer synthesis was finding conditions for attaching a sufficient number of dye molecules to each polymer chain. Although attachment of a terminal maleimide to the polymers was not as efficient as anticipated, the end-functional polymers were still effective in labeling Abs. Secondary goat antimouse IgG was labeled with the four dual-label polymers as well as a control polymer, and while the resultant antibody-polymer conjugates showed positive performance in mass cytometric and fluorescent assays, some trials showed problems such as low signal and nonspecific adsorption. Four primary antibody conjugates were prepared and used to stain cells in 4-plex assays. The results of both primary assays are bittersweet in that the CD3-FITC and CD45-DyLight 649 conjugates performed well, while the CD13-DyLight 405 and the CD38-DyLight 549 conjugates did not. 23391254 A continuous network of lipid nanotubes fabricated from the gliding motility of kinesin powered microtubule filaments. Synthetic interconnected lipid nanotube networks were fabricated on the millimeter scale based on the simple, cooperative interaction between phospholipid vesicles and kinesin-microtubule (MT) transport systems. More specifically, taxol-stabilized MTs, in constant 2D motion via surface absorbed kinesin, extracted and extended lipid nanotube networks from large Lα phase multilamellar liposomes (5-25 μm). Based on the properties of the inverted motility geometry, the total size of these nanofluidic networks was limited by MT surface density, molecular motor energy source (ATP), and total amount and physical properties of lipid source material. Interactions between MTs and extended lipid nanotubes resulted in bifurcation of the nanotubes and ultimately the generation of highly branched networks of fluidically connected nanotubes. The network bifurcation was easily tuned by changing the density of microtubules on the surface to increase or decrease the frequency of branching. The ability of these networks to capture nanomaterials at the membrane surface with high fidelity was subsequently demonstrated using quantum dots as a model system. The diffusive transport of quantum dots was also characterized with respect to using these nanotube networks for mass transport applications. 23629675 Improved Nutritive Quality and Salt Resistance in Transgenic Maize by Simultaneously Overexpression of a Natural Lysine-Rich Protein Gene, SBgLR, and an ERF Transcription Factor Gene, TSRF1. Maize (Zea mays L.), as one of the most important crops in the world, is deficient in lysine and tryptophan. Environmental conditions greatly impact plant growth, development and productivity. In this study, we used particle bombardment mediated co-transformation to obtain marker-free transgenic maize inbred X178 lines harboring a lysine-rich protein gene SBgLR from potato and an ethylene responsive factor (ERF) transcription factor gene, TSRF1, from tomato. Both of the target genes were successfully expressed and showed various expression levels in different transgenic lines. Analysis showed that the protein and lysine content in T1 transgenic maize seeds increased significantly. Compared to non-transformed maize, the protein and lysine content increased by 7.7% to 24.38% and 8.70% to 30.43%, respectively. Moreover, transgenic maize exhibited more tolerance to salt stress. When treated with 200 mM NaCl for 48 h, both non-transformed and transgenic plant leaves displayed wilting and losing green symptoms and dramatic increase of the free proline contents. However, the degree of control seedlings was much more serious than that of transgenic lines and much more increases of the free proline contents in the transgenic lines than that in the control seedlings were observed. Meanwhile, lower extent decreases of the chlorophyll contents were detected in the transgenic seedlings. Quantitative RT-PCR was performed to analyze the expression of ten stress-related genes, including stress responsive transcription factor genes, ZmMYB59 and ZmMYC1, proline synthesis related genes, ZmP5CS1 and ZmP5CS2, photosynthesis-related genes, ZmELIP, ZmPSI-N, ZmOEE, Zmrbcs and ZmPLAS, and one ABA biosynthesis related gene, ZmSDR. The results showed that with the exception of ZmP5CS1 and ZmP5CS2 in line 9-10 and 19-11, ZmMYC1 in line 19-11 and ZmSDR in line 19-11, the expression of other stress-related genes were inhibited in transgenic lines under normal conditions. After salt treatment, the expressions of the ten stress-related genes were significantly induced in both wild-type (WT) and transgenic lines. However, compared to WT, the increases of ZmP5CS1 in all these three transgenic lines and ZmP5CS2 in line 9-10 were less than WT plants. This study provides an effective approach of maize genetic engineering for improved nutritive quality and salt tolerance. 23347151 Effects of hydrogen bonding on internal conversion of GFP-like chromophores. I. The para-amino systems. To understand the effects of solvent-solute hydrogen bonding (SSHB) on the excited-state dynamics of two GFP-like chromophores, p-ABDI and p-CFABDI, we have determined the quantum yields for fluorescence (Φf) and the isomerization Z → E (ΦZE) and the femtosecond fluorescence and transient infrared absorption in selected solvents. The behavior that ΦZE ≅ 0.50 in aprotic solvents, such as CH3CN, indicates that the E-Z photoisomerization adopts a one-bond-flip mechanism through the torsion of the exocyclic C═C bond (the τ torsion) to form a perpendicular species (τ ∼90°) in the singlet excited state followed by internal conversion (IC) to the ground state and partition to form the E and Z isomers with equal probabilities. The observed ΦZE decreased from 0.50 to 0.15-0.28 when CH3CN was replaced with the protic solvents CH3OH and CF3CH2OH. In conjunction with the solvent-independent rapid (<1 ps) kinetics for the fluorescence decay and the solvent-dependent slow (7-20 ps) kinetics for the ground-state recovery, we conclude that the SSHB modifies the potential energy surface for the τ torsion in a way that the IC occurs also for the twisted intermediates with a τ-torsion angle smaller than 90°, which favors the formation of the Z isomers. The possibility of IC induced by torsion of the exocyclic C-C bond (the φ torsion) is also considered but excluded. 23193276 KEGG OC: a large-scale automatic construction of taxonomy-based ortholog clusters. The identification of orthologous genes in an increasing number of fully sequenced genomes is a challenging issue in recent genome science. Here we present KEGG OC (http://www.genome.jp/tools/oc/), a novel database of ortholog clusters (OCs). The current version of KEGG OC contains 1 176 030 OCs, obtained by clustering 8 357 175 genes in 2112 complete genomes (153 eukaryotes, 1830 bacteria and 129 archaea). The OCs were constructed by applying the quasi-clique-based clustering method to all possible protein coding genes in all complete genomes, based on their amino acid sequence similarities. It is computationally efficient to calculate OCs, which enables to regularly update the contents. KEGG OC has the following two features: (i) It consists of all complete genomes of a wide variety of organisms from three domains of life, and the number of organisms is the largest among the existing databases; and (ii) It is compatible with the KEGG database by sharing the same sets of genes and identifiers, which leads to seamless integration of OCs with useful components in KEGG such as biological pathways, pathway modules, functional hierarchy, diseases and drugs. The KEGG OC resources are accessible via OC Viewer that provides an interactive visualization of OCs at different taxonomic levels. 23570561 Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors. RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC). Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease. In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents. These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (∼7 mmHg). (22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied. The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed. Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered. 23330549 A molecular platinum cluster junction: a single-molecule switch. We present a theoretical study of electron transport through single-molecule junctions incorporating a Pt(6) metal cluster bound within an organic framework. The insertion of this molecule between a pair of electrodes leads to a fully atomically engineered nanometallic device with high conductance at the Fermi level and two sequential high on/off switching states. The origin of this property can be traced back to the existence of a degenerate HOMO consisting of two asymmetric orbitals with energies close to the Fermi level of the metal leads. The degeneracy is broken when the molecule is contacted to the leads, giving rise to two resonances that become pinned to the Fermi level and display destructive interference. 23418017 Cytophilic/Cytophobic Design of Nanomaterials at Biointerfaces. To control interactions between cells and nanomaterials has been a great challenge because numerous nanomaterials have been intensively explored in the fields of biology and medicine. However, current surface modification of nanomaterials is mainly carried out in an empirical way. Herein, a general strategy to tune the surface chemistry of nanomaterials is proposed based on cell affinity, that is, cytophilic or cytophobic. The cell affinity of nanomaterials directly affects cellular response to materials at the very early stage of cell-material interactions before other events, such as endocytosis, cell spreading, and cell differentiation, occur. In this Concept, it is suggested that there is a developing library of cytophilic and cytophobic moieties, and how the cell affinity of nanomaterials functions at biointerfaces is discussed by exemplifying several applications, namely therapy, tissue engineering, and biosensors. It is believed that control of the cytophilic/cytophobic property will be helpful in guiding the design of functional nanomaterials for their biomedical applications. 23188714 Pyrimidine salvage in Trypanosoma brucei bloodstream forms and the trypanocidal action of halogenated pyrimidines. African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host. However, uptake of pyrimidines in bloodstream form trypanosomes has not been investigated, making it difficult to judge the relative importance of salvage and synthesis or to design a pyrimidine-based chemotherapy. Detailed characterization of pyrimidine transport activities in bloodstream form Trypanosoma brucei brucei found that these cells express a high-affinity uracil transporter (designated TbU3) that is clearly distinct from the procyclic pyrimidine transporters. This transporter had low affinity for uridine and 2'deoxyuridine and was the sole pyrimidine transporter expressed in these cells. In addition, thymidine was taken up inefficiently through a P1-type nucleoside transporter. Of importance, the anticancer drug 5-fluorouracil was an excellent substrate for TbU3, and several 5-fluoropyrimidine analogs were investigated for uptake and trypanocidal activity; 5F-orotic acid, 5F-2'deoxyuridine displayed activity in the low micromolar range. The metabolism and mode of action of these analogs was determined using metabolomic assessments of T. brucei clonal lines adapted to high levels of these pyrimidine analogs, and of the sensitive parental strains. The analysis showed that 5-fluorouracil is incorporated into a large number of metabolites but likely exerts toxicity through incorporation into RNA. 5F-2'dUrd and 5F-2'dCtd are not incorporated into nucleic acids but act as prodrugs by inhibiting thymidylate synthase as 5F-dUMP. We present the most complete model of pyrimidine salvage in T. brucei to date, supported by genome-wide profiling of the predicted pyrimidine biosynthesis and conversion enzymes. 23192895 Synthesis and thermal decomposition behaviors of magnesium borohydride ammoniates with controllable composition as hydrogen storage materials. An ammonia-redistribution strategy for synthesizing metal borohydride ammoniates with controllable coordination number of NH(3) was proposed, and a series of magnesium borohydride ammoniates were easily synthesized by a mechanochemical reaction between Mg(BH(4))(2) and its hexaammoniate. A strong dependence of the dehydrogenation temperature and purity of the released hydrogen upon heating on the coordination number of NH(3) was elaborated for Mg(BH(4))(2)·xNH(3) owing to the change in the molar ratio of H(δ+) and H(δ-), the charge distribution on H(δ+) and H(δ-), and the strength of the coordinate bond N:→Mg(2+). The monoammoniate of magnesium borohydride (Mg(BH(4))(2)·NH(3)) was obtained for the first time. It can release 6.5% pure hydrogen within 50 minutes at 180 °C. 23225365 In vitro antileishmanial activity of resveratrol originates from its cytotoxic potential against host cells. In addition to a range of beneficial pharmacological activities, resveratrol is recently reported to have potential antileishmanial activities in vitro. The present study was conducted to evaluate the effect of resveratrol on promastigotes and amastigotes of transgenic Leishmania major expressing green fluorescent protein in comparison with its direct cytotoxic effects on host cells (bone marrow-derived and J774-G8 macrophages, respectively). As assessed by FACS analysis, resveratrol showed moderate antipromastigote activity at <35 µg/mL (153.2 µM) and promising effects at higher sample concentrations. In contrast, the green fluorescent protein signal as a measure of the intracellular parasites' viability was reduced in a concentration-dependent manner. Resveratrol strongly inhibited NO production, but did not display direct NO-scavenging activity in sodium nitroprusside solution. Western blotting indicated that resveratrol reduced recombinant interferon-γ/LPS-induced expression of iNOS protein. Microscopic studies, MTT evaluation, and FACS analysis showed significant cytotoxic effects on host cells in a concentration-dependent manner. This finding suggests that the in vitro antileishmanial activity of resveratrol is due to cytotoxic effects on host cells rather than attributable to a specific antiparasitic potential. 23210779 Natural cures for type 1 diabetes: a review of phytochemicals, biological actions, and clinical potential. Autoimmune diseases are the third largest category of illness in the industrialized world, following cardiovascular diseases and cancers. Among them, type 1 diabetes, also named autoimmune diabetes, afflicts 10 million people worldwide. This disease is caused by autoimmunity-mediated destruction of pancreatic β-cells, leading to insulin deficiency, hyperglycemia and complications. Currently, there is no cure for type 1 diabetes. Insulin injection is the only medication; however, it accompanies serious medical complications. Current strategies to cure type 1 diabetes include immunotherapy, replacement therapy, and combination therapy. Despite recent advances in anti-diabetic strategies, no strategy is clinically successful. How to cure type 1 diabetes without undesirable side effects still remains a formidable challenge in drug research and development. Plants provide an extraordinary source of natural medicines for different diseases. Moreover, secondary metabolites of plant origin serve as an invaluable chemical library for drug discovery and current medicinal chemistry in the pharmaceutical industry. Over the past 25 years, 50% of prescription drugs have been developed from natural products and their derivatives. In this article, we review more than 20 plant compounds and extracts reported in the literature to prevent and treat type-1 diabetes. Emphasis is placed on their chemistry and biology in terms of regulation of immune cells and pancreatic β-cells. We summarize recent progress in understanding the biological actions, mechanisms and therapeutic potential of the compounds and extracts of plant origin in type 1 diabetes. New views on phytocompound-based strategies for prevention and treatment of type 1 diabetes are also discussed. 23194502 An isoquinoline alkaloid from the Chinese herbal plant Corydalis yanhusuo W.T. Wang inhibits P-glycoprotein and multidrug resistance-associate protein 1. Overexpression of P-glycoprotein (P-gp) and multidrug resistance-associate protein 1 (MRP1) is a major mechanism leading to multidrug resistance (MDR) of cancer cells. These transporters expel anti-cancer drugs and greatly impair therapeutic efficacy of chemotherapy. A Chinese herbal plant Yanhusuo (Corydalis yanhusuo W.T. Wang, YHS) is frequently used in functional food and traditional Chinese medicine to improve the efficacy of chemotherapy. The objective of this work was to study effects of glaucine, an alkaloid component of YHS, on P-gp and MRP1 in resistant cancer cells. The resistant cancer cell line, MCF-7/ADR and corresponding parental sensitive cells were employed to determine reversal properties of glaucine. Glaucine inhibits P-gp and MRP1-mediated efflux and activates ATPase activities of the transporters, indicating that it is a substrate and inhibits P-gp and MRP1 competitively. Furthermore, glaucine suppresses expression of ABC transporter genes. It reverses the resistance of MCF-7/ADR to adriamycin and mitoxantrone effectively. 23163395 Does catch and release affect the mating system and individual reproductive success of wild Atlantic salmon (Salmo salar L.)? In this study, we documented the breeding system of a wild population of Atlantic salmon (Salmo salar L.) by genetically sampling every returning adult and assessed the determinants of individual fitness. We then quantified the impacts of catch and release (C&R) on mating and reproductive success. Both sexes showed high variance in individual reproductive success, and the estimated standardized variance was higher for males (2.86) than for females (0.73). We found a weak positive relationship between body size and fitness and observed that fitness was positively correlated with the number of mates, especially in males. Mature male parr sired 44% of the analysed offspring. The impact of C&R on the number of offspring was size dependent, as the reproductive success of larger fish was more impaired than smaller ones. Also, there was an interactive negative effect of water temperature and air exposure time on reproductive success of C&R salmon. This study improves our understanding of the complex reproductive biology of the Atlantic salmon and is the first to investigate the impact of C&R on reproductive success. Our study expands the management toolbox of appropriate C&R practices that promote conservation of salmon populations and limit negative impacts on mating and reproductive success. 23313376 Pterostilbene exerts antitumor activity against human osteosarcoma cells by inhibiting the JAK2/STAT3 signaling pathway. Osteosarcoma is a high-grade malignant bone tumor. Pterostilbene (PTE) is a natural, dimethylated analog of resveratrol with higher bioavailability. While PTE has been shown to have potent antitumor activity against various types of cancer, the molecular mechanisms underlying the effects of PTE remain largely unknown. The Janus kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) signaling pathway plays a crucial role in tumorigenesis and immune development. In this study, we assessed the antitumor activity of PTE against human osteosarcoma cells and explored the role of JAK2/STAT3 and apoptosis-related signaling pathways on the activity of PTE. PTE treatment resulted in a dose- and time-dependent inhibition of osteosarcoma cell viability. Additionally, PTE exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration and mitochondrial membrane potential (MMP) but also by increases in the apoptotic index, reactive oxygen species (ROS) and several biochemical parameters. Furthermore, PTE treatment directly inhibited the phosphorylation of JAK2 at Tyr 1007 and the downstream activation of STAT3. PTE also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27. PTE, used in combination with a known JAK2/STAT3 inhibitor, AG490, further decreased the viability of osteosarcoma cells. Taken together, PTE is a potent inhibitor of osteosarcoma cell growth that targets the JAK2/STAT3 signaling pathway. These data suggest that inhibition of JAK2/STAT3 signaling is a novel mechanism of action for PTE during therapeutic intervention in osteosarcoma cancers. 23566514 Discovery and synthesis of novel 4-aminopyrrolopyrimidine Tie-2 kinase inhibitors for the treatment of solid tumors. The synthesis and biological evaluation of novel Tie-2 kinase inhibitors are presented. Based on the pyrrolopyrimidine chemotype, several new series are described, including the benzimidazole series by linking a benzimidazole to the C5-position of the 4-amino-pyrrolopyrimidine core and the ketophenyl series synthesized by incorporating a ketophenyl group to the C5-position. Medicinal chemistry efforts led to potent Tie-2 inhibitors. Compound 15, a ketophenyl pyrrolopyrimidine urea analog with improved physicochemical properties, demonstrated favorable in vitro attributes as well as dose responsive and robust oral tumor growth inhibition in animal models. 23562995 Optical modulation of ZnO microwire optical resonators with a parallelogram cross-section. A novel ZnO microwire optical resonator with a parallelogram cross-section is fabricated, which can effectively control the light field in two dimensions. Wave-guided Fabry-Pérot modes with different polarizations are directly observed and further investigated systematically. Such a ZnO optical resonator offers another building block for the development of optoelectronic devices. 23578651 Development and validation of ethylenethiourea determination in foods using methanol-based extraction, solid-phase extraction cleanup and LC-MS/MS. To response to the need for a rapid, cost-effective, eco-friendly and efficient extraction process, a sensitive method for the determination of ethylenethiourea (ETU) in food matrices by high-performance liquid chromatography-mass spectrometry (HPLC-LC/MS) was developed and validated. ETU was extracted from food commodities with methanol, cleaned up by alumina-SPE column, and then determined by HPLC-MS/MS. The MS detection was operated in positive ionization mode. For confirmation of target compound, two precursor ion>product ion transitions were selected by multi-reaction monitoring mode (MRM). The method showed good linearity with correlation coefficient higher than 0.9950. Recoveries at three spiked levels (10, 50, 100ng/g) in random selected food matrices were in range of 71-121% with RSDs not larger than 25%. The limit of quantitation for the analyte was estimated at 5ng/g. 23525674 Cavitation during tensile deformation of isothermally crystallized polypropylene and high-density polyethylene. The cavitation phenomenon was studied in isothermally and non-isothermally crystallized polypropylene and high-density polyethylene. It was found that nano-voids were not present in the crystallized samples, but were formed during their tensile deformation. The process of cavitation was initiated before reaching the yield point. The ellipsoidal voids were initially elongated perpendicularly to the deformation direction, but if the polymer (i.e., high-density polyethylene) was able to deform beyond the yield, then the reorientation of voids into the deformation direction was observed at local strains of 100-200 %. This behavior was similar to that observed previously in the samples crystallized without an exact control of solidification conditions. The calculations of Guinier's radius showed that voids in deformed polypropylene samples were characterized by the gyration radii of 28-50 nm. Smaller voids were observed in polyethylene. The scale of cavitation during deformation, studied on the example of polyethylene, depended on the preceding crystallization process and was most intensive for the specimens crystallized at the highest temperature of 125 °C. 23200253 Further exploration of M₁ allosteric agonists: subtle structural changes abolish M₁ allosteric agonism and result in pan-mAChR orthosteric antagonism. This letter describes the further exploration of two series of M(1) allosteric agonists, TBPB and VU0357017, previously reported from our lab. Within the TPBP scaffold, either electronic or steric perturbations to the central piperidine ring led to a loss of selective M(1) allosteric agonism and afforded pan-mAChR antagonism, which was demonstrated to be mediated via the orthosteric site. Additional SAR around a related M(1) allosteric agonist family (VU0357017) identified similar, subtle 'molecular switches' that modulated modes of pharmacology from allosteric agonism to pan-mAChR orthosteric antagonism. Therefore, all of these ligands are best classified as bi-topic ligands that possess high affinity binding at an allosteric site to engender selective M(1) activation, but all bind, at higher concentrations, to the orthosteric ACh site, leading to non-selective orthosteric site binding and mAChR antagonism. 23399323 Inhibition of ghrelin O-acyltransferase attenuates food deprivation-induced increases in ingestive behavior. Ghrelin is an orexigenic hormone produced by the stomach in direct proportion to the time since the last meal and has therefore been called a 'hunger signal'. The octanoylation of ghrelin is critical for its orexigenic functions and is dependent upon ghrelin O-acyltransferase (GOAT) catalyzation. The GOAT inhibitor, GO-CoA-Tat, decreases the circulating concentrations of octanoylated ghrelin and attenuates weight gain on a high fat diet in mice. Unlike rats and mice, Siberian hamsters and humans do not increase food intake after food deprivation, but increase food hoarding after food deprivation. In Siberian hamsters, exogenous ghrelin increases ingestive behaviors similarly to 48-56h food deprivation. Therefore, we tested the necessity of increased ghrelin in food-deprived Siberian hamsters to stimulate ingestive behaviors. To do so we used our simulated natural housing system that allows hamsters to forage for and hoard food. Animals were given an injection of GO-CoA-Tat (i.p., 11μmol/kg) every 6h because that is the duration of its effective inhibition of octanoylated ghrelin concentrations during a 48h food deprivation. We found that GO-CoA-Tat attenuated food foraging (0-1h), food intake (0-1 and 2-4h), and food hoarding (0-1h and 2 and 3days) post-refeeding compared with saline treated animals. This suggests that increased octanoylated ghrelin concentrations play a role in the food deprivation-induced increases in ingestive behavior. Therefore, ghrelin is a critical aspect of the multi-faceted mechanisms that stimulate ingestive behaviors, and might be a critical point for a successful clinical intervention scheme in humans. 23080539 Pluripotent stem cells escape from senescence-associated DNA methylation changes. Pluripotent stem cells evade replicative senescence, whereas other primary cells lose their proliferation and differentiation potential after a limited number of cell divisions, and this is accompanied by specific senescence-associated DNA methylation (SA-DNAm) changes. Here, we investigate SA-DNAm changes in mesenchymal stromal cells (MSC) upon long-term culture, irradiation-induced senescence, immortalization, and reprogramming into induced pluripotent stem cells (iPSC) using high-density HumanMethylation450 BeadChips. SA-DNAm changes are highly reproducible and they are enriched in intergenic and nonpromoter regions of developmental genes. Furthermore, SA-hypomethylation in particular appears to be associated with H3K9me3, H3K27me3, and Polycomb-group 2 target genes. We demonstrate that ionizing irradiation, although associated with a senescence phenotype, does not affect SA-DNAm. Furthermore, overexpression of the catalytic subunit of the human telomerase (TERT) or conditional immortalization with a doxycycline-inducible system (TERT and SV40-TAg) result in telomere extension, but do not prevent SA-DNAm. In contrast, we demonstrate that reprogramming into iPSC prevents almost the entire set of SA-DNAm changes. Our results indicate that long-term culture is associated with an epigenetically controlled process that stalls cells in a particular functional state, whereas irradiation-induced senescence and immortalization are not causally related to this process. Absence of SA-DNAm in pluripotent cells may play a central role for their escape from cellular senescence. 23354070 Evidence for a new binding mode to GSK-3: allosteric regulation by the marine compound palinurin. Glycogen synthase kinase 3β (GSK-3β) is widely recognised as a relevant player in the pathogenesis of several highly prevalent disorders such as Alzheimer's disease, mood disorders, diabetes and cancer. Therefore, this enzyme constitutes a highly attractive therapeutic target for the development of selective inhibitors as new promising drugs for the treatment of these pathologies. We describe here the isolation and biochemical characterization of the marine natural sesquiterpene palinurin as a GSK-3β inhibitor. Experimental studies performed for characterizing the inhibitory mechanism indicate that GSK-3β inhibition by palinurin cannot be competed out by ATP nor peptide substrate. Molecular modelling techniques have enabled us to propose an unconventional binding mode to GSK-3β. Moreover, molecular dynamics simulations have identified an allosteric mechanism by which binding of palinurin leads to GSK-3β inhibition. The inhibitory activities determined for a series of structurally related analogues support the proposed binding mode of palinurin, which is the first compound described to target this allosteric site. The results offer new opportunities for designing and developing selective inhibitors with novel mechanisms of action. 23074088 Resolving sub-molecular binding and electrical switching mechanisms of single proteins at electroactive conducting polymers. Polymer-based electrodes for interfacing biological tissues are becoming increasingly sophisticated. Their many functions place them at the cross-roads of electromaterials, biomaterials, and drug-delivery systems. For conducting polymers, the mechanism of conductivity requires doping with anionic molecules such as extracellular matrix molecules, a process that distinguishes them as biomaterials and provides a means to control interactions at the cellular-electrode interface. However, due to their complex structure, directly observing the selective binding of target molecules or proteins has so far eluded researchers. This situation is compounded by the polymer's ability to adopt different electronic states that alter the polymer-dopant interactions. Here, the ability to resolve sub-molecular binding specificity between sulfate and carboxyl groups of dopants and heparin binding domains of human plasma fibronectin is demonstrated. The interaction exploits a form of biological 'charge complementarity' to enable specificity. When an electrical signal is applied to the polymer, the specific interaction is switched to a non-specific, high-affinity binding state that can be reversibly controlled using electrochemical processes. Both the specific and non-specific interactions are integral for controlling protein conformation and dynamics. These details, which represent the first direct measurement of biomolecular recognition between a single protein and any type of organic conductor, give new molecular insight into controlling cellular interactions on these polymer surfaces. 23408434 Neuronatin-mediated aberrant calcium signaling and endoplasmic reticulum stress underlie neuropathology in Lafora disease. Lafora disease (LD) is a teenage-onset inherited progressive myoclonus epilepsy characterized by the accumulations of intracellular inclusions called Lafora bodies and caused by mutations in protein phosphatase laforin or ubiquitin ligase malin. But how the loss of function of either laforin or malin causes disease pathogenesis is poorly understood. Recently, neuronatin was identified as a novel substrate of malin that regulates glycogen synthesis. Here we demonstrate that the level of neuronatin is significantly up-regulated in the skin biopsy sample of LD patients having mutations in both malin and laforin. Neuronatin is highly expressed in human fetal brain with gradual decrease in expression in developing and adult brain. However, in adult brain, neuronatin is predominantly expressed in parvalbumin-positive GABAergic interneurons and localized in their processes. The level of neuronatin is increased and accumulated as insoluble aggregates in the cortical area of LD brain biopsy samples, and there is also a dramatic loss of parvalbumin-positive GABAergic interneurons. Ectopic expression of neuronatin in cultured neuronal cells results in increased intracellular Ca(2+), endoplasmic reticulum stress, proteasomal dysfunction, and cell death that can be partially rescued by malin. These findings suggest that the neuronatin-induced aberrant Ca(2+) signaling and endoplasmic reticulum stress might underlie LD pathogenesis. 23340333 Hepatic transcriptome profiling indicates differential mRNA expression of apoptosis and immune related genes in eelpout (Zoarces viviparus) caught at Göteborg harbor, Sweden. The physiology and reproductive performance of eelpout (Zoarces viviparus) have been monitored along the Swedish coast for more than three decades. In this study, transcriptomic profiling was applied for the first time as an exploratory tool to search for new potential candidate biomarkers and to investigate possible stress responses in fish collected from a chronically polluted area. An oligonucleotide microarray with more than 15,000 sequences was used to assess differentially expressed hepatic mRNA levels in female eelpout collected from the contaminated area at Göteborg harbor compared to fish from a national reference site, Fjällbacka. Genes involved in apoptosis and DNA damage (e.g., SMAC/diablo homolog and DDIT4/DNA-damage-inducible protein transcript 4) had higher mRNA expression levels in eelpout from the harbor compared to the reference site, whereas mRNA expression of genes involved in the innate immune system (e.g., complement components and hepcidin) and protein transport/folding (e.g., signal recognition particle and protein disulfide-isomerase) were expressed at lower levels. Gene Ontology enrichment analysis revealed that genes involved biological processes associated with protein folding, immune responses and complement activation were differentially expressed in the harbor eelpout compared to the reference site. The differential mRNA expression of selected genes involved in apoptosis/DNA damage and in the innate immune system was verified by quantitative PCR, using the same fish in addition to eelpout captured four years later. Thus, our approach has identified new potential biomarkers of pollutant exposure and has generated hypotheses on disturbed physiological processes in eelpout. Despite a higher mRNA expression of genes related to apoptosis (e.g., diablo homolog) in eelpout captured in the harbor there were no significant differences in the number of TUNEL-positive apoptotic cells between sites. The mRNA level of genes involved in apoptosis/DNA damage and the status of the innate immune system in fish species captured in polluted environments should be studied in more detail to lay the groundwork for future biomonitoring studies. 23183413 Mortality, bioaccumulation and physiological responses in juvenile freshwater mussels (Lampsilis siliquoidea) chronically exposed to copper. Several studies have indicated that the early life stages of freshwater mussels are among the most sensitive aquatic organisms to inorganic chemicals, including copper. However, little is known about the toxic mode of action and sub-lethal effects of copper exposure in this group of imperiled animals. In this study, the physiological effects of long-term copper exposure (survival, growth, copper bioaccumulation, whole-body ion content, oxygen consumption, filtration rate, ATPase activities, and biomarkers of oxidative stress) were evaluated in juvenile (6 month old) mussels (Lampsilis siliquoidea). The mussels' recovery capacity and their ability to withstand further acute copper challenge were also evaluated in secondary experiments following the 28 day exposure by assessing survival, copper bioaccumulation and whole-body ion content. Mussels chronically exposed to 2 and 12 μg Cu/L showed significantly higher mortality than those held under control conditions (mortality 20.9, 69.9 and 12.5%, respectively), indicating that juvenile L. siliquoidea is underprotected by the U.S. Environmental Protection Agency (USEPA) biotic ligand model (BLM)-derived chronic water quality criteria (WQC) (2.18 μg Cu/L) and the hardness-derived USEPA WQC (12.16 μg Cu/L). Soft tissue copper burden increased equally for both copper exposures, suggesting that chronic toxicity is not associated with copper bioaccumulation. Several physiological disturbances were also observed during chronic copper exposure. Most relevant was a decrease in whole-body sodium content paralleled by an inhibition of Na(+) K(+)-ATPase activity, indicating a metal-induced ionoregulatory disturbance. Filtration and oxygen consumption rates were also affected. Redox parameters (reactive oxygen production, antioxidant capacity against peroxyl radicals, glutathione-S-transferase (GST) activity, and glutathione (GSH) concentration) did not show clear responses, but membrane damage as lipid peroxidation (LPO) was observed in both copper exposures. Mussels previously held in control conditions or pre-exposed to 2 μg dissolved Cu/L were able to maintain their ionic homeostasis and did not experience mortality after the 4-d recovery period. In contrast, those previously exposed to 12 μg dissolved Cu/L exhibited 50% mortality indicating that they had already reached a 'point of no return'. Pre-exposure to copper did not influence mussel response to the copper challenge test. As observed for the chronic exposure, mortality of mussels held in the absence of copper and submitted to the challenge test was also associated with an ionoregulatory disturbance. These results indicate that ionoregulatory disruption in freshwater mussels chronically exposed to copper is the main mechanism of toxicity and that redox parameters do not appear to be useful as indicators of sub-lethal copper toxicity in these animals. 23307790 Calorie-restricted weight loss reverses high-fat diet-induced ghrelin resistance, which contributes to rebound weight gain in a ghrelin-dependent manner. Twelve weeks of high-fat diet feeding causes ghrelin resistance in arcuate neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons. In the current study, we investigated whether diet-induced weight loss could restore NPY/AgRP neuronal responsiveness to ghrelin and whether ghrelin mediates rebound weight gain after calorie-restricted (CR) weight loss. Diet-induced obese (DIO) mice were allocated to one of two dietary interventions until they reached the weight of age-matched lean controls. DIO mice received chow diet ad libitum or chow diet with 40% CR. Chow-fed and high-fat-fed mice served as controls. Both dietary interventions normalized body weight, glucose tolerance, and plasma insulin. We show that diet-induced weight loss with CR increases total plasma ghrelin, restores ghrelin sensitivity, and increases hypothalamic NPY and AgRP mRNA expression. We propose that long-term DIO creates a higher body weight set-point and that weight loss induced by CR, as seen in the high-fat CR group, provokes the brain to protect the new higher set-point. This adaptation to weight loss likely contributes to rebound weight gain by increasing peripheral ghrelin concentrations and restoring the function of ghrelin-responsive neuronal populations in the hypothalamic arcuate nucleus. Indeed, we also show that DIO ghrelin-knockout mice exhibit reduced body weight regain after CR weight loss compared with ghrelin wild-type mice, suggesting ghrelin mediates rebound weight gain after CR weight loss. 23339547 Comparative single-dose pharmacokinetics of rasagiline in minipigs after oral dosing or transdermal administration via a newly developed patch. Abstract 1. A rasagiline transdermal patch was developed for the treatment of early and advanced Parkinson's disease. Relevant pharmacokinetic parameters of rasagiline obtained after transdermal administration to minipigs were compared with those of rasagiline after oral administration. 2. A total of 18 minipigs were randomly divided into three groups (six animals for each group). A single dose of 1 mg rasagiline tablet was orally administrated to one group. Meanwhile, single dose of 1.25 and 2.5 mg (2 and 4 cm(2)) rasagiline patches were given (at the postauricular skin) to the other two groups, respectively. The pharmacokinetic parameters such as plasma half-life (t(1/2)), time to peak plasma-concentration (T(max)), mean residence time (MRT), area under the curve (AUC((0-)(t)())) were significantly (p < 0.05) different between transdermal and oral administrations. 3. The plasma half-life (t(1/2)) of rasagiline (1.25 mg patch: 11.8 ± 6.5 h, 2.5 mg patch: 12.5 ± 4.7 h) in minipig following transdermal administration was significantly prolonged as compared with that following the oral administration (1 mg tablet: 4.7 ± 2.5 h). The dose-normalized relative bioavailability of rasagiline patch in minipig were 178.5% and 156.4%, respectively, for 1.25 and 2.5 mg patches compared with 1 mg rasagiline tablet. The prolonged t(1/2) and increased bioavailability of rasagiline patch suggested a possible longer dosing interval compared with oral tablet. 23611120 D - Glucose hydrogenation over Ru Nanoparticles Embedded in Mesoporous Hypercrosslinked Polystyrene. The kinetics of D-glucose hydrogenation on the catalyst containing Ru nanoparticles in the matrix of hypercrosslinked polystyrene was studied. Two routes of the hydrogenation reaction were revealed, their rates differ by several digits. The first route includes the interaction of D-glucose with the spilled-over hydrogen supplied by the catalyst; the second one includes classical interaction of the sorbed substrate with incident hydrogen from the reaction medium. Mathematical description of D-glucose conversion and the change of the catalyst activity by the fist way of D-glucose hydrogenation were obtained. The most probable scheme of the process flow was suggested. The main kinetic parameters were calculated. The role of hydrogen spillover phenomenon in the kinetics of the processes is discussed. 23566299 Determination of the α-Conotoxin Vc1.1 Binding Site on the α9α10 Nicotinic Acetylcholine Receptor. α-Conotoxin Vc1.1 specifically and potently inhibits the nicotinic acetylcholine receptor subtype α9α10 (α9α10 nAChR) and is a potential novel treatment for neuropathic pain. Here, we used a combination of computational modeling and electrophysiology experiments to determine the Vc1.1 binding site on the α9α10 nAChR. Interactions of Vc1.1 with two probable binding sites, α9α10 and α10α9, were modeled. Mutational energies calculated by assuming specific interactions in the α10α9 binding site correlated better with electrophysiological recordings than those assuming interactions with the α9α10 binding site. Two novel Vc1.1 analogues, [N9F]Vc1.1 and [N9W]Vc1.1, were predicted to have large differences in affinity between the two binding sites. Data from functional studies were consistent with computational predictions that assumed preferred binding of Vc1.1 to the α10α9 pocket. Moreover, our modeling study suggested that a single hydrogen bond formed between Vc1.1 and position 59 of the α10α9 pocket confers specificity to rat versus human α9α10 nAChRs. 23441829 Double C-H bond activation of hydrocarbons by a gas phase neutral oxide cluster: the importance of spin state. The neutral cluster V2O5 is generated and detected in the gas phase. Its reactivity toward butane is studied both experimentally and theoretically. Experimental results show clearly that neutral V2O5 can react with n-butane (C4H10) to generate V2O5H2, indicating double hydrogen atom transfer from C4H10 to V2O5 to produce C4H8. Further experimental evidence indicates that V2O5 is only partially reacted even at very high concentrations of C4H10. Density functional theory (DFT) studies show that the lowest energy triplet state of V2O5 is reactive toward C4H10, whereas the ground state singlet V2O5 is inert. Calculated results are in agreement with experimental findings, and a detailed reaction mechanism is provided. Reactions of V2O5H2 with several oxidants are also studied theoretically to find a path to regenerate V2O5. Neutral (3)V2O5 can also react with C2H6 to form V2O5H2 and C2H4, but only as a minor reaction channel; the major product is the adsorption product V2O5(C2H6). 23349486 Reduced Adipose Tissue Macrophage Content Is Associated With Improved Insulin Sensitivity in Thiazolidinedione-Treated Diabetic Humans. Obesity is associated with increased adipose tissue macrophage (ATM) infiltration, and rodent studies suggest that inflammatory factors produced by ATMs contribute to insulin resistance and type 2 diabetes. However, a relationship between ATM content and insulin resistance has not been clearly established in humans. Since thiazolidinediones attenuate adipose tissue inflammation and improve insulin sensitivity, we examined the temporal relationship of the effects of pioglitazone on these two parameters. The effect of 10 and 21 days of pioglitazone treatment on insulin sensitivity in 26 diabetic subjects was assessed by hyperinsulinemic-euglycemic clamp studies. Because chemoattractant factors, cytokines, and immune cells have been implicated in regulating the recruitment of ATMs, we studied their temporal relationship to changes in ATM content. Improved hepatic and peripheral insulin sensitivity was seen after 21 days of pioglitazone. We found early reductions in macrophage chemoattractant factors after only 10 days of pioglitazone, followed by a 69% reduction in ATM content at 21 days and reduced ATM activation at both time points. Although markers for dendritic cells and neutrophils were reduced at both time points, there were no significant changes in regulatory T cells. These results are consistent with an association between adipose macrophage content and systemic insulin resistance in humans. 23404198 TRIM16 overexpression induces apoptosis through activation of caspase-2 in cancer cells. TRIM16 exhibits tumour suppressor functions by interacting with cytoplasmic vimentin and nuclear E2F1 proteins in neuroblastoma and squamous cell carcinoma cells, reducing cell migration and replication. Reduced TRIM16 expression in a range of human primary malignant tissues correlates with increased malignant potential. TRIM16 also induces apoptosis in breast and lung cancer cells, by unknown mechanisms. Here we show that overexpression of TRIM16 induces apoptosis in human breast cancer (MCF7) and neuroblastoma (BE(2)-C) cells, but not in non-malignant HEK293 cells. TRIM16 increased procaspase-2 protein levels in MCF7 and induced caspase-2 activity in both MCF7 and BE(2)-C cells. We show that TRIM16 and caspase-2 proteins directly interact in both MCF7 and BE(2)-C cells and co-localise in MCF7 cells. Most importantly, the induction of caspase-2 activity is required for TRIM16 to initiate apoptosis. Our data suggest a novel mechanism by which TRIM16 can promote apoptosis by directly modulating caspase-2 activity. 23327491 Surfactant-mediated control of colloid pattern assembly and attachment strength in evaporating droplets. This study demonstrates that the pattern assembly and attachment strength of colloids in an evaporating sessile droplet resting on a smooth substrate can be controlled by adding nonionic solutes (surfactant) to the solution. As expected, increasing the surfactant concentration leads to a decrease in initial surface tension of the drop, σ(0). For the range of initial surface tensions investigated (39-72 mN m(-1)), three distinct deposition patterns were produced: amorphous stains (σ(0) = 63-72 mN m(-1)), coffee-ring stains (σ(0) = 48-53 mN m(-1)), and concentric rings (σ(0) = 39-45 mN m(-1)). A flow-displacement system was used to measure the attachment strength of the dried colloids. Characteristic drying regimes associated with the three unique pattern formations are attributed to abrupt transitions of contact line dynamics during evaporation. The first transition from slipping- to pinned-contact line was found to be a direct result of the competition between mechanical instability of the droplet and the friction generated by pinned colloids at the contact line. The second transition from pinned- to recurrent-stick-rip-slip-contact line was caused by repeated liquid film rupturing from evaporation-intensified surfactant concentration. Data from flow-displacement tests indicate that attachment strength of dried particles is strongest for amorphous stains (lowest surfactant concentration) and weakest for concentric rings (highest surfactant concentration). The mechanism behind these observations was ascribed to the formation and adsorption of micelles onto colloid and substrate surfaces as the droplet solution evaporates. The range of attachment forces observed between the colloids and the solid substrate were well captured by extended-DLVO interactions accounting for van der Waals attraction, electric double layer repulsion, and micelle-protrusion repulsion. Both empirical and theoretical results suggest that an increasingly dense layer of adsorbed micellar-protrusions on colloid and substrate surfaces acts as a physical barrier that hinders strong van der Waals attractive interactions at close proximity. Thereby, colloid stains dried at higher surfactant concentrations are more easily detached from the substrate when dislodging forces are applied than stains dried at lower surfactant concentrations. 23600807 Secondary metabolites from the endophytic fungi Penicillium polonicum and Aspergillus fumigatus. Two new compounds, rhodostegone (1) from endophytic fungus Penicillium polonicum and cyclo-(l-Val-l-Leu) (2) from Aspergillus fumigatus, together with six known diketopiperazines (3-8), were isolated. The structures of these compounds were characterized through a combination of extensive IR, MS, NMR, and CD analysis. 23443628 A population-based study of dosing and persistence with anti-dementia medications. PURPOSE: Cholinesterase inhibitors and memantine are the mainstay of pharmacological intervention for the cognitive symptoms of Alzheimer's disease (AD). This study assessed the adequacy of dosing and persistence with AD medications and the predictors of these variables in the 'real world' (outside the clinical trial setting). METHODS: The Health Service Executive-Primary Care Reimbursement Services prescription claims database in the Republic of Ireland contains prescription information for 1.6 million people. Patients aged >70 years who received at least two prescriptions for donepezil, rivastigmine, galantamine and memantine between January 2006 and December 2010 were included in the study. Rates of dose-maximisation were recorded by examining the initiation dose of each AD drug commenced during the study period and any subsequent dose titrations. Non-persistence was defined by a gap in prescribing of more than 63 consecutive days. Predictors of dose-maximisation and non-persistence were also analysed. RESULTS: Between January 2006 and December 2010, 20,729 patients aged >70 years received a prescription for an AD medication. Despite most patients on donepezil and memantine receiving a prescription for the maximum drug dose, this dose was maintained for 2 consecutive months in only two-thirds of patients. Patients were significantly more likely to have their doses of donepezil and memantine maximised if prescribed in more recent years (2010 vs. 2007). Rates of non-persistence were 30.1 % at 6 months and 43.8 % at 12 months. Older age [75+ vs. <75 years; hazards ratio (HR) 1.16, 95 % confidence interval (CI) 1.06-1.27] and drug type (rivastigmine vs. donepezil; HR 1.15, 95 % CI 1.03-1.27) increased the risk of non-persistence. Non-persistence was lower for those commencing therapy in more recent years (2010 vs. 2007; HR 0.81, 95 % CI 0.73-0.89, p < 0.001) and for those on multiple anti-dementia medications (HR 0.59, 95 % CI 0.54-0.65, p < 0.001). Persistence was significantly higher when memantine was co-prescribed with donepezil (p < 0.0001). CONCLUSION: Future studies should explore the reasons underlying non-persistence and failure to maintain dose-maximisation in patients on AD medications. There may be scope to improve the dosing and persistence with these medications in the community. 23225241 Ovariectomy Stimulates Hepatic Fat and Cholesterol Accumulation in High-fat Diet-fed Rats. This study was designed to determine how estrogens withdrawal during a high-fat (HF) diet regimen affects liver triacylglycerol (TAG) and cholesterol accumulation. Female Sprague-Dawley rats were submitted to a HF (42% energy as fat) or a standard (SD) diet for 6 weeks before being either ovariectomized (Ovx) or sham operated (Sham). Thereafter, Ovx and Sham rats were kept on the same diet for another 6 weeks leading to euthanasia. Liver TAG content was increased (p<0.01) in Ovx rats but not by the HF diet alone. However, the combination of HF diet and Ovx resulted in a greater liver TAG accumulation (p<0.06) than that observed in Ovx-SD/SD. Measurement of molecular markers of liver lipid metabolism revealed an increase in transcripts of markers of lipid oxidation (CPT-1 and PGC1; p<0.05) in rats fed the HF diet. This increase was, however, substantially less if HF fed rats were Ovx. Liver total cholesterol levels were increased (p<0.01) only in the Ovx-HF/HF rats while plasma cholesterol levels were increased in Ovx-SD/SD and in SHAM-HF/HF and Ovx-HF/HF rats. Transcripts of molecular markers of cholesterol metabolism suggest that biliary acids synthesis (CYP7a-1) was reduced in Ovx-SD/SD and Sham-HF/HF rats and even more so in Ovx-HF/HF rats. It is concluded that the effects of a HF diet on liver TAG accumulation are especially observed in Ovx rats possibly through a reduction in hepatic lipid oxidation. The combination of Ovx and HF diet also acts synergistically to favor liver cholesterol accumulation. 23135547 Mechanisms of hepatocellular toxicity associated with dronedarone--a comparison to amiodarone. Dronedarone is a new antiarrhythmic drug with an amiodarone-like benzofuran structure. Shortly after its introduction, dronedarone became implicated in causing severe liver injury. Amiodarone is a well-known mitochondrial toxicant. The aim of our study was to investigate mechanisms of hepatotoxicity of dronedarone in vitro and to compare them with amiodarone. We used isolated rat liver mitochondria, primary human hepatocytes, and the human hepatoma cell line HepG2, which were exposed acutely or up to 24h. After exposure of primary hepatocytes or HepG2 cells for 24h, dronedarone and amiodarone caused cytotoxicity and apoptosis starting at 20 and 50 µM, respectively. The cellular ATP content started to decrease at 20 µM for both drugs, suggesting mitochondrial toxicity. Inhibition of the respiratory chain required concentrations of ~10 µM and was caused by an impairment of complexes I and II for both drugs. In parallel, mitochondrial accumulation of reactive oxygen species (ROS) was observed. In isolated rat liver mitochondria, acute treatment with dronedarone decreased the mitochondrial membrane potential, inhibited complex I, and uncoupled the respiratory chain. Furthermore, in acutely treated rat liver mitochondria and in HepG2 cells exposed for 24h, dronedarone started to inhibit mitochondrial β-oxidation at 10 µM and amiodarone at 20 µM. Similar to amiodarone, dronedarone is an uncoupler and an inhibitor of the mitochondrial respiratory chain and of β-oxidation both acutely and after exposure for 24h. Inhibition of mitochondrial function leads to accumulation of ROS and fatty acids, eventually leading to apoptosis and/or necrosis of hepatocytes. Mitochondrial toxicity may be an explanation for hepatotoxicity of dronedarone in vivo. 23497896 Inhibition of citral degradation in an acidic aqueous environment by polyoxyethylene alkylether surfactants. Citral is a flavour component widely used in food and cosmetic industries, but is chemically unstable and degrades over time in aqueous solutions due to acid-catalysed and oxidative reactions leading to loss of desirable flavour. The present study reveals the effect of non-ionic micellar solutions of Brij30 and Brij35 on the extent of solubilisation and stabilisation of citral. The rate of chemical degradation of citral in acidic aqueous solutions was found to be highest, which was subsequently reduced significantly within these studied surfactant systems, suggesting protection of citral from an acidic environment once it is incorporated into the micelles. The work concludes that polyoxyethylene alkylether surfactants with lower HLB value, less dense hydrophilic corona and more hydrophobic core volume are efficient in solubilising and stabilising citral against an acidic environment. 23229539 Surgical trauma induces iron accumulation and oxidative stress in a rodent model of postoperative cognitive dysfunction. Postoperative cognitive dysfunction (POCD) is recognized as a complication after surgery in the elderly. The exact pathogenic mechanisms of POCD are still unknown. In this study, we investigated the role of iron accumulation within the central nervous system in the development of cognitive dysfunction in rats following splenectomy. Cognitive function was assessed using a Morris water maze on postoperative days 1, 3, and 7. Impaired cognitive function was observed on days 1 and 3 after splenectomy, while an anesthesia-alone group showed no significant difference from the control. Serum iron levels decreased and brain iron content increased on days 1 and 3 after surgery, which was in parallel with the impairment of cognitive function. Furthermore, the levels of proteins involved in the maintenance of brain iron homeostasis, including ferritin, transferrin receptor 1, and iron regulatory protein 2, were significantly different at postoperative days 1 and 3 in the hippocampus of splenectomized animals when compared with those of the control. The alterations in iron homeostasis were accompanied by intensified oxidative stress as measured by increases in the lipid peroxidation product, malondialdehyde, and a decrease in the levels of superoxide dismutase activity. Overall, these findings suggest that the impaired cognitive function was primarily due to surgical trauma rather than anesthesia. Increased iron accumulation and oxidative stress in the brain, especially in the hippocampus, may be involved in the pathogenesis of POCD. 23389045 Self-assembly of pyridine-modified lipoic Acid derivatives on gold and their interaction with thyroxine (t4). Pyridyl derivatives of lipoic acid were prepared as ligands for the study of the interaction with thyroxine (T4). Thin self-assembled films of the ligands were prepared in 70% ethanol on gold and their interaction with T4 was studied by titration experiments in an aqueous buffer solution using Surface Plasmon Resonance (SPR). The thickness and refractive index of the ligand layers were calculated from SPR spectra recorded in two media, also allowing for surface coverage and the density of the layers to be estimated. Two ligands, a 4-pyridyl and a bis(2-hydroxyethyl) derivative of lipoic acid, were selected to investigate the feasibility for producing molecularly imprinted self-assembled layers on gold for T4. The methodology was to co-assemble T4 and the ligand onto the gold surface, elute the T4 from the layer under alkaline conditions, and study the rebinding of T4 to the layer. Multiple elution/rebinding cycles were conducted in different buffer solutions, and rebinding of T4 could be observed, with a moderate binding affinity that depended greatly on the solvent used. More optimal binding was observed in HBS buffer, and the affinity of the interaction could be slightly increased when the 4-pyridyl and bis(2-hydroxy-ethyl) derivatives of lipoic acid were combined in the imprinted layer. 23591995 Selective kinin receptor agonists as cardioprotective agents in myocardial ischemia and diabetes. Cardiac ischemia is a leading cause of death, especially in diabetic patients. The diabetic ischemic heart is resistant experimentally to established cardioprotective treatments. New pharmacological approaches to cardiac protection are warranted. The kallikrein-kinin system is involved in myocardial protection in ischemia. Respective role of B1 (B1R) and B2 (B2R) receptors remains controversial. We tested whether pharmacological activation of kinin receptors may have therapeutic effect in cardiac ischemia-reperfusion in non diabetic (NDiab) and diabetic (Diab) mice. We assessed effect on infarct size (IS) and signaling pathways involved in myocardial protection of potent selective pharmacological agonists of B1R or B2R given at reperfusion. In NDiab mice, a B2R agonist reduced significantly IS by 47%, similarly to ramiprilat or ischemic postconditioning, via activation of PI3K/Akt pathway leading to inhibition of GSK3β. B1R agonist has no effect on IS. In contrast, in Diab mice, the B2R agonist, ramiprilat or ischemic postconditioning failed to reduce IS but a B1R agonist significantly reduced IS by 44% via activation of PI3K/Akt and ERK1/2, both leading to GSK3β inhibition. Differential effect of B2R or B1R agonists in NDiab and Diab mice can be linked to inactivation of B2R signaling and induction of B1R in heart of Diab mice. Thus, a pharmacological B2R agonist is cardioprotective in acute ischemia in non diabetic animals. B1R agonist overcomes resistance of diabetic heart to cardioprotective treatments. Pharmacological activation of B1R and B2R may become treatment for diabetic and non diabetic patients respectively in acute coronary syndromes. 23601710 Optimization of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of HIV capsid assembly inhibitors 2: Structure-activity relationships (SAR) of the C3-phenyl moiety. Detailed structure-activity relationships of the C3-phenyl moiety that allow for the optimization of antiviral potency of a series of 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione inhibitors of HIV capsid (CA) assembly are described. Combination of favorable substitutions gave additive SAR and allowed for the identification of the most potent compound in the series, analog 27. Productive SAR also transferred to the benzotriazepine and spirobenzodiazepine scaffolds, providing a solution to the labile stereocenter at the C3 position. The molecular basis of how compound 27 inhibits mature CA assembly is rationalized using high-resolution structural information. Our understanding of how compound 27 may inhibit immature Gag assembly is also discussed. 23620283 Homeodomain-interacting protein kinase 2-dependent repression of myogenic differentiation is relieved by its caspase-mediated cleavage. Differentiation of skeletal muscle cells is accompanied by drastic changes in gene expression programs that depend on activation and repression of genes at defined time points. Here we identify the serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) as a corepressor that inhibits myocyte enhancer factor 2 (MEF2)-dependent gene expression in undifferentiated myoblasts. Downregulation of HIPK2 expression by shRNAs results in elevated expression of muscle-specific genes, whereas overexpression of the kinase dampens transcription of these genes. HIPK2 is constitutively associated with a multi-protein complex containing histone deacetylase (HDAC)3 and HDAC4 that serves to silence MEF2C-dependent transcription in undifferentiated myoblasts. HIPK2 interferes with gene expression on phosphorylation and HDAC3-dependent deacetylation of MEF2C. Ongoing muscle differentiation is accompanied by elevated caspase activity, which results in caspase-mediated cleavage of HIPK2 following aspartic acids 916 and 977 and the generation of a C-terminally truncated HIPK2 protein. The short form of the kinase loses its affinity to the repressive multi-protein complex and its ability to bind HDAC3 and HDAC4, thus alleviating its repressive function for expression of muscle genes. This study identifies HIPK2 as a further protein that determines the threshold and kinetics of gene expression in proliferating myoblasts and during the initial steps of myogenesis. 23376697 Developmental abnormalities and changes in cholinesterase activity in sea urchin embryos and larvae from sperm exposed to engineered nanoparticles. The objective of this study is to examine the toxicity of engineered nanoparticles (NPs) that are dispersed in sea water by using an in vivo model. Because many products of nanotechnology contain NPs and are commonly used and well-established in the market, the accidental release of NPs into the air and water is quite possible. Indeed, at the end of their life cycle, some NPs are inevitably released into waste water and can reach marine ecosystem and affect the organisms there. Although there are few data on the presence of NPs in the marine environment, our awareness of their potential impact on environmental and organismal health is growing. Shallow-water benthonic organisms such as sea urchins provide planktonic larvae as a trophic base for finfish juveniles and are exposed to water from estuaries and precipitation. Such organisms can therefore be directly affected by NPs that are dispersed into those media. We evaluated the effects of exposure to different concentrations of nanosilver, titanium oxide and cobalt NPs on the sperm of the sea urchin Paracentrotus lividus by analyzing the functionality and the morphology and biochemistry of the first developmental stages of the sea urchin. Sperm were exposed to sea water containing suspensions of NPs ranging from 0.0001 mg/L to 1 mg/L. Fertilization ability was not affected, but developmental anomalies were identified in embryos from the gastrula to pluteus stages, including morphological alterations of the skeletal rods. In addition, the enzymatic activity (cholinesterase, ChE) of the larvae was measured. Acetylcholinesterase (AChE) and propionylcholinesterase activity (PrChE) was affected in all of the exposed samples. The results did not vary consistently with the concentration of NP, but controls were significantly different from exposed samples. Exposure of sea urchin to these NPs may cause neurotoxic damage, and the altered ChE activity may be involved in skeletogenic aberrations. In conclusion, the sea urchin represents a suitable and sensitive model for testing the toxicity and effects of engineered NPs that are dispersed in sea water. 23421714 (M)- and (P)-Bicelaphanol A, Dimeric Trinorditerpenes with Promising Neuroprotective Activity from Celastrus orbiculatus. (M)-Bicelaphanol A (1) and (P)-bicelaphanol A (2), two unprecedented dimeric trinorditerpenes existing as atropisomers, together with their monomer celaphanol A (3), were isolated from the root bark of Celastrus orbiculatus. The structures and absolute configurations of 1 and 2 were determined by spectroscopic and single-crystal X-ray diffraction analyses. Compound 1 exhibited a significant in vitro neuroprotective effect against a hydrogen peroxide-induced cell viability decrease in PC12 cells at 1 μM, while compounds 2 and 3 showed such effects at 10 μM. 23218717 Synthesis and insecticidal evaluation of novel N-pyridylpyrazolecarboxamides containing cyano substituent in the ortho-position. In an attempt to search for potent insecticides targeting the ryanodine receptor (RyR), a series of novel N-pyridylpyrazolecarboxamides containing cyano substituent in the ortho-position were designed and synthesized. Their insecticidal activities of target compounds against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) indicated that most of the compounds showed moderate to high activities at the tested concentrations. In particular, compound 6l and 6o showed 86% larvicidal activities against Plutella xylostella at the concentration of 0.1mg/L, while the activity of compound 6h against Mythimna separate was 80% at 1mg/L. The calcium imaging technique was applied to investigate the effects of some title compounds on the intracellular calcium ion concentration ([Ca(2+)](i)), experimental results demonstrated that compound 6h stimulates a transient elevation in [Ca(2+)](i) in the absence of external calcium after the central neurons dye loading with fluo-3 AM. However, when the central neurons were dyed with fluo-5N and incubated with 2-APB, [Ca(2+)]i decreased transiently by treated of compound 6h. All of the calcium imaging technique experiments demonstrated that these novel compounds deliver calcium from endoplasmic reticulum to cytoplasm, which proved that the title compounds were the possible activators of insect RyR. 23220413 Exposure of zebrafish embryos/larvae to TDCPP alters concentrations of thyroid hormones and transcriptions of genes involved in the hypothalamic-pituitary-thyroid axis. Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) has been frequently detected in the environment and in various biota, including fish, and has been implicated in disruption of the thyroid endocrine system. In the present study, zebrafish (Danio rerio) embryos were exposed to different concentrations of TDCPP (10, 50, 100, 300 and 600 μg/L) from 2 h post-fertilization (hpf) to 144 hpf. Developmental endpoints, and whole-body concentrations of thyroid hormones and transcriptional profiles of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were examined. Exposure to TDCPP caused a dose-dependent developmental toxicity, including decreased body weight, reduced hatching, survival and heartbeat rates, and increased malformation (spinal curvature). Treatment with the positive control chemical 3,3',5-triiodo-l-thyronine (T3) significantly decreased whole-body thyroxin (T4) concentrations, increased whole-body T3 concentrations, and upregulated mRNA expression involved in the HPT axis as a compensatory mechanism. These results suggested that the HPT axis in 144-hpf zebrafish larvae was responsive to chemical exposure and could be used to evaluate the effects of chemicals on the thyroid endocrine system. TDCPP exposure significantly decreased whole-body T4 concentrations and increased whole-body T3 concentrations, indicating thyroid endocrine disruption. The upregulation of genes related to thyroid hormone metabolism (dio1 and ugt1ab) might be responsible for decreased T4 concentrations. Treatment with TDCPP also significantly increased transcription of genes involved in thyroid hormone synthesis (tshβ, slc5a5 and tg) and thyroid development (hhex, nkx2.1 and pax8) as a compensatory mechanism for decreased T4 concentrations. Taken together, these results suggest that TDCPP alters the transcription of genes involved in the HPT axis and changes whole-body concentrations of thyroid hormones in zebrafish embryos/larvae, thus causing an endocrine disruption of the thyroid system. 23546605 Ovarian Expression of Insulin-Like Peptide 3 (INSL3) and Its Receptor (RXFP2) During Development of Bovine Antral Follicles and Corpora Lutea and Measurement of Circulating INSL3 Levels During Synchronized Estrous Cycles. Insulin-like peptide 3 (INSL3), a major product of testicular Leydig cells, is also expressed by the ovary, but its functional role remains poorly understood. Here, we quantified expression of INSL3 and its receptor RXFP2 in theca interna cell (TIC) and granulosa cell compartments of developing bovine antral follicles and in corpora lutea (CL). INSL3 and RXFP2 mRNA levels were much higher in TIC than granulosa cell and increased progressively during follicle maturation with INSL3 peaking in large (11-18 mm) estrogen-active follicles and RXFP2 peaking in 9- to 10-mm follicles before declining in larger (11-18 mm) follicles. Expression of both INSL3 and RXFP2 in CL was much lower than in TIC. In situ hybridization and immunohistochemistry confirmed abundant expression of INSL3 mRNA and protein in TIC. These observations indicate follicular TIC rather than CL as the primary site of both INSL3 production and action, implying a predominantly autocrine/paracrine role in TIC. To corroborate the above findings, we showed that in vitro exposure of TIC to a luteinizing concentration of LH greatly attenuated expression of both INSL3 and its receptor while increasing progesterone secretion and expression of STAR and CYP11A1. Moreover, in vivo, a significant cyclic variation in plasma INSL3 was observed during synchronized estrous cycles. INSL3 and estradiol-17β followed a similar pattern, both increasing after luteolysis, before falling sharply after the LH surge. Thus, theca-derived INSL3, likely from the dominant preovulatory follicle, is detectable in peripheral blood of cattle, and expression is down-regulated during luteinization induced by the preovulatory LH surge. Collectively, these findings underscore the likely role of INSL3 as an important intrafollicular modulator of TIC function/steroidogenesis, while raising doubts about its potential contribution to CL function. 23625909 Optimization of conventional water treatment plant using dynamic programming. In this research, the mathematical models, indicating the capability of various units, such as rapid mixing, coagulation and flocculation, sedimentation, and the rapid sand filtration are used. Moreover, cost functions were used for the formulation of conventional water and wastewater treatment plant by applying Clark's formula (Clark, 1982). Also, by applying dynamic programming algorithm, it is easy to design a conventional treatment system with minimal cost. The application of the model for a case reduced the annual cost. This reduction was approximately in the range of 4.5-9.5% considering variable limitations. Sensitivity analysis and prediction of system's feedbacks were performed for different alterations in proportion from parameters optimized amounts. The results indicated (1) that the objective function is more sensitive to design flow rate (Q), (2) the variations in the alum dosage (A), and (3) the sand filter head loss (H). Increasing the inflow by 20%, the total annual cost would increase to about 12.6%, while 20% reduction in inflow leads to 15.2% decrease in the total annual cost. Similarly, 20% increase in alum dosage causes 7.1% increase in the total annual cost, while 20% decrease results in 7.9% decrease in the total annual cost. Furthermore, the pressure decrease causes 2.95 and 3.39% increase and decrease in total annual cost of treatment plants. 23315996 The pH Taxis of an Intelligent Catalytic Microbot. A Pd nanoparticle-containing polymer microsphere moves with increasing speed across a pH gradient, following differential catalytic decomposition of aqueous hydrogen peroxide. The directional motion is akin to the pH taxis of living microorganisms. The artificial pH taxis exhibits random walk, translation, vertical, hopping, and pulsed motion, when the size of the motor and the imposed pH gradient are modulated. 23092395 Chemical profile and biological activities of Deguelia duckeana A.M.G. Azevedo (Fabaceae). Deguelia duckeana is popularly known as timbó and used by indigenous people as ictiotoxic. On account of there being no literature pertaining to the chemical profile or biological activity of this plant, the hexane, methanol and aqueous crude extracts from leaves, stems and roots were assayed that presented very high cytotoxic potential against Artemia salina, achieving 100% mortality in up to 5.0 µg mL(-1) concentration, but lower antioxidant potential on 2,2-diphenyl-1-picryl-hydrazyl and Fe(3+)/Phenanthroline assays. The phytochemical analysis of crude extracts showed the presence of flavonoids and related compounds as major constituents as well as steroids in all of them, and tannins in polar extracts. All the extracts were assayed for antibacterial activity but only the hexane extract of stems showed moderate activity on Staphylococcus aureus, which was fractionated and yielded a mixture of 3,5,4'-trimethoxy-4-prenylstilbene, lonchocarpine, 4-hydroxylonchocarpine and derricidine, reported for the first time in D. duckeana and other fraction with β-sitosterol and stigmasterol mixture. 23470080 Copeptin as a biomarker in cardiac disease. The introduction of biochemical biomarkers in the evaluation of patients with cardiovascular disease has led to practice-changing advancements in the way these patients are diagnosed and managed. Measurements of cardiac troponins or brain-type natriuretic peptide (BNP) and its precursor, N-terminal brain-type natriuretic peptide (NT-proBNP), have become indispensable in the evaluation of patients with acute coronary syndromes and heart failure, respectively, constituting an integral part of the diagnostic algorithm and risk stratification of these conditions. Copeptin, a glycopeptide, part of the prehormone molecule of the antidiuretic hormone - or arginine-vasopressin - has shown considerable promise in this field. There is evidence that copeptin might be useful as a diagnostic or prognostic biomarker and risk-stratifier in a range of cardiovascular disease conditions. The main clinical scenarios where copeptin has been studied as a biomarker are: early rule-out of myocardial infarction in patients with acute chest pain, diagnosis of heart failure in patients with acute dyspnea and determining the prognosis of destabilized or chronic stable heart failure. The present review is aimed at providing concise information about the molecular structure and biosynthesis of copeptin, the available medical chemistry methods of quantification, and the potential clinical uses of this molecule in patients with heart disease. 23293970 Tobacco smoke modulates ozone-induced toxicity in rat lungs and central nervous system. Adult Sprague-Dawley (SD) male rats were exposed for a single 3 h period to air, ozone (O₃) or O₃) followed by tobacco smoke (O₃/TS). For pulmonary effects, bronchoalveolar lavage (BAL) cells and fluid were analyzed. Data revealed a significant increase in polymorphonuclear leukocytes (PMN), total protein and albumin concentrations in the O₃ group, reflecting inflammatory and toxic responses. A subsequent exposure to TS attenuated PMN infiltration into the airspaces and their recovery in the BAL. A similar reduction was observed for BAL protein and albumin in the O₃/TS group, but it was not statistically significant. We also observed a significant increase in BAL total antioxidant capacity following O₃ exposure, suggesting development of protective mechanisms for oxidative stress damage from O₃. Exposure to TS attenuated the levels of total antioxidant capacity. Lung tissue protein analysis showed a significant reduction of extracellular superoxide dismutase (EC-SOD) in the O₃ or O₃/TS group and catalase in the O₃/TS group. TS further altered O₃-induced EC-SOD and catalase protein expression, but the reductions were not significant. For effects in the central nervous system (CNS), we measured striatal dopamine levels by HPLC with electrochemical detection. O₃ exposure produced a nonsignificant decrease in the striatal dopamine content. The effect was partially reversed in the O₃/TS group. Overall, the results show that the toxicity of O₃ in the lung is modulated by TS exposure, and the attenuating trend, though nonsignificant in many cases, is contrary to the synergistic toxicity predicted for TS and O₃, suggesting limited cross-tolerance following such exposures. 23564642 A Microscale Neuron and Schwann Cell Coculture Model for Increasing Detection Sensitivity of Botulinum Neurotoxin Type A. Botulinum neurotoxin (BoNT) is a potent and specific biomolecule that is both implicated as a potential threat in bioterrorism and used in therapeutics. Highly sensitive and robust assays that measure BoNT activity are needed to manage outbreak or controlled distribution of BoNT. Current in vivo and in vitro assays have limitations, including high costs and variability for mouse bioassays, extensive preparations for primary and stem cell-derived neurons, and inherent low sensitivity for cell lines. Sensitivity of cell lines can be increased by direct differentiation and with their physiological relevance (compared with cell-free strategies) and robustness (compared with primary cell strategies); adopting cell lines is an attractive alternative to in vivo assays. Here, we present two distinct strategies that improved sensitivity of a cell line to BoNT serotype A (BoNT/A) without direct differentiation. We developed a cell-based BoNT assay using microscale culture and coculture of neuronal and Schwann cell lines, NG108-15 and S16, respectively, to improve both sensitivity and physiological relevance. Results showed that NG108-15 and S16 coculture decreased EC50 from 12.5 to 0.8ng/µl (p < 0.001) in macroscale and from 2.6 to 1.1ng/µl (p = 0.006) in microscale. In addition, NG108-15 monoculture at microscale decreased EC50 from 12.5 to 2.6ng/µl (p < 0.001) compared with macroscale. Finally, controlling the spatial arrangement of microscale coculture revealed that S16-derived soluble factors can increase sensitivity. Thus, our study demonstrates two distinct strategies for increasing the sensitivity of a cell line to BoNT using coculture and microscale culture, thereby advancing assay technology for BoNT detection. 23525786 Combinatorial Design of Hydrolytically Degradable, Bone-like Biocomposites Based on PHEMA and Hydroxyapatite. With advantages such as design flexibility in modifying degradation, surface chemistry, and topography, synthetic bone-graft substitutes are increasingly demanded in orthopedic tissue engineering to meet various requirements in the growing numbers of cases of skeletal impairment worldwide. Using a combinatorial approach, we developed a series of biocompatible, hydrolytically degradable, elastomeric, bone-like biocomposites, comprising 60 wt% poly(2-hydroxyethyl methacrylate-co-methacrylic acid), poly(HEMA-co-MA), and 40 wt% bioceramic hydroxyapatite (HA). Hydrolytic degradation of the biocomposites is rendered by a degradable macromer/crosslinker, dimethacrylated poly(lactide-b-ethylene glycol-b-lactide), which first degrades to break up 3-D hydrogel networks, followed by dissolution of linear pHEMA macromolecules and bioceramic particles. Swelling and degradation were examined at Hank's balanced salt solution at 37 °C in a 12-week period of time. The degradation is strongly modulated by altering the concentration of the co-monomer of methacrylic acid and of the macromer, and chain length/molecular weight of the macromer. 95% weight loss in mass is achieved after degradation for 12 weeks in a composition consisting of HEMA/MA/Macromer = 0/60/40, while 90% weight loss is seen after degradation only for 4 weeks in a composition composed of HEMA/MA/Macromer = 27/13/60 using a longer chain macromer. For compositions without a co-monomer, only about 14% is achieved in weight loss after 12-week degradation. These novel biomaterials offer numerous possibilities as drug delivery carriers and bone grafts particularly for low and medium load-bearing applications. 23281917 Design and development of multiple emulsion for enhancement of oral bioavailability of acyclovir. The objective of this investigation was to design and develop water-in-oil-in-water type multiple emulsions (w/o/w emulsions) entrapping acyclovir for improving its oral bioavailability. Multiple emulsions (MEs) were prepared and optimized using Span-80 and Span-83 as lipophilic surfactant and Brij-35 as hydrophilic surfactant. The physio-chemical properties of the w/o/w emulsions - particle size, viscosity, phase separation (centrifugation test) and entrapment efficiency were measured and evaluated along with macroscopic and microscopic observations to confirm multiple nature, homogeneity and globule size. Stability study, in vitro and ex vivo release studies were performed followed by in vivo studies in rats. Stable w/o/w emulsions with a particle size of 33.098 ± 2.985 µm and 85.25 ± 4.865% entrapment efficiency were obtained. Stability studies showed that the concentration of lipophilic surfactant was very important for stability of MEs. Drug release from the prepared formulations showed initial rapid release followed by a much slower release. In vivo studies in rats indicated prolonged release and better oral bioavailability as compared to drug solution. The overall results of this study show the potential of the w/o/w emulsions as promising drug delivery systems for acyclovir. 23643664 Sustained resistance to acute MPTP toxicity by hypothalamic dopamine neurons following chronic neurotoxicant exposure is associated with sustained up-regulation of parkin protein. Hypothalamic tuberoinfundibular dopamine (TIDA) neurons remain unaffected in Parkinson disease (PD) while there is significant degeneration of midbrain nigrostriatal dopamine (NSDA) neurons. A similar pattern of susceptibility is observed following acute exposure to the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and the resistance of TIDA neurons to MPTP is associated with increased expression of parkin and ubiquitin carboxy-terminal hydrolase L-1 (UCHL- 1). In the present study, the response of TIDA and NSDA neurons to acute MPTP administration following chronic MPTP exposure was examined. Mice were treated with ten injections of either MPTP (20 mg/kg; s.c.; every 3.5 days) or saline vehicle (10 ml/kg; s.c.; every 3.5 days). Following a 21 day recovery period, chronic saline- and MPTP-treated mice received an additional injection of either saline (10 ml/kg; s.c.) or MPTP (20 mg/kg; s.c.) and were sacrificed 24 h later. NSDA neurons displayed significant axon terminal degeneration (as indexed by decreases in DA, tyrosine hydroxylase (TH) and DA transporter concentrations in the striatum) as well as loss of TH-immunoreactive (IR) neurons in the substantia nigra (SN) following MPTP, whereas TIDA neurons revealed no overt axon terminal pathology or loss of TH-IR cell bodies. NSDA neuronal pathology was associated with transient decreases in concentrations of parkin and UCHL-1 protein in the SN, which returned to normal levels by 21 days following cessation of chronic neurotoxicant exposure. Resistance of TIDA neurons to MPTP toxicity was correlated with a transient increase in UCHL-1 and a sustained elevation in parkin in the arcuate nucleus. TIDA neurons represent a DA neuron population with a unique and inherent ability to adapt to acute and chronic toxicant administration with a sustained elevation of the neuroprotective protein parkin. The correlation between the ability to increase parkin and UCHL-1 expression and the resistance of DA neurons to neurotoxicant exposure is consistent with a functional link between these features and an underlying differential susceptibility to toxicant-associated neurodegeneration. 23613080 Hierarchical NiO microflake films with high coloration efficiency, cyclic stability and low power consumption for applications in a complementary electrochromic device. We have demonstrated that thin films of hierarchical NiO microflakes assembled from nanoleaves can be grown directly on FTO-coated glass substrates using a facile and template-free hydrothermal technique. This hierarchical structure holds the advantages of both nanometre-sized building blocks and microsized assemblies. Thus, the films exhibit highly enhanced electrochromic performances and cyclic stability due to their high surface area and good electrochemical stability. Moreover, a complementary electrochromic device combining the hierarchical NiO microflake film with a self-weaving WO3 nanoflake film is fabricated to further improve the electrochromic performance. As a result, the complementary electrochromic device shows a high optical modulation (73.2% at 550 nm), large coloration efficiency (146.9 cm(2) C(-1) at 550 nm by applying a low coloration voltage of -1.0 V) and fast switching responses with a coloring time of 1.8 s and a bleaching time of 3.2 s. It is also observed that there is no significant degradation of the electrochromic properties after 2000 continuous coloration/bleaching cycles, making it attractive for practical applications. 23539547 Use of human in vitro skin models for accurate and ethical risk assessment: metabolic considerations. Several human skin models employing primary cells and immortalised cell lines, used as monocultures or combined to produce reconstituted 3D skin constructs, have been developed. Furthermore, these models have been included in European genotoxicity and sensitization/irritation assay validation projects. In order to help interpret data, Cosmetics Europe (formerly COLIPA) facilitated research projects that measured a variety of defined phase 1 and 2 enzyme activities and created a complete proteomic profile of xenobiotic metabolising enzymes (XMEs) in native human skin and compared them with data obtained from a number of in vitro models of human skin. Here, we have summarised our findings on the current knowledge of the metabolic capacity of native human skin and in vitro models, and make an overall assessment of the metabolic capacity from gene expression, proteomic expression and substrate metabolism data. The known low expression and function of phase 1 enzymes in native whole skin was reflected in the in vitro models. Some XMEs in whole skin were not detected in in vitro models and vice versa, and some major hepatic XMEs such as cytochrome P450-monooxygenases were absent or measured only at very low levels in the skin. Conversely, despite varying mRNA and protein levels of phase 2 enzymes, functional activity of glutathione S-transferases, N-acetyltransferase 1, and UDP-glucuronosyltransferases were all readily measurable in whole skin and in vitro skin models at activity levels similar to those measured in the liver. These projects have enabled a better understanding of the contribution of XMEs to toxicity endpoints. 23570839 New dimeric and trimeric coumarin glucosides from Daphne retusa Hemsl. New dimeric and a trimeric coumarin glucosides namely Daphneretusin A (1) Daphneretusin B (2) along with three known oligomers (3-5) were obtained as a result of bioassay guided fractionation of Daphne retusa Hemsl. Fractions (n-hexane, CHCl3, AcOEt, CH3OH and water) exhibited potent radical scavenging activity in relevant non-physiological bioassays. The structures of isolated compounds were elucidated by UV, IR, EIMS, FAB-MS, 1D, and 2D NMR spectroscopic analysis. 23382448 Dicer1 is required to repress neuronal fate during endocrine cell maturation. MicroRNAs (miRNAs) are important regulators of gene expression programs in the pancreas; however, little is known about the role of miRNA pathways during endocrine cell specification and maturation during neonatal life. In this study, we deleted Dicer1, an essential RNase for active miRNAs biogenesis, specifically from NGN3+ endocrine progenitor cells. We found that deletion of Dicer1 in endocrine progenitors did not affect the specification of hormone-expressing endocrine cells. However, the islets in the mutant mice in the neonatal period exhibited morphological defects in organization and loss of hormone expression, and the mutant mice subsequently developed diabetes. Dicer1-deficient β-cells lost insulin expression while maintaining the expression of β-cell transcription factors such as Pdx1 and Nkx6.1 early in the postnatal period. Surprisingly, transcriptional profiling showed that that the Dicer1-deficient endocrine cells expressed neuronal genes before the onset of diabetes. The derepression of neuronal genes was associated with a loss in binding of the neuronal transcriptional repressor RE-1-silencing transcription factor to its targets in Dicer1-deficient β-cells. These studies suggest that miRNAs play a critical role in suppressing neuronal genes during the maturation of endocrine cells. 23103297 (-)-Carvone: antispasmodic effect and mode of action. (-)-Carvone is a monoterpene ketone found in spearmint (Mentha spicata var. crispa) essential oil that is widely used as an odor and flavor additive. An intestinal antispasmodic effect was recently reported for (-)-carvone, and it has been shown to be more potent than its (+)-antipode. The mechanism of (-)-carvone action in the intestines has not been investigated. To gain a better understanding of the (-)-carvone antispasmodic effect, we investigated its pharmacological effects in the guinea pig ileum. Terminal portions of the ileum were mounted for isotonic contraction recordings. The effect of (-)-carvone was compared with that of the classical calcium channel blocker (CCB) verapamil. In isolated ileal smooth muscle, (-)-carvone did not produce direct contractile or relaxation responses and did not modify electrically elicited contractions or low K(+)-evoked contractions. The submaximal contractions induced by histamine (p<0.001), BaCl2 (p<0.05), and carbachol (p<0.01) were significantly reduced by (-)-carvone. The contractile response elicited by high concentrations of carbachol was reduced but not abolished by (-)-carvone. No additive action was detected with co-incubation of (-)-carvone and verapamil on carbachol-induced contraction. (-)-Carvone reduced the contraction induced by high K(+) and was almost 100 times more potent than verapamil. Thus, (-)-carvone showed a typical and potent CCB-like action. Many effects described for both (-)-carvone and spearmint oil can be explained as a CCB-like mode of action. 23131177 Characterization of substituted phenylpropylamides as highly selective agonists at the melatonin MT2 receptor. Melatonin is a widely distributed hormone that regulates several major physiological processes, including the circadian rhythm and seasonal adaptation. The two subtypes of mammalian G protein-coupled melatonin receptors are primarily responsible for mediating the actions of melatonin. Because synthetic melatonin agonists have considerable therapeutic potentials in modulating insomnia and circadian- related sleep disorders, it is highly desirable to develop subtype-selective melatoninergic compounds. The pharmacological potencies of a series of substituted N-[3-(3-methoxyphenyl)propyl] amides towards human melatonin MT(1) and MT(2) receptors were evaluated by the FLIPR high-throughput screening assay, whilst their subtype-selectivity was subsequently verified with ERK phosphorylation and cAMP assays. Structure-activity relationship analysis of highly potent subtype-selective ligands (MT(2) EC(50) 10-90 pM) revealed that a benzyloxyl substituent incorporated at C6 position of the 3-methoxyphenyl ring dramatically enhanced the MT(2) potency and at the same time decreased MT(1) potency. Incorporation of structural moieties conferring the subtype selectivity produced several extremely potent MT(2)-selective ligands. The most potent subtype-selective ligand, 2q had a substantially higher potency for MT(2) receptor than melatonin for elevation of [Ca(2+)]i and inhibition of forskolin-elevated cAMP. Representative MT(2)-selective ligands also induced ERK phosphorylation in both recombinant and native cell lines, and no cross-reactivity to 17 other GPCRs could be detected. These ligands represent invaluable tools for delineating the functional roles of distinct melatonin receptor subtypes and are viable candidates for drug development. 22889721 Microcrack density and nanomechanical properties in the subchondral region of the immature piglet femoral head following ischemic osteonecrosis. Development of a subchondral fracture is one of the earliest signs of structural failure of the immature femoral head following ischemic osteonecrosis, and this eventually leads to a flattening deformity of the femoral head. The mechanical and mineralization changes in the femoral head preceding subchondral fracture have not been elucidated. We hypothesized that ischemic osteonecrosis leads to early material and mechanical alterations in the bone of the subchondral region. The purpose of this investigation was to assess the bone of the subchondral region for changes in the histology of bone cells, microcrack density, mineral content, and nanoindentation properties at an early stage of ischemic osteonecrosis in a piglet model. This large animal model has been shown to develop a subchondral fracture and femoral head deformity resembling juvenile femoral head osteonecrosis. The unoperated, left femoral head of each piglet (n=8) was used as a normal control, while the right side had a surgical ischemia induced by disrupting the femoral neck vessels with a ligature. Hematoxylin and eosin (H&E) staining and TUNEL assay were performed on femoral heads from 3 piglets. Quantitative backscattered electron imaging, nanoindentation, and microcrack assessments were performed on the subchondral region of both control and ischemic femoral heads from 5 piglets. H&E staining and TUNEL assay showed extensive cell death and an absence of osteoblasts in the ischemic side compared to the normal control. Microcrack density in the ischemic side (3.2±0.79 cracks/mm(2)) was significantly higher compared to the normal side (0.27±0.27 cracks/mm(2)) in the subchondral region (p<0.05). The weighted mean of the weight percent distribution of calcium (CaMean) also was significantly higher in the ischemic subchondral region (p<0.05). Furthermore, the nanoindentation modulus within localized areas of subchondral bone was significantly increased in the ischemic side (16.8±2.7GPa) compared to the normal control (13.3±3.2GPa) (p<0.05). Taken together, these results support the hypothesis that the nanoindentation modulus of the subchondral trabecular bone is increased in the early stage of ischemic osteonecrosis of the immature femoral head and makes it more susceptible to microcrack formation. We postulate that continued loading of the hip joint when there is a lack of bone cells to repair the microcracks due to ischemic osteonecrosis leads to microcrack accumulation and subsequent subchondral fracture. 23627902 Structural Characterization and Molecular Order of Rodlike Mesogens with Three- and Four-Ring Core by XRD and (13)C NMR Spectroscopy. Structural characterizations using XRD and (13)C NMR spectroscopy of two rodlike mesogens consisting of (i) three phenyl ring core with a polar cyano terminal and (ii) four phenyl ring core with flexible dodecyl terminal chain are presented. The three-ring-core mesogen with cyano terminal exhibits enantiotropic smectic A phase while the four-ring mesogen reveals polymesomorphism and shows enantiotropic nematic, smectic C, and tilted hexatic phases. The molecular organization in the three-ring mesogen is found to be partial bilayer smectic Ad type, and the interdigitation of the molecules in the neighboring layers is attributed to the presence of the polar terminal group. For the four-ring mesogen, the XRD results confirm the existence of the smectic C and the tilted hexatic mesophases. A thermal variation of the layer spacing across the smectic C phase followed by a discrete jump at the transition to the tilted hexatic phase is also observed. The tilt angles have been estimated to be about 45° in the smectic C phase and about 40° in tilted hexatic phase. (13)C NMR results indicate that in the mesophase the molecules are aligned parallel to the magnetic field. From the (13)C-(1)H dipolar couplings determined from the 2D experiments, the overall order parameter for the three-ring mesogen in its smectic A phase has been estimated to be 0.72 while values ranging from 0.88 to 0.44 have been obtained for the four-ring mesogen as it passes from the tilted hexatic to the nematic phase. The orientations of the different rings of the core unit with respect to each other and also with respect to the long axis of the molecule have also been obtained. 23511088 Derivatives of Dictyostelium discoideum differentiation-inducing factor-3 suppress the activities of Trypanosoma cruzi in vitro and in vivo. Chagas disease (human American trypanosomiasis), which is caused by the protozoan parasite Trypanosoma cruzi, is responsible for numerous deaths each year; however, established treatments for the disease are limited. Differentiation-inducing factor-1 (DIF-1) and DIF-3 are chlorinated alkylphenones originally found in the cellular slime mold Dictyostelium discoideum that have been shown to possess pharmacological activities. Here, we investigated the effects of DIF-3 derivatives on the infection rate and growth of T. cruzi by using an in vitro assay system utilizing host human fibrosarcoma HT1080 cells. Certain DIF-3 derivatives, such as butoxy-DIF-3 (Bu-DIF-3), at micro-molar levels strongly suppressed both the infection rate and growth of T. cruzi in HT1080 cells and exhibited little toxicity for HT1080 cells. For example, the IC50 of DIF-3 and Bu-DIF-3 versus the growth of T. cruzi in HT1080 cells were 3.95 and 0.72μM, respectively, and the LD50 of the two compounds versus HT1080 cells were both greater than 100μM. We also examined the effects of DIF-3 and Bu-DIF-3 on T. cruzi activity in C57BL/6 mice. Intraperitoneally administered Bu-DIF-3 (50mg/kg) significantly suppressed the number of trypomastigotes in blood with no apparent adverse effects. These results strongly suggest that DIF-3 derivatives could be new lead compounds in the development of anti-trypanosomiasis drugs. 23527619 Novel Cellulose Polyampholyte-Gold Nanoparticle-Based Colorimetric Competition Assay for the Detection of Cysteine and Mercury(II). We provide a highly sensitive and selective assay to detect cysteine (Cys) and Hg(2+) in aqueous solutions using Au nanoparticles (NPs) stabilized by carboxylethyl quaternized cellulose (CEQC). This method is based on the thiophilicity of Hg(2+) and Au NPs as well as the unique optical properties of CEQC-stabilized Au NPs. CEQC chains are good stabilizing agents for Au NPs even in a high-salt solution. The addition of Cys results in the aggregation of CEQC-stabilized Au NPs, which induces the visible color change and obvious redshift in UV-visible absorption spectra. On the other hand, Hg(2+) is more apt to interact with thiols than Au NPs; thus, it can remove the Cys and trigger Au NP aggregate redispersion again. By taking advantage of this mechanism, a novel off-on colorimetric sensor has been established for Cys and Hg(2+) detection. This new assay could selectively detect Cys and Hg(2+) with the detection limits as low as 20 and 40 nM in aqueous solutions, respectively. 23561124 Comparison of biogenic amine and polyphenol profiles of grape berries and wines obtained following conventional, organic and biodynamic agricultural and oenological practices. The bio-active compounds present in food and beverages have a high potential influence on the future health of humans. The levels of biogenic amines, anthocyanins, polyphenols and antioxidant activity were measured in white (Pignoletto) and red (Sangiovese) grape berries and wines from the Emilia-Romagna region (Italy) obtained following conventional, organic and biodynamic agricultural and oenological practices. No significant difference was shown among the samples coming from different agricultural and winemaking practices. Principal Component Analysis was also performed. Biogenic amine amounts were higher in red than in white berries, while in the wines an opposite trend was observed, with histamine, tyramine and putrescine being the most abundant in Pignoletto wines. Red grapes and wines were richer in anthocyanins and showed higher antioxidant activity than white ones. The total level of polyphenols was similar in red and white berries, but with different metabolite profiles depending on the grape variety. 22985735 Comparative cytological responses of lung epithelial and pleural mesothelial cells following in vitro exposure to nanoscale SiO2. Due to unique surface chemistries and the ability to easily functionalize their surface, amorphous silica nanoparticles are being assimilated into medicinal and consumer products at an increasing rate. Subsequently, there is an emergent need to understand the interactions of these particulates with biological systems in an attempt to mitigate toxicity. The identification of susceptible or resistant cell types of the pulmonary system remains a critical step in the development of toxicity assessments for nanoparticle-based platforms. Specific to this study, the cellular responses of A549 lung epithelial and MeT-5A pleural mesothelial cell lines as a means of detecting nanoparticle-induced oxidative stress were examined. Basal expression and cellular antioxidant activity, including SOD, CAT, and GSH, were examined prior to H(2)O(2) and ~30 nm SiO(2) (0.01-100mg/L) exposures. Dose-response observations were made regarding oxidant production, cytotoxicity, GSH depletion and NRF2 transcription factor activation. Results indicated that, while both cell types exhibited susceptibility to H(2)O(2) and SiO(2)-induced oxidative stress and damage, the A549 cell line was relatively more resilient. 23280951 The impact of structure on oxidatively generated DNA damage products resulting from the C3'-thymidinyl radical. What's the damage? Trapping the C3'-thymidinyl radical in biologically significant architectures delivers both the repaired oligomer and 1-(2'-deoxy-β-D-threo-pentofuranosyl)thymidine-containing substrates. The stereoselectivity of the reduction was found to be dependent upon the DNA structure. 23122068 Separation and purification of sulforaphene from radish seeds using macroporous resin and preparative high-performance liquid chromatography. This present study described a rapid and cost-effective method for the separation and purification of natural sulforaphene from radish seeds by SP-700 macroporous resin and preparative high-performance liquid chromatography (HPLC). Sulforaphene with high purity and recovery was obtained by preparative HPLC with a C18 column and 30% methanol in ultra-pure water as the mobile phase. 12.5 kg of radish seeds, which contained 87.5 g of sulforaphene, produced 117.5 g of sulforaphene-rich extract of 65.8% sulforaphene after primary separation by SP-700 macroporous resin. 5.9 g of 96.5% sulforaphene was obtained from 9.5 g of the sulforaphene-rich extract after purification by preparative HPLC. The purified compound was assessed by analytical HPLC and characterised by ESI/MS, (1)H NMR and (13)C NMR. Standard curve was developed using the purified sulforaphene to allow quantification of sulforaphene in the extracts of radish seeds by analytical HPLC. 23469924 Identification of a RhoA- and SRF-Dependent Mechanism of Androgen Action that is Associated with Prostate Cancer Progression. Androgen receptor (AR) action is critical for prostate cancer (CaP) progression, but is not inhibited fully by available androgen deprivation therapy (ADT). One of the limitations to current ADT is that it targets all androgen action in CaP, and other, cells irrespective of clinical relevance. The resulting off-target effects are responsible for ADT associated side effects that affect negatively a patient's quality of life. Isolation of the AR-dependent events that drive CaP progression may lead to novel forms of ADT that are at least as effective but more selective. Here, an approach is described that starts from insights in the basic mechanism(s) by which AR regulates target gene expression to identify novel drugable targets downstream of AR. Exploration of the molecular events that underlie androgen regulation of the ARassociated coregulator FHL2 led to the isolation of a novel indirect mechanism of androgen action that is mediated by the secondary transcription factor Serum Response Factor (SRF). Using a combination of oligoarray and in silico analyses, an SRF-dependent fraction of AR action was identified that is enriched in CaP tissues, is able to discriminate between benign and malignant prostate, and correlates with aggressive disease and biochemical failure. The RhoA signaling axis, a well known upstream stimulator of SRF action that harbors drugable targets, conveyed androgen-responsiveness to SRF, and was activated in CaP where it correlates with increased CaP aggressiveness and poor outcome after surgery. 22954283 Can first-trimester screening program detect women at high risk for gestational diabetes mellitus? This study was designed to compare first-trimester maternal serum biochemical markers of aneuploidy and fetal nuchal translucency in pregnancies complicated by gestational diabetes mellitus and those of a control group. The study included 60 gestational diabetic and 60 control women who attended the first-trimester combined screening program for Down syndrome between 11 and 14 gestational weeks with complete follow-up data and delivered in our institution. Maternal serum free β-human chorionic gonadotropin, pregnancy-associated plasma protein-A and fetal nuchal translucency were investigated. The combined risks, double test risks and age risks were calculated by PRISCA software version 4.0. Comparison of the results between the two groups yielded no significant differences in serum levels of free β-human chorionic gonadotropin and fetal nuchal translucency. However, women who developed gestational diabetes mellitus had significantly lower pregnancy-associated plasma protein-A. And also, the combined risks and double test risks calculated by PRISCA software were statistically higher in gestational diabetic women than normal pregnant women. These results suggest that differences can be seen between diabetic and healthy pregnant women in first-trimester maternal serum biochemical markers of aneuploidy. 23410038 The metalloproteases meprin α and meprin β: unique enzymes in inflammation, neurodegeneration, cancer and fibrosis. The metalloproteases meprin α and meprin β exhibit structural and functional features that are unique among all extracellular proteases. Although meprins were discovered more than 30 years ago, their precise substrates and physiological roles have been elusive. Both enzymes were originally found to be highly expressed in kidney and intestine, which focused research on these particular tissues and associated pathologies. Only recently it has become evident that meprins exhibit a much broader expression pattern, implicating functions in angiogenesis, cancer, inflammation, fibrosis and neurodegenerative diseases. Different animal models, as well as proteomics approaches for the identification of protease substrates, have helped to reveal more precise molecular signalling events mediated by meprin activity, such as activation and release of pro-inflammatory cytokines. APP (amyloid precursor protein) is cleaved by meprin β in vivo, reminiscent of the β-secretase BACE1 (β-site APP-cleaving enzyme 1). The subsequent release of Aβ (amyloid β) peptides is thought to be the major cause of the neurodegenerative Alzheimer's disease. On the other hand, ADAM10 (a disintegrin and metalloprotease domain 10), which is the constitutive α-secretase, was shown to be activated by meprin β, which is itself shed from the cell surface by ADAM10. In skin, both meprins are overexpressed in fibrotic tumours, characterized by massive accumulation of fibrillar collagens. Indeed, procollagen III is processed to its mature form by meprin α and meprin β, an essential step in collagen fibril assembly. The recently solved crystal structure of meprin β and the unique cleavage specificity of these proteases identified by proteomics will help to generate specific inhibitors that could be used as therapeutics to target meprins under certain pathological conditions. 23127598 Absorption of triphenylmethane dyes Brilliant Blue and Patent Blue through intact skin, shaven skin and lingual mucosa from daily life products. Currently, there is evidence of health risks of triphenylmethane dyes after systemic absorption. This paper investigates the fate of Brilliant Blue (BB) and Patent Blue (PB) after 24-h in vitro diffusion, firstly through intact and secondly through shaven pig-ear skin (stored by freezing) from four leave-on cosmetics under in-use conditions. Both dyes showed no measurable permeation through intact skin but significant permeation was found through shaven skin. From 250 ng/cm(2) of dye in one applied dose there were found 52 ng/cm(2) of BB and 91 ng/cm(2) of PB from ethanol-based after-shave, 39 ng/cm(2) of BB and 86 ng/cm(2) of PB from ethanol-free facial-cleanser, 35 ng/cm(2) of BB and 43 ng/cm(2) of PB from O/W emulsion, and no amount from W/O emulsion, as available to become systemically absorbed. Thirdly, the paper focuses on lingual mucosa after licking lollipops. Ex vivo porcine tongue dorsum was exposed to human saliva with 15,000 ng/cm(2) of dye for 20 min. 24-h diffusion resulted in 34 ng/cm(2) of BB and 86 ng/cm(2) of PB which can be directly absorbed into the blood system. Findings are troubling, particularly with regard to the frequent use of after-shave products by the male population and repeated lollipops licking by children. 23380305 Selective brain region activation by histamine H3 receptor antagonist/inverse agonist ABT-239 enhances acetylcholine and histamine release and increases c-Fos expression. Histamine axons originate solely from the tuberomamillary nucleus (TMN) to innervate almost all brain regions. This feature is consistent with a function for histamine over a host of physiological processes, including regulation of appetite, body temperature, cognitive processes, pain perception and sleep-wake cycle. An important question is whether these diverse physiological roles are served by different histamine neuronal subpopulations. Here we report that systemic administration of the non-imidazole histamine H3 receptor antagonist 4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile (ABT-239, 3 mg/kg) increased c-Fos expression dose-dependently in rat cortex and nucleus basalis magnocellularis (NBM) but not in the nucleus accumbens (NAcc) nor striatum, and augmented acetylcholine and histamine release from rat prefrontal cortex. To further understand functional histaminergic pathways in the brain, dual-probe microdialysis was used to pharmacologically block H3 receptors in the TMN. Perfusion of the TMN with ABT-239 (10 μM) increased histamine release from the TMN, NBM, and cortex, but not from the striatum or NAcc. When administered locally, ABT-239 increased histamine release from the NBM, but not from the NAcc. Systemic as well as intra-TMN administration of ABT-239 increased c-Fos expression in the NBM, and cortex, but not in the striatum or NAcc. Thus, as defined by their sensitivity to ABT-239, histaminergic neurons establish distinct pathways according to their terminal projections, and can differentially modulate neurotransmitter release in a brain region-specific manner. This implies independent functions of subsets of histamine neurons according to their terminal projections, with relevant consequences for the development of specific compounds that affect only subsets of histamine neurones, thus increasing target specificity. 23352929 Suppressive effects of Indigofera suffruticosa Mill extracts on lipopolysaccharide-induced inflammatory responses in murine RAW 264.7 macrophages. Indigofera suffruticosa Mill is used as an herbal medicine for the treatment of inflammation. The aim of this study is to assess the anti-inflammatory potency of I. suffruticosa and its likely molecular mechanisms of action in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Both water and ethanolic extracts of I. suffruticosa significantly decreased LPS-induced nitric oxide (NO) as well as the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α, and pro-interleukin-1β. Moreover, LPS-induced inhibitory factor-κB-α phosphorylation, nuclear factor-κB (NF-κB) nuclear protein-DNA binding affinity, and NF-κB reporter gene activity were dramatically inhibited by I. suffruticosa extracts. Exogenous addition of I. suffruticosa significantly induced heme oxygenase-1 (HO-1) expression, and the presence of HO-1 small interfering RNA partly reversed the inhibitory effects of I. suffruticosa on LPS-induced NO production and iNOS expression. Furthermore, I. suffruticosa induced HO-1 expression may be through activation of the ERK/nuclear factor E2-related factor 2 pathway. Eight phenolic compounds were found in the I. suffruticosa extracts, but salicylic acid was the only one detected in the plasma of mice fed with I. suffruticosa extracts. In summary, I. suffruticosa have a strong anti-inflammatory property that diminishes pro-inflammatory mediator expressions by lessening LPS-induced NF-κB activation and inducing HO-1 expression in macrophages. 23393163 Vesnarinone Suppresses TNFα mRNA Expression by Inhibiting Valosin-Containing Protein. Vesnarinone is a synthetic quinolinone derivative used in the treatment of cardiac failure and cancer. It is also known to cause agranulocytosis as a side effect, which restricts its use, although the mechanism underlying agranulocytosis is not well understood. Here, we show that vesnarinone binds to valosin-containing protein (VCP), which interacts with polyubiquitinated proteins and is essential for the degradation of IκBα to activate nuclear factor (NF)κB. We show that vesnarinone impairs the degradation of IκBα, and that the impairment of the degradation of IκBα is the result of the inhibition of the interaction between VCP and the 26S proteasome by vesnarinone. These results suggest that vesnarinone suppresses NFκB activation by inhibiting the VCP-dependent degradation of polyubiquitinated IκBα, resulting in the suppression of tumor necrosis factor-α mRNA expression. 23584277 Kinetics and mechanism of oxygen reduction in a protic ionic liquid. The oxygen reduction reaction (ORR) has been studied at Pt surfaces in the protic ionic liquid diethylmethylammonium trifluoromethanesulfonate. Water content measurements suggested that the ORR proceeded in the ionic liquid predominantly via a 4-electron reduction to water. A mechanistic analysis using rotating ring-disk electrode (RRDE) voltammetry confirmed that negligible amounts of hydrogen peroxide were formed during the ORR. A kinetic analysis of the ORR was performed using rotating disk electrode (RDE) voltammetry and the importance of correcting for ohmic (iR) drop prior to performing kinetic measurements in the ionic liquid is demonstrated. A Tafel analysis of the RDE voltammetry data revealed a change in the ORR Tafel slope from 70 mV per decade at low ORR overpotentials to 117 mV per decade at high overpotentials, and the reason for this change is discussed. The change in the Tafel slope for the ORR with increasing overpotential meant that the exchange current density for the ORR varied from 0.007 nA cm(-2) to 10 nA cm(-2), depending on the applied potential. Finally, the implications of these results for the development of protic ionic liquid fuel cells are discussed. 23206861 Tetrahydro-β-carboline derivatives targeting fatty acid amide hydrolase (FAAH) and transient receptor potential (TRP) channels. A series of twenty-five derivatives of tetrahydro-β-carbolines 1-3 was synthesized and assayed on FAAH and TRPV1 and TRPA1 channels. Four carbamates, that is, 5a,c,e, and 9b inhibited FAAH with significant potency and interacted also effectively with TRPV1 and TRPA1 nociceptive receptors, while ureas 7b,d,f, and 8a,b were endowed with specific submicromolar TRPV1 modulating activities. 23301495 Cyanide antidotes for mass casualties: water-soluble salts of the dithiane (sulfanegen) from 3-mercaptopyruvate for intramuscular administration. Current cyanide antidotes are administered by IV infusion, which is suboptimal for mass casualties. Therefore, in a cyanide disaster, intramuscular (IM) injectable antidotes would be more appropriate. We report the discovery of the highly water-soluble sulfanegen triethanolamine as a promising lead for development as an IM injectable cyanide antidote. 23177256 Pharmacophore identification of c-Myc inhibitor 10074-G5. A structure-activity relationship (SAR) study of the c-Myc (Myc) inhibitor 10074-G5 (N-([1,1'-biphenyl]-2-yl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine, 1) - which targets a hydrophobic domain of the Myc oncoprotein that is flanked by arginine residues - was executed in order to determine its pharmacophore. Whilst the 7-nitrobenzofurazan was found to be critical for inhibitory activity, the ortho-biphenyl could be replaced with a para-carboxyphenyl group to furnish the new inhibitor JY-3-094 (3q). Around five times as potent as the lead with an IC(50) of 33 μM for disruption of the Myc-Max heterodimer, JY-3-094 demonstrated excellent selectivity over Max-Max homodimers, with no apparent effect at 100 μM. Importantly, the carboxylic acid of JY-3-094 improves the physicochemical properties of the lead compound, which will facilitate the incorporation of additional hydrophobicity that might enhance Myc inhibitory activity further still. 23550722 Thermal Stability of Peroxy Acyl Nitrates Formed in the Oxidation of CxF2x+1CH2C(O)H (x = 1,6) in the Presence of NO2. The formation of CxF2x+1CH2C(O)OONO2 (x = 1,6) from the photooxidation of CxF2x+1CH2C(O)H (x = 1,6) in the presence of NO2 was investigated. The infrared spectrum of C6F13CH2C(O)OONO2 is reported for the first time, and thermal stability for both peroxynitrates at 295 K and 9.0 mbar is informed. Kinetic parameters (activation energy and pre-exponential factor) for CF3CH2C(O)OONO2 at 9.0 and 1000 mbar are: 108 ± 2 kJ/mol, 1.5 × 10(15) and 114 ± 2 kJ/mol, 2.4 × 10(16), respectively. A comparison is made between fluoro and hydrogenated peroxy acyl nitrates. 23408116 The UDP-Glucuronosyltransferase (UGT) 1A Polymorphism c.2042C>G (rs8330) Is Associated with Increased Human Liver Acetaminophen Glucuronidation, Increased UGT1A Exon 5a/5b Splice Variant mRNA Ratio, and Decreased Risk of Unintentional Acetaminophen-Induced Acute Liver Failure. Acetaminophen is cleared primarily by hepatic glucuronidation. Polymorphisms in genes encoding the acetaminophen UDP-glucuronosyltransferase (UGT) enzymes could explain interindividual variability in acetaminophen glucuronidation and variable risk for liver injury after acetaminophen overdose. In this study, human liver bank samples were phenotyped for acetaminophen glucuronidation activity and genotyped for the major acetaminophen-glucuronidating enzymes (UGTs 1A1, 1A6, 1A9, and 2B15). Of these, only three linked single nucleotide polymorphisms (SNPs) located in the shared UGT1A-3'UTR region (rs10929303, rs1042640, rs8330) were associated with acetaminophen glucuronidation activity, with rs8330 consistently showing higher acetaminophen glucuronidation at all the tested concentrations of acetaminophen. Mechanistic studies using luciferase-UGT1A-3'UTR reporters indicated that these SNPs do not alter mRNA stability or translation efficiency. However, there was evidence for allelic imbalance and a gene-dose proportional increase in the amount of exon 5a versus exon 5b containing UGT1A mRNA spliced transcripts in livers with the rs8330 variant allele. Cotransfection studies demonstrated an inhibitory effect of exon 5b containing cDNAs on acetaminophen glucuronidation by UGT1A1 and UGT1A6 cDNAs containing exon 5a. In silico analysis predicted that rs8330 creates an exon splice enhancer site that could favor exon 5a (over exon 5b) utilization during splicing. Finally, the prevalence of rs8330 was significantly lower (P = 0.027, χ(2) test) in patients who had acute liver failure from unintentional acetaminophen overdose compared with patients with acute liver failure from other causes or a race- or ethnicity-matched population. Together, these findings suggest that rs8330 is an important determinant of acetaminophen glucuronidation and could affect an individual's risk for acetaminophen-induced liver injury. 23383423 International Union of Pharmacology. LXXXVII. Complement peptide C5a, C4a, and C3a receptors. The activation of the complement cascade, a cornerstone of the innate immune response, produces a number of small (74-77 amino acid) fragments, originally termed anaphylatoxins, that are potent chemoattractants and secretagogues that act on a wide variety of cell types. These fragments, C5a, C4a, and C3a, participate at all levels of the immune response and are also involved in other processes such as neural development and organ regeneration. Their primary function, however, is in inflammation, so they are important targets for the development of antiinflammatory therapies. Only three receptors for complement peptides have been found, but there are no satisfactory antagonists as yet, despite intensive investigation. In humans, there is a single receptor for C3a (C3a receptor), no known receptor for C4a, and two receptors for C5a (C5a₁ receptor and C5a₂ receptor). The most recently characterized receptor, the C5a₂ receptor (previously known as C5L2 or GPR77), has been regarded as a passive binding protein, but signaling activities are now ascribed to it, so we propose that it be formally identified as a receptor and be given a name to reflect this. Here, we describe the complex biology of the complement peptides, introduce a new suggested nomenclature, and review our current knowledge of receptor pharmacology. 23580421 Large Areal Mass, Flexible and Free-Standing Reduced Graphene Oxide/Manganese Dioxide Paper for Asymmetric Supercapacitor Device. Well-separated RGO sheets decorated with MnO2 nanoparticles facilitate easy access of the electrolyte ions to the high surface area of the paper electrode, enabling fabrication of thicker electrode with heavier areal mass and higher areal capacitance (up to 897 mF cm(-2) ). Electrochemical performance of the bent asymmetric device with total active mass of 15 mg remains similar to the one in the flat configuration, demonstrating good mechanical robustness of the device. 23511718 PEG as a spacer arm markedly increases the immunogenicity of meningococcal group Y polysaccharide conjugate vaccine. Neisseria meningitidis is a life-threatening pathogen that causes meningitis and other clinical manifestations. As a key virulence determinant, meningococcal capsular polysaccharide (PS) can be used to prevent meningococcal diseases. Conjugation of PS to carrier protein can significantly improve the immunogenicity of PS and induce memory response in infants and young children. However, the conjugate vaccine may suffer from steric shielding of antigenic PS epitopes by carrier protein. Here, a heterobifunctional polyethylene glycol (PEG) was used as a spacer arm to conjugate meningococcal group Y capsular PS with tetanus toxoid (TT). PEG can avoid self-crosslink of PS and increase the PS/TT ratio of the vaccine. Significant structural change in TT and PS was not observed upon conjugation. As compared to the vaccine without PEG, immunization with the vaccine using PEG as the spacer arm led to 3.0-fold increase in the PS-specific IgG titers and a prolonged immune persistence. Paradoxically, PEG, a non-immunogenic hydrophilic polymer has been widely used to couple therapeutic protein for increasing its circulatory time and decreasing its immunogenicity. Presumably, PEG can fully decrease the steric shielding effect of TT on antigenic epitopes of PS and suppress the immunogenicity of TT. In addition, PEG can prolong the immune persistence of the conjugate vaccine and improve its ability to elicit cellular immunity. Thus, PEG can be used as a spacer arm to develop more effective PS conjugate vaccine for prevention of bacterial infection. 23617807 The Differences in the Sublimation Energy of Benzene and Hexahalogenbenzenes Are Caused by Dispersion Energy. The crystals of benzene and hexahalogenbenzenes have been studied by means of the density-functional theory augmented by an empirical dispersion correction term as well as by the symmetry-adapted perturbation theory. In order to elucidate the nature of noncovalent binding, pairwise interactions have been investigated. It has been demonstrated that the structures of dimers with the highest stabilization energy differ notably along the crystals. It has been shown that the differences in the experimental sublimation energies might be attributed to the dispersion interaction. To our surprise, the dihalogen bonding observed in the hexachloro- and hexabromobenzenes plays a rather minor role in energy stabilization, because they are energetically comparable with the other binding motifs. However, the dihalogen bond is by far the most frequent binding motif in hexachloro- and hexabromobenzenes. 22874922 Novel non-canonical TGF-β signaling networks: emerging roles in airway smooth muscle phenotype and function. The airway smooth muscle (ASM) plays an important role in the pathophysiology of asthma and chronic obstructive pulmonary disease (COPD). ASM cells express a wide range of receptors involved in contraction, growth, matrix protein production and the secretion of cytokines and chemokines. Transforming growth factor beta (TGF-β) is one of the major players in determining the structural and functional abnormalities of the ASM in asthma and COPD. It is increasingly evident that TGF-β functions as a master switch, controlling a network of intracellular and autocrine signaling loops that effect ASM phenotype and function. In this review, the various elements that participate in non-canonical TGF-β signaling, including MAPK, PI3K, WNT/β-catenin, and Ca(2+), are discussed, focusing on their effect on ASM phenotype and function. In addition, new aspects of ASM biology and their possible association with non-canonical TGF-β signaling will be discussed. 23116144 Multivalent agents: a novel concept and preliminary practice in Anti-HIV drug discovery. The term multivalency (polyvalency) in the biological science is defined as the simultaneous binding of multiple ligands to one receptor (or multiple receptors to one ligand). The possibility of gaining potency and selectivity was significantly increased through the use of multivalent ligand as a homo- or hetero-dimer, thus multivalent ligands provided a more attractive strategy to design novel anti-HIV agents with therapeutic applications. Moreover, similar to phenomenon of multivalency, an alternative strategy is called the "mixed sites inhibitor", viz. a single molecule that possesses enough chemical space to maximize interactions with its complementary binding pocket, or to bind simultaneously in more than one regions in a target. Actually, the addition of a third heterocyclic nucleus to the parent compound resulted in "mixed sites" anti-HIV agents with broad spectrum of activities against the mutant HIV-1 strains. Based on current representative examples, the present article provided a brief review on the rationale for the design of different classes of multivalency anti-HIV agents and also discussed the advantages over their monomeric counterparts, providing a novel paradigm to facilitate the development of anti-HIV/AIDS therapeutic agents in treatment of HIV infected community. 23312279 Damned if you do, damned if you don't: the conundrum of adipose tissue vascularization. The plasticity of adipose tissue requires highly regulated changes in accompanying blood vessels. In obesity, adipose tissue angiogenesis plays a complex role to support tissue growth and promote metabolic disease. Emerging research (Sung et al., 2013) indicates that exploiting the mediators of adipose tissue angiogenesis may offer the possibility for therapeutic interventions. 23180796 Animal QTLdb: an improved database tool for livestock animal QTL/association data dissemination in the post-genome era. The Animal QTL database (QTLdb; http://www.animalgenome.org/QTLdb) is designed to house all publicly available QTL and single-nucleotide polymorphism/gene association data on livestock animal species. An earlier version was published in the Nucleic Acids Research Database issue in 2007. Since then, we have continued our efforts to develop new and improved database tools to allow more data types, parameters and functions. Our efforts have transformed the Animal QTLdb into a tool that actively serves the research community as a quality data repository and more importantly, a provider of easily accessible tools and functions to disseminate QTL and gene association information. The QTLdb has been heavily used by the livestock genomics community since its first public release in 2004. To date, there are 5920 cattle, 3442 chicken, 7451 pigs, 753 sheep and 88 rainbow trout data points in the database, and at least 290 publications that cite use of the database. The rapid advancement in genomic studies of cattle, chicken, pigs, sheep and other livestock animals has presented us with challenges, as well as opportunities for the QTLdb to meet the evolving needs of the research community. Here, we report our progress over the recent years and highlight new functions and services available to the general public. 23600432 5-Lipoxygenase inhibitors: a review of recent patents (2010 - 2012). Introduction: 5-Lipoxygenase (5-LO) is a crucial enzyme of the arachidonic acid (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) with the help of FLAP, the 5-LO-activating protein. LTs are inflammatory mediators playing a pathophysiological role in different diseases like asthma, allergic rhinitis as well as cardiovascular diseases and certain types of cancer. With the rising number of indications for anti-LT therapy, 5-LO inhibitor drug development becomes increasingly important. Areas covered: Here, both recent findings regarding the pathophysiological role of 5-LO and the patents claimed for 5-LO inhibitors are discussed. Focusing on direct inhibitors, several patents disclosing FLAP antagonists are also subject of this review. Novel compounds include 1,5-diarylpyrazoles, indolizines and indoles and several natural product extracts. Expert opinion: Evaluation of the patent activities revealed only quite moderate action. Nevertheless, several auspicious drug-like molecules were disclosed. It seems that in the near future, FLAP inhibitors can be expected to enter the market for the treatment of asthma. With the resolved structure of 5-LO, structure-based drug design is now applicable. Together with the identification of downstream enzyme inhibitors and dual-targeting drugs within the AA cascade, several tools are at hand to cope with 5-LOs increasing pathophysiological roles. 23245696 Exonuclease 1 preferentially repairs mismatches generated by DNA polymerase α. The Saccharomyces cerevisiae EXO1 gene encodes a 5' exonuclease that participates in mismatch repair (MMR) of DNA replication errors. Deleting EXO1 was previously shown to increase mutation rates to a greater extent when combined with a mutator variant (pol3-L612M) of the lagging strand replicase, DNA polymerase δ (Pol δ), than when combined with a mutator variant (pol2-M644G) of the leading strand replicase, DNA polymerase ɛ (Pol ɛ). Here we confirm that result, and extend the approach to examine the effect of deleting EXO1 in a mutator variant (pol1-L868M) of Pol α, the proofreading-deficient and least accurate of the three nuclear replicases that is responsible for initiating Okazaki fragment synthesis. We find that deleting EXO1 increases the mutation rate in the Pol α mutator strain to a significantly greater extent than in the Pol δ or Pol ɛ mutator strains, thereby preferentially reducing the efficiency of MMR of replication errors generated by Pol α. Because these mismatches are closer to the 5' ends of Okazaki fragments than are mismatches made by Pol δ or Pol ɛ, the results not only support the previous suggestion that Exo1 preferentially excises lagging strand replication errors during mismatch repair, they further imply that the 5' ends serve as entry points for 5' excision of replication errors made by Pol α, and possibly as strand discrimination signals for MMR. Nonetheless, mutation rates in the Pol α mutator strain are 5- to 25-fold lower in an exo1Δ strain as compared to an msh2Δ strain completely lacking MMR, indicating that in the absence of Exo1, most replication errors made by Pol α can still be removed in an Msh2-dependent manner by other nucleases and/or by strand displacement. 23331770 Food-related impulsivity in obesity and Binge Eating Disorder - a systematic review. Impulsivity towards food has been recognized as a potential factor leading to increased food intake in obesity. Patients suffering from binge eating disorder (BED) form a specific subgroup of obese people that might be characterized by increased impulsivity. These assumptions, although, have yet to be verified. Therefore, this review evaluates evidence for food-related impulsivity in obese people with and without BED and examines possible differences between both populations. More precisely, evidence for the two components of impulsivity is analyzed separately: evidence for reward sensitivity, specifically, the urge for appetitive stimuli and evidence for rash-spontaneous behaviour such as acting disinhibited with no regard for the consequences. Our search resulted in 51 articles demonstrating generally increased food-related impulsivity. We found particular emphasis on increased reward sensitivity in obese people, which appeared to be more pronounced in people with BED. There was little and conflicting evidence, however, concerning increased rash-spontaneous behaviour in obese people without BED, but consistent evidence of an increase in obese people with BED. All in all, the evidence supports the view that BED represents a specific phenotype of obesity with increased food-related impulsivity. Taking these specific deficits into account can enhance the effectiveness of weight reduction programmes and psychotherapy. 23357626 Apoptosis-inducing activity of the actin-depolymerizing agent aplyronine A and its side-chain derivatives. Aplyronine A (1) and mycalolide B (2), which are cytotoxic actin-depolymerizing marine macrolides, were revealed to induce apoptosis in human leukemia HL60 cells and human epithelial carcinoma HeLa S(3) cells. Based on these results, actin-depolymerizing compounds were expected to exhibit apoptosis-inducing activity in cancer cells. Compounds 3-6, which were synthesized based on the side-chain structure of aplyronine A, were evaluated for their actin-depolymerizing activities in vitro and cytotoxicities against HL60 cells. The growth-inhibitory activities of 3-6 were well correlated with their actin-depolymerizing activities, and derivative 6 was shown to induce the disruption of actin filaments and apoptosis in HL60 cells. These results suggested that actin-depolymerizing agents 1, 2, and 6-induced apoptosis in HL60 cells may have been due to their actin-depolymerizing activity. 23410745 Association of nephrolithiasis with metabolic syndrome and its components. OBJECTIVE: Both metabolic syndrome (MetS) and nephrolithiasis (NL) are common and clinically important disorders. Therefore, we conducted this study to assess the association of MetS and NL. MATERIALS/METHODS: Data were obtained from 116,536 individuals who underwent health screening tests between January 2010 and December 2010 at a health promotion center in Seoul, Korea. All subjects were asked to respond to a questionnaire including medical history of each subject. Anthropometric and biochemical measurements were applied to each subject. Presence of NL was evaluated by an abdominal ultrasonography. The subjects were classified into MetS and non-MetS group according to the criteria for MetS (National Cholesterol Education Program Adult Treatment Panel III). Compared to the non-MetS group, we estimated the Odds Ratios (ORs) and 95% Confidence Intervals (CIs) of the presence of NL in the MetS group adjusting for age, serum levels of creatinine and uric acid, and past medical history of NL based on the multivariate logistic regression analysis. RESULTS: The prevalence of MetS was 15.9% (N=1129/7107) in the NL group, and 11.2% (N=12,287/109,429) in the non-NL group, respectively. After adjusting for the potential confounding factors, male MetS patients had a higher presence of NL than non-MetS subjects (OR 1.11; 95% CI 1.02-1.20; p=0.01). Of MetS components, only high blood pressure (BP) was a significantly related factor to the presence of NL (male; OR 1.08; 95% CI 1.01-1.15; p=0.043, female; OR 1.24; 95% CI 1.08-1.42; p=0.002). As the number MetS components increased, the presence of NL was significantly higher in male subjects (P for trend<0.001), but not in female subjects (P for trend=0.961). CONCLUSIONS: We found that NL was associated with MetS and high BP. 23528611 Epidermal growth factor receptor inhibitor PKI-166 governs cardiovascular protection without beneficial effects on the kidney in hypertensive 5/6 nephrectomised rats. Transactivation of epidermal growth factor receptor (EGFR) signaling by G-protein-coupled receptors has been implicated in several cardiovascular (CV) conditions, including hypertension, heart failure, cardiac and vascular hypertrophy. However, the therapeutic potential of EGFR inhibition in these conditions is currently unknown. Main objective of the present study was to investigate cardiac, vascular and renal effects of EGFR inhibition by PKI-166 in the hypertensive chronic kidney disease (CKD) model. Rats underwent 5/6 nephrectomy (5/6Nx) and were treated with PKI-166 or lisinopril or vehicle from week 6 after disease induction until week 12. Sham animals received either PKI-166 or vehicle. Treatment with PKI-166 did not affect the development of the characteristic renal features in 5/6Nx including proteinuria, diminished creatinine clearance and increased glomerulosclerosis, whereas these were attenuated by lisinopril. Despite absence of effects on progressive renal damage, PKI-166 attenuated the progression of hypertension and maintained cardiac function (LVEDP) to a similar extent as lisinopril. Also, PKI-166 attenuated the increase in phosphorylated EGFR in heart as induced by 5/6Nx. Moreover, PKI-166 and lisinopril restored the impaired contraction of isolated thoracic aortic rings to phenylephrine and angiotensin II and impaired myogenic constriction of small mesenteric arteries in 5/6Nx rats. Blockade of the EGFR displays a CV benefit independently of limiting the progression of renal injury. Our findings extend the evidence on EGFR signaling as a target in CV disorders. 23437926 Evidence for the Involvement of Descending Pain-Inhibitory Mechanisms in the Antinociceptive Effect of Hecogenin Acetate. Hecogenin is a sapogenin present in the leaves of species from the Agave genus, with a wide spectrum of reported pharmacological activities. The present study was undertaken to evaluate whether hecogenin acetate (1) has antinociceptive properties and to determine its mechanism of action. The nociceptive threshold was evaluated using the tail flick test in mice. Mice motor performance was evaluated in a Rotarod test. By using Fos expression as a marker of neural activation, the involvement of the periaqueductal gray in 1-induced antinociception was evaluated. Intraperitoneal administration of 1 (5-40 mg/kg) produced a dose-dependent increase in the tail flick latency time compared to vehicle-treated group (p < 0.01). Mice treated with 1 (40 mg/kg) did not show motor performance alterations. The antinociception of 1 (40 mg/kg) was prevented by naloxone (nonselective opioid receptor antagonist; 5 mg/kg), CTOP (μ-opioid receptor antagonist; 1 mg/kg), nor-BNI (κ-opioid receptor antagonist; 0.5 mg/kg), naltrindole (δ-opioid receptor antagonist; 3 mg/kg), or glibenclamide (ATP-sensitive K(+) channel blocker; 2 mg/kg). Systemic administration of 1 (5-40 mg/kg) increased the number of Fos positive cells in the periaqueductal gray. The present study has demonstrated for the first time that 1 produces consistent antinociception mediated by opioid receptors and endogenous analgesic mechanisms. 23563356 No mutations in the serotonin related TPH1 and HTR1B genes in patients with monogenic sclerosing bone disorders. Since the identification of LRP5 as the causative gene for the osteoporosis pseudoglioma syndrome (OPPG) as well as the high bone mass (HBM) phenotype, LRP5 and the Wnt/β-catenin signaling have been extensively studied for their role in the differentiation and proliferation of osteoblasts, in the apoptosis of osteoblasts and osteocytes and in the response of bone to mechanical loading. However, more recently the direct effect of LRP5 on osteoblasts and bone formation has been questioned. Gene expression studies showed that mice lacking lrp5 have increased expression of tph1, the rate limiting enzyme for the production of serotonin in the gut. Furthermore mice lacking either tph1 or htr1B, the receptor for serotonin on the osteoblasts, were reported to have an increased bone mass due to increased bone formation. This led to the still controversial hypothesis that LRP5 influences bone formation indirectly by regulating the expression of thp1 and as a consequence influencing the production of serotonin in the gut. Based on these data we decided to evaluate the role of TPH1 and HTR1B in the development of craniotubular hyperostoses, a group of monogenic sclerosing bone dysplasias. We screened the coding regions of both genes in 53 patients lacking a mutation in the known causative genes LRP5, LRP4 and SOST. We could not find disease-causing coding variants in neither of the tested genes and therefore, we cannot provide support for an important function of TPH1 and HTR1B in the pathogenesis of sclerosing bone dysplasias in our tested patient cohort. 23063590 Artemisinic acid inhibits melanogenesis through downregulation of C/EBP α-dependent expression of HMG-CoA reductase gene. Cholesterol is associated with the regulation of melanogenesis which is the major physiological defense against solar irradiation. The present study was designed to determine the effects of artemisinic acid on melanogenesis and its mechanisms of action in human epidermal melanocytes. In this study, we found that artemisinic acid inhibited melanin content. The mRNA levels of microphthalmia-associated transcription factor (MITF) and its downstream genes tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were reduced by artemisinic acid treatment. Additionally, the mRNA levels of melanogenesis-related genes (c-KIT, stem cell factor (SCF), and macrophage migration inhibitory factor (MIF)) were down-regulated by artemisinic acid. Furthermore, cAMP production and protein kinase A (PKA) activity were suppressed by artemisinic acid. Moreover, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that artemisinic acid regulated melanogenesis by inhibiting cholesterol synthesis through downregulation of the hydroxymethylglutaryl CoA (HMG CoA) reductase gene, which was mediated through reduced expression of the CCAAT/enhancer-binding protein (C/EBP) α gene. Taken together, these findings indicate that the inhibition of melanogenesis by artemisinic acid occurs through reduced expression of the HMG CoA reductase gene, which is mediated by C/EBP α inhibition and suggest that artemisinic acid may be useful as a hyperpigmentation inhibitor. 23335450 TGF-β1 Conjugated to Gold Nanoparticles Results in Protein Conformational Changes and Attenuates the Biological Function. Gold nanoparticles (AuNPs) are widely used as carriers or therapeutic agents due to their great biocompatibility and unique physical properties. Transforming growth factor-beta 1 (TGF-β1), a member of the cysteine-knot structural superfamily, plays a pivotal role in many diseases and is known as an immunosuppressive agent that attenuates immune response resulting in tumor growth. The results reported herein reflect strong interactions between TGF-β1 and the surface of AuNPs when incubated with serum-containing medium, and demonstrate a time- and dose-dependent pattern. Compared with other serum proteins that can also bind to the AuNP surface, AuNP-TGFβ1 conjugate is a thermodynamically favored compound. Epithelial cells undergo epithelial-mesenchymal transition (EMT) upon treatment with TGF-β1; however, treatment with AuNPs reverses this effect, as detected by cell morphology and expression levels of EMT markers. TGF-β1 is found to bind to AuNPs through S-Au bonds by X-ray photoelectron spectroscopy. Fourier transform infrared spectroscopy is employed to analyze the conformational changes of TGF-β1 on the surface of AuNPs. The results indicate that TGF-β1 undergoes significant conformational changes at both secondary and tertiary structural levels after conjugation to the AuNP surface, which results in the deactivation of TGF-β1 protein. An in vivo experiment also shows that addition of AuNPs attenuates the growth of TGF-β1-secreting murine bladder tumor 2 cells in syngeneic C3H/HeN mice, but not in immunocompromised NOD-SCID mice, and this is associated with an increase in the number of tumor-infiltrating CD4(+) and CD8(+) T lymphocytes and a decrease in the number of intrasplenic Foxp3(+) lymphocytes. The findings demonstrate that AuNPs may be a promising agent for modulating tumor immunity through inhibiting immunosuppressive TGF-β1 signaling. 23395652 Structural analogs of huperzine A improve survival in guinea pigs exposed to soman. Chemical warfare nerve agents such as soman exert their toxic effects through an irreversible inhibition of acetylcholinesterase (AChE) and subsequently glutamatergic function, leading to uncontrolled seizures. The natural alkaloid (-)-huperzine A is a potent inhibitor of AChE and has been demonstrated to exert neuroprotection at an appropriate dose. It is hypothesized that analogs of both (+)- and (-)-huperzine A with an improved ability to interact with NMDA receptors together with reduced AChE inhibition will exhibit more effective neuroprotection against nerve agents. In this manuscript, the tested huperzine A analogs 2 and 3 were demonstrated to improve survival of guinea pigs exposed to soman at either 1.2 or 2×LD(50). 23585358 Bottom-up Synthesis of Nanoscale Conjugation-Interrupted Frameworks and Their Electrical Properties. Soluble covalent organic nanoframeworks up to generation 2.5 (G2.5) are synthesized with self-similar H-shaped conformations by using a bottom-up approach including iterative C-H bond functionalization. The electrical characteristics of nanoscale thin-film semiconductors of the conjugation-interrupted frameworks can be tuned by post-modification with diazonium salt. 23224775 DFT and TDDFT study on the electronic structure and photoelectrochemical properties of dyes derived from cochineal and lac insects as photosensitizer for dye-sensitized solar cells. Essential parameters related to the photoelectrochemical properties, such as ground state geometries, electronic structures, oxidation potential and electron driving force, of cochineal insect dyes were investigated by DFT and TDDFT at the B3LYP/6-31+G(d,p) level of the theory. The results show that the major charge flow dynamic for all dyes is the HOMO→LUMO transition. The bi-coordinated binding mode, in which the dye uses one carboxyl- and hydroxyl oxygen bound to Ti(IV), is found for all dye-TiO(2) systems. Additionally, the doubly bi-coordinated binding mode in which the dye used both carboxyl groups bound to two Ti(IV) is also possible due to high energy distribution occupied at anchoring groups. This study highlights that most of these insect dyes can be good photosensitizers in dye-sensitized solar cells based on their strong binding to the TiO(2) surface, good computed excited state oxidation potential and thermodynamically favored electron driving force. 23225075 Metal concentrations in cerebrospinal fluid and blood plasma from patients with amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons. The cause of this degeneration is unknown, and different causal hypotheses include genetic, viral, traumatic and environmental mechanisms. In this study, we have analyzed metal concentrations in cerebrospinal fluid (CSF) and blood plasma in a well-defined cohort (n = 17) of ALS patients diagnosed with quantitative electromyography. Metal analyses were performed with high-resolution inductively coupled plasma mass spectrometry. Statistically significant higher concentrations of manganese, aluminium, cadmium, cobalt, copper, zinc, lead, vanadium and uranium were found in ALS CSF compared to control CSF. We also report higher concentrations of these metals in ALS CSF than in ALS blood plasma, which indicate mechanisms of accumulation, e.g. inward directed transport. A pattern of multiple toxic metals is seen in ALS CSF. The results support the hypothesis that metals with neurotoxic effects are involved in the pathogenesis of ALS. 23632081 Identification of an Allosteric Modulator of Serotonin Transporter with Novel Mechanism of Action. Serotonin transporters (SERT) play an essential role in the termination and regulation of serotonin signaling in the brain. SERT is also the target of antidepressants and psychostimulants. Molecules with novel activities and modes of interaction with regard to SERT function are of great scientific and clinical interest. We explored structural regions outside the putative serotonin translocation pathway to identify potential binding sites for allosteric transporter modulators (ATMs). Mutational studies revealed a pocket of amino acids outside the orthosteric substrate binding sites located in the interface between extracellular loops 1 and 3 that when mutated affect transporter function. Using the structure of the bacterial transporter homologue leucine transporter as a template, we developed a structural model of SERT. We performed molecular dynamics simulations to further characterize the allosteric pocket that was identified by site-directed mutagenesis studies and employed this pocket in a virtual screen for small-molecule modulators of SERT function. In functional transport assays, we found that one of the identified molecules, ATM7, increased the reuptake of serotonin, possibly by facilitating the interaction of serotonin with transport-ready conformations of SERT when concentrations of serotonin were low and rate limiting. In addition, ATM7 potentiates 3,4-methylenedioxy-N-methylamphetamine (MDMA, "Ecstasy")-induced reversed transport by SERT. Taking advantage of a conformationally sensitive residue in transmembrane domain 6, we demonstrate that ATM7 mechanistically stabilizes an outward-facing conformation of SERT. Taken together these observations demonstrate that ATM7 acts through a novel mechanism that involves allosteric modulation of SERT function. 23628829 Improved group contribution parameter set for the application of solubility parameters to melt extrusion. Hot-melt extrusion is gaining importance for the production of amorphous solid solutions; in parallel, predictive tools for estimating drug solubility in polymers are increasingly demanded. The Hansen solubility parameter (SP) approach is well acknowledged for its predictive power of the miscibility of liquids as well as the solubility of some amorphous solids in liquid solvents. By solely using the molecular structure, group contribution (GC) methods allow the calculation of Hansen SPs. The GC parameter sets available were derived from liquids and polymers which conflicts with the object of prediction, the solubility of solid drugs. The present study takes a step from the liquid based SPs toward their application to solid solutes. On the basis of published experimental Hansen SPs of solid drugs and excipients only, a new GC parameter set was developed. In comparison with established parameter sets by van Krevelen/Hoftyzer, Beerbower/Hansen, Breitkreutz and Stefanis/Panayiotou, the new GC parameter set provides the highest overall predictive power for solubility experiments (correlation coefficient r=-0.87 to -0.91) as well as for literature data on melt extrudates and casted films (r=-0.78 to -0.96). 23579044 Effects of chronic methylphenidate on cocaine self-administration under a progressive-ratio schedule of reinforcement in rhesus monkeys. It has been hypothesized that drugs that serve as substrates for dopamine (DA) and norepinephrine (NE) transporters may be more suitable medications for cocaine dependence than drugs that inhibit DA and NE uptake by binding to transporters. Previous studies have shown that the DA/NE releaser d-amphetamine can decrease cocaine self-administration in preclinical and clinical studies. The present study examined the effects of methylphenidate (MPD), a DA uptake inhibitor, for its ability to decrease cocaine self-administration under conditions designed to reflect clinically relevant regimens of cocaine exposure and pharmacotherapy. Each morning, rhesus monkeys pressed a lever to receive food pellets under a fixed-ratio 50 schedule of reinforcement; cocaine was self-administered under a progressiveratio schedule of reinforcement in the evening. After cocaine (0.003-0.56 mg/kg per injection, i.v.) dose-response curves were determined, self-administration sessions were suspended and MPD (0.003-0.0056 mg/kg per hr, i.v. or 1.0-9.0 mg/kg p.o., b.i.d.) was administered for several weeks. A cocaine self-administration session was conducted every 7 days. When a MPD dose was reached that either persistently decreased cocaine self-administration or produced disruptive effects, the cocaine dose-effect curve was re-determined. In most cases, MPD treatment either produced behaviorally disruptive effects or increased cocaine selfadministration; it took several weeks for these effects to dissipate. These data are consistent with the largely negative results of clinical trials with MPD. In contrast to the positive effects with the monoamine releaser d-amphetamine under identical conditions, these results do not support use of monoamine uptake inhibitors like MPD as a medication for cocaine dependence. 23233454 Determining and reporting purity of organic molecules: why qNMR. Although NMR has been routinely used to determine/estimate relative number of protons for structure elucidation, it has been rarely used to determine and report the purity of organic compounds. Through this paper, we want to emphasize on routine use of quantitative NMR (qNMR) for this purpose. The results of qNMR can be routinely considered as documentation of purity much like other established methods (HPLC, elemental analysis and differential scanning calorimetry). qNMR is a fast, easy, accurate and non-destructive alternate to speed up the whole analytical process and serves the purpose of both identification and purity determination of compounds using single technique. 23588682 Oromucosal delivery of venlafaxine by linseed mucilage based gel: in vitro and in vivo evaluation in rabbits. Linseed is the crop that is used as a foodstuff in European and Asian countries. The objective of the present work was to extract mucilage from linseed, utilize it as mucoadhesive gelling agent along with synthetic polymers and administration of venlafaxine by buccal route in the gel form. Buccal administration of venlafaxine will avoid first pass metabolism, which will increase the bioavailability of the drug. Linseed mucilage based buccal mucoadhesive gel preparations in combination with chitosan, carbopol 934P, carboxy methylcellulose and polyvinyl pyrrolidone were formulated and the viscosity, gel strength, percentage mucoadhesion and in vitro diffusion of the formulation was evaluated. Formulation (F2) was subjected to in vivo analysis in rabbits. Formulation F2, which contained linseed mucilage (2 %) and chitosan (0.5 %), showed the highest percentage of mucoadhesion, gel strength and sustained drug diffusion. The bioavailability by the oral route and buccal route were compared with that of the intravenous route. The bioavailability of venlafaxine in the formulation F2 was 63.08 ± 1.28 % by buccal route, which was higher than by the oral route (39.21 ± 6.18 %). Based on these results, the combination of linseed mucilage and chitosan can be used to form a buccal mucoadhesive gel and increase the bioavailability of venlafaxine. 23442025 On the generation of the hydrated electron during the sonolysis of aqueous solutions. The formation of the hydrated electron through the secondary reaction, H + OH(–) → H(2)O + e(aq), has been examined in the sonolysis of argon-saturated aqueous solutions at an ultrasound frequency of 355 kHz. The detection of the hydrated electron was achieved by measuring its reaction with the one-electron acceptors Fe(CN)(6)(3–) and methyl viologen. The results obtained indicate that hydrated electrons are produced predominately at the bubble/aqueous solution interface at comparatively high local concentrations, estimated to be >1.5 × 10(–3) M. The half life of the hydrated electron under such conditions is estimated to be <60 ns. 23024176 In vitro perturbations of targets in cancer hallmark processes predict rodent chemical carcinogenesis. Thousands of untested chemicals in the environment require efficient characterization of carcinogenic potential in humans. A proposed solution is rapid testing of chemicals using in vitro high-throughput screening (HTS) assays for targets in pathways linked to disease processes to build models for priority setting and further testing. We describe a model for predicting rodent carcinogenicity based on HTS data from 292 chemicals tested in 672 assays mapping to 455 genes. All data come from the EPA ToxCast project. The model was trained on a subset of 232 chemicals with in vivo rodent carcinogenicity data in the Toxicity Reference Database (ToxRefDB). Individual HTS assays strongly associated with rodent cancers in ToxRefDB were linked to genes, pathways, and hallmark processes documented to be involved in tumor biology and cancer progression. Rodent liver cancer endpoints were linked to well-documented pathways such as peroxisome proliferator-activated receptor signaling and TP53 and novel targets such as PDE5A and PLAUR. Cancer hallmark genes associated with rodent thyroid tumors were found to be linked to human thyroid tumors and autoimmune thyroid disease. A model was developed in which these genes/pathways function as hypothetical enhancers or promoters of rat thyroid tumors, acting secondary to the key initiating event of thyroid hormone disruption. A simple scoring function was generated to identify chemicals with significant in vitro evidence that was predictive of in vivo carcinogenicity in different rat tissues and organs. This scoring function was applied to an external test set of 33 compounds with carcinogenicity classifications from the EPA's Office of Pesticide Programs and successfully (p = 0.024) differentiated between chemicals classified as "possible"/"probable"/"likely" carcinogens and those designated as "not likely" or with "evidence of noncarcinogenicity." This model represents a chemical carcinogenicity prioritization tool supporting targeted testing and functional validation of cancer pathways. 23274353 Changes in physiological responses of an Antarctic fish, the emerald rock cod (Trematomus bernacchii), following exposure to polybrominated diphenyl ethers (PBDEs). Although polybrominated diphenyl ethers (PBDEs) have the ability to undergo long-range atmospheric transport to remote ecosystems like Antarctica, a recent study found evidence for a local source within the Antarctic. PBDEs from sewage treatment outfalls of McMurdo Station and Scott Base on Ross Island have been attributed to the high concentrations measured in emerald rock cod (Trematomus bernacchii). The potential impact of PBDEs on Antarctic fish physiology is unknown and therefore, the aim of this study was to obtain a greater understanding of physiological responses of emerald rock cod for assessing changes in ecosystem quality. A PBDE mixture (ΣPBDE 8 congeners) was administered fortnightly over 42 days and physiological changes were observed throughout this period and for a further 14 days thereafter. Changes in liver composition, molecular level changes and enzyme activities of selected detoxification-mediated and antioxidant defence markers were measured. Changes in total lipid, lipid peroxide and protein carbonyl concentrations in emerald rock cod liver were consistent with increases in nucleus surface area in the PBDE-treated groups, suggesting alterations in cellular function. Changes in the activities of selected antioxidant enzymes indirectly indicated oxidative stress, possibly resulting in the changes in liver composition. Additionally, glutathione-S-transferase (GST) activity reached its peak faster than that of ethoxyresorufin-O-deethylase (EROD), suggesting that during the early response to PBDE exposures there could be a greater involvement of GST-mediated detoxification. Thus, for at least the species examined here, protein carbonyl and lipid peroxides were useful and informative biomarkers for cellular level responses following PBDE-related exposure. Furthermore, our findings suggest that emerald rock cod exposed to PBDEs develop oxidative stress - a condition with potential consequences for fish growth, health and reproduction. 23412396 Repeated Low Dose Administration of the Monoacylglycerol Lipase Inhibitor JZL184 Retains CB1 Receptor Mediated Antinociceptive and Gastroprotective Effects. The monoacylglycerol lipase (MAGL) inhibitor JZL184 produces antinociceptive and anti-inflammatory effects. However, repeated administration of high dose JZL184 (40 mg/kg) causes dependence, antinociceptive tolerance, cross-tolerance to the pharmacological effects of cannabinoid receptor agonists, and CB(1) receptor downregulation and desensitization. This functional CB(1) receptor tolerance poses a hurdle in the development of MAGL inhibitors for therapeutic use. Consequently, the present study tested whether repeated administration of low dose JZL184 maintains its antinociceptive actions in the chronic constrictive injury (CCI) of the sciatic nerve neuropathic pain model and protective effects in a model of NSAlD-induced gastric hemorrhages. Mice given daily injections of high dose JZL184 (≥16 mg/kg) for six days displayed decreased CB(1) receptor density and function in brain, as assessed in [(3)H]SR141716A binding and CP55,940-stimulated [(35)S]GTPγS binding assays, respectively. In contrast, normal CB(1) receptor expression and function were maintained following repeated administration of low dose JZL184 (≤8 mg/kg). Likewise, the antinociceptive and gastroprotective effects of high dose JZL184 underwent tolerance following repeated administration, but these effects were maintained following repeated low dose JZL184 treatment. Consistent with these observations, repeated high dose JZL184, but not repeated low dose JZL184, elicited cross-tolerance to the common pharmacological effects of Δ(9)-tetrahydrocannabinol (THC). This same pattern of effects was found in a rimonabant-precipitated withdrawal model of cannabinoid dependence. Taken together, these results indicate that prolonged, partial MAGL inhibition maintains potentially beneficial antinociceptive and anti-inflammatory effects, without producing functional CB(1) receptor tachyphylaxsis/tolerance or cannabinoid dependence. 22906573 Comparison of two in vitro systems to assess cellular effects of nanoparticles-containing aerosols. Inhalation treatment with nanoparticle containing aerosols appears a promising new therapeutic option but new formulations have to be assessed for efficacy and toxicity. We evaluated the utility of a VITROCELL®6 PT-CF+PARI LC SPRINT® Baby Nebulizer (PARI BOY) system compared with a conventional MicroSprayer. A549 cells were cultured in the air-liquid interface, exposed to nanoparticle aerosols and characterized by measurement of transepithelial electrical resistance and staining for tight junction proteins. Deposition and distribution rates of polystyrene particles and of carbon nanotubes on the cells were assessed. In addition, cytotoxicity of aerosols containing polystyrene particles was compared with cytotoxicity of polystyrene particles in suspension tested in submersed cultures. Exposure by itself in both exposure systems did not damage the cells. Deposition rates of aerosolized polystyrene particles were about 700 times and that of carbon nanotubes about 4 times higher in the MicroSprayer than in the VITROCELL®6 PT-CF system. Cytotoxicity of amine-functionalized polystyrene nanoparticles was significantly higher when applied as an aerosol on cell cultured in air-liquid interface culture compared with nanoparticle suspensions tested in submersed culture. The higher cytotoxicity of aerosolized nanoparticles underscores the importance of relevant exposure systems. 23495911 Chromium supplementation in overweight and obesity: a systematic review and meta-analysis of randomized clinical trials. The increased prevalence of obesity has made the use of dietary supplements as weight reducing agents highly popular, but their efficacy has not been proven. One such supplement is chromium. The purpose of this review was to evaluate the evidence for or against the efficacy of chromium supplementation in overweight and obese individuals. Electronic searches were conducted in Medline, Embase, Amed and The Cochrane Library. The bibliographies of located articles were also searched. No age, gender or language restrictions were imposed. The reporting quality of identified randomized clinical trials (RCTs) was assessed using a methodological checklist adapted from the Consolidated Standard of Reporting Trials Statement and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirty-nine trials were identified and 20 were included. There were variations in reporting quality of included studies. A meta-analysis of 11 studies showed a statistically significant difference in weight loss favouring chromium over placebo (mean difference (MD): -0.50 kg; 95% confidence interval (CI): -0.97, -0.03). There was a high statistical heterogeneity. Adverse events included watery stools, vertigo, headaches and urticaria. The evidence from available RCTs shows that chromium supplementation generates statistically significant reductions in body weight. The magnitude of the effect is small, and the clinical relevance is uncertain. Future trials should last at least 16 weeks and greater uniformity in the measuring and assessment tools for body composition is recommended. 23536582 Fasting Plasma Glucose at 24-28 Weeks to Screen for Gestational Diabetes Mellitus: New evidence from China. OBJECTIVETo evaluate the usefulness of a fasting plasma glucose (FPG) at 24-28 weeks' gestation to screen for gestational diabetes mellitus (GDM).RESEARCH DESIGN AND METHODSThe medical records and results of a 75-g 2-h oral glucose tolerance test (OGTT) of 24,854 pregnant women without known pre-GDM attending prenatal clinics in 15 hospitals in China were examined.RESULTSFPG cutoff value of 5.1 mmol/L identified 3,149 (12.1%) pregnant women with GDM. FPG cutoff value of 4.4 mmol/L ruled out GDM in 15,369 (38.2%) women. With use of this cutoff point, 12.2% of patients with mild GDM will be missed. The positive predictive value is 0.322, and the negative predictive value is 0.928.CONCLUSIONSFPG at 24-28 weeks' gestation could be used as a screening test to identify GDM patients in low-resource regions. Women with an FPG between ≥4.4 and ≤5.0 mmol/L would require a 75-g OGTT to diagnose GDM. This would help to avoid approximately one-half (50.3%) of the formal 75-g OGTTs in China. 23353741 Synthesis and biological evaluation of some novel resveratrol amide derivatives as potential anti-tumor agents. Three series of novel resveratrol amide derivatives (1a-q, 2a-h, 3a-l) were synthesized and evaluated for their biological activities. All compounds were characterized by (1)H NMR, (13)C NMR, MS and elemental analysis. Furthermore, compound 3e was also characterized by X-ray crystallography. All the compounds were evaluated for their anti-tumor activity against MCF-7, A549 and B16-F10 tumor cell lines as well as cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) inhibitory activity of murine macrophage RAW 264.7 cell line. Among them, compounds 1c, 1g and 3e displayed the most potent COX-2 inhibitory activity with the IC50 values of 1.02, 1.27 and 1.98 μM, respectively. Molecular docking studies were performed to position compounds 1c and 3e into the active site of COX-2 to determine the probable binding modes. 23373772 Catalytic hydrotrifluoromethylation of unactivated alkenes. A visible-light-mediated hydrotrifluoromethylation of unactivated alkenes that uses the Umemoto reagent as the CF(3) source and MeOH as the reductant is disclosed. This effective transformation operates at room temperature in the presence of 5 mol % Ru(bpy)(3)Cl(2); the process is characterized by its operational simplicity and functional group tolerance. 23281636 Paeoniflorin acts as a liver X receptor agonist. Paeoniflorin is one of the active ingredients of Paeonia lactiflora Pall., a novel traditional herbal medicine exerting pharmacological effects including antihyperlipidemic, neuroprotective, and anti-hepatofibrosis effects. Liver X receptor (LXR) acts as a ligand-activated transcription factor to exhibit antihyperlipidemic and neuroprotective effects. In this study, the activity of paeoniflorin against LXR was evaluated by the mammalian one-hybrid and transient transfection reporter assays. The results showed that paeoniflorin transactivated GAL4, rat cholesterol 7 α-hydroxylase, phospholipid transfer protein, and ATP-binding cassette A1 gene promoters in dose-dependent manner. Furthermore, the docking study demonstrated that paeoniflorin resided in the LXR ligand-binding pocket in the similar manner as GSK 3987, a novel LXR agonist. These results indicated that paeoniflorin might exert pharmacological effects through LXR pathway. 23221006 Role of organic cation/carnitine transporter 1 in uptake of phenformin and inhibitory effect on complex I respiration in mitochondria. Phenformin causes lactic acidosis in clinical situations due to inhibition of mitochondrial respiratory chain complex I. It is reportedly taken up by hepatocytes and exhibits mitochondrial toxicity in the liver. In this study, uptake of phenformin and [(14)C]tetraethylammonium (TEA) and complex I inhibition by phenformin were examined in isolated liver and heart mitochondria. Uptake of phenformin into isolated rat liver mitochondria was higher than that into heart mitochondria. It was inhibited by several cat ionic compounds, which suggests the involvement of multispecific transport system(s). Similar characteristics were also observed for uptake of TEA; however, uptake of phenformin into mitochondria of organic cation/carnitine transporter 1 (OCTN1) knockout mice was lower than that in wild-type mice, whereas uptake of TEA was comparable between the two strains, suggesting the involvement of distinct transport mechanisms for these two cations in mitochondria. Inhibition by phenformin of oxygen consumption via complex I respiration in isolated rat liver mitochondria was greater than that in heart mitochondria, whereas inhibitory effect of phenformin on complex I respiration was similar in inside-out structured submitochondrial particles prepared from rat livers and hearts. Lactic acidosis provoked by iv infusion of phenformin was weaker in octn1(-/-) mice than that in wild-type mice. These observations suggest that uptake of phenformin into liver mitochondria is at least partly mediated by OCTN1 and functionally relevant to its inhibition potential of complex I respiration. This study was, thus, the first to demonstrate OCTN1-mediated mitochondrial transport and toxicity of biguanide in vivo in rodents. 23625887 5'-Trityl-Substituted Thymidine Derivatives as a Novel Class of Antileishmanial Agents: Leishmania infantum EndoG as a Potential Target. Two series of 5'-triphenylmethyl (trityl)-substituted thymidine derivatives were synthesized and tested against Leishmania infantum axenic promastigotes and amastigotes. Several of these compounds show significant antileishmanial activity, with IC50 values in the low micromolar range. Among these, 3'-O-(isoleucylisoleucyl)-5'-O-(3,3,3-triphenylpropanoyl)thymidine displays particularly good activity against intracellular amastigotes. Assays performed to characterize the nature of parasite cell death in the presence of the tritylthymidines indicated significant alterations in mitochondrial transmembrane potential, an increase in superoxide concentrations, and also significant decreases in DNA degradation during the cell death process. Results point to the mitochondrial nuclease LiEndoG as a target for the action of this family of compounds. 23643739 Glycerol and urea can be used to increase skin permeability in reduced hydration conditions. The natural moisturizing factor (NMF) is a group of hygroscopic molecules that is naturally present in skin and protects from severe drying. Glycerol and urea are two examples of NMF components that are also used in skin care applications. In the present study, we investigate the influence of glycerol and urea on the permeability of a model drug (metronidazole, Mz) across excised pig skin membranes at different hydrating conditions. The degree of skin hydration is regulated by the gradient in water activity across the membrane, which in turn depends on the water activity of the formulation in contact with the skin membrane. Here, we determine the water activity of all formulations employed using an isothermal calorimetric method. Thus, the gradient in water activity is controlled by a novel experimental set-up with well-defined boundary conditions on both sides of the skin membrane. The results demonstrate that glycerol and urea can retain high steady state flux of Mz across skin membranes at dehydrating conditions, which otherwise would decrease the permeability due to dehydration. X-ray diffraction measurements are performed to give insight into the effects of glycerol and urea on SC molecular organization. The novel steady state flux results can be related to the observation that water, glycerol, and urea all affect the structural features of the SC molecular components in a similar manner. 22765159 Bioactive alkaloids produced by Pseudomonas brassicacearum subsp. Neoaurantiaca, an endophytic bacterium from Salvia miltiorrhiza. Eleven compounds were isolated from the culture of an endophytic bacterium Pseudomonas brassicacearum subsp. Neoaurantiaca in Salvia miltiorrhiza Bunge. Their structures were elucidated by spectroscopic methods as cyclo-(Gly-L-Ala) (1), cyclo-(L-Ala-L-Ala) (2), cyclo-(L-Pro-Gly) (3), cyclo-(L-Pro-L-Ser) (4), cyclo-(L-Ala-trans-4-hydroxy-L-Pro) (5), cyclo-(L-Val-L-Pro) (6), cyclo-(Gly-L-Tyr) (7), cyclo-(L-Ala-L-Tyr) (8), cyclo-(L-Tyr-trans-4-hydroxy-L-Pro) (9), 3-methylhydantoin (10) and 2-piperidinone (11). All these compounds were isolated from this bacterium for the first time. The brine shrimp lethality, antifungal and antibacterial activities of these compounds were evaluated. The results indicated that some cyclodipeptides may play an important role in plant-bacteria interactions. 23444389 Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides. Panax ginseng is one of the most popular herbal remedies. Ginsenosides, major bioactive constituents in P. ginseng, have shown good antidiabetic action, but the precise mechanism was not fully understood. Glucagon-like peptide-1 (GLP1) is considered to be an important incretin that can regulate glucose homeostasis in the gastrointestinal tract after meals. The aim of this study was to investigate whether ginseng total saponins (GTS) exerts its antidiabetic effects via modulating GLP1 release. Ginsenoside Rb1 (Rb1), the most abundant constituent in GTS, was selected to further explore the underlying mechanisms in cultured NCI-H716 cells. Diabetic rats were developed by a combination of high-fat diet and low-dose streptozotocin injection. The diabetic rats orally received GTS (150 or 300 mg/kg) daily for 4 weeks. It was found that GTS treatment significantly ameliorated hyperglycemia and dyslipidemia, accompanied by a significant increase in glucose-induced GLP1 secretion and upregulation of proglucagon gene expression. Data from NCI-H716 cells showed that both GTS and Rb1 promoted GLP1 secretion. It was observed that Rb1 increased the ratio of intracellular ATP to ADP concentration and intracellular Ca(2)(+) concentration. The metabolic inhibitor azide (3 mM), the KATP channel opener diazoxide (340 μM), and the Ca(2)(+) channel blocker nifedipine (20 μM) significantly reversed Rb1-mediated GLP1 secretion. All these results drew a conclusion that ginsenosides stimulated GLP1 secretion both in vivo and in vitro. The antidiabetic effects of ginsenosides may be a result of enhanced GLP1 secretion. 23223445 The chemical synthesis of DNA/RNA: our gift to science. It is a great privilege to contribute to the Reflections essays. In my particular case, this essay has allowed me to weave some of my major scientific contributions into a tapestry held together by what I have learned from three colleagues (Robert Letsinger, Gobind Khorana, and George Rathmann) who molded my career at every important junction. To these individuals, I remain eternally grateful, as they always led by example and showed many of us how to break new ground in both science and biotechnology. Relative to my scientific career, I have focused primarily on two related areas. The first is methodologies we developed for chemically synthesizing DNA and RNA. Synthetic DNA and RNA continue to be an essential research tool for biologists, biochemists, and molecular biologists. The second is developing new approaches for solving important biological problems using synthetic DNA, RNA, and their analogs. 23624383 Venom toxins in the exploration of molecular, physiological and pathophysiological functions of Acid-Sensing Ion Channels. Acid-sensing ion channels (ASICs) are voltage-independent proton-gated cation channels that are largely expressed in the nervous system as well as in some non-neuronal tissues. In rodents, six different isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) can associate into homo- or hetero-trimers to form a functional channel. Specific polypeptide toxins targeting ASIC channels have been isolated from the venoms of spider (PcTx1), sea anemone (APETx2) and snakes (MitTx and mambalgins). They exhibit different and sometimes partially overlapping pharmacological profiles and are usually blockers of ASIC channels, except for MitTx which is a potent activator. This review focuses on the use of these toxins to explore the structure-function relationships, the physiological and the pathophysiological roles of ASIC channels, illustrating at the same time the therapeutic potential of some of these natural compounds. 23353743 Design and synthesis of novel 1,2,3-triazole-dithiocarbamate hybrids as potential anticancer agents. A series of novel 1,2,3-triazole-dithiocarbamate hybrids were designed, synthesized and evaluated for anticancer activity against four selected human tumor cell lines (MGC-803, MCF-7, PC-3, EC-109). Majority of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 3a and 3c showed excellent broad spectrum anticancer activity with IC50 values ranging from 0.73 to 11.61 μM and 0.49-12.45 μM, respectively. Particularly, compound 3a was more potent than 5-fluorouracil against all tested human cancer cell lines. Flow cytometry analysis demonstrated that treatment of MGC-803 with 3c led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death after 12 h. 23561152 Probing the binding between norbixin and dairy proteins by spectroscopy methods. Annatto (norbixin) has been used to color cheeses for centuries, but there is very little knowledge about interactions between the pigment and dairy proteins. In this study, binding of norbixin with whey protein isolate (WPI), sodium caseinate (NaCN), and 6 individual dairy proteins was investigated by using fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD) and differential scanning calorimetry (DSC). Norbixin was observed to effectively quench the fluorescence of WPI and NaCN by forming complexes. The binding affinity between NaCN and norbixin was higher than that of WPI-norbixin. For individual proteins, bovine serum albumin had higher binding affinity with norbixin than β-lactoglobulin and α-lactalbumin, while κ-casein bound with norbixin better than α- and β-caseins. Binding changed the conformation of WPI and NaCN, but the extent and trend varied for individual proteins. 23256621 Universal concept for the implementation of a single cleavable unit at tunable position in functional poly(ethylene glycol)s. Poly(ethylene glycol) (PEG) with acid-sensitive moieties gained attention particularly for various biomedical applications, such as the covalent attachment of PEG (PEGylation) to protein therapeutics, the synthesis of stealth liposomes, and polymeric carriers for low-molecular-weight drugs. Cleavable PEGs are favored over their inert analogues because of superior pharmacodynamic and/or pharmacokinetic properties of their formulations. However, synthetic routes to acetal-containing PEGs published up to date either require enormous efforts or result in ill-defined materials with a lack of control over the molecular weight. Herein, we describe a novel methodology to implement a single acetaldehyde acetal in well-defined (hetero)functional poly(ethylene glycol)s with total control over its position. To underline its general applicability, a diverse set of initiators for the anionic polymerization of ethylene oxide (cholesterol, dibenzylamino ethanol, and poly(ethylene glycol) monomethyl ether (mPEG)) was modified and used to synthesize the analogous labile PEGs. The polyether bearing the cleavable lipid had a degree of polymerization of 46, was amphiphilic and exhibited a critical micelle concentration of 4.20 mg·L(-1). From dibenzylamino ethanol, three heterofunctional PEGs with different molecular weights and labile amino termini were generated. The transformation of the amino functionality into the corresponding squaric acid ester amide demonstrated the accessibility of the cleavable functional group and activated the PEG for protein PEGylation, which was exemplarily shown by the attachment to bovine serum albumin (BSA). Furthermore, turning mPEG into a macroinitiator with a cleavable hydroxyl group granted access to a well-defined poly(ethylene glycol) derivative bearing a single cleavable moiety within its backbone. All the acetal-containing PEGs and PEG/protein conjugates were proven to degrade upon acidic treatment. 23180652 Stability of pharmaceuticals and other polar organic compounds stored on polar organic chemical integrative samplers and solid-phase extraction cartridges. The stability of 24 chemicals, including pharmaceuticals and personal care products, and some agrochemicals on extraction media was evaluated by preloading them onto Oasis hydrophilic lipophilic balanced solid-phase extraction (SPE) cartridges and polar organic chemical integrative samplers (POCIS) followed by storage at -20°C over time. After 20 months, the average loss was 11% on POCIS, with only 2,4-dichlorophenoxyacetic acid, atrazine, chlorpyrifos, and gemfibrozil showing a statistically significant decline compared with initial concentrations. Losses on SPE cartridges were below 19%, with an average loss of 9%. In addition to laboratory spiked samples, multiple POCIS deployed in wastewater-impacted surface waters and SPE extracts of these waters were stored in their original coextracted matrix for nearly two years with minimal observed losses. Errors from typical sampling, handling, and concentration estimates from POCIS sampling rates were typically ± 15 to 30% relative standard deviation, so observed storage losses are minimal for most POCIS applications. While losses during storage on SPE cartridges for 20 months were small but statistically significant for many compounds, addition of labeled internal standards prior to freezing should correct for such losses. Thus, storage of processed water samples for analysis of polar organic pollutants is viable for archival purposes or studies for which samples cannot be analyzed in the short term. 23030706 Use of precision-cut renal cortical slices in nephrotoxicity studies. 1.Unlike cell lines and primary cells in culture, precision-cut tissue slices remain metabolically differentiated for at least 24-48 h and allow to study the effect of xenobiotics during short-term and long-term incubations. 2.In this article, we illustrate the use of such an experimental model to study the nephrotoxic effects of (i) chloroacetaldehyde, a metabolite of the anticancer drug ifosfamide, (ii) of cobalt chloride, a potential leakage product of the cobalt-containing nanoparticles, and (iii) of valproate, a widely used antiepileptic drug. 3.Since all the latter test compounds, like many toxic compounds, negatively interact with cellular metabolic pathways, we also illustrate our biochemical toxicology approach in which we used not only enzymatic but also carbon 13 NMR measurements and mathematical modelling of metabolic pathways. 4.This original approach, which can be applied to any tissue, allows to predict the nephrotoxic effects of milligram amounts of test compounds very early during the research and development processes of drugs and chemicals. This approach, combined with the use of cells that retain their in vivo metabolic properties and, therefore, are predictive, reduces the risk, the time and cost of such processes. 23632309 Investigation of in vivo metabolic profile of Abelmoschus Manihot based on pattern recognition analysis. ETHNOPHARMACOLOGICAL RELEVANCE:: Abelmoschus manihot (L.) Medik. var. manihot is one of the most commonly used Chinese medicines and has played an important role in treating chronic glomerulonephritis and diabetic nephropathy. AIM OF THE STUDY:: Metabolites identification of traditional Chinese medicine (TCM) is a complex and time-consuming process due to the complicity of TCM and subsequent large number of detected ions. In this paper, UPLC-MS combined with pattern recognition analysis approach were used to simplify and quicken the identification of the metabolites of Abelmoschus Manihot. MATERIALS AND METHODS:: Rat urine samples were collected before (as control sample) and after Abelmoschus Manihot administration. Pattern recognition analysis method was used to differentiate components between Abelmoschus Manihot-treated group and its controlled comparison. These components could be considered as Abelmoschus Manihot-related metabolites in vivo. RESULTS:: LC-MS based metabolomics could be an advanced tool to help us find metabolites with regards to its capacity of processing large datasets, differentiating and classifying of sample groups, as well as its indiscriminative nature of biomarker and metabolite identification. Using this method, seven metabolites were identified, which are flavonoid aglycone glucuronidation, sulfatation, and methylation metabolites. CONCLUSION:: Our results showed that UPLC-MS based- pattern recognition analysis approach can be used to quickly identify Abelmoschus Manihot related metabolites in biological fluids. Furthermore, this work demonstrates the potential application of combining the UPLC-MS approach with the metabolomics approach in identifying the metabolites of TCM. 23265507 2012: no trans fatty acids in Spanish bakery products. Trans fatty acids (TFA) are strongly correlated with an increased risk of cardiovascular and other chronic diseases. Current dietary recommendations exclude bakery products from frequent consumption basically due to their traditionally high content of TFA. The aim of this work was to analyse the lipid profile of different bakery products currently commercialised in Spain and with a conventionally high fat and TFA content. Premium and store brands for each product were included in the study. No significant amounts of TFA were found in any of the analysed products, regardless the brand. TFA content ranged between 0.17 g and 0.22 g/100 g product (mean=0.19 g/100 g product). Expressed on percentage of fatty acids, the maximum value was 0.87 g/100 g fatty acids and the mean value was 0.68%. These data are significantly lower than those observed in previously published papers for these types of products, and highlighted the importance of updating food composition databases in order to accurately estimate the real and current intake of TFA. 23325492 Stability of citrate-capped silver nanoparticles in exposure media and their effects on the development of embryonic zebrafish (Danio rerio). The stability of citrate-capped silver nanoparticles (AgNPs) and the embryonic developmental toxicity were evaluated in the fish test water. Serious aggregation of AgNPs was observed in undiluted fish water (DM-100) in which high concentration of ionic salts exist. However, AgNPs were found to be stable for 7 days in DM-10, prepared by diluting the original fish water (DM-100) with deionized water to 10 %. The normal physiology of zebrafish embryos were evaluated in DM-10 to see if DM-10 can be used as a control vehicle for the embryonic fish toxicity test. As results, DM-10 without AgNPs did not induce any significant adverse effects on embryonic development of zebrafish determined by mortality, hatching, malformations and heart rate. When embryonic toxicity of AgNPs was tested in both DM-10 and in DM-100, AgNPs showed higher toxicity in DM-10 than in DM-100. This means that the big-sized aggregates of AgNPs were low toxic compared to the nano-sized AgNPs. AgNPs induced delayed hatching, decreased heart rate, pericardial edema, and embryo death. Accumulation of AgNPs in the embryo bodies was also observed. Based on this study, citrate-capped AgNPs are not aggregated in DM-10 and it can be used as a control vehicle in the toxicity test of fish embryonic development. 23473024 Nanoparticle film assemblies as platforms for electrochemical biosensing-factors affecting the amperometric signal enhancement of hydrogen peroxide. Factors affecting the enhanced amperometric signal observed at electrodes modified with polyelectrolyte-gold nanoparticle (Au-NP) composite films, which are potential interfaces for first-generation biosensors, were systematically investigated and optimized for hydrogen peroxide (H2O2) detection. Polyelectrolyte multilayer films embedded with citrate-stabilized gold nanoparticles exhibited high sensitivity toward the oxidation of H2O2. From this Au-NP film assembly, the importance of Au-NP ligand protection, film permeability, the density of Au-NPs within the film, and electronic coupling between Au-NPs (interparticle) and between the film and the electrode (interfacial) were evaluated. Using alternative Au-NPs, including those stabilized with thiols, polymers, and bulky ligands, suggests that the amperometric enhancement of H2O2 is optimized at poly-l-lysine-linked film assemblies embedded with Au-NPs possessing small, charged, and conductive (conjugated) peripheral ligands. As a potential application of these Au-NP film assemblies, an enhanced amperometric signal for H2O2 oxidation was shown for modified "needle" electrodes. The overall aim of this research is to gain a greater understanding of designing electrochemical sensing strategies that incorporate Au-NPs and target specific analytes. 23339604 Supramolecular organization and magnetic properties of mesogen-hybridized mixed-valent manganese single molecule magnets [Mn(III)8Mn(IV)4O12(L(x,y,z-CB))16(H2O)4]. Single molecule magnets (SMM) may be considered for the construction of future integrated nanodevices, provided however that some degree of ordering is imparted to these molecules (surfaces nanostructuration). Combining such nanoobjects with liquid-crystalline orderings to control their assembly and to potentially address them individually therefore appears as one promising strategy. Four mesomorphic, mixed-valent [Mn(III)(8)Mn(IV)(4)O(12)(L(x,y,z-CB))(16)(H(2)O)(4)] SMM, differing in the number of liquid-crystalline promoters, (L(x,y,z-CB)), were synthesized, and their self-organizing and magnetic properties were investigated. The influence of the peripheral modifications, and precisely how supramolecular ordering and magnetic properties may be affected by the evolution of the proto-mesogenic cyanobiphenyl-based ligands substitution pattern, was explored. Small-angle X-ray scattering studies revealed that all of the hybridized clusters self-organize into room-temperature bilayer smectic phases, mandated by the specific mesogenic functionalization and that the polymetallic cores are further organized according to a short-range pseudo-2D lattice with hexagonal and/or square symmetry. All mesomorphous hybridized dodecamanganese complexes still behave as SMM: they exhibit blocking of the magnetization at about 2.6 K as evidenced by the occurrence of frequency-dependent out-of-phase ac susceptibility signals as well as an opening of the hysteresis cycle with coercive fields varying between 0.13 and 0.6 T, depending on the surface ligands topology. Comparison of the magnetic properties within this series reveals intricate correlations between the structural features of the mesomorphous molecule magnet (i.e., symmetry of the ligands substitution patterns, molecular conformation, average intercluster distances, and respective inclination) with respect to the relative proportion of slow- and fast-relaxing species and the absolute values of the coercive fields. 23281330 Production of hybrid diesel fuel precursors from carbohydrates and petrochemicals using formic acid as a reactive solvent. We report the one-pot alkylation of mesitylene with carbohydrate-derived 5-(hydroxymethyl)furfural (HMF) as a step toward diesel-range liquids. Using FeCl(3) as a catalyst, HMF is shown to alkylate toluene, xylene, and mesitylene in high yields in CH(2)Cl(2) and MeNO(2) solvents. Efforts to extend this reaction to greener or safer solvents showed that most ether-based solvents are unsatisfactory. Acid catalysts (e.g, p-TsOH) also proved to be ineffective. Using formic acid as a reactive solvent, mesitylene could be alkylated to give mesitylmethylfurfural (MMF) starting from fructose with yields up to approximately 70 %. The reaction of fructose with formic acid in the absence of mesitylene gave rise to low yields of the formate ester of HMF, which indicates the stabilizing effect of replacing the hydroxyl substituent with mesityl. The arene also serves as a second phase into which the product is extracted. Even by using formic acid, the mesitylation of less expensive precursors such as glucose and cellulose proceeded only in modest yields (ca. 20 %). These simpler substrates were found to undergo mesitylation by using hydrogen chloride/formic acid via the intermediate chloromethylfurfural. 23245697 Ribonucleotide incorporation, proofreading and bypass by human DNA polymerase δ. In both budding and fission yeast, a large number of ribonucleotides are incorporated into DNA during replication by the major replicative polymerases (Pols α, δ and ɛ). They are subsequently removed by RNase H2-dependent repair, which if defective leads to replication stress and genome instability. To extend these studies to humans, where an RNase H2 defect results in an autoimmune disease, here we compare the ability of human and yeast Pol δ to incorporate, proofread, and bypass ribonucleotides during DNA synthesis. In reactions containing nucleotide concentrations estimated to be present in mammalian cells, human Pol δ stably incorporates one rNTP for approximately 2000 dNTPs, a ratio similar to that for yeast Pol δ. This result predicts that human Pol δ may introduce more than a million ribonucleotides into the nuclear genome per replication cycle, an amount recently reported to be present in the genome of RNase H2-defective mouse cells. Consistent with such abundant stable incorporation, we show that the 3'-exonuclease activity of yeast and human Pol δ largely fails to edit ribonucleotides during polymerization. We also show that, like yeast Pol δ, human Pol δ pauses as it bypasses ribonucleotides in DNA templates, with four consecutive ribonucleotides in a DNA template being more problematic than single ribonucleotides. In conjunction with recent studies in yeast and mice, this ribonucleotide incorporation may be relevant to impaired development and disease when RNase H2 is defective in mammals. As one tool to investigate ribonucleotide incorporation by Pol δ in human cells, we show that human Pol δ containing a Leu606Met substitution in the polymerase active site incorporates 7-fold more ribonucleotides into DNA than does wild type Pol δ. 23115324 BET bromodomain proteins mediate downstream signaling events following growth factor stimulation in human lung fibroblasts and are involved in bleomycin-induced pulmonary fibrosis. Epigenetic alterations, such as histone acetylation, regulate the signaling outcomes and phenotypic responses of fibroblasts after growth factor stimulation. The bromodomain and extra-terminal domain-containing proteins (Brd) bind to acetylated histone residues, resulting in recruitment of components of the transcriptional machinery and subsequent gene transcription. Given the central importance of fibroblasts in tissue fibrosis, this study sought to determine the role of Brd proteins in human lung fibroblasts (LFs) after growth factor stimulation and in the murine bleomycin model of lung fibrosis. Using small interfering RNA against human Brd2 and Brd4 and pharmacologic Brd inhibitors, this study found that Brd2 and Brd4 are essential in mediating the phenotypic responses of LFs downstream of multiple growth factor pathways. Growth factor stimulation of LFs causes increased histone acetylation, association of Brd4 with growth factor-responsive genes, and enhanced transcription of these genes that could be attenuated with pharmacologic Brd inhibitors. Of note, lung fibrosis induced after intratracheal bleomycin challenge in mice could be prevented by pretreatment of animals with pharmacologic inhibitors of Brd proteins. This study is the first demonstration of a role for Brd2 and Brd4 proteins in mediating the responses of LFs after growth factor stimulation and in driving the induction of lung fibrosis in mice in response to bleomycin challenge. 22872607 AKRs expression in peripheral blood lymphocytes from smokers: The role of body mass index. Aldo-keto reductases (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis. Exposure to PAHs, their metabolites, and ROS further increase AKRs isoform expression that may amplify oxidative damage. Human AKR enzymes are highly polymorphic, and allelic variants may contribute to different AKRs expression in individuals. Despite the importance of AKRs in PAHs metabolism, there are no studies that evaluate, in general human populations, the effect of PAHs on AKRs expression in peripheral blood lymphocytes (PBLs). The aim of this study was to determine the effect of tobacco smoke exposure, and AKR1A1*2 and AKR1C3*2 polymorphisms, on AKR1A1 and AKR1C1-AKR1C3 messenger RNA (mRNA) levels in PBLs from smokers. In the smoker group, there is a statistically significant positive association between AKR1A1, AKR1C1, and AKR1C3 mRNA induction and urine cotinine levels in individuals with a body mass index (BMI) less than 25. However, AKR1A1*2 and AKR1C3*2 alleles did not influence AKR1A1 and AKR1C1-AKR1C3 mRNA levels. These results suggest that AKRs induction by PAHs in smokers' PBLs is associated with BMI; therefore, the role of adipose tissue accumulation in PAHs' effects needs further investigation. 23379962 High-yield dispersions of large-diameter semiconducting single-walled carbon nanotubes with tunable narrow chirality distributions. Here, we report a thorough study on the ability of fluorene-based semiconducting polymers to disperse large-diameter (average diameter ⟨d⟩ ≈ 1.3 nm) laser vaporization (LV) single-walled carbon nanotubes (SWCNTs). We demonstrate the ability to select purely semiconducting species using poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(6,6'-{2,2'-bipyridine})] (PFO-BPy) and poly[(9,9-dihexylfluorenyl-2,7-diyl)-co-(9,10-anthracene)] (PFH-A), producing samples with narrow and bright excitonic emission relative to comparable aqueous dispersions. Rapid processing and high yields offer the ability to easily incorporate these semiconducting SWCNTs into commercially scalable applications, as demonstrated by large-area thin films prepared by ultrasonic spraying. By modifying the growth temperature of the LV synthesis, we demonstrate the ability to tune the range of diameters and chiralities within dispersions by exerting synthetic control over the composition of the starting material. This synthetic control allows us to show that PFH-A preferentially disperses near-armchair semiconducting SWCNTs over a large range of diameters (0.8 nm < d < 1.4 nm) and induces unique solvatochromic shifts for the excitonic transitions of nanotubes with particular chiral indices. 23419813 Dextran-pegylated microparticles for enhanced cellular uptake of hydrophobic drugs. Polyethylene glycol monosubstituted with a polymerizable acrylic moiety was linked to 6-carboxy free position on dextran side chains and then subjected to radical polymerization with a comonomer in order to obtain microspheres for the oral controlled release of ketoconazole, a hydrophobic model drug. Microparticles were submitted to studies on their ability to absorb and retain water. Cell uptake studies, in the presence and absence of mucus, across two different monolayers, respectively, HT29-MTX-E12 and Caco-2, were done. Cytotoxicity studies were carried out to calculate the IC50 value. The ability of microspheres to open monolayers tight junctions was tested by measuring their TEER values. Images of cell uptake were visualized by CLSM. In HT29-MTX-E12 cells, more mucoadhesion and drug internalization is seen thanks to the presence of PEG and dextran chains. 22955948 IKK-β mediates hydrogen peroxide induced cell death through p85 S6K1. The IκB kinase (IKK)/NF-κB pathway has been shown to be a major regulator in cell survival. However, the mechanisms through which IKK mediates cell death are not clear. In this study, we showed that IKK-β contributed to hydrogen peroxide (H(2)O(2))-induced cell death independent of the NF-κB pathway. Our results demonstrated that the pro-death function of IKK-β under oxidative stress was mediated by p85 S6K1 (S6 kinase 1), but not p70 S6K1 through a rapamycin-insensitive and mammalian target of rapamycin complex 1 kinase-independent mechanism. We found that IKK-β associated with p85, but not p70 S6K1, which was required for H(2)O(2)-induced activation of p85 S6K1. IKK-β and p85 S6K1 contributed to H(2)O(2)-induced phosphorylation of Mdm2 (S166) and p53 accumulation. p85 S6K1 is critical for IKK-β-mediated cell death. Thus, these findings established a novel oxidative stress-responsive pathway that involves IKK-β, p85 S6K1 and Mdm2, which is response for H(2)O(2)-induced cell death. Our results have important implications for IKK-β and p85 S6K1 as potential targets for the prevention of diseases involved in oxidative stress-induced aberrant cell death. 23288360 A popular engagement at the ends. Three recent studies converged on a specific protein-protein interface between TPP1 and telomerase as being crucial for the regulation of both telomerase recruitment and processivity in mammalian cells. An equivalent interaction appears to exist in budding yeast, making this a nearly universal means of telomerase regulation. 23602733 Evaluation of reproductive and developmental toxicities of Pu-erh black tea (Camellia sinensis var. assamica) extract in Sprague Dawley rats. ETHNOPHARMACOLOGICAL RELEVANCE: Pu-erh black tea, which is obtained by first parching crude green tea leaves and followed by secondary fermentation with microorganisms, has been believed to be beneficial beverages for health in PR China. But its potential toxicity when administered at a high dose as concentrated extract has not been completely investigated. AIM OF THE STUDY: The present study was aimed at evaluating potential reproductive and developmental toxicities of Pu-erh black tea extract (BTE) in Sprague Dawley rats. MATERIALS AND METHODS: Growing rats were given BTE by gavage at levels of 0, 200, 700 and 2500mg/kg/day as the F0 generation in reproductive toxicity study. Additionally, BTE was administered to mate female rats from gestation day 0.5 through 19.5 at the doses of 0, 200, 700 and 2500mg/kg/day to evaluate the developmental toxicity. RESULTS: In the reproductive toxicity study, only 2500mg/kg/day BTE reduced the body weight gain and altered the relative organ weights including testes, prostata and ovary both for F0 parents and F1 offspring compared to the controls. High dose of BTE (2500mg/kg/day) administration caused developmental disturbances in embryo-to-foetus period including resorbed embryos, decreased embryo size and skeletal anomalies. CONCLUSION: In conclusion, the no-observed-adverse-effect level of BTE is 700mg/kg/day both for reproductive toxicity and developmental toxicities. 23391133 Hydrolytic activities of crystalline cellulose nanofibers. Cellulose is commonly believed to be inactive to organic substances; this inertness is an essential requirement for raw materials in industrial products. Here we demonstrate the contradictory but promising properties, which are the hydrolytic activities of crystalline cellulose nanofibers for the ester, monophosphate, and even amide bonds of small organic substrates under extremely mild conditions (neutral pH, moderate temperature, and atmospheric pressure). The hydrolytic activities were significantly extended to decompose the coat proteins of model viruses, followed by a drastic decrease in their infection capabilities to the host cells. 23462193 Identification of nuclear factor-κB sites in the Slc2a4 gene promoter. Glucose transporter GLUT4 protein, codified by Slc2a4 gene plays a key role in glycemic homeostasis. Insulin resistance, as in obesity, has been associated to inflammatory state, in which decreased GLUT4 is a feature. Inflammatory NF-κB transcriptional factor has been proposed as a repressor of Slc2a4; although, the binding site(s) in Slc2a4 promoter and the direct repressor effect have never been reported yet. A motif-based sequence analysis of mouse Slc2a4 promoter revealed two putative κB sites located inside -83/-62 and -134/-113bp. Eletrophoretic mobility assay showed that p50 and p65 NF-κB subunits bind to both putative κB sites. Chromatin immunoprecipitation assay using genomic DNA from adipocytes confirmed p50- and p65-binding to Slc2a4 promoter. Moreover, transfection experiments revealed that NF-κB binds to the -134/-113bp region of the mouse Slc2a4 gene promoter, inhibiting the Slc2a4 gene transcription. The current findings demonstrate the existence of two κB sites in Slc2a4 gene promote, and that NF-κB has a direct repressor effect upon the Slc2a4 gene, providing an important link between insulin resistance and inflammation. 23600612 Chemical constituents from Solidago canadensis with hypolipidemic effects in HFD-fed hamsters. Two new compounds, 8-dehydroxymethylvisanol (1) and 9-O-[3-O-acetyl-β-d-glucopyranosyl]-4-hydroxy-cinnamic acid (4), together with two known lignans, visanol (2) and 9-aldehydevibsanol (3), were isolated from the 80% EtOH extract of Solidago canadensis. The structures of the two new compounds were elucidated on the basis of 1D, 2D NMR, and mass spectral analysis. All the lignans exhibited moderate hypolipidemic activity in high-fat diet-fed hamsters. 23331263 On the origin of thermal untwisting of DNA. In aqueous solutions, the helical twist of DNA decreases with temperature. This phenomenon was noticed and studied experimentally several decades ago, but its physical origin remains elusive. The present paper shows that the thermal untwisting can be predicted from the specific properties of the torsional elasticity of the double helix revealed in recent computational studies. The temperature coefficient of untwisting estimated using coarse-grained models fitted to all-atom MD data accounts for the experimental results nearly quantitatively. The agreement is further improved with the computed torsional rigidity scaled to remove the discrepancy from experiment. The results confirm that the torsional rigidity of DNA is strongly anharmonic. They indicate that for random DNA, its value grows with small twisting and decreases with untwisting. 23465865 Changes in hypothalamic-pituitary-adrenal stress responsiveness before and after puberty in rats. This article is part of a Special Issue "Puberty and Adolescence". Many endocrine changes are associated with pubertal and adolescent development. One such change is the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to physical and/or psychological stressors. Recent human and non-human animal studies have shown that hormonal stress reactivity increases significantly throughout puberty and adolescence. Specifically, exposure to various stressors results in greater adrenocorticotropic hormone (ACTH) and glucocorticoid responses in peripubertal compared to adult animals. This review will focus on how stress reactivity changes throughout puberty and adolescence, as well as potential mechanisms that mediate these changes in stress responsiveness. Though the implications of these pubertal shifts in stress responsiveness are not fully understood, the significant increase in stress-related mental and physical dysfunctions during this stage of development highlights the importance of studying pubertal and adolescent maturation of HPA function and its reactivity to stress. 23487486 Effects of progesterone and medroxyprogesterone on actin remodeling and neuronal spine formation. Sex steroids are important regulators of neuronal cell morphology, and this is critical for gender differences in brain function and dysfunction. Neuronal morphology is controlled by multiprotein complexes including moesin (a member of the ezrin/radixin/moesin family), focal adhesion kinase (FAK), or the Wiskott-Aldrich syndrome protein-family verprolin homologous (WAVE1) protein, controlling dynamic remodeling of the cytoskeleton and cell membrane. We investigated the actions of natural progesterone (P) and of the synthetic progestin medroxyprogesterone acetate (MPA) on actin remodeling, focal adhesion complex formation, and actin branching in rat cortical neurons. Treatment with P and, to a lesser extent, MPA, increases the number and density of dendritic spines. P increases the phosphorylation of moesin, FAK, and WAVE1, and their redistribution toward cell membrane sites where spines are formed. Signaling to moesin is achieved by PR via a Gα/Gβ-dependent signaling to the small GTPase Ras homolog gene family, member A and its related kinase, Rho-associated kinase-2. In parallel, WAVE1 recruitment is triggered by a Gαi/Gβ-dependent signaling of PR to c-Src, FAK, and Rac1 GTPase. Rac1 recruits cyclin-dependent kinase-5, which phosphorylates WAVE1. Silencing of moesin, FAK, or WAVE1 abrogates the increase in dendritic spines induced by progesterone. In all applications, MPA is found to act similar to P, albeit with a lower efficacy. In conclusion, our findings indicate that the control of actin polymerization and branching and focal adhesion complex formation via moesin, FAK, and WAVE1 is a key function of progesterone receptor in neurons, which may be relevant for the regulation of dendritic spine turnover and neuronal plasticity. 23376242 Liposomes modified with P-aminophenyl-α-d-mannopyranoside: A carrier for targeting cerebral functional regions in mice. Targeting of intracerebral functional regions has been limited by the inability to transport drugs across the blood-brain barrier (BBB) and by poor accumulation in these regions. To overcome these hurdles, liposomes modified with P-aminophenyl-α-d-mannopyranoside (MAN) were used as a fluorescent dye carrier through the BBB and used the specific distribution of liposomes (LIP) modified with MAN (MAN-LIP) to target various functional regions of the brain. An in vitro BBB model was established to evaluate the transendothelial ability of MAN-LIP, and liposomes uptake by C6 glioma cells was analyzed by flow cytometry and live cell imaging. Liposome targeting was evaluated using in vivo and ex vivo imaging. After MAN-LIP administration, the transendothelial ability and the delivery of fluorescent dye to the brain significantly increased. MAN-LIP concentrated in the cortex at 4h, shifting distribution to the cerebellum and brainstem at 12h. The fluorescence intensity in the hippocampus and pontine nuclei remained high and stable over a period of 12h. The results demonstrate that MAN-LIP is able to enhance cellular uptake in vitro and also promotes penetration through the BBB and accumulation in the brain with a distinct spatio-temporal pattern. 23551856 Effect of pioglitazone on body composition and bone density in subjects with prediabetes in the ACT NOW trial. AIMS: This study examined the effects of pioglitazone on body weight and bone mineral density (BMD) prospectively in patients with impaired glucose tolerance as pioglitazone (TZD) increases body weight and body fat in diabetic patients and increases the risk of bone fractures. METHODS: A total of 71 men and 163 women aged 49.3 (10.7) years [mean (s.d.)]; body mass index (BMI), 34.5 (5.9) kg/m(2) were recruited at five sites for measurements of body composition by dual energy X-ray absorptiometry at baseline and at conversion to diabetes or study end, if they had not converted. RESULTS: Mean follow-up was 33.6 months in the pioglitazone group and 32.1 months in the placebo group. Body weight increased 4.63 ± 0.60 (m ± s.e.) kg in the pioglitazone group compared to 0.98 ± 0.62 kg in the PIO group (p < 0.0001). Body fat rose 4.89 ± 0.42 kg in the pioglitazone group compared to 1.41 ± 0.44 kg, (p < 0.0001) in placebo-treated subjects. The increase in fat was greater in legs and trunk than in the arms. BMD was higher in all regions in men and significantly so in most. PIO decreased BMD significantly in the pelvis in men and women, decreased BMD in the thoracic spine and ribs of women and the lumbar spine and legs of men. Bone mineral content also decreased significantly in arms, legs, trunk and in the total body. CONCLUSIONS: Pioglitazone increased peripheral fat more than truncal fat and decreased BMD in several regions of the body. 23256769 Effects of formation conditions on the physicochemical properties, aggregation, and phase transformation of iron oxide nanoparticles. In this work, hematite transformation from a precursor 6-line ferrihydrite phase was investigated by systematically altering the forced hydrolysis hematite synthesis. Specifically, we used a combination of in situ and ex situ characterization techniques to examine the effects of varying the Fe(III) injection rates and cooling methods on the hematite and 6-line ferrihydrite nanoparticle size, isoelectric point, mineral phase, and aggregation. Finally, As(V) adsorption experiments were performed to determine how the two iron oxide phases existed in the reaction system. Nanoparticle synthesis thermodynamics and kinetics were found to control the extent of distinct 6-line ferrihydrite phases in the iron oxide nanoparticle solutions, as well as the particle size and isoelectric point. Conversion of 6-line ferrihydrite to hematite was greatly influenced by the degree of aggregation (determined by synthesis conditions) during drying. As(V) adsorption experiments revealed that 6-line ferrihydrite and hematite exist as a linear combination of two separate phases. These results provide unique information regarding how in situ iron oxide nanoparticle properties can direct their ex situ behavior. 23415714 Androgen/androgen receptor pathway regulates expression of the genes for cyclooxygenase-2 and amphiregulin in periovulatory granulosa cells. It is well known that the androgen/androgen receptor (AR) pathway is involved in both male and female fertility in mammals. AR knockout female mice are reported to exhibit various abnormalities in follicle development, and a subfertile phenotype. In exogenous gonadotropin-induced superovulation, serum androgen levels were robustly elevated in female mice at the periovulatory stage after human chorionic gonadotropin (hCG) treatment. At this stage, ovarian AR proteins were strongly expressed in cumulus cells. Because these results suggested that the androgen/AR pathway is involved in ovulation, we investigated the expression of ovulation-related genes in the mouse ovary treated with the nonaromatizable androgen, 5α-dihydrotestosterone (DHT). DHT treatment induced the expression of the genes for cyclooxyganase-2 (Cox-2 or prostaglandin endoperoxidase synthase 2) and the epidermal growth factor-like factor, amphiregulin (Areg), in the ovary, whereas their hCG-induced expression was suppressed by the AR antagonist flutamide. These genes were also induced by DHT in AR-expressing primary granulosa and granulosa tumor-derived cells. Reporter assays, electrophoretic shift mobility assays and chromatin immunoprecipitation assays demonstrated that androgen response sequence(s) existing upstream of each gene were responsible for androgen responsiveness and were occupied by the AR in periovulatory granulosa cells. Our results suggest that the androgen/AR pathway is involved in the ovulatory process via expression of the Cox-2 and Areg genes in periovulatory granulosa cells. 23252610 Analysis of 4-Hydroxy-1-(3-pyridyl)-1-butanone (HPB)-Releasing DNA Adducts in Human Exfoliated Oral Mucosa Cells by Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry. Quantitation of DNA adducts could provide critical information on the relationship between exposure to tobacco smoke and cancer risk in smokers. In this study, we developed a robust and sensitive liquid chromatography-tandem mass spectrometry method for the analysis of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing DNA adducts in human oral cells, a noninvasive source of DNA for biomarker studies. Isolated DNA undergoes acid hydrolysis, after which samples are purified by solid-phase extraction and analyzed by LC-ESI-MS/MS. The developed method was applied to the analysis of samples obtained via collection with a commercial mouthwash from 30 smokers and 15 nonsmokers. In smokers, the levels of HPB-releasing DNA adducts averaged 12.0 pmol HPB/mg DNA (detected in 20 out of 28 samples with quantifiable DNA yield), and in nonsmokers, the levels of adducts averaged 0.23 pmol/mg DNA (detected in 3 out of 15 samples). For the 30 smoking subjects, matching buccal brushings were also analyzed, and HPB-releasing DNA adducts were detected in 24 out of 27 samples with quantifiable DNA yield, averaging 44.7 pmol HPB/mg DNA. The levels of adducts in buccal brushings correlated with those in mouthwash samples of smokers (R = 0.73, p < 0.0001). Potentially, the method can be applied in studies of individual susceptibility to tobacco-induced cancers in humans. 22872141 The impact of FANCD2 deficiency on formaldehyde-induced toxicity in human lymphoblastoid cell lines. Formaldehyde (FA), a major industrial chemical and ubiquitous environmental pollutant, has recently been classified by the International Agency for Research on Cancer as a human leukemogen. The major mode of action of FA is thought to be the formation of DNA-protein cross-links (DPCs). Repair of DPCs may be mediated by the Fanconi anemia pathway; however, data supporting the involvement of this pathway are limited, particularly in human hematopoietic cells. Therefore, we assessed the role of FANCD2, a critical component of the Fanconi anemia pathway, in FA-induced toxicity in human lymphoblast cell models of FANCD2 deficiency (PD20 cells) and FANCD2 sufficiency (PD20-D2 cells). After treatment of the cells with 0-150 μM FA for 24 h, DPCs were increased in a dose-dependent manner in both cell lines, with greater increases in FANCD2-deficient PD20 cells. FA also induced cytotoxicity, micronuclei, chromosome aberrations, and apoptosis in a dose-dependent manner in both cell lines, with greater increases in cytotoxicity and apoptosis in PD20 cells. Increased levels of γ-ATR and γ-H2AX in both cell lines suggested the recognition of FA-induced DNA damage; however, the induction of BRCA2 was compromised in FANCD2-deficient PD20 cells, potentially reducing the capacity to repair DPCs. Together, these findings suggest that FANCD2 protein and the Fanconi anemia pathway are essential to protect human lymphoblastoid cells against FA toxicity. Future studies are needed to delineate the role of this pathway in mitigating FA-induced toxicity, particularly in hematopoietic stem cells, the target cells in leukemia. 23601605 Empirical evidence does not support an association between less ambitious pre-treatment goals and better treatment outcomes: a meta-analysis. Setting realistic weight loss goals may play a role in weight loss. We abstracted data from randomized controlled trials and observational studies conducted between 1998 and 2012 concerning the association of weight loss goals with weight loss. Studies included those that (i) were conducted in humans; (ii) delivered a weight loss intervention; (iii) lasted ≥6 weeks; (iv) assessed baseline weight loss goals; (vi) assessed pre- and post-weight either in the form of body mass index or some other measure that could be converted to weight loss based on information included in the original study or later provided by the author(s); and (vii) assessed the correlation between weight loss goals and final weight loss or provided data to calculate the correlation. Studies that included interventions to modify weight loss goals were excluded. Eleven studies met inclusion criteria. The overall correlation between goal weight and weight at intervention completion was small and statistically insignificant ( ρ ̂ = 0.0 5 ; P = 0.20). The current evidence does not demonstrate that setting realistic goals leads to more favourable weight loss outcomes. Thus, our field may wish to reconsider the value of setting realistic goals in successful weight loss. 23254196 Phytoestrogen genistein protects against endothelial barrier dysfunction in vascular endothelial cells through PKA-mediated suppression of RhoA signaling. The soy-derived phytoestrogen genistein has received attention for its potential to improve vascular function, but its mechanism remains unclear. Here, we report that genistein at physiologically relevant concentrations (0.1-10 μM) significantly inhibited thrombin-induced increase in endothelial monolayer permeability. Genistein also reduced the formation of stress fibers by thrombin and suppressed thrombin-induced phosphorylation of myosin light chain (MLC) on Ser(19)/Thr(18) in endothelial cells (ECs). Genistein had no effect on resting intracellular [Ca(2+)] or thrombin-induced increase in Ca(2+) mobilization. Addition of the inhibitors of endothelial nitric oxide synthase or estrogen receptor did not alter the protective effect of genistein. RhoA is a small GTPase that plays an important role in actin-myosin contraction and endothelial barrier dysfunction. RhoA inhibitor blocked the protective effect of genistein on endothelial permeability and also ablated thrombin-induced MLC-phosphorylation in ECs. Inhibition of PKA significantly attenuated the effect of genistein on thrombin-induced EC permeability, MLC phosphorylation, and RhoA membrane translocation in ECs. Furthermore, thrombin diminished cAMP production in ECs, which were prevented by treatment with genistein. These findings demonstrated that genistein improves thrombin-induced endothelial barrier dysfunction in ECs through PKA-mediated suppression of RhoA signaling. 23168241 Merit of quinacrine in the decrease of ingested sulfite-induced toxic action in rat brain. We aimed at investigating the effects of sulfite-induced lipid peroxidation and apoptosis mediated by secretory phospholipase A2 (sPLA2) on somatosensory evoked potentials (SEP) alterations in rats. Thirty male albino Wistar rats were randomized into three experimental groups as follows; control (C), sodium metabisulfite treated (S), sodium metabisulfite+quinacrine treated (SQ). Sodium metabisulfite (100 mg/kg/day) was given by gastric gavage for 5 weeks and 10 mg/kg/day quinacrine was applied as a single dose of intraperitoneal injection for the same period. The latencies of SEP components were significantly prolonged in the S group and returned to control levels following quinacrine administration. Plasma-S-sulfonate level was increased in S and SQ groups. TBARS levels in the S group were significantly higher than those detected in controls. Quinacrine significantly decreased brain TBARS levels in the SQ group compared with the S group. Quinacrine treatment did not have an effect on the increased sPLA2 level of the sulfite administered group. Immunohistochemistry showed that sulfite caused an increase in caspase-3 and TUNEL positive cells, restored to control levels via quinacrine administration. This study showed that sPLA2 might play a role in ingested sulfite-induced SEP alterations, oxidative stress, apoptotic cell death and DNA damage in the brain. 23347052 Self-healing mussel-inspired multi-pH-responsive hydrogels. Self-healing hydrogels can be made using either reversible covalent cross-links or coordination chemistry bonds. Here we present a multi-pH-responsive system inspired by the chemistry of blue mussel adhesive proteins. By attaching DOPA to an amine-functionalized polymer, a multiresponsive system is formed upon reaction with iron. The degree of polymer cross-linking is pH controlled through the pH-dependent DOPA/iron coordination chemistry. This leads to the formation of rapidly self-healing high-strength hydrogels when pH is raised from acidic toward basic values. Close to the pK(a) value, or more precisely the pI value, of the polymer, the gel collapses due to reduced repulsion between polymer chains. Thereby a bistable gel-system is obtained. The present polymer system more closely resembles mussel adhesive proteins than those previously reported and thus also serves as a model system for mussel adhesive chemistry. 23321916 Assessment of permethylated transition-metal sandwich complexes as internal reference redox systems in ionic liquids. This work reports the voltammetric behaviour of decamethylcobaltocenium, DmCc(+), in different ionic liquids for the first time. Its redox potential was studied relative to that of decamethylferrocene, DmFc, and it is shown that the difference in the mid-point potential between these two permethylated transition-metal sandwich complexes is independent of the ionic liquid composition. A variable difference in mid-point potential, in contrast, was observed for ferrocene and cobaltocenium relative to that of DmFc in similar ionic liquids. In addition, different limitations in the application of DmFc(0/+) and DmCc(+/0) couples as internal reference redox systems in ILs are discussed. From these, the observed spontaneous reaction between DmFc and oxygen leads to important implications toward the establishment of particular conditions for DmFc applications. 23440404 Conformation-dependent conductance through a molecular break junction. Ab initio molecular dynamics simulations have been performed of a gold-1,4-benzenedithiol (BDT)-gold nanojunction under mechanical stress. For three different pulling rates between 10 and 40 m s(-1), it is found that the nanowire always ruptures between the second and third Au atom from the thiol sulfur. Larger rupture forces and longer extensions are required at higher pulling rates and vice versa. The electrical conductance was calculated along a pulling trajectory using the DFT-NEGF method to study the effect of thermal and stress-induced structural changes on the electrical transport properties. While the mechanically induced stretching of the junction is seen to lower the time-averaged conductance, thermal conformational changes are capable of altering the conductance by one order of magnitude. No single geometric quantity could be identified as the main contributor to the conductance fluctuations. Small modulations, however, can be explained in terms of C=C double bond vibrations in the BDT molecule. The dependence of the conductance on different geometric variables has further been investigated systematically by performing constrained geometry optimizations along a number of angle and dihedral coordinates. The largest changes in the conductance are observed when the Au-S-C angle and the Au-S-C-C dihedral are simultaneously constrained. 23590473 Hair as an alternative matrix in bioanalysis. Alternative matrices are steadily gaining recognition as biological samples for toxicological analyses. Hair presents many advantages over traditional matrices, such as urine and blood, since it provides retrospective information regarding drug exposure, can distinguish between chronic and acute or recent drug use by segmental analysis, is easy to obtain, and has considerable stability for long periods of time. For this reason, it has been employed in a wide variety of contexts, namely to evaluate workplace drug exposure, drug-facilitated sexual assault, pre-natal drug exposure, anti-doping control, pharmacological monitoring and alcohol abuse. In this article, issues concerning hair structure, collection, storage and analysis are reviewed. The mechanisms of drug incorporation into hair are briefly discussed. Analytical techniques for simultaneous drug quantification in hair are addressed. Finally, representative examples of drug quantification using hair are summarized, emphasizing its potentialities and limitations as an alternative biological matrix for toxicological analyses. 23451803 Digitized charge transfer magnitude determined by metal-organic coordination number. Well-ordered metal-organic nanostructures of Fe-PTCDA (perylene-3,4,9,10-tetracarboxylic-3,4,9,10-dianhydride) chains and networks are grown on a Au(111) surface. These structures are investigated by high-resolution scanning tunneling microscopy. Digitized frontier orbital shifts are followed in scanning tunneling spectroscopy. By comparing the frontier energies with the molecular coordination environments, we conclude that the specific coordination affects the magnitude of charge transfer onto each PTCDA in the Fe-PTCDA hybridization system. A basic model is derived, which captures the essential underlying physics and correlates the observed energetic shift of the frontier orbital with the charge transfer. 23094599 Silicon surface functionalization targeting Si-N linkages. Silicon substrates have been a fascinating topic of fundamental and applied research for well over 50 years. They have attracted even more attention over the last couple of decades with advances in chemical functionalization that made oxide-free silicon surfaces a reality. Fundamentally new electronic properties and chemical reactivity became available, and the focus of chemical research turned more toward targeting specific chemical bonds and functionalities on silicon. Although thermodynamics clearly drives most processes under ambient conditions toward the formation of an oxide layer, kinetic control of the oxidation processes and thermodynamic tricks based on gaining stability of surface monolayers with high-density assembly have allowed for the formation of stable Si-C bonds and Si-O-C linkages on oxide-free silicon crystals. This feature article targets recent advances in making Si-N linkages on the same oxide-free single crystals. It covers the range of chemical approaches to achieving this goal and offers possible chemistry that can take advantage of the systems produced. The present status of the field and the future directions of its development will be considered. 23418087 Lifelong exposure to bisphenol a alters cardiac structure/function, protein expression, and DNA methylation in adult mice. Bisphenol A (BPA) is an estrogenizing endocrine disruptor compound of concern. Our objective was to test whether lifelong BPA would impact cardiac structure/function, calcium homeostasis protein expression, and the DNA methylation of cardiac genes. We delivered 0.5 and 5.0 µg/kg/day BPA lifelong from gestation day 11 or 200 µg/kg/day from gestation day 11 to postnatal day 21 via the drinking water to C57bl/6n mice. BPA 5.0 males and females had increased body weight, body mass index, body surface area, and adiposity. Echocardiography identified concentric remodeling in all BPA-treated males. Systolic and diastolic cardiac functions were essentially similar, but lifelong BPA enhanced male and reduced female sex-specific differences in velocity of circumferential shortening and ascending aorta velocity time integral. Diastolic blood pressure was increased in all BPA females. The calcium homeostasis proteins sarcoendoplasmic reticulum ATPase 2a (SERCA2a), sodium calcium exchanger-1, phospholamban (PLB), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation. Changes in their expression suggest increased calcium mobility in males and reduced calcium mobility in females supporting the cardiac function changes. DNA methyltransferase 3a expression was increased in all BPA males and BPA 0.5 females and reduced in BPA 200 females. Global DNA methylation was increased in BPA 0.5 males and reduced in BPA 0.5 females. BPA induced sex-specific altered DNA methylation in specific CpG pairs in the calsequestrin 2 CpG island. These results suggest that continual exposure to BPA impacts cardiac structure/function, protein expression, and epigenetic DNA methylation marks in males and females. 23432007 (89)Zr-PET Radiochemistry in the Development and Application of Therapeutic Monoclonal Antibodies and Other Biologicals. Positron emission tomography with (89)Zr can be used to follow the behaviour of therapeutic monoclonal antibodies (mAbs) and other biologicals in vivo. The favourable radiophysical characteristics of (89)Zr allow multiple days PET scanning after injection. For the coupling of (89)Zr to proteins six desferrioxamine (DFO)-based bifunctional chelators have been described, five of which forming stable complexes in vivo. Of the methods that give stable complexes three are based on random lysine modification of mAbs and two on site-specific engineering. Up to now only two methods, random lysine modification with N-suc-DFO or DFO-Bz-NCS, have been used in clinical studies. In this review firstly aspects of the physicochemical properties and production of (89)Zr are emphasized as well as important items that have to be taken into account for current good manufacturing practice (cGMP) compliant production of (89)Zr-labeled proteins. Next, the different DFO-based conjugation strategies will be discussed with respect to synthesis, and their (pre)clinical evaluation particularly in the field of oncology. 23333261 Contribution of single-minded 2 to hyperglycaemia-induced neurotoxicity. Diabetes mellitus is associated to central nervous system damage, which results in impairment of brain functions and cognitive deficits and decline in memory. However, the mechanisms mediating the actions of glucose on the neurons remained elusive. Single-minded 2 (Sim2), a basic helix-loop-helix (bHLH)-PAS transcriptional repressor, is thought to be involved in some symptoms of Down syndrome. We hypothesized that Sim2 mediated hyperglycaemia-induced neuronal injury and impairment of learning and memory. It was found that expression of Sim2 protein in cortical neurons was increased in streptozotocin-induced diabetes mellitus rat model. Drebrin, down-regulated by Sim2, was subsequently decreased as detected by confocal laser scanning microscopy and Western blot analysis. The expression pattern of Sim2 and Drebrin correspond to 50mmol/L glucose (hyperglycaemia) was also found in primary cultured neurons. Curcumin, one neuroprotective agent, inhibited hyperglycaemia-induced neurotoxicity. Moreover, curcumin alleviated Sim2 expression, and reversely raised Drebrin expression in neurons treated with hyperglycaemia. Finally, we found that silencing Sim2 expression decreased hyperglycaemia-induced neuronal injury. In conclusion, Sim2 may mediate neurotoxicity during hyperglycaemia and thereby play a critical role in the development of hyperglycaemia-induced cognitive deficits. 23234812 Strontium Ranelate affects signaling from mechanically-stimulated osteocytes towards osteoclasts and osteoblasts. Strontium Ranelate (SrRan) is used to decrease the risk of bone fractures. Any factor that alters the release of paracrine signals by osteocytes in response to mechanical stimuli potentially affects bone mass and structure, and thus fracture resistance. We hypothesized that SrRan affects paracrine signaling from mechanically-stimulated osteocytes towards osteoclast-precursors and osteoblasts. MLO-Y4 osteocytes were cultured for 24h with SrRan (0.1-3mM) and either or not mechanically stimulated by pulsating fluid flow (PFF; 0.7 ± 0.3 Pa, 5 Hz) for 60 min. Nitric oxide (NO) and prostaglandin E(2) (PGE(2)) release, and expression of mechanoresponsive genes were quantified. Conditioned medium (CM) from osteocytes was added to mouse bone marrow cells for 7 days to assess osteoclastogenesis, or MC3T3-E1 osteoblasts for 4-16 days to measure osteogenic gene expression. SrRan (3mM) enhanced NO and PGE(2) release to the same extent in static osteocytes (NO: 1.6-fold; PGE(2): 2.8-fold) and PFF-stimulated osteocytes (NO: 1.3-fold; PGE(2): 2.6-fold). CM from PFF-treated osteocytes without SrRan enhanced Ki67 expression but reduced Runx2 and Ocn expression in osteoblasts. This effect on gene expression was not observed with CM obtained from osteocytes treated with the combination of PFF and 3mM SrRan. CM from PFF-treated osteocytes inhibited osteoclastogenesis by 1.9-fold. The combination of PFF and 3mM SrRan reduced osteocyte-stimulated osteoclastogenesis even more strongly (4.3-fold). In conclusion, SrRan affects paracrine signaling between mechanically-stimulated MLO-Y4 osteocytes and both osteoblasts and osteoclast precursors. The positive effects of SrRan on bone fracture resistance may thus be partly explained by altered paracrine signaling by osteocytes. 23411195 Odour quality of spray-dried hens' egg powders: the influence of composition, processing and storage conditions. This study aimed to determine whether compositional or processing parameters have an influence on the odour quality of egg powders. The parameters tested were: whole egg vs. egg yolk, polyunsaturated fatty acid (PUFA) enrichment, spray-drying temperature (160°C vs. 180°C), production scale (industrial vs. pilot plant), storage temperature (15°C vs. 30°C) and time (1, 2, 4 and 8 months). The quality of egg powders was evaluated by sensory analysis using free sorting, and by gas chromatography coupled to mass spectrometry and olfactometry. PUFA enrichment and spray-drying temperature do not affect the odour of egg yolk powders. There are significant differences between the odour of whole-egg and egg-yolk powders as well as between powders produced on an industrial scale or in a pilot plant. An increase in the odour intensity of egg powders was observed during storage, while unpleasant odours were perceived when the egg powders were stored at 30°C. 23421617 Impact of model perfume molecules on the self-assembly of anionic surfactant sodium dodecyl 6-benzene sulfonate. The impact of two model perfumes with differing degrees of hydrophobicity/hydrophilicity, linalool (LL) and phenylethanol (PE), on the solution structure of anionic surfactant sodium dodecyl 6-benzene sulfonate, LAS-6, has been studied by small angle neutron scattering, SANS. For both types of perfume molecules, complex phase behavior is observed. The phase behavior depends upon the concentration, surfactant/perfume composition, and type of perfume. The more hydrophilic perfume PE promotes the formation of more highly curved structures. At relatively low surfactant concentrations, small globular micelles, L1, are formed. These become perfume droplets, L(sm), stabilized by the surfactant at much higher perfume solution compositions. At higher surfactant concentrations, the tendency of LAS-6 to form more planar structures is evident. The more hydrophobic linalool promotes the formation of more planar structures. Combined with the greater tendency of LAS-6 to form planar structures, this results in the planar structures dominating the phase behavior for the LAS-6/linalool mixtures. For the LAS-6/linalool mixture, the self-assembly is in the form of micelles only at the lowest surfactant and perfume concentrations. Over most of the concentration-composition space explored, the structures are predominantly lamellar, L(α), or vesicle, L(v), or in the form of a lamellar/micellar coexistence. At low and intermediate amounts of LL, a significantly different structure is observed, and the aggregates are in the form of small, relatively monodisperse vesicles (i.e., nanovesicles), L(sv). 22840199 Pelargonium graveolens L'Her. and Artemisia arborescens L. essential oils: Chemical composition, antifungal activity against Rhizoctonia solani and insecticidal activity against Rhysopertha dominica. The chemical composition of the Pelargonium graveolens essential oil allowed the identification of 15 compounds (93.86% of the total essential oil). The major fractions were citronellol (35%) and geraniol (28.8%). The chemical composition of the Artemisia arborescens essential oil revealed twenty-one compounds representing 93.57% of the total essential oil. The main compounds were chamazulene (31.9%) and camphor (25.8%). The insecticidal effects were tested towards the insect Rhysopertha dominica. Results revealed that these two essential oils were highly effective against R. dominica at the dose of 50 µL on Petri dish of 8.5 cm of diameter. The antifungal activity was evaluated against Rhizoctonia solani and results showed that both of the essential oils were highly active at a dose of 12.5 µL/20 mL of PDA. Moreover, the inhibitory effect of P. graveolens essential oil was evidenced as stronger than that of the A. arborescens oil for all the tested doses. 23624376 Polyglycerol coatings of glass vials for protein resistance. Proteins are surface active molecules which undergo non-specific adsorption when getting in contact with surfaces such as the primary packaging material. This process is critical as it may cause a loss of protein content or protein aggregation. To prevent unspecific adsorption, protein repellent coatings are of high interest. We describe the coating of industrial relevant borosilicate glass vials with linear methoxylated polyglycerol, hyperbranched polyglycerol, and hyperbranched methoxylated polyglycerol. All coatings provide excellent protein repellent effects. The hyperbranched, non-methoxylated coating performed best. The protein repellent properties were maintained also after applying industrial relevant sterilization methods (⩾200°C). Marginal differences in antibody stability between formulations stored in bare glass vials and coated vials were detected after 3months storage; the protein repellent effect remained largely stable. Here, we describe a new material suitable for the coating of primary packaging material of proteins which significantly reduces the protein adsorption and thus could present an interesting new possibility for biomedical applications. 23122114 Hair mercury levels and food consumption in residents from the Pearl River Delta: South China. The Pearl River Delta (PRD) is located in the Southern part of China and is the main region for fish culture in Guangdong Province. In order to assess the potential health risks associated with dietary consumption of mercury, hair samples from 91 urban, town and fishing village residents, 37 species of fish, cereal, vegetables, and meat samples were collected. The average total mercury (THg) and methylmercury (MeHg) concentrations in hair were 1.08 ± 0.94 and 0.58 ± 0.59 μg/g, respectively. Daily Hg intake via fish consumption is significantly correlated with THg and MeHg accumulated in human hair (r=0.48, p<0.01; r=0.43, p<0.01). The estimated daily intake of Hg via different food types showed that both fish and cereal consumption were the two main routes of Hg exposure for residents in the sampling areas. Besides food intake, smoking was also an important source for daily THg intake in the smoke group, contributing 11-18% to EDI of THg. 23411284 Thermal protection of β-carotene in re-assembled casein micelles during different processing technologies applied in food industry. β-Carotene is a carotenoid usually applied in the food industry as a precursor of vitamin A or as a colourant. β-Carotene is a labile compound easily degraded by light, heat and oxygen. Casein micelles were used as nanostructures to encapsulate, stabilise and protect β-carotene from degradation during processing in the food industry. Self-assembly method was applied to re-assemble nanomicelles containing β-carotene. The protective effect of the nanostructures against degradation during the most common industrial treatments (sterilisation, pasteurisation, high hydrostatic pressure and baking) was proven. Casein micelles protected β-carotene from degradation during heat stabilisation, high pressure processing and the processes most commonly used in the food industry including baking. This opens new possibilities for introducing thermolabile ingredients in bakery products. 23583765 Systematic characterization of structure-activity relationships and ADMET compliance: a case study. Traditionally, activity landscape modeling has been focused on analyzing SAR, despite the fact that lead optimization in drug discovery involves concurrent enhancements of activity and ADMET properties of leads. As a case study, we discuss the systematic analysis of activity landscapes, incorporating ADMET considerations, using a dataset of 166 compounds screened for kappa-opioid receptor activity. Pairwise MACCS/Tanimoto structure similarities, property similarities utilizing 33 ADMET descriptors and a 35-dimensional 'violation bit vector' representing drug-likeness are analyzed. We address the question about the range of ADMET property violations that arise from structural changes, subtle and significant. Pairs of compounds are identified bearing identical, comparable and significantly different drug-likeness in the three informative regions of structure-activity landscapes. 23456097 Combining NMR and small angle X-ray and neutron scattering in the structural analysis of a ternary protein-RNA complex. Many processes in the regulation of gene expression and signaling involve the formation of protein complexes involving multi-domain proteins. Individual domains that mediate protein-protein and protein-nucleic acid interactions are typically connected by flexible linkers, which contribute to conformational dynamics and enable the formation of complexes with distinct binding partners. Solution techniques are therefore required for structural analysis and to characterize potential conformational dynamics. Nuclear magnetic resonance spectroscopy (NMR) provides such information but often only sparse data are obtained with increasing molecular weight of the complexes. It is therefore beneficial to combine NMR data with additional structural restraints from complementary solution techniques. Small angle X-ray/neutron scattering (SAXS/SANS) data can be efficiently combined with NMR-derived information, either for validation or by providing additional restraints for structural analysis. Here, we show that the combination of SAXS and SANS data can help to refine structural models obtained from data-driven docking using HADDOCK based on sparse NMR data. The approach is demonstrated with the ternary protein-protein-RNA complex involving two RNA recognition motif (RRM) domains of Sex-lethal, the N-terminal cold shock domain of Upstream-to-N-Ras, and msl-2 mRNA. Based on chemical shift perturbations we have mapped protein-protein and protein-RNA interfaces and complemented this NMR-derived information with SAXS data, as well as SANS measurements on subunit-selectively deuterated samples of the ternary complex. Our results show that, while the use of SAXS data is beneficial, the additional combination with contrast variation in SANS data resolves remaining ambiguities and improves the docking based on chemical shift perturbations of the ternary protein-RNA complex. 23266453 Targeted adenovirus mediated inhibition of NF-κB-dependent inflammatory gene expression in endothelial cells in vitro and in vivo. In chronic inflammatory diseases the endothelium expresses mediators responsible for harmful leukocyte infiltration. We investigated whether targeted delivery of a therapeutic transgene that inhibits nuclear factor κB signal transduction could silence the proinflammatory activation status of endothelial cells. For this, an adenovirus encoding dominant-negative IκB (dnIκB) as a therapeutic transgene was employed. Selectivity for the endothelial cells was achieved by introduction of antibodies specific for inflammatory endothelial adhesion molecules E-selectin or VCAM-1 chemically linked to the virus via polyethylene glycol. In vitro, the retargeted adenoviruses selectively infected cytokine-activated endothelial cells to express functional transgene. The comparison of transductional capacity of both retargeted viruses revealed that E-selectin based transgene delivery exerted superior pharmacological effects. Targeted delivery mediated dnIκB transgene expression in endothelial cells inhibited the induced expression of several inflammatory genes, including adhesion molecules, cytokines, and chemokines. In vivo, in mice suffering from glomerulonephritis, E-selectin-retargeted adenovirus selectively homed in the kidney to microvascular glomerular endothelium. Subsequent downregulation of endothelial adhesion molecule expression 2 days after induction of inflammation demonstrated the pharmacological potential of this gene therapy approach. The data justify further studies towards therapeutic virus design and optimization of treatment schedules to investigate their capacity to interfere with inflammatory disease progression. 23623493 Synthesis, characterization and cytotoxic activity on breast cancer cells of new half-titanocene derivatives. A series of novel titanocene-complexes has been prepared and evaluated for their growth regulatory effects in MCF7 and SkBr3 breast cancer cells. The capability of some of these compound to elicit relevant repressive effects on cancer cell growth could be taken into account towards novel pharmacological approaches in cancer therapy. 23207252 Effects of the herbal medicine composition "Saiko-ka-ryukotsu-borei-To" on the function of endothelial progenitor cells in hypertensive rats. Endothelial progenitor cells (EPCs) are known to repair vascular injuries. Recent studies suggest that Saiko-ka-ryukotsu-borei-To (SKRBT), a traditional herbal medicine that has been used to treat stress-related neuropsychiatric disorders, has protective effects on cardiovascular diseases such as hypertension and arteriosclerosis. Spontaneously hypertensive rats (SHRs) were fed diets containing lyophilized SKRBT extract for 6 weeks. Peripheral blood mononuclear cells (MNCs) were isolated and cultured to assay EPC colony formation. Oxidative stress in MNCs was evaluated by thiobarbituric acid reactive substance (TBARS) assay and flowcytometric analyses. Treatment with SKRBT increased EPC colony numbers significantly (p<0.05) with decrease in oxidative stress and without affecting blood pressure in SHRs. Treatment with SKRBT did not reduce the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits in cardiovascular organs. Serum IL-6 level was significantly reduced. SKRBT is a feasible herbal medicine that protects against cardiovascular diseases through an increase in EPC function along with anti-oxidative effects, and may affect the link between chronic inflammation and cardiovascular disease. 23224291 Proteomic and metabolomic responses to connexin43 silencing in primary hepatocyte cultures. Freshly established cultures of primary hepatocytes progressively adopt a foetal-like phenotype and display increased production of connexin43. The latter is a multifaceted cellular entity with variable subcellular locations, including the mitochondrial compartment. Cx43 forms hemichannels and gap junctions that are involved in a plethora of physiological and pathological processes, such as apoptosis. The present study was conducted with the goal of shedding more light onto the role of connexin43 in primary hepatocyte cultures. Connexin43 expression was suppressed by means of RNA interference technology, and the overall outcome of this treatment on the hepatocellular proteome and metabolome was investigated using tandem mass tag-based differential protein profiling and (1)H NMR spectroscopy, respectively. Global protein profiling revealed a number of targets of the connexin43 knock-down procedure, including mitochondrial proteins (heat shock protein 60, glucose-regulated protein 75, thiosulphate sulphurtransferase and adenosine triphosphate synthase) and detoxifying enzymes (glutathione S-transferase μ 2 and cytochrome P450 2C70). At the metabolomic level, connexin43 silencing caused no overt changes, though there was some evidence for a subtle increase in intracellular glycine quantities. Collectively, these data could further substantiate the established existence of a mitochondrial connexin pool and could be reconciled with the previously reported involvement of connexin43 signalling in spontaneously occurring apoptosis in primary hepatocyte cultures. 23376696 Tissue distributions of fluoride and its toxicity in the gills of a freshwater teleost, Cyprinus carpio. Fish take up fluoride directly from water and are susceptible to fluoride contamination of their environment. In this study, we examined the tissue distributions of fluoride and its toxicity in the gills of the common carp (Cyprinus carpio) chronically exposed to fluoride. Carp were exposed to a range of aqueous fluoride (35-124 mg/L) and sampled at 30, 60 and 90 days. The accumulation of fluoride in the tissues increased with the level and duration of exposure. Steady state was not achieved under the experimental conditions. The gills accumulated the highest levels of fluoride followed by the liver>brain>kidney>muscle>intestine. A dose-dependent inhibition was observed for the enzyme activities of Na(+)-K(+)-ATPase and Ca(2+)-ATPase in the gills after the fish were exposed for 90 days. Also, accumulation of fluoride was associated with the inhibition of superoxide dismutase (SOD) activities and a dose-dependent stimulation of malondialdehyde (MDA) levels in the gill tissues, suggesting that fluoride promoted oxidative stress in the fish. Microscopic examinations revealed injuries to gill tissues and chloride cells, with the severity of injury increasing with exposure concentration. These results suggest that chronic exposure to elevated concentrations of fluoride may induce toxicity in the common carp. 22914985 Effects of mycophenolic acid alone and in combination with its metabolite mycophenolic acid glucuronide on rat embryos in vitro. Mycophenolic acid (MPA) is an immunosuppressive agent that acts as a selective, non-reversible inhibitor of the enzyme inosine-5'-monophosphate dehydrogenase (IMPDH). Malformations have been described in children after maternal exposure to mycophenolate. However, the causal link is unclear in most cases because women had been treated with a combination of drugs and birth defects may have other causes. Therefore, it is important to study the action of this drug and its main metabolite on embryonic tissue. We studied the teratogenic potential of MPA and its major metabolite, the mycophenolic acid glucuronide (MPAG) in the rat whole-embryo culture. A total of 147 day 9.5 embryos were cultivated for 48 h in the standard medium containing 85 % serum. We tested MPA at concentrations of 0.1; 0.25; 0.5; 0.75 mg/l (0.31; 0.78; 1.56; 2.34 μM) and MPA glucuronide at concentrations of 3; 10; 30; 100 mg/l (6.04; 20.14; 60.43; 201.43 μM). Both substances are highly protein bound, and MPA glucuronide might displace MPA from protein binding. Therefore, we examined whether the effects of MPA can be enhanced when studied in combination with the glucuronide. Furthermore, the focus was on additional endpoints to the standard evaluation of cultivated embryos, such as development of cranial nerves [trigeminal nerve (V), facial nerve (VII), glossopharyngeal nerve (IX), vagus nerve (X)] after staining with an antibody against 2H3 neurofilament. Ultrastructural changes were evaluated by electron microscopy. At a concentration of 0.75 mg MPA/l medium, all embryos showed dysmorphic changes. Embryos exposed to 0.25 mg MPA/l medium showed impaired development of nerves, and at 0.1 mg/l, no effects were detectable. Concentration-dependent ultrastructural changes, such as signs of apoptosis, were found by electron microscopy. The examination of the metabolite in this assay showed that at a concentration of 100 mg MPAG/l, the embryos exhibited distinct malformations. This is probably caused by MPA, which was detectable at 0.6 % in the material used for our experiments. The combination of the parent compound (0.03; 0.1; 0.25 mg/l) with its metabolite MPAG (3 mg/l) did not cause enhanced toxicity under our experimental conditions. IMPDH, the target enzyme of MPA, could be detected in rat embryos on day 9.5 of embryonic development as well as at the end of the culture period 48 h later. In summary, MPA impairs embryonic development at low, therapeutically relevant concentrations, but the glucuronide does not exhibit such a potential. Activity of MPA is not enhanced by MPAG. 23276633 Testosterone metabolites mediate its effects on myocardial damage induced by ischemia/reperfusion in male Wistar rats. The role of testosterone in cardiovascular (CV) homeostasis is in controversy, and the exact effects of testosterone on the cardiovascular system remain poorly understood. Testosterone is metabolized by aromatase into 17β-estradiol and by 5α-reductase into dihydrotestosterone (DHT). Thus, identification of these metabolites in the heart may help to explain the controversy regarding the cardiovascular effects of testosterone. We analyzed the expression patterns of these testosterone-metabolizing enzymes and assessed the effect of its enzymatic activity inhibition on ischemia (40 min)/reperfusion (4h, I/R) via the left anterior descendent coronary artery in intact and gonadectomized male rats. Myocardial damage was measured as percentage of infarcted area vs. area at risk. Aromatase and 5α-reductase protein expression was found in the left ventricle of intact and orchidectomized rats. Exogenous testosterone had no effect on I/R induced myocardial damage in intact male rats, meanwhile exogenous testosterone protects against I/R injury in orchidectomized rats. However, enzymatic inhibition of aromatase increased myocardial damage in the presence of testosterone, while enzymatic inhibition of 5α-reductase significantly decreased the level of myocardial damage. Our results also showed that sub-chronic inhibition of 5α-reductase resulted in myocardial protection in both groups. Furthermore, in orchidectomized and intact male rats IV treatment with DHT induces a significant increase in the myocardial damage induced by I/R. Thus, the effect of testosterone on cardiovascular pathophysiology could be related, at least in part to changes in the balance of testosterone 5α-reduction and aromatization. 23339654 Type I collagen self-assembly: the roles of substrate and concentration. Collagen molecules, self-assembled into macroscopic hierarchical tissue networks, are the main organic building block of many biological tissues. A particularly common and important form of this self-assembly consists of type I collagen fibrils, which exhibit a nanoscopic signature, D-periodic gap/overlap spacing, with a distribution of values centered at approximately 67 nm. In order to better understand the relationship between type I collagen self-assembly and D-spacing distribution, we investigated surface-mediated collagen self-assembly as a function of substrate and incubation concentration. Collagen fibril assembly on phlogopite and muscovite mica as well as fibrillar gel coextrusion in glass capillary tubes all exhibited D-spacing distributions similar to those commonly observed in biological tissues. The observation of D-spacing distribution by self-assembly of type I collagen alone is significant as it eliminates the necessity to invoke other preassembly or postassembly hypotheses, such as variation in the content of collagen types, enzymatic cross-linking, or other post-translational modifications, as mechanistic origins of D-spacing distribution. The D-spacing distribution on phlogopite mica is independent of type I collagen concentration, but on muscovite mica D-spacing distributions showed increased negative skewness at 20 μg/mL and higher concentrations. Tilted D-spacing angles were found to correlate with decreased D-spacing measurements, an effect that can be removed with a tilt angle correction, resulting in no concentration dependence of D-spacing distribution on muscovite mica. We then demonstrated that tilted D-spacing is uncommon in biological tissues and it does not explain previous observations of low D-spacing values in ovariectomized dermis and bone. 23281179 Correct Spectral Conversion between Surface-Enhanced Raman and Plasmon Resonance Scattering from Nanoparticle Dimers for Single-Molecule Detection. Simultaneous measurement of surface-enhanced Raman scattering (SERS) and localized surface plasmon resonance (LSPR) in nanoparticle dimers presents outstanding opportunities in molecular identification and in the elucidation of physical properties, such as the size, distance, and deformation of target species. SERS-LSPR instrumentation exists and has been used under limited conditions, but the extraction of SERS and LSPR readouts from a single measurement is still a challenge. Herein, the extraction of LSPR spectra from SERS signals is reported and a tool for measuring the interparticle distance from Raman enhancement data by the standardization of the SERS signal is proposed. The SERS nanoruler mechanism incorporates two important aspects (the LSPR scattering peak shift and the Raman shift for measuring interparticle distance), and signifies their exact one-to-one correspondence after spectral correction. The developed methodology is applied to calculate the interparticle distance between nanoparticle dimers from SERS signals, to detect and quantify DNA at the single-molecule level in a base-pair-specific manner. It is also shown that the SERS nanoruler concept can be used in structural analysis for the specific detection of the interaction of immunoglobulin G (IgG) with its target from bianalyte Raman signals with identical shaping at single-molecule resolution. The SERS profile shaping approach not only offers a new detection mechanism for single molecules, but also has excellent potential for studying protein interactions and the intracellular detection of mRNA. 23462104 Effects of seaweed-restructured pork diets enriched or not with cholesterol on rat cholesterolaemia and liver damage. Seaweed enriched-restructured pork (RP) is a potential functional food. However, indications of adverse effects associated with herbal medications, which include among others liver failure, toxic hepatitis, and death have been reported. Cholesterol feeding produces hepatomegalia and fat liver infiltration. The effect of seaweed-RP diet, cholesterol-enriched or not, on plasma cholesterol, liver damage markers, structure, and cytochrome CYP4A-1 were evaluated after 5wk. Eight rat groups were fed a mix of 85% AIN-93M rodent-diet plus 15% RP. The Cholesterol-control (CC), Cholesterol-Wakame (CW), Cholesterol-Nori (CN) and Cholesterol-Sea Spaghetti (CS) groups respectively consumed similar diets to control (C), Wakame (W), Nori (N), and Sea Spaghetti (S) but as part of hypercholesterolaemic diets. CN and CS significantly blocked the hypercholesterolaemic effect observed in CC group. After 5-wk, N and S diets increased the CYP4A-1 expression. However, seaweed-RPs were unable to reduce the histological liver alterations observed in CC group. Larger and more abundant hepatocellular alterations were found in CS and CN rats suggesting that the hypocholesterolaemic effects of these seaweed-RPs seem to be a two-edged sword as they increased liver damage. Future studies are needed to understand the involved mechanisms. 23063411 Characterisation of the roles of ABCB1, ABCC1, ABCC2 and ABCG2 in the transport and pharmacokinetics of actinomycin D in vitro and in vivo. Actinomycin D plays a key role in the successful treatment of Wilms tumour. However, associated liver toxicities remain a drawback to potentially curative treatment. We have used MDCKII cells over-expressing ABCB1, ABCC1, ABCC2 and ABCG2, alongside knockout mouse models to characterise actinomycin D transport and its impact on pharmacokinetics. Growth inhibition, intracellular accumulation and cellular efflux assays were utilised. A 59-fold difference in GI(50) was observed between MDCKII-WT and MDCKII-ABCB1 cells (12.7 nM vs. 745 nM, p<0.0001). Reduced sensitivity was also seen in MDCKII-ABCC1 and ABCC2 cells (GI(50) 25.7 and 40.4 nM respectively, p<0.0001). Lower intracellular accumulation of actinomycin D was observed in MDCKII-ABCB1 cells as compared to MDCKII-WT (0.98 nM vs. 0.1 nM, p<0.0001), which was reversed upon ABCB1 inhibition. Lower accumulation was also seen in MDCKII-ABCC1 and ABCC2 cells. Actinomycin D efflux over 2 h was most pronounced in MDCKII-ABCB1 cells, with 5.5-fold lower intracellular levels compared to WT. In vivo studies showed that actinomycin D plasma concentrations were significantly higher in Abcb1a/1b(-/-) as compared to WT mice following administration of 0.5 mg/kg actinomycin D (AUC(0-6 h) 242 vs. 152 μg/Lh respectively). While comparable actinomycin D concentrations were observed in the kidneys and livers of Abcb1a/1b(-/-) and Abcc2(-/-) mice, concentrations in the brain were significantly higher at 6h following drug administration in Abcb1a/1b(-/-) mice compared to WT. Results confirm actinomycin D as a substrate for ABCB1, ABCC1 and ABCC2, and indicate that Abcb1a/1b and Abcc2 can influence the in vivo disposition of actinomycin D. These data have implications for ongoing clinical pharmacology trials involving children treated with actinomycin D. 23567034 Antibacterial, cytotoxic activities and chemical composition of fruits of two Cameroonian Zanthoxylum species. ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum leprieurii (Syn. Fagara leprieurii) is a plant extensively used by traditional healers in Cameroon for the treatment of stomach disorders, gonorrhea, intestinal parasites and sterility. The infusion from the fruit is taken in Cameroon for the treatment of sickle cell anemia, as well. Similarly, the roots of Zanthoxylum zanthoxyloides (Syn. Fagara zanthoxyloides) are also used for wound dressing, sickle cell anemia and as pain reliever, in addition to the uses mentioned for Zanthoxylum leprieurii. AIM OF THE STUDY: To scientifically validate their traditional use, the in vitro antimicrobial and anticancer assays were performed. In addition, chemical compositions of their fruit extracts and essential oils were also studied. MATERIAL AND METHODS: The chemical compositions of their essential oils and methanol extracts were studied. GC and GC-MS were used for analyzing the essential oils while various chromatographic methods were used to isolate the pure compounds from methanol extracts. MTT assay was used for the cytotoxic studies of methanol extracts, their fractions and some pure compounds. Antimicrobial activity of methanol extracts, some isolated compounds as well as essential oils was tested against a panel of human pathogenic bacteria by diffusion and dilution methods. RESULTS: The principal constituents of the essential oil of Zanthoxylum zanthoxyloides were identified as citronellol and geraniol whereas Zanthoxylum leprieurii was rich in E-β-ocimene. Furthermore, we report for the first time, the presence of 7,8-dimethoxycoumarin and sinapic acid in the methanol extract of Zanthoxylum leprieurii. In vitro bioassays reveal that the methanol extracts, essential oil and some of the isolated compounds from fruits of both the plants exhibit moderate anticancer and antimicrobial activities. CONCLUSION: Altogether, the present findings justify the traditional use of Zanthoxylum zanthoxyloides and Zanthoxylum leprieurii in the treatment of stomach disorders and cancer disease. The antimicrobial properties in the essential oil of Zanthoxylum zanthoxyloides are of additional significance. 23515282 Functional Diversity of HDL Cargo. For decades high-density lipoproteins (HDL) and HDL-cholesterol (HDL-C) levels were viewed as synonymous and modulation of HDL-C levels by drug therapy held great promise for the prevention and treatment of cardiovascular disease. Nevertheless, recent failures of drugs that raise HDL-C to reduce cardiovascular risk and the now greater understanding of the complexity of HDL composition and biology have prompted researchers in the field to redefine HDL. As such, the focus of HDL has now started to shift away from a cholesterol centric view towards HDL particle number, subclasses, and other alternative metrics of HDL. Many of the recently discovered functions of HDL are, in fact, not strictly conferred by its ability to promote cholesterol flux, but by the other molecules it transports, including a diverse set of proteins, small RNAs, hormones, carotenoids, vitamins, and bioactive lipids. Based on the ability of HDL to interact with almost all cells and transport and deliver fat-soluble cargo, HDL has the remarkable capacity to affect a wide-variety of endocrine-like systems. Here in this review, we characterize the unique cargo on HDL and address the functional relevance and consequences of HDL transport and delivery of non-cholesterol molecules to recipient cells and tissues. 23537747 Nobiletin attenuates metastasis via both ERK and PI3K/Akt pathways in HGF-treated liver cancer HepG2 cells. Hepatocyte growth factor (HGF), and its receptor, c-Met activation has recently been shown to play important roles in cancer invasion and metastasis in a wide variety of tumor cells. We use HGF as an invasive inducer of human HepG2 cells to investigate the effect of four flavones including apigenin, tricetin, tangeretin, and nobiletin on HGF/c-Met-mediated tumor invasion and metastasis. Among them, nobiletin markedly inhibited HGF-induced the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and transwell-chamber invasion/migration assay under non-cytotoxic concentrations. Data also showed nobiletin inhibited HGF-induced cell scattering and cytoskeleton changed such as filopodia and lamellipodia. Furthermore, nobiletin could inhibit HGF-induced the membrane localization of phosphorylated c-Met, ERK2, and Akt, but not phosphorylated JNK1/2 and p38. Next, nobiletin significantly decreased the levels of phospho-ERK2 and phospho-Akt in ERK2 or Akt siRNA-transfected cells concomitantly with a marked reduction on cell invasion and migration. In conclusion, nobiletin attenuates HGF-induced HepG2 cells metastasis involving both ERK and PI3K/Akt pathways and are potentially useful as anti-metastatic agents for the treatment of hepatoma. 23639188 Antiangiogenetic effects of anthranoids from Alternaria sp., an endophytic fungus in a Thai medicinal plant Erythrina variegata. Endophytic fungi are known as a prolific source for the discovery of structurally interesting and biologically active secondary metabolites, some of which are promising candidates for drug development. In the present study, three anthranoids were isolated from an Alternaria sp. endophytic fungus and evaluated for their antiangiogenic activity in a rat aortic sprouting assay, an ex vivo model of angiogenesis. Of these three compounds, altersolanol (2) was further characterized and found to show a promising activity in ex vivo, in vitro and in vivo angiogenesis asssays. Using human umbilical vein endothelial cells as an in vitro model, the angiogenic effect of 2 was found to occur via suppression of all three main functions of endothelial cells, namely proliferation, tube formation and migration. 23485991 A Rice Immunophilin Gene, OsFKBP16-3, Confers Tolerance to Environmental Stress in Arabidopsis and Rice. The putative thylakoid lumen immunophilin, FKBP16-3, has not yet been characterized, although this protein is known to be regulated by thioredoxin and possesses a well-conserved CxxxC motif in photosynthetic organisms. Here, we characterized rice OsFKBP16-3 and examined the role of this gene in the regulation of abiotic stress in plants. FKBP16-3s are well conserved in eukaryotic photosynthetic organisms, including the presence of a unique disulfide-forming CxxxC motif in their N-terminal regions. OsFKBP16-3 was mainly expressed in rice leaf tissues and was upregulated by various abiotic stresses, including salt, drought, high light, hydrogen peroxide, heat and methyl viologen. The chloroplast localization of OsFKBP16-3-GFP was confirmed through the transient expression of OsFKBP16-3 in Nicotiana benthamiana leaves. Transgenic Arabidopsis and transgenic rice plants that constitutively expressed OsFKBP16-3 exhibited increased tolerance to salinity, drought and oxidative stresses, but showed no change in growth or phenotype, compared with vector control plants, when grown under non-stressed conditions. This is the first report to demonstrate the potential role of FKBP16-3 in the environmental stress response, which may be regulated by a redox relay process in the thylakoid lumen, suggesting that artificial regulation of FKBP16-3 expression is a candidate for stress-tolerant crop breeding. 22876956 Nitrogen, oxygen or sulfur containing heterocyclic compounds as analgesic drugs used as modulators of the nitroxidative stress. Numerous lines of evidence suggest that heterocyclic compounds used as analgesic, anti-inflammatory and anti-migraine agents can be potent regulators of the nitroxidative stress and targeting free nitrogen and oxygen radicals is a very promising strategy for future pain management. Both classical analgesics (nonsteroidal anti-inflammatory drugs, opioid drugs) and many analgesic adjuvants, including desipramine, duloxetine, fluoxetine, paroxetine, escitalopram, phenytoin or carbamazepine and α-lipoic acid can modulate the balance between pro-oxidant and antioxidant processes in the mammalian tissues and these properties of drugs such as indomethacin, meloxicam, tenoxicam, valdecoxib or some metabolites of analgesic drugs formed by the activity of tissue peroxidases may contribute to their clinical efficacy and drug-related toxic effects, including gastrointestinal ulcers, hepatic failure, agranulocytosis, aplastic anemia, neutropenia, opiate-induced hyperalgesia and tolerance. The antioxidant capacities of novel heterocyclic compounds, including the compounds acting either by prevention of formation or catalyzed decomposition of peroxynitrite anion (ONOO-), namely the peroxynitrite decomposition catalysts or as superoxide (O2 •-)-scavengers which are the functional mimetics of superoxide dismutase (SOD) enzymes (SODm), as well as the derivatives of 6-nitro-3,4-methylenedioxyphenyl-Nacylhydrazone (LASSBio-881) or γ-butyrolactone (LPP1, BM113, BM113A, BM138 and BM138A) are also discussed as potent and promising future heterocyclic analgesics. 23298140 Honey as a source of dietary antioxidants: structures, bioavailability and evidence of protective effects against human chronic diseases. In the long human tradition honey has been used not only as a nutrient but also as a medicine. Its composition is rather variable and depends on the floral source and on external factors, such as seasonal, environmental conditions and processing. In this review, specific attention is focused on absorption, metabolism, and beneficial biological activities of honey compounds in human. Honey is a supersaturated solution of sugars, mainly composed of fructose (38%) and glucose (31%), containing also minerals, proteins, free amino acids, enzymes, vitamins and polyphenols. Among polyphenols, flavonoids are the most abundant and are closely related to its biological functions. Honey positively affects risk factors for cardiovascular diseases by inhibiting inflammation, improving endothelial function, as well as the plasma lipid profile, and increasing low-density lipoprotein resistance to oxidation. Honey also displays an important antitumoral capacity, where polyphenols again are considered responsible for its complementary and overlapping mechanisms of chemopreventive activity in multistage carcinogenesis, by inhibiting mutagenesis or inducing apoptosis. Moreover, honey positively modulates the glycemic response by reducing blood glucose, serum fructosamine or glycosylated hemoglobin concentrations and exerts antibacterial properties caused by its consistent amount of hydrogen peroxide and non-peroxide factors as flavonoids, methylglyoxal and defensin-1 peptide. In conclusion, the evidence of the biological actions of honey can be ascribed to its polyphenolic contents which, in turn, are usually associated to its antioxidant and anti-inflammatory actions, as well as to its cardiovascular, antiproliferative and antimicrobial benefits. 23060096 A sensitive H2O2 assay based on dumbbell-like PtPd-Fe3O4 nanoparticles. Dumbbell-like Pt(48)Pd(52)-Fe(3)O(4) nanoparticles are synthesized and functionalized with oleylamine-polyethyleneglycol to serve as an efficient catalyst for H(2)O(2) reduction and tetramethylbenzidine (TMB) oxidation in biological solutions. The Pt(48)Pd(52)-Fe(3)O(4)/TMB kit is even more active than the natural enzyme for H(2)O(2) detection with a detection limit reaching 2 μM, and is successfully used to quantitatively monitor the extracellular H(2)O(2) generated by neutrophils. 23340981 Effects of acute and sub-chronic nicotine on impulsive choice in rats in a probabilistic delay-discounting task. RATIONALE: Cigarette smokers typically display impulsivity by preferring immediate rewards over larger, delayed rewards at shorter delays than do non-smokers. Suggesting causality, nicotine injections in rats increase the choice for an immediate reward over a larger, delayed reward. OBJECTIVES: To examine the generality of this latter effect, the present study employed a delay-discounting task to determine if acute and sub-chronic nicotine will also increase impulsive choice when subjective reward value is manipulated by changes in the probability, rather than magnitude, of reward. MATERIALS AND METHODS: Rats were presented with two levers, one of which delivered an immediate water reward on half of the trials, while the other lever delivered the same reward on every trial, but only after one of five increasing delays. RESULTS: Acute injections of 1.2 mg/kg, but not 0.8 mg/kg, of nicotine increased the preference for the immediate (but less certain) reward lever at intermediate delays. Moreover, twice-daily injections of 0.8 mg/kg of nicotine for 6 days progressively increased the preference for the immediate reward. Latency to make the first response on each trial was not affected by nicotine. CONCLUSIONS: The similar increases in impulsive choice produced by both acute and sub-chronic nicotine in delay-discounting paradigms whether subjective reward value is manipulated by changes in reward magnitude or probability suggests that nicotine may be increasing what is common to these paradigms, namely delay discounting. Whatever the mechanism, these data indicate that both acute and sub-chronic nicotine may help develop and maintain an addiction by increasing impulsivity. 22809021 Live-birth rates after HP-hMG stimulation in the long GnRH agonist protocol: association with mid-follicular hCG and progesterone concentrations, but not with LH concentrations. The aim of this retrospective study was to investigate the impact of endogenous and exogenous luteinizing hormone (LH) activity on treatment outcome, when taking into consideration potential confounding variables. Data were derived from IVF patients (n = 358) stimulated with highly purified menotrophin (HP-hMG) in a long gonadotrophin-releasing hormone (GnRH) agonist protocol. Simple retrospective logistic regression analysis showed that the mid-follicular exogenous concentrations of human chorionic gonadotrophin (hCG) (p = 0.027), provided by the HP-hMG preparation, and female age (p = 0.009) were significantly associated with live-birth rate, while the mid-follicular progesterone concentration (p = 0.075), the estradiol concentration on last stimulation day (p = 0.075) and number of embryos transferred (p = 0.071) were borderline significant. Endogenous LH was not associated with live-birth rate; neither at start of stimulation (p = 0.123), nor in the mid-follicular phase (p = 0.933) or on the last day of stimulation (p = 0.589). In the multiple regression analysis of life birth, mid-follicular hCG (p = 0.016) was identified as a positive predictor, and age (p = 0.004) and mid-follicular progesterone (p = 0.029) as negative predictors. In conclusion, mid-follicular concentrations of exogenous hCG and progesterone, but not endogenous LH, are associated with live-birth rate in IVF patients treated with HP-hMG in a long GnRH agonist cycle. 23404443 Effects of induced hyperinsulinaemia with and without hyperglycaemia on measures of cardiac vagal control. AIMS/HYPOTHESIS: We examined the effects of serum insulin levels on vagal control over the heart and tested the hypothesis that higher fasting insulin levels are associated with lower vagal control. We also examined whether experimentally induced increases in insulin by beta cell secretagogues, including glucagon-like peptide-1 (GLP-1), will decrease vagal control. METHODS: Respiration and ECGs were recorded for 130 healthy participants undergoing clamps. Three variables of cardiac vagal effects (the root mean square of successive differences [rMSSD] in the interbeat interval of the heart rate [IBI], heart-rate variability [HRV] caused by peak-valley respiratory sinus arrhythmia [pvRSA], and high-frequency power [HF]) and heart rate (HR) were obtained at seven time points during the clamps, characterised by increasing levels of insulin (achieved by administering insulin plus glucose, glucose only, glucose and GLP-1, and glucose and GLP-1 combined with arginine). RESULTS: Serum insulin level was positively associated with HR at all time points during the clamps except the first-phase hyperglycaemic clamp. Insulin levels were negatively correlated with variables of vagal control, reaching significance for rMSSD and log(10)HF, but not for pvRSA, during the last four phases of the hyperglycaemic clamp (hyperglycaemic second phase, GLP-1 first and second phases, and arginine). These associations disappeared when adjusted for age, BMI and insulin sensitivity. Administration of the beta cell secretagogues GLP-1 and arginine led to a significant increase in HR, but this was not paired with a significant reduction in HRV measures. CONCLUSION/INTERPRETATION: Experimentally induced hyperinsulinaemia is not correlated with cardiac vagal control or HR when adjusting for age, BMI and insulin sensitivity index. Our findings suggest that exposure to a GLP-1 during hyperglycaemia leads to a small acute increase in HR but not to an acute decrease in cardiac vagal control. 23280997 Electrophoretic deposition of CdSe/ZnS quantum dots for light-emitting devices. The electrophoretic deposition of thin films of colloidal quantum dots is an alternative to spin-casting and printing for large-area, high-throughput processing of quantum-dot (QD) optoelectronics. In this study, QD light-emitting diodes (QD-LEDs) fabricated with electrophoretically deposited films of CdSe/ZnS core/shell QDs are demonstrated for the first time. 23097351 Antiulcerogenic activities of the extracts and isolated flavonoids of Euphorbia cuneata Vahl. The total alcohol extracts of Euphorbia cuneata Vahl.(Euphorbiaceae) were screened for antiulcerogenic activity using an ethanol-induced ulcer model at doses of 125, 250 and 500 mg/kg. The extracts possessed antiulcerogenic activity in a dose-dependent manner. Four flavonoidal compounds were isolated and identified as naringenin, aromadendrin, apigenin and 4'-O-methoxy-luteolin-7-O-rhamnoglucoside, each demonstrating antiulcerogenic activity with curative ratios ranging from 75.78% to 88.23%. In addition, the alcohol extracts and isolated compounds were shown to scavenge the 1,1-diphenyl,2-picrylhydrazyl radical by different ratio, with the most effective being 4'-O-methoxy-luteolin-7-O-rhamnoglucoside (91.14%). The antioxidant activity of the alcohol extracts and the isolated compounds may explain the antiulcerogenic properties. No side effects were observed on either liver or kidney functions. 23520132 Effects of Prior Intensive versus Conventional Therapy and History of Glycemia on Cardiac Function in Type 1 Diabetes in the DCCT/EDIC. Intensive diabetes therapy reduces the prevalence of coronary calcification and progression of atherosclerosis, and the risk of cardiovascular disease events in the DCCT/EDIC study. The effects of intensive therapy on measures of cardiac function and structure and their association with glycemia have not been explored in type 1 diabetes (T1DM). We assess whether intensive treatment compared to conventional treatment during the DCCT led to differences in these parameters during EDIC. After 6.5 years of intensive versus conventional therapy in the DCCT, and 15 years additional follow-up in EDIC, left ventricular indices were measured by cardiac magnetic resonance (CMR) imaging in 1017 of the 1371 members of the DCCT cohort. There were no differences between the DCCT intensive versus conventional treatment in end diastolic volume, end systolic volume, stroke volume, cardiac output, left ventricular mass, ejection fraction, LV mass/EDV, nor aortic distensibility. Mean DCCT/EDIC HbA1c over time was associated with EDV, SV, CO, LVmass, LVmass/EDV, and AD. These associations persisted after adjustment for CVD risk factors. Cardiac function and remodeling in T1DM assessed by CMR in the EDIC cohort was associated with prior glycemic exposure, but there was no effect of intensive versus conventional treatment during the DCCT on cardiac parameters. 23255384 Structural and stereochemical studies of hydroxyanthraquinone derivatives from the endophytic fungus Coniothyrium sp. Four known hydroxyanthraquinones (1-4) together with four new derivatives having a tetralone moiety, namely coniothyrinones A-D (5-8), were isolated from the culture of Coniothyrium sp., an endophytic fungus isolated from Salsola oppostifolia from Gomera in the Canary Islands. The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configurations of coniothyrinones A (5), B (6), and D (8) were determined by TDDFT calculations of CD spectra, allowing the determination of the absolute configuration of coniothyrinone C (7) as well. Coniothyrinones A (5), B (6), and D (8) could be used as ECD reference compounds in the determination of absolute configuration for related tetralone derivatives. This is the first report of anthraquinones and derivatives from an isolate of the genus Coniothyrium sp. These compounds showed inhibitory effects against the fungus Microbotryum violaceum, the alga Chlorella fusca, and the bacteria Escherichia coli and Bacillus megaterium. 23333639 Exposure to 1800 MHz radiofrequency electromagnetic radiation induces oxidative DNA base damage in a mouse spermatocyte-derived cell line. Whether exposure to radiofrequency electromagnetic radiation (RF-EMR) emitted from mobile phones can induce DNA damage in male germ cells remains unclear. In this study, we conducted a 24h intermittent exposure (5 min on and 10 min off) of a mouse spermatocyte-derived GC-2 cell line to 1800 MHz Global System for Mobile Communication (GSM) signals in GSM-Talk mode at specific absorption rates (SAR) of 1 W/kg, 2 W/kg or 4 W/kg. Subsequently, through the use of formamidopyrimidine DNA glycosylase (FPG) in a modified comet assay, we determined that the extent of DNA migration was significantly increased at a SAR of 4 W/kg. Flow cytometry analysis demonstrated that levels of the DNA adduct 8-oxoguanine (8-oxoG) were also increased at a SAR of 4 W/kg. These increases were concomitant with similar increases in the generation of reactive oxygen species (ROS); these phenomena were mitigated by co-treatment with the antioxidant α-tocopherol. However, no detectable DNA strand breakage was observed by the alkaline comet assay. Taking together, these findings may imply the novel possibility that RF-EMR with insufficient energy for the direct induction of DNA strand breaks may produce genotoxicity through oxidative DNA base damage in male germ cells. 23313245 Novel diaryl ureas with efficacy in a mouse model of malaria. Exploration of triclosan analogs has led to novel diaryl ureas with significant potency against in vitro cultures of drug-resistant and drug-sensitive strains of the human malaria parasite Plasmodium falciparum. Compound 18 demonstrated EC(50) values of 37 and 55 nM versus in vitro cultured parasite strains and promising in vivo efficacy in a Plasmodium berghei antimalarial mouse model, with >50% survival at day 31 post-treatment when administered subcutaneously at 256 mg/kg. This series of compounds provides a chemical scaffold of novel architecture, as validated by cheminformatics analysis, to pursue antimalarial drug discovery efforts. 23575765 Solution processed zinc oxide nanopyramid/silver nanowire transparent network films with highly tunable light scattering properties. Metal nanowire transparent networks are promising replacements to indium tin oxide (ITO) transparent electrodes for optoelectronic devices. While the transparency and sheet resistance are key metrics for transparent electrode performance, independent control of the film light scattering properties is important to developing multifunctional electrodes for improved photovoltaic absorption. Here we show that controlled incorporation of ZnO nanopyramids into a metal nanowire network film affords independent, highly tunable control of the scattering properties (haze) with minimal effects on the transparency and sheet resistance. Varying the zinc oxide/silver nanostructure ratios prior to spray deposition results in sheet resistances, transmission (600 nm), and haze (600 nm) of 6-30 Ω □(-1), 68-86%, and 34-66%, respectively. Incorporation of zinc oxide nanopyramid scattering agents into the conducting nanowire mesh has a negligible effect on mesh connectivity, providing a straightforward method of controlling electrode scattering properties. The decoupling of the film scattering power and electrical characteristics makes these films promising candidates for highly scattering transparent electrodes in optoelectronic devices and can be generalized to other metal nanowire films as well as carbon nanotube transparent electrodes. 22935104 In silico drug repositioning: what we need to know. Drug repositioning, exemplified by sildenafil and thalidomide, is a promising way to explore alternative indications for existing drugs. Recent research has shown that bioinformatics-based approaches have the potential to offer systematic insights into the complex relationships among drugs, targets and diseases necessary for successful repositioning. In this article, we propose the key bioinformatics steps essential for discovering valuable repositioning methods. The proposed steps (repurposing with a purpose, repurposing with a strategy and repurposing with confidence) are aimed at providing a repurposing pipeline, with particular focus on the proposed Drugs of New Indications (DNI) database, which can be used alongside currently available resources to improve in silico drug repositioning. 23086197 NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology. This is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2012 meeting in San Diego, California, on April 25, 2012. The symposium speakers summarized and critically evaluated our current understanding of the physiologic, pharmacological, and toxicological roles of NADPH-cytochrome P450 oxidoreductase (POR), a flavoprotein involved in electron transfer to microsomal cytochromes P450 (P450), cytochrome b(5), squalene mono-oxygenase, and heme oxygenase. Considerable insight has been derived from the development and characterization of mouse models with conditional Por deletion in particular tissues or partial suppression of POR expression in all tissues. Additional mouse models with global or conditional hepatic deletion of cytochrome b(5) are helping to clarify the P450 isoform- and substrate-specific influences of cytochrome b(5) on P450 electron transfer and catalytic function. This symposium also considered studies using siRNA to suppress POR expression in a hepatoma cell-culture model to explore the basis of the hepatic lipidosis phenotype observed in mice with conditional deletion of Por in liver. The symposium concluded with a strong translational perspective, relating the basic science of human POR structure and function to the impacts of POR genetic variation on human drug and steroid metabolism. 23153456 IFNα converts IL-22 into a cytokine efficiently activating STAT1 and its downstream targets. Besides their antiviral activity, type I Interferons (IFN) display context-specific immunomodulation. In contrast to long-known IFNα/β, Interleukin (IL)-22 is an anti-bacterial, largely tissue protective cytokine that recently gained attention. Herein, cellular IFNα/IL-22 interactions are investigated. We report that pre-conditioning of epithelial cells with IFNα initiated dramatic changes in IL-22 signaling normally dominated by signal transducer and activator of transcription (STAT)-3. Specifically, by using human DLD1 colon epithelial/carcinoma cells we demonstrate that, upon IFNα, IL-22 converts into a cytokine robustly activating STAT1 and its downstream pro-inflammatory targets CXCL9, CXCL10, and inducible nitric oxide synthase (iNOS). Accordingly, only after IFNα pre-incubation was IL-22-induced STAT1 binding to the CXCL10 promoter detectable. Using the viral mimic polyinosinic:polycytidylic acid and the IFNα/β antagonist B18R we furthermore demonstrate the capability of endogenous IFN to promote IL-22-induced STAT1 activation and expression of CXCL10. IL-22-induced STAT1 activation subsequent to IFNα priming became likewise apparent in human Caco2 colon epithelial/carcinoma cells, HepG2 hepatoma cells, and primary keratinocytes. Current observations may relate to characteristics of IFNα/β in clinical therapy and expose margins of tissue protection by IL-22 application. 23169387 Excited-state proton coupled charge transfer modulated by molecular structure and media polarization. Charge and proton transfer reactions in the excited states of organic dyes can be coupled in many different ways. Despite the complementarity of charges, they can occur on different time scales and in different directions of the molecular framework. In certain cases, excited-state equilibrium can be established between the charge-transfer and proton-transfer species. The interplay of these reactions can be modulated and even reversed by variations in dye molecular structures and changes of the surrounding media. With knowledge of the mechanisms of these processes, desired rates and directions can be achieved, and thus the multiple emission spectral features can be harnessed. These features have found versatile applications in a number of cutting-edge technological areas, particularly in fluorescence sensing and imaging. 23406469 Cell type determines the light-induced endosomal escape kinetics of multifunctional mesoporous silica nanoparticles. We investigated uptake and individual endosome lysis events in fibroblast, normal, and carcinoma cell lines using a colloidal mesoporous silica (CMS) nanoparticle (NP)-based reporter system with a covalently attached photosensitizer. Endosome lysis was induced through the activation of protoporphyrin IX (PpIX). Surprisingly, this release-on-demand system resulted in more broadly distributed lysis times than expected, particularly for Renca, a renal carcinoma cell line. An analysis of the NP load per endosome, endosome size, and uptake characteristics indicate that Renca cells not only take up a lower amount of NPs in comparison with the fibroblast cells but also have larger endosomes and a lower NP load per endosome. We then created a stochastic model detailing steps downstream of uptake to understand how much factors that cannot be directly measured, such as variations in the PpIX load per NP, affect the lysis time distributions. Model results indicate that the distributions are primarily determined by the endosome properties, rather than variations across NPs. 23268927 Association between beta cell function and future glycemic control in patients with type 2 diabetes. The aim of this study was to clarify the association between C-peptide immunoreactivity (CPR), a marker of beta cell function, and future glycemic control in patients with type 2 diabetes. We conducted a retrospective analysis of 513 consecutive patients with type 2 diabetes who were admitted to our hospital between 2000 and 2007 and followed up for 2 years. Serum and urinary CPR levels were measured during admission, and CPR index was calculated as the ratio of CPR to plasma glucose. The associations between these markers at baseline and glycemic control after 2 years were assessed by means of logistic regression models. After 2 years, 167 patients (32.6%) showed good glycemic control (HbA1c <6.9%). Baseline serum and urinary CPR indices were significantly associated with good glycemic control after 2 years, and the postprandial CPR to plasma glucose ratio (postprandial CPR index) showed the strongest association (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.12-1.50, P = 0.001) among CPR indices. Multivariate analyses showed consistent results (OR 1.23, 95%CI 1.03-1.48, P = 0.021). In conclusion, preserved beta cell function at baseline was associated with better glycemic control thereafter in patients with type 2 diabetes. 23259536 Photonic modulation of electron transfer with switchable phase inversion. Photochromes may be reversibly photoisomerized between two metastable states and their properties can influence, and be influenced by, other chromophores in the same molecule through energy or electron transfer. In the photochemically active molecular tetrad described here, a porphyrin has been covalently linked to a fullerene electron acceptor, a quinoline-derived dihydroindolizine photochrome, and a dithienylethene photochrome. The porphyrin first excited singlet state undergoes photoinduced electron transfer to the fullerene to generate a charge-separated state. The quantum yield of charge separation is modulated by the two photochromes: one isomer of each quenches the porphyrin excited state, reducing the quantum yield of electron transfer to near zero. Interestingly, when the molecule is illuminated with white light, the quantum yield decreases as the white light intensity is increased, generating an out-of-phase response of the quantum yield to white light. However, when the same experiment is performed in the presence of additional, steady-state UV illumination, a phase inversion occurs. The quantum yield of electron transfer now increases with increasing white light intensity. Such effects illustrate emergent complexity in a relatively simple system and could find applications in molecular logic, photochemical labeling and drug delivery, and photoprotection for artificial photosynthetic molecules. The photochemistry leading to this behavior is discussed. 23411183 Quality enhancement in refrigerated red drum (Sciaenops ocellatus) fillets using chitosan coatings containing natural preservatives. The present work was undertaken to examine the influence of grape seed extract (GS) and tea polyphenols (TP), as natural preservatives, combined with chitosan (Ch), on the quality of red drum (Sciaenops ocellatus) fillets during refrigerated storage. Two different treatments (Ch+GS and Ch+TP) and a control were prepared. The samples were stored (4 ± 1°C) for 20 days and the sampling was done at 0, 4, 8, 12, 16, 20 days. Microbiological, physicochemical and sensory attributes were periodically assessed. The results indicated that the two pretreatments could more effectively maintain quality and could extend the shelf life by 6-8 days compared with the control group during refrigerated storage. 23609109 Application of Medicinal Plants in Maternal Healthcare and Infertility: A South African Perspective. Plants have played significant roles as medicine during pregnancy, birth, and postpartum care in many rural areas of the world. In addition to this, plants have been used for centuries to treat infertility and related reproduction problems. The aim of this paper was to review the current status of plant species used in maternal healthcare, including infertility, in South Africa, in terms of scientific evaluation for efficacy and safety. In addition to this, the role of medicinal plants as a tool in achieving the MDG5 of reducing maternal mortality by 2015 was evaluated. A search was done with the aid of Google Scholar, PubMed, Science Direct, peer-reviewed papers, and books, using keywords such as child birth, labour pain, maternal health, maternal mortality, menstrual pains, and postpartum. The plants listed in the different research articles were classified according to their use and the target effect of a plant extract or compound on reproductive function. Eighty-four plant species were found to be used to treat infertility and related problems. Twenty plant species are used during pregnancy, while 26 plant species are used to ease childbirth. For postpartum healing and any problems after childbirth, nine plant species were recorded. Unhealthy pregnancy and birth complications are among the factors that contribute to the loss of cognitive potential in the developing world's children, condemning them to impoverished lives. The best way to keep a country poor is to rob its children of their full developmental potential. In this respect, medicinal plants play a significant role in reducing maternal mortality and ensuring the birth of healthy children. 23369344 Endothelium-dependent vasodilatation effects of the essential oil from Fructus alpiniae zerumbet (EOFAZ) on rat thoracic aortic rings in vitro. Fructus Alpiniae Zerumbet (FAZ) is an herb widely used to treat vascular disorders in Guizhou province, China, the essential oil has been identified as one of it vasodilation effect active components, and especial, the composition was significantly difference from the leaves. Vasodilation effects and mechanism of essential oil from FAZ (EOFAZ) were investigated. The EOFAZ showed significant vasodilation effect on endothelium-with rat thoracic aortic rings preincubated with norepinephrine (NE, 1.0μM) or KCl (60mM) in a concentration-dependent manner (1.14-72.96μg/ml). The non-selective nitric oxide synthase inhibitor l-NAME, as well as the soluble guanylate cyclase inhibitor MB, attenuated the relaxation of EOFAZ in endothelium-intact rat thoracic aortic rings. However, there were not significantly affected the vasodilation effects pretreated with cyclooxygenase inhibition by indomethacin (Indo) or β-noradrenergic inhibition by propranolol (Prop). The present results first demonstrated that vasodilation effect of EOFAZ depending upon the endothelium and concentration, and the mechanism involvement of NOS-cGMP system. In contrast, prostacyclin and β-adrenoceptor may not be associated with EOFAZ-induced vasorelaxation. 23458617 MDM2 Non-Genotoxic Inhibitors as Innovative Therapeutic Approaches for the Treatment of Pediatric Malignancies. Since the discovery of p53 as "guardian of the genome" , a large number of efforts have been put in place in order to find molecular strategies aiming to restore p53 wild-type functions, particularly in the light of the fact that its pathway results ineffective in most tumors even though they have non-mutated p53. In this context, pediatric cancers, that are mostly p53 wild-type at the time of diagnosis, represent an ideal target for such therapeutic approach. Within the several mechanisms and proteins ruling p53 activity, the murine double minute 2 (MDM2) is its crucial negative regulator, frequently found overexpressed in p53-wild-type tumors. The development of new technologies such as nuclear magnetic resonance structure analyses, computational structure-based design studies, and library peptides screening have recently led to the discovery and characterization of a large number of compounds belonging to different chemical families that are able to target the interaction p53-MDM2, rescuing the p53 wild-type pathway with an overall pro-apoptotic and anticancer activity. Within the preclinical assessment of these molecules, the cis-imidazoline analogue Nutlin-3 has definitely attracted great interest for its in vitro and in vivo antitumor activity in several pediatric cancer models, either as single agent on in combination with standard chemotherapy. In this light, the aim of this review is to summarize the main preclinical evidences of the potential of MDM2 inhibitors for the treatment of childhood cancers and the key suggestions coming from their assessment in the treatment of adult cancers as proof of concept for future pediatric clinical studies. 23243659 Sponge-like Ni(OH)2-NiF2 composite film with excellent electrochemical performance. Sponge-like porous Ni(OH)(2)-NiF(2) composite (PNC) film was successfully synthesized by the anodization of nickel in a NH(4)F and H(3)PO(4) containing electrolyte. Thanks to the good conductivity and the highly porous architecture, PNC exhibited not only a high specific capacitance, but also a superior rate capability and a good cyclability (2090 F g(-1) at 10 mV s(-1), capacitance >1200 F g(-1) at 100 A g(-1) after 2000 cycles). Anodization of nickel is proven to be fast and facile and can be easily scaled up. The method described here is promising for the fabrication of supercapacitor electrodes with excellent performance. 23313638 Total synthesis of bicyclic depsipeptides spiruchostatins C and D and investigation of their histone deacetylase inhibitory and antiproliferative activities. The bicyclic depsipeptide histone deacetylase (HDAC) inhibitors spiruchostatins C and D were synthesized for the first time in a highly convergent and unified manner. The method features the amide coupling of a D-leucine-D-cysteine- or D-valine-D-cysteine-containing segment with a D-alanine- or D-valine-containing segment to directly assemble the corresponding seco-acids, key precursors of macrolactonization. The HDAC inhibitory assay and cell-growth inhibition analysis of the synthesized depsipeptides determined the order of potency of spiruchostatins A-D in comparison with the clinically approved depsipeptide FK228 (romidepsin). Novel aspects of structure-activity relationships (SAR) were revealed. 23426982 Theoretical Study on the Photodegradation Mechanism of Nona-BDEs in Methanol. Polybrominated diphenyl ethers (PBDEs) have received special environmental concern due to their potential toxicity to humans and wildlife worldwide, however, it is difficult to reveal their dominant photochemical degradation pathways by experiment. We explored the reaction mechanisms of photochemical degradation-debromination of three nona-BDEs in methanol using theoretical calculations, in which time-dependent density functional theory (TDDFT) combined with the polarizable continuum (PCM) model is applied. The selectivity of debromination was studied, and the major octa-BDE products photochemically debrominated from nona-BDEs were identified. We find that the debromination reaction results from the electronic transitions from π to σ* orbitals when nona-BDEs are exposed to UV-light in the sunlight region, at which point the two low-lying excited states for each nona-BDE are πσ*(5Br) and πσ*(4Br), which correlate to the σ* orbitals located on the penta-Br and tetra-Br substituted phenyls, respectively. Our calculations indicate that each nona-BDE may degrade to form three kinds of octa-BDE products via the πσ*(5Br) state, whereas only one kind of octa-BDEs can be formed via the πσ*(4Br) state. Our calculations can interpret the recent experiments successfully. 23209192 Cotinine in human placenta predicts induction of gene expression in fetal tissues. Maternal cigarette smoking during pregnancy is associated with increased risk of perinatal morbidity and mortality. However, the mechanisms underlying adverse birth outcomes following prenatal exposure to cigarette smoke remain unknown due, in part, to the absence or unreliability of information regarding maternal cigarette smoke exposure during pregnancy. Our goal was to determine if placental cotinine could be a reliable biomarker of fetal cigarette smoke exposure during pregnancy. Cotinine levels were determined in placentas from 47 women who reported smoking during pregnancy and from 10 women who denied cigarette smoke exposure. Cotinine levels were significantly higher in placentas from women reporting cigarette smoking (median = 27.2 ng/g) versus women who reported no smoke exposure (2.3 ng/g, P < 0.001). Receiver operating characteristic curve analysis identified an optimal cut point of 7.5 ng/g (sensitivity = 78.7%, specificity = 100%) to classify placenta samples from mothers who smoked versus those from mothers who did not. Among 415 placentas for which maternal cigarette smoking status was unavailable, 167 had cotinine levels > 7.5 ng/g and would be considered positive for cigarette smoke exposure. Data from quantitative reverse-transcription polymerase chain reaction analyses demonstrated that in utero cigarette smoke exposure predicted by cotinine in placenta is associated with changes in the expression of xenobiotic-metabolizing enzymes in fetal tissues. CYP1A1 mRNA in fetal lung and liver tissue and CYP1B1 mRNA in fetal lung tissue were significantly induced when cotinine was detected in placenta. These findings indicate that cotinine in placenta is a reliable biomarker for fetal exposure and response to maternal cigarette smoking during pregnancy. 23384446 The effect of inorganic arsenic on endothelium-dependent relaxation: Role of NADPH oxidase and hydrogen peroxide. Chronic arsenic ingestion predisposes to vascular disease, but underlying mechanisms are poorly understood. In the present study we have analyzed the effects of short-term arsenite exposure on vascular function and endothelium-dependent relaxation. Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the G protein-coupled receptor agonist acetylcholine (ACh) and by cyclopiazonic acid (CPA), which promotes store-operated Ca(2+) entry by inhibiting the endothelial SERCA pump. Production of reactive oxygen species (ROS) in the endothelium of rabbit aortic valve leaflets and endothelium-denuded RIA and aortic rings was assessed by imaging of dihydroethidium. In the iliac artery, exposure to 100μM arsenite for 30min potentiated EDHF-type relaxations evoked by both CPA and ACh. Potentiation was prevented by catalase, the catalase/superoxide dismutase mimetic manganese porphyrin and the NADPH oxidase inhibitor apocynin. By contrast in aortic rings, that exhibited negligible EDHF-type responses, endothelium-dependent NO-mediated relaxations evoked by CPA and ACh were unaffected by arsenite. Arsenite induced apocynin-sensitive increases in ROS production in the aortic valve endothelium, but not in the media and adventitia of the iliac artery and aorta. Our results suggest that arsenite can potentiate EDHF-type relaxations via a mechanism that is dependent on hydrogen peroxide, thus demonstrating that dismutation of the superoxide anion generated by NADPH oxidase can potentially offset loss of NO bioavailability under conditions of reduced eNOS activity. By contrast, selective increases in endothelial ROS production following exposure to arsenite failed to modify relaxations mediated by endogenous NO. 23122116 Quantitative analysis of fungicide azoxystrobin in agricultural samples with rapid, simple and reliable monoclonal immunoassay. This work presents analytical performance of a kit-based direct competitive enzyme-linked immunosorbent assay (dc-ELISA) for azoxystrobin detection in agricultural products. The dc-ELISA was sufficiently sensitive for analysis of residue levels close to the maximum residue limits. The dc-ELISA did not show cross-reactivity to other strobilurin analogues. Absorbance decreased with the increase of methanol concentration in sample solution from 2% to 40%, while the standard curve became most linear when the sample solution contained 10% methanol. Agricultural samples were extracted with methanol, and the extracts were diluted with water to 10% methanol adequate. No significant matrix interference was observed. Satisfying recovery was found for all of spiked samples and the results were well agreed with the analysis with liquid chromatography. These results clearly indicate that the kit-based dc-ELISA is suitable for the rapid, simple, quantitative and reliable determination of the fungicide. 23495161 Two novel potent α-amylase inhibitors from the family of acarviostatins isolated from the culture of Streptomyces coelicoflavus ZG0656. Two novel aminooligosaccharides were separated from the culture filtrate of Streptomyces coelicoflavus ZG0656. Their chemical structures were determined by acidic hydrolysis, electrospray-ionization tandem mass spectrometry (ESI-MS/MS), and NMR spectroscopy. The compounds were named acarviostatins III0(-1) and III23 according to the nomenclature of this group of metabolites. The two novel acarviostatins were both mixed noncompetitive inhibitors of porcine pancreatic α-amylase (PPA). The inhibition constants (K(i)) for acarviostatins III0(-1) and III23 were 0.009 and 0.026 μM, respectively, 151 and 52 times more potent than acarbose. 23266731 Wound-healing plants from TCM: in vitro investigations on selected TCM plants and their influence on human dermal fibroblasts and keratinocytes. Wound-healing plants from Traditional Chinese Medicine and described for wound healing in the Pharmacopoeia of People's Republic of China (2005 ed.) were investigated by in vitro bioassay on human skin cells. Therefore water and EtOH-water extracts (6:4, v/v) from 12 plants were tested on human primary dermal fibroblasts (pNHDF) and human HaCaT keratinocyte cell line by quantification of cell viability (MTT assay) and cellular proliferation (BrdU incorporation ELISA). No functional activity was found for extracts from Achyranthis bidentatae rhizoma, Cimicifugae rhizoma, Corydalis rhizoma, Gardeniae fructus, Houttuyniae herba, Lonicerae japonicae caulis, Paeoniae rubrae radix and Rehmanniae radix. Extracts from Notoginseng radix et rhizoma, Angelicae sinensis radix and Lonicerae japonicae flos showed moderate activity, while extracts from Moutan cortex (the root bark of Paeonia suffruticosa Andr., Ranunculaceae) increased cell viability of HaCaT keratinocytes and pNHDF in a dose-dependent manner significantly. Bioassay-guided fractionation yielded paeonol 1, the flavan-3-ols catechin 2 and epicatechin-3-O-gallate 3, the dimeric proanthocyanidin epicatechin-(4β→8)-catechin 4, a mixture of trigalloyl-glucoses 5 and 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG) 6. The proanthocyanidin-containing fractions as well as PGG-containing fractions contributed substantially to the stimulating effects. Especially PGG-containing fractions enhanced cell viability and cellular proliferation of HaCaT keratinocytes at concentration of 100nM. From these data we conclude that indication claims for TCM herbal materials must be carefully investigated in order to establish evidence-driven use of such plants. In case of Moutan cortex skin cell stimulating effects have clearly been proven. These effects can be related to the polyphenol fractions of condensed and hydrolysable tannins. 23380082 Use of the Combination Index to determine interactions between plant-derived phenolic acids on hepatotoxicity endpoints in human and rat hepatoma cells. The beneficial or adverse effects of isolated phytochemicals are not always concordant with effects of the botanical dietary supplements from which they were derived. This disparity could be due to interactions between the various phytochemicals present in the whole plant. The phenolic acids, rosmarinic acid (RA), caffeic acid (CA) and ferulic acid (FA) are widely present in foods and dietary supplements, and they are assumed to exert various beneficial biological effects. However, there is little data on the potential biological interactions of these three phenolic acids which commonly occur together and are linked metabolically. In the present study, liver toxicity of the three phenolic acids was assessed on the three compounds singly and in various binary and one ternary combinations. A series of in vitro endpoints relevant to liver toxicity were evaluated in both a human (HepG2/C3A) and rat (MH1C1) hepatocyte cell line. The Combination Index (CI) was calculated for each endpoint from both the concentration responses of the single compounds and the responses of the various binary and ternary mixtures. Both synergistic and antagonistic interactions were observed for some endpoints and some combinations of test agents. Interactions were most prevalent in measures of oxidative stress and cytochrome P450 activities in both cell types. There was only a 53% concordance between the rat and human cells which may be suggestive of species differences. The data suggest an approach for better characterizing the beneficial or adverse effects of complex botanical products through evaluation of interactions between individual phytochemical components. 23266452 N-acetylgalactosamine functionalized mixed micellar nanoparticles for targeted delivery of siRNA to liver. Due to its efficient and specific gene silencing ability, RNA interference has shown great potential in the treatment of liver diseases. However, achieving in vivo delivery of siRNA to critical liver cells remains the biggest obstacle for this technique to be a real clinic therapeutic modality. Here, we describe a promising liver targeting siRNA delivery system based on N-acetylgalactosamine functionalized mixed micellar nanoparticles (Gal-MNP), which can efficiently deliver siRNA to hepatocytes and silence the target gene expression after systemic administration. The Gal-MNP were assembled in aqueous solution from mixed N-acetylgalactosamine functionalized poly(ethylene glycol)-b-poly(ε-caprolactone) and cationic poly(ε-caprolactone)-b-poly(2-aminoethyl ethylene phosphate) (PCL-b-PPEEA); the properties of nanoparticles, including particle size, zeta potential and the density of poly(ethylene glycol) could be easily regulated. The hepatocyte-targeting effect of Gal-MNP was demonstrated by significant enriching of fluorescent siRNA in primary hepatocytes in vitro and in vivo. Successful down-regulation of liver-specific apolipoprotein B (apoB) expression was achieved in mouse liver, at both the transcriptional and protein level, following intravenous injection of Gal-MNP/siapoB to BALB/c mice. Systemic delivery of Gal-MNP/siRNA did not induce the innate immune response or positive hepatotoxicity. The results of this study suggested therapeutic potential for the Gal-MNP/siRNA system in liver disease. 23282101 Catalytic enantioselective cyclization and C3-fluorination of polyenes. (Xylyl-phanephos)Pt(2+) in combination with XeF(2) mediates the consecutive diastereoselective cation-olefin cyclization/fluorination of polyene substrates. Isolated yields were typically in the 60-69% range while enantioselectivities reached as high as 87%. The data are consistent with a stereoretentive fluorination of a P(2)Pt-alkyl cation intermediate. 23287056 Synthesis and biological evaluation of new N-alkylcarbazole derivatives as STAT3 inhibitors: preliminary study. The signalling pathway of Janus tyrosine Kinases-Signal Transducers and Activators of Transcription (JAK-STAT) is activated by a number of cytokines, hormones (GH, erythropoietin and prolactin), and growth factors. JAK-STAT signalling is involved in regulation of cell proliferation, differentiation and apoptosis. These activities are due to different members of JAK-STAT family consisting of: JAK1, JAK2, JAK3, Tyk2 and STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6. Recent studies suggest a key role for STAT family proteins, in particular for STAT3, in selectively inducing and maintaining a pro-carcinogenic inflammatory microenvironment, that promote tumour cells transformation. Moreover, a striking correlation between cancer development/progression and STAT3 persistent activation exists, probably due to STAT3 promoting of the pro-oncogenic inflammatory pathways, like NF-kB, IL-6 and JAK family kinases. Recent study demonstrated that carbazoles can inhibit STAT3 mediated transcription. From these evidences, STAT3 represents a therapeutic target, so we have synthesized a new set of N-alkylcarbazole derivatives substituted in positions 2, 4 and 6, to evaluate their activity on STAT3. Some of these compounds showed an interesting activity as STAT3 selective inhibitors; in particular, compounds 9a 9b and 9c revealed to inhibit the STAT3 activation for the 50%, 90% and 95%, respectively. 23343172 Size-matching effect on inorganic nanosheets: control of distance, alignment, and orientation of molecular adsorption as a bottom-up methodology for nanomaterials. We have been investigating complexes composed of nanolayered materials with anionic charges such as clay nanosheets and dye molecules such as cationic porphyrins. It was found that the structure of dye assembly on the layered materials can be effectively controlled by the use of electrostatic host-guest interaction. The intermolecular distance, the molecular orientation angle, the segregation/integration behavior, and the immobilization strength of the dyes can be controlled in the clay-dye complexes. The mechanism to control these structural factors has been discussed and was established as a size-matching effect. Unique photochemical reactions such as energy transfer through the use of this methodology have been examined. Almost 100% efficiency of the energy-transfer reaction was achieved in the clay-porphyrin complexes as a typical example for an artificial light-harvesting system. Control of the molecular orientation angle is found to be useful in regulating the energy-transfer efficiency and in preparing photofunctional materials exhibiting solvatochromic behavior. Through our study, clay minerals turned out to serve as protein-like media to control the molecular position, modify the properties of the molecule, and provide a unique environment for chemical reactions. 23330542 PXR antagonists and implication in drug metabolism. Adopted orphan nuclear receptor (NR), pregnane X receptor (PXR), plays a central role in the regulation of xeno- and endobiotic metabolism. Since the discovery of the functional role of PXR in 1998, there is evolving evidence for the role of PXR agonists in abrogating metabolic pathophysiology (e.g., cholestasis, hypercholesterolemia, and inflammation). However, more recently, it is clear that PXR is also an important mediator of adverse xeno- (e.g., enhances acetaminophen toxicity) and endobiotic (e.g., hepatic steatosis) metabolic phenotypes. Moreover, in cancer therapeutics, PXR activation can induce drug resistance, and there is growing evidence for tissue-specific enhancement of the malignant phenotype. Thus, in these instances, there may be a role for PXR antagonists. However, as opposed to the discovery efforts for PXR agonists, there are only a few antagonists described. The mode of action of these antagonists (e.g., sulforaphane) remains less clear. Our laboratory efforts have focused on this question. Since the original discovery of azoles analogs as PXR antagonists, we have preliminarily defined an important PXR antagonist pharmacophore and developed less-toxic PXR antagonists. In this review, we describe our published and unpublished findings on recent structure-function studies involving the azole chemical scaffold. Further work in the future is needed to fully define potent, more-selective PXR antagonists that may be useful in clinical application. 23562270 Social information signaling by neurons in primate striatum. Social decisions depend on reliable information about others. Consequently, social primates are motivated to acquire information about the identity, social status, and reproductive quality of others [1]. Neurophysiological [2] and neuroimaging [3, 4] studies implicate the striatum in the motivational control of behavior. Neuroimaging studies specifically implicate the ventromedial striatum in signaling motivational aspects of social interaction [5]. Despite this evidence, precisely how striatal neurons encode social information remains unknown. Therefore, we probed the activity of single striatal neurons in monkeys choosing between visual social information at the potential expense of fluid reward. We show for the first time that a population of neurons located primarily in medial striatum selectively signals social information. Surprisingly, representation of social information was unrelated to simultaneously expressed social preferences. A largely nonoverlapping population of neurons that was not restricted to the medial striatum signaled information about fluid reward. Our findings demonstrate that information about social context and nutritive reward are maintained largely independently in striatum, even when both influence decisions to execute a single action. 22834411 The alignment of barium ferrite nanoparticles from their suspensions in electric and magnetic fields. The alignment of plate-like barium ferrite nanoparticles, with diameters of 10-350 nm and thicknesses of 3-10 nm, in electric and/or magnetic fields was studied. Stable suspensions were prepared in 1-butanol with dodecylbenzenesulphonic acid as a surfactant. The deposits were produced from the suspensions with classic electrophoretic deposition, electrophoretic deposition in a magnetic field, and with drying in a magnetic field. The experiments, supported by theoretical calculations, show that the alignment of the nanoplates in the deposits was determined by the interplay between the hydrodynamic, electric, and magnetic forces. The preferential alignment of the nanoplates in plane with the substrate coincided with their magnetic orientation, and it increased with the shape anisotropy of the particles. The deposits were sintered at 1150 °C for 5 h to obtain ceramic films, which showed a magnetic orientation up to 90%. 23443405 Low temperature solution-processed high performance photodiode based on Si-ZnO core-shell structure. Radial heterojunction photodiodes based on a silicon nanowire arrays (SiNWs)-zinc oxide (ZnO) core-shell structure is demonstrated in this report. The heterojunction can be constructed by spin-coating ZnO nanoparticles onto SiNWs and a low temperature post-annealing process (<270 °C). The photodiode displays typical diode rectifying characteristics with an ideality factor of as low as 1.28, and shows an excellent photoresponse in both visible and near infrared regions in which a peak value of 0.54 A/W at zero bias was attained. The sensitivity is superior to that of previously reported devices fabricated with vacuum-deposition methods. In contrast, the planar silicon-ZnO junction only displays the peak photoresponsivity of 0.34 A/W. The superior performance of radial junction is ascribed to the highlight-harvesting capability, large interfacial area and efficient charge carrier collection arising from the core (SiNWs)-shell (ZnO) structure. Here, high temperature processes are dispensable by using facile solution-processed techniques, which avoid thermal minority lifetime degradation of silicon and simplify the fabrication process of the photodiodes. 23200004 Determination of mercury in rice by MSFIA and cold vapour atomic fluorescence spectrometry. In the present paper the use of a MSFIA system for determination of mercury in rice by cold vapour atomic fluorescence spectrometry (CV AFS) is proposed. The sample digestion is performed in a microwave oven using nitric acid and hydrogen peroxide. The experimental conditions for vapour generation were determined using a full two-level factorial design involving the following factors: nitric acid and tin chloride concentrations and sample flow rate. Employing the conditions optimised, the method allows the determination of mercury using the external calibration technique with aqueous standards. The reached limits of detection and quantification were 0.48 and 1.61 ng g⁻¹ respectively, and the precision (as relative standard deviation) was 3.28% and 1.56% for rice samples with a mercury content of 3.63 and 5.81 ng g⁻¹, respectively. The method accuracy was confirmed analysing a certified reference material of rice flour furnished by National Institute of Standard and Technology. The interference of nitrous acid and nitrous oxides are removed using potassium dichromate. The method was applied to mercury determination in twelve rice samples acquired in Palma de Mallorca (Spain) between the months of January and April of 2012. The mercury content found varied from 2.15 to 7.25 ng g⁻¹. These results agree with those reported by others authors. 23256723 Effect of rehabilitative exercise training on peripheral muscle remodelling in patients with COPD: targeting beyond the lungs. Locomotor muscle dysfunction and weakness are frequently observed in patients with Chronic Obstructive Pulmonary Disease (COPD). In addition to intolerable sensations of dyspnoea which importantly contribute to exercise limitation, intrinsic muscle abnormalities have also been implicated in inducing leg muscle fatigue/discomfort during exercise in these patients. It is, however, uncertain whether these intrinsic muscle abnormalities are linked to a specific 'myopathy' or they constitute a consequence of the disease. Besides muscle disuse, other factors which may contribute to peripheral muscle dysfunction include systemic inflammation, oxidative and nitrosative stress, chronic hypoxia, corticosteroid use and malnutrition. There is clear evidence that rehabilitative exercise training induces significant skeletal muscle fibre remodelling and improvements in functionality in the absence of changes in lung function. The ultimate purpose of this review is to identify and summarize the results of studies implementing diverse types of exercise training on peripheral muscle fibre phenotypic and genotypic modifications in patients with COPD. 23010164 The long road of research on snake venom serine proteinases. It has long been recognized that snake venom serine proteinases (SVSPs) affect various physiological functions including blood coagulation, fibrinolysis, blood pressure and platelet aggregation. Therefore, SVSPs have been used as refined tools to study molecular mechanisms involved in the activation of key factors that control hemostasis and as therapeutic agents in various thrombotic and hemostatic conditions. The aim of this review is to highlight the state of our knowledge on the advances made in SVSP research since the 18th century. It includes the personal accounts of some distinguished scientists that addressed specific problems and contributed to advance the field. 23237533 Magnetic assembly and patterning of general nanoscale materials through nonmagnetic templates. Applied magnetic field represents an effective tool to rapidly assemble micro- and nanoscale magnetic objects into defined structures. Ordered assembly is typically achieved by using magnetic micropatterns, for which the downside is that they require advanced microfabrication techniques to produce. In addition, most conventional magnetic assembly strategies are restricted to target objects that possess magnetic properties. Herein we present a general strategy that allows convenient magnetically driven assembly of nonmagnetic objects in defined locations with high spatial resolution. The process involves immersing a polymer relief pattern in a uniformly magnetized ferrofluid, which modulates the local magnetic fields around the pattern. Nonmagnetic target objects dispersed in the same ferrofluid can then be magnetically assembled at positions defined by the polymer pattern. As the nonmagnetic polymer patterns can be conveniently fabricated at low cost through photolithography and soft-lithography processes, our method provides a general yet very effective means to assemble a wide range of nonmagnetic objects with controlled spatial distribution, paving the way toward patterning functional microstructures. 23333716 Antibacterial activity of Veronica montana L. extract and of protocatechuic acid incorporated in a food system. This study was designed to evaluate the antibacterial activity of the Veronica montana L. water extract and its main phenolic compound, protocatechuic acid. The antibacterial activity was determined by microdilution assay against six strains of Gram-positive and Gram-negative bacteria. Listeria monocytogenes was the most sensitive of the tested bacterial species. Antibacterial preserving properties of protocatechuic acid were also evaluated after its incorporation in cream cheese, using L. monocytogenes as commonly cheese contaminant. The compound successfully inhibited L. monocytogenes development in cream cheese, at room temperature and in refrigerator (25°C and 4°C, respectively), after 3days of inoculation. Sensory evaluation was carried out in order to validate the mentioned food system. A possible mode of action of the tested compound towards bacterial cells was assessed and appears to be direct lysis of pathogenic cytoplasmic membrane. Prediction of pharmacokinetic properties was also performed using computational analyzes. The obtained results can serve as an important platform for the development of effective natural preservatives. 23602732 In vitro and in vivo safety evaluation of Acer tegmentosum. ETHNOPHARMACOLOGICAL RELEVANCE: Acer tegmentosum, which contains salidroside and tyrosol, has been used for the treatment of hepatic disorders in eastern Asia. However, little is known about its safety. AIM OF THE STUDY: To determine the safety of Acer tegmentosum, we evaluated its acute oral toxicity and genotoxicity profiles. MATERIALS AND METHODS: Salidroside and tyrosol present in Acer tegmentosum were quantified using high-performance liquid chromatography. Acute oral toxicity testing of Acer tegmentosum was performed in rats. Genotoxicity of Acer tegmentosum was assessed by bacterial reverse mutation, chromosomal aberration, and bone marrow micronucleus tests. All the tests were conducted in accordance with the good laboratory practices. RESULTS: The amounts of salidroside and tyrosol in Acer tegmentosum were found to be 85.01±1.21mg/g and 3.12±0.04mg/g, respectively. In the bacterial reverse mutation test, Acer tegmentosum increased the number of revertant Salmonella typhimurium TA98 colonies, regardless of metabolic activation by S9 mixture. In contrast, Acer tegmentosum application did not significantly increase the number of chromosomal aberrations in Chinese hamster ovary (CHO)-K1 cells and micronucleated polychromatic erythrocytes in mice. In the acute oral toxicity test, the median lethal dose (LD50) of Acer tegmentosum was found to be >2000mg/kg in rats. CONCLUSION: Take together, Acer tegmentosum exhibits mutagenicity, which was evident from the bacterial reverse mutation test. Further studies are needed to identify the components responsible for such an effect and the underlying mechanisms. 23526745 The Mechanisms of Radical SAM/Cobalamin Methylations: An Evolving Working Hypothesis. All about Me: Pierre and co-workers have revealed mechanistic details of a tryptophan methyltransferase (TsrM) involved in the biosynthesis of the thiopeptide antibiotic, thiostrepton. Utilising cobalamin and a [4Fe-4S] cluster to generate 2-methyltryptophan from tryptophan, a key difference between this enzyme and other radical SAM methyltransferases is that the reaction is not initiated by a single-electron reduction of SAM to generate 5'-dA⋅. 23585380 Dual Growth Factor Delivery Using Biocompatible Core-Shell Microcapsules for Angiogenesis. An optimized electrodropping system produces homogeneous core-shell microcapsules (C-S MCs) by using poly(L-lactic-co-glycolic acid) (PLGA) and alginate. Fluorescence imaging clearly shows the C-S domain in the MC. For release control, the use of high-molecular-weight PLGA (HMW 270 000) restrains the initial burst release of protein compared to that of low-MW PLGA (LMW 40 000). Layer-by-layer (LBL) assembly of chitosan and alginate on MCs is also useful in controlling the release profile of biomolecules. LBL (7-layer) treatment is effective in suppressing the initial burst release of protein compared to no LBL (0-layer). The difference of cumulative albumin release between HMW (7-layer LBL) and LMW (0-layer LBL) PLGA is determined to be more than 40% on day 5. When dual angiogenic growth factors (GFs), such as platelet-derived GF (PDGF) and vascular endothelial GF (VEGF), are encapsulated separately in the core and shell domains, respectively, the VEGF release rate is much greater than that of PDGF, and the difference of the cumulative release percentage between the two GFs is about 30% on day 7 with LMW core PLGA and more than 45% with HMW core PLGA. As for the angiogenic potential of MC GFs with human umbilical vein endothelial cells (HUVECs), the fluorescence signal of CD31+ suggests that the angiogenic sprout of ECs is more active in MC-mediated GF delivery than conventional GF delivery, and this difference is significant, based on the number of capillary branches in the unit area. This study demonstrates that the fabrication of biocompatible C-S MCs is possible, and that the release control of biomolecules is adjustable. Furthermore, MC-mediated GFs remain in an active form and can upregulate the angiogenic activity of ECs. 23560844 Metal-dependent protein phosphatase 1A functions as an extracellular signal-regulated kinase phosphatase. Protein phosphorylation is an important post-translational modification that regulates almost every aspect of signal transduction in cells. Activation of the mitogen-activated protein kinase (MAPK) family kinase extracellular signal-regulated kinase (ERK) is a point of convergence for many cellular activities in response to external stimulation. With stimuli, ERK activity is significantly increased by the phosphorylation of Thr202 and Tyr204 at its activation loop. Downregulation of ERK phosphorylation at these two sites by several phosphatases, such as protein phosphatase 2A, HePTP and MAPK phosphatase 3, is essential for maintaining appropriate ERK function in different cellular processes. However, it is unknown whether metal-dependent protein phosphatase (PPM) family phosphatases directly dephosphorylate ERK. In this study, we found that PPM1A negatively regulated ERK by directly dephosphorylating its pThr202 position early in EGF stimulation. Additional kinetic studies revealed that key residues participated in phospho-ERK recognition by PPM1A. Importantly, PPM1A preferred the phospho-ERK peptide sequence over a panel of other phosphopeptides through the interactions of basic residues in the active site of PPM1A with the pThr-Glu-pTyr motif of ERK. Whereas Lys165 and Arg33 were required for efficient catalysis or phosphosubstrate binding of PPM1A, Gln185 and Arg186 were determinants of PPM1A substrate specificity. The interaction between Arg186 of PPM1A and Glu203 and pTyr204 of phospho-ERK was identified as a hot-spot for phospho-ERK-PPM1A interaction. STRUCTURED DIGITAL ABSTRACT: PPM1A physically interacts with ERK2 by pull down (View interaction) PPM1A dephosphorylates p38 by phosphatase assay (View Interaction: 1, 2) PPM1A binds to ERK2 by pull down (View interaction) PPM1A dephosphorylates ERK2 by phosphatase assay (View Interaction: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20). 23396041 Dissolved azaspiracids are absorbed and metabolized by blue mussels (Mytilus edulis). The relationship between azaspiracid shellfish poisoning and a small dinoflagellate, Azadinium spinosum, has been shown recently. The organism produces AZA1 and -2, while AZA3 and other analogues are metabolic products formed in shellfish. We evaluated whether mussels were capable of accumulating dissolved AZA1 and -2, and compared the toxin profiles of these mussels at 24 h with profiles of those exposed to live or lysed A. spinosum. We also assessed the possibility of preparative production of AZA metabolites by exposing mussels to semi-purified AZA1. We exposed mussels to similar concentration of AZAs: dissolved AZA1 + 2 (crude extract) at 7.5 and 0.75 μg L(-1), dissolved AZA1+2 (7.5 μg L(-1)) in combination with Isochrysis affinis galbana, and lysed and live A. spinosum cells at 1 × 10(5) and 1 × 10(4) cell mL(-1) (containing equivalent amounts of AZA1 + 2). Subsequently, we dissected and analysed digestive glands, gills and remaining flesh. Mussels (whole flesh) accumulated AZAs to levels above the regulatory limit, except at the lower levels of dissolved AZAs. The toxin profile of the mussels varied significantly with treatment. The gills contained 42-46% and the digestive glands 23-24% of the total toxin load using dissolved AZAs, compared to 3-12% and 75-90%, respectively, in mussels exposed to live A. spinosum. Exposure of mussels to semi-purified AZA1 produced the metabolites AZA17 (16.5%) and AZA3 (1.7%) after 4 days of exposure, but the conversion efficiency was too low to justify using this procedure for preparative isolation. 23612421 Urinary metabonomic study of the surface layer of poria cocos as an effective treatment for chronic renal injury in rats. ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos Wolf (Polyporaceae) is a well-known medicinal fungus. the epidermis of the sclerotia ("Fu-Ling-Pi" in Chinese) is used as a diuretic and traditionally used for promoting urination and reduce edema. AIM OF THE STUDY: Traditional Chinese medicines (TCM) treat many diseases through multi-components, multi-ways and multi-targets. However, the molecular mechanisms of TCM are not yet well understood. In the present work, ultra performance liquid chromatography-based metabonomics analysis was applied to investigate the urinary metabolite profiling of the renoprotective effect of FLP on adenine-induced chronic kidney disease (CKD) rat model and involved possible mechanism. MATERIAL AND METHODS: A metabonomic approach based on ultra performance liquid chromatography coupled with quadrupole time-of-flight high-sensitivity mass spectrometry and a novel mass spectrometry(Elevated Energy) data collection technique was developed. The resulting dataset was analyzed by principal component analysis and partial least squares discriminant analysis. The identification of all potential biomarkers was performed using reference standard by comparing their mass spectra, MS(E) fragments information, isotopic pattern and MassLynx i-FIT algorithm. RESULTS: By partial least squares-discriminate analysis analyses, 15 biomarkers in rat urine were identified and 11 of them were related to the pathway of adenine metabolism and amino acid metabolism. Among these biomarkers, eight biomarkers like adenine, L-acetylcarnitine, 8-hydroxyadenine, hypoxanthine, creatine, methionine, phytosphingosine and phenylalanine were reversed to the control level in FLP-treated groups and six biomarkers like 2,8-dihydroxyadenine, indole-3-carboxylic acid, 3-methyldioxyindole, ethyl-N2-acetyl-L-argininate, 3-O-methyldopa and xanthurenic acid were reversed to high normal group by FLP, which indicates that the urinary metabolic pattern significantly changed after FLP treatment. CONCLUSIONS: Our study indicates that FLP treatment can ameliorate CKD by intervening in some dominating metabolic pathways, such as adenine metabolism and amino acid metabolism. The metabonomic results not only supplied a systematic view of the development and progression of CKD and mechanism studies of FLP but also provided the theoretical basis for the prevention or treatment of CKD. 23369933 Mercuric chloride-induced testicular toxicity in rats and the protective role of sodium selenite and vitamin E. Mercury has been recognized as an environmental pollutant that adversely affects male reproductive systems of animals. This study examined the effects of mercuric chloride on the antioxidant system and histopathological changes and also evaluated the ameliorating effects of sodium selenite and/or vitamin E in the rat testis tissues. Sexually mature male Wistar rats (weighing 300-320g and each group six animals) were given mercuric chloride (1mg/kg bw) and/or sodium selenite (0.25mg/kg bw)+vitamin E (100mg/kg) daily via gavage for 4weeks. In the present study, mercuric chloride exposure resulted in an increase in the TBARS level and a decrease in the SOD, CAT, GPx activities, with respect to the control. Further, light microscopic investigation revealed that mercury exposure induced histopathological alterations in the testis tissues. Supplementation of sodium selenite and/or vitamin E to mercury-induced groups declined lipid peroxidation, increased SOD, CAT, GPx activities. While some histopathological changes were detected in mercuric chloride treated group, milder histopathological changes were observed in animal co-treated with sodium selenite and/or vitamin E supplementation to mercuric chloride-treated rats. As a result, mercuric chloride induced testicular toxicity is reduced by sodium selenite and/or vitamin E, but not ameliorate completely. 23418011 Structural insights into the recovery of aldolase activity in N-acetylneuraminic acid lyase by replacement of the catalytically active lysine with γ-thialysine by using a chemical mutagenesis strategy. Chemical modification has been used to introduce the unnatural amino acid γ-thialysine in place of the catalytically important Lys165 in the enzyme N-acetylneuraminic acid lyase (NAL). The Staphylococcus aureus nanA gene, encoding NAL, was cloned and expressed in E. coli. The protein, purified in high yield, has all the properties expected of a class I NAL. The S. aureus NAL which contains no natural cysteine residues was subjected to site-directed mutagenesis to introduce a cysteine in place of Lys165 in the enzyme active site. Subsequently chemical mutagenesis completely converted the cysteine into γ-thialysine through dehydroalanine (Dha) as demonstrated by ESI-MS. Initial kinetic characterisation showed that the protein containing γ-thialysine regained 17 % of the wild-type activity. To understand the reason for this lower activity, we solved X-ray crystal structures of the wild-type S. aureus NAL, both in the absence of, and in complex with, pyruvate. We also report the structures of the K165C variant, and the K165-γ-thialysine enzyme in the presence, or absence, of pyruvate. These structures reveal that γ-thialysine in NAL is an excellent structural mimic of lysine. Measurement of the pH-activity profile of the thialysine modified enzyme revealed that its pH optimum is shifted from 7.4 to 6.8. At its optimum pH, the thialysine-containing enzyme showed almost 30 % of the activity of the wild-type enzyme at its pH optimum. The lowered activity and altered pH profile of the unnatural amino acid-containing enzyme can be rationalised by imbalances of the ionisation states of residues within the active site when the pK(a) of the residue at position 165 is perturbed by replacement with γ-thialysine. The results reveal the utility of chemical mutagenesis for the modification of enzyme active sites and the exquisite sensitivity of catalysis to the local structural and electrostatic environment in NAL. 23416115 Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by ampk activation. Chlorogenic acid (CGA) has been shown to stimulate glucose uptake in skeletal muscle through the activation of AMPK. However, its effect on other metabolic pathways and likewise its effects after long-term consumption have yet to be understood. We investigated the effects of CGA on glucose tolerance, insulin sensitivity, hepatic gluconeogenesis, lipid metabolism and skeletal muscle glucose uptake in Lepr(db/db) mice. Hepatoma HepG2 was used to investigate CGA's effect on hepatic glucose production and fatty acid synthesis. Subsequently, we attempted to evaluate whether these effects of CGA are associated with the activation of AMPK. In Lepr(db/db) mice, acute treatment with CGA lowered AUCglucose in an OGTT. Chronic administration of CGA inhibited hepatic G6Pase expression and activity, attenuated hepatic steatosis, improved lipid profiles and skeletal muscle glucose uptake, which in turn improved fasting glucose level, glucose tolerance, insulin sensitivity and dyslipidemia in Lepr(db/db) mice. CGA activated AMPK, leading to subsequent beneficial metabolic outcomes, such as suppression of hepatic glucose production and fatty acid synthesis. Inhibition and knockdown of AMPK abrogated these metabolic alterations. In conclusion, CGA improved glucose and lipid metabolism, via the activation of AMPK. 23535351 Management of schizophrenia: clinical experience with asenapine. Schizophrenia is a chronic brain disorder comprising a range of clinical features, including positive and negative symptoms, cognitive dysfunction and mood symptoms (particularly depression and anxiety). The management of schizophrenia requires effective short- and long-term treatment with antipsychotic medication that is effective across these symptom domains, while being well tolerated over the long term. Asenapine is the first tetracyclic atypical antipsychotic to be licensed in the USA and several other countries outside Europe for the acute and maintenance treatment of schizophrenia in adults. It has a unique receptor-binding profile and a broad range of therapeutic effects. Since clinical trials are conducted under strict conditions in tightly defined patient populations, evidence of an agent's efficacy and tolerability under 'real-world' clinical practice conditions is also required. As in clinical trials, real-life case reports demonstrate that asenapine is effective in treating the positive symptoms of schizophrenia, both in the acute setting and for relapse prevention. It is also effective in treating negative symptoms and shows promise in the treatment of depressive symptoms associated with schizophrenia. Asenapine has a favourable tolerability profile, having a minimal impact on weight and metabolic parameters. As such, asenapine is valuable option for the treatment of schizophrenia in adults. 23512824 Recruiting the Host's Immune System to Target Helicobacter pylori's Surface Glycans. Due to the increased prevalence of bacterial strains that are resistant to existing antibiotics, there is an urgent need for new antibacterial strategies. Bacterial glycans are an attractive target for new treatments, as they are frequently linked to pathogenesis and contain distinctive structures that are absent in humans. We set out to develop a novel targeting strategy based on surface glycans present on the gastric pathogen Helicobacter pylori (Hp). In this study, metabolic labeling of bacterial glycans with an azide-containing sugar allowed selective delivery of immune stimulants to azide-covered Hp. We established that Hp's surface glycans are labeled by treatment with the metabolic substrate peracetylated N-azidoacetylglucosamine (Ac4 GlcNAz). By contrast, mammalian cells treated with Ac4 GlcNAz exhibited no incorporation of the chemical label within extracellular glycans. We further demonstrated that the Staudinger ligation between azides and phosphines proceeds under acidic conditions with only a small loss of efficiency. We then targeted azide-covered Hp with phosphines conjugated to the immune stimulant 2,4-dinitrophenyl (DNP), a compound capable of directing a host immune response against these cells. Finally, we report that immune effector cells catalyze selective damage in vitro to DNP-covered Hp in the presence of anti-DNP antibodies. The technology reported herein represents a novel strategy to target Hp based on its glycans. 23171045 New 2-(aryloxy)-3-phenylpropanoic acids as peroxisome proliferator-activated receptor α/γ dual agonists able to upregulate mitochondrial carnitine shuttle system gene expression. The preparation of a series of 2-(aryloxy)-3-phenylpropanoic acids, resulting from the introduction of different substituents into the biphenyl system of the previously reported peroxisome proliferator-activated receptor α/γ (PPARα/γ) dual agonist 1, allowed the identification of new ligands with higher potency on PPARα and fine-tuned moderate PPARγ activity. For the most promising stereoisomer (S)-16, X-ray and calorimetric studies in PPARγ revealed, at high ligand concentration, the presence of two molecules simultaneously bound to the receptor. On the basis of these results and docking experiments in both receptor subtypes, a molecular explanation was provided for its different behavior as a full and partial agonist of PPARα and PPARγ, respectively. The effects of (S)-16 on mitochondrial acylcarnitine carrier and carnitine-palmitoyl-transferase 1 gene expression, two key components of the carnitine shuttle system, were also investigated, allowing the hypothesis of a more beneficial pharmacological profile of this compound compared to the less potent PPARα agonist fibrates currently used in therapy. 22451355 Antiproliferative and antiangiogenic properties of horse chestnut extract. This study was designed to examine the in vitro antiproliferative effect of the horse chestnut extract (HCE) on cancer cell lines. Furthermore, we have investigated the in vitro effect of HCE on some angiogenic events by using human umbilical vein endothelial cells. The cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and anchorage-independent growth by colony-forming assay. To understand the growth inhibitory effects, carcinoma cell lines (Jurkat, CEM, HeLa, and MCF-7) were treated with various concentrations of HCE. Incubation of Jurkat, CEM, HeLa, and MCF-7 cancer cells with HCE at 125 µg/mL for 72 h caused 93.7%, 32.3%, 20.4% and 40.4% reduction in cell survival. Colony-forming assay also confirmed growth-inhibitory effects of the compound studied. In HeLa HCE-treated cells, we found a significant increase in cells having sub-G(0) /G(1) DNA content which is considered to be a marker of apoptotic cell death. Apoptosis was also further confirmed by DNA fragmentation analysis.Furthermore, HCE inhibited migration of human umbilical vein endothelial cells as well as decreased secretion of matrix metalloproteinase and vascular endothelial growth factor.In conclusion, the present study has assessed the in vitro antiproliferative/antiangiogenic potential of HCE. These results generate a rationale for in vivo efficacy studies with horse chestnut in preclinical cancer models. 22849972 Increased expression of transthyretin in leptin-deficient ob/ob mice is not causative for their major phenotypic abnormalities. The hormone leptin is a critical regulator of adipogenesis and energy metabolism. Similarly, leptin-deficient ob/ob mice display various metabolic abnormalities, including not only obesity and insulin resistance, but also hypogonadism and high bone mass. By genome-wide expression analysis using hypothalamus RNA from wild-type and ob/ob mice, we observed the increased expression of the gene for transthyretin (Ttr) in the latter, as confirmed by quantitative real-time-polymerase chain reaction. Because Ttr encodes a carrier protein for retinol transport, and because we further found increased retinol levels in the serum of ob/ob mice, we investigated whether the additional absence of Ttr would influence the ob/ob phenotype. It was found that Ttr-deficient ob/ob mice were indistinguishable from ob/ob littermates in terms of body weight, as well as serum glucose, insulin and cholesterol levels. Although all of these parameters were identical to wild-type controls in Ttr-deficient mice, we found that the sole deletion of Ttr caused a significant increase of trabecular bone mass, bone marrow adiposity and mean adipocyte area in white adipose tissue. Interestingly, all these latter parameters were highest in Ttr-deficient ob/ob mice, and only in these mice did we observe a full penetrance of liver steatosis at 24 weeks of age. Taken together, our data demonstrate that the increased expression of Ttr in ob/ob mice does not cause (but rather attenuates) their phenotypic abnormalities. 22982773 A common mechanism for resistance to oxime reactivation of acetylcholinesterase inhibited by organophosphorus compounds. Administration of oxime therapy is currently the standard approach used to reverse the acute toxicity of organophosphorus (OP) compounds, which is usually attributed to OP inhibition of acetylcholinesterase (AChE). Rate constants for reactivation of OP-inhibited AChE by even the best oximes, such as HI-6 and obidoxime, can vary >100-fold between OP-AChE conjugates that are easily reactivated and those that are difficult to reactivate. To gain a better understanding of this oxime specificity problem for future design of improved reactivators, we conducted a QSAR analysis for oxime reactivation of AChE inhibited by OP agents and their analogues. Our objective was to identify common mechanism(s) among OP-AChE conjugates of phosphates, phosphonates and phosphoramidates that result in resistance to oxime reactivation. Our evaluation of oxime reactivation of AChE inhibited by a sarin analogue, O-methyl isopropylphosphonofluoridate, or a cyclosarin analogue, O-methyl cyclohexylphosphonofluoridate, indicated that AChE inhibited by these analogues was at least 70-fold more difficult to reactivate than AChE inhibited by sarin or cyclosarin. In addition, AChE inhibited by an analogue of tabun (i.e., O-ethyl isopropylphosphonofluoridate) was nearly as resistant to reactivation as tabun-inhibited AChE. QSAR analysis of oxime reactivation of AChE inhibited by these OP compounds and others suggested that the presence of both a large substituent (i.e., ⩾the size of dimethylamine) and an alkoxy substituent in the structure of OP compounds is the common feature that results in resistance to oxime reactivation of OP-AChE conjugates whether the OP is a phosphate, phosphonate or phosphoramidate. 23280958 Spectroscopic fingerprints of toroidal nuclear quantum delocalization via ab initio path integral simulations. We investigate the quantum-mechanical delocalization of hydrogen in rotational symmetric molecular systems. To this purpose, we perform ab initio path integral molecular dynamics simulations of a methanol molecule to characterize the quantum properties of hydrogen atoms in a representative system by means of their real-space and momentum-space densities. In particular, we compute the spherically averaged momentum distribution n(k) and the pseudoangular momentum distribution n(kθ). We interpret our results by comparing them to path integral samplings of a bare proton in an ideal torus potential. We find that the hydroxyl hydrogen exhibits a toroidal delocalization, which leads to characteristic fingerprints in the line shapes of the momentum distributions. We can describe these specific spectroscopic patterns quantitatively and compute their onset as a function of temperature and potential energy landscape. The delocalization patterns in the projected momentum distribution provide a promising computational tool to address the intriguing phenomenon of quantum delocalization in condensed matter and its spectroscopic characterization. As the momentum distribution n(k) is also accessible through Nuclear Compton Scattering experiments, our results will help to interpret and understand future measurements more thoroughly. 23252823 Pyrenyl-linker-glucono gelators. Correlations of gel properties with gelator structures and characterization of solvent effects. A series of glucono-appended 1-pyrenesulfonyl derivatives containing α,ω-diaminoalkane spacers (Pn, where n, the number of methylene units separating the amino groups, is 2, 3, 4, 6, 7, and 8) have been prepared. Careful analyses of correlations between the structures of these molecules and their gels have provided important insights into the factors responsible for one-dimensional aggregation of small molecules containing both lipophilic and hydrophilic parts. The gelation behavior has been examined in 30 liquids of diverse structure and polarity, and the properties of their gels and the gelation mechanisms have been investigated using a variety of techniques. Possible reasons are discussed regarding why the Pn are better gelators than the corresponding naphthyl analogues (Nn) which had been investigated previously. P2 and P3 are ambidextrous gelators (i.e., they gelate both water and some organic liquids), and P4-P8 gelate some organic liquids which are protic and aprotic, but not water. In at least one of the liquids examined, P3, P4, P6, P7, and P8 form gels at less than 1 w/v % concentrations, and some of the gels in 1-decanol are thixotropic. Analyses of the gelation abilities using Hansen solubility parameters yield both qualitative and quantitative insights into the role of liquid-gelator interactions. For example, the critical gelation concentrations increase generally with increasing polar and hydrogen bonding interactions between the gelators and their liquid components. As revealed by FT-IR, (1)H NMR, UV-vis, and fluorescence spectra, hydrogen-bonding between glucono units and π-π stacking between pyrenyl groups are important in the formation and maintenance of the gel networks. The results from this study, especially those relating the aggregation modes and liquid properties, offer insights for the design of new surfactant-containing low-molecular-mass gelators with predefined gelating abilities. 23201451 Application of OECD Guideline 423 in assessing the acute oral toxicity of moniliformin. Moniliformin is a Fusarium mycotoxin highly prevalent in grains and grain-based products worldwide. In this study, the acute oral toxicity of moniliformin was assessed in Sprague-Dawley male rats according to OECD Guideline 423 with a single-dose exposure. Clinical observations and histopathological changes were recorded together with the excretion of moniliformin via urine and feces, utilizing a novel liquid chromatography-mass spectrometry method. According to our study, moniliformin is acutely toxic to rats with a rather narrow range of toxicity. Moniliformin can be classified into category 2 (LD(50) cut-off value 25 mg/kg b.w.), according to the Globally Harmonized System for the classification of chemicals. The clinical observations included muscular weakness, respiratory distress and heart muscle damage. Pathological findings confirmed that heart is the main target tissue of acute moniliformin toxicity. A significant proportion (about 38%) of the administered moniliformin was rapidly excreted in urine in less than 6 h. However, the toxicokinetics of the majority of the administered dose still requires clarification, as the total excretion was only close to 42%. Considering the worldwide occurrence of moniliformin together with its high acute toxicity, research into the subchronic toxicity is of vital importance to identify the possible risk in human/animal health. 23501108 Synthesis and anticancer activity of novel 2-pyridyl hexahyrocyclooctathieno[2,3-d]pyrimidine derivatives. A series of new 2-pyridyl hexahydrocycloocta [4,5]thieno[2,3-d]pyrimidines with different substituents as C-4 position was synthesized. The anticancer activity of the newly synthesized compounds was tested in vitro using a two-stage process utilizing 60 different human tumor cell lines representing leukemia, melanoma and cancers of lung, colon, central nervous system, ovary, kidney, prostate as well as breast. Compounds 4a, 6a, 7a, 7d and 7g showed potent anticancer activity at low concentrations against most of the used human tumor cell lines comparable with doxorubicin as standard potent anticancer drug (average log10 GI50 over all cell lines = -6.85). Also, compound 4b was selective against SNB-75 (CNS cancer) log10 GI50 = -5.57. Interestingly, compound 7e exhibited promising selectivity against 13 tumor cell lines showing growth inhibition percentages between 54.05 and 89.23. 23436742 Thermal and Electrical Conduction in Ultrathin Metallic Films: 7 nm down to Sub-Nanometer Thickness. For ultrathin metallic films (e.g., less than 5 nm), no knowledge is yet available on how electron scattering at surface and grain boundaries reduces the electrical and thermal transport. The thermal and electrical conduction of metallic films is characterized down to 0.6 nm average thickness. The electrical and thermal conductivities of 0.6 nm Ir film are reduced by 82% and 50% from the respective bulk values. The Lorenz number is measured as 7.08 × 10(-8) W Ω K(-2) , almost a twofold increase of the bulk value. The Mayadas-Shatzkes model is used to interpret the experimental results and reveals very strong electron reflection (>90%) at grain boundaries. 23485151 Postsynthesis modification of a porous coordination polymer by LiCl To enhance H+ transport. A Ca(2+) porous coordination polymer with 1D channels was functionalized by the postsynthesis addition of LiCl to enhance the H(+) conductivity. The compound showed over 10(-2) S cm(-1) at 25 °C and 20% relative humidity. Pulse-field gradient NMR elucidated that the fast H(+) conductivity was achieved by the support of Li(+) ion movements in the channel. 23619611 Novel oral anticoagulants: clinical pharmacology, indications and practical considerations. BACKGROUND: Novel oral anticoagulants are approved in several indications: rivaroxaban, apixaban, and dabigatran for the prevention of venous thromboembolism after elective hip or knee replacement surgery, and edoxaban for hip or knee replacement surgery and hip fracture surgery (in Japan only); rivaroxaban for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE; and rivaroxaban, apixaban, and dabigatran for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. These agents overcome some limitations of traditional anticoagulants, are suggested to have no requirement for routine coagulation monitoring, and are administered orally. Rivaroxaban, apixaban, and dabigatran have different pharmacological characteristics, and guidance is needed on optimum doses and dosing intervals and the effects of renal or hepatic impairment, age, food, and other drugs. Dabigatran has stricter prescribing advice than rivaroxaban or apixaban for patients with moderate-to-severe renal impairment. All three drugs have restrictions on use in patients with hepatic impairment. Apixaban requires twice-daily dosing in all indications, whereas rivaroxaban and dabigatran are dosed once- or twice-daily depending on indication. Although head-to-head comparisons are lacking, the novel oral anticoagulants may show favorable cost-benefit relations compared with traditional vitamin K antagonists or no therapy. AIM: This review summarizes the pharmacology of rivaroxaban, apixaban, edoxaban, and dabigatran, and the indications for which they are approved. Issues regarding the optimization of the use of these anticoagulants for the management of thromboembolic disorders will also be discussed. 23462665 Exenatide-Induced Reduction in Energy Intake Is Associated With Increase in Hypothalamic Connectivity. OBJECTIVEGlucagon-like peptide-1 receptor agonists like exenatide are known to influence neural activity in the hypothalamus of animals and to reduce energy intake. In humans, however, significant weight loss has been observed in only a subgroup of patients. Why only some individuals respond with weight loss and others do not remains unclear. In this functional magnetic resonance imaging (fMRI) study, we investigated differences in hypothalamic connectivity between "responders" (reduction in energy intake after exenatide infusion) and "nonresponders."RESEARCH DESIGN AND METHODSWe performed a randomized, double-blinded, placebo-controlled, cross-over fMRI study with intravenous administration of exenatide in obese male volunteers. During brain scanning with continuous exenatide or placebo administration, participants rated food and nonfood images. After each scanning session, energy intake was measured using an ad libitum buffet. Functional hypothalamic connectivity was assessed by eigenvector centrality mapping, a measure of connectedness throughout the brain.RESULTSResponders showed significantly higher connectedness of the hypothalamus, which was specific for the food pictures condition, in the exenatide condition compared with placebo. Nonresponders did not show any significant exenatide-induced changes in hypothalamic connectedness.CONCLUSIONSOur results demonstrate a central hypothalamic effect of peripherally administered exenatide that occurred only in the group that showed an exenatide-dependent anorexigenic effect. These findings indicate that the hypothalamic response seems to be the crucial factor for the effect of exenatide on energy intake. 23411232 Quantification of vitamin D3 and its hydroxylated metabolites in waxy leaf nightshade (Solanum glaucophyllum Desf.), tomato (Solanum lycopersicum L.) and bell pepper (Capsicum annuum L.). Changes in vitamin D(3) and its metabolites were investigated following UVB- and heat-treatment in the leaves of Solanum glaucophyllum Desf., Solanum lycopersicum L. and Capsicum annuum L. The analytical method used was a sensitive and selective liquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS) method including Diels-Alder derivatisation. Vitamin D(3) and 25-hydroxy vitamin D(3) were found in the leaves of all plants after UVB-treatment. S. glaucophyllum had the highest content, 200 ng vitamin D(3)/g dry weight and 31 ng 25-hydroxy vitamin D(3)/g dry weight, and was the only plant that also contained 1,25 dihydroxy vitamin D(3) in both free (32 ng/g dry weight) and glycosylated form (17 ng/g dry weight). 23597507 Phα1β toxin prevents capsaicin-induced nociceptive behavior and mechanical hypersensitivity without acting on TRPV1 channels. Phα1β toxin is a peptide purified from the venom of the armed spider Phoneutria nigriventer, with markedly antinociceptive action in models of acute and persistent pain in rats. Similarly to ziconotide, its analgesic action is related to inhibition of high voltage activated calcium channels with more selectivity for N-type. In this study we evaluated the effect of Phα1β when injected peripherally or intrathecally in a rat model of spontaneous pain induced by capsaicin. We also investigated the effect of Phα1β on Ca(2+) transients in cultured dorsal root ganglia (DRG) neurons and HEK293 cells expressing the TRPV1 receptor. Intraplantar or intrathecal administered Phα1β reduced both nocifensive behavior and mechanical hypersensitivity induced by capsaicin similarly to that observed with SB366791, a specific TRPV1 antagonist. Peripheral nifedipine and mibefradil did also decrease nociceptive behavior induced by intraplantar capsaicin. In contrast, ω-conotoxin MVIIA (a selective N-type Ca(2+) channel blocker) was effective only when administered intrathecally. Phα1β, MVIIA and SB366791 inhibited, with similar potency, the capsaicin-induced Ca(2+) transients in DRG neurons. The simultaneous administration of Phα1β and SB366791 inhibited the capsaicin-induced Ca(2+) transients that were additive suggesting that they act through different targets. Moreover, Phα1β did not inhibit capsaicin-activated currents in patch-clamp recordings of HEK293 cells that expressed TRPV1 receptors. Our results show that Phα1β may be effective as a therapeutic strategy for pain and this effect is not related to the inhibition of TRPV1 receptors. 23444387 Significance of reductive metabolism in human intestine and quantitative prediction of intestinal first-pass metabolism by cytosolic reductive enzymes. The number of new drug candidates that are cleared via non-cytochrome P450 (P450) enzymes has increased. However, unlike oxidation by P450, the roles of reductive enzymes are less understood. The metabolism in intestine is especially not well known. The purposes of this study were to investigate the significance of reductive metabolism in human intestine, and to establish a quantitative prediction method of intestinal first-pass metabolism by cytosolic reductive enzymes, using haloperidol, mebendazole, and ziprasidone. First, we estimated the metabolic activities for these compounds in intestine and liver using subcellular fractions. Metabolic activities were detected in human intestinal cytosol (HIC) for all three compounds, and the intrinsic clearance values were higher than those in human liver cytosol for haloperidol and mebendazole. These metabolic activities in HIC were NADPH- and/or NADH-dependent. Furthermore, the metabolic activities for all three compounds in HIC were largely inhibited by menadione, which has been used as a carbonyl reductase (CBR)-selective chemical inhibitor. Therefore, considering subcellular location, cofactor requirement, and chemical inhibition, these compounds might be metabolized by CBRs in human intestine. Subsequently, we tried to quantitatively predict intestinal availability (Fg) for these compounds using human intestinal S9 (HIS9). Our prediction model using apparent permeability of parallel artificial membrane permeability assay and metabolic activities in HIS9 could predict Fg in humans for the three compounds well. In conclusion, CBRs might have higher metabolic activities in human intestine than in human liver. Furthermore, our prediction method of human Fg using HIS9 is applicable to substrates of cytosolic reductive enzymes. 23632007 Development of a method for extraction and assay of human erythrocyte acetylcholinesterase and pesticide inhibition. A method of extracting membranes from red blood cells (RBCs) is described, which were in turn used to assay acetylcholinesterase (AChE) activity. The evidence for the enzyme activity was established by selective inhibition using 1,5-bis(4-allyldimethylammoniumphenyl) pentan-3-one dibromide, tetraisopropyl pyrophosphoramide and neostigmine. Blood samples were exposed to three organophosphorus (dichlorvos, chlorpyrifos and diazinon) and two carbamate (carbaryl and carbofuran) pesticides. Afterwards AChE activities in RBC membranes were determined. The concentrations capable to inhibit the enzyme activity by 50% (IC50) for the pesticides were 10.66 µM (dichlorvos), 21.42 µM (chlorpyrifos), 109.98 µM (carbaryl) and 5.44 µM (carbofuran). The results related to 20% enzyme inhibition (level used in the estimation of threshold limits for anticholinesterase compounds) were below those acceptable daily intake values enacted by relevant national and international regulations. These results suggest that the proposed AChE extraction from RBC and assay could be a suitable method for monitoring occupational exposure to pesticides. 23489623 Synthesis of (R)-norbgugaine and its potential as quorum sensing inhibitor against Pseudomonas aeruginosa. (R)-Bgugaine is a natural pyrrolidine alkaloid from Arisarum vulgare, which shows antifungal and antibacterial activity. In this Letter, we have accomplished the simple synthesis of norbgugaine (demethylated form of natural bgugaine) employing Wittig olefination and cat. hydrogenation as the key steps and its biological studies are reported for the first time. The synthesized norbgugaine was evaluated for inhibition of quorum sensing mediated virulence factors (motility, biofilm formation, pyocyanin pigmentation, rhamnolipid production and LasA protease) in Pseudomonas aeruginosa wherein swarming motility is reduced by 95%, and biofilm formation by 83%. 23007555 Effect of ifenprodil on GluN1/GluN2B N-methyl-D-aspartate receptor gating. Ifenprodil is an allosteric inhibitor of GluN1/GluN2B N-methyl-D-aspartate receptors. Despite its widespread use as a prototype for drug development and a subtype-selective tool for physiologic experiments, its precise effect on GluN1/GluN2B gating is yet to be fully understood. Interestingly, recent crystallographic evidence identified that ifenprodil, unlike zinc, binds at the interface of the GluN1/GluN2B amino terminal domain dimer by an induced-fit mechanism. To delineate the effect of this unique binding on GluN1/GluN2B receptor gating, we recorded steady-state currents from cell-attached and outside-out patches. At pH 7.9 in cell-attached patches, ifenprodil increased the occupancy of the long-lived shut conformations, thereby reducing the open probability of the receptor with no change in the mean open time. In addition, ifenprodil selectively affected the area of shut time constants, but not the time constants themselves. Kinetic analyses suggested that ifenprodil prevents the transition of the receptor to an open state and increases its dwell time in an intrinsically occurring closed conformation or desensitized state. We found distinct differences in the action of ifenprodil at GluN1/GluN2B in comparison with previous studies on the effect of zinc on GluN1/GluN2A gating, which may arise due to their unique binding sites. Our data also uncover the potential pH-dependent action of ifenprodil on gating. At a low pH (pH 7.4), but not pH 7.9, ifenprodil reduces the mean open time of GluN1/GluN2B receptors, which may be responsible for its usefulness as a context-dependent inhibitor in conditions like ischemia and stroke, when the pH of the extracellular milieu becomes acidic. 22960471 Differential cell-specific cytotoxic responses of oral cavity cells to tobacco preparations. To examine the effects of standardized (reference) tobacco preparations on human oral cavity cells, two oral squamous cell carcinoma cell lines (101A, 101B) and normal human gingival epithelial cells (HGEC) were treated with cigarette smoke total particulate matter (TPM), smokeless tobacco extracted with complete artificial saliva (ST/CAS), or whole-smoke conditioned media (WS-CM). EC-50 values, as determined by sulforhodamine B assays, varied among the cell types and agents. When normalized to nicotine content, cytotoxicity for WS-CM and TPM was higher compared to that observed with ST/CAS. Nicotine alone had no or only minimal cytotoxicity for all cell types in the applied range. Activation of pro-apoptotic caspase-3 was examined in all cell types at their respective EC-50 doses for the three agents. TPM, but not ST/CAS or WS-CM significantly activated caspase-3 in all three cell types. Fluorescence-activated cell sorting (FACS) for expression of the early apoptosis marker Annexin V and for nuclear staining by 7-aminoactinomycin (7-AAD) revealed different extents of apoptosis versus non-apoptotic cell death for the three agents. These data characterize differential responses of normal and malignant oral cells after exposure to TPM, ST/CAS, or WS-CM. They assist in understanding differential effects of combustible versus non-combustible tobacco products, and in identifying novel biomarkers for tobacco smoke exposure and effect in the oral cavity. 23524188 Mild hyperthermia triggered doxorubicin release from optimized stealth thermosensitive liposomes improves intratumoral drug delivery and efficacy. Liposome mediated anticancer drug delivery has the advantage of reducing cytotoxicity in healthy tissues. However, undesired slow drug release impedes the therapeutic efficacy of clinically applied PEG-liposomal doxorubicin (Dox). The aim of this study is to combine stealth thermosensitive liposomes (TSL) and local mild hyperthermia (HT) to increase bioavailable Dox levels in tumors. Dox was encapsulated in stealth TSL (~80nm) with optimized PEG concentration in the membrane, and compared with lysolipid-based Dox-LTSL for in vitro stability, release kinetics, and in vivo tumor growth control. In vitro cytotoxicity of Dox-TSL against murine BFS-1 sarcoma and, human BLM melanoma cell lines and Human Umbilical Vein Endothelial Cells (HUVEC) under normothermia (37°C) and HT (42°C) was compared with non-encapsulated Dox. In vitro Dox uptake in nuclei was imaged in BLM and HUVEC. In vivo intravascular Dox release from TSL in BFS-1 tumors under local mild HT in dorsal skin flap window chamber models was captured by intravital confocal microscopy. Intravascular Dox-TSL release kinetics, penetration depth and interstitial Dox density were subjected to quantitative image analysis. Systemic Dox-TSL administration in combination with local mild HT on subcutaneous tumor growth control was compared to Dox-LTSL plus local mild HT. Dox-TSL was stable at 37°C, while released over 95% Dox within 1min in 90% serum at 42°C. Dox-TSL demonstrated efficient in vivo intratumoral Dox release under local mild HT, followed by significant Dox uptake by tumor and tumor vascular endothelial cells. Dox-TSL plus mild HT showed improved tumor growth control over Dox-LTSL plus mild HT. Survival after a single treatment of Dox-TSL plus mild HT was 67%, while survival after Dox-LTSL plus mild HT was 22%. This combination of Dox-TSL and local mild HT offers promising clinical opportunities to improve liposomal Dox delivery to solid tumors. 23552268 Potential anticancer activity of carvone in N2a neuroblastoma cell line. Carvone (CVN) is a monocyclic monoterpene found in the essential oils of Mentha spicata var. crispa (Lamiaceae) and Carum carvi L. (Apiaceae) plants and has been reported to have antioxidant, antimicrobial, anticonvulsant, and antitumor activities. The beneficial health properties of CVN have encouraged us to look into its anticancer activity. To the best of our knowledge, reports are not available on the anticancer activity of CVN in cultured primary rat neuron and N2a neuroblastoma (NB) cells. Therefore, the present study is an attempt toward exploring the potential anticancer activity of CVN, if any, in cultured primary rat neuron and N2a NB cells. Our results indicated that CVN (only at 25 mg/L) treatment led to an increase in the total antioxidant capacity levels in cultured primary rat neuron cells compared with control cells. Also, CVN (at concentrations higher than 100 mg/L) treatment led to an increase in the total oxidative stress levels in both cell types. The mean values of the total scores of cells showing DNA damage (for comet assay) were not found to be significantly different from the control values in both cells (p > 0.05). On the other hand, after 24 h treatment with CVN, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay showed that CVN application significantly reduced the cell viability rates in both cell types at concentrations higher than 100 mg/L. Summarizing, our data suggest that CVN represents little potential for promising anticancer agent to improve brain tumors therapy. 23307927 Loss and gain of Drosophila TDP-43 impair synaptic efficacy and motor control leading to age-related neurodegeneration by loss-of-function phenotypes. Cytoplasmic accumulation and nuclear clearance of TDP-43 characterize familial and sporadic forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, suggesting that either loss or gain of TDP-43 function, or both, cause disease formation. Here we have systematically compared loss- and gain-of-function of Drosophila TDP-43, TAR DNA Binding Protein Homolog (TBPH), in synaptic function and morphology, motor control, and age-related neuronal survival. Both loss and gain of TBPH severely affect development and result in premature lethality. TBPH dysfunction caused impaired synaptic transmission at the larval neuromuscular junction (NMJ) and in the adult. Tissue-specific knockdown together with electrophysiological recordings at the larval NMJ also revealed that alterations of TBPH function predominantly affect pre-synaptic efficacy, suggesting that impaired pre-synaptic transmission is one of the earliest events in TDP-43-related pathogenesis. Prolonged loss and gain of TBPH in adults resulted in synaptic defects and age-related, progressive degeneration of neurons involved in motor control. Toxic gain of TBPH did not downregulate or mislocalize its own expression, indicating that a dominant-negative effect leads to progressive neurodegeneration also seen with mutational inactivation of TBPH. Together these data suggest that dysfunction of Drosophila TDP-43 triggers a cascade of events leading to loss-of-function phenotypes whereby impaired synaptic transmission results in defective motor behavior and progressive deconstruction of neuronal connections, ultimately causing age-related neurodegeneration. 23197649 Allosteric modulation of a chemogenetically modified G protein-coupled receptor. Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetically modified muscarinic acetylcholine receptors (mAChRs) that have minimal responsiveness to acetylcholine (ACh) but are potently and efficaciously activated by an otherwise inert synthetic ligand, clozapine-N-oxide (CNO). DREADDs have been used as tools for selectively modulating signal transduction pathways in vitro and in vivo. Recent comprehensive studies have validated how the pharmacology of a CNO-bound DREADD mirrors that of an ACh-bound wild-type (WT) mAChR. However, nothing is known about whether this equivalence extends to the allosteric modulation of DREADDs by small molecules. To address this, we investigated the actions at an M(1) DREADD of benzyl quinolone carboxylic acid (BQCA), a positive allosteric modulator of ACh binding and function that is known to behave according to a simple two-state mechanism at the WT receptor. We found that allosteric modulation of the CNO-bound DREADD receptor is not equivalent to the corresponding modulation of the ACh-bound WT receptor. We also found that BQCA engenders stimulus bias at the M(1) DREADD, having differential types of cooperativity depending on the signaling pathway. Furthermore, the modulation of ACh itself by BQCA at the DREADD is not compatible with the two-state model that we previously applied to the M(1) WT receptor. 23481650 N-substituted azaindoles as potent inhibitors of Cdc7 kinase. Cdc7 kinase is responsible for the initiation and regulation of DNA replication and has been proposed as a target for cancer therapy. We have identified a class of Cdc7 inhibitors based on a substituted indole core. Synthesis of focused indole and azaindole analogs yielded potent and selective 5-azaindole Cdc7 inhibitors with improved intrinsic metabolic stability (ie 36). In parallel, quantum mechanical conformational analysis helped to rationalize SAR observations, led to a proposal of the preferred binding conformation in the absence of co-crystallography data, and allowed the design of 7-azaindole 37 as a second lead in this series. 23361587 Anti-aging molecule, Sirt1: a novel therapeutic target for diabetic nephropathy. Caloric restriction prolongs the lifespan of many species. Therefore, investigators have researched the usefulness of caloric restriction for healthy lifespan extension. Sirt1, an NAD(+)-dependent deacetylase, was identified as a molecule necessary for caloric restriction-related anti-aging strategies. Sirt1 functions as an intracellular energy sensor to detect the concentration of NAD(+), and controls in vivo metabolic changes under caloric restriction and starvation through its deacetylase activity to many targets including histones, nuclear transcriptional factors, and enzymes. During the past decade, investigators have reported the relationship between disturbance of Sirt1 activation and the onset of aging- and obesity-associated diseases such as diabetes, cardiovascular disease and neurodegenerative disorders. Consequently, a calorie restriction-mimetic action of Sirt1 is now expected as a new therapy for these diseases. In addition, recent studies have gradually clarified the role of Sirt1 in the onset of kidney disease. Its activation may also become a new target of treatment in the patients with chronic kidney disease including diabetic nephropathy. In this article, we would like to review the role of Sirt1 in the onset of kidney disease based on previous studies, and discuss its possibility as the target of treatment in diabetic nephropathy. 23420703 Systematic and efficient side chain optimization for molecular docking using a cheapest-path procedure. Molecular docking of small-molecules is an important procedure for computer-aided drug design. Modeling receptor side chain flexibility is often important or even crucial, as it allows the receptor to adopt new conformations as induced by ligand binding. However, the accurate and efficient incorporation of receptor side chain flexibility has proven to be a challenge due to the huge computational complexity required to adequately address this problem. Here we describe a new docking approach with a very fast, graph-based optimization algorithm for assignment of the near-optimal set of residue rotamers. We extensively validate our approach using the 40 DUD target benchmarks commonly used to assess virtual screening performance and demonstrate a large improvement using the developed side chain optimization over rigid receptor docking (average ROC AUC of 0.693 vs. 0.623). Compared to numerous benchmarks, the overall performance is better than nearly all other commonly used procedures. Furthermore, we provide a detailed analysis of the level of receptor flexibility observed in docking results for different classes of residues and elucidate potential avenues for further improvement. © 2013 Wiley Periodicals, Inc. 23160529 HLA-A*24 is an independent predictor of 5-year progression to diabetes in autoantibody-positive first-degree relatives of type 1 diabetic patients. We investigated whether HLA-A*24 typing complements screening for HLA-DQ and for antibodies (Abs) against insulin, GAD, IA-2 (IA-2A), and zinc transporter-8 (ZnT8A) for prediction of rapid progression to type 1 diabetes (T1D). Persistently Ab(+) siblings/offspring (n = 288; aged 0-39 years) of T1D patients were genotyped for HLA-DQA1-DQB1 and HLA-A*24 and monitored for development of diabetes within 5 years of first Ab(+). HLA-A*24 (P = 0.009), HLA-DQ2/DQ8 (P = 0.001), and positivity for IA-2A ± ZnT8A (P < 0.001) were associated with development of T1D in multivariate analysis. The 5-year risk increased with the number of the above three markers present (n = 0: 6%; n = 1: 18%; n = 2: 46%; n = 3: 100%). Positivity for one or more markers identified a subgroup of 171 (59%) containing 88% of rapid progressors. The combined presence of HLA-A*24 and IA-2A(+) ± ZnT8A(+) defined a subgroup of 18 (6%) with an 82% diabetes risk. Among IA-2A(+) ± ZnT8A(+) relatives, identification of HLA-A*24 carriers in addition to HLA-DQ2/DQ8 carriers increased screening sensitivity for relatives at high Ab- and HLA-inferred risk (64% progression; P = 0.002). In conclusion, HLA-A*24 independently predicts rapid progression to T1D in Ab(+) relatives and complements IA-2A, ZnT8A, and HLA-DQ2/DQ8 for identifying participants in immunointervention trials. 23402972 Exploring food effects on indinavir absorption with human intestinal fluids in the mouse intestine. Food can have a significant impact on the pharmacokinetics of orally administered drugs, as it may affect drug solubility as well as permeability. Since fed state conditions cannot easily be implemented in the presently available permeability tools, including the frequently used Caco-2 system, exploring food effects during drug development can be quite challenging. In this study, we investigated the effect of fasted and fed state conditions on the intestinal absorption of the HIV protease inhibitor indinavir using simulated and human intestinal fluids in the in situ intestinal perfusion technique in mice. Although the solubility of indinavir was 6-fold higher in fed state human intestinal fluids (FeHIF) as compared to fasted state HIF (FaHIF), the intestinal permeation of indinavir was 22-fold lower in FeHIF as compared to FaHIF. Dialysis experiments showed that only a small fraction of indinavir is accessible for absorption in FeHIF due to micellar entrapment, possibly explaining its low intestinal permeation. The presence of ritonavir, a known P-gp inhibitor, increased the intestinal permeation of indinavir by 2-fold in FaHIF, while there was no increase when using FeHIF. These data confirm that drug-food interactions form a complex interplay between solubility and permeability effects. The use of HIF in in situ intestinal perfusions holds great promise for biorelevant absorption evaluation as it allows to directly explore this complex solubility/permeability interplay on drug absorption. 23238662 Acute-Phase Serum Amyloid A Protein and Its Implication in the Development of Type 2 Diabetes in the KORA S4/F4 Study. OBJECTIVE We sought to investigate whether elevated levels of acute-phase serum amyloid A (A-SAA) protein precede the onset of type 2 diabetes independently of other risk factors, including parameters of glucose metabolism. RESEARCH DESIGN AND METHODS Within the population-based Cooperative Health Research in the Region of Augsburg (KORA) S4 study, we measured A-SAA concentrations in 836 initially nondiabetic subjects (55-74 years of age) without clinically overt inflammation who participated in a 7-year follow-up examination including an oral glucose tolerance test. RESULTS A-SAA concentrations were significantly associated with incident type 2 diabetes (odds ratio [OR] for a one-SD increase of A-SAA adjusted for age and sex = 1.28 [95% CI 1.08-1.53], P = 0.005), particularly in younger subjects (P value for interaction = 0.047). The association attenuated when adjusting for parameters of glucose metabolism (fasting glucose, fasting insulin, HbA1c, and 2-h glucose; OR 1.16 [0.95-1.42], P = 0.15). Similar analyses for high-sensitive C-reactive protein (hs-CRP) yielded the following ORs: 1.39 (1.10-1.68, P = 0.0006) and 1.13 (0.88-1.45, P = 0.34), respectively. In contrast, A-SAA concentrations were significantly associated with 2-h glucose levels at follow-up even after adjustment for parameters of glucose metabolism (P = 0.008, n = 803). CONCLUSIONS Our findings indicate similarly strong prospective associations with type 2 diabetes for A-SAA and hs-CRP and suggest a potential causal link via postchallenge hyperglycemia. 23115119 STAAR: statistical analysis of aromatic rings. The statistical analysis of aromatic rings program allows for an automated search for anion-π interactions between phenylalanine residues and carboxylic acid moieties of neighboring aspartic acid or glutamic acid residues in protein data bank (PDB) structures. The program is written in C++ and is available both as a standalone code and through a web implementation that allows users to upload and analyze biomolecular structures in PDB format. The program outputs lists of Phe/Glu or Phe/Asp pairs involved in potential anion-π interactions, together with geometrical (distance and angle between the Phe's center of mass and Glu or Asp's center of charge) and energetic (quantum mechanical Kitaura-Morokuma interaction energy between the residues) descriptions of each anion-π interaction. Application of the program on the latest content of the PDB shows that anion-π interactions are present in thousands of protein structures and can possess strong energies, as low as -8.72 kcal/mol. 23600717 Three new Lycopodium alkaloids from Lycopodium obscurum. Chemical investigation on the crude alkaloid portion of Lycopodium obscurum led to isolation of three new fawcettimine-type Lycopodium alkaloids, lycobscurines A-C (1-3), together with three known compounds. Their structures were determined by spectroscopic methods including HR-ESI-MS and NMR techniques. All compounds were tested in an assay for acetylcholinesterase inhibitory activity. 22889561 The human Aurora kinase inhibitor danusertib is a lead compound for anti-trypanosomal drug discovery via target repurposing. New drugs for neglected tropical diseases such as human African trypanosomiasis (HAT) are needed, yet drug discovery efforts are not often focused on this area due to cost. Target repurposing, achieved by the matching of essential parasite enzymes to those human enzymes that have been successfully inhibited by small molecule drugs, provides an attractive means by which new drug optimization programs can be pragmatically initiated. In this report we describe our results in repurposing an established class of human Aurora kinase inhibitors, typified by danusertib (1), which we have observed to be an inhibitor of trypanosomal Aurora kinase 1 (TbAUK1) and effective in parasite killing in vitro. Informed by homology modeling and docking, a series of analogs of 1 were prepared that explored the scope of the chemotype and provided a nearly 25-fold improvement in cellular selectivity for parasite cells over human cells. 23315585 Low-level domoic acid protects mouse cerebellar granule neurons from acute neurotoxicity: role of glutathione. Domoic acid (DomA) is a potent marine neurotoxin. By activating α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid/kainate receptors, DomA induces oxidative stress-mediated apoptotic cell death in neurons. The effect of prolonged (10 days) exposure to a low, nontoxic concentration (5nM) of DomA on acute (intermediate concentration) neurotoxicity of this toxin was investigated in cerebellar granule neurons (CGNs) from wild-type mice and mice lacking the glutamate cysteine ligase (GCL) modifier subunit (Gclm (/)). CGNs from Gclm (/) mice have very low glutathione (GSH) levels and are very sensitive to DomA toxicity. In CGNs from wild-type mice, prolonged exposure to 5nM DomA did not cause any overt toxicity but reduced oxidative stress-mediated apoptotic cell death induced by exposure to an intermediate concentration (100nM for 24h) of DomA. This protection was not observed in CGNs from Gclm (/) mice. Prolonged DomA exposure increased GSH levels in CGNs of wild-type but not Gclm (/) mice. Levels of GCLC (the catalytic subunit of GCL) protein and mRNA were increased in CGNs of both mouse strains, whereas levels of GCLM protein and mRNA, activity of GCL, and levels of GCL holoenzyme were only increased in CGNs of wild-type mice. Chronic DomA exposure also protected wild-type CGNs from acute toxicity of other oxidants. The results indicate that CGNs from Gclm (/) mice, which are already more sensitive to DomA toxicity, are unable to upregulate their GSH levels. As Gclm (/) mice may represent a model for a common human polymorphism in GCLM, such individuals may be at particular risk for DomA-induced neurotoxicity. 22972178 GH and cortisol responses following an acute session of respiratory muscle endurance training in severely obese patients. It is well established that obese patients are hypo-responsive to classical GH-releasing stimuli, including aerobic exercise. Recently, we have demonstrated that whole body vibration was able to markedly stimulate GH secretion in obese patients, thus suggesting that this refractoriness is not absolute but dependent on the GH-releasing stimulus. Furthermore, we have shown the ability of a respiratory muscle endurance training (RMET) to stimulate GH and cortisol secretion in healthy subjects. The objective of this study was to evaluate the effects of RMET on GH and cortisol responses in severely obese patients. Eight severely obese patients (4 M/4 F, mean age±SEM: 22.8±1.6 years, body mass index, BMI: 39.9±1.1 kg/m2) underwent an incremental progressive RMET protocol of 11 daily sessions, obtained through the use of a specifically designed respiratory device (Spiro Tiger®). The 12th session of RMET (15 min duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) was associated with blood samplings for determination of GH, cortisol, and lactate (LA) levels. An age- and sex-matched normal-weighted control group (n=7, 4 M/3 F, age: 26.1±3.1 years, BMI: 22.4±0.6 kg/m2) was also recruited. In both normal-weighted subjects and obese patients, GH secretion significantly increased after a 15-min RMET session. Although serum GH levels at 30 min were higher in normal-weighted subjects than in obese patients, there was no statistically significant difference in either GH peaks or net GH areas under the curve between the 2 groups. RMET significantly increased serum cortisol levels in normal-weighted subjects, but was associated to a progressive cortisol decline in obese patients. RMET stimulated LA production, with no significant differences in normal-weighted subjects and in obese patients. A 15-min RMET session was capable to induce a GH response in severely obese patients, which was comparable to that recorded in normal-weighted subjects. A progressive decline in serum cortisol levels occurred in obese patients after RMET, while an opposite pattern (i. e., a significant cortisol increase) was found in normal-weighted subjects. Optimization of long-term RMET protocols could represent a valid strategy to (physiologically) stimulate GH/IGF-I system in those GH hyposecretory states such as obesity. 23276161 Thermodynamically consistent force fields for the assembly of inorganic, organic, and biological nanostructures: the INTERFACE force field. The complexity of the molecular recognition and assembly of biotic-abiotic interfaces on a scale of 1 to 1000 nm can be understood more effectively using simulation tools along with laboratory instrumentation. We discuss the current capabilities and limitations of atomistic force fields and explain a strategy to obtain dependable parameters for inorganic compounds that has been developed and tested over the past decade. Parameter developments include several silicates, aluminates, metals, oxides, sulfates, and apatites that are summarized in what we call the INTERFACE force field. The INTERFACE force field operates as an extension of common harmonic force fields (PCFF, COMPASS, CHARMM, AMBER, GROMACS, and OPLS-AA) by employing the same functional form and combination rules to enable simulations of inorganic-organic and inorganic-biomolecular interfaces. The parametrization builds on an in-depth understanding of physical-chemical properties on the atomic scale to assign each parameter, especially atomic charges and van der Waals constants, as well as on the validation of macroscale physical-chemical properties for each compound in comparison to measurements. The approach eliminates large discrepancies between computed and measured bulk and surface properties of up to 2 orders of magnitude using other parametrization protocols and increases the transferability of the parameters by introducing thermodynamic consistency. As a result, a wide range of properties can be computed in quantitative agreement with experiment, including densities, surface energies, solid-water interface tensions, anisotropies of interfacial energies of different crystal facets, adsorption energies of biomolecules, and thermal and mechanical properties. Applications include insight into the assembly of inorganic-organic multiphase materials, the recognition of inorganic facets by biomolecules, growth and shape preferences of nanocrystals and nanoparticles, as well as thermal transitions and nanomechanics. Limitations and opportunities for further development are also described. 23534440 Bioinformatics and Molecular Dynamics Simulation Study of L1 Stalk Non-Canonical rRNA Elements: Kink-Turns, Loops, and Tetraloops. The L1 stalk is a prominent mobile element of the large ribosomal subunit. We explore the structure and dynamics of its non-canonical rRNA elements, which include two kink-turns, an internal loop, and a tetraloop. We use bioinformatics to identify the L1 stalk RNA conservation patterns and carry out over 11.5 μs of MD simulations for a set of systems ranging from isolated RNA building blocks up to complexes of L1 stalk rRNA with the L1 protein and tRNA fragment. We show that the L1 stalk tetraloop has an unusual GNNA or UNNG conservation pattern deviating from major GNRA and YNMG RNA tetraloop families. We suggest that this deviation is related to a highly conserved tertiary contact within the L1 stalk. The available X-ray structures contain only UCCG tetraloops which in addition differ in orientation (anti vs syn) of the guanine. Our analysis suggests that the anti orientation might be a mis-refinement, although even the anti interaction would be compatible with the sequence pattern and observed tertiary interaction. Alternatively, the anti conformation may be a real substate whose population could be pH-dependent, since the guanine syn orientation requires protonation of cytosine in the tertiary contact. In absence of structural data, we use molecular modeling to explore the GCCA tetraloop that is dominant in bacteria and suggest that the GCCA tetraloop is structurally similar to the YNMG tetraloop. Kink-turn Kt-77 is unusual due to its 11-nucleotide bulge. The simulations indicate that the long bulge is a stalk-specific eight-nucleotide insertion into consensual kink-turn only subtly modifying its structural dynamics. We discuss a possible evolutionary role of helix H78 and a mechanism of L1 stalk interaction with tRNA. We also assess the simulation methodology. The simulations provide a good description of the studied systems with the latest bsc0χOL3 force field showing improved performance. Still, even bsc0χOL3 is unable to fully stabilize an essential sugar-edge H-bond between the bulge and non-canonical stem of the kink-turn. Inclusion of Mg(2+) ions may deteriorate the simulations. On the other hand, monovalent ions can in simulations readily occupy experimental Mg(2+) binding sites. 23220514 Effect of linalool as a component of Humulus lupulus on doxorubicin-induced antitumor activity. As malignant neoplasm is a major public health problem, there is a need for the development of a novel modulator that enhances antitumor activity and reduces adverse reactions to antitumor agents. In this study, the effects of some volatile oil components in Humulus lupulus on doxorubicin (DOX) permeability in tumor cells and DOX-induced antitumor activity were examined. In vitro, DOX levels in tumor cells by combined linalool as its component significantly increased in the DOX influx system, and the increased effect by linalool on DOX cytotoxicity was shown. In vivo, the combination of DOX with linalool significantly decreased tumor weight compared with that of DOX alone treated group. The promotion of DOX influx level by combined linalool did not depend on energy, whereas it was suppressed by the absence of Na(+). This promoting effect was suppressed by the presence of S-(4-nitrobenzyl)-6-thioinosine and inhibited dependently on phlorizin concentration. It is considered that linalool promoted DOX influx in tumor cells because of its action on DOX transport through concentrative Na(+)-dependent nucleoside transporter 3, which increased DOX concentration in tumor cells and thus enhanced the antitumor activity of DOX. Therefore, linalool as a food component is anticipated to be an effective DOX modulator. 23456816 A novel model approach for esophageal burns in rats: A comparison of three methods. BACKGROUND: Corrosive esophageal injury causes serious clinical problems. We aimed to create a new experimental esophageal burn model using a single catheter without a surgical procedure. Materials and methods: We conducted the study with two groups of 12 male rats that fasted for 12 h before application. A modified Foley balloon catheter was inserted into the esophageal lumen. The control group was given 0.9% sodium chloride, while the experimental group was given 37.5% sodium hydroxide with the other part of the catheter. After 60s, esophagus was washed with distilled water. The killed rats were examined using histopathological methods after 28 days. RESULTS: In comparison with the histopathological changes experienced by the study groups, the control groups were observed to have no pathological changes. Basal cell degeneration, dermal edema, and a slight increase in the keratin layer and collagen density of submucosa due to stenosis were all observed in the group subjected to esophageal corrosion. CONCLUSION: A new burn model can thus, we believe, be created without the involvement of invasive laparoscopic surgery and general anesthesia. The burn in our experiment was formed in both the distal and proximal esophagus, as in other models; it can also be formed optionally in the entire esophagus. 23497887 Kinetics of protein physicochemical changes induced by heating in meat using mimetic models: (2) effects of fibre type, peroxides and antioxidants. Heating-induced changes in meat proteins were investigated using models made of aqueous suspensions of myofibrils according to muscle fibre types and cellular compounds (oxidants and antioxidants). These changes were evaluated by measurements of carbonyl groups and protein surface hydrophobicity. Model results were compared to trial results obtained on pork meat (M. Longissimus dorsi) heated under the same conditions (45 and 75°C, from 5 to 120 min). Myofibrillar proteins from α-white fibres were more sensitive to oxidation and thermal denaturation than those from β-red fibres. At 45°C, there were negligible differences due to peroxide or antioxidant types. At 75°C, organic peroxides (ROOH) were less oxidative than hydrogen peroxide (H2O2), and antioxidant enzymes were less efficient than vitamin E and carnosine at protecting proteins against oxidation. Protein oxidation observed in meat is lower than in the mimetic models and the increase in hydrophobicity remained limited in meat. 23017414 Soymilk phenolic compounds, isoflavones and antioxidant activity as affected by in vitro gastrointestinal digestion. The aim of this research was to evaluate changes in the phenolic compounds, isoflavones and antioxidant activity of soymilk following in vitro gastrointestinal digestion (including dialysis). Gastric digestion significantly influenced the release of bioactive substances from the soymilk matrix, increasing the concentration of total phenolic components (35% as the sum of individuals and 14% by Folin-Ciocalteu [F-C] method), total isoflavone content (22%) and total antioxidant activity (76%). The concentration of all those compounds was reduced significantly in the duodenal fraction in comparison to gastric digestion and their lowest concentration was observed in the dialysed fraction, where phenolic acids were not detected. The bioaccessibility of soymilk phenolic compounds was 15% as the sum of individuals and 20% by F-C assay; isoflavones 36% and constituents with antioxidant activity 27%. Results suggest that most of these compounds were sufficiently available to be absorbed and could contribute health benefits. 23184251 Substrate ambiguity among the nudix hydrolases: biologically significant, evolutionary remnant, or both? Many members of the nudix hydrolase family exhibit considerable substrate multispecificity and ambiguity, which raises significant issues when assessing their functions in vivo and gives rise to errors in database annotation. Several display low antimutator activity when expressed in bacterial tester strains as well as some degree of activity in vitro towards mutagenic, oxidized nucleotides such as 8-oxo-dGTP. However, many of these show greater activity towards other nucleotides such as ADP-ribose or diadenosine tetraphosphate (Ap(4)A). The antimutator activities have tended to gain prominence in the literature, whereas they may in fact represent the residual activity of an ancestral antimutator enzyme that has become secondary to the more recently evolved major activity after gene duplication. Whether any meaningful antimutagenic function has also been retained in vivo requires very careful assessment. Then again, other examples of substrate ambiguity may indicate as yet unexplored regulatory systems. For example, bacterial Ap(4)A hydrolases also efficiently remove pyrophosphate from the 5' termini of mRNAs, suggesting a potential role for Ap(4)A in the control of bacterial mRNA turnover, while the ability of some eukaryotic mRNA decapping enzymes to degrade IDP and dIDP or diphosphoinositol polyphosphates (DIPs) may also be indicative of new regulatory networks in RNA metabolism. DIP phosphohydrolases also degrade diadenosine polyphosphates and inorganic polyphosphates, suggesting further avenues for investigation. This article uses these and other examples to highlight the need for a greater awareness of the possible significance of substrate ambiguity among the nudix hydrolases as well as the need to exert caution when interpreting incomplete analyses. 23516024 Multifocal motor neuropathy: current therapies and novel strategies. Multifocal motor neuropathy (MMN) is a purely motor mononeuritis multiplex characterized by the presence of conduction block on motor but not on sensory nerves and by the presence of high titers of anti-GM1 antibodies. Several data point to a pathogenetic role of the immune system in this neuropathy, although this has not yet been proved. Several uncontrolled studies and randomized controlled trials have demonstrated the efficacy of therapy with high-dose intravenous immunoglobulin (IVIg) in MMN. However, this therapy has a short-lasting effect that needs to be maintained with periodic infusions. This can be partly overcome by the use of subcutaneous immunoglobulin (SCIg) at the same dose. The high cost and need for repeated infusions have led to the search for other immune therapies, the efficacy of which have not yet been confirmed in randomized trials. In addition, some therapies, including corticosteroids and plasma exchange, are not only ineffective but have been associated with clinical worsening. More recently, a number of novel therapies have been investigated in MMN, including interferon-β1a, the anti-CD20 monoclonal antibody rituximab and the complement inhibitor eculizumab. Preliminary data from open-label uncontrolled studies show that some patients improve after these therapies; however, randomized controlled trials are needed to confirm efficacy. Until then, IVIg (and SCIg) remains the mainstay of treatment in MMN, and the use of other immune therapies should only be considered for patients not responding to, or becoming resistant to, IVIg. 23376437 In vitro biokinetics of chlorpromazine and the influence of different dose metrics on effect concentrations for cytotoxicity in Balb/c 3T3, Caco-2 and HepaRG cell cultures. The extrapolation of in vitro to in vivo toxicity data is a challenge. Differences in sensitivity between cell systems may be due to intrinsic properties of the cell but also because of differences in exposure. In this study, the cytotoxicity and biokinetics of the antipsychotic chlorpromazine (CPZ) were studied in in vitro assays using different cell types and exposure conditions. Different dose metrics were assessed to express the sensitivity to CPZ. The biokinetics of CPZ were measured in cell cultures of Balb/c 3T3, Caco-2 and HepaRG cells. Cytotoxicity was measured by Alamar Blue and expressed using different dose metrics, including the nominal, measured total and measured free CPZ medium concentrations. CPZ was taken up by the cells; the highest amounts in the cell compartments were found in the Caco-2 and HepaRG cells. CPZ was highly protein-bound in the Caco-2 cell medium containing 10% fetal bovine serum, resulting in lower bioavailable exposure concentrations. Moreover, also uptake into the cells strongly influenced the concentration in the medium. The Balb/c 3T3 cells were the most sensitive to the toxic effect of CPZ. The use of different dose metrics influenced the cytotoxicity results found in the three cell types. The data show that in comparing the sensitivity of the tested cell systems, the freely dissolved concentration is a more appropriate dose metric than total concentration in the medium. The ranking in sensitivity of the three cell types for CPZ was dependent on the dose metric used. 23439033 Orthogonal patterning of multiple biomolecules using an organic fluorinated resist and imprint lithography. The ability to spatially deposit multiple biomolecules onto a single surface with high-resolution while retaining biomolecule stability and integrity is critical to the development of micro- and nanoscale biodevices. While conventional lithographic patterning methods are attractive for this application, they typically require the use of UV exposure and/or harsh solvents and imaging materials, which may be damaging to fragile biomolecules. Here, we report the development of a new patterning process based on a fluorinated patterning material that is soluble in hydrofluoroether solvents, which we show to be benign to biomolecules, including proteins and DNA. We demonstrate the implementation of these materials into an orthogonal processing system for patterning multibiomolecule arrays by imprint lithography at room temperature. We further showcase this method's capacity for fabricating patterns of receptor-specific ligands for fundamental cell studies. 23534413 Virtual and in vitro bioassay screening of phytochemical inhibitors from flavonoids and isoflavones against xanthine oxidase and cyclooxygenase-2 for gout treatment. Synthetic drugs such as allopurinol and benzbromarone are commonly used to treat the complex pathogenesis of gout, a metabolic disease that results from an inflammation of the joints caused by precipitation of uric acid. We seek to discover novel phytochemicals that could treat gout, by targeting the xanthine oxidase and cyclooxygenase-2 enzymes. In this study, we report the screening of nine compounds of flavonoids from the ZINC and PubChem databases (containing 2092 flavonoids) using the IGEMDOCK software tool against the xanthine oxidase and cyclooxygenase-2 3D protein structures. Each compound was also evaluated by an in vitro bioassay testing the inhibition of xanthine oxidase and cyclooxygenase-2. Myricetin and luteolin were found to be the potential dual inhibitors of xanthine oxidase and cyclooxygenase-2 as demonstrated by IC(50): 62.7 and 3.29 μg/mL (xanthine oxidase)/70.8 and 16.38 μg/mL (cyclooxygenase-2), respectively. In addition, structure-activity relationships and other important factors of the flavonoids binding to the active site of xanthine oxidase and cyclooxygenase-2 were discussed, which is expected for further rational drug design. 23307290 Natalizumab therapy for multiple sclerosis. The treatment of relapsing remitting multiple sclerosis has witnessed major progress since the first effective disease modifying treatment, ß-interferon, became available in 1993. One of the most remarkable new treatments has been natalizumab. This review describes the evolution of this humanized anti-α4ß1 monoclonal antibody, from preclinical experimental research through proof-of-concept (phase 1/2) and pivotal (phase 3) clinical trials to the now extensive experience of its use in clinical practice. The future potential and challenges of natalizumab and oral therapies with a similar mechanism of action are also discussed. 23066090 A novel EPAC-specific inhibitor suppresses pancreatic cancer cell migration and invasion. Exchange protein directly activated by cAMP (EPAC) and cAMP-dependent protein kinase (PKA) are two intracellular receptors that mediate the effects of the prototypic second messenger cAMP. Identifying pharmacological probes for selectively modulating EPAC activity represents a significant unmet need within the research field. Herein, we report the identification and characterization of 3-(5-tert-butyl-isoxazol-3-yl)-2-[(3-chloro-phenyl)-hydrazono]-3-oxo-propionitrile (ESI-09), a novel noncyclic nucleotide EPAC antagonist that is capable of specifically blocking intracellular EPAC-mediated Rap1 activation and Akt phosphorylation, as well as EPAC-mediated insulin secretion in pancreatic β cells. Using this novel EPAC-specific inhibitor, we have probed the functional roles of overexpression of EPAC1 in pancreatic cancer cells. Our studies show that EPAC1 plays an important role in pancreatic cancer cell migration and invasion, and thus represents a potential target for developing novel therapeutic strategies for pancreatic cancer. 23273412 Synthesis and antioxidant activity of thymol and carvacrol based Schiff bases. Thymol and carvacrol are well known antioxidants found in the extract of the plants of thyme species. The Schiff bases of 2-iso-propyl-5-methyl-phenol (thymol/1a), 2-tert-butyl-5-methyl-phenol (1b) and 5-iso-propyl-2-methyl-phenol (carvacrol/1c) exhibited much better antioxidant activity than thymol and carvacrol in DPPH assay. Ten compounds (4k, 4l, 4r, 5k, 5l, 5q, 5r, 6k, 6l and 6r) showed better or similar activity as compared to the reference compound ascorbic acid. Twenty-four most active compounds were also screened by ABTS method and showed 60-90% inhibition at 5 μg/mL concentration. 23635005 An Antioxidative Carbohydrate Polymer from Enhydra fluctuans and Its Interaction with Bovine Serum Albumin. Enhydra fluctuans leaves are traditionally sold on Indian markets for various health benefits. However no phytochemical study on its high molecular weight compound has so far been performed. Chemical, chromatographic, ESI-TOF-MS and NMR analyses of the water extracted carbohydrate polymer (CP) of E. fluctuans leaves showed the presence of a 24 kDa arabinogalactan having a (1,3)-linked β-D-Galp main chain, substituted at O-6 by (1,6)-linked β-D-Galp side chains. The latter residues were substituted at O-3 by (1,3)-, (1,5)- and (1,3,5)-linked α-L-Araf chains, and nonreducing end-units of α-L-Araf and β-D-Galp. This polymer contained esterified phenolic acids. Biochemical analysis revealed similarity in antioxidative potential between the identified carbohydrate polymer and known standard antioxidants. The highly branched side chains and the phenolic acid residues of the arabinogalactan might be the functional sites. Fluorimetric and ultraviolet spectrometric analyses showed that the studied carbohydrate polymer can form complex with bovine serum albumin having binding constant K=2.42×10(6)/M and changes its microenvironment. Thus, traditional aqueous extraction method provides a carbohydrate polymer, which stimulates a fair biological response: this could represent an interesting approach in phytotherapeutic treatments. 23441753 Loading and distribution of a model small molecule drug in poly(N-isopropylacrylamide) brushes: a neutron reflectometry and AFM study. The structure of a hydrated poly(N-isopropylacrylamide) brush loaded with 5 vol % Isoniazid is studied as a function of temperature using neutron reflectometry (NR) and atomic force microscopy (AFM). NR measurements show that Isoniazid increases the thickness of the brush before, during and after the polymer collapse, and it is retained inside the brush at all measured temperatures. The Isoniazid concentration in the expanded brush is ~14% higher than in the bulk solution, and the concentration nearly doubles in the collapsed polymer, suggesting stronger binding between Isoniazid and the polymer compared to water, even at temperatures below the lower critical solution temperature (LCST) where the polymer is hydrophilic. Typically, additives that bind strongly to the polymer backbone and increase the hydrophilicity of the polymer will delay the onset of the LCST, which is suggested by AFM and NR measurements. The extent of small-molecule loading and distribution throughout a thermo-responsive polymer brush, such as pNIPAAm, will have important consequences for applications such as drug delivery and gating. 23116113 In vivo DNA electrotransfer for immunotherapy of cancer and neurodegenerative diseases. Electroporation is the process commonly referred to the transient increase in the permeability of cell membranes on submission to electric field pulses. Electroporation has become an increasingly extensive method to enhance in vivo DNA delivery for both gene therapy applications as well as for delivery of DNA vaccines, mostly against cancer. In vivo gene electrotransfer is of special interest since it is the most efficient non-viral strategy for gene delivery and it is worthy of low manufacturing costs, ease of realization and favorable safety profile. No adverse findings observed in toxicology and biodistribution/integration studies have been warranted for the evaluation of this approach in humans. Therefore, gene delivery followed by electroporation is currently being investigated in several clinical trials. The positive outcomes of early studies suggest that the efficacy of gene delivery and immunogenicity has greatly improved by electroporation. This review briefly summarizes salient features and recent findings that have contributed to the rapid progress of electroimmunotherapy as well as an overview of advanced clinical studies in oncology. Translation of in vivo DNA electrovaccination for neurodegenerative diseases as well as future expectations are also discussed. 23323680 In situ TEM of two-phase lithiation of amorphous silicon nanospheres. To utilize high-capacity Si anodes in next-generation Li-ion batteries, the physical and chemical transformations during the Li-Si reaction must be better understood. Here, in situ transmission electron microscopy is used to observe the lithiation/delithiation of amorphous Si nanospheres; amorphous Si is an important anode material that has been less studied than crystalline Si. Unexpectedly, the experiments reveal that the first lithiation occurs via a two-phase mechanism, which is contrary to previous understanding and has important consequences for mechanical stress evolution during lithiation. On the basis of kinetics measurements, this behavior is suggested to be due to the rate-limiting effect of Si-Si bond breaking. In addition, the results show that amorphous Si has more favorable kinetics and fracture behavior when reacting with Li than does crystalline Si, making it advantageous to use in battery electrodes. Amorphous spheres up to 870 nm in diameter do not fracture upon lithiation; this is much larger than the 150 nm critical fracture diameter previously identified for crystalline Si spheres. 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------------------------------------------------------------------- This directory contains the training abstracts, manual annotations and updated annotation guidelines. 1) chemdner_abs_training.txt : Training set abstracts This file contains plain-text, UTF8-encoded PubMed abstracts in a tab-separated format with the following three columns: 1- Article identifier (PMID, PubMed identifier) 2- Title of the article 3- Abstract of the article In total 3,500 abstracts are provided in this training set. Note that the test set will be provided in the same format. 2) Annotation Guidelines: chemdner_data_preparation_v17july31.pdf This document describes the article selection process as well as the updated manual data annotation guidelines used for the CHEMDNER task. 3) Training data annotations: chemdner_ann_training_13-07-31.txt This file contains manually generated annotations of chemical entities of the training dataset. It consists of tab-separated fields containing: 1- Article identifier (PMID) 2- Type of text from which the annotation was derived (T: Title, A: Abstract) 3- Start offset 4- End offset 5- Text string of the entity mention 6- Type of chemical entity mention (ABBREVIATION,FAMILY,FORMULA,IDENTIFIERS,MULTIPLE,SYSTEMATIC,TRIVIAL) 4) Training data Gold Standard file for the Chemical document indexing (CDI) sub-task: cdi_ann_training_13-07-31.txt Given a set of documents, for this subtask, the participants are asked to return for each of them a ranked list of chemical entities described within each of these documents. You are not required to provide the specific type of chemical entity class. It consists of tab-separated fields containing: 1- Article identifier (PMID) 2- Text string of the entity mention An example is shown below: 22258629 malondialdehyde 22288603 mikanolide 5) Training data Gold Standard file for the Chemical entity mention recognition (CEM) sub-task: cem_ann_training_13-07-31.txt Given a set of documents, for this subtask, the participants have to return the start and end indices corresponding to all the chemical entities mentioned in this document. You are not requested to provide the specific type of chemical entity subclass. It consists of tab-separated columns containing: 1- Article identifier (PMID) 2- Offset string consisting in a triplet joined by the ':' character. You have to provide the text type (T: Title, A:Abstract), the start offset and the end offset. An example illustrating the format is shown below: 21826085 A:946:957 22080034 A:1072:1081 22080034 A:1305:1314 22080034 A:1383:1392 22080034 A:190:199 Additional comments ------------------- To evaluate the performance of your system we recommend you to use the BioCreative evaluation library scripts. You can also directly download it from the BioCreative Resources page at: http://www.biocreative.org/resources/biocreative-ii5/evaluation-library/ This webpage explains in detail how to install the library and how it works. For both of the tasks you should use the --INT evaluation option like shown below: bc-evaluate --INT prediction_file evaluation_file As the --INT option is chosen by default, you can also run this script without the argument: bc-evaluate prediction_file evaluation_file Example evaluation files for both subtasks were described above. A) Prediction format for the CDI subtask Please make sure that your predictions are compliant with the formatting information provided for the --INT option of the evaluation library (The webpage and the bc-evaluate -h and bc-evaluate -d option provide you with more details.) In short, you have to provide a tab-separated file with: 1- Article identifier 2- The chemical entity mention string 3- The rank of the chemical entity returned for this document 4- A confidence score Example cases are provided online in the CHEMDNER sample set (June 25, 2013) (http://www.biocreative.org/resources/corpora/bc-iv-chemdner-corpus/#bc-iv-chemdner-corpus:downloads) An example prediction for the sample set is shown below: 6780324 LHRH 1 0.9 6780324 FSH 2 0.857142857143 6780324 3H2O 3 0.75 6780324 (Bu)2cAMP 4 0.75 6780324 vitro 5 0.666666666667 6780324 plasminogen 6 0.5 6780324 ethylamide 7 0.5 6780324 beta-3H]testosterone 8 0.5 6780324 NIH-FSH-S13 9 0.5 6780324 D-Ser-(But),6 10 0.5 6780324 4-h 11 0.5 6780324 3-isobutyl-l-methylxanthine 12 0.5 2231607 thymidylate 1 0.666666666667 2231607 acid 2 0.666666666667 2231607 TS 3 0.666666666667 B) Prediction format for the CEM subtask Please make sure that your predictions are compliant with the formatting information provided for the --INT option of the evaluation library (The webpage and the bc-evaluate -h and bc-evaluate -d option provide you with more details.) In short, you have to provide a tab-separated file with: 1- Article identifier (PMID) 2- Offset string consisting in a triplet joined by the ':' character. You have to provide the text type (T: Title, A:Abstract), the start offset and the end offset. 3- The rank of the chemical entity returned for this document 4- A confidence score Example from the sample set (from June 25, 2013) is shown below: 6780324 A:104:107 1 0.5 6780324 A:1136:1147 2 0.5 6780324 A:1497:1500 3 0.5 6780324 A:162:167 4 0.5 6780324 A:17:21 5 0.5 6780324 A:319:330 6 0.5 6780324 A:448:452 7 0.5 CHEMDNER_TRAIN_V01/cdi_ann_training_13-07-31.txt0000644002344200234200000125644612176242610022172 0ustar mkrallingerBioinfoUnix21826085 haloperidol 22080034 aflatoxin 22080035 S 22080035 arsenic 22080035 cadmium 22080035 copper 22080035 glutathione 22080035 malondialdehyde 22080035 superoxide 22080037 Mercury 22080037 mercury 22080037 nitric oxide 22258629 Chromium 22258629 chromium 22258629 graphite 22258629 malondialdehyde 22288603 mikanolide 22294443 PCAHs 22294443 Polycyclic aromatic hydrocarbons 22294443 benzo(a)anthracene 22294443 benzo(a)pyrene 22294443 benzo(e)pyrene 22294443 benzoflouroanthene 22294443 cyclohexane 22294443 fluoranthene 22294443 methanolic potassium hydroxide 22294443 polycyclic aromatic hydrocarbons 22294443 pyrene 22301816 Thiovit 22301816 captafol 22301816 captan 22301818 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide 22301818 MTT 22303963 acetonitrile 22303963 formic acid 22303963 steroidal saponins 22304302 (25S)-1β,3β,4β-trihydroxyspirostan-5β-yl-O-β-D-glucopyranoside 22304302 MTT 22304302 furostanol 22304302 kitigenin-5β-O-β-D-glucopyranoside 22304302 reinocarnoside A (1), B (2) and C (3) 22304302 spirostanols 22304302 steroidal glycosides 22310169 O 22310169 PAH 22310169 PAHs 22310169 S 22310169 ethoxyresorufine 22310169 glutathione 22310169 polycyclic aromatic hydrocarbons 22310169 thiobarbituric 22310170 TCS 22310170 phosphate 22310170 triclosan 22312034 4aα,7β,7aα-nepetalactone 22312034 SDS 22312034 elemol 22312034 germacrene 22312034 polyacrylamide 22312034 sodium dodecyl sulphate 22317823 Al 22317823 Aluminum 22317823 aluminum 22349814 PI(3,4,5)P3 22349814 monoglyceride 22349814 phosphatidic acid 22349814 phosphatidylinositol 22349814 phosphoinositides 22349814 phosphoinositol(3,4)P2 22349814 phosphoinositol(3,4,5)P3 22349814 phosphoinositol(3,5)P2 22360797 acacetin 22360797 acacetin 7-methyl ether 22360797 acetone 22360797 betulin aldehyde 22360797 betulinic acid 22360797 betulon aldehyde 22360797 betulonic acid 22360797 flavonoids 22360797 lupenone 22360797 lupeol 22360797 morolic acid 22360797 moronic acid 22360797 oleanolic acid 22360797 oleanolic aldehyde 22360797 squalene, α- and β-amyrin 22360797 stigmasterol 22360797 triacontanol 22360797 β-sitosterol 22360797 β-sitosteryl and stigmasteryl linoleates 22370634 RAP 22370634 Rapamycin 22370634 rapamycin 22370645 WP1066 22370645 gefitinib 22370645 phosphatidyl inositol 22385272 isomenthone 22385272 isopulegone 22385272 limonene 22385272 menthone 22385272 pulegone 22394118 Carbon 22394118 carbon 22394118 sucrose 22394118 withanolide A 22397600 nimesulide 22397675 2-pyrrolidone 22397675 IVM 22397675 Ivermectin 22397675 N-methyl-2-pyrrolidone 22397675 NMP 22397675 PLA 22397675 benzyl benzoate 22397675 ivermectin 22397675 poly(D,L-lactide) 22397675 triacetine 22401597 1α,3β,25-trihydroxy-9(11)-ene-16-one-9,10-seco-9,19-cyclolanostane 22401597 9,10-seco-9,19-cyclolanostane 22401597 fatty alcohols 22401597 triterpene 22404642 24-methylenecicloartan-3β-ol 22404642 3,3'-di-O-methylellagic acid 22404642 3β-O-octadecanoyllupeol 22404642 cicloart-23-ene-3β,25-diol 22404642 ellagic acid 22404642 glut-5-en-3β-ol 22404642 triterpenoids 22420410 Trans-cyclo-(D-tryptophanyl-L-tyrosyl) 22420410 amino acid 22420410 diketopiperazine 22420410 trans-cyclo-(D-tryptophanyl-L-tyrosyl) 22424088 DPPH 22424088 eugenol 22424088 superoxide 22424117 8-O-cafeoyl massenoside 22424117 8-O-trans-cinnamoyl caryoptoside 22424117 8-O-trans-cinnamoyl mussaenoside 22424117 8-O-trans-cinnamoyl shanzhiside methylester 22424117 acetyl 22424117 ethylacetate 22424117 iridoid glucosides 22424117 iridoids 22430207 glucose 22445601 Glutamate 22445601 LY541850 22445601 amphetamine 22445601 glutamate 22445601 phencyclidine 22451355 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide 22455800 3-alkyl-2,6-diarylpiperidin-4-one 22455800 4-hydroxy-3,4-dialkyl-2,6-diaryl-piperidine 22455800 Grignard reagent 22455800 piperdin-4-ol 22468693 acetone 22468693 chloroform 22468693 diethyl ether 22468693 eicosane 22468693 oleic acid 22468693 saponins 22468693 stigmasterol 22468693 vitamin E 22468741 Isoleucine 22468741 arsenic 22468741 calcium 22468741 magnesium 22468741 potassium 22468741 sodium dodecyl sulphate polyacrylamide 22469981 doxycycline 22469981 tetracycline 22469988 ATP 22469988 fatty acids 22469988 glucose 22469988 oxygen 22475014 C(21) 22475014 C21 22475014 Glaucogenin E 22475014 steroid 22480291 acetonitrile 22480291 boeravinone B 22480291 boeravinone E 22480291 boeravinone E and B 22480291 orthophosphoric acid 22480291 rotenoids 22489960 17β-estradiol 22489960 7-ethoxyresorufin 22489960 GSH 22489960 O 22489960 benzo(a)pyrene 22489960 glutathione 22489960 testosterone 22489960 triglyceride 22497567 18F 22497567 18F-IMC 22497567 F-IMC 22497567 IMC 22497567 fluoro-indomethacin 22497567 indomethacin 22502647 furostanol 22502647 polyhydroxyl 22502647 saponin 22502647 saponins 22507666 (R,S)-3,5-dihydroxyphenylglycine 22507666 2-methyl-6-(phenylethynyl)pyridine hydrochloride 22507666 AMPA 22507666 DHPG 22507666 Glutamate 22507666 MPEP 22507666 Ser 22507666 adenosine 22507666 cAMP 22507666 dopamine 22507666 glutamate 22510064 NaOH 22510064 Poloxamer 407 22510064 poloxamer 407 22510064 rebamipide 22510064 sodium hydroxide 22512590 Nikkomycin Z 22512590 nikkomycin 22512590 polyoxin 22516666 CO(2) 22516666 Venlafaxine 22516666 benzodiazepines 22516666 carbon dioxide 22516666 lorazepam 22516666 paroxetine 22516666 pregabalin 22516666 venlafaxine 22533550 2-bromoacetic acid 22533550 N-isobutyl-4,5-epoxy-2(E)-decenamide 22533550 Octanal 22533550 amide 22546615 (S)-3,4-DCPG 22546615 (S)-3,4-dicarboxyphenylglycine 22546615 6-hydroxydopamine 22546615 DCPG 22546615 Glutamate 22546615 decanoate salt 22546615 dopamine 22546615 glutamate 22546615 haloperidol 22546615 reserpine 22546616 GABA 22546616 [(11)C]Ro15-4513 22546616 benzodiazepine 22546616 gamma-amino-butyric-acid 22548348 C-geranylated flavonoids 22548348 Tomentomimulol 22548348 methanol 22548348 mimulone B 22548348 tanariflavanone D 22548348 tomentomimulol 22548364 (3R,4S,5R,6R)-3,4,5,6-tetrahydro-4-hydroxy-3,5,6-trimethyl-2H-pyran-2-one 22548364 2-phenylacetamide 22548364 N-trans-cinnamoyl 2-amino-3a,4,5,6,7,8,9,10,11,12,13,13a-dodecahydrocyclododeca[d]oxazole 22548364 cyclododeca[d]oxazole 22548364 di(1H-pyrrol-2-yl)methanone 22548364 indolyl-3-carboxylic acid 22548364 pimprinine 22551786 GRN-529 22551786 MTEP 22551786 glutamate 22559719 Citronellal 22559719 carbon dioxide 22559719 citronellal 22559719 oxygenated monoterpenes 22561337 estrogen 22563917 BBH 22563917 Berberine hydrochloride 22563917 Tween-80 22563917 berberine hydrochloride 22563917 ethyl linoleate 22563917 glycerol 22563917 oleic acid 22579656 GABA 22579656 THDOC 22579656 allopregnanolone 22579656 allotetrahydrodeoxycorticosterone 22579656 estrogens 22579656 progesterone 22583008 Fatty acid 22583008 Saturated fatty acids 22583008 arachidonic (C20 : 4ω-6) and eicosapentaenoic (C20 : 5ω-3) acids 22583008 fatty acid 22583008 fatty acids 22583008 monounsaturated fatty acids 22583008 polyunsaturated fatty acids 22585425 APC 22585425 Allylpyrocatechol 22585425 GSH 22585425 acetate 22585425 allylpyrocatechol 22585425 myristate 22585425 oxygen 22585425 phorbol 22585425 sodium ascorbate 22585425 superoxide 22585450 N-[3(aminomethyl) benzyl]-acetamidine 22585450 STZ 22585450 acetylcholine 22585450 dihydrochloride 22585450 malondialdehite 22585450 nitrate 22585450 nitric oxide 22585450 nitrite 22585450 noradrenaline 22585450 streptozotocin 22594605 1,3-dimethylpyrimidine-2,4(1H,3H)-dione 22594605 9-acetyl-1,3,7-trimethyl-pyrimidinedione 22594605 caffeine 22594605 pyrimidinedione 22610853 Curcumin 22610853 cholesterol 22610853 curcumin 22610853 curcuminoids 22610853 triglycerides 22616559 apigenin 7-O-β-D-cellobioside 22616559 apigenin 7-O-β-D-cellobiosyl-4'-O-β-D-glucopyranoside 22616559 naringenin 22616577 24-hydroxytormentic acid 22616577 3-O-β-D-glucopyranosylsitosterol 22616577 Arjunolic acid 22616577 C-C 22616577 NaIO4 22616577 SiO2 22616577 THF 22616577 acetal triterpenes 22616577 bicyclotriacetal of β-sitosterol 22616577 hydroxyl 22616577 lactol pentacyclic triterpenes 22616577 silica gel 22616577 sodium periodate 22616577 vicinal diol 22619070 terpene 22619070 terpinen-4-ol 22623520 Methiocarb 22623520 carbamate 22623520 glutathione 22623520 malondialdehyde 22623520 methiocarb 22623520 superoxide 22623520 taurine 22623520 vitamin E 22625411 sulfonamide 22625411 sulfonamides 22625416 omega-3 fatty acids 22625416 sterols 22625416 terpenes 22625416 terpenoid 22625416 tocochromanols 22628017 H2 O2 22628017 Succinate 22628017 anthocyanin 22628017 anthocyanins 22628017 cyanidin-3-galactoside 22628017 malate 22628017 malvidin-3-galactoside 22628017 malvidin-3-glucoside 22628017 pyruvate 22628265 4-O-methylhonokiol 22628265 Ethanol 22628265 ethanol 22628265 honokiol 22628265 magnolol 22628265 neolignan 22628265 nitric oxide 22628265 obovatol 22634360 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 22634360 6-hydroxydopamine 22634360 Glutamate 22634360 L-AP4 22634360 MPTP 22634360 VU0155041 22634360 glutamate 22640571 (1)H 22640571 16-Isopropyl-5, 9-dimethyltetracyclo [10.2.2.0(1, 10).0(4, 9)] hexadec-15-ene-5, 14-dicarboxylic acid 22640571 16-isopropyl-5, 9-dimethyltetracyclo [10.2.2.0(1, 10).0(4, 9)] hexadec-15-ene-5, 14-dicarboxylic acid 22640571 Schiff bases 22641218 Celastrol 22644836 cholesterol 22644836 glucose 22644836 triglycerides 22648529 flavonoids 22648529 hopane 22648529 methanol 22648529 oleanane 22648529 saponins 22658648 Myo-inositol 22658648 glucose 22658648 inositol 22658648 myo-inositol 22659473 Glutamate 22659473 glutamate 22660443 Azole 22660443 azoles 22660443 corticosteroids 22661401 Cu(2+) 22661401 Mn(2+) 22661401 Ni(2+) 22661401 Zn(2+) 22669363 N-acetylgalactosamine 22670797 (E)-2-(4-tert-butylbenzylidene) hydrazinecarbothioamide 22670797 4-tert-butylphenylthiourea 22670797 QNT3-18 22670797 QNT3-20 22670797 octanol 22677475 TBBPA 22677475 Tetrabromobisphenol A 22677475 tetrabrombisphenol A 22678994 H2 O2 22678994 Polymethoxylated flavones 22678994 acetoxymethyl ester 22678994 calcium 22678994 nobiletin 22678994 poly (ADP-ribose) 22678994 tangeretin 22683935 2,4-dinitrochlorobenzene 22683935 ammonium-hexachloroplatinate 22683935 cinnamaldehyde 22683935 cinnamic-alcohol 22683935 eugenol 22683935 isoeugenol 22683935 nickel-sulfate 22683935 octanoic acid 22683935 paraphenylendiamine 22683935 phenol 22683935 salicylic acid 22683935 sodium lauryl sulfate 22683935 tetramethylthiuram disulfide 22693035 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) 22693035 2,2-diphenyl-1-picrylhydrazyl 22693035 8-hydroxycirsimaritin 22693035 ABTS 22693035 Apigenin-7-O-glucoside 22693035 DPPH 22693035 Fe(II) 22693035 Nepetanudoside B 22693035 apigenin 22693035 butylhydroxytoluene 22693035 cirsimaritin 22693035 ethyl acetate 22693035 ixoroside 22693035 luteolin 22693035 methanol 22693035 n-Butanol 22693035 n-butanol 22693035 n-hexane 22693035 oleanolic acid 22693035 ursolic acid 22694738 -3,5-di-O-β-glucosides of delphinidin 22694738 Anthocyanins 22694738 acylated anthocyanins 22694738 anthocyanin 22694738 anthocyanins 22694738 cyanidin 22694738 cyanidin-3-O-[6-O-(4-O-E-caffeoyl-O-α-rhamnopyranosyl)-β-glucopyrano]-5-O-β-glucopyranoside 22694738 cyanidin-3-O-[6-O-(4-O-E-p-coumaroyl-O-α-rhamnopyranosyl)-β-glucopyrano]-5-O-β-glucopyranoside 22694738 cyanidine 22694738 malvidin 22694738 pelargonidin-3-O-[6-O-(4-O-E-p-coumaroyl-O-α-rhamnopyranosyl)-β-glucopyrano]-5-O-β-glucopyranoside 22694738 peonidin 22694738 peonidin-3-O-β-glucoside 22694738 petunidin 22705340 Glutamate 22705340 MTEP 22705340 VU0360172 22705340 polyphosphoinositide 22709945 CORT 22709945 corticosterone 22712581 peristrophine 22712581 phenoxazine 22712621 arbutin 22718275 3β,5α-dihydroxycholest-7-en-6-one 22718275 3β-hydroxysterol 22718275 7-DHC 22718275 7-Dehydrocholesterol 22718275 DHCEO 22718275 IsoPs 22718275 NeuroPs 22718275 arachidonic acid 22718275 docosahexaenoic acid 22718275 isoprostanes 22718275 neuroprostanes 22718275 oxysterol 22718275 oxysterols 22724545 (22R)-hydroxylanosta-7,9(11),24-trien-3-one 22724545 6,8-dihydroxy-3-methyl-3,4-dihydroisocoumarin 22724545 ergosterol 22724545 isocoumarin 22724545 methanol 22728231 DNCB 22728231 lactic acid 22728231 pPD 22728231 resorcinol 22728761 D-Serine 22728761 D-serine 22728761 cocaine 22732443 AMPA 22732443 Ro25-6981 22736593 20(S)-Protopanaxatriol 22736593 20(S)-protopanaxatriol 22736593 UDP 22736593 ginsenosides 22736593 ppt 22743159 Glutamate 22743159 glutamate 22745189 Sulpiride 22745189 sulpiride 22750050 ATP 22750050 adenosine monophosphate 22750050 adenosine triphosphate 22750050 fatty acid 22750050 glucose 22750050 serine 22750050 threonine 22750079 Mirtazapine 22750079 mirtazapine 22751286 Cisplatin 22751286 cis-diamminedichloroplatinum II 22751286 cisplatin 22751286 glutathione 22751286 sulfhydryl 22751286 ω-3 polyunsaturated fatty acid 22760156 bicarbonate 22760156 citrate 22760156 lactate 22760156 lanthanide 22760156 urate 22765022 5,2',4'-trihydroxy-flavone-8-C-α-arabinopyranoside-7-O-β-glucopyranoside 22765022 Flavonoid 22765022 apigenin 22765022 apigenin 7-O-gentobioside 22765022 apigenin-7-O-β-glucopyranoside 22765022 daidzein 22765022 flavonoid 22765022 luteolin 22765022 luteolin-7-O-β-glucopyranoside 22765022 quercetin-3,7-di-O-β-glucopyranoside 22765022 quercetin-3,7-di-O-β-glucopyranoside 4'-O-α-rhamnopyranoside 22765022 quercetin-3-O-β-glucopyranoside-7-O-α-rhamnopyranoside 22765159 2-piperidinone 22765159 3-methylhydantoin 22765159 cyclo-(Gly-L-Ala) 22765159 cyclo-(Gly-L-Tyr) 22765159 cyclo-(L-Ala-L-Ala) 22765159 cyclo-(L-Ala-L-Tyr) 22765159 cyclo-(L-Ala-trans-4-hydroxy-L-Pro) 22765159 cyclo-(L-Pro-Gly) 22765159 cyclo-(L-Pro-L-Ser) 22765159 cyclo-(L-Tyr-trans-4-hydroxy-L-Pro) 22765159 cyclodipeptides 22765159 yclo-(L-Val-L-Pro) 22766173 KI 22766173 iodide 22766173 terephthalic acid 22766394 Modafinil 22766394 modafinil 22771462 AP5 22771462 CNQX 22771462 CPCCOEt 22771462 DHPG 22771462 Glutamate 22771462 MPEP 22771462 TBOA 22771462 antagonist MPEP 22771462 glutamate 22776039 glucose 22780426 (+)-2-heptadecyl-4-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one 22780426 (-)-(4S)-2-[(Z)-1'-(6″,7″-dihydroxyphenethyl-amino)octadec-11'-enylidene]-4-hydroxycyclohexane-1,3-dione 22780426 2-(1,3-dihydroxyphenyl)-octacosan-1'-one 22780426 Dindygulerione C 22780426 acylresorcinol 22780426 dindyguleranone 22780426 dindygulerione C 22780426 dindygulerione D 22780426 octaketide 22780426 polyketide 22780563 Ca (CH(3)COO)(2) 22780563 Calcium acetate 22780563 H(3)PO(4) 22780563 Hydroxyapatite 22780563 Ti 22780563 carbon 22780563 hydroxyapatite 22780563 n-butanol 22780563 phosphoric acid 22788542 flavonoids 22788542 quercetin 22788542 rutin 22788700 CaA 22788700 Polyphenol 22788700 caffeic 22788700 chlorogenic 22788700 ferulic acids 22788700 polyphenol 22788700 polyphenols 22788700 rutin 22788743 folate 22788743 phenolic 22788743 vitamin C 22789395 methyl, ethyl, n-propyl and n-butyl parabens 22789395 p-hydroxybenzoic acid 22789395 parabens 22799569 Flavonoid 22799569 Flavonoids 22799569 flavonoids 22799569 quercetin 3-O-glucoside 22799569 quercetin 3-O-rhamnoside 22799569 quercetin 3-O-rhamnosyl-(1 → 2)-[rhamnosyl-(1 → 6)]-glucoside 22799569 quercetin 3-O-rhamnosyl-(1 → 6)-glucoside 22804459 DPPH 22804459 Trolox 22804459 caffeic acid 22804459 ethanol 22804459 ferric 22804459 lithospermic acid 22804459 methanol 22804459 rosmarinic acid 22804459 salvianolic acid C 22809021 estradiol 22809021 progesterone 22809387 Li 22809387 LiFePO(4) 22809387 LiPF(6) 22809387 PEI 22809387 polyethyleneimine 22813628 MBuP 22813628 MBzP 22813628 MEHP 22813628 MMP 22813628 mono-(2-ethylhexyl) phthalate 22813628 monobenzyl phthalate 22813628 monobutyl phthalate 22813628 monomethyl phthalate 22813628 monophthalates 22813628 phthalate monoester 22813628 phthalate monoesters 22815230 1,1-diphenyl-2-picryl hydrazyl 22815230 DPPH 22815230 FeSO4 22815230 acetone 22815230 ferric 22815230 ferrous 22815230 methanol 22815230 trypan blue 22815248 CCl4 22815248 GSH 22815248 MDA 22815248 N 22815248 Saponin 22815248 alanine 22815248 aniline 22815248 aspartate 22815248 carbon tetrachloride 22815248 ethylmorphine 22815248 glutathione 22815248 lactate 22815248 malondialdehyde 22815248 paracetamol 22815248 saponin 22815248 silymarin 22818587 tryptophan 22820275 ATM 22820275 Atomoxetine 22820275 isoflurane 22820275 norepinephrine 22824787 FLX 22824787 fluoxetine 22824788 cadmium 22827445 C(60) 22827445 C60 22827445 POT-co-DOT 22827445 acetonitrile 22827445 poly(3-octylthiophene-2,5-diyl-co-3-decyloxythiophene-2,5-diyl) 22827445 thiophene 22827445 toluene 22827894 bispyridinium oximes 22827894 organophosphorus 22827894 oxime 22827894 oximes 22830982 1-OH-midazolam 22830982 Fluorescein diacetate 22830982 acetaminophen 22830982 caffeine 22830982 dextromethorpahn 22830982 dextromethorphan 22830982 dextrorphan 22830982 hydroxy-omeprazole 22830982 hydroxyl-repaglinide 22830982 midazolam 22830982 omeprazole 22830982 omeprazole sulfone 22830982 paraxanthine 22830982 repaglinide 22830982 tolbutamide 22832075 Vitamin A 22832075 all-trans-retinoic acid 22832075 retinoic acid 22832075 retinoids 22832075 retinol 22832075 vitamin A 22832075 vitamin-A 22834411 1-butanol 22834411 barium ferrite 22834411 dodecylbenzenesulphonic acid 22836659 Cys 22836659 Gly 22836881 aspirin 22836881 nitrates 22838394 (1)H 22838394 (13)C 22838394 2,3-demethoxy-secoisolintetralin diacetate 22838394 2,3-demethoxy-secoisolintetralin monoacetate 22838394 9-acetyl-9'-pentadecanoil-dihydroclusin 22838394 diarylbutane lignans 22838394 dihydroclusin diacetate 22838394 dihydroclusin monoacetate 22840199 camphor 22840199 chamazulene 22840199 citronellol 22840199 geraniol 22840229 10(Z)-cyclonerotriol 22840229 cyclonerodiol 22840229 cyclonerol 22840229 sesquiterpene 22841391 Methylselenol 22841391 methylselenol 22841391 selenium 22841397 Biotin 22841397 acetyl-CoA 22841397 biotin 22841397 glucose 22841916 Caffeine 22841916 adenosine 22841916 caffeine 22841917 DHA 22841917 EPA 22841917 Omega-(n)-3 polyunsaturated fatty acids 22841917 PUFA 22841917 PUFAs 22841917 docosahexaenoic acid 22841917 eicosapentaenoic acid 22841917 omega-3 fatty acids 22846225 Chelerythrine 22846225 ZIP 22846225 chelerythrine 22846225 myristoylated ζ-pseudosubstrate peptide 22846225 staurosporine 22849656 neurotensin 22849656 tyrosine 22849972 cholesterol 22849972 glucose 22859660 Ach 22859660 ISO 22859660 SNP 22859660 acetylcholine 22859660 fenofibrate 22859660 glycerol 22859660 isoproterenol 22859660 phenylepherine 22859660 sodium nitroprusside 22862926 glucose 22865292 H(+) 22865292 chloroquine 22867274 GSH 22867274 N 22867274 NADPH 22867274 amide 22867274 aryl amine 22867274 benzothiazole amide 22867274 glutathione 22872141 Formaldehyde 22872141 formaldehyde 22872607 Aldo-keto 22872607 PAHs 22872607 cotinine 22872607 o-quinones 22872607 oxygen 22872607 polycyclic aromatic hydrocarbons 22874922 Ca(2+) 22876956 6-nitro-3,4-methylenedioxyphenyl-Nacylhydrazone 22876956 LASSBio-881 22876956 Nitrogen 22876956 O2 •- 22876956 ONOO- 22876956 carbamazepine 22876956 desipramine 22876956 duloxetine 22876956 escitalopram 22876956 fluoxetine 22876956 indomethacin 22876956 meloxicam 22876956 nitrogen 22876956 oxygen 22876956 paroxetine 22876956 peroxynitrite 22876956 phenytoin 22876956 sulfur 22876956 superoxide 22876956 tenoxicam 22876956 valdecoxib 22876956 α-lipoic acid 22876956 γ-butyrolactone 22889561 danusertib 22889612 BaP 22889612 RVT 22889612 benzo(a)pyrene 22889612 resveratrol 22889721 Hematoxylin 22889721 calcium 22889721 eosin 22891663 GPV 22891663 N,β-D-glucopyranosyl vincosamide 22891663 chlorophyll 22891663 hydrogen peroxide 22891663 hydroxyl 22891663 indole alkaloid 22891663 oxygen 22891663 superoxide 22898132 boric acid 22898132 caffeine 22898132 glucose 22898132 hydroxyurea 22898132 methoxyacetic acid 22898132 paraoxon-methyl 22898132 retinoic acid 22898132 sodium salicylate 22898132 valproic acid 22898132 valproic and methoxyacetic acid 22903180 silver 22906569 bilirubin 22906569 biliverdin 22906572 ATP 22906572 Ca(2+) 22906572 Heptylamine 22906572 amine 22906572 calcium 22906572 heptylamine 22906573 amine 22906573 carbon 22906573 polystyrene 22911509 Teflon 22911509 graphene 22914985 MPA 22914985 MPA glucuronide 22914985 MPAG 22914985 Mycophenolic acid 22914985 inosine-5'-monophosphate 22914985 mycophenolate 22914985 mycophenolic acid 22914985 mycophenolic acid glucuronide 22917637 (+)- and (-)-cocaine 22917637 (+)-cocaine 22917637 (-)-cocaine 22917637 [(11)C](+)-cocaine 22917637 [(11)C](-)-cocaine 22917637 cocaine 22921987 MDA 22921987 Psoralen 22921987 malonaldehyde 22923473 fructose 22923473 glucose 22926048 GSH 22926048 GSSG 22926048 HEDS 22926048 NADPH 22926048 glucose 22926048 glutathione 22926048 hydroxyethyl disulfide 22926048 pentose phosphate 22926048 thiol 22931186 Etoposide 22931186 creatinine 22931186 etoposide 22931212 5-phosphoribose 22931212 ADP 22931212 H 22931212 NAD 22931212 NADH 22931212 NADP 22931212 NMN 22931212 Rib 22931212 adenine 22931212 adenine dinucleotide phosphate 22931212 amino acid 22931212 carboxylic acid 22931212 phenyl 22931212 pyrazole 22931212 ribose 22931212 sulfur 22931212 thiazole 22931212 β-nicotinamide mononucleotide 22935104 sildenafil 22935104 thalidomide 22940283 thiocholine esters 22940855 4-amino-5-(2-hydroxyphenyl)-2H-1,2,4-triazole-3(4H)-thione 22940855 H 22940855 H2 22940855 H3B 22940855 N2 22940855 N3 22940855 O1 22940855 S1 22940855 chloroform 22940855 hydrogen 22940855 methanol 22940855 thiol dimer 22940855 thione 22940855 thione and thiol dimers 22940855 thione dimer 22940855 thione-thiol 22940855 triazole 22945693 CpG 22945693 sodium-iodide 22949511 hydroxylates 22949511 lysines 22949511 lysyl 22949511 prolyl 22954532 Na 22954532 TTX 22954532 Tungsten carbide 22954532 WC 22954532 sodium 22954532 tetrodotoxin 22954532 tungsten carbide 22955948 H(2)O(2) 22955948 hydrogen peroxide 22955948 rapamycin 22956629 TiO(2) 22956629 titanium dioxide 22956630 4-hydroxybenzoic acid 22956630 OH 22956630 Paraben esters and their salts 22956630 Parabens 22956630 alkyl esters 22956630 benzoic acid 22956630 benzylparaben 22956630 butyl- and benzylparaben 22956630 butylparaben 22956630 ethyl 22956630 ethylparaben 22956630 methyl 22956630 methylparaben 22956630 p-hydroxybenzoic acid 22956630 parabens 22956630 propyl 22956630 propylparaben 22958332 carbon dioxide 22958332 oxygen 22960471 7-AAD 22960471 7-aminoactinomycin 22960471 Nicotine 22960471 nicotine 22960471 sulforhodamine B 22961087 triglycerides 22961200 alanine dipeptide 22963367 GdOCl 22963367 ITO 22963367 Tb-doped GdOCl 22963367 cyclohexane 22963367 indium tin oxide 22963553 Ipratropium bromide 22963553 Oxitropium bromide 22963553 Tiotropium bromide 22963553 aclidinium bromide 22963553 glycopyrrolate bromide 22963553 ipratropium bromide 22963553 oxitropium bromide 22963553 tiotropium 22963553 tiotropium bromide 22963554 corticosteroid 22963554 macrolides 22963554 nortriptyline 22963554 theophylline 22963619 (99m)Tc 22963619 99mTc 22963619 DTPA 22963619 Methionin 22963619 Methionine 22963619 amino acid 22963619 amino acids 22963619 methionine 22966070 O(2) 22966070 glucose 22966070 tyr 22966070 tyrosine 22967722 Glabridin 22967722 carbon dioxide 22967722 carnitine 22967722 glabridin 22967722 glucose 22967722 isoflavan 22967722 phosphoenolpyruvate 22968089 AMN082 22968089 LY379268 22968089 MPEP 22968089 glutamate 22972178 cortisol 22972178 lactate 22972179 2-Deoxyglucose 22972179 2-deoxyglucose 22972179 Ser 22972179 Thr 22972179 rapamycin 22972222 glucose 22972222 vildagliptin 22972396 platinum 22975146 (α)-asarone 22975146 Alpha-asarone 22975146 GABA 22975146 Mg(2+) 22975146 bicuculline 22975146 glycine 22975146 kainate 22975146 pentylenetetrazole 22975146 picotoxin 22975146 strychnine 22975146 α-asarone 22975155 2PAM 22975155 MMB4 22975155 N-substituted 2-hydroxyiminoacetamido alkylamines 22975155 RS194B 22975155 RS41A 22975155 cyclosarin 22975155 oxime 22975155 oximes 22975155 paraoxon 22975155 pyridinium 22975155 sarin 22975155 tabun 22977168 diisocyanate 22977168 hexamethylene diisocyanate 22981737 C 22981737 acetylcholine 22981737 tyrosine 22982206 Verrucarin A 22982206 oxygen 22982206 salubrinal 22982206 verrucarin A 22982773 HI-6 22982773 O-ethyl isopropylphosphonofluoridate 22982773 O-methyl cyclohexylphosphonofluoridate 22982773 O-methyl isopropylphosphonofluoridate 22982773 alkoxy 22982773 cyclosarin 22982773 dimethylamine 22982773 obidoxime 22982773 organophosphorus 22982773 oxime 22982773 phosphate 22982773 phosphates 22982773 phosphonate 22982773 phosphonates 22982773 phosphoramidate 22982773 phosphoramidates 22982773 sarin 22982773 tabun 22983118 2,5-dimethoxy-4-iodoamphetamine hydrochloride 22983118 3,4-Methylenedioxymethamphetamine 22983118 5-HT 22983118 DOI 22983118 Ecstasy 22983118 MDMA 22983118 MTT 22983118 amphetamine 22983118 amphetamines 22983118 lactate 22983118 tetrazolium 22983652 PMMA 22983652 Poly(methyl methacrylate) 22983652 carbon 22985735 GSH 22985735 H(2)O(2) 22985735 SiO(2) 22985735 SiO2 22985735 silica 22985953 MMT 22985953 Na(+) 22985953 Na+ 22985953 carbohydrates 22985953 glycerol 22985953 hydroxyl 22985953 montmorillonite 22985953 sugar alcohol 22985953 sugar alcohols 22985953 xylitol 22986217 fatty acids 22986217 glucose 22986217 isoflavones 22986456 cholesterol 22986456 glucose 22986456 triglyceride 22989703 8-OHdG 22989703 H(2)O(2) 22989703 H2O2 22989703 apo-10'-lycopenoic acid 22989703 apo-14'-lycopenoic acid 22989703 apo-lycopenoic acids 22989703 lycopene 22989704 NiCl(2) 22989704 Nickel 22989704 all-trans retinoid acid 22989704 atRA 22989704 nickel 22989704 nickel chloride 22989704 oxygen 22989705 BADGE 22989705 Bisphenol A diglycidyl ether 22989705 Cisplatin 22989705 GSH 22989705 MDA 22989705 Pioglitazone 22989705 cisplatin 22989705 glutathione 22989705 malondialdehyde 22989705 pioglitazone 22991234 Calcium 22991234 calcium 22991234 calcium citrate 22991330 Nitrogen-bisphosphonates 22991330 aminobisphosphonate 22991330 aminobisphosphonates 22991330 bisphosphonate 22991330 n-BP 22992330 O 22992330 catechol 22993196 Glucose 22993196 TAG 22993196 glucose 22993196 triacylglycerol 22993196 triglyceride 22995755 PEI 22995755 PEIs 22995755 disulfide 22995755 polyethylenimine 22995755 polyethylenimines 22995849 nucleotide 22996261 DACA 22996261 N-[(2-dimethylamino)ethyl]acridine-4-carboxamide 22996261 Raloxifene 22996261 aldehyde 22996261 phthalazine 22996261 raloxifene 22997060 15-ADON 22997060 15-acetyldeoxynivalenol 22997060 3-ADON 22997060 3-acetyldeoxynivalenol 22997060 8-ketotrichothecenes 22997060 8-ketotrichothecenes deoxynivalenol 22997060 DON 22997060 NIV 22997060 deoxynivalenol 22997060 fusarenon X 22997060 kaolin 22997060 nivalenol 22997060 trichothecene 22997060 trichothecenes 22997060 vomitoxin 22998180 SiC 22998180 carbon 23000250 Amino acid 23000250 acetylcholine 23000251 Flavonoids 23000251 MTT 23000251 Quercetin 23000251 flavonoids 23000251 methylquercetin 23000251 methylrutin 23000251 quercetin 23000251 quercetin glucuronide 23000251 rutin 23000251 rutin glucuronide 23000251 rutin sulphate 23000251 tetrazolium 23000251 trypan blue 23000442 Mollugin 23000442 O 23000442 mollugin 23000442 phenacetin 23000447 glyphosate 23000449 carbamate 23000449 organophosphate 23000449 organophosphates 23000450 cholesterol 23000450 triglyceride 23000450 triglycerides 23000451 (-)-cocaine 23000451 Cocaine 23000451 cocaine 23000507 6-OHDA 23000507 6-hydroxydopamine 23000507 ISO 23000507 PRO 23000507 isoproterenol 23000507 propranolol 23000507 tyrosine 23001627 L-T4 23001627 Levothyroxine 23001627 MDA 23001627 PTU 23001627 Vit E 23001627 levothyroxine 23001627 malondialdehyde 23001627 nitroblue tetrazolium 23001627 superoxide 23001627 thiobarbituric-acid 23001627 vitamin E 23002087 statins 23007555 Ifenprodil 23007555 N-methyl-D-aspartate 23007555 amino 23007555 ifenprodil 23007555 ifenprodil, 23007555 zinc 23007559 EtOH 23007559 NO 23007559 ethanol 23008099 (1R)-Normetanephrine 23008099 (1R)-normetanephrine 23008099 (1S)-normetanephrine 23008099 3'-phosphoadenosine-5'-phosphosulfate 23008099 adrenergic amines 23008099 normetanephrine 23008229 Au 23008229 C(60) 23008229 Fullerenes 23008229 fullerene 23008229 thiol 23010164 serine 23010165 l-amino acid 23010362 (-)-reboxetine 23010362 Ca(2+) 23010362 [(3)H]imipramine 23010362 acetylcholine 23010362 imipramine 23010362 norepinephrine 23010695 (R)-2-pentyl-4-pentynoic acid 23010695 (S)-2-pentyl-4-pentynoic acid 23010695 VPA 23010695 valproic acid 23010867 sulfonylurea 23010870 (13)C 23010870 (15)N 23010870 Hg 23010870 Mercury 23010870 mercury 23011663 CAPE 23011663 MDA 23011663 caffeic acid phenethyl ester 23011663 copper 23011663 malondialdehyde 23011663 superoxide 23011663 zinc 23012257 4-(2-Butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid 23012257 DCPIB 23012257 amino acid 23012257 cystine 23012257 d-[(3)H]aspartate 23012257 glutamate 23012257 l-[(14)C]cystine 23012257 l-[(3)H]glutamate 23016524 Ca2+ 23016524 inositol 23017385 Rosmarinic acid 23017385 caffeic acid 23017385 flavonoid 23017385 luteolin-3'-O-glucuronide 23017388 5-FU 23017388 Pulsatilla saponin D 23017388 SB365 23017389 (1)H 23017389 (13)C 23017389 DPPH 23017389 Fe(2+) 23017389 Fe(3+) 23017389 chrysoeriol 23017389 chrysoeriol-7-O-[2″-O-E-feruloyl]-β-d-glucoside 23017389 ethyl acetate 23017389 ferric 23017389 ferric thiocyanate 23017389 ferrous 23017389 flavones 23017389 flavonoids 23017389 isorhamnetin-3-β-d-glucoside 23017389 methanol 23017389 silica gel 23017393 (+)-catechin 23017393 Catechin 23017393 FTSC 23017393 catechin 23017393 creatine 23017393 fluorescein-5-thiosemicarbazide 23017393 glyceraldehyde 23017393 pyruvate 23017401 Genistein 23017401 dicarboximide 23017401 genistein 23017401 genistin 23017401 genistin, its β-glycosylated 23017401 iprodione 23017401 procymidone 23017401 vinclozolin 23017404 Sugar 23017404 fructose 23017404 glucose 23017404 hexose 23017404 hexoses 23017404 sucrose 23017404 sugar 23017406 GABA 23017406 Glu 23017406 polyamine 23017406 polyamines 23017406 γ-aminobutyric acid 23017414 isoflavone 23017414 isoflavones 23017414 phenolic 23017414 phenolic acids 23017417 (+)-catechin 23017417 (-)-epicatechin 23017417 (E)-resveratrol 23017417 Anthocyanins 23017417 gallic acid 23017417 polyphenol 23017417 polyphenols 23017423 DHA 23017423 dehydroascorbic acid 23017423 glucose 23017423 l-ascorbic acid 23017423 sucrose 23017423 sugar 23018143 estrogen 23019137 5,6,7,13-tetrahydro-13-methyl-5-oxo-12H-indolo[2,3-a]pyrrolo[3,4c]carbazole-12-propanenitrile 23019137 5-HT 23019137 Gö6976 23019137 Serotonin 23019137 dopamine 23019137 neurotensin 23019137 quinpirole 23019137 serotonin 23019217 Mith 23019217 Mithramycin A 23019217 mithramycin A 23019274 N-acetyl 23019274 aristolochic acid 23019274 creatinine 23019274 nitrogen 23019274 urea 23022069 CYA 23022069 MEL 23022069 cyanurate 23022069 cyanuric acid 23022069 melamine 23022398 AP7 23022398 NMDA 23022398 PILO 23022398 pilocarpine 23022398 urethane 23023024 BAs 23023024 MDA 23023024 Malondialdehyde 23023024 bile acids 23023024 superoxide 23023024 α-tocopherol 23023136 Arsenic trioxide 23023136 As(2)O(3) 23023136 GSH 23023136 GSSG 23023136 Resveratrol 23023136 arsenic 23023136 arsenic trioxide 23023136 oxidized glutathione 23023136 reduced glutathione 23023136 resveratrol 23023136 superoxide 23023933 octanol 23023933 perfluoroalkyl acids 23026700 AMP 23026700 acetyl-CoA 23026700 carnitine palmitoyl 23026700 ethanol 23026700 fatty acid 23026700 sterol 23026700 triglyceride 23028140 N-desmethylimatinib 23028140 imatinib 23030346 Ge 23030346 Si 23030680 5-hydroxyelzasonan 23030680 N 23030680 elzasonan 23030680 elzasonan N-oxide 23030680 iminium 23030680 indole 23030706 carbon 13 23030706 chloroacetaldehyde 23030706 cobalt 23030706 cobalt chloride 23030706 ifosfamide 23030706 valproate 23030766 amino acid 23032515 8-Hydroxycalamenene 23032515 8-hydroxycalamenene 23032515 BSO 23032515 N-methyl-d-aspartate 23032515 S 23032515 glutamate 23032515 glutathione 23032515 hexane 23032515 l-buthionine-(S,R)-sulfoximine 23033256 Bisulfite 23034931 S 23034931 nitro 23034931 nitrogen 23034931 oxy 23036893 4-nonylphenol 23036893 EE2 23036893 bisphenol A 23036893 estrogen 23036893 ethinylestradiol 23036893 genistein 23038668 Calcium manganese oxide 23038668 H+ 23038668 O(2) 23038668 oxygen 23041228 ser 23041228 thr 23041228 tyrosine 23041510 1α,25 (OH) 2D3 23041510 2β-hydroxypropyloxy 23041510 ALF 23041510 ALN 23041510 Alendronate 23041510 ELD 23041510 Eldecalcitol 23041510 alendronate 23041510 alfacalcidol 23041510 bisphosphonate 23041510 eldecalcitol 23041538 NASPM 23041538 SCH 58261 23041538 adenosine 23041538 calcium 23041538 glucose 23041538 oxygen 23041538 spermine 23041661 ATP 23041661 Arg 23041661 Glu 23041661 adenosine-5'-triphosphate 23041661 disulfide 23041661 γ-phosphate oxygen 23041725 17β-estradiol 23041725 Organochlorine 23041725 dieldrin 23041725 estrogen 23041725 organochlorine 23042728 VPA 23042728 VPD 23042728 Valpromide 23042728 amide 23042728 valproic acid 23042730 AMD 23042730 Amiodarone 23042730 N-acetylcysteine 23042730 TOCO 23042730 amiodarone 23042730 ascorbate 23042730 glutathione 23042730 oxygen 23042730 trolox 23042730 α-TOCO 23042730 α-tocopherol 23042808 CBD 23042808 Cannabidiol 23042808 THC 23042808 cannabidiol 23042808 Δ⁹-tetrahydrocannabinol 23042953 amino acids 23042953 cholesterol 23042953 triglycerides 23042954 (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid 23042954 AMPA 23042954 HI-6 23042954 LY293558 23042954 oxime 23042954 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 23043137 C 23043137 amino acid 23043137 disulfide 23043137 pVIc 23043441 azide-alkyne 23043441 copper(I) 23044047 phalloidin 23044489 KET 23044489 Ketamine 23044489 MK-801 23044489 NMDA 23044489 Organophosphorus 23044489 atropine sulfate 23044489 benzodiazepine 23044489 soman 23046872 NaAsc 23046872 Pt(IV) 23046872 cisplatin 23046872 cisplatin(II) 23046872 cisplatin(IV) 23046872 nucleobases 23046872 sodium ascorbate 23047001 ATP 23047001 BTZ 23047001 BTZs 23047001 benzothiazepinones 23047024 K048 23047024 Organophosphorus 23047024 organophosphates 23047024 oxime 23047024 oximes 23047024 tabun 23047287 5(6)-carboxyfluorescein 23047287 Arg-Gly-Asp 23047287 adamantine 23047287 amantadine 23047287 cyclic RGD 23047287 graphene 23047287 β-CD 23047287 β-cyclodextrin 23047912 (14)C 23047912 L-BMAA 23047912 oxygen 23047912 vitamin E 23047912 β-N-methylamino-L-alanine 23050902 6-mercaptopurine 23050902 GTP 23050902 Ribavirin 23050902 inosine-5'-monophosphate 23050902 lysine 23050902 mycophenolic acid 23050902 ribavirin 23050902 vitamin K 23052192 Co 23052192 Co(2+) 23052192 CoCl(2) 23052192 WC 23052192 cobalt 23052192 oxygen 23052192 tungsten carbide 23052195 PPA 23052195 c-AMP 23052195 glutathione 23052195 phenylpropanolamine 23055393 TiO(2) 23055453 HCl 23055453 OPE 23055453 cholesterol 23055453 ethanediamine 23055453 imino 23055453 oligo(p-phenyleneethynylene) 23055539 AngIV 23055539 Angiotensin IV 23055539 C 23055539 N 23055539 N-hexanoic-Tyr-Ile-(6) aminohexanoic amide 23055539 Nle-Tyr-Ile 23055539 amino acids 23055539 angiotensin IV 23055539 dihexa 23055539 hydrogen 23055539 norleucine 23055539 scopolamine 23055539 tripeptide 23057615 copper 23057615 moxifloxacin 23057615 phenanthroline 23057615 quinolone 23057692 ciclopirox 23059626 Met 23060096 H(2)O(2) 23060096 H2O2 23060096 Pt(48)Pd(52)-Fe(3)O(4) 23060096 PtPd-Fe3O4 23060096 TMB 23060096 oleylamine 23060096 polyethyleneglycol 23060096 tetramethylbenzidine 23061607 Organosilicon 23061607 organosilicon 23061607 silicon 23061635 GABA 23061635 Menthol 23061635 calcium 23061635 menthol 23061635 monoterpene 23061635 nicotine 23061635 sodium 23063002 chlorpyrifos 23063002 oxygen 23063002 penoxsulam 23063066 esfenvalerate 23063069 DDT 23063069 PBDEs 23063069 PCB 23063069 PCBs 23063069 dichlorodiphenyltrichloroethane 23063069 polybrominated diphenyl ethers 23063069 polychlorinated biphenyls 23063411 Actinomycin D 23063411 actinomycin D 23063590 Artemisinic acid 23063590 Cholesterol 23063590 HMG CoA 23063590 HMG-CoA 23063590 artemisinic acid 23063590 cAMP 23063590 cholesterol 23063590 hydroxymethylglutaryl CoA 23063593 HER 23063593 Herbacetin 23063593 LY294002 23063593 N-Acetyl-l-cysteine 23063593 NAC 23063593 flavonoid 23063593 phosphatidylinositol 23063593 poly (ADP-ribose) 23065696 (13) C 23065696 carbon 23066090 3-(5-tert-butyl-isoxazol-3-yl)-2-[(3-chloro-phenyl)-hydrazono]-3-oxo-propionitrile 23066090 ESI-09 23066090 cAMP 23066090 nucleotide 23066821 callyimine A 23066821 callylactam A 23066949 2-acetamino 23066949 Asp 23066949 GlcNAcstatin 23066949 aspartate 23066949 imidazole 23066949 nitrogen 23068419 6-OHDA 23068419 6-hydroxydopamine 23068419 Methylparaben 23068419 apomorphine 23068419 hydrogen peroxide 23068419 methylparaben 23068419 oxygen 23068419 tyrosine 23069619 ibuprofen 23069627 calcium 23069627 glucose 23069627 palmitic acid 23070981 GeTe 23071106 2-APB 23071106 2-aminoethoxydiphenylborate 23071106 8-pCPT-2'-O-Me-cAMP-AM 23071106 ATP 23071106 Ca(2+) 23071106 K 23071106 Tolbutamide 23071106 bisindolylmaleimide I 23071106 cAMP 23071106 gliclazide 23071106 nicardipine 23071106 sulfonylurea 23071106 thapsigargin 23071106 tolbutamide 23071294 cholesterol 23073171 CLA 23073171 glucose 23073171 linoleic acid 23074021 MEG 23074021 Methyleugenol 23074021 S 23074021 glutathione 23074021 methyleugenol 23074035 PMMA 23074035 PMMA-b-PNIPAAm 23074035 PNIPAAm 23074088 carboxyl 23074173 (59)Fe 23074173 DFO 23074173 Deferasirox 23074173 Fe 23074173 deferasirox 23074173 desferrioxamine 23074173 iron 23074173 poly(ADP-ribose) 23076553 CH3 23076553 Cl 23076553 F 23076553 Lewis acid 23076553 Lewis base 23076553 Lewis bases 23076553 N 23076553 N(CH3)3 23076553 NF3 23076553 NHn(X3-n) 23076553 halogen 23077105 7α,17β-[9-[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol 23077105 ICI182/780 23077105 actinomycin D 23077105 bile salts 23077105 estrogen 23077105 ethynylestradiol 23077105 glutathione 23078542 dopamine 23079231 (3)H-thymidine 23079231 Curcumin 23079231 curcumin 23079231 sirolimus 23080539 doxycycline 23081912 2,3,7,8-tetrachlorodibenzo-p-dioxin 23081912 Hoechst H33342 23081912 Ko143 23081912 TCDD 23081912 aryl hydrocarbon 23081912 arylhydrocarbon 23081912 dioxin 23081912 imidazole 23081912 prochloraz 23081912 salicyl amide 23081947 Au 23081947 AuCl 23081947 Chlorine 23081947 chlorine 23085085 acetyl 23085085 lysine 23085266 GF109203X 23085266 NADPH 23085266 PMA 23085266 SB203580 23085266 Ser 23085266 UO126 23085266 fMLF 23085266 formyl-methionyl-leucyl-phenylalanine 23085266 genistein 23085266 oxygen 23085266 phorbol myristate acetate 23085266 tyrosine 23085266 wortmannin 23085330 Curcumin 23085330 HPβCD 23085330 Hydroxypropyl 23085330 curcumin 23085330 hydroxypropyl-β-cyclodextrin 23085435 BPs 23085435 GGPP 23085435 N 23085435 Nitrogen 23085435 bisphosphonates 23085435 geranylgeranyl pyrophosphate 23085979 2,3,7,8-tetrachlorodibenzo-p-dioxin 23085979 Aryl hydrocarbon 23085979 TCDD 23085979 aryl hydrocarbon 23085979 polycyclic aromatic hydrocarbons 23086035 acylcarnitines 23086035 glucose 23086035 sphingosine 23086038 glucose 23086038 phosphoinositide (3,4,5)-triphosphate 23086197 NADPH 23086197 heme 23086197 squalene 23086197 steroid 23086198 1-OH-pyrene 23086198 1-hydroxy-(OH)-pyrene 23086198 1-naphthol 23086198 PAH 23086198 PAHs 23086198 UDP 23086198 diols 23086198 heterocyclic amines 23086198 hydroxylated benzo(a)pyrene 23086198 monohydroxylated PAH 23086198 nitrosamines 23086198 polycyclic aromatic hydrocarbons 23086703 1,1,3,3-tetramethyl-2-propylguanidine 23086703 1,4-phenylenedimethanamine 23086703 1-naphthylmethyl 23086703 1-propylguanidine 23086703 2-pyridylmethyl 23086703 FC131 23086703 [1,1'-biphenyl]-4,4'-diyldimethanamine 23086703 bis(pyridin-2-ylmethyl)amine 23086703 cyclic pentapeptide 23086703 dipicolylamine 23086703 naphthalene-2,6-diyldimethanamine 23086703 zinc(II) 23087261 Lys 23087261 Lysine 23087261 lysine 23089896 ATP 23089896 Rho123 23089896 itraconazole 23089896 rhodamine123 23091169 androstane 23091169 glutamine 23091169 phenobarbital 23091189 (14)C 23091189 Inavir 23091189 Laninamivir octanoate 23091189 ester 23091189 laninamivir 23091189 laninamivir octanoate 23092136 hydrogen 23092237 ZnO 23092395 2,2-diphenyl-1-picryl-hydrazyl 23092395 3,5,4'-trimethoxy-4-prenylstilbene 23092395 4-hydroxylonchocarpine 23092395 Fe(3+) 23092395 Phenanthroline 23092395 derricidine 23092395 flavonoids 23092395 hexane 23092395 lonchocarpine 23092395 methanol 23092395 steroids 23092395 stigmasterol 23092395 tannins 23092395 β-sitosterol 23092723 MTT 23092723 celastrol 23092723 dichloromethane 23092723 ethanol 23092723 hexanes 23092723 methanol 23092877 nandrolone 23092877 nandrolone decanoate 23092877 steroid 23092894 Glutamate 23092894 glutamate 23094599 Si-C 23094599 Si-N 23094599 Si-O-C 23094599 Silicon 23094599 silicon 23094864 STS 23094864 Sodium tanshinone IIA sulfonate 23094864 TSIIA 23094864 Tanshinone 23094864 Tanshinone IIA 23094864 cryptotanshinone 23094864 tanshinone 23094864 tanshinone I 23095167 Kainate 23095167 glutamate 23095167 kainate 23095244 Ecstasy 23095244 ecstasy 23097024 NO 23097024 nitric oxide 23097351 1,1-diphenyl,2-picrylhydrazyl 23097351 4'-O-methoxy-luteolin-7-O-rhamnoglucoside 23097351 alcohol 23097351 apigenin 23097351 aromadendrin 23097351 ethanol 23097351 flavonoidal 23097351 flavonoids 23097351 naringenin 23098805 cocaine 23098805 estradiol 23098805 estrogen 23098805 progesterone 23098818 5-methoxytryptamine 23098818 O 23098818 fluoxetine 23098818 quinine 23098818 serotonin 23098879 1α, 6α-epoxy-9-oxo-10β-hydroxyl-furanoeremophilane 23098879 9-oxo-1α, 6β, 10β-trihydroxy-furanoeremophilane 23098879 C1-C6 23098879 furanoeremophilane 23098879 furanoeremophilanes 23098879 oxygen 23098993 HC 030031 23098993 capsaicin 23099337 Caffeine 23099337 cadmium 23099337 caffeine 23099337 glutathione 23099337 superoxide 23099339 folic acid 23099339 glucose 23099339 hydroxybutyrate 23099339 resazurin 23099339 vitamin C 23099645 5-Aza-2'-deoxycytidine 23099645 trichostatin A 23099811 (13)C 23099811 (15)N 23099811 Hg 23099811 MeHg 23099811 N 23099811 carbon 23099811 mercury 23099811 methylmercury 23099811 nitrogen 23102508 Miltirone 23102508 abietane 23102508 cryptotanshinone 23102508 dihydrotanshinone 23102508 diterpene quinone 23102508 miltirone 23102508 tanshinone I 23102508 tanshinone IIA 23102508 tanshinones 23103297 (-)-Carvone 23103297 (-)-carvone 23103297 BaCl2 23103297 K(+) 23103297 calcium 23103297 carbachol 23103297 histamine 23103297 monoterpene ketone 23103297 verapamil 23103426 (PhSe)(2) 23103426 (PhTe)(2) 23103426 GSH 23103426 NADH 23103426 diphenyl diselenide 23103426 diphenyl ditelluride 23103426 organochalcogen 23103426 organochalcogens 23103426 reduced glutathione 23103426 superoxide 23103426 thiol 23103568 Estrogen 23103568 estradiol 23103568 estrogen 23103568 estrogens 23103568 lapatinib 23103568 tyrosine 23104244 7-ethoxyresorufin 23104244 7-pentoxyresorufin 23104244 O 23104244 chlorzoxazone 23104244 midazolam 23104245 1,4-BD 23104245 1,4-butanediol 23104245 GBL 23104245 GHB 23104245 Gamma-hydroxybutyrate 23104245 gamma-butyrolactone 23104245 gamma-hydroxybutyrate 23104419 Androgen 23104419 androgen 23104419 creatine 23104419 estradiol 23104419 lactate 23104419 methimazole 23104419 testosterone 23104982 Ala-Pro-7-amido-4-trifluoromethylcoumarin 23104982 serine 23106229 beauvericin 23106229 depsipeptide 23106482 (2R*,3S*,5S*)-N,2-dimethyl-3-hydroxy-5-(10-phenyldecyl)pyrrolidine 23106482 (S)-1-(1'-hydroxyethyl)-β-carboline 23106482 1-(β-carboline-1-yl)-3,4,5-trihydroxy-1-pentanone 23106482 1-methoxycarbonyl-β-carboline 23106482 3-O-β-d-galactopyranosyl-hederagenin 28-O-β-d-xylopyranosyl(1 → 6)-β-d-galactopyranosyl ester 23106482 4-hydroxycinnamic acid methyl ester 23106482 N-methyl 23106482 bergenin 23106482 caffeic acid 23106482 coniferin 23106482 emodin 23106482 gagaminine 23106482 indolo[2,3-α]carbazole 23106482 methyl 4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethyl] ferulate 23106482 methylconiferin 23106482 nobiletin 23106482 perlolyrine 23106482 pyrrolidine alkaloid 23106482 qingyangshengenin 23106482 syringaresinol 4'-O-β-d-glucopyranoside 23108214 carbohydrates 23109233 Ag 23109233 Ag(+) 23109233 Cu 23109233 Cu(2+) 23109233 Cu(2+) -Ag(+) 23109233 Cu(2+) -Zn(2+) 23109233 Zn 23109233 Zn(2+) 23109279 Fipronil 23109279 fipronil 23109279 fipronil sulfide 23109279 fipronil sulfone 23110522 carbon dioxide 23110522 carboxylic acid 23110522 graphene 23110522 graphite 23110522 hydrogen 23110522 oxygen 23110522 platinum 23110522 sulfonic acid 23110522 sulfur 23110522 sulfur trioxide 23111282 cholesterol 23111282 fatty acid 23111374 2-PAM 23111374 2-Pralidoxime 23111374 HI-6 23111374 Obidoxime 23111374 Organophosphorus 23111374 P-O 23111374 obidoxime 23111374 organophosphorus 23111374 oxime 23111374 oximes 23111374 pyridinium and bis-pyridinium aldoximes 23111374 serine 23111374 tabun 23111684 4,10-dinitro-2,6,8,12-tetraoxa-4,10-diazaisowurtzitane 23111684 4,8,11,14,15-pentanitro-2,6,9,13-tetraoxa-4,8,11,14,15-pentaazaheptacyclo [5.5.1.1(3,11).1(5,9)]pentadecane 23111684 4,8,11,14,15-pentanitro-2,6,9,13-tetraoxa-4,8,11,14,15-pentaazaheptacyclo[5.5.1.1(3,11).1(5,9)] pentadecane 23111684 N-NO(2) 23111684 PNTOPAHP 23111684 TEX 23111879 Fe 23111879 FeCl3 23111879 FeCl3 • 6H2O 23111879 Ferric chloride 23111879 HCl 23111879 Iron 23111879 bromide 23111879 ferric chloride 23111883 Cadmium chloride 23111883 Cd 23111883 CdCl2 23111883 alanine 23111883 aspartate 23111883 bilirubin 23111883 cadmium 23111883 cholesterol 23111883 creatinine 23111883 glucose 23111883 triglycerides 23111883 urea 23111883 uric acid 23111883 vitamins C and B 23111884 amphetamine 23111884 ethanol 23111884 tetrahydrocannabinol 23111885 NaC 23111885 NaDC 23111885 Tween 61 23111885 cholesterol 23111885 ethanol 23111885 phosphate 23111885 sodium cholate 23111885 sodium deoxycholate 23111887 clonidine 23111887 dexmedetomidine 23115086 fentanyl 23115086 midazolam 23115086 morphine 23115086 propofol 23115119 Asp 23115119 Glu 23115119 Phe 23115119 aspartic acid 23115119 carboxylic acid 23115119 glutamic acid 23115119 phenylalanine 23115324 bleomycin 23115325 ATP 23115325 Hydrogen sulfide 23115325 K 23115325 K(+) 23115325 LEVC 23115325 NaHS 23115325 levcromakalim 23115325 potassium 23115325 sodium hydrogen sulfide 23115325 sulfonylurea 23115325 trinitrobenzene sulfonic acid 23116643 3-NT 23116643 3-nitrotyrosine 23116643 CCl(4) 23116643 Cu 23116643 Rosmarinic acid 23116643 Zn 23116643 carbon tetrachloride 23116643 rosmarinic acid 23116643 superoxide 23116643 thiobarbituric acid 23117790 N-(2-methyl-6-benzoxazolyl)-N'-1,5-naphthyridin-4-yl urea 23117790 SB334867 23117790 glucose 23118018 5-HT 23118018 5-hydroxytryptamine 23118018 GABA 23118018 alcohol 23118018 dopamine 23118018 ethanol 23118018 gamma-aminobutyric acid 23118018 glutamate 23118018 serotonin 23118019 5'-(2-aminomethyl) naltrindole 23118019 5'-AMN 23118019 5'-MABN 23118019 N-((Naltrindol-5-yl) methyl) pentanimidamide 23118019 U50,488 23118019 [(3)H]-diprenorphine 23118019 [(35)S]-GTPγS 23118019 guanosine-5'-O-(3-[35S]-thio) triphosphate 23118019 naltrindole 23121767 bicarbonate 23121934 (+)8-OH-DPAT 23121934 1-hydroxybenzotriazole 23121934 3,4,5-trimethoxycinnamic acid 23121934 WAY 100635 23121934 amides 23121934 esters 23121934 ethyl(dimethylaminopropryl)carbodiimide 23121934 ketones 23121934 morphine 23121934 naloxone 23122060 Q3G 23122060 d-glucose 23122060 quercetin 23122060 quercetin glucoside 23122060 quercetin glycoside 23122060 quercetin glycosides 23122060 quercetin-3-O-β-d-glucoside 23122060 saccharide 23122061 (1)H 23122061 (13)C 23122061 ethanol 23122061 glucoalkaloid 23122061 harmanyl β-d-glucopyranoside 23122061 β-carboline 23122064 amphetamine 23122064 cocaine 23122066 bile acid 23122066 cholesterol 23122066 silica gel 23122066 sphingolipids 23122066 sterol esters 23122066 triacylglycerols 23122068 (1)H 23122068 (13)C 23122068 Sulforaphene 23122068 methanol 23122068 sulforaphene 23122077 2,2-diphenyl-1-picrylhydrazyl 23122077 DPPH 23122077 H(2)O(2) 23122085 diacylglycerol ether 23122085 diacylglycerol ethers 23122085 ethanol 23122085 fatty acid ethyl esters 23122085 monoacylglycerol ethers 23122085 squalene 23122085 triacylglycerol 23122085 triacylglycerols 23122086 GalA 23122086 galacturonic acid 23122089 C 23122089 GABA 23122089 Linoleic and linolenic acid 23122089 N 23122089 amino acids 23122089 carbon 23122089 isoflavone 23122089 isoflavones 23122089 nitrogen 23122089 sugars 23122089 tocopherol 23122089 tocopherols 23122089 unsaturated fatty acids 23122092 1-octen-3-one 23122092 Methional 23122092 phenols 23122097 (2E)-hexenal 23122097 1-Octen-3-ol 23122097 alcohols 23122097 aldehydes 23122097 carboxylic acid 23122097 ester 23122097 esters 23122097 fatty acids 23122097 hydrocarbons 23122097 ketones 23122105 Allura Red AC 23122105 aromatic amine or amide 23122105 ascorbic acid 23122105 citric acid 23122105 sucrose 23122108 Ginnalin A 23122108 Ginnalins A-C 23122108 Polyphenols 23122108 ginnalin A 23122108 ginnalins A-C 23122108 ginnalins B and C 23122108 polyphenols 23122108 sugar 23122114 Hg 23122114 MeHg 23122114 mercury 23122114 methylmercury 23122116 azoxystrobin 23122116 methanol 23122116 strobilurin 23122118 organophosphorus 23122129 D-galactose 23122129 amino acid 23122135 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) 23122135 2,2-diphenyl-1-picrylhydrazyl 23122135 ABTS 23122135 DPPH 23122135 apigenin 23122135 apigenin-7-O-glucoside 23122135 caffeic acid 23122135 caffeic acid-3-O-glucoside 23122135 chrysoeriol 23122135 luteolin 23122135 luteolin-7-O-glucoside 23122135 methanol 23122135 rosmarinic acid 23122135 rosmarinic acid-3-O-glucoside 23122136 anthocyanins 23122137 Vescalagin 23122137 cholesterol 23122137 fatty acid 23122137 fructosamine 23122137 fructose 23122137 glucose 23122137 triglyceride 23122137 vescalagin 23122140 DPPH 23122140 H(2)O(2) 23122141 behenic acid 23122141 fatty acids 23122141 triacylglycerols 23122145 catechin 23122145 epicatechin 23122145 epicatechin-3-O-gallate 23122145 epigallocatechin 23122145 proanthocyanidin 23122145 proanthocyanidins 23122152 phenol 23122152 secoiridoid aglycones 23122155 AcOEt 23122155 HEX 23122155 betulinic acid 23122155 carnosol 23122155 ethyl acetate 23122155 hexane 23122160 MNG 23122160 acetonitrile and salts 23122160 ammonium bicarbonate 23122160 dinotefuran 23122160 primary secondary amine 23122165 E-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid 23122165 PPAG 23122165 Z-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid 23122165 sugar 23122167 Schisarisanlactone A 23122167 Schisarisanlactones A and B 23122167 nortriterpenoids 23122167 schisarisanlactones A (1) and B 23122169 15-O-methylgraciliflorin F 23122169 15-hydroxy-1-oxosalvibretol 23122169 15-hydroxy-20-deoxocarnosol 23122169 16-acetoxylsugiol 23122169 3α-hinokiol 23122169 3β-hydroxysempervirol 23122169 6,12,15-trihydroxy-5,8,11,13-abietatetraen-7-one 23122169 Abietane 23122169 abieta-8,11,13-triene-14,19-diol 23122169 abietane 23122169 diterpenoids 23122169 graciliflorin E 23122169 graciliflorin F 23123188 PGT 23123188 ethanol 23123188 oxygen 23123188 phosphate 23123188 propoxylated glyceryl triacylate 23123188 timolol 23123248 carbamate 23123248 carbamates 23123248 rivastigmine 23123254 chlorpyrifos 23123254 chlorpyrifos oxon 23123254 cyclosarin 23123254 diazinon 23123254 diazoxon 23123254 organophosphorus 23123254 sarin 23123254 soman 23123254 tabun 23123331 Na(2)CO(3) 23123331 SLB 23123331 silica 23123331 silybin 23123737 lutein 23123743 17β-Estradiol 23123743 DPN 23123743 Estrogen 23123743 G-15 23123743 ICI 182,780 23123743 PP2 23123743 PPT 23123743 [³H]-inositol phosphate 23123743 estrogen 23123743 inositol phosphate 23123743 tyrosine 23123945 ATR 23123945 Atrazine 23123945 DOPAC 23123945 HVA 23123945 Mn 23123945 amphetamine 23123945 atrazine 23123945 dopamine 23123945 monoamine 23124677 Cadmium 23124677 Cd 23124677 cadmium 23124677 nitrogen 23124905 1,2-sn- dicaprin 23124905 1,2-sn-dicaprin 23124905 1,3-sn-dicaprin 23124905 2,3-sn-dicaprin 23124905 dicaprin 23124905 diglyceride 23124905 ester 23124950 silicon 23124950 silver 23125070 Testosterone 23125070 androstenedione 23125070 testosterone 23127598 Brilliant Blue 23127598 Patent Blue 23127598 ethanol 23127598 triphenylmethane 23127599 Res 23127599 fatty acid 23127599 resveratrol 23127599 sucrose 23127601 mercury 23127826 flavone 23127826 pyridinium 23128829 cocaine 23131177 3-methoxyphenyl 23131177 Ca(2+) 23131177 Melatonin 23131177 N-[3-(3-methoxyphenyl)propyl] amides 23131177 benzyloxyl 23131177 cAMP 23131177 melatonin 23131177 phenylpropylamides 23131797 octanol 23131798 1,3,5-triazine 23131798 2,4,6-trisubstituted 1,3,5-triazines 23131798 2,4,6-trisubstituted-1,3,5-triazines 23131798 N-cyclopentyl-4-ethoxy-6-(4-methylpiperidin-1-yl)-1,3,5-triazin-2-amine 23132334 DTG 23132334 Dolutegravir 23132334 S/GSK1349572 23132334 UDP 23132334 creatinine 23132334 dolutegravir 23132743 1,25-dihydroxyvitamin D 23132743 vitamin D 23132751 CO(2) 23132751 CaCO(3) 23132751 CaO 23132751 MgO 23132843 3,4-dihydropyrimidin-2(1H)-ones 23132843 4-Aryl-3,4-dihydropyrimidin-2(1H)-ones 23132843 iodide 23132843 iodine 23132843 pyrimidone 23132843 sodium iodide 23135547 ATP 23135547 Amiodarone 23135547 Dronedarone 23135547 amiodarone 23135547 benzofuran 23135547 dronedarone 23135547 fatty acids 23135547 oxygen 23135548 2,3,7,8-tetrachlorodibenzo-p-dioxin 23135548 Dioxin 23135548 TCDD 23135548 aryl hydrocarbon 23135548 dioxin 23137833 dexamethasone 23137833 resveratrol 23137957 DON 23137957 deoxynivalenol 23137957 trichothecenes 23138333 Cu 23138333 chl a 23138333 chlorophyll a 23138333 copper 23138381 Formaldehyde 23138381 formaldehyde 23138972 Ir 23138972 Pd 23138972 Rh 23138972 Ru 23138972 enamines 23138972 heteroarenes 23138972 imines 23138972 ketones 23138972 olefins 23138972 palladium 23139020 19- and 20-hydroxyeicosatetraenoic acid 23139020 arachidonic acid 23139020 epoxyeicosatrienoic acids 23139378 gemfibrozil 23139378 gemfibrozil and its glucuronide 23139378 gemfibrozil glucuronide 23139378 itraconazole 23139378 repaglinide 23139413 Gln 23139413 Ile 23139413 Sar 23139413 cysteines 23139413 losartan 23140132 triacylglyceride 23140132 triglycerides 23141425 EGCG 23141425 Epigallocatechin-3-gallate 23141425 polyphenol 23142020 BAY 41-8543 23142020 polystyrene 23142538 2,3,7,8-Tetrachlorodibenzo-p-dioxin 23142538 TCDD 23142538 dioxin 23142558 17-β-oestradiol 23142558 Oestrogens 23142558 oestrogens 23142699 estradiol 23142699 estrogen 23142699 estrogens 23142753 1,1'-dichloro-2,2'-bis(p-chlorophenyl)ethylene 23142753 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane 23142753 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)-ethane 23142753 DDT 23142753 Dichlorodiphenyltrichloroethane 23142753 Organochlorine 23142753 o,p'-DDT 23142753 p,p'-DDE 23142753 p,p'-DDT 23143036 BHT 23143036 Cadmium 23143036 Cd 23143036 Cu 23143036 N-acetylcysteine 23143036 NAC 23143036 Zn 23143036 butylhydroxytoluene 23143036 d-mannitol 23143036 hydrogen peroxide 23143036 oxygen 23143036 paraquat 23143036 superoxide 23143039 Cadmium 23143039 cadmium 23143039 carbonyl 23143039 gluconate 23143039 glucose 23143039 glutathione 23143039 malondialdehyde 23143620 2,4-dinitrochlorobenzene 23143674 clemizole 23144001 perylene 23146662 Bryostatin 1 23146662 Merle 23 23146662 bryostatin 23146662 bryostatin 1 23146662 bryostatins 23146662 phorbol ester 23146662 phorbol esters 23146690 Ly294002 23146690 clofarabine 23146690 phosphoinositide 23146690 resveratrol 23146692 1,1-diphenyl-2-picrylhydrazyl 23146692 2,2-azobis-(2-amidino-propane) dihydrochloride 23146692 AAPH 23146692 CAAP 23146692 Cys-Ala-Ala-Pro 23146692 DPPH 23146692 VCSV 23146692 Val-Cys-Ser-Val 23146692 amino acid 23146692 oxygen 23146694 BPA 23146694 Bisphenol A 23146694 N 23146694 polycarbonate 23146765 (1)H 23146765 1H 23146765 B12 23146765 CCl(4) 23146765 carbon tetrachloride 23146765 choline 23146765 folate 23146765 formate 23146765 glucose 23146765 lactate 23146766 AFB 23146766 AFB(1) 23146766 Aflatoxin B(1) 23146766 Lys 23146766 aflatoxin 23146766 aflatoxin B1 23146766 lysine 23146838 anastrozole 23146838 estrogen 23146838 estrogens 23146838 glucose 23146838 saccharin 23146838 sugar 23146871 Alexa green 23146871 Fe 23146871 Fe(3+) 23146871 Manganese 23146871 Mn 23146871 Mn(2+) 23146871 Mn(3+) 23146871 iron 23146871 manganese 23147005 phosphodiester 23147376 Superoxide 23147376 methacholine 23147376 streptozotocin 23147377 Fe(2)O(3) 23147377 Iron oxide 23147377 iron oxide 23147415 BW284c51 23147415 bambuterol 23147415 choline 23147415 donepezil 23147415 glucose 23147415 physostigmine 23147416 CTAP 23147416 D-Ala(1)-peptide T-NH(2,) 23147416 DAPTA 23147416 d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 23147416 naloxone 23147475 C 23147475 K(+) 23147475 O 23147475 O=C 23147475 fluorenone 23147475 fluorenone carbonyl 23147475 zeolite L 23147567 PAH 23147567 PAHs 23147567 anthracene 23147567 naphthalene 23147567 phenanthrene 23147567 poly(dimethylsiloxane) 23147567 polycyclic aromatic hydrocarbons 23147567 pyrene 23147567 silicone 23147715 Cr(2)O(3 23147715 Cr(2)O(7)(2-) 23147715 Cr(III) 23147715 Cr(OH)(3) 23147715 Cr(VI) 23147715 CrO(4)(2-) 23147715 H(2) 23147715 H(2)O(2) 23147715 OH 23147715 chromium 23147715 chromium oxide 23147715 dichromate 23147750 Ca(+) 23147750 Ca(2+) 23147750 HCO 3(-) 23147750 Mg(+) 23147750 Mg(2+) 23147750 SO 4(-) 23147750 SO 4(2-) 23147750 coal 23147837 BDE-47 23147837 BDE-99 23147837 PBDE 23147837 PBDEs 23147837 Polybrominated diphenyl ethers 23147837 polybrominated diphenyl ethers 23149337 adenosine 23149337 histamine 23149908 glucose 23150491 BPA 23150491 BPA-Gluc 23150491 BPA-glucuronide 23150491 bisphenol A 23150491 bisphenol a 23151003 Purine 23151003 adenosine 23151003 nucleoside tri- and di-phosphates 23151003 nucleotides 23151003 pyrimidine 23151610 Carbohelicenes 23151610 benzenoid 23151610 carbohelicene 23151610 carbohelicenes 23151610 helicene 23151610 helicenes 23151611 5-HIAA 23151611 5-HT 23151611 5-hydroxyindoleacetic acid 23151611 dopamine 23151611 norepinephrine 23151611 oleanolic acid 23151611 serotonin 23151612 aspirin 23151612 minocycline 23151612 neurosteroids 23151612 omega-3 fatty acids 23151612 steroidal 23152186 Arsenic 23152186 As(III) 23152186 arsenic 23152186 dexamethasone 23152186 glucose 23152186 sphingosine-1-phosphate 23153029 estradiol 23153029 estrogens 23153029 progesterone 23153054 alprazolam 23153054 clonazepam 23153054 dexamethasone 23153054 diltiazem 23153054 midazolam 23153054 nifedipine 23153054 quinidine 23153054 tacrolimus 23153054 verapamil 23153057 bupropion 23153057 diclofenac 23153057 midazolam 23153057 phenacetin 23153057 phenobarbital 23153057 rifampicin 23153057 salicylamide 23153057 β-naphthoflavone 23153322 RAI 23153322 radioactive iodine 23153456 nitric oxide 23153456 polyinosinic:polycytidylic acid 23153512 (1)H 23153512 (31)P 23153512 FEN 23153512 NO2 23153512 fenitrothion 23153512 methylene blue 23154127 AME 23154127 AOH 23154127 DCF 23154127 S 23154127 alternariol 23154127 alternariol monomethyl ether 23154127 dichlorofluorescein 23154127 formamidopyrimidine 23154127 glutathione 23154127 monomethylether 23154127 γ-glutamylcysteine 23154304 ADP 23154304 adenosine diphosphate 23154304 arachidonic acid 23154304 hydrazone 23154304 indole hydrazone 23154304 indomethacin 23154865 BH3 23155201 99mTc 23155201 MDP 23155201 methylendiphosphonate 23155201 technetium-99m 23157442 Gentamicin 23157635 oxygen 23157637 dopamine 23157637 haloperidol 23157637 olanzapine 23157637 oxygen 23157637 quetiapine 23157637 risperidone 23157640 anthracyclines 23157640 cisplatin 23157640 platinum 23157640 taxanes 23159106 Ethanol 23159106 Oxygen 23159106 ethanol 23159106 oxygen 23159331 (±)-methamphetamine 23159331 Methamphetamine 23159331 dopamine 23159331 methamphetamine 23159331 serotonin 23159396 4',6'-diamidino-2-phenylindole 23159396 DAPI 23159396 Evans blue 23159396 FITC 23159396 fluorescein isothiocyanate 23159397 CaNa(2)EDTA 23159397 calcium disodium ethylenediaminetetraacetic acid 23159479 Oxytocin 23159479 oxytocin 23159529 14C 23159529 17864 23159529 Glutaraldehyde 23159529 PEG 23159529 methionine 23159529 platinum 23159529 polyethylene glycol 23159529 sunitinib 23159662 Venlafaxine 23159662 venlafaxine 23159666 5,10,15,20-tetra(m-hydroxyphenyl)chlorin 23159666 Foscan 23159666 PEG 23159666 polyethylene glycol 23159667 8-Chloro-adenosine 23159667 8-chloro-adenosine 23159667 8-chloro-adenosine-5'-O-stearate 23159667 8CA 23159667 8CAS 23159667 MTT 23159667 PEG-DSPE 23159667 cholesterol 23159667 distearoyl phosphatidylethanolamine 23159667 octadecanoyl 23159667 phosphatidylcholine 23159667 poly (ethylene glycol) 23159712 Carbopol 23159712 Compritol 23159712 PEG 400 23159712 Poloxamer 23159712 lidocaine 23159712 triethyl citrate 23159729 Naphthenic acid 23159729 Naphthenic acids 23159729 benzo[a]pyrene 23159729 naphthenic acids 23159732 N'-formylkynurenine 23159732 NFK 23159732 O2 23159732 Trp 23159732 methylene blue 23159732 oxygen 23159790 Gly 23159790 Ser 23159790 amino acid 23159790 amino acids 23159790 nucleotide 23159790 proline 23159888 Alcohol 23159888 S 23159888 alcohol 23159888 glutathione 23160003 bicyclic phenols 23160003 dienone-phenol 23160003 phenol 23160003 polycyclic cyclohexadienones 23160089 5,7,3',5'-tetrahydroxy-flavanone 23160089 5,7,3',5'-tetrahydroxy-flavanone-7-O-neohesperidoside 23160089 5,7,3',5'-tetrahydroxy-flavanone-7-O-β-d-glucopyranoside 23160089 MTT 23160089 chromone glycosides 23160089 drynachromoside A 23160089 drynachromoside B 23160089 flavanones 23160089 flavonoids 23160092 (1)H 23160092 (13)C 23160092 alcohol 23160092 curcumenone 23160092 ethanol 23160092 n-hexane 23160419 H(2)O 23160419 HONO 23160419 NO(2) 23160419 Nitrogen dioxide 23160419 hydrogen 23160419 nitrogen 23160419 oxygen 23160419 oxygens 23160527 glucose 23160529 zinc 23160934 Cu(2+) 23160934 α-syn12 peptide 23160940 CP55940 23160940 Org 27569 23160940 PSNCBAM-1 23160940 WIN55212 23160940 [(3)H]CP55940 23160940 [(3)H]WIN55212 23160940 [(35)S]GTPγS 23160940 cAMP 23160940 forskolin 23160940 guanosine 5'-O-(3-[(35)S]thio)triphosphate 23160961 Ser 23160961 acyl 23160961 fatty acids 23160961 triacylglyceride 23160964 1,25-Dihydroxyvitamin D3 23160964 1,25-dihydroxyvitamin D 23160964 RO-27-5646 23160964 Vitamin D 23160964 vitamin D 23161217 5-bromo-2'-deoxyuridine 23161217 BrdU 23161217 Suramin 23161217 alanine 23161217 bilirubin 23161217 ethanol 23161217 phospho 23161217 polysulfonated naphthylurea 23161217 suramin 23161424 Arg 23161424 Asp 23161424 Evodiamine 23161424 evodiamine 23161648 Cl(-) 23161648 HCO (3)- 23161648 SO (4)2- 23161648 coal 23161664 Cadmium 23161664 Cd 23161664 Co 23161664 CoCl2 23161664 Lysyl 23161664 cadmium 23161664 cobalt 23161664 lysyl 23161664 oxygen 23161673 tamoxifen 23161677 guanine 23161677 nucleic acid 23161804 (18-Crown-6)-2,3,11,12-tetracarboxylic acid 23161804 (18-crown-6)-2,3,11,12-tetracarboxylic acid 23161804 Isoxazoline 23161804 amine 23161804 crown ether 23161804 hydrochloride 23161804 hydrogen 23161804 isoxazoline 23161804 methanol 23161804 oxygen 23161804 β-amino acid 23163430 polyethylene glycol 23163508 chlorophyll 23163696 H-89 23163696 U-73122 23163696 benzodiazepine 23163696 cyclo(1-8) [DLeu(5) ]OP 23163696 flumazenil 23163696 inositol 1,4,5-trisphosphate 23164613 5-HT 23164613 8-OH-DPAT 23164613 LP-211 23164613 SB-269970 23164613 U0126 23164613 cycloheximide 23164613 roscovitine 23164613 serotonin 23164615 (S)-3,4-dicarboxyphenylglycine 23164615 AZ12216052 23164615 DCPG 23164615 glutamate 23164711 ZINC 23164711 monosulfated benzofurans 23164711 sulfate 23164711 sulfated benzofurans 23164931 DCG-IV 23164931 MPEP 23164931 Procyclidine 23164931 caramiphen 23164931 glutamate 23164931 procyclidine 23164984 As 23164984 Cd 23164984 Hg 23164984 Pb 23164984 arsenic 23164984 cadmium 23164984 mercury 23168241 Quinacrine 23168241 S 23168241 Sodium metabisulfite 23168241 quinacrine 23168241 sodium metabisulfite 23168241 sulfite 23168241 sulfonate 23168915 H(2) 23168915 NiO 23168915 nickel oxide 23169614 carbon 23169614 graphene 23170796 7-dimethylamino-6-dimethyl-6-deoxytetracycline 23170796 Minocycline 23170796 minocycline 23170796 tetracycline 23170798 ethanol 23171045 2-(aryloxy)-3-phenylpropanoic acids 23171045 acylcarnitine 23171045 biphenyl 23171045 carnitine 23171045 palmitoyl 23172038 titanium dioxide 23172121 polyurethane 23172121 polyurethanes 23172229 Cardiolipin 23172229 cardiolipin 23172229 phosphatidylcholine 23172229 phosphatidylethanolamine 23174213 calcium 23174457 Cd(2+) 23174457 Mn(2+) 23174457 cadmium 23174457 paraoxon 23174539 3-phenoxybenzoic acid 23174539 5-HT 23174539 PERM 23174539 dopamine 23174539 monoamine 23174539 noradrenaline 23174539 permethrin 23174539 pyrethroid 23174539 serotonin 23174746 Ritalin 23174746 amphetamine 23174746 methylphenidate 23177255 DPPH 23177255 glucose 23177255 scutellarein 23177255 scutellarin 23177256 10074-G5 23177256 7-nitrobenzofurazan 23177256 JY-3-094 23177256 N-([1,1'-biphenyl]-2-yl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine 23177256 arginine 23177256 ortho-biphenyl 23177256 para-carboxyphenyl 23177784 1,10-phenanthroline 23177784 1,10-phenanthroline-2,9-diacid 23177784 5-amino-2'-deoxycytidine 23177784 diketone 23177784 europium 23177784 lanthanide 23177784 nucleoside 23177784 nucleosides 23177784 phenanthroline 23177784 polypyridine ruthenium 23177784 ruthenium 23178170 C 23178170 Ca(2+) 23178170 calcium 23178170 potassium 23178178 Na(+)K(+) 23178178 Ti 23178178 TiO(2) 23178178 Titanium dioxide 23178178 glutathione 23178178 lactate 23178178 titanium dioxide 23178179 2-Mercaptobenzothiazole 23178179 2-mercaptobenzothiazole 23178179 MBT 23178179 iodo-amino acids 23178179 sodium-iodide 23178182 MK-801 23178182 N-Methyl-d-aspartate 23178182 NMDA 23178182 NO 23178182 UCCB01-125 23178182 nitric oxide 23178221 7-xylosyl taxanes 23178221 OH 23178221 diglycoside taxanes 23178221 xylosyl 23178221 xylosyl-containing taxanes 23178221 α-d-glucose 23178243 8-OH-dG 23178243 8-hydroxyguanine 23178243 8-hydroxyguanosine 23178243 8-oxoguanine 23178243 Aerosil 23178243 PAR 23178243 Printex 23178243 carbon black 23178243 paraffin 23178243 poly(ADP-ribose) 23178243 silica 23178279 dexamethasone 23178339 DHA 23178339 TEA 23178339 amine 23178339 docosahexaenoic acid 23178339 doxorubicin 23178339 polyunsaturated fatty acid 23178339 triethanolamine 23178949 formaldehyde 23179351 nickel chloride 23179765 benzene 23179765 hydrogen 23179765 pyrrole 23179966 5-HT 23179966 N-methyl-D-aspartate 23179966 NMDA 23179966 Serotonin 23179966 dopamine 23179966 glutamate 23179966 serotonin 23180370 NaCl 23180370 SO4 23180370 sulphate 23180382 graphene 23180382 graphenes 23180652 2,4-dichlorophenoxyacetic acid 23180652 atrazine 23180652 chlorpyrifos 23180652 gemfibrozil 23180692 malathion 23180762 magnesium 23180762 tartrate 23181488 (CH(3))(2)HC-CO-CH(CH(3))(2) 23181488 diisopropyl ketone 23181488 isopropyl 23181488 methyl 23183084 20-keto 23183084 3-keto 23183084 5α-dihydroprogestrone 23183084 Progestin 23183084 dienogest 23183084 dydrogesterone 23183084 medroxyprogesterone acetate 23183084 progesterone 23183084 progestin 23183084 progestins 23183186 2,2'-dihydroxy-1,1'-dinaphthyldisulfide 23183186 IPA3 23183186 Ser 23183186 Thr 23183186 cAMP 23183186 glucose 23183413 Cu 23183413 GSH 23183413 K(+) 23183413 Na(+) 23183413 S 23183413 copper 23183413 glutathione 23183413 oxygen 23183413 peroxyl 23183413 sodium 23183532 amino acid 23183532 amino acids 23183532 ammonia 23183532 fatty acids 23183532 nitrogen 23183532 sulfide 23184251 8-oxo-dGTP 23184251 ADP 23184251 Ap(4)A 23184251 DIP 23184251 DIPs 23184251 IDP 23184251 dIDP 23184251 diadenosine polyphosphates 23184251 diadenosine tetraphosphate 23184251 diphosphoinositol polyphosphates 23184251 nucleotides 23184251 oxidized nucleotides 23184251 polyphosphates 23184251 pyrophosphate 23184251 ribose 23184951 ATP 23185990 2'-OH 23185990 Ala 23185990 Amino acids 23185990 Aminoacyl 23185990 Cys 23185990 Pro 23185990 Prolyl 23185990 aminoacyl 23185990 ester 23186623 TTX 23186623 tetrodotoxin 23186624 Catapresan 23186624 Clonidine 23186624 NaCl 23186624 clonidine 23186624 creatinine 23186624 diethylether 23186624 formalin 23186624 nitrogen 23186624 urea 23188714 2'deoxyuridine 23188714 5-fluoropyrimidine 23188714 5-fluorouracil 23188714 5F-2'dCtd 23188714 5F-2'dUrd 23188714 5F-2'deoxyuridine 23188714 5F-dUMP 23188714 5F-orotic acid 23188714 Pyrimidine 23188714 halogenated pyrimidines 23188714 nucleoside 23188714 pyrimidine 23188714 pyrimidines 23188714 thymidine 23188714 uracil 23188714 uridine 23189968 iron 23190030 (poly)phenolic 23190030 Phenolic 23190030 flavonoid 23190030 nitrogen 23190030 oxygen 23190172 17β-Oestradiol 23190172 17β-oestradiol 23190172 H(2) O(2) 23190172 oestrogen 23192895 H(δ+) 23192895 H(δ-) 23192895 Mg(BH(4))(2) 23192895 Mg(BH(4))(2)·NH(3) 23192895 Mg(BH(4))(2)·xNH(3) 23192895 N:→Mg(2+) 23192895 NH(3) 23192895 ammonia 23192895 hexaammoniate 23192895 hydrogen 23192895 magnesium borohydride 23192895 magnesium borohydride ammoniates 23192895 metal borohydride ammoniates 23192982 17β-estradiol 23192982 cholesterol 23192982 estrogen 23193276 amino acid 23194502 Glaucine 23194502 adriamycin 23194502 glaucine 23194502 isoquinoline alkaloid 23194502 mitoxantrone 23194504 3',5'-Di-C-β-glucopyranosylphloretin 23194504 3',5'-di-C-β-glucopyranosylphloretin 23194504 Trolox 23194504 flavonoids 23194504 hesperidin 23194504 naringin 23194504 nobiletin 23194504 oxygen 23194504 superoxide 23194504 tangeretin 23194505 ethanol 23194507 cis-isomers of lycopene and β-carotene 23194507 lutein 23194507 lycopene 23194507 zeaxanthin 23194507 β-carotene 23194510 4(5)-methylimidazole 23194510 4-MI 23194510 D-glucose 23194510 NH(3) 23194510 Sulphite 23194510 pyrazine 23194510 sulphite 23194512 MTT 23194512 Micranthin B 23194512 Podocarpane 23194512 abietane 23194512 diterpenoids 23194512 graciliflorin C 23194512 graciliflorin D 23194512 graciliflorins A (1) and B 23194512 isopimarane 23194512 isopimarane acetal 23194512 micranthin B 23194512 podocarpa-8,11,13-triene-3α,13-diol 23194512 podocarpanes 23194517 amino acid 23194517 amino acids 23194517 astaxanthin 23194517 carbonyl 23194517 fatty acid 23194517 sulfhydryl 23194517 tocopherol 23194522 ABTS 23194522 phenolic acids 23194522 polyphenol 23194522 polyphenols 23194524 acetone 23194524 phloridzin 23194524 polyphenol 23194525 Hexose 23194526 cholesterol 23194528 1-propanol 23194528 2-furaldehyde 23194528 2-methyl-1-butanol 23194528 2-methyl-1-propanol 23194528 3-methyl-1-butanol 23194528 5-(Hydroxymethyl)-2-furaldehyde 23194528 5-(hydroxymethyl)-2-furaldehyde 23194528 ethyl acetate 23194528 furan 23194528 silver 23194531 anthocyanin 23194531 anthocyanins 23194531 ethanol 23194533 Fatty acids 23194533 fatty acids 23194533 lauric acid 23194533 saturated fatty acids 23194540 boscalid 23194543 sodium 23194544 Asparagine 23194544 acrylamide 23194544 asparagine 23194544 fructose 23194544 glucose 23194544 sucrose 23194544 sugars 23194555 Cd(II) 23194555 Hg(II) 23194555 Zn(II) 23194555 mercury 23194566 TTX 23194566 Tetrodotoxin 23194566 tetrodotoxin 23194750 10-DEBC 23194750 GW9662 23194750 KCl 23194750 LNNA 23194750 LY294002 23194750 N(G)-nitro-L-arginine 23194750 NO 23194750 Thiazolidinediones 23194750 glitazones 23194750 phenylephrine 23194750 pioglitazone 23194750 rosiglitazone 23194750 ser 23194750 thiazolidinedione 23194750 thiazolidinediones 23194750 troglitazone 23194825 12-O-tetradecanoyl-phorbol-13-acetate 23194825 3,4-methylenedioxymethamphetamine 23194825 BSO 23194825 Ecstasy 23194825 GBR 12909 23194825 GSH 23194825 MDMA 23194825 N-Me-α-MeDA 23194825 N-acetylcysteine 23194825 N-methyl-α-methyldopamine 23194825 NAC 23194825 buthionine sulfoximine 23194825 catechol 23194825 dopamine 23194825 ecstasy 23194825 glutathione 23194825 retinoic acid 23194825 superoxide 23194825 α-MeDA 23194825 α-methyldopamine 23194825 γ-glutamylcysteine 23195954 Asp 23195954 C 23195954 Ca(2+) 23195954 His 23195954 N 23195954 Ser 23195954 Serine 23195954 Zn(2+) 23195954 Zn2+ 23195954 serine 23195960 K 23195960 Na 23195960 Na(+) 23195960 ouabain 23196320 Ag 23196320 AuAg 23197649 ACh 23197649 BQCA 23197649 CNO 23197649 acetylcholine 23197649 benzyl quinolone carboxylic acid 23197649 clozapine-N-oxide 23197771 TAPI-0 23197771 tyrosine 23198810 naphthalimide 23198810 quinone 23198819 MTM 23198819 Montmorillonite 23198819 quartz 23198831 H(+) 23198831 H(2) 23198831 Hydrogen 23198831 Pt 23198831 Ru 23198831 hydrogen 23198958 GaAs 23198958 In(Ga)As 23199028 amine 23199028 amino acid 23199028 carbohydrate 23199028 glycyrrhizin 23199983 1-lactulose 23199983 Fructose 23199983 Lactose 23199983 fructose 23199983 galactosyl 23199983 lactose 23199983 lactulose 23199984 TAG 23199984 sodium methoxide 23199984 stearin 23199984 triacylglycerol 23199992 4-aminobutyrate 23199992 GABA 23199992 O-phosphocholine 23199992 acetate 23199992 asparagine 23199992 isoleucine 23199992 leucine 23199992 phenylacetate 23199992 phenylalanine 23199992 succinate 23199992 sucrose 23199992 tyrosine 23199992 valine 23199992 ¹H 23199999 malondialdehyde 23200004 hydrogen peroxide 23200004 mercury 23200004 nitric acid 23200004 nitrous acid 23200004 nitrous oxides 23200004 potassium dichromate 23200004 tin chloride 23200005 Fe 23200005 K 23200005 P 23200005 Se 23200005 SeCys 23200005 SeMet 23200005 Selenium 23200005 Zn 23200005 adenosine 23200005 cordycepin 23200005 iron 23200005 methylselenocysteine 23200005 phosphorus 23200005 potassium 23200005 selenium 23200005 selenomethionine 23200005 zinc 23200006 alcoholic 23200006 cadmium 23200006 carbon 23200006 copper 23200006 graphite 23200246 12-hydroxy-scabrolide A 23200246 13-epi-scabrolide C 23200246 norditerpenoids 23200253 TBPB 23200253 TPBP 23200253 VU0357017 23200253 piperidine 23200747 Organophosphorus 23200778 BEP 23200778 S 23200778 aldehyde 23200778 bleomycin 23200778 cisplatin 23200778 etoposide 23200778 glutathione 23200887 3,5,4'-trihydroxy-trans stilbene 23200887 ADP 23200887 H(2)O(2) 23200887 Resveratrol 23200887 resveratrol 23200901 Aconitum alkaloids 23200901 BAC 23200901 BHA 23200901 BMA 23200901 Ko143 23200901 MK571 23200901 aconine 23200901 aconitine 23200901 benzoylaconine 23200901 benzoylhypaconine 23200901 benzoylmesaconine 23200901 cyclosporine A 23200901 hypaconitine 23200901 mesaconine 23200901 mesaconitine 23200901 verapamil 23201003 1,25(OH)(2)D(3) 23201003 1α,25-dihydroxyvitamin D(3) 23201003 1α,25-dihydroxyvitamin D₃ 23201003 JBP485 23201055 PLGA 23201055 Poly(lactic-co-glycolic acid) 23201124 N 23201309 3'-hydroxyl 23201309 3-phosphoglycerate 23201309 ADP 23201309 Nucleoside 23201309 creatine 23201309 nucleoside diphosphate 23201309 nucleotide 23201309 pyruvate 23201309 tenofovir 23201309 tenofovir mono- or diphosphate 23201309 tenofovir monophosphate 23201331 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide 23201331 MTT 23201331 Sweroside 23201331 sweroside 23201370 alanine 23201370 amino 23201370 aspartate 23201370 cholesterol 23201370 triglycerides 23201439 carbon 23201439 cyclosarin 23201439 organophosphorus 23201439 β-cyclodextrin 23201442 Estrogen 23201442 Fatty acids 23201442 H₂O₂ 23201442 NADH 23201442 NAD⁺ 23201442 Raloxifene 23201442 acetoacetate 23201442 estrogen 23201442 fatty acid 23201442 fatty acids 23201442 oxygen 23201442 phenoxyl 23201442 raloxifene 23201442 ¹⁴CO₂ 23201442 β-hydroxybutyrate 23201451 Moniliformin 23201451 moniliformin 23202250 TiO(2) 23202250 carbon 23202250 titanium dioxide 23202585 ATP 23202585 C 23202880 N(2) 23202880 NO(3) 23202880 NO3 23202880 branched alkane 23202880 nitrate 23202880 squalane 23202880 squalene 23203454 CHDA 23203454 DINCH 23203454 DINP 23203454 Hexamoll 23203454 MINCH 23203454 OH 23203454 carboxy 23203454 cyclohexane-1,2-dicarboxylic acid 23203454 di-iso-nonylphthalate 23203454 diisononyl-cyclohexane-1,2-dicarboxylate 23203454 mono-isononyl-cyclohexane-1,2-dicarboxylate 23203454 monoester 23203454 monoesters 23203454 oxo 23203454 phthalate 23203870 zinc 23203920 N-3-oxododecanoyl-L-homoserine lactone 23203920 OHN 23204325 glucose 23204443 Sphingosine 1-phosphate 23205571 (2S,4R)-4-(naphthalene-2-ylmethyl)pyrrolidine-2-carboxylic acid 23205571 Ica 23205571 N 23205571 [Mpa(1), Ica(2), D-Arg(8)]VP 23205571 [Mpa(1),Ica(2),Val(4),D-Arg(8)]VP 23205571 arginine vasopressin 23205571 indoline-2-carboxylic acid 23205571 oxytocin 23205571 proline 23205763 alkyne 23205763 azide 23205763 indocyanine green 23205763 metal-oxide 23205778 1,4-benzoquinone 23205778 2-chlorofuran 23205778 2-chlorothiophene 23205778 Br 23205778 Cl 23205778 C≡N 23205778 F 23205778 OH 23205778 anthracene 23205778 aromatic heterocycles 23205778 benzene 23205778 benzenes 23205778 benzimidazole 23205778 benzisoxazole 23205778 benzo[b]thiophene 23205778 benzo[c]thiophene 23205778 benzonitrile 23205778 benzothiazole 23205778 benzoxazole 23205778 bromobenzene 23205778 carbon 23205778 chlorobenzene 23205778 di-, tri-, and hexachlorobenzene 23205778 dihydroxybenzene 23205778 fluorobenzene 23205778 fused-ring heterocycles 23205778 hydrogen 23205778 indazole 23205778 indole 23205778 isoindole 23205778 methanol 23205778 naphthalen-2-ol 23205778 naphthalene 23205778 naphthalene-2-carbonitrile 23205778 phenanthrene 23205778 phenol 23205778 polycyclic aromatic 23205778 polycyclic aromatic hydrocarbons 23205778 purine 23205778 quinoline 23206503 2-AG 23206503 2-arachidonoylglycerol 23206503 AEA 23206503 GW6471 23206503 N-palmitoylethanolamine 23206503 PEA 23206503 SR141716 23206503 anandamide 23206503 cannabinoids 23206503 fatty acid ethanolamide 23206861 Tetrahydro-β-carboline 23206861 carbamates 23206861 fatty acid amide 23206861 tetrahydro-β-carbolines 23206990 Estrogen 23207166 Misoprostol 23207166 misoprostol 23207252 NADPH 23207252 nicotinamide adenine dinucleotide phosphate 23207252 thiobarbituric acid 23207328 AZT 23207328 PPG-5-CETETH-20 23207328 oleic acid 23207328 zidovudine 23207477 Co 23207477 Cobalt 23207477 cobalt 23208007 sialic acid 23208609 1-chloro-4-propoxy-TX 23208609 1-chloro-4-propoxythioxanthone 23208609 17ß-estradiol 23208609 2,4-diethyl-TX 23208609 2,4-diethylthio xanthone 23208609 2-ITX 23208609 2-chloro-TX 23208609 2-chlorothioxanthone 23208609 2-isopropylthioxanthone 23208609 4-ITX 23208609 4-isopropylthioxanthone 23208609 androgen 23208609 estrogen 23208609 estrone 23208609 pregnenolone 23208609 progesterone 23208609 steroid 23208609 thioxanthone 23208666 Poly(2-oxazoline) 23208666 poly(2-nonyl-2-oxazoline)s 23208666 poly(2-oxazoline) 23209192 Cotinine 23209192 cotinine 23210481 6,6'-bis-O-(3-nonyldodecanoyl)-α,α'-trehalose 23210481 TDCM 23210481 Vizantin 23210481 trehalose 6,6'-dicorynomycolate 23210481 trehalose-6,6'-dicorynomycolate 23210481 vizantin 23210547 carbon 23210662 PAMAM 23210662 doxorubicin 23210662 ethynyl 23210851 ATP 23211364 Candesartan 23211364 PD-123319 23211364 candesartan 23211525 androgens 23211525 dehydroepiandrosterone 23211525 hydroxysteroid 23211525 retinoid 23211525 sulfonate bile acids 23212787 Ginsenoside 23212787 Ginsenosides Ra1-3, Rb2-3, and Rc 23212787 ginsenosides 23212970 MTT 23212970 PCL diol 23212970 TDI 23212970 butanediol 23212970 monoglyceride 23212970 pentaerythritol 23212970 polyurethane 23212970 polyurethanes 23212975 PEG 23212975 PVP 23212975 Poly(N-vinylpyrrolidone) 23212975 poly(ethylene glycol) 23214415 PAA 23214415 PEO 23214415 poly(acrylic acid) 23214415 poly(ethylene oxide) 23214423 Br(2) 23214423 BrF(3) 23214423 C(2)F 23214423 C2F 23214423 carbon 23214423 fluorine 23214423 graphene 23214423 graphite 23214423 graphite fluoride 23214430 Au 23214430 silica 23214714 C 23214714 CH(3)OH 23214714 CO(2) 23214714 CO(2)(-) 23214714 CO2 23214714 N 23214714 Py(-) 23214714 PyCOO(-) 23214714 PyCOOH(0) 23214714 PyH(+) 23214714 PyH(0) 23214714 Py·CO(2) 23214714 formaldehyde 23214714 formic acid 23214714 pyridine 23214926 ADP 23214926 AMF-26 23214926 Δ¹,²-octalin 23214979 3-Amido pyrrolopyrazine 23214979 3-amido-5-cyclopropylpyrrolopyrazines 23214990 poly(N-isopropyl acrylamide) 23215007 1,3,5,6-tetramethyluracil 23215007 1,3,5-trimethyluracil 23215007 5,6-dimethyl-, 1,3,5-trimethyl-, and 1,3,5,6-tetramethyl 23215007 5,6-dimethyl-, 1,3,5-trimethyl-, and 1,3,5,6-tetramethyluracils 23215007 5,6-dimethyluracil 23215007 N(2) 23215007 methylated uracils 23215007 uracils 23215148 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium 23215148 1,2-dioleoyl-sn-glycero-3-phospho-L-serine 23215148 1,2-dioleoyl-sn-glycero-3-phosphocholine 23215148 1,2-dipalmitoyl-sn-glycero-3-phosphocholine 23215148 DOPC 23215148 DOPS 23215148 DPPC 23215148 TR-DHPE 23215148 Texas Red 23215238 EDTA 23215238 calcium carbonate 23215461 carbohydrate 23216335 androgens 23217961 Am80 23217961 Cinnamic acid 23217961 benzoic acid 23217961 carboxyl 23217961 carboxylic acid 23217961 diphenylamine 23217961 methyl 23217961 phenylpropionic acid 23217961 retinoid 23217961 retinoids 23218712 YH-GKA 23218712 benzamide 23218712 glucose 23218712 phenylethyl benzamide 23218713 bisulfite 23218713 cysteine 23218713 dipeptidyl aldehydes 23218713 serine 23218713 α-ketoamides 23218713 α-ketoesters 23218713 α-ketoheterocycles 23218716 Indoleamine 23218716 Tsitsikammamine A 23218716 Tsitsikammamines 23218716 pyrroloiminoquinone 23218716 tryptophan 23218716 tsitsikammamine 23218716 tsitsikammamine A 23218717 2-APB 23218717 Ca(2+) 23218717 N-pyridylpyrazolecarboxamides 23218717 calcium 23218717 cyano 23218717 fluo-3 AM 23218717 ryanodine 23219161 C 23219161 N 23219325 Leucine 23219325 cinnoline 23219325 cinnoline-3-carboxamides 23219339 N-methyl-D-aspartate 23219339 NMDA 23219339 OMT 23219339 Oxymatrine 23219339 calcium 23219339 oxymatrine 23219469 cholesterol 23219525 ambrisentan 23219525 bosentan 23219525 pregnane 23219525 sildenafil 23219525 tadalafil 23219590 BAPTA 23219590 Ca(2+) 23219590 Ca2+ 23219590 Maprotiline 23219590 maprotiline 23219590 norepinephrine 23219658 N-methyl-d-Aspartate 23219658 N-methyl-d-aspartate 23219658 NMDA 23219658 glutamate 23219696 Bisphenol-A 23219696 estradiol 23219696 nonylphenol 23219696 progesterone 23219696 steroid 23219696 steroids 23219696 testosterone 23219778 MeOH 23219778 methanol 23219778 nitric oxide 23219979 EtOAc 23219979 cis-stilbenoids 23219979 sciryagarol I (1) and II 23220002 esters 23220002 glucose 23220002 organophosphorus 23220003 Fructose 23220003 GSH 23220003 Glyoxal 23220003 alkyl 23220003 curcumin 23220003 dicarbonyl 23220003 dicarbonyls 23220003 dihydroxyacetone 23220003 ethyl gallate 23220003 fructose 23220003 gallate 23220003 gallates 23220003 gallic acid 23220003 glyceraldehyde 23220003 glycoaldehyde 23220003 glyoxal 23220003 hydroxypyruvate 23220003 methyl gallate 23220003 methylglyoxal 23220003 oxygen 23220003 polyphenol 23220003 polyphenols 23220003 propyl gallate 23220003 rutin 23220004 4-methyl 23220004 NAD 23220004 Retinaldehyde 23220004 UVI2008 23220004 aldehyde 23220004 carboxyl 23220004 retinaldehyde 23220004 retinoic acid 23220004 retinoid 23220004 retinoids 23220004 retinol 23220291 limonene 23220291 ozone 23220293 5-HT 23220293 catecholamine 23220293 citalopram 23220293 desipramine 23220293 dopamine 23220293 monoamine 23220293 monoamines 23220293 norepinephrine 23220293 serotonin 23220295 amphetamine 23220295 dopamine 23220412 Metolachlor 23220412 chloroacetanilide 23220412 chlorophyll a 23220412 chlorophyll a, b or c 23220412 glutathione 23220412 metolachlor 23220413 3,3',5-triiodo-l-thyronine 23220413 TDCPP 23220413 Tris(1,3-dichloro-2-propyl) phosphate 23220413 thyroxin (T4) 23220513 (32)P 23220513 MEG 23220513 Methyleugenol 23220513 S 23220513 glutathione 23220513 phenobarbital 23220514 DOX 23220514 Na(+) 23220514 S-(4-nitrobenzyl)-6-thioinosine 23220514 doxorubicin 23220514 linalool 23220514 nucleoside 23220514 phlorizin 23220560 MeHg 23220560 methylmercury 23220562 DAPI 23220562 MTT 23220562 SB-203580 23220562 SP-600125 23220562 U-0126 23220562 clopidogrel 23220586 PEG 23220586 organophosphorus 23220586 polyethylene glycol 23220586 soman 23220588 2-mercaptoethane sulfonate 23220588 Acrolein 23220588 Aldehyde 23220588 CAA 23220588 Cyclophosphamide 23220588 H2O2 23220588 MESNA 23220588 N-acetylcysteine 23220588 Trolox 23220588 Trypan blue 23220588 acrolein 23220588 amines 23220588 aminoguanidine 23220588 ascorbic acid 23220588 carbonyl 23220588 chloroacetaldehyde 23220588 cyanamide 23220588 cyclophosphamide 23220588 cysteine 23220588 glutathione 23220588 hydralazine 23220588 hydroxylamine 23220588 ifosfamide 23220588 oxygen 23220588 penicillamine 23220588 sodium bisulfite 23220588 sodium borohydride 23220588 thiol 23220589 2-PAM 23220589 BT-03 23220589 BT-05 23220589 BT-07-4M 23220589 BT-08 23220589 HI-6 23220589 Organophosphorus 23220589 TMB-4 23220589 Toxidin 23220589 dichlorvos 23220589 obidoxime 23220589 oximes 23220589 paraoxon 23220589 tabun 23220612 20-HETE 23220612 27-hydroxycholesterol 23220612 27-hydroxycholestrol 23220612 5(S)-, 8(S)-, 12(S)- and 15(S)-HETE 23220612 5(S)-HETE 23220612 7-ketocholesterol 23220612 7β-hydroxycholesterol 23220612 9(S)-, 11(S)- and 20-HETE 23220612 Arachidonate 23220612 H(2)O(2) 23220612 cholesterol 23220612 docosahexaenoate 23220612 eicosapentaenoate 23220612 gluthathione 23220612 isoprostanes 23220612 neuroprostanes 23220612 oxygen 23220612 polyunsaturated fatty acids 23220612 resolvin D1 23220617 3-nitrotyrosine 23220617 carbonyl 23220617 cyclophosphamide 23220617 doxorubicin 23220635 aryl hydrocarbon 23220644 5-hydroxytryptamine 23220644 5-hydroxytryptamines 23220644 JMC08-4 23220644 arachidonic acid 23220646 3H-indazole 23220646 5-phenyl-1H-pyrazole 23220646 TLCK 23220646 benzimidazole 23220646 benzoheterocyclic 23220646 benzothiazole 23220646 isoxazolecarbaldehyde 23221006 Phenformin 23221006 TEA 23221006 [(14)C]tetraethylammonium 23221006 carnitine 23221006 oxygen 23221006 phenformin 23221633 oxygen 23221633 phospho 23222689 valproic acid 23223023 fatty acids 23223023 oleic and stearic acid 23223023 palmitic acid 23223234 6-azauracil 23223234 nucleotide 23223345 CARB 23223345 Carbohydrate 23223345 carbohydrate 23223345 glucose 23223551 C-H 23223551 CuO(+) 23223551 CuOH(+) 23223551 copper hydroxide 23223551 copper oxide 23223551 hydrocarbons 23223551 methane 23223551 oxygen 23223551 transition metal 23223639 polydimethylsiloxane 23223641 zeolite 23223641 zeolites 23223708 Nafion 23223708 PVDF 23223708 Polyvinylidene fluoride 23223708 vanadium 23223801 Lanthanide 23223801 Ln(3+) 23223801 Trivalent lanthanide 23223857 Carbon 23223857 carbon 23224291 (1)H 23224291 S 23224291 adenosine triphosphate 23224291 glucose 23224291 glutathione 23224291 glycine 23224291 thiosulphate 23224775 Ti(IV) 23224775 TiO(2) 23224775 carboxyl 23224775 carboxyl- and hydroxyl oxygen 23224942 epoxy 23224942 epoxy graphene oxide 23224942 graphene 23224942 graphene oxide 23225075 aluminium 23225075 cadmium 23225075 cobalt 23225075 copper 23225075 manganese 23225075 uranium 23225075 vanadium 23225075 zinc 23225241 Cholesterol 23225241 TAG 23225241 biliary acids 23225241 cholesterol 23225241 estrogens 23225241 triacylglycerol 23225365 MTT 23225365 NO 23225365 Resveratrol 23225365 resveratrol 23225365 sodium nitroprusside 23225366 9,19-cycloartane 23225366 cimigenol 23225366 cycloartane 23225366 triterpenes 23225536 Cd(2+) 23225536 Cu(2+) 23225536 GSH 23225536 Ni(2+) 23225536 PAHs 23225536 Zn(2+) 23225536 benzo[a]pyrene 23225536 chlorophyll a 23225536 fluoranthene 23225536 fluorene 23225536 glutathione 23225536 phenanthrene 23225536 polycyclic aromatic hydrocarbons 23225536 pyrene 23225536 superoxide 23225542 Fe(3)O(4) 23225542 Fe3O4 23225542 ICG 23225542 PAH 23225542 indocyanine green 23225542 poly(allylamine hydrochloride) 23225638 1-anilinonaphthalene-8-sulfonic acid 23225638 2-azido-1,3-propanediol 23225638 PEG 23225638 azido glycerol 23225638 diethylester 23225638 octadecyl 23225638 polyethylene glycol 23225638 polyglycerols 23225638 pyrene 23225671 nucleic acids 23225671 purine 23225764 L-lysines 23225764 poly(methacrylate)s 23225770 genipin 23225780 N-Cyano sulfoximines 23225780 N-cyano sulfoximines 23227887 FDV 23227887 Fosdevirine 23227887 GSH 23227887 GSK2248761 23227887 cysteine 23227887 glutathione 23227887 nucleoside 23227887 trans-phenyl acrylonitrile 23228028 Al 23228028 Ga 23228028 In(2)O(3) 23228028 In2O3 23228028 Mg 23228193 denbinobin B 23228193 phenanthrenequinone 23228193 phenanthrenes 23228469 3,5-bis(4-chlorobenzylidene)-1-[4-{2-(4-morpholinyl)ethoxy}phenyl-carbonyl]-4-piperidone hydrochloride 23228469 glutathione 23228471 2-(3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles 23228471 EtOH 23228471 HCl 23228471 chalcones 23228471 phenacyl bromide 23228471 thiazolyl-pyrazoline 23228471 thiosemicarbazide 23228475 2,3,7,8-tetrachlorodibenzo-p-dioxin 23228475 BaP 23228475 Benzo[a]pyrene 23228475 Cyprodinil 23228475 Dexamethasone 23228475 TCDD 23228475 aryl hydrocarbon 23228475 cyprodinil 23228475 dexamethasone 23228475 pyrimidinamine 23228696 Metformin 23228696 SB202190 23228696 Taxol 23228696 metformin 23228696 paclitaxel 23228696 platinum 23228697 Orlistat 23228697 PPD 23228697 doxazolidine 23228697 irinotecan 23228697 orlistat 23228697 p-aminobenzyl carbamate 23228697 pentyl carbamate 23229055 (1)H 23229055 (13)C 23229055 2H-indazol-3-ol 23229055 6-carbethoxy-2-cyclohexen-1-one 23229055 Cyclohexenone 23229055 Indazole 23229055 chalcone 23229055 chalcones 23229511 17-AAG 23229511 17-Allylamino-17-demethoxygeldanamycin 23229511 Aryl hydrocarbon 23229511 NAD(P)H 23229511 aryl hydrocarbon 23229511 quinone 23229539 iron 23229539 malondialdehyde 23229539 superoxide 23230131 2',2'-difluorodeoxycytidine 23230131 2',2'-difluorodeoxyuridine 23230131 Ara-C 23230131 Gemcitabine 23230131 cytarabine 23230131 cytidine 23230131 dFdC 23230131 dFdU 23230131 deoxycytidine 23230131 gemcitabine 23230274 arsenite 23230274 oxygen 23230281 peroxynitrite 23231350 methyl mercury 23231350 sulfonamides 23231439 (R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide 23231439 CID: 46897844 23231439 ML188 23231439 N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides 23231439 dipeptide 23231457 poly-L-lysine 23231809 Dopamine 23231809 dopamine 23231967 N-(2,6-diarylpyrimidin-4-yl)acetamide 23231967 adenosine 23231967 methoxyaryl 23231967 methoxyphenyl 23232056 amides 23232056 diphenylpropanamide 23232059 Cynaropicrin 23232059 cynaropicrin 23232059 sesquiterpene lactone 23232150 alcohol 23232150 estradiol 23232150 formate 23232150 glycerol 23232150 histidinol-phosphate 23232150 steroid 23232150 steroids 23232333 corticosterone 23232461 K 23232461 Na 23232461 Organotin 23232461 organotin 23232461 organotins 23232866 Fluo-4 23232866 PDMS 23232866 calcium 23232866 poly(dimethylsiloxane) 23232941 C=C 23232941 Cu(100) 23232941 C≡N 23232941 acrylonitrile 23232941 cyano 23232941 vinyl 23233034 citrate 23233034 silver 23233456 DGL 23233456 Dendritic poly(L-lysines) 23233456 jetPEI 23233456 poly(L-lysines) 23234246 (99m)Tc 23234246 (99m)Tc(CO)(3) 23234246 (99m)Tc(CO)(3)}(+) 23234246 99mTc 23234246 M(CO)(3) 23234246 Re 23234246 benzenesulfonamide 23234246 benzenesulfonamide rhenium 23234246 technetium tricarbonyl 23234246 {(99m)Tc(CO)(3)}(+) 23234313 poly(propylene imine) 23234313 poly(propylene-imine) 23234537 P3HT 23234537 carbon 23234537 poly(3-hexylthiophene) 23234607 2-oxoglutarate 23234607 2OG 23234812 NO 23234812 Nitric oxide 23234812 PGE(2) 23234812 SrRan 23234812 Strontium Ranelate 23234812 prostaglandin E(2) 23234855 2,2'-bipyridine 23234855 2,2'-bipyridine-4,4'-dicarboxylic acid 23234855 COOH 23234855 Ru(II) 23234855 [RuCl(HL)(AsPh(3))(2)(CO)] 23234855 [RuCl(HL)(PPh(3))(2)(CO)] 23234855 [RuHCl(bpy)(AsPh(3))(CO)] 23234855 [RuHCl(bpy)(PPh(3))(CO)] 23234855 bipyridine 23234855 bpy 23234855 carboxylic acid 23234855 ruthenium (II) polypyridyl complexes 23235151 C 23235151 N 23235151 histamine 23235151 sulfate 23235158 Asp 23235158 Tyr 23235158 amino acids 23235158 aspartate 23235158 chlorite 23235158 heme 23235158 hydrogen peroxide 23235158 iron 23235158 tyrosine 23235435 Co(ii) 23235435 Cr(iii) 23235435 bis(1,4,7-triazacyclononane) 23235435 transition metal 23235435 triazacyclononane 23235742 Pt 23235742 levulinic acid 23237482 As 23237482 GaAs 23237546 Au 23237546 calcium 23237546 glucose 23237590 silica 23237828 Cycloheximide 23237828 PD98059 23237828 SP600125 23237828 U0126 23237828 actinomycin D 23237828 cycloheximide 23237939 NU7441 23237939 cisplatin 23237974 6,7-secoschisantherol A 23237974 Lignans 23237974 dibenzocyclooctene 23237974 epoxy 23237974 lignan 23237974 lignans 23237974 schisandrin A1 23237974 schisantherin A 23238233 chikusetsusaponin FK2 23238233 chikusetsusaponin FK6 23238233 chikusetsusaponin FK7 23238233 chikusetsusaponin FT1 23238233 chikusetsusaponin IVa 23238233 chikusetsusaponin L10 23238233 chikusetsusaponin L5 23238233 chikusetsusaponin L9a 23238233 chikusetsusaponin L9bc 23238233 chikusetsusaponin LM1 23238233 chikusetsusaponin LM2 23238233 chikusetsusaponin LM3 23238233 chikusetsusaponin LM4 23238233 chikusetsusaponin LM5 23238233 chikusetsusaponin LM6 23238233 chikusetsusaponin V 23238233 chikusetsusaponins 23238233 dammarane 23238233 ginsenoside F3 23238233 ginsenoside F5 23238233 ginsenoside F6 23238233 ginsenoside Rb3 23238233 ginsenoside Rc 23238233 ginsenoside Rd 23238233 ginsenoside Re 23238233 ginsenoside Rg1 23238233 triterpenoid saponins 23238235 4-HHE 23238235 4-ONE 23238235 4-hydroxy-hexenal 23238235 4-oxo-2-nonenal 23238235 acrolein 23238235 crotonaldehyde 23238236 DPPH(·) 23238236 Sterols 23238236 fatty acids 23238236 nitric oxide 23238236 superoxide 23238236 triterpenes 23238352 H(2)O 23238352 H(2)S 23238352 Zinc oxide 23238352 ZnO 23238352 ZnS 23238352 oxygen 23238352 wurtzite 23238352 zinc 23238425 Nafion 23238425 Pt 23238425 SO(3)H 23238425 SO3H 23238425 Si 23238425 fluorine 23238425 glassy carbon 23238425 oxygen 23238425 platinum 23238425 silicon 23238611 magnesium 23238657 N(ε)-carboxymethyllisine 23238657 nitrate 23238657 nitric oxide 23238657 nitrite 23238662 glucose 23238783 Wellbutrin SR 23238783 bupropion 23238783 hydroxybupropion 23238991 CFSE 23238991 MTT 23238991 silica 23239015 Graphene Oxide 23239015 Octacationic 23239015 Pc(8+) 23239015 Poly-Ortho-Functionalizable Tetraarylporphycene 23239015 graphene oxide 23239015 poly-ortho-substituted tetraarylporphycene 23239601 hydrogen 23239639 HPMA 23239639 SDS 23239639 ester 23239639 maleimide 23239639 pentafluorophenyl methacrylate 23239639 poly(N-(2-hydroxypropyl)-methacrylamide) 23239639 poly-HPMA 23239825 carboxyl 23239825 serine 23239825 threonine 23240655 Al(2)O(3) 23240655 MoS(2) 23240655 MoS2 23240655 graphene 23240655 scandium 23240993 (1)H 23240993 (129)Xe 23240993 (13)C 23240993 (19)F 23240993 (29)Si 23240993 129Xe 23240993 Ar 23240993 Ar(l) 23240993 Me(2)DABCO(2+) 23240993 Xe 23240993 Xe(l) 23241030 9-diphenylthiophosphinoylanthracene 23241354 tyrosine 23243659 H(3)PO(4) 23243659 NH(4)F 23243659 Ni(OH)(2) 23243659 Ni(OH)2 23243659 NiF(2) 23243659 NiF2 23243659 nickel 23243660 H(2) 23243660 O–H 23243660 chromone 23243660 flavone 23243660 flavonoids 23243660 myricetin 23243660 naringenin 23243660 quercetin 23244178 aluminum oxide 23244178 amine 23244178 amines 23244178 aryl azide 23244178 aryl azides 23244178 aryl thiol 23244178 azides 23244178 diazirine 23244178 oligo(ethylene glycol) 23244178 phosphonic acids 23244178 primary amine 23244178 primary amines 23244178 thiols 23244521 ethanol 23245188 (Si-H)(2) 23245188 H 23245188 H(2)O(2) 23245188 O 23245188 OPD 23245188 Si 23245188 Silicon 23245188 o-phenylenediamine 23245188 oxygen 23245188 silicon 23245512 3-methylbutanoyl 23245512 acetyl 23245512 acetyl, propionyl and butanoyl esters 23245512 acyl 23245512 alkyne 23245512 azide 23245512 butanoyl 23245512 carbohydrate 23245512 copper 23245512 ester 23245512 glycopyranosyl azides 23245512 isovaleryl 23245512 mono-, di- and tri-acylated 23245512 pentanoyl 23245512 pentanoyl and 3-methylbutanoyl esters 23245512 propionyl 23245512 valeryl 23245514 PBI-18-Man 23245514 mannose 23245514 perylene 23245514 perylene bisimide 23245514 α-D-mannoses 23245697 Ribonucleotide 23245697 dNTPs 23245697 nucleotide 23245697 rNTP 23245697 ribonucleotide 23245697 ribonucleotides 23246428 Ergosta-4,6,8(14),22-tetraen-3-one 23246428 adenine 23246428 bile acid 23246428 ergone 23246428 ergosta-4,6,8(14),22-tetraen-3-one 23246436 C 23246531 KNT-127 23246531 SNC80 23246531 benzodiazepine 23246531 benzodiazepines 23246531 diazepam 23246531 ethanol 23246531 naltrindole 23246700 DEHA 23246700 DEHP 23246700 DiBP 23246700 DnBP 23246700 Phthalate 23246700 Phthalates 23246700 di-(2-ethylhexyl) adipate 23246700 di-2-ethylhexyl phthalate 23246700 di-isobutyl phthalate 23246700 di-isononyl phthalate 23246700 di-n-butyl phthalate 23246700 phthalate 23246700 phthalates 23246701 Curcumin 23246701 PFOS 23246701 Perfluorooctane sulfonate 23246701 curcumin 23246701 perfluorooctane sulfonate 23246701 polyphenolic 23246865 BIC 23246865 GABA 23246865 MUS 23246865 Pb 23246865 PbNO(3) 23246865 amino cupric silver 23246865 bicuculline 23246865 muscimol 23246865 γ-aminobutyric acid 23246867 IPA3 23246867 ML-141 23246867 PD0325901 23246867 glucose 23247009 Aldose 23247009 BGG 23247009 Beta-glucogallin 23247009 alcohol 23247009 aldehydes 23247009 aldose 23247009 sorbitol 23247010 BHA 23247010 anthracycline 23247010 butylated hydroxyanisole 23247010 carbonyl 23247010 isatin 23247010 monoamine 23247010 nucleotide 23247010 prostaglandins 23247040 α-Amino acid-N-carboxyanhydride 23247298 OH 23247298 serine 23247504 COOH 23247504 KCl 23247504 carbohydrate 23247504 ferrihydrite 23247504 iron oxide 23247504 maghemite 23247824 acetylcholine 23247824 dopamine 23247824 nicotine 23248173 glucose 23248196 Statin 23248196 Statins 23248196 atorvastatin 23248196 simvastatin 23248196 statin 23248196 statins 23248236 2-phenyl-1,2 benzisoselenazol-3(2H)-one 23248236 Ebselen 23248236 Ebsulfur 23248236 GSH 23248236 NADPH 23248236 benzisoselenazol 23248236 benzisothiazol 23248236 dithiol 23248236 ebselen 23248236 ebsulfur 23248236 glutathione 23248236 methicillin 23248236 sulfur 23249244 4-(dimethylamino)benzonitrile 23249244 DMABN 23249244 acetonitrile 23249244 dimethylamino 23249338 Zn(II) 23249338 [5,15-bis[4-(pyridyl)ethynyl]-10,20-diphenylporphinato]zinc(II) 23249338 [5,15-dipyridyl-10,20-bis(pentafluorophenyl)porphinato]zinc(II) 23249338 acetylene 23249338 chlorophylls 23249338 porphyrin 23249341 H(2)O 23249341 H(2)O(2) 23249341 NO(2) 23249341 OH 23249525 8-OH-DPAT 23249525 8-hydroxy-2-(di-n-propylamino) tetralin 23249525 Quinpirole 23249525 dopamine 23249525 quinpirole 23249525 serotonin 23249745 sparsomycin 23250357 Colesevelam 23250357 bile acid 23250357 glucose 23250357 metformin 23250541 Ca 23250541 Cr 23250541 Cr(III) 23250541 Cr3 23250541 Cr3 ([Cr(3)O(propionate)(6)(H(2)O)(3)](+)) 23250541 CrCl(3) 23250541 Cu 23250541 Fe 23250541 Mg 23250541 Zn 23250541 [Cr(pic)(3)] 23250541 chromium 23250541 chromium picolinate 23250541 fatty rats 23250811 2,4,6-trinitrobenzene sulfonic acid 23250811 Curcumin 23250811 curcumin 23250811 sulfasalazine 23252421 octylamine 23252481 Fe(III) 23252481 catharanthine 23252481 vinblastine 23252481 vindoline 23252610 4-Hydroxy-1-(3-pyridyl)-1-butanone 23252610 4-hydroxy-1-(3-pyridyl)-1-butanone 23252610 HPB 23252823 (1)H 23252823 1-decanol 23252823 1-pyrenesulfonyl 23252823 Pyrenyl 23252823 amino 23252823 glucono 23252823 hydrogen 23252823 methylene 23252823 naphthyl 23252823 pyrenyl 23252823 α,ω-diaminoalkane 23252848 MTS 23252848 withametelin L 23252848 withanolide 23252848 withanolides 23252848 withanolides 1-5 23252848 withawrightolide 23253441 oxadiazepines 23253441 oxadiazine 23253856 hydroxyurea 23254196 Ca(2+) 23254196 Genistein 23254196 Ser 23254196 Thr 23254196 cAMP 23254196 estrogen 23254196 genistein 23254196 nitric oxide 23255050 Fe 23255050 Gd 23255050 Iron oxide 23255050 acetylcholine 23255050 gadolinium 23255050 glutathione 23255050 iron 23255050 iron oxide 23255050 polyvinylpyrrolidone 23255284 L-dipeptides 23255284 Ser-His 23255284 carboxyl 23255284 dipeptide 23255284 dipeptide-mononucleotide 23255284 dipeptides 23255284 histidine 23255284 imidazole 23255284 nucleotide 23255284 phosphodiester 23255384 Coniothyrinones A (5), B (6), and D 23255384 anthraquinones 23255384 coniothyrinone C 23255384 coniothyrinones A (5), B (6), and D 23255384 coniothyrinones A-D 23255384 hydroxyanthraquinone 23255384 hydroxyanthraquinones 23255384 tetralone 23255471 C(3)N(4) 23255471 H(2) 23255471 H(2)O 23255471 Na 23255471 O(2) 23255471 SrTiO(3) 23255471 Tungsten carbide 23255471 W(2)C 23255471 WC 23255471 hydrogen 23255471 oxygen 23255471 platinum 23255471 tungsten 23255471 tungsten carbide 23255471 tungsten carbides 23256442 GSH 23256442 MDA 23256442 alanine 23256442 choline 23256442 malondialdehyde 23256442 methionine 23256442 reduced GSH 23256442 reduced glutathione 23256442 triglyceride 23256445 8-hydroxydeoxyguanosine 23256445 NADPH 23256445 TRG 23256445 Trigonelline 23256445 carbohydrate 23256445 glutathione 23256445 oxygen 23256445 thiobarbituric acid 23256445 trigonelline 23256446 cholesterol 23256446 glucose 23256446 triglycerides 23256510 F8BT 23256510 PFB 23256510 poly(9,9'-dioctylfluorene-co-benzothiadiazole 23256510 poly(9,9'-dioctylfluorene-co-bis-N,N'-(4-butylphenyl)-bis-N,N'-phenyl-1,4-phenylene-diamine 23256510 polyfluorene 23256609 Benzoic acid 23256609 benzoic acid 23256609 carboxylic acid 23256609 hydrogen 23256609 mono- and dihydrates 23256621 (hetero)functional poly(ethylene glycol)s 23256621 PEG 23256621 PEGs 23256621 Poly(ethylene glycol) 23256621 acetal 23256621 acetaldehyde acetal 23256621 amino 23256621 cholesterol 23256621 dibenzylamino ethanol 23256621 ethylene oxide 23256621 hydroxyl 23256621 mPEG 23256621 poly(ethylene glycol) 23256621 poly(ethylene glycol) monomethyl ether 23256621 poly(ethylene glycol)s 23256621 polyether 23256621 squaric acid ester amide 23256643 Mn 23256643 Mn(II) 23256643 acetyl acetonate 23256643 m-PyNO 23256643 manganese(II) diacetylacetonate and dihexafluoroacetylacetonate 23256643 pyridine 23256643 pyridine nitrogen 23256719 N-acetyl-L-cysteine 23256719 NAC 23256719 NO 23256719 Thiol 23256719 carbocysteine 23256719 corticosteroids 23256719 erdosteine 23256719 fudosteine 23256719 glutathione 23256719 superoxide 23256724 CO2 23256724 Clonazepam 23256724 clonazepam 23256724 serotonin 23256769 As(V) 23256769 Fe(III) 23256769 ferrihydrite 23256769 hematite 23256769 iron oxide 23256816 calcium 23256816 pentamidine 23256819 ((13)C)methyldodecanesulfonate 23256819 Amino Acids 23256819 amino 23256819 amino acids 23256819 cysteine 23256819 histidine 23256819 lysine 23256819 methionine 23258537 Magnesium 23258537 ferrous 23258537 potassium 23258537 ribonucleotides 23258671 W 23258671 beta-tungsten 23258671 nitrogen 23258671 tungsten 23258742 2,2',4,4',5-pentabromodiphenyl ether 23258742 BDE-99 23258742 DMSO 23258742 PBDE 23258742 PBDE-99 23258742 PBDEs 23258742 dimethylsulfoxide 23258742 polybrominated diphenyl ethers 23258773 Aroclors 1016 and 1254 23258773 PCB 23258773 PCBs 23258773 polychlorinated biphenyls 23258773 polyethylene 23259536 dihydroindolizine 23259536 dithienylethene 23259536 fullerene 23259536 porphyrin 23259536 quinoline 23259666 (D)-Ala-(D)-Ala 23259666 (D)-Ala-(D)-Lac 23259666 C 23259666 PAMAM 23259666 Vancomycin 23259666 iron oxide 23259666 poly(amidoamine) 23259666 vancomycin 23259742 ZrO(2) 23259742 carbon 23259742 oxygen 23259773 Si 23259773 carbon 23259773 platinum 23259773 silicon 23259865 camptothecin 23259865 indenoisoquinolines 23259866 PCHD 23259866 poly(1,3-cyclohexadiene) 23259866 poly(cyclohexadiene) 23259866 polybutadiene 23259866 polyisoprene 23259866 polystyrene 23259985 PLL 23259985 Polyplex 23259985 poly((L)-lysine) 23259985 polyplex 23259985 polyplexes 23260032 Asparagine 23260032 Bismuth 23260032 asparagine 23260032 bismuth 23260347 Diphenylphosphinic amides 23260347 diphenylphosphine oxides 23260347 diphenylphosphinic amides 23260347 potassium 23260352 Mannich base 23260352 amodiaquine 23260352 hydroxy-ethyl-amine 23261524 nutlin-3 23261527 prostaglandins 23261528 flavonoid 23261528 icariin 23261528 sodium 23261528 steroid 23261528 sulfate 23261588 BPA-f 23261588 Boron 23261588 Calcein-AM 23261588 MTT 23261588 Propidium Iodide 23261588 boronophenylalanine 23261588 calcein-AM 23261588 fructose 23261590 Neoechinulin A 23261590 PGE2 23261590 indole 23261590 neoechinulin A 23261590 nitric oxide 23261590 nitrogen 23261590 oxygen 23261590 prostaglandin E2 23261644 MMS 23261644 methylmethanesulphonate 23261645 Jaspamide 23261645 NSC-613009 23261645 cyclodepsipeptide 23261645 jaspamide 23261645 jasplakinolide 23261645 mitoxantrone 23261667 copper 23261676 (-) Epicatechin 23261676 (-) epicatechin 23261676 Isoproterenol 23261676 NADH 23261676 adenosine triphosphate 23261676 calcium 23261676 glutathione 23261676 hydroxyl 23261676 isocitrate 23261676 isoproterenol 23261676 malate 23261676 reduced glutathione 23261676 succinate 23261676 superoxide 23261676 tricarboxylic acid 23261676 α-ketoglutarate 23261705 rapamycin 23261715 4-oxo-2-nonenal 23261715 Cys 23261715 GSSG 23261715 NADPH 23261715 SH 23261715 aldehyde 23261715 aldose 23261715 amino acid 23261715 dithiothreitol 23261715 glutathione 23261715 glutathione disulfide 23261715 oxidized glutathione 23261715 p-chloromercuribenzoic acid 23261715 p-chloromercuriphenylsulfonic acid 23261820 TCS 23261820 Triclosan 23261820 estrogen 23261820 ethinyl estradiol 23261820 triclosan 23262162 DPPH 23262162 Resveratrol 23262162 Vitamin E 23262162 ethanol 23262162 polyamide 23262162 resveratrol 23262162 trolox 23262203 Gadolinium 23262203 HPMA 23262203 N-(2-hydroxypropyl)methacrylamide 23262279 2-hydroxy-4-[4-(5Z)-5-[(E)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]butanoylamino]benzoic acid 23262279 4-{(Z)-[(2Z)-2-(2-fluorobenzylidene)-4-oxo-1,3-thiazolidin-5-ylidene]methyl}benzoic acid 23262279 ML-145 23262390 Manganese 23262390 Mn 23262390 manganese 23263987 cAMP 23263987 cyclic AMP 23263987 glucose 23264030 Fluoxetine 23264030 fluoxetine 23264030 hydrochloride 23264030 serotonin 23264615 Cortisol 23264615 PF 915275 23264615 cortisol 23264615 hydroxysteroid 23264615 keto 23264615 meloxicam 23264615 progesterone 23264615 prostaglandins 23265282 Cys 23265282 N 23265282 α-thioester 23265282 α-thioesters 23265296 PGMA 23265296 POEGMA 23265296 amino 23265296 biotin 23265296 epoxide 23265296 poly(glycidyl methacrylate) 23265296 poly(oligo(ethylene glycol) methacrylate) 23265296 silicon 23265429 As 23265429 As(2)O(3) 23265429 Ga(l) 23265429 GaAs 23265429 as 23265429 gallium 23265452 Polyphenolic 23265452 apigenin 23265452 chrysin 23265452 flavonoid 23265452 flavonoids 23265452 galangin 23265452 gallic acid 23265452 p-Coumaric acid 23265452 phenolic acids 23265452 pinocembrin 23265456 polyphenols 23265458 ABTS(+) 23265458 ADP 23265462 6-O-caffeoylsophorose 23265462 Benzoic acid 23265462 caffeic acid 23265462 monocarboxylic acid 23265462 phloretin 23265462 quercetin 23265462 sophorose 23265462 sugar 23265467 As(V) 23265467 HCl 23265467 HFO 23265467 NaOH 23265467 arsenic 23265467 carboxyl 23265467 hydrated ferric oxide 23265467 hydrous ferric oxide 23265467 hydroxyl 23265469 CO(2) 23265469 fructosyl nystose 23265469 kestose 23265469 n-butane 23265469 nystose 23265469 propane 23265469 sucrose 23265483 Se 23265483 selenium 23265488 ser 23265491 alcohol 23265491 genistein-7-O-gentiobioside 23265491 glutathione 23265491 isoflavone 23265491 isoflavones 23265492 DEAE 23265492 arabinose 23265492 mannose 23265492 sulphate 23265501 Citric, malic, and ascorbic acids 23265501 Fructose 23265501 anthocyanins 23265501 gallic acid 23265501 glucose 23265501 sucrose 23265501 sugars 23265502 Ascorbic acid 23265502 Nitrate 23265502 ascorbic acid 23265502 nitrate 23265502 nitrite 23265502 vitamin C 23265504 DPPH 23265504 catechin 23265504 citric acid 23265504 fructose 23265504 malic acid 23265504 phenols 23265504 quercetin 23265504 sinapic acid 23265504 succinic acid 23265504 sucrose 23265504 sugar 23265504 β-carotene 23265504 ρ-coumaric acid 23265504 ρ-hydroxybenzoic acid 23265506 DPPH(·) 23265506 DPPH· 23265506 acetylcysteine 23265506 ascorbic acid 23265506 caffeic acid 23265506 catechin 23265506 chlorogenic acid 23265506 quercetin 23265507 TFA 23265507 Trans fatty acids 23265507 fatty acids 23265507 trans fatty acids 23265517 glutathione 23265517 malondialdehyde 23265517 streptozotocin 23265517 superoxide 23265526 Fe(2+) 23265529 ethyl acetate 23265529 formic acid 23265529 primary secondary amine 23265529 sodium sulphate 23265533 sodium 23265542 artemisia ketone 23265542 borneol 23265542 cis-chrysanthenyl acetate 23265542 germacrene B 23265546 lactones 23265843 Lucidone 23265843 cholesterol 23265843 glucose 23265843 lucidone 23265843 triglyceride 23265880 (123)I 23265880 (2-((2-((dimethylamino)methyl)-4-iodophenyl)thio)phenyl)methanol 23265880 FLIP-IDAM 23265880 [(125)I]-IDAM 23265880 [(125)I]Flip-IDAM 23265880 biphenylthiol 23265880 serotonin 23265892 4-Br 23265892 4-CF(3) 23265892 SCH 900229 23265892 arylsulfone 23265892 sulfone 23265892 tricyclic bispyran sulfone 23265896 5- and 6-methoxybenzimidazole-1,3,5-triazines 23265896 5- and 6-methoxysubstituted benzimidazole 23265896 5-methoxy 23265896 6-methoxy 23265896 ZSTK474 23265896 benzimidazole 23265899 C5-Ethynylbenzenesulfonamide-modified nucleotide 23265899 C5-ethynylbenzenesulfonamide-modified nucleotides 23265899 EBNA 23265899 nucleotide 23265899 nucleotides 23265901 8-oxoadenine 23265901 8-oxoadenines 23265901 DSR-6434 23265901 N 23265901 adenine 23265901 amino 23265901 tertiary amines 23265902 9-fluoro 23265902 SCH 900229 23265902 Selectfluor 23265902 difluoroquinone 23265902 quinone 23265902 sulfone 23265903 (E)-1-(2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl)-4-(3-hydroxyphenyl)but-3-en-2-one 23265903 C-cinnamoyl glycoside 23265903 C-cinnamoyl glycosides 23265903 phenol 23265904 5-carboxy-2-thiazole 23265904 CoA 23265904 amides 23265904 benzo-fused spirocyclic oxazepine 23265904 benzylic 23265904 glycine amides 23265904 nitrogen 23265904 oxazepine 23265904 piperidine 23265904 spirocyclic piperidine 23265904 stearoyl-CoA 23265904 stearoyl-coenzyme A 23265904 thiazoles 23266447 rhodamine 23266452 N-acetylgalactosamine 23266452 PCL-b-PPEEA 23266452 poly(ethylene glycol) 23266452 poly(ethylene glycol)-b-poly(ε-caprolactone) 23266452 poly(ε-caprolactone)-b-poly(2-aminoethyl ethylene phosphate) 23266453 polyethylene glycol 23266501 4',5,7-trihydroxyflavone 23266501 Apigenin 23266501 apigenin 23266501 oxygen 23266502 Carbamate 23266502 Urea 23266502 methomyl 23266674 2,3,7,8,-tetrachloro-dibenzo-p-dioxin 23266674 TCDD 23266674 androgen 23266674 aryl hydrocarbon 23266674 polyaromatic hydrocarbons 23266719 carbon 23266722 12-O-tetradecanoylphorbol-13-acetate 23266722 7,12-dimethylbenz[a]anthrancene 23266722 DMBA 23266722 TPA 23266722 phorbol ester 23266731 1,2,3,4,6-penta-O-galloyl-β-d-glucose 23266731 EtOH 23266731 MTT 23266731 PGG 23266731 catechin 23266731 epicatechin-(4β→8)-catechin 23266731 epicatechin-3-O-gallate 23266731 flavan-3-ols 23266731 paeonol 23266731 polyphenol 23266731 proanthocyanidin 23266731 trigalloyl-glucoses 23266732 6-keto prostaglandin F(1α) 23266732 6-keto-PGF(1α) 23266732 NO 23266732 TXB(2) 23266732 nitric oxide 23266732 thromboxane B(2) 23266737 Triterpenoid saponins 23266737 creatine 23266737 lactate 23266737 saponins 23266737 triterpenoid saponins 23267837 Cetrorelix 23267837 somatostatin 23267855 glucose 23267855 metformin 23267862 Ca(2+) 23267862 Mg(2+) 23268927 glucose 23270527 N-isopropylacrylamide 23270527 N-isopropylmethacrylamide 23270527 NIPAm 23270527 NIPMa 23270527 alkoxyamine 23270527 aminooxy 23270527 benzylalkoxyamine 23270527 carbohydrates 23270527 ketone 23270527 methacrylamide 23270527 oxime 23270527 poly(ethylene glycol) 23270527 pyridoxal-5'-phosphate 23270527 sugars 23270704 APO 23270704 Apocynin 23270704 H2O2 23270704 NADPH 23270704 apocynin 23270704 calcium 23270704 raisanberine 23270704 testosterone 23270993 KYNA 23270993 Kynurenic acid 23270993 acetylcholine 23270993 glutamate 23270993 tryptophan 23271737 acylsulfonamide 23271742 Arsenic 23271742 arsenic 23271742 arsenic trioxide 23273150 C=O 23273150 CH 23273150 CO 23273150 H 23273150 N-methylacetamide 23273150 NH 23273150 NMA 23273150 O 23273150 O H 23273150 amide 23273150 carbonyl 23273225 Porphyrin 23273225 porphyrin 23273225 tetrakis(3,5-di-t-butyl-4-hydroxyphenyl)porphyrin 23273225 tetrakis(4-pyridyl)porphyrin 23273412 2-iso-propyl-5-methyl-phenol 23273412 2-tert-butyl-5-methyl-phenol 23273412 5-iso-propyl-2-methyl-phenol 23273412 ABTS 23273412 DPPH 23273412 Schiff bases 23273412 Thymol 23273412 ascorbic acid 23273412 carvacrol 23273412 thymol 23274352 Co 23274352 Cu 23274352 Ni 23274352 Pb 23274353 O 23274353 PBDE 23274353 PBDEs 23274353 S 23274353 carbonyl 23274353 ethoxyresorufin 23274353 glutathione 23274353 peroxide 23274353 polybrominated diphenyl ethers 23274746 chlorogenic acids 23274746 flavonoids 23274768 ATP 23274768 Zinc 23274768 Zn 23274768 ZnSO4 23274768 lactate 23274768 zinc 23274768 zinc sulfate 23274903 glucose 23274903 oxygen 23274917 EMS 23274917 ethyl methane sulfonate 23274917 formalin 23275110 PHEA-IB-p(MANa(+)) 23275110 PHEA-graft-polymethacrylate 23275110 calcium 23275110 β-poly(N-2-hydroxyethyl)-graft-{N-2-ethylene[2-poly(methacrylic acid sodium salt)isobutyrate]}-d,l-aspartamide 23275111 DOX 23275111 Doxorubicin 23275111 PLA 23275111 PTX 23275111 lactide 23275111 paclitaxel 23275111 polyethylene glycol 23275111 polylactide 23275113 Fujicalin 23275113 Neusilin 23276135 Au 23276135 carbohydrate 23276161 aluminates 23276161 apatites 23276161 oxides 23276161 silicates 23276161 sulfates 23276627 1-meA 23276627 1-methyladenine 23276627 3-meC 23276627 3-methylcytosine 23276627 MMS 23276627 methyl methanesulfonate 23276627 nucleotides 23276633 17β-estradiol 23276633 DHT 23276633 Testosterone 23276633 dihydrotestosterone 23276633 testosterone 23277104 3,3',4,4',5-polychlorinated biphenyl 23277104 6-formylindolo[3,2-b]carbazole 23277104 Aroclor 1254 23277104 BNF 23277104 FICZ 23277104 PCB126 23277104 PCBs 23277104 aryl hydrocarbon 23277104 β-naphthoflavone 23277230 ABTS 23277230 DPPH 23277230 Fisetin 23277230 NO 23277230 STZ 23277230 bioflavonoid 23277230 fisetin 23277230 glucose 23277230 nitric oxide 23277230 streptozotocin 23278398 Cu 23278398 Trp 23278398 Zn 23278398 catecholamines 23278398 quinazoline 23278398 superoxide 23278633 H 23278633 N(3)-Substituted Xanthines 23278633 graphite 23278633 nucleobases 23278633 xanthine 23278633 xanthines 23279802 4-aminoquinazoline 23279841 ethanol 23279841 nitrate 23279841 nitrite 23279844 CCl4 23279844 alanine 23279844 aspartate 23279844 carbon tetrachloride 23279844 flavonoid 23279844 flavonoids 23279844 glutathione 23279844 malondialdehyde 23279844 superoxide 23279943 Al 23279943 Cu 23279943 Fe 23279943 GSH 23279943 MDA 23279943 Mn 23279943 Se 23279943 Zn 23279943 donepezil 23279943 glutathione 23279943 malondialdehyde 23279943 superoxide 23280101 PpIX 23280101 oxygen 23280101 protoporphyrin IX 23280620 Hg 23280620 mercury 23280766 organophosphate 23280766 pyrethroid 23280951 1-(2'-deoxy-β-D-threo-pentofuranosyl)thymidine 23280951 C3'-thymidinyl 23280958 hydrogen 23280958 hydroxyl hydrogen 23280958 methanol 23280997 CdSe 23280997 ZnS 23281069 Diaromatic-substituted ortho- and meta-carboranes 23281069 carboranes 23281069 diaryl-substituted carboranes 23281069 manassantin A 23281101 Butyltin(IV) benzoates 23281101 Organotin 23281101 di- and tri-n-butyltin(IV) carboxylates 23281101 di-n-butyltin(IV) 23281101 tin(IV) 23281242 Pt 23281242 Ru 23281242 pt 23281242 ru 23281242 silica 23281330 5-(hydroxymethyl)furfural 23281330 CH(2)Cl(2) 23281330 FeCl(3) 23281330 HMF 23281330 MMF 23281330 MeNO(2) 23281330 arene 23281330 carbohydrate 23281330 carbohydrates 23281330 chloromethylfurfural 23281330 ether 23281330 formate ester 23281330 formic acid 23281330 fructose 23281330 glucose 23281330 hydrogen chloride 23281330 hydroxyl 23281330 mesityl 23281330 mesitylene 23281330 mesitylmethylfurfural 23281330 p-TsOH 23281330 toluene 23281330 xylene 23281578 Glycofullerenes 23281578 carbohydrates 23281578 glycofullerenes 23281578 hexakis-adduct of [60]fullerene 23281578 mannoses 23281613 callicarpic acid 23281613 diterpenes 23281613 ent-3,4-seco-labdane 23281613 ent-3,4-seco-labdane diterpenoids 23281613 methylcallicarpate 23281636 ATP 23281636 GSK 3987 23281636 Paeoniflorin 23281636 cholesterol 23281636 paeoniflorin 23281847 hydrogen 23281917 Brij-35 23281917 Span-80 23281917 Span-83 23281917 acyclovir 23281937 (11)B 23281937 (31)P 23281937 11B 23281937 31P 23281937 B 23281937 Na(+) 23281937 Na(2)O 23281937 Na2O 23281937 P 23281937 P-O-B 23281937 [xB(2)O(3) + (1 - x)P(2)O(5)] 23281937 [xB2O3 + (1 - x)P2O5] 23281937 boron 23281937 oxygens 23281937 phosphorus 23281937 sodium 23281937 sodium borate 23281937 sodium borophosphate 23281937 sodium phosphate 23282017 Indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] 23282017 KP1019 23282017 KP1339 23282017 carbonate 23282017 citrate 23282017 glutathione 23282017 indazolium trans-[Tetrachlorobis(1H-indazole)ruthenate(III)] 23282017 ruthenium 23282017 sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] 23282066 MDZ 23282066 TRZ 23282066 midazolam 23282066 triazolam 23282101 (Xylyl-phanephos)Pt(2+) 23282101 P(2)Pt-alkyl 23282101 XeF(2) 23282101 olefin 23282101 polyene 23282101 polyenes 23282576 metal-oxide 23282999 Al 23282999 Zinc sulphate 23282999 aluminium 23282999 aluminium sulphate 23282999 cholesterol 23282999 testosterone 23282999 vitamin E 23282999 zinc sulphate 23284002 DPI 23284002 GSH 23284002 H(2)O(2) 23284002 N-acetyl-cysteine 23284002 NAC 23284002 NAD(P)H 23284002 TSA 23284002 Trichostatin A 23284002 diphenyleneiodonium 23284002 glutathione 23284002 oxygen 23284002 sulforaphane 23284082 Amide 23284082 amide 23284082 bis-sulfonamide 23284082 creatinine 23284082 prostaglandin E 23284082 urea 23286198 CTAB 23286198 NaOL 23286198 hexadecyltrimethylammonium bromide 23286198 sodium oleate 23286240 chloroquine 23286240 dimeric phloroglucinols 23286240 ethanol 23286240 mallotojaponins B (1) and C (2) 23286240 mallotophenone 23287045 Copper 23287045 Cu 23287045 Cu salts 23287045 CuO 23287045 CuSO4 23287045 copper (II) oxide 23287045 copper salts 23287045 copper sulfate 23287045 oxygen 23287045 transition metal 23287056 N-alkylcarbazole 23287056 carbazoles 23287056 tyrosine 23287389 PBDEs 23287389 PCBs 23287389 PFHxS 23287389 PFOA 23287389 PFOS 23287389 Perfluoroalkyl acids 23287389 bisphenol A 23287389 nicotine 23287389 perfluoroalkyl acid 23287389 perfluoroalkyl acids 23287389 perfluorohexane sulfonate 23287538 amphetamine 23287538 ethanol 23287538 sucrose 23287700 AM4054 23287700 AM4113 23287700 Cannabinoid 23287700 SR141716A 23287700 rimonabant 23287700 Δ(9)-tetrahydrocannabinol 23287710 acrylamide 23287710 glycidamide 23287728 L-Leu 23287728 L-amino acid 23287728 amino-acid 23288049 2,2',4,4'-tetrabromodiphenyl ether 23288049 2,2',4,5'-tetrabromodiphenyl ether 23288049 BDE-47 23288049 BDE-49 23288049 Br 23288049 PBDE 23288049 PBDEs 23288049 Polybrominated diphenyl ethers 23288052 CCl(4) 23288052 DEN 23288052 carbon tetrachloride 23288052 diethylnitrosamine 23288091 carbamazepine 23288091 clobazam 23288091 clonazepam 23288091 eslicarbazepine acetate 23288091 ethosuximide 23288091 felbamate 23288091 gabapentin 23288091 lacosamide 23288091 lamotrigine 23288091 levetiracetam 23288091 oxcarbazepine 23288091 phenobarbital 23288091 phenytoin 23288091 pregabalin 23288091 primidone 23288091 retigabine 23288091 rufinamide 23288091 stiripentol 23288091 tiagabine 23288091 topiramate 23288091 valproic acid 23288091 vigabatrin 23288091 zonisamide 23288103 Si 23288103 Sn 23288103 Ti 23288103 hematite 23288103 oxygen 23288103 α-Fe(2)O(3) 23288866 aminobenzotriazole 23288866 loperamide 23289403 PLL 23289403 poly(l-lysine) 23289403 vinylbenzyl 23289412 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole 23289412 carbon 23289412 nitrogen 23289412 triazoles 23289585 2'-deoxyadenosine-5'-monophosphate 23289585 2'-deoxycytidine-5'-monophosphate 23289585 2'-deoxyguanosine-5'-monophosphate 23289585 2'-deoxymononucleotides 23289585 T5'p 23289585 dA5'p 23289585 dC5'p 23289585 dG5'p 23289585 mononucleotides 23289585 nucleobase 23289585 phosphate ester 23289585 ribose 23289585 thymidine-5'-monophosphate 23289615 2-propanol 23289615 alcohol 23289624 amide 23289646 poly(ethylene glycol) 23289710 Sec 23289710 Ser 23289710 [(14)C]dimethylallyl pyrophosphate 23289710 amino acid 23289710 dimethylallyl 23289710 isopentenyl 23289710 selenocysteine 23289872 (1)H 23289872 (15)N 23289872 (19)F 23289872 CF(3) 23289872 CF3 23289872 F-C 23289872 FF 23289872 FH 23289872 FN 23289872 N-H 23289872 NH 23289872 fluorine 23289872 hydrogen 23290050 (1)H 23290050 (13)C 23290050 indole 23290050 indoxyl red 23290050 silica 23290262 Alkyladenine 23290262 MMS 23290262 methyl methanesulfonate 23290724 C 23290724 N 23290724 Zinc 23290724 Zn²⁺ 23290724 copper 23290724 zinc 23291118 5- and 8-methoxypsoralen 23291118 8-MOP 23291118 MOP 23291118 MOPs 23291118 N-bromosaccharin 23291118 acrylate 23291118 benzoate 23291118 butyl acrylate 23291118 cinnamate 23291118 indomethacin 23291118 methoxypsoralen 23291118 psoralen 23291118 tert-butyl cinnamate 23291264 cis-diamminedichloroplatinum II 23291264 cisplatin 23291264 creatinine 23291264 nitrogen 23291264 urea 23292343 amino acid 23292343 amino acids 23292343 ribulose-1, 5-bisphosphate 23292752 Dabigatran 23292752 Dabigatran etexilate 23292752 apixaban 23292752 argatroban 23292752 dabigatran 23292752 dabigatran etexilate 23292752 rivaroxaban 23292752 vitamin K 23292753 Sugar 23292753 alkyne 23292753 azide 23292753 cyclopropene 23292753 mannosamine 23292753 mannosamines 23292753 methylcyclopropenes 23292753 sugars 23292753 tetrazine 23292768 C 23292768 C-OH 23292768 CD 23292768 CH2OH 23292768 C≡C-H 23292768 D 23292768 H-O 23292768 O-H 23292768 OD 23292768 OH 23292768 methanol 23292768 propargyl alcohol 23292797 5-HT 23292797 5-hydroxytryptamine 23292797 [(35)S]guanosine 5'-(3-O-thio)triphosphate 23292797 adenylyl 23292797 cAMP 23292881 aluminum 23292881 zeolite 23292881 zeolites 23292988 LaFeO3 23292988 Sm2 CuO4 23292988 Sm2CuO4 23293000 phosphate 23293000 sugar 23293094 PCB 23293094 polychlorinated biphenyl 23293950 pyrene 23293962 iron 23293966 graphene 23293966 peroxide 23293966 quarteranthene 23293970 O₃ 23293970 dopamine 23293970 ozone 23293970 superoxide 23293971 NiO 23293971 nickel oxide 23294326 ganglioside 23294566 Androgen 23294566 Androgens 23294566 androgen 23294566 androgens 23294566 oestradiol 23294566 oestrogen 23294566 oestrogens 23294699 Pentacyclic hemiacetal sterol 23294699 acetyl 23294699 nephthoacetal 23294699 pentacyclic hemiacetal sterol 23294699 sterol 23294895 Aspirin 23294895 aspirin 23295156 L-Carnitine 23295156 NADPH 23295156 fatty acids 23295156 l-Carnitine 23295156 l-NAME 23295223 3,17β-Hydroxysteroid 23295223 3,17β-hydroxysteroid 23295223 carbon 23295223 cholesterol 23295223 estradiol 23295223 polycyclic aromatic hydrocarbons 23295223 steroid 23295223 steroids 23295223 testosterone 23295224 2,3-butanediol 23295224 NADPH 23295224 acetoin 23295224 alpha-hydroxy ketones 23295224 diketones 23295224 diols 23295224 glucose-6-phosphate 23295224 keto 23295224 vicinal diketones 23295224 vicinal diols 23295224 α-hydroxy ketones 23295229 Aldehyde 23295229 Mg(2+) 23295229 NAD(+) 23295229 NADH 23295229 aldehyde 23295229 aldehydes 23295229 butyraldehyde 23295229 carboxylic acids 23295229 magnesium 23295582 HCl 23295582 TBF 23295582 Terbinafine 23295582 Terbinafine hydrochloride 23295582 poloxamer gel 23295739 Methylprednisolone 23295739 corticosterone 23295739 methylprednisolone 23295740 TAM 23295740 Tamoxifen 23295740 estrogen 23295740 tamoxifen 23295740 zinc 23296019 GDP 23296019 GTP 23296100 GSH 23296100 Manganese 23296100 Mn 23296100 Mn(2+) 23296100 N-acetylcysteine 23296100 NAC 23296100 glutathione 23296100 propidium iodide 23296100 thymine 23296102 Acrolein 23296102 malondialdehyde 23296102 superoxide 23296105 UO₂ 23296105 Uranium 23296105 uranium 23296122 magnesium 23296122 magnesium and zinc porphyrins 23296122 metalloporphyrins 23296122 zinc 23296156 chromium-51 23296368 3-MGA 23296368 3-methylglutaconic 23296368 3-methylglutaconic aci 23296368 3-methylglutaconic acid 23296368 3-methylglutaconyl-CoA 23296368 leucine 23296837 EHT 23296837 MPP(+) 23296837 MPTP 23296837 dopamine 23296837 eicosanoyl-5-hydroxytryptamide 23296837 nitric oxide 23296837 tyrosine 23296902 Cr 23296902 chromium 23296902 glucose 23296902 graphite 23296902 iron 23296950 ACh 23296950 Chrysin 23296950 KCl 23296950 Luteolin 23296950 NO 23296950 STZ 23296950 TGs 23296950 acetylcholine 23296950 cholesterol 23296950 chrysin 23296950 flavonoids 23296950 glucose 23296950 luteolin 23296950 phenylephrine 23296950 streptozotocin 23296950 triglycerides 23296979 ATP 23296979 Ca(2+) 23296979 EATN 23296979 Erythro-(7S,8R)-7-acetoxy-3,4,3`,5`-tetramethoxy-8-O-4`-neolignan 23296979 arachidonic acid 23296979 cAMP 23296979 cyclic AMP 23296979 erythro-(7S,8R)-7-acetoxy-3,4,3`,5`-tetramethoxy-8-O-4`-neolignan 23296979 neolignan 23296979 serotonin 23296979 thromboxane B(2) 23297346 3-mercaptopyruvate 23297346 H(2)S 23297346 Hydrogen sulfide 23297346 carbon monoxide 23297346 cystathionine 23297346 nitric oxide 23297689 sabinene 23297712 cubecol-1-epi 23297712 dexamethasone 23297712 hinesol 23297712 ledol 23297712 muurola-3,5-diene 23297712 sesquiterpenes 23297712 silphiperfol-5-en-3-ol 23297712 z-caryophyllene 23297712 β-maaliene 23297712 γ-gurjunene 23297713 acetic acid 23297713 carbon dioxide 23297713 hydroxyproline 23297755 1α-hydroxy-3βH-3α,4α-epoxy-4,10-dimethyl-5αH,7αH,8βH,10αH-guai-11(13)-ene-7,8-olide 23297755 1αH-4α-hydroxy-4,10-dimethyl-5αH,7αH,8βH,10αH-guai-11(13)-ene-7,8-olide 23297755 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide 23297755 CH(2)Cl(2) 23297755 EFV 23297755 Efavirenz 23297755 cis-fused guaianolides 23297755 sesquiterpene lactone 23297755 sesquiterpene lactones 23297817 1/2O(2) 23297817 Au 23297817 Au(0.75)Pd(0.25) 23297817 Au(0.80)Pd(0.20) 23297817 Au(0.80)Pd(0.20)-Fe(x)O(y) 23297817 CO 23297817 CO(2) 23297817 Fe(x)O(y) 23297817 Pd 23297817 alumina 23297817 metal oxide 23298140 flavonoids 23298140 free amino acids 23298140 fructosamine 23298140 fructose 23298140 glucose 23298140 hydrogen peroxide 23298140 methylglyoxal 23298140 peroxide 23298140 polyphenols 23298140 sugars 23298158 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane 23298158 Alumina 23298158 F4-TCNQ 23298158 F4-TNCQ 23298158 Fluorinated Tetracyanoquinodimethane 23298158 P3HT 23298158 Poly(3-hexylthiophene) 23298158 aluminum oxide 23298158 poly(3-hexylthiophene) 23298322 2-(dimethylamino)ethyl acrylate 23298322 DMAEA 23298322 acrylic acid 23298810 PF-04693627 23298810 benzoxazole 23298810 benzoxazoles 23298810 cyclohexane 23298810 prostaglandin E(2) 23299191 dimethylarginine 23299191 sodium chloride 23299194 hydroxyproline 23299194 nitrofurazone 23299909 N 23300000 Ce(3+) 23300000 La(3+) 23300000 Nd(3+) 23300000 ammonia 23300000 flavonoid 23300000 phenylalanine 23300000 superoxide 23300056 arylpiperazine 23300056 arylpiperazines 23300056 dopamine 23300227 Morphine 23300227 TRV130 23300227 [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethyl})amine 23300227 morphine 23300338 Lys 23300338 rapamycin 23301246 FTO 23301246 NiO 23301246 fluorine 23301246 iodide 23301246 nickel oxide 23301246 tin oxide 23301246 triiodide 23301495 3-mercaptopyruvate 23301495 Cyanide 23301495 cyanide 23301495 dithiane 23301495 sulfanegen 23301495 triethanolamine 23301701 1,3-dimethylimidazolium dimethylphosphate 23301701 1-butyl-3-methylimidazolium chloride 23301701 1-ethyl-3-methylimidazolium acetate 23301701 [bmim]Cl 23301701 [dmim][DMP] 23301701 [emim][Ac] 23301701 hydrogen 23301701 imidazolium 23301853 BTH-II0204-207:A 23301853 Benzoquinones 23301853 benzoquinones 23301853 betulinan A 23301853 betulinan C 23301853 terphenyl 23301948 amide 23302583 7-mercaptocoumarin 23302583 phenylpiperazine 23302583 prazosin 23302594 4-pyridone 23302594 Himeic acids E-G 23302594 himeic acid A 23302594 himeic acids E-G 23303191 GlcNAc 23303191 Glucose 23303191 N-acetyl glucosamine 23303191 N-acetylglucosamine 23303191 N-acetylhexosamines 23303191 UDP 23303191 glucosamine 23303191 glucuronic acid 23303191 sugar 23303191 sugars 23303198 glucose 23303198 olmesartan 23303198 telmisartan 23303441 ATP 23303441 Paroxetine 23303441 [(3)H]paroxetine 23303441 paroxetine 23303441 sulfate 23303486 amide 23303486 biotin 23303486 thioether 23303710 Myriaporone 3/4 23303710 myriaporone 3/4 23305110 LaAlO(3) 23305110 LaAlO3 23305110 Si 23305110 SrTiO(3) 23305110 SrTiO3 23305294 Li(3)PS(4) 23305294 Lithium 23305294 lithium 23305444 6-Hydroxy-benzofuran-5-carboxylic acid 23305444 benzofuran salicylic acid 23305444 salicylic acid 23305444 tyrosine 23305465 6a,7,8,9,10,10a-hexahydro-3,6,9-trimethyl-6-(4-methyl-3-penten-1-yl)-1,9-epoxy-6H-dibenzo[b,d]pyran 23305465 Albatrelin F 23305465 Confluentin 23305465 Meroterpenoid 23305465 albatrelins A-C 23305465 albatrelins D-F 23305465 confluentin 23305465 grifolin 23305465 meroterpenoid 23305777 3'-methoxymiliumollin 23305777 4'-O-methylmiliumollin 23305777 7-methoxymiliumollin 23305777 8-O-4' neolignan 23305777 Miliumollin 23305777 Miliumollinone 23305777 Neolignans 23305777 dihydrobenzofuran neolignans 23305777 miliumollin 23305777 miliumollinone 23305777 miliusamollin 23305807 Estrogens 23305807 RES 23305807 S 23305807 alanine 23305807 bile acid 23305807 bilirubin 23305807 estrogen 23305807 ethinylestradiol 23305807 glutamyl 23305807 glutathione 23305807 malondialdehyde 23305807 nitric oxide 23305807 resveratrol 23305807 sulfhydryl 23305807 superoxide 23305918 ma'edamines 23305918 ma'edamines A (18) and B 23305918 ma'edamines A and B 23305918 pyrazine-2-(1H)-one 23305993 (5Z)-5-[(5-bromo-1H-indol-3-yl)methylene]-3-(4-chlorobenzyl)-thiazolidine-2,4-dione 23305993 GW9962 23305993 LYSO-07 23305993 LYSO-7 23305993 NO 23305993 nitric oxide 23306171 diterpenes 23306171 diterpenoid 23306171 leptoclalin A 23306171 norcembranoid 23306171 spatane 23306172 2-hydroxy-5-((6-hydroxy-4-oxo-4H-pyran-2-yl)methyl)-2- propylchroman-4-one 23306172 2-hydroxy-γ-pyrone 23306172 4-hydroxy-α-pyrone 23306172 CD(3)OD 23306172 deuterium 23306172 hydroxypyrone 23306172 methicillin 23306790 MG132 23306790 N-acetyl-l-cysteine 23306790 Verrucarin A 23306790 glutathione 23306790 verrucarin A 23306791 PEG-PVA 23306791 Polyethylene glycol 23306791 polyvinyl alcohol 23307185 serine 23307185 threonine 23307790 glucose 23311296 carbon 23311700 RAI 23311718 (1)H 23311718 [C(2)mim][TF(2)N] 23311718 [C(4)mim][AOT] 23311718 [C(4)mim][BF(4)] 23311718 [C(4)mim][PF(6)] 23311718 [C(4)mim][TF(2)N] 23311718 [C(6)mim][TF(2)N] 23311718 benzene 23311754 MnO(2) 23311754 MnO2 23311754 PEDOT 23311754 V(2)O(5) 23311754 V2O5 23311754 lithium 23311754 poly(3,4-ethylenedioxythiophene) 23311754 vanadium pentoxide 23312946 4-hydroxyisoquinoline 23312946 6-hydroxyisoquinoline 23312946 flavin 23312946 hydroxyl 23312946 isoquinolines 23312946 monocillin II 23313176 carbon 23313176 dendrimers 23313245 diaryl ureas 23313376 AG490 23313376 PTE 23313376 Pterostilbene 23313376 Tyr 23313376 oxygen 23313376 resveratrol 23313448 ADP 23313448 amino acids 23313621 1-nitro-2-phenylethane 23313621 BaCl(2) 23313621 Ca(2+) 23313621 CaCl(2) 23313621 K(+) 23313621 KCl 23313621 PHE 23313621 caffeine 23313621 phenylephrine 23313621 phorbol dibutyrate 23313638 D-alanine 23313638 D-leucine-D-cysteine 23313638 D-valine 23313638 D-valine-D-cysteine 23313638 FK228 23313638 amide 23313638 romidepsin 23313638 spiruchostatins A-D 23313638 spiruchostatins C and D 23313639 2,3,4-trimethoxy-6-(1-phenylvinyl)biphenyls 23313639 3,4-(1,3-dioxolane) 23313639 3,4-difluoro 23313639 4,5,6-trimethoxybiphenyl-2-carbaldehydes 23313639 E-2,3,4-trimethoxy-6-styrylbiphenyls 23313639 biaryl aryl stilbenes 23313639 colchicine 23313639 ethylenes 23313712 PHMB 23313712 neutral red 23313712 phosphatidylcholine 23313712 polyhexamethylene biguanide hydrochloride 23313797 5'-adenosine monophosphate 23313797 EtOH 23313797 Hoechst 33342 23313797 Res 23313797 dUTP 23313797 ethanol 23313797 glutathione 23313797 malondialdehyde 23313797 nicotinamide 23313797 nitrite 23313797 oxygen 23313797 resveratrol 23313797 superoxide 23313961 PCL 23313961 PEG 23313961 Triamcinolone acetonide 23313961 benzyl alcohol 23313961 folate 23313961 poly(ethylene glycol) 23313961 polycaprolactone 23313961 triamcinolone 23313962 (14)C-temoporfin 23313962 PEG2000-DSPE 23313962 cholesterol 23313962 glycerols 23313962 temoporfin 23314045 Gly 23314045 Pro 23314045 benzisoxazole 23314045 bromine 23314045 glycine 23314045 methoxy 23314045 proline 23314045 rutin 23314045 thiourea 23314045 urea 23314276 17β-trenbolone 23314276 androgen 23314276 androgens 23314277 S 23314277 TiSiO(4) 23314277 alanine 23314277 glutathione 23314277 lactate 23314277 titanium silicate 23314331 Copper 23314331 Cu 23314757 AgInS(2) 23314757 COOH 23314757 ZnS 23314757 amine 23314757 carboxyl 23314757 folate 23314757 hydroxyl 23314757 thiol 23315090 cholesterol 23315090 triglyceride 23315216 pentose phosphate 23315496 ATP 23315496 oATP 23315496 rapamycin 23315585 DomA 23315585 Domoic acid 23315585 GSH 23315585 cysteine 23315585 domoic acid 23315585 glutamate 23315585 glutathione 23315585 kainate 23315585 α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid 23315601 Glucose 23315601 glucose 23315683 C60 23315683 ICBA 23315683 InP 23315683 N 23315683 P3HT 23315683 bisadduct 23315683 carbon 23315683 indene 23315683 poly(3-hexylthiophene) 23315791 (1)H 23315791 (R,R)-G(2)DPENBoc 23315791 N-Boc-protected 1,2-diphenylethylenediamine 23315791 hydrogen 23315791 poly(benzyl ether) 23315938 acyl carnitines 23315938 amino acid 23315938 amino acids 23315938 fatty acid 23315938 glucose 23315938 steroid 23315996 Pd 23315996 hydrogen peroxide 23316021 Fluorescein 23316021 Gadolinium 23316021 Gd-F-βCD 23316021 TiO2 23316021 gadolinium(III) 23316021 rhodamine 23316021 titanium dioxide 23316021 β-cyclodextrin 23316913 BSO 23316913 BaSnO₃ 23316913 OH 23316913 TiCl₄ 23316913 TiO₂ 23316913 oxides 23316913 perovskite 23316965 doxycycline 23316966 doxycycline 23317100 FITC 23317100 MTT 23317100 SZ-685C 23317159 ATP 23317159 CEP701 23317159 LY2784544 23317159 Ruxolitinib 23317159 SAR302503 23317159 SB1518 23317159 TG101348 23317159 tasocitinib 23317159 tyrosine 23317163 acetylcholine 23317450 2,2,6,6-tetramethylpiperidine-N-oxyl 23317450 Cu 23317450 Cu(2)O(2) 23317450 Cu(I) 23317450 Cu(II) 23317450 H 23317450 N-methylimidazole 23317450 NMI 23317450 O(2) 23317450 TEMPO 23317450 alcohol 23317450 alcohols 23317450 aliphatic alcohols 23317450 alkoxide 23317450 benzylic alcohols 23317450 benzylic and aliphatic alcohols 23317450 copper(I) 23317450 nitroxyl 23317497 Pyrroloquinoxalines 23317497 pyrroloquinoxalines 23317498 nucleoside 23317498 nucleosides 23317572 isoflavonoid rotenone 23317572 rotenoisins A 23317572 rotenone 23318226 APO 23318226 ATP 23318226 DPI 23318226 Gö6983 23318226 N-acetyl-l-cysteine 23318226 NAC 23318226 NADPH 23318226 PGE(2) 23318226 PGE2 23318226 Ro-318220 23318226 Rottlerin 23318226 apocynin 23318226 diphenyleneiodonium chloride 23318226 nucleotides 23318425 acetyl 23318425 lysine 23318445 oxygen 23318445 superoxide 23318645 iodine 23318729 Isotretinoin 23318729 isotretinoin 23318729 retinoic acid 23318729 retinoids 23318730 Platinum folate 23318730 folic acid 23318730 platinum 23318730 platinum folate 23318905 (2,5-dihydroxyphenyl)(5-hydroxy-1-benzofuran-3-yl)methanone 23318905 Asn 23318905 H 23318905 Ile 23318905 NAD(+) 23318905 Phe 23318905 benzofuran-3-yl(phenyl)methanone 23318905 benzofuran-3-yl(phenyl)methanones 23318905 hydroxyl 23318905 hydroxyls 23318905 nicotinamide 23318905 phenyl 23319584 Ca(2+) 23319584 Calcium 23319584 nucleotide 23319591 lysine 23320385 1-chloro-2,4-dinitrobenzene 23320385 Anthocyanidins 23320385 Anthocyanins 23320385 Cyanidin 23320385 Delphinidin 23320385 S 23320385 UDP 23320385 anthocyanidins 23320385 carbonyl 23320385 cyanidin 23320385 delphinidin 23320385 flavonoids 23320385 glutathione 23320385 malvidin 23320385 menadione 23320385 p-nitrophenol 23320385 pelargonidin 23320412 sulfate 23320521 Dideoxy bicyclic pyrimidine nucleoside 23320521 cidofovir 23320521 ddBCNAs 23320521 ether 23320521 l-dideoxy bicyclic nucleoside 23320521 n-C(9)H(18)-O-n-C(5)H(11) 23320931 catechol 23320931 europium 23320931 isophthalic acid 23320931 lanthanide 23320931 terbium 23320940 PDT 23320940 perdeuterated tempone 23321054 5-HT 23321054 5-Hydroxytryptamine 23321054 AVE8488 23321054 Eplivanserin 23321054 Volinanserin 23321054 eplivanserin 23321054 volinanserin 23321054 zolpidem 23321916 DmCc(+) 23321916 DmCc(+/0) 23321916 DmFc 23321916 DmFc(0/+) 23321916 cobaltocenium 23321916 decamethylcobaltocenium 23321916 decamethylferrocene 23321916 ferrocene 23321916 permethylated transition-metal 23322164 Acylcarnitines 23322164 Carnitine 23322164 acyl-CoA 23322164 acyl-CoAs 23322164 acylcarnitine 23322164 acylcarnitines 23322164 carnitine 23322164 decanoic acid 23322164 fatty acid 23322164 octanoylcarnitine 23322347 Ca(++) 23322347 calcium 23322347 iron 23322508 Copper 23322508 copper 23322559 cimicifugolides A-C 23322559 monoterpene lactones 23322648 1-O-Hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-α-D-glucopyranosyl)-sn-glycerol 23322648 1-O-hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol 23322648 O 23322648 amino 23322648 azide 23322648 glucosamine 23322648 glycero 23322648 guanidino 23322648 thioglycosidic 23322709 CO 23322709 alkyl formates 23322709 carbon monoxide 23322709 esters 23322709 formates 23322709 olefins 23322709 palladium 23323677 (1)H 23323677 (13)C 23323677 2-methoxy-4-methylphenol 23323677 CO2 23323677 N2 23323677 acetaldehyde 23323677 alkylated creosols 23323677 bis(cyanate) esters 23323677 bisphenols 23323677 creosol 23323677 cyanate esters 23323677 formaldehyde 23323677 isocyanic acid 23323677 methylene 23323677 phenol 23323677 phenols 23323677 propionaldehyde 23323680 Li 23323680 Li-Si 23323680 Si 23323680 Si-Si 23323680 silicon 23323691 aldose 23323691 carboxylic acids 23323763 9α-epi-tuberospironine 23323763 pyrrolo[1,2-α]azepine 23323763 tuberostemonoxirine 23323829 9,10-bis[4-(3-sulfonatopropoxyl)-styryl]anthracene sodium salt 23323829 BSPSA 23323829 anthracene 23323829 guanidine hydrochloride 23323854 1,2-dioleoyl-3-timethylammonium propane 23323854 1,2-dioleoyl-sn-glycerol-3-phosphocholine 23323854 3β-{N-[(N',N'-dimethylamino)ethyl]carbamoyl}cholesterol 23323854 C=O 23323854 DC-Ch 23323854 DOPC 23323854 DOTAP 23323854 PO(2)(-) 23323854 adenine 23323854 carbonyl 23323854 cytosine 23323854 guanine 23323854 phosphate 23323987 acerifolin A 23323987 acerifolin B 23323987 cisplantin 23323987 diterpenoid 23323987 diterpenoids 23323987 isopimarane 23323987 tigliane 23324400 LEVOTHYROXINE 23324400 LT4 23324400 levothyroxine 23324437 Acarbose 23324437 Glucose 23324437 Nateglinide 23324437 Natelinide 23324437 glucose 23325046 DPPH 23325046 hexane 23325046 oxygen 23325046 α,α-diphenyl-β-picrylhydrazyl 23325050 PEG-OPOCl(2) 23325050 aromatic aldehydes 23325050 bis(indolyl) methanes 23325050 bisindolylmethanes 23325050 dichlorophosphate 23325050 indole 23325373 Fructose 23325373 fructose 23325373 glucose 23325486 Glu 23325486 Thr 23325486 Tyr 23325486 amino acid 23325489 3,5-di-O-caffeoylquinic acid 23325489 Linarin 23325489 PTZ 23325489 acacetin 23325489 acacetin 7-O-β-D-glucopyranosyl-(1 → 2)[α-L-rhamnopyranosyl-(1 → 6)]-β-D-glucopyranoside 23325489 chlorogenic acid 23325489 flavone glycoside 23325489 linarin 23325489 pentobarbital 23325489 pentylenetetrazole 23325492 citrate 23325492 silver 23325530 DCF 23325530 Diclofenac 23325631 3-nitrophenylacetic acid 23325631 CO(2) 23325631 bicarbonate 23327112 Coumarins 23327112 clauexcavatins A (1) and B (2) 23327112 coumarins 23327360 TiO(2) 23327360 amino acid 23327360 amino acids 23327360 phosphoryl 23327360 quartz 23327360 titanium dioxide 23327494 catechin 23327494 epigallocatechin 23327494 flavanols 23327494 speciophylline 23327494 uncarine E 23327494 uncarine F 23327532 4-nitrophenol 23327532 4-vinylphenol 23327532 Styrene 23327532 Styrene glycol 23327532 Styrene oxide 23327532 styrene 23327534 germacrene B 23327534 globulol 23327534 viridiflorene 23327534 α-cadinol 23327534 τ-cadinol 23327557 (-)-epicatechin 23327557 Procyanidins 23327557 galacturonic acid 23327557 procyanidin 23327557 procyanidins 23327580 doxorubicin 23327668 abietane 23327668 diterpenoids 23327668 ent-kaurane 23327668 ent-kauranoids 23327668 isoabietenins A-C 23327668 nitric oxide 23327668 tenuifolins A-M 23327794 7'-(3',4'-dihydroxyphenyl)-N-[4-methoxyphenyl)ethyl]propenamide 23327794 acetylcholine 23327794 chloroform 23327794 liriodenine 23327794 microcosamine A 23327794 microgrewiapine A 23327794 microgrewiapine A 3-acetate 23327794 microgrewiapines A-C 23327794 piperidine alkaloids 23327993 AD4 23327993 AuF 23327993 NAC 23327993 NAc-Cys-Pro-Cys amide 23327993 ascorbic acid 23327993 auranofin 23327993 disulfide 23328072 1,25(OH)₂D3 23328072 1,25(OH)₂D₃ 23328072 1,25-dihydroxyvitamin D₃ 23328072 vitamin D 23328072 vitamin D₃ 23328126 Omega-3 Fatty acids 23328126 Omega-3-Acid Ethyl Esters 23328126 ω-3 fatty acid 23328126 ω-3 fatty acids 23328252 17-β estradiol 23328252 2,4-Dihydroxybenzophenone 23328252 BP-1 23328252 Benzophenone-1 23328252 ICI 182,780 23328252 benzophenone-1 23328252 estrogen 23329065 dopamine 23329065 quinpirole 23329065 urethane 23329125 2,3,7,8-tetrachlorodibenzo-p-dioxin 23329125 PCB 23329125 PCBs 23329125 S 23329125 TCDD 23329125 aryl hydrocarbon 23329125 glutathione 23329125 polychlorinated biphenyls 23329125 superoxide 23329125 tBHQ 23329125 tert-butylhydroquinone 23329180 theaflavin 23329180 theaflavins 23329180 tyrosine 23330542 acetaminophen 23330542 azole 23330542 azoles 23330542 pregnane 23330542 sulforaphane 23330549 Pt(6) 23330549 platinum 23330613 5-methylthioadenosine 23330613 Polyamine 23330613 ornithine 23330613 phosphoinositide 23330613 polyamine 23330613 putrescine 23330613 spermidine 23330789 silanes 23330847 Hydroxy 23330847 carbonyl di-imidazole 23330847 cholesterol 23330847 hydroxy 23330847 polyethylene glycol 23330848 C2H3OH 23330848 H 23330848 choline 23330848 coumarin 23330848 galanthamine 23330848 tacrine 23330908 C 23330908 zanamivir 23330971 Ag 23330971 CIGSSe 23330971 Cu(In,Ga)(S,Se)₂ 23330971 ZnO 23330971 indium 23330971 oxide 23330971 silver 23331178 Au(111) 23331178 DMPC 23331178 DMPE 23331178 carbonyl 23331178 dimyristoyl phosphatidylcholine 23331178 dimyristoyl phosphatidylethanolamine 23331178 hydrocarbon 23331178 phosphate 23331539 hydrogen 23331539 quinazolinon 23331618 4-Aminoquinoline-Triazine 23331618 4-amino-7-chloroquinolines 23331618 7-chloro-4-aminoquinoline-triazine 23331618 chloroquine 23331618 triazine 23332347 Belviq 23332347 Qsymia 23332347 orlistat 23332347 sibutramine 23332762 Ser 23332762 serine 23333093 catechin 23333093 cholesterol 23333261 Curcumin 23333261 curcumin 23333261 glucose 23333261 streptozotocin 23333575 APAP 23333575 GSH 23333575 Genistein 23333575 UDP 23333575 acetaminophen 23333575 alanine 23333575 genistein 23333575 glucuronide 23333575 glutathione 23333575 lactate 23333575 malondialdehyde 23333575 uridine diphosphate 23333639 8-oxoG 23333639 8-oxoguanine 23333639 formamidopyrimidine 23333639 oxygen 23333639 α-tocopherol 23333641 11β-hydroxysteroid 23333641 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane 23333641 2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane 23333641 HPTE 23333641 MXC 23333641 Methoxychlor 23333641 methoxychlor 23333716 phenolic 23333716 protocatechuic acid 23333834 Arg 23333834 Asp 23333834 Glu 23333834 Leu 23333834 Tyr 23333834 YR-11 23333834 celecoxib 23333834 cysteine 23333834 serine 23333899 DOXIL 23333899 Dox 23333899 Doxorubicin 23333899 Lipodox 23333899 PEG-DOPE 23333899 R8-PEG-PE 23333899 doxorubicin 23333899 octa-arginine 23333899 polyethylene glycol-dioleoyl phosphatidylethanolamine 23333900 CBZ 23333900 Soluplus 23333900 carbamazepine 23333900 polyethyleneglycol 23333900 polyvinyl acetate 23333900 polyvinyl caprolactam 23333908 Anthocyanins 23333908 Captropril 23333908 Lisinopril 23333908 anthocyanins 23333908 cholesterol 23333908 hibiscus acid 23333908 polyphenols 23333908 triglycerides 23334176 glucose 23334176 sugar 23334322 B6 23334322 PLP 23334322 Pyridoxal-5'-phosphate 23334322 aldehyde 23334322 homocysteine 23334322 pyridoxal 23334322 pyridoxine 23334322 vitamin B6 23334583 Ca(+2) 23335034 (14) C 23335034 Carbon 23335034 carbon 23335034 phenanthrene 23335220 ATP 23335220 biotin 23335220 phosphorylbiotin 23335243 sesquiterpene 23335243 sesquiterpenes 23335243 terpenes 23335320 N 23335320 N-heterocyclic carbene 23335320 Pd 23335320 amino acid 23335320 carbene 23335320 palladacycles 23335320 pyridine 23335320 α-carbon 23335450 S-Au 23335450 cysteine 23335565 5-azacytidine 23335565 oxygen 23335565 phytic Acid 23335565 phytic acid 23335833 1,2-dipalmitoyl-sn-glycero-3-phosphocholine 23335833 DPPC 23335833 diiodomethane 23335833 formamide 23335833 poly(methyl methacrylate) 23336337 diterpenes 23336337 ester 23336337 jolkinol D 23336337 lathyrane diterpene 23336337 octanol 23336368 flavonoids 23336368 homoflavanol 23336368 kaempferol 23336368 quercetin 23336729 acetylcholine 23336729 dimethylaminoethyl methacrylate 23336729 hydroxyl 23336729 methacrylate 23336729 poly(ethylene glycol) 23336729 poly-l-lysine 23337202 [Au(CN)(2)]- 23337397 MTT 23337397 Trypan blue 23337599 indole 23337599 indoles 23337599 pyrolidinyl-1,2-dione 23337599 tosyl 23337599 zileuton 23337600 (99m)Tc-(Me)FGCDEVD 23337600 (Me)FGC(Bz)DEVD 23337600 cisplatin 23337600 technetium-99m 23337600 ⁹⁹mTc-(Me)FGCDEVD 23337925 acetylene 23337941 QQT(CN)4 23337941 quinoidal oligothiophene 23337941 quinoidal quaterthiophene 23338525 Ir 23338525 IrO(2) 23338525 Nafion 23338525 O(2) 23338525 O2 23338525 Sn 23338525 SnO(2) 23338525 bi-metal oxides 23338525 hydrogen 23338525 oxygen 23338537 Aprokam 23338537 cefuroxime 23339036 estrogens 23339036 tamoxifen 23339547 rasagiline 23339572 (2E)-1-phenyl-3-[4-(trifluoromethyl)-phenyl]prop-2-en-1-one 23339572 (2E)-1-phenyl-3-pyrimidin-2-ylprop-2-en-1-one 23339572 1,3-diphenylprop-2-yn-1-one 23339572 4-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]benzonitrile 23339572 4-hydroxynonenal 23339572 5,5'-dithiobis-(2-nitrobenzoic acid) 23339572 BAP 23339572 Chalcones 23339572 N-acetylcysteine 23339572 benzalacetophenone 23339572 chalcone 23339572 chalcones 23339572 dimethylfumarate 23339572 sulforaphane 23339572 thiol 23339572 thiols 23339572 α,β-unsaturated carbonyl 23339577 AcS-C6H4-C≡C-(fc)n-C≡C-C6H4-SAc 23339577 Au 23339577 Au(111) 23339577 acetyl 23339577 fc-C≡C-C6H4-SAc 23339577 ferrocenyl 23339577 organometallic 23339604 Mn(III)(8)Mn(IV)(4)O(12)(L(x,y,z-CB))(16)(H(2)O)(4) 23339604 Mn(III)8Mn(IV)4O12(L(x,y,z-CB))16(H2O)4 23339604 dodecamanganese 23339604 manganese 23339678 ketorolac 23339974 gly-gly-lys 23340331 HCl 23340331 Pb 23340331 Pb(2+) 23340331 carbon dioxide 23340331 carbonate 23340331 hydroxide 23340332 Cl(-) 23340332 Cu(2+) 23340332 K(+) 23340332 Na(+) 23340332 copper 23340333 disulfide 23340334 Toluene 23340334 oxygen 23340334 toluene 23340646 Fe(3)O(4) 23340646 Fe3O4 23340646 Li(4)Ti(5)O(12) 23340646 graphite 23340646 lithium 23340646 sodium 23340858 GaZnSeAs 23340977 Fe 23340977 Mn 23340977 NH3 23340977 ammonia 23340981 nicotine 23341175 Pyrethroids 23341175 carbamate 23341175 organochlorine 23341175 organophorous 23341175 permethrin 23341175 pyrethroid 23341175 pyrethroids 23341248 Ag 23341248 Silver 23341248 oxygen 23341248 silver 23341258 Ca(2+) 23341258 GSH 23341258 Nonivamide 23341258 capsaicin 23341258 glutathione 23341258 nonivamide 23341258 oxygen 23341258 superoxide 23343117 Cd 23343117 Cd(2+) 23343117 Cd(II) 23343117 N 23343117 O 23343117 OH(-) 23343117 Zn 23343117 Zn(2+) 23343117 Zn(II) 23343117 amide 23343117 amide and amine nitrogens 23343117 amine 23343117 coumarin 23343117 dipicolylamine 23343117 hydroxide 23343117 pyridine 23343172 porphyrin 23343172 porphyrins 23343324 3 μ-ISF 23343324 polyferrocenylethylmethylsilane 23343324 polyisoprene 23343324 polystyrene 23343325 Co(II) 23343325 Eu(III) 23343325 EuS 23343325 Fe(II) 23343325 Mn(II) 23343325 dithiocarbamate 23343325 tetraphenylphosphonium tetrakis(diethyldithiocarbamate)europium(III) 23343325 transition-metal 23343474 C-S 23343474 Penta(tert-butylthio)corannulene 23343474 corannulene penta-thioethers 23343474 penta(4-dimethylaminophenylthio)corannulene 23343474 sulfur 23343474 thioether 23343474 thiolates 23343595 olanzapine 23344429 FAD 23344429 L-lysine 23344429 L-pipecolic acid 23344429 NADH 23344429 amine 23344429 haem 23344820 2-DG 23344820 2-deoxglucose 23344820 2-deoxyglucose 23344820 7,12-dimethylbenz(a)anthracene 23344820 DMBA 23344820 MDA 23344820 NO 23344820 adenosine-5'-triphosphate 23344820 glutathione 23344820 malonate 23344820 malondialdehyde 23344820 nitric oxide 23344820 sodium malonate 23344820 superoxide 23344824 saponins 23344824 tannins 23344824 terpenoids 23344825 Cd 23344825 Cr 23344825 Fe 23344825 Pb 23344825 Zn 23344825 cadmium 23344825 chromium 23344825 iron 23344825 zinc 23344975 Copper 23344975 Cu(+) 23344975 copper 23345132 17α-Hydroxyprogesterone 23345132 17α-hydroxypregnenolone 23345132 17α-hydroxyprogesterone 23345132 4-androstenedione 23345132 Androgen 23345132 androgen 23345132 dehydroepiandrosterone 23345132 dihydrotestosterone 23345132 steroid 23345132 testosterone 23346898 Ni(II) 23346898 [Ni(Me(6)tren)Br](Br) 23346898 [Ni(Me(6)tren)Cl](ClO(4)) 23346898 trigonal bipyramidal Ni(II) 23347052 DOPA 23347052 amine 23347052 iron 23347151 C-C 23347151 CF3CH2OH 23347151 CH3CN 23347151 CH3OH 23347151 C═C 23347151 hydrogen 23347151 para-amino 23347422 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine 23347422 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphoethanolamine 23347422 DiynePC 23347422 DiynePE 23347422 PDMS 23347422 diacetylene 23347422 ethanolamine 23347422 polydimethylsiloxan 23347547 Quercetin 23347547 acetic acid 23347547 flavonoid 23347547 quercetin 23347683 3-(phenoxy-phenyl-methyl)-pyrrolidine 23347683 3-(phenoxy-phenyl-methyl)-pyrrolidines 23347683 5-HT 23347683 5-hydroxytryptamine 23347683 norepinephrine 23347683 serotonin 23347684 1-azabicyclo[2.2.1]heptanes 23347684 2-(4-Chloro-2-cyano-2-phenylbutyl)aziridines 23347684 2-(4-chloro-2-cyano-2-phenylbutyl)aziridines 23347684 2-aminomethyl-4-phenyl-1-azabicyclo[2.2.1]heptanes 23347684 LiAlH(4) 23347684 LiAlH₄ 23347684 azaheterobicyclic 23347684 endo- and exo-2-aminomethyl-4-phenyl-1-azabicyclo[2.2.1]heptanes 23347875 22(R)-hydroxycholesterol 23347875 3β-hydroxysteroid 23347875 HBCDD 23347875 Hexabromocyclododecane 23347875 cAMP 23347875 cholesterol 23347875 forskolin 23347875 hexabromocyclododecane 23347875 nucleotide 23348152 (p-CH(3)O-C(6)H(4)Se)(2) 23348152 (p-Cl-C(6)H(4)Se)(2) 23348152 Cu(2+) 23348152 NADPH 23348152 RSeH 23348152 diaryl diselenides 23348152 p-chloro-diphenyl diselenide 23348152 p-methoxyl-diphenyl diselenide 23348152 selenol 23348152 thiols 23348499 glucose 23348501 2,5-dimethylfuran-3-thiol 23348501 2-oxoclopidogrel 23348501 3-nitropyridine-2-thiol 23348501 6-chloropyridazine-3-thiol 23348501 CPT 23348501 GSH 23348501 NPT 23348501 clopidogrel 23348501 disulfide 23348501 glutathione 23348501 thiol 23348501 thiols 23348514 Metformin 23348514 alanine 23348514 fatty acid 23348514 glucose 23348514 metformin 23348754 3,4-methylenedioxymethamphetamine 23348754 Ecstasy 23348754 MDMA 23348754 Oxytocin 23348754 cocaine 23348754 methamphetamine 23348754 oxytocin 23349486 Thiazolidinedione 23349486 pioglitazone 23349486 thiazolidinediones 23349498 glucose 23349500 Glucose 23349500 cAMP 23349500 calcium 23349500 glucose 23349501 17-HDHA 23349501 17-hydroxydocosahexaenoic acid 23349501 DHA 23349501 EPA 23349501 docosahexaenoic acid 23349501 eicosapentaenoic acid 23349501 glucose 23349501 polyunsaturated fatty acids 23349501 protectin D1 23349501 resolvin D1 23349501 resolvins 23350730 calcium 23350730 vitamin D 23350797 7-Chloro-4-quinolinyl Hydrazones 23350797 7-chloro-4-quinolinyl hydrazone 23350797 nitric oxide 23350945 Al(2)O(3) 23350945 Al(OH)(3) 23350945 Al-OH 23350945 Al2O3 23350945 AlO(OH) 23350945 DMMP 23350945 H(2)O 23350945 O 23350945 P═O 23350945 dimethyl methylphosphonate 23350945 hydrogen 23350945 methoxy 23350945 oxide 23351082 10-hydroxy-2-decenoic acid 23351082 esters 23351082 fatty acids 23351082 medium-chain fatty acids 23351082 mono- or dicarboxylic acid 23351096 doxorubicin 23351096 iron oxide 23351096 poly(N-isopropylacrylamide-co-acrylamide)-block-poly(ε-caprolactone) 23351139 ATP 23351139 AZT-TP 23351139 adenosine triphosphate 23351139 azidothymidine triphosphate 23351139 nucleotide 23351139 nucleotides 23351961 3-(4,5-dimethyl-thiazol-2-yl)-2-5-diphenyltetrazolium-bromide 23351961 Curcumin 23351961 MTT 23351961 SDS 23351961 curcumin 23352141 nocapyrones 23352141 pyrone polyketides 23352141 γ-pyrones 23352430 CpG 23352430 cytidine 23352430 dinucleotides 23352430 hydroxyurea 23352650 2,4diMeOBA 23352650 2,4diOHBA 23352650 GTS-21 23352650 H 23352650 PNU-120596 23352650 acetylcholine 23352650 benzylidene 23352650 benzylidene anabaseine 23352650 benzylidene anabaseines 23352650 dihydroxy 23352650 hydrogen 23352650 hydroxyl 23352650 serine 23352910 1, 1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine iodide 23352910 DiR 23352910 poly-l-arginine 23352929 NO 23352929 nitric oxide 23352929 phenolic 23352929 salicylic acid 23353026 GSH 23353026 H2O2 23353026 Mn 23353026 lactate 23353026 manganese 23353026 oxygen 23353026 propidium iodide 23353026 superoxide 23353027 DMAG 23353027 GSH 23353027 GSSG 23353027 H2O2 23353027 S 23353027 arsenic 23353027 arsenite 23353027 dimethylarsinic glutathione 23353027 nitrogen 23353027 oxygen 23353027 thio-DMA 23353027 thio-dimethylarsinic acid 23353058 Cu 23353058 K 23353058 Na 23353058 copper 23353658 Coumarins 23353658 acetonitrile 23353658 cnidilin 23353658 coumarins 23353658 imperatorin 23353658 isoimperatorin 23353659 MTT 23353659 Phenolic glycosides 23353659 chlorophenolic glucosides 23353659 curculigine E 23353659 curculigine F 23353659 curculigine G 23353659 curculigine H 23353659 curculigine I 23353659 orcinoside H 23353659 phenolic glycoside 23353659 phenolic glycosides 23353698 ABT-737 23353698 flavonoid 23353698 quercetin 23353699 AG1296 23353699 AG1478 23353699 LY294002 23353699 PP1 23353699 SB202190 23353699 SH-5 23353699 SP600125 23353699 Tanshinone IIA 23353699 U0126 23353733 1,4-di-substituted 2-aminoimidazole 23353733 1,4-di-substituted 2-aminoimidazoles 23353733 2-AITs 23353733 2-aminoimidazoles 23353733 pyrrole-imidazole alkaloids 23353733 triazoles 23353733 β-lactams 23353741 (1)H 23353741 (13)C 23353741 PGE2 23353741 prostaglandin E2 23353741 resveratrol amide 23353743 1,2,3-triazole-dithiocarbamate 23353743 5-fluorouracil 23353815 Cd 23353815 Fe 23353815 Hex 23353815 Zn 23353815 cadmium 23353815 iron 23353815 n-hexane 23353815 zinc 23353816 As(III) 23353816 As(V) 23353816 DMA(III) 23353816 DMA(V) 23353816 GSH 23353816 MMA(III) 23353816 MMA(V) 23353816 arsenic 23353816 dimethylarsinic acid 23353816 dimethylarsinous acid 23353816 glutathione 23353816 monomethylarsonic acid 23353816 monomethylarsonous acid 23353816 oxygen 23354070 ATP 23354070 palinurin 23354070 sesquiterpene 23354072 2-(2-benzoyl-β-D-glucopyranosyloxy)-7-(1α,2α,6α-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol 23354072 2-(6-benzoyl-β-D-glucopyranosyloxy)-7-(1α,2α,6α-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol 23354072 catechin-[5,6-e]-4β-(3,4-dihydroxyphenyl)dihydro-2(3H)-pyranone 23354072 chloroquine 23354072 chrysoeriol-7-O-β-D-glucopyranoside 23354072 hematin 23354072 heme 23354072 mururin A 23354072 phenolic glycoside 23354072 poliothrysoside 23354072 β-hematin 23354391 Ca 23354391 Daidzein 23354391 calcium 23354391 daidzein 23354391 estrogen 23354727 steroids 23354755 coal 23355287 TiO2 23355287 carbon 23355467 carbohydrate 23355467 carbon 23355467 fatty acid 23355467 fatty acids 23355467 glucose 23355467 stearoyl-CoA 23355467 sugar 23355467 triglycerides 23355488 actinomycin D 23355488 cystine 23355488 romidepsin 23355488 vancomycin 23355489 Ser 23355489 poly(ADP-ribose) 23355489 serine 23355616 CpG 23355616 CpGs 23355616 dinucleotides 23355616 nucleotide 23356207 monoglycerides 23356207 triterpene 23356207 triterpenes 23356740 Octopamine 23356740 Tyramine 23356740 adrenaline 23356740 amines 23356740 catecholamines 23356740 cyclic AMP 23356740 dopamine 23356740 noradrenaline 23356740 octopamine 23356740 phenolamines 23356740 tyramine 23356791 Formaldehyde 23356791 formaldehyde 23356791 formate 23356791 glucose 23356791 glutathione 23356791 lactate 23356859 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide 23356859 MTT 23356859 tetrazolium 23356867 carbohydrate 23356867 cellohexaose 23356867 cellotetraose 23356867 saccharide 23356907 Phthalocyanine 23356907 acetylenic bombesin 23356907 arginine 23356907 aspartic acid 23356907 bombesin 23356907 glycine 23356907 phthalocyanine 23356907 zinc phthalocyanine 23356946 3'-O-methylepicatechin 23356946 4'-O-methylepicatechin 23356946 epicatechin 23356946 epicatechin glucuronides and sulfates 23356946 glucuronides 23356946 monoglucuronides 23356946 sulfates 23356964 7-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)]-β-d-glucopyranosyl 23356964 DPPH 23356964 Flavone tetraglycosides 23356964 acyl 23356964 benzyl alcohol glycosides 23356964 glycosyl 23356964 lavone tetraglycosides 23356964 phenylpropanoylquinic acid 23357308 2-(3-pyridyl)-4,5-disubstituted thiazoles 23357308 5-acetyl-4-methyl-2-(3-pyridyl)thiazole 23357308 amphotricin B 23357308 ampicillin 23357308 thiazole 23357312 2',7'-dichlorofluorescein diacetate 23357312 DCFH-DA 23357312 Hoechst 33342 23357312 Paeonol 23357312 lactate 23357312 oxygen 23357312 paeonol 23357362 Ba(2+) 23357362 Vicenin 2 23357362 acetylcholine 23357565 N-ethylmaleimide 23357565 NO 23357565 SH 23357565 Silymarin 23357565 aspirin 23357565 capsaicin 23357565 capsazepine 23357565 ethanol 23357565 l-NAME 23357565 nitric oxide 23357565 silymarin 23357565 sulfhydryl 23357565 sulfhydryls 23357626 Aplyronine A 23357626 aplyronine A 23357626 mycalolide B 23357627 Boc-Phe-Leu-Glu(P)(OC(6)H(4))(2) 23357627 Phosphonic 23357627 glutamic acid 23357627 phosphonic glutamic acid 23357628 DPPH 23357628 MTT 23357628 curcumin 23357628 dimethylaminomethyl-substituted curcumin 23357628 galvinoxyl 23357629 (1)H 23357629 (13)C 23357629 1-methyl-5-(2,4,6-trimethoxy-phenyl)-1H-pyrazole 23357629 OH 23357629 acetic acid 23357629 flavones 23357629 keto 23357629 phenolic 23357629 pyrazole 23357633 C-(3-aminomethyl-cyclohexyl)-methylamine 23357633 benzene 23357633 ethambutol 23357633 t-butyl 23357976 11β-hydroxysteroid 23357976 cortisol 23357976 cortisone 23357976 glucose 23359435 benzocyclobutene 23359435 oxetane 23359435 triscarbazole 23359520 cholesterol 23359520 glucose 23359520 triglycerides 23359538 Cd(2+) 23359538 Cu(2+) 23359538 Hg(2+) 23359538 aluminosilica 23359538 cadmium 23359538 copper 23359538 mercury 23359555 C(60) 23359555 N-alkylcarbazole 23359555 fullerene 23359587 hydroxyapatite 23359587 tricalcium phosphate 23360142 CO 23360142 carbon monoxide 23360180 Ag 23360180 Oxygen 23360180 PLGA 23360180 oxygen 23360180 silver 23360230 Au 23360230 PEG 23360232 PEG 23360232 histidine 23360232 lysine 23360361 DMAPODA 23360361 Decanoic acid 23360361 N-[3-(Dimethylamino)propyl]-Octadecanamide 23360361 N-[3-(dimethylamino)propyl]-octadecanamide 23360361 amino 23360361 behenic acid 23360361 carboxylic 23360361 fatty acid 23360361 fatty acids 23360361 myristic acid 23360361 stearic acid 23360392 Cisplatin 23360392 Flavonol 23360392 cisplatin 23360392 flavonols 23360392 hydroxyl 23360392 hydroxyls 23360392 quartz 23360412 2,6-dichlorobenzonitrile 23360412 8-methoxypsoralen 23360412 DCBN 23360412 glutathione 23360619 7-ethyl-10-hydroxycamptothecin glucuronide 23360619 UDP 23360619 glucuronic acid 23361101 Caffeine 23361101 caffeine 23361383 AmB 23361383 N-acetylcysteine 23361383 Potassium 23361383 amiloride 23361383 amphotericin B 23361383 mannitol 23361383 potassium 23361383 spironolactone 23361517 EYYTO 23361517 Er(3+) 23361517 Er3+ 23361517 Y(2)Ti(2)O(7) 23361517 Y2Ti2O7 23361517 YTO 23361517 Yb(3+) 23361517 Yb3+ 23361587 NAD(+) 23361914 (S)-argininamide 23361914 [(3)H]UR-PLN196 23361914 [2,3-(3)H]propionyl 23361914 guanidine 23362105 GlcNAcβ(1→4)MurNAc 23362105 MDP 23362105 MurNAcβ(1→4)GlcNAc 23362105 Nucleotide 23362105 disaccharide 23362105 muramyl dipeptide 23362105 tetrasaccharide 23362239 Ca²⁺ 23362239 ryanodine 23362923 Amino Acids 23362923 amino acids 23362923 cyclic pentapeptides 23362942 (1)H 23362942 amino acid 23362942 amino acids 23362942 pillar[n]arene (n = 5, 6) 23362960 biotins 23363072 H 23363072 H-B 23363072 Hydrogen 23363072 KNMe(2)BH(3) 23363072 LiNMe(2)BH(3) 23363072 alkali metal amidoboranes 23363072 dihydrogen 23363072 hydrogen 23363335 CpG 23363335 CpG dinucleotide 23363335 cytosine 23363335 cytosines 23363335 guanine 23363335 hydrogen 23363335 pyrimidine 23363407 6-mercaptohexanol 23363407 oxygen 23363407 silica 23363425 (2S,4R)hydroxyproline 23363425 (poly-)amines 23363425 C 23363425 Hyp 23363425 Pro-Hyp-Gly 23363425 Silica 23363425 phosphate 23363425 silica 23363425 silicic acid 23363574 2',5'-ADP-sepharose-4B 23363574 d-glucose 6-phosphate 23363574 Ag(+) 23363574 As(5+) 23363574 Co(2+) 23363574 Glucose 6-phosphate 23363574 NADP(+) 23363574 TI(+) 23363574 Tl(+) 23363574 arsenic (V) oxide 23363574 cobalt (II) nitrate 23363574 glucose 6-phosphate 23363574 pentose phosphate 23363574 polyacrylamide 23363574 silver nitrate 23363574 sodium dodecyl sulfate 23363574 thallium sulphate 23363576 EtOH 23363576 alanine 23363576 aspartate 23363576 ethanol 23363576 glutathione 23363576 hydrogen peroxide 23363576 malondialdehyde 23363576 superoxide 23363577 Se 23363577 diethylenetriaminepentaacetic acid 23363577 selenium 23364612 1,4-dihydropyridines 23364612 11B 23364612 13C 23364612 1H 23364612 3,4-dihydropyrimidinones 23364612 boron 23364612 ethanol 23364612 formylphenylboronic acids 23364612 thioglycerol 23364615 TiO2 23364615 Titanium dioxide 23364615 metal oxides 23364615 titanium dioxide 23364884 E-64 23364884 cysteine 23364884 serotonine 23368510 glucose 23368510 metformin 23368777 Ser 23368777 Tyr 23368777 alanine 23368777 aspartate 23368777 lysine 23368777 sucrose 23368884 BRD9757 23368884 Hydroxamic acids 23369033 (-)-tylophorine 23369033 levorotatory tylophorine 23369033 phenanthroindolizidine alkaloid 23369343 alloxan 23369343 bilirubin 23369343 carbonyl 23369343 d-galactose 23369343 glucose 23369343 nitric oxide 23369343 peroxide 23369343 peroxides 23369343 sulfhydryl 23369343 superoxide 23369343 α-santalol 23369344 Indo 23369344 Prop 23369344 cGMP 23369344 guanylate 23369344 indomethacin 23369344 l-NAME 23369344 nitric oxide 23369344 propranolol 23369344 prostacyclin 23369537 chalcones 23369833 N 23369833 N-sulfocarbamoyl 23369833 carbamate 23369833 carbamate and N-sulfocarbamoyl 23369933 Mercuric chloride 23369933 Mercury 23369933 mercuric chloride 23369933 mercury 23369933 sodium selenite 23369933 vitamin E 23370006 Uranium 23370006 manganese 23370006 uranium 23370006 zinc 23370180 DES 23370180 DHT 23370180 diethylstilbestrol 23370180 dihydrotestosterone 23370180 testosterone 23370306 2-methylbutyric acid 23370306 Diterpenoids 23370306 Nor-Diterpenoids 23370306 crotocascarins 23370306 crotocascarins A-H 23370306 crotofolane 23370306 crotofolanes 23370306 diterpene 23370306 diterpenoids 23370306 nor-diterpenoids 23370306 γ-lactone 23370795 buprenorphine 23371032 carbamate 23371032 chlorocyclodiene 23371032 chlorpyrifos 23371032 cypermethrin 23371032 deltamethrin 23371032 endosulfan 23371032 methomyl 23371032 organochlorine 23371032 organophosphate 23371032 organophosphates 23371032 pyrethroid 23371032 pyrethroids 23371303 AVE1330A 23371303 Avibactam 23371303 Ceftazidime 23371303 NXL104 23371303 avibactam 23371303 carbapenem 23371303 ceftazidime 23371303 cephalosporin 23371303 cephem 23371303 creatinine 23371303 metronidazole 23371303 β-lactam 23371451 BrdU 23371451 Cysteamine 23371451 GSH 23371451 bromodeoxyuridine 23371451 cysteamine 23371451 glutathione 23371451 tetrazolium salt-1 23371488 Nicotine 23371488 nicotine 23371488 polycarbonate 23371489 MDPV 23371489 Mephedrone 23371489 cathinone 23371489 cocaine 23371489 dopamine 23371489 mephedrone 23371489 methamphetamine 23371489 methcathinone 23371489 methylenedioxypyrovalerone 23371760 15,16-epoxyisopimaric acid 23371760 15-hydroxyabietic acid 23371760 15-hydroxydehydroabietic acid 23371760 CH 23371760 Resin acid 23371760 abietic acid 23371760 dehydroabietic acid 23371760 diterpenoid 23371760 diterpenoids 23371760 isopimaric acid 23371760 resin acids 23371760 sulfonylurea 23371760 vitamin D(3) 23371763 Eu(III) 23371763 carbon 23371965 Cys 23371965 GSH 23371965 PEITC 23371965 PIC 23371965 Phenethylisothiocyanate 23371965 glutathione 23371965 isothiocyanate 23371965 parathion 23371965 phenethyl isocyanate 23371965 phenethyl isothiocyanate 23371965 phenethylamine 23371965 sulfur 23373444 Al(III) 23373444 Au(III) 23373444 Ca(II) 23373444 Cr(III) 23373444 Cu(II) 23373444 H(I) 23373444 Mg(II) 23373444 Na(I) 23373444 Ni(II) 23373444 Zn(II) 23373444 Zr(IV) 23373444 glucose 23373444 α-Zr(IV) phosphate 23373444 α-ZrP 23373444 α-zirconium(IV) phosphate 23373463 cobalt 23373463 hydroxide 23373463 α- to β-cobalt hydroxide 23373463 α-Co(OH)2 23373463 β-Co(OH)2 23373530 PPPX 23373530 poly(2-phenyl-1,4-xylylene) 23373544 Deoxyschisandrin 23373544 Eudragit 23373544 lignans 23373544 poloxamer 188 23373544 schisantherin A 23373590 AMPS 23373590 Ca(2+) 23373590 CaCl2 23373590 NaCl 23373590 acrylic acid 23373590 calcium 23373590 citrate 23373590 iron oxide 23373590 poly(2-methyl-2-acrylamidopropanesulfonate-co-acrylic acid) 23373590 poly(AMPS-co-AA) 23373590 poly(styrenesulfonate-alt-maleic acid) 23373590 poly(styrenesulfonate-block-acrylic acid) 23373590 sodium 23373613 iron oxide 23373648 steroidal hormones 23373648 tyrosine 23373724 (1)H 23373724 1β-d-Arabinofuranosylcytosine 23373724 1β-d-arabinofuranosyluracil 23373724 Ara-C 23373724 Ara-U 23373724 Cytarabine 23373724 OH 23373724 PAMAM 23373724 PEG 23373724 cytidine 23373724 hydroxyl 23373772 CF(3) 23373772 MeOH 23373772 Ru(bpy)(3)Cl(2) 23373772 alkenes 23373965 1-en-3-one 23373965 2,20-dinitrile 23373965 3-oxo-29-noroleana-1,9(11),12-trien-2,20-dicarbonitrile 23373965 9(11),12-diene 23373965 NO 23373965 glycyrrhetinic acid 23374865 Cu(I) 23374865 acetone 23374865 azide-alkyne 23374865 bile acid 23374865 cresol red sodium 23374865 pyrene 23374868 1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones 23374868 1-(4-phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanone 23374868 [(125)I]-CCL3 23374869 2-benzofuran-1(3H)-one 23374869 6-benzyloxyphthalides 23374869 Br 23374869 C 23374869 CF(3) 23374869 CH(3) 23374869 Cl 23374869 F 23374869 H 23374869 I 23374869 Phthalide 23374869 isatin 23374869 monoamine 23374869 phenyl 23374869 phthalide 23374869 phthalides 23374869 phthalimide 23374871 1-methylimidazole 23374871 2-phenyl-1-methylimidazole 23374871 imidazole 23374871 imidazolium 23374872 (11)C 23374872 (18)F 23374872 tariquidar 23375260 guanine nucleotide 23375851 11-ketotestosterone 23375851 ACE 23375851 CBZ 23375851 GEM 23375851 VEN 23375851 acetaminophen 23375851 carbamazepine 23375851 gemfibrozil 23375851 venlafaxaine 23376090 Chlordecone 23376090 chlordecone 23376090 organochlorine 23376110 1,3-thiazolane-4-carboxylic acid 23376110 16-spiro steroids 23376110 Spiro-7'-(aryl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazolo-trans-androsterone 23376110 acenaphthylene-1,2-dione 23376110 azomethine 23376110 dehydroandrosterone 23376110 spiro[5'.2″]acenaphthylene-1″-one-spiro[16.6']-(7'-aryl)-tetrahydro-1H-pyrrolo [1,2-c][1,3]thiazolo-trans-androsterone 23376110 trans-androsterone 23376110 trans-dehydroandrosterone 23376119 PJ34 23376119 Poly(ADP-ribose) 23376119 TPT 23376119 camptothecin 23376119 poly(ADP-ribose) 23376119 topotecan 23376162 Sesquiterpenes 23376162 [Rh2(OCOCF3)4] 23376162 bisabolenes 23376162 nitric oxide 23376162 sesquiterpenes 23376242 MAN 23376242 P-aminophenyl-α-d-mannopyranoside 23376245 Bpv (phen) 23376245 N-methyl-d-aspartate 23376245 NMDA 23376245 Tyr 23376245 Tyrosine 23376245 glutamate 23376245 orthovanadate 23376245 tyrosine 23376249 1,3,4-thiadiazole 23376249 acetyl 23376353 DOX 23376353 PLGA 23376353 VER 23376353 carboxyl 23376353 cyclo(Arg-Gly-Asp-D-Phe-Lys) 23376353 doxorubicin 23376353 verapamil 23376354 Ca(2+) 23376354 K(+) 23376412 indole alkaloids 23376437 CPZ 23376437 chlorpromazine 23376439 alkanes 23376439 decane 23376439 hexadecane 23376439 hexane 23376439 hydrocarbon 23376439 hydrocarbons 23376439 methyl esters 23376477 Ca(2+) 23376477 Ca²⁺ 23376477 K(+) 23376477 K⁺ 23376477 Nonylphenol 23376477 estrogen 23376477 nonylphenol 23376477 xenoestrogen 23376608 Apigenin 23376608 apigenin 23376696 Ca(2+) 23376696 K(+) 23376696 MDA 23376696 Na(+) 23376696 chloride 23376696 fluoride 23376696 malondialdehyde 23376696 superoxide 23376697 cobalt 23376697 titanium oxide 23376712 BHF177 23376712 Baclofen 23376712 N-([1R,2R,4S]-bicyclo[2.2.1]hept-2-yl)-2-methyl-5-(4-[trifluoromethyl]phenyl)-4-pyrimidinamine 23376712 baclofen 23376712 chlordiazepoxide 23376712 γ-Aminobutyric acid 23376780 eugenol 23376780 pyrethrins 23376780 rotenone 23376780 β-asarone 23376817 BrdU 23376817 DMA(III) 23376817 DMA(V) 23376817 arsenic 23376817 bromodeoxyuridine 23376817 dimethylarsinous acid 23376817 methylate arsenicals 23376997 Arylsulfonamide 23376997 arylsulfonamido 23376997 hydroxamates 23377100 Cd 23377100 Cd(2+) 23377100 PTFE 23377100 ascorbate 23377100 cadmium 23377100 oxygen 23377100 polytetrafluoroethylene 23377115 calcium diglutamate 23377115 glutamates 23377115 magnesium diglutamate 23377115 monoammonium glutamate 23377115 monopotassium glutamate 23377115 monosodium glutamate 23377609 1-(4-aminobenzyl) ethylenediamine N,N,N',N'-tetraacetic acid 23377609 1-(4-isothiocyanobenzyl) ethylenediamine N,N,N',N'-tetraacetic acid 23377609 EDTA 23377609 ITCBE 23377609 aminobenzyl-EDTA 23377609 cadmium 23377617 GSH 23377617 Zn 23377617 dopamine 23377617 glutathione 23377617 zinc 23377617 γ-Glutamylcysteine 23378200 Baicalin 23378200 baicalin 23378608 Fatty acids 23378608 celecoxib 23378626 (2R,3R,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-3-yl 4-O-(6-deoxy-β-d-glucopyranosyl)-α-d-glucopyranoside 23378626 CS-1036 23378626 [(14)C]CS-1036 23378626 glucose 23378627 androstane 23378820 Iron 23378820 Selenate 23378820 bicarbonate 23378820 ferrous 23378820 ferrous hydroxide 23378820 hydroxide 23378820 iron 23378820 oxygen 23378820 selenate 23379362 Petroacetylene 23379362 petroacetylene 23379362 polyacetylene 23379369 2-fluoroethyl azide 23379369 C-C-N-N 23379369 F-C-C-N 23379369 FCH2CH2N3 23379369 azido 23379369 fluorine 23379686 (1)H 23379686 1,3-didecyl-2-methylimidazolium chloride 23379686 4-methoxybenzenesulfonyl chloride 23379686 D2O 23379686 MBSC 23379686 Nile red 23379686 [C10C10mim]Cl 23379686 pyrene 23379686 rhodamine B 23379723 Spiropyran 23379723 acetone 23379723 acetonitrile 23379723 ethanol 23379723 merocyanine 23379723 methanol 23379723 silica 23379723 spiropyran 23379723 tetrahydrofuran 23379723 toluene 23379784 H 23379784 Polystyrene 23379784 poly(ethylene oxide) 23379784 polystyrene 23379962 PFH-A 23379962 PFO-BPy 23379962 carbon 23379962 fluorene 23379962 poly[(9,9-dihexylfluorenyl-2,7-diyl)-co-(9,10-anthracene)] 23379962 poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(6,6'-{2,2'-bipyridine})] 23380082 caffeic acid 23380082 ferulic acid 23380082 phenolic acids 23380082 rosmarinic acid 23380243 arsenic 23380305 4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile 23380305 ABT-239 23380305 Histamine 23380305 acetylcholine 23380305 histamine 23380477 CoCl(2) 23380477 CoCl2 23380477 cobalt chloride 23380477 oxygen 23380917 GABA 23380917 N-methyl D-aspartate 23380917 PCP 23380917 phencyclidine 23380917 γ-aminobutyric acid 23381681 GSH 23381681 Se 23381681 Selenium 23381681 Thyroxine 23381681 glutathione 23381681 selenium 23381681 seleno 23381681 sodium selenite 23381681 triiodothyronine 23381882 Fexofenadine 23381882 Midazolam 23381882 Pravastatin 23381882 Ritonavir 23381882 Saquinavir 23381882 fexofenadine 23381882 midazolam 23381882 pravastatin 23381882 ritonavir 23381882 saquinavir 23381951 Allopurinol 23381951 abacavir 23381951 allopurinol 23381951 carbamazepine 23382013 octanol 23382105 MMF 23382105 MPA 23382105 cyclosporine 23382105 mycophenolate mofetil 23382105 mycophenolic acid 23382105 tacrolimus 23382380 AMPA 23382380 glutamate 23383423 amino acid 23383594 CH4 23383594 CO2 23383594 carbon 23383594 carbon dioxide 23383594 methane 23383594 zeolite 23383710 DMAAPS 23383710 N,N-dimethyl(acrylamidopropyl)ammonium propane sulfonate 23383710 PEI 23383710 polyethylenimine 23383723 F68 23383723 NaTDC 23383723 Pluronic 23383723 Pluronic F127 23383723 Pluronic F127 or F68 23383723 Pluronics 23383723 Pluronics (F127 and F68) 23383723 bile salt 23383723 bile salts 23383746 CA-Tam 23383746 DCA-Tam 23383746 DPH 23383746 DPPC 23383746 LA-Tam 23383746 N-desmethylated tamoxifen 23383746 Prodan 23383746 TamNHMe 23383746 amine 23383746 bile acid 23383746 bile acids 23383746 cholic acid 23383746 deoxycholic acid 23383746 lithocholic acid 23383746 tamoxifen 23383750 3-n-pentadecylphenol 23383750 PDP 23383750 PS-P4VP 23383750 hydrogen 23383750 polystyrene-poly(4-vinyl pyridine) 23383871 cyclohexene 23383871 estrogen 23383871 steroid 23384042 CH2Cl2 23384042 perylene 23384363 nitrogen 23384387 Oleoyl-L-valinolamide 23384387 acylethanolamide 23384387 elaidoyl-D-valinolamide 23384387 elaidoyl-L-valinolamide 23384387 glucose 23384387 oleoyl-D-valinolamide 23384387 oleoyl-L-valinolamide 23384387 palmitoyl-L-valinolamide 23384387 stearoyl-L-valinolamide 23384446 ACh 23384446 Arsenite 23384446 CPA 23384446 Ca(2+) 23384446 NADPH 23384446 NO 23384446 acetylcholine 23384446 apocynin 23384446 arsenic 23384446 arsenite 23384446 cyclopiazonic acid 23384446 dihydroethidium 23384446 hydrogen peroxide 23384446 manganese porphyrin 23384446 nitric oxide 23384446 oxygen 23384446 superoxide 23384967 BPA 23384967 Bisphenol A 23384967 DES 23384967 bisphenol A 23384967 diethylstilbestrol 23384967 steroid 23384996 NH4HCO3 23384996 alanine 23384996 amino acid 23384996 amino acids 23384996 ammonia 23384996 aspartate 23384996 glutamate 23384996 glutamine 23385211 Imipramine 23385211 N 23385211 amine 23385211 desipramine 23385211 ethylene glycol 23385211 imipramine 23385211 imipramines 23385211 lithium aluminium hydride 23385211 serotonin 23385214 H 23385214 OH 23386250 Ca(2+) 23386250 FK-506 23386250 K(+) 23386250 tacrolimus 23386468 2'-Fluoro-2'-deoxyguanosine 23386468 2'-deoxy-2'-fluoro-6-chloroguanosine 23386468 2'-fluoro-2'-deoxyguanosine 23386468 2'-fluoro-2'-deoxyguanosine 5'-monophosphate 23386468 5'-O-naphthyl(ethoxy-L-alaninyl) 23386468 5'-O-naphthyl(methoxy-L-alaninyl) 23386468 6-O-ethyl-2'-fluoro-2'-deoxyguanosine 23386468 6-O-methyl-2'-fluoro-2'-deoxyguanosine 23386468 L-alaninyl 23386468 adenosine 23386468 guanine 23386468 nucleoside 5'-monophosphates 23386468 nucleosides 23386468 phosphoramidate 23386468 purine 2'-fluoro-2'-deoxyriboside 23386597 Ezogabine 23386597 ethyl N-(2-amino-4-[{fluorophenyl}methlamino]phenylcarbamate) 23386597 ezogabine 23386597 potassium 23386597 retigabine 23386599 amides 23386599 carbamates 23386599 carboxylic acid 23386599 ester 23386599 esters 23386599 statins 23386599 thioesters 23386616 NADPH 23386616 oxygen 23386704 25-hydroxyvitamin D 23386704 4β-hydroxycholesterol 23386704 vitamin D 23386780 ECH 23386780 Epichlorohydrin 23386780 amino 23386780 dUTP 23386780 epichlorohydrin 23387796 (1)H 23387796 (13)C 23387796 (15)N 23387796 Amberlite XAD-16 23387796 Geralcin C 23387796 geralcin C 23387796 geralcins A and B 23387796 geralcins C-E 23387796 geralcins D and E 23387796 hydrazides 23387796 methanol 23387851 ANAVEX 2-73 23387851 E-52862 23387851 SA4503 23387865 (13)C 23387865 (E)-olefinic carbons 23387865 1-enol-3,7-diketo 23387865 3-enol-1,7-diketo 23387865 CD(3)OH 23387865 DMSO-d(6) 23387865 HSYA 23387865 Hydroxysafflor yellow A 23387865 hydroxysafflor yellow A 23387865 keto-enol 23387865 pyridine-d(5) 23387865 quinochalcone C-glycoside 23387865 quinochalcone C-glycosides 23389039 curcumin 23389045 4-pyridyl 23389045 Pyridyl 23389045 bis(2-hydroxy-ethyl) 23389045 bis(2-hydroxyethyl) 23389045 ethanol 23389045 lipoic Acid 23389045 lipoic acid 23389045 pyridine 23389045 thyroxine (T4) 23389045 thyroxine (t4) 23389625 C 23389625 Carbon 23389625 LiFePO(4) 23389625 LiFePO4 23389625 carbon 23389625 lithium 23389625 sucrose 23389738 ETBE 23389738 ethyl tertiary-butyl ether 23389956 betamethasone 23389956 cortisol 23389956 sGC 23391096 PAMAM 23391096 Paclitaxel 23391096 Taxol 23391096 paclitaxel 23391096 polyamidoamine 23391096 tertiary amines 23391133 amide 23391133 ester 23391133 monophosphate 23391162 Amino Acid 23391162 DO3A-N-α-aminopropionate 23391162 Gd 23391162 Gd(DOTAla) 23391162 Gd(III) 23391254 ATP 23391254 taxol 23391441 Alexa Fluor 488 23391441 FITC 23391441 Texas Red 23391441 biotin 23391441 biotin-fluorescein isothiocyanate 23391441 gentamicin 23391441 phalloidin 23391442 oxygen 23391443 cAMP 23391484 PFCA 23391484 PFOA 23391484 PFT 23391484 Perfluorooctanoic acid 23391484 carbon 23391484 fluoropolymers 23391484 perfluorinated carboxylic acids 23391485 17-β-estrodiol 23391485 BPA 23391485 Bisphenol A 23391485 DMSO 23391598 As 23391598 Cd 23391598 Co 23391598 Cr 23391598 Cu 23391598 Fe 23391598 Hg 23391598 I 23391598 Mn 23391598 Mo 23391598 Ni 23391598 Pb 23391598 Se 23391598 Zn 23391631 Pb(2+) 23391631 aryl hydrocarbon 23391631 creatine 23391631 lactate 23391631 resveratrol 23391632 11β-hydroxysteroid 23391632 3β-hydroxysteroid 23391632 DEHP 23391632 EDS 23391632 di(2-ethylhexyl) phthalate 23391632 ethane dimethanesulfonate 23391632 testosterone 23391637 Ca(2+) 23391637 K(+) 23391637 Na(+) 23392568 Hg 23392568 HgCl2 23392568 mercury chloride 23392606 PLLA 23392606 PVP 23392606 poly(l-lactic acid) 23392606 polyvinylpyrrolidone 23393163 Vesnarinone 23393163 quinolinone 23393163 vesnarinone 23393209 Metformin 23393209 Triglycerides 23393209 glucose 23393209 metformin 23393209 triglyceride 23393209 triglycerides 23393216 25-OHD 23393216 25-hydroxycholecalciferol 23393216 Vitamin D 23393216 cholesterol 23393216 glucose 23393216 triglycerides 23393216 vitamin D 23393219 Repaglinide 23393219 Rifampicin 23393219 repaglinide 23393219 rifampicin 23394218 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide 23394218 AZD5363 23394309 H 23394309 H(+) 23394309 Hydrocarbons 23394309 O 23394309 OH(-) 23394309 [Nb6O19Hx]((8-x)-) 23394309 oxygen 23394318 abietane 23394318 aquilarabietic acid K 23394318 aquilarabietic acids A-J 23394318 diterpenoid 23394318 diterpenoids 23394318 ethanol 23394318 norepinephrine 23394318 petroleum ether 23394318 podocarpane 23394432 CdS 23394432 cadmium sulfide 23394469 graphite 23394469 met-enkephalin 23394469 pentapeptide 23394480 Ge 23394480 Si 23394542 (31)P 23394542 CdSe 23394542 carbon 23394542 chlorine 23395165 glutathione 23395165 purine 23395165 serine 23395652 (+)- and (-)-huperzine A 23395652 (-)-huperzine A 23395652 NMDA 23395652 huperzine A 23395656 Mitoxantrone 23395656 indazolo[4,3-gh]isoquinolinone 23395656 indazolo[4,3-gh]isoquinolinones 23395663 Lactose 23395663 [2,9(10),16(17),23(24)-tetrakis((1-(β-d-lactose-2-yl)-1H-1,2,3-triazol-4-yl)methoxyl)phthalocyaninato] zinc(II) 23395663 lactose 23395663 zinc phthalocyanine 23395665 3-(1H-indol-3-yl)-3-oxo-2-(2-oxoindolin-3-ylidene)propanenitrile 23395665 acenaphthenequinone 23395665 azomethine 23395665 dispirooxindole-pyrrolidine 23395665 isatin 23395665 sarcosine 23395689 DOPE 23395689 Gadolinium 23395689 Gd 23395689 Gd(3+) 23395689 Manganese 23395689 Mn 23395689 Mn oxide 23395689 MnO 23395689 Oleic acid 23395689 PEG-2000 23395689 cholesterol 23395689 dioleoyl-phosphatidylethanolamine 23395689 doxorubicin 23395689 manganese 23395689 phosphatidylethanolamine 23395689 polyethylene glycol 23395717 PD98059 23395717 Xestospongin C 23395717 bis-1-oxaquinolizidines 23395717 nitroblue tetrazolium 23395719 caffeoyl glucose 23395719 coumaroyl hexose 23395719 dihydroferulic acid 4-O-β-d-glucuronide 23395719 dihydroxybenzoic acid 23395719 methoxyquercetin 3-O-galactoside 23395719 myricetin 23395719 phenolic 23395719 polyphenols 23395719 quercetin 23395719 scopoletin 23395783 Cadmium 23395783 CdCl2 23395783 ORY 23395783 S 23395783 ascorbic acid 23395783 cadmium 23395783 glutathione 23395783 superoxide 23395783 thiols 23395783 γ-Oryzanol 23395783 γ-oryzanol 23395783 δ-ALA 23395783 δ-aminolevulic acid 23395914 darunavir 23395914 ketoconazole 23395914 zosuquidar 23396041 AZA 23396041 AZA1 23396041 AZA1 + 2 23396041 AZA1 and -2 23396041 AZA1+2 23396041 AZA17 23396041 AZA3 23396041 AZAs 23396041 azaspiracid 23396041 azaspiracids 23396116 TTX 23396116 tetrodotoxin 23396441 ATP 23396441 sucrose 23396442 ACN 23396442 DMSO 23396442 acetonitrile 23396442 dimethyl sulfoxide 23397032 Dexamethasone 23397032 dexamethasone 23397049 Paliperidone 23397049 paliperidone 23398290 Dex 23398290 Retinoids 23398290 Vitamin A 23398290 dexamethasone 23398290 retinoic acid 23399323 O 23399639 Laulimalide 23399639 Taccalonolide AJ 23399639 fijianolide B 23399639 laulimalide 23399639 paclitaxel 23399639 taccalonolide AJ 23399641 CB1954 23399641 PR-104A 23400262 MgO 23400262 TiO(2) 23400262 TiO2 23400270 silica 23400270 silicas 23400782 ADP 23400782 ATP 23400782 C 23400782 N 23400795 organotin 23400795 tributyltin 23400795 triphenyltin chloride 23400796 Co 23400796 Cr 23400796 Cu 23400796 Mn 23400796 Zn 23400888 acetylcholine 23400925 (13) C 23400925 (15) N 23400925 Hg 23400925 MMHg 23400925 Se 23400925 carbon 23400925 mercury 23400925 monomethylmercury 23400925 nitrogen 23400925 selenium 23400943 clobazam 23400943 clonazepam 23400943 stiripentol 23400943 valproic acid 23400943 vigabatrin 23401139 C10-C16 23401139 C16-C23 23401139 C23-C34 23401139 PHC 23401139 PHCs 23401139 Petroleum hydrocarbons 23401139 petroleum hydrocarbon 23401211 Hg 23401211 mercury 23401211 nitrogen 23401217 alloxan 23401244 C60 23401244 DDE 23401244 DDT 23401244 FULLERENES 23401244 dichlorodiphenyldichloroethylene 23401244 fullerene 23401244 fullerenes 23401244 p,p'-DDE 23401262 Phenytoin 23401262 phenytoin 23401281 Al 23401281 Cd 23401281 Cu 23401281 Fe 23401281 Mn 23401281 Pb 23401281 Zn 23401281 carbon 23401291 (E)-N-((3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)methylene)hexadecan-1-amine 23401291 Fatty acid 23401291 Schiff base 23401291 Schiff-base 23401291 acyl 23401291 fatty acid 23401291 β-ketoacyl 23401303 carbon 23401303 carboxylic 23401303 phenolic 23401303 pyrethroid 23401303 pyrethroids 23401323 MNG 23401323 maltose-neopentyl glycol 23401324 PCBs 23401324 organochlorine 23401324 polybrominated diphenyl ethers 23401324 polychlorinated biphenyls 23401355 Co 23401355 Li 23401355 Li2O 23401355 Mn 23401355 MnCO3 23401355 MnO 23401355 lithium 23401470 N 23401472 5-Aza-dC 23401472 5-aza-2'-deoxycytidine 23401472 Bisulfite 23401472 CpG 23401472 SN-38 23401472 UDP 23401472 bilirubin 23401602 fatty acids 23401602 linoleic acid 23402270 PAEMH 23402270 poly(2-aminoethylmethacrylate hydrochloride) 23402270 polystyrene 23402341 GSH 23402341 MFA 23402341 MFA-1-O-G 23402341 MFA-1-O-acyl-glucuronide 23402341 MFA-AMP 23402341 MFA-CoA 23402341 MFA-GSH 23402341 MFA-S-acyl-CoA 23402341 MFA-S-acyl-glutathione 23402341 Mefenamic acid 23402341 S 23402341 acyl 23402341 acyl-CoA 23402341 adenylate 23402341 carboxylic acid 23402341 glutathione 23402341 mefenamic Acid 23402341 mefenamic acid 23402341 mefenamyl 23402364 (·)NO 23402364 Etoposide 23402364 H2O2 23402364 Nitric oxide 23402364 VP-16 23402364 VP-16,213 23402364 chloroform 23402364 etoposide 23402364 iminoxyl 23402364 nitric oxide 23402364 nitrogen oxide 23402364 nitroxide 23402364 o-quinone 23402364 o-quinone- and nitroso-VP-16 23402364 oxygen 23402364 phenoxy 23402423 CdTe 23402423 monothiol 23402636 cholesterol 23402636 sterols 23402636 triglyceride 23402636 γ-linolenic acid 23402638 Iron(II) 23402638 amino alcohols 23402638 hydroxylamine 23402638 hydroxylamines 23402638 iron nitrenoid 23402638 iron(II) 23402638 olefins 23402647 1-Butyl 23402647 2-methylimidazolium tetrafluoroborate 23402647 Eu 23402647 GdF3 23402647 diethylene glycol 23402647 europium(III) 23402647 fluoride 23402647 gadolinium(III) fluoride 23402647 lanthanide chlorides 23402855 CH2Cl2 23402855 NO 23402855 fucoxanthin 23402855 nitric oxide 23402855 pheophorbide a 23402855 pheophytin a 23402855 porphyrin 23402859 Chlorpyrifos 23402859 alanine 23402859 aspartate 23402859 catechin 23402859 chlorpyrifos 23402859 cholesterol 23402859 glutathione 23402859 lactate 23402859 malondialdehyde 23402859 organophosphorus 23402859 quercetin 23402859 superoxide 23402859 trigliceride 23402860 (-)-Cubebin 23402860 (-)-cubebin 23402860 CUB 23402860 DXR 23402860 URE 23402860 doxorubicin 23402860 lignan 23402860 urethane 23402938 IR3535 23402971 benzimidazole 23402971 benztriazole 23402972 indinavir 23402972 ritonavir 23403080 (S)-2-aminoethyl 23403080 2-hydrazino-1,3-thiazole 23403080 hydrazino-1,3-thiazole 23403080 hydrazone 23403080 indolyl 23403080 thiazole 23403395 COOH 23403395 PLA-TPGS 23403395 TPGS 23403395 Taxotere 23403395 carboxyl 23403395 cisplatin 23403395 d-alpha-tocopheryl-co-poly(ethylene glycol) 1000 succinate 23403395 docetaxel 23403395 poly(lactic acid)-TPGS 23403395 vitamin E 23403537 tetrapeptide 23403537 tetrapeptides 23404062 SCH23390 23404062 dopamine 23404062 naloxone 23404062 sulpiride 23404443 arginine 23404443 glucose 23404458 Al 23404458 Au 23404458 Ca 23404458 Cr 23404458 Cu 23404458 Hg 23404458 Mg 23404458 Ni 23404458 P 23404458 Pb 23404458 Pt 23404458 Si 23404458 Sn 23404458 Sr 23404458 W 23404458 Zn 23404458 calcium 23404458 calcium hydroxyapatite 23404458 cholesterol 23404739 19,20-anhydrosipholenol A 4β-4-chlorobenzoate 23404739 19,20-anhydrosipholenol A 4β-benzoate ester 23404739 Sipholenol A 23404739 Sipholenol A 4β-4-chlorobenzoate 23404739 carbamate 23404739 ester 23404739 esters 23404739 ether 23404739 oxime 23404739 sipholane triterpene 23404739 sipholane triterpenoids 23404739 sipholanes 23404739 sipholenol A 23404739 sipholenol A 4β-4-chlorobenzoate 23404739 sipholenol A succinate 23404739 sipholenols 23404739 sipholenone A 23404739 triterpene 23404739 tyrosine 23404750 Phe 23405943 1,1-diphenyl-2-picrylhydrazyl 23405943 4-aminophenol 23405943 Fe(2+) 23405943 ascorbic acid 23405943 benzoyl 23405943 paracetamol 23405943 salicylate 23405943 salicylic acid 23405943 thiobarbituric acid 23406166 2'-hydroxy-3,4-dimethoxychalcone 23406166 3',4'-dimethoxy-7-(γ,γ-dimethylallyloxy)flavonol 23406166 O-prenylated flavonol 23406166 biochanin A 23406166 kaempferol-3-O-β-d-glucopyranoside 23406277 PVA 23406277 [μ-(11,11'-bidppz)(phen)4Ru2](4+) 23406277 poly(vinyl alcohol) 23406277 ruthenium 23406277 ruthenium(II) 23406348 alkyl acrylates 23406348 ethyl (n-butyl) acrylate 23406348 ethyl acrylate 23406348 hydrogen 23406348 methyl 23406348 methyl acrylate 23406348 methyl, ethyl, and n-butyl acrylate 23406348 methylene 23406348 n-butyl acrylate 23406429 triaryl 23406429 triaryl sulfonamide 23406429 triaryl sulfonamides 23406469 PpIX 23406469 protoporphyrin IX 23406469 silica 23407893 H3AsO3 23407893 H3AsO4 23407893 H3PO3 23407893 H3PO4 23407893 Imogolite 23407893 aluminogermanate 23407893 aluminosilicate 23407893 arsenate 23407893 arsenic 23407893 arsenite 23407893 germanate 23407893 imogolite 23407893 phosphate 23407893 phosphite 23407893 phosphorous 23407893 silicate 23408116 Acetaminophen 23408116 UDP 23408116 acetaminophen 23408270 (+)-Limonene epoxide 23408270 (+)-limonene epoxide 23408270 praziquantel 23408434 Ca(2+) 23408434 calcium 23408851 C 23408851 N 23408851 amino acid 23409716 A967079 23409716 AP18 23409716 Chembridge-5861528 23409716 JNJ17203212 23409716 JTS653 23409716 SB705498 23409716 capsaicin 23409716 menthol 23409719 FPP 23409719 Farnesyl diphosphate 23409719 aryl azides 23409719 benzophenones 23409719 diazotrifluoropropionates 23409719 farnesyl diphosphate 23409719 isoprenoid 23409719 isoprenoids 23409719 sesquiterpenes 23409765 phenylalanine 23409765 porphobilinogen 23409765 pyruvate 23409842 (1)H 23409842 (13)C 23409842 (15)N 23409842 Arg 23409842 amide nitrogen 23409842 polyethylene glycol 23409925 5-FU 23409925 FITC 23409925 carboxymethyl 23409925 folate 23409952 Azide 23409952 CaN3(+) 23409952 DMSO 23409952 LiN3 23409952 MgN3(+) 23409952 NH4N3 23409952 NaN3 23409952 azide 23409952 dimethylsulfoxide 23409952 metal azide 23410078 Axistatins 1-3 23410078 agelasine F 23410078 axistatins 1 (1), 2 (2), and 3 (3) 23410078 axistatins 1-3 23410078 diterpenes 23410078 formamide 23410078 formamides 23410078 pyrimidine 23410105 X-NO2 23410105 nitro 23410168 anthracycline 23410168 naphthalimide 23410168 phenylaminopyrimidine 23410172 ARA 23410172 Arachidonic acid 23410172 eicosanoid 23410172 oxylipin 23410634 carbonyl 23410634 glutathione 23410634 hydrogen peroxide 23410634 menadione 23410634 oxygen 23410634 tert-butyl hydroperoxide 23410745 Cholesterol 23410745 creatinine 23410745 uric acid 23411075 Arylglycine 23411075 arylglycine 23411075 icilin 23411076 (99m)Tc 23411076 2-arylbenzothiazoles 23411076 2-phenylbenzothiazole 23411076 Re 23411076 Re 2-arylbenzothiazoles 23411076 rhenium 2-arylbenzothiazoles 23411079 NO 23411079 Steroidal 23411079 longipenane 23411079 longipenane 26-O-β-d-glucopyranoside 23411079 neogitogenin 3-O-α-l-rhamnopyranosyl-(1→2)-O-[β-d-glucopyranosyl-(1→4)]-β-d-galactopyranoside 23411079 nitric oxide 23411079 steroidal 23411079 steroidal saponins 23411082 (1)O2 23411082 Al(3+) 23411082 Al3+ 23411082 Hypocrellin A 23411082 oxygen 23411168 AOT 23411168 diene 23411168 isooctane 23411168 linoleic acid 23411173 Palmitic 23411173 carbohydrates 23411173 linoleic 23411173 oleic 23411173 oxalate 23411173 phytate 23411173 saponin 23411173 stearic 23411175 polyacrylamide 23411175 polyphenol 23411175 polyphenols 23411177 cholesterol oxides 23411177 eicosapentaenoic-docosahexaenoic acid 23411177 polyunsaturated fatty acids 23411177 saturated fatty acids 23411178 1-HOP 23411178 1-hydroxypyrene 23411178 2-NAP 23411178 2-naphthol 23411178 KOH 23411178 l-hydroxypyrene 23411181 1β-acetoxyfuranoeudesm-4(15)-ene 23411181 ABTS 23411181 DPPH 23411181 Isofuranodiene 23411181 MTT 23411181 furanosesquiterpenes 23411182 Ag 23411182 Cu 23411182 Ir 23411182 Ni 23411182 Pt 23411182 Rh 23411182 ascorbic acid 23411182 ascorbic, citric and malic acids 23411182 citric and malic acids 23411183 polyphenols 23411184 acetonitrile 23411184 avermectins 23411185 Iron 23411185 iron 23411185 zinc 23411189 Citrate 23411189 EDTA 23411189 Fe(III) 23411189 ethylenediaminetetraacetic acid 23411189 malate 23411191 Ginsenoside Re 23411191 Ginsenosides 23411191 carbon 23411191 carbons 23411191 diol 23411191 ginsenoside Re 23411191 ginsenosides 23411191 ginsenosides, namely Rg(2), Rg(6) and F(4) 23411191 glucosyl 23411191 lysine 23411191 sugar 23411191 triol 23411194 quinic acid 23411195 PUFA 23411195 polyunsaturated fatty acid 23411199 anthocyanins 23411199 dihydrochalcones 23411199 flavan-3-ols 23411199 flavanones 23411199 flavonols 23411199 hydroxybenzoic acids 23411199 hydroxycinnamic acids 23411199 polyphenol 23411199 polyphenols 23411199 stilbenes 23411206 ammonium sulphate 23411206 dicyandiamide 23411206 melamine 23411206 urea 23411208 doxorubicin 23411208 vitamin E 23411208 α-TOS 23411208 α-Tocopherol 23411208 α-tocopherol 23411208 α-tocopheryl succinate 23411210 6-OHDA 23411210 6-hydroxydopamine 23411210 MDA 23411210 gallic acid 23411210 glutathione 23411210 malondialdehyde 23411210 thiol 23411211 3-MA 23411211 3-methyladenine 23411211 Cannabisin B 23411211 cannabisin B 23411211 rapamycin 23411212 25-hydroxyvitamin D 23411212 25OH-Vit D 23411212 Deuterium 23411212 Vit D 23411212 Vitamin D 23411212 vitamin D 23411213 acetonitrile 23411213 aflatoxin B(1) 23411213 ammonium acetate 23411213 ochratoxin A 23411217 Ara 23411217 Araf 23411217 Gal 23411217 GalA 23411217 GlcA 23411217 Rha 23411219 1,2,3-trioleyl 23411219 1,2-dilinoleoyl-3-oleyl 23411219 1,2-dioleyl-3-palmitoyl 23411219 1-oleoyl-2-linoleoyl-3-linolenoyl 23411219 OLL 23411219 OLLn 23411219 OOL 23411219 OOO 23411219 POO 23411219 dioleoyl linoleoyl 23411219 fatty acid 23411219 heneicosanoic acid 23411219 hexacosanoic acid 23411219 triacylglycerol 23411219 triacylglycerols 23411220 H(2)O(2) 23411220 hydrogen peroxide 23411223 Ag 23411223 Co 23411223 Cr 23411223 Cu 23411223 Mn 23411223 Ni 23411223 Pb 23411223 Rb 23411223 Sr 23411223 V 23411223 Zn 23411232 1,25 dihydroxy vitamin D(3) 23411232 25-hydroxy vitamin D(3) 23411232 Vitamin D(3) 23411232 vitamin D(3) 23411232 vitamin D3 23411236 N-acetylglucosamine 23411236 chitobiose 23411236 chitotriose 23411239 Organophosphorus 23411239 cypermethrin 23411239 diazinon 23411239 fenitrothion 23411239 organophosphorus 23411239 permethrin 23411239 pyrethroid 23411248 zinc 23411250 3-hydroxy-4-nitroso-2,7-naphthalenedisulfonic acid 23411250 Fe(II) 23411250 Fe(III) 23411250 NRS 23411250 polyphenols 23411250 pyrogallic acid 23411252 lutein 23411252 lycopene 23411252 phytoene 23411252 phytofluene 23411252 vitamin A 23411252 zeaxanthin 23411252 α-carotene 23411252 β-carotene 23411252 β-cryptoxanthin 23411255 ascorbate 23411255 ascorbic acid 23411255 carbonyls 23411255 glutathione 23411255 peroxides 23411265 Phytosterols 23411265 Phytosteryl sinapates 23411265 oxygen 23411265 phenolic acids 23411265 phytosterols 23411265 phytosteryl esters of fatty acids 23411265 phytosteryl phenolates 23411265 phytosteryl sinapates 23411265 phytosteryl vanillates 23411265 sinapic or vanillic acid 23411265 vanillates 23411265 vanillic acid 23411265 vinyl vanillate 23411268 (1)H 23411268 1H 23411271 azo 23411271 caffeates 23411271 caffeic and dihydrocaffeic esters 23411271 cysteinyl thiol 23411271 methyl caffeate 23411271 methyl dihydrocaffeate 23411271 thiol 23411272 carbonyl 23411272 carbonyls 23411272 catechin 23411272 glucose 23411272 methylglyoxal 23411272 procyanidins 23411283 Biguanide 23411283 Biguanides 23411283 biguanide 23411283 biguanides 23411283 guanidine 23411283 metformin 23411284 oxygen 23411284 vitamin A 23411284 β-Carotene 23411284 β-carotene 23411306 Allura red 23411306 Azophloxine 23411306 Erythrosine 23411306 Ethanol 23411306 Orange II 23411306 Ponceau 4RC 23411306 Ponceau xylidine 23411306 Sunset yellow 23411306 ammonia 23411306 sulfonate 23411307 Fatty acid 23411307 MUFA 23411307 PUFA 23411307 SFA 23411307 fatty acid 23411307 fatty acids 23411311 C11:0 23411311 C8:0 23411311 SFA 23411311 SFAs 23411311 UFA 23411311 UFAs 23411311 caprylic acid 23411311 dienoic acid 23411311 fatty acids 23411311 p-anisidine 23411311 saturated fatty acids 23411311 sesamol 23411311 unsaturated fatty acids 23411312 5-hydroxymethylfurfural 23411312 ACs 23411312 HMF 23411312 anthocyanin 23411312 anthocyanins 23411312 polyphenols 23411312 sugars 23411314 DPPH 23411314 fatty acids 23411314 fucosterol 23411314 hydroxyl 23411314 mannitol 23411314 nitric oxide 23411314 oleic, arachidonic and eicosapentaenoic acids 23411314 phloroglucinol 23411314 proline 23411314 sterols 23411314 superoxide 23411334 EGCG 23411334 L-5-methyltetrahydrofolate 23411334 catechin 23411334 catechins 23411334 epigallocatechin-gallate 23411334 hydrogen 23411334 l-5-MTHF 23411334 l-5-methyltetrahydrofolate 23411335 ascorbic acid 23411335 natamycin 23411335 sugar 23411340 ascorbic acid 23411340 barium diphenylamine sulphonate 23411340 diphenylamine 23411340 manganese(III) 23411340 manganese(III) sulphate 23411340 vitamin C 23411342 2,2'- azobisisobutyronitrile 23411342 2-vinylpyridine 23411342 HCl 23411342 Pb(II) 23411342 Pb(NO(3))(2) 23411342 acetonitril 23411342 diphenylcarbazone 23411342 ethylene glycol dimethacrylate 23411351 carbaryl 23411351 carbohydrate 23412078 (14)C-glucose 23412078 (3)H-glucose 23412078 Canagliflozin 23412078 Glucose 23412078 acetaminophen 23412078 canagliflozin 23412078 glucose 23412078 sodium 23412396 (35)S 23412396 CP55,940 23412396 JZL184 23412396 Monoacylglycerol 23412396 THC 23412396 [(3)H]SR141716A 23412396 monoacylglycerol 23412396 rimonabant 23412396 Δ(9)-tetrahydrocannabinol 23412992 ATP 23412992 K+ 23412992 Na+ 23412992 NaK 23412992 potassium 23412992 sodium 23412992 steroid 23412992 steroids 23413033 Potassium 23413033 potassium 23413101 nitric oxide 23414252 hydrogen 23414252 methyl 23414433 METH 23414433 dopamine 23414433 methamphetamine 23414802 2-hydroxydiarylamide 23414802 serine 23414841 (99m)Tc 23414841 (99m)TcN-[G3-c(RGDfK)]2 23414841 Arg-Gly-Asp 23414841 G3-c(RGDfK) 23414841 G3=Gly-Gly-Gly 23414841 K=Lys 23414841 [(99m)TcN](+2) 23414841 dithiocarbamate 23414841 f=Phe 23415714 5α-dihydrotestosterone 23415714 Androgen 23415714 DHT 23415714 androgen 23415714 flutamide 23415714 prostaglandin 23415893 2-glucosamine 23415893 glucosamine 23415893 prednisolone 23415893 prednisolone carbamate 23416001 isatin 23416001 ketone 23416001 spirocycles 23416011 Celecoxib 23416011 budesonide 23416011 celecoxib 23416011 nitro 23416011 nitro-substituted 21-ester 23416011 nitro-substituted acylsulfonamide 23416011 nitropheny 23416011 prednisolone 23416070 fatty acid 23416070 glucose 23416115 CGA 23416115 Chlorogenic acid 23416115 chlorogenic acid 23416115 fatty acid 23416115 glucose 23416191 HJC0123 23416191 estrogen 23416192 2-(5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles 23416192 3-(2-bromoacetyl)coumarins 23416192 5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-thiocarboxamides 23416192 cefixime 23416192 indomethacin 23416192 thiosemicarbazide 23416192 trifluoromethyl-β-diketones 23416229 acetylcholine 23416262 oxygen 23416264 2,5-dimethylfuran 23416264 Formaldehyde 23416264 acetaldehyde 23416264 acrolein 23416264 aldehyde 23416264 aldehydes 23416264 formaldehyde 23416264 hydroquinone 23416264 nicotine 23416326 (32)P 23416326 PAH 23416326 PAHs 23416326 nucleotides 23416409 Hg 23416409 HgCl2 23416409 Mercury 23416409 mercuric chloride 23416409 mercury 23416650 urushiol 23416930 rapamycin 23416930 resveratrol 23416930 spermidine 23417420 5α-dihydrotestosterone 23417420 DHT 23417420 androgen 23417717 copper 23417790 Hg 23417790 mercury 23417790 methylmercury 23418006 Catechols 23418006 catechol 23418011 Dha 23418011 Lys 23418011 N-acetylneuraminic acid 23418011 amino acid 23418011 cysteine 23418011 dehydroalanine 23418011 lysine 23418011 pyruvate 23418011 thialysine 23418011 γ-thialysine 23418059 polybrominated diphenylether 23418059 polychlorinated biphenyls 23418087 BPA 23418087 Bisphenol A 23418087 CpG 23418087 bisphenol a 23418087 calcium 23418087 phospho 23418087 sodium 23418674 EtOAc 23418674 berberine 23418859 LY294002 23418859 Salidroside 23418859 dUTP 23418859 salidroside 23418880 (-)-sukhodianine-β-N-oxide 23418880 corydalmine 23418880 corynoxidine 23418880 crebanine N-oxide 23418880 dehydrocorydalmine 23418880 demethylaristofolin C 23418880 denitroaristolochic acid 23418880 methicillin 23418880 palmatine 23418960 CO(2) 23418960 D-α-tocopheryl PEG 1000 succinate 23418960 Gelucire 23418960 PEG 23418960 PGN 23418960 TPGS 23418960 carbon dioxide 23418960 polyethylene glycol 23418960 progesterone 23419007 ketosteroid 23419139 1'-hydroxymidazolam 23419139 4-hydroxymidazolam 23419139 midazolam 23419139 thalidomide 23419143 Au 23419143 Cu 23419143 Pd 23419143 Si 23419143 copper 23419593 K(+) 23419638 2,3,7,8-tetrachlorodibenzodioxin 23419638 Pelargonidin 23419638 TCDD 23419638 anthocyanidins 23419638 aryl hydrocarbon 23419638 cyanidin 23419638 delphinidin 23419638 malvidin 23419638 pelargonidin 23419638 peonidin 23419638 petunidin 23419783 Metformin 23419783 Sulfonylureas 23419783 metformin 23419783 sulfonylurea 23419783 sulfonylureas 23419813 6-carboxy 23419813 PEG 23419813 Polyethylene glycol 23419813 acrylic 23419813 ketoconazole 23419814 fentanyl 23419950 PEG 23419950 hydroxyl 23419950 mannose 23419950 mannoside 23419950 methoxy 23420115 Caffeine 23420115 Theobromine 23420115 caffeine 23420115 methylxanthine 23420115 theobromine 23420400 1,3,5,7-tetranitro-1,3,5,7-tetrazocine 23420400 C-NO(2) 23420400 HMX 23420400 N(3) 23420400 NH(2) 23420400 NHC(NO(2))(3) 23420400 NO(2) 23420400 Trinitromethyl-substituted aminotetrazoles 23420400 nitro 23420400 tetrazole 23420400 trinitromethyl-substituted aminotetrazole 23420471 P3HT 23420471 PCBM 23420471 TiO2 23421331 glucose 23421331 metformin 23421617 LAS-6 23421617 linalool 23421617 phenylethanol 23421617 sodium dodecyl 6-benzene sulfonate 23421714 (M)- and (P)-Bicelaphanol A 23421714 (M)-Bicelaphanol A 23421714 (P)-bicelaphanol A 23421714 Trinorditerpenes 23421714 celaphanol A 23421714 hydrogen peroxide 23421737 15β,16α-dihydroxyl-17βH-bufalin 23421737 3-epi-desacetylcinobufagin 23421737 3-keton-desacetylcinobufagin 23421737 bufadienolide A 23421737 desacetylcinobufagin 23421743 1,2-diacyl-sn-glycero-3-dehydrophenylalanine ester 23421743 ABTS 23421743 CHCl(3) 23421743 Dehydrophenylalanine 23421743 Dorsamin-A 23421743 Ester 23421743 Trolox 23421743 dorsamin-A 23421743 dorsamin-A763, -A737, -A765, -A739, and -A767 23421877 4(R),15-dihydroxyatractylenolide II 23421877 4(R),15-epoxy-13-hydroxyatractylenolide II 23421877 4(R),15-epoxy-1β-hydroxyatractylenolide II 23421877 4(R),15-epoxy-atractylenolide II 23421877 atractylenolide II 23421877 eudesmane 23421877 sesquiterpenoid lactones 23421877 sodium phenobarbital 23422033 AMP 23422033 Resveratrol 23422033 resveratrol 23422034 phenol 23422034 phenols 23422226 2-hydroxy-24-methylenelanostan-1,8-dien-3-one 23422226 6-O-acyl-β-d-glucosyl-β-sitosterol 23422226 Lanostane 23422226 klainedoxalanostenone 23422226 klainedoxasterol 23422226 lanostane 23422226 lanostane triterpenoid 23422226 steroid 23422226 steroids 23422226 tanins 23422226 triterpenoid 23422226 triterpenoids 23422226 xanthine 23422227 chloroform 23422227 sesquiterpenes 23422263 17β-estradiol-2,3-quinone 23422263 17β-estradiol-3,4-quinone 23422263 E2-2,3-Q 23422263 E2-3,4-Q 23422263 cysteinyl 23422263 estrogen 23422263 estrogen quinones 23422263 estrogen-3,4-quinone 23422733 Diclofenac sodium 23422733 PEO 23422733 Soluplus 23422733 polycaprolactone 23422872 peramivir 23423243 acetylsalicylic acid 23423243 warfarin 23423353 Hoechst 33258 23423468 4',6-diamidino-2-phenylindole 23423468 DAPI 23423468 amidine 23423695 glucose 23423695 triglycerides 23423710 5-Aza-2'-deoxycytidine 23423710 Aza-CdR 23423710 MTT 23423942 17β-estradiol 23423942 17β-trenbolone 23423942 estradiol 23423942 trenbolone 23423972 N-nitroso 23423972 hexahydro-1,3,5-trinitro-1,3,5-triazine 23423972 hexahydro-1,3,5-trinitroso-1,3,5-triazine 23423972 hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine 23423972 hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine 23423972 γ-aminobutyric acid 23424012 MTT 23424012 longicarposides A-I 23424012 oleanane 23424012 saponins 23424012 sugar 23424012 triterpenoid saponins 23424028 Permethrin 23424028 carbon 23424028 permethrin 23424028 pyrethoid permethrin 23424207 3β-hydroxysteroid 23424207 Cadmium 23424207 Cd 23424207 GSH 23424207 RUT 23424207 Rutin 23424207 S 23424207 Se 23424207 Selenium 23424207 cadmium 23424207 glutathione 23424207 lactate 23424207 rutin 23424207 selenium 23424207 superoxide 23424207 testosterone 23424208 3-hydroxy-3-methylglutaryl 23424208 3β-hydroxysterol 23424208 Probucol 23424208 Simvastatin 23424208 Triparanol 23424208 cholesterol 23424208 potassium 23424208 probucol 23424208 simvastatin 23424208 triparanol 23424212 Aspartate 23424212 MTX 23424212 RVT 23424212 Resveratrol 23424212 S 23424212 alanine 23424212 glutathione 23424212 methotrexate 23424212 resveratrol 23424212 thiobarbituric acid 23424212 trans-3,5,4'-trihydroxystilbene 23424213 GSH 23424213 MDA 23424213 NO 23424213 alanine 23424213 aspartate 23424213 bilirubin 23424213 eosin 23424213 glutathione 23424213 hematoxylin 23424213 malondialdehyde 23424213 nitric oxide 23424213 nitrogen 23424213 superoxide 23424213 urea 23425339 Fe(H2O)6(2+) 23425339 Fe(II) 23425339 Fe(III) 23425339 FeCl2 23425339 [FeCl4](-) 23425339 acetone 23425339 iron 23425601 1β, 3β, 21β-trihydroxy-urs-12-en-28-oic acid 23425601 21-oxo-1β, 3β-dihydroxy-urs-12-en-28-oic acid 23425601 3β, 21β-dihydroxy-urs-11-en-28-oic acid-13-lactone 23425601 3β, 7β, 21β-trihydroxy-urs-1-en-28-oic acid-13-lactone 23425601 3β, 7β, 21β-trihydroxy-urs-12-en-28-oic acid 23425601 3β-hydroxy-urs-12-en-28-oic acid 23425601 ursolic acid 23425604 N (2)-ethylidene-dG 23425604 N(2)-ethylidene-dG 23425604 [(13)C2]-acetaldehyde 23425604 [13C2]-Acetaldehyde 23425604 acetaldehyde 23425605 3-hydroxybenzylhydrazine 23425605 MeHg 23425605 calcium 23425605 catecholamine 23425605 dopamine 23425605 methylmercury 23425605 tyrosine 23425605 α-methyltyrosine 23426609 ethosuximide 23426609 lacosamide 23426609 levitiracetam 23426609 phenobarbital 23426609 phenytoin 23426609 tiagabin 23426609 valproic acid 23426609 vigabatrin 23426609 zonisamide 23426718 Paricalcitol 23426718 calcitriol 23426718 paricalcitol 23426718 vitamin D 23426954 (-)-3cis -[2-hydroxyl-4-(1,1-dimethyl-heptyl)phenyl]-trans-4-[3-hydroxyl-propyl] cyclohexan-1-ol 23426954 (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]-pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthalenyl)-methanone mesylate 23426954 CP55,940 23426954 N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride 23426954 SR141716A 23426954 WIN55,212-2 23426954 alanine 23426954 aspartate 23426954 guanosine 5'-3-O-(thio)triphosphate 23426982 Br 23426982 Methanol 23426982 Nona-BDEs 23426982 PBDEs 23426982 Polybrominated diphenyl ethers 23426982 methanol 23426982 nona-BDE 23426982 nona-BDEs 23426982 octa-BDE 23426982 octa-BDEs 23426982 penta-Br 23426982 phenyls 23426982 tetra-Br 23427007 25-hydroxyvitamin D 23427007 25OHD 23427007 vitamin D 23427007 vitamin D(3) 23427056 creatinine 23427056 glucose 23427063 Disperse Red 1 23427063 poly(methyl metha-acrylate) 23427064 Cd 23427064 cadmium 23427074 1,3- and 1,5-DP 23427074 Dechlorane Plus 23427074 Dechlorane plus 23427074 carbon 23427076 Au 23427076 SiO2 23427088 Titanium dioxide 23427088 pyrophosphate 23427137 4-cyanoresorcinol 23427137 azobenzene 23427850 PDMS 23428155 (pyridin-3-yl) benzoxazinyl-oxazolidinones 23428155 Oxazolidinone 23428155 benzoxazinyl-oxazolidinone 23428155 imidazolidinone 23428155 linezolid 23428155 pyridyl 23428212 2,2,6,6-tetramethylpiperidine-1-oxyl 23428212 Carbon 23428212 TEMPO 23428212 carbon 23428212 graphene 23428212 sodium carboxyl 23428325 brassinosteroid 23428325 brassinosteroids 23428347 Bortezomib 23428347 bortezomib 23428841 Lecithin 23428841 TAM 23428841 Tamoxifen 23428841 Tamoxifen citrate 23428841 lecithin 23428841 tamoxifen 23428841 tamoxifen citrate 23429043 1,2-Benzisothiazolin-3-one 23429043 1,2-benzisothiazolin-3-one 23429043 2634-33-5 23429043 BIT 23429184 Ca(2+) 23429184 N 23429184 PMSF 23429184 lactose 23429184 serine 23429231 N-vinylpyrrolidone 23429231 NVP 23429231 RhodaminB 23429231 poly[acrylonitrile-co-(N-vinylpyrrolidone)] 23429282 avarol 23429282 avarol and its monoacetate 23429282 sesquiterpenoids 23429889 Rosuvastatin 23429889 cholesterol 23429889 rosuvastatin 23429911 7-OH-DPAT 23429911 7-hydroxy-N,N-dipropyl-2-aminotetralin 23429911 dexamethasone 23429911 dopamine 23429911 retinoic acid 23430408 (14)C 23430408 thiamethoxam 23430761 P188 23430761 P407 23430761 hydroxypropylmethyl 23430761 ondansetron 23430761 poloxamers 23432004 Gd 23432004 gadolinium 23432007 (89)Zr 23432007 DFO 23432007 DFO-Bz-NCS 23432007 N-suc-DFO 23432007 desferrioxamine 23432007 lysine 23432061 Ca2+ 23432095 17β-hydroxysteroid 23432095 2'-des-methyl-indomethacin 23432095 5α-dihydrotestosterone 23432095 Indomethacin 23432095 NADP(+) 23432095 androgen 23432095 androgens 23432095 indomethacin 23432095 testosterone 23432151 2-dodecanyl-7-β isopranyl monoscodilone 23432151 2-n-butyloxo-6-β-hydroxy-7-β-isoprenyl ankaflavin 23432151 2-n-undecanyloxo-7-β-isoprenyl ankaflavin 23432151 9H-1-isoprenyl-benzopyran-5-isopropanoic acid-6-ol-6-n-decanoate 23432151 Silica gel 23432151 acetonitrile 23432151 benzopranyl capriate 23432151 carbon tetrachloride 23432151 ethyl acetate 23432151 hordeumflavin B 23432151 n-octadec-8,11-dien-7α-ol-1-oic acid 23432151 shorghumoic acid 23432151 sorghumflavin A 23432151 vulgaredilone 23432203 N 23432203 amino acids 23432203 p-chloroamphetamine 23432203 α-amino 23432335 (Z)-13,15-hexadecadien-2,4-diyn-1-ol 23432335 Montiporic acid D 23432335 montiporic acid D 23432335 polyacetylene alcohol 23432335 polyacetylene carboxylic acid 23432582 BSC 23432582 Bisacylimidoselenocarbamate 23432582 Bisacylimidoselenocarbamates 23432582 phosphatidylserine 23432582 z-VAD-fmk 23432586 Ca(2+) 23432586 Ca2+ 23432586 FK506 23432586 rapamycin 23432586 sirolimus 23432586 tacrolimus 23432587 Aminophosphonate 23432587 aminophosphonate 23432587 aminophosphonic acids 23432587 gadolinium 23432587 phosphonate 23432587 platinum 23432587 rhenium 23432587 samarium 23432587 technetium 23432708 CS 23432708 Carbon monosulfide 23433812 ATP 23433812 arsenate 23433812 dNTP 23434226 Tyr 23434226 tyrosine 23434228 6-bromo-7-hydroxycoumarin 23434228 6-bromo-7-methoxycoumarin 23434228 6-diethylaminocoumarin 23434228 BHC 23434228 BMCM 23434228 DEACM 23434228 cholesterol 23434228 cholesterols 23434228 coumarin 23434322 5-(hydroxy)methylcytosine 23434322 5-carboxylcytosine 23434322 5-formyl 23434322 5-hydroxymethyl 23434322 5-methylcytosine 23434322 caC 23434322 cytosine 23434322 hmC 23434422 Euryspongins A-C 23434422 bicyclic furanosesquiterpene 23434422 dehydroeuryspongin A 23434422 euryspongins A-C 23434422 furan 23434422 sesquiterpenes 23434422 α,β-unsaturated-γ-lactone 23434491 17β-estradiol 23434491 7-ethoxyresorufin 23434491 E2 23434491 KTC 23434491 O 23434491 estrogen 23434491 ketoconazole 23434491 steroid 23434641 1,3,4-oxadiazoles 23434641 2-benzylsulfanyl-nicotinic acid 23434641 5-(2-benzylsulfanyl-pyridin-3-yl)-2-(substituted)-sulfanyl-1,3,4-oxadiazoles 23434641 5-(2-benzylsulfanyl-pyridin-3-yl)-3H-[1,3,4]oxadiazole-2-thione 23434641 C 23434641 H 23434641 N 23434641 ampicillin 23434641 benzothiazole 23434641 haloacetate 23434641 haloalkyl 23434641 morpholine 23434641 rifampicin 23434641 triazole 23434648 C 23434648 LPA 23434669 ATP 23434669 Rapamycin 23434669 rapamycin 23434929 Catecholamine 23434929 Corticosterone 23434929 Somatostatin 23434929 Streptozotocin 23434929 corticosterone 23434929 somatostatin 23434931 oxygen 23434931 tunicamycin 23434934 nucleotide 23435179 acetylcholine 23435179 disulfide 23435356 5-HT 23435356 Serotonin 23435356 Tryptophan 23435615 (R)- and (S)-omeprazole 23435615 (R)-5-hydroxyomeprazole 23435615 (R)-omeprazole 23435615 (S)-5-hydroxyomeprazole 23435615 (S)-omeprazole 23435615 Omeprazole 23435615 omeprazole 23435615 omeprazole sulfone 23435615 racemic omeprazole 23435615 racemic-omeprazole 23435910 DMN 23435910 Sinapic acid 23435910 alanine 23435910 aspartate 23435910 dimethylnitrosamine 23435910 hydroxyproline 23435910 malondialdehyde 23435910 phenylpropanoid 23435910 sinapic acid 23435913 Tadalafil 23435913 acebutolol 23435913 acetonitrile 23435913 formic acid 23435913 tadalafil 23435913 tert-butyl methyl ether 23435916 NO 23435916 Pristimerin 23435916 nitric oxide 23435916 pristimerin 23435916 prostaglandin E2 23435916 quinonemethide triterpenoid 23435942 acetylcholine 23435942 coumarin 23435942 donepezil 23435942 flavonoid 23435942 galantamine 23435942 para-aminobenzoic acid 23435942 pyrrolo-isoxazole 23435942 rivastigmine 23435942 tacrine 23435942 xanthostigmine 23435948 1,5-dicaffeoylquinic acid 23435948 3,4-dicaffeoylquinic acid 23435948 3,5-dicaffeoylquinic acid 23435948 3,5-dicaffeoylquinic acid methyl ester 23435948 3-caffeoylquinic acid 23435948 4,5-dicaffeoylquinic acid 23435948 6-methoxy artemicapin C 23435948 7-methoxy coumarin 23435948 acarbose 23435948 arcapillin 23435948 capillarisin 23435948 chromone 23435948 cirsilineol 23435948 coumarins 23435948 daphnetin 23435948 dicaffeoylquinic acids 23435948 esculetin 23435948 esculin 23435948 flavonoids 23435948 hyperoside 23435948 isorhamnetin 23435948 isorhamnetin 3-glucoiside 23435948 isorhamnetin 3-robinobioside 23435948 isoscopolin 23435948 linarin 23435948 methanol 23435948 phenolic 23435948 quercetin 23435948 scoparone 23435948 scopoletin 23435948 scopolin 23435948 tyrosine 23435948 umbelliferone 23436129 Acamprosate 23436129 GABA 23436129 acamprosate 23436129 gamma-aminobutyric acid 23436129 glutamate 23436266 Allopurinol 23436266 alanine 23436266 allopurinol 23436266 aspartate 23436266 cholesterol 23436266 colchicine 23436266 colchicines 23436266 statins 23436266 uric acid 23436544 Vemurafenib 23436544 vemurafenib 23436791 2-aminothiazole 23436791 2-aminothiazoles 23436791 ATP 23436791 indolyl-pyrrolone 23436791 paclitaxel 23436791 serine 23436791 threonine 23437766 4-(adamantan-1-ylaminomethyl)-benzene-1,3-diol 23437766 amantadine 23437766 benzyl 23437766 rimantadine 23437926 ATP 23437926 CTOP 23437926 Hecogenin 23437926 Hecogenin Acetate 23437926 K(+) 23437926 glibenclamide 23437926 hecogenin acetate 23437926 naloxone 23437926 naltrindole 23437926 nor-BNI 23438500 Br(-) 23438500 Br- 23438500 Pd 23438503 Atomoxetine 23438503 atomoxetine 23438503 methylphenidate 23439033 hydrofluoroether 23439131 PEG 23439131 poly(ethylene glycol) 23439223 cortisol 23439223 estradiol 23439223 steroid 23439223 testosterone 23439241 bupropion 23439241 phenacetin 23439561 NADPH 23439561 PGE2 23439561 Prostaglandin E 23439561 calcium 23439561 prostaglandin E 23439561 prostaglandin E2 23439561 thymidine 23439649 (125)I 23439649 Phe 23439649 oxyester 23439649 thioester 23439660 Aryl hydrocarbon 23439660 androstane 23439660 noroxycodone 23439660 oxycodone 23439660 oxymorphone 23440404 Au 23440404 Au-S-C 23440404 Au-S-C-C 23440404 BDT 23440404 C=C 23440404 gold-1,4-benzenedithiol 23440404 thiol sulfur 23440664 HCl 23440664 Nikkomycin Z 23440664 cGMP 23440956 Graphene 23440956 Lithium 23440956 Si 23440956 Silicon 23440956 graphene 23440956 graphene oxide 23440956 lithium 23441753 Isoniazid 23441753 hydrated poly(N-isopropylacrylamide) 23441753 pNIPAAm 23441753 poly(N-isopropylacrylamide) 23441816 Ca(2+) 23441829 C-H 23441829 C2H4 23441829 C2H6 23441829 C4H10 23441829 C4H8 23441829 V2O5 23441829 V2O5H2 23441829 hydrocarbons 23441829 hydrogen 23441829 n-butane 23441829 oxide 23441843 Bisulfite 23441843 Lig 23441843 Z-Ligustilide 23441843 Z-ligustilide 23441878 Br 23441878 C 23441878 CCl4 23441878 CHBr2 23441878 CHBr3 23441878 CHI2 23441878 CHI3 23441878 H 23441878 I 23441878 halogen 23441878 polyhalomethanes 23442005 3-methylbutanal 23442005 Aliphatic Aldehydes 23442005 C 23442005 aldehyde 23442005 aldehydes 23442005 aliphatic aldehyde 23442005 aliphatic aldehydes 23442005 amino sulfonamide 23442005 carbonyl 23442005 enamine 23442005 proline 23442005 α-chloroaldehydes 23442005 α-methylene 23442025 Fe(CN)(6)(3–) 23442025 H 23442025 H(2)O 23442025 OH(–) 23442025 argon 23442025 methyl 23442151 H 23442151 H2 23442151 H2O2 23442151 NaCl 23442151 Phenol 23442151 Sodium hypochlorite 23442151 benzene 23442151 chlorine 23442151 oxygen 23442151 phenol 23442151 sodium hypochlorite 23442151 •OH 23442197 A-74528 23442197 C30 polyketide 23442197 fredericamycin 23443405 Si 23443405 ZnO 23443405 silicon 23443405 zinc oxide 23443408 O-Ti-O 23443408 TiO2 23443408 Titanium dioxide 23443408 nucleotide 23443408 oxygen 23443408 titanium dioxide 23443628 donepezil 23443628 galantamine 23443628 memantine 23443628 rivastigmine 23443957 PtTFPP 23443957 oxygen 23443957 platinum(ii)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorphenyl)-porphyrin 23444256 Emtricitabine 23444256 FTC 23444256 TDF 23444256 Truvada 23444256 emtricitabine 23444256 tenofovir disoproxil fumarate 23444284 nevirapine 23444335 iron 23444335 selenium 23444335 zinc 23444387 NADH 23444387 NADPH 23444387 carbonyl 23444387 haloperidol 23444387 mebendazole 23444387 menadione 23444387 ziprasidone 23444389 ADP 23444389 ATP 23444389 Ca(2)(+) 23444389 Ginsenoside Rb1 23444389 Ginsenosides 23444389 Rb1 23444389 azide 23444389 diazoxide 23444389 ginsenosides 23444389 glucose 23444389 nifedipine 23444389 saponins 23444389 streptozotocin 23444429 poly(ADP-ribose) 23444773 MMC 23444773 cisplatin 23444773 mitomycin C 23444782 alanine 23444782 aspartate 23444782 sibutramin 23444783 Glu 23444783 glutamate 23444785 MDA 23444785 Malondialdehyde 23444785 superoxide 23444833 4,8-diamino-3-hydroxyoctanoic acid 23444833 Asn 23444833 Dhb 23444833 FOHOrn 23444833 Iron 23444833 LySta 23444833 Lystabactins 23444833 Ser 23444833 amino acid 23444833 asparagine 23444833 dihydroxy benzoic acid 23444833 formylated/hydroxylated ornithines 23444833 lystabactins 23444833 lystabactins A, B, and C 23444833 nonproteinogenic amino acid 23444833 serine 23445125 amines 23445125 erythromycin 23445362 Arylazanylpyrazolone 23445362 Cu 23445362 Zn 23445362 arylazanylpyrazolone 23445362 arylazanylpyrazolones 23445362 aryloxanylpyrazolone 23445362 arylsulfanylpyrazolone 23445362 phenol 23445362 pyrazolone 23445362 superoxide 23445497 O-carboxyanhydrides 23445497 Phe-OCA 23445497 PheLA 23445497 camptothecin 23445497 docetaxel 23445497 doxorubicin 23445497 hydroxyl 23445497 paclitaxel 23445497 phenyl O-carboxyanhydride 23445497 poly(O-carboxyanhydride) 23445497 polylactide 23446230 EETs 23446230 arachidonic acids 23446230 epoxyeicosatrienoic acids 23446276 Mg(2+) 23446276 adenine 23446276 urea 23447132 cAMP 23447132 calcium 23447132 nucleotide 23447427 Cu(2+) 23447427 H2 23447427 ZnIn2 S4 23447427 copper 23447427 hydrogen 23447427 sulphide 23447538 serine 23447538 tryptic 23448196 glucose 23448202 cadmium telluride 23448384 2,3-di(2-pyridinyl)pyrazine 23448384 H2ba 23448384 H2ca 23448384 H2fa 23448384 H2xa 23448384 Hfa(-) 23448384 MeOH 23448384 [H(1.5)-dppz]2[Hba]3 23448384 [H-dppz(+)][Hfa(-)] 23448384 [H-dppz(+)][Hfa(-)]·MeOH 23448384 [H-dppz]2[Hba]2[H2ba] 23448384 [H-dppz][Hba] 23448384 [H-dppz][Hca] 23448384 [dppz][H2fa] 23448384 anilic acids 23448384 bromanilic acid 23448384 chloranilic acid 23448384 dppz 23448384 ethanol 23448384 fluoranilic acid 23448384 hydrogen 23448384 methanol 23448620 carbazochrome sodium sulfonate 23448620 tinidazole 23448682 PEG 23448682 dinorbornene 23448682 ene 23448682 norbornene 23448682 tetrazine 23448682 thiol 23448860 Mn 23448860 manganese 23448861 crotonaldehyde 23448861 ethenone 23448861 oxygen 23449201 Lactose 23449201 hydroxypropyl 23449201 hydroxypropyl methyl 23449201 lactose 23449201 polyvinylpyrrolidone 23449205 (3R),(5S)-5-hydroxylasiodiplodin 23449205 (3R)-lasiodiplodin 23449205 (3S),(6R)-6-hydroxylasiodiplodin 23449205 EtOH 23449205 Lasiodiplodin 23449205 lactone 23449220 5-fluoro-2'-deoxyuridine 23449220 FdU 23449220 FdUMP 23449220 deoxythymidine 23450151 Ag 23450151 Cd 23450151 DHLA-PEG 23450151 In 23450151 S 23450151 ZAIS 23450151 Zn 23450151 cadmium 23450151 folate 23450752 4-aryl-1,2,3,4-tetrahydropyrimidines 23450752 4-aryl-1,4-dihydropyridines 23450752 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines 23450752 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines 23450752 5,5-dimethyl 23450752 hydrogen 23450752 racemic 4-aryl-1,4-dihydropyridines 23450752 sulfur 23450752 tetraproline 23450777 C 23450777 C3 N4 23450777 Graphitic carbon nitride 23450777 N 23450777 carbon nitride 23450777 graphitic carbon nitride 23450777 hydrogen 23450829 Ti 23450829 TiO2 23451707 QAOs 23451707 sulfated quinazolin-4(3H)-ones 23451758 4-substituted imidazole 23451758 C2-D 23451758 C2-H 23451758 Cu(2+) 23451758 H 23451758 His 23451758 amino acid 23451758 deuterium 23451758 histidine 23451758 hydrogen 23451758 imidazole 23451797 Sesquiterpene Lactones 23451797 alantolides 23451797 racemosalactones A-E 23451797 sesquiterpene lactones 23451797 sesquiterpene latones 23451803 Au 23451803 Fe-PTCDA 23451803 PTCDA 23451803 perylene-3,4,9,10-tetracarboxylic-3,4,9,10-dianhydride 23451823 3'-deoxycapsanthin-5,6-epoxide 23451823 Cryptocapsin-5,6-epoxide 23451823 Cryptocapsinepoxide 23451823 cryptocapsin 23451823 cryptocapsin-5,6-epoxide 23451823 cryptocapsin-5,8-epoxide 23451823 cryptocapsin-5,8-epoxides 23451983 PFCE 23451983 fluorine 23451983 perfluoro-1,5-crown ether 23452042 N 23452042 N-hydroxyarylamine 23452042 NAD(+) 23452042 O 23452042 lysine 23452147 C 23452147 N 23452219 Purine 23452219 Theophylline 23452219 adenine 23452219 caffeine 23452219 guanine 23452219 methyl 23452219 purine 23452219 theophylline 23452254 (R, R)-[(R*PO3)2M5O15](2-) 23452254 (R, R)-[(R*PO3)2W5O15](2-) 23452254 CH3CH(NH3) 23452254 Mo 23452254 POMs 23452254 W 23452254 oxygen 23452254 polyoxometalates 23452254 transition metal 23452855 glutamate 23452855 glycine 23452857 N-methyl-D-aspartate 23452857 NMDA 23452857 serine 23453039 calcium 23453039 cholesterol 23453039 glucose 23453039 streptozotocin 23453039 triglyceride 23453067 2'-C-methyl-6-O-methyl guanosine nucleoside 23453067 2'-C-methyl-6-O-methyl- 23453067 2'-C-methyl-6-O-methylguanosine 23453067 2'-C-methylguanosine 23453067 6-O-methyl 23453067 L-Alanine ester phosphoramidates 23453067 N 23453067 guanine 23453067 guanine nucleosides 23453067 guanosine 23453067 nucleobase 23453067 nucleotide 23453068 4-alkylamino-7-aryl-3-cyanoquinoline 23453068 4-alkylamino-7-aryl-3-cyanoquinolines 23453068 Ser 23453068 leucine 23453303 MDA 23453831 4″-O-β-d-glucosyl-6'-O-(4-O-β-d-glucosylcaffeoyl)-linearoside 23453831 BHT 23453831 DPPH 23453831 Gentiopicroside 23453831 Gentioside 23453831 Gentisin 23453831 Iridoid glucosides 23453831 Isogentisin 23453831 Loganic acid 23453831 Norswertianolin 23453831 SRB 23453831 Sweroside 23453831 Swertiamarin 23453831 Swertianolin 23453831 Swertisin 23453831 catechin 23453831 flavonoid 23453831 flavonoids 23453831 hydroxyl 23453831 iridoid glucosides 23453831 iridoids 23453831 methanol 23453831 secoiridoids 23453831 sulphorhodamine B 23453831 xanthones 23453831 α-tocopherol 23454011 aluminum silicate 23454011 cholesterol 23454011 montmorillonite 23454011 stigmastanol 23454011 vitamin D3 23454011 vitamin D3 and K1 23454011 vitamin K1 23454011 vitamins 23454011 vitamins D3 and K1 23454052 ZnO 23454052 zinc oxide 23454054 IMC 23454054 SAC 23454054 indomethacin 23454054 methanol 23454054 saccharin 23454133 H 23454133 olanzapine 23454133 simvastatin 23454148 5-Fluorouracil 23454148 5-fluorouracil 23454148 Cisplatin 23454148 MMC 23454148 N 23454148 S 23454148 cisplatin 23454148 cysteine 23454148 dihydropyrimidine 23454148 glutathione 23454148 mitomycin C 23454148 prostaglandin E2 23454148 quinone 23454148 xanthine 23454208 N 23454208 bafilomycin A1 23454208 flavonoid 23454208 luteolin 23454297 ADP 23454297 ATP 23454297 Caffeic acid 23454297 adenine nucleotide 23454297 adenosine 23454297 caffeic acid 23454297 nucleoside triphosphate 23454297 nucleotide 23454308 Al(3+) 23454308 alumina 23454308 aluminium oxide 23454309 (15)N 23454309 Hg 23454309 mercury 23454309 methyl 23454310 silver 23454529 LZ-11 23454529 N-(2-(quinazolin-2-yl)phenyl)benzamide 23454529 QPB 23454529 benzofuroquinoline 23454529 hydrogen 23454529 indoloquinoline 23454529 phenyl 23454529 quinazoline 23454648 PAMAM 23454648 Polyamidoamine 23454648 amino 23454648 oxygen 23454648 polyamidoamine 23454829 (2R,3R,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-3-yl 4-O-(6-deoxy-β-D-glucopyranosyl)-α-D-glucopyranoside 23454829 8,11,14-eicosatrienoic acid 23454829 CS-1036 23454829 [(14)C]CS-1036 23454829 [14C]CS-1036 23454829 alanine 23454829 amino acid 23454829 amino acids 23454829 aspartic acid 23454829 fatty acids 23454829 glutamic acid 23454829 oleic acid 23454829 palmitic acid 23454829 proline 23455056 amide 23455056 bis(pinacolato)diboron 23455056 boron 23455056 boronate ester 23455056 oleanane 23455056 oleanolic acid 23455056 oleanolic vinyl boronates 23455056 palladium 23455056 triterpenoids 23455056 vinyl triflates 23455057 MTT 23455057 Ru(II) 23455057 [(C6H6)Ru(L)Cl]Cl·2H2O 23455057 arene 23455057 arene ruthenium(II) 23455057 p-BrPIP 23455057 p-CF3PIP 23455057 p-COOHPIP 23455057 p-HOPIP 23455057 p-MeOPIP 23455057 p-NMe2PIP 23455057 phenanthroimidazole 23455229 Au 23455312 Ca(2+ 23455312 Cholane 23455312 HENA 23455312 K(+) 23455312 LCA 23455312 Steroid 23455312 Thr 23455312 lithocholic acid 23455312 sodium 3-hydroxyolean-12-en-30-oate 23455312 steroid 23455314 (3-chlorophenyl)(6,7-dimethoxy-1-((4-methoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone 23455314 CIQ 23455314 N-methyl-d-aspartate 23455314 NMDA 23455314 amino 23455373 C18H37 23455373 OSiMe2 23455373 POSS 23455373 Polyhedral oligomeric silsesquioxane 23455373 Q8C18 23455373 T8C18 23455373 octa-n-octadecyloctasilsesquioxane 23455373 octakis(n-octadecyldimethylsiloxy)octasilsesquioxane 23455373 polyhedral oligomeric silsesquioxanes 23455513 O 23455513 carbohydrate 23455995 Spinosad 23455995 spinosad 23455995 λ-cyhalothrin 23456038 (1)H 23456038 (15)N 23456038 amide 23456038 phosphate 23456038 phospho 23456038 serine 23456038 threonine 23456097 N 23456248 amino acid 23456248 nitrogen 23456248 phosphatidylinositol 23456735 glucose 23456814 GSH 23456814 MDA 23456814 deoxyuridine triphosphate 23456814 glutathione 23456814 malondialdehyde 23456814 superoxide 23456816 sodium chloride 23456816 sodium hydroxide 23456892 ALN 23456892 RSG 23456892 Rosiglitazone 23456892 alendronate 23456892 deoxypyridinoline 23456892 rosiglitazone 23457119 MK-801 23457119 N-methyl-d-aspartate 23457119 NMDA 23457119 Scopolamine 23457119 [(18)F]FDG 23457119 [(18)F]fluoro-2-deoxy-d-glucose 23457119 [18F]FDG 23457119 glucose 23458167 silicon 23458385 poly(styrene sulfonate) 23458385 saccharide 23458422 PNB 23458422 Poly(NIPAM-co-BMA) 23458422 poly(N-isopropylacrylamide-co-butyl methacrylate) 23458422 sulfuric acid 23458573 Cocaine 23458573 cocaine 23458575 oxygen 23458617 Nutlin-3 23458617 cis-imidazoline 23458621 silica 23458727 A12 23458727 N-(3-carboxy-4-hydroxyphenyl)-2,5-dimethylpyrrole 23458727 N-(4-carboxy-3-hydroxyphenyl)-2,5-dimethylpyrrole 23458727 NB-2 23458730 Baicalin 23458730 DXM 23458730 baicalin 23458730 dextromethorphan 23458895 NAD(P)H 23458895 STZ 23458895 glucose 23458895 quinone 23458895 streptozotocin 23459146 NaF 23459146 eosin 23459146 estradiol 23459146 hematoxylin 23459146 progesterone 23459146 sodium fluoride 23459146 testosterone 23459233 H+ 23459233 N2 23459233 P 23459233 Phosphorus 23459233 succinate 23460347 PEG-DMA 23460347 poly(ethylene glycol)-dimethacrylate 23460383 1,4-butanediol 23460383 4,4'-methylenebis(phenylisocyanate) 23460383 Polyurethanes 23460383 Undecylenic Acid 23460383 diol 23460383 polyurethanes 23460383 telechelic diols 23460383 undecylenic acid 23461617 (-)-[R,R]- and (+)-[S,S]-1,2-DHD-6-NC 23461617 (-)-[R,R]- and (+)-[S,S]-1,2-Dihydroxy-1,2-dihydro-6-nitrochrysene 23461617 (±)-1,2-DHD-6-NC 23461617 (±)-trans-1,2-dihydroxy-1,2-dihydro-6-nitrochrysene 23461617 1,2-DHD-6-NC 23461617 6-NC 23461617 6-Nitrochrysene 23461617 6-nitrochrysene 23461650 cyanine 23461784 Germanium 23461784 germanium 23461784 lithium 23461784 silicon 23461821 4-aminophenol 23461821 4-nitrophenol 23461821 NaBH4 23461821 Silver 23461821 norbornene 23461821 polyamino oxanorbornenes 23461821 polyguanidino oxanorbornenes 23461821 polynorbornenes 23461821 silver 23461841 aldosterone 23461841 fatty acid 23461841 fatty acids 23461841 glucose 23461841 magnesium oxide 23461841 spironolactone 23461969 Ala 23461969 Arg 23461969 Asp 23461969 Gln 23461969 Glu 23461969 His 23461969 Ile 23461969 Pro 23461969 Trp 23461969 Tyr 23461969 phenyl 23462104 Cholesterol 23462104 cholesterol 23462193 Glucose 23462194 (125)I 23462194 Hoechst 33258 23462194 Iodine 23462194 MTT 23462194 Nevirapine 23462194 iodine 23462194 methly thiazolyl tetrazolium 23462194 nevirapine 23462212 Chebulinic acid 23462212 H(+) 23462212 K(+) 23462212 Sucralfate 23462212 alcohol 23462212 aspirin 23462212 chebulinic acid 23462212 omeprazole 23462213 VPA 23462213 Valproic acid 23462213 fluorescein 23462213 monocarboxylate 23462213 valproic acid 23462281 Thiamine 23462281 nicotinamide adenine dinucleotide phosphate 23462281 thiamine 23462281 tyrosine 23462379 N 23462380 neostigmine 23462505 17β-estradiol 23462505 Estrogen 23462505 bazedoxifene 23462505 estrogen 23462505 fulvestrant 23462505 raloxifene 23462505 tamoxifen 23462666 glucose 23463333 acetonitrile 23463333 formic acid 23463333 hexane 23463333 methanol 23463333 robenidine 23463333 trifluoroacetic acid 23463334 nifedipine 23463334 polyvinyl pyrrolidone 23463334 stearic acid 23463336 acetic acid 23463609 carbon 23463634 graphene 23463732 PFBV 23463732 PMMA 23463732 polyfluorene-bis-vinylphenylene 23463898 daunomycin 23464618 Carbon 23464618 carbon 23464667 Liquiritigenin 23464667 lactate 23464667 liquiritigenin 23464789 PHA 23464789 PHB 23464789 ester 23464789 hydroxyl 23464789 lithium borohydride 23464789 oligo(hydroxyalkanoate)diols 23464789 poly(3-hydroxybutyrate-co-4-hydroxybutyrate) 23464789 poly(3HB-co-4HB) 23464789 poly[(R,S)-3-hydroxybutyrate] 23464789 polyester 23464789 polyhydroxyalkanoates 23464859 silicon 23464990 BDP-G 23464990 BDP-Y 23464990 BODIPY 23464990 O2 23464990 Pt(II) 23464990 PtTPBP 23464990 SiO2 23464990 tetrabenzoporphyrin 23464990 tetraphenyl 23465066 GaS 23465066 MoS2 23465066 PET 23465066 Si 23465066 SiO2 23465066 graphene 23465066 polyethylene terephthalate 23465066 silicon 23465072 A1443 23465072 GABA 23465072 Glutamate 23465072 [(3)H]A1443 23465072 [(3)H]EBOB 23465072 [(3)H]Isoxazoline 23465072 [(3)H]ethynylbicycloorthobenzoate 23465072 avermectin 23465072 chloride 23465072 glutamate 23465072 isoxazoline 23465072 phenyl 23465594 AMP 23465594 Ethanol 23465594 Ser 23465594 Thr 23465594 acetyl CoA 23465594 acyl-CoA 23465594 alanine 23465594 carbohydrate 23465594 ethanol 23465594 fatty acid 23465594 stearoyl CoA 23465594 sterol 23465594 triglycerides 23465612 aspartates 23465612 carboxylic acid 23465612 dihydroisoquinoline 23465612 hydrogen 23466228 (11)C 23466228 1-fluoro-2-nitrobenzene 23466228 N 23466228 Olanzapine 23466228 [(11)C]CH3OTf 23466228 [(11)C]CO2 23466228 [(11)C]Olanzapine 23466228 [11C]olanzapine 23466228 malononitrile 23466228 piperazine 23466228 propionaldehyde 23466231 17α-bromo-21-iodo-3β-acetoxypregn-5-en-20-one 23466231 25-hydroxycholesterol 23466231 Pregna-5,17(20)-dien-21-oyl amides 23466231 [17(20)E]-pregna-5,17(20)-dien-21-oyl amides 23466231 [17(20)Z]- and [17(20)E]-pregna-5,17(20)-dien-21-oyl amides 23466231 [17(20)Z]-pregna-5,17(20)-dien-21-oyl amides 23466231 amide 23466231 sterol 23466231 triglyceride 23466235 Asp 23466235 hydrogen 23466444 oxygen 23466459 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 23466459 PhIP 23466459 heterocyclic amine 23466459 heterocyclic amines 23466461 FB1 23466461 FB2 23466461 Fumonisins 23466461 fumonisin B1 and B2 23466461 fumonisins 23466461 fumonisins B1 and B2 23466488 NTM 23466488 STZ 23466488 amide 23466488 amino acid 23466488 glucose 23466488 glutathione 23466488 l-glutamine 23466488 malondialdehyde 23466488 nicotinamide 23466488 sitagliptin 23466488 streptozotocin 23466488 stretpozotocin 23466488 sugar 23466874 glucose 23466874 phlorotannins 23466874 polyphenols 23466874 tyrosine 23468099 choline 23468099 glucose 23468310 5,7,4'-trihydroxy-3,6,8-trimethoxyflavone 23468310 Sarothrin 23468310 flavonoid 23468310 sarothrin 23468426 ACV 23468426 AhCV 23468426 AhCaG 23468426 AhCmC 23468426 Fe(II) 23468426 IPN 23468426 Isopenicillin N 23468426 cephalosporin 23468426 cysteinyl 23468426 iron 23468426 isopenicillin N 23468426 lactam 23468426 methylene 23468426 monocyclic hydroxy-lactam 23468426 penicillin 23468426 thioether 23468426 valinyl 23468426 δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine 23468426 δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-S-methylcysteine 23468426 δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-Xaa 23468426 δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-allylglycine 23468426 δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-valine 23469688 8-(Tosylamino)quinoline 23469688 8-(tosylamino)quinoline 23469688 8-TQ 23469688 BAY 11-7082 23469688 LY294002 23469688 U0126 23469781 Imiquimod 23469781 Quinolines 23469781 quinoline 23469781 quinolines 23469781 sitamaquinine 23469924 Androgen 23469924 androgen 23470034 3,7-dioxo-11β-hydroxy-5α-tirucalla-8,24(Z)-dien-26-oic acid 23470034 mastichinoic acid A 23470034 tetracyclic triterpenoid 23470076 amino acid 23470076 cysteine 23470076 cysteinyl 23470080 N 23470080 arginine 23470104 CH 23470104 CH2OH 23470104 CH3OH 23470104 Cl 23470104 Cl2 23470104 H 23470104 HCl 23470104 Hydroxymethyl 23470104 hydroxymethyl 23470105 guanine 23470152 Au(111) 23470152 adamantane 23470152 au(111) 23470152 ferrocene 23470152 ferrocenyl 23470152 phenyleneethynylene 23470152 sulfur 23470152 trithiol 23470280 ISO 23470280 catecholamine 23470280 catecholamines 23470280 dopamine 23470280 glutamate 23470280 isoproterenol 23470359 PFAAs 23470359 carboxylates 23470359 perfluoroalkyl acids 23470359 sulfonates 23470418 BPA 23470418 BPAF 23470418 BPF 23470418 BPZ 23470418 Bisphenol A 23470418 DMBPA 23470418 GSH 23470418 NADPH 23470418 benzene 23470418 bisphenol A 23470418 diphenylmethanes 23470418 glutathione 23470418 para-hydroxy 23470922 NADH 23470922 NADPH 23470922 nicotinamide adenine dinucleotide phosphate 23470922 plastoquinone 23471029 DHA 23471029 EPA 23471029 Mono- and dihydroxy 23471029 Resolvins 23471029 all-cis-4,7,10,13,16,19-docosahexaenoic acid 23471029 all-cis-5,8,11,14,17-eicosapentaenoic acid 23471029 cis-1,4,7,10-undecatetraene 23471029 fatty acid 23471029 mono- and dihydroxy 23471029 mono- and dihydroxy-resolvins 23471029 omega-3 and omega-6 fatty acid 23471029 omega-3 fatty acids 23471029 polyunsaturated fatty acids 23471029 resolvin 23471156 CeO2 23471156 Co3O4 23471156 CuO 23471156 NiO 23471156 ZnO 23471156 metal oxide 23471156 metal oxides 23471156 silver 23471218 oxygen 23471440 propionic acid 23471440 quinolones 23471488 glucose 23471488 lauric acid 23471488 metformin 23471504 Olmesartan medoxomil 23471504 olmesartan 23471504 olmesartan medoxomil 23471539 amino acids 23471561 Anthraquinone 23471561 bis-anthraquinone 23471710 amoxicillin 23471710 carbohydrate 23471710 clarithromycin 23471710 glucose 23471710 omeprazole 23471969 amino acid 23471969 amino acids 23472709 B 23472709 E-H 23472709 Fe-BPh 23472709 Fe-diphosphineborane 23472709 Fe≡NNR2 23472709 H 23472709 H-H 23472709 H2 23472709 Iron aminoimides 23472709 N2 23472709 PhSiH3 23472709 Si-H 23472738 Au25 23472738 SCH2CH2Ph 23472738 [Au25L18](-) 23472738 trialkylacryloylphosphonium salts 23472745 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid 23472745 2,2-diphenyl-1-picrylhydrazyl 23472745 N,N-dimethyl-p-phenylenediamine dihydrochloride 23472745 anthocyanin 23472745 anthocyanins 23472745 polyphenolic 23472803 Au 23472803 PMMA 23472803 au 23472803 poly(methyl methacrylate) 23472803 polystyrene 23472840 Pluronic F127 23472840 aspirin 23472840 erythromycin 23472840 ibuprofen 23472886 carboxyl 23472886 indenoisoquinoline 23472886 indenoisoquinoline rexinoids 23472886 indenoisoquinolines 23473024 Au 23473024 H2O2 23473024 citrate 23473024 hydrogen peroxide 23473024 poly-l-lysine 23473024 thiols 23473030 Iron 23473030 iron 23473037 leucine 23473037 nitric oxide 23473037 proline 23473444 GdIO 23473444 dopamine sulfonate 23473444 gadolinium 23473444 iron oxide 23473444 iron-oxide 23473664 glutamate 23473681 MAC13243 23473681 S-(4-chlorobenzyl)isothiourea 23473681 thiourea 23473801 ADP 23473801 Hinokitiol 23473801 ODQ 23473801 OH 23473801 SQ22536 23473801 arachidonic acid 23473801 calcium 23473801 hinokitiol 23473801 hydroxyl 23473802 cystine 23473802 disulfide 23473802 sodium 23473804 27-hydroxycholesterol 23473804 27OHC 23473804 7-ketocholesterol 23473804 7KC 23473804 7β-hydroxycholesterol 23473804 7βOHC 23473804 Ca(2+) 23473804 Fura-2 23473804 calcium 23473804 cholesterol 23473804 ellagic acid 23473804 ionomycin 23473804 oxysterol 23473804 oxysterols 23473804 resveratrol 23473804 α-tocopherol 23474013 cocaine 23474217 10-hydroxycamptothecine 23474217 20-deoxycamptothecine 23474217 9-methoxycamptothecine 23474217 camptothecine 23474319 Copper 23474319 Cu 23474319 GSH 23474319 MDA 23474319 S 23474319 carbonyl 23474319 copper 23474319 glutathione 23474319 lactate 23474319 malondialdehyde 23474319 myo-inositol 23474319 reduced GSH 23474319 reduced glutathione 23474319 superoxide 23474320 Cu 23474321 K(+) 23474321 Na(+) 23474323 cholesterol 23474323 creatinine 23474323 polyphenols 23474323 tannins 23474356 4-quinolone-3-carboxylic acid 23474356 C 23474356 Macrolones 23474356 azithromycin 23474356 clarithromycin 23474356 hydrogen 23474356 macrolide 23474356 macrolides 23474356 macrolone 23474356 macrolones 23474356 octanol 23474356 quinolone 23474356 secondary amide 23474357 IPM 23474357 caffeine 23474357 certramide 23474357 certramides 23474357 cortisone 23474357 diclofenac sodium 23474357 ethanol 23474357 isopropyl myristate 23474357 mannitol 23474357 propylene glycol 23474357 salicylic acid 23474357 testosterone 23474382 HMG-CoA 23474382 alcian blue 23474382 simvastatin 23474382 statins 23474386 5-(benzyloxy)pyridin-2(1H)-one 23474386 5-(benzyloxy)pyridin-2(1H)-ones 23474386 amides 23474386 benzoimidazoles 23474441 estradiol 23474645 4,4',4''-tris(carbazol-9-yl)-triphenylamine 23474645 4,4-N,N-dicarbazole-biphenyl 23474645 CBP 23474645 CdS 23474645 CdSe 23474645 TCTA 23474645 TiO2 23474645 ZnS 23474645 titanium dioxide 23474688 C 23474688 Nitrogen 23474688 Pt 23474688 carbon 23474688 graphene 23474688 hydrazine 23474688 nitrogen 23474688 oxygen 23474899 tetrahydropentaazacyclopenta[a]anthracenes 23474899 tetrahydropyrimido[4,5-b]quinolines 23474899 tetrahydroquinolines 23474899 tricyclic pyrimido[4,5-b]quinolines 23474972 NaCl 23474972 carbon 23474972 hydrogen 23475901 Ca(2+) 23475901 Calcium 23475901 calcium 23477344 Carbon 23477344 Proline 23477344 carbon 23477344 proline 23477419 (2-furyl)Map 23477419 (R)-βPro 23477419 (R/S)-βPro 23477419 (ph)Map 23477419 Dmt 23477419 EM-1 23477419 Endomorphin-1 23477419 Forskolin 23477419 Map 23477419 Trp 23477419 cAMP 23477419 endomorphin-1 23477419 morphine 23477419 α-methylene-β-aminopropanoic acids 23477451 Benzofurans 23477451 Isocoumarin 23477451 benzofurans 23477451 hydroisocoumarins 23477451 isocoumarin 23477451 isocoumarins 23477451 penicifuran A 23477451 penicifurans A-D 23477451 penicimarins A-C 23477451 penicimarins D-F 23477623 2,2-diphenyl-1-picrylhydrazyl 23477623 CE-OOH 23477623 DPPH 23477623 Fe(2+) 23477623 Sal B 23477623 cholesteryl ester hydroperoxide 23477623 copper 23477623 phenolic 23477623 salvianolic acid B 23478800 Cucurbitacin I 23478800 N-acetyl l-cysteine 23478800 cucurbitacin I 23478800 guanine nucleotide 23478800 oxygen 23478800 tyrosine 23479193 4-phenyl-5-pyridin-4-yl-2,3-dihydro-3H-1,2,4-triazole-3-thiones 23479193 Mannich bases 23479193 S-alkyl 23479193 celocoxib 23479193 diaryltriazole 23479194 7,8,3',4'-tetrahydroxyflavone 23479194 8-methoxy-7,3',4'-trihydroxyflavone 23479194 Lupinifolin 23479194 lupeol 23479194 lupinifolin 23479194 sterols 23479194 stigmasta-5,22-dien-3-one 23479194 stigmasterol 23479194 triterpenoid 23479194 β-sitosterol 23479194 β-sitosterone 23479318 Cd 23479318 Pb 23479318 cadmium 23479389 [6]-Gingerol 23479389 [6]-gingerol 23479390 2-Phenoxychromones 23479390 2-phenoxychromone 23479390 3'-O-β-D-glucoside 23479390 Peltogynoids 23479390 dichloromethane 23479390 estrogen 23479390 ophioglonin 23479407 Gefitinib 23479407 afatinib 23479407 dacomitinib 23479407 erlotinib 23479407 tyrosine 23479455 5-hydroxytryptamine 23479455 EMD 386088 23479455 clozapine 23479455 ketamine 23479455 serotonin 23479738 Cys 23479738 H2O2 23479738 NO 23479738 S 23479738 S-Nitrosothiols 23479738 S-nitrosocysteine 23479738 S-nitrosoglutathione 23479738 SNO 23479738 SNOs 23479738 cys 23479738 cysteines 23479738 disulfide 23479738 hydrogen peroxide 23479738 nitric oxide 23479738 oxygen 23479738 thiol 23480196 COOH 23480196 HCl 23480196 HNO(3) 23480196 Ni 23480196 carbon 23480279 colchicine 23480279 colchicinoids 23480279 thiocolchicine 23480348 PAH 23480348 Pd 23480348 Pd icosahedra 23480348 Polyallylamine 23480348 Pt black 23480348 ethanol 23480348 oxygen 23480348 palladium icosahedra 23480446 amino acid 23480446 amino acids 23480446 aromatic amino acids 23480446 hydrogen 23480446 phenylalanine 23480446 tryptophan 23480446 tyrosine 23480532 lactose 23480532 lactose monohydrate 23480597 polyamine 23480798 2F-ethanol 23480798 Cl 23480798 F 23480798 OCCF 23480798 carbon tetrachloride 23480798 cl 23480798 ethanol 23480798 f 23480798 hydrogen 23480798 o-h 23480798 phenol 23480798 trihydrate 23480848 2D 23480848 Fe(II) 23480848 Fe-NO 23480848 NO 23480848 Na2[Fe(CN)5NO]·2H2O 23480848 Nitrosyl 23480848 SNP 23480848 cyanide 23480848 deuterium oxide 23480848 dimethyl sulfoxide 23480848 ethanol 23480848 ethylene glycol 23480848 formamide 23480848 heme 23480848 methanol 23480848 nitric oxide 23480848 nitrosyl 23480848 sodium nitroprusside 23480848 trans-CN 23481139 Nicotinic acid 23481139 TBTU 23481139 nicotinic acid 23481236 DAGs 23481236 Ser 23481236 TAGs 23481236 ceramides 23481236 diglycerides 23481236 fatty acids 23481236 glucose 23481236 palmitic and stearic acids 23481236 phosphatidylinositol 23481236 serine 23481236 triglycerides 23481236 tyrosine 23481236 wortmannin 23481281 Aphanamgrandiol A 23481281 bicyclo[3,2,1]octane 23481281 carbon 23481281 triterpenoid 23481650 5-azaindole 23481650 7-azaindole 23481650 N-substituted azaindoles 23481650 azaindole 23481650 indole 23481677 Chloroazaphilones 23481677 Helicusin E 23481677 Isochromophilone X 23481677 Isochromophilone XI 23481677 bartanolide 23481677 chloroazaphilones 23481677 deacetylsclerotiorin 23481677 helicusin A 23481677 helicusin E 23481677 isochromophilone X 23481677 isochromophilone XI 23481677 pentaketide 23483327 cadmium 23483327 phenanthrene 23484490 Carbon 23484490 carbon 23484546 acetylene 23484546 graphene 23484546 hydrocarbon 23484546 hydrogen 23484622 Benzo[a]pyrene 23484622 ZnO 23484622 benzo[a]pyrene 23484622 oxygen 23484622 p-benzoquinone 23484622 zinc oxide 23484851 Asp 23484851 Phe 23484851 aspartic acid 23484851 phenylalanine 23484851 pyrene 23484974 quartz 23485065 dopamine 23485151 Ca(2+) 23485151 H(+) 23485151 H+ 23485151 Li(+) 23485151 LiCl 23485441 ADP 23485441 NAD(+) 23485441 Poly(ADP-ribose) 23485441 amino acid 23485441 ribose 23485441 ribosyl 23485450 DOX 23485450 Fe 23485450 PEG 23485450 acylhydrazone 23485450 doxorubicin 23485450 iron-oxide 23485450 poly(ethylene glycol) 23485613 Gossypol 23485613 gossypol 23485991 N 23485991 disulfide 23485991 hydrogen peroxide 23485991 methyl viologen 23486187 Trp 23487486 MPA 23487486 medroxyprogesterone 23487486 medroxyprogesterone acetate 23487486 progesterone 23487486 progestin 23487486 steroids 23488728 Si(111) 23488728 amine 23488728 ascorbic acid 23488728 carbon 23488728 citrate 23488728 oxide 23488728 silicon 23488739 H2O 23488739 diamond 23488739 dimethylsulfoxide 23488739 ethylene glycol 23488739 glycidol 23488739 hydrogen 23488739 octane 23488739 oleic acid 23488739 poly(glycidol) 23488739 toluene 23488748 hydrogen 23488987 6-Aminoquinoline 23488987 6-Nitroquinoline 23488987 6-aminoquinoline 23488987 6-hydroxylaminoquinoline 23488987 6-nitroquinolin-2(1H)-one 23488987 6-nitroquinoline 23488987 Nitroaryl 23488987 amino 23488987 hydroxylamino 23488987 nitroaryl 23488987 nitroso 23488987 oxygen 23488987 xanthine 23489135 1,2,4,5-tetraoxane 23489135 1,2,4-trioxane 23489135 1,2,4-trioxolane 23489135 1,2,4-trioxolanes 23489135 1,2-dioxolane 23489135 OZ277 23489135 OZ439 23489135 dioxolanes 23489135 dispiro ozonides 23489135 ozonides 23489135 peroxides 23489135 tetraoxane 23489135 trioxane 23489135 trioxolane 23489301 aloglipin 23489301 alogliptin 23489301 metformin 23489301 sulfonylureas 23489301 thiazolidinediones 23489623 (R)-Bgugaine 23489623 (R)-norbgugaine 23489623 bgugaine 23489623 norbgugaine 23489623 pyocyanin 23489623 pyrrolidine alkaloid 23489624 MTT 23489629 11β-hydroxysteroid 23489629 N-(Pyridin-2-yl) arylsulfonamide 23489629 N-(Pyridin-2-yl) arylsulfonamides 23489629 N-(pyridin-2-yl) arylsulfonamides 23489629 PF-915275 23489629 glutathione 23489976 Cortisol 23489976 cortisol 23490078 Haloalkane 23490078 asparagine 23490078 carbon 23490078 halide 23490078 haloalkane 23490078 halogen 23490078 hydrogen 23490078 tryptophan 23490078 tryptophans 23490078 tyrosine 23491602 5'-phosphate 23491602 Mn(2+) 23491602 amino acid 23492810 17β-estradiol 23492810 VTG 23492810 fadrozole 23492810 vitellogenin 23493317 adenosine-3',5'-cyclic monophosphate 23493317 cAMP 23493317 glucose 23493317 nucleotide 23493374 (m)CpG 23493374 (m)CpGs 23493374 5-aza-2'-deoxycytidine 23493374 CpG 23493374 bisulfite 23493374 glucose 23493374 methyl 23493374 trichostatin A 23493449 Indole 23493449 N-Hydroxycinnamamide 23493449 N-hydroxycinnamamide 23493449 SAHA 23493449 indole 23494106 AM-694 23494106 JWH-018 23494106 JWH-073 23494106 JWH-122 23494106 JWH-210 23494106 benzoylindole 23494106 cannabinoid 23494106 cannabinoids 23494106 naphthoylindole 23494106 tetrahydrocannabinol 23494232 AMPA 23494232 Ketamine 23494232 SCH23390 23494232 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 23494232 dopamine 23494232 ketamine 23494233 1-(2-[trifluoromethyl]phenyl) imidazole 23494233 1400W 23494233 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide 23494233 Carboxy-PTIO 23494233 Ethanol 23494233 L-NAME 23494233 L-arginine 23494233 N (G)-nitro-L-arginine methyl ester 23494233 N-([3-(aminomethyl)phenyl]methyl) ethanimidamide dihydrochloride 23494233 NO 23494233 Nitric oxide 23494233 TRIM 23494233 carboxy-PTIO 23494233 ethanol 23494233 nitric oxide 23494732 ABG 23494732 Ascorbigen 23494732 eosin 23494732 hematoxylin 23494732 indole 23494763 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium 23494763 MTT 23494763 Safranal 23494763 propidium iodide 23494763 safranal 23494802 Curcuminoid 23494802 Curcuminoids 23494802 curcuminoid 23494802 curcuminoids 23494810 (R)- and (S)-nicotine 23494810 (S)-nicotine 23494810 (S)-nornicotine 23494810 N 23494810 Nicotine 23494810 Nornicotine 23494810 nicotine 23494810 pyridyl 23494810 pyrrolidyl 23494831 2-hydroperoxycoelenterazine 23494831 C2(-) 23494831 Ca(2+) 23494831 Coelenterazine 23494831 His 23494831 N7 23494831 Oxygen 23494831 coelenterazine 23494831 oxygen 23494831 peroxy 23494834 Graphene 23494834 graphene 23495001 Cholesterol 23495001 Glucosinolates 23495001 cholesterol 23495001 glucosinolates 23495001 isothiocyanates 23495151 H 23495151 H(2)O 23495151 H(3)O(+) 23495151 O 23495151 hydronium 23495161 acarviostatins 23495161 acarviostatins III0(-1) and III23 23495163 C 23495163 carbon 23495163 hexane 23495163 n-alkanes 23495163 nonacosan-10-ol 23495190 Artemisinin 23495190 Artemisinins 23495190 artemisinin 23495190 polypyrrole 23495719 HMF 23495719 furfural 23495719 hydroxymethyl furfural 23495769 Ag 23495769 Au 23495769 silver 23495911 Chromium 23495911 chromium 23496305 fluorescein 23496349 W3 23496349 W3(-) 23496349 W3(2-) 23496349 W3O 23496349 W3O(-) 23496349 W3O2 23496349 W3O2(-) 23496349 W3Ox(-) 23496349 W3Ox(-/0) 23496349 oxygen 23496349 tritungsten 23496349 tritungsten oxide 23496412 Calcium Carbonate 23496412 Kaolinite 23496412 calcium carbonate 23496412 kaolinite 23496412 metal oxide 23497227 1H 23497227 Alkylideno/arylideno-bis-ureas 23497227 N-Aryl pyrido-quinazolines 23497227 pyrido-quinazolines 23497227 tyrosine 23497860 astaxanthin 23497860 canthaxanthin 23497860 lutein 23497860 β-carotene 23497864 (8R)-piperitone-4-en-9-O-β-d-glucopyranoside 23497864 1-O-β-d-(4-hydroxybenzoyl)glucose 23497864 6'-O-β-glucopyranosylalbiflorin 23497864 albiflorin 23497864 formic acid 23497864 methanol 23497864 monoterpene glycosides 23497864 oxypaeoniflorin 23497864 paeoniflorin 23497864 phenolic and monoterpene glycosides 23497864 phenolic glycoside 23497864 pyridylpaeoniflorin 23497864 β-gentiobiosylpaeoniflorin 23497866 ethanol 23497866 flavonoids 23497866 isorhamnetin 23497866 kaempferol 23497866 quercetin 23497867 Ser 23497867 Thr 23497875 DPPH 23497875 Fe 23497875 FeEDTA 23497875 ascorbate 23497875 iron 23497875 nitrate 23497876 Al(13) 23497876 Al(3+) 23497876 NADH 23497876 alcohol 23497876 carbon 23497876 ethanol 23497876 graphene oxide 23497876 reduced nicotinamide adenine dinucleotide 23497876 tridecameric aluminium 23497878 cholesterol 23497878 ethyl-acetate 23497879 AαC 23497879 HCAs 23497879 MeAαC 23497879 Trp-P-1 23497879 Trp-P-2 23497881 alcohols 23497881 esters 23497881 l-malic acid 23497882 DEAE 23497882 Trolox 23497882 galactose 23497882 glucose 23497882 mannose 23497882 oxygen 23497887 H2O2 23497887 ROOH 23497887 carbonyl 23497887 carnosine 23497887 hydrogen peroxide 23497887 organic peroxides 23497887 peroxide 23497887 peroxides 23497887 vitamin E 23497894 1,1-diphenyl-2-picryl-hydrazyl 23497894 SCFA 23497894 hydroxyl 23497894 n-butyric acid 23497894 propionic acid 23497894 short-chain fatty acid 23497894 superoxide 23497896 Citral 23497896 citral 23497896 polyoxyethylene alkylether 23497898 phosphatidylcholine 23497908 mercury 23499236 enoyl 23499236 rhodanine 23499237 UDP 23499237 UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine 23499237 amino acid 23499237 hydroxamate 23499237 zinc 23499237 α-amino acid 23499664 5-HT 23499664 Duloxetine 23499664 F2695 23499664 LVM 23499664 Levomilnacipran 23499664 duloxetine 23499664 milnacipran 23499664 norepinephrine 23499664 serotonin 23499664 venlafaxine 23499758 Raloxifene 23499758 UDP 23499758 amino acid 23499758 mycophenolic acid 23499758 raloxifene 23499823 (4'R)- and (4'S)- 2'-{[(E)-3β-hydroxyandrost-5-en-17-ylidene]-methyl} oxazolines 23499823 (4'R)- and (4'S)- 4'-substituted 2'-{[(E)-androst-5-en-17-ylidene]-methyl}oxazolines 23499823 (D)-serine methyl ester 23499823 (L)-serine methyl ester 23499823 17α-bromo-21-iodo-3β-acetoxypregn-5-en-20-one 23499823 4'-hydroxymethyl 23499823 4'-methoxycarbonyl 23499823 amides 23499823 methyl 2'-{[(E)-3β-acetoxyandrost-5-en-17-ylidene]methyl}-(4'R)-4',5'-dihydro-1',3'-oxazole-4'-carboxylate 23499823 methyl 2'-{[(E)-3β-acetoxyandrost-5-en-17-ylidene]methyl}-(4'S)-4',5'-dihydro-1',3'-oxazole-4'-carboxylate 23499823 methyl N-[3β-acetoxy-21-oxopregna-5,17(20)-dien-21-yl]-(D)-serinate 23499823 methyl N-[3β-acetoxy-21-oxopregna-5,17(20)-dien-21-yl]-(L)-serinate 23499925 N 23500061 deoxycholic acid 23500061 polyethyleneimine 23500061 tyrosine 23500065 Lys 23500065 proanthocyanidin 23500115 (1)H 23500115 (31)P 23500115 Ketoprofen 23500115 ketoprofen 23500115 phosphate 23500335 BPA 23500335 Bisphenol A 23500335 bisphenol A 23500335 epoxy 23500335 estradiol 23500335 polycarbonate 23500335 tyrosine 23500411 OH 23500411 hecogenin acetate 23500411 ritterazine G 23500537 BHT 23500537 EDTA 23500537 Oxyphytosterol 23500537 Trolox 23500537 butylated hydroxytoluene 23500537 campesterol 23500537 copper 23500537 iron 23500537 oxycampesterol 23500537 oxyphytosterol 23500537 oxyphytosterols 23500537 oxysitosterol 23500537 sitosterol 23500537 stanol 23500537 stanol ester 23500537 sterol 23500537 sterol esters 23500537 α-tocopherol 23500547 cholesterol 23500550 C 23500550 N 23500768 Astaxanthin 23500768 astaxanthin 23500768 bleomycin 23500768 hydroxyproline 23500770 DON 23500770 deoxynivalenol 23500772 EtOH 23500772 MDA 23500772 ethanol 23500772 glucose 23500778 BSO 23500778 Hirsutenone 23500778 MTT 23500778 N-methyl-d-aspartate 23500778 NMDA 23500778 SNP 23500778 dUTP 23500778 glutamate 23500778 hirsutenone 23500778 l-buthionine-(S,R)-sulfoximine 23500778 propidium iodide 23500778 sodium nitroprusside 23501108 2-pyridyl hexahydrocycloocta [4,5]thieno[2,3-d]pyrimidines 23501108 2-pyridyl hexahyrocyclooctathieno[2,3-d]pyrimidine 23501108 doxorubicin 23501109 14-O-[(2-aminobenzamide-2-methylpropane-2-yl) thioacetate] mutilin 23501109 14-O-[(4-aminobenzamide-2-methylpropane-2-yl) thioacetate] mutilin 23501109 14-O-[(4-methoxybenzamide-2- methylpropane-2-yl) thioacetate] mutilin 23501109 methicillin 23501109 pleuromutilin 23503472 Cyclosporine 23503472 cyclosporine 23503923 PAA 23503923 PLGA 23503923 poly(acrylic acid) 23503923 poly(lactide-co-glycolide) 23503927 (8S,9R)-tert-butylcarbamoylquinine 23503927 DNB 23503927 K(+) 23503927 Leu 23503927 Li(+) 23503927 N-3,5-dinitrobenzoyl-(S,R)-leucine 23503927 Na(+) 23503927 R-Leu 23503927 S-Leu 23503927 S/R-leucine 23503927 [tBuCQN·DNB-R-Leu·Li](+) 23503927 [tBuCQN·DNB-S-Leu·Li](+) 23503927 [tBuCQN·DNB-S/R-Leu·Na](+) 23503927 carboxylate 23503927 lithium 23503927 potassium 23503927 sodium 23503927 tBuCQN 23504247 1,3,4-benzotriazepin-5-one 23504247 2-amino-1,3,4-benzotriazepin-5-one 23504247 asperlicin 23504247 devazepide 23504356 fenfluramine 23504356 oxytocin 23504645 SO2 23504645 benzene 23504923 BMS-690514 23504923 Ketoconazole 23504923 Tyrosine 23504923 ketoconazole 23505091 oxygen 23505146 N 23505146 glucose 23505146 mannose 23505344 CO 23505344 H2O 23505344 Leu 23505344 Xe 23505344 Xe2 23505344 Xe3 23505344 Xe4 23505344 histidine 23505344 xenon 23506052 (2,2,6,6-tetramethylpiperidin-1-yl)oxyl 23506052 1,2-dioleoyl-sn-glycero-3-phosphocholine 23506052 1,2-dipalmitoyl-sn-glycero-3-phosphocholine 23506052 1,6-diphenyl-1,3,5-hexatriene 23506052 6-lauroyl-2-dimethylamino naphthalene 23506052 DOPC 23506052 DPH 23506052 DPPC 23506052 Laurdan 23506052 TEMPO 23506052 cholesterol 23506073 FMN 23506073 N-ethylmaleimide 23506073 carbonyl 23506073 disulphide 23506073 glyoxal 23506073 glyoxals 23506073 quinones 23506497 calcium 23506497 catecholamines 23506497 dobutamine 23506497 istaroxime 23506497 ivabradine 23506497 levosimendan 23506497 norepinephrine 23506497 omecamtiv mecarbil 23506497 oxygen 23506497 pyruvate 23506497 succinate 23506741 1-ethyl-5-methyl-2-phenyl-1H-benzo[d]imidazole 23506741 Fc11a 23506741 Fc11a-2 23506741 benzo[d]imidazole 23506741 sodium 23506741 sulfate 23507565 cocaine 23507565 heroin 23507573 tyrosine 23508304 glucose 23508887 5-hydroxymethylcytosine 23508887 5-methylcytosine 23508961 cholesterol 23508961 leupeptin 23509039 (4-biphenyl-4-ylthiazol-2-yl)-(6-methylpyridin-2-yl)-amine 23509039 (6-methylpyridin-2-yl)-[4-(4-pyridin-3-yl-phenyl)thiazol-2-yl]amine 23509039 2-aminothiazoles 23509039 aminothiazole 23509039 cyclopropanecarboxylic acid (4-biphenylthiazol-2-yl)amide 23509853 CF3COO(-) 23509853 CF3COOH 23509853 Copper(II) 23509853 Cu(I) 23509853 Cu(II) 23509853 Dioxygen 23509853 H2O2 23509853 Hydrogen Peroxide 23509853 O2 23509853 PV-tmpa 23509853 [(PV-tmpa)Cu(II)](ClO4)2 23509853 [(tmpa)Cu(II)](ClO4)2 23509853 acetone 23509853 bis(pyrid-2-ylmethyl){[6-(pivalamido)pyrid-2-yl]methyl}amine 23509853 copper 23509853 decamethylferrocene 23509853 decamethylferrocenium 23509853 pivalamido 23509853 tmpa 23509853 trifluoroacetic acid 23509853 tris(2-pyridylmethyl)amine 23509904 aspartyl 23510192 nucleotide 23510192 phosphate 23510479 poly(1,2-butadiene) 23511016 DOTA 23511016 Gd 23511016 Gd(3+) 23511016 pantoprazole 23511018 (+)-lycoricidine 23511022 DMP(V)TPP 23511022 P(V)porphyrin 23511022 amino acid 23511022 dimethoxyP(V)tetraphenylporphyrin chloride 23511022 dimethoxyphosphorus(V) tetraphenylporphyrin 23511022 oxygen 23511022 porphyrin 23511022 sodium azide 23511022 tryptophan 23511088 alkylphenones 23511088 butoxy 23511125 Donepezil 23511125 acetylcholine 23511125 donepezil 23511125 glutamate 23511125 mecamylamine 23511125 methyllycaconitine 23511311 glucose 23511711 Ketoconazole 23511711 Midazolam 23511711 ketoconazole 23511711 midazolam 23511718 PEG 23511718 polyethylene glycol 23512337 PAA 23512337 polyamidoamine 23512337 polyethyleneimine 23512409 Polythiophene 23512409 polythiophene 23512438 alphamethrin 23512438 citric and acetic acids 23512438 endosulfan 23512438 gluconic acid 23512438 imidacloprid 23512438 monocrotophos 23512438 phosphate 23512438 phosphorus 23512754 1-Cinnamoyl-3,11-Dihydroxymeliacarpin 23512754 1-cinnamoyl-3,11-dihydroxymeliacarpin 23512754 CDM 23512754 MTT 23512824 2,4-dinitrophenyl 23512824 Ac4 GlcNAz 23512824 DNP 23512824 azide 23512824 azides 23512824 peracetylated N-azidoacetylglucosamine 23512824 phosphines 23512927 DOX 23512927 Doxorubicin 23512927 PEG-b-P(S-co-PPSEMA) 23512927 PPSEMA 23512927 doxorubicin 23512927 poly(ethylene glycol)-b-poly[styrene-co-(2-(1,2,3,4,5-pentaphenyl-1H-silol-1-yloxy)ethyl methacrylate)] 23514378 5-HT 23514378 serotonin 23514599 4-(1-methyl-1H-pyrrol-3-yl)benzenamine 23514599 Biaryl 23514599 KMR-28-39 23514599 MPB 23514599 PBD 23514599 PBD-MPB 23514599 Pyrrolobenzodiazepine 23514599 pyrrolo[2,1-c][1,4]benzodiazepine 23515282 cholesterol 23515497 Aroclor 1221 23515497 PCB 180 23515497 PCBs 23515497 endosulfan 23515497 formaldehyde 23515497 mirex 23515497 oestradiol 23515497 organochlorinated 23515497 polychlorinated biphenyls 23515582 Escitalopram 23515582 escitalopram 23515582 serotonin 23515934 5-HT 23515934 Oleanolic acid 23515934 acetic acid 23515934 formalin 23515934 glutamate 23515934 methysergide 23515934 naloxone 23515934 oleanolic acid 23515934 yohimbine 23517008 carbon 23517008 graphene 23517008 graphite 23517010 Au 23517028 Arylpiperazine 23517028 arylpiperazine 23517028 indole 23517028 quinoline 23517093 FR901464 23517093 Thailanstatins 23517093 Thailanstatins A, B, and C 23517093 carboxyl 23517093 hydroxyl 23517093 phosphate 23517093 thailanstatins 23517126 1β-p-coumaroyloxypolygodial 23517126 1β-p-hydroxy-E-cinnamoyl-5α-hydroxydrimeninol 23517126 1β-p-hydroxy-E-cinnamoyldrimeninol 23517126 3'-deoxyisozygolone A 23517126 4'-O-methylzygolone A 23517126 Sesquiterpenoids 23517126 Tetralones 23517126 calothyrlone A 23517126 cinnamolide 23517126 isozygolone A 23517126 methyl ether of 1β-p-hydroxy-E-cinnamoyl-12α-methoxydrimeninol 23517126 sesquiterpenoids 23517126 tetralones 23517126 zygolone A 23517145 11α-hydroxy-3,7-dioxolanost-8,24(E)-dien-26- oic acid 23517145 15-O-acetylganolucidate A 23517145 3,11,15,23-tetraoxo-27ξ-lanosta-8,16-dien-26-oic acid 23517145 3,7,11-trioxo-5α-lanosta-8,24(E)-dien-26-oic acid 23517145 3-(4-methoxy-2-oxo-2H-pyran-6-yl)propanoic acid 23517145 5-hydroxy-5-(methoxymethyl)-4-methylfuran-2(5H)-one 23517145 Lactone 23517145 Lanostanoids 23517145 NO 23517145 ethyl 3,7,11,12,15,23-hexaoxo-5α-lanost-8-en-26-oate 23517145 ethyl lucidenate A 23517145 ethyl lucidenate F 23517145 lactone 23517145 lanostanoids 23517145 methyl 3,7,11,12,15,23-hexaoxo-5α-lanost-8-en-26-oate 23517379 2,5-dialkoxy-phenylene-thienylene 23517379 graphene 23517379 thiophene 23517470 Ca(2+) 23517474 Amides 23517474 Ca(2+) 23517474 K(+) 23517474 Li(+) 23517474 Mg(2+) 23517474 Na(+) 23517474 amide 23517474 amide carbonyl oxygen 23517474 amides 23517474 butyramide 23517474 chloride 23517541 N(ω)-hydroxy-nor-L-arginine 23517541 nor-NOHA 23517546 (Ga,Mn)As 23517546 Ga 23517546 GaAs 23517546 Mn 23517546 Si 23517546 Zinc-Blende 23517546 zinc-blende 23517565 N-Methyldihydroquinazolinone 23517565 dihydroquinazolinone 23517621 2,2,6,6-Tetramethylpiperidine-1-oxyl 23517621 Nitroxide 23517621 TEMPO 23517621 glutathione 23517621 oxygen 23517636 17-hydroxyprogesterone 23517636 DHEA-S 23517636 Testosterone 23517636 androgen 23517636 androstenedione 23517636 dehydroepiandrosterone sulfate 23517729 2,7,12-tris(α-pyridinio-p-tolyl)-17-(p-(methoxymethyl)phenyl) porphycene 23517729 Py3MeO-TBPo 23517729 oxygen 23517729 porphycene 23517729 sodium azide 23518155 N 23518155 cAMP 23518155 glucose 23518321 Acetaminophen 23518321 H2O2 23518321 HOCl 23518321 acetaminophen 23518321 glutathione 23518321 phorbol myristate acetate 23518599 (R2O3)x(R'2O3)y(P2O5)1-(x+y) 23518599 Ce 23518599 Er 23518599 La 23518599 Nd 23518599 O 23518599 P 23518599 P-O 23518599 RP3O9 23518599 RP5O14 23518599 Rare-earth 23518599 metaphosphate 23518599 rare-earth 23518599 rare-earth phosphate 23518599 ultraphosphate 23518857 C-HF 23518857 CH2F2H2CO 23518857 CH2O 23518857 FCF 23518857 difluoromethane 23518857 formaldehyde 23518857 hydrogen 23519059 acetylacetonate 23519059 bis(4,6-difluorophenyl) pyridinato-N,C [dfppy] iridium(iii) 23519059 iridium(iii) 23519059 picolinate 23519059 pyridylpyrazolate 23519153 Copper 23519153 Fe 23519153 S-adenosylhomocysteine 23519153 adenosylhomocysteine 23519153 copper 23519153 iron 23520074 (125) I 23520074 C 23520074 N 23520074 amino 23520074 phospho 23520074 serine 23521014 Carbon 23521014 carbon 23521318 α-terpineol 23521360 3,4'-dimethoxy-7-O-β-(6″-galloyl-glucopyranoside) quercetin 23521360 3-methoxy-7-O-β-(6″-galloylgluco-pyranoside) kaempferol 23521360 3-methoxy-7-O-β-(6″-galloylgluco-pyranoside) quercetin 23521360 ethyl acetate 23521360 flavonols 23521360 methylated flavonol glucosides 23521567 1,2-dipalmitoyl-sn-glycero-3-phosphocholine 23521567 DPPC 23522182 AZD1656 23522182 glucose 23522564 C 23522564 Ile 23522564 N 23522564 amino acid 23522564 cholesterol 23522564 lysine 23522833 Cu(OTf)2 23522833 isatin 23522833 kojic acid 23522833 methylenes 23522833 spiro[indoline-3,4'-pyrano[3,2-b]pyran 23522833 spiropyrano[3,2-b]pyran-4(8H)-ones 23523142 Ginkgetin 23523142 Z-DEVD-fmk 23523142 biflavonoid 23523142 ginkgetin 23523258 1'-hydroxy midazolam 23523258 Sch B 23523258 Schisandrin B 23523258 ketoconazole 23523258 midazolam 23523546 ITZ 23523546 Itraconazole 23523546 itraconazole 23523546 mannitol 23523557 HC 030031 23523557 cyclophosphamide 23523780 Ca(2+) 23523780 bicuculline 23523781 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 23523781 3,4-dihydroxyphenylacetic acid 23523781 DOPAC 23523781 HVA 23523781 MPTP 23523781 dopamine 23523781 homovanillic acid 23523781 paraquat 23523781 paraquat dichloride 23523781 silver 23523781 tyrosine 23523906 Berberine 23523906 berberine 23523906 bleomycin 23523906 histamine 23523906 hydroxyproline 23523906 nitric oxide 23523949 Creatine 23523949 Crocin 23523949 DZN 23523949 GSH 23523949 MDA 23523949 crocin 23523949 diazinon 23523949 glutathione 23523949 malondealdehyde 23523949 vitamin E 23523991 FNA 23523991 creatinine 23523991 morphine 23523991 naloxone 23523991 nitrogen 23523991 tyrosine 23523991 urea 23523991 β-funaltrexamine 23524160 (1)H 23524160 (13)C 23524160 3-(1H-indol-3-yl)pyrrolidine-2,5-dione 23524160 pyrrolidine-2,5-dione 23524160 serotonin 23524188 Dox 23524188 PEG 23524188 doxorubicin 23524189 TPPS 23524189 meso-tetrakis (4-sulfonatophenyl) porphyrin 23524189 oxygen 23524189 porphyrin 23524254 (1)H 23524254 (13)C 23524254 (15)N 23524254 PVP 23524254 PVP-K30 23524254 hydrogen 23524254 vincamine 23524305 oxygen 23524983 TFMO 23524983 hydroxamate 23524983 hydroxamates 23524983 trifluoromethyloxadiazole 23524983 zinc 23525092 1,6-anhydrosugar 23525092 levoglucosan 23525092 phenyl α- and β-d-glucosides 23525112 4α-PDD 23525112 4α-phorbol 12, 13-didecanoate 23525112 Ca(2+) 23525112 Gö6976 23525112 H2O2 23525112 Oxygen 23525112 PMA 23525112 oxygen 23525112 phorbol 12-myristate 13-acetate 23525112 trichostatin A 23525167 (13)C 23525167 (2)H 23525167 ethanol 23525167 formoterol fumarate 23525167 fumarate 23525167 methyl 23525167 phenyl 23525215 CORT 23525215 corticosterone 23525215 zinc 23525330 Cysteine 23525330 Etomidate 23525330 GABA 23525330 Para-chloromercuribenzene sulfonate 23525330 cysteine 23525330 etomidate 23525330 pCMBS 23525330 suflhydryl 23525330 sulfhydryls 23525662 steroid 23525674 polyethylene 23525674 polypropylene 23525786 HEMA 23525786 Hydroxyapatite 23525786 PHEMA 23525786 dimethacrylated poly(lactide-b-ethylene glycol-b-lactide) 23525786 hydroxyapatite 23525786 methacrylic acid 23525786 pHEMA 23525786 poly(2-hydroxyethyl methacrylate-co-methacrylic acid) 23525786 poly(HEMA-co-MA) 23525902 1NMPP1 23525902 ATP 23525902 RO3306 23525902 phosphates 23526144 Ca 23526144 Cu 23526144 Fe 23526144 Mg 23526144 Zn 23526231 (+)-10-O-methylhernovine N-oxide 23526231 (+)-3-hydroxy-anhydrolycorine N-oxide 23526231 (+)-N-methoxycarbonyl-lindcarpine 23526231 (+)-N-methoxylcarbonyl-nandigerine 23526231 (1)H 23526231 ethanol 23526571 Thiazole 23526571 thiazole 23526674 Vancomycin 23526674 creatinine 23526674 nitrogen 23526674 urea 23526674 vancomycin 23526745 2-methyltryptophan 23526745 4Fe-4S 23526745 Cobalamin 23526745 cobalamin 23526745 thiostrepton 23526745 tryptophan 23526814 2'-aminoanilides 23526814 SAHA 23526814 benzene 23526814 hydroxamates 23526814 pyrrole 23526814 pyrrole anilide 23526814 tert-Butylcarbamate 23526814 tert-butylcarbamate 23526919 Carbocyanine 23527317 N 23527317 N-1,2(R)-dihydroxypropyl 23527317 [(3)H]dihydrotetrabenazine 23527317 [(3)H]dopamine 23527317 lobelane 23527317 methamphetamine 23527317 monoamine 23527317 nor-lobelane 23527551 Aryl Diazonium 23527551 N(+)(Me)3 23527551 SO3(-) 23527551 aryl diazonium 23527551 glassy carbon 23527551 phenyl 23527585 3,3',4,4',5-pentachlorobiphenyl 23527585 Aryl-hydrocarbon 23527585 Copper 23527585 PCB 23527585 PCB126 23527585 copper 23527585 glutathione 23527585 hydroxyl 23527585 iron 23527585 manganese 23527585 polychlorinated biphenyl 23527585 selenium 23527585 zinc 23527619 Au 23527619 Cys 23527619 Cysteine 23527619 Hg(2+) 23527619 Mercury(II) 23527619 carboxylethyl 23527619 cysteine 23527619 thiols 23528109 CaCl2 23528109 POPC 23528109 Si3N4 23528109 organosilane 23528109 silicon 23528109 silicon nitride 23528251 5'-AMP 23528251 Cobalt chloride 23528251 Phenobarbital 23528251 androstane 23528252 BPA 23528252 androgen 23528252 bisphenol A 23528252 testosterone 23528300 2-substituted benzoxazoles 23528300 benzoxazole 23528300 oxamic acid 23528390 Quinolones 23528390 oxygen 23528390 quinolone 23528390 quinolones 23528611 PKI-166 23528611 creatinine 23528611 lisinopril 23528611 phenylephrine 23529571 carbon 23529571 graphene 23529671 glucose 23529894 Flinderoles A, B, and C 23529894 borrerine 23529894 borreverines 23529894 dimethylisoborreverine 23529894 enone 23529894 flinderoles 23529894 flinderoles A, B, and C 23529894 indole 23529894 isoborreverine 23529894 tryptamine 23529898 PHB 23529898 Poly(3-Hydroxybutyrate) 23529898 TiO2 23529898 poly(3-hydroxybutyrate) 23529905 PAA 23529905 PCL 23529905 poly(α,β)-DL-aspartic acid 23529905 polycaprolactone 23530011 Carbohydrate 23530011 carbohydrates 23530011 cholesterol 23530011 fatty acids 23530011 glucose 23530011 triglycerides 23530018 ATP 23530018 CGP 23530018 CGPs 23530018 Chalcogenopyrylium 23530018 E217βG 23530018 Se 23530018 Te 23530018 [(3)H]E217βG 23530018 [(3)H]estradiol glucuronide 23530018 calcein 23530018 chalcogen 23530018 chalcogenopyrylium 23530018 methine 23530018 pyrylium 23530018 trimethine 23530019 C-8-xanthate 23530019 Nicotine 23530019 bupropion 23530019 cotinine 23530019 coumarin 23530019 nicotine 23530020 2,6-xylidine 23530020 4- and 6-hydroxy-o-toluidine 23530020 4-hydroxy-2,6-xylidine 23530020 Lidocaine 23530020 Prilocaine 23530020 amide 23530020 bis-(4-nitrophenyl) phosphate 23530020 diisopropyl fluorophosphate 23530020 lidocaine 23530020 o-Toluidine 23530020 o-toluidine 23530020 prilocaine 23530036 tyrosine 23530765 Bis(l-histidinato)cadmium Dihydrate 23530765 Copper 23530765 Cu(II) 23530765 bis(l-histidinato)cadmium dihydrate 23530765 copper 23530765 histidine 23531107 Metal Oxide 23531107 PbS 23531107 PbSe 23531107 ZnO 23531107 metal oxide 23531107 nitrogen 23531107 oxide 23531119 (15)N 23531119 2-carbonyl 23531119 5-bromo 23531119 5-bromouridine 23531119 5-fluoro 23531119 5-substituted uracil 23531119 NHN 23531119 Uridine 23531119 enol 23531119 guanine 23531119 halogens 23531119 halouracils 23531119 hydrogen 23531119 nucleosides 23531119 thymine 23531119 uracil 23531160 5-HT 23531160 TRP 23531160 indoleamine 23531160 monoamine 23531160 monoamines 23531160 serotonin 23531160 tryptophan 23531217 bis-pyridinium mono-aldoxime 23531217 octadecyl silica 23531217 organophosphate 23531217 organophosphonate 23532446 polypropylene 23532446 titanium dioxide 23532897 Proline 23532897 inositol phosphate 23532897 proline 23532897 thiazolidine 23533220 17β-estradiol 23533220 cAMP 23533220 catecholamine 23533220 dopamine 23533220 testosterone 23534412 3-(5-hydroxy-2,2-dimethyl-chroman-6-yl)-N-{2-[3-(5-hydroxy-2,2-dimethyl-chroman-6-yl)-propionylamino]-ethyl}-propionamide 23534412 ADP 23534412 arachidonic acid 23534412 coumarin 23534412 epinephrine 23534412 ferric chloride 23534412 seselin 23534413 Myricetin 23534413 allopurinol 23534413 benzbromarone 23534413 flavonoids 23534413 isoflavones 23534413 luteolin 23534413 uric acid 23534413 xanthine 23534440 H 23534440 Mg(2+) 23534440 cytosine 23534440 guanine 23534440 nucleotide 23534440 sugar 23534442 (1)H 23534442 (13)C 23534442 1,5-diarylpyrrole nitrooxyalkyl ethers 23534442 3-substituted 1,5-diarylpyrroles 23534442 NO 23534442 Nitrooxy 23534442 alcohols 23534442 carbonates 23534442 esters 23534442 ethers 23534442 nitric oxide 23534442 nitrooxyalkyl 23534442 nitrooxyalkyl ester and ether 23534442 nitrooxyalkyl ethers 23534442 pyrrole 23534827 C-(N)-A-S-H 23534827 aluminate 23534827 calcium (alumino)silicate 23534827 calcium-sodium aluminosilicate 23534827 calcium-sodium aluminosilicate hydrate 23534827 silicate 23534827 tobermorite 23535167 5'-methylthioadenosine 23535167 MTA 23535167 Met 23535167 Methionine 23535167 S-adenosylmethionine 23535167 SAM 23535167 amino acids 23535167 aspartate 23535167 ethylene 23535167 methionine 23535167 methyl 23535167 nicotianamine 23535167 sulfur 23535185 Galangin 23535185 N 23535185 calcium 23535185 cromolyn 23535185 galangin 23535185 histamine 23535185 phorbol 12-mystate 13-acetate 23535186 N 23535186 Scoparone 23535186 d-GalN 23535186 d-galactosamine 23535186 scoparone 23535288 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine 23535288 BHA 23535288 SDM 23535288 butylated hydroxyanisole 23535288 caprolactam 23535288 catechol 23535288 chenodeoxycholic acid 23535288 phenylethyl isothiocyanate 23535288 sulfadimethoxine 23535320 1,2,3-triazoles 23535320 1,4-naphthoquinones 23535320 Nor-α-lapachone 23535320 alkyne 23535320 azide 23535320 copper 23535320 naphthoquinones 23535320 nor-β-lapachone 23535320 α- and nor-α-lapachone 23535320 α-lapachone 23535321 ClBi(5-RC6H3-2-SO2C6H4-1'-) 23535321 Heterocyclic bismuth carboxylates 23535321 RCO2Bi(C6H4-2-SO2C6H4-1'-) 23535321 bismuth 23535321 carboxylate 23535321 diphenyl sulfone 23535321 heterocyclic organobismuth(III) carboxylates 23535326 BP1.4160 23535326 alcohol 23535326 cyclohexanol 23535326 histamine 23535326 hydroxyl 23535334 hydroxycinnamates 23535334 p-coumaryl, coniferyl and sinapyl alcohols 23535351 Asenapine 23535351 asenapine 23535360 Amino Acids 23535360 amino acids 23535360 cysteine 23535360 lysine 23535394 Saxitoxin 23535394 calcium 23535394 potassium 23535394 saxitoxin 23535394 sodium 23535516 AG490 23535516 D-Phe 23535516 N 23535516 Nle 23535516 U0126 23535870 potassium 23535915 atrazine 23536271 amino 23536271 β-Ionone 23536271 β-ionone 23536315 ASA 23536315 BAY 11-7082 23536315 BAY-11-7082 23536315 Ro 106-9920 23536315 acetylsalicylic acid 23536315 dexamethasone 23536582 Glucose 23536582 glucose 23536584 Metformin 23536584 glucose 23536584 metformin 23536728 Pregnane 23537133 Ag 23537133 AgCl 23537133 C 23537133 RSiMe3 23537133 TMS(+) 23537133 acetonitrile 23537133 allyl 23537133 benzyl 23537133 carbon 23537133 carbons 23537133 fullerene 23537133 glassy carbon 23537133 graphite 23537133 tetraalkyammonium 23537133 trimethylsilanes 23537133 trimethylsilyl 23537315 Co(I) 23537315 Hydrocarbon 23537315 Ni(I) 23537315 hydrocarbon 23537315 nitrogen 23537315 phosphoranimide 23537315 unsaturated hydrocarbons 23537321 carbon 23537321 li 23537321 lithium 23537321 silicon 23537339 3-substitued 3-azidooxindoles 23537339 Fe 23537339 Iron 23537339 Oxindoles 23537339 oxindoles 23537339 α-azido-β-keto esters 23537339 β-Keto Esters 23537339 β-keto esters 23537597 CaLac 23537597 FeSO4 23537597 ZnSO4 23537597 calcium lactate 23537597 ferrous sulfate 23537597 protoporphyrins 23537597 vitamin C 23537597 zinc sulfate 23537597 δ-aminolevulinic acid 23537599 methanabol 23537599 turinabol 23537661 PC-dibenzodioxins 23537661 PC-dibenzofurans 23537661 PCBs 23537661 hydrocarbon 23537661 methylmercury 23537661 non-ortho PCB 23537661 organochlorine 23537661 polychlorinated biphenyls 23537700 7 beta-hydroxycholesterol 23537700 7b-HC 23537700 7β-hydroxycholesterol 23537700 Oxysterols 23537700 glutamine 23537700 phosphoenol pyruvate 23537700 pyruvate 23537747 Nobiletin 23537747 apigenin 23537747 nobiletin 23537747 phospho 23537747 tangeretin 23537747 tricetin 23537748 AMP 23537748 CCM 23537748 CIP 23537748 Curcumin 23537748 Methicillin 23537748 NOR 23537748 OXI 23537748 ampicillin 23537748 ciprofloxacin 23537748 curcumin 23537748 methicillin 23537748 norfloxacin 23537748 oxacillin 23537748 polyphenolic flavonoid 23537942 5-benzylidene thiazolidine-2,4-dione 23537942 N-3-substituted-5-arylidene thiazolidine-2,4-diones 23537942 arylidene 23537942 phenyl 23537942 thiazolidine-2,4-dione 23537942 α-bromoacryloylamido 23538843 carbohydrates 23538843 proline 23538868 (3Z,6E)-1-N-methyl-3-benzy lidene-6-(2S-methyl-3-hydroxypropylidene)piperazine-2,5-dione 23538868 (3Z,6E)-1-N-methyl-3-benzylidene-6-(2R-methyl-3-hydroxypropylidene)piperazine-2,5-dione 23538868 (3Z,6S)-3-benzylidene-6-(2S-but-2-yl)piperazine-2,5-dione 23538868 (3Z,6S)-3-benzylidene-6-isobutylpiperazine-2,5-dione 23538868 (3Z,6Z)-3- (4-hydroxybenzylidene)-6-isobutylidenepiperazine-2,5-dione 23538868 (3Z,6Z)-3-((1H-imidazol-5-yl)-methylene)-6-isobutylidenepiperazine-2,5-dione 23538868 13C 23538868 Diketopiperazine 23538868 diketopiperazine 23538871 Kocurin 23538871 Thiazolyl 23538871 kocurin 23538871 methicillin 23538871 thiazolyl 23539511 creatinine 23539547 N 23539547 S 23539547 UDP 23539547 glutathione 23539641 GW823296 23539641 [(11)C]GR205171 23539641 orvepitant 23540754 PLLA 23540754 Polylactide 23540754 l-lactide 23540754 poly(l-lactide) 23541399 Androgen 23541399 androgen 23541399 testosterone 23541436 NO 23541436 PGE2 23541436 limonene 23541436 nitric oxide 23541436 prostaglandin E2 23541436 γ-terpinene 23541637 Aldosterone 23541637 K(+) 23541637 Na(+) 23541637 aldosterone 23541637 ouabain 23541637 phosphatidylinositol 23541646 Glycyrrhetinic acid 23541646 MTT 23541646 amide 23541646 benzyl amide 23541646 glycyrrhetinic acid 23541646 octylamide 23541670 5H-pyrrolo[2,3-b]pyrazine 23541670 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers 23541670 ATP 23541768 histidine 23541949 RFRP-3 23541949 RFamide-related peptide-3 23541949 steroid 23541950 dehydroepiandrosterone sulfate 23541950 steroid 23541950 testosterone 23542008 2'-fluoro 23542008 2'-hydroxyl 23542008 hydrogen 23542039 Neutral Red 23542039 glycerol 23542039 polyphenols 23542041 NO 23542041 O2(-) 23542041 nitric oxide 23542126 GSH 23542126 Thiobarbituric-acid 23542126 carbonyls 23542126 glutathione 23542239 PEG 23542239 iron oxide 23542239 poly(amino acid)s 23542239 poly(ethylene glycol) 23542440 5-HIAA 23542440 5-HT 23542440 5-hydroxyindolacetic acid 23542440 CORT 23542440 SB-656104 23542440 Serotonin 23542440 corticosterone 23542440 tryptophan 23542513 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone 23542513 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone 23542513 5HHMF 23542513 CoPP 23542513 NO 23542513 PDTC 23542513 Pyrrolidine dithiocarbamate 23542513 ZnPP 23542513 cobalt protoporphyrin 23542513 nitric oxide 23542513 zinc protoporphyrin 23542608 Carbon 23542608 carbon 23542652 17-α-ethinylestradiol 23542652 EE2 23542652 estradiol 23542652 estrogens 23543321 Polyamines 23543321 S-adenosylmethionine 23543321 polyamine 23543321 polyamines 23543413 Cisplatin 23543413 Cu 23543413 Pt 23543413 cDDP 23543413 copper 23543413 platinum 23543460 (131)I 23543460 MTT 23543460 Radioiodide 23544667 hydroxyl 23544667 sulfates 23544698 (NaNO3, nH2O)x 23544698 (NaNO3,1H2O)x 23544698 (NaNO3,nH2O)3 23544698 Hydrated Nitrate 23544698 NaNO3 23545002 1,3 diketo 23545002 1,3-diketones 23545002 diketo 23545002 iron 23545002 steel 23545108 nucleoside 23545161 Acetaminophen 23545161 acetaminophen 23545161 aspirin 23545161 prostaglandin 23545161 prostaglandin E 23545161 prostaglandin E2 23545348 ACh 23545348 KCl 23545348 acetylcholine 23545458 saponins 23545806 Methylone 23545806 N-hydroxy-methylone 23545806 dihydro-methylone 23545806 dihydroxymethcathinone 23545806 methylenedioxymethcathinone 23545806 methylone 23545999 3,4',5-trihydroxy-3',7,8-trimethoxyflavone 23545999 4',5,7-trihydroxy-3,3',8-trimethoxyflavone 23545999 4',5,7-trihydroxy-3,3'-dimethoxyflavone 23545999 4',7-dihydroxy-3,3',5,8-tetramethoxyflavone 23545999 4',7-dihydroxy-3,3',5-trimethoxyflavone 23545999 5,7-dihydroxy-3-methoxy-3',4'-methylenedioxyflavone 23545999 5,8-dihydroxy-3,7-dimethoxy-3',4'-methylenedioxyflavone 23545999 7-(2,3-dihydroxy-3-methylbutoxy)-3,3',4',5,8-pentamethoxyflavone 23545999 7-(2,3-dihydroxy-3-methylbutoxy)-3,3',4',5-tetramethoxyflavone 23545999 7-(2,3-dihydroxy-3-methylbutoxy)-3,5-dimethoxy-3',4'-methylenedioxyflavone 23545999 7-hydroxy-3,5-dimethoxy-3',4'-methylenedioxyflavone 23545999 Flavonoids 23545999 flavonoids 23546003 2,3-Bis(halomethyl)quinoxaline 23546003 Quinoxaline 23546003 bis(chloromethyl) 23546003 bis(fluoromethyl) 23546003 bis(iodomethyl) 23546003 halomethyl 23546003 quinoxaline 23546004 Acylated Sucroses 23546004 Acylated quinic acid 23546004 acylated sucroses 23546004 aldose 23546004 mumeic acid-A 23546004 mumeoses F-J 23546395 (-)-epicatechin 23546395 Thiobarbituric acid 23546395 cyclophosphamide 23546395 gallic acid 23546525 Azidoacetylene 23546525 azidoacetylene 23546600 androgen 23546601 Estrogen 23546601 Tamoxifen 23546601 estrogen 23546601 tamoxifen 23546605 estradiol-17β 23546605 estrogen 23546605 progesterone 23546867 oxygen 23546879 C 23546879 GalNAc 23546879 N 23546879 O 23546879 cysteine 23546879 threonine 23547584 Biphalin 23547584 Phe 23547584 homo-β(3) amino acids 23547584 hβ(3) Phe 23547652 3-HPT 23547652 3-Hydroxypyridin-2-thione 23547652 3-hydroxypyridin-2-thione 23547652 3HPT 23547652 Zinc 23547652 hydroxamic acid 23547652 zinc 23547706 Oxadiazole-isopropylamides 23547706 PI-1833 23547706 PI-1840 23547706 amide 23547706 butyl 23547706 meta-pyridyl 23547706 oxadiazole-isopropylamide 23547706 phenyl 23547706 propyl 23547757 Belactosin A 23547757 Cis-Cyclopropane 23547757 belactosin A 23547757 cis-cyclopropane 23547757 threonine 23547757 trans-cyclopropane 23547757 β-lactone 23547776 LDN-212854 23547786 DTP 23547786 PGS 23547786 dodecyl triphenyl phosphonium bromide 23547786 palygorskite 23547786 quaternary phosphonium salt 23548149 Fru-2,6-P2 23548149 H2O2 23548149 NaCl 23548149 Ser 23548149 anisomycin 23548149 carbohydrate 23548149 fructose-2,6-bisphosphate 23548896 C 23548896 amino acids 23548896 phosphotyrosine 23548896 tyrosine 23548974 PUFA 23548974 PUFAs 23548974 mercury 23548974 methylmercury 23548974 polyunsaturated fatty acids 23549285 Spongiatriol 23549285 furanoditerpenoid 23549672 11β-hydroxysteroid 23549672 cortisol 23549672 cortisone 23549673 androgen 23549673 androgens 23549673 testosterone 23549673 testosterone propionate 23550066 Ketamine 23550066 ThioTEPA 23550066 ketamine 23550066 norketamine 23550066 troleandomycin 23550656 CO 23550656 CO2 23550656 H 23550656 H2O 23550656 HCO 23550656 HOCO 23550656 OH 23550656 trans-HOCO 23550722 C6F13CH2C(O)OONO2 23550722 CF3CH2C(O)OONO2 23550722 CxF2x+1CH2C(O)H 23550722 CxF2x+1CH2C(O)OONO2 23550722 NO2 23550722 Peroxy Acyl Nitrates 23550722 peroxy acyl nitrates 23551856 Pioglitazone 23551856 TZD 23551856 glucose 23551856 pioglitazone 23552101 PI(4)P 23552101 PI(4,5)P2 23552101 glucose 23552101 phosphatidylinositol 4-phosphate 23552101 phosphatidylinositol-4,5-bisphosphate 23552264 carbon 23552268 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide 23552268 CVN 23552268 Carvone 23552268 carvone 23552268 monocyclic monoterpene 23552398 C 23552398 C-O 23552398 CO 23552398 CO2 23552398 COH 23552398 COOH 23552398 H2O 23552398 Pt(111) 23552398 hydrogen 23552398 oxygen 23552482 CH3 23552482 H 23552482 O 23552482 RO 23552482 RX 23552482 RX-Y 23552482 S 23552482 allyl 23552482 allyl phenyl ether 23552482 cyclohexane 23552482 ether 23552482 p-methylthioanisole 23552482 p-methylthiophenol 23552482 phenol 23552482 thioanisole 23552482 thiophenol 23552830 amino acid 23552843 PDMAEMA 23552843 disulfide 23552843 poly(2-dimethylaminoethyl methacrylate) 23552843 silica 23552852 azole 23552852 azoles 23552852 cyproconazole 23552852 fluconazole 23552852 flusilazole 23552852 imazalil 23552852 tebuconazole 23552852 triadimefon 23552852 triadimenol 23552899 ZnO 23552899 graphene 23552899 metal oxide 23552908 Au(111) 23552908 DFA 23552908 acetylene 23552908 benzene 23552908 cyclopentadienyl 23552908 diferrocenylacetylene 23552908 ferrocene 23552908 ferrocenes 23553560 Axitinib 23553560 axitinib 23553595 Diskus 23553595 fluticasone propionate 23553632 C 23553632 N 23553632 biotin 23553655 Tyrosine 23553655 bosutinib 23553655 dasatinib 23553655 imatinib 23553655 nilotinib 23553655 tyrosine 23553677 Silver 23553677 silver 23553679 Gabapentin 23553679 gabapentin 23553708 Sildenafil 23553708 sildenafil 23553811 Vernakalant 23553811 alcohol 23553811 aldosterone 23553811 apixaban 23553811 aspirin 23553811 clopidogrel 23553811 dabigatran 23553811 dronedarone 23553811 polyunsaturated fatty acids 23553811 rivaroxaban 23553811 statins 23553811 warfarin 23553905 Alcian blue 23553905 Alizarin red 23553961 CO 23553961 O 23553961 Pt 23553961 oxides 23554029 glutathione 23554029 malondialdehyde 23554029 superoxide 23554215 fluorine 23554215 fluoroximes 23554215 nitrogen 23554335 2,4-dinitroaniline 23554335 2,4-dinitrophenyl 23554335 CH 23554335 Pt 23554335 dodecanethiol 23556445 hydroxyurea 23556446 ATP 23556448 methamphetamine 23557487 HNO3 23557487 NO2 23557487 OH 23557487 nitric acid 23557931 MPA 23557931 cyclosporine 23557931 mycophenolic acid 23557931 tacrolimus 23557933 RES 23557933 glucose 23557933 resveratrol 23558233 5-HIAAA 23558233 DOPAC 23558233 HVA 23558233 MPTP 23558233 Serotonin 23558233 dopamine 23558233 iron 23558233 serotonin 23558233 tyrosine 23558236 MTT 23558236 rotundic acid 23558446 tyrosine 23558646 H 23558646 N(3)-alkylated xanthine 23558646 melamine 23558646 xanthine 23558682 N 23558682 arginine 23558682 carbonyl 23558682 cysteine 23558682 histidine 23558682 hydrogen 23558682 sugar 23558686 C 23558747 N 23558747 methyl 23559221 Glucose 23559221 glucose 23559436 (di)unsaturated hydrocarbons 23559436 H 23559436 Peroxide 23559436 alkyl peroxide 23559436 hydrocarbons 23559436 oxygen 23559436 peroxide 23560557 catecholamine 23560844 Arg 23560844 Gln 23560844 Glu 23560844 Lys 23560844 Thr 23560844 Tyr 23560844 pThr-Glu-pTyr 23560844 phospho 23560989 2-(dimethylamino)ethyl methacrylate 23560989 DMAEMA 23560989 EGDMA 23560989 PEG 23560989 Poly(ethylene glycol) 23560989 ethylene glycol dimethacrylate 23561072 1-deoxynojirimycin 23561072 DNJ 23561072 triacylglycerol 23561075 (epi)afzelechin 23561075 Catechin 23561075 Proanthocyanidin 23561075 catechin-7-O-glucoside 23561075 catechin-O-glucoside 23561075 flavan-3-ol 23561075 flavan-3-ols 23561076 anthocyanin 23561076 anthocyanins 23561079 nitrogen 23561089 Gallic acid 23561089 ethanol 23561089 methanol 23561089 phenolic 23561089 polyphenolic 23561089 trolox 23561091 (2S)-3',4'-methylenedioxy-5-methoxy-7-hydroxyflavan 23561091 Flavonoids 23561091 MTT 23561091 eriocaulin A 23561091 eriocaulosides A-C 23561091 flavan 23561091 flavone acyl glucosides 23561091 flavones 23561091 flavonoids 23561091 hispidulin 7-O-β-d-(6-O-cinnamoyl)glucopyranoside 23561091 isoflavones 23561091 jaceosidin 7-O-β-d-(6-O-p-coumaroyl)glucopyranoside 23561091 jaceosidin 7-O-β-d-(6-O-p-hydroxybenzoyl)glucopyranoside 23561093 Anisidine 23561093 DHA 23561093 EPA 23561093 astaxanthin 23561093 docosahexaenoic acid 23561093 eicosapentaenoic acid 23561093 palmitic acid 23561093 thiobarbituric acid 23561093 tocopherol 23561103 Vitamin A 23561103 vitamin A 23561103 β-carotene 23561109 ABTS 23561109 DPPH 23561113 Hoechst 33342 23561120 FAD 23561120 IPTG 23561120 NADH 23561120 Phenol 23561120 hydroxytyrosol 23561120 isopropyl-β-d-thiogalactopyranoside 23561120 monophenols 23561120 phenol 23561120 tyrosol 23561124 amine 23561124 amines 23561124 anthocyanins 23561124 histamine 23561124 polyphenol 23561124 polyphenols 23561124 putrescine 23561124 tyramine 23561128 nitrite 23561128 sodium nitrite 23561128 sulfur 23561131 8,4″-dihydroxy-3″,4″-dihydrocapnolactone-2',3'-diol 23561131 8,4″-dihydroxy-3″4″-dihydrocapnolactone-2',3'-diol 23561131 8-hydroxy-3″,4″-dihydrocapnolactone-2',3'-diol 23561131 8-hydroxyisocapnolactone-2',3'-diol 23561131 clauslactone E 23561131 coumarins 23561131 minutin A 23561131 minutin B 23561131 monoterpene coumarins 23561135 4-Methyl-7-hydroxycoumarin 23561135 4-thiazolidinones 23561135 7-hydroxy-4-methylcoumarin 23561135 DPPH 23561135 ascorbic acid 23561135 coumarin 23561135 coumarinyl thiosemicarbazides 23561135 galvinoxyl 23561135 thiazolidinone 23561135 thiosemicarbazide 23561135 thiosemicarbazides 23561137 3β-hydroxy-8,24-dien-21-al 23561137 NO 23561137 ergosterol 23561137 ergosterol peroxide 23561137 ethyl acetate 23561137 inotodiol 23561137 lanosterol 23561137 petroleum ether 23561137 trametenolic acid 23561138 6- and 8-methyl shogaols 23561138 6-Gingerol 23561138 6-gingerol 23561138 6-paradol 23561138 acetone 23561138 ethanol 23561138 gingerol 23561138 polyphenol 23561139 acrylamide 23561139 ascorbic acid 23561139 glucosinolates 23561139 vitamins 23561139 vitamins B 23561140 anthocyanin 23561140 anthocyanins 23561140 polyphenol 23561140 procyanidins 23561140 quercetin rutinoside 23561141 astaxanthin 23561147 FAs 23561147 Fatty acid 23561147 fatty acids 23561152 Annatto 23561152 Norbixin 23561152 norbixin 23561152 sodium 23561157 (1)H 23561157 KOH 23561157 O2 23561157 fatty acids 23561157 iodine 23561157 myristic acid 23561157 oleic acid 23561157 palmitelaidic acid 23561157 palmitic acid 23561157 peroxide 23561157 stearic acid 23561158 DHA 23561158 EPA 23561158 Li-RACOOH 23561158 R'ACHCHCOOH 23561158 R'BCHCHCOOH 23561158 TAGs 23561158 acyl 23561158 diacylglycerol 23561158 docosahexaenoic acids 23561158 eicosapentaenoic 23561158 fatty acid 23561158 lithiated TAG 23561158 polyunsaturated triacylglycerols 23561158 triacylglycerols 23561158 α,β-unsaturated fatty acid 23561161 CaCl2 23561161 CaO 23561161 CaSO4 23561161 calcium 23561161 calcium acetate 23561161 calcium gluconate 23561161 fatty acid 23561161 fatty acids 23561161 phosphate 23561165 carbonyl 23561165 sulphydryl 23561169 C8-C16 23561169 chlorophyll 23561169 fatty acids 23561169 isoprenoids 23561169 lutein 23561169 tocopherols 23561169 xanthophyll 23561169 β-carotene 23561171 H 23561171 Na 23561171 OH 23561171 acyl 23561171 di-malonyl 23561171 ginsenosides 23561171 malonyl 23561171 protopanaxadiol 23561171 protopanaxatriol 23561171 saponins 23561171 sugar 23561176 (+)-catechin 23561176 (-)-epicatechin 23561176 (-)-epigallocatechin 23561176 (-)-epigallocatechin-3-gallate 23561176 BHT 23561176 BTH 23561176 EGC 23561176 EGCG 23561176 H 23561176 butylated hydroxytoluene 23561176 flavonoid 23561176 hydrogen 23561176 phosphatidylcholine 23561176 sphingomyelin 23561177 Folates 23561177 folate 23561177 folates 23561178 amino acids 23561178 hydroperoxide 23561178 linoleic acid 23561178 linolenic acid 23561183 Catechin 23561183 Methylene chloride 23561183 PAC 23561183 PAC-A2 23561183 PAC-B1 23561183 catechin 23561183 ethyl acetate 23561183 formic acid 23561183 proanthocyanidin 23561183 vanillin hydrochloric 23561185 fatty acids 23561185 triacylglycerols 23561185 triglyceride 23561185 β-carotene 23561188 C-20 oxygenated ent-kaurane 23561188 C-20 oxygenated ent-kauranes 23561188 Effusanin E 23561188 butanol 23561188 effusanin E 23561188 effusanin F 23561188 ethanol 23561188 ethyl acetate 23561188 lasiodin 23561188 methyl rosmarinate 23561188 pedalitin 23561188 petroleum ether 23561188 rabdosichuanin D 23561188 rosmarinic acid 23561190 (1)H 23561190 (13)C 23561190 24-mCAF 23561190 24-methylene cycloartanyl ferulate 23561190 CAF 23561190 acetonitrile 23561190 cycloartenyl ferulate 23561190 n-hexane 23561190 triterpene alcohol 23561191 3,5-dihydroxybenzoic acid 23561191 3-(3,5-dihydroxyphenyl)-1-propanoic acid 23561191 Alkylresorcinols 23561191 DHPPA 23561191 alkylresorcinols 23561191 phenolic 23561192 Anthocyanin 23561192 NaCl 23561192 fructose 23561192 glucose 23561192 sodium chloride 23561192 sucrose 23561192 sugars 23561192 tartaric and malic acids 23561194 Ca(2+) 23561194 Oxalic acid 23561194 oxalate 23561194 oxalic acid 23561194 polyphenols 23561194 quinic acid 23561194 tartaric acid 23561197 Fe3O4 23561197 ascorbic acid 23561197 sucrose 23561197 urea 23561197 xanthine 23561198 FeCl3 23561198 carbon 23561198 lactic acid 23561198 lactose 23561198 nitrogen 23561198 thiamine 23561203 Pyronine B 23561203 SDS 23561203 Se(IV) 23561203 selenium 23561203 sodium dodecyl sulphate 23561208 Vanillin 23561208 anthocyanins 23561208 furfuryl alcohol 23561208 proanthocyanidins 23561208 syringaldehyde 23561213 (dihydro) hydroxycinnamic acid 23561213 5-O-feruloyl quinic acid 23561213 ChA 23561213 HCA 23561213 HCAs 23561213 N(1),N(10)-bis-(dihydrocaffeoyl) spermidine 23561213 N(1),N(14)-bis-(dihydrocaffeoyl) spermine 23561213 N(1),N(5),N(14)-tris-(dihydrocaffeoyl) spermine 23561213 anthocyanin 23561213 caffeic acid 23561213 caffeoyl putrescine 23561213 chlorogenic acid 23561213 cis-ChA 23561213 crypto-ChA 23561213 didydrohydroxycinnamic acid 23561213 feruloyl octopamine 23561213 hydroxycinnamic acid 23561213 neo-ChA 23561213 sinapoyl hexose 23561222 CAPE 23561222 Caffeic acid phenethyl ester 23561222 caffeic acid 23561222 caffeic acid phenethyl ester 23562076 glucose 23562245 (13)C7 23562245 IAA 23562245 N-ethylmaleimide 23562245 NEM 23562245 cysteine 23562245 d5 23562245 iodoacetanilide 23562369 1, 10-phenantroline 23562369 EDTA 23562369 EGTA 23562369 LPA 23562369 LPC 23562369 choline 23562369 lysophosphatidic acid 23562369 lysophosphatidylcholine 23562369 phosphatidylcholine 23562369 phosphatidylserine 23562369 sphingomyelin 23562597 19-cyclopropyl acetate 23562597 19-hydroxy 23562597 4',19-Diacetate 23562597 4'-esters 23562597 Ilicicolin H 23562597 N 23562597 O 23562597 ilicicolin H 23562633 PEG 23562633 PEG-FA 23562633 alanine 23562633 aspartate 23562633 folate 23562633 folic acid 23562633 polyethylene glycol 23562634 DP-TAT-59 23562634 TAT-59 23562634 miproxifen phosphate 23562706 DON 23562706 FB1 23562706 MTT 23562706 NIV 23562706 ZEA 23562706 deoxynivalenol 23562706 fumonisin B1 23562706 fumonisins B1 23562706 nivalenol 23562706 zearalenone 23562707 2,6-dimethylaniline 23562707 2-methoxi-5-methylaniline 23562707 4,4'-diaminodiphenylmethane 23562707 4,4'-oxydianiline 23562707 4-aminobiphenyl 23562707 Sudan III 23562707 aniline 23562707 aromatic amines 23562707 azo 23562707 ironporphyrin 23562707 o-anisidine 23562765 17β-estradiol 23562765 BPA 23562765 BPAF 23562765 BPS 23562765 Bisphenol A 23562765 R1881 23562765 androgen 23562765 bisphenol AF 23562765 bisphenol S 23562765 estrogen 23562995 ZnO 23563049 Ketoprofen 23563049 ketoprofen 23563049 prostaglandin 23563055 2,2-diphenyl-1-picrylhydrazyl 23563205 thiazolidinediones 23563356 serotonin 23564211 cetirizine 23564211 oxygen 23564211 verapamil 23564329 Al 23564329 CO 23564329 Si 23564329 graphene 23564329 graphenes 23564643 6-OH-PBDE-47 23564643 PBDE 23564643 PBDE-47 23564643 PBDEs 23564643 Polybrominated diphenyl ethers 23564643 organobromine 23564646 2,4-dinitrochlorobenzene 23564646 CinA 23564646 DNCB 23564646 IPDI 23564646 TMA 23564646 cinnamaldehyde 23564646 cysteine 23564646 isophorone diisocyanate 23564646 lysine 23564646 oxygen 23564646 trimellitic anhydride 23564918 NH2 23565585 PEG 23565585 PLA 23565585 PLGA 23565585 glucose 23565585 poly(lactic acid) 23565585 poly(lactide-co-glycolide) 23565585 polyethylene glycol 23565749 Ag 23565749 AgCl 23565749 AgNO3 23565749 NaCl 23565749 Silver 23565749 Silver Chloride 23565749 ethylene glycol 23565749 halide 23565749 polyol 23565749 silver 23565753 Androgen 23565753 Androgens 23565753 androgen 23565753 androgens 23565754 N 23565754 androgen 23565754 androgens 23565776 Amino Acid 23565776 amino Acid 23565776 amino acid 23565776 amino acids 23565776 aminoacid 23565776 nucleotide 23565776 phenylalanine 23565776 phenylanaline 23565776 saturated or unsaturated diacyl glycerol 23565776 thymidine 23565822 LSCO 23565822 Oxygen 23565822 lanthanum strontium cobaltite 23565822 oxygen 23565822 perovskite 23566174 Bis-urea 23566174 Hydrogen 23566174 bis-urea 23566174 hydrogen 23566269 3-Hydroxy-5-(2-phenylethyl)pyridine-2(1H)-one 23566269 3-hydroxy-pyridine-2(1H)-one 23566269 4-Hydroxypyridazin-3(2H)-one 23566269 4-hydroxypyridazin-3(2H)-one 23566269 6-[2-(3,5-Difluorophenyl)ethyl]-4-hydroxypyridazin-3(2H)-one 23566269 MK-801 23566269 N-methyl-d-aspartate 23566269 Tyr 23566269 d-Amino Acid 23566269 d-Amino acid 23566269 d-amino acids 23566269 d-serine 23566299 Acetylcholine 23566299 acetylcholine 23566299 hydrogen 23566514 4-amino-pyrrolopyrimidine 23566514 4-aminopyrrolopyrimidine 23566514 benzimidazole 23566514 ketophenyl 23566514 ketophenyl pyrrolopyrimidine urea 23566514 pyrrolopyrimidine 23566899 acetaminophen 23567034 7,8-dimethoxycoumarin 23567034 E-β-ocimene 23567034 MTT 23567034 citronellol 23567034 geraniol 23567034 methanol 23567034 sinapic acid 23567037 oxygen 23567037 superoxide 23567041 Fluorescein 23567041 Nile red 23567041 fluorescein 23567045 Lac-DOPE 23567045 N-lactobionyl-dioleoyl phosphatidylethanolamine 23567046 Au 23567046 DOX 23567046 doxorubicin 23567046 iron oxide 23567242 BPA 23567242 Bisphenol A 23567242 epoxy 23567242 polycarbonate 23567269 oxygen 23567314 PFAA 23567314 PFAAs 23567314 PFDA 23567314 PFOA 23567314 PFOS 23567314 Wy14,643 23567314 androstane 23567314 carboxylates 23567314 perfluoroalkyl acid 23567314 perfluoroalkyl acids 23567314 perfluorooctane sulfonate 23567314 perfluorooctanoic acid 23567318 N 23567318 carbohydrate 23567318 xylobiose 23567318 xylohexaose 23567318 xylopentaose 23567318 xylotetraose 23567318 xylotriose 23567486 HES-HEMA 23567486 HES-MA 23567486 HES-P(EG)6MA 23567486 PEG 23567486 hydroxyethyl 23567486 hydroxyethyl methacrylate 23567486 methacrylate 23567486 polyethylene glycol 23567486 polyethylene glycol methacrylate 23567861 7-O-galloyl-d-sedoheptulose 23567861 N 23567861 cholesterol 23567861 fatty acids 23567861 glucose 23567861 nitric oxide 23567861 oxygen 23567861 sterol 23567861 thiobarbituric acid 23567861 triglycerides 23567954 2,2-diallyl-1,1,3,3-tetraethylguanidinium chloride 23567954 2,2-diallyl-1,1,3,3-tetraethylguanidiniumchloride and tris(diethylamino)diallylaminophosphonium salts 23567954 H2O2 23567954 N-benzyl-2-azanorbornene-5 23567954 Polysulfones 23567954 ascorbate 23567954 azanorbornenes 23567954 hydrogen peroxide 23567954 iron 23567954 polysulfone 23567954 polysulfones 23567959 (1)H 23567959 (13)C 23567959 1,3,5-substituted-2,3-dihydro-2-imino-benzimidazoles 23567959 5-substituted-2-aminobenzimidazoles 23567959 5-substituted-2-iminobenzimidazole 23567959 acetate 23567959 hydrazone 23567999 cysteine 23567999 τ-CnVA 23568274 tyrosine 23568429 tritium 23568455 LY294002 23568455 Phosphatidylinositol 23568455 phosphatidylinositol 23568455 tetrazolyl 23568508 Rhenium 23568508 Rhenium(I) indolato complexes 23568508 oxygen 23568512 AA-GSH 23568512 AAMA 23568512 Acrylamide 23568512 GAMA 23568512 GSH 23568512 N-acetyl-S-(2-carbamoylethyl)cysteine 23568512 N-acetyl-S-(2-hydroxy-2-carbamoylethyl)cysteine 23568512 N7-(2-carbamoyl-2-hydroxyethyl)guanine 23568512 N7-GA-Gua 23568512 acrylamide 23568512 asparagine 23568512 carbohydrates 23568512 glutathione 23568512 glycidamide 23568512 mercapturic acids 23568578 GABA 23568578 alanine 23568578 amino acid 23568578 amino acids 23568578 glutamate 23568578 glutamine 23568578 threonine 23568578 γ-aminobutyric acid 23568579 cocaine 23570266 silica 23570328 2,2,6,6-tetramethylpiperidine-N-oxyl 23570328 4-acetamido-TEMPO 23570328 C-C 23570328 HCl 23570328 HNO3 23570328 TEMPO 23570328 benzylic alcohols 23570394 C 23570394 Graphene 23570394 O 23570394 Pt(111) 23570394 Ru 23570394 SiC 23570394 SiO2 23570394 graphene 23570451 PMMA 23570451 acetone 23570451 poly(methyl methacrylate) 23570500 (1)H 23570500 DOX 23570500 FITC 23570500 PEO45 23570500 PtNEA 23570500 doxorubicin 23570500 fluorescein isothiocyanate 23570500 poly(ethylene oxide) 23570500 tNEA 23570500 trans-N-(2-ethoxy-1,3-dioxan-5-yl) acrylamide 23570514 NAD(+) 23570514 Thieno[3,2-d]pyrimidine-6-carboxamides 23570514 carboxamide 23570514 nicotinamide 23570533 HB-C12 23570533 Quartz 23570533 dodecyl 3,4,5-trihydroxybenzoate 23570533 lignin 23570552 Cinnamaldehyde 23570552 cinnamaldehyde 23570561 Urea 23570561 urea 23570609 Lac-α-CDE 23570609 PEG 23570609 PEG-LαC 23570609 PEG-LαCs 23570609 lactose 23570609 polyamidoamine 23570609 polyethylene glycol 23570609 α-cyclodextrin 23570839 AcOEt 23570839 CH3OH 23570839 CHCl3 23570839 Daphneretusin A 23570839 Daphneretusin B 23570839 coumarin 23570839 n-hexane 23570840 Goniolandrene A and B 23570840 Goniothalamin 23570840 butanol 23570840 chloroform 23570840 goniolandrene B 23570840 goniolandrene-A (1), -B (2) 23570840 methanol 23570840 n-hexane 23570914 bleomycin 23570914 caffeic acid phenethyl ester 23570914 glutathione 23570914 oxygen 23570914 superoxide 23570914 thiobarbituric acid 23570992 Arsenic 23570992 arsenic 23570992 hydroxysteroid 23570992 sodium arsenite 23570993 Carbon 23570993 carbon 23570998 Quercetin 23570998 flavonoids 23570998 quercetin 23570998 rutin 23571415 sodium fluorescein 23572409 Pomalidomide 23572409 Pomalyst 23572409 bortezomib 23572409 dexamethasone 23572409 lenalidomide 23572409 pomalidomide 23572409 thalidomide 23572520 CysNO 23572520 GSH 23572520 NO 23572520 S 23572520 cysteine 23572520 glutathione 23572520 nitric oxide 23573957 E-stilbene 23573957 prolinamide 23573957 prolinamides 23573990 PEO 23573990 helium 23573990 nitrogen 23573990 polyethylene oxide 23573990 sPS 23573990 syndiotactic polystyrene 23573990 tetrahydrofuran 23574008 7-butoxy-2H-chromen-2-one 23574008 C12EO4 23574008 C4-C-N-PEG9 23574008 H2O 23574008 PhyEO20 23574008 cinnamic acid 23574008 coumarin 23574008 polyoxyethylene 23574008 polyoxyethylene phytosterol ether 23574008 tetraoxyethylene dodecyl ether 23574014 DTPA 23574014 diethylenetriaminepentaacetic acid 23574014 maleimide 23574014 poly(N-alkylacrylamide) 23574534 Cd 23574534 He 23574534 SnO2 23574984 Naloxone 23574984 PGE2 23574984 acetic acid 23574984 prostaglandin E2 23575765 ITO 23575765 ZnO 23575765 carbon 23575765 indium tin oxide 23575765 silver 23575765 zinc oxide 23576174 Mono- and Dimeric Alkenylphenols 23576174 Sarmentosumols A to F 23576174 dimeric alkenylphenols 23576174 sarmentosumol A 23576174 sarmentosumols A to F 23576286 Ca-GP 23576286 OPF 23576286 Oligo(poly(ethylene glycol) Fumarate 23576286 alizarin red 23576286 calcium 23576286 calcium glycerophosphate 23576286 oligo(poly(ethylene glycol)fumarate) 23576297 Formic Acid 23576297 Palladium 23576297 Pd 23576297 Porphyrin 23576297 formic acid 23576297 porphyrin 23576306 (13) C 23576306 Alkylcarbonate 23576306 CO2 23576306 Carboxylate 23576306 Tetramethylammonium 23576306 alcohol 23576306 amines 23576306 amino 23576306 bicarbonate 23576306 carboxylate 23576306 ethylene glycol 23576306 hydrogen 23576306 hydroxyethylcarbonate 23576306 methanol 23576306 methyl acrylate 23576306 methylcarbonate 23576306 tetramethylammonium hydroxide 23576306 β-Amino Acid 23576306 β-amino acid 23576341 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide 23576341 ATP 23576341 MTT 23576341 biphenyl 23576341 urea 23576355 (23R,24S)-23,24,25-trihydroxytirucall-7-ene-3,6-dione 23576355 21α-methylmelianodiol 23576355 21β-methylmelianodiol 23576355 24-epipiscidinol A 23576355 EtOH 23576355 NO 23576355 Tirucallane 23576355 Triterpenoids 23576355 brumollisols A-C 23576355 piscidinol A 23576355 tirucallane 23576355 triterpenoids 23576378 Demethylvancomycin 23576378 N-(6-phenylheptyl)demethylvancomycin 23576378 demethylvancomycin 23576378 gentamicin 23576378 methicillin 23576378 vancomycin 23577042 biotin 23577589 glucose 23577701 (1)H 23577701 (13)C 23577701 apetalactone 23577701 canophyllol 23577701 dipyranocoumarin 23577701 friedelin 23577701 inophyllum C 23577701 α-hydroxytomentolide A 23577749 flavonoids 23577749 gallic acid 23577749 phenolic 23577749 phenols 23577749 terpenoids 23578584 ATP 23578584 calcium 23578610 baicalein 23578623 NaCl 23578627 2″-hydroxyoleuropein 23578627 3,4-Dihydroxyphenylglycol 23578627 DHPG 23578627 isoverbascoside 23578627 phenol 3,4-dihydroxyphenylglycol 23578627 phenolic 23578627 verbascoside 23578627 β-hydroxy 23578627 β-hydroxyacteoside 23578627 β-hydroxyisoacteoside 23578632 1,1-diphenyl-2-picrylhydrazyl 23578632 DPPH 23578632 DPPH(·) 23578632 Polyphenols 23578632 butylated hydroxytoluene 23578632 ethanol 23578632 ferric 23578632 omega-3 polyunsaturated fatty acid 23578632 polyphenols 23578632 thiobarbituric acid 23578632 α-tocopherol 23578632 ω3 PUFA 23578633 PFOA 23578633 PFOS 23578633 perfluorooctane sulfonate 23578633 perfluorooctane sulfonic acid 23578633 perfluorooctanoic acid 23578634 Ca-propionate 23578634 FeNa-EDTA 23578634 FeNa-ethylenediaminetetraacetic acid 23578634 KCl 23578634 NaCl 23578636 Anthocyanins 23578636 alcohol 23578636 alcoholic 23578636 phenolic 23578636 tannins 23578642 ammonium sulphate 23578643 5-HMF 23578643 5-hydroxymethylfurfural 23578643 glucose 23578643 oxygen 23578651 ETU 23578651 alumina 23578651 ethylenethiourea 23578651 methanol 23578652 ATP 23578652 NMDA 23578652 S-allylcystein 23578652 hydroethanolic 23578652 hydroxyl 23578652 oxygen 23578652 peroxyl 23578652 peroxynitrite 23578652 superoxide 23578690 amine 23578690 cytarabine 23578690 doxorubicin 23578690 oxygen 23578690 tethered amine 23578763 prednisone 23578968 MBP 23578968 MEHP 23578968 MEP 23578968 MMP 23578968 Monoesters 23578968 carbon 23578968 carbons 23578968 monoesters 23578968 phthalate 23578968 phthalate esters 23578968 phthalates 23578968 steroid 23578968 testosterone 23579044 MPD 23579044 cocaine 23579044 d-amphetamine 23579044 dopamine 23579044 methylphenidate 23579044 monoamine 23579044 norepinephrine 23579182 N 23579333 Co 23579333 Co(iii) 23579333 Ni 23579333 hydroxide 23579333 hydroxides 23579333 iodine 23579333 oxygen 23579333 potassium phosphate 23579427 alcohol 23579486 APR19 23579486 Progesterone 23579486 RU486 23579486 homosteroid 23579486 hydrogen 23579486 mifepristone 23579486 progesterone 23579486 serine 23579486 steroid 23579487 glucose 23579487 phosphatidylinositol 23580169 (Ca,Eu)2SiS4 23580169 Ca 23580169 Ca2SiS4 23580169 Eu 23580169 europium 23580169 monoclinic Eu2SiS4 23580169 thiosilicate 23580257 Baicalin 23580257 baicalin 23580257 dexamethasone 23580257 eosin 23580257 hematoxylin 23580402 cholesterol 23580402 sodium 23580402 sugars 23580402 vitamin C 23580402 vitamin E 23580402 zinc 23580402 β-carotene 23580404 PbS 23580421 Graphene Oxide 23580421 Manganese Dioxide 23580421 MnO2 23580652 aspartic acid 23580652 calcium 23580652 glycine 23581295 4-octylphenyldiazenido 23581295 4-octylphenyldiazonium 23581295 LiBHEt3 23581295 V-N═N-Ar 23581295 VCl4 23581295 diazenido 23581295 superhydride 23581295 vanadium 23581492 Arg-Arg 23581492 Arg-Arg-Asp 23581492 Glu 23581492 acidic amino acids 23581492 arginine 23581492 carbon 23581965 ATO 23581965 Antimony-Doped Tin Oxide 23581965 Hematite 23581965 antimony-doped tin oxide 23581965 hematite 23581965 oxide 23581965 polystyrene 23581993 ATP 23581993 carbon 23582235 Poly(ADP-ribose) 23582235 Zinc 23582235 zinc 23582235 zinc chloride 23582330 Glucose 23582330 Sugar 23582330 glucose 23582330 haloacid 23582330 phosphosugars 23582330 sugar 23582779 glucose 23583168 fatty-acid 23583203 TPP 23583203 celastrol 23583437 (1α, 3β, 25R)-spirost-5-ene-2-diol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl(1→4)]-O-β-d-glucopyranoside 23583437 (2α, 3β, 12β, 25R)-spirost-5-ene-2, 3, 12-triol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-O-β-d-glucopyranoside 23583437 (3β, 12β, 25R)-spirost-5-ene-3,12-diol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-O-β-d-glucopyranoside 23583437 (3β, 7β, 12β, 25R)-spirost-5-ene-3, 7, 12-triol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-O-β-d-glucopyranoside 23583437 EtOH 23583437 steroidal saponins 23583454 3,4-Methylenedioxypyrovalerone 23583454 3,4-methylendioxymethamphetamine 23583454 4-fluoromethcathinone 23583454 5-HT 23583454 Butylone 23583454 MDMA 23583454 METH 23583454 [(3)H] 23583454 amphetamine 23583454 cocaine 23583454 dopamine 23583454 mephedrone 23583454 methamphetamine 23583454 methcathinone 23583454 methcathinones 23583454 methylone 23583454 monoamine 23583454 naphyrone 23583454 norepinephrine 23583454 serotonin 23583513 1,5-dihydro-benzo[f][1,3,5]triazepine-2,4-dione 23583513 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 23583513 diazepine 23583641 MTT 23583641 NO 23583641 methanol 23583641 polyurethane 23583735 (1)H 23583735 As2S2 23583735 Realgar 23583735 amino acid 23583735 choline 23583735 realgar 23583882 methoxychlor 23583882 organochlorine 23583882 organophosphate 23583882 parathion 23583882 piperonyl butoxide 23583910 2,3-oxidosqualen 23583910 Aminopropylindenes 23583910 Grundmann's ketone 23583910 N,N-dimethylaminopropyl 23583910 aminopropylindenes 23583910 cholesterol 23583910 lanosterol 23583910 oxidosqualene 23583928 JNJ 10191584 23583928 VUF 8430 23583928 diazepam 23583928 histamine 23583928 scopolamine 23583929 quinolinic acid 23584090 CpG 23584277 diethylmethylammonium trifluoromethanesulfonate 23584277 hydrogen peroxide 23584277 oxygen 23584358 8-iso-prostane 23584358 Agomelatine 23584358 N-acetylcysteine 23584358 NAC 23584358 Paracetamol 23584358 agomelatine 23584358 alanine 23584358 aspartate 23584358 glutathione 23584358 melatonin 23584358 paracetamol 23584358 superoxide 23584418 Al(3+) 23584418 Aluminium 23584418 aluminium 23584426 As(V) 23584426 Fe3O4 23584426 arsenic 23584426 arsenics 23584426 ferroferric oxide 23584427 Cr 23584427 Cr(VI) 23584427 Hexavalent chromium 23584427 hexavalent chromium 23584427 oxygen 23584541 1,2,3-triazole 23584541 3-O-propargylated betulinic acid and its 1,2,3-triazoles 23584541 3{1N(2-cyanophenyl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid 23584541 3{1N(5-hydroxy-naphth-1yl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid 23584541 C 23584541 betulinic acid 23584545 Schiff's base 23584545 quinoline 23584556 C 23584556 N 23584556 amino acid 23584556 zinc 23584636 Al2O3 23584636 Au 23584636 ITO 23584636 ZnO 23584636 indium-tin-oxide 23584857 2-deoxyglucose 23584886 Ketoconazole 23584886 ketoconazole 23584886 midazolam 23584948 Caprelsa 23584948 Vandetanib 23584948 tyrosine 23585058 APV 23585058 BAPTA-AM 23585058 Ca2+ 23585058 GABA 23585058 NMDA 23585058 UO126 23585058 calcium 23585058 γ amino-butyric acid 23585235 D 23585235 D2 23585235 H 23585235 H2 23585235 HD 23585235 Pd 23585235 Pd(111) 23585235 hydrogen 23585358 C-H 23585358 diazonium 23585380 PLGA 23585380 poly(L-lactic-co-glycolic acid) 23585383 Ag 23585383 Fe2 O3 23585383 iron oxide 23585770 Ni 23586441 (1)H 23586441 Acridine 23586441 acridine 23586441 acridinium 23586441 aliphatic ammonium 23586441 nitrogen 23586441 tetraamine 23586441 triethylentetraamine 23586519 2-propanol 23586519 P2VP 23586519 PDMS 23586519 PFS 23586519 THF 23586519 decane 23586519 poly(2-vinylpyridine 23586519 poly(ferrocenyldimethylsilane) 23586519 polydimethylsiloxane 23586638 C 23586638 CH3C(O)O(•)CHCH2OH 23586638 CH3C(O)OCH(OH)(•)CH2 23586638 CH3COOC2H3 23586638 H 23586638 NO 23586638 O2 23586638 OH 23586638 Vinyl Acetate 23586638 Vinyl acetate 23586638 acetic acid 23586638 ethylenic 23586638 formaldehyde 23586638 formic acetic anhydride 23586839 2H 23586839 C 23586839 CH 23586839 CH2 23586839 H 23586839 H2 23586839 Ir 23586839 Methane 23586839 Pt 23586839 Ta 23586839 Transition Metal 23586839 W 23586839 carbene 23586839 carbyne 23586839 hydrido-methylidyne 23586839 hydrogen 23586839 methane 23586839 transition metal 23587048 3-Hydroperoxy-N-nitrosomorpholine 23587048 3-oxapentanal 23587048 6-(2-{2-[(9H-purin-6-yl)amino]ethoxy}ethoxy)-9H-purin-2-amine 23587048 Ade 23587048 Gua 23587048 N 23587048 N-Nitrosomorpholine 23587048 Na(AcO)3BH 23587048 NaBH4 23587048 NaNCBH3 23587048 O 23587048 Purine 23587048 ascorbate 23587048 borohydride 23587048 diazonium 23587048 hydride 23587048 hydroperoxide 23587048 imine 23587048 iminium 23587048 nicotinamide 23587048 α-hydroxynitrosamine 23587423 lysine 23587426 2-amino-2-hydroxymethyl-propane-1,3-diol 23587426 4-alkyloxybenzaldehyde 23587426 aromatic amino alcohols 23587426 methicillin 23587660 alcohol 23588093 5-hydroxytriptamine 23588093 Ca(2+) 23588093 CaCl2 23588093 KCl 23588093 Luteolin 23588093 calcium 23588093 chrysoeriol 23588093 glibenclamide 23588093 indomethacin 23588093 isovitexin 23588093 l-NAME 23588093 luteolin 23588093 norepinephrine 23588093 p-coumaric acid 23588093 phenylephrine 23588093 tetraethylammonium 23588094 chloroform 23588094 cinnamyl alcohol 23588094 ethanol 23588094 n-butanol 23588094 styrene 23588094 α-pinene 23588312 5-FU 23588312 5-Fluorouracil 23588312 dihydropyrimidine 23588390 4-(N)-stearoyl 23588390 BrdU 23588390 GEM-C18 23588390 GEM-C18-PLGA 23588390 PLGA 23588390 gemcitabine 23588390 stearoyl 23588390 stearoyl gemcitabine 23588558 statin 23588560 TAC 23588560 Tacrolimus 23588560 tacrolimus 23588562 CBD 23588562 THC 23588562 cannabidiol 23588562 tetrahydrocannabinol 23588681 Emodin-6-O-β-D-glucoside 23588681 PMA 23588681 emodin-6-O-β-D-glucoside 23588681 phorbol-12-myristate 13-acetate 23588682 carboxy 23588682 polyvinyl pyrrolidone 23588682 venlafaxine 23588796 polyaniline 23588997 ZrH2 23588997 hydrogen 23588997 zirconium 23588997 zirconium hydrides 23589223 C60 23589223 Fullerene 23589223 fullerene 23589329 Arsenic 23589329 arsenic 23589329 sulforaphane 23589329 tBHQ 23589329 tert-butylhydroquinone 23589462 (1) H 23589462 (13) C 23589462 (15) N 23589462 Cu(II) 23589462 N-C 23589462 Zn(II) 23589462 amino acids 23589476 glucose 23589501 Cu 23589501 NaCl 23589501 O2 23589501 dioxygen 23589501 hydrogen 23589501 neocuproine 23589501 oxygen 23589501 pyrene 23589624 amino acid 23589624 amino acids 23589624 p-azido-l-phenylalanine 23589624 p-propargyloxy-l-phenylalanine 23589624 pAzF 23589624 pPaF 23590189 H2O2 23590189 PVO 23590189 Vanillin 23590189 acetal 23590189 hydrogen peroxide 23590189 oxygen 23590189 peroxalate ester 23590189 poly(vanillin oxalate) 23590189 vanillin 23590386 CS2 23590386 P3AT 23590386 P3ATs 23590386 P3DDT 23590386 PQT12 23590386 Poly(3-alkylthiophene)s 23590386 carbon disulfide 23590386 chloroform 23590386 dichloromethane 23590386 pBTTT12 23590386 poly(2,5-bis(3-dodecylthiophen-2-yl)thieno[3,2-b]thiophene) 23590386 poly(3,3‴-didodecyl-quaterthiophene) 23590386 poly(3-alkylthiophene)s 23590386 poly(3-dodecylthiophene) 23590386 tetrahydrofuran 23590473 alcohol 23590667 MoS2 23590689 Cl(+) 23590689 ClF2(+) 23590689 ClFn 23590689 ClFn(+) 23590689 F 23590689 HF 23590689 PFn 23590689 S 23590689 SCln 23590689 SF2 23590689 SFn 23590689 SFnCl 23590882 Ca(2+) 23590882 Glutamate 23590882 amino acid 23590882 amino acids 23590892 DHA 23590892 Docosahexaenoic acid 23590892 Paraquat 23590892 hydroxyproline 23590892 paraquat 23591044 6-STM 23591044 6-sulfatoxymelatonin 23591044 Ethanol 23591044 Melatonin 23591044 androgen 23591044 estradiol 23591044 estrogen 23591044 ethanol 23591044 melatonin 23591044 progesterone 23591044 steroid 23591111 SAHA 23591111 hydroxamic acid 23591111 vorinostat 23591111 zinc 23591111 β-cyclodextrin 23591111 βCD 23591660 C60 23591660 Ga 23591660 carbon 23591777 CCl4 23591777 MDA 23591777 MSM 23591777 carbon tetrachloride 23591777 malondialdehyde 23591777 methylsulfonylmethane 23591777 superoxide 23591995 ramiprilat 23592429 Abiraterone acetate 23592429 androgen 23592429 androgens 23592429 enzalutamide 23592516 L-amino acid 23592516 NK-252 23592516 OPZ 23592516 choline 23592516 oltipraz 23592516 thiol 23592516 urea 23592568 Trimethine Cyanine 23592568 trimethine cyanines 23592779 vitamin B12 23593923 serine 23593960 Diacetyl 23593960 TDI 23593960 diacetyl 23593960 toluene-2,4-diisocyanate 23594296 C 23594296 Cl 23594296 HP-βCD 23594296 Tween 80 23594296 chloroform 23594296 dichloromethane 23594296 ethanol 23594296 ethyl acetate 23594296 hydrogen 23594296 hydroxyl 23594296 hydroxypropyl β-cyclodextrin 23594296 methanol 23594296 octanol 23594296 phosphate 23594296 sodium citrate 23594296 taxol 23594789 6-n-propyl-2-thiouracil 23594789 PTU 23594789 Thyroid hormones 23594789 thyroid hormone 23594789 triiodothyronine 23595055 MeOH 23595055 brominated tyrosine 23595055 bromine 23595055 bromotyrosine 23595419 Ag 23595419 K 23595419 Li 23595419 Mg 23595419 MnO2 23595419 Na 23595419 chloride 23595419 lithium 23595419 lithium iron phosphate 23595419 magnesium 23595419 sodium 23595510 (1)H 23595510 (13)C 23595510 carbide 23595510 carbon 23595510 carbons 23595554 bromadiolone 23595554 difenacoum 23595692 Pine Oil 23595692 adenosine triphosphate 23595692 capsaicin 23595692 pine oil 23595692 pine-oil 23596084 Poly(N-alkyl Acrylamide) 23596084 benzophenone 23596084 poly(alkylacrylamide) 23596091 FITC 23596091 FITC-labeled mPEG-PCL 23596091 Fluorescein isothiocyanate 23596091 mPEG-PCL 23596091 monomethoxy poly(ethylene glycol)-block-poly(ε-caprolactone) 23596325 fatty acid 23596325 glucose 23596325 sucrose 23596325 unsaturated fatty acid 23596359 Cyclic Tetrapeptides 23596359 Cyclic tetrapeptides 23596359 cyclic tetrapeptides 23596359 d-amino acids 23596359 hydrogen 23596359 proline 23596972 VA64 23597047 Adenosine 23597047 nucleosides/tides 23597047 nucleotides 23597071 biotin 23597099 2-Methoxyjuglone 23597099 2-methoxyjuglone 23597099 EtOAc 23597099 ethanol 23597099 propidium iodide 23597133 CO 23597133 H 23597133 H-CO(X̃(2)A') 23597133 HCO 23597450 O-methylated isoflavone 23597450 Prunetin 23597450 nitric oxide 23597450 prostaglandin E2 23597450 prunetin 23597490 Embelin 23597490 STZ 23597490 benzoquinone 23597490 embelin 23597490 glucose 23597490 glutathione 23597490 malondialdehyde 23597490 streptozotocin 23597490 superoxide 23597507 Ca(2+) 23597507 SB366791 23597507 calcium 23597507 capsaicin 23597507 mibefradil 23597507 nifedipine 23597510 Nicotine 23597510 SAHA 23597510 Suberoylanilide hydroxamic acid 23597510 alcohol 23597510 cocaine 23597510 nicotine 23597793 (1)H 23597793 (13)C 23597793 11β-hydroxysteroid 23597793 Asp 23597793 NADP(+) 23597793 Ser 23597793 Tyr 23597793 clofibrate 23597793 clofibric acid 23597793 glucose 23597793 nicotinamide 23597793 tetrazole 23598462 graphene 23598904 AgNO3 23598904 Cd 23598904 Cd(2+) 23598904 CdCl2 23598904 HgCl2 23598904 Mn 23598904 Mn(2+) 23598904 MnCl2 23598904 cadmium 23598904 manganese 23599006 7-O-(β-D-glucopyranosyl)-galactin 23599006 alanine 23599006 aspartate 23599431 TC14012 23599433 serine 23599433 threonine 23600432 1,5-diarylpyrazoles 23600432 arachidonic acid 23600432 indoles 23600432 indolizines 23600486 (cAAC)2Zn 23600486 (cAACH)2Zn 23600486 CO2 23600486 KC8 23600486 LiB(sec-Bu)3H 23600486 Zinc 23600486 ZnCl2 23600486 cAAC 23600486 cyclic alkylaminocarbene 23600486 dicarbene zinc 23600486 zinc 23600612 8-dehydroxymethylvisanol 23600612 9-O-[3-O-acetyl-β-d-glucopyranosyl]-4-hydroxy-cinnamic acid 23600612 9-aldehydevibsanol 23600612 EtOH 23600612 lignans 23600612 visanol 23600626 PolyHis 23600626 ethylene glycol 23600626 poly(aspartic acid) 23600626 poly-l-glutamic acid 23600626 poly-l-histidine 23600626 polyAsp 23600626 polyGlu 23600626 polyHis 23600646 Fe3O4 23600646 TiO2 23600646 bisphenol A 23600646 dibutyl phthalate 23600648 (-)-4-hydroxybenzoic acid-4-O-[6'-O-(2″-methylbutyryl)-β-D-glucopyranoside] 23600648 dioxaspirocycle 23600648 quinochalcone glycoside 23600648 saffloquinoside C 23600656 1,2-dipalmitoyl-sn-glycero-3-phosphacholine 23600656 Brucine 23600656 DPPC 23600656 brucine 23600656 phosphatidylcholine 23600717 fawcettimine 23600717 lycobscurines A-C 23600735 Anthraquinones 23600735 flavonoids 23600735 terpenoids 23600754 3,4-secocycloarta-4(28),17(20)(Z),24(Z)-triene-7β-hydroxy-16β-methoxy-3,26-dioic acid 23600754 3,4-secocycloarta-4(28),17(20),24(Z)-triene-7β-hydroxy-16β,26-lactone-3-oic acid 23600754 3,4-secocycloarta-4(28),24(Z)-diene-3,26-dioic acid 23600754 3,4-secocycloartane 23600754 ester 23600754 lactone 23600754 nigranoic acid 23600800 ATP 23600800 MG-132 23600800 calcium 23600800 serine 23600807 cyclo-(l-Val-l-Leu) 23600807 diketopiperazines 23600807 rhodostegone 23600887 (25R)-26-O-[β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranosyl]-5-ene-furost-1β,3β,22α,26-tetraol-3-O-α-l-rhamnopyranosyl-(1 → 2)-[β-d-xylopyranosyl-(1 → 4)]-β-d-glucopyranoside 23600887 (25R)-26-O-[β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyl]-5-ene-furost-1β,3β,22α,26-tetraol-3-O-α-l-rhamnopyranosyl-(1 → 2)-[β-d-xylopyranosyl-(1 → 4)]-β-d-glucopyranoside 23600887 C-26 hydroxy 23600887 Furostanol 23600887 disaccharide 23600887 furostanol 23600887 ophiopogonin P 23600887 ophiopogonin Q 23600887 saponins 23600887 steroidal saponins 23600914 24(S)-hydroxycholesterol 23600914 24-OHC 23600914 TO901317 23600914 cholesterol 23600914 retinoic acid 23600925 Diaminothiazole 23600925 diaminothiazole 23600925 serine 23600925 threonine 23601387 25-hydroxy-vitamin D3 23601387 25OHD3 23601387 vitamin D 23601387 vitamin D3 23601391 sugar 23601393 Ascorbic acid 23601393 Potassium 23601393 ascorbic acid 23601393 calcium 23601393 copper 23601393 magnesium 23601393 phosphorous 23601393 zinc 23601396 calcium 23601396 carbohydrates 23601396 copper 23601396 iron 23601396 magnesium 23601396 manganese 23601396 phosphorus 23601396 potassium 23601396 selenium 23601396 sodium 23601396 zinc 23601409 Glucose 23601409 arabinose 23601409 ethanol 23601409 galactose 23601409 mannose 23601409 monosaccharide 23601409 xylose 23601709 DMSO 23601709 EMPA 23601709 O 23601709 [(11)C]CH3I 23601709 [(11)C]EMPA 23601709 [(11)C]N-ethyl-2-(N-(6-methoxypyridin-3-yl)-2-methylphenylsulfonamido)-N-(pyridin-3-ylmethyl)acetamide 23601709 [(3)H]-EMPA 23601709 carbon 23601709 cesium carbonate 23601709 chlorotrimethylsilane 23601709 sodium iodide 23601710 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 23601710 benzotriazepine 23601710 phenyl 23601710 spirobenzodiazepine 23601711 6-bromo-8-ethoxy-3-nitro-2H-chromene 23601711 8-ethoxy-2-(4-fluorophenyl)-3-nitro-2H-chromene 23601711 BENC-511 23601711 S14161 23601711 l-proline 23601711 triethylamine 23602400 2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d]pyrimidine 23602400 4-amino 23602400 4-amino-2-phenylpyrimidine 23602400 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine 23602400 N-propylacetamide 23602400 pyrimidines 23602442 amine 23602442 diarylurea 23602442 diarylureas 23602516 Cisplatin 23602516 cisplatin 23602732 Salidroside 23602732 salidroside 23602732 tyrosol 23602891 HCQ 23602891 Hydroxychloroquine 23602891 hydroxychloroquine 23602903 H2O2 23602903 Monoterpene pyridine alkaloids 23602903 Scrophularianines A-C 23602903 cyclopenta [c] pyridine 23602903 iridoids 23602903 monoterpene pyridine 23602903 monoterpene pyridine alkaloids 23602903 phenolics 23602986 COT 23602986 Cotinine 23602986 DHβE 23602986 MEC 23602986 MLA 23602986 NIC 23602986 cotinine 23602986 dihydro-beta-eritroidine 23602986 mecamylamine 23602986 methyllycaconitine 23602986 nicotine 23602989 Ca(2) 23602989 Ca(2+) 23602989 GABA 23602989 K(+) 23602989 KN-62 23602989 PD 128,907 23602989 SKF 38393 23602989 [(3)H]GABA 23602989 cAMP 23602989 dopamine 23602989 ionomycin 23602989 nifedipine 23603053 2'-OH-BDE-007 23603053 3'-OH-BDE-007 23603053 3'-OH-BDE-028 23603053 3-OH-BDE-047 23603053 4'-OH-BDE-017 23603053 4'-OH-BDE-049 23603053 5'-OH-BDE-099 23603053 6'-OH-BDE-099 23603053 6-OH-BDE-047 23603053 OH-PBDE 23603053 OH-PBDEs 23603053 PBDE 23603053 PBDEs 23603053 Polybrominated diphenyl ethers 23603053 estrogen 23603053 hydroxylated polybrominated diphenyl ethers 23603059 Arsenic 23603059 N 23603059 N-acetylcysteine 23603059 NAC 23603059 SP6001325 23603059 arsenic 23603059 oxygen 23603059 sodium arsenite 23603112 BMPCP-4P2 23603112 TMPCP 23603112 TMPCP-4P 23603112 bi-cationic meso-5,10-bis(4-N-methylpyridyl)-15,20-di-(4-carboxyphenyl)porphyrin 23603112 porphyrin 23603112 porphyrins 23603112 tetrapeptide 23603112 tetrapeptides 23603112 tri-cationic meso-tri(4-N-methylpyridyl)-mono-(4-carboxyphenyl)porphyrin 23603193 MDA 23603193 NO 23603193 PTZ 23603193 Val 23603193 Valproate 23603193 nitric oxide 23603193 pentylenetetrazol 23603293 Toluquinol 23603293 methylhydroquinone 23603293 toluquinol 23603339 3-methylcholanthrene 23603339 7-ethoxyresorufin 23603339 DHEA 23603339 Dehydroepiandrosterone 23603339 O 23603339 actinomycin D 23603339 androgen 23603339 bicalutamide 23603339 dehydroepiandrosterone 23603339 estrogen 23603339 phenacetin 23603380 Piperidine 23603380 acetylcholine 23603380 alpha conotoxin GI 23603380 anabasine 23603380 lobeline 23603380 myosmine 23603380 pyridine alkaloid 23603381 BLM 23603381 Ellagic acid 23603381 GSH 23603381 bleomycin 23603381 carbonyl 23603381 cyclophosphamide 23603381 hydroxyproline 23603381 nitric oxide 23603385 TiO2 23603385 titanium dioxide 23603635 benzoquinones 23603635 tyrosine 23603635 vanadium 23604140 Bodipy 23604140 Bodipy [558/568] 23604140 gallamine 23604140 indocarbazolole 23604140 pirenzepine 23604592 As 23604592 Cd 23604592 Pb 23604592 oxygen 23604719 flavonoids 23604719 β-CD 23604719 β-cyclodextrin 23604721 flavan 23604721 flavonoid 23604721 methanol 23604819 1-Substituted-N-tosyl-1,2,3,4-tetrahydroisoquinoline 23604819 N-tosyl-1,2,3,4-tetrahydroisoquinoline 23604819 Trimethoxy 23604819 o-hydroxy 23604819 p-methoxy 23604819 tetrahydroisoquinolines 23605905 thyroxin 23605905 triiodothyronine 23606243 CdSe 23606243 FTO 23606243 TiO2 23606278 Statins 23606278 cholesterol 23606278 statins 23606301 Oxygen 23606301 PDMS 23606301 oxygen 23606301 polydimethylsiloxane 23606318 dabigatran 23606318 rivaroxaban 23606318 warfarin 23606463 amino 23606463 carbonyl 23606629 (E)-5-(2-bromovinyl)-2'-deoxyuridine 23606629 BVDU 23606629 IDA-POM 23606629 L-alanine 23606629 Phosphoramidate 23606629 nucleoside 23606629 nucleoside monophosphates 23606629 nucleosides 23606629 nucleotide 23606629 phosphoramidate 23606629 phosphoramidate triester 23606629 phosphoramidates 23606629 pivaloyloxymethyl iminodiacetate 23606629 thymidine 23607523 C7 23607523 N 23607523 O 23607523 Pyralomicin 23607523 benzopyranopyrrole 23607523 cyclitol 23607523 glucose 23607523 phosphate 23607523 pyralomicin 23607523 sugar 23607578 Carbon 23607578 carbon 23607578 carbon black 23607669 HB(C6F5)2 23607669 amines 23607669 borane 23607669 dienes 23607669 imines 23607866 1H 23607866 N-(2-benzoyloxypropyl methacrylamide 23607866 N-(2-hydroxypropyl) methacrylamide monolactate 23607866 Paclitaxel 23607866 docetaxel 23607866 ethanol 23607866 naphthoyl 23607866 paclitaxel 23607866 polyethylene glycol 23607869 C-C 23607869 C-f 23607869 C-h 23608109 crizotinib 23608241 Mitragynine 23608241 cAMP 23608241 cyclic AMP 23608241 forskolin 23608241 foskolin 23608241 indole alkaloid 23608241 mitragynine 23608241 morphine 23608241 nitrogen 23608613 albuterol sulfate 23608613 l-leucine 23608613 mannitol 23608613 poloxamer 188 23608699 11-KT 23608699 11-ketotestosterone 23608699 17α-ethinylestradiol 23608699 17β-estradiol 23608699 25-OH-cholesterol 23608699 EE2 23608699 estrogen 23608699 pregnenolone 23608699 testosterone 23608896 Cu2O 23608896 Ni 23608896 polystyrene 23609128 (H2 O)5 (+) 23609128 (H2 O)n 23609128 H2 O 23609128 H3 O(+) 23609128 hydronium 23609128 hydroxyl 23609145 Bicarbonate 23609145 Bisulfite 23609145 Folate 23609145 Monocarboxylates 23609145 acetate 23609145 bicarbonate 23609145 bisulfite 23609145 citrate 23609145 folate 23609145 glycine 23609145 nitrate 23609145 nitrite 23609145 phosphate 23609145 pyruvate 23609145 sulfate 23609438 Ca(2+) 23609438 Calcium 23609438 Potassium 23609438 cAMP 23609438 calcium 23609438 potassium 23609606 NADPH 23609606 UDPGA 23609606 [(14)C]-fenclozic acid 23609606 acyl glucuronide 23609606 carboxylic acid 23609606 fenclozic acid 23609606 taurine 23609769 Amphetamine 23609769 MDMA 23609769 amphetamine 23609769 ecstasy 23609769 methylendioxymethamphetamine 23609769 serotonin 23609770 remifentanil 23609782 BG-12 23609782 Fingolimod 23609782 Laquinimod 23609782 Teriflunomide 23609944 amino acid 23609944 amino acids 23609963 cholesterol 23609963 fatty acid 23610077 SBA-15 23610077 Silanol 23610077 alkoxysilanes 23610077 bis-silylamine 23610077 chlorosilanes 23610077 nitrobenzene 23610077 silanol 23610077 silica 23610086 -(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)ethanone 23610086 1,2,4-thiadiazole 23610086 1-(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(2-methylimidazo[2,1-b]thiazol-6-yl)ethanone 23610086 1-(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(imidazo[2,1-b]thiazol-6-yl)ethanone 23610086 18O 23610086 2-methylimidazo[2,1-b]thiazole 23610086 Imidazo- and 2-Methylimidazo[2,1-b]thiazole 23610086 NADPH 23610086 S-oxide 23610086 glutathione 23610086 glutathione-S-oxide 23610086 glutathionyl 23610086 imidazo[2,1-b]thiazole 23610086 potassium cyanide 23610086 thiazole 23610086 thiol 23611120 D - Glucose 23611120 D-glucose 23611120 Polystyrene 23611120 Ru 23611120 hydrogen 23611120 polystyrene 23611124 Indolecarboxamide 23611124 indole-2-carboxamide 23611338 m-MitoPhB(OH)2O•- 23611338 o-, m-, and p-MitoPhB(OH)2 23611338 o-MitoPhB(OH)2 23611338 o-MitoPhB(OH)2O•- 23611338 o-MitoPhNO2 23611338 o-MitoPhOH 23611338 ortho-MitoPhB(OH)2 23611338 p-MitoPhB(OH)2O•- 23611338 •NO2 23611338 Aromatic boronic acids 23611338 ONOO- 23611338 PhB(OH)2 23611338 PhB(OH)2O•- 23611338 TPP 23611338 arylboronate 23611338 arylboronates 23611338 peroxynitrite 23611338 phenolic 23611338 phenols 23611338 phenyl 23611338 triphenylphosphonium 23611338 triphenylphosphonium-substituted arylboronic acid 23611508 polystyrene 23611538 EGCG 23611538 Epigallocatechin-3-gallate 23611538 Schiff bases 23611538 amines 23611538 polyphenol 23611538 thioflavin T 23611809 UDP 23611809 afloqualone 23611809 amine 23611809 amitriptyline 23611809 carbamazepine 23611809 cyclic amines 23611809 desipramine 23611809 diphenhydramine 23611809 hecogenin 23611809 imidazole 23611809 imipramine 23611809 ketoconazole 23611809 ketotifen 23611809 midazolam 23611809 nicotine 23611809 nortriptyline 23611809 olanzapine 23611809 pizotifen 23611809 secondary or primary amines 23611809 tamoxifen 23611809 tertiary aliphatic amines 23611809 tertiary amines 23611809 tertiary cyclic amine 23611809 trifluoperazine 23612242 S 23612242 glutathione 23612242 polycyclic aromatic hydrocarbons 23612242 superoxide 23612421 2,8-dihydroxyadenine 23612421 3-O-methyldopa 23612421 3-methyldioxyindole, 23612421 8-hydroxyadenine 23612421 L-acetylcarnitine 23612421 adenine 23612421 amino acid 23612421 creatine 23612421 ethyl-N2-acetyl-L-argininate, 23612421 hypoxanthine 23612421 indole-3-carboxylic acid 23612421 methionine 23612421 phenylalanine 23612421 phytosphingosine 23612421 xanthurenic acid 23612423 ATP 23612423 DPPH 23612423 MDA 23612423 chloroform 23612423 creatine 23612423 ethanol 23612423 malate 23612423 nitric oxide 23612487 S1P 23612487 Sphingosine-1-phosphate 23612487 phosphatidylinositol 23612487 sphingolipid 23612709 calcium 23612720 ferro 23612720 graphane 23612720 graphene 23612720 graphenes 23612720 hydrogen 23613012 Cholesterol 23613012 Testosterone 23613012 cholesterol 23613012 testosterone 23613012 testosterone esters 23613012 triglyceride 23613080 FTO 23613080 NiO 23613080 WO3 23613312 4-benzyloxybenzaldehyde 23613312 alkene 23613312 cyclopropane 23613312 cyclopropyl 23613312 estrogen 23613312 raloxifene 23613312 stilbene 23613312 tamoxifen 23613425 DOX 23613425 Doxorubicin 23613425 PLA 23613425 doxorubicin 23613425 mPEG 23613425 methoxy 23613425 poly(D,L-lactic acid) 23613425 poly(ethylene glycol) 23614379 ( - )-(7R,7'R,8S,8'R)-4,4'-dihydroxy-3,3'-dimethoxy-7,7'-epoxylignan-4'-O-β-d-glucopyranoside 23614379 ( - )-(7R,7'R,8S,8'R)-4,4'-dihydroxy-3,3'-dimethoxy-7,7'-epoxylignan-4-O-β-d-glucopyranoside 23614379 ( - )-(7R,8R)-syringylglycerol-8-O-β-d-glucopyranoside 23614379 ( - )-(8S,8'R)-4,4'-dihydroxy-3,3',5'-trimethoxylignan-4'-O-β-d-glucopyranoside 23614379 ( - )-3-hydroxy-2-methyl-4-pyrone-3-O-β-d-xylopyranosyl-(1 → 6)-O-β-d-glucopyranoside 23614379 ( - )-nectandrin B-β-d-glucopyranoside 23614492 11α-hydroxypimara-8(14),15-diene 23614492 1β,11α-dihydroxypimara-8(14),15-diene 23614492 2,3-secoaromadendrane 23614492 7β,11α-dihydroxypimara-8(14),15-diene 23614492 Terpenoids 23614492 diterpenoids 23614492 ethyoxyplagiochiline A2 23614492 fusicoccane 23614492 pimarane 23614492 sesquiterpenoids 23614571 (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine 23614571 (S)-CCG-IV 23614571 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine 23614571 N-methyl-D-aspartic acid 23614571 NMDA 23614635 bisphosphonates 23614635 estrogen 23614635 strontium ranelate 23614643 SU5402 23614643 bis- and tris-xylosides 23614643 mono-xylosides 23614643 xyloside 23614643 xylosides 23614652 AA-I 23614652 Aristolic Acid 23614652 Aristolochic Acid I 23614652 Aristolochic acid I 23614652 Cysteine 23614652 Glutathione 23614652 aristolic acid 23614652 cysteine 23614652 glutathione 23614652 nitro 23614728 Eosin 23614728 Haematoxylin 23614728 phosgene 23614815 amino-acid 23614815 disulphide 23614827 (+)-anwulignan(erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane) 23614827 (7S,8R,7'R,8'R)-7-(3,4-methylenedioxyphenyl)-8,8'-dimethyl-8'-hydroxyl-7'-methoxyl-7'-(3',4'-methylenedioxyphenyl)-tetrahydrofuran 23614827 ( - )-zuonin-A 23614827 2-hydroxy-11,12-dehydrocalamenene 23614827 erythro-1-(3,4-dimethoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane 23614827 lignans 23614831 Cilnidipine 23614831 N-vinylpyrrolidone 23614831 PVP 23614831 Soluplus 23614831 calcium 23614831 cilnidipine 23614831 dihydropyridine 23614831 hydrogen 23614904 Atorvastatin 23614904 Bile Acid 23614904 Sterol 23614904 atorvastatin 23614904 bile acid 23614904 bile acids 23614904 cholesterol 23614904 cholesterol ester 23615074 flavanoids 23615074 oxygen 23616238 Met 23616238 metformin 23616238 triacylglycerol 23616376 DPh-DNTT 23616387 azide-alkyne 23616387 copper 23616387 triazole 23616387 triazoles 23617226 2,9-dimethyl-1,10-phenanthroline 23617226 Bis(2,9-dimethyl-1,10-phenanthroline)copper(I) 23617226 Copper(I) Phenanthroline 23617226 Cu 23617226 [Cu(dmp)2]+ 23617226 acetonitrile 23617226 dichloromethane 23617226 dmp 23617279 Carbon 23617279 Formaldehyde 23617279 Resorcinol 23617279 carbon 23617279 formaldehyde 23617279 potassium carbonate 23617279 resorcinol 23617430 3-carboranyl thymidine 23617430 N3-substituted thymidine 23617430 boron 23617430 carborane 23617439 PZQ 23617439 Praziquantel 23617439 bromine 23617439 praziquantel 23617439 praziquentel 23617462 Di-hydroxy and Tri-hydroxy Bile Salts 23617462 NaC 23617462 NaDC 23617462 NaGDC 23617462 NaTC 23617462 amino acid 23617462 amino acids 23617462 bile salts 23617462 decane 23617462 dexocycholate 23617462 glycodeoxycholate 23617462 sodium 23617462 sodium cholate 23617462 taurocholate 23617753 BRD0476 23617753 naphthyl 23617753 quinoline 23617807 Benzene 23617807 Hexahalogenbenzenes 23617807 benzene 23617807 dihalogen 23617807 hexachloro- and hexabromobenzenes 23617807 hexahalogenbenzenes 23618528 ethanol 23618624 7β-OH spermine 23618624 Squalamine 23618624 aminosterol 23618624 hydroxyl 23618624 polyamine 23618624 sterol 23618624 tetraammonium spermine polyamine 23618624 trisammonium spermidine polyamine 23618921 Fisetin 23618921 Flavonoid 23618921 GSH 23618921 Glutathione 23618921 fisetin 23618921 flavonoid 23619019 Captopril 23619019 ginsenoside Ro 23619019 ginsenosides 23619019 ginsenosides Rb1, Rg1, Rf, Rh1, Rc, Rb2, Ro, and Rg3 23619611 Apixaban 23619611 Dabigatran 23619611 Rivaroxaban 23619611 apixaban 23619611 dabigatran 23619611 edoxaban 23619611 rivaroxaban 23619611 vitamin K 23619613 bleomycin 23619613 polySia 23619613 polysialic acid 23620060 Diacylglycerol 23620060 Glucose 23620060 glucose 23620060 sphingomyelin 23620162 Al(3+) 23620162 Al2O3 23620162 AlY20 23620162 Y(3+) 23620162 Y2O3 23620162 oxygen 23620199 DM1 23620199 MCC 23620199 N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate 23620199 SMCC 23620199 maytansine 23620199 mertansine 23620199 taxane 23620199 thioether 23620200 glucose 23620256 glucose 23620256 propidium iodide 23620256 yo pro-1 23620266 (R)-1-phenylethylamine 23620266 2-APA 23620266 2-arylpropionic acid 23620266 2-arylpropionic acids 23620266 Naproxen 23620266 PEA 23620266 amide 23620266 ibuprofen 23620266 ketoprofen 23620266 naproxen 23620283 C 23620283 serine 23620283 threonine 23620487 5'-O-desmethylomeprazole 23620487 5-hydroxyomeprazole 23620487 Omeprazole 23620487 carboxyomeprazole 23620487 omeprazole 23620487 omeprazole sulfone 23621358 GAL 23621358 PHEA-EDA 23621358 PHEA-EDA-PLA-GAL 23621358 PLA 23621358 RBV 23621358 RBV tripalmitate 23621358 RIBAVIRIN 23621358 alpha,beta-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide 23621358 carbohydrate 23621358 galactosylated polylactide-polyaminoacid 23621358 lactose 23621358 polylactic acid 23621358 ribavirin 23621493 Oxytetracycline 23621493 Tetracyclines 23621493 anhydrotetracycline 23621493 oxytetracycline 23621493 tetracycline 23621616 Graphene 23621616 graphene 23621857 Acylated Brefeldin A 23621857 BFA 23621857 BFA 4,7-O-dibenzoate 23621857 BFA 7-O-benzoate 23621857 BFA 7-O-biotin carboxylate 23621857 Brefeldin A 23621857 guanine nucleotide 23621857 hydroxyl 23621857 monoacylated and diacylated BFA 23623416 Echinocandins 23623416 acyl 23623416 anidulafungin 23623416 branched chain saturated fatty acid 23623416 caspofungin 23623416 cyclohexapeptides 23623416 diphenylisoxazoloyl 23623416 echinocandins 23623416 hydroxy-glutamine 23623416 lipocyclohexapeptides 23623416 micafungin 23623416 pentyloxyl 23623416 pneumocandins 23623416 threonine 23623416 unsaturated linear fatty acid 23623419 1,2,3-triazoles 23623419 2-arylimidazo[1,2-a]pyridines 23623419 diazepam 23623419 imidazo[1,2-a]pyridines 23623493 half-titanocene 23623493 titanocene 23623743 1,3-DNB 23623743 1,3-dinitrobenzene 23623743 3-CPD 23623743 3-NPA 23623743 3-chloropropanediol 23623743 3-nitropropionic acid 23623743 TMRM 23623743 deferoxamine 23623743 polyacrylamide 23623743 tetramethyl rhodamine methyl ester 23623751 Dopamine 23623751 Methylphenidate 23623751 cocaine 23623751 dopamine 23623751 methylphenidate 23623751 norepinephrine 23623795 sodium phosphate 23623843 8-iso-PGF2a 23623843 CCl4 23623843 DPPH 23623843 GSH 23623843 MDA 23623843 O2(-) 23623843 OH 23623843 carbon tetrachloride 23623843 ferric 23623843 monosaccharides 23624029 17-hydroxyprogesterone 23624029 androgen 23624029 steroid 23624240 Co3O4 23624240 cobalt 23624240 cobalt oxide 23624376 Polyglycerol 23624376 borosilicate 23624376 hyperbranched methoxylated polyglycerol 23624376 hyperbranched polyglycerol 23624376 linear methoxylated polyglycerol 23624419 Vildagliptin 23624419 arginine 23624419 metformin 23624419 vildaglipin 23624419 vildagliptin 23624423 17β-Estradiol 23624423 4-Hydroxytamoxifen 23624423 OHT 23624423 Tamoxifen 23624423 estrogen 23624423 tamoxifen 23624706 C 23624706 Fe2O3 23624706 Li 23624706 SnO2 23624706 carbon black 23624706 lithium 23624706 molten salt 23624810 oxytocin 23624862 GDP 23624862 GTP 23625160 Fe 23625160 MSG 23625160 Monosodium L-Glutamate 23625160 iron 23625160 monosodium L-glutamate 23625194 orlistat 23625194 rimonabant 23625194 sibutramine 23625745 Cholesterol 23625745 cholesterol 23625745 triglycerides 23625750 (1-deoxy-1-6[[(3-iodophenyl) methyl]amino]-9H-purin-9-yl)-N-methyl-B-D-ribofuronamide 23625750 IB-MECA 23625750 adenosine 23625750 sodium taurocholate 23625769 Furosemide 23625769 furosemide 23625769 torsemide 23625779 Amino 23625779 MCM-41 23625779 Silica 23625779 amino 23625779 saponins 23625779 silica 23625787 Warfarin 23625787 warfarin 23625887 3'-O-(isoleucylisoleucyl)-5'-O-(3,3,3-triphenylpropanoyl)thymidine 23625887 5'-Trityl 23625887 5'-triphenylmethyl (trityl) 23625887 Thymidine 23625887 superoxide 23625887 thymidine 23625887 tritylthymidines 23625905 Cr 23625905 Cr(VI) 23625905 GSH 23625905 K2Cr2O7 23625905 chromium (VI) 23625905 copper 23625905 glutathione 23625905 hexavalent chromium 23625905 iron 23625905 thiobarbituric acid 23625905 zinc 23625909 alum 23625912 Al 23625912 Al chloride 23625912 AlCl3 23625912 Aluminum 23625912 Cu 23625912 Fe 23625912 Zn 23625912 aluminum chloride 23625912 copper 23625912 iron 23625912 zinc 23627275 2-(2-methoxyethoxy)ethyl methacrylate 23627275 MEO2MA 23627275 OEGMA 23627275 Pdop 23627275 Rh6G 23627275 SiO2 23627275 methyl orange 23627275 oligo(ethylene glycol) methacrylate 23627275 polydopamine 23627275 rhodamine 6G 23627396 N-methyltyroscherin 23627396 tyroscherin 23627438 Sciadopitysin 23627438 ethanol 23627438 sciadopitysin 23627438 taxane diterpenoids 23627438 thioflavin-T 23627443 Tween 23627443 amphotericin B 23627597 1,2-acyloxy 23627597 1,6-Diyne Carbonates and Esters 23627597 1,6-diyne carbonates and esters 23627597 2,4a-Dihydro-1H-fluorenes 23627597 2,4a-dihydro-1H-fluorenes 23627597 Au 23627597 cyclopropene 23627597 gold(I) 23627605 Graphene 23627605 SiO2 23627605 graphene 23627685 Zinc 23627685 Zn 23627685 ZnO 23627685 carbon 23627685 hydrogen 23627685 oxide 23627717 cyclodextrin (i.e. ,  or ) 23627717 di-n-decyldimethylammonium chloride 23627717 octaethylene glycol monododecyl ether 23627806 2-methacryloylethyl acrylate 23627806 MEA 23627806 acrylic acid 23627806 citric acid 23627806 iron oxide 23627806 poly(N-isopropylacrylamide) 23627806 poly(ethylene glycol) 23627834 Dox 23627834 Doxorubicin 23627834 NIPAM 23627834 Poly(N-isopropylacrylamide)-b-poly(l-histidine) 23627834 doxorubicin 23627834 p(NIPAM)55-b-p(His)n 23627834 poly(N-isopropylacrylamide)55-block-poly(l-histidine)n 23627834 α-amino acid N-carboxyanhydrides 23627902 (1)H 23627902 (13)C 23627902 cyano 23627902 dodecyl 23627902 phenyl 23628154 baicalein 23628154 baicalin 23628154 berberine 23628154 gardenoside 23628154 palmatine 23628332 1-hydroxy-6-oxo-2-cyclohexenecarboxylate 23628332 6-(oxymethyl)-2-hydroxyphenyl-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside 23628332 CHCl3 23628332 Idescarpin 23628332 idescarpin 23628332 methanol 23628332 n-BuOH 23628333 2-thio-6-oxo-1,6-dihydropyrimidine 23628333 2-thio-6-oxo-1,6-dihydropyrimidines 23628333 NADH 23628333 lactate 23628455 ACh 23628455 L-NAME 23628455 NaCl 23628455 Spironolactone 23628455 acetylcholine 23628455 aldosterone 23628455 enalaprilate 23628455 losartan 23628455 sodium 23628455 spironolactone 23628508 Aspidin BB 23628508 aspidin BB 23628508 phloroglucinol 23628508 poly ADP-ribose 23628508 propidium iodide 23628509 B[a]P 23628509 B[c]Ph 23628509 CP-PAHs 23628509 CP[c]Ph 23628509 CP[c]Phs 23628509 Cyclopenta[c]phenanthrenes 23628509 alkyl 23628509 benzo[a]pyrene 23628509 cyclopenta-fused polycyclic aromatic hydrocarbons 23628509 cyclopenta[c]phenanthrenes 23628509 cyclopentane 23628509 estrogen 23628509 phenanthrene 23628605 3β-hydroxysteroid 23628605 Steroid 23628605 aldosterone 23628605 cholesterol 23628605 pregnenolone 23628605 steroid 23628605 vitamin D 23628621 cholesterol 23628674 Tacrolimus 23628674 deoxyshisandrin 23628674 ethanol 23628674 schisandrin 23628674 schisandrol B 23628674 schisanhenol 23628674 schisantherin A 23628674 tacolimus 23628674 tacrolimus 23629055 C 23629055 Porphyrin 23629055 carboxyl 23629055 cyanoacrylic acid 23629055 dioctyloxy 23629055 meso-phenyl 23629055 meso-phenyls 23629055 meta di-tert-butylphenyl-substituted porphyrins 23629055 meta-substituted porphyrins 23629055 ortho-octyloxy 23629055 porphyrin 23629516 TCPP 23629516 TDCPP 23629516 Tris(1-chloro-2-propyl) phosphate 23629516 organophosphate 23629516 tris(1,3-dichloro-2-propyl) phosphate 23629675 Lysine 23629675 NaCl 23629675 ethylene 23629675 lysine 23629675 proline 23629675 tryptophan 23630043 5-(1,2,4-Triazol-3-yl)tetrazoles 23630043 5-(1,2,4-triazol-3-yl)tetrazoles 23630043 CC 23630043 azido 23630043 nitrimino 23630043 nitro 23630043 tetrazole 23630043 triazole 23631351 (1)H 23631351 (13)C 23631351 1,1-diphenyl-2-picrylhydrazyl 23631351 5,3',5″,4″'-tetrahydroxy-3″',5″'dimethoxy-biflavone (4' → 8″)-7-O-((2-rhamnoside) rhamnoside) 23631351 acetylated chalcone 23631351 acetylated chalcone glycoside 23631351 biflavonoid glycosides 23631351 ethyl acetate 23631351 methanol 23631351 trans-2',6'-dihydroxy-4'-O-(4″-acetyl-rhamnoside)-4-methoxychalcone 23631427 2-(3-chlorophenoxy)-N-(4-oxo-4H-3,1-benzothiazin-2-yl)acetamide 23631427 Adenosine 23631427 Benzothiazinones 23631427 Monoamine 23631427 N-(4-oxo-4H-3,1-benzothiazin-2-yl)-4-phenylbutanamide 23631427 adenosine 23631427 benzothiazinones 23631427 chlorobenzylpiperazinylbenzamido 23631427 cinnamoylamino 23631427 methoxy 23631427 monoamine 23631427 phenylbutyrylamino 23631427 xanthine 23631490 Polyphenols 23631490 polyphenols 23631493 Lycopene 23631493 lycopene 23631499 AlCl3 23631499 acetylcholine 23631499 rivastigmine 23631553 1H 23631553 Hydrogen 23631553 Polybenzoxazine 23631553 TEPA 23631553 acetic acid 23631553 benzoxazine 23631553 bisphenol-A 23631553 formalin 23631553 polybenzoxazine 23631553 tetraethylenepentamine 23632007 1,5-bis(4-allyldimethylammoniumphenyl) pentan-3-one dibromide 23632007 carbamate 23632007 carbaryl 23632007 carbofuran 23632007 chlorpyrifos 23632007 diazinon 23632007 dichlorvos 23632007 neostigmine 23632007 organophosphorus 23632007 tetraisopropyl pyrophosphoramide 23632081 3,4-methylenedioxy-N-methylamphetamine 23632081 MDMA 23632081 Serotonin 23632081 amino acids 23632081 leucine 23632081 serotonin 23632082 2-APB 23632082 Ba(2+) 23632082 Ca(2+) 23632082 K(+) 23632082 KB-R7943 23632082 La(3+) 23632082 ML204 23632082 Na(+) 23632082 SCH 23390 23632082 TRH 23632082 TTX 23632082 capsazepine 23632082 flufenamic acid 23632082 thyrotropin 23632158 glutamate 23632309 flavonoid 23633521 glucose 23633529 clindamycin phosphate 23633529 dexamethasone phosphate 23633529 fosphenytoin 23633529 oxymethyl 23633529 phosphate 23633529 phosphates 23633529 ritonavir oxymethyl phosphate 23633529 ritonavir phosphate 23633532 11-dehydrocorticosterone 23633532 11DHC 23633532 11β-hydroxysteroid 23633532 AMP 23633532 CORT 23633532 Dexamethasone 23633532 Ser 23633532 Thr 23633532 acetyl-CoA 23633532 corticosterone 23633532 dexamethasone 23633532 diacylglyderide 23633563 glucose 23634786 3-hydroxy-3-methylglutaryl 23634786 Lanostane Triterpenoids 23634786 MeOH 23634786 fasciculol G 23634786 lanostane triterpenoids 23634786 nitric oxide 23634899 $^{17}$OH 23634899 Hydroxyl 23634899 OH 23635005 Carbohydrate 23635005 carbohydrate 23635005 esterified phenolic acids 23635005 phenolic acid 23635005 α-L-Araf 23635005 β-D-Galp 23635023 AlGaAs 23635023 GaAs 23636303 MDL72222 23636303 RS79948 23636303 citalopram 23636303 methiothepin 23636303 noradrenaline 23636303 serotonin 23636446 hydrocortisone 23636584 biotin 23636886 MgCl2 23636886 glucose 23637306 alanine 23637306 aspartate 23637306 benzene 23637306 cholesterol 23637306 creatinine 23637306 superoxide 23637306 toluene 23637306 xylene 23638641 5-N-acetylcystenyl-[6]-shogaol 23638641 5-cysteinyl-[6]-shogaol 23638641 5-glutathionyl-[6]-shogaol 23638641 Cysteine 23638641 Shogaols 23638641 [6]-shogaol 23638641 cysteine 23638641 glutathione 23638641 mercapturic acid 23638641 thiol 23638641 thiols 23638658 Chalcopyrite 23638658 Copper Indium Diselenide 23638658 Cu 23638658 CuInSe2 23638658 In 23638658 Se 23638658 copper 23638658 indium 23638985 (1)H 23638985 3β,12β,20S,26-tetrahydroxydammar-24E-en-6α-O-β-d-glucopyranosyl-(1 → 2)-O-β-d-glucopyranoside 23638985 Ginsenjilinol 23638985 NO 23638985 dammarane 23638985 ginsenjilinol 23638985 ginsenoside Re5 23638985 ginsenoside Rf 23638985 indomethacin 23638985 nitric oxide 23638985 panajaponol A 23638985 protopanaxatriol 23638985 saponin 23638985 saponins 23638985 triterpene 23639075 (1)H 23639075 (13)C 23639075 iridoid esters 23639075 patriheterdoid B, C 23639096 Calcium 23639096 calcium 23639096 catechol 23639096 catechols 23639096 dopamine 23639188 altersolanol 23639188 anthranoids 23639192 ICI 182,780 23639192 Puerarin 23639192 cisplatin 23639192 estrogen 23639192 isoflavone glycoside 23639192 puerarin 23639248 hydroxyproline 23639248 silica 23639361 calcium 23639361 cortistatin-8 23639361 naringenin 23639361 naringin 23639430 cocaine 23639430 dopamine 23639430 quinine 23639430 saccharin 23639437 Nicotine 23639437 nicotine 23639537 indeno[1,2-d]thiazole 23639537 indeno[1,2-d]thiazole hydroxamic acids 23639543 2'-α-fluorine 23639543 2'-α-fluoro 23639543 Ribonucleoside phosphonate 23639543 adenine 23639543 cytidine 23639543 diphosphophosphonate 23639543 nucleoside phosphonates 23639543 triphosphate 23639545 (1)H 23639545 Cs(+) 23639545 K(+) 23639545 Li(+) 23639545 Na(+) 23639545 Rb(+) 23639545 acetamido 23639545 amino 23639545 bis(choloyl) 23639545 l-α-phosphatidylcholine 23639545 p-bis(aminomethyl)benzene 23639545 p-phenylenediamine 23639627 Anthracycline 23639627 DXR 23639627 Doxorubicin 23639627 doxorubicin 23639652 chalcone 23639652 chalcones 23639652 sulfonamide 23639652 sulfonamides 23639652 tyrosine 23639738 Cholesterol 23639738 PEC 23639738 poly(ethylene carbonate) 23639739 6-OHDA 23639741 HCl 23639741 K 23639741 Na 23639741 potassium 23639741 sodium 23639992 PDMS 23639992 polydimethylsiloxane 23640282 Fe3O4 23640282 FePt 23640471 1-butyl-3-methylimidazolium 23640471 C4MIM 23640471 [B(hfip)4](-) 23640471 [BF4](-) 23640471 [C4MIM](+) 23640471 [Cl](-) 23640471 [NTf2](-) 23640471 [OTf](-) 23640471 [PF6](-) 23640722 2-(4-methylpiperazin-1-yl)quinoxaline 23640722 2-amino-3-(4-methylpiperazin-1-yl)quinoxaline 23640722 2-chloro-3-(4-methylpiperazin-1-yl)quinoxaline 23640722 3-(4-methylpiperazin-1-yl)quinoxalin-2-ol 23640722 Quinoxaline 23640722 VUF10166 23640722 [(3) H]granisetron 23640867 arginine 23640867 citrulline 23640867 trypsin 23640872 7β-hydroxytropane 23640872 N 23640872 N-methyl 23640872 OH 23640872 Scopoline 23640872 Tropane 23640872 epoxy 23640872 hydrogen 23640872 hydroxy 23640872 oscine 23640872 scopine 23640872 scopoline 23640872 tropane 23640962 isoflavonoids 23640962 nitric oxide 23640962 prostaglandin E2 23640962 saponins 23641017 cholesterol 23641017 triglyceride 23641017 triglycerides 23641685 Cl2 23641685 HCHO 23641685 HCOOH 23641685 HMP 23641685 HO2 23641685 HOCH2OO 23641685 HOOH 23641685 Hydroxy-Methyl-Peroxy 23641685 O2 23641685 OCOH 23641685 OH 23641685 OOCO 23641685 formaldehyde 23641685 hydroperoxy 23641685 hydroxyl-methyl-peroxy 23641955 MK-0524 23641955 UDP 23641955 laropiprant 23641955 prostaglandin D2 23641955 uridine diphosphate 23642029 BTX-B 23642029 Brevetoxin B 23642029 N-palmitoyl-S-desoxy-BTX-B2 23642029 S-desoxy-BTX-B2 23642029 [14C] 23642029 [14C] N-palmitoyl-S-desoxy-BTX-B2 23642029 [3H] 23642029 [3H] S-desoxy-BTX-B2 23642029 [3H] dihydro-BTX-B 23642029 aldehyde 23642029 amide 23642029 amino acid 23642029 brevetoxin 23642029 cysteine 23642029 cysteine brevetoxin B 23642029 dihydro-BTX-B 23642029 fatty acid 23642029 olefinic 23642029 α,β-unsaturated aldehyde 23642965 7-oxabicyclo[2.2.1]hept-5-en-2-yl 23642965 boron trifluoride diethyl etherate 23643542 18β-GA 23643542 18β-glycyrrhetinic acid 23643542 glycyrrhizin 23643664 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 23643664 MPTP 23643664 carboxy 23643664 dopamine 23643664 tyrosine 23643700 Ascorbic acid 23643700 Vitamin C 23643700 ascorbic acid 23643700 vitamin C 23643725 ascorbate 23643725 chl-a 23643725 glutathione 23643725 oxyfluorfen 23643730 DHT 23643730 Hoechst 33342 23643730 Juglone 23643730 MTT 23643730 androgen 23643730 dihydrotestosterone 23643730 juglone 23643737 1,4-Substituted 4-(1H)-pyridylene-hydrazone 23643737 1,4-substituted 4-(1H)-pyridylene-hydrazone 23643737 acetyl 23643737 acetylcholine 23643739 Glycerol 23643739 glycerol 23643739 metronidazole 23643739 urea 23643744 ADX47273 23643744 NMDA 23643744 PCP 23643744 SSR180711 23643744 THIP 23643744 acetylcholine 23643744 glutamate 23643744 phencyclidine 23643745 Amisulpride 23643745 L-3,4-dihydroxyphenylalanine 23643745 S33084 23643745 SCH23390 23643745 amisulpride 23643745 dopamine 23643745 pramipexole 23643745 raclopride 23643748 oxytocin 23643792 Tween 80 23643792 Tween-80 23643792 poly(-caprolactone) 23643839 glucose 23643839 serine 23643839 threonine 23643933 TSA 23643933 Trichostatin A 23643933 trichostatin 23644192 (99m)Tc 23644192 (99m)Tc-labeled dibenzylideneacetone 23644192 rhenium 23644195 (1)H 23644195 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one 23644195 RVX-208 23644195 carboxylate 23644195 carboxylic acid 23644195 glucuronic acid 23644195 primary hydroxyl 23644200 disaccharide 23644200 galactose 23644200 glycosylated isomalyngamide A 23644200 isomalyngamide A 23644200 lactose 23644200 mannose 23644200 monosaccharide 23644201 2-oxo-1,2-dihydroquinoline-3-carbaldehyde 23644201 4N-substituted thiosemicarbazones 23644201 Et 23644201 H 23644201 H2-Qtsc-R 23644201 Me 23644201 Ni(II) 23644201 Ph 23644201 [Ni(H2-Qtsc-R)2](NO3)2 23644214 4-aminothieno[2,3-d]pyrimidine-6-carbonitrile 23644214 C 23644214 PCl5 23644214 POCl3 23644214 amines 23644214 ampicillin 23644214 chloro 23644214 greseofulvin 23644214 nitrile 23644214 oxothieno[2,3-d]pyrimidine-6-carboxamide 23644256 IBU 23644256 ISDN 23644256 Ibuprofen 23644256 Isosorbide Dinitrate 23644256 ibuprofen 23644256 isosorbide dinitrate 23644525 carbon 23645248 17beta-oestradiol 23645248 Oestrogen 23645248 oestrogen 23645248 sodium iodide 23645249 2,3-bis (4-hydroxyphenyl)-propionitrile 23645249 DPN 23645249 Genistein 23645249 estrogen 23645249 fatty acid 23645249 genistein 23645249 isoflavone 23645249 triglyceride CHEMDNER_TRAIN_V01/cem_ann_training_13-07-31.txt0000644002344200234200000211053312176243037022166 0ustar mkrallingerBioinfoUnix21826085 A:946:957 22080034 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22394118 A:270:283 22394118 A:342:349 22394118 A:703:716 22394118 T:0:6 22394118 T:104:117 22397600 A:159:169 22397600 A:241:251 22397600 T:49:59 22397675 A:1132:1135 22397675 A:1219:1222 22397675 A:1487:1490 22397675 A:1615:1618 22397675 A:345:355 22397675 A:357:360 22397675 A:414:417 22397675 A:462:484 22397675 A:486:489 22397675 A:492:505 22397675 A:512:522 22397675 A:532:547 22397675 A:76:93 22397675 A:888:891 22397675 A:95:98 22397675 T:11:14 22397675 T:72:82 22401597 A:131:141 22401597 A:145:211 22401597 A:227:241 22401597 T:0:29 22401597 T:30:40 22404642 A:148:161 22404642 A:163:186 22404642 A:192:207 22404642 A:213:241 22404642 A:250:276 22404642 A:316:328 22404642 A:337:365 22420410 A:14:30 22420410 A:479:489 22420410 A:571:609 22420410 A:724:762 22420410 T:39:55 22424088 A:539:546 22424088 A:617:621 22424088 A:626:636 22424088 A:735:742 22424117 A:141:159 22424117 A:167:199 22424117 A:205:248 22424117 A:254:286 22424117 A:295:318 22424117 A:39:51 22424117 A:533:541 22424117 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A:768:777 22678994 A:782:792 22678994 A:87:94 22678994 A:959:964 22683935 A:706:730 22683935 A:732:751 22683935 A:753:767 22683935 A:769:779 22683935 A:781:795 22683935 A:797:825 22683935 A:827:834 22683935 A:836:852 22683935 A:854:882 22683935 A:927:948 22683935 A:950:964 22683935 A:966:972 22683935 A:974:987 22693035 A:1123:1135 22693035 A:1137:1151 22693035 A:1153:1161 22693035 A:1163:1171 22693035 A:1176:1185 22693035 A:1187:1209 22693035 A:1211:1232 22693035 A:1237:1249 22693035 A:1296:1309 22693035 A:1328:1344 22693035 A:1367:1376 22693035 A:260:289 22693035 A:291:295 22693035 A:298:353 22693035 A:355:359 22693035 A:447:455 22693035 A:503:511 22693035 A:513:526 22693035 A:531:540 22693035 A:558:566 22693035 A:627:633 22693035 A:667:686 22693035 A:696:702 22693035 A:733:737 22693035 A:839:852 22693035 A:857:866 22693035 A:892:901 22694738 A:1081:1179 22694738 A:11:22 22694738 A:172:184 22694738 A:325:346 22694738 A:382:394 22694738 A:473:485 22694738 A:622:659 22694738 A:661:669 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A:492:506 23440956 A:559:561 23440956 A:608:622 23440956 A:632:634 23440956 A:656:670 23440956 A:695:697 23440956 A:69:76 23440956 A:761:763 23440956 A:790:798 23440956 A:812:814 23440956 A:897:905 23440956 A:9:11 23440956 T:0:8 23440956 T:34:36 23440956 T:55:62 23441753 A:1030:1037 23441753 A:19:55 23441753 A:226:235 23441753 A:390:399 23441753 A:577:586 23441753 A:82:91 23441753 T:59:86 23441816 A:299:305 23441816 A:4:10 23441816 A:537:543 23441816 T:0:6 23441829 A:195:199 23441829 A:20:24 23441829 A:215:223 23441829 A:225:230 23441829 A:244:250 23441829 A:270:278 23441829 A:298:303 23441829 A:307:311 23441829 A:323:327 23441829 A:374:378 23441829 A:441:446 23441829 A:533:537 23441829 A:557:562 23441829 A:597:601 23441829 A:736:742 23441829 A:825:829 23441829 A:842:846 23441829 A:867:871 23441829 A:880:886 23441829 A:891:895 23441829 A:979:983 23441829 A:984:988 23441829 T:30:42 23441829 T:66:71 23441829 T:7:10 23441843 A:1070:1073 23441843 A:1178:1181 23441843 A:1287:1290 23441843 A:1592:1595 23441843 A:535:548 23441843 A:550:553 23441843 A:631:634 23441843 A:726:729 23441843 A:863:872 23441843 A:906:909 23441843 T:99:112 23441878 A:104:109 23441878 A:1140:1142 23441878 A:1165:1170 23441878 A:120:124 23441878 A:1270:1275 23441878 A:1276:1278 23441878 A:135:139 23441878 A:205:206 23441878 A:207:208 23441878 A:243:259 23441878 A:308:309 23441878 A:310:311 23441878 A:375:382 23441878 A:406:407 23441878 A:470:475 23441878 A:476:478 23441878 A:506:510 23441878 A:511:512 23441878 A:929:934 23441878 T:34:39 23441878 T:44:48 23442005 A:1022:1039 23442005 A:1044:1051 23442005 A:153:162 23442005 A:308:315 23442005 A:339:357 23442005 A:449:464 23442005 A:471:478 23442005 A:493:510 23442005 A:516:524 23442005 A:52:59 23442005 A:602:603 23442005 A:604:605 23442005 A:633:640 23442005 A:670:678 23442005 A:692:699 23442005 A:711:728 23442005 A:79:96 23442005 A:883:902 23442005 A:916:927 23442005 T:78:97 23442025 A:136:141 23442025 A:319:332 23442025 A:337:343 23442025 A:71:72 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A:457:467 23619611 A:742:753 23619611 A:755:763 23619611 A:75:86 23619611 A:769:779 23619611 A:88:96 23619611 A:965:975 23619613 A:1131:1138 23619613 A:1160:1167 23619613 A:1399:1406 23619613 A:335:342 23619613 A:422:429 23619613 A:631:638 23619613 A:765:774 23619613 A:78:93 23619613 A:907:914 23619613 A:95:102 23620060 A:1024:1031 23620060 A:1159:1173 23620060 A:1359:1372 23620060 A:391:398 23620060 A:612:619 23620162 A:1058:1064 23620162 A:38:43 23620162 A:48:52 23620162 A:518:522 23620162 A:524:529 23620162 A:783:789 23620162 A:794:799 23620162 A:847:852 23620162 A:853:858 23620162 T:34:39 23620162 T:40:44 23620199 A:1469:1475 23620199 A:208:218 23620199 A:222:232 23620199 A:259:262 23620199 A:386:396 23620199 A:542:551 23620199 A:560:622 23620199 A:624:628 23620199 A:641:644 23620200 A:230:237 23620200 A:341:348 23620256 A:1516:1523 23620256 A:1712:1719 23620256 A:2114:2121 23620256 A:802:810 23620256 A:815:831 23620256 A:995:1002 23620266 A:1005:1014 23620266 A:1016:1024 23620266 A:258:263 23620266 A:317:339 23620266 A:341:344 23620266 A:35:55 23620266 A:572:581 23620266 A:57:62 23620266 A:71:80 23620266 A:722:732 23620266 A:82:90 23620266 A:893:903 23620266 A:96:106 23620266 T:39:60 23620283 A:1056:1057 23620283 A:198:204 23620283 A:205:214 23620487 A:1031:1041 23620487 A:1292:1302 23620487 A:148:158 23620487 A:230:249 23620487 A:251:275 23620487 A:277:295 23620487 A:300:317 23620487 A:433:443 23620487 A:535:545 23620487 A:547:565 23620487 A:570:594 23620487 A:650:660 23620487 A:665:689 23620487 A:887:897 23620487 T:36:46 23621358 A:1037:1040 23621358 A:114:126 23621358 A:181:221 23621358 A:282:354 23621358 A:356:364 23621358 A:371:386 23621358 A:388:391 23621358 A:423:430 23621358 A:442:458 23621358 A:540:543 23621358 A:558:574 23621358 A:622:625 23621358 A:62:71 23621358 A:709:725 23621358 A:73:76 23621358 A:780:796 23621358 A:893:909 23621358 A:917:933 23621358 T:30:39 23621493 A:0:13 23621493 A:189:208 23621493 A:218:233 23621493 A:918:930 23621493 T:56:71 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A:943:949 23643748 A:1041:1049 23643748 A:1197:1205 23643748 A:1554:1562 23643748 A:32:40 23643748 A:646:654 23643748 A:706:714 23643748 A:779:787 23643748 A:915:923 23643748 A:970:978 23643748 T:21:29 23643792 A:1123:1131 23643792 A:1402:1410 23643792 A:352:371 23643792 A:731:739 23643839 A:179:186 23643839 A:202:208 23643839 A:209:218 23643839 A:52:58 23643839 A:59:68 23643933 A:1013:1016 23643933 A:1028:1031 23643933 A:1273:1276 23643933 A:1362:1365 23643933 A:1454:1457 23643933 A:1501:1504 23643933 A:197:211 23643933 A:213:216 23643933 A:345:348 23643933 T:84:96 23644192 A:207:214 23644192 A:417:424 23644192 A:5:41 23644192 A:677:684 23644192 A:72:79 23644192 T:0:36 23644195 A:1017:1028 23644195 A:1032:1039 23644195 A:1136:1140 23644195 A:1266:1282 23644195 A:1292:1299 23644195 A:1303:1318 23644195 A:344:351 23644195 A:532:539 23644195 A:65:72 23644195 A:708:712 23644195 A:784:800 23644195 A:810:817 23644195 A:822:837 23644195 T:161:168 23644195 T:83:159 23644200 A:248:255 23644200 A:260:269 23644200 A:28:57 23644200 A:476:483 23644200 A:548:562 23644200 A:575:587 23644200 A:606:622 23644200 T:56:72 23644201 A:118:159 23644201 A:171:172 23644201 A:178:180 23644201 A:186:188 23644201 A:197:199 23644201 A:45:67 23644201 A:69:78 23644201 A:81:114 23644201 A:9:15 23644201 T:109:142 23644201 T:146:187 23644201 T:89:95 23644214 A:102:106 23644214 A:125:126 23644214 A:148:155 23644214 A:273:279 23644214 A:298:304 23644214 A:327:372 23644214 A:44:84 23644214 A:830:840 23644214 A:908:920 23644214 A:92:97 23644214 T:34:79 23644256 A:1406:1409 23644256 A:1410:1414 23644256 A:298:301 23644256 A:306:310 23644256 A:33:42 23644256 A:44:47 23644256 A:497:500 23644256 A:514:518 23644256 A:53:73 23644256 A:75:79 23644256 A:946:949 23644256 A:950:954 23644256 T:0:9 23644256 T:15:35 23644525 A:245:251 23645248 A:1014:1031 23645248 A:1195:1208 23645248 A:1251:1268 23645248 A:1284:1293 23645248 A:139:148 23645248 A:1511:1520 23645248 A:334:343 23645248 A:429:446 23645248 A:498:507 23645248 A:536:553 23645248 A:675:688 23645248 A:726:743 23645248 A:869:878 23645248 A:945:954 23645248 T:0:9 23645249 A:1077:1086 23645249 A:1134:1146 23645249 A:1175:1185 23645249 A:1214:1223 23645249 A:1291:1299 23645249 A:1388:1427 23645249 A:1429:1432 23645249 A:1606:1615 23645249 A:1624:1627 23645249 A:1653:1662 23645249 A:1847:1856 23645249 A:605:615 23645249 A:616:625 23645249 A:784:793 23645249 A:898:907 23645249 T:38:47 CHEMDNER_TRAIN_V01/chemdner_ann_training_13-07-31.txt0000644002344200234200000433734412176241433023222 0ustar mkrallingerBioinfoUnix21826085 A 946 957 haloperidol TRIVIAL 22080034 A 1072 1081 aflatoxin FAMILY 22080034 A 1305 1314 aflatoxin FAMILY 22080034 A 1383 1392 aflatoxin FAMILY 22080034 A 190 199 aflatoxin FAMILY 22080034 A 594 603 aflatoxin FAMILY 22080034 A 718 727 aflatoxin FAMILY 22080035 A 1002 1012 superoxide TRIVIAL 22080035 A 1027 1038 glutathione TRIVIAL 22080035 A 1081 1092 glutathione TRIVIAL 22080035 A 1093 1094 S FORMULA 22080035 A 262 268 copper SYSTEMATIC 22080035 A 546 553 cadmium SYSTEMATIC 22080035 A 558 565 arsenic SYSTEMATIC 22080035 A 723 738 malondialdehyde TRIVIAL 22080035 A 964 975 glutathione TRIVIAL 22080037 A 285 297 nitric oxide SYSTEMATIC 22080037 A 340 347 mercury SYSTEMATIC 22080037 A 395 402 mercury SYSTEMATIC 22080037 A 649 656 mercury SYSTEMATIC 22080037 A 769 776 mercury SYSTEMATIC 22080037 T 0 7 Mercury SYSTEMATIC 22080037 T 65 77 nitric oxide SYSTEMATIC 22258629 A 0 8 Chromium SYSTEMATIC 22258629 A 1136 1144 chromium SYSTEMATIC 22258629 A 1452 1460 chromium SYSTEMATIC 22258629 A 1520 1528 chromium SYSTEMATIC 22258629 A 203 211 chromium SYSTEMATIC 22258629 A 428 443 malondialdehyde TRIVIAL 22258629 A 514 522 Chromium SYSTEMATIC 22258629 A 575 583 graphite TRIVIAL 22258629 T 17 25 chromium SYSTEMATIC 22288603 A 336 346 mikanolide TRIVIAL 22288603 A 638 648 mikanolide TRIVIAL 22294443 A 0 32 Polycyclic aromatic hydrocarbons FAMILY 22294443 A 1030 1042 fluoranthene SYSTEMATIC 22294443 A 1047 1061 benzo(a)pyrene SYSTEMATIC 22294443 A 206 211 PCAHs ABBREVIATION 22294443 A 34 39 PCAHs ABBREVIATION 22294443 A 412 417 PCAHs ABBREVIATION 22294443 A 428 434 pyrene SYSTEMATIC 22294443 A 436 454 benzo(a)anthracene SYSTEMATIC 22294443 A 456 470 benzo(e)pyrene SYSTEMATIC 22294443 A 472 490 benzoflouroanthene SYSTEMATIC 22294443 A 496 510 benzo(a)pyrene SYSTEMATIC 22294443 A 563 593 methanolic potassium hydroxide SYSTEMATIC 22294443 A 611 622 cyclohexane SYSTEMATIC 22294443 A 755 760 PCAHs ABBREVIATION 22294443 A 884 889 PCAHs ABBREVIATION 22294443 A 956 961 PCAHs ABBREVIATION 22294443 T 13 45 polycyclic aromatic hydrocarbons FAMILY 22301816 A 198 205 Thiovit TRIVIAL 22301816 A 502 509 Thiovit TRIVIAL 22301816 A 588 594 captan TRIVIAL 22301816 A 599 607 captafol TRIVIAL 22301816 A 898 905 Thiovit TRIVIAL 22301816 T 10 17 Thiovit TRIVIAL 22301818 A 495 498 MTT ABBREVIATION 22301818 A 500 559 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide SYSTEMATIC 22303963 A 380 391 formic acid SYSTEMATIC 22303963 A 417 428 formic acid SYSTEMATIC 22303963 A 432 444 acetonitrile SYSTEMATIC 22303963 A 839 857 steroidal saponins FAMILY 22303963 A 95 113 steroidal saponins FAMILY 22303963 T 23 41 steroidal saponins FAMILY 22304302 A 167 229 (25S)-1β,3β,4β-trihydroxyspirostan-5β-yl-O-β-D-glucopyranoside SYSTEMATIC 22304302 A 235 269 kitigenin-5β-O-β-D-glucopyranoside SYSTEMATIC 22304302 A 31 41 furostanol TRIVIAL 22304302 A 43 80 reinocarnoside A (1), B (2) and C (3) MULTIPLE 22304302 A 449 452 MTT ABBREVIATION 22304302 A 8 20 spirostanols FAMILY 22304302 T 10 30 steroidal glycosides FAMILY 22310169 A 1044 1060 ethoxyresorufine SYSTEMATIC 22310169 A 1061 1062 O FORMULA 22310169 A 1166 1198 polycyclic aromatic hydrocarbons FAMILY 22310169 A 1200 1204 PAHs ABBREVIATION 22310169 A 1237 1240 PAH ABBREVIATION 22310169 A 836 847 glutathione TRIVIAL 22310169 A 866 877 glutathione TRIVIAL 22310169 A 878 879 S FORMULA 22310169 A 932 946 thiobarbituric SYSTEMATIC 22310170 A 1319 1322 TCS ABBREVIATION 22310170 A 1453 1462 phosphate SYSTEMATIC 22310170 A 1588 1591 TCS ABBREVIATION 22310170 A 1670 1673 TCS ABBREVIATION 22310170 A 512 521 triclosan TRIVIAL 22310170 A 523 526 TCS ABBREVIATION 22310170 A 664 667 TCS ABBREVIATION 22310170 A 881 884 TCS ABBREVIATION 22310170 A 930 933 TCS ABBREVIATION 22310170 A 958 961 TCS ABBREVIATION 22310170 T 60 69 triclosan TRIVIAL 22312034 A 209 233 4aα,7β,7aα-nepetalactone SYSTEMATIC 22312034 A 244 254 germacrene TRIVIAL 22312034 A 268 274 elemol TRIVIAL 22312034 A 744 767 sodium dodecyl sulphate SYSTEMATIC 22312034 A 768 782 polyacrylamide SYSTEMATIC 22312034 A 804 807 SDS ABBREVIATION 22317823 A 134 142 aluminum SYSTEMATIC 22317823 A 1452 1454 Al FORMULA 22317823 A 1607 1609 Al FORMULA 22317823 A 1774 1776 Al FORMULA 22317823 A 339 341 Al FORMULA 22317823 A 387 389 Al FORMULA 22317823 A 412 414 Al FORMULA 22317823 A 426 434 Aluminum SYSTEMATIC 22317823 A 448 450 Al FORMULA 22317823 A 637 639 Al FORMULA 22317823 A 883 885 Al FORMULA 22317823 T 46 54 aluminum SYSTEMATIC 22349814 A 1199 1219 phosphatidylinositol TRIVIAL 22349814 A 6 19 monoglyceride SYSTEMATIC 22349814 A 733 750 phosphatidic acid FAMILY 22349814 A 755 779 phosphoinositol(3,4,5)P3 SYSTEMATIC 22349814 A 781 803 phosphoinositol(3,5)P2 SYSTEMATIC 22349814 A 805 827 phosphoinositol(3,4)P2 SYSTEMATIC 22349814 A 846 863 phosphoinositides FAMILY 22349814 A 879 896 phosphoinositides FAMILY 22349814 A 928 939 PI(3,4,5)P3 SYSTEMATIC 22349814 T 36 49 monoglyceride SYSTEMATIC 22360797 A 231 243 morolic acid TRIVIAL 22360797 A 316 323 acetone SYSTEMATIC 22360797 A 397 437 β-sitosteryl and stigmasteryl linoleates MULTIPLE 22360797 A 439 451 β-sitosterol TRIVIAL 22360797 A 453 465 stigmasterol TRIVIAL 22360797 A 467 479 triacontanol TRIVIAL 22360797 A 481 506 squalene, α- and β-amyrin MULTIPLE 22360797 A 508 514 lupeol TRIVIAL 22360797 A 516 524 lupenone TRIVIAL 22360797 A 526 542 betulin aldehyde TRIVIAL 22360797 A 544 560 betulon aldehyde TRIVIAL 22360797 A 562 580 oleanolic aldehyde TRIVIAL 22360797 A 582 596 betulinic acid TRIVIAL 22360797 A 598 612 betulonic acid TRIVIAL 22360797 A 614 626 moronic acid TRIVIAL 22360797 A 628 640 morolic acid TRIVIAL 22360797 A 642 656 oleanolic acid TRIVIAL 22360797 A 658 668 flavonoids FAMILY 22360797 A 669 677 acacetin TRIVIAL 22360797 A 682 705 acacetin 7-methyl ether SYSTEMATIC 22370634 A 1104 1107 RAP ABBREVIATION 22370634 A 1229 1232 RAP ABBREVIATION 22370634 A 1461 1464 RAP ABBREVIATION 22370634 A 421 430 Rapamycin TRIVIAL 22370634 A 432 435 RAP ABBREVIATION 22370634 A 712 715 RAP ABBREVIATION 22370634 A 948 951 RAP ABBREVIATION 22370634 T 46 55 rapamycin TRIVIAL 22370645 A 1199 1205 WP1066 IDENTIFIER 22370645 A 274 283 gefitinib TRIVIAL 22370645 A 951 972 phosphatidyl inositol TRIVIAL 22385272 A 322 330 pulegone TRIVIAL 22385272 A 338 346 menthone TRIVIAL 22385272 A 355 366 isomenthone TRIVIAL 22385272 A 374 385 isopulegone TRIVIAL 22385272 A 397 405 limonene TRIVIAL 22394118 A 154 167 withanolide A TRIVIAL 22394118 A 202 208 carbon SYSTEMATIC 22394118 A 270 283 withanolide A TRIVIAL 22394118 A 342 349 sucrose TRIVIAL 22394118 A 703 716 withanolide A TRIVIAL 22394118 T 0 6 Carbon SYSTEMATIC 22394118 T 104 117 withanolide A TRIVIAL 22397600 A 159 169 nimesulide TRIVIAL 22397600 A 241 251 nimesulide TRIVIAL 22397600 T 49 59 nimesulide TRIVIAL 22397675 A 1132 1135 NMP ABBREVIATION 22397675 A 1219 1222 IVM ABBREVIATION 22397675 A 1487 1490 IVM ABBREVIATION 22397675 A 1615 1618 PLA ABBREVIATION 22397675 A 345 355 ivermectin TRIVIAL 22397675 A 357 360 IVM ABBREVIATION 22397675 A 414 417 PLA ABBREVIATION 22397675 A 462 484 N-methyl-2-pyrrolidone SYSTEMATIC 22397675 A 486 489 NMP ABBREVIATION 22397675 A 492 505 2-pyrrolidone SYSTEMATIC 22397675 A 512 522 triacetine TRIVIAL 22397675 A 532 547 benzyl benzoate SYSTEMATIC 22397675 A 76 93 poly(D,L-lactide) SYSTEMATIC 22397675 A 888 891 IVM ABBREVIATION 22397675 A 95 98 PLA ABBREVIATION 22397675 T 11 14 PLA ABBREVIATION 22397675 T 72 82 Ivermectin TRIVIAL 22401597 A 131 141 triterpene FAMILY 22401597 A 145 211 1α,3β,25-trihydroxy-9(11)-ene-16-one-9,10-seco-9,19-cyclolanostane SYSTEMATIC 22401597 A 227 241 fatty alcohols SYSTEMATIC 22401597 T 0 29 9,10-seco-9,19-cyclolanostane SYSTEMATIC 22401597 T 30 40 triterpene FAMILY 22404642 A 148 161 triterpenoids FAMILY 22404642 A 163 186 3β-O-octadecanoyllupeol SYSTEMATIC 22404642 A 192 207 glut-5-en-3β-ol SYSTEMATIC 22404642 A 213 241 24-methylenecicloartan-3β-ol SYSTEMATIC 22404642 A 250 276 cicloart-23-ene-3β,25-diol SYSTEMATIC 22404642 A 316 328 ellagic acid TRIVIAL 22404642 A 337 365 3,3'-di-O-methylellagic acid SYSTEMATIC 22420410 A 14 30 diketopiperazine FAMILY 22420410 A 479 489 amino acid FAMILY 22420410 A 571 609 trans-cyclo-(D-tryptophanyl-L-tyrosyl) SYSTEMATIC 22420410 A 724 762 Trans-cyclo-(D-tryptophanyl-L-tyrosyl) SYSTEMATIC 22420410 T 39 55 diketopiperazine FAMILY 22424088 A 539 546 eugenol TRIVIAL 22424088 A 617 621 DPPH ABBREVIATION 22424088 A 626 636 superoxide TRIVIAL 22424088 A 735 742 eugenol TRIVIAL 22424117 A 141 159 iridoid glucosides FAMILY 22424117 A 167 199 8-O-trans-cinnamoyl caryoptoside SYSTEMATIC 22424117 A 205 248 8-O-trans-cinnamoyl shanzhiside methylester SYSTEMATIC 22424117 A 254 286 8-O-trans-cinnamoyl mussaenoside SYSTEMATIC 22424117 A 295 318 8-O-cafeoyl massenoside SYSTEMATIC 22424117 A 39 51 ethylacetate SYSTEMATIC 22424117 A 533 541 iridoids FAMILY 22424117 A 747 753 acetyl SYSTEMATIC 22424117 A 816 834 iridoid glucosides FAMILY 22424117 A 869 875 acetyl SYSTEMATIC 22424117 T 44 62 iridoid glucosides FAMILY 22430207 A 460 467 glucose TRIVIAL 22430207 A 933 940 glucose TRIVIAL 22445601 A 1103 1111 LY541850 IDENTIFIER 22445601 A 1234 1242 LY541850 IDENTIFIER 22445601 A 1320 1333 phencyclidine TRIVIAL 22445601 A 1338 1349 amphetamine TRIVIAL 22445601 A 1546 1555 Glutamate TRIVIAL 22445601 A 207 215 LY541850 IDENTIFIER 22445601 A 401 409 LY541850 IDENTIFIER 22445601 A 606 614 LY541850 IDENTIFIER 22445601 A 69 78 glutamate TRIVIAL 22445601 A 865 873 LY541850 IDENTIFIER 22445601 A 970 978 LY541850 IDENTIFIER 22445601 T 61 69 LY541850 IDENTIFIER 22451355 A 307 367 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide SYSTEMATIC 22455800 A 101 134 3-alkyl-2,6-diarylpiperidin-4-one FAMILY 22455800 A 12 55 4-hydroxy-3,4-dialkyl-2,6-diaryl-piperidine FAMILY 22455800 A 145 161 Grignard reagent FAMILY 22455800 A 287 300 piperdin-4-ol SYSTEMATIC 22455800 T 13 56 4-hydroxy-3,4-dialkyl-2,6-diaryl-piperidine FAMILY 22468693 A 151 161 chloroform TRIVIAL 22468693 A 267 280 diethyl ether SYSTEMATIC 22468693 A 285 292 acetone SYSTEMATIC 22468693 A 315 325 chloroform TRIVIAL 22468693 A 544 554 chloroform TRIVIAL 22468693 A 57 65 saponins FAMILY 22468693 A 605 613 eicosane SYSTEMATIC 22468693 A 615 625 oleic acid TRIVIAL 22468693 A 627 639 stigmasterol TRIVIAL 22468693 A 644 653 vitamin E FAMILY 22468741 A 353 391 sodium dodecyl sulphate polyacrylamide SYSTEMATIC 22468741 A 540 550 Isoleucine TRIVIAL 22468741 A 705 712 calcium SYSTEMATIC 22468741 A 714 723 magnesium SYSTEMATIC 22468741 A 728 737 potassium SYSTEMATIC 22468741 A 823 830 arsenic SYSTEMATIC 22469981 A 1025 1036 doxycycline TRIVIAL 22469981 A 382 394 tetracycline FAMILY 22469988 A 114 120 oxygen SYSTEMATIC 22469988 A 1399 1406 glucose TRIVIAL 22469988 A 198 201 ATP ABBREVIATION 22469988 A 206 217 fatty acids FAMILY 22475014 A 0 13 Glaucogenin E TRIVIAL 22475014 A 25 30 C(21) FORMULA 22475014 A 31 38 steroid FAMILY 22475014 T 0 13 Glaucogenin E TRIVIAL 22475014 T 21 24 C21 FORMULA 22475014 T 25 32 steroid FAMILY 22480291 A 123 132 rotenoids FAMILY 22480291 A 134 147 boeravinone E TRIVIAL 22480291 A 152 165 boeravinone B TRIVIAL 22480291 A 340 360 orthophosphoric acid SYSTEMATIC 22480291 A 374 386 acetonitrile SYSTEMATIC 22480291 A 631 650 boeravinone E and B MULTIPLE 22480291 T 52 65 boeravinone E TRIVIAL 22480291 T 70 83 boeravinone B TRIVIAL 22489960 A 309 326 7-ethoxyresorufin SYSTEMATIC 22489960 A 327 328 O FORMULA 22489960 A 348 362 benzo(a)pyrene SYSTEMATIC 22489960 A 414 425 glutathione TRIVIAL 22489960 A 427 430 GSH ABBREVIATION 22489960 A 433 445 testosterone TRIVIAL 22489960 A 447 460 17β-estradiol SYSTEMATIC 22489960 A 497 509 triglyceride FAMILY 22489960 A 630 633 GSH ABBREVIATION 22497567 A 1008 1011 IMC ABBREVIATION 22497567 A 1014 1033 fluoro-indomethacin FAMILY 22497567 A 1035 1040 F-IMC ABBREVIATION 22497567 A 1116 1119 IMC ABBREVIATION 22497567 A 1191 1194 IMC ABBREVIATION 22497567 A 1199 1204 F-IMC ABBREVIATION 22497567 A 1285 1290 F-IMC ABBREVIATION 22497567 A 1314 1317 IMC ABBREVIATION 22497567 A 1322 1327 F-IMC ABBREVIATION 22497567 A 1640 1643 IMC ABBREVIATION 22497567 A 1648 1653 F-IMC ABBREVIATION 22497567 A 1881 1884 IMC ABBREVIATION 22497567 A 1889 1894 F-IMC ABBREVIATION 22497567 A 2043 2050 18F-IMC FORMULA 22497567 A 606 609 18F FORMULA 22497567 A 829 841 indomethacin TRIVIAL 22497567 A 994 1006 indomethacin TRIVIAL 22497567 T 70 89 fluoro-indomethacin FAMILY 22502647 A 10 20 furostanol TRIVIAL 22502647 A 21 29 saponins FAMILY 22502647 A 49 61 polyhydroxyl SYSTEMATIC 22502647 A 62 69 saponin FAMILY 22502647 T 15 23 saponins FAMILY 22502647 T 4 14 furostanol TRIVIAL 22507666 A 1078 1086 dopamine TRIVIAL 22507666 A 1092 1096 cAMP ABBREVIATION 22507666 A 1230 1234 DHPG ABBREVIATION 22507666 A 1358 1361 Ser FORMULA 22507666 A 1392 1396 DHPG ABBREVIATION 22507666 A 1690 1699 Glutamate TRIVIAL 22507666 A 21 30 glutamate TRIVIAL 22507666 A 319 323 AMPA ABBREVIATION 22507666 A 324 333 glutamate TRIVIAL 22507666 A 425 457 (R,S)-3,5-dihydroxyphenylglycine SYSTEMATIC 22507666 A 459 463 DHPG ABBREVIATION 22507666 A 503 507 cAMP ABBREVIATION 22507666 A 545 548 Ser FORMULA 22507666 A 581 629 2-methyl-6-(phenylethynyl)pyridine hydrochloride SYSTEMATIC 22507666 A 631 635 MPEP ABBREVIATION 22507666 A 719 723 DHPG ABBREVIATION 22507666 A 757 766 adenosine TRIVIAL 22507666 A 817 821 cAMP ABBREVIATION 22507666 A 920 929 adenosine TRIVIAL 22507666 A 945 954 adenosine TRIVIAL 22507666 A 981 985 DHPG ABBREVIATION 22507666 T 16 25 glutamate TRIVIAL 22507666 T 26 30 AMPA ABBREVIATION 22510064 A 379 395 sodium hydroxide SYSTEMATIC 22510064 A 397 401 NaOH FORMULA 22510064 A 484 497 Poloxamer 407 TRIVIAL 22510064 A 64 74 rebamipide TRIVIAL 22510064 A 834 847 poloxamer 407 TRIVIAL 22510064 T 102 112 rebamipide TRIVIAL 22510064 T 118 131 poloxamer 407 TRIVIAL 22512590 A 503 515 Nikkomycin Z TRIVIAL 22512590 A 772 782 nikkomycin TRIVIAL 22512590 A 787 795 polyoxin FAMILY 22516666 A 1188 1193 CO(2) FORMULA 22516666 A 1251 1262 venlafaxine TRIVIAL 22516666 A 1287 1297 pregabalin TRIVIAL 22516666 A 1354 1369 benzodiazepines FAMILY 22516666 A 1399 1404 CO(2) FORMULA 22516666 A 1468 1473 CO(2) FORMULA 22516666 A 152 161 lorazepam TRIVIAL 22516666 A 1615 1620 CO(2) FORMULA 22516666 A 187 197 paroxetine TRIVIAL 22516666 A 199 210 Venlafaxine TRIVIAL 22516666 A 215 225 pregabalin TRIVIAL 22516666 A 341 346 CO(2) FORMULA 22516666 A 455 466 venlafaxine TRIVIAL 22516666 A 470 480 pregabalin TRIVIAL 22516666 A 581 592 venlafaxine TRIVIAL 22516666 A 603 613 pregabalin TRIVIAL 22516666 A 621 626 CO(2) FORMULA 22516666 A 677 682 CO(2) FORMULA 22516666 A 774 779 CO(2) FORMULA 22516666 A 866 871 CO(2) FORMULA 22516666 A 94 99 CO(2) FORMULA 22516666 T 29 40 venlafaxine TRIVIAL 22516666 T 45 55 pregabalin TRIVIAL 22516666 T 63 77 carbon dioxide SYSTEMATIC 22533550 A 200 207 Octanal SYSTEMATIC 22533550 A 212 230 2-bromoacetic acid SYSTEMATIC 22533550 A 55 60 amide FAMILY 22533550 A 71 107 N-isobutyl-4,5-epoxy-2(E)-decenamide SYSTEMATIC 22533550 T 32 68 N-isobutyl-4,5-epoxy-2(E)-decenamide SYSTEMATIC 22546615 A 1027 1038 haloperidol TRIVIAL 22546615 A 1083 1092 reserpine TRIVIAL 22546615 A 1104 1108 DCPG ABBREVIATION 22546615 A 1127 1138 haloperidol TRIVIAL 22546615 A 1161 1170 reserpine TRIVIAL 22546615 A 1202 1206 DCPG ABBREVIATION 22546615 A 1296 1310 decanoate salt SYSTEMATIC 22546615 A 13 22 glutamate TRIVIAL 22546615 A 1314 1325 haloperidol TRIVIAL 22546615 A 1358 1362 DCPG ABBREVIATION 22546615 A 1419 1436 6-hydroxydopamine SYSTEMATIC 22546615 A 1464 1472 dopamine TRIVIAL 22546615 A 1628 1636 dopamine TRIVIAL 22546615 A 1672 1680 dopamine TRIVIAL 22546615 A 1902 1911 Glutamate TRIVIAL 22546615 A 822 852 (S)-3,4-dicarboxyphenylglycine SYSTEMATIC 22546615 A 854 858 DCPG ABBREVIATION 22546615 A 954 965 haloperidol TRIVIAL 22546615 A 969 978 reserpine TRIVIAL 22546615 T 17 26 glutamate TRIVIAL 22546615 T 46 58 (S)-3,4-DCPG SYSTEMATIC 22546616 A 0 4 GABA ABBREVIATION 22546616 A 1189 1193 GABA ABBREVIATION 22546616 A 198 202 GABA ABBREVIATION 22546616 A 448 462 benzodiazepine FAMILY 22546616 A 483 499 [(11)C]Ro15-4513 IDENTIFIER 22546616 A 6 30 gamma-amino-butyric-acid SYSTEMATIC 22546616 A 715 731 [(11)C]Ro15-4513 IDENTIFIER 22546616 T 10 14 GABA ABBREVIATION 22546616 T 15 29 benzodiazepine FAMILY 22546616 T 92 108 [(11)C]Ro15-4513 IDENTIFIER 22548348 A 105 113 methanol SYSTEMATIC 22548348 A 19 43 C-geranylated flavonoids FAMILY 22548348 A 258 275 tanariflavanone D TRIVIAL 22548348 A 44 58 tomentomimulol TRIVIAL 22548348 A 67 77 mimulone B TRIVIAL 22548348 T 0 14 Tomentomimulol TRIVIAL 22548348 T 19 29 mimulone B TRIVIAL 22548348 T 39 63 C-geranylated flavonoids FAMILY 22548364 A 202 212 pimprinine TRIVIAL 22548364 A 218 291 (3R,4S,5R,6R)-3,4,5,6-tetrahydro-4-hydroxy-3,5,6-trimethyl-2H-pyran-2-one SYSTEMATIC 22548364 A 297 322 indolyl-3-carboxylic acid SYSTEMATIC 22548364 A 30 119 N-trans-cinnamoyl 2-amino-3a,4,5,6,7,8,9,10,11,12,13,13a-dodecahydrocyclododeca[d]oxazole SYSTEMATIC 22548364 A 328 345 2-phenylacetamide SYSTEMATIC 22548364 A 354 381 di(1H-pyrrol-2-yl)methanone SYSTEMATIC 22548364 T 6 27 cyclododeca[d]oxazole SYSTEMATIC 22551786 A 1367 1374 GRN-529 IDENTIFIER 22551786 A 1419 1426 GRN-529 IDENTIFIER 22551786 A 1592 1599 GRN-529 IDENTIFIER 22551786 A 1709 1713 MTEP ABBREVIATION 22551786 A 2120 2127 GRN-529 IDENTIFIER 22551786 A 508 517 glutamate TRIVIAL 22551786 A 586 593 GRN-529 IDENTIFIER 22551786 A 655 664 glutamate TRIVIAL 22551786 A 721 728 GRN-529 IDENTIFIER 22551786 A 865 872 GRN-529 IDENTIFIER 22551786 T 47 56 glutamate TRIVIAL 22559719 A 165 179 carbon dioxide SYSTEMATIC 22559719 A 277 288 Citronellal TRIVIAL 22559719 A 780 803 oxygenated monoterpenes FAMILY 22559719 A 999 1010 citronellal TRIVIAL 22561337 A 329 337 estrogen FAMILY 22561337 A 388 396 estrogen FAMILY 22561337 A 554 562 estrogen FAMILY 22561337 A 762 770 estrogen FAMILY 22561337 A 822 830 estrogen FAMILY 22561337 A 934 942 estrogen FAMILY 22561337 T 49 57 estrogen FAMILY 22563917 A 1008 1011 BBH ABBREVIATION 22563917 A 1129 1132 BBH ABBREVIATION 22563917 A 1331 1334 BBH ABBREVIATION 22563917 A 134 157 Berberine hydrochloride SYSTEMATIC 22563917 A 159 162 BBH ABBREVIATION 22563917 A 674 689 ethyl linoleate SYSTEMATIC 22563917 A 694 704 oleic acid TRIVIAL 22563917 A 722 730 Tween-80 TRIVIAL 22563917 A 745 753 glycerol TRIVIAL 22563917 A 769 772 BBH ABBREVIATION 22563917 A 854 857 BBH ABBREVIATION 22563917 T 98 121 berberine hydrochloride SYSTEMATIC 22579656 A 1027 1032 THDOC ABBREVIATION 22579656 A 1053 1057 GABA ABBREVIATION 22579656 A 1110 1114 GABA ABBREVIATION 22579656 A 572 581 estrogens FAMILY 22579656 A 586 598 progesterone TRIVIAL 22579656 A 699 715 allopregnanolone TRIVIAL 22579656 A 725 758 allotetrahydrodeoxycorticosterone TRIVIAL 22579656 A 760 765 THDOC ABBREVIATION 22579656 A 882 886 GABA ABBREVIATION 22583008 A 139 149 fatty acid FAMILY 22583008 A 321 342 Saturated fatty acids FAMILY 22583008 A 448 475 monounsaturated fatty acids FAMILY 22583008 A 543 570 polyunsaturated fatty acids FAMILY 22583008 A 605 669 arachidonic (C20 : 4ω-6) and eicosapentaenoic (C20 : 5ω-3) acids MULTIPLE 22583008 A 787 798 fatty acids FAMILY 22583008 T 0 10 Fatty acid FAMILY 22585425 A 0 17 Allylpyrocatechol SYSTEMATIC 22585425 A 19 22 APC ABBREVIATION 22585425 A 258 261 APC ABBREVIATION 22585425 A 263 266 APC ABBREVIATION 22585425 A 287 294 phorbol TRIVIAL 22585425 A 295 304 myristate TRIVIAL 22585425 A 305 312 acetate SYSTEMATIC 22585425 A 344 350 oxygen SYSTEMATIC 22585425 A 363 373 superoxide TRIVIAL 22585425 A 562 578 sodium ascorbate SYSTEMATIC 22585425 A 597 600 APC ABBREVIATION 22585425 A 688 691 APC ABBREVIATION 22585425 A 745 748 GSH ABBREVIATION 22585425 A 812 815 APC ABBREVIATION 22585425 T 28 45 allylpyrocatechol SYSTEMATIC 22585450 A 1031 1068 N-[3(aminomethyl) benzyl]-acetamidine SYSTEMATIC 22585450 A 1070 1085 dihydrochloride SYSTEMATIC 22585450 A 1312 1315 STZ ABBREVIATION 22585450 A 229 243 streptozotocin TRIVIAL 22585450 A 245 248 STZ ABBREVIATION 22585450 A 356 368 nitric oxide SYSTEMATIC 22585450 A 606 619 acetylcholine SYSTEMATIC 22585450 A 642 655 noradrenaline TRIVIAL 22585450 A 777 784 nitrite SYSTEMATIC 22585450 A 785 792 nitrate SYSTEMATIC 22585450 A 798 813 malondialdehite TRIVIAL 22585450 T 60 74 streptozotocin TRIVIAL 22594605 A 176 184 caffeine TRIVIAL 22594605 A 193 232 1,3-dimethylpyrimidine-2,4(1H,3H)-dione SYSTEMATIC 22594605 A 34 74 9-acetyl-1,3,7-trimethyl-pyrimidinedione SYSTEMATIC 22594605 A 6 21 pyrimidinedione FAMILY 22594605 T 6 21 pyrimidinedione FAMILY 22610853 A 1010 1018 curcumin TRIVIAL 22610853 A 1057 1069 curcuminoids FAMILY 22610853 A 106 114 Curcumin TRIVIAL 22610853 A 1117 1128 cholesterol TRIVIAL 22610853 A 1154 1165 cholesterol TRIVIAL 22610853 A 1192 1203 cholesterol TRIVIAL 22610853 A 1410 1423 triglycerides FAMILY 22610853 A 286 294 curcumin TRIVIAL 22610853 A 357 369 curcuminoids FAMILY 22610853 A 490 501 cholesterol TRIVIAL 22610853 A 503 516 triglycerides FAMILY 22610853 A 542 553 cholesterol TRIVIAL 22610853 A 583 594 cholesterol TRIVIAL 22610853 A 959 972 triglycerides FAMILY 22610853 T 32 44 curcuminoids FAMILY 22616559 A 284 294 naringenin TRIVIAL 22616559 A 29 58 apigenin 7-O-β-D-cellobioside SYSTEMATIC 22616559 A 67 120 apigenin 7-O-β-D-cellobiosyl-4'-O-β-D-glucopyranoside SYSTEMATIC 22616559 T 29 82 apigenin 7-O-β-D-cellobiosyl-4'-O-β-D-glucopyranoside SYSTEMATIC 22616577 A 110 124 Arjunolic acid TRIVIAL 22616577 A 130 154 24-hydroxytormentic acid SYSTEMATIC 22616577 A 163 195 3-O-β-D-glucopyranosylsitosterol SYSTEMATIC 22616577 A 205 221 sodium periodate SYSTEMATIC 22616577 A 226 236 silica gel TRIVIAL 22616577 A 246 249 THF ABBREVIATION 22616577 A 289 297 hydroxyl SYSTEMATIC 22616577 A 29 41 vicinal diol FAMILY 22616577 A 347 377 lactol pentacyclic triterpenes FAMILY 22616577 A 391 423 bicyclotriacetal of β-sitosterol TRIVIAL 22616577 A 8 11 C-C FORMULA 22616577 T 133 138 NaIO4 FORMULA 22616577 T 139 143 SiO2 FORMULA 22616577 T 151 154 THF ABBREVIATION 22616577 T 30 48 acetal triterpenes FAMILY 22616577 T 62 74 vicinal diol FAMILY 22619070 A 1105 1112 terpene FAMILY 22619070 A 1114 1127 terpinen-4-ol SYSTEMATIC 22623520 A 0 10 Methiocarb TRIVIAL 22623520 A 1080 1095 malondialdehyde TRIVIAL 22623520 A 1165 1176 glutathione TRIVIAL 22623520 A 1195 1205 superoxide TRIVIAL 22623520 A 1230 1241 glutathione TRIVIAL 22623520 A 130 139 carbamate FAMILY 22623520 A 1301 1312 glutathione TRIVIAL 22623520 A 1553 1562 vitamin E FAMILY 22623520 A 1567 1574 taurine TRIVIAL 22623520 A 1999 2008 vitamin E FAMILY 22623520 A 2013 2020 taurine TRIVIAL 22623520 A 33 42 carbamate FAMILY 22623520 A 473 482 vitamin E FAMILY 22623520 A 487 494 taurine TRIVIAL 22623520 A 632 641 vitamin E FAMILY 22623520 A 704 711 taurine TRIVIAL 22623520 A 883 892 vitamin E FAMILY 22623520 A 914 921 taurine TRIVIAL 22623520 T 17 27 methiocarb TRIVIAL 22623520 T 78 87 vitamin E FAMILY 22623520 T 92 99 taurine TRIVIAL 22625411 A 185 196 sulfonamide SYSTEMATIC 22625411 A 371 383 sulfonamides FAMILY 22625411 A 593 604 sulfonamide SYSTEMATIC 22625411 A 676 688 sulfonamides FAMILY 22625411 T 42 54 sulfonamides FAMILY 22625416 A 156 165 terpenoid FAMILY 22625416 A 198 212 tocochromanols FAMILY 22625416 A 217 224 sterols FAMILY 22625416 A 337 345 terpenes FAMILY 22625416 A 93 112 omega-3 fatty acids FAMILY 22625416 T 5 14 terpenoid FAMILY 22628017 A 117 129 anthocyanins FAMILY 22628017 A 356 364 pyruvate TRIVIAL 22628017 A 370 376 malate TRIVIAL 22628017 A 547 556 Succinate TRIVIAL 22628017 A 591 603 anthocyanins FAMILY 22628017 A 643 663 malvidin-3-glucoside SYSTEMATIC 22628017 A 665 687 malvidin-3-galactoside SYSTEMATIC 22628017 A 693 715 cyanidin-3-galactoside SYSTEMATIC 22628017 A 747 755 pyruvate TRIVIAL 22628017 A 761 767 malate TRIVIAL 22628017 A 809 814 H2 O2 FORMULA 22628017 A 934 945 anthocyanin FAMILY 22628265 A 1036 1043 ethanol SYSTEMATIC 22628265 A 109 118 neolignan FAMILY 22628265 A 1245 1252 ethanol SYSTEMATIC 22628265 A 1399 1406 ethanol SYSTEMATIC 22628265 A 258 265 ethanol SYSTEMATIC 22628265 A 49 57 magnolol TRIVIAL 22628265 A 505 512 ethanol SYSTEMATIC 22628265 A 559 566 ethanol SYSTEMATIC 22628265 A 59 67 honokiol TRIVIAL 22628265 A 69 87 4-O-methylhonokiol SYSTEMATIC 22628265 A 735 742 ethanol SYSTEMATIC 22628265 A 89 97 obovatol TRIVIAL 22628265 A 900 912 nitric oxide SYSTEMATIC 22628265 T 0 7 Ethanol SYSTEMATIC 22634360 A 1047 1091 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine SYSTEMATIC 22634360 A 1093 1097 MPTP ABBREVIATION 22634360 A 1724 1728 MPTP ABBREVIATION 22634360 A 1801 1806 L-AP4 IDENTIFIER 22634360 A 2052 2057 L-AP4 IDENTIFIER 22634360 A 2071 2080 VU0155041 IDENTIFIER 22634360 A 208 225 6-hydroxydopamine SYSTEMATIC 22634360 A 23 32 glutamate TRIVIAL 22634360 A 2347 2352 L-AP4 IDENTIFIER 22634360 A 2391 2400 glutamate TRIVIAL 22634360 A 2661 2670 Glutamate TRIVIAL 22634360 A 866 871 L-AP4 IDENTIFIER 22634360 A 917 926 VU0155041 IDENTIFIER 22634360 T 13 22 glutamate TRIVIAL 22640571 A 0 101 16-Isopropyl-5, 9-dimethyltetracyclo [10.2.2.0(1, 10).0(4, 9)] hexadec-15-ene-5, 14-dicarboxylic acid SYSTEMATIC 22640571 A 189 201 Schiff bases FAMILY 22640571 A 277 281 (1)H FORMULA 22640571 A 370 382 Schiff bases FAMILY 22640571 T 40 52 Schiff bases FAMILY 22640571 T 58 159 16-isopropyl-5, 9-dimethyltetracyclo [10.2.2.0(1, 10).0(4, 9)] hexadec-15-ene-5, 14-dicarboxylic acid SYSTEMATIC 22641218 A 1308 1317 Celastrol TRIVIAL 22641218 A 1577 1586 Celastrol TRIVIAL 22641218 A 2141 2150 Celastrol TRIVIAL 22644836 A 919 926 glucose TRIVIAL 22644836 A 928 941 triglycerides FAMILY 22644836 A 951 962 cholesterol TRIVIAL 22648529 A 1097 1103 hopane TRIVIAL 22648529 A 1112 1120 saponins FAMILY 22648529 A 1207 1215 saponins FAMILY 22648529 A 344 352 methanol SYSTEMATIC 22648529 A 768 776 saponins FAMILY 22648529 A 821 831 flavonoids FAMILY 22648529 A 836 844 oleanane TRIVIAL 22648529 A 850 858 saponins FAMILY 22648529 A 862 870 oleanane TRIVIAL 22648529 A 876 884 saponins FAMILY 22648529 A 932 938 hopane TRIVIAL 22648529 A 944 952 saponins FAMILY 22658648 A 1111 1123 myo-inositol TRIVIAL 22658648 A 1193 1205 Myo-inositol TRIVIAL 22658648 A 161 169 inositol TRIVIAL 22658648 A 387 399 myo-inositol TRIVIAL 22658648 A 433 441 inositol TRIVIAL 22658648 A 454 466 myo-inositol TRIVIAL 22658648 A 567 574 glucose TRIVIAL 22658648 A 641 653 myo-inositol TRIVIAL 22658648 A 956 968 myo-inositol TRIVIAL 22658648 T 23 35 myo-inositol TRIVIAL 22659473 A 108 117 glutamate TRIVIAL 22659473 A 554 563 Glutamate TRIVIAL 22659473 T 51 60 glutamate TRIVIAL 22660443 A 348 354 azoles FAMILY 22660443 A 488 494 azoles FAMILY 22660443 A 522 537 corticosteroids FAMILY 22660443 T 0 5 Azole FAMILY 22661401 A 207 213 Cu(2+) FORMULA 22661401 A 215 221 Zn(2+) FORMULA 22661401 A 223 229 Mn(2+) FORMULA 22661401 A 234 240 Ni(2+) FORMULA 22669363 A 329 350 N-acetylgalactosamine SYSTEMATIC 22670797 A 1012 1019 octanol SYSTEMATIC 22670797 A 107 133 4-tert-butylphenylthiourea SYSTEMATIC 22670797 A 1109 1116 QNT3-18 IDENTIFIER 22670797 A 1150 1157 QNT3-20 IDENTIFIER 22670797 A 1219 1226 QNT3-18 IDENTIFIER 22670797 A 135 142 QNT3-20 IDENTIFIER 22670797 A 1418 1425 QNT3-18 IDENTIFIER 22670797 A 1502 1509 QNT3-18 IDENTIFIER 22670797 A 1608 1615 QNT3-18 IDENTIFIER 22670797 A 38 93 (E)-2-(4-tert-butylbenzylidene) hydrazinecarbothioamide SYSTEMATIC 22670797 A 411 418 QNT3-18 IDENTIFIER 22670797 A 422 429 QNT3-20 IDENTIFIER 22670797 A 576 583 QNT3-18 IDENTIFIER 22670797 A 588 595 QNT3-20 IDENTIFIER 22670797 A 695 702 QNT3-18 IDENTIFIER 22670797 A 726 733 QNT3-20 IDENTIFIER 22670797 A 786 793 QNT3-18 IDENTIFIER 22670797 A 797 804 QNT3-20 IDENTIFIER 22670797 A 95 102 QNT3-18 IDENTIFIER 22670797 T 52 59 QNT3-18 IDENTIFIER 22677475 A 0 21 Tetrabromobisphenol A SYSTEMATIC 22677475 A 23 28 TBBPA ABBREVIATION 22677475 A 265 270 TBBPA ABBREVIATION 22677475 A 356 361 TBBPA ABBREVIATION 22677475 A 91 96 TBBPA ABBREVIATION 22677475 A 944 949 TBBPA ABBREVIATION 22677475 T 10 30 tetrabrombisphenol A SYSTEMATIC 22678994 A 1065 1070 H2 O2 FORMULA 22678994 A 1162 1179 poly (ADP-ribose) SYSTEMATIC 22678994 A 1278 1283 H2 O2 FORMULA 22678994 A 1333 1352 acetoxymethyl ester SYSTEMATIC 22678994 A 433 440 calcium SYSTEMATIC 22678994 A 734 759 Polymethoxylated flavones FAMILY 22678994 A 768 777 nobiletin TRIVIAL 22678994 A 782 792 tangeretin TRIVIAL 22678994 A 87 94 calcium SYSTEMATIC 22678994 A 959 964 H2 O2 FORMULA 22683935 A 706 730 2,4-dinitrochlorobenzene SYSTEMATIC 22683935 A 732 751 paraphenylendiamine SYSTEMATIC 22683935 A 753 767 cinnamaldehyde TRIVIAL 22683935 A 769 779 isoeugenol TRIVIAL 22683935 A 781 795 nickel-sulfate SYSTEMATIC 22683935 A 797 825 tetramethylthiuram disulfide SYSTEMATIC 22683935 A 827 834 eugenol TRIVIAL 22683935 A 836 852 cinnamic-alcohol SYSTEMATIC 22683935 A 854 882 ammonium-hexachloroplatinate SYSTEMATIC 22683935 A 927 948 sodium lauryl sulfate SYSTEMATIC 22683935 A 950 964 salicylic acid TRIVIAL 22683935 A 966 972 phenol SYSTEMATIC 22683935 A 974 987 octanoic acid SYSTEMATIC 22693035 A 1123 1135 ursolic acid TRIVIAL 22693035 A 1137 1151 oleanolic acid TRIVIAL 22693035 A 1153 1161 apigenin TRIVIAL 22693035 A 1163 1171 luteolin TRIVIAL 22693035 A 1176 1185 ixoroside TRIVIAL 22693035 A 1187 1209 Apigenin-7-O-glucoside SYSTEMATIC 22693035 A 1211 1232 8-hydroxycirsimaritin SYSTEMATIC 22693035 A 1237 1249 cirsimaritin TRIVIAL 22693035 A 1296 1309 ethyl acetate SYSTEMATIC 22693035 A 1328 1344 Nepetanudoside B TRIVIAL 22693035 A 1367 1376 n-butanol SYSTEMATIC 22693035 A 260 289 2,2-diphenyl-1-picrylhydrazyl SYSTEMATIC 22693035 A 291 295 DPPH ABBREVIATION 22693035 A 298 353 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) SYSTEMATIC 22693035 A 355 359 ABTS ABBREVIATION 22693035 A 447 455 methanol SYSTEMATIC 22693035 A 503 511 n-hexane SYSTEMATIC 22693035 A 513 526 ethyl acetate SYSTEMATIC 22693035 A 531 540 n-butanol SYSTEMATIC 22693035 A 558 566 methanol SYSTEMATIC 22693035 A 627 633 Fe(II) FORMULA 22693035 A 667 686 butylhydroxytoluene SYSTEMATIC 22693035 A 696 702 Fe(II) FORMULA 22693035 A 733 737 DPPH ABBREVIATION 22693035 A 839 852 ethyl acetate SYSTEMATIC 22693035 A 857 866 n-butanol SYSTEMATIC 22693035 A 892 901 n-Butanol SYSTEMATIC 22694738 A 1081 1179 pelargonidin-3-O-[6-O-(4-O-E-p-coumaroyl-O-α-rhamnopyranosyl)-β-glucopyrano]-5-O-β-glucopyranoside SYSTEMATIC 22694738 A 11 22 anthocyanin FAMILY 22694738 A 172 184 anthocyanins FAMILY 22694738 A 325 346 acylated anthocyanins FAMILY 22694738 A 382 394 Anthocyanins FAMILY 22694738 A 473 485 anthocyanins FAMILY 22694738 A 622 659 -3,5-di-O-β-glucosides of delphinidin SYSTEMATIC 22694738 A 661 669 cyanidin TRIVIAL 22694738 A 671 680 petunidin TRIVIAL 22694738 A 682 690 malvidin TRIVIAL 22694738 A 695 703 peonidin TRIVIAL 22694738 A 715 724 cyanidine TRIVIAL 22694738 A 729 753 peonidin-3-O-β-glucoside SYSTEMATIC 22694738 A 772 866 cyanidin-3-O-[6-O-(4-O-E-p-coumaroyl-O-α-rhamnopyranosyl)-β-glucopyrano]-5-O-β-glucopyranoside SYSTEMATIC 22694738 A 881 892 anthocyanin FAMILY 22694738 A 932 943 anthocyanin FAMILY 22694738 A 985 1076 cyanidin-3-O-[6-O-(4-O-E-caffeoyl-O-α-rhamnopyranosyl)-β-glucopyrano]-5-O-β-glucopyranoside SYSTEMATIC 22694738 T 32 44 anthocyanins FAMILY 22705340 A 1125 1129 MTEP ABBREVIATION 22705340 A 1243 1252 VU0360172 IDENTIFIER 22705340 A 1325 1334 VU0360172 IDENTIFIER 22705340 A 1370 1374 MTEP ABBREVIATION 22705340 A 1669 1678 Glutamate TRIVIAL 22705340 A 743 763 polyphosphoinositide SYSTEMATIC 22705340 T 57 66 VU0360172 IDENTIFIER 22709945 A 1211 1215 CORT ABBREVIATION 22709945 A 384 398 corticosterone TRIVIAL 22709945 A 625 639 corticosterone TRIVIAL 22709945 A 983 997 corticosterone TRIVIAL 22709945 A 999 1003 CORT ABBREVIATION 22709945 T 30 44 corticosterone TRIVIAL 22712581 A 235 248 peristrophine TRIVIAL 22712581 A 743 756 peristrophine TRIVIAL 22712581 A 881 894 peristrophine TRIVIAL 22712581 T 59 70 phenoxazine SYSTEMATIC 22712621 A 815 822 arbutin TRIVIAL 22718275 A 0 20 7-Dehydrocholesterol SYSTEMATIC 22718275 A 1032 1037 IsoPs ABBREVIATION 22718275 A 1042 1049 NeuroPs ABBREVIATION 22718275 A 1151 1156 IsoPs ABBREVIATION 22718275 A 1161 1168 NeuroPs ABBREVIATION 22718275 A 1316 1321 7-DHC SYSTEMATIC 22718275 A 1330 1340 oxysterols FAMILY 22718275 A 1380 1385 IsoPs ABBREVIATION 22718275 A 1390 1397 NeuroPs ABBREVIATION 22718275 A 165 181 3β-hydroxysterol FAMILY 22718275 A 22 27 7-DHC SYSTEMATIC 22718275 A 232 237 7-DHC SYSTEMATIC 22718275 A 332 342 oxysterols FAMILY 22718275 A 392 397 7-DHC SYSTEMATIC 22718275 A 440 445 7-DHC SYSTEMATIC 22718275 A 599 609 oxysterols FAMILY 22718275 A 611 623 isoprostanes FAMILY 22718275 A 625 630 IsoPs ABBREVIATION 22718275 A 637 651 neuroprostanes FAMILY 22718275 A 653 660 NeuroPs ABBREVIATION 22718275 A 700 705 7-DHC SYSTEMATIC 22718275 A 707 723 arachidonic acid TRIVIAL 22718275 A 728 748 docosahexaenoic acid SYSTEMATIC 22718275 A 802 811 oxysterol FAMILY 22718275 A 813 846 3β,5α-dihydroxycholest-7-en-6-one SYSTEMATIC 22718275 A 848 853 DHCEO ABBREVIATION 22718275 A 917 927 oxysterols FAMILY 22724545 A 191 236 6,8-dihydroxy-3-methyl-3,4-dihydroisocoumarin SYSTEMATIC 22724545 A 242 285 (22R)-hydroxylanosta-7,9(11),24-trien-3-one SYSTEMATIC 22724545 A 27 35 methanol SYSTEMATIC 22724545 A 294 304 ergosterol TRIVIAL 22724545 A 599 610 isocoumarin TRIVIAL 22728231 A 1024 1028 DNCB ABBREVIATION 22728231 A 1030 1040 resorcinol TRIVIAL 22728231 A 1042 1045 pPD ABBREVIATION 22728231 A 1069 1080 lactic acid TRIVIAL 22728231 A 1144 1148 DNCB ABBREVIATION 22728231 A 1162 1172 resorcinol TRIVIAL 22728761 A 1067 1074 cocaine TRIVIAL 22728761 A 1166 1174 D-serine TRIVIAL 22728761 A 1277 1285 D-serine TRIVIAL 22728761 A 1345 1353 D-serine TRIVIAL 22728761 A 1481 1488 cocaine TRIVIAL 22728761 A 1531 1539 D-serine TRIVIAL 22728761 A 1647 1654 cocaine TRIVIAL 22728761 A 635 643 D-serine TRIVIAL 22728761 A 735 742 cocaine TRIVIAL 22728761 A 786 794 D-serine TRIVIAL 22728761 A 846 853 cocaine TRIVIAL 22728761 A 920 928 D-serine TRIVIAL 22728761 T 0 8 D-Serine TRIVIAL 22728761 T 92 99 cocaine TRIVIAL 22732443 A 538 547 Ro25-6981 IDENTIFIER 22732443 A 659 663 AMPA ABBREVIATION 22736593 A 169 181 ginsenosides FAMILY 22736593 A 354 366 ginsenosides FAMILY 22736593 A 375 378 UDP ABBREVIATION 22736593 A 456 478 20(S)-protopanaxatriol SYSTEMATIC 22736593 A 480 483 ppt ABBREVIATION 22736593 T 25 47 20(S)-Protopanaxatriol SYSTEMATIC 22736593 T 49 52 ppt ABBREVIATION 22743159 A 1325 1334 Glutamate TRIVIAL 22743159 A 311 320 glutamate TRIVIAL 22743159 T 21 30 glutamate TRIVIAL 22745189 A 465 474 sulpiride TRIVIAL 22745189 A 639 648 sulpiride TRIVIAL 22745189 A 716 725 sulpiride TRIVIAL 22745189 A 932 941 sulpiride TRIVIAL 22745189 A 966 975 Sulpiride TRIVIAL 22745189 T 16 25 sulpiride TRIVIAL 22750050 A 128 131 ATP ABBREVIATION 22750050 A 28 50 adenosine triphosphate SYSTEMATIC 22750050 A 365 371 serine TRIVIAL 22750050 A 372 381 threonine TRIVIAL 22750050 A 450 473 adenosine monophosphate SYSTEMATIC 22750050 A 52 55 ATP ABBREVIATION 22750050 A 793 803 fatty acid FAMILY 22750050 A 808 815 glucose TRIVIAL 22750079 A 186 197 mirtazapine TRIVIAL 22750079 A 268 279 Mirtazapine TRIVIAL 22750079 A 447 458 mirtazapine TRIVIAL 22750079 A 80 91 mirtazapine TRIVIAL 22750079 A 829 840 Mirtazapine TRIVIAL 22750079 T 35 46 mirtazapine TRIVIAL 22751286 A 0 9 Cisplatin TRIVIAL 22751286 A 15 46 cis-diamminedichloroplatinum II SYSTEMATIC 22751286 A 222 252 ω-3 polyunsaturated fatty acid FAMILY 22751286 A 835 845 sulfhydryl FAMILY 22751286 A 968 979 glutathione TRIVIAL 22751286 T 63 72 cisplatin TRIVIAL 22760156 A 28 38 lanthanide FAMILY 22760156 A 358 368 lanthanide FAMILY 22760156 A 871 882 bicarbonate SYSTEMATIC 22760156 A 884 891 lactate FAMILY 22760156 A 893 900 citrate FAMILY 22760156 A 905 910 urate SYSTEMATIC 22760156 T 26 36 lanthanide FAMILY 22765022 A 159 231 5,2',4'-trihydroxy-flavone-8-C-α-arabinopyranoside-7-O-β-glucopyranoside SYSTEMATIC 22765022 A 246 254 apigenin TRIVIAL 22765022 A 256 286 apigenin-7-O-β-glucopyranoside SYSTEMATIC 22765022 A 288 313 apigenin 7-O-gentobioside SYSTEMATIC 22765022 A 315 323 luteolin TRIVIAL 22765022 A 325 355 luteolin-7-O-β-glucopyranoside SYSTEMATIC 22765022 A 357 393 quercetin-3,7-di-O-β-glucopyranoside SYSTEMATIC 22765022 A 395 449 quercetin-3-O-β-glucopyranoside-7-O-α-rhamnopyranoside SYSTEMATIC 22765022 A 454 462 daidzein TRIVIAL 22765022 A 8 17 flavonoid FAMILY 22765022 A 94 154 quercetin-3,7-di-O-β-glucopyranoside 4'-O-α-rhamnopyranoside SYSTEMATIC 22765022 T 0 9 Flavonoid FAMILY 22765159 A 214 231 cyclo-(Gly-L-Ala) SYSTEMATIC 22765159 A 237 256 cyclo-(L-Ala-L-Ala) SYSTEMATIC 22765159 A 262 279 cyclo-(L-Pro-Gly) SYSTEMATIC 22765159 A 285 304 cyclo-(L-Pro-L-Ser) SYSTEMATIC 22765159 A 310 345 cyclo-(L-Ala-trans-4-hydroxy-L-Pro) SYSTEMATIC 22765159 A 352 370 yclo-(L-Val-L-Pro) SYSTEMATIC 22765159 A 376 393 cyclo-(Gly-L-Tyr) SYSTEMATIC 22765159 A 399 418 cyclo-(L-Ala-L-Tyr) SYSTEMATIC 22765159 A 424 459 cyclo-(L-Tyr-trans-4-hydroxy-L-Pro) SYSTEMATIC 22765159 A 465 482 3-methylhydantoin SYSTEMATIC 22765159 A 492 506 2-piperidinone SYSTEMATIC 22765159 A 722 737 cyclodipeptides FAMILY 22766173 A 1687 1693 iodide SYSTEMATIC 22766173 A 1708 1725 terephthalic acid TRIVIAL 22766173 A 271 277 iodide SYSTEMATIC 22766173 A 292 309 terephthalic acid TRIVIAL 22766173 A 409 415 iodide SYSTEMATIC 22766173 A 420 437 terephthalic acid TRIVIAL 22766173 A 593 595 KI FORMULA 22766173 A 664 681 terephthalic acid TRIVIAL 22766173 T 20 26 iodide SYSTEMATIC 22766173 T 41 58 terephthalic acid TRIVIAL 22766394 A 1245 1254 modafinil TRIVIAL 22766394 A 1572 1581 Modafinil TRIVIAL 22766394 A 1752 1761 modafinil TRIVIAL 22766394 A 1863 1872 modafinil TRIVIAL 22766394 A 2034 2043 modafinil TRIVIAL 22766394 A 468 477 modafinil TRIVIAL 22766394 A 634 643 modafinil TRIVIAL 22766394 T 82 91 modafinil TRIVIAL 22771462 A 1062 1066 TBOA ABBREVIATION 22771462 A 1080 1084 TBOA ABBREVIATION 22771462 A 1128 1132 MPEP ABBREVIATION 22771462 A 1138 1145 CPCCOEt FORMULA 22771462 A 1198 1207 glutamate TRIVIAL 22771462 A 13 22 glutamate TRIVIAL 22771462 A 1560 1569 Glutamate TRIVIAL 22771462 A 296 300 DHPG ABBREVIATION 22771462 A 605 609 DHPG ABBREVIATION 22771462 A 709 716 CPCCOEt FORMULA 22771462 A 754 761 CPCCOEt FORMULA 22771462 A 792 807 antagonist MPEP ABBREVIATION 22771462 A 821 830 glutamate TRIVIAL 22771462 A 849 853 TBOA ABBREVIATION 22771462 A 934 938 CNQX ABBREVIATION 22771462 A 952 955 AP5 ABBREVIATION 22776039 A 1029 1036 glucose TRIVIAL 22776039 A 1213 1220 glucose TRIVIAL 22776039 A 1644 1651 glucose TRIVIAL 22776039 A 363 370 glucose TRIVIAL 22776039 A 719 726 glucose TRIVIAL 22776039 A 765 772 glucose TRIVIAL 22776039 A 887 894 glucose TRIVIAL 22776039 A 917 924 glucose TRIVIAL 22776039 T 82 89 glucose TRIVIAL 22780426 A 109 119 octaketide SYSTEMATIC 22780426 A 132 148 dindygulerione D TRIVIAL 22780426 A 165 179 acylresorcinol SYSTEMATIC 22780426 A 191 206 dindyguleranone TRIVIAL 22780426 A 329 345 Dindygulerione C TRIVIAL 22780426 A 392 402 polyketide FAMILY 22780426 A 473 577 (-)-(4S)-2-[(Z)-1'-(6″,7″-dihydroxyphenethyl-amino)octadec-11'-enylidene]-4-hydroxycyclohexane-1,3-dione SYSTEMATIC 22780426 A 56 66 polyketide FAMILY 22780426 A 583 649 (+)-2-heptadecyl-4-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one SYSTEMATIC 22780426 A 658 698 2-(1,3-dihydroxyphenyl)-octacosan-1'-one SYSTEMATIC 22780426 A 79 95 dindygulerione C TRIVIAL 22780563 A 0 14 Hydroxyapatite TRIVIAL 22780563 A 151 157 carbon SYSTEMATIC 22780563 A 331 337 carbon SYSTEMATIC 22780563 A 384 399 Calcium acetate SYSTEMATIC 22780563 A 401 417 Ca (CH(3)COO)(2) FORMULA 22780563 A 423 438 phosphoric acid SYSTEMATIC 22780563 A 440 449 H(3)PO(4) FORMULA 22780563 A 680 682 Ti FORMULA 22780563 A 757 766 n-butanol SYSTEMATIC 22780563 T 21 35 hydroxyapatite TRIVIAL 22780563 T 46 52 carbon SYSTEMATIC 22788542 A 199 204 rutin TRIVIAL 22788542 A 209 218 quercetin TRIVIAL 22788542 A 219 229 flavonoids FAMILY 22788542 A 413 418 rutin TRIVIAL 22788542 A 423 432 quercetin TRIVIAL 22788542 A 624 629 rutin TRIVIAL 22788542 A 634 643 quercetin TRIVIAL 22788700 A 21 32 polyphenols FAMILY 22788700 A 34 45 chlorogenic FAMILY 22788700 A 361 371 polyphenol FAMILY 22788700 A 430 441 polyphenols FAMILY 22788700 A 47 54 caffeic FAMILY 22788700 A 505 516 polyphenols FAMILY 22788700 A 537 542 rutin TRIVIAL 22788700 A 56 59 CaA ABBREVIATION 22788700 A 622 632 polyphenol FAMILY 22788700 A 65 78 ferulic acids FAMILY 22788700 A 756 766 polyphenol FAMILY 22788700 A 817 820 CaA ABBREVIATION 22788700 A 84 89 rutin TRIVIAL 22788700 T 0 10 Polyphenol FAMILY 22788743 A 110 119 vitamin C TRIVIAL 22788743 A 121 127 folate TRIVIAL 22788743 A 132 140 phenolic FAMILY 22789395 A 168 189 p-hydroxybenzoic acid SYSTEMATIC 22789395 A 259 267 parabens FAMILY 22789395 A 68 112 methyl, ethyl, n-propyl and n-butyl parabens MULTIPLE 22789395 A 825 833 parabens FAMILY 22789395 A 882 890 parabens FAMILY 22789395 T 21 29 parabens FAMILY 22799569 A 0 10 Flavonoids FAMILY 22799569 A 295 305 Flavonoids FAMILY 22799569 A 344 354 flavonoids FAMILY 22799569 A 360 383 quercetin 3-O-glucoside SYSTEMATIC 22799569 A 389 413 quercetin 3-O-rhamnoside SYSTEMATIC 22799569 A 419 460 quercetin 3-O-rhamnosyl-(1 → 6)-glucoside SYSTEMATIC 22799569 A 469 530 quercetin 3-O-rhamnosyl-(1 → 2)-[rhamnosyl-(1 → 6)]-glucoside SYSTEMATIC 22799569 A 550 559 Flavonoid FAMILY 22799569 T 0 10 Flavonoids FAMILY 22804459 A 410 417 ethanol SYSTEMATIC 22804459 A 431 438 ethanol SYSTEMATIC 22804459 A 443 451 methanol SYSTEMATIC 22804459 A 557 572 rosmarinic acid TRIVIAL 22804459 A 574 586 caffeic acid TRIVIAL 22804459 A 588 605 lithospermic acid TRIVIAL 22804459 A 610 628 salvianolic acid C TRIVIAL 22804459 A 728 734 Trolox TRIVIAL 22804459 A 751 758 ethanol SYSTEMATIC 22804459 A 824 828 DPPH ABBREVIATION 22804459 A 833 839 ferric SYSTEMATIC 22809021 A 1209 1221 progesterone TRIVIAL 22809021 A 1324 1336 progesterone TRIVIAL 22809021 A 678 690 progesterone TRIVIAL 22809021 A 722 731 estradiol TRIVIAL 22809021 T 117 129 progesterone TRIVIAL 22809387 A 228 245 polyethyleneimine SYSTEMATIC 22809387 A 413 422 LiFePO(4) FORMULA 22809387 A 423 425 Li FORMULA 22809387 A 496 503 LiPF(6) FORMULA 22809387 T 50 53 PEI ABBREVIATION 22809387 T 97 99 Li FORMULA 22813628 A 292 312 phthalate monoesters FAMILY 22813628 A 314 333 monobutyl phthalate SYSTEMATIC 22813628 A 335 339 MBuP FORMULA 22813628 A 342 362 monobenzyl phthalate SYSTEMATIC 22813628 A 364 368 MBzP FORMULA 22813628 A 374 403 mono-(2-ethylhexyl) phthalate SYSTEMATIC 22813628 A 405 409 MEHP ABBREVIATION 22813628 A 435 455 monomethyl phthalate SYSTEMATIC 22813628 A 457 460 MMP ABBREVIATION 22813628 A 663 683 phthalate monoesters FAMILY 22813628 A 851 855 MEHP ABBREVIATION 22813628 A 856 860 MBzP FORMULA 22813628 A 861 865 MBuP FORMULA 22813628 A 866 869 MMP ABBREVIATION 22813628 A 997 1016 phthalate monoester SYSTEMATIC 22813628 T 26 40 monophthalates FAMILY 22815230 A 1011 1015 DPPH ABBREVIATION 22815230 A 361 368 acetone SYSTEMATIC 22815230 A 369 377 methanol SYSTEMATIC 22815230 A 507 537 1,1-diphenyl-2-picryl hydrazyl SYSTEMATIC 22815230 A 569 573 DPPH ABBREVIATION 22815230 A 576 583 ferrous SYSTEMATIC 22815230 A 618 624 ferric SYSTEMATIC 22815230 A 818 829 trypan blue TRIVIAL 22815230 A 977 982 FeSO4 FORMULA 22815248 A 1027 1040 ethylmorphine SYSTEMATIC 22815248 A 1041 1042 N FORMULA 22815248 A 1059 1066 aniline SYSTEMATIC 22815248 A 1127 1131 CCl4 FORMULA 22815248 A 1152 1161 silymarin FAMILY 22815248 A 1337 1341 CCl4 FORMULA 22815248 A 1392 1401 silymarin FAMILY 22815248 A 207 218 paracetamol TRIVIAL 22815248 A 228 248 carbon tetrachloride SYSTEMATIC 22815248 A 250 254 CCl4 FORMULA 22815248 A 296 305 silymarin FAMILY 22815248 A 356 360 CCl4 FORMULA 22815248 A 434 443 silymarin FAMILY 22815248 A 483 492 aspartate TRIVIAL 22815248 A 49 56 saponin FAMILY 22815248 A 511 518 alanine TRIVIAL 22815248 A 537 544 lactate FAMILY 22815248 A 580 591 glutathione TRIVIAL 22815248 A 593 596 GSH ABBREVIATION 22815248 A 624 639 malondialdehyde TRIVIAL 22815248 A 641 644 MDA ABBREVIATION 22815248 A 674 678 CCl4 FORMULA 22815248 A 779 782 MDA ABBREVIATION 22815248 A 833 836 GSH ABBREVIATION 22815248 A 914 918 CCl4 FORMULA 22815248 A 967 976 silymarin FAMILY 22815248 T 33 40 Saponin FAMILY 22818587 A 1118 1128 tryptophan TRIVIAL 22820275 A 0 11 Atomoxetine TRIVIAL 22820275 A 1014 1024 isoflurane TRIVIAL 22820275 A 1044 1047 ATM ABBREVIATION 22820275 A 13 16 ATM ABBREVIATION 22820275 A 1324 1327 ATM ABBREVIATION 22820275 A 1400 1403 ATM ABBREVIATION 22820275 A 1500 1503 ATM ABBREVIATION 22820275 A 1936 1939 ATM ABBREVIATION 22820275 A 2052 2055 ATM ABBREVIATION 22820275 A 2208 2211 ATM ABBREVIATION 22820275 A 2416 2419 ATM ABBREVIATION 22820275 A 247 250 ATM ABBREVIATION 22820275 A 30 44 norepinephrine TRIVIAL 22820275 A 470 473 ATM ABBREVIATION 22820275 A 576 579 ATM ABBREVIATION 22820275 A 735 738 ATM ABBREVIATION 22820275 A 905 908 ATM ABBREVIATION 22820275 T 0 11 Atomoxetine TRIVIAL 22824787 A 244 254 fluoxetine TRIVIAL 22824787 A 256 259 FLX ABBREVIATION 22824787 A 393 396 FLX ABBREVIATION 22824787 A 626 629 FLX ABBREVIATION 22824787 A 780 783 FLX ABBREVIATION 22824787 T 47 57 fluoxetine TRIVIAL 22824788 A 259 266 cadmium SYSTEMATIC 22824788 A 432 439 cadmium SYSTEMATIC 22824788 A 607 614 cadmium SYSTEMATIC 22824788 A 704 711 cadmium SYSTEMATIC 22824788 A 807 814 cadmium SYSTEMATIC 22827445 A 1100 1105 C(60) TRIVIAL 22827445 A 1161 1166 C(60) TRIVIAL 22827445 A 1296 1306 POT-co-DOT ABBREVIATION 22827445 A 1307 1312 C(60) TRIVIAL 22827445 A 1454 1464 POT-co-DOT ABBREVIATION 22827445 A 443 452 thiophene SYSTEMATIC 22827445 A 467 530 poly(3-octylthiophene-2,5-diyl-co-3-decyloxythiophene-2,5-diyl) SYSTEMATIC 22827445 A 532 542 POT-co-DOT ABBREVIATION 22827445 A 639 649 POT-co-DOT ABBREVIATION 22827445 A 722 729 toluene TRIVIAL 22827445 A 758 770 acetonitrile SYSTEMATIC 22827445 A 962 972 POT-co-DOT ABBREVIATION 22827445 A 977 982 C(60) TRIVIAL 22827445 T 34 43 thiophene SYSTEMATIC 22827445 T 84 87 C60 TRIVIAL 22827894 A 1028 1033 oxime SYSTEMATIC 22827894 A 1189 1194 oxime SYSTEMATIC 22827894 A 1265 1270 oxime SYSTEMATIC 22827894 A 128 134 oximes FAMILY 22827894 A 1354 1359 oxime SYSTEMATIC 22827894 A 1555 1561 oximes FAMILY 22827894 A 1602 1607 oxime SYSTEMATIC 22827894 A 286 292 oximes FAMILY 22827894 A 34 50 organophosphorus FAMILY 22827894 A 492 498 oximes FAMILY 22827894 A 721 727 oximes FAMILY 22827894 A 973 993 bispyridinium oximes FAMILY 22827894 T 139 145 oximes FAMILY 22827894 T 38 44 oximes FAMILY 22830982 A 1010 1028 hydroxy-omeprazole SYSTEMATIC 22830982 A 1056 1067 dextrorphan TRIVIAL 22830982 A 1321 1337 dextromethorpahn TRIVIAL 22830982 A 1342 1352 omeprazole TRIVIAL 22830982 A 545 566 Fluorescein diacetate SYSTEMATIC 22830982 A 686 695 midazolam TRIVIAL 22830982 A 697 708 tolbutamide TRIVIAL 22830982 A 710 718 caffeine TRIVIAL 22830982 A 720 730 omeprazole TRIVIAL 22830982 A 732 748 dextromethorphan TRIVIAL 22830982 A 750 763 acetaminophen TRIVIAL 22830982 A 768 779 repaglinide TRIVIAL 22830982 A 874 886 paraxanthine TRIVIAL 22830982 A 901 915 1-OH-midazolam TRIVIAL 22830982 A 921 939 omeprazole sulfone TRIVIAL 22830982 A 964 984 hydroxyl-repaglinide SYSTEMATIC 22832075 A 0 9 Vitamin A FAMILY 22832075 A 1308 1317 vitamin-A FAMILY 22832075 A 1338 1351 retinoic acid TRIVIAL 22832075 A 1471 1480 vitamin A FAMILY 22832075 A 1617 1630 retinoic acid TRIVIAL 22832075 A 243 252 retinoids FAMILY 22832075 A 342 355 retinoic acid TRIVIAL 22832075 A 386 395 vitamin A FAMILY 22832075 A 426 435 vitamin A FAMILY 22832075 A 611 634 all-trans-retinoic acid TRIVIAL 22832075 A 666 673 retinol TRIVIAL 22832075 A 732 741 vitamin-A FAMILY 22832075 A 788 811 all-trans-retinoic acid TRIVIAL 22832075 A 895 904 vitamin-A FAMILY 22832075 T 0 9 Vitamin A FAMILY 22832075 T 158 171 retinoic acid TRIVIAL 22834411 A 198 207 1-butanol SYSTEMATIC 22834411 A 213 241 dodecylbenzenesulphonic acid SYSTEMATIC 22834411 A 28 42 barium ferrite SYSTEMATIC 22834411 T 17 31 barium ferrite SYSTEMATIC 22836659 A 711 714 Gly FORMULA 22836659 A 715 718 Cys FORMULA 22836881 A 889 896 aspirin TRIVIAL 22836881 A 922 930 nitrates FAMILY 22838394 A 10 30 diarylbutane lignans FAMILY 22838394 A 136 161 dihydroclusin monoacetate SYSTEMATIC 22838394 A 254 296 2,3-demethoxy-secoisolintetralin diacetate SYSTEMATIC 22838394 A 305 328 dihydroclusin diacetate SYSTEMATIC 22838394 A 38 77 9-acetyl-9'-pentadecanoil-dihydroclusin SYSTEMATIC 22838394 A 395 399 (1)H FORMULA 22838394 A 404 409 (13)C FORMULA 22838394 A 83 127 2,3-demethoxy-secoisolintetralin monoacetate SYSTEMATIC 22838394 T 10 30 diarylbutane lignans FAMILY 22840199 A 174 185 citronellol TRIVIAL 22840199 A 196 204 geraniol TRIVIAL 22840199 A 384 395 chamazulene TRIVIAL 22840199 A 408 415 camphor TRIVIAL 22840229 A 146 159 cyclonerodiol TRIVIAL 22840229 A 168 188 10(Z)-cyclonerotriol TRIVIAL 22840229 A 6 19 sesquiterpene FAMILY 22840229 T 6 16 cyclonerol TRIVIAL 22841391 A 1147 1160 methylselenol SYSTEMATIC 22841391 A 274 287 methylselenol SYSTEMATIC 22841391 A 33 46 methylselenol SYSTEMATIC 22841391 A 358 371 methylselenol SYSTEMATIC 22841391 A 574 587 methylselenol SYSTEMATIC 22841391 A 61 69 selenium SYSTEMATIC 22841391 A 762 775 methylselenol SYSTEMATIC 22841391 A 995 1008 methylselenol SYSTEMATIC 22841391 T 0 13 Methylselenol SYSTEMATIC 22841391 T 17 25 selenium SYSTEMATIC 22841397 A 1074 1084 acetyl-CoA SYSTEMATIC 22841397 A 1157 1164 glucose TRIVIAL 22841397 A 1189 1196 glucose TRIVIAL 22841397 A 1242 1248 biotin TRIVIAL 22841397 A 1295 1302 glucose TRIVIAL 22841397 A 1332 1338 Biotin TRIVIAL 22841397 A 1654 1660 biotin TRIVIAL 22841397 A 166 172 biotin TRIVIAL 22841397 A 1743 1749 biotin TRIVIAL 22841397 A 1849 1855 biotin TRIVIAL 22841397 A 318 324 biotin TRIVIAL 22841397 A 44 50 biotin TRIVIAL 22841397 A 445 451 biotin TRIVIAL 22841397 A 578 584 biotin TRIVIAL 22841397 A 643 650 glucose TRIVIAL 22841397 A 780 786 biotin TRIVIAL 22841397 T 11 17 biotin TRIVIAL 22841397 T 91 98 glucose TRIVIAL 22841916 A 1131 1139 caffeine TRIVIAL 22841916 A 22 30 caffeine TRIVIAL 22841916 A 309 318 adenosine TRIVIAL 22841916 A 387 395 caffeine TRIVIAL 22841916 A 436 444 caffeine TRIVIAL 22841916 A 641 649 Caffeine TRIVIAL 22841916 A 849 857 caffeine TRIVIAL 22841916 T 8 16 caffeine TRIVIAL 22841917 A 0 39 Omega-(n)-3 polyunsaturated fatty acids FAMILY 22841917 A 113 116 EPA ABBREVIATION 22841917 A 1150 1154 PUFA ABBREVIATION 22841917 A 336 340 PUFA ABBREVIATION 22841917 A 41 46 PUFAs ABBREVIATION 22841917 A 562 566 PUFA ABBREVIATION 22841917 A 59 79 docosahexaenoic acid SYSTEMATIC 22841917 A 81 84 DHA ABBREVIATION 22841917 A 90 111 eicosapentaenoic acid SYSTEMATIC 22841917 A 908 912 PUFA ABBREVIATION 22841917 T 25 44 omega-3 fatty acids FAMILY 22846225 A 1140 1143 ZIP ABBREVIATION 22846225 A 1148 1161 chelerythrine TRIVIAL 22846225 A 1582 1585 ZIP ABBREVIATION 22846225 A 1605 1608 ZIP ABBREVIATION 22846225 A 1778 1791 staurosporine TRIVIAL 22846225 A 182 221 myristoylated ζ-pseudosubstrate peptide TRIVIAL 22846225 A 2063 2076 staurosporine TRIVIAL 22846225 A 223 226 ZIP ABBREVIATION 22846225 A 2267 2270 ZIP ABBREVIATION 22846225 A 2275 2288 chelerythrine TRIVIAL 22846225 A 2314 2317 ZIP ABBREVIATION 22846225 A 2322 2335 staurosporine TRIVIAL 22846225 A 465 468 ZIP ABBREVIATION 22846225 A 545 558 Chelerythrine TRIVIAL 22846225 T 55 58 ZIP ABBREVIATION 22849656 A 159 170 neurotensin TRIVIAL 22849656 A 190 198 tyrosine TRIVIAL 22849972 A 863 870 glucose TRIVIAL 22849972 A 884 895 cholesterol TRIVIAL 22859660 A 1014 1017 ISO ABBREVIATION 22859660 A 104 118 phenylepherine TRIVIAL 22859660 A 1059 1070 fenofibrate TRIVIAL 22859660 A 1100 1103 Ach ABBREVIATION 22859660 A 1105 1108 SNP ABBREVIATION 22859660 A 1113 1116 ISO ABBREVIATION 22859660 A 1176 1187 fenofibrate TRIVIAL 22859660 A 1225 1236 fenofibrate TRIVIAL 22859660 A 1343 1346 Ach ABBREVIATION 22859660 A 1348 1351 SNP ABBREVIATION 22859660 A 1356 1359 ISO ABBREVIATION 22859660 A 167 180 acetylcholine SYSTEMATIC 22859660 A 182 185 Ach ABBREVIATION 22859660 A 188 208 sodium nitroprusside SYSTEMATIC 22859660 A 210 213 SNP ABBREVIATION 22859660 A 219 232 isoproterenol TRIVIAL 22859660 A 234 237 ISO ABBREVIATION 22859660 A 257 265 glycerol TRIVIAL 22859660 A 323 334 fenofibrate TRIVIAL 22859660 A 468 479 fenofibrate TRIVIAL 22859660 A 630 641 fenofibrate TRIVIAL 22859660 A 852 863 fenofibrate TRIVIAL 22859660 A 954 957 Ach ABBREVIATION 22859660 A 959 962 SNP ABBREVIATION 22859660 A 967 970 ISO ABBREVIATION 22859660 T 11 22 fenofibrate TRIVIAL 22859660 T 65 73 glycerol TRIVIAL 22862926 A 195 202 glucose TRIVIAL 22862926 A 325 332 glucose TRIVIAL 22862926 A 377 384 glucose TRIVIAL 22862926 A 423 430 glucose TRIVIAL 22862926 A 906 913 glucose TRIVIAL 22862926 A 983 990 glucose TRIVIAL 22865292 A 1416 1427 chloroquine TRIVIAL 22865292 A 9 13 H(+) FORMULA 22867274 A 436 455 benzothiazole amide SYSTEMATIC 22867274 A 565 575 aryl amine FAMILY 22867274 A 609 610 N FORMULA 22867274 A 708 719 glutathione TRIVIAL 22867274 A 721 724 GSH ABBREVIATION 22867274 A 772 777 amide FAMILY 22867274 A 818 821 GSH ABBREVIATION 22867274 A 856 861 NADPH ABBREVIATION 22867274 A 866 869 GSH ABBREVIATION 22867274 T 48 67 benzothiazole amide SYSTEMATIC 22872141 A 0 12 Formaldehyde SYSTEMATIC 22872141 T 35 47 formaldehyde SYSTEMATIC 22872607 A 0 9 Aldo-keto SYSTEMATIC 22872607 A 1025 1033 cotinine TRIVIAL 22872607 A 111 115 PAHs ABBREVIATION 22872607 A 1239 1243 PAHs ABBREVIATION 22872607 A 1339 1343 PAHs ABBREVIATION 22872607 A 142 152 o-quinones FAMILY 22872607 A 167 173 oxygen SYSTEMATIC 22872607 A 263 267 PAHs ABBREVIATION 22872607 A 529 533 PAHs ABBREVIATION 22872607 A 626 630 PAHs ABBREVIATION 22872607 A 77 109 polycyclic aromatic hydrocarbons FAMILY 22874922 A 752 758 Ca(2+) FORMULA 22876956 A 1146 1159 peroxynitrite SYSTEMATIC 22876956 A 1167 1172 ONOO- FORMULA 22876956 A 1186 1199 peroxynitrite SYSTEMATIC 22876956 A 1230 1240 superoxide TRIVIAL 22876956 A 1242 1247 O2 •- FORMULA 22876956 A 1297 1307 superoxide TRIVIAL 22876956 A 1370 1417 6-nitro-3,4-methylenedioxyphenyl-Nacylhydrazone SYSTEMATIC 22876956 A 1419 1430 LASSBio-881 IDENTIFIER 22876956 A 1435 1450 γ-butyrolactone SYSTEMATIC 22876956 A 197 205 nitrogen SYSTEMATIC 22876956 A 210 216 oxygen SYSTEMATIC 22876956 A 402 413 desipramine TRIVIAL 22876956 A 415 425 duloxetine TRIVIAL 22876956 A 427 437 fluoxetine TRIVIAL 22876956 A 439 449 paroxetine TRIVIAL 22876956 A 451 463 escitalopram TRIVIAL 22876956 A 465 474 phenytoin TRIVIAL 22876956 A 478 491 carbamazepine TRIVIAL 22876956 A 496 509 α-lipoic acid TRIVIAL 22876956 A 644 656 indomethacin TRIVIAL 22876956 A 658 667 meloxicam TRIVIAL 22876956 A 669 678 tenoxicam TRIVIAL 22876956 A 680 690 valdecoxib TRIVIAL 22876956 T 0 8 Nitrogen SYSTEMATIC 22876956 T 10 16 oxygen SYSTEMATIC 22876956 T 20 26 sulfur SYSTEMATIC 22889561 A 557 567 danusertib TRIVIAL 22889561 T 34 44 danusertib TRIVIAL 22889612 A 1017 1020 BaP ABBREVIATION 22889612 A 104 107 BaP ABBREVIATION 22889612 A 1085 1088 BaP ABBREVIATION 22889612 A 1148 1151 RVT ABBREVIATION 22889612 A 1231 1234 BaP ABBREVIATION 22889612 A 1361 1364 RVT ABBREVIATION 22889612 A 1369 1372 BaP ABBREVIATION 22889612 A 1391 1394 RVT ABBREVIATION 22889612 A 1478 1481 BaP ABBREVIATION 22889612 A 1527 1530 RVT ABBREVIATION 22889612 A 1585 1588 BaP ABBREVIATION 22889612 A 26 40 benzo(a)pyrene SYSTEMATIC 22889612 A 369 380 resveratrol TRIVIAL 22889612 A 382 385 RVT ABBREVIATION 22889612 A 390 393 BaP ABBREVIATION 22889612 A 42 45 BaP ABBREVIATION 22889612 A 484 487 BaP ABBREVIATION 22889612 A 602 605 RVT ABBREVIATION 22889612 A 630 633 BaP ABBREVIATION 22889612 A 678 681 RVT ABBREVIATION 22889612 A 719 722 BaP ABBREVIATION 22889612 A 801 804 BaP ABBREVIATION 22889612 A 809 812 RVT ABBREVIATION 22889612 A 899 902 RVT ABBREVIATION 22889612 A 943 946 BaP ABBREVIATION 22889612 A 947 950 RVT ABBREVIATION 22889612 T 19 33 benzo(a)pyrene SYSTEMATIC 22889612 T 73 84 resveratrol TRIVIAL 22889721 A 1078 1089 Hematoxylin TRIVIAL 22889721 A 1094 1099 eosin FAMILY 22889721 A 1742 1749 calcium SYSTEMATIC 22891663 A 0 32 N,β-D-glucopyranosyl vincosamide TRIVIAL 22891663 A 271 274 GPV ABBREVIATION 22891663 A 34 37 GPV ABBREVIATION 22891663 A 514 531 hydrogen peroxide SYSTEMATIC 22891663 A 535 538 GPV ABBREVIATION 22891663 A 601 604 GPV ABBREVIATION 22891663 A 608 619 chlorophyll FAMILY 22891663 A 729 735 oxygen SYSTEMATIC 22891663 A 737 747 superoxide TRIVIAL 22891663 A 759 767 hydroxyl SYSTEMATIC 22891663 A 830 833 GPV ABBREVIATION 22891663 T 10 25 indole alkaloid FAMILY 22891663 T 26 58 N,β-D-glucopyranosyl vincosamide TRIVIAL 22898132 A 472 485 valproic acid TRIVIAL 22898132 A 487 500 retinoic acid TRIVIAL 22898132 A 502 510 caffeine TRIVIAL 22898132 A 512 529 sodium salicylate SYSTEMATIC 22898132 A 531 538 glucose TRIVIAL 22898132 A 540 551 hydroxyurea SYSTEMATIC 22898132 A 553 571 methoxyacetic acid SYSTEMATIC 22898132 A 573 583 boric acid SYSTEMATIC 22898132 A 588 603 paraoxon-methyl SYSTEMATIC 22898132 A 921 952 valproic and methoxyacetic acid MULTIPLE 22903180 T 38 44 silver SYSTEMATIC 22906569 A 1007 1016 bilirubin TRIVIAL 22906569 A 1021 1031 biliverdin TRIVIAL 22906569 A 445 454 bilirubin TRIVIAL 22906569 A 466 476 biliverdin TRIVIAL 22906572 A 1037 1040 ATP ABBREVIATION 22906572 A 1130 1136 Ca(2+) FORMULA 22906572 A 1218 1224 Ca(2+) FORMULA 22906572 A 14 20 Ca(2+) FORMULA 22906572 A 215 221 Ca(2+) FORMULA 22906572 A 589 595 Ca(2+) FORMULA 22906572 A 731 737 Ca(2+) FORMULA 22906572 A 805 810 amine SYSTEMATIC 22906572 A 811 822 heptylamine SYSTEMATIC 22906572 A 888 894 Ca(2+) FORMULA 22906572 A 896 907 Heptylamine SYSTEMATIC 22906572 A 926 929 ATP ABBREVIATION 22906572 A 997 1003 Ca(2+) FORMULA 22906572 T 76 83 calcium SYSTEMATIC 22906573 A 1064 1069 amine SYSTEMATIC 22906573 A 1085 1096 polystyrene SYSTEMATIC 22906573 A 550 561 polystyrene SYSTEMATIC 22906573 A 579 585 carbon SYSTEMATIC 22906573 A 673 684 polystyrene SYSTEMATIC 22906573 A 729 740 polystyrene SYSTEMATIC 22906573 A 897 908 polystyrene SYSTEMATIC 22906573 A 952 958 carbon SYSTEMATIC 22911509 A 267 275 graphene TRIVIAL 22911509 A 304 310 Teflon TRIVIAL 22911509 A 50 58 graphene TRIVIAL 22911509 A 652 660 graphene TRIVIAL 22911509 T 17 25 graphene TRIVIAL 22914985 A 0 17 Mycophenolic acid TRIVIAL 22914985 A 1016 1019 MPA ABBREVIATION 22914985 A 1088 1091 MPA ABBREVIATION 22914985 A 119 143 inosine-5'-monophosphate SYSTEMATIC 22914985 A 1538 1541 MPA ABBREVIATION 22914985 A 1618 1621 MPA ABBREVIATION 22914985 A 19 22 MPA ABBREVIATION 22914985 A 1916 1920 MPAG ABBREVIATION 22914985 A 1997 2000 MPA ABBREVIATION 22914985 A 2156 2160 MPAG ABBREVIATION 22914985 A 2265 2268 MPA ABBREVIATION 22914985 A 240 253 mycophenolate TRIVIAL 22914985 A 2407 2410 MPA ABBREVIATION 22914985 A 2557 2560 MPA ABBREVIATION 22914985 A 2580 2584 MPAG ABBREVIATION 22914985 A 550 553 MPA ABBREVIATION 22914985 A 584 613 mycophenolic acid glucuronide TRIVIAL 22914985 A 615 619 MPAG ABBREVIATION 22914985 A 766 769 MPA ABBREVIATION 22914985 A 849 864 MPA glucuronide TRIVIAL 22914985 A 985 1000 MPA glucuronide TRIVIAL 22914985 T 11 28 mycophenolic acid TRIVIAL 22914985 T 74 103 mycophenolic acid glucuronide TRIVIAL 22917637 A 1136 1147 (-)-cocaine TRIVIAL 22917637 A 1330 1350 (+)- and (-)-cocaine MULTIPLE 22917637 A 1546 1566 (+)- and (-)-cocaine MULTIPLE 22917637 A 1647 1658 (-)-cocaine TRIVIAL 22917637 A 1737 1748 (+)-cocaine TRIVIAL 22917637 A 1802 1813 (-)-cocaine TRIVIAL 22917637 A 183 190 cocaine TRIVIAL 22917637 A 36 43 cocaine TRIVIAL 22917637 A 366 377 (-)-cocaine TRIVIAL 22917637 A 464 475 (+)-cocaine TRIVIAL 22917637 A 558 576 [(11)C](-)-cocaine SYSTEMATIC 22917637 A 581 599 [(11)C](+)-cocaine SYSTEMATIC 22917637 A 632 650 [(11)C](-)-cocaine SYSTEMATIC 22917637 A 701 719 [(11)C](+)-cocaine SYSTEMATIC 22917637 A 837 844 cocaine TRIVIAL 22917637 A 85 92 cocaine TRIVIAL 22917637 A 873 880 cocaine TRIVIAL 22917637 A 935 946 (-)-cocaine TRIVIAL 22917637 A 992 1003 (+)-cocaine TRIVIAL 22917637 T 26 33 cocaine TRIVIAL 22917637 T 96 116 (+)- and (-)-cocaine MULTIPLE 22921987 A 412 425 malonaldehyde TRIVIAL 22921987 A 427 430 MDA ABBREVIATION 22921987 A 739 742 MDA ABBREVIATION 22921987 A 94 102 Psoralen TRIVIAL 22923473 A 161 168 glucose TRIVIAL 22923473 A 272 280 fructose TRIVIAL 22923473 A 402 410 fructose TRIVIAL 22923473 A 558 565 glucose TRIVIAL 22923473 A 645 652 glucose TRIVIAL 22923473 T 109 116 glucose TRIVIAL 22926048 A 1011 1015 HEDS ABBREVIATION 22926048 A 1063 1070 glucose TRIVIAL 22926048 A 1241 1248 glucose TRIVIAL 22926048 A 184 191 glucose TRIVIAL 22926048 A 24 31 glucose TRIVIAL 22926048 A 297 319 hydroxyethyl disulfide SYSTEMATIC 22926048 A 321 325 HEDS ABBREVIATION 22926048 A 330 335 NADPH ABBREVIATION 22926048 A 337 340 GSH ABBREVIATION 22926048 A 342 346 GSSG ABBREVIATION 22926048 A 354 365 glutathione TRIVIAL 22926048 A 525 532 glucose TRIVIAL 22926048 A 536 543 glucose TRIVIAL 22926048 A 565 569 HEDS ABBREVIATION 22926048 A 57 74 pentose phosphate FAMILY 22926048 A 602 609 glucose TRIVIAL 22926048 A 662 669 glucose TRIVIAL 22926048 A 705 710 NADPH ABBREVIATION 22926048 A 736 741 thiol FAMILY 22926048 A 910 914 HEDS ABBREVIATION 22926048 A 98 103 thiol FAMILY 22926048 T 105 112 glucose TRIVIAL 22926048 T 35 52 pentose phosphate FAMILY 22931186 A 1131 1141 creatinine TRIVIAL 22931186 A 1297 1306 etoposide TRIVIAL 22931186 A 182 191 etoposide TRIVIAL 22931186 A 228 237 Etoposide TRIVIAL 22931186 A 332 342 creatinine TRIVIAL 22931186 A 483 492 etoposide TRIVIAL 22931186 T 25 34 etoposide TRIVIAL 22931212 A 1046 1054 thiazole SYSTEMATIC 22931212 A 1076 1082 phenyl SYSTEMATIC 22931212 A 1123 1133 amino acid FAMILY 22931212 A 1195 1201 sulfur SYSTEMATIC 22931212 A 1214 1222 thiazole SYSTEMATIC 22931212 A 1333 1339 ribose TRIVIAL 22931212 A 185 189 NADP ABBREVIATION 22931212 A 191 192 H FORMULA 22931212 A 194 197 NAD ABBREVIATION 22931212 A 199 200 H FORMULA 22931212 A 206 235 β-nicotinamide mononucleotide FAMILY 22931212 A 237 240 NMN ABBREVIATION 22931212 A 282 312 adenine dinucleotide phosphate SYSTEMATIC 22931212 A 324 327 ADP ABBREVIATION 22931212 A 332 339 adenine TRIVIAL 22931212 A 375 390 5-phosphoribose SYSTEMATIC 22931212 A 38 44 ribose TRIVIAL 22931212 A 402 405 Rib ABBREVIATION 22931212 A 471 477 ribose TRIVIAL 22931212 A 490 493 Rib ABBREVIATION 22931212 A 502 508 ribose TRIVIAL 22931212 A 520 523 Rib ABBREVIATION 22931212 A 537 552 carboxylic acid SYSTEMATIC 22931212 A 556 559 Rib ABBREVIATION 22931212 A 564 567 Rib ABBREVIATION 22931212 A 66 70 NADH ABBREVIATION 22931212 A 744 750 ribose TRIVIAL 22931212 A 773 776 NAD ABBREVIATION 22931212 A 778 779 H FORMULA 22931212 A 823 826 Rib ABBREVIATION 22931212 A 834 837 Rib ABBREVIATION 22931212 A 91 99 pyrazole SYSTEMATIC 22931212 A 943 946 Rib ABBREVIATION 22931212 T 32 38 ribose TRIVIAL 22931212 T 56 64 pyrazole SYSTEMATIC 22935104 A 35 45 sildenafil TRIVIAL 22935104 A 50 61 thalidomide TRIVIAL 22940283 A 1122 1140 thiocholine esters FAMILY 22940855 A 1000 1012 thione dimer FAMILY 22940855 A 1016 1027 thiol dimer FAMILY 22940855 A 102 110 hydrogen SYSTEMATIC 22940855 A 1087 1098 thiol dimer FAMILY 22940855 A 1102 1114 thione dimer FAMILY 22940855 A 118 141 thione and thiol dimers MULTIPLE 22940855 A 1276 1284 hydrogen SYSTEMATIC 22940855 A 1470 1471 H FORMULA 22940855 A 1500 1502 S1 FORMULA 22940855 A 1503 1505 H2 FORMULA 22940855 A 1508 1510 N2 FORMULA 22940855 A 1511 1513 N2 FORMULA 22940855 A 1514 1516 H2 FORMULA 22940855 A 1519 1521 S1 FORMULA 22940855 A 1522 1524 N3 FORMULA 22940855 A 1525 1528 H3B FORMULA 22940855 A 1531 1533 O1 FORMULA 22940855 A 155 163 triazole FAMILY 22940855 A 19 31 thione-thiol FAMILY 22940855 A 363 373 chloroform TRIVIAL 22940855 A 375 383 methanol SYSTEMATIC 22940855 A 494 500 thione FAMILY 22940855 A 775 787 thione dimer FAMILY 22940855 A 820 831 thiol dimer FAMILY 22940855 T 127 185 4-amino-5-(2-hydroxyphenyl)-2H-1,2,4-triazole-3(4H)-thione SYSTEMATIC 22940855 T 94 102 hydrogen SYSTEMATIC 22945693 A 1412 1415 CpG ABBREVIATION 22945693 A 837 840 CpG ABBREVIATION 22945693 T 22 35 sodium-iodide SYSTEMATIC 22949511 A 1162 1167 lysyl TRIVIAL 22949511 A 1352 1364 hydroxylates FAMILY 22949511 A 1381 1386 lysyl TRIVIAL 22949511 A 336 342 prolyl TRIVIAL 22949511 T 141 148 lysines FAMILY 22954532 A 1118 1120 WC FORMULA 22954532 A 1248 1254 sodium SYSTEMATIC 22954532 A 141 157 Tungsten carbide SYSTEMATIC 22954532 A 178 180 WC FORMULA 22954532 A 297 299 WC FORMULA 22954532 A 389 391 WC FORMULA 22954532 A 395 407 tetrodotoxin TRIVIAL 22954532 A 409 412 TTX ABBREVIATION 22954532 A 442 448 sodium SYSTEMATIC 22954532 A 460 462 Na FORMULA 22954532 A 546 548 WC FORMULA 22954532 A 585 587 Na FORMULA 22954532 A 699 701 WC FORMULA 22954532 A 780 782 Na FORMULA 22954532 A 868 870 Na FORMULA 22954532 A 913 915 Na FORMULA 22954532 A 965 967 WC FORMULA 22954532 T 21 37 tungsten carbide SYSTEMATIC 22954532 T 69 75 sodium SYSTEMATIC 22955948 A 220 237 hydrogen peroxide SYSTEMATIC 22955948 A 239 247 H(2)O(2) FORMULA 22955948 A 454 463 rapamycin TRIVIAL 22955948 A 500 509 rapamycin TRIVIAL 22955948 A 632 640 H(2)O(2) FORMULA 22955948 A 707 715 H(2)O(2) FORMULA 22955948 A 968 976 H(2)O(2) FORMULA 22955948 T 15 32 hydrogen peroxide SYSTEMATIC 22956629 A 14 30 titanium dioxide SYSTEMATIC 22956629 A 1605 1611 TiO(2) FORMULA 22956629 A 32 38 TiO(2) FORMULA 22956629 T 63 79 titanium dioxide SYSTEMATIC 22956630 A 0 8 Parabens FAMILY 22956630 A 104 117 propylparaben SYSTEMATIC 22956630 A 1060 1081 4-hydroxybenzoic acid SYSTEMATIC 22956630 A 1112 1120 parabens FAMILY 22956630 A 1151 1163 benzoic acid SYSTEMATIC 22956630 A 1177 1179 OH FORMULA 22956630 A 119 131 butylparaben SYSTEMATIC 22956630 A 1251 1259 parabens FAMILY 22956630 A 137 150 benzylparaben SYSTEMATIC 22956630 A 1479 1487 parabens FAMILY 22956630 A 152 182 Paraben esters and their salts MULTIPLE 22956630 A 1563 1571 parabens FAMILY 22956630 A 1573 1597 butyl- and benzylparaben MULTIPLE 22956630 A 1722 1730 parabens FAMILY 22956630 A 1783 1791 parabens FAMILY 22956630 A 24 36 alkyl esters FAMILY 22956630 A 291 299 parabens FAMILY 22956630 A 40 61 p-hydroxybenzoic acid SYSTEMATIC 22956630 A 417 425 parabens FAMILY 22956630 A 467 475 parabens FAMILY 22956630 A 555 563 parabens FAMILY 22956630 A 75 88 methylparaben SYSTEMATIC 22956630 A 778 786 parabens FAMILY 22956630 A 889 895 methyl SYSTEMATIC 22956630 A 899 904 ethyl SYSTEMATIC 22956630 A 90 102 ethylparaben SYSTEMATIC 22956630 A 908 914 propyl SYSTEMATIC 22956630 A 918 930 butylparaben SYSTEMATIC 22956630 A 997 1010 benzylparaben SYSTEMATIC 22956630 T 11 19 parabens FAMILY 22958332 A 1130 1136 oxygen SYSTEMATIC 22958332 A 1153 1167 carbon dioxide SYSTEMATIC 22960471 A 1028 1046 7-aminoactinomycin SYSTEMATIC 22960471 A 1048 1053 7-AAD SYSTEMATIC 22960471 A 416 432 sulforhodamine B TRIVIAL 22960471 A 500 508 nicotine TRIVIAL 22960471 A 599 607 Nicotine TRIVIAL 22961087 A 1045 1058 triglycerides FAMILY 22961200 A 789 806 alanine dipeptide FAMILY 22963367 A 1393 1398 GdOCl FORMULA 22963367 A 1524 1538 Tb-doped GdOCl FORMULA 22963367 A 1552 1568 indium tin oxide SYSTEMATIC 22963367 A 1570 1573 ITO ABBREVIATION 22963367 A 463 468 GdOCl FORMULA 22963367 A 602 607 GdOCl FORMULA 22963367 A 884 889 GdOCl FORMULA 22963367 A 909 920 cyclohexane SYSTEMATIC 22963367 T 39 44 GdOCl FORMULA 22963553 A 1009 1028 Ipratropium bromide TRIVIAL 22963553 A 1105 1123 Oxitropium bromide TRIVIAL 22963553 A 1153 1171 Tiotropium bromide TRIVIAL 22963553 A 1292 1310 aclidinium bromide TRIVIAL 22963553 A 1315 1337 glycopyrrolate bromide TRIVIAL 22963553 A 1498 1508 tiotropium TRIVIAL 22963553 A 945 964 ipratropium bromide TRIVIAL 22963553 A 966 984 oxitropium bromide TRIVIAL 22963553 A 989 1007 tiotropium bromide TRIVIAL 22963554 A 1312 1326 corticosteroid TRIVIAL 22963554 A 1451 1463 theophylline TRIVIAL 22963554 A 1465 1478 nortriptyline TRIVIAL 22963554 A 1483 1493 macrolides FAMILY 22963619 A 104 114 methionine TRIVIAL 22963619 A 151 161 amino acid FAMILY 22963619 A 281 291 methionine TRIVIAL 22963619 A 374 383 Methionin TRIVIAL 22963619 A 389 393 DTPA ABBREVIATION 22963619 A 394 404 Methionine TRIVIAL 22963619 A 454 461 (99m)Tc FORMULA 22963619 A 657 664 (99m)Tc FORMULA 22963619 A 680 689 Methionin TRIVIAL 22963619 A 746 751 99mTc FORMULA 22963619 A 752 756 DTPA ABBREVIATION 22963619 A 757 767 Methionine TRIVIAL 22963619 A 796 803 (99m)Tc FORMULA 22963619 A 819 828 Methionin TRIVIAL 22963619 A 82 93 amino acids FAMILY 22963619 A 832 837 99mTc FORMULA 22963619 A 838 842 DTPA ABBREVIATION 22963619 A 844 854 Methionine TRIVIAL 22963619 T 69 79 methionine TRIVIAL 22966070 A 1002 1006 O(2) FORMULA 22966070 A 1280 1283 tyr FORMULA 22966070 A 1349 1357 tyrosine TRIVIAL 22966070 A 339 346 glucose TRIVIAL 22966070 A 588 596 tyrosine TRIVIAL 22966070 A 620 623 tyr FORMULA 22966070 A 700 708 tyrosine TRIVIAL 22966070 A 955 962 glucose TRIVIAL 22966070 A 976 983 glucose TRIVIAL 22967722 A 1053 1072 phosphoenolpyruvate SYSTEMATIC 22967722 A 1091 1098 glucose TRIVIAL 22967722 A 1157 1166 carnitine TRIVIAL 22967722 A 1232 1241 glabridin TRIVIAL 22967722 A 1246 1255 glabridin TRIVIAL 22967722 A 180 189 glabridin TRIVIAL 22967722 A 194 203 glabridin TRIVIAL 22967722 A 256 265 Glabridin TRIVIAL 22967722 A 72 81 glabridin TRIVIAL 22967722 A 88 97 isoflavan FAMILY 22967722 T 24 33 glabridin TRIVIAL 22967722 T 53 67 carbon dioxide SYSTEMATIC 22968089 A 13 22 glutamate TRIVIAL 22968089 A 438 446 LY379268 IDENTIFIER 22968089 A 479 483 MPEP ABBREVIATION 22968089 A 520 526 AMN082 IDENTIFIER 22968089 A 634 642 LY379268 IDENTIFIER 22968089 A 683 687 MPEP ABBREVIATION 22968089 A 727 733 AMN082 IDENTIFIER 22968089 T 24 33 glutamate TRIVIAL 22972178 A 1099 1107 cortisol TRIVIAL 22972178 A 1113 1120 lactate FAMILY 22972178 A 1641 1649 cortisol TRIVIAL 22972178 A 1722 1730 cortisol TRIVIAL 22972178 A 2056 2064 cortisol TRIVIAL 22972178 A 2159 2167 cortisol TRIVIAL 22972178 A 456 464 cortisol TRIVIAL 22972178 A 570 578 cortisol TRIVIAL 22972178 T 7 15 cortisol TRIVIAL 22972179 A 1277 1280 Ser FORMULA 22972179 A 256 270 2-deoxyglucose SYSTEMATIC 22972179 A 320 329 rapamycin TRIVIAL 22972179 A 430 433 Thr FORMULA 22972179 A 543 557 2-deoxyglucose SYSTEMATIC 22972179 A 907 921 2-deoxyglucose SYSTEMATIC 22972179 A 932 946 2-Deoxyglucose SYSTEMATIC 22972222 A 1125 1132 glucose TRIVIAL 22972222 A 133 140 glucose TRIVIAL 22972222 A 1447 1454 glucose TRIVIAL 22972222 A 1570 1582 vildagliptin TRIVIAL 22972222 A 1590 1597 glucose TRIVIAL 22972222 A 284 296 vildagliptin TRIVIAL 22972222 A 427 439 vildagliptin TRIVIAL 22972222 A 56 63 glucose TRIVIAL 22972222 A 630 642 vildagliptin TRIVIAL 22972222 A 83 95 vildagliptin TRIVIAL 22972222 A 844 856 vildagliptin TRIVIAL 22972222 T 108 115 glucose TRIVIAL 22972222 T 28 35 glucose TRIVIAL 22972222 T 55 67 vildagliptin TRIVIAL 22972396 A 47 55 platinum SYSTEMATIC 22972396 T 20 28 platinum SYSTEMATIC 22975146 A 1019 1028 α-asarone TRIVIAL 22975146 A 1124 1142 pentylenetetrazole SYSTEMATIC 22975146 A 1147 1154 kainate TRIVIAL 22975146 A 1171 1180 α-asarone TRIVIAL 22975146 A 1392 1396 GABA ABBREVIATION 22975146 A 1448 1457 α-asarone TRIVIAL 22975146 A 276 285 α-asarone TRIVIAL 22975146 A 385 403 pentylenetetrazole SYSTEMATIC 22975146 A 407 414 kainate TRIVIAL 22975146 A 540 549 α-asarone TRIVIAL 22975146 A 579 585 Mg(2+) FORMULA 22975146 A 6 17 (α)-asarone TRIVIAL 22975146 A 759 763 GABA ABBREVIATION 22975146 A 784 793 picotoxin TRIVIAL 22975146 A 812 816 GABA ABBREVIATION 22975146 A 840 851 bicuculline TRIVIAL 22975146 A 871 878 glycine TRIVIAL 22975146 A 898 908 strychnine TRIVIAL 22975146 A 931 935 GABA ABBREVIATION 22975146 T 0 13 Alpha-asarone TRIVIAL 22975146 T 77 81 GABA ABBREVIATION 22975155 A 1081 1086 RS41A NO CLASS 22975155 A 1091 1097 RS194B NO CLASS 22975155 A 1316 1322 RS194B NO CLASS 22975155 A 1548 1554 RS194B NO CLASS 22975155 A 1661 1666 oxime SYSTEMATIC 22975155 A 175 180 sarin TRIVIAL 22975155 A 182 192 cyclosarin TRIVIAL 22975155 A 198 206 paraoxon TRIVIAL 22975155 A 211 216 tabun TRIVIAL 22975155 A 218 267 N-substituted 2-hydroxyiminoacetamido alkylamines FAMILY 22975155 A 343 349 oximes FAMILY 22975155 A 351 356 RS41A NO CLASS 22975155 A 361 367 RS194B NO CLASS 22975155 A 416 426 pyridinium SYSTEMATIC 22975155 A 43 48 oxime SYSTEMATIC 22975155 A 441 445 2PAM ABBREVIATION 22975155 A 450 454 MMB4 IDENTIFIER 22975155 A 481 486 RS41A NO CLASS 22975155 A 740 745 RS41A NO CLASS 22975155 A 806 812 RS194B NO CLASS 22975155 A 859 865 RS194B NO CLASS 22975155 A 965 971 RS194B NO CLASS 22977168 A 224 236 diisocyanate SYSTEMATIC 22977168 A 551 563 diisocyanate SYSTEMATIC 22977168 A 776 802 hexamethylene diisocyanate SYSTEMATIC 22977168 T 53 65 diisocyanate SYSTEMATIC 22981737 A 192 193 C FORMULA 22981737 A 262 270 tyrosine TRIVIAL 22981737 A 306 319 acetylcholine SYSTEMATIC 22982206 A 1053 1063 salubrinal TRIVIAL 22982206 A 1473 1479 oxygen SYSTEMATIC 22982206 A 396 408 verrucarin A TRIVIAL 22982206 T 0 12 Verrucarin A TRIVIAL 22982773 A 105 121 organophosphorus FAMILY 22982773 A 1128 1133 sarin TRIVIAL 22982773 A 1137 1147 cyclosarin TRIVIAL 22982773 A 1195 1200 tabun TRIVIAL 22982773 A 1208 1244 O-ethyl isopropylphosphonofluoridate SYSTEMATIC 22982773 A 1289 1294 tabun TRIVIAL 22982773 A 1474 1487 dimethylamine SYSTEMATIC 22982773 A 1496 1502 alkoxy FAMILY 22982773 A 1600 1605 oxime SYSTEMATIC 22982773 A 1661 1670 phosphate SYSTEMATIC 22982773 A 1672 1683 phosphonate SYSTEMATIC 22982773 A 1687 1702 phosphoramidate SYSTEMATIC 22982773 A 18 23 oxime SYSTEMATIC 22982773 A 301 305 HI-6 IDENTIFIER 22982773 A 310 319 obidoxime TRIVIAL 22982773 A 478 483 oxime SYSTEMATIC 22982773 A 581 586 oxime SYSTEMATIC 22982773 A 730 740 phosphates FAMILY 22982773 A 742 754 phosphonates FAMILY 22982773 A 759 775 phosphoramidates FAMILY 22982773 A 805 810 oxime SYSTEMATIC 22982773 A 843 848 oxime SYSTEMATIC 22982773 A 901 938 O-methyl isopropylphosphonofluoridate SYSTEMATIC 22982773 A 945 955 cyclosarin TRIVIAL 22982773 A 966 1004 O-methyl cyclohexylphosphonofluoridate SYSTEMATIC 22982773 T 37 42 oxime SYSTEMATIC 22982773 T 93 109 organophosphorus FAMILY 22983118 A 0 33 3,4-Methylenedioxymethamphetamine SYSTEMATIC 22983118 A 1025 1028 DOI ABBREVIATION 22983118 A 1032 1036 MDMA ABBREVIATION 22983118 A 105 108 DOI ABBREVIATION 22983118 A 1167 1170 DOI ABBREVIATION 22983118 A 129 141 amphetamines FAMILY 22983118 A 1300 1304 5-HT SYSTEMATIC 22983118 A 1410 1413 DOI ABBREVIATION 22983118 A 1417 1421 MDMA ABBREVIATION 22983118 A 1453 1465 amphetamines FAMILY 22983118 A 1653 1657 5-HT SYSTEMATIC 22983118 A 257 268 amphetamine TRIVIAL 22983118 A 320 323 DOI ABBREVIATION 22983118 A 328 332 MDMA ABBREVIATION 22983118 A 35 39 MDMA ABBREVIATION 22983118 A 44 51 Ecstasy TRIVIAL 22983118 A 504 508 MDMA ABBREVIATION 22983118 A 525 528 DOI ABBREVIATION 22983118 A 551 558 lactate FAMILY 22983118 A 58 103 2,5-dimethoxy-4-iodoamphetamine hydrochloride SYSTEMATIC 22983118 A 595 606 tetrazolium SYSTEMATIC 22983118 A 614 617 MTT ABBREVIATION 22983118 A 894 897 DOI ABBREVIATION 22983118 A 963 967 MDMA ABBREVIATION 22983118 T 36 48 amphetamines FAMILY 22983652 A 224 249 Poly(methyl methacrylate) SYSTEMATIC 22983652 A 251 255 PMMA ABBREVIATION 22983652 A 278 284 carbon SYSTEMATIC 22983652 A 410 414 PMMA ABBREVIATION 22983652 A 519 523 PMMA ABBREVIATION 22983652 A 541 547 carbon SYSTEMATIC 22983652 A 671 675 PMMA ABBREVIATION 22983652 A 715 719 PMMA ABBREVIATION 22983652 A 813 819 carbon SYSTEMATIC 22983652 T 59 84 Poly(methyl methacrylate) SYSTEMATIC 22983652 T 85 91 carbon SYSTEMATIC 22985735 A 1096 1104 H(2)O(2) FORMULA 22985735 A 1109 1115 SiO(2) FORMULA 22985735 A 804 807 GSH ABBREVIATION 22985735 A 832 840 H(2)O(2) FORMULA 22985735 A 852 858 SiO(2) FORMULA 22985735 A 966 969 GSH ABBREVIATION 22985735 A 99 105 silica TRIVIAL 22985735 T 124 128 SiO2 FORMULA 22985953 A 0 5 Na(+) FORMULA 22985953 A 1222 1225 MMT ABBREVIATION 22985953 A 1282 1290 glycerol TRIVIAL 22985953 A 1295 1302 xylitol TRIVIAL 22985953 A 1342 1345 MMT ABBREVIATION 22985953 A 381 394 carbohydrates FAMILY 22985953 A 53 56 MMT ABBREVIATION 22985953 A 6 21 montmorillonite TRIVIAL 22985953 A 640 643 MMT ABBREVIATION 22985953 A 712 726 sugar alcohols FAMILY 22985953 A 728 736 glycerol TRIVIAL 22985953 A 738 745 xylitol TRIVIAL 22985953 A 759 767 hydroxyl SYSTEMATIC 22985953 A 825 828 MMT ABBREVIATION 22985953 A 859 862 MMT ABBREVIATION 22985953 A 984 987 MMT ABBREVIATION 22985953 T 38 51 sugar alcohol FAMILY 22985953 T 61 64 Na+ FORMULA 22985953 T 65 80 montmorillonite TRIVIAL 22986217 A 1025 1036 isoflavones FAMILY 22986217 A 1054 1061 glucose TRIVIAL 22986217 A 1157 1168 isoflavones FAMILY 22986217 A 227 238 isoflavones FAMILY 22986217 A 528 539 isoflavones FAMILY 22986217 A 54 65 isoflavones FAMILY 22986217 A 564 575 isoflavones FAMILY 22986217 A 697 708 fatty acids FAMILY 22986217 T 4 15 isoflavones FAMILY 22986456 A 1005 1012 glucose TRIVIAL 22986456 A 1140 1147 glucose TRIVIAL 22986456 A 1177 1188 cholesterol TRIVIAL 22986456 A 1253 1264 cholesterol TRIVIAL 22986456 A 1269 1281 triglyceride FAMILY 22986456 A 1348 1355 glucose TRIVIAL 22989703 A 1079 1102 apo-14'-lycopenoic acid SYSTEMATIC 22989703 A 1147 1170 apo-10'-lycopenoic acid SYSTEMATIC 22989703 A 1214 1222 lycopene TRIVIAL 22989703 A 1257 1277 apo-lycopenoic acids FAMILY 22989703 A 1296 1319 apo-14'-lycopenoic acid SYSTEMATIC 22989703 A 252 260 lycopene TRIVIAL 22989703 A 375 383 lycopene TRIVIAL 22989703 A 41 49 lycopene TRIVIAL 22989703 A 412 435 apo-10'-lycopenoic acid SYSTEMATIC 22989703 A 440 463 apo-14'-lycopenoic acid SYSTEMATIC 22989703 A 506 514 H(2)O(2) FORMULA 22989703 A 576 599 apo-10'-lycopenoic acid SYSTEMATIC 22989703 A 604 627 apo-14'-lycopenoic acid SYSTEMATIC 22989703 A 665 673 H(2)O(2) FORMULA 22989703 A 878 898 apo-lycopenoic acids FAMILY 22989703 A 942 948 8-OHdG SYSTEMATIC 22989703 T 129 133 H2O2 FORMULA 22989703 T 45 68 apo-10'-lycopenoic acid SYSTEMATIC 22989703 T 73 96 apo-14'-lycopenoic acid SYSTEMATIC 22989704 A 0 6 Nickel SYSTEMATIC 22989704 A 1026 1030 atRA ABBREVIATION 22989704 A 1053 1060 NiCl(2) FORMULA 22989704 A 108 131 all-trans retinoid acid SYSTEMATIC 22989704 A 1116 1120 atRA ABBREVIATION 22989704 A 1192 1198 nickel SYSTEMATIC 22989704 A 133 137 atRA ABBREVIATION 22989704 A 251 255 atRA ABBREVIATION 22989704 A 296 302 nickel SYSTEMATIC 22989704 A 417 432 nickel chloride SYSTEMATIC 22989704 A 434 441 NiCl(2) FORMULA 22989704 A 496 502 oxygen SYSTEMATIC 22989704 A 536 543 NiCl(2) FORMULA 22989704 A 643 647 atRA ABBREVIATION 22989704 A 703 710 NiCl(2) FORMULA 22989704 A 794 801 NiCl(2) FORMULA 22989704 A 840 847 NiCl(2) FORMULA 22989704 A 941 948 NiCl(2) FORMULA 22989704 T 12 35 all-trans retinoid acid SYSTEMATIC 22989704 T 50 56 nickel SYSTEMATIC 22989705 A 0 9 Cisplatin TRIVIAL 22989705 A 1005 1016 glutathione TRIVIAL 22989705 A 1018 1021 GSH ABBREVIATION 22989705 A 1119 1124 BADGE ABBREVIATION 22989705 A 1126 1138 Pioglitazone TRIVIAL 22989705 A 1180 1189 cisplatin TRIVIAL 22989705 A 1259 1264 BADGE ABBREVIATION 22989705 A 1328 1340 pioglitazone TRIVIAL 22989705 A 1359 1368 cisplatin TRIVIAL 22989705 A 1477 1489 pioglitazone TRIVIAL 22989705 A 1556 1565 cisplatin TRIVIAL 22989705 A 167 179 pioglitazone TRIVIAL 22989705 A 194 203 cisplatin TRIVIAL 22989705 A 357 366 cisplatin TRIVIAL 22989705 A 407 419 Pioglitazone TRIVIAL 22989705 A 421 449 Bisphenol A diglycidyl ether SYSTEMATIC 22989705 A 451 456 BADGE ABBREVIATION 22989705 A 606 615 cisplatin TRIVIAL 22989705 A 769 781 pioglitazone TRIVIAL 22989705 A 837 852 malondialdehyde TRIVIAL 22989705 A 854 857 MDA ABBREVIATION 22989705 A 948 957 cisplatin TRIVIAL 22989705 T 0 12 Pioglitazone TRIVIAL 22989705 T 30 39 cisplatin TRIVIAL 22991234 A 0 7 Calcium SYSTEMATIC 22991234 A 1197 1204 calcium SYSTEMATIC 22991234 A 1295 1310 calcium citrate SYSTEMATIC 22991234 A 1389 1404 calcium citrate SYSTEMATIC 22991234 A 1653 1660 calcium SYSTEMATIC 22991234 A 1773 1780 calcium SYSTEMATIC 22991234 A 1791 1798 calcium SYSTEMATIC 22991234 A 2025 2032 calcium SYSTEMATIC 22991234 A 2145 2152 calcium SYSTEMATIC 22991234 A 264 271 Calcium SYSTEMATIC 22991234 A 335 342 calcium SYSTEMATIC 22991234 A 453 460 calcium SYSTEMATIC 22991234 A 471 478 calcium SYSTEMATIC 22991234 A 735 742 calcium SYSTEMATIC 22991234 A 837 852 calcium citrate SYSTEMATIC 22991234 T 16 31 calcium citrate SYSTEMATIC 22991234 T 41 48 calcium SYSTEMATIC 22991330 A 0 24 Nitrogen-bisphosphonates FAMILY 22991330 A 1737 1741 n-BP ABBREVIATION 22991330 A 26 30 n-BP ABBREVIATION 22991330 A 275 289 bisphosphonate SYSTEMATIC 22991330 A 335 339 n-BP ABBREVIATION 22991330 A 54 74 aminobisphosphonates FAMILY 22991330 A 624 628 n-BP ABBREVIATION 22991330 A 766 770 n-BP ABBREVIATION 22991330 A 876 880 n-BP ABBREVIATION 22991330 T 126 145 aminobisphosphonate FAMILY 22992330 A 279 287 catechol TRIVIAL 22992330 A 288 289 O FORMULA 22993196 A 1016 1019 TAG ABBREVIATION 22993196 A 1075 1082 glucose TRIVIAL 22993196 A 1185 1192 glucose TRIVIAL 22993196 A 1226 1233 glucose TRIVIAL 22993196 A 1343 1350 glucose TRIVIAL 22993196 A 1383 1390 glucose TRIVIAL 22993196 A 1460 1463 TAG ABBREVIATION 22993196 A 266 273 glucose TRIVIAL 22993196 A 304 311 Glucose TRIVIAL 22993196 A 466 473 Glucose TRIVIAL 22993196 A 54 69 triacylglycerol FAMILY 22993196 A 71 74 TAG ABBREVIATION 22993196 A 772 775 TAG ABBREVIATION 22993196 A 785 792 Glucose TRIVIAL 22993196 A 8 20 triglyceride FAMILY 22993196 A 853 860 glucose TRIVIAL 22993196 A 921 928 glucose TRIVIAL 22993196 T 33 40 glucose TRIVIAL 22995755 A 1057 1060 PEI ABBREVIATION 22995755 A 1123 1132 disulfide SYSTEMATIC 22995755 A 1169 1178 disulfide SYSTEMATIC 22995755 A 12 29 polyethylenimines FAMILY 22995755 A 1259 1262 PEI ABBREVIATION 22995755 A 180 183 PEI ABBREVIATION 22995755 A 31 35 PEIs ABBREVIATION 22995755 A 318 327 disulfide SYSTEMATIC 22995755 A 484 487 PEI ABBREVIATION 22995755 A 519 528 disulfide SYSTEMATIC 22995755 T 19 35 polyethylenimine SYSTEMATIC 22995849 A 442 452 nucleotide FAMILY 22996261 A 1122 1132 Raloxifene TRIVIAL 22996261 A 1179 1183 DACA ABBREVIATION 22996261 A 1230 1240 raloxifene TRIVIAL 22996261 A 130 138 aldehyde SYSTEMATIC 22996261 A 1354 1362 aldehyde SYSTEMATIC 22996261 A 318 366 N-[(2-dimethylamino)ethyl]acridine-4-carboxamide SYSTEMATIC 22996261 A 368 372 DACA ABBREVIATION 22996261 A 375 379 DACA ABBREVIATION 22996261 A 584 588 DACA ABBREVIATION 22996261 A 688 699 phthalazine TRIVIAL 22996261 A 816 820 DACA ABBREVIATION 22996261 A 833 844 phthalazine TRIVIAL 22996261 A 883 893 raloxifene TRIVIAL 22996261 T 69 77 aldehyde SYSTEMATIC 22997060 A 1068 1071 DON ABBREVIATION 22997060 A 1251 1264 trichothecene FAMILY 22997060 A 1334 1340 kaolin TRIVIAL 22997060 A 1611 1614 DON ABBREVIATION 22997060 A 1625 1639 trichothecenes FAMILY 22997060 A 231 251 8-ketotrichothecenes FAMILY 22997060 A 36 49 trichothecene FAMILY 22997060 A 364 367 DON ABBREVIATION 22997060 A 369 392 15-acetyldeoxynivalenol SYSTEMATIC 22997060 A 394 401 15-ADON SYSTEMATIC 22997060 A 404 426 3-acetyldeoxynivalenol SYSTEMATIC 22997060 A 428 434 3-ADON SYSTEMATIC 22997060 A 437 448 fusarenon X TRIVIAL 22997060 A 459 468 nivalenol TRIVIAL 22997060 A 470 473 NIV ABBREVIATION 22997060 A 60 74 deoxynivalenol TRIVIAL 22997060 A 76 79 DON ABBREVIATION 22997060 A 83 92 vomitoxin TRIVIAL 22997060 A 876 879 DON ABBREVIATION 22997060 A 881 888 15-ADON SYSTEMATIC 22997060 A 890 896 3-ADON SYSTEMATIC 22997060 A 906 909 NIV ABBREVIATION 22997060 T 100 122 3-acetyldeoxynivalenol SYSTEMATIC 22997060 T 124 135 fusarenon X TRIVIAL 22997060 T 141 150 nivalenol TRIVIAL 22997060 T 38 73 8-ketotrichothecenes deoxynivalenol SYSTEMATIC 22997060 T 75 98 15-acetyldeoxynivalenol SYSTEMATIC 22998180 A 100 106 carbon SYSTEMATIC 22998180 A 150 153 SiC FORMULA 22998180 A 695 698 SiC FORMULA 22998180 A 73 76 SiC FORMULA 22998180 T 0 3 SiC FORMULA 23000250 A 369 382 acetylcholine SYSTEMATIC 23000250 A 515 528 acetylcholine SYSTEMATIC 23000250 A 89 99 Amino acid FAMILY 23000251 A 0 9 Quercetin TRIVIAL 23000251 A 14 19 rutin TRIVIAL 23000251 A 163 172 quercetin TRIVIAL 23000251 A 177 182 rutin TRIVIAL 23000251 A 265 275 Flavonoids FAMILY 23000251 A 325 335 flavonoids FAMILY 23000251 A 34 44 flavonoids FAMILY 23000251 A 366 375 Quercetin TRIVIAL 23000251 A 406 421 methylquercetin SYSTEMATIC 23000251 A 430 451 quercetin glucuronide TRIVIAL 23000251 A 460 465 rutin TRIVIAL 23000251 A 482 496 rutin sulphate SYSTEMATIC 23000251 A 502 513 methylrutin SYSTEMATIC 23000251 A 522 539 rutin glucuronide TRIVIAL 23000251 A 566 571 rutin TRIVIAL 23000251 A 573 582 quercetin TRIVIAL 23000251 A 620 623 MTT ABBREVIATION 23000251 A 624 635 tetrazolium SYSTEMATIC 23000251 A 659 670 trypan blue TRIVIAL 23000251 A 784 789 rutin TRIVIAL 23000251 A 794 808 rutin sulphate SYSTEMATIC 23000251 A 902 911 quercetin TRIVIAL 23000251 T 17 26 quercetin TRIVIAL 23000251 T 31 36 rutin TRIVIAL 23000442 A 0 8 Mollugin TRIVIAL 23000442 A 261 269 mollugin TRIVIAL 23000442 A 394 402 mollugin TRIVIAL 23000442 A 469 479 phenacetin TRIVIAL 23000442 A 480 481 O FORMULA 23000442 A 584 592 Mollugin TRIVIAL 23000442 A 614 624 phenacetin TRIVIAL 23000442 A 625 626 O FORMULA 23000442 A 805 813 mollugin TRIVIAL 23000442 A 925 933 mollugin TRIVIAL 23000442 T 32 40 mollugin TRIVIAL 23000447 A 1164 1174 glyphosate TRIVIAL 23000447 A 203 213 glyphosate TRIVIAL 23000447 A 305 315 glyphosate TRIVIAL 23000447 T 26 36 glyphosate TRIVIAL 23000449 A 117 126 carbamate FAMILY 23000449 A 947 962 organophosphate FAMILY 23000449 A 99 115 organophosphates FAMILY 23000450 A 1025 1037 triglyceride FAMILY 23000450 A 1101 1114 triglycerides FAMILY 23000450 A 83 94 cholesterol TRIVIAL 23000450 A 918 930 triglyceride FAMILY 23000450 A 99 111 triglyceride FAMILY 23000451 A 0 7 Cocaine TRIVIAL 23000451 A 1124 1131 cocaine TRIVIAL 23000451 A 582 593 (-)-cocaine TRIVIAL 23000451 A 866 877 (-)-cocaine TRIVIAL 23000451 A 942 949 cocaine TRIVIAL 23000451 A 95 102 Cocaine TRIVIAL 23000451 T 75 82 cocaine TRIVIAL 23000507 A 1074 1077 ISO ABBREVIATION 23000507 A 1234 1237 PRO ABBREVIATION 23000507 A 1296 1299 ISO ABBREVIATION 23000507 A 1407 1424 6-hydroxydopamine SYSTEMATIC 23000507 A 1426 1432 6-OHDA SYSTEMATIC 23000507 A 1480 1483 PRO ABBREVIATION 23000507 A 585 593 tyrosine TRIVIAL 23000507 A 816 827 propranolol TRIVIAL 23000507 A 829 832 PRO ABBREVIATION 23000507 A 864 877 isoproterenol TRIVIAL 23000507 A 879 882 ISO ABBREVIATION 23000507 A 920 923 PRO ABBREVIATION 23001627 A 1119 1122 PTU ABBREVIATION 23001627 A 1125 1130 Vit E ABBREVIATION 23001627 A 1206 1209 PTU ABBREVIATION 23001627 A 1239 1242 PTU ABBREVIATION 23001627 A 1245 1249 L-T4 ABBREVIATION 23001627 A 1252 1257 Vit E ABBREVIATION 23001627 A 1326 1329 PTU ABBREVIATION 23001627 A 1332 1336 L-T4 ABBREVIATION 23001627 A 1623 1626 MDA ABBREVIATION 23001627 A 1670 1673 PTU ABBREVIATION 23001627 A 1676 1681 Vit E ABBREVIATION 23001627 A 1686 1689 PTU ABBREVIATION 23001627 A 1692 1696 L-T4 ABBREVIATION 23001627 A 1699 1704 Vit E ABBREVIATION 23001627 A 1721 1724 PTU ABBREVIATION 23001627 A 1729 1732 PTU ABBREVIATION 23001627 A 1735 1739 L-T4 ABBREVIATION 23001627 A 178 187 vitamin E FAMILY 23001627 A 1788 1801 levothyroxine TRIVIAL 23001627 A 1827 1836 vitamin E FAMILY 23001627 A 1889 1892 PTU ABBREVIATION 23001627 A 493 506 levothyroxine TRIVIAL 23001627 A 532 541 vitamin E FAMILY 23001627 A 655 658 PTU ABBREVIATION 23001627 A 666 669 PTU ABBREVIATION 23001627 A 672 677 Vit E ABBREVIATION 23001627 A 685 688 PTU ABBREVIATION 23001627 A 691 695 L-T4 ABBREVIATION 23001627 A 707 710 PTU ABBREVIATION 23001627 A 713 717 L-T4 ABBREVIATION 23001627 A 720 725 Vit E ABBREVIATION 23001627 A 755 770 malondialdehyde TRIVIAL 23001627 A 772 775 MDA ABBREVIATION 23001627 A 810 829 thiobarbituric-acid SYSTEMATIC 23001627 A 88 101 levothyroxine TRIVIAL 23001627 A 880 890 superoxide TRIVIAL 23001627 A 988 1009 nitroblue tetrazolium TRIVIAL 23001627 T 0 13 Levothyroxine TRIVIAL 23001627 T 39 48 vitamin E FAMILY 23002087 A 264 271 statins FAMILY 23007555 A 0 10 Ifenprodil TRIVIAL 23007555 A 1194 1204 ifenprodil TRIVIAL 23007555 A 1274 1278 zinc SYSTEMATIC 23007555 A 1413 1423 ifenprodil TRIVIAL 23007555 A 1473 1483 ifenprodil TRIVIAL 23007555 A 344 355 ifenprodil, TRIVIAL 23007555 A 363 367 zinc SYSTEMATIC 23007555 A 412 417 amino FAMILY 23007555 A 54 74 N-methyl-D-aspartate SYSTEMATIC 23007555 A 663 673 ifenprodil TRIVIAL 23007555 A 841 851 ifenprodil TRIVIAL 23007555 A 977 987 ifenprodil TRIVIAL 23007555 T 10 20 ifenprodil TRIVIAL 23007555 T 37 57 N-methyl-D-aspartate SYSTEMATIC 23007559 A 1095 1097 NO FORMULA 23007559 A 1229 1233 EtOH FORMULA 23007559 A 1317 1319 NO FORMULA 23007559 A 1469 1473 EtOH FORMULA 23007559 A 1671 1673 NO FORMULA 23007559 A 383 390 ethanol SYSTEMATIC 23007559 A 392 396 EtOH FORMULA 23007559 A 503 507 EtOH FORMULA 23007559 A 566 570 EtOH FORMULA 23007559 A 894 898 EtOH FORMULA 23007559 T 32 39 ethanol SYSTEMATIC 23008099 A 0 20 (1R)-Normetanephrine TRIVIAL 23008099 A 239 256 adrenergic amines FAMILY 23008099 A 361 381 (1R)-normetanephrine TRIVIAL 23008099 A 386 406 (1S)-normetanephrine TRIVIAL 23008099 A 463 478 normetanephrine TRIVIAL 23008099 A 511 548 3'-phosphoadenosine-5'-phosphosulfate SYSTEMATIC 23008099 A 722 742 (1R)-normetanephrine TRIVIAL 23008099 A 744 764 (1S)-normetanephrine TRIVIAL 23008099 A 778 793 normetanephrine TRIVIAL 23008099 T 72 87 normetanephrine TRIVIAL 23008229 A 0 10 Fullerenes FAMILY 23008229 A 154 163 fullerene TRIVIAL 23008229 A 231 236 thiol FAMILY 23008229 A 357 362 C(60) TRIVIAL 23008229 A 382 387 C(60) TRIVIAL 23008229 A 446 448 Au FORMULA 23008229 A 453 458 C(60) TRIVIAL 23008229 T 47 56 fullerene TRIVIAL 23008229 T 61 70 fullerene TRIVIAL 23010164 A 45 51 serine TRIVIAL 23010164 T 41 47 serine TRIVIAL 23010165 A 510 522 l-amino acid FAMILY 23010165 T 87 99 l-amino acid FAMILY 23010362 A 112 125 acetylcholine SYSTEMATIC 23010362 A 1188 1202 (-)-reboxetine TRIVIAL 23010362 A 1246 1256 imipramine TRIVIAL 23010362 A 1317 1331 (-)-reboxetine TRIVIAL 23010362 A 1461 1475 (-)-reboxetine TRIVIAL 23010362 A 1534 1544 imipramine TRIVIAL 23010362 A 1697 1711 (-)-reboxetine TRIVIAL 23010362 A 255 261 Ca(2+) FORMULA 23010362 A 291 305 (-)-reboxetine TRIVIAL 23010362 A 33 47 norepinephrine TRIVIAL 23010362 A 550 564 (-)-reboxetine TRIVIAL 23010362 A 67 81 (-)-reboxetine TRIVIAL 23010362 A 717 731 (-)-reboxetine TRIVIAL 23010362 A 753 769 [(3)H]imipramine SYSTEMATIC 23010362 A 812 826 (-)-reboxetine TRIVIAL 23010362 A 984 998 (-)-reboxetine TRIVIAL 23010362 T 41 55 (-)-reboxetine TRIVIAL 23010362 T 86 99 acetylcholine SYSTEMATIC 23010695 A 185 188 VPA ABBREVIATION 23010695 A 309 312 VPA ABBREVIATION 23010695 A 325 354 (S)-2-pentyl-4-pentynoic acid SYSTEMATIC 23010695 A 38 51 valproic acid TRIVIAL 23010695 A 53 56 VPA ABBREVIATION 23010695 A 671 700 (S)-2-pentyl-4-pentynoic acid SYSTEMATIC 23010695 A 746 749 VPA ABBREVIATION 23010695 A 777 806 (R)-2-pentyl-4-pentynoic acid SYSTEMATIC 23010695 A 811 814 VPA ABBREVIATION 23010695 A 931 960 (S)-2-pentyl-4-pentynoic acid SYSTEMATIC 23010695 A 986 989 VPA ABBREVIATION 23010867 A 944 956 sulfonylurea FAMILY 23010867 T 69 81 sulfonylurea FAMILY 23010870 A 1034 1039 (13)C FORMULA 23010870 A 1045 1050 (15)N FORMULA 23010870 A 1145 1147 Hg FORMULA 23010870 A 1305 1307 Hg FORMULA 23010870 A 216 218 Hg FORMULA 23010870 A 461 468 Mercury SYSTEMATIC 23010870 A 67 74 mercury SYSTEMATIC 23010870 A 76 78 Hg FORMULA 23010870 A 888 890 Hg FORMULA 23010870 T 26 33 mercury SYSTEMATIC 23011663 A 1006 1009 MDA ABBREVIATION 23011663 A 1062 1066 zinc SYSTEMATIC 23011663 A 1071 1077 copper SYSTEMATIC 23011663 A 1248 1251 MDA ABBREVIATION 23011663 A 1298 1301 MDA ABBREVIATION 23011663 A 1409 1412 MDA ABBREVIATION 23011663 A 1478 1482 CAPE ABBREVIATION 23011663 A 1562 1566 zinc SYSTEMATIC 23011663 A 1571 1577 copper SYSTEMATIC 23011663 A 1637 1641 CAPE ABBREVIATION 23011663 A 1800 1804 CAPE ABBREVIATION 23011663 A 1997 2001 CAPE ABBREVIATION 23011663 A 2095 2099 CAPE ABBREVIATION 23011663 A 361 365 CAPE ABBREVIATION 23011663 A 408 412 CAPE ABBREVIATION 23011663 A 508 512 CAPE ABBREVIATION 23011663 A 56 84 caffeic acid phenethyl ester SYSTEMATIC 23011663 A 668 672 CAPE ABBREVIATION 23011663 A 792 796 CAPE ABBREVIATION 23011663 A 86 90 CAPE ABBREVIATION 23011663 A 938 948 superoxide TRIVIAL 23011663 A 989 1004 malondialdehyde TRIVIAL 23011663 T 141 147 copper SYSTEMATIC 23011663 T 152 156 zinc SYSTEMATIC 23011663 T 50 78 caffeic acid phenethyl ester SYSTEMATIC 23011663 T 80 84 CAPE ABBREVIATION 23012257 A 0 70 4-(2-Butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid SYSTEMATIC 23012257 A 1027 1032 DCPIB ABBREVIATION 23012257 A 1067 1076 glutamate TRIVIAL 23012257 A 1120 1127 cystine TRIVIAL 23012257 A 1128 1137 glutamate TRIVIAL 23012257 A 1205 1214 glutamate TRIVIAL 23012257 A 1251 1260 glutamate TRIVIAL 23012257 A 1330 1335 DCPIB ABBREVIATION 23012257 A 1473 1478 DCPIB ABBREVIATION 23012257 A 1498 1507 glutamate TRIVIAL 23012257 A 289 294 DCPIB ABBREVIATION 23012257 A 425 434 glutamate TRIVIAL 23012257 A 482 491 glutamate TRIVIAL 23012257 A 590 595 DCPIB ABBREVIATION 23012257 A 641 650 glutamate TRIVIAL 23012257 A 691 708 l-[(3)H]glutamate SYSTEMATIC 23012257 A 710 727 d-[(3)H]aspartate SYSTEMATIC 23012257 A 72 77 DCPIB ABBREVIATION 23012257 A 733 749 l-[(14)C]cystine TRIVIAL 23012257 A 769 779 amino acid FAMILY 23012257 A 868 873 DCPIB ABBREVIATION 23012257 A 893 902 glutamate TRIVIAL 23012257 A 941 950 glutamate TRIVIAL 23012257 A 966 975 glutamate TRIVIAL 23012257 T 0 5 DCPIB ABBREVIATION 23012257 T 91 100 glutamate TRIVIAL 23016524 A 518 522 Ca2+ FORMULA 23016524 A 582 590 inositol TRIVIAL 23017385 A 602 617 Rosmarinic acid TRIVIAL 23017385 A 833 845 caffeic acid TRIVIAL 23017385 A 920 929 flavonoid FAMILY 23017385 A 931 956 luteolin-3'-O-glucuronide SYSTEMATIC 23017388 A 144 149 SB365 IDENTIFIER 23017388 A 151 171 Pulsatilla saponin D TRIVIAL 23017388 A 265 270 SB365 IDENTIFIER 23017388 A 377 382 SB365 IDENTIFIER 23017388 A 526 531 SB365 IDENTIFIER 23017388 A 669 673 5-FU SYSTEMATIC 23017388 A 727 732 SB365 IDENTIFIER 23017388 A 848 853 SB365 IDENTIFIER 23017388 A 994 999 SB365 IDENTIFIER 23017388 T 0 5 SB365 IDENTIFIER 23017388 T 7 27 Pulsatilla saponin D TRIVIAL 23017389 A 1029 1036 ferrous SYSTEMATIC 23017389 A 1042 1048 Fe(2+) FORMULA 23017389 A 1080 1084 DPPH ABBREVIATION 23017389 A 1137 1150 ethyl acetate SYSTEMATIC 23017389 A 1155 1163 methanol SYSTEMATIC 23017389 A 247 260 ethyl acetate SYSTEMATIC 23017389 A 271 281 flavonoids FAMILY 23017389 A 382 392 silica gel TRIVIAL 23017389 A 515 519 (1)H FORMULA 23017389 A 525 530 (13)C FORMULA 23017389 A 597 644 chrysoeriol-7-O-[2″-O-E-feruloyl]-β-d-glucoside SYSTEMATIC 23017389 A 650 661 chrysoeriol TRIVIAL 23017389 A 671 699 isorhamnetin-3-β-d-glucoside SYSTEMATIC 23017389 A 941 959 ferric thiocyanate SYSTEMATIC 23017389 A 968 974 ferric SYSTEMATIC 23017389 A 980 986 Fe(3+) FORMULA 23017389 T 40 48 flavones FAMILY 23017393 A 1031 1039 catechin TRIVIAL 23017393 A 1118 1126 Catechin TRIVIAL 23017393 A 1227 1235 pyruvate TRIVIAL 23017393 A 1271 1279 creatine TRIVIAL 23017393 A 1300 1308 catechin TRIVIAL 23017393 A 1439 1447 catechin TRIVIAL 23017393 A 1524 1532 catechin TRIVIAL 23017393 A 216 228 (+)-catechin TRIVIAL 23017393 A 384 415 fluorescein-5-thiosemicarbazide SYSTEMATIC 23017393 A 417 421 FTSC ABBREVIATION 23017393 A 556 564 pyruvate TRIVIAL 23017393 A 585 593 creatine TRIVIAL 23017393 A 631 645 glyceraldehyde TRIVIAL 23017393 A 893 901 catechin TRIVIAL 23017393 T 95 103 catechin TRIVIAL 23017401 A 162 171 genistein TRIVIAL 23017401 A 173 181 genistin TRIVIAL 23017401 A 183 192 iprodione TRIVIAL 23017401 A 194 205 vinclozolin TRIVIAL 23017401 A 210 221 procymidone TRIVIAL 23017401 A 518 527 iprodione TRIVIAL 23017401 A 626 635 genistein TRIVIAL 23017401 A 697 725 genistin, its β-glycosylated MULTIPLE 23017401 T 0 9 Genistein TRIVIAL 23017401 T 14 27 dicarboximide SYSTEMATIC 23017404 A 368 375 glucose TRIVIAL 23017404 A 380 388 fructose TRIVIAL 23017404 A 414 421 sucrose TRIVIAL 23017404 A 45 50 sugar FAMILY 23017404 A 451 458 sucrose TRIVIAL 23017404 A 643 649 hexose TRIVIAL 23017404 A 669 674 sugar FAMILY 23017404 A 743 750 hexoses FAMILY 23017404 A 769 775 hexose TRIVIAL 23017404 T 0 5 Sugar FAMILY 23017406 A 0 4 GABA ABBREVIATION 23017406 A 145 149 GABA ABBREVIATION 23017406 A 15 24 polyamine FAMILY 23017406 A 234 237 Glu FORMULA 23017406 A 242 251 polyamine FAMILY 23017406 A 325 329 GABA ABBREVIATION 23017406 A 354 358 GABA ABBREVIATION 23017406 A 449 452 Glu FORMULA 23017406 A 457 467 polyamines FAMILY 23017406 A 48 67 γ-aminobutyric acid SYSTEMATIC 23017406 A 69 73 GABA ABBREVIATION 23017406 A 758 762 GABA ABBREVIATION 23017406 A 892 896 GABA ABBREVIATION 23017406 A 959 968 polyamine FAMILY 23017406 T 0 4 GABA ABBREVIATION 23017406 T 15 24 polyamine FAMILY 23017406 T 48 67 γ-aminobutyric acid SYSTEMATIC 23017414 A 334 342 phenolic FAMILY 23017414 A 433 443 isoflavone FAMILY 23017414 A 56 64 phenolic FAMILY 23017414 A 699 713 phenolic acids FAMILY 23017414 A 76 87 isoflavones FAMILY 23017414 A 765 773 phenolic FAMILY 23017414 A 840 851 isoflavones FAMILY 23017414 T 28 39 isoflavones FAMILY 23017414 T 8 16 phenolic FAMILY 23017417 A 319 330 polyphenols FAMILY 23017417 A 520 531 gallic acid TRIVIAL 23017417 A 533 545 (+)-catechin TRIVIAL 23017417 A 547 562 (-)-epicatechin SYSTEMATIC 23017417 A 568 583 (E)-resveratrol TRIVIAL 23017417 A 585 597 Anthocyanins FAMILY 23017417 A 828 838 polyphenol FAMILY 23017423 A 202 209 glucose TRIVIAL 23017423 A 220 225 sugar FAMILY 23017423 A 231 238 sucrose TRIVIAL 23017423 A 445 460 l-ascorbic acid TRIVIAL 23017423 A 561 581 dehydroascorbic acid TRIVIAL 23017423 A 583 586 DHA ABBREVIATION 23017423 A 695 698 DHA ABBREVIATION 23017423 A 991 996 sugar FAMILY 23017423 T 49 54 sugar FAMILY 23017423 T 59 74 l-ascorbic acid TRIVIAL 23018143 A 11 19 estrogen FAMILY 23018143 T 87 95 estrogen FAMILY 23019137 A 1006 1015 Serotonin TRIVIAL 23019137 A 1027 1038 neurotensin TRIVIAL 23019137 A 1118 1211 5,6,7,13-tetrahydro-13-methyl-5-oxo-12H-indolo[2,3-a]pyrrolo[3,4c]carbazole-12-propanenitrile SYSTEMATIC 23019137 A 1213 1219 Gö6976 IDENTIFIER 23019137 A 182 190 dopamine TRIVIAL 23019137 A 493 497 5-HT SYSTEMATIC 23019137 A 504 515 neurotensin TRIVIAL 23019137 A 931 941 quinpirole TRIVIAL 23019137 A 958 967 serotonin TRIVIAL 23019137 A 983 994 neurotensin TRIVIAL 23019137 T 12 20 dopamine TRIVIAL 23019217 A 1100 1104 Mith ABBREVIATION 23019217 A 1229 1233 Mith ABBREVIATION 23019217 A 1456 1460 Mith ABBREVIATION 23019217 A 598 611 mithramycin A TRIVIAL 23019217 A 613 617 Mith ABBREVIATION 23019217 A 863 867 Mith ABBREVIATION 23019217 T 0 13 Mithramycin A TRIVIAL 23019274 A 1333 1343 creatinine TRIVIAL 23019274 A 1357 1361 urea TRIVIAL 23019274 A 1362 1370 nitrogen SYSTEMATIC 23019274 A 1372 1380 N-acetyl SYSTEMATIC 23019274 A 716 733 aristolochic acid FAMILY 23022069 A 285 293 melamine TRIVIAL 23022069 A 295 298 MEL ABBREVIATION 23022069 A 365 368 MEL ABBREVIATION 23022069 A 373 386 cyanuric acid TRIVIAL 23022069 A 388 391 CYA ABBREVIATION 23022069 A 404 412 melamine TRIVIAL 23022069 A 413 422 cyanurate TRIVIAL 23022069 A 692 695 MEL ABBREVIATION 23022069 A 700 703 CYA ABBREVIATION 23022069 T 107 120 cyanuric acid TRIVIAL 23022069 T 94 102 melamine TRIVIAL 23022398 A 1102 1106 PILO ABBREVIATION 23022398 A 1200 1204 NMDA ABBREVIATION 23022398 A 1307 1310 AP7 IDENTIFIER 23022398 A 1421 1425 PILO ABBREVIATION 23022398 A 1440 1443 AP7 IDENTIFIER 23022398 A 1627 1631 PILO ABBREVIATION 23022398 A 381 389 urethane TRIVIAL 23022398 A 503 514 pilocarpine TRIVIAL 23022398 A 516 520 PILO ABBREVIATION 23022398 A 586 590 PILO ABBREVIATION 23022398 A 771 775 NMDA ABBREVIATION 23022398 A 797 800 AP7 IDENTIFIER 23022398 A 851 855 PILO ABBREVIATION 23022398 A 967 971 PILO ABBREVIATION 23022398 T 0 4 NMDA ABBREVIATION 23023024 A 1076 1079 MDA ABBREVIATION 23023024 A 118 128 bile acids FAMILY 23023024 A 130 133 BAs ABBREVIATION 23023024 A 1346 1349 BAs ABBREVIATION 23023024 A 360 370 bile acids FAMILY 23023024 A 495 510 Malondialdehyde TRIVIAL 23023024 A 51 63 α-tocopherol TRIVIAL 23023024 A 512 515 MDA ABBREVIATION 23023024 A 565 575 superoxide TRIVIAL 23023024 A 981 984 MDA ABBREVIATION 23023024 T 15 27 α-tocopherol TRIVIAL 23023136 A 0 16 Arsenic trioxide SYSTEMATIC 23023136 A 1069 1076 arsenic SYSTEMATIC 23023136 A 1141 1150 As(2)O(3) FORMULA 23023136 A 1172 1183 resveratrol TRIVIAL 23023136 A 1195 1204 As(2)O(3) FORMULA 23023136 A 1263 1270 arsenic SYSTEMATIC 23023136 A 1329 1340 resveratrol TRIVIAL 23023136 A 1434 1441 arsenic SYSTEMATIC 23023136 A 1455 1462 arsenic SYSTEMATIC 23023136 A 18 27 As(2)O(3) FORMULA 23023136 A 217 226 As(2)O(3) FORMULA 23023136 A 276 287 Resveratrol TRIVIAL 23023136 A 390 399 As(2)O(3) FORMULA 23023136 A 420 431 resveratrol TRIVIAL 23023136 A 459 466 arsenic SYSTEMATIC 23023136 A 588 597 As(2)O(3) FORMULA 23023136 A 617 628 resveratrol TRIVIAL 23023136 A 665 674 As(2)O(3) FORMULA 23023136 A 795 814 reduced glutathione TRIVIAL 23023136 A 816 819 GSH ABBREVIATION 23023136 A 824 844 oxidized glutathione TRIVIAL 23023136 A 846 850 GSSG ABBREVIATION 23023136 A 857 864 arsenic SYSTEMATIC 23023136 A 899 910 resveratrol TRIVIAL 23023136 A 911 920 As(2)O(3) FORMULA 23023136 A 942 952 superoxide TRIVIAL 23023136 A 986 989 GSH ABBREVIATION 23023136 A 990 994 GSSG ABBREVIATION 23023136 T 0 11 Resveratrol TRIVIAL 23023136 T 57 73 arsenic trioxide SYSTEMATIC 23023933 A 1112 1132 perfluoroalkyl acids FAMILY 23023933 A 256 276 perfluoroalkyl acids FAMILY 23023933 A 650 657 octanol SYSTEMATIC 23026700 A 256 263 ethanol SYSTEMATIC 23026700 A 563 566 AMP ABBREVIATION 23026700 A 644 654 acetyl-CoA SYSTEMATIC 23026700 A 704 723 carnitine palmitoyl TRIVIAL 23026700 A 758 764 sterol FAMILY 23026700 A 806 816 fatty acid FAMILY 23026700 A 937 949 triglyceride FAMILY 23028140 A 1112 1120 imatinib TRIVIAL 23028140 A 1325 1333 imatinib TRIVIAL 23028140 A 1392 1400 imatinib TRIVIAL 23028140 A 1458 1466 imatinib TRIVIAL 23028140 A 1722 1730 imatinib TRIVIAL 23028140 A 197 205 imatinib TRIVIAL 23028140 A 249 257 imatinib TRIVIAL 23028140 A 408 416 imatinib TRIVIAL 23028140 A 47 55 imatinib TRIVIAL 23028140 A 511 519 imatinib TRIVIAL 23028140 A 551 559 imatinib TRIVIAL 23028140 A 651 659 imatinib TRIVIAL 23028140 A 733 741 imatinib TRIVIAL 23028140 A 743 762 N-desmethylimatinib SYSTEMATIC 23028140 A 825 833 imatinib TRIVIAL 23028140 A 890 898 imatinib TRIVIAL 23028140 A 935 943 imatinib TRIVIAL 23028140 T 62 70 imatinib TRIVIAL 23030346 A 1061 1063 Ge FORMULA 23030346 A 1079 1081 Si FORMULA 23030346 A 1226 1228 Si FORMULA 23030346 A 1229 1231 Ge FORMULA 23030346 A 372 374 Ge FORMULA 23030346 A 375 377 Si FORMULA 23030680 A 1099 1117 5-hydroxyelzasonan SYSTEMATIC 23030680 A 18 27 elzasonan TRIVIAL 23030680 A 195 196 N FORMULA 23030680 A 254 271 elzasonan N-oxide SYSTEMATIC 23030680 A 281 299 5-hydroxyelzasonan SYSTEMATIC 23030680 A 331 340 elzasonan TRIVIAL 23030680 A 391 397 indole SYSTEMATIC 23030680 A 463 470 iminium SYSTEMATIC 23030680 A 663 672 elzasonan TRIVIAL 23030680 T 69 78 elzasonan TRIVIAL 23030706 A 336 354 chloroacetaldehyde SYSTEMATIC 23030706 A 392 402 ifosfamide TRIVIAL 23030706 A 412 427 cobalt chloride SYSTEMATIC 23030706 A 464 470 cobalt SYSTEMATIC 23030706 A 510 519 valproate SYSTEMATIC 23030706 A 775 784 carbon 13 SYSTEMATIC 23030766 A 547 557 amino acid FAMILY 23032515 A 1005 1024 8-hydroxycalamenene SYSTEMATIC 23032515 A 123 142 8-hydroxycalamenene SYSTEMATIC 23032515 A 165 171 hexane SYSTEMATIC 23032515 A 221 240 8-hydroxycalamenene SYSTEMATIC 23032515 A 429 459 l-buthionine-(S,R)-sulfoximine SYSTEMATIC 23032515 A 461 464 BSO ABBREVIATION 23032515 A 471 480 glutamate TRIVIAL 23032515 A 496 507 glutathione TRIVIAL 23032515 A 512 523 glutathione TRIVIAL 23032515 A 524 525 S FORMULA 23032515 A 574 593 8-hydroxycalamenene SYSTEMATIC 23032515 A 680 689 glutamate TRIVIAL 23032515 A 690 693 BSO ABBREVIATION 23032515 A 721 741 N-methyl-d-aspartate SYSTEMATIC 23032515 A 880 899 8-hydroxycalamenene SYSTEMATIC 23032515 T 0 19 8-Hydroxycalamenene SYSTEMATIC 23033256 A 671 680 Bisulfite SYSTEMATIC 23034931 A 17 25 nitrogen SYSTEMATIC 23034931 A 463 464 S FORMULA 23034931 A 791 794 oxy SYSTEMATIC 23034931 A 795 800 nitro SYSTEMATIC 23036893 A 1078 1087 genistein TRIVIAL 23036893 A 1092 1103 bisphenol A TRIVIAL 23036893 A 1191 1194 EE2 ABBREVIATION 23036893 A 317 328 bisphenol A TRIVIAL 23036893 A 330 339 genistein TRIVIAL 23036893 A 345 358 4-nonylphenol SYSTEMATIC 23036893 A 372 388 ethinylestradiol SYSTEMATIC 23036893 A 390 393 EE2 ABBREVIATION 23036893 A 416 424 estrogen FAMILY 23036893 A 559 562 EE2 ABBREVIATION 23036893 A 740 743 EE2 ABBREVIATION 23038668 A 0 23 Calcium manganese oxide SYSTEMATIC 23038668 A 224 230 oxygen SYSTEMATIC 23038668 A 310 314 O(2) FORMULA 23038668 T 72 78 oxygen SYSTEMATIC 23038668 T 83 85 H+ FORMULA 23041228 A 257 265 tyrosine TRIVIAL 23041228 A 35 38 ser FORMULA 23041228 A 39 42 thr FORMULA 23041510 A 0 12 Eldecalcitol TRIVIAL 23041510 A 1000 1003 ALN ABBREVIATION 23041510 A 1051 1054 ALN ABBREVIATION 23041510 A 1106 1109 ELD ABBREVIATION 23041510 A 1110 1113 ALN ABBREVIATION 23041510 A 1158 1161 ALF ABBREVIATION 23041510 A 116 128 alfacalcidol TRIVIAL 23041510 A 1162 1165 ALN ABBREVIATION 23041510 A 1223 1226 ELD ABBREVIATION 23041510 A 1231 1234 ALF ABBREVIATION 23041510 A 1294 1297 ELD ABBREVIATION 23041510 A 1298 1301 ALN ABBREVIATION 23041510 A 130 133 ALF ABBREVIATION 23041510 A 1306 1309 ALF ABBREVIATION 23041510 A 1310 1313 ALN ABBREVIATION 23041510 A 1370 1373 ALN ABBREVIATION 23041510 A 14 17 ELD ABBREVIATION 23041510 A 1401 1404 ELD ABBREVIATION 23041510 A 1406 1409 ELD ABBREVIATION 23041510 A 1410 1413 ALN ABBREVIATION 23041510 A 1419 1422 ALF ABBREVIATION 23041510 A 1423 1426 ALN ABBREVIATION 23041510 A 1521 1524 ELD ABBREVIATION 23041510 A 1525 1528 ALN ABBREVIATION 23041510 A 1583 1586 ALN ABBREVIATION 23041510 A 1641 1644 ELD ABBREVIATION 23041510 A 1661 1664 ELD ABBREVIATION 23041510 A 1665 1668 ALN ABBREVIATION 23041510 A 1890 1893 ALF ABBREVIATION 23041510 A 1898 1901 ALF ABBREVIATION 23041510 A 1902 1905 ALN ABBREVIATION 23041510 A 2024 2027 ELD ABBREVIATION 23041510 A 2031 2034 ALF ABBREVIATION 23041510 A 2060 2063 ALN ABBREVIATION 23041510 A 2096 2099 ALN ABBREVIATION 23041510 A 2118 2121 ELD ABBREVIATION 23041510 A 2122 2125 ALN ABBREVIATION 23041510 A 22 41 2β-hydroxypropyloxy SYSTEMATIC 23041510 A 226 237 Alendronate TRIVIAL 23041510 A 2304 2307 ALF ABBREVIATION 23041510 A 2308 2311 ALN ABBREVIATION 23041510 A 239 242 ALN ABBREVIATION 23041510 A 270 284 bisphosphonate SYSTEMATIC 23041510 A 472 475 ELD ABBREVIATION 23041510 A 480 483 ALN ABBREVIATION 23041510 A 492 495 ALF ABBREVIATION 23041510 A 500 503 ALN ABBREVIATION 23041510 A 56 70 1α,25 (OH) 2D3 SYSTEMATIC 23041510 A 677 680 ELD ABBREVIATION 23041510 A 695 698 ALF ABBREVIATION 23041510 A 713 716 ALN ABBREVIATION 23041510 A 731 734 ELD ABBREVIATION 23041510 A 735 738 ALN ABBREVIATION 23041510 A 757 760 ALF ABBREVIATION 23041510 A 761 764 ALN ABBREVIATION 23041510 A 806 809 ELD ABBREVIATION 23041510 A 825 828 ALF ABBREVIATION 23041510 A 848 851 ALN ABBREVIATION 23041510 A 923 926 ELD ABBREVIATION 23041510 A 931 934 ALF ABBREVIATION 23041510 A 984 987 ELD ABBREVIATION 23041510 A 988 991 ALN ABBREVIATION 23041510 A 996 999 ALF ABBREVIATION 23041510 T 169 181 alfacalcidol TRIVIAL 23041510 T 186 197 alendronate TRIVIAL 23041510 T 35 47 eldecalcitol TRIVIAL 23041510 T 52 63 alendronate TRIVIAL 23041538 A 1026 1034 spermine TRIVIAL 23041538 A 1061 1066 NASPM ABBREVIATION 23041538 A 1147 1156 SCH 58261 IDENTIFIER 23041538 A 1310 1319 SCH 58261 IDENTIFIER 23041538 A 1345 1350 NASPM ABBREVIATION 23041538 A 1482 1491 SCH 58261 IDENTIFIER 23041538 A 372 379 calcium SYSTEMATIC 23041538 A 496 505 adenosine TRIVIAL 23041538 A 679 685 oxygen SYSTEMATIC 23041538 A 686 693 glucose TRIVIAL 23041538 T 68 75 calcium SYSTEMATIC 23041661 A 1048 1051 Glu FORMULA 23041661 A 1055 1058 Arg FORMULA 23041661 A 1139 1142 Arg FORMULA 23041661 A 1152 1170 γ-phosphate oxygen SYSTEMATIC 23041661 A 1174 1177 ATP ABBREVIATION 23041661 A 1262 1265 Arg FORMULA 23041661 A 1269 1272 Glu FORMULA 23041661 A 1279 1282 Arg FORMULA 23041661 A 1286 1289 ATP ABBREVIATION 23041661 A 1401 1404 ATP ABBREVIATION 23041661 A 1412 1415 ATP ABBREVIATION 23041661 A 27 52 adenosine-5'-triphosphate SYSTEMATIC 23041661 A 284 287 Glu FORMULA 23041661 A 295 298 Arg FORMULA 23041661 A 352 355 ATP ABBREVIATION 23041661 A 503 506 Glu FORMULA 23041661 A 514 517 Arg FORMULA 23041661 A 54 57 ATP ABBREVIATION 23041661 A 569 578 disulfide SYSTEMATIC 23041661 A 621 624 Glu FORMULA 23041661 A 632 635 Arg FORMULA 23041661 A 695 698 ATP ABBREVIATION 23041661 A 777 780 Glu FORMULA 23041661 A 784 787 Arg FORMULA 23041661 A 953 956 Glu FORMULA 23041661 A 964 967 Arg FORMULA 23041661 T 27 30 Arg FORMULA 23041661 T 34 37 Glu FORMULA 23041661 T 44 47 Arg FORMULA 23041661 T 51 54 ATP ABBREVIATION 23041725 A 0 14 Organochlorine FAMILY 23041725 A 1019 1027 dieldrin TRIVIAL 23041725 A 1247 1255 dieldrin TRIVIAL 23041725 A 1398 1406 dieldrin TRIVIAL 23041725 A 1458 1466 dieldrin TRIVIAL 23041725 A 1604 1612 dieldrin TRIVIAL 23041725 A 265 273 dieldrin TRIVIAL 23041725 A 390 398 dieldrin TRIVIAL 23041725 A 41 49 dieldrin TRIVIAL 23041725 A 485 493 dieldrin TRIVIAL 23041725 A 558 571 17β-estradiol SYSTEMATIC 23041725 A 650 658 dieldrin TRIVIAL 23041725 A 686 694 estrogen FAMILY 23041725 A 696 704 dieldrin TRIVIAL 23041725 T 123 131 dieldrin TRIVIAL 23041725 T 98 112 organochlorine FAMILY 23042728 A 1209 1212 VPD ABBREVIATION 23042728 A 127 137 Valpromide TRIVIAL 23042728 A 139 142 VPD ABBREVIATION 23042728 A 149 154 amide FAMILY 23042728 A 169 172 VPA ABBREVIATION 23042728 A 21 34 valproic acid TRIVIAL 23042728 A 274 277 VPA ABBREVIATION 23042728 A 36 39 VPA ABBREVIATION 23042728 A 362 365 VPA ABBREVIATION 23042728 A 563 566 VPA ABBREVIATION 23042728 A 570 573 VPD ABBREVIATION 23042728 A 604 607 VPA ABBREVIATION 23042728 A 833 836 VPA ABBREVIATION 23042728 A 851 854 VPD ABBREVIATION 23042728 A 976 979 VPA ABBREVIATION 23042728 T 12 25 valproic acid TRIVIAL 23042730 A 0 10 Amiodarone TRIVIAL 23042730 A 1029 1041 α-tocopherol TRIVIAL 23042730 A 1043 1047 TOCO ABBREVIATION 23042730 A 1113 1116 AMD ABBREVIATION 23042730 A 1179 1182 AMD ABBREVIATION 23042730 A 12 15 AMD ABBREVIATION 23042730 A 1200 1206 α-TOCO SYSTEMATIC 23042730 A 1256 1259 AMD ABBREVIATION 23042730 A 1362 1365 AMD ABBREVIATION 23042730 A 1460 1463 AMD ABBREVIATION 23042730 A 216 219 AMD ABBREVIATION 23042730 A 400 403 AMD ABBREVIATION 23042730 A 418 421 AMD ABBREVIATION 23042730 A 555 558 AMD ABBREVIATION 23042730 A 671 677 oxygen SYSTEMATIC 23042730 A 761 764 AMD ABBREVIATION 23042730 A 846 852 trolox TRIVIAL 23042730 A 854 870 N-acetylcysteine SYSTEMATIC 23042730 A 872 883 glutathione TRIVIAL 23042730 A 888 897 ascorbate TRIVIAL 23042730 A 934 937 AMD ABBREVIATION 23042730 A 999 1002 AMD ABBREVIATION 23042730 T 60 70 amiodarone TRIVIAL 23042808 A 1030 1033 CBD ABBREVIATION 23042808 A 113 124 cannabidiol TRIVIAL 23042808 A 126 129 CBD ABBREVIATION 23042808 A 1280 1283 CBD ABBREVIATION 23042808 A 1366 1369 THC ABBREVIATION 23042808 A 1374 1377 CBD ABBREVIATION 23042808 A 246 249 THC ABBREVIATION 23042808 A 254 257 CBD ABBREVIATION 23042808 A 400 403 CBD ABBREVIATION 23042808 A 414 417 THC ABBREVIATION 23042808 A 516 519 CBD ABBREVIATION 23042808 A 587 590 THC ABBREVIATION 23042808 A 606 609 THC ABBREVIATION 23042808 A 657 660 CBD ABBREVIATION 23042808 A 72 95 Δ⁹-tetrahydrocannabinol SYSTEMATIC 23042808 A 844 847 CBD ABBREVIATION 23042808 A 946 949 THC ABBREVIATION 23042808 A 97 100 THC ABBREVIATION 23042808 T 0 11 Cannabidiol TRIVIAL 23042808 T 21 24 THC ABBREVIATION 23042953 A 1084 1097 triglycerides FAMILY 23042953 A 1254 1265 cholesterol TRIVIAL 23042953 A 1648 1659 cholesterol TRIVIAL 23042953 A 370 381 amino acids FAMILY 23042953 A 57 68 cholesterol TRIVIAL 23042953 A 635 646 amino acids FAMILY 23042953 A 889 900 cholesterol TRIVIAL 23042953 A 993 1004 cholesterol TRIVIAL 23042953 T 113 124 cholesterol TRIVIAL 23042953 T 12 23 amino acids FAMILY 23042954 A 1039 1047 LY293558 IDENTIFIER 23042954 A 1133 1141 LY293558 IDENTIFIER 23042954 A 1191 1196 oxime SYSTEMATIC 23042954 A 1197 1201 HI-6 IDENTIFIER 23042954 A 1301 1309 LY293558 IDENTIFIER 23042954 A 1484 1492 LY293558 IDENTIFIER 23042954 A 1692 1700 LY293558 IDENTIFIER 23042954 A 746 798 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid SYSTEMATIC 23042954 A 800 804 AMPA ABBREVIATION 23042954 A 826 914 (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid SYSTEMATIC 23042954 A 916 924 LY293558 IDENTIFIER 23042954 T 22 26 AMPA ABBREVIATION 23042954 T 47 55 LY293558 IDENTIFIER 23043137 A 1001 1005 pVIc ABBREVIATION 23043137 A 192 196 pVIc ABBREVIATION 23043137 A 204 214 amino acid FAMILY 23043137 A 244 245 C FORMULA 23043137 A 875 879 pVIc ABBREVIATION 23043137 A 930 934 pVIc ABBREVIATION 23043137 A 948 957 disulfide SYSTEMATIC 23043441 A 186 195 copper(I) SYSTEMATIC 23043441 A 206 218 azide-alkyne FAMILY 23044047 A 947 957 phalloidin TRIVIAL 23044489 A 0 16 Organophosphorus FAMILY 23044489 A 1403 1406 KET ABBREVIATION 23044489 A 1428 1444 atropine sulfate SYSTEMATIC 23044489 A 1469 1483 benzodiazepine FAMILY 23044489 A 1506 1511 soman TRIVIAL 23044489 A 1625 1630 soman TRIVIAL 23044489 A 1790 1796 MK-801 IDENTIFIER 23044489 A 1798 1801 KET ABBREVIATION 23044489 A 1896 1899 KET ABBREVIATION 23044489 A 768 772 NMDA ABBREVIATION 23044489 A 953 961 Ketamine TRIVIAL 23044489 A 963 966 KET ABBREVIATION 23044489 A 980 984 NMDA ABBREVIATION 23044489 T 0 8 Ketamine TRIVIAL 23044489 T 49 54 soman TRIVIAL 23046872 A 1033 1046 cisplatin(II) TRIVIAL 23046872 A 1051 1064 cisplatin(IV) TRIVIAL 23046872 A 1092 1101 cisplatin TRIVIAL 23046872 A 12 25 cisplatin(IV) TRIVIAL 23046872 A 164 177 cisplatin(IV) TRIVIAL 23046872 A 466 482 sodium ascorbate SYSTEMATIC 23046872 A 484 489 NaAsc FORMULA 23046872 A 622 635 cisplatin(II) TRIVIAL 23046872 A 675 688 cisplatin(II) TRIVIAL 23046872 A 708 719 nucleobases FAMILY 23046872 A 74 80 Pt(IV) FORMULA 23046872 A 773 782 cisplatin TRIVIAL 23046872 A 859 872 cisplatin(II) TRIVIAL 23046872 A 877 890 cisplatin(IV) TRIVIAL 23046872 T 54 67 cisplatin(IV) TRIVIAL 23047001 A 113 116 ATP ABBREVIATION 23047001 A 255 273 benzothiazepinones FAMILY 23047001 A 275 279 BTZs ABBREVIATION 23047001 A 294 297 ATP ABBREVIATION 23047001 A 434 437 BTZ ABBREVIATION 23047001 T 47 65 benzothiazepinones FAMILY 23047001 T 67 71 BTZs ABBREVIATION 23047001 T 86 89 ATP ABBREVIATION 23047024 A 0 16 Organophosphorus FAMILY 23047024 A 1112 1117 tabun TRIVIAL 23047024 A 1391 1396 oxime SYSTEMATIC 23047024 A 1397 1401 K048 IDENTIFIER 23047024 A 1437 1441 K048 IDENTIFIER 23047024 A 1460 1465 tabun TRIVIAL 23047024 A 1612 1618 oximes FAMILY 23047024 A 1727 1733 oximes FAMILY 23047024 A 359 364 tabun TRIVIAL 23047024 A 369 374 oxime SYSTEMATIC 23047024 A 37 43 oximes FAMILY 23047024 A 375 379 K048 IDENTIFIER 23047024 A 863 868 tabun TRIVIAL 23047024 A 869 873 K048 IDENTIFIER 23047024 A 897 902 tabun TRIVIAL 23047024 A 907 911 K048 IDENTIFIER 23047024 T 47 63 organophosphates FAMILY 23047024 T 68 74 oximes FAMILY 23047287 A 1031 1035 β-CD ABBREVIATION 23047287 A 1331 1341 amantadine TRIVIAL 23047287 A 1360 1383 5(6)-carboxyfluorescein SYSTEMATIC 23047287 A 1390 1401 Arg-Gly-Asp FORMULA 23047287 A 1449 1459 adamantine TRIVIAL 23047287 A 1489 1512 5(6)-carboxyfluorescein SYSTEMATIC 23047287 A 1581 1591 cyclic RGD TRIVIAL 23047287 A 38 46 graphene TRIVIAL 23047287 A 429 443 β-cyclodextrin TRIVIAL 23047287 A 617 631 β-cyclodextrin TRIVIAL 23047287 A 633 637 β-CD ABBREVIATION 23047287 A 742 750 graphene TRIVIAL 23047287 A 800 808 graphene TRIVIAL 23047287 A 824 828 β-CD ABBREVIATION 23047287 A 961 969 graphene TRIVIAL 23047287 T 40 54 β-cyclodextrin TRIVIAL 23047287 T 79 87 graphene TRIVIAL 23047912 A 1038 1044 L-BMAA ABBREVIATION 23047912 A 1093 1099 oxygen SYSTEMATIC 23047912 A 1187 1196 vitamin E FAMILY 23047912 A 1198 1204 L-BMAA ABBREVIATION 23047912 A 1263 1269 L-BMAA ABBREVIATION 23047912 A 1336 1342 L-BMAA ABBREVIATION 23047912 A 19 44 β-N-methylamino-L-alanine SYSTEMATIC 23047912 A 281 287 L-BMAA ABBREVIATION 23047912 A 407 413 L-BMAA ABBREVIATION 23047912 A 46 52 L-BMAA ABBREVIATION 23047912 A 512 518 L-BMAA ABBREVIATION 23047912 A 647 653 L-BMAA ABBREVIATION 23047912 A 744 749 (14)C FORMULA 23047912 A 750 756 L-BMAA ABBREVIATION 23047912 A 786 792 L-BMAA ABBREVIATION 23047912 T 0 6 L-BMAA ABBREVIATION 23050902 A 1067 1076 ribavirin TRIVIAL 23050902 A 1110 1119 Ribavirin TRIVIAL 23050902 A 1222 1231 ribavirin TRIVIAL 23050902 A 1254 1257 GTP ABBREVIATION 23050902 A 1450 1459 ribavirin TRIVIAL 23050902 A 174 183 ribavirin TRIVIAL 23050902 A 35 44 vitamin K FAMILY 23050902 A 360 369 ribavirin TRIVIAL 23050902 A 474 477 GTP ABBREVIATION 23050902 A 491 500 ribavirin TRIVIAL 23050902 A 525 549 inosine-5'-monophosphate SYSTEMATIC 23050902 A 585 602 mycophenolic acid TRIVIAL 23050902 A 607 623 6-mercaptopurine TRIVIAL 23050902 A 861 870 Ribavirin TRIVIAL 23050902 A 904 910 lysine TRIVIAL 23050902 A 987 996 ribavirin TRIVIAL 23050902 T 0 9 Ribavirin TRIVIAL 23050902 T 32 35 GTP ABBREVIATION 23052192 A 1158 1160 WC FORMULA 23052192 A 1161 1163 Co FORMULA 23052192 A 1178 1180 Co FORMULA 23052192 A 1230 1237 CoCl(2) FORMULA 23052192 A 1241 1243 WC FORMULA 23052192 A 1545 1547 WC FORMULA 23052192 A 1548 1550 Co FORMULA 23052192 A 233 235 Co FORMULA 23052192 A 24 40 tungsten carbide SYSTEMATIC 23052192 A 309 311 WC FORMULA 23052192 A 312 314 Co FORMULA 23052192 A 42 44 WC FORMULA 23052192 A 428 430 WC FORMULA 23052192 A 431 433 Co FORMULA 23052192 A 475 481 oxygen SYSTEMATIC 23052192 A 59 65 cobalt SYSTEMATIC 23052192 A 67 69 Co FORMULA 23052192 A 752 754 WC FORMULA 23052192 A 755 757 Co FORMULA 23052192 A 805 807 WC FORMULA 23052192 A 808 810 Co FORMULA 23052192 A 818 824 Co(2+) FORMULA 23052192 A 831 838 CoCl(2) FORMULA 23052192 A 942 944 WC FORMULA 23052192 A 945 947 Co FORMULA 23052192 T 12 14 WC FORMULA 23052192 T 15 17 Co FORMULA 23052195 A 1106 1109 PPA ABBREVIATION 23052195 A 1195 1198 PPA ABBREVIATION 23052195 A 148 167 phenylpropanolamine SYSTEMATIC 23052195 A 169 172 PPA ABBREVIATION 23052195 A 320 323 PPA ABBREVIATION 23052195 A 373 384 glutathione TRIVIAL 23052195 A 672 675 PPA ABBREVIATION 23052195 A 75 80 c-AMP ABBREVIATION 23052195 A 853 856 PPA ABBREVIATION 23052195 T 117 136 phenylpropanolamine SYSTEMATIC 23052195 T 48 59 glutathione TRIVIAL 23052195 T 75 80 c-AMP ABBREVIATION 23055393 A 239 245 TiO(2) FORMULA 23055453 A 108 136 oligo(p-phenyleneethynylene) SYSTEMATIC 23055453 A 1144 1147 HCl FORMULA 23055453 A 138 141 OPE ABBREVIATION 23055453 A 159 170 cholesterol TRIVIAL 23055453 A 199 212 ethanediamine SYSTEMATIC 23055453 A 316 319 OPE ABBREVIATION 23055453 A 571 574 HCl FORMULA 23055453 A 687 692 imino SYSTEMATIC 23055453 T 126 129 HCl FORMULA 23055539 A 0 14 Angiotensin IV TRIVIAL 23055539 A 1117 1125 hydrogen SYSTEMATIC 23055539 A 1218 1260 N-hexanoic-Tyr-Ile-(6) aminohexanoic amide SYSTEMATIC 23055539 A 1262 1268 dihexa ABBREVIATION 23055539 A 1324 1335 scopolamine TRIVIAL 23055539 A 1414 1420 dihexa ABBREVIATION 23055539 A 16 21 AngIV ABBREVIATION 23055539 A 459 464 AngIV ABBREVIATION 23055539 A 473 483 norleucine TRIVIAL 23055539 A 487 501 angiotensin IV TRIVIAL 23055539 A 524 525 N FORMULA 23055539 A 535 546 amino acids FAMILY 23055539 A 548 559 Nle-Tyr-Ile FORMULA 23055539 A 616 626 tripeptide FAMILY 23055539 A 804 805 N FORMULA 23055539 A 811 812 C FORMULA 23055539 A 920 931 scopolamine TRIVIAL 23055539 T 39 53 angiotensin IV TRIVIAL 23057615 A 459 473 phenanthroline SYSTEMATIC 23057615 A 544 556 moxifloxacin TRIVIAL 23057615 A 578 587 quinolone FAMILY 23057615 A 630 636 copper SYSTEMATIC 23057615 A 785 797 moxifloxacin TRIVIAL 23057615 T 101 113 moxifloxacin TRIVIAL 23057615 T 78 90 moxifloxacin TRIVIAL 23057692 A 236 246 ciclopirox TRIVIAL 23059626 A 1239 1242 Met FORMULA 23059626 A 675 678 Met FORMULA 23059626 A 964 967 Met FORMULA 23059626 A 976 979 Met FORMULA 23060096 A 102 120 polyethyleneglycol SYSTEMATIC 23060096 A 14 36 Pt(48)Pd(52)-Fe(3)O(4) FORMULA 23060096 A 159 167 H(2)O(2) FORMULA 23060096 A 182 202 tetramethylbenzidine SYSTEMATIC 23060096 A 204 207 TMB ABBREVIATION 23060096 A 248 270 Pt(48)Pd(52)-Fe(3)O(4) FORMULA 23060096 A 271 274 TMB ABBREVIATION 23060096 A 327 335 H(2)O(2) FORMULA 23060096 A 453 461 H(2)O(2) FORMULA 23060096 A 91 101 oleylamine SYSTEMATIC 23060096 T 12 16 H2O2 FORMULA 23060096 T 46 56 PtPd-Fe3O4 FORMULA 23061607 A 165 178 organosilicon FAMILY 23061607 A 21 28 silicon SYSTEMATIC 23061607 A 46 59 organosilicon FAMILY 23061607 T 0 13 Organosilicon FAMILY 23061635 A 0 7 Menthol TRIVIAL 23061635 A 1028 1035 menthol TRIVIAL 23061635 A 1165 1169 GABA ABBREVIATION 23061635 A 1184 1190 sodium SYSTEMATIC 23061635 A 1270 1277 menthol TRIVIAL 23061635 A 1364 1372 nicotine TRIVIAL 23061635 A 1476 1483 Menthol TRIVIAL 23061635 A 276 283 menthol TRIVIAL 23061635 A 490 497 Menthol TRIVIAL 23061635 A 861 868 calcium SYSTEMATIC 23061635 A 87 98 monoterpene FAMILY 23061635 A 884 891 calcium SYSTEMATIC 23061635 T 0 7 Menthol TRIVIAL 23063002 A 103 115 chlorpyrifos TRIVIAL 23063002 A 120 130 penoxsulam TRIVIAL 23063002 A 225 231 oxygen SYSTEMATIC 23063002 A 443 455 chlorpyrifos TRIVIAL 23063002 A 460 470 penoxsulam TRIVIAL 23063002 T 119 131 chlorpyrifos TRIVIAL 23063002 T 136 146 penoxsulam TRIVIAL 23063066 A 344 357 esfenvalerate TRIVIAL 23063066 A 502 515 esfenvalerate TRIVIAL 23063069 A 1005 1008 PCB ABBREVIATION 23063069 A 1013 1016 DDT ABBREVIATION 23063069 A 583 613 polybrominated diphenyl ethers FAMILY 23063069 A 615 620 PBDEs ABBREVIATION 23063069 A 623 648 polychlorinated biphenyls FAMILY 23063069 A 650 654 PCBs ABBREVIATION 23063069 A 660 691 dichlorodiphenyltrichloroethane SYSTEMATIC 23063069 A 878 883 PBDEs ABBREVIATION 23063411 A 0 13 Actinomycin D TRIVIAL 23063411 A 1076 1089 actinomycin D TRIVIAL 23063411 A 1217 1230 actinomycin D TRIVIAL 23063411 A 1293 1306 actinomycin D TRIVIAL 23063411 A 1546 1559 actinomycin D TRIVIAL 23063411 A 1682 1695 actinomycin D TRIVIAL 23063411 A 1799 1812 actinomycin D TRIVIAL 23063411 A 287 300 actinomycin D TRIVIAL 23063411 A 704 717 actinomycin D TRIVIAL 23063411 A 918 931 Actinomycin D TRIVIAL 23063411 T 104 117 actinomycin D TRIVIAL 23063590 A 0 11 Cholesterol TRIVIAL 23063590 A 1015 1026 cholesterol TRIVIAL 23063590 A 1067 1092 hydroxymethylglutaryl CoA SYSTEMATIC 23063590 A 1094 1101 HMG CoA ABBREVIATION 23063590 A 1299 1315 artemisinic acid TRIVIAL 23063590 A 1357 1364 HMG CoA ABBREVIATION 23063590 A 1438 1454 artemisinic acid TRIVIAL 23063590 A 190 206 artemisinic acid TRIVIAL 23063590 A 314 330 artemisinic acid TRIVIAL 23063590 A 530 546 artemisinic acid TRIVIAL 23063590 A 724 740 artemisinic acid TRIVIAL 23063590 A 755 759 cAMP ABBREVIATION 23063590 A 826 842 artemisinic acid TRIVIAL 23063590 A 912 928 artemisinic acid TRIVIAL 23063590 A 960 976 artemisinic acid TRIVIAL 23063590 T 0 16 Artemisinic acid TRIVIAL 23063590 T 98 105 HMG-CoA ABBREVIATION 23063593 A 0 10 Herbacetin TRIVIAL 23063593 A 1046 1049 HER ABBREVIATION 23063593 A 1107 1127 phosphatidylinositol TRIVIAL 23063593 A 1154 1162 LY294002 IDENTIFIER 23063593 A 1198 1201 HER ABBREVIATION 23063593 A 12 15 HER ABBREVIATION 23063593 A 1264 1267 HER ABBREVIATION 23063593 A 225 228 HER ABBREVIATION 23063593 A 30 39 flavonoid FAMILY 23063593 A 400 403 HER ABBREVIATION 23063593 A 470 487 poly (ADP-ribose) SYSTEMATIC 23063593 A 516 519 HER ABBREVIATION 23063593 A 836 839 HER ABBREVIATION 23063593 A 901 920 N-Acetyl-l-cysteine SYSTEMATIC 23063593 A 922 925 NAC ABBREVIATION 23063593 A 977 980 HER ABBREVIATION 23063593 T 0 10 Herbacetin TRIVIAL 23065696 A 1283 1289 (13) C FORMULA 23065696 A 197 203 (13) C FORMULA 23065696 A 359 365 (13) C FORMULA 23065696 A 621 627 carbon SYSTEMATIC 23066090 A 183 187 cAMP ABBREVIATION 23066090 A 389 471 3-(5-tert-butyl-isoxazol-3-yl)-2-[(3-chloro-phenyl)-hydrazono]-3-oxo-propionitrile SYSTEMATIC 23066090 A 39 43 cAMP ABBREVIATION 23066090 A 473 479 ESI-09 IDENTIFIER 23066090 A 500 510 nucleotide FAMILY 23066090 A 55 59 cAMP ABBREVIATION 23066821 A 19 32 callylactam A TRIVIAL 23066821 A 41 53 callyimine A TRIVIAL 23066949 A 1083 1095 GlcNAcstatin FAMILY 23066949 A 352 364 GlcNAcstatin FAMILY 23066949 A 4 16 GlcNAcstatin FAMILY 23066949 A 458 467 imidazole SYSTEMATIC 23066949 A 468 476 nitrogen SYSTEMATIC 23066949 A 485 497 GlcNAcstatin FAMILY 23066949 A 57 68 2-acetamino SYSTEMATIC 23066949 A 690 699 aspartate TRIVIAL 23066949 A 849 852 Asp FORMULA 23066949 A 857 860 Asp FORMULA 23066949 A 869 872 Asp FORMULA 23066949 A 893 905 GlcNAcstatin FAMILY 23066949 T 58 70 GlcNAcstatin FAMILY 23068419 A 1262 1270 tyrosine TRIVIAL 23068419 A 1366 1372 6-OHDA SYSTEMATIC 23068419 A 297 310 methylparaben SYSTEMATIC 23068419 A 365 382 6-hydroxydopamine SYSTEMATIC 23068419 A 384 390 6-OHDA SYSTEMATIC 23068419 A 532 538 6-OHDA SYSTEMATIC 23068419 A 544 561 hydrogen peroxide SYSTEMATIC 23068419 A 614 620 oxygen SYSTEMATIC 23068419 A 642 648 6-OHDA SYSTEMATIC 23068419 A 794 800 6-OHDA SYSTEMATIC 23068419 A 901 912 apomorphine TRIVIAL 23068419 A 986 992 6-OHDA SYSTEMATIC 23068419 T 0 13 Methylparaben SYSTEMATIC 23068419 T 23 40 6-hydroxydopamine SYSTEMATIC 23069619 A 132 141 ibuprofen TRIVIAL 23069619 A 887 896 ibuprofen TRIVIAL 23069627 A 1030 1043 palmitic acid TRIVIAL 23069627 A 531 538 calcium SYSTEMATIC 23069627 A 636 643 glucose TRIVIAL 23070981 A 235 239 GeTe FORMULA 23070981 T 52 56 GeTe FORMULA 23071106 A 0 11 Tolbutamide TRIVIAL 23071106 A 1055 1077 8-pCPT-2'-O-Me-cAMP-AM SYSTEMATIC 23071106 A 1159 1165 Ca(2+) FORMULA 23071106 A 1236 1263 2-aminoethoxydiphenylborate SYSTEMATIC 23071106 A 1265 1270 2-APB SYSTEMATIC 23071106 A 1304 1310 Ca(2+) FORMULA 23071106 A 1312 1334 8-pCPT-2'-O-Me-cAMP-AM SYSTEMATIC 23071106 A 1383 1394 tolbutamide TRIVIAL 23071106 A 1421 1426 2-APB SYSTEMATIC 23071106 A 1469 1490 bisindolylmaleimide I SYSTEMATIC 23071106 A 1545 1556 tolbutamide TRIVIAL 23071106 A 1561 1571 gliclazide TRIVIAL 23071106 A 1600 1622 8-pCPT-2'-O-Me-cAMP-AM SYSTEMATIC 23071106 A 1629 1639 gliclazide TRIVIAL 23071106 A 1741 1763 8-pCPT-2'-O-Me-cAMP-AM SYSTEMATIC 23071106 A 1827 1832 2-APB SYSTEMATIC 23071106 A 1843 1849 Ca(2+) FORMULA 23071106 A 205 209 cAMP ABBREVIATION 23071106 A 217 239 8-pCPT-2'-O-Me-cAMP-AM SYSTEMATIC 23071106 A 369 380 tolbutamide TRIVIAL 23071106 A 391 401 gliclazide TRIVIAL 23071106 A 486 498 thapsigargin TRIVIAL 23071106 A 520 526 Ca(2+) FORMULA 23071106 A 543 554 nicardipine TRIVIAL 23071106 A 585 607 8-pCPT-2'-O-Me-cAMP-AM SYSTEMATIC 23071106 A 648 654 Ca(2+) FORMULA 23071106 A 687 698 tolbutamide TRIVIAL 23071106 A 702 712 gliclazide TRIVIAL 23071106 A 731 743 thapsigargin TRIVIAL 23071106 A 747 758 nicardipine TRIVIAL 23071106 A 847 858 tolbutamide TRIVIAL 23071106 A 863 873 gliclazide TRIVIAL 23071106 A 925 935 gliclazide TRIVIAL 23071106 A 976 977 K FORMULA 23071106 A 978 981 ATP ABBREVIATION 23071106 T 115 125 gliclazide TRIVIAL 23071106 T 16 28 sulfonylurea FAMILY 23071106 T 57 61 cAMP ABBREVIATION 23071106 T 99 110 tolbutamide TRIVIAL 23071294 A 763 774 cholesterol TRIVIAL 23071294 A 899 910 cholesterol TRIVIAL 23073171 A 1198 1201 CLA ABBREVIATION 23073171 A 1260 1263 CLA ABBREVIATION 23073171 A 394 397 CLA ABBREVIATION 23073171 A 497 500 CLA ABBREVIATION 23073171 A 65 78 linoleic acid TRIVIAL 23073171 A 654 661 glucose TRIVIAL 23073171 A 80 83 CLA ABBREVIATION 23073171 A 988 991 CLA ABBREVIATION 23073171 T 148 155 glucose TRIVIAL 23073171 T 22 35 linoleic acid TRIVIAL 23074021 A 0 13 Methyleugenol TRIVIAL 23074021 A 1115 1118 MEG ABBREVIATION 23074021 A 1379 1382 MEG ABBREVIATION 23074021 A 15 18 MEG ABBREVIATION 23074021 A 274 277 MEG ABBREVIATION 23074021 A 412 415 MEG ABBREVIATION 23074021 A 547 550 MEG ABBREVIATION 23074021 A 717 720 MEG ABBREVIATION 23074021 A 807 810 MEG ABBREVIATION 23074021 A 877 888 glutathione TRIVIAL 23074021 A 889 890 S FORMULA 23074021 T 24 37 methyleugenol SYSTEMATIC 23074035 A 168 175 PNIPAAm ABBREVIATION 23074035 A 269 276 PNIPAAm ABBREVIATION 23074035 A 281 285 PMMA ABBREVIATION 23074035 A 77 91 PMMA-b-PNIPAAm ABBREVIATION 23074088 A 843 851 carboxyl SYSTEMATIC 23074173 A 0 11 Deferasirox TRIVIAL 23074173 A 1106 1117 deferasirox TRIVIAL 23074173 A 1268 1279 deferasirox TRIVIAL 23074173 A 1584 1600 poly(ADP-ribose) SYSTEMATIC 23074173 A 1649 1660 deferasirox TRIVIAL 23074173 A 186 201 desferrioxamine TRIVIAL 23074173 A 203 206 DFO ABBREVIATION 23074173 A 243 246 DFO ABBREVIATION 23074173 A 322 326 iron SYSTEMATIC 23074173 A 35 39 iron SYSTEMATIC 23074173 A 41 43 Fe FORMULA 23074173 A 516 527 deferasirox TRIVIAL 23074173 A 562 573 Deferasirox TRIVIAL 23074173 A 711 714 DFO ABBREVIATION 23074173 A 729 740 deferasirox TRIVIAL 23074173 A 795 798 DFO ABBREVIATION 23074173 A 822 828 (59)Fe FORMULA 23074173 A 90 94 iron SYSTEMATIC 23074173 A 916 927 deferasirox TRIVIAL 23074173 T 19 30 deferasirox TRIVIAL 23074173 T 4 8 iron SYSTEMATIC 23076553 A 1007 1014 halogen FAMILY 23076553 A 1159 1166 halogen FAMILY 23076553 A 116 125 NHn(X3-n) FAMILY 23076553 A 1240 1247 halogen FAMILY 23076553 A 1379 1389 Lewis base FAMILY 23076553 A 1398 1405 halogen FAMILY 23076553 A 1438 1448 Lewis acid FAMILY 23076553 A 1507 1514 halogen FAMILY 23076553 A 156 159 CH3 FORMULA 23076553 A 162 163 F FORMULA 23076553 A 168 179 Lewis bases FAMILY 23076553 A 1717 1718 N FORMULA 23076553 A 1739 1741 Cl FORMULA 23076553 A 1765 1766 N FORMULA 23076553 A 1767 1769 Cl FORMULA 23076553 A 184 185 F FORMULA 23076553 A 186 188 Cl FORMULA 23076553 A 201 211 Lewis acid FAMILY 23076553 A 452 453 F FORMULA 23076553 A 454 456 Cl FORMULA 23076553 A 459 462 NF3 FORMULA 23076553 A 46 48 Cl FORMULA 23076553 A 486 487 F FORMULA 23076553 A 488 490 Cl FORMULA 23076553 A 493 500 N(CH3)3 FORMULA 23076553 A 51 52 N FORMULA 23076553 T 10 17 halogen FAMILY 23077105 A 1080 1093 actinomycin D TRIVIAL 23077105 A 1189 1276 7α,17β-[9-[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol SYSTEMATIC 23077105 A 1278 1288 ICI182/780 IDENTIFIER 23077105 A 151 167 ethynylestradiol SYSTEMATIC 23077105 A 1606 1616 ICI182/780 IDENTIFIER 23077105 A 198 206 estrogen FAMILY 23077105 A 514 522 estrogen FAMILY 23077105 A 685 695 bile salts FAMILY 23077105 A 700 711 glutathione TRIVIAL 23077105 T 129 137 estrogen FAMILY 23077105 T 66 82 ethynylestradiol SYSTEMATIC 23078542 A 533 541 dopamine TRIVIAL 23079231 A 1071 1080 sirolimus TRIVIAL 23079231 A 1210 1218 curcumin TRIVIAL 23079231 A 1270 1279 sirolimus TRIVIAL 23079231 A 1367 1375 curcumin TRIVIAL 23079231 A 1395 1404 sirolimus TRIVIAL 23079231 A 1473 1481 curcumin TRIVIAL 23079231 A 1500 1509 sirolimus TRIVIAL 23079231 A 1528 1537 sirolimus TRIVIAL 23079231 A 1560 1568 curcumin TRIVIAL 23079231 A 1663 1671 curcumin TRIVIAL 23079231 A 1676 1685 sirolimus TRIVIAL 23079231 A 1756 1764 curcumin TRIVIAL 23079231 A 1769 1778 sirolimus TRIVIAL 23079231 A 205 214 sirolimus TRIVIAL 23079231 A 22 31 sirolimus TRIVIAL 23079231 A 257 265 curcumin TRIVIAL 23079231 A 36 44 curcumin TRIVIAL 23079231 A 705 719 (3)H-thymidine SYSTEMATIC 23079231 A 748 756 curcumin TRIVIAL 23079231 A 877 885 Curcumin TRIVIAL 23079231 A 956 964 curcumin TRIVIAL 23079231 T 60 69 sirolimus TRIVIAL 23079231 T 92 100 curcumin TRIVIAL 23080539 A 1019 1030 doxycycline TRIVIAL 23081912 A 106 110 TCDD ABBREVIATION 23081912 A 1110 1123 salicyl amide TRIVIAL 23081912 A 1145 1149 TCDD ABBREVIATION 23081912 A 1154 1164 prochloraz TRIVIAL 23081912 A 127 136 imidazole SYSTEMATIC 23081912 A 147 157 prochloraz TRIVIAL 23081912 A 1559 1569 prochloraz TRIVIAL 23081912 A 1574 1580 dioxin FAMILY 23081912 A 288 304 aryl hydrocarbon FAMILY 23081912 A 342 348 dioxin FAMILY 23081912 A 586 590 TCDD ABBREVIATION 23081912 A 595 605 prochloraz TRIVIAL 23081912 A 69 104 2,3,7,8-tetrachlorodibenzo-p-dioxin SYSTEMATIC 23081912 A 758 762 TCDD ABBREVIATION 23081912 A 766 776 prochloraz TRIVIAL 23081912 A 800 814 Hoechst H33342 IDENTIFIER 23081912 A 897 902 Ko143 IDENTIFIER 23081912 T 10 20 prochloraz TRIVIAL 23081912 T 127 142 arylhydrocarbon FAMILY 23081912 T 49 55 dioxin FAMILY 23081947 A 211 219 chlorine SYSTEMATIC 23081947 A 255 259 AuCl FORMULA 23081947 A 342 350 chlorine SYSTEMATIC 23081947 A 418 426 Chlorine SYSTEMATIC 23081947 A 73 75 Au FORMULA 23081947 A 902 910 chlorine SYSTEMATIC 23081947 A 95 103 chlorine SYSTEMATIC 23081947 T 0 8 Chlorine SYSTEMATIC 23081947 T 38 40 Au FORMULA 23085085 A 63 69 acetyl SYSTEMATIC 23085085 A 82 88 lysine TRIVIAL 23085266 A 1014 1024 wortmannin TRIVIAL 23085266 A 1048 1057 GF109203X IDENTIFIER 23085266 A 1114 1117 Ser FORMULA 23085266 A 1125 1128 Ser FORMULA 23085266 A 1133 1141 SB203580 IDENTIFIER 23085266 A 1146 1151 UO126 IDENTIFIER 23085266 A 1249 1252 Ser FORMULA 23085266 A 1316 1325 genistein TRIVIAL 23085266 A 1330 1340 wortmannin TRIVIAL 23085266 A 1368 1376 SB203580 IDENTIFIER 23085266 A 1378 1383 UO126 IDENTIFIER 23085266 A 1388 1397 GF109203X IDENTIFIER 23085266 A 1457 1462 NADPH ABBREVIATION 23085266 A 1566 1574 tyrosine TRIVIAL 23085266 A 429 466 formyl-methionyl-leucyl-phenylalanine SYSTEMATIC 23085266 A 468 472 fMLF ABBREVIATION 23085266 A 482 507 phorbol myristate acetate SYSTEMATIC 23085266 A 509 512 PMA ABBREVIATION 23085266 A 59 64 NADPH ABBREVIATION 23085266 A 712 717 NADPH ABBREVIATION 23085266 A 781 784 Ser FORMULA 23085266 A 789 792 Ser FORMULA 23085266 A 800 803 Ser FORMULA 23085266 A 9 15 oxygen SYSTEMATIC 23085266 A 949 958 genistein TRIVIAL 23085266 A 981 989 tyrosine TRIVIAL 23085266 T 156 164 tyrosine TRIVIAL 23085266 T 16 21 NADPH ABBREVIATION 23085330 A 0 8 Curcumin TRIVIAL 23085330 A 1174 1179 HPβCD ABBREVIATION 23085330 A 1184 1192 curcumin TRIVIAL 23085330 A 1312 1320 curcumin TRIVIAL 23085330 A 1407 1415 curcumin TRIVIAL 23085330 A 143 151 curcumin TRIVIAL 23085330 A 1466 1474 curcumin TRIVIAL 23085330 A 1559 1567 curcumin TRIVIAL 23085330 A 1701 1709 curcumin TRIVIAL 23085330 A 349 357 curcumin TRIVIAL 23085330 A 554 562 curcumin TRIVIAL 23085330 A 648 656 curcumin TRIVIAL 23085330 A 754 782 hydroxypropyl-β-cyclodextrin SYSTEMATIC 23085330 A 784 789 HPβCD ABBREVIATION 23085330 A 791 799 curcumin TRIVIAL 23085330 A 817 830 Hydroxypropyl SYSTEMATIC 23085330 A 867 875 curcumin TRIVIAL 23085330 T 131 139 curcumin TRIVIAL 23085435 A 0 8 Nitrogen SYSTEMATIC 23085435 A 1094 1095 N FORMULA 23085435 A 20 35 bisphosphonates FAMILY 23085435 A 260 261 N FORMULA 23085435 A 262 265 BPs ABBREVIATION 23085435 A 37 38 N FORMULA 23085435 A 39 42 BPs ABBREVIATION 23085435 A 396 424 geranylgeranyl pyrophosphate SYSTEMATIC 23085435 A 426 430 GGPP ABBREVIATION 23085435 A 459 460 N FORMULA 23085435 A 461 464 BPs ABBREVIATION 23085435 A 656 657 N FORMULA 23085435 A 658 661 BPs ABBREVIATION 23085435 A 900 901 N FORMULA 23085435 A 902 905 BPs ABBREVIATION 23085435 T 0 8 Nitrogen SYSTEMATIC 23085435 T 20 35 bisphosphonates FAMILY 23085979 A 1130 1134 TCDD ABBREVIATION 23085979 A 4 20 aryl hydrocarbon FAMILY 23085979 A 716 751 2,3,7,8-tetrachlorodibenzo-p-dioxin SYSTEMATIC 23085979 A 753 757 TCDD ABBREVIATION 23085979 A 762 794 polycyclic aromatic hydrocarbons FAMILY 23085979 T 0 16 Aryl hydrocarbon FAMILY 23086035 A 639 646 glucose TRIVIAL 23086035 A 718 732 acylcarnitines FAMILY 23086035 A 737 748 sphingosine TRIVIAL 23086035 T 16 23 glucose TRIVIAL 23086038 A 1004 1011 glucose TRIVIAL 23086038 A 596 633 phosphoinositide (3,4,5)-triphosphate SYSTEMATIC 23086197 A 1396 1403 steroid FAMILY 23086197 A 357 362 NADPH ABBREVIATION 23086197 A 502 510 squalene TRIVIAL 23086197 A 531 535 heme FAMILY 23086197 T 0 5 NADPH ABBREVIATION 23086198 A 0 3 UDP ABBREVIATION 23086198 A 1072 1093 1-hydroxy-(OH)-pyrene SYSTEMATIC 23086198 A 1095 1105 1-naphthol SYSTEMATIC 23086198 A 1111 1138 hydroxylated benzo(a)pyrene FAMILY 23086198 A 1257 1261 PAHs ABBREVIATION 23086198 A 1267 1278 1-OH-pyrene SYSTEMATIC 23086198 A 1283 1293 1-naphthol SYSTEMATIC 23086198 A 129 133 PAHs ABBREVIATION 23086198 A 1612 1615 PAH ABBREVIATION 23086198 A 1656 1668 nitrosamines FAMILY 23086198 A 1673 1692 heterocyclic amines FAMILY 23086198 A 1775 1778 PAH ABBREVIATION 23086198 A 1812 1815 PAH ABBREVIATION 23086198 A 1816 1821 diols FAMILY 23086198 A 1916 1936 monohydroxylated PAH FAMILY 23086198 A 193 196 PAH ABBREVIATION 23086198 A 95 127 polycyclic aromatic hydrocarbons FAMILY 23086198 T 14 17 UDP ABBREVIATION 23086703 A 104 123 cyclic pentapeptide FAMILY 23086703 A 124 129 FC131 IDENTIFIER 23086703 A 153 167 dipicolylamine FAMILY 23086703 A 253 279 1,4-phenylenedimethanamine SYSTEMATIC 23086703 A 281 314 naphthalene-2,6-diyldimethanamine SYSTEMATIC 23086703 A 320 358 [1,1'-biphenyl]-4,4'-diyldimethanamine SYSTEMATIC 23086703 A 431 446 2-pyridylmethyl SYSTEMATIC 23086703 A 451 467 1-naphthylmethyl SYSTEMATIC 23086703 A 559 576 1-propylguanidine SYSTEMATIC 23086703 A 581 618 1,1,3,3-tetramethyl-2-propylguanidine SYSTEMATIC 23086703 A 700 708 zinc(II) SYSTEMATIC 23086703 A 725 753 bis(pyridin-2-ylmethyl)amine SYSTEMATIC 23087261 A 1135 1141 lysine TRIVIAL 23087261 A 1264 1267 Lys FORMULA 23087261 A 1424 1427 Lys FORMULA 23087261 T 0 6 Lysine TRIVIAL 23089896 A 1175 1181 Rho123 ABBREVIATION 23089896 A 16 19 ATP ABBREVIATION 23089896 A 230 242 rhodamine123 TRIVIAL 23089896 A 244 250 Rho123 ABBREVIATION 23089896 A 850 862 itraconazole TRIVIAL 23089896 A 909 915 Rho123 ABBREVIATION 23089896 A 998 1004 Rho123 ABBREVIATION 23089896 T 0 3 ATP ABBREVIATION 23091169 A 1083 1093 androstane TRIVIAL 23091169 A 285 298 phenobarbital TRIVIAL 23091169 A 802 811 glutamine TRIVIAL 23091189 A 0 21 Laninamivir octanoate SYSTEMATIC 23091189 A 110 121 laninamivir TRIVIAL 23091189 A 1111 1122 laninamivir TRIVIAL 23091189 A 1346 1357 laninamivir TRIVIAL 23091189 A 1509 1520 laninamivir TRIVIAL 23091189 A 1587 1598 laninamivir TRIVIAL 23091189 A 181 192 laninamivir TRIVIAL 23091189 A 28 34 Inavir TRIVIAL 23091189 A 565 576 laninamivir TRIVIAL 23091189 A 65 70 ester FAMILY 23091189 A 708 719 laninamivir TRIVIAL 23091189 A 824 829 (14)C FORMULA 23091189 T 158 179 laninamivir octanoate SYSTEMATIC 23091189 T 70 81 laninamivir TRIVIAL 23092136 A 1164 1172 hydrogen SYSTEMATIC 23092237 A 141 144 ZnO FORMULA 23092237 T 62 65 ZnO FORMULA 23092395 A 1067 1079 β-sitosterol TRIVIAL 23092395 A 1084 1096 stigmasterol TRIVIAL 23092395 A 208 214 hexane SYSTEMATIC 23092395 A 216 224 methanol SYSTEMATIC 23092395 A 461 491 2,2-diphenyl-1-picryl-hydrazyl SYSTEMATIC 23092395 A 496 502 Fe(3+) FORMULA 23092395 A 503 517 Phenanthroline TRIVIAL 23092395 A 594 604 flavonoids FAMILY 23092395 A 660 668 steroids FAMILY 23092395 A 689 696 tannins FAMILY 23092395 A 786 792 hexane SYSTEMATIC 23092395 A 909 943 3,5,4'-trimethoxy-4-prenylstilbene SYSTEMATIC 23092395 A 945 958 lonchocarpine TRIVIAL 23092395 A 960 982 4-hydroxylonchocarpine SYSTEMATIC 23092395 A 987 998 derricidine TRIVIAL 23092723 A 1217 1225 methanol SYSTEMATIC 23092723 A 1227 1234 ethanol SYSTEMATIC 23092723 A 180 187 hexanes FAMILY 23092723 A 189 197 methanol SYSTEMATIC 23092723 A 202 217 dichloromethane SYSTEMATIC 23092723 A 327 330 MTT ABBREVIATION 23092723 A 405 412 ethanol SYSTEMATIC 23092723 A 588 597 celastrol TRIVIAL 23092723 A 675 683 methanol SYSTEMATIC 23092723 A 685 692 ethanol SYSTEMATIC 23092723 A 790 798 methanol SYSTEMATIC 23092723 A 904 919 dichloromethane SYSTEMATIC 23092877 A 1053 1063 nandrolone TRIVIAL 23092877 A 1552 1559 steroid FAMILY 23092877 A 205 212 steroid FAMILY 23092877 A 213 223 nandrolone TRIVIAL 23092877 A 251 271 nandrolone decanoate SYSTEMATIC 23092877 A 991 1001 nandrolone TRIVIAL 23092894 A 183 192 Glutamate TRIVIAL 23092894 A 32 41 glutamate TRIVIAL 23092894 A 346 355 Glutamate TRIVIAL 23092894 A 433 442 Glutamate TRIVIAL 23092894 A 644 653 Glutamate TRIVIAL 23092894 A 994 1003 glutamate TRIVIAL 23092894 T 26 35 glutamate TRIVIAL 23094599 A 0 7 Silicon SYSTEMATIC 23094599 A 246 253 silicon SYSTEMATIC 23094599 A 467 474 silicon SYSTEMATIC 23094599 A 780 784 Si-C FORMULA 23094599 A 795 801 Si-O-C FORMULA 23094599 A 825 832 silicon SYSTEMATIC 23094599 A 898 902 Si-N FORMULA 23094599 T 0 7 Silicon SYSTEMATIC 23094599 T 44 48 Si-N FORMULA 23094864 A 1115 1120 TSIIA ABBREVIATION 23094864 A 14 28 Tanshinone IIA TRIVIAL 23094864 A 144 175 Sodium tanshinone IIA sulfonate SYSTEMATIC 23094864 A 177 180 STS ABBREVIATION 23094864 A 215 220 TSIIA ABBREVIATION 23094864 A 30 35 TSIIA ABBREVIATION 23094864 A 38 54 cryptotanshinone TRIVIAL 23094864 A 438 443 TSIIA ABBREVIATION 23094864 A 471 481 tanshinone FAMILY 23094864 A 588 593 TSIIA ABBREVIATION 23094864 A 59 71 tanshinone I TRIVIAL 23094864 A 799 804 TSIIA ABBREVIATION 23094864 A 874 879 TSIIA ABBREVIATION 23094864 A 884 896 tanshinone I TRIVIAL 23094864 A 996 1006 tanshinone FAMILY 23094864 T 0 10 Tanshinone FAMILY 23095167 A 144 151 kainate TRIVIAL 23095167 A 171 180 glutamate TRIVIAL 23095167 A 354 361 Kainate TRIVIAL 23095167 A 560 567 kainate TRIVIAL 23095167 A 763 770 kainate TRIVIAL 23095167 T 0 7 Kainate TRIVIAL 23095244 A 0 7 Ecstasy TRIVIAL 23095244 A 1316 1323 ecstasy TRIVIAL 23095244 A 186 193 Ecstasy TRIVIAL 23095244 A 260 267 ecstasy TRIVIAL 23095244 A 397 404 ecstasy TRIVIAL 23095244 A 468 475 ecstasy TRIVIAL 23095244 A 946 953 Ecstasy TRIVIAL 23095244 T 20 27 ecstasy TRIVIAL 23097024 A 1454 1456 NO FORMULA 23097024 A 970 982 nitric oxide SYSTEMATIC 23097351 A 10 17 alcohol FAMILY 23097351 A 121 128 ethanol SYSTEMATIC 23097351 A 266 277 flavonoidal FAMILY 23097351 A 320 330 naringenin TRIVIAL 23097351 A 332 344 aromadendrin TRIVIAL 23097351 A 346 354 apigenin TRIVIAL 23097351 A 359 400 4'-O-methoxy-luteolin-7-O-rhamnoglucoside SYSTEMATIC 23097351 A 515 522 alcohol FAMILY 23097351 A 582 611 1,1-diphenyl,2-picrylhydrazyl SYSTEMATIC 23097351 A 670 711 4'-O-methoxy-luteolin-7-O-rhamnoglucoside SYSTEMATIC 23097351 A 754 761 alcohol FAMILY 23097351 T 56 66 flavonoids FAMILY 23098805 A 1034 1041 cocaine TRIVIAL 23098805 A 1076 1083 cocaine TRIVIAL 23098805 A 117 124 cocaine TRIVIAL 23098805 A 1191 1200 estradiol TRIVIAL 23098805 A 1205 1217 progesterone TRIVIAL 23098805 A 1224 1232 estrogen FAMILY 23098805 A 1284 1296 progesterone TRIVIAL 23098805 A 1393 1400 cocaine TRIVIAL 23098805 A 1568 1575 cocaine TRIVIAL 23098805 A 253 260 cocaine TRIVIAL 23098805 A 546 553 cocaine TRIVIAL 23098805 A 77 84 cocaine TRIVIAL 23098805 A 891 900 estradiol TRIVIAL 23098805 A 905 917 progesterone TRIVIAL 23098805 T 36 43 cocaine TRIVIAL 23098818 A 1028 1035 quinine TRIVIAL 23098818 A 1040 1050 fluoxetine TRIVIAL 23098818 A 1111 1130 5-methoxytryptamine SYSTEMATIC 23098818 A 1134 1143 serotonin TRIVIAL 23098818 A 1287 1296 serotonin TRIVIAL 23098818 A 1302 1321 5-methoxytryptamine SYSTEMATIC 23098818 A 1382 1391 serotonin TRIVIAL 23098818 A 264 265 O FORMULA 23098818 A 283 302 5-methoxytryptamine SYSTEMATIC 23098818 A 306 315 serotonin TRIVIAL 23098818 A 369 378 serotonin TRIVIAL 23098818 A 6 15 serotonin TRIVIAL 23098818 A 752 753 O FORMULA 23098818 A 771 790 5-methoxytryptamine SYSTEMATIC 23098818 A 794 803 serotonin TRIVIAL 23098818 A 934 953 5-methoxytryptamine SYSTEMATIC 23098818 A 957 966 serotonin TRIVIAL 23098818 T 64 73 serotonin TRIVIAL 23098818 T 79 98 5-methoxytryptamine SYSTEMATIC 23098879 A 29 79 1α, 6α-epoxy-9-oxo-10β-hydroxyl-furanoeremophilane SYSTEMATIC 23098879 A 314 319 C1-C6 FORMULA 23098879 A 320 326 oxygen SYSTEMATIC 23098879 A 337 355 furanoeremophilane FAMILY 23098879 A 8 27 furanoeremophilanes FAMILY 23098879 A 89 136 9-oxo-1α, 6β, 10β-trihydroxy-furanoeremophilane SYSTEMATIC 23098879 T 43 49 oxygen SYSTEMATIC 23098879 T 8 26 furanoeremophilane FAMILY 23098993 A 595 604 HC 030031 IDENTIFIER 23098993 A 729 738 capsaicin TRIVIAL 23099337 A 177 184 cadmium SYSTEMATIC 23099337 A 254 262 Caffeine TRIVIAL 23099337 A 275 282 cadmium SYSTEMATIC 23099337 A 333 340 cadmium SYSTEMATIC 23099337 A 381 391 superoxide TRIVIAL 23099337 A 436 444 Caffeine TRIVIAL 23099337 A 482 493 glutathione TRIVIAL 23099337 A 529 536 cadmium SYSTEMATIC 23099337 A 56 64 caffeine TRIVIAL 23099337 A 746 753 cadmium SYSTEMATIC 23099337 A 85 92 cadmium SYSTEMATIC 23099337 A 853 861 Caffeine TRIVIAL 23099337 A 885 892 cadmium SYSTEMATIC 23099337 T 0 8 Caffeine TRIVIAL 23099337 T 17 24 cadmium SYSTEMATIC 23099339 A 110 119 vitamin C TRIVIAL 23099339 A 384 394 folic acid TRIVIAL 23099339 A 399 408 vitamin C TRIVIAL 23099339 A 448 457 resazurin TRIVIAL 23099339 A 598 607 vitamin C TRIVIAL 23099339 A 621 631 folic acid TRIVIAL 23099339 A 778 785 glucose TRIVIAL 23099339 A 786 801 hydroxybutyrate SYSTEMATIC 23099339 A 95 105 folic acid TRIVIAL 23099339 T 122 131 vitamin C TRIVIAL 23099339 T 136 146 folic acid TRIVIAL 23099645 A 1215 1237 5-Aza-2'-deoxycytidine SYSTEMATIC 23099645 A 1343 1357 trichostatin A TRIVIAL 23099811 A 1039 1052 methylmercury SYSTEMATIC 23099811 A 1054 1058 MeHg FORMULA 23099811 A 1087 1088 N FORMULA 23099811 A 1127 1132 (15)N FORMULA 23099811 A 1159 1164 (13)C FORMULA 23099811 A 1340 1345 (13)C FORMULA 23099811 A 1389 1394 (13)C FORMULA 23099811 A 1463 1468 (13)C FORMULA 23099811 A 155 161 carbon SYSTEMATIC 23099811 A 1571 1577 carbon SYSTEMATIC 23099811 A 1778 1784 carbon SYSTEMATIC 23099811 A 2048 2052 MeHg FORMULA 23099811 A 2217 2221 MeHg FORMULA 23099811 A 246 253 mercury SYSTEMATIC 23099811 A 45 52 mercury SYSTEMATIC 23099811 A 492 499 mercury SYSTEMATIC 23099811 A 501 503 Hg FORMULA 23099811 A 528 534 carbon SYSTEMATIC 23099811 A 537 542 (13)C FORMULA 23099811 A 548 556 nitrogen SYSTEMATIC 23099811 A 559 564 (15)N FORMULA 23099811 A 626 630 MeHg FORMULA 23099811 A 650 655 (13)C FORMULA 23099811 A 705 710 (13)C FORMULA 23099811 A 764 768 MeHg FORMULA 23099811 A 820 825 (15)N FORMULA 23099811 A 871 876 (13)C FORMULA 23099811 A 916 918 Hg FORMULA 23099811 T 21 27 carbon SYSTEMATIC 23099811 T 31 38 mercury SYSTEMATIC 23102508 A 1021 1030 miltirone TRIVIAL 23102508 A 1176 1187 tanshinones FAMILY 23102508 A 1225 1234 miltirone TRIVIAL 23102508 A 1252 1269 dihydrotanshinone SYSTEMATIC 23102508 A 1289 1305 cryptotanshinone TRIVIAL 23102508 A 1307 1319 tanshinone I TRIVIAL 23102508 A 1324 1338 tanshinone IIA TRIVIAL 23102508 A 231 240 Miltirone TRIVIAL 23102508 A 250 258 abietane TRIVIAL 23102508 A 264 281 diterpene quinone FAMILY 23102508 A 39 50 tanshinones FAMILY 23102508 A 432 441 miltirone TRIVIAL 23102508 A 548 557 Miltirone TRIVIAL 23102508 A 754 763 miltirone TRIVIAL 23102508 T 68 77 miltirone TRIVIAL 23103297 A 0 11 (-)-Carvone TRIVIAL 23103297 A 1017 1028 (-)-carvone TRIVIAL 23103297 A 1090 1099 carbachol TRIVIAL 23103297 A 1133 1144 (-)-carvone TRIVIAL 23103297 A 1200 1211 (-)-carvone TRIVIAL 23103297 A 1216 1225 verapamil TRIVIAL 23103297 A 1229 1238 carbachol TRIVIAL 23103297 A 1260 1271 (-)-Carvone TRIVIAL 23103297 A 1312 1316 K(+) FORMULA 23103297 A 1359 1368 verapamil TRIVIAL 23103297 A 1376 1387 (-)-carvone TRIVIAL 23103297 A 1465 1476 (-)-carvone TRIVIAL 23103297 A 17 35 monoterpene ketone FAMILY 23103297 A 211 222 (-)-carvone TRIVIAL 23103297 A 304 315 (-)-carvone TRIVIAL 23103297 A 406 417 (-)-carvone TRIVIAL 23103297 A 604 615 (-)-carvone TRIVIAL 23103297 A 656 663 calcium SYSTEMATIC 23103297 A 686 695 verapamil TRIVIAL 23103297 A 730 741 (-)-carvone TRIVIAL 23103297 A 862 866 K(+) FORMULA 23103297 A 927 936 histamine TRIVIAL 23103297 A 948 953 BaCl2 FORMULA 23103297 A 968 977 carbachol TRIVIAL 23103297 T 0 11 (-)-Carvone TRIVIAL 23103426 A 1064 1073 (PhSe)(2) FORMULA 23103426 A 1078 1087 (PhTe)(2) FORMULA 23103426 A 1132 1136 NADH ABBREVIATION 23103426 A 1188 1198 superoxide TRIVIAL 23103426 A 1234 1250 organochalcogens FAMILY 23103426 A 1317 1336 reduced glutathione TRIVIAL 23103426 A 1338 1341 GSH ABBREVIATION 23103426 A 1364 1373 (PhSe)(2) FORMULA 23103426 A 1378 1387 (PhTe)(2) FORMULA 23103426 A 1610 1625 organochalcogen FAMILY 23103426 A 1703 1708 thiol FAMILY 23103426 A 1740 1749 (PhSe)(2) FORMULA 23103426 A 1754 1763 (PhTe)(2) FORMULA 23103426 A 190 209 diphenyl diselenide SYSTEMATIC 23103426 A 1929 1938 (PhSe)(2) FORMULA 23103426 A 1943 1952 (PhTe)(2) FORMULA 23103426 A 211 220 (PhSe)(2) FORMULA 23103426 A 226 246 diphenyl ditelluride SYSTEMATIC 23103426 A 248 257 (PhTe)(2) FORMULA 23103426 A 410 426 organochalcogens FAMILY 23103426 A 440 456 organochalcogens FAMILY 23103426 A 552 561 (PhTe)(2) FORMULA 23103426 A 757 766 (PhSe)(2) FORMULA 23103426 A 897 913 organochalcogens FAMILY 23103426 A 928 944 organochalcogens FAMILY 23103426 T 72 88 organochalcogens FAMILY 23103568 A 1297 1305 estrogen FAMILY 23103568 A 176 185 estrogens FAMILY 23103568 A 257 265 estrogen FAMILY 23103568 A 339 348 lapatinib TRIVIAL 23103568 A 388 396 Estrogen FAMILY 23103568 A 522 530 estrogen FAMILY 23103568 A 64 73 estradiol TRIVIAL 23103568 A 843 851 tyrosine TRIVIAL 23103568 T 0 8 Estrogen FAMILY 23104244 A 1183 1200 7-ethoxyresorufin SYSTEMATIC 23104244 A 1215 1233 7-pentoxyresorufin SYSTEMATIC 23104244 A 1253 1266 chlorzoxazone SYSTEMATIC 23104244 A 807 824 7-ethoxyresorufin SYSTEMATIC 23104244 A 825 826 O FORMULA 23104244 A 839 857 7-pentoxyresorufin SYSTEMATIC 23104244 A 858 859 O FORMULA 23104244 A 877 890 chlorzoxazone SYSTEMATIC 23104244 A 914 923 midazolam TRIVIAL 23104245 A 0 21 Gamma-hydroxybutyrate SYSTEMATIC 23104245 A 1013 1019 1,4-BD SYSTEMATIC 23104245 A 1024 1027 GBL ABBREVIATION 23104245 A 1071 1074 GHB ABBREVIATION 23104245 A 1112 1118 1,4-BD SYSTEMATIC 23104245 A 1123 1126 GBL ABBREVIATION 23104245 A 1132 1135 GHB ABBREVIATION 23104245 A 198 201 GHB ABBREVIATION 23104245 A 214 220 1,4-BD SYSTEMATIC 23104245 A 23 26 GHB ABBREVIATION 23104245 A 236 239 GBL ABBREVIATION 23104245 A 313 316 GHB ABBREVIATION 23104245 A 318 324 1,4-BD SYSTEMATIC 23104245 A 326 329 GBL ABBREVIATION 23104245 A 48 62 1,4-butanediol SYSTEMATIC 23104245 A 590 593 GHB ABBREVIATION 23104245 A 64 70 1,4-BD SYSTEMATIC 23104245 A 828 831 GBL ABBREVIATION 23104245 A 835 841 1,4-BD SYSTEMATIC 23104245 A 97 100 GBL ABBREVIATION 23104245 A 996 999 GHB ABBREVIATION 23104245 T 118 121 GBL ABBREVIATION 23104245 T 40 61 gamma-hydroxybutyrate SYSTEMATIC 23104245 T 63 66 GHB ABBREVIATION 23104245 T 69 83 1,4-butanediol SYSTEMATIC 23104245 T 85 91 1,4-BD SYSTEMATIC 23104245 T 97 116 gamma-butyrolactone SYSTEMATIC 23104419 A 1184 1191 lactate FAMILY 23104419 A 1251 1259 creatine TRIVIAL 23104419 A 1380 1391 methimazole TRIVIAL 23104419 A 273 284 methimazole TRIVIAL 23104419 A 499 507 Androgen FAMILY 23104419 A 59 67 androgen FAMILY 23104419 A 622 634 testosterone TRIVIAL 23104419 A 639 648 estradiol TRIVIAL 23104419 A 710 722 testosterone TRIVIAL 23104419 A 743 752 estradiol TRIVIAL 23104419 A 815 823 Androgen FAMILY 23104419 T 78 86 androgen FAMILY 23104982 A 41 47 serine TRIVIAL 23104982 A 741 782 Ala-Pro-7-amido-4-trifluoromethylcoumarin SYSTEMATIC 23106229 A 863 874 beauvericin TRIVIAL 23106229 A 878 890 depsipeptide FAMILY 23106482 A 213 221 bergenin TRIVIAL 23106482 A 227 233 emodin TRIVIAL 23106482 A 239 251 caffeic acid TRIVIAL 23106482 A 257 266 nobiletin TRIVIAL 23106482 A 272 365 3-O-β-d-galactopyranosyl-hederagenin 28-O-β-d-xylopyranosyl(1 → 6)-β-d-galactopyranosyl ester SYSTEMATIC 23106482 A 30 96 (2R*,3S*,5S*)-N,2-dimethyl-3-hydroxy-5-(10-phenyldecyl)pyrrolidine SYSTEMATIC 23106482 A 371 380 coniferin TRIVIAL 23106482 A 386 403 qingyangshengenin TRIVIAL 23106482 A 409 424 methylconiferin SYSTEMATIC 23106482 A 430 469 syringaresinol 4'-O-β-d-glucopyranoside SYSTEMATIC 23106482 A 476 486 gagaminine TRIVIAL 23106482 A 493 504 perlolyrine TRIVIAL 23106482 A 511 546 (S)-1-(1'-hydroxyethyl)-β-carboline SYSTEMATIC 23106482 A 553 602 1-(β-carboline-1-yl)-3,4,5-trihydroxy-1-pentanone SYSTEMATIC 23106482 A 609 638 1-methoxycarbonyl-β-carboline SYSTEMATIC 23106482 A 645 667 indolo[2,3-α]carbazole SYSTEMATIC 23106482 A 674 709 4-hydroxycinnamic acid methyl ester SYSTEMATIC 23106482 A 720 802 methyl 4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethyl] ferulate SYSTEMATIC 23106482 A 8 28 pyrrolidine alkaloid FAMILY 23106482 A 857 865 N-methyl SYSTEMATIC 23108214 A 342 355 carbohydrates FAMILY 23109233 A 1194 1200 Cu(2+) FORMULA 23109233 A 1218 1232 Cu(2+) -Zn(2+) FORMULA 23109233 A 1285 1298 Cu(2+) -Ag(+) FORMULA 23109233 A 170 175 Ag(+) FORMULA 23109233 A 180 186 Zn(2+) FORMULA 23109233 A 193 195 Cu FORMULA 23109233 A 222 224 Ag FORMULA 23109233 A 251 253 Zn FORMULA 23109233 A 396 401 Ag(+) FORMULA 23109233 A 424 426 Ag FORMULA 23109233 A 440 442 Cu FORMULA 23109233 A 456 458 Zn FORMULA 23109233 A 469 475 Cu(2+) FORMULA 23109233 A 534 539 Ag(+) FORMULA 23109233 A 544 550 Zn(2+) FORMULA 23109233 A 653 655 Cu FORMULA 23109233 A 673 675 Ag FORMULA 23109233 A 693 695 Zn FORMULA 23109233 A 823 837 Cu(2+) -Zn(2+) FORMULA 23109233 A 842 855 Cu(2+) -Ag(+) FORMULA 23109233 A 96 102 Cu(2+) FORMULA 23109233 T 44 57 Cu(2+) -Ag(+) FORMULA 23109233 T 60 74 Cu(2+) -Zn(2+) FORMULA 23109279 A 0 8 Fipronil TRIVIAL 23109279 A 1009 1017 fipronil TRIVIAL 23109279 A 1059 1075 fipronil sulfide SYSTEMATIC 23109279 A 1116 1124 fipronil TRIVIAL 23109279 A 1132 1148 fipronil sulfide SYSTEMATIC 23109279 A 1181 1197 fipronil sulfone SYSTEMATIC 23109279 A 1528 1536 fipronil TRIVIAL 23109279 A 196 204 fipronil TRIVIAL 23109279 A 371 379 fipronil TRIVIAL 23109279 A 499 507 fipronil TRIVIAL 23109279 A 568 576 fipronil TRIVIAL 23109279 T 49 57 fipronil TRIVIAL 23110522 A 1032 1040 platinum SYSTEMATIC 23110522 A 150 158 graphite TRIVIAL 23110522 A 178 186 hydrogen SYSTEMATIC 23110522 A 188 202 carbon dioxide SYSTEMATIC 23110522 A 204 219 sulfur trioxide SYSTEMATIC 23110522 A 224 238 carbon dioxide SYSTEMATIC 23110522 A 239 254 sulfur trioxide SYSTEMATIC 23110522 A 309 317 hydrogen SYSTEMATIC 23110522 A 32 40 graphene TRIVIAL 23110522 A 327 342 carboxylic acid SYSTEMATIC 23110522 A 352 365 sulfonic acid SYSTEMATIC 23110522 A 379 394 carboxylic acid SYSTEMATIC 23110522 A 395 408 sulfonic acid SYSTEMATIC 23110522 A 570 576 oxygen SYSTEMATIC 23110522 A 895 903 graphite TRIVIAL 23110522 A 927 933 sulfur SYSTEMATIC 23110522 T 147 153 oxygen SYSTEMATIC 23110522 T 58 66 graphene TRIVIAL 23111282 A 599 609 fatty acid FAMILY 23111282 A 614 625 cholesterol TRIVIAL 23111374 A 0 16 Organophosphorus FAMILY 23111374 A 1024 1030 oximes FAMILY 23111374 A 1031 1035 HI-6 IDENTIFIER 23111374 A 1037 1046 Obidoxime TRIVIAL 23111374 A 1051 1064 2-Pralidoxime SYSTEMATIC 23111374 A 1066 1071 2-PAM SYSTEMATIC 23111374 A 1187 1192 2-PAM SYSTEMATIC 23111374 A 1236 1245 obidoxime TRIVIAL 23111374 A 1250 1254 HI-6 IDENTIFIER 23111374 A 1378 1383 2-PAM SYSTEMATIC 23111374 A 233 236 P-O FORMULA 23111374 A 261 267 serine TRIVIAL 23111374 A 324 363 pyridinium and bis-pyridinium aldoximes MULTIPLE 23111374 A 658 664 oximes FAMILY 23111374 A 748 753 tabun TRIVIAL 23111374 A 868 873 oxime SYSTEMATIC 23111374 T 105 121 organophosphorus FAMILY 23111684 A 140 148 PNTOPAHP ABBREVIATION 23111684 A 32 139 4,8,11,14,15-pentanitro-2,6,9,13-tetraoxa-4,8,11,14,15-pentaazaheptacyclo [5.5.1.1(3,11).1(5,9)]pentadecane SYSTEMATIC 23111684 A 823 877 4,10-dinitro-2,6,8,12-tetraoxa-4,10-diazaisowurtzitane SYSTEMATIC 23111684 A 878 881 TEX ABBREVIATION 23111684 A 959 962 TEX ABBREVIATION 23111684 A 977 984 N-NO(2) FORMULA 23111684 T 64 171 4,8,11,14,15-pentanitro-2,6,9,13-tetraoxa-4,8,11,14,15-pentaazaheptacyclo[5.5.1.1(3,11).1(5,9)] pentadecane SYSTEMATIC 23111879 A 1072 1075 HCl FORMULA 23111879 A 1172 1177 FeCl3 FORMULA 23111879 A 1420 1425 FeCl3 FORMULA 23111879 A 1461 1463 Fe FORMULA 23111879 A 296 311 Ferric chloride SYSTEMATIC 23111879 A 444 451 bromide SYSTEMATIC 23111879 A 453 457 Iron SYSTEMATIC 23111879 A 515 520 FeCl3 FORMULA 23111879 A 564 567 HCl FORMULA 23111879 A 629 641 FeCl3 • 6H2O FORMULA 23111879 A 762 767 FeCl3 FORMULA 23111879 A 826 831 FeCl3 FORMULA 23111879 A 930 935 FeCl3 FORMULA 23111879 A 946 948 Fe FORMULA 23111879 A 978 983 FeCl3 FORMULA 23111879 T 55 70 ferric chloride SYSTEMATIC 23111883 A 153 169 vitamins C and B MULTIPLE 23111883 A 195 197 Cd FORMULA 23111883 A 219 235 Cadmium chloride SYSTEMATIC 23111883 A 237 242 CdCl2 FORMULA 23111883 A 360 367 glucose TRIVIAL 23111883 A 369 382 triglycerides FAMILY 23111883 A 384 395 cholesterol TRIVIAL 23111883 A 431 435 urea TRIVIAL 23111883 A 440 450 creatinine TRIVIAL 23111883 A 496 501 CdCl2 FORMULA 23111883 A 52 59 cadmium SYSTEMATIC 23111883 A 539 548 uric acid TRIVIAL 23111883 A 550 559 aspartate TRIVIAL 23111883 A 578 585 alanine TRIVIAL 23111883 A 61 63 Cd FORMULA 23111883 A 629 638 bilirubin TRIVIAL 23111883 A 879 884 CdCl2 FORMULA 23111883 A 910 926 vitamins C and B MULTIPLE 23111883 A 993 995 Cd FORMULA 23111883 T 12 19 cadmium SYSTEMATIC 23111883 T 56 72 vitamins C and B MULTIPLE 23111884 A 455 462 ethanol SYSTEMATIC 23111884 T 173 184 amphetamine TRIVIAL 23111884 T 186 206 tetrahydrocannabinol SYSTEMATIC 23111885 A 1001 1004 NaC ABBREVIATION 23111885 A 130 138 Tween 61 TRIVIAL 23111885 A 150 161 cholesterol TRIVIAL 23111885 A 212 226 sodium cholate SYSTEMATIC 23111885 A 228 231 NaC ABBREVIATION 23111885 A 237 256 sodium deoxycholate SYSTEMATIC 23111885 A 258 262 NaDC FORMULA 23111885 A 300 307 ethanol SYSTEMATIC 23111885 A 387 396 phosphate SYSTEMATIC 23111885 A 533 542 phosphate SYSTEMATIC 23111885 A 736 740 NaDC FORMULA 23111885 A 750 753 NaC ABBREVIATION 23111885 A 765 772 ethanol SYSTEMATIC 23111885 A 816 819 NaC ABBREVIATION 23111887 A 22 37 dexmedetomidine TRIVIAL 23111887 A 359 374 dexmedetomidine TRIVIAL 23111887 A 415 424 clonidine TRIVIAL 23111887 A 588 597 clonidine TRIVIAL 23111887 A 658 673 dexmedetomidine TRIVIAL 23111887 T 19 34 dexmedetomidine TRIVIAL 23115086 A 1000 1009 midazolam TRIVIAL 23115086 A 1022 1030 fentanyl TRIVIAL 23115086 A 1035 1043 propofol TRIVIAL 23115086 A 1110 1118 fentanyl TRIVIAL 23115086 A 1166 1174 propofol TRIVIAL 23115086 A 1303 1311 morphine TRIVIAL 23115086 A 1380 1388 morphine TRIVIAL 23115086 A 139 147 morphine TRIVIAL 23115086 A 1390 1398 fentanyl TRIVIAL 23115086 A 1404 1412 propofol TRIVIAL 23115086 A 1425 1434 midazolam TRIVIAL 23115086 A 1467 1475 morphine TRIVIAL 23115086 A 1477 1485 fentanyl TRIVIAL 23115086 A 149 158 midazolam TRIVIAL 23115086 A 1491 1499 propofol TRIVIAL 23115086 A 160 168 fentanyl TRIVIAL 23115086 A 174 182 propofol TRIVIAL 23115086 A 376 384 morphine TRIVIAL 23115086 A 389 398 midazolam TRIVIAL 23115086 A 443 451 fentanyl TRIVIAL 23115086 A 456 464 propofol TRIVIAL 23115086 A 684 692 morphine TRIVIAL 23115086 T 45 53 morphine TRIVIAL 23115086 T 55 64 midazolam TRIVIAL 23115086 T 66 74 fentanyl TRIVIAL 23115086 T 80 88 propofol TRIVIAL 23115119 A 115 128 phenylalanine TRIVIAL 23115119 A 142 157 carboxylic acid SYSTEMATIC 23115119 A 182 195 aspartic acid TRIVIAL 23115119 A 199 212 glutamic acid TRIVIAL 23115119 A 475 478 Phe FORMULA 23115119 A 479 482 Glu FORMULA 23115119 A 486 489 Phe FORMULA 23115119 A 490 493 Asp FORMULA 23115119 A 602 605 Phe FORMULA 23115119 A 627 630 Glu FORMULA 23115119 A 634 637 Asp FORMULA 23115324 A 1119 1128 bleomycin FAMILY 23115324 A 1450 1459 bleomycin FAMILY 23115324 A 572 581 bleomycin FAMILY 23115324 T 143 152 bleomycin FAMILY 23115325 A 1121 1125 LEVC ABBREVIATION 23115325 A 1155 1178 sodium hydrogen sulfide SYSTEMATIC 23115325 A 1180 1184 NaHS FORMULA 23115325 A 1202 1203 K FORMULA 23115325 A 1204 1207 ATP ABBREVIATION 23115325 A 1330 1334 NaHS FORMULA 23115325 A 143 155 sulfonylurea FAMILY 23115325 A 1433 1445 sulfonylurea FAMILY 23115325 A 1481 1485 NaHS FORMULA 23115325 A 1592 1593 K FORMULA 23115325 A 1594 1597 ATP ABBREVIATION 23115325 A 18 27 potassium SYSTEMATIC 23115325 A 37 38 K FORMULA 23115325 A 389 390 K FORMULA 23115325 A 39 42 ATP ABBREVIATION 23115325 A 391 394 ATP ABBREVIATION 23115325 A 4 7 ATP ABBREVIATION 23115325 A 538 567 trinitrobenzene sulfonic acid SYSTEMATIC 23115325 A 569 570 K FORMULA 23115325 A 571 574 ATP ABBREVIATION 23115325 A 640 644 K(+) FORMULA 23115325 A 694 707 levcromakalim TRIVIAL 23115325 A 709 713 LEVC ABBREVIATION 23115325 A 718 719 K FORMULA 23115325 A 720 723 ATP ABBREVIATION 23115325 A 865 869 LEVC ABBREVIATION 23115325 T 0 16 Hydrogen sulfide SYSTEMATIC 23115325 T 47 50 ATP ABBREVIATION 23115325 T 61 70 potassium SYSTEMATIC 23116643 A 1168 1174 CCl(4) FORMULA 23116643 A 250 256 CCl(4) FORMULA 23116643 A 271 277 CCl(4) FORMULA 23116643 A 420 435 3-nitrotyrosine SYSTEMATIC 23116643 A 437 441 3-NT SYSTEMATIC 23116643 A 447 466 thiobarbituric acid SYSTEMATIC 23116643 A 535 537 Cu FORMULA 23116643 A 538 540 Zn FORMULA 23116643 A 541 551 superoxide TRIVIAL 23116643 A 578 584 CCl(4) FORMULA 23116643 A 70 85 rosmarinic acid TRIVIAL 23116643 T 0 15 Rosmarinic acid TRIVIAL 23116643 T 67 87 carbon tetrachloride SYSTEMATIC 23117790 A 1191 1198 glucose TRIVIAL 23117790 A 12 19 glucose TRIVIAL 23117790 A 1471 1479 SB334867 IDENTIFIER 23117790 A 1578 1585 glucose TRIVIAL 23117790 A 210 217 glucose TRIVIAL 23117790 A 288 295 glucose TRIVIAL 23117790 A 783 791 SB334867 IDENTIFIER 23117790 A 793 850 N-(2-methyl-6-benzoxazolyl)-N'-1,5-naphthyridin-4-yl urea SYSTEMATIC 23117790 T 33 40 glucose TRIVIAL 23118018 A 1033 1040 alcohol FAMILY 23118018 A 104 111 alcohol FAMILY 23118018 A 119 128 serotonin TRIVIAL 23118018 A 140 159 5-hydroxytryptamine SYSTEMATIC 23118018 A 229 236 alcohol FAMILY 23118018 A 343 350 alcohol FAMILY 23118018 A 473 480 alcohol FAMILY 23118018 A 545 552 alcohol FAMILY 23118018 A 614 618 5-HT SYSTEMATIC 23118018 A 620 643 gamma-aminobutyric acid SYSTEMATIC 23118018 A 645 649 GABA ABBREVIATION 23118018 A 652 660 dopamine TRIVIAL 23118018 A 666 675 glutamate TRIVIAL 23118018 A 795 802 alcohol FAMILY 23118018 A 909 916 alcohol FAMILY 23118018 T 71 78 ethanol SYSTEMATIC 23118018 T 8 27 5-hydroxytryptamine SYSTEMATIC 23118019 A 1231 1237 5'-AMN FORMULA 23118019 A 1242 1249 5'-MABN FORMULA 23118019 A 1341 1348 U50,488 IDENTIFIER 23118019 A 1429 1435 5'-AMN FORMULA 23118019 A 1440 1447 5'-MABN FORMULA 23118019 A 313 343 5'-(2-aminomethyl) naltrindole SYSTEMATIC 23118019 A 345 351 5'-AMN FORMULA 23118019 A 357 401 N-((Naltrindol-5-yl) methyl) pentanimidamide SYSTEMATIC 23118019 A 403 410 5'-MABN FORMULA 23118019 A 454 465 naltrindole TRIVIAL 23118019 A 580 600 [(3)H]-diprenorphine SYSTEMATIC 23118019 A 610 652 guanosine-5'-O-(3-[35S]-thio) triphosphate SYSTEMATIC 23118019 A 654 667 [(35)S]-GTPγS SYSTEMATIC 23118019 A 736 742 5'-AMN FORMULA 23118019 A 747 754 5'-MABN FORMULA 23118019 A 936 942 5'-AMN FORMULA 23118019 A 947 954 5'-MABN FORMULA 23118019 T 41 52 naltrindole TRIVIAL 23121767 A 47 58 bicarbonate SYSTEMATIC 23121934 A 1081 1110 3,4,5-trimethoxycinnamic acid SYSTEMATIC 23121934 A 109 117 morphine TRIVIAL 23121934 A 1195 1205 WAY 100635 IDENTIFIER 23121934 A 12 41 3,4,5-trimethoxycinnamic acid SYSTEMATIC 23121934 A 1250 1279 3,4,5-trimethoxycinnamic acid SYSTEMATIC 23121934 A 238 245 ketones FAMILY 23121934 A 251 257 esters FAMILY 23121934 A 298 304 amides FAMILY 23121934 A 339 361 1-hydroxybenzotriazole SYSTEMATIC 23121934 A 362 401 ethyl(dimethylaminopropryl)carbodiimide SYSTEMATIC 23121934 A 442 450 naloxone TRIVIAL 23121934 A 459 467 morphine TRIVIAL 23121934 A 534 563 3,4,5-trimethoxycinnamic acid SYSTEMATIC 23121934 A 600 629 3,4,5-trimethoxycinnamic acid SYSTEMATIC 23121934 A 701 709 naloxone TRIVIAL 23121934 A 718 726 morphine TRIVIAL 23121934 A 765 777 (+)8-OH-DPAT SYSTEMATIC 23121934 A 858 870 (+)8-OH-DPAT SYSTEMATIC 23121934 A 975 985 WAY 100635 IDENTIFIER 23121934 T 40 69 3,4,5-trimethoxycinnamic acid SYSTEMATIC 23122060 A 1019 1038 quercetin glucoside TRIVIAL 23122060 A 113 140 quercetin-3-O-β-d-glucoside SYSTEMATIC 23122060 A 1187 1190 Q3G SYSTEMATIC 23122060 A 142 145 Q3G SYSTEMATIC 23122060 A 189 198 d-glucose TRIVIAL 23122060 A 231 240 d-glucose TRIVIAL 23122060 A 251 254 Q3G SYSTEMATIC 23122060 A 608 618 saccharide FAMILY 23122060 A 661 670 quercetin TRIVIAL 23122060 A 78 98 quercetin glycosides FAMILY 23122060 A 794 797 Q3G SYSTEMATIC 23122060 A 811 820 quercetin TRIVIAL 23122060 A 932 935 Q3G SYSTEMATIC 23122060 T 39 58 quercetin glycoside FAMILY 23122061 A 191 202 β-carboline TRIVIAL 23122061 A 203 216 glucoalkaloid FAMILY 23122061 A 218 246 harmanyl β-d-glucopyranoside TRIVIAL 23122061 A 289 293 (1)H FORMULA 23122061 A 299 304 (13)C FORMULA 23122061 A 310 314 (1)H FORMULA 23122061 A 315 319 (1)H FORMULA 23122061 A 38 45 ethanol SYSTEMATIC 23122064 A 857 864 cocaine TRIVIAL 23122064 A 870 881 amphetamine TRIVIAL 23122066 A 145 155 silica gel TRIVIAL 23122066 A 299 310 cholesterol TRIVIAL 23122066 A 465 476 cholesterol TRIVIAL 23122066 A 507 518 cholesterol TRIVIAL 23122066 A 586 597 cholesterol TRIVIAL 23122066 A 640 649 bile acid FAMILY 23122066 A 726 739 sphingolipids FAMILY 23122066 A 768 784 triacylglycerols FAMILY 23122066 A 789 802 sterol esters FAMILY 23122066 A 853 866 sphingolipids FAMILY 23122066 A 868 884 triacylglycerols FAMILY 23122066 A 890 903 sterol esters FAMILY 23122068 A 110 122 sulforaphene TRIVIAL 23122068 A 232 244 Sulforaphene TRIVIAL 23122068 A 334 342 methanol SYSTEMATIC 23122068 A 435 447 sulforaphene TRIVIAL 23122068 A 469 481 sulforaphene TRIVIAL 23122068 A 504 516 sulforaphene TRIVIAL 23122068 A 586 598 sulforaphene TRIVIAL 23122068 A 630 642 sulforaphene TRIVIAL 23122068 A 779 783 (1)H FORMULA 23122068 A 792 797 (13)C FORMULA 23122068 A 851 863 sulforaphene TRIVIAL 23122068 A 891 903 sulforaphene TRIVIAL 23122068 T 31 43 sulforaphene TRIVIAL 23122077 A 441 449 H(2)O(2) FORMULA 23122077 A 491 520 2,2-diphenyl-1-picrylhydrazyl SYSTEMATIC 23122077 A 522 526 DPPH ABBREVIATION 23122085 A 1056 1079 monoacylglycerol ethers FAMILY 23122085 A 1092 1115 fatty acid ethyl esters FAMILY 23122085 A 134 154 diacylglycerol ether FAMILY 23122085 A 159 175 triacylglycerols FAMILY 23122085 A 217 237 diacylglycerol ether FAMILY 23122085 A 301 308 ethanol SYSTEMATIC 23122085 A 32 40 squalene TRIVIAL 23122085 A 482 502 diacylglycerol ether FAMILY 23122085 A 743 758 triacylglycerol FAMILY 23122085 A 808 829 diacylglycerol ethers FAMILY 23122085 A 839 862 monoacylglycerol ethers FAMILY 23122085 A 875 898 fatty acid ethyl esters FAMILY 23122085 A 939 946 ethanol SYSTEMATIC 23122085 A 957 978 diacylglycerol ethers FAMILY 23122085 T 23 44 diacylglycerol ethers FAMILY 23122086 A 340 357 galacturonic acid TRIVIAL 23122086 A 359 363 GalA ABBREVIATION 23122089 A 271 277 carbon SYSTEMATIC 23122089 A 281 289 nitrogen SYSTEMATIC 23122089 A 291 292 C FORMULA 23122089 A 293 294 N FORMULA 23122089 A 318 329 amino acids FAMILY 23122089 A 340 344 GABA ABBREVIATION 23122089 A 379 385 sugars FAMILY 23122089 A 397 424 Linoleic and linolenic acid MULTIPLE 23122089 A 448 471 unsaturated fatty acids FAMILY 23122089 A 530 540 tocopherol FAMILY 23122089 A 545 555 isoflavone FAMILY 23122089 A 660 664 GABA ABBREVIATION 23122089 A 666 677 isoflavones FAMILY 23122089 A 682 693 tocopherols FAMILY 23122092 A 1062 1075 1-octen-3-one SYSTEMATIC 23122092 A 976 985 Methional TRIVIAL 23122092 A 995 1002 phenols FAMILY 23122097 A 266 274 alcohols FAMILY 23122097 A 276 285 aldehydes FAMILY 23122097 A 287 299 hydrocarbons FAMILY 23122097 A 301 308 ketones FAMILY 23122097 A 310 325 carboxylic acid SYSTEMATIC 23122097 A 327 332 ester FAMILY 23122097 A 521 533 1-Octen-3-ol SYSTEMATIC 23122097 A 538 550 (2E)-hexenal SYSTEMATIC 23122097 A 886 897 fatty acids FAMILY 23122097 A 902 908 esters FAMILY 23122105 A 153 166 Allura Red AC TRIVIAL 23122105 A 721 734 ascorbic acid TRIVIAL 23122105 A 736 747 citric acid TRIVIAL 23122105 A 749 756 sucrose TRIVIAL 23122105 A 835 858 aromatic amine or amide MULTIPLE 23122105 T 24 37 Allura Red AC TRIVIAL 23122108 A 0 11 Polyphenols FAMILY 23122108 A 130 135 sugar FAMILY 23122108 A 248 261 ginnalins A-C MULTIPLE 23122108 A 454 467 Ginnalins A-C MULTIPLE 23122108 A 560 571 polyphenols FAMILY 23122108 A 573 583 ginnalin A TRIVIAL 23122108 A 58 71 Ginnalins A-C MULTIPLE 23122108 A 635 652 ginnalins B and C MULTIPLE 23122108 A 705 715 Ginnalin A TRIVIAL 23122108 A 76 87 polyphenols FAMILY 23122108 A 895 906 polyphenols FAMILY 23122108 T 19 32 ginnalins A-C MULTIPLE 23122108 T 6 17 polyphenols FAMILY 23122114 A 217 224 mercury SYSTEMATIC 23122114 A 381 388 mercury SYSTEMATIC 23122114 A 399 412 methylmercury SYSTEMATIC 23122114 A 414 418 MeHg FORMULA 23122114 A 502 504 Hg FORMULA 23122114 A 574 578 MeHg FORMULA 23122114 A 669 671 Hg FORMULA 23122114 A 770 772 Hg FORMULA 23122114 T 5 12 mercury SYSTEMATIC 23122116 A 125 137 azoxystrobin TRIVIAL 23122116 A 334 345 strobilurin FAMILY 23122116 A 399 407 methanol SYSTEMATIC 23122116 A 540 548 methanol SYSTEMATIC 23122116 A 591 599 methanol SYSTEMATIC 23122116 A 649 657 methanol SYSTEMATIC 23122116 T 35 47 azoxystrobin TRIVIAL 23122118 A 162 178 organophosphorus FAMILY 23122118 T 23 39 organophosphorus FAMILY 23122129 A 38 48 amino acid FAMILY 23122129 T 28 39 D-galactose TRIVIAL 23122135 A 176 184 methanol SYSTEMATIC 23122135 A 265 294 2,2-diphenyl-1-picrylhydrazyl SYSTEMATIC 23122135 A 296 300 DPPH ABBREVIATION 23122135 A 306 360 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) SYSTEMATIC 23122135 A 362 366 ABTS ABBREVIATION 23122135 A 636 662 caffeic acid-3-O-glucoside SYSTEMATIC 23122135 A 668 680 caffeic acid TRIVIAL 23122135 A 686 708 luteolin-7-O-glucoside SYSTEMATIC 23122135 A 714 736 apigenin-7-O-glucoside SYSTEMATIC 23122135 A 742 771 rosmarinic acid-3-O-glucoside SYSTEMATIC 23122135 A 777 792 rosmarinic acid TRIVIAL 23122135 A 798 806 luteolin TRIVIAL 23122135 A 812 820 apigenin TRIVIAL 23122135 A 830 841 chrysoeriol TRIVIAL 23122135 A 928 957 rosmarinic acid-3-O-glucoside SYSTEMATIC 23122135 A 966 981 rosmarinic acid TRIVIAL 23122136 A 34 46 anthocyanins FAMILY 23122136 T 24 36 anthocyanins FAMILY 23122137 A 0 10 Vescalagin TRIVIAL 23122137 A 123 130 glucose TRIVIAL 23122137 A 317 325 fructose TRIVIAL 23122137 A 427 437 vescalagin TRIVIAL 23122137 A 553 560 glucose TRIVIAL 23122137 A 573 585 fructosamine SYSTEMATIC 23122137 A 587 599 triglyceride FAMILY 23122137 A 609 619 fatty acid FAMILY 23122137 A 745 755 vescalagin TRIVIAL 23122137 A 877 888 cholesterol TRIVIAL 23122137 A 945 955 vescalagin TRIVIAL 23122137 A 988 998 vescalagin TRIVIAL 23122137 T 146 154 fructose TRIVIAL 23122137 T 48 58 vescalagin TRIVIAL 23122140 A 507 511 DPPH ABBREVIATION 23122140 A 683 691 H(2)O(2) FORMULA 23122140 T 119 127 H(2)O(2) FORMULA 23122141 A 160 171 fatty acids FAMILY 23122141 A 216 227 fatty acids FAMILY 23122141 A 284 295 fatty acids FAMILY 23122141 A 30 41 fatty acids FAMILY 23122141 A 673 689 triacylglycerols FAMILY 23122141 A 713 724 fatty acids FAMILY 23122141 T 17 29 behenic acid TRIVIAL 23122145 A 518 526 catechin TRIVIAL 23122145 A 531 542 epicatechin TRIVIAL 23122145 A 552 575 epicatechin-3-O-gallate SYSTEMATIC 23122145 A 615 631 epigallocatechin TRIVIAL 23122145 A 663 674 epicatechin TRIVIAL 23122145 A 679 702 epicatechin-3-O-gallate SYSTEMATIC 23122145 A 71 87 proanthocyanidin FAMILY 23122145 T 96 113 proanthocyanidins FAMILY 23122152 A 366 387 secoiridoid aglycones FAMILY 23122152 A 950 956 phenol SYSTEMATIC 23122155 A 1037 1045 carnosol TRIVIAL 23122155 A 1050 1064 betulinic acid TRIVIAL 23122155 A 117 130 ethyl acetate SYSTEMATIC 23122155 A 140 145 AcOEt FORMULA 23122155 A 155 161 hexane SYSTEMATIC 23122155 A 163 166 HEX ABBREVIATION 23122155 A 274 282 carnosol TRIVIAL 23122155 A 287 301 betulinic acid TRIVIAL 23122155 A 610 615 AcOEt FORMULA 23122155 A 675 678 HEX ABBREVIATION 23122155 A 702 707 AcOEt FORMULA 23122155 A 737 745 carnosol TRIVIAL 23122155 A 786 789 HEX ABBREVIATION 23122155 A 803 817 betulinic acid TRIVIAL 23122155 A 853 858 AcOEt FORMULA 23122155 A 864 869 AcOEt FORMULA 23122155 T 57 65 carnosol TRIVIAL 23122155 T 70 84 betulinic acid TRIVIAL 23122160 A 1412 1423 dinotefuran TRIVIAL 23122160 A 1504 1515 dinotefuran TRIVIAL 23122160 A 42 53 dinotefuran TRIVIAL 23122160 A 501 521 ammonium bicarbonate SYSTEMATIC 23122160 A 671 694 primary secondary amine MULTIPLE 23122160 A 75 78 MNG ABBREVIATION 23122160 A 901 923 acetonitrile and salts MULTIPLE 23122160 T 56 67 dinotefuran TRIVIAL 23122165 A 0 50 Z-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid SYSTEMATIC 23122165 A 388 393 sugar FAMILY 23122165 A 439 489 E-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid SYSTEMATIC 23122165 A 52 56 PPAG ABBREVIATION 23122165 A 624 628 PPAG ABBREVIATION 23122165 A 815 819 PPAG ABBREVIATION 23122165 T 37 87 Z-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid SYSTEMATIC 23122167 A 28 44 nortriterpenoids FAMILY 23122167 A 422 442 Schisarisanlactone A TRIVIAL 23122167 A 46 77 schisarisanlactones A (1) and B MULTIPLE 23122167 T 0 27 Schisarisanlactones A and B MULTIPLE 23122167 T 44 60 nortriterpenoids FAMILY 23122169 A 265 282 16-acetoxylsugiol SYSTEMATIC 23122169 A 288 303 graciliflorin E TRIVIAL 23122169 A 309 324 graciliflorin F TRIVIAL 23122169 A 330 356 15-O-methylgraciliflorin F SYSTEMATIC 23122169 A 362 389 15-hydroxy-20-deoxocarnosol SYSTEMATIC 23122169 A 39 47 abietane TRIVIAL 23122169 A 395 416 3β-hydroxysempervirol SYSTEMATIC 23122169 A 422 449 15-hydroxy-1-oxosalvibretol SYSTEMATIC 23122169 A 455 487 abieta-8,11,13-triene-14,19-diol SYSTEMATIC 23122169 A 48 60 diterpenoids FAMILY 23122169 A 493 541 6,12,15-trihydroxy-5,8,11,13-abietatetraen-7-one SYSTEMATIC 23122169 A 551 562 3α-hinokiol TRIVIAL 23122169 T 0 8 Abietane TRIVIAL 23122169 T 9 21 diterpenoids FAMILY 23123188 A 1219 1225 oxygen SYSTEMATIC 23123188 A 1397 1404 timolol TRIVIAL 23123188 A 513 516 PGT ABBREVIATION 23123188 A 518 550 propoxylated glyceryl triacylate FAMILY 23123188 A 581 588 timolol TRIVIAL 23123188 A 701 708 ethanol SYSTEMATIC 23123188 A 747 754 timolol TRIVIAL 23123188 A 758 767 phosphate SYSTEMATIC 23123188 A 915 922 timolol TRIVIAL 23123188 A 930 933 PGT ABBREVIATION 23123188 T 40 47 timolol TRIVIAL 23123248 A 587 596 carbamate FAMILY 23123248 A 701 713 rivastigmine TRIVIAL 23123248 A 884 894 carbamates FAMILY 23123254 A 440 445 tabun TRIVIAL 23123254 A 452 457 sarin TRIVIAL 23123254 A 464 469 soman TRIVIAL 23123254 A 480 490 cyclosarin TRIVIAL 23123254 A 500 517 chlorpyrifos oxon TRIVIAL 23123254 A 560 572 chlorpyrifos TRIVIAL 23123254 A 743 751 diazoxon TRIVIAL 23123254 A 78 94 organophosphorus FAMILY 23123254 A 794 802 diazinon TRIVIAL 23123331 A 1052 1055 SLB ABBREVIATION 23123331 A 1060 1067 silybin TRIVIAL 23123331 A 1125 1128 SLB ABBREVIATION 23123331 A 1205 1215 Na(2)CO(3) FORMULA 23123331 A 155 161 silica TRIVIAL 23123331 A 539 542 SLB ABBREVIATION 23123331 A 547 554 silybin TRIVIAL 23123331 A 621 631 Na(2)CO(3) FORMULA 23123331 A 663 673 Na(2)CO(3) FORMULA 23123331 A 715 722 silybin TRIVIAL 23123331 A 73 80 silybin TRIVIAL 23123331 A 751 754 SLB ABBREVIATION 23123331 A 858 861 SLB ABBREVIATION 23123331 A 866 873 silybin TRIVIAL 23123331 A 87 90 SLB ABBREVIATION 23123331 A 937 947 Na(2)CO(3) FORMULA 23123331 T 64 71 silybin TRIVIAL 23123331 T 88 94 silica TRIVIAL 23123737 A 421 427 lutein TRIVIAL 23123743 A 1136 1139 PPT ABBREVIATION 23123743 A 1448 1451 PPT ABBREVIATION 23123743 A 1620 1638 inositol phosphate SYSTEMATIC 23123743 A 1695 1703 estrogen FAMILY 23123743 A 220 233 17β-Estradiol SYSTEMATIC 23123743 A 266 269 PPT ABBREVIATION 23123743 A 302 305 DPN ABBREVIATION 23123743 A 341 364 [³H]-inositol phosphate SYSTEMATIC 23123743 A 516 539 [³H]-inositol phosphate SYSTEMATIC 23123743 A 601 612 ICI 182,780 IDENTIFIER 23123743 A 643 647 G-15 IDENTIFIER 23123743 A 667 690 [³H]-inositol phosphate SYSTEMATIC 23123743 A 67 75 estrogen FAMILY 23123743 A 722 725 PPT ABBREVIATION 23123743 A 822 830 tyrosine TRIVIAL 23123743 A 849 852 PP2 ABBREVIATION 23123743 A 871 894 [³H]-inositol phosphate SYSTEMATIC 23123743 A 926 929 PPT ABBREVIATION 23123743 T 0 8 Estrogen FAMILY 23123743 T 53 71 inositol phosphate SYSTEMATIC 23123945 A 0 8 Atrazine TRIVIAL 23123945 A 10 13 ATR ABBREVIATION 23123945 A 1024 1027 ATR ABBREVIATION 23123945 A 1088 1091 ATR ABBREVIATION 23123945 A 1195 1204 monoamine FAMILY 23123945 A 1269 1272 ATR ABBREVIATION 23123945 A 1296 1307 amphetamine TRIVIAL 23123945 A 1355 1358 ATR ABBREVIATION 23123945 A 1457 1460 ATR ABBREVIATION 23123945 A 1514 1517 ATR ABBREVIATION 23123945 A 244 247 ATR ABBREVIATION 23123945 A 352 360 dopamine TRIVIAL 23123945 A 428 431 ATR ABBREVIATION 23123945 A 464 473 monoamine FAMILY 23123945 A 569 572 ATR ABBREVIATION 23123945 A 618 621 ATR ABBREVIATION 23123945 A 746 751 DOPAC ABBREVIATION 23123945 A 757 760 HVA ABBREVIATION 23123945 A 828 830 Mn FORMULA 23123945 A 918 927 monoamine FAMILY 23123945 T 35 43 atrazine TRIVIAL 23124677 A 1110 1117 Cadmium SYSTEMATIC 23124677 A 1259 1266 cadmium SYSTEMATIC 23124677 A 1365 1372 Cadmium SYSTEMATIC 23124677 A 1580 1582 Cd FORMULA 23124677 A 1679 1681 Cd FORMULA 23124677 A 450 457 cadmium SYSTEMATIC 23124677 A 601 608 cadmium SYSTEMATIC 23124677 A 725 727 Cd FORMULA 23124677 A 795 803 nitrogen SYSTEMATIC 23124677 T 0 7 Cadmium SYSTEMATIC 23124905 A 279 287 dicaprin TRIVIAL 23124905 A 465 476 diglyceride FAMILY 23124905 A 478 494 1,2-sn- dicaprin SYSTEMATIC 23124905 A 499 514 2,3-sn-dicaprin SYSTEMATIC 23124905 A 540 555 1,3-sn-dicaprin SYSTEMATIC 23124905 A 640 645 ester FAMILY 23124905 A 660 671 diglyceride FAMILY 23124905 A 681 696 1,2-sn-dicaprin SYSTEMATIC 23124905 A 701 716 2,3-sn-dicaprin SYSTEMATIC 23124905 A 860 868 dicaprin TRIVIAL 23124950 A 175 181 silver SYSTEMATIC 23124950 A 308 315 silicon SYSTEMATIC 23125070 A 0 12 Testosterone TRIVIAL 23125070 A 1317 1332 androstenedione TRIVIAL 23125070 A 1406 1421 androstenedione TRIVIAL 23125070 A 1425 1437 testosterone TRIVIAL 23125070 A 1477 1489 testosterone TRIVIAL 23125070 A 1588 1600 testosterone TRIVIAL 23125070 A 426 438 testosterone TRIVIAL 23125070 A 514 526 testosterone TRIVIAL 23125070 A 557 569 testosterone TRIVIAL 23125070 T 44 56 testosterone TRIVIAL 23127598 A 133 147 Brilliant Blue TRIVIAL 23127598 A 157 168 Patent Blue TRIVIAL 23127598 A 48 64 triphenylmethane SYSTEMATIC 23127598 A 571 578 ethanol SYSTEMATIC 23127598 A 643 650 ethanol SYSTEMATIC 23127598 T 14 30 triphenylmethane SYSTEMATIC 23127598 T 36 50 Brilliant Blue TRIVIAL 23127598 T 55 66 Patent Blue TRIVIAL 23127599 A 1068 1071 Res ABBREVIATION 23127599 A 1125 1128 Res ABBREVIATION 23127599 A 1279 1282 Res ABBREVIATION 23127599 A 227 238 resveratrol TRIVIAL 23127599 A 240 243 Res ABBREVIATION 23127599 A 279 289 fatty acid FAMILY 23127599 A 546 553 sucrose TRIVIAL 23127599 A 581 592 resveratrol TRIVIAL 23127599 A 753 756 Res ABBREVIATION 23127599 A 781 784 Res ABBREVIATION 23127599 A 934 937 Res ABBREVIATION 23127599 T 23 34 resveratrol TRIVIAL 23127601 A 1169 1176 mercury SYSTEMATIC 23127601 A 1279 1286 mercury SYSTEMATIC 23127601 A 278 285 mercury SYSTEMATIC 23127601 A 542 549 mercury SYSTEMATIC 23127601 A 734 741 mercury SYSTEMATIC 23127601 A 922 929 mercury SYSTEMATIC 23127601 T 62 69 mercury SYSTEMATIC 23127826 A 1059 1066 flavone TRIVIAL 23127826 A 121 128 flavone TRIVIAL 23127826 A 287 294 flavone TRIVIAL 23127826 A 327 337 pyridinium SYSTEMATIC 23127826 A 487 494 flavone TRIVIAL 23127826 A 57 64 flavone TRIVIAL 23127826 A 923 930 flavone TRIVIAL 23127826 T 26 33 flavone TRIVIAL 23128829 A 88 95 cocaine TRIVIAL 23131177 A 0 9 Melatonin TRIVIAL 23131177 A 1335 1344 melatonin TRIVIAL 23131177 A 1363 1369 Ca(2+) FORMULA 23131177 A 1681 1690 melatonin TRIVIAL 23131177 A 275 284 melatonin TRIVIAL 23131177 A 304 313 melatonin TRIVIAL 23131177 A 562 598 N-[3-(3-methoxyphenyl)propyl] amides FAMILY 23131177 A 613 622 melatonin TRIVIAL 23131177 A 798 802 cAMP ABBREVIATION 23131177 A 935 945 benzyloxyl SYSTEMATIC 23131177 A 993 1008 3-methoxyphenyl SYSTEMATIC 23131177 T 32 50 phenylpropylamides FAMILY 23131177 T 87 96 melatonin TRIVIAL 23131797 A 1230 1237 octanol SYSTEMATIC 23131798 A 334 405 N-cyclopentyl-4-ethoxy-6-(4-methylpiperidin-1-yl)-1,3,5-triazin-2-amine SYSTEMATIC 23131798 A 517 531 1,3,5-triazine SYSTEMATIC 23131798 A 616 652 2,4,6-trisubstituted-1,3,5-triazines FAMILY 23131798 T 104 140 2,4,6-trisubstituted 1,3,5-triazines FAMILY 23132334 A 0 12 Dolutegravir TRIVIAL 23132334 A 1085 1088 DTG ABBREVIATION 23132334 A 1163 1166 DTG ABBREVIATION 23132334 A 1293 1303 creatinine TRIVIAL 23132334 A 1390 1393 DTG ABBREVIATION 23132334 A 14 17 DTG ABBREVIATION 23132334 A 1536 1539 DTG ABBREVIATION 23132334 A 19 31 S/GSK1349572 IDENTIFIER 23132334 A 253 256 DTG ABBREVIATION 23132334 A 321 324 DTG ABBREVIATION 23132334 A 526 529 DTG ABBREVIATION 23132334 A 555 558 UDP ABBREVIATION 23132334 A 646 649 DTG ABBREVIATION 23132334 A 764 767 DTG ABBREVIATION 23132334 T 129 141 dolutegravir TRIVIAL 23132743 A 353 376 1,25-dihydroxyvitamin D SYSTEMATIC 23132743 A 38 61 1,25-dihydroxyvitamin D SYSTEMATIC 23132743 A 4 13 vitamin D FAMILY 23132743 A 454 477 1,25-dihydroxyvitamin D SYSTEMATIC 23132743 A 665 674 vitamin D FAMILY 23132743 T 32 41 vitamin D FAMILY 23132751 A 26 29 CaO FORMULA 23132751 A 428 431 MgO FORMULA 23132751 A 44 51 CaCO(3) FORMULA 23132751 A 491 498 CaCO(3) FORMULA 23132751 A 535 538 MgO FORMULA 23132751 A 544 551 CaCO(3) FORMULA 23132751 A 626 629 MgO FORMULA 23132751 A 73 78 CO(2) FORMULA 23132751 T 25 28 CaO FORMULA 23132751 T 50 55 CO(2) FORMULA 23132843 A 250 256 iodine SYSTEMATIC 23132843 A 266 304 4-Aryl-3,4-dihydropyrimidin-2(1H)-ones FAMILY 23132843 A 4 17 sodium iodide SYSTEMATIC 23132843 A 516 526 pyrimidone SYSTEMATIC 23132843 A 73 79 iodide SYSTEMATIC 23132843 T 28 59 3,4-dihydropyrimidin-2(1H)-ones FAMILY 23132843 T 63 76 sodium iodide SYSTEMATIC 23135547 A 0 11 Dronedarone TRIVIAL 23135547 A 1063 1074 dronedarone TRIVIAL 23135547 A 119 130 dronedarone TRIVIAL 23135547 A 1272 1283 dronedarone TRIVIAL 23135547 A 1342 1352 amiodarone TRIVIAL 23135547 A 1374 1384 amiodarone TRIVIAL 23135547 A 1386 1397 dronedarone TRIVIAL 23135547 A 1600 1611 fatty acids FAMILY 23135547 A 181 191 Amiodarone TRIVIAL 23135547 A 304 315 dronedarone TRIVIAL 23135547 A 350 360 amiodarone TRIVIAL 23135547 A 49 59 amiodarone TRIVIAL 23135547 A 573 584 dronedarone TRIVIAL 23135547 A 589 599 amiodarone TRIVIAL 23135547 A 65 75 benzofuran SYSTEMATIC 23135547 A 687 690 ATP ABBREVIATION 23135547 A 971 977 oxygen SYSTEMATIC 23135547 T 54 65 dronedarone TRIVIAL 23135547 T 83 93 amiodarone TRIVIAL 23135548 A 1165 1169 TCDD ABBREVIATION 23135548 A 1236 1240 TCDD ABBREVIATION 23135548 A 128 132 TCDD ABBREVIATION 23135548 A 134 140 dioxin FAMILY 23135548 A 1425 1429 TCDD ABBREVIATION 23135548 A 1603 1607 TCDD ABBREVIATION 23135548 A 293 297 TCDD ABBREVIATION 23135548 A 361 365 TCDD ABBREVIATION 23135548 A 470 474 TCDD ABBREVIATION 23135548 A 56 72 aryl hydrocarbon FAMILY 23135548 A 663 667 TCDD ABBREVIATION 23135548 A 669 673 TCDD ABBREVIATION 23135548 A 775 779 TCDD ABBREVIATION 23135548 A 876 880 TCDD ABBREVIATION 23135548 A 91 126 2,3,7,8-tetrachlorodibenzo-p-dioxin SYSTEMATIC 23135548 A 984 988 TCDD ABBREVIATION 23135548 T 0 6 Dioxin FAMILY 23137833 A 1035 1046 resveratrol TRIVIAL 23137833 A 1252 1265 dexamethasone TRIVIAL 23137833 A 1375 1386 resveratrol TRIVIAL 23137833 A 353 364 resveratrol TRIVIAL 23137833 A 468 479 resveratrol TRIVIAL 23137833 A 706 717 resveratrol TRIVIAL 23137833 A 765 776 resveratrol TRIVIAL 23137833 A 884 897 dexamethasone TRIVIAL 23137833 A 965 976 resveratrol TRIVIAL 23137833 T 13 24 resveratrol TRIVIAL 23137957 A 1195 1209 trichothecenes FAMILY 23137957 A 754 768 deoxynivalenol TRIVIAL 23137957 A 770 773 DON ABBREVIATION 23138333 A 1238 1240 Cu FORMULA 23138333 A 1283 1296 chlorophyll a TRIVIAL 23138333 A 1298 1303 chl a ABBREVIATION 23138333 A 324 330 copper SYSTEMATIC 23138333 A 949 955 copper SYSTEMATIC 23138333 T 14 20 copper SYSTEMATIC 23138381 A 35 47 formaldehyde SYSTEMATIC 23138381 A 541 553 formaldehyde SYSTEMATIC 23138381 A 88 100 Formaldehyde SYSTEMATIC 23138381 T 15 27 formaldehyde SYSTEMATIC 23138381 T 51 63 Formaldehyde SYSTEMATIC 23138972 A 200 202 Pd FORMULA 23138972 A 326 328 Ru FORMULA 23138972 A 330 332 Rh FORMULA 23138972 A 337 339 Ir FORMULA 23138972 A 427 433 imines FAMILY 23138972 A 435 443 enamines FAMILY 23138972 A 445 452 olefins FAMILY 23138972 A 454 461 ketones FAMILY 23138972 A 466 478 heteroarenes FAMILY 23138972 A 503 512 palladium SYSTEMATIC 23138972 A 720 729 palladium SYSTEMATIC 23138972 T 12 21 palladium SYSTEMATIC 23139020 A 1001 1026 epoxyeicosatrienoic acids FAMILY 23139020 A 1031 1070 19- and 20-hydroxyeicosatetraenoic acid MULTIPLE 23139020 A 31 47 arachidonic acid TRIVIAL 23139020 T 30 46 arachidonic acid TRIVIAL 23139378 A 1108 1120 itraconazole TRIVIAL 23139378 A 1149 1160 gemfibrozil TRIVIAL 23139378 A 1194 1217 gemfibrozil glucuronide TRIVIAL 23139378 A 121 133 itraconazole TRIVIAL 23139378 A 1255 1266 repaglinide TRIVIAL 23139378 A 138 149 gemfibrozil TRIVIAL 23139378 A 1448 1459 repaglinide TRIVIAL 23139378 A 1507 1518 gemfibrozil TRIVIAL 23139378 A 1635 1646 repaglinide TRIVIAL 23139378 A 1817 1828 repaglinide TRIVIAL 23139378 A 28 39 repaglinide TRIVIAL 23139378 A 433 445 itraconazole TRIVIAL 23139378 A 447 458 gemfibrozil TRIVIAL 23139378 A 464 487 gemfibrozil glucuronide TRIVIAL 23139378 A 602 613 repaglinide TRIVIAL 23139378 A 736 748 itraconazole TRIVIAL 23139378 A 790 813 gemfibrozil glucuronide TRIVIAL 23139378 A 886 917 gemfibrozil and its glucuronide MULTIPLE 23139378 A 956 967 repaglinide TRIVIAL 23139378 T 63 74 gemfibrozil TRIVIAL 23139378 T 79 91 itraconazole TRIVIAL 23139413 A 1556 1559 Sar ABBREVIATION 23139413 A 1563 1566 Gln FORMULA 23139413 A 1570 1573 Ile FORMULA 23139413 A 741 750 cysteines FAMILY 23139413 A 904 912 losartan TRIVIAL 23139413 A 969 978 cysteines FAMILY 23140132 A 1331 1344 triglycerides FAMILY 23140132 A 1516 1532 triacylglyceride FAMILY 23141425 A 1306 1310 EGCG ABBREVIATION 23141425 A 1468 1472 EGCG ABBREVIATION 23141425 A 363 389 Epigallocatechin-3-gallate TRIVIAL 23141425 A 391 395 EGCG ABBREVIATION 23141425 A 408 418 polyphenol FAMILY 23141425 A 576 580 EGCG ABBREVIATION 23141425 A 675 679 EGCG ABBREVIATION 23141425 A 949 953 EGCG ABBREVIATION 23141425 T 0 4 EGCG ABBREVIATION 23142020 A 1022 1033 BAY 41-8543 IDENTIFIER 23142020 A 1249 1260 BAY 41-8543 IDENTIFIER 23142020 A 201 212 BAY 41-8543 IDENTIFIER 23142020 A 365 376 polystyrene SYSTEMATIC 23142020 A 572 583 BAY 41-8543 IDENTIFIER 23142020 T 40 51 BAY 41-8543 IDENTIFIER 23142538 A 0 35 2,3,7,8-Tetrachlorodibenzo-p-dioxin SYSTEMATIC 23142538 A 167 171 TCDD ABBREVIATION 23142538 A 37 41 TCDD ABBREVIATION 23142538 A 415 419 TCDD ABBREVIATION 23142538 A 617 621 TCDD ABBREVIATION 23142538 A 759 763 TCDD ABBREVIATION 23142538 T 24 30 dioxin FAMILY 23142558 A 1019 1029 oestrogens FAMILY 23142558 A 322 332 Oestrogens FAMILY 23142558 A 807 822 17-β-oestradiol SYSTEMATIC 23142558 A 912 922 oestrogens FAMILY 23142558 T 4 19 17-β-oestradiol SYSTEMATIC 23142699 A 228 237 estradiol TRIVIAL 23142699 A 882 891 estrogens FAMILY 23142699 T 32 40 estrogen FAMILY 23142753 A 0 14 Organochlorine FAMILY 23142753 A 1017 1025 p,p'-DDT ABBREVIATION 23142753 A 1030 1038 p,p'-DDE SYSTEMATIC 23142753 A 334 379 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane SYSTEMATIC 23142753 A 381 389 p,p'-DDT ABBREVIATION 23142753 A 416 462 1,1'-dichloro-2,2'-bis(p-chlorophenyl)ethylene SYSTEMATIC 23142753 A 464 472 p,p'-DDE SYSTEMATIC 23142753 A 495 555 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)-ethane SYSTEMATIC 23142753 A 557 565 o,p'-DDT ABBREVIATION 23142753 A 641 649 p,p'-DDT ABBREVIATION 23142753 A 723 731 p,p'-DDE SYSTEMATIC 23142753 A 736 744 o,p'-DDT ABBREVIATION 23142753 A 766 774 p,p'-DDT ABBREVIATION 23142753 A 785 793 o,p'-DDT ABBREVIATION 23142753 A 798 806 p,p'-DDE SYSTEMATIC 23142753 A 852 860 p,p'-DDE SYSTEMATIC 23142753 A 929 937 p,p'-DDT ABBREVIATION 23142753 A 942 950 o,p'-DDT ABBREVIATION 23142753 T 0 31 Dichlorodiphenyltrichloroethane SYSTEMATIC 23142753 T 33 36 DDT ABBREVIATION 23142753 T 39 42 DDT ABBREVIATION 23143036 A 1217 1236 butylhydroxytoluene SYSTEMATIC 23143036 A 1238 1241 BHT ABBREVIATION 23143036 A 1244 1254 d-mannitol TRIVIAL 23143036 A 1258 1274 N-acetylcysteine SYSTEMATIC 23143036 A 1276 1279 NAC ABBREVIATION 23143036 A 1301 1303 Cd FORMULA 23143036 A 1389 1391 Cd FORMULA 23143036 A 1535 1543 paraquat TRIVIAL 23143036 A 1556 1562 oxygen SYSTEMATIC 23143036 A 1602 1619 hydrogen peroxide SYSTEMATIC 23143036 A 1638 1640 Cd FORMULA 23143036 A 1850 1852 Cd FORMULA 23143036 A 194 201 Cadmium SYSTEMATIC 23143036 A 203 205 Cd FORMULA 23143036 A 2031 2033 Cd FORMULA 23143036 A 373 375 Cd FORMULA 23143036 A 436 438 Cd FORMULA 23143036 A 554 556 Cd FORMULA 23143036 A 725 727 Cd FORMULA 23143036 A 797 799 Cu FORMULA 23143036 A 800 802 Zn FORMULA 23143036 A 803 813 superoxide TRIVIAL 23143036 A 825 827 Cu FORMULA 23143036 A 828 830 Zn FORMULA 23143036 A 956 958 Cd FORMULA 23143036 T 0 7 Cadmium SYSTEMATIC 23143036 T 8 10 Cd FORMULA 23143039 A 1105 1112 glucose TRIVIAL 23143039 A 1134 1143 gluconate TRIVIAL 23143039 A 1162 1173 glutathione TRIVIAL 23143039 A 1304 1311 cadmium SYSTEMATIC 23143039 A 1346 1353 cadmium SYSTEMATIC 23143039 A 1426 1433 cadmium SYSTEMATIC 23143039 A 1540 1547 cadmium SYSTEMATIC 23143039 A 1644 1651 cadmium SYSTEMATIC 23143039 A 1675 1682 cadmium SYSTEMATIC 23143039 A 1716 1724 carbonyl FAMILY 23143039 A 1865 1872 cadmium SYSTEMATIC 23143039 A 189 196 cadmium SYSTEMATIC 23143039 A 337 344 cadmium SYSTEMATIC 23143039 A 538 545 cadmium SYSTEMATIC 23143039 A 606 613 Cadmium SYSTEMATIC 23143039 A 764 771 cadmium SYSTEMATIC 23143039 A 874 882 carbonyl FAMILY 23143039 A 926 941 malondialdehyde TRIVIAL 23143039 T 36 43 cadmium SYSTEMATIC 23143620 A 379 403 2,4-dinitrochlorobenzene SYSTEMATIC 23143674 A 1061 1070 clemizole TRIVIAL 23143674 A 512 521 clemizole TRIVIAL 23143674 A 832 841 clemizole TRIVIAL 23144001 A 16 24 perylene SYSTEMATIC 23144001 T 87 95 perylene SYSTEMATIC 23146662 A 0 12 Bryostatin 1 TRIVIAL 23146662 A 1057 1070 phorbol ester FAMILY 23146662 A 1218 1226 Merle 23 IDENTIFIER 23146662 A 1295 1306 bryostatins FAMILY 23146662 A 132 145 phorbol ester FAMILY 23146662 A 1337 1349 bryostatin 1 TRIVIAL 23146662 A 1358 1371 phorbol ester FAMILY 23146662 A 221 233 bryostatin 1 TRIVIAL 23146662 A 23 37 phorbol esters FAMILY 23146662 A 235 248 phorbol ester FAMILY 23146662 A 258 270 bryostatin 1 TRIVIAL 23146662 A 282 290 Merle 23 IDENTIFIER 23146662 A 339 351 Bryostatin 1 TRIVIAL 23146662 A 378 391 phorbol ester FAMILY 23146662 A 441 449 Merle 23 IDENTIFIER 23146662 A 460 473 phorbol ester FAMILY 23146662 A 496 508 bryostatin 1 TRIVIAL 23146662 A 758 770 bryostatin 1 TRIVIAL 23146662 A 795 808 phorbol ester FAMILY 23146662 A 889 901 bryostatin 1 TRIVIAL 23146662 A 921 933 bryostatin 1 TRIVIAL 23146662 A 949 962 phorbol ester FAMILY 23146662 A 992 1000 Merle 23 IDENTIFIER 23146662 T 42 55 phorbol ester FAMILY 23146662 T 57 69 bryostatin 1 TRIVIAL 23146662 T 75 85 bryostatin FAMILY 23146690 A 1193 1204 resveratrol TRIVIAL 23146690 A 1209 1220 clofarabine TRIVIAL 23146690 A 316 327 clofarabine TRIVIAL 23146690 A 433 444 resveratrol TRIVIAL 23146690 A 449 460 clofarabine TRIVIAL 23146690 A 744 755 clofarabine TRIVIAL 23146690 A 772 783 resveratrol TRIVIAL 23146690 A 920 936 phosphoinositide FAMILY 23146690 A 952 960 Ly294002 IDENTIFIER 23146690 T 35 46 resveratrol TRIVIAL 23146690 T 74 85 clofarabine TRIVIAL 23146692 A 1030 1034 AAPH ABBREVIATION 23146692 A 1086 1092 oxygen SYSTEMATIC 23146692 A 1160 1164 AAPH ABBREVIATION 23146692 A 1221 1225 CAAP ABBREVIATION 23146692 A 673 683 amino acid FAMILY 23146692 A 711 726 Val-Cys-Ser-Val FORMULA 23146692 A 728 732 VCSV ABBREVIATION 23146692 A 738 753 Cys-Ala-Ala-Pro FORMULA 23146692 A 755 759 CAAP ABBREVIATION 23146692 A 838 867 1,1-diphenyl-2-picrylhydrazyl SYSTEMATIC 23146692 A 869 873 DPPH ABBREVIATION 23146692 A 982 1028 2,2-azobis-(2-amidino-propane) dihydrochloride SYSTEMATIC 23146694 A 0 11 Bisphenol A TRIVIAL 23146694 A 1005 1006 N FORMULA 23146694 A 1126 1129 BPA ABBREVIATION 23146694 A 13 16 BPA ABBREVIATION 23146694 A 158 161 BPA ABBREVIATION 23146694 A 476 479 BPA ABBREVIATION 23146694 A 508 511 BPA ABBREVIATION 23146694 A 61 74 polycarbonate FAMILY 23146694 A 641 644 BPA ABBREVIATION 23146694 A 954 957 BPA ABBREVIATION 23146694 T 0 11 Bisphenol A TRIVIAL 23146765 A 1270 1277 glucose TRIVIAL 23146765 A 1279 1286 lactate FAMILY 23146765 A 1288 1295 choline FAMILY 23146765 A 1297 1304 formate SYSTEMATIC 23146765 A 1337 1343 CCl(4) FORMULA 23146765 A 1506 1509 B12 TRIVIAL 23146765 A 1514 1520 folate TRIVIAL 23146765 A 1618 1621 B12 TRIVIAL 23146765 A 1671 1677 CCl(4) FORMULA 23146765 A 22 42 carbon tetrachloride SYSTEMATIC 23146765 A 223 229 CCl(4) FORMULA 23146765 A 407 413 CCl(4) FORMULA 23146765 A 44 50 CCl(4) FORMULA 23146765 A 581 585 (1)H FORMULA 23146765 T 0 2 1H FORMULA 23146766 A 0 14 Aflatoxin B(1) TRIVIAL 23146766 A 1048 1051 AFB ABBREVIATION 23146766 A 1052 1055 Lys FORMULA 23146766 A 1228 1231 AFB ABBREVIATION 23146766 A 1232 1235 Lys FORMULA 23146766 A 15 21 lysine TRIVIAL 23146766 A 240 246 AFB(1) ABBREVIATION 23146766 A 279 282 AFB ABBREVIATION 23146766 A 283 286 Lys FORMULA 23146766 A 30 33 AFB ABBREVIATION 23146766 A 34 37 Lys FORMULA 23146766 A 348 354 AFB(1) ABBREVIATION 23146766 A 371 374 AFB ABBREVIATION 23146766 A 375 378 Lys FORMULA 23146766 A 623 629 AFB(1) ABBREVIATION 23146766 A 660 663 AFB ABBREVIATION 23146766 A 664 667 Lys FORMULA 23146766 A 67 76 aflatoxin FAMILY 23146766 A 729 735 AFB(1) ABBREVIATION 23146766 A 796 799 AFB ABBREVIATION 23146766 A 800 803 Lys FORMULA 23146766 A 869 872 AFB ABBREVIATION 23146766 A 873 876 Lys FORMULA 23146766 T 46 58 aflatoxin B1 TRIVIAL 23146766 T 59 65 lysine TRIVIAL 23146838 A 1112 1121 saccharin TRIVIAL 23146838 A 1144 1151 glucose TRIVIAL 23146838 A 1295 1304 estrogens FAMILY 23146838 A 1349 1360 anastrozole TRIVIAL 23146838 A 1378 1387 saccharin TRIVIAL 23146838 A 1470 1477 glucose TRIVIAL 23146838 A 1614 1623 saccharin TRIVIAL 23146838 A 1734 1743 saccharin TRIVIAL 23146838 A 1758 1765 glucose TRIVIAL 23146838 A 1794 1805 anastrozole TRIVIAL 23146838 A 1983 1991 estrogen FAMILY 23146838 A 403 408 sugar FAMILY 23146838 A 541 550 saccharin TRIVIAL 23146838 A 640 645 sugar FAMILY 23146838 A 794 803 estrogens FAMILY 23146838 T 37 46 estrogens FAMILY 23146871 A 10 19 manganese SYSTEMATIC 23146871 A 1060 1066 Mn(3+) FORMULA 23146871 A 1125 1131 Fe(3+) FORMULA 23146871 A 118 124 Mn(2+) FORMULA 23146871 A 1203 1205 Mn FORMULA 23146871 A 1288 1294 Mn(3+) FORMULA 23146871 A 1343 1349 Fe(3+) FORMULA 23146871 A 1372 1378 Mn(3+) FORMULA 23146871 A 1421 1423 Mn FORMULA 23146871 A 1496 1498 Mn FORMULA 23146871 A 185 191 Mn(3+) FORMULA 23146871 A 21 23 Mn FORMULA 23146871 A 235 239 iron SYSTEMATIC 23146871 A 241 243 Fe FORMULA 23146871 A 290 292 Mn FORMULA 23146871 A 371 373 Mn FORMULA 23146871 A 419 425 Mn(2+) FORMULA 23146871 A 427 433 Mn(3+) FORMULA 23146871 A 560 562 Mn FORMULA 23146871 A 589 595 Fe(3+) FORMULA 23146871 A 647 653 Mn(3+) FORMULA 23146871 A 731 737 Mn(3+) FORMULA 23146871 A 824 835 Alexa green TRIVIAL 23146871 A 869 875 Mn(3+) FORMULA 23146871 A 945 951 Mn(3+) FORMULA 23146871 A 987 989 Mn FORMULA 23146871 T 0 9 Manganese SYSTEMATIC 23147005 A 277 291 phosphodiester SYSTEMATIC 23147005 T 84 98 phosphodiester SYSTEMATIC 23147376 A 1603 1613 Superoxide TRIVIAL 23147376 A 332 346 streptozotocin TRIVIAL 23147376 A 545 557 methacholine TRIVIAL 23147377 A 101 110 Fe(2)O(3) FORMULA 23147377 A 793 803 iron oxide SYSTEMATIC 23147377 A 89 99 iron oxide SYSTEMATIC 23147377 T 0 10 Iron oxide SYSTEMATIC 23147415 A 1044 1053 donepezil TRIVIAL 23147415 A 1077 1090 physostigmine TRIVIAL 23147415 A 1177 1184 glucose TRIVIAL 23147415 A 1267 1276 donepezil TRIVIAL 23147415 A 683 690 choline FAMILY 23147415 A 738 745 choline FAMILY 23147415 A 858 866 BW284c51 IDENTIFIER 23147415 A 937 947 bambuterol TRIVIAL 23147416 A 1245 1253 naloxone TRIVIAL 23147416 A 1258 1297 d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 FORMULA 23147416 A 1299 1303 CTAP ABBREVIATION 23147416 A 730 755 D-Ala(1)-peptide T-NH(2,) FORMULA 23147416 A 756 761 DAPTA ABBREVIATION 23147475 A 1037 1047 fluorenone SYSTEMATIC 23147475 A 1158 1168 fluorenone SYSTEMATIC 23147475 A 27 37 fluorenone SYSTEMATIC 23147475 A 398 407 zeolite L TRIVIAL 23147475 A 41 50 zeolite L TRIVIAL 23147475 A 582 592 fluorenone SYSTEMATIC 23147475 A 607 611 K(+) FORMULA 23147475 A 614 617 O=C FORMULA 23147475 A 692 696 K(+) FORMULA 23147475 A 705 724 fluorenone carbonyl SYSTEMATIC 23147475 A 771 772 C FORMULA 23147475 A 803 804 O FORMULA 23147475 T 55 65 fluorenone SYSTEMATIC 23147475 T 69 78 zeolite L TRIVIAL 23147567 A 1075 1086 naphthalene SYSTEMATIC 23147567 A 1091 1097 pyrene SYSTEMATIC 23147567 A 1366 1377 naphthalene SYSTEMATIC 23147567 A 1382 1394 phenanthrene SYSTEMATIC 23147567 A 166 188 poly(dimethylsiloxane) SYSTEMATIC 23147567 A 272 304 polycyclic aromatic hydrocarbons FAMILY 23147567 A 306 310 PAHs ABBREVIATION 23147567 A 400 403 PAH ABBREVIATION 23147567 A 411 419 silicone FAMILY 23147567 A 531 542 naphthalene SYSTEMATIC 23147567 A 544 554 anthracene SYSTEMATIC 23147567 A 560 566 pyrene SYSTEMATIC 23147567 A 708 719 naphthalene SYSTEMATIC 23147567 A 721 733 phenanthrene SYSTEMATIC 23147567 A 739 745 pyrene SYSTEMATIC 23147567 T 23 55 polycyclic aromatic hydrocarbons FAMILY 23147715 A 165 171 Cr(VI) FORMULA 23147715 A 17 31 chromium oxide SYSTEMATIC 23147715 A 200 206 Cr(VI) FORMULA 23147715 A 238 245 Cr(III) FORMULA 23147715 A 258 262 H(2) FORMULA 23147715 A 355 361 Cr(VI) FORMULA 23147715 A 383 390 Cr(III) FORMULA 23147715 A 470 477 Cr(III) FORMULA 23147715 A 506 515 Cr(OH)(3) FORMULA 23147715 A 610 618 Cr(2)O(3 FORMULA 23147715 A 677 683 Cr(VI) FORMULA 23147715 A 69 75 Cr(VI) FORMULA 23147715 A 742 751 Cr(OH)(3) FORMULA 23147715 A 77 87 CrO(4)(2-) FORMULA 23147715 A 779 787 chromium SYSTEMATIC 23147715 A 907 914 Cr(III) FORMULA 23147715 A 91 104 Cr(2)O(7)(2-) FORMULA 23147715 A 921 923 OH FORMULA 23147715 A 928 936 H(2)O(2) FORMULA 23147715 A 955 961 Cr(VI) FORMULA 23147715 A 981 989 H(2)O(2) FORMULA 23147715 T 37 51 chromium oxide SYSTEMATIC 23147715 T 81 91 dichromate SYSTEMATIC 23147750 A 1102 1110 HCO 3(-) FORMULA 23147750 A 1112 1120 SO 4(2-) FORMULA 23147750 A 1122 1128 Ca(2+) FORMULA 23147750 A 1134 1140 Mg(2+) FORMULA 23147750 A 669 674 Ca(+) FORMULA 23147750 A 676 681 Mg(+) FORMULA 23147750 A 683 691 HCO 3(-) FORMULA 23147750 A 697 704 SO 4(-) FORMULA 23147750 A 826 830 coal TRIVIAL 23147837 A 0 30 Polybrominated diphenyl ethers FAMILY 23147837 A 1061 1067 BDE-47 ABBREVIATION 23147837 A 1117 1123 BDE-99 ABBREVIATION 23147837 A 1138 1144 BDE-99 ABBREVIATION 23147837 A 1177 1183 BDE-47 ABBREVIATION 23147837 A 1362 1368 BDE-47 ABBREVIATION 23147837 A 258 262 PBDE ABBREVIATION 23147837 A 273 279 BDE-47 ABBREVIATION 23147837 A 284 290 BDE-99 ABBREVIATION 23147837 A 32 37 PBDEs ABBREVIATION 23147837 A 611 617 BDE-47 ABBREVIATION 23147837 A 627 633 BDE-99 ABBREVIATION 23147837 A 759 765 BDE-47 ABBREVIATION 23147837 A 776 782 BDE-99 ABBREVIATION 23147837 A 884 890 BDE-47 ABBREVIATION 23147837 A 922 928 BDE-99 ABBREVIATION 23147837 T 33 63 polybrominated diphenyl ethers FAMILY 23147837 T 64 70 BDE-47 ABBREVIATION 23147837 T 75 81 BDE-99 ABBREVIATION 23149337 A 1022 1031 adenosine TRIVIAL 23149337 A 1099 1108 adenosine TRIVIAL 23149337 A 492 501 histamine TRIVIAL 23149337 A 855 864 adenosine TRIVIAL 23149337 T 11 20 adenosine TRIVIAL 23149908 A 1755 1762 glucose TRIVIAL 23150491 A 1289 1292 BPA ABBREVIATION 23150491 A 1444 1447 BPA ABBREVIATION 23150491 A 382 385 BPA ABBREVIATION 23150491 A 410 425 BPA-glucuronide SYSTEMATIC 23150491 A 46 57 bisphenol A TRIVIAL 23150491 A 537 540 BPA ABBREVIATION 23150491 A 59 62 BPA ABBREVIATION 23150491 A 622 625 BPA ABBREVIATION 23150491 A 855 863 BPA-Gluc ABBREVIATION 23150491 A 921 924 BPA ABBREVIATION 23150491 A 970 973 BPA ABBREVIATION 23150491 T 31 42 bisphenol a TRIVIAL 23151003 A 1076 1085 adenosine TRIVIAL 23151003 A 1108 1141 nucleoside tri- and di-phosphates MULTIPLE 23151003 A 584 590 Purine TRIVIAL 23151003 A 595 605 pyrimidine SYSTEMATIC 23151003 A 606 617 nucleotides FAMILY 23151610 A 0 14 Carbohelicenes FAMILY 23151610 A 108 117 benzenoid FAMILY 23151610 A 1297 1311 carbohelicenes FAMILY 23151610 A 1418 1431 carbohelicene FAMILY 23151610 A 1555 1564 helicenes FAMILY 23151610 A 1659 1668 helicenes FAMILY 23151610 A 317 326 helicenes FAMILY 23151610 A 448 462 carbohelicenes FAMILY 23151610 A 708 716 helicene FAMILY 23151610 A 981 995 carbohelicenes FAMILY 23151610 T 101 115 carbohelicenes FAMILY 23151610 T 21 29 helicene FAMILY 23151611 A 1199 1213 oleanolic acid TRIVIAL 23151611 A 1238 1247 serotonin TRIVIAL 23151611 A 1249 1253 5-HT SYSTEMATIC 23151611 A 1376 1402 5-hydroxyindoleacetic acid SYSTEMATIC 23151611 A 1404 1410 5-HIAA SYSTEMATIC 23151611 A 1412 1416 5-HT SYSTEMATIC 23151611 A 1529 1543 norepinephrine TRIVIAL 23151611 A 1605 1613 dopamine TRIVIAL 23151611 A 1704 1718 oleanolic acid TRIVIAL 23151611 A 1866 1870 5-HT SYSTEMATIC 23151611 A 1937 1951 oleanolic acid TRIVIAL 23151611 A 276 290 oleanolic acid TRIVIAL 23151611 A 61 75 oleanolic acid TRIVIAL 23151611 A 882 896 oleanolic acid TRIVIAL 23151611 T 30 44 oleanolic acid TRIVIAL 23151612 A 705 714 steroidal FAMILY 23151612 A 794 801 aspirin TRIVIAL 23151612 A 803 822 omega-3 fatty acids FAMILY 23151612 A 824 837 neurosteroids FAMILY 23151612 A 842 853 minocycline TRIVIAL 23152186 A 1163 1170 As(III) FORMULA 23152186 A 1288 1295 As(III) FORMULA 23152186 A 1408 1431 sphingosine-1-phosphate SYSTEMATIC 23152186 A 1477 1484 As(III) FORMULA 23152186 A 149 156 Arsenic SYSTEMATIC 23152186 A 1570 1577 As(III) FORMULA 23152186 A 158 165 As(III) FORMULA 23152186 A 1623 1630 arsenic SYSTEMATIC 23152186 A 1720 1727 As(III) FORMULA 23152186 A 1854 1861 arsenic SYSTEMATIC 23152186 A 24 31 glucose TRIVIAL 23152186 A 391 398 As(III) FORMULA 23152186 A 633 640 As(III) FORMULA 23152186 A 809 816 As(III) FORMULA 23152186 A 841 854 dexamethasone TRIVIAL 23152186 T 0 7 Arsenic SYSTEMATIC 23153029 A 1134 1143 estrogens FAMILY 23153029 A 1177 1189 progesterone TRIVIAL 23153029 A 1297 1306 estradiol TRIVIAL 23153029 A 1311 1323 progesterone TRIVIAL 23153029 A 217 229 progesterone TRIVIAL 23153029 A 477 486 estradiol TRIVIAL 23153029 A 534 543 estradiol TRIVIAL 23153029 A 613 622 estradiol TRIVIAL 23153029 A 696 708 progesterone TRIVIAL 23153029 T 4 16 progesterone TRIVIAL 23153054 A 394 404 alprazolam TRIVIAL 23153054 A 406 416 clonazepam TRIVIAL 23153054 A 418 427 diltiazem TRIVIAL 23153054 A 429 438 midazolam TRIVIAL 23153054 A 440 450 nifedipine TRIVIAL 23153054 A 456 465 quinidine TRIVIAL 23153054 A 806 819 dexamethasone TRIVIAL 23153054 A 821 831 nifedipine TRIVIAL 23153054 A 833 842 midazolam TRIVIAL 23153054 A 844 853 quinidine TRIVIAL 23153054 A 855 865 tacrolimus TRIVIAL 23153054 A 871 880 verapamil TRIVIAL 23153057 A 1554 1566 salicylamide TRIVIAL 23153057 A 1693 1705 salicylamide TRIVIAL 23153057 A 325 335 phenacetin TRIVIAL 23153057 A 337 346 bupropion TRIVIAL 23153057 A 348 358 diclofenac TRIVIAL 23153057 A 363 372 midazolam TRIVIAL 23153057 A 483 499 β-naphthoflavone TRIVIAL 23153057 A 509 522 phenobarbital TRIVIAL 23153057 A 536 546 rifampicin TRIVIAL 23153057 A 743 755 salicylamide TRIVIAL 23153322 A 109 112 RAI ABBREVIATION 23153322 A 1514 1517 RAI ABBREVIATION 23153322 A 179 182 RAI ABBREVIATION 23153322 A 1988 1991 RAI ABBREVIATION 23153322 A 2054 2057 RAI ABBREVIATION 23153322 A 379 382 RAI ABBREVIATION 23153322 A 432 435 RAI ABBREVIATION 23153322 A 474 477 RAI ABBREVIATION 23153322 A 89 107 radioactive iodine SYSTEMATIC 23153322 T 38 56 radioactive iodine SYSTEMATIC 23153456 A 722 734 nitric oxide SYSTEMATIC 23153456 A 885 916 polyinosinic:polycytidylic acid MULTIPLE 23153512 A 1024 1027 FEN ABBREVIATION 23153512 A 237 240 FEN ABBREVIATION 23153512 A 374 377 FEN ABBREVIATION 23153512 A 443 457 methylene blue TRIVIAL 23153512 A 522 525 FEN ABBREVIATION 23153512 A 541 544 FEN ABBREVIATION 23153512 A 585 599 methylene blue TRIVIAL 23153512 A 61 73 fenitrothion TRIVIAL 23153512 A 661 665 (1)H FORMULA 23153512 A 682 685 FEN ABBREVIATION 23153512 A 749 754 (31)P FORMULA 23153512 A 75 78 FEN ABBREVIATION 23153512 A 771 774 FEN ABBREVIATION 23153512 A 808 811 NO2 FORMULA 23153512 T 105 110 (31)P FORMULA 23153512 T 116 120 (1)H FORMULA 23153512 T 48 60 fenitrothion TRIVIAL 23154127 A 1127 1146 formamidopyrimidine SYSTEMATIC 23154127 A 1264 1267 AOH FORMULA 23154127 A 1272 1275 AME ABBREVIATION 23154127 A 1391 1394 AOH FORMULA 23154127 A 1399 1402 AME ABBREVIATION 23154127 A 14 25 alternariol TRIVIAL 23154127 A 27 30 AOH FORMULA 23154127 A 286 289 AOH FORMULA 23154127 A 317 332 monomethylether SYSTEMATIC 23154127 A 334 337 AME ABBREVIATION 23154127 A 347 366 dichlorofluorescein SYSTEMATIC 23154127 A 368 371 DCF ABBREVIATION 23154127 A 438 457 dichlorofluorescein SYSTEMATIC 23154127 A 499 510 glutathione TRIVIAL 23154127 A 583 586 DCF ABBREVIATION 23154127 A 594 597 AOH FORMULA 23154127 A 602 605 AME ABBREVIATION 23154127 A 723 741 γ-glutamylcysteine SYSTEMATIC 23154127 A 761 772 glutathione TRIVIAL 23154127 A 773 774 S FORMULA 23154127 A 975 978 DCF ABBREVIATION 23154127 T 65 76 alternariol TRIVIAL 23154127 T 81 109 alternariol monomethyl ether SYSTEMATIC 23154304 A 116 132 indole hydrazone FAMILY 23154304 A 319 335 indole hydrazone FAMILY 23154304 A 424 445 adenosine diphosphate TRIVIAL 23154304 A 447 450 ADP ABBREVIATION 23154304 A 456 472 arachidonic acid TRIVIAL 23154304 A 537 553 arachidonic acid TRIVIAL 23154304 A 624 636 indomethacin TRIVIAL 23154304 A 712 715 ADP ABBREVIATION 23154304 A 81 90 hydrazone FAMILY 23154304 T 19 35 indole hydrazone FAMILY 23154865 A 515 518 BH3 FORMULA 23155201 A 587 601 technetium-99m SYSTEMATIC 23155201 A 603 608 99mTc FORMULA 23155201 A 610 631 methylendiphosphonate SYSTEMATIC 23155201 A 633 636 MDP ABBREVIATION 23157442 A 342 352 Gentamicin FAMILY 23157635 A 334 340 oxygen SYSTEMATIC 23157637 A 1217 1228 haloperidol TRIVIAL 23157637 A 1230 1240 olanzapine TRIVIAL 23157637 A 1242 1252 quetiapine TRIVIAL 23157637 A 1257 1268 risperidone TRIVIAL 23157637 A 1313 1321 dopamine TRIVIAL 23157637 A 139 145 oxygen SYSTEMATIC 23157640 A 1253 1261 platinum SYSTEMATIC 23157640 A 459 468 cisplatin TRIVIAL 23157640 A 470 484 anthracyclines FAMILY 23157640 A 490 497 taxanes FAMILY 23159106 A 1179 1186 ethanol SYSTEMATIC 23159106 A 296 303 ethanol SYSTEMATIC 23159106 A 548 555 ethanol SYSTEMATIC 23159106 A 586 592 oxygen SYSTEMATIC 23159106 A 83 90 ethanol SYSTEMATIC 23159106 A 951 957 Oxygen SYSTEMATIC 23159106 T 0 7 Ethanol SYSTEMATIC 23159331 A 0 15 Methamphetamine TRIVIAL 23159331 A 1238 1253 methamphetamine TRIVIAL 23159331 A 138 153 methamphetamine TRIVIAL 23159331 A 1445 1460 methamphetamine TRIVIAL 23159331 A 1654 1663 serotonin TRIVIAL 23159331 A 1770 1785 methamphetamine TRIVIAL 23159331 A 1905 1914 serotonin TRIVIAL 23159331 A 385 400 methamphetamine TRIVIAL 23159331 A 473 492 (±)-methamphetamine TRIVIAL 23159331 A 884 899 Methamphetamine TRIVIAL 23159331 A 942 950 dopamine TRIVIAL 23159331 A 966 975 serotonin TRIVIAL 23159331 A 977 992 Methamphetamine TRIVIAL 23159331 T 36 51 methamphetamine TRIVIAL 23159396 A 1226 1230 FITC ABBREVIATION 23159396 A 1255 1259 FITC ABBREVIATION 23159396 A 126 130 FITC ABBREVIATION 23159396 A 1539 1543 FITC ABBREVIATION 23159396 A 385 389 FITC ABBREVIATION 23159396 A 427 431 DAPI ABBREVIATION 23159396 A 433 463 4',6'-diamidino-2-phenylindole SYSTEMATIC 23159396 A 469 479 Evans blue TRIVIAL 23159396 A 481 485 FITC ABBREVIATION 23159396 A 571 575 FITC ABBREVIATION 23159396 A 584 588 FITC ABBREVIATION 23159396 A 703 707 FITC ABBREVIATION 23159396 A 716 720 FITC ABBREVIATION 23159396 A 98 124 fluorescein isothiocyanate TRIVIAL 23159397 A 583 631 calcium disodium ethylenediaminetetraacetic acid SYSTEMATIC 23159397 A 633 644 CaNa(2)EDTA FORMULA 23159479 A 310 318 oxytocin TRIVIAL 23159479 A 54 62 oxytocin TRIVIAL 23159479 A 640 648 oxytocin TRIVIAL 23159479 A 704 712 oxytocin TRIVIAL 23159479 A 817 825 Oxytocin TRIVIAL 23159479 T 14 22 oxytocin TRIVIAL 23159529 A 1088 1091 14C FORMULA 23159529 A 204 209 17864 IDENTIFIER 23159529 A 217 225 platinum SYSTEMATIC 23159529 A 232 241 sunitinib TRIVIAL 23159529 A 277 287 methionine TRIVIAL 23159529 A 412 431 polyethylene glycol SYSTEMATIC 23159529 A 438 441 PEG ABBREVIATION 23159529 A 565 568 PEG ABBREVIATION 23159529 A 647 650 14C FORMULA 23159529 A 729 734 17864 IDENTIFIER 23159529 A 752 755 PEG ABBREVIATION 23159529 A 77 91 Glutaraldehyde TRIVIAL 23159529 T 84 89 17864 IDENTIFIER 23159662 A 0 11 Venlafaxine TRIVIAL 23159662 A 1200 1211 venlafaxine TRIVIAL 23159662 A 1540 1551 venlafaxine TRIVIAL 23159662 A 1663 1674 venlafaxine TRIVIAL 23159662 A 318 329 venlafaxine TRIVIAL 23159662 A 394 405 venlafaxine TRIVIAL 23159662 A 527 538 venlafaxine TRIVIAL 23159662 A 586 597 venlafaxine TRIVIAL 23159662 A 833 844 venlafaxine TRIVIAL 23159662 A 898 909 venlafaxine TRIVIAL 23159662 T 38 49 venlafaxine TRIVIAL 23159666 A 196 215 polyethylene glycol SYSTEMATIC 23159666 A 217 220 PEG ABBREVIATION 23159666 A 284 324 5,10,15,20-tetra(m-hydroxyphenyl)chlorin SYSTEMATIC 23159666 A 326 332 Foscan TRIVIAL 23159666 A 574 580 Foscan TRIVIAL 23159666 A 798 804 Foscan TRIVIAL 23159666 A 831 834 PEG ABBREVIATION 23159666 A 948 954 Foscan TRIVIAL 23159666 T 70 76 Foscan TRIVIAL 23159667 A 0 18 8-Chloro-adenosine SYSTEMATIC 23159667 A 126 129 8CA SYSTEMATIC 23159667 A 1260 1263 8CA SYSTEMATIC 23159667 A 1340 1343 8CA SYSTEMATIC 23159667 A 1347 1351 8CAS SYSTEMATIC 23159667 A 1442 1445 8CA SYSTEMATIC 23159667 A 1471 1475 8CAS SYSTEMATIC 23159667 A 1535 1538 8CA SYSTEMATIC 23159667 A 20 23 8CA SYSTEMATIC 23159667 A 269 272 8CA SYSTEMATIC 23159667 A 329 361 8-chloro-adenosine-5'-O-stearate SYSTEMATIC 23159667 A 363 367 8CAS SYSTEMATIC 23159667 A 383 395 octadecanoyl SYSTEMATIC 23159667 A 408 411 8CA SYSTEMATIC 23159667 A 502 521 phosphatidylcholine FAMILY 23159667 A 523 534 cholesterol TRIVIAL 23159667 A 539 561 poly (ethylene glycol) SYSTEMATIC 23159667 A 567 602 distearoyl phosphatidylethanolamine SYSTEMATIC 23159667 A 604 612 PEG-DSPE ABBREVIATION 23159667 A 698 701 MTT ABBREVIATION 23159667 A 741 745 8CAS SYSTEMATIC 23159667 A 775 779 8CAS SYSTEMATIC 23159667 A 906 909 8CA SYSTEMATIC 23159667 A 990 994 8CAS SYSTEMATIC 23159667 T 62 80 8-chloro-adenosine SYSTEMATIC 23159712 A 176 185 lidocaine TRIVIAL 23159712 A 356 364 Carbopol TRIVIAL 23159712 A 366 375 Poloxamer TRIVIAL 23159712 A 420 427 PEG 400 ABBREVIATION 23159712 A 429 445 triethyl citrate SYSTEMATIC 23159712 A 570 579 lidocaine TRIVIAL 23159712 A 580 589 Compritol TRIVIAL 23159712 A 691 700 lidocaine TRIVIAL 23159712 A 95 104 lidocaine TRIVIAL 23159712 T 79 88 lidocaine TRIVIAL 23159729 A 0 16 Naphthenic acids FAMILY 23159729 A 1204 1220 naphthenic acids FAMILY 23159729 A 1250 1265 Naphthenic acid FAMILY 23159729 A 1383 1399 naphthenic acids FAMILY 23159729 A 1430 1444 benzo[a]pyrene SYSTEMATIC 23159729 A 1592 1608 naphthenic acids FAMILY 23159729 A 177 193 naphthenic acids FAMILY 23159729 A 334 350 naphthenic acids FAMILY 23159729 A 606 620 benzo[a]pyrene SYSTEMATIC 23159729 T 41 57 naphthenic acids FAMILY 23159732 A 1013 1016 Trp FORMULA 23159732 A 1027 1030 Trp FORMULA 23159732 A 1049 1052 Trp FORMULA 23159732 A 1082 1085 Trp FORMULA 23159732 A 1185 1188 NFK ABBREVIATION 23159732 A 1383 1385 O2 FORMULA 23159732 A 21 35 methylene blue TRIVIAL 23159732 A 60 66 oxygen SYSTEMATIC 23159732 A 71 73 O2 FORMULA 23159732 A 897 916 N'-formylkynurenine TRIVIAL 23159732 A 918 921 NFK ABBREVIATION 23159732 A 961 964 NFK ABBREVIATION 23159732 T 48 62 methylene blue TRIVIAL 23159790 A 1082 1092 nucleotide FAMILY 23159790 A 1144 1155 amino acids FAMILY 23159790 A 1630 1633 Gly FORMULA 23159790 A 1636 1639 Ser FORMULA 23159790 A 1642 1645 Gly FORMULA 23159790 A 1931 1938 proline TRIVIAL 23159790 A 2024 2031 proline TRIVIAL 23159790 A 972 982 amino acid FAMILY 23159888 A 0 7 Alcohol SYSTEMATIC 23159888 A 191 198 alcohol FAMILY 23159888 A 60 67 alcohol FAMILY 23159888 A 827 838 glutathione TRIVIAL 23159888 A 839 840 S FORMULA 23159888 T 22 29 alcohol FAMILY 23160003 A 533 549 bicyclic phenols FAMILY 23160003 A 558 586 polycyclic cyclohexadienones FAMILY 23160003 A 795 809 dienone-phenol SYSTEMATIC 23160003 A 863 869 phenol SYSTEMATIC 23160089 A 110 142 5,7,3',5'-tetrahydroxy-flavanone SYSTEMATIC 23160089 A 148 204 5,7,3',5'-tetrahydroxy-flavanone-7-O-β-d-glucopyranoside SYSTEMATIC 23160089 A 214 267 5,7,3',5'-tetrahydroxy-flavanone-7-O-neohesperidoside SYSTEMATIC 23160089 A 29 46 drynachromoside A TRIVIAL 23160089 A 52 69 drynachromoside B TRIVIAL 23160089 A 522 532 flavonoids FAMILY 23160089 A 565 568 MTT ABBREVIATION 23160089 A 8 27 chromone glycosides FAMILY 23160089 A 98 108 flavanones FAMILY 23160089 T 8 27 chromone glycosides FAMILY 23160092 A 1107 1118 curcumenone TRIVIAL 23160092 A 1160 1167 alcohol FAMILY 23160092 A 1207 1214 alcohol FAMILY 23160092 A 159 166 alcohol FAMILY 23160092 A 284 291 alcohol FAMILY 23160092 A 322 329 alcohol FAMILY 23160092 A 362 369 ethanol SYSTEMATIC 23160092 A 459 466 alcohol FAMILY 23160092 A 487 495 n-hexane SYSTEMATIC 23160092 A 624 632 n-hexane SYSTEMATIC 23160092 A 703 710 alcohol FAMILY 23160092 A 749 756 alcohol FAMILY 23160092 A 863 870 alcohol FAMILY 23160092 A 918 929 curcumenone TRIVIAL 23160092 A 956 960 (1)H FORMULA 23160092 A 966 971 (13)C FORMULA 23160092 T 102 109 alcohol FAMILY 23160092 T 47 58 curcumenone TRIVIAL 23160419 A 1076 1081 NO(2) FORMULA 23160419 A 1112 1117 NO(2) FORMULA 23160419 A 1128 1133 NO(2) FORMULA 23160419 A 1191 1198 oxygens FAMILY 23160419 A 1305 1310 NO(2) FORMULA 23160419 A 1364 1369 NO(2) FORMULA 23160419 A 1464 1469 NO(2) FORMULA 23160419 A 1530 1534 HONO FORMULA 23160419 A 170 175 NO(2) FORMULA 23160419 A 19 24 NO(2) FORMULA 23160419 A 239 244 NO(2) FORMULA 23160419 A 245 250 H(2)O FORMULA 23160419 A 367 372 NO(2) FORMULA 23160419 A 373 378 H(2)O FORMULA 23160419 A 477 482 NO(2) FORMULA 23160419 A 611 616 NO(2) FORMULA 23160419 A 857 862 NO(2) FORMULA 23160419 A 929 937 nitrogen SYSTEMATIC 23160419 A 951 957 oxygen SYSTEMATIC 23160419 A 980 988 hydrogen SYSTEMATIC 23160419 T 0 16 Nitrogen dioxide SYSTEMATIC 23160527 A 36 43 glucose TRIVIAL 23160527 A 382 389 glucose TRIVIAL 23160527 A 434 441 glucose TRIVIAL 23160529 A 138 142 zinc SYSTEMATIC 23160934 A 1114 1120 Cu(2+) FORMULA 23160934 A 124 139 α-syn12 peptide TRIVIAL 23160934 A 1262 1277 α-syn12 peptide TRIVIAL 23160934 A 1345 1351 Cu(2+) FORMULA 23160934 A 1388 1403 α-syn12 peptide TRIVIAL 23160934 A 15 21 Cu(2+) FORMULA 23160934 A 267 273 Cu(2+) FORMULA 23160934 A 292 307 α-syn12 peptide TRIVIAL 23160934 A 433 448 α-syn12 peptide TRIVIAL 23160934 A 782 797 α-syn12 peptide TRIVIAL 23160934 A 850 856 Cu(2+) FORMULA 23160934 A 863 878 α-syn12 peptide TRIVIAL 23160934 A 960 966 Cu(2+) FORMULA 23160934 A 985 1000 α-syn12 peptide TRIVIAL 23160934 T 48 54 Cu(2+) FORMULA 23160934 T 73 88 α-syn12 peptide TRIVIAL 23160940 A 1050 1092 guanosine 5'-O-(3-[(35)S]thio)triphosphate SYSTEMATIC 23160940 A 1094 1106 [(35)S]GTPγS SYSTEMATIC 23160940 A 1181 1185 cAMP ABBREVIATION 23160940 A 1371 1375 cAMP ABBREVIATION 23160940 A 1481 1490 Org 27569 IDENTIFIER 23160940 A 1495 1504 PSNCBAM-1 IDENTIFIER 23160940 A 225 238 [(3)H]CP55940 IDENTIFIER 23160940 A 507 519 [(35)S]GTPγS SYSTEMATIC 23160940 A 560 569 forskolin TRIVIAL 23160940 A 581 585 cAMP ABBREVIATION 23160940 A 87 96 Org 27569 IDENTIFIER 23160940 A 880 887 CP55940 IDENTIFIER 23160940 A 915 923 WIN55212 IDENTIFIER 23160940 A 952 966 [(3)H]WIN55212 IDENTIFIER 23160940 A 976 985 Org 27569 IDENTIFIER 23160940 A 98 107 PSNCBAM-1 IDENTIFIER 23160961 A 1049 1053 acyl FAMILY 23160961 A 1072 1076 acyl FAMILY 23160961 A 1111 1127 triacylglyceride FAMILY 23160961 A 1275 1279 acyl FAMILY 23160961 A 1319 1323 acyl FAMILY 23160961 A 158 161 Ser FORMULA 23160961 A 919 930 fatty acids FAMILY 23160964 A 1013 1036 1,25-dihydroxyvitamin D SYSTEMATIC 23160964 A 1149 1172 1,25-dihydroxyvitamin D SYSTEMATIC 23160964 A 1253 1262 vitamin D FAMILY 23160964 A 179 188 vitamin D FAMILY 23160964 A 259 268 vitamin D FAMILY 23160964 A 449 458 vitamin D FAMILY 23160964 A 559 568 vitamin D FAMILY 23160964 A 650 659 vitamin D FAMILY 23160964 A 667 677 RO-27-5646 IDENTIFIER 23160964 A 805 828 1,25-dihydroxyvitamin D SYSTEMATIC 23160964 A 94 103 Vitamin D FAMILY 23160964 T 0 24 1,25-Dihydroxyvitamin D3 SYSTEMATIC 23161217 A 1115 1122 Suramin TRIVIAL 23161217 A 1303 1310 Suramin TRIVIAL 23161217 A 1396 1403 phospho SYSTEMATIC 23161217 A 1473 1480 suramin TRIVIAL 23161217 A 1560 1567 suramin TRIVIAL 23161217 A 169 176 suramin TRIVIAL 23161217 A 180 207 polysulfonated naphthylurea FAMILY 23161217 A 287 294 ethanol SYSTEMATIC 23161217 A 394 401 alanine TRIVIAL 23161217 A 435 444 bilirubin TRIVIAL 23161217 A 604 611 Suramin TRIVIAL 23161217 A 761 784 5-bromo-2'-deoxyuridine SYSTEMATIC 23161217 A 786 790 BrdU ABBREVIATION 23161217 A 980 987 Suramin TRIVIAL 23161217 A 998 1002 BrdU ABBREVIATION 23161217 T 0 7 Suramin TRIVIAL 23161217 T 54 61 ethanol SYSTEMATIC 23161424 A 125 135 evodiamine TRIVIAL 23161424 A 208 218 Evodiamine TRIVIAL 23161424 A 359 362 Arg FORMULA 23161424 A 370 373 Asp FORMULA 23161424 A 419 429 evodiamine TRIVIAL 23161424 A 474 484 evodiamine TRIVIAL 23161424 A 536 546 Evodiamine TRIVIAL 23161424 A 744 754 evodiamine TRIVIAL 23161424 T 26 36 evodiamine TRIVIAL 23161648 A 211 215 coal TRIVIAL 23161648 A 534 542 SO (4)2- FORMULA 23161648 A 545 553 HCO (3)- FORMULA 23161648 A 556 561 Cl(-) FORMULA 23161664 A 0 5 Lysyl TRIVIAL 23161664 A 1024 1026 Co FORMULA 23161664 A 1311 1313 Co FORMULA 23161664 A 1380 1387 Cadmium SYSTEMATIC 23161664 A 1389 1391 Cd FORMULA 23161664 A 1417 1423 oxygen SYSTEMATIC 23161664 A 1503 1505 Co FORMULA 23161664 A 1613 1615 Co FORMULA 23161664 A 1620 1622 Cd FORMULA 23161664 A 673 678 CoCl2 FORMULA 23161664 A 680 682 Co FORMULA 23161664 A 886 892 cobalt SYSTEMATIC 23161664 A 894 896 Co FORMULA 23161664 T 112 118 cobalt SYSTEMATIC 23161664 T 123 130 cadmium SYSTEMATIC 23161664 T 78 83 lysyl TRIVIAL 23161673 A 1197 1206 tamoxifen TRIVIAL 23161673 A 1473 1482 tamoxifen TRIVIAL 23161677 A 207 214 guanine TRIVIAL 23161677 A 220 232 nucleic acid FAMILY 23161804 A 0 43 (18-Crown-6)-2,3,11,12-tetracarboxylic acid SYSTEMATIC 23161804 A 105 117 β-amino acid FAMILY 23161804 A 131 142 Isoxazoline FAMILY 23161804 A 176 189 hydrochloride FAMILY 23161804 A 199 207 methanol SYSTEMATIC 23161804 A 285 293 hydrogen SYSTEMATIC 23161804 A 323 328 amine SYSTEMATIC 23161804 A 333 344 crown ether FAMILY 23161804 A 345 351 oxygen SYSTEMATIC 23161804 A 87 98 isoxazoline SYSTEMATIC 23161804 T 31 42 isoxazoline SYSTEMATIC 23161804 T 49 61 β-amino acid FAMILY 23161804 T 80 123 (18-crown-6)-2,3,11,12-tetracarboxylic acid SYSTEMATIC 23163430 A 1026 1045 polyethylene glycol SYSTEMATIC 23163508 A 533 544 chlorophyll FAMILY 23163696 A 1035 1039 H-89 TRIVIAL 23163696 A 1286 1314 inositol 1,4,5-trisphosphate SYSTEMATIC 23163696 A 773 796 cyclo(1-8) [DLeu(5) ]OP FORMULA 23163696 A 838 852 benzodiazepine FAMILY 23163696 A 873 883 flumazenil TRIVIAL 23163696 A 977 984 U-73122 IDENTIFIER 23164613 A 107 116 serotonin TRIVIAL 23164613 A 285 294 8-OH-DPAT SYSTEMATIC 23164613 A 299 305 LP-211 IDENTIFIER 23164613 A 409 418 SB-269970 IDENTIFIER 23164613 A 441 446 U0126 IDENTIFIER 23164613 A 498 509 roscovitine TRIVIAL 23164613 A 525 538 cycloheximide TRIVIAL 23164613 A 70 74 5-HT SYSTEMATIC 23164613 T 4 13 serotonin TRIVIAL 23164615 A 169 179 AZ12216052 IDENTIFIER 23164615 A 229 259 (S)-3,4-dicarboxyphenylglycine SYSTEMATIC 23164615 A 261 265 DCPG ABBREVIATION 23164615 A 394 398 DCPG ABBREVIATION 23164615 A 749 758 glutamate TRIVIAL 23164615 A 865 874 glutamate TRIVIAL 23164615 A 983 987 DCPG ABBREVIATION 23164615 T 108 117 glutamate TRIVIAL 23164711 A 280 284 ZINC SYSTEMATIC 23164711 A 302 309 sulfate SYSTEMATIC 23164711 A 715 739 monosulfated benzofurans FAMILY 23164711 A 852 856 ZINC SYSTEMATIC 23164711 A 970 990 sulfated benzofurans FAMILY 23164931 A 1006 1010 MPEP ABBREVIATION 23164931 A 461 473 procyclidine TRIVIAL 23164931 A 478 488 caramiphen TRIVIAL 23164931 A 509 518 glutamate TRIVIAL 23164931 A 530 536 DCG-IV IDENTIFIER 23164931 A 541 545 MPEP ABBREVIATION 23164931 A 728 738 caramiphen TRIVIAL 23164931 A 871 883 Procyclidine TRIVIAL 23164931 A 996 1002 DCG-IV IDENTIFIER 23164984 A 193 195 Hg FORMULA 23164984 A 197 199 Cd FORMULA 23164984 A 201 203 Pb FORMULA 23164984 A 208 210 As FORMULA 23164984 A 377 379 Hg FORMULA 23164984 A 40 47 mercury SYSTEMATIC 23164984 A 49 51 Hg FORMULA 23164984 A 54 61 cadmium SYSTEMATIC 23164984 A 63 65 Cd FORMULA 23164984 A 74 76 Pb FORMULA 23164984 A 781 783 Hg FORMULA 23164984 A 82 89 arsenic SYSTEMATIC 23164984 A 91 93 As FORMULA 23164984 T 28 35 mercury SYSTEMATIC 23164984 T 43 50 cadmium SYSTEMATIC 23164984 T 56 63 arsenic SYSTEMATIC 23168241 A 1033 1040 sulfite SYSTEMATIC 23168241 A 1094 1101 sulfite SYSTEMATIC 23168241 A 1191 1201 quinacrine TRIVIAL 23168241 A 1277 1284 sulfite SYSTEMATIC 23168241 A 302 322 sodium metabisulfite SYSTEMATIC 23168241 A 336 356 sodium metabisulfite SYSTEMATIC 23168241 A 357 367 quinacrine TRIVIAL 23168241 A 382 402 Sodium metabisulfite SYSTEMATIC 23168241 A 41 48 sulfite SYSTEMATIC 23168241 A 476 486 quinacrine TRIVIAL 23168241 A 683 693 quinacrine TRIVIAL 23168241 A 717 718 S FORMULA 23168241 A 719 728 sulfonate SYSTEMATIC 23168241 A 856 866 Quinacrine TRIVIAL 23168241 A 953 963 Quinacrine TRIVIAL 23168241 T 48 55 sulfite SYSTEMATIC 23168241 T 9 19 quinacrine TRIVIAL 23168915 A 112 115 NiO FORMULA 23168915 A 67 71 H(2) FORMULA 23168915 T 73 85 nickel oxide SYSTEMATIC 23169614 A 1079 1085 carbon SYSTEMATIC 23169614 A 21 29 graphene TRIVIAL 23169614 A 211 219 graphene TRIVIAL 23169614 A 335 343 graphene TRIVIAL 23169614 A 621 627 carbon SYSTEMATIC 23169614 A 923 931 graphene TRIVIAL 23169614 T 36 44 graphene TRIVIAL 23170796 A 1031 1042 minocycline TRIVIAL 23170796 A 1187 1198 minocycline TRIVIAL 23170796 A 1253 1264 minocycline TRIVIAL 23170796 A 283 294 Minocycline TRIVIAL 23170796 A 332 344 tetracycline FAMILY 23170796 A 353 399 7-dimethylamino-6-dimethyl-6-deoxytetracycline SYSTEMATIC 23170796 A 538 549 minocycline TRIVIAL 23170796 A 916 927 minocycline TRIVIAL 23170796 T 0 11 Minocycline TRIVIAL 23170798 A 191 198 ethanol SYSTEMATIC 23170798 A 615 622 ethanol SYSTEMATIC 23170798 A 767 774 ethanol SYSTEMATIC 23170798 A 972 979 ethanol SYSTEMATIC 23170798 T 31 38 ethanol SYSTEMATIC 23171045 A 135 143 biphenyl SYSTEMATIC 23171045 A 31 66 2-(aryloxy)-3-phenylpropanoic acids FAMILY 23171045 A 802 815 acylcarnitine SYSTEMATIC 23171045 A 828 837 carnitine TRIVIAL 23171045 A 838 847 palmitoyl TRIVIAL 23171045 A 905 914 carnitine TRIVIAL 23171045 T 137 146 carnitine TRIVIAL 23171045 T 4 39 2-(aryloxy)-3-phenylpropanoic acids FAMILY 23172038 A 767 783 titanium dioxide SYSTEMATIC 23172121 A 973 986 polyurethanes FAMILY 23172121 T 12 24 polyurethane SYSTEMATIC 23172229 A 1026 1037 cardiolipin TRIVIAL 23172229 A 1092 1103 cardiolipin TRIVIAL 23172229 A 1349 1360 cardiolipin TRIVIAL 23172229 A 1401 1412 cardiolipin TRIVIAL 23172229 A 1447 1458 cardiolipin TRIVIAL 23172229 A 1509 1520 cardiolipin TRIVIAL 23172229 A 1573 1584 cardiolipin TRIVIAL 23172229 A 251 262 cardiolipin TRIVIAL 23172229 A 306 317 cardiolipin TRIVIAL 23172229 A 606 625 phosphatidylcholine FAMILY 23172229 A 630 654 phosphatidylethanolamine SYSTEMATIC 23172229 A 897 908 cardiolipin TRIVIAL 23172229 T 0 11 Cardiolipin TRIVIAL 23174213 A 894 901 calcium SYSTEMATIC 23174457 A 1000 1006 Mn(2+) FORMULA 23174457 A 568 574 Mn(2+) FORMULA 23174457 A 675 681 Mn(2+) FORMULA 23174457 A 823 830 cadmium SYSTEMATIC 23174457 A 854 860 Mn(2+) FORMULA 23174457 A 917 925 paraoxon TRIVIAL 23174457 A 964 970 Cd(2+) FORMULA 23174457 T 0 6 Mn(2+) FORMULA 23174539 A 1037 1041 PERM ABBREVIATION 23174539 A 1217 1225 dopamine TRIVIAL 23174539 A 1266 1275 serotonin TRIVIAL 23174539 A 1277 1281 5-HT SYSTEMATIC 23174539 A 1287 1300 noradrenaline TRIVIAL 23174539 A 1466 1470 PERM ABBREVIATION 23174539 A 1565 1575 pyrethroid FAMILY 23174539 A 1586 1607 3-phenoxybenzoic acid SYSTEMATIC 23174539 A 174 184 permethrin TRIVIAL 23174539 A 186 190 PERM ABBREVIATION 23174539 A 340 344 PERM ABBREVIATION 23174539 A 479 487 dopamine TRIVIAL 23174539 A 669 673 PERM ABBREVIATION 23174539 T 22 32 permethrin TRIVIAL 23174539 T 75 84 monoamine FAMILY 23174746 A 0 7 Ritalin TRIVIAL 23174746 A 10 25 methylphenidate SYSTEMATIC 23174746 A 206 213 Ritalin TRIVIAL 23174746 A 33 44 amphetamine TRIVIAL 23174746 A 505 512 Ritalin TRIVIAL 23174746 T 38 45 Ritalin TRIVIAL 23174746 T 50 65 methylphenidate SYSTEMATIC 23177255 A 137 144 glucose TRIVIAL 23177255 A 156 168 scutellarein TRIVIAL 23177255 A 239 246 glucose TRIVIAL 23177255 A 273 285 scutellarein TRIVIAL 23177255 A 32 43 scutellarin TRIVIAL 23177255 A 358 365 glucose TRIVIAL 23177255 A 377 389 scutellarein TRIVIAL 23177255 A 419 423 DPPH ABBREVIATION 23177255 A 57 68 scutellarin TRIVIAL 23177255 A 631 638 glucose TRIVIAL 23177255 A 692 699 glucose TRIVIAL 23177255 A 710 722 scutellarein TRIVIAL 23177255 A 94 106 scutellarein TRIVIAL 23177255 T 149 160 scutellarin TRIVIAL 23177255 T 47 54 glucose TRIVIAL 23177255 T 66 78 scutellarein TRIVIAL 23177256 A 233 241 arginine TRIVIAL 23177256 A 318 337 7-nitrobenzofurazan SYSTEMATIC 23177256 A 392 406 ortho-biphenyl SYSTEMATIC 23177256 A 432 450 para-carboxyphenyl SYSTEMATIC 23177256 A 486 494 JY-3-094 IDENTIFIER 23177256 A 608 616 JY-3-094 IDENTIFIER 23177256 A 748 756 JY-3-094 IDENTIFIER 23177256 A 75 83 10074-G5 IDENTIFIER 23177256 A 85 149 N-([1,1'-biphenyl]-2-yl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine SYSTEMATIC 23177256 T 48 56 10074-G5 IDENTIFIER 23177784 A 103 114 nucleosides FAMILY 23177784 A 171 195 5-amino-2'-deoxycytidine SYSTEMATIC 23177784 A 219 227 diketone SYSTEMATIC 23177784 A 233 242 ruthenium SYSTEMATIC 23177784 A 25 34 ruthenium SYSTEMATIC 23177784 A 295 317 polypyridine ruthenium SYSTEMATIC 23177784 A 39 47 europium SYSTEMATIC 23177784 A 394 402 europium SYSTEMATIC 23177784 A 410 440 1,10-phenanthroline-2,9-diacid SYSTEMATIC 23177784 A 455 465 lanthanide FAMILY 23177784 A 474 484 nucleoside FAMILY 23177784 A 595 609 phenanthroline SYSTEMATIC 23177784 A 623 633 lanthanide FAMILY 23177784 A 642 652 nucleoside FAMILY 23177784 A 72 91 1,10-phenanthroline SYSTEMATIC 23177784 A 744 752 europium SYSTEMATIC 23177784 T 18 32 phenanthroline SYSTEMATIC 23177784 T 41 52 nucleosides FAMILY 23177784 T 65 74 ruthenium SYSTEMATIC 23177784 T 79 87 europium SYSTEMATIC 23178170 A 1025 1031 Ca(2+) FORMULA 23178170 A 1171 1177 Ca(2+) FORMULA 23178170 A 1328 1335 calcium SYSTEMATIC 23178170 A 1428 1434 Ca(2+) FORMULA 23178170 A 445 451 Ca(2+) FORMULA 23178170 A 468 469 C FORMULA 23178170 A 639 640 C FORMULA 23178170 A 728 734 Ca(2+) FORMULA 23178170 A 74 83 potassium SYSTEMATIC 23178170 A 753 754 C FORMULA 23178170 A 832 839 calcium SYSTEMATIC 23178170 A 979 985 Ca(2+) FORMULA 23178170 T 15 21 Ca(2+) FORMULA 23178178 A 1003 1009 TiO(2) FORMULA 23178178 A 1236 1243 lactate FAMILY 23178178 A 1261 1267 TiO(2) FORMULA 23178178 A 1750 1761 glutathione TRIVIAL 23178178 A 1788 1797 Na(+)K(+) FORMULA 23178178 A 183 199 titanium dioxide SYSTEMATIC 23178178 A 215 221 TiO(2) FORMULA 23178178 A 344 350 TiO(2) FORMULA 23178178 A 364 370 TiO(2) FORMULA 23178178 A 394 400 TiO(2) FORMULA 23178178 A 414 430 Titanium dioxide SYSTEMATIC 23178178 A 498 500 Ti FORMULA 23178178 A 595 597 Ti FORMULA 23178178 A 681 687 TiO(2) FORMULA 23178178 A 884 890 TiO(2) FORMULA 23178178 A 947 953 TiO(2) FORMULA 23178178 T 79 95 titanium dioxide SYSTEMATIC 23178179 A 1047 1050 MBT ABBREVIATION 23178179 A 1182 1185 MBT ABBREVIATION 23178179 A 286 309 2-Mercaptobenzothiazole SYSTEMATIC 23178179 A 311 314 MBT ABBREVIATION 23178179 A 544 547 MBT ABBREVIATION 23178179 A 659 662 MBT ABBREVIATION 23178179 A 804 817 sodium-iodide SYSTEMATIC 23178179 A 879 895 iodo-amino acids FAMILY 23178179 A 934 937 MBT ABBREVIATION 23178179 T 63 86 2-mercaptobenzothiazole SYSTEMATIC 23178182 A 10 30 N-Methyl-d-aspartate SYSTEMATIC 23178182 A 1020 1030 UCCB01-125 IDENTIFIER 23178182 A 1035 1041 MK-801 IDENTIFIER 23178182 A 1152 1158 MK-801 IDENTIFIER 23178182 A 1163 1173 UCCB01-125 IDENTIFIER 23178182 A 1281 1291 UCCB01-125 IDENTIFIER 23178182 A 1464 1470 MK-801 IDENTIFIER 23178182 A 1565 1575 UCCB01-125 IDENTIFIER 23178182 A 264 266 NO FORMULA 23178182 A 349 351 NO FORMULA 23178182 A 679 681 NO FORMULA 23178182 A 72 84 nitric oxide SYSTEMATIC 23178182 A 811 821 UCCB01-125 IDENTIFIER 23178182 A 849 855 MK-801 IDENTIFIER 23178182 A 86 88 NO FORMULA 23178182 T 0 10 UCCB01-125 IDENTIFIER 23178182 T 140 144 NMDA ABBREVIATION 23178182 T 165 171 MK-801 IDENTIFIER 23178221 A 10 29 diglycoside taxanes FAMILY 23178221 A 168 170 OH FORMULA 23178221 A 180 187 xylosyl TRIVIAL 23178221 A 200 217 7-xylosyl taxanes FAMILY 23178221 A 61 72 α-d-glucose TRIVIAL 23178221 T 39 65 xylosyl-containing taxanes FAMILY 23178243 A 1331 1338 Printex TRIVIAL 23178243 A 1387 1394 8-OH-dG SYSTEMATIC 23178243 A 1480 1487 Aerosil TRIVIAL 23178243 A 1523 1530 8-OH-dG SYSTEMATIC 23178243 A 1764 1771 8-OH-dG SYSTEMATIC 23178243 A 2052 2068 8-hydroxyguanine SYSTEMATIC 23178243 A 276 292 poly(ADP-ribose) SYSTEMATIC 23178243 A 294 297 PAR ABBREVIATION 23178243 A 330 348 8-hydroxyguanosine SYSTEMATIC 23178243 A 350 357 8-OH-dG SYSTEMATIC 23178243 A 364 376 8-oxoguanine SYSTEMATIC 23178243 A 403 411 paraffin FAMILY 23178243 A 651 657 silica TRIVIAL 23178243 A 659 666 Aerosil TRIVIAL 23178243 A 679 691 carbon black TRIVIAL 23178243 A 693 700 Printex TRIVIAL 23178279 A 684 697 dexamethasone TRIVIAL 23178339 A 112 132 docosahexaenoic acid SYSTEMATIC 23178339 A 1144 1147 DHA ABBREVIATION 23178339 A 1148 1159 doxorubicin TRIVIAL 23178339 A 134 137 DHA ABBREVIATION 23178339 A 142 168 polyunsaturated fatty acid FAMILY 23178339 A 549 552 DHA ABBREVIATION 23178339 A 557 572 triethanolamine SYSTEMATIC 23178339 A 574 577 TEA ABBREVIATION 23178339 A 580 585 amine SYSTEMATIC 23178339 A 621 632 doxorubicin TRIVIAL 23178339 A 72 83 doxorubicin TRIVIAL 23178339 A 733 736 DHA ABBREVIATION 23178339 A 764 775 doxorubicin TRIVIAL 23178339 A 933 944 doxorubicin TRIVIAL 23178339 A 945 948 DHA ABBREVIATION 23178339 A 970 981 doxorubicin TRIVIAL 23178339 A 982 985 DHA ABBREVIATION 23178339 T 64 75 doxorubicin TRIVIAL 23178949 A 1087 1099 formaldehyde SYSTEMATIC 23179351 A 345 360 nickel chloride SYSTEMATIC 23179351 A 605 620 nickel chloride SYSTEMATIC 23179351 A 880 895 nickel chloride SYSTEMATIC 23179351 T 82 97 nickel chloride SYSTEMATIC 23179765 A 1015 1022 benzene SYSTEMATIC 23179765 A 1033 1040 pyrrole SYSTEMATIC 23179765 A 165 173 hydrogen SYSTEMATIC 23179765 A 187 194 benzene SYSTEMATIC 23179765 A 205 212 pyrrole SYSTEMATIC 23179765 T 11 18 benzene SYSTEMATIC 23179765 T 29 36 pyrrole SYSTEMATIC 23179966 A 1059 1067 dopamine TRIVIAL 23179966 A 1315 1323 dopamine TRIVIAL 23179966 A 1325 1334 serotonin TRIVIAL 23179966 A 1340 1349 glutamate TRIVIAL 23179966 A 1422 1431 glutamate TRIVIAL 23179966 A 1432 1440 dopamine TRIVIAL 23179966 A 1441 1450 serotonin TRIVIAL 23179966 A 1619 1628 serotonin TRIVIAL 23179966 A 1629 1638 glutamate TRIVIAL 23179966 A 1643 1652 serotonin TRIVIAL 23179966 A 1653 1661 dopamine TRIVIAL 23179966 A 248 257 glutamate TRIVIAL 23179966 A 281 290 serotonin TRIVIAL 23179966 A 291 295 5-HT SYSTEMATIC 23179966 A 445 449 5-HT SYSTEMATIC 23179966 A 49 58 serotonin TRIVIAL 23179966 A 526 530 5-HT SYSTEMATIC 23179966 A 59 68 glutamate TRIVIAL 23179966 A 73 82 serotonin TRIVIAL 23179966 A 793 813 N-methyl-D-aspartate SYSTEMATIC 23179966 A 815 819 NMDA ABBREVIATION 23179966 A 83 91 dopamine TRIVIAL 23179966 A 831 835 5-HT SYSTEMATIC 23179966 T 0 9 Serotonin TRIVIAL 23179966 T 10 19 glutamate TRIVIAL 23179966 T 24 33 serotonin TRIVIAL 23179966 T 34 42 dopamine TRIVIAL 23180370 A 1004 1012 sulphate SYSTEMATIC 23180370 A 1245 1249 NaCl FORMULA 23180370 A 1251 1254 SO4 FORMULA 23180370 A 412 420 sulphate SYSTEMATIC 23180382 A 165 173 graphene TRIVIAL 23180382 A 286 294 graphene TRIVIAL 23180382 A 40 48 graphene TRIVIAL 23180382 A 491 499 graphene TRIVIAL 23180382 A 645 654 graphenes FAMILY 23180382 A 876 885 graphenes FAMILY 23180382 T 9 18 graphenes FAMILY 23180652 A 402 432 2,4-dichlorophenoxyacetic acid SYSTEMATIC 23180652 A 434 442 atrazine TRIVIAL 23180652 A 444 456 chlorpyrifos TRIVIAL 23180652 A 462 473 gemfibrozil TRIVIAL 23180692 A 1117 1126 malathion TRIVIAL 23180692 A 1171 1180 malathion TRIVIAL 23180692 A 1292 1301 malathion TRIVIAL 23180692 A 896 905 malathion TRIVIAL 23180762 A 587 596 magnesium SYSTEMATIC 23180762 A 69 77 tartrate TRIVIAL 23181488 A 1038 1047 isopropyl SYSTEMATIC 23181488 A 1303 1309 methyl SYSTEMATIC 23181488 A 240 258 diisopropyl ketone SYSTEMATIC 23181488 A 71 89 diisopropyl ketone SYSTEMATIC 23181488 A 91 119 (CH(3))(2)HC-CO-CH(CH(3))(2) FORMULA 23181488 T 28 46 diisopropyl ketone SYSTEMATIC 23183084 A 1099 1111 progesterone TRIVIAL 23183084 A 1228 1240 progesterone TRIVIAL 23183084 A 1244 1265 5α-dihydroprogestrone SYSTEMATIC 23183084 A 1323 1329 3-keto SYSTEMATIC 23183084 A 1334 1341 20-keto SYSTEMATIC 23183084 A 1423 1432 dienogest TRIVIAL 23183084 A 1585 1597 progesterone TRIVIAL 23183084 A 167 179 progesterone TRIVIAL 23183084 A 1698 1725 medroxyprogesterone acetate TRIVIAL 23183084 A 1825 1837 progesterone TRIVIAL 23183084 A 1879 1891 progesterone TRIVIAL 23183084 A 2002 2011 progestin FAMILY 23183084 A 2116 2128 progesterone TRIVIAL 23183084 A 237 249 progesterone TRIVIAL 23183084 A 305 317 progesterone TRIVIAL 23183084 A 355 365 progestins FAMILY 23183084 A 380 392 progesterone TRIVIAL 23183084 A 541 551 progestins FAMILY 23183084 A 552 579 medroxyprogesterone acetate TRIVIAL 23183084 A 581 595 dydrogesterone TRIVIAL 23183084 A 600 609 dienogest TRIVIAL 23183084 A 622 634 progesterone TRIVIAL 23183084 A 686 698 progesterone TRIVIAL 23183084 A 816 826 progestins FAMILY 23183084 A 928 942 dydrogesterone TRIVIAL 23183084 A 947 956 dienogest TRIVIAL 23183084 A 975 989 dydrogesterone TRIVIAL 23183084 T 0 9 Progestin FAMILY 23183186 A 1076 1083 glucose TRIVIAL 23183186 A 1251 1254 Ser FORMULA 23183186 A 1462 1469 glucose TRIVIAL 23183186 A 421 428 glucose TRIVIAL 23183186 A 500 503 Thr FORMULA 23183186 A 653 692 2,2'-dihydroxy-1,1'-dinaphthyldisulfide SYSTEMATIC 23183186 A 694 698 IPA3 ABBREVIATION 23183186 A 744 748 cAMP ABBREVIATION 23183186 A 782 785 Ser FORMULA 23183186 A 958 965 glucose TRIVIAL 23183186 A 996 1003 glucose TRIVIAL 23183186 T 148 155 glucose TRIVIAL 23183413 A 1283 1289 copper SYSTEMATIC 23183413 A 1324 1330 copper SYSTEMATIC 23183413 A 1398 1404 copper SYSTEMATIC 23183413 A 1491 1497 copper SYSTEMATIC 23183413 A 1551 1557 sodium SYSTEMATIC 23183413 A 1597 1602 Na(+) FORMULA 23183413 A 1603 1607 K(+) FORMULA 23183413 A 161 167 copper SYSTEMATIC 23183413 A 1695 1701 oxygen SYSTEMATIC 23183413 A 1767 1773 oxygen SYSTEMATIC 23183413 A 1815 1822 peroxyl SYSTEMATIC 23183413 A 1833 1844 glutathione TRIVIAL 23183413 A 1845 1846 S FORMULA 23183413 A 1879 1890 glutathione TRIVIAL 23183413 A 1892 1895 GSH ABBREVIATION 23183413 A 2011 2017 copper SYSTEMATIC 23183413 A 2108 2110 Cu FORMULA 23183413 A 2280 2282 Cu FORMULA 23183413 A 2390 2396 copper SYSTEMATIC 23183413 A 2438 2444 copper SYSTEMATIC 23183413 A 251 257 copper SYSTEMATIC 23183413 A 2543 2549 copper SYSTEMATIC 23183413 A 2741 2747 copper SYSTEMATIC 23183413 A 2863 2869 copper SYSTEMATIC 23183413 A 357 363 copper SYSTEMATIC 23183413 A 392 398 copper SYSTEMATIC 23183413 A 440 446 oxygen SYSTEMATIC 23183413 A 682 688 copper SYSTEMATIC 23183413 A 797 803 copper SYSTEMATIC 23183413 T 133 139 copper SYSTEMATIC 23183532 A 1080 1091 fatty acids FAMILY 23183532 A 1204 1211 sulfide SYSTEMATIC 23183532 A 1216 1223 ammonia SYSTEMATIC 23183532 A 224 235 amino acids FAMILY 23183532 A 295 306 amino acids FAMILY 23183532 A 329 339 amino acid FAMILY 23183532 A 525 536 amino acids FAMILY 23183532 A 808 819 amino acids FAMILY 23183532 A 845 856 amino acids FAMILY 23183532 T 19 27 nitrogen SYSTEMATIC 23184251 A 1042 1048 Ap(4)A ABBREVIATION 23184251 A 1084 1097 pyrophosphate SYSTEMATIC 23184251 A 1160 1166 Ap(4)A ABBREVIATION 23184251 A 1281 1284 IDP ABBREVIATION 23184251 A 1289 1293 dIDP ABBREVIATION 23184251 A 1297 1329 diphosphoinositol polyphosphates FAMILY 23184251 A 1331 1335 DIPs ABBREVIATION 23184251 A 1406 1409 DIP ABBREVIATION 23184251 A 1441 1467 diadenosine polyphosphates FAMILY 23184251 A 1482 1496 polyphosphates FAMILY 23184251 A 373 393 oxidized nucleotides FAMILY 23184251 A 402 412 8-oxo-dGTP SYSTEMATIC 23184251 A 473 484 nucleotides FAMILY 23184251 A 493 496 ADP ABBREVIATION 23184251 A 497 503 ribose TRIVIAL 23184251 A 507 533 diadenosine tetraphosphate SYSTEMATIC 23184251 A 535 541 Ap(4)A ABBREVIATION 23184951 A 247 250 ATP ABBREVIATION 23184951 A 520 523 ATP ABBREVIATION 23184951 A 665 668 ATP ABBREVIATION 23184951 A 717 720 ATP ABBREVIATION 23184951 T 0 3 ATP ABBREVIATION 23185990 A 0 11 Amino acids FAMILY 23185990 A 1188 1193 2'-OH SYSTEMATIC 23185990 A 224 230 Prolyl TRIVIAL 23185990 A 283 286 Pro FORMULA 23185990 A 293 296 Ala FORMULA 23185990 A 301 304 Cys FORMULA 23185990 A 355 358 Ala FORMULA 23185990 A 378 381 Cys FORMULA 23185990 A 387 390 Pro FORMULA 23185990 A 84 93 aminoacyl SYSTEMATIC 23185990 A 939 942 Cys FORMULA 23185990 A 970 973 Cys FORMULA 23185990 A 979 984 ester FAMILY 23185990 T 0 9 Aminoacyl SYSTEMATIC 23186623 A 1146 1149 TTX ABBREVIATION 23186623 A 1236 1239 TTX ABBREVIATION 23186623 A 1325 1328 TTX ABBREVIATION 23186623 A 1631 1634 TTX ABBREVIATION 23186623 A 1670 1673 TTX ABBREVIATION 23186623 A 62 74 tetrodotoxin TRIVIAL 23186623 A 686 689 TTX ABBREVIATION 23186623 A 76 79 TTX ABBREVIATION 23186623 A 987 990 TTX ABBREVIATION 23186623 T 62 74 tetrodotoxin TRIVIAL 23186624 A 1034 1043 clonidine TRIVIAL 23186624 A 1205 1214 clonidine TRIVIAL 23186624 A 140 144 urea TRIVIAL 23186624 A 1447 1456 clonidine TRIVIAL 23186624 A 145 153 nitrogen SYSTEMATIC 23186624 A 1544 1553 Clonidine TRIVIAL 23186624 A 1592 1602 creatinine TRIVIAL 23186624 A 167 177 creatinine TRIVIAL 23186624 A 1695 1704 clonidine TRIVIAL 23186624 A 46 55 clonidine TRIVIAL 23186624 A 494 503 clonidine TRIVIAL 23186624 A 505 515 Catapresan TRIVIAL 23186624 A 528 532 NaCl FORMULA 23186624 A 632 644 diethylether SYSTEMATIC 23186624 A 802 810 formalin TRIVIAL 23186624 A 915 924 clonidine TRIVIAL 23186624 T 10 19 clonidine TRIVIAL 23188714 A 1013 1030 5F-2'deoxyuridine SYSTEMATIC 23188714 A 1233 1243 pyrimidine SYSTEMATIC 23188714 A 1317 1331 5-fluorouracil SYSTEMATIC 23188714 A 136 147 pyrimidines FAMILY 23188714 A 1442 1451 5F-2'dUrd SYSTEMATIC 23188714 A 1456 1465 5F-2'dCtd SYSTEMATIC 23188714 A 1564 1571 5F-dUMP SYSTEMATIC 23188714 A 1611 1621 pyrimidine SYSTEMATIC 23188714 A 1704 1714 pyrimidine SYSTEMATIC 23188714 A 301 311 pyrimidine SYSTEMATIC 23188714 A 361 371 pyrimidine SYSTEMATIC 23188714 A 41 51 pyrimidine SYSTEMATIC 23188714 A 486 492 uracil TRIVIAL 23188714 A 567 577 pyrimidine SYSTEMATIC 23188714 A 630 637 uridine TRIVIAL 23188714 A 642 656 2'deoxyuridine SYSTEMATIC 23188714 A 674 684 pyrimidine SYSTEMATIC 23188714 A 736 745 thymidine TRIVIAL 23188714 A 791 801 nucleoside FAMILY 23188714 A 850 864 5-fluorouracil SYSTEMATIC 23188714 A 90 101 pyrimidines FAMILY 23188714 A 914 932 5-fluoropyrimidine SYSTEMATIC 23188714 A 997 1011 5F-orotic acid SYSTEMATIC 23188714 T 0 10 Pyrimidine SYSTEMATIC 23188714 T 90 113 halogenated pyrimidines FAMILY 23189968 A 517 521 iron SYSTEMATIC 23190030 A 265 279 (poly)phenolic FAMILY 23190030 A 473 479 oxygen SYSTEMATIC 23190030 A 490 498 nitrogen SYSTEMATIC 23190030 A 592 601 flavonoid FAMILY 23190030 A 940 954 (poly)phenolic FAMILY 23190030 T 0 8 Phenolic FAMILY 23190172 A 228 242 17β-oestradiol SYSTEMATIC 23190172 A 336 345 H(2) O(2) FORMULA 23190172 A 747 756 oestrogen FAMILY 23190172 T 0 14 17β-Oestradiol SYSTEMATIC 23190172 T 71 80 oestrogen FAMILY 23192895 A 122 127 NH(3) FORMULA 23192895 A 158 190 magnesium borohydride ammoniates FAMILY 23192895 A 253 265 Mg(BH(4))(2) FORMULA 23192895 A 274 287 hexaammoniate SYSTEMATIC 23192895 A 3 10 ammonia SYSTEMATIC 23192895 A 371 379 hydrogen SYSTEMATIC 23192895 A 423 428 NH(3) FORMULA 23192895 A 448 467 Mg(BH(4))(2)·xNH(3) FAMILY 23192895 A 510 515 H(δ+) FORMULA 23192895 A 52 80 metal borohydride ammoniates FAMILY 23192895 A 520 525 H(δ-) FORMULA 23192895 A 554 559 H(δ+) FORMULA 23192895 A 564 569 H(δ-) FORMULA 23192895 A 611 620 N:→Mg(2+) FORMULA 23192895 A 643 664 magnesium borohydride SYSTEMATIC 23192895 A 666 684 Mg(BH(4))(2)·NH(3) FORMULA 23192895 A 744 752 hydrogen SYSTEMATIC 23192895 T 115 123 hydrogen SYSTEMATIC 23192895 T 49 81 magnesium borohydride ammoniates FAMILY 23192982 A 1010 1021 cholesterol TRIVIAL 23192982 A 1130 1141 cholesterol TRIVIAL 23192982 A 117 128 cholesterol TRIVIAL 23192982 A 1255 1266 cholesterol TRIVIAL 23192982 A 161 172 cholesterol TRIVIAL 23192982 A 241 254 17β-estradiol SYSTEMATIC 23192982 A 317 325 estrogen FAMILY 23192982 A 409 417 estrogen FAMILY 23192982 A 913 924 cholesterol TRIVIAL 23192982 T 100 111 cholesterol TRIVIAL 23192982 T 72 80 estrogen FAMILY 23193276 A 566 576 amino acid FAMILY 23194502 A 1018 1028 adriamycin TRIVIAL 23194502 A 1033 1045 mitoxantrone TRIVIAL 23194502 A 499 507 glaucine TRIVIAL 23194502 A 718 726 glaucine TRIVIAL 23194502 A 728 736 Glaucine TRIVIAL 23194502 T 3 24 isoquinoline alkaloid FAMILY 23194504 A 196 202 oxygen SYSTEMATIC 23194504 A 259 269 superoxide TRIVIAL 23194504 A 289 325 3',5'-Di-C-β-glucopyranosylphloretin SYSTEMATIC 23194504 A 327 335 naringin TRIVIAL 23194504 A 33 43 flavonoids FAMILY 23194504 A 337 347 hesperidin TRIVIAL 23194504 A 349 358 nobiletin TRIVIAL 23194504 A 364 374 tangeretin TRIVIAL 23194504 A 394 404 flavonoids FAMILY 23194504 A 546 555 nobiletin TRIVIAL 23194504 A 560 570 tangeretin TRIVIAL 23194504 A 754 760 Trolox TRIVIAL 23194504 A 809 817 naringin TRIVIAL 23194504 A 822 832 hesperidin TRIVIAL 23194504 A 942 978 3',5'-di-C-β-glucopyranosylphloretin SYSTEMATIC 23194505 A 150 157 ethanol SYSTEMATIC 23194507 A 100 110 zeaxanthin TRIVIAL 23194507 A 67 77 β-carotene TRIVIAL 23194507 A 670 678 lycopene TRIVIAL 23194507 A 781 791 β-carotene TRIVIAL 23194507 A 79 87 lycopene TRIVIAL 23194507 A 866 876 β-carotene TRIVIAL 23194507 A 89 95 lutein TRIVIAL 23194507 A 910 948 cis-isomers of lycopene and β-carotene MULTIPLE 23194510 A 126 146 4(5)-methylimidazole MULTIPLE 23194510 A 148 152 4-MI SYSTEMATIC 23194510 A 246 254 sulphite SYSTEMATIC 23194510 A 286 290 4-MI SYSTEMATIC 23194510 A 351 359 sulphite SYSTEMATIC 23194510 A 380 388 sulphite SYSTEMATIC 23194510 A 425 429 4-MI SYSTEMATIC 23194510 A 44 53 D-glucose SYSTEMATIC 23194510 A 486 494 sulphite SYSTEMATIC 23194510 A 518 526 sulphite SYSTEMATIC 23194510 A 54 59 NH(3) FORMULA 23194510 A 544 552 sulphite SYSTEMATIC 23194510 A 60 68 sulphite SYSTEMATIC 23194510 A 610 614 4-MI SYSTEMATIC 23194510 A 660 668 sulphite SYSTEMATIC 23194510 A 733 741 sulphite SYSTEMATIC 23194510 A 793 801 Sulphite SYSTEMATIC 23194510 A 873 881 pyrazine SYSTEMATIC 23194510 A 918 926 sulphite SYSTEMATIC 23194510 A 966 970 4-MI SYSTEMATIC 23194510 T 26 46 4(5)-methylimidazole MULTIPLE 23194510 T 83 91 sulphite SYSTEMATIC 23194512 A 105 120 graciliflorin C TRIVIAL 23194512 A 143 151 abietane TRIVIAL 23194512 A 153 168 graciliflorin D TRIVIAL 23194512 A 275 310 podocarpa-8,11,13-triene-3α,13-diol SYSTEMATIC 23194512 A 319 331 micranthin B TRIVIAL 23194512 A 36 48 podocarpanes FAMILY 23194512 A 50 76 graciliflorins A (1) and B MULTIPLE 23194512 A 534 537 MTT ABBREVIATION 23194512 A 559 571 Micranthin B TRIVIAL 23194512 A 85 103 isopimarane acetal SYSTEMATIC 23194512 A 9 21 diterpenoids FAMILY 23194512 T 0 11 Podocarpane TRIVIAL 23194512 T 13 24 isopimarane TRIVIAL 23194512 T 30 38 abietane TRIVIAL 23194512 T 39 51 diterpenoids FAMILY 23194517 A 1173 1183 amino acid FAMILY 23194517 A 613 623 fatty acid FAMILY 23194517 A 628 638 amino acid FAMILY 23194517 A 700 711 astaxanthin TRIVIAL 23194517 A 716 726 tocopherol FAMILY 23194517 A 788 796 carbonyl FAMILY 23194517 A 815 826 amino acids FAMILY 23194517 A 828 838 sulfhydryl FAMILY 23194517 A 874 882 carbonyl FAMILY 23194517 A 932 942 fatty acid FAMILY 23194522 A 1031 1041 polyphenol FAMILY 23194522 A 260 271 polyphenols FAMILY 23194522 A 355 359 ABTS ABBREVIATION 23194522 A 413 423 polyphenol FAMILY 23194522 A 541 551 polyphenol FAMILY 23194522 A 569 583 phenolic acids FAMILY 23194522 A 60 70 polyphenol FAMILY 23194522 A 728 739 polyphenols FAMILY 23194522 A 884 894 polyphenol FAMILY 23194522 T 33 44 polyphenols FAMILY 23194524 A 396 403 acetone SYSTEMATIC 23194524 A 639 649 phloridzin TRIVIAL 23194524 A 704 714 polyphenol FAMILY 23194524 A 910 920 phloridzin TRIVIAL 23194525 A 7 13 Hexose TRIVIAL 23194525 T 34 40 Hexose TRIVIAL 23194526 A 316 327 cholesterol TRIVIAL 23194526 A 390 401 cholesterol TRIVIAL 23194526 A 425 436 cholesterol TRIVIAL 23194526 A 609 620 cholesterol TRIVIAL 23194526 A 674 685 cholesterol TRIVIAL 23194526 A 771 782 cholesterol TRIVIAL 23194526 A 826 837 cholesterol TRIVIAL 23194526 A 979 990 cholesterol TRIVIAL 23194528 A 115 133 3-methyl-1-butanol SYSTEMATIC 23194528 A 138 156 2-methyl-1-butanol SYSTEMATIC 23194528 A 161 166 furan SYSTEMATIC 23194528 A 184 215 5-(hydroxymethyl)-2-furaldehyde SYSTEMATIC 23194528 A 19 25 silver SYSTEMATIC 23194528 A 220 233 2-furaldehyde SYSTEMATIC 23194528 A 271 281 1-propanol SYSTEMATIC 23194528 A 283 296 ethyl acetate SYSTEMATIC 23194528 A 298 317 2-methyl-1-propanol SYSTEMATIC 23194528 A 319 337 3-methyl-1-butanol SYSTEMATIC 23194528 A 342 360 2-methyl-1-butanol SYSTEMATIC 23194528 A 465 496 5-(Hydroxymethyl)-2-furaldehyde SYSTEMATIC 23194528 A 501 514 2-furaldehyde SYSTEMATIC 23194528 A 67 77 1-propanol SYSTEMATIC 23194528 A 79 92 ethyl acetate SYSTEMATIC 23194528 A 94 113 2-methyl-1-propanol SYSTEMATIC 23194531 A 216 223 ethanol SYSTEMATIC 23194531 A 359 370 anthocyanin FAMILY 23194531 A 62 73 anthocyanin FAMILY 23194531 A 751 758 ethanol SYSTEMATIC 23194531 A 963 970 ethanol SYSTEMATIC 23194531 T 45 57 anthocyanins FAMILY 23194533 A 0 11 Fatty acids FAMILY 23194533 A 484 495 fatty acids FAMILY 23194533 A 566 577 lauric acid TRIVIAL 23194533 A 589 600 fatty acids FAMILY 23194533 A 637 648 fatty acids FAMILY 23194533 T 27 48 saturated fatty acids FAMILY 23194540 A 678 686 boscalid TRIVIAL 23194540 A 818 826 boscalid TRIVIAL 23194540 A 922 930 boscalid TRIVIAL 23194543 A 527 533 sodium SYSTEMATIC 23194543 A 73 79 sodium SYSTEMATIC 23194544 A 117 127 acrylamide TRIVIAL 23194544 A 193 203 acrylamide TRIVIAL 23194544 A 407 417 Asparagine TRIVIAL 23194544 A 419 426 glucose TRIVIAL 23194544 A 428 436 fructose TRIVIAL 23194544 A 441 448 sucrose TRIVIAL 23194544 A 517 527 acrylamide TRIVIAL 23194544 A 683 693 acrylamide TRIVIAL 23194544 A 756 766 asparagine TRIVIAL 23194544 A 780 786 sugars FAMILY 23194544 A 867 877 acrylamide TRIVIAL 23194544 T 17 27 acrylamide TRIVIAL 23194555 A 112 118 Hg(II) FORMULA 23194555 A 196 202 Hg(II) FORMULA 23194555 A 693 699 Hg(II) FORMULA 23194555 A 828 835 mercury SYSTEMATIC 23194555 A 896 903 mercury SYSTEMATIC 23194555 A 923 929 Zn(II) FORMULA 23194555 A 934 940 Cd(II) FORMULA 23194555 T 52 58 Hg(II) FORMULA 23194566 A 0 12 Tetrodotoxin TRIVIAL 23194566 A 14 17 TTX ABBREVIATION 23194566 A 360 363 TTX ABBREVIATION 23194566 A 608 611 TTX ABBREVIATION 23194566 A 872 875 TTX ABBREVIATION 23194566 A 914 917 TTX ABBREVIATION 23194566 A 966 969 TTX ABBREVIATION 23194566 T 106 118 tetrodotoxin TRIVIAL 23194750 A 0 18 Thiazolidinediones FAMILY 23194750 A 1002 1008 GW9662 IDENTIFIER 23194750 A 1036 1057 N(G)-nitro-L-arginine SYSTEMATIC 23194750 A 1059 1063 LNNA ABBREVIATION 23194750 A 1081 1083 NO FORMULA 23194750 A 1124 1127 ser FORMULA 23194750 A 1192 1210 thiazolidinediones FAMILY 23194750 A 1212 1220 LY294002 IDENTIFIER 23194750 A 1225 1232 10-DEBC SYSTEMATIC 23194750 A 1474 1492 Thiazolidinediones FAMILY 23194750 A 1598 1608 glitazones FAMILY 23194750 A 258 275 thiazolidinedione FAMILY 23194750 A 40 50 glitazones FAMILY 23194750 A 507 525 thiazolidinediones FAMILY 23194750 A 694 697 KCl FORMULA 23194750 A 701 714 phenylephrine TRIVIAL 23194750 A 751 763 troglitazone TRIVIAL 23194750 A 765 778 rosiglitazone TRIVIAL 23194750 A 780 792 pioglitazone TRIVIAL 23194750 A 794 802 LY294002 IDENTIFIER 23194750 A 824 831 10-DEBC SYSTEMATIC 23194750 A 916 919 KCl FORMULA 23194750 T 45 63 thiazolidinediones FAMILY 23194825 A 1 8 Ecstasy TRIVIAL 23194825 A 1021 1031 superoxide TRIVIAL 23194825 A 1083 1091 dopamine TRIVIAL 23194825 A 11 44 3,4-methylenedioxymethamphetamine SYSTEMATIC 23194825 A 1110 1119 GBR 12909 IDENTIFIER 23194825 A 1175 1181 α-MeDA ABBREVIATION 23194825 A 1218 1229 glutathione TRIVIAL 23194825 A 1231 1234 GSH ABBREVIATION 23194825 A 1321 1339 γ-glutamylcysteine SYSTEMATIC 23194825 A 1431 1453 buthionine sulfoximine SYSTEMATIC 23194825 A 1455 1458 BSO ABBREVIATION 23194825 A 1494 1500 α-MeDA ABBREVIATION 23194825 A 1521 1524 GSH ABBREVIATION 23194825 A 1592 1595 BSO ABBREVIATION 23194825 A 1620 1623 NAC ABBREVIATION 23194825 A 1651 1657 α-MeDA ABBREVIATION 23194825 A 1712 1715 GSH ABBREVIATION 23194825 A 174 178 MDMA ABBREVIATION 23194825 A 1774 1777 BSO ABBREVIATION 23194825 A 1788 1799 N-Me-α-MeDA ABBREVIATION 23194825 A 1850 1853 NAC ABBREVIATION 23194825 A 1886 1890 MDMA ABBREVIATION 23194825 A 1891 1899 catechol TRIVIAL 23194825 A 221 225 MDMA ABBREVIATION 23194825 A 280 284 MDMA ABBREVIATION 23194825 A 293 301 catechol TRIVIAL 23194825 A 315 331 α-methyldopamine SYSTEMATIC 23194825 A 333 339 α-MeDA ABBREVIATION 23194825 A 345 370 N-methyl-α-methyldopamine SYSTEMATIC 23194825 A 372 383 N-Me-α-MeDA ABBREVIATION 23194825 A 441 454 retinoic acid TRIVIAL 23194825 A 459 496 12-O-tetradecanoyl-phorbol-13-acetate SYSTEMATIC 23194825 A 48 52 MDMA ABBREVIATION 23194825 A 571 579 dopamine TRIVIAL 23194825 A 610 618 dopamine TRIVIAL 23194825 A 634 638 MDMA ABBREVIATION 23194825 A 639 647 catechol TRIVIAL 23194825 A 787 791 MDMA ABBREVIATION 23194825 A 887 898 glutathione TRIVIAL 23194825 A 910 926 N-acetylcysteine SYSTEMATIC 23194825 A 928 931 NAC ABBREVIATION 23194825 A 976 980 MDMA ABBREVIATION 23194825 T 18 25 ecstasy TRIVIAL 23195954 A 1077 1083 Ca(2+) FORMULA 23195954 A 1103 1109 Zn(2+) FORMULA 23195954 A 1147 1153 Zn(2+) FORMULA 23195954 A 192 198 serine TRIVIAL 23195954 A 217 220 Ser FORMULA 23195954 A 241 244 Asp FORMULA 23195954 A 267 270 His FORMULA 23195954 A 33 39 Ca(2+) FORMULA 23195954 A 342 343 C FORMULA 23195954 A 393 399 Zn(2+) FORMULA 23195954 A 479 485 Zn(2+) FORMULA 23195954 A 509 510 N FORMULA 23195954 A 561 567 Zn(2+) FORMULA 23195954 A 620 626 serine TRIVIAL 23195954 A 743 749 Ca(2+) FORMULA 23195954 A 906 912 Zn(2+) FORMULA 23195954 T 0 6 Serine TRIVIAL 23195954 T 50 54 Zn2+ FORMULA 23195960 A 1080 1085 Na(+) FORMULA 23195960 A 1109 1116 ouabain TRIVIAL 23195960 A 1380 1385 Na(+) FORMULA 23195960 A 1502 1507 Na(+) FORMULA 23195960 A 290 295 Na(+) FORMULA 23195960 A 50 52 Na FORMULA 23195960 A 502 509 ouabain TRIVIAL 23195960 A 53 54 K FORMULA 23195960 A 558 563 Na(+) FORMULA 23195960 A 580 585 Na(+) FORMULA 23195960 A 702 707 Na(+) FORMULA 23195960 A 871 876 Na(+) FORMULA 23195960 A 917 919 Na FORMULA 23195960 A 920 921 K FORMULA 23195960 A 978 983 Na(+) FORMULA 23195960 T 34 36 Na FORMULA 23195960 T 37 38 K FORMULA 23196320 A 1082 1086 AuAg FORMULA 23196320 A 138 140 Ag FORMULA 23196320 A 89 93 AuAg FORMULA 23196320 A 988 992 AuAg FORMULA 23197649 A 1061 1064 ACh ABBREVIATION 23197649 A 110 123 acetylcholine SYSTEMATIC 23197649 A 1103 1107 BQCA ABBREVIATION 23197649 A 1262 1265 ACh ABBREVIATION 23197649 A 1276 1280 BQCA ABBREVIATION 23197649 A 179 192 acetylcholine SYSTEMATIC 23197649 A 194 197 ACh ABBREVIATION 23197649 A 284 301 clozapine-N-oxide SYSTEMATIC 23197649 A 303 306 CNO ABBREVIATION 23197649 A 489 492 CNO ABBREVIATION 23197649 A 525 528 ACh ABBREVIATION 23197649 A 748 780 benzyl quinolone carboxylic acid SYSTEMATIC 23197649 A 782 786 BQCA ABBREVIATION 23197649 A 824 827 ACh ABBREVIATION 23197649 A 978 981 CNO ABBREVIATION 23197771 A 1057 1063 TAPI-0 IDENTIFIER 23197771 A 1227 1233 TAPI-0 IDENTIFIER 23197771 A 13 21 tyrosine TRIVIAL 23197771 A 1494 1500 TAPI-0 IDENTIFIER 23197771 A 1705 1711 TAPI-0 IDENTIFIER 23197771 A 568 574 TAPI-0 IDENTIFIER 23197771 A 843 849 TAPI-0 IDENTIFIER 23197771 T 29 37 tyrosine TRIVIAL 23198810 A 1005 1012 quinone FAMILY 23198810 A 1062 1069 quinone FAMILY 23198810 A 696 709 naphthalimide FAMILY 23198810 A 750 757 quinone FAMILY 23198810 A 852 859 quinone FAMILY 23198819 A 1003 1006 MTM ABBREVIATION 23198819 A 335 350 Montmorillonite TRIVIAL 23198819 A 352 355 MTM ABBREVIATION 23198819 A 520 523 MTM ABBREVIATION 23198819 A 539 545 quartz TRIVIAL 23198819 A 985 988 MTM ABBREVIATION 23198831 A 240 248 hydrogen SYSTEMATIC 23198831 A 477 481 H(+) FORMULA 23198831 A 482 486 H(2) FORMULA 23198831 T 0 8 Hydrogen SYSTEMATIC 23198831 T 24 26 Pt FORMULA 23198831 T 27 29 Ru FORMULA 23198958 A 188 196 In(Ga)As FORMULA 23198958 A 197 201 GaAs FORMULA 23199028 A 127 139 carbohydrate FAMILY 23199028 A 6 18 glycyrrhizin TRIVIAL 23199028 A 89 94 amine SYSTEMATIC 23199028 A 98 108 amino acid FAMILY 23199028 T 60 72 glycyrrhizin TRIVIAL 23199983 A 1020 1027 lactose TRIVIAL 23199983 A 111 119 fructose TRIVIAL 23199983 A 1132 1140 fructose TRIVIAL 23199983 A 14 25 1-lactulose SYSTEMATIC 23199983 A 186 193 Lactose TRIVIAL 23199983 A 278 289 1-lactulose SYSTEMATIC 23199983 A 30 39 lactulose TRIVIAL 23199983 A 311 320 lactulose TRIVIAL 23199983 A 333 341 fructose TRIVIAL 23199983 A 480 491 1-lactulose SYSTEMATIC 23199983 A 492 501 lactulose TRIVIAL 23199983 A 593 604 1-lactulose SYSTEMATIC 23199983 A 609 618 lactulose TRIVIAL 23199983 A 670 678 fructose TRIVIAL 23199983 A 719 726 Lactose TRIVIAL 23199983 A 771 779 fructose TRIVIAL 23199983 A 965 973 Fructose TRIVIAL 23199983 A 995 1005 galactosyl TRIVIAL 23199983 T 118 126 fructose TRIVIAL 23199983 T 14 25 1-lactulose SYSTEMATIC 23199983 T 30 39 lactulose TRIVIAL 23199984 A 15 22 stearin TRIVIAL 23199984 A 298 314 sodium methoxide SYSTEMATIC 23199984 A 361 376 triacylglycerol FAMILY 23199984 A 378 381 TAG ABBREVIATION 23199984 A 868 875 stearin TRIVIAL 23199984 T 111 118 stearin TRIVIAL 23199992 A 1071 1073 ¹H FORMULA 23199992 A 328 330 ¹H FORMULA 23199992 A 686 701 4-aminobutyrate SYSTEMATIC 23199992 A 703 707 GABA ABBREVIATION 23199992 A 710 717 acetate SYSTEMATIC 23199992 A 719 729 asparagine TRIVIAL 23199992 A 731 738 leucine TRIVIAL 23199992 A 740 750 isoleucine TRIVIAL 23199992 A 752 768 O-phosphocholine SYSTEMATIC 23199992 A 770 783 phenylacetate SYSTEMATIC 23199992 A 785 798 phenylalanine TRIVIAL 23199992 A 800 809 succinate TRIVIAL 23199992 A 811 818 sucrose TRIVIAL 23199992 A 820 828 tyrosine TRIVIAL 23199992 A 834 840 valine TRIVIAL 23199992 T 112 114 ¹H FORMULA 23199999 A 670 685 malondialdehyde TRIVIAL 23200004 A 1012 1024 nitrous acid SYSTEMATIC 23200004 A 1029 1043 nitrous oxides FAMILY 23200004 A 1062 1082 potassium dichromate SYSTEMATIC 23200004 A 1110 1117 mercury SYSTEMATIC 23200004 A 1246 1253 mercury SYSTEMATIC 23200004 A 214 225 nitric acid SYSTEMATIC 23200004 A 230 247 hydrogen peroxide SYSTEMATIC 23200004 A 388 399 nitric acid SYSTEMATIC 23200004 A 404 416 tin chloride SYSTEMATIC 23200004 A 529 536 mercury SYSTEMATIC 23200004 A 68 75 mercury SYSTEMATIC 23200004 A 788 795 mercury SYSTEMATIC 23200004 T 17 24 mercury SYSTEMATIC 23200005 A 0 8 Selenium SYSTEMATIC 23200005 A 169 177 selenium SYSTEMATIC 23200005 A 264 272 selenium SYSTEMATIC 23200005 A 313 321 selenium SYSTEMATIC 23200005 A 375 380 SeMet FORMULA 23200005 A 382 398 selenomethionine SYSTEMATIC 23200005 A 414 422 selenium SYSTEMATIC 23200005 A 470 475 SeMet FORMULA 23200005 A 480 485 SeCys FORMULA 23200005 A 487 507 methylselenocysteine SYSTEMATIC 23200005 A 528 530 Se FORMULA 23200005 A 532 540 selenium SYSTEMATIC 23200005 A 543 545 Zn FORMULA 23200005 A 547 551 zinc SYSTEMATIC 23200005 A 554 556 Fe FORMULA 23200005 A 558 562 iron SYSTEMATIC 23200005 A 598 607 adenosine TRIVIAL 23200005 A 609 619 cordycepin TRIVIAL 23200005 A 699 700 P FORMULA 23200005 A 702 712 phosphorus SYSTEMATIC 23200005 A 718 719 K FORMULA 23200005 A 721 730 potassium SYSTEMATIC 23200005 T 62 70 selenium SYSTEMATIC 23200006 A 28 35 cadmium SYSTEMATIC 23200006 A 576 585 alcoholic FAMILY 23200006 A 66 72 copper SYSTEMATIC 23200006 A 90 98 graphite TRIVIAL 23200006 A 99 105 carbon SYSTEMATIC 23200006 T 38 47 alcoholic FAMILY 23200246 A 139 162 12-hydroxy-scabrolide A SYSTEMATIC 23200246 A 171 190 13-epi-scabrolide C SYSTEMATIC 23200246 A 93 108 norditerpenoids FAMILY 23200246 T 18 33 norditerpenoids FAMILY 23200253 A 154 158 TPBP ABBREVIATION 23200253 A 226 236 piperidine SYSTEMATIC 23200253 A 456 465 VU0357017 IDENTIFIER 23200253 A 89 93 TBPB ABBREVIATION 23200253 A 98 107 VU0357017 IDENTIFIER 23200747 A 0 16 Organophosphorus FAMILY 23200778 A 341 350 bleomycin FAMILY 23200778 A 352 361 etoposide TRIVIAL 23200778 A 367 376 cisplatin TRIVIAL 23200778 A 378 381 BEP ABBREVIATION 23200778 A 481 492 glutathione TRIVIAL 23200778 A 493 494 S FORMULA 23200778 A 526 529 BEP ABBREVIATION 23200778 A 595 603 aldehyde SYSTEMATIC 23200778 A 818 821 BEP ABBREVIATION 23200778 A 905 908 BEP ABBREVIATION 23200778 T 23 34 glutathione TRIVIAL 23200778 T 35 36 S FORMULA 23200887 A 0 11 Resveratrol TRIVIAL 23200887 A 1054 1065 resveratrol TRIVIAL 23200887 A 1099 1110 resveratrol TRIVIAL 23200887 A 1251 1262 resveratrol TRIVIAL 23200887 A 13 45 3,5,4'-trihydroxy-trans stilbene SYSTEMATIC 23200887 A 1344 1355 resveratrol TRIVIAL 23200887 A 344 355 resveratrol TRIVIAL 23200887 A 618 626 H(2)O(2) FORMULA 23200887 A 686 697 Resveratrol TRIVIAL 23200887 A 851 862 resveratrol TRIVIAL 23200887 A 980 983 ADP ABBREVIATION 23200887 T 0 11 Resveratrol TRIVIAL 23200901 A 0 18 Aconitum alkaloids FAMILY 23200901 A 1000 1007 aconine TRIVIAL 23200901 A 1012 1022 mesaconine TRIVIAL 23200901 A 129 143 benzoylaconine SYSTEMATIC 23200901 A 1369 1372 BAC ABBREVIATION 23200901 A 1374 1377 BMA ABBREVIATION 23200901 A 1382 1385 BHA ABBREVIATION 23200901 A 145 148 BAC ABBREVIATION 23200901 A 151 168 benzoylmesaconine SYSTEMATIC 23200901 A 170 173 BMA ABBREVIATION 23200901 A 176 193 benzoylhypaconine TRIVIAL 23200901 A 195 198 BHA ABBREVIATION 23200901 A 201 208 aconine TRIVIAL 23200901 A 214 224 mesaconine TRIVIAL 23200901 A 29 38 aconitine TRIVIAL 23200901 A 45 57 mesaconitine TRIVIAL 23200901 A 584 602 Aconitum alkaloids FAMILY 23200901 A 64 76 hypaconitine TRIVIAL 23200901 A 699 717 Aconitum alkaloids FAMILY 23200901 A 755 769 cyclosporine A TRIVIAL 23200901 A 774 783 verapamil TRIVIAL 23200901 A 792 797 Ko143 IDENTIFIER 23200901 A 809 814 MK571 IDENTIFIER 23200901 A 947 950 BAC ABBREVIATION 23200901 A 952 955 BMA ABBREVIATION 23200901 A 961 964 BHA ABBREVIATION 23200901 T 65 74 aconitine TRIVIAL 23200901 T 76 88 mesaconitine TRIVIAL 23200901 T 90 102 hypaconitine TRIVIAL 23201003 A 1005 1011 JBP485 IDENTIFIER 23201003 A 1023 1038 1,25(OH)(2)D(3) FORMULA 23201003 A 105 132 1α,25-dihydroxyvitamin D(3) SYSTEMATIC 23201003 A 1154 1160 JBP485 IDENTIFIER 23201003 A 1165 1180 1,25(OH)(2)D(3) FORMULA 23201003 A 1249 1255 JBP485 IDENTIFIER 23201003 A 1260 1275 1,25(OH)(2)D(3) FORMULA 23201003 A 1336 1351 1,25(OH)(2)D(3) FORMULA 23201003 A 134 149 1,25(OH)(2)D(3) FORMULA 23201003 A 211 226 1,25(OH)(2)D(3) FORMULA 23201003 A 298 304 JBP485 IDENTIFIER 23201003 A 356 362 JBP485 IDENTIFIER 23201003 A 693 708 1,25(OH)(2)D(3) FORMULA 23201003 A 758 764 JBP485 IDENTIFIER 23201003 A 824 830 JBP485 IDENTIFIER 23201003 A 845 851 JBP485 IDENTIFIER 23201003 A 904 919 1,25(OH)(2)D(3) FORMULA 23201003 A 94 100 JBP485 IDENTIFIER 23201003 A 960 975 1,25(OH)(2)D(3) FORMULA 23201003 T 21 46 1α,25-dihydroxyvitamin D₃ SYSTEMATIC 23201003 T 63 69 JBP485 IDENTIFIER 23201055 A 122 126 PLGA ABBREVIATION 23201055 A 281 285 PLGA ABBREVIATION 23201055 A 491 495 PLGA ABBREVIATION 23201055 A 91 120 Poly(lactic-co-glycolic acid) SYSTEMATIC 23201055 T 61 65 PLGA ABBREVIATION 23201124 A 689 690 N FORMULA 23201309 A 0 10 Nucleoside FAMILY 23201309 A 1043 1053 nucleotide FAMILY 23201309 A 1170 1200 tenofovir mono- or diphosphate MULTIPLE 23201309 A 1433 1456 tenofovir monophosphate SYSTEMATIC 23201309 A 234 245 3'-hydroxyl SYSTEMATIC 23201309 A 367 390 tenofovir monophosphate SYSTEMATIC 23201309 A 433 455 nucleoside diphosphate FAMILY 23201309 A 471 489 3-phosphoglycerate SYSTEMATIC 23201309 A 504 512 creatine TRIVIAL 23201309 A 529 537 pyruvate TRIVIAL 23201309 A 598 621 tenofovir monophosphate SYSTEMATIC 23201309 A 699 702 ADP ABBREVIATION 23201309 A 815 818 ADP ABBREVIATION 23201309 A 892 915 tenofovir monophosphate SYSTEMATIC 23201309 A 980 989 tenofovir TRIVIAL 23201309 T 44 53 tenofovir TRIVIAL 23201331 A 1040 1049 sweroside TRIVIAL 23201331 A 1101 1110 sweroside TRIVIAL 23201331 A 1148 1157 Sweroside TRIVIAL 23201331 A 1380 1389 sweroside TRIVIAL 23201331 A 1457 1466 sweroside TRIVIAL 23201331 A 146 155 Sweroside TRIVIAL 23201331 A 542 551 sweroside TRIVIAL 23201331 A 598 658 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide SYSTEMATIC 23201331 A 660 663 MTT ABBREVIATION 23201331 A 704 713 sweroside TRIVIAL 23201331 A 854 863 Sweroside TRIVIAL 23201331 T 22 31 sweroside TRIVIAL 23201370 A 554 563 aspartate TRIVIAL 23201370 A 588 595 alanine TRIVIAL 23201370 A 596 601 amino FAMILY 23201370 A 776 787 cholesterol TRIVIAL 23201370 A 789 802 triglycerides FAMILY 23201439 A 1125 1141 organophosphorus FAMILY 23201439 A 171 185 β-cyclodextrin TRIVIAL 23201439 A 22 38 organophosphorus FAMILY 23201439 A 495 509 β-cyclodextrin TRIVIAL 23201439 A 728 734 carbon SYSTEMATIC 23201439 A 826 836 cyclosarin TRIVIAL 23201439 T 13 27 β-cyclodextrin TRIVIAL 23201442 A 0 8 Estrogen FAMILY 23201442 A 1006 1016 raloxifene TRIVIAL 23201442 A 1052 1056 H₂O₂ FORMULA 23201442 A 1124 1132 phenoxyl SYSTEMATIC 23201442 A 1156 1166 raloxifene TRIVIAL 23201442 A 1211 1215 NADH ABBREVIATION 23201442 A 1370 1374 NADH ABBREVIATION 23201442 A 1375 1379 NAD⁺ ABBREVIATION 23201442 A 258 268 raloxifene TRIVIAL 23201442 A 282 290 estrogen FAMILY 23201442 A 375 385 fatty acid FAMILY 23201442 A 406 417 Fatty acids FAMILY 23201442 A 574 584 raloxifene TRIVIAL 23201442 A 644 654 raloxifene TRIVIAL 23201442 A 709 720 fatty acids FAMILY 23201442 A 739 756 β-hydroxybutyrate SYSTEMATIC 23201442 A 757 769 acetoacetate SYSTEMATIC 23201442 A 792 797 ¹⁴CO₂ FORMULA 23201442 A 844 850 oxygen SYSTEMATIC 23201442 A 878 888 raloxifene TRIVIAL 23201442 A 911 915 NADH ABBREVIATION 23201442 T 0 10 Raloxifene TRIVIAL 23201442 T 19 29 fatty acid FAMILY 23201451 A 0 12 Moniliformin TRIVIAL 23201451 A 1226 1238 moniliformin TRIVIAL 23201451 A 142 154 moniliformin TRIVIAL 23201451 A 354 366 moniliformin TRIVIAL 23201451 A 478 490 moniliformin TRIVIAL 23201451 A 556 568 Moniliformin TRIVIAL 23201451 A 900 912 moniliformin TRIVIAL 23201451 A 980 992 moniliformin TRIVIAL 23201451 T 74 86 moniliformin TRIVIAL 23202250 A 1407 1413 TiO(2) FORMULA 23202250 A 1571 1577 TiO(2) FORMULA 23202250 A 22 38 titanium dioxide SYSTEMATIC 23202250 A 270 276 TiO(2) FORMULA 23202250 A 55 61 TiO(2) FORMULA 23202250 A 620 626 TiO(2) FORMULA 23202250 A 853 859 carbon SYSTEMATIC 23202585 A 214 215 C FORMULA 23202585 A 570 573 ATP ABBREVIATION 23202880 A 147 151 N(2) FORMULA 23202880 A 168 176 squalane TRIVIAL 23202880 A 180 195 branched alkane FAMILY 23202880 A 199 204 NO(3) FORMULA 23202880 A 241 249 squalene TRIVIAL 23202880 A 283 288 NO(3) FORMULA 23202880 A 40 47 nitrate SYSTEMATIC 23202880 A 443 448 NO(3) FORMULA 23202880 A 463 471 squalene TRIVIAL 23202880 A 57 62 NO(3) FORMULA 23202880 A 633 638 NO(3) FORMULA 23202880 A 661 669 squalene TRIVIAL 23202880 A 696 704 squalene TRIVIAL 23202880 A 84 92 squalane TRIVIAL 23202880 A 944 952 squalene TRIVIAL 23202880 A 97 105 squalene TRIVIAL 23202880 A 983 988 NO(3) FORMULA 23202880 T 53 56 NO3 FORMULA 23202880 T 72 80 squalane TRIVIAL 23202880 T 85 93 squalene TRIVIAL 23203454 A 0 8 Hexamoll TRIVIAL 23203454 A 1045 1055 monoesters FAMILY 23203454 A 1100 1102 OH FORMULA 23203454 A 1103 1108 MINCH ABBREVIATION 23203454 A 113 122 phthalate FAMILY 23203454 A 1130 1133 oxo SYSTEMATIC 23203454 A 1134 1139 MINCH ABBREVIATION 23203454 A 1162 1169 carboxy SYSTEMATIC 23203454 A 1170 1175 MINCH ABBREVIATION 23203454 A 12 17 DINCH ABBREVIATION 23203454 A 1236 1245 monoester SYSTEMATIC 23203454 A 1246 1251 MINCH ABBREVIATION 23203454 A 1289 1294 DINCH ABBREVIATION 23203454 A 1585 1590 DINCH ABBREVIATION 23203454 A 168 173 DINCH ABBREVIATION 23203454 A 1680 1685 DINCH ABBREVIATION 23203454 A 22 62 diisononyl-cyclohexane-1,2-dicarboxylate SYSTEMATIC 23203454 A 259 267 Hexamoll TRIVIAL 23203454 A 271 276 DINCH ABBREVIATION 23203454 A 429 450 di-iso-nonylphthalate SYSTEMATIC 23203454 A 452 456 DINP ABBREVIATION 23203454 A 495 504 monoester SYSTEMATIC 23203454 A 505 548 mono-isononyl-cyclohexane-1,2-dicarboxylate SYSTEMATIC 23203454 A 550 555 MINCH ABBREVIATION 23203454 A 710 743 cyclohexane-1,2-dicarboxylic acid SYSTEMATIC 23203454 A 745 749 CHDA ABBREVIATION 23203454 A 855 859 CHDA ABBREVIATION 23203454 T 34 43 phthalate FAMILY 23203454 T 55 95 diisononyl-cyclohexane-1,2-dicarboxylate SYSTEMATIC 23203454 T 97 102 DINCH ABBREVIATION 23203870 A 209 213 zinc SYSTEMATIC 23203920 A 731 769 N-3-oxododecanoyl-L-homoserine lactone SYSTEMATIC 23203920 A 771 774 OHN ABBREVIATION 23203920 A 883 886 OHN ABBREVIATION 23204325 A 728 735 glucose TRIVIAL 23204443 A 0 23 Sphingosine 1-phosphate SYSTEMATIC 23204443 T 0 23 Sphingosine 1-phosphate SYSTEMATIC 23205571 A 128 129 N FORMULA 23205571 A 165 172 proline TRIVIAL 23205571 A 186 212 indoline-2-carboxylic acid SYSTEMATIC 23205571 A 214 217 Ica ABBREVIATION 23205571 A 223 286 (2S,4R)-4-(naphthalene-2-ylmethyl)pyrrolidine-2-carboxylic acid SYSTEMATIC 23205571 A 434 442 oxytocin TRIVIAL 23205571 A 457 460 Ica ABBREVIATION 23205571 A 546 574 [Mpa(1), Ica(2), D-Arg(8)]VP FORMULA 23205571 A 579 612 [Mpa(1),Ica(2),Val(4),D-Arg(8)]VP FORMULA 23205571 A 694 757 (2S,4R)-4-(naphthalene-2-ylmethyl)pyrrolidine-2-carboxylic acid SYSTEMATIC 23205571 A 869 889 arginine vasopressin TRIVIAL 23205571 A 91 111 arginine vasopressin TRIVIAL 23205571 A 989 1009 arginine vasopressin TRIVIAL 23205571 T 103 110 proline TRIVIAL 23205571 T 61 81 arginine vasopressin TRIVIAL 23205763 A 232 243 metal-oxide FAMILY 23205763 A 330 336 alkyne FAMILY 23205763 A 703 708 azide SYSTEMATIC 23205763 A 718 735 indocyanine green TRIVIAL 23205763 A 887 904 indocyanine green TRIVIAL 23205778 A 1002 1008 purine TRIVIAL 23205778 A 1010 1020 anthracene SYSTEMATIC 23205778 A 1026 1038 phenanthrene SYSTEMATIC 23205778 A 13 21 hydrogen SYSTEMATIC 23205778 A 141 149 benzenes FAMILY 23205778 A 1426 1433 benzene SYSTEMATIC 23205778 A 1434 1446 benzonitrile SYSTEMATIC 23205778 A 1448 1455 benzene SYSTEMATIC 23205778 A 1456 1462 phenol SYSTEMATIC 23205778 A 1468 1479 naphthalene SYSTEMATIC 23205778 A 1480 1488 methanol SYSTEMATIC 23205778 A 1616 1624 hydrogen SYSTEMATIC 23205778 A 203 204 F FORMULA 23205778 A 207 209 Cl FORMULA 23205778 A 212 214 Br FORMULA 23205778 A 217 220 C≡N FORMULA 23205778 A 227 229 OH FORMULA 23205778 A 237 269 polycyclic aromatic hydrocarbons FAMILY 23205778 A 321 327 carbon SYSTEMATIC 23205778 A 364 370 carbon SYSTEMATIC 23205778 A 414 435 aromatic heterocycles FAMILY 23205778 A 466 489 fused-ring heterocycles FAMILY 23205778 A 622 635 fluorobenzene SYSTEMATIC 23205778 A 637 650 chlorobenzene SYSTEMATIC 23205778 A 652 664 bromobenzene SYSTEMATIC 23205778 A 666 698 di-, tri-, and hexachlorobenzene MULTIPLE 23205778 A 708 721 2-chlorofuran SYSTEMATIC 23205778 A 723 740 2-chlorothiophene SYSTEMATIC 23205778 A 742 754 benzonitrile SYSTEMATIC 23205778 A 756 762 phenol SYSTEMATIC 23205778 A 764 780 dihydroxybenzene FAMILY 23205778 A 790 806 1,4-benzoquinone SYSTEMATIC 23205778 A 808 819 naphthalene SYSTEMATIC 23205778 A 821 847 naphthalene-2-carbonitrile SYSTEMATIC 23205778 A 849 864 naphthalen-2-ol SYSTEMATIC 23205778 A 866 875 quinoline SYSTEMATIC 23205778 A 877 894 benzo[b]thiophene SYSTEMATIC 23205778 A 896 913 benzo[c]thiophene SYSTEMATIC 23205778 A 915 926 benzoxazole SYSTEMATIC 23205778 A 928 941 benzisoxazole SYSTEMATIC 23205778 A 943 956 benzimidazole SYSTEMATIC 23205778 A 958 971 benzothiazole SYSTEMATIC 23205778 A 973 979 indole SYSTEMATIC 23205778 A 981 990 isoindole SYSTEMATIC 23205778 A 992 1000 indazole SYSTEMATIC 23205778 T 108 127 polycyclic aromatic FAMILY 23205778 T 59 67 hydrogen SYSTEMATIC 23205778 T 95 103 benzenes FAMILY 23206503 A 0 23 N-palmitoylethanolamine SYSTEMATIC 23206503 A 1063 1069 GW6471 IDENTIFIER 23206503 A 1098 1106 SR141716 IDENTIFIER 23206503 A 1157 1165 SR141716 IDENTIFIER 23206503 A 1171 1174 PEA ABBREVIATION 23206503 A 1178 1181 AEA ABBREVIATION 23206503 A 1246 1252 GW6471 IDENTIFIER 23206503 A 1265 1268 PEA ABBREVIATION 23206503 A 1305 1308 AEA ABBREVIATION 23206503 A 1355 1358 PEA ABBREVIATION 23206503 A 1360 1363 AEA ABBREVIATION 23206503 A 1368 1372 2-AG ABBREVIATION 23206503 A 1374 1396 2-arachidonoylglycerol SYSTEMATIC 23206503 A 1500 1503 PEA ABBREVIATION 23206503 A 1608 1611 PEA ABBREVIATION 23206503 A 25 28 PEA ABBREVIATION 23206503 A 253 265 cannabinoids FAMILY 23206503 A 434 437 PEA ABBREVIATION 23206503 A 45 68 fatty acid ethanolamide FAMILY 23206503 A 510 513 PEA ABBREVIATION 23206503 A 515 525 anandamide TRIVIAL 23206503 A 527 530 AEA ABBREVIATION 23206503 A 554 560 GW6471 IDENTIFIER 23206503 A 619 627 SR141716 IDENTIFIER 23206503 A 788 791 PEA ABBREVIATION 23206503 A 815 823 SR141716 IDENTIFIER 23206503 A 828 834 GW6471 IDENTIFIER 23206503 A 876 879 AEA ABBREVIATION 23206503 A 892 895 PEA ABBREVIATION 23206503 A 963 966 PEA ABBREVIATION 23206503 A 971 974 AEA ABBREVIATION 23206503 T 24 47 N-palmitoylethanolamine SYSTEMATIC 23206861 A 138 148 carbamates FAMILY 23206861 A 39 62 tetrahydro-β-carbolines FAMILY 23206861 T 0 22 Tetrahydro-β-carboline SYSTEMATIC 23206861 T 45 61 fatty acid amide FAMILY 23206990 A 392 400 Estrogen FAMILY 23207166 A 0 11 Misoprostol TRIVIAL 23207166 A 332 343 misoprostol TRIVIAL 23207166 A 641 652 misoprostol TRIVIAL 23207166 A 732 743 misoprostol TRIVIAL 23207166 A 930 941 misoprostol TRIVIAL 23207166 T 32 43 misoprostol TRIVIAL 23207252 A 579 598 thiobarbituric acid SYSTEMATIC 23207252 A 868 911 nicotinamide adenine dinucleotide phosphate SYSTEMATIC 23207252 A 913 918 NADPH ABBREVIATION 23207328 A 1034 1037 AZT ABBREVIATION 23207328 A 1110 1113 AZT ABBREVIATION 23207328 A 123 133 zidovudine TRIVIAL 23207328 A 1253 1268 PPG-5-CETETH-20 FORMULA 23207328 A 1270 1280 oleic acid TRIVIAL 23207328 A 135 138 AZT ABBREVIATION 23207328 A 1403 1406 AZT ABBREVIATION 23207328 A 1464 1467 AZT ABBREVIATION 23207328 A 1562 1565 AZT ABBREVIATION 23207328 A 1596 1599 AZT ABBREVIATION 23207328 A 1884 1887 AZT ABBREVIATION 23207328 A 1956 1959 AZT ABBREVIATION 23207328 A 350 365 PPG-5-CETETH-20 FORMULA 23207328 A 367 377 oleic acid TRIVIAL 23207477 A 1106 1108 Co FORMULA 23207477 A 1336 1338 Co FORMULA 23207477 A 202 208 Cobalt SYSTEMATIC 23207477 A 374 380 cobalt SYSTEMATIC 23207477 A 382 384 Co FORMULA 23207477 A 460 462 Co FORMULA 23207477 A 496 498 Co FORMULA 23207477 A 602 604 Co FORMULA 23207477 A 624 626 Co FORMULA 23207477 A 677 679 Co FORMULA 23207477 A 850 852 Co FORMULA 23207477 A 926 928 Co FORMULA 23207477 A 961 963 Co FORMULA 23207477 T 0 6 Cobalt SYSTEMATIC 23207477 T 102 108 cobalt SYSTEMATIC 23208007 A 94 105 sialic acid TRIVIAL 23208609 A 1025 1038 17ß-estradiol SYSTEMATIC 23208609 A 1043 1050 estrone TRIVIAL 23208609 A 1079 1084 2-ITX SYSTEMATIC 23208609 A 1119 1127 androgen FAMILY 23208609 A 1142 1154 pregnenolone TRIVIAL 23208609 A 1159 1171 progesterone TRIVIAL 23208609 A 1345 1350 2-ITX SYSTEMATIC 23208609 A 1352 1357 4-ITX SYSTEMATIC 23208609 A 1363 1377 2,4-diethyl-TX SYSTEMATIC 23208609 A 1431 1436 2-ITX SYSTEMATIC 23208609 A 1561 1573 thioxanthone SYSTEMATIC 23208609 A 1680 1687 steroid FAMILY 23208609 A 178 183 2-ITX SYSTEMATIC 23208609 A 256 261 2-ITX SYSTEMATIC 23208609 A 263 286 4-isopropylthioxanthone SYSTEMATIC 23208609 A 288 293 4-ITX SYSTEMATIC 23208609 A 296 320 2,4-diethylthio xanthone SYSTEMATIC 23208609 A 322 336 2,4-diethyl-TX SYSTEMATIC 23208609 A 339 359 2-chlorothioxanthone SYSTEMATIC 23208609 A 361 372 2-chloro-TX SYSTEMATIC 23208609 A 379 409 1-chloro-4-propoxythioxanthone SYSTEMATIC 23208609 A 411 432 1-chloro-4-propoxy-TX SYSTEMATIC 23208609 A 457 465 androgen FAMILY 23208609 A 470 478 estrogen FAMILY 23208609 A 52 75 2-isopropylthioxanthone SYSTEMATIC 23208609 A 762 767 2-ITX SYSTEMATIC 23208609 A 769 774 4-ITX SYSTEMATIC 23208609 A 77 82 2-ITX SYSTEMATIC 23208609 A 780 794 2,4-diethyl-TX SYSTEMATIC 23208609 A 804 815 2-chloro-TX SYSTEMATIC 23208609 T 32 44 thioxanthone SYSTEMATIC 23208666 A 469 495 poly(2-nonyl-2-oxazoline)s FAMILY 23208666 A 9 26 poly(2-oxazoline) SYSTEMATIC 23208666 T 0 17 Poly(2-oxazoline) SYSTEMATIC 23209192 A 1139 1147 cotinine TRIVIAL 23209192 A 1374 1382 cotinine TRIVIAL 23209192 A 1605 1613 cotinine TRIVIAL 23209192 A 1669 1677 cotinine TRIVIAL 23209192 A 398 406 cotinine TRIVIAL 23209192 A 489 497 Cotinine TRIVIAL 23209192 A 641 649 Cotinine TRIVIAL 23209192 T 0 8 Cotinine TRIVIAL 23210481 A 0 8 Vizantin TRIVIAL 23210481 A 10 55 6,6'-bis-O-(3-nonyldodecanoyl)-α,α'-trehalose SYSTEMATIC 23210481 A 165 196 trehalose 6,6'-dicorynomycolate SYSTEMATIC 23210481 A 198 202 TDCM ABBREVIATION 23210481 A 235 243 vizantin TRIVIAL 23210481 A 293 297 TDCM ABBREVIATION 23210481 A 424 432 vizantin TRIVIAL 23210481 T 15 23 vizantin TRIVIAL 23210481 T 97 128 trehalose-6,6'-dicorynomycolate SYSTEMATIC 23210547 A 786 792 carbon SYSTEMATIC 23210547 A 79 85 carbon SYSTEMATIC 23210547 T 96 102 carbon SYSTEMATIC 23210662 A 195 202 ethynyl SYSTEMATIC 23210662 A 208 213 PAMAM ABBREVIATION 23210662 A 217 224 ethynyl SYSTEMATIC 23210662 A 230 235 PAMAM ABBREVIATION 23210662 A 459 466 ethynyl SYSTEMATIC 23210662 A 472 477 PAMAM ABBREVIATION 23210662 A 631 636 PAMAM ABBREVIATION 23210662 A 676 687 doxorubicin TRIVIAL 23210662 A 880 891 doxorubicin TRIVIAL 23210851 A 1021 1024 ATP ABBREVIATION 23210851 A 975 978 ATP ABBREVIATION 23211364 A 0 11 Candesartan TRIVIAL 23211364 A 1056 1067 Candesartan TRIVIAL 23211364 A 1151 1162 candesartan TRIVIAL 23211364 A 1262 1273 candesartan TRIVIAL 23211364 A 1358 1367 PD-123319 IDENTIFIER 23211364 A 1517 1528 candesartan TRIVIAL 23211364 A 163 174 candesartan TRIVIAL 23211364 A 674 685 candesartan TRIVIAL 23211364 A 929 940 candesartan TRIVIAL 23211364 A 975 986 candesartan TRIVIAL 23211525 A 224 238 hydroxysteroid FAMILY 23211525 A 306 326 sulfonate bile acids FAMILY 23211525 A 328 342 hydroxysteroid FAMILY 23211525 A 343 365 dehydroepiandrosterone TRIVIAL 23211525 A 379 388 androgens FAMILY 23211525 A 4 12 retinoid FAMILY 23211525 T 24 38 hydroxysteroid FAMILY 23212787 A 227 239 ginsenosides FAMILY 23212787 A 627 639 ginsenosides FAMILY 23212787 A 661 672 Ginsenoside FAMILY 23212787 A 780 813 Ginsenosides Ra1-3, Rb2-3, and Rc MULTIPLE 23212970 A 14 27 polyurethanes FAMILY 23212970 A 149 162 monoglyceride SYSTEMATIC 23212970 A 328 331 MTT ABBREVIATION 23212970 A 50 53 TDI ABBREVIATION 23212970 A 55 63 PCL diol SYSTEMATIC 23212970 A 65 75 butanediol SYSTEMATIC 23212970 A 81 96 pentaerythritol SYSTEMATIC 23212970 T 56 68 polyurethane SYSTEMATIC 23212975 A 0 24 Poly(N-vinylpyrrolidone) SYSTEMATIC 23212975 A 185 188 PVP ABBREVIATION 23212975 A 26 29 PVP ABBREVIATION 23212975 A 310 313 PVP ABBREVIATION 23212975 A 429 432 PVP ABBREVIATION 23212975 A 513 534 poly(ethylene glycol) SYSTEMATIC 23212975 A 536 539 PEG ABBREVIATION 23212975 A 611 614 PVP ABBREVIATION 23212975 A 695 698 PVP ABBREVIATION 23212975 A 782 785 PVP ABBREVIATION 23212975 T 0 24 Poly(N-vinylpyrrolidone) SYSTEMATIC 23214415 A 118 121 PEO ABBREVIATION 23214415 A 1186 1189 PEO ABBREVIATION 23214415 A 1318 1321 PEO ABBREVIATION 23214415 A 1322 1325 PAA ABBREVIATION 23214415 A 1626 1629 PEO ABBREVIATION 23214415 A 1634 1637 PAA ABBREVIATION 23214415 A 223 241 poly(acrylic acid) SYSTEMATIC 23214415 A 243 246 PAA ABBREVIATION 23214415 A 96 116 poly(ethylene oxide) SYSTEMATIC 23214415 T 16 19 PEO ABBREVIATION 23214415 T 20 23 PAA ABBREVIATION 23214423 A 1150 1167 graphite fluoride TRIVIAL 23214423 A 131 137 BrF(3) FORMULA 23214423 A 143 148 Br(2) FORMULA 23214423 A 26 34 graphite TRIVIAL 23214423 A 294 299 Br(2) FORMULA 23214423 A 341 349 graphene TRIVIAL 23214423 A 372 377 C(2)F FORMULA 23214423 A 442 450 graphite TRIVIAL 23214423 A 705 722 graphite fluoride TRIVIAL 23214423 A 775 781 carbon SYSTEMATIC 23214423 A 815 823 fluorine SYSTEMATIC 23214423 A 967 972 C(2)F FORMULA 23214423 A 993 1001 fluorine SYSTEMATIC 23214423 T 50 58 graphite TRIVIAL 23214423 T 59 62 C2F FORMULA 23214430 A 815 817 Au FORMULA 23214430 A 935 941 silica TRIVIAL 23214714 A 103 111 pyridine SYSTEMATIC 23214714 A 1193 1199 PyH(0) FORMULA 23214714 A 1309 1318 PyCOOH(0) FORMULA 23214714 A 1341 1347 PyH(0) FORMULA 23214714 A 1393 1399 PyH(0) FORMULA 23214714 A 1403 1408 CO(2) FORMULA 23214714 A 1489 1494 CO(2) FORMULA 23214714 A 1504 1512 Py·CO(2) FORMULA 23214714 A 154 159 CO(2) FORMULA 23214714 A 1596 1604 PyCOO(-) FORMULA 23214714 A 1637 1645 CO(2)(-) FORMULA 23214714 A 1650 1655 Py(-) ABBREVIATION 23214714 A 1706 1711 CO(2) FORMULA 23214714 A 1749 1757 pyridine SYSTEMATIC 23214714 A 1803 1808 CO(2) FORMULA 23214714 A 1854 1863 PyCOOH(0) FORMULA 23214714 A 191 200 PyCOOH(0) FORMULA 23214714 A 1982 1993 formic acid SYSTEMATIC 23214714 A 1998 2010 formaldehyde SYSTEMATIC 23214714 A 2036 2043 CH(3)OH FORMULA 23214714 A 2123 2128 CO(2) FORMULA 23214714 A 2184 2190 PyH(+) FORMULA 23214714 A 2194 2200 PyH(0) FORMULA 23214714 A 237 243 PyH(+) FORMULA 23214714 A 259 265 PyH(0) FORMULA 23214714 A 271 277 PyH(0) FORMULA 23214714 A 291 296 CO(2) FORMULA 23214714 A 358 359 N FORMULA 23214714 A 377 378 C FORMULA 23214714 A 382 387 CO(2) FORMULA 23214714 A 431 437 PyH(0) FORMULA 23214714 A 441 446 CO(2) FORMULA 23214714 A 456 465 PyCOOH(0) FORMULA 23214714 A 578 584 PyH(0) FORMULA 23214714 A 588 593 CO(2) FORMULA 23214714 A 84 89 CO(2) FORMULA 23214714 T 38 41 CO2 FORMULA 23214714 T 45 53 pyridine SYSTEMATIC 23214926 A 152 155 ADP ABBREVIATION 23214926 A 50 56 AMF-26 IDENTIFIER 23214926 A 866 878 Δ¹,²-octalin TRIVIAL 23214926 T 19 25 AMF-26 IDENTIFIER 23214926 T 92 95 ADP ABBREVIATION 23214979 A 241 278 3-amido-5-cyclopropylpyrrolopyrazines SYSTEMATIC 23214979 T 0 23 3-Amido pyrrolopyrazine SYSTEMATIC 23214990 A 147 175 poly(N-isopropyl acrylamide) SYSTEMATIC 23214990 T 96 124 poly(N-isopropyl acrylamide) SYSTEMATIC 23215007 A 1036 1054 methylated uracils FAMILY 23215007 A 121 177 5,6-dimethyl-, 1,3,5-trimethyl-, and 1,3,5,6-tetramethyl MULTIPLE 23215007 A 624 628 N(2) FORMULA 23215007 A 770 788 5,6-dimethyluracil SYSTEMATIC 23215007 A 790 811 1,3,5-trimethyluracil SYSTEMATIC 23215007 A 817 842 1,3,5,6-tetramethyluracil SYSTEMATIC 23215007 T 19 26 uracils FAMILY 23215007 T 86 149 5,6-dimethyl-, 1,3,5-trimethyl-, and 1,3,5,6-tetramethyluracils MULTIPLE 23215148 A 1196 1200 DPPC ABBREVIATION 23215148 A 1201 1205 DPPC ABBREVIATION 23215148 A 1397 1401 DPPC ABBREVIATION 23215148 A 1402 1406 DPPC ABBREVIATION 23215148 A 1548 1552 DPPC ABBREVIATION 23215148 A 1569 1573 DOPC ABBREVIATION 23215148 A 392 432 1,2-dioleoyl-sn-glycero-3-phosphocholine SYSTEMATIC 23215148 A 434 438 DOPC ABBREVIATION 23215148 A 440 483 1,2-dipalmitoyl-sn-glycero-3-phosphocholine SYSTEMATIC 23215148 A 485 489 DPPC ABBREVIATION 23215148 A 512 516 DOPC ABBREVIATION 23215148 A 517 521 DPPC ABBREVIATION 23215148 A 522 564 1,2-dioleoyl-sn-glycero-3-phospho-L-serine SYSTEMATIC 23215148 A 566 570 DOPS ABBREVIATION 23215148 A 596 605 Texas Red TRIVIAL 23215148 A 606 674 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium SYSTEMATIC 23215148 A 681 688 TR-DHPE ABBREVIATION 23215148 A 754 758 DPPC ABBREVIATION 23215148 A 943 947 DOPC ABBREVIATION 23215148 A 948 952 DPPC ABBREVIATION 23215148 A 958 962 DOPC ABBREVIATION 23215148 A 988 992 DPPC ABBREVIATION 23215238 A 124 141 calcium carbonate SYSTEMATIC 23215238 A 404 421 calcium carbonate SYSTEMATIC 23215238 A 507 524 calcium carbonate SYSTEMATIC 23215238 A 548 552 EDTA ABBREVIATION 23215461 A 381 393 carbohydrate FAMILY 23216335 A 555 564 androgens FAMILY 23217961 A 159 167 retinoid FAMILY 23217961 A 209 222 Cinnamic acid TRIVIAL 23217961 A 241 261 phenylpropionic acid SYSTEMATIC 23217961 A 283 291 retinoid FAMILY 23217961 A 442 457 carboxylic acid SYSTEMATIC 23217961 A 488 501 diphenylamine SYSTEMATIC 23217961 A 534 540 methyl SYSTEMATIC 23217961 A 56 68 benzoic acid SYSTEMATIC 23217961 A 575 583 carboxyl SYSTEMATIC 23217961 A 691 695 Am80 IDENTIFIER 23217961 A 77 90 diphenylamine SYSTEMATIC 23217961 A 97 106 retinoids FAMILY 23217961 T 41 53 benzoic acid SYSTEMATIC 23217961 T 62 75 diphenylamine SYSTEMATIC 23217961 T 82 91 retinoids FAMILY 23218712 A 135 142 glucose TRIVIAL 23218712 A 188 194 YH-GKA IDENTIFIER 23218712 A 265 271 YH-GKA IDENTIFIER 23218712 A 287 294 glucose TRIVIAL 23218712 A 484 491 glucose TRIVIAL 23218712 A 548 554 YH-GKA IDENTIFIER 23218712 A 592 599 glucose TRIVIAL 23218712 A 6 15 benzamide SYSTEMATIC 23218712 A 675 681 YH-GKA IDENTIFIER 23218712 T 21 42 phenylethyl benzamide SYSTEMATIC 23218713 A 284 293 bisulfite SYSTEMATIC 23218713 A 359 379 dipeptidyl aldehydes FAMILY 23218713 A 384 396 α-ketoamides FAMILY 23218713 A 608 617 bisulfite SYSTEMATIC 23218713 A 821 830 bisulfite SYSTEMATIC 23218713 A 890 896 serine TRIVIAL 23218713 A 901 909 cysteine TRIVIAL 23218713 A 929 947 α-ketoheterocycles FAMILY 23218713 A 952 964 α-ketoesters FAMILY 23218713 T 40 49 bisulfite SYSTEMATIC 23218716 A 0 16 Tsitsikammamines FAMILY 23218716 A 306 317 Indoleamine SYSTEMATIC 23218716 A 516 531 tsitsikammamine FAMILY 23218716 A 558 575 Tsitsikammamine A TRIVIAL 23218716 A 70 89 pyrroloiminoquinone SYSTEMATIC 23218716 A 747 757 tryptophan TRIVIAL 23218716 T 0 11 Indoleamine SYSTEMATIC 23218716 T 82 99 tsitsikammamine A TRIVIAL 23218717 A 106 135 N-pyridylpyrazolecarboxamides FAMILY 23218717 A 1084 1089 2-APB SYSTEMATIC 23218717 A 1092 1098 Ca(2+) FORMULA 23218717 A 1161 1168 calcium SYSTEMATIC 23218717 A 1247 1254 calcium SYSTEMATIC 23218717 A 147 152 cyano FAMILY 23218717 A 62 71 ryanodine TRIVIAL 23218717 A 669 676 calcium SYSTEMATIC 23218717 A 779 786 calcium SYSTEMATIC 23218717 A 807 813 Ca(2+) FORMULA 23218717 A 908 914 Ca(2+) FORMULA 23218717 A 946 953 calcium SYSTEMATIC 23218717 A 997 1006 fluo-3 AM TRIVIAL 23218717 T 47 76 N-pyridylpyrazolecarboxamides FAMILY 23218717 T 88 93 cyano FAMILY 23219161 A 361 362 N FORMULA 23219161 A 396 397 C FORMULA 23219325 A 0 7 Leucine TRIVIAL 23219325 A 254 278 cinnoline-3-carboxamides FAMILY 23219325 T 6 15 cinnoline TRIVIAL 23219339 A 0 10 Oxymatrine TRIVIAL 23219339 A 1018 1025 calcium SYSTEMATIC 23219339 A 1081 1085 NMDA ABBREVIATION 23219339 A 1087 1090 OMT ABBREVIATION 23219339 A 1180 1184 NMDA ABBREVIATION 23219339 A 12 15 OMT ABBREVIATION 23219339 A 304 307 OMT ABBREVIATION 23219339 A 396 400 NMDA ABBREVIATION 23219339 A 433 436 OMT ABBREVIATION 23219339 A 606 626 N-methyl-D-aspartate SYSTEMATIC 23219339 A 628 632 NMDA ABBREVIATION 23219339 A 719 722 OMT ABBREVIATION 23219339 A 785 789 NMDA ABBREVIATION 23219339 A 836 839 OMT ABBREVIATION 23219339 A 947 950 OMT ABBREVIATION 23219339 T 114 118 NMDA ABBREVIATION 23219339 T 27 37 oxymatrine TRIVIAL 23219469 A 392 403 cholesterol TRIVIAL 23219469 T 71 82 cholesterol TRIVIAL 23219525 A 1007 1015 bosentan TRIVIAL 23219525 A 1020 1031 ambrisentan TRIVIAL 23219525 A 1100 1110 sildenafil TRIVIAL 23219525 A 1114 1123 tadalafil TRIVIAL 23219525 A 122 132 sildenafil TRIVIAL 23219525 A 136 145 tadalafil TRIVIAL 23219525 A 1400 1409 tadalafil TRIVIAL 23219525 A 1423 1434 ambrisentan TRIVIAL 23219525 A 1447 1457 sildenafil TRIVIAL 23219525 A 1474 1482 pregnane TRIVIAL 23219525 A 1547 1557 sildenafil TRIVIAL 23219525 A 1562 1571 tadalafil TRIVIAL 23219525 A 1618 1626 bosentan TRIVIAL 23219525 A 1631 1642 ambrisentan TRIVIAL 23219525 A 290 298 bosentan TRIVIAL 23219525 A 319 329 sildenafil TRIVIAL 23219525 A 495 505 sildenafil TRIVIAL 23219525 A 510 519 tadalafil TRIVIAL 23219525 A 575 583 bosentan TRIVIAL 23219525 A 58 66 bosentan TRIVIAL 23219525 A 587 598 ambrisentan TRIVIAL 23219525 A 671 679 bosentan TRIVIAL 23219525 A 684 695 ambrisentan TRIVIAL 23219525 A 70 81 ambrisentan TRIVIAL 23219525 A 845 855 sildenafil TRIVIAL 23219525 A 859 868 tadalafil TRIVIAL 23219525 T 102 113 ambrisentan TRIVIAL 23219525 T 13 23 sildenafil TRIVIAL 23219525 T 89 97 bosentan TRIVIAL 23219590 A 1065 1076 Maprotiline TRIVIAL 23219590 A 1130 1136 Ca(2+) FORMULA 23219590 A 224 235 Maprotiline TRIVIAL 23219590 A 301 315 norepinephrine TRIVIAL 23219590 A 348 359 maprotiline TRIVIAL 23219590 A 450 461 Maprotiline TRIVIAL 23219590 A 547 558 maprotiline TRIVIAL 23219590 A 631 642 Maprotiline TRIVIAL 23219590 A 657 663 Ca(2+) FORMULA 23219590 A 727 733 Ca(2+) FORMULA 23219590 A 789 794 BAPTA ABBREVIATION 23219590 A 801 807 Ca(2+) FORMULA 23219590 A 829 840 maprotiline TRIVIAL 23219590 A 914 925 maprotiline TRIVIAL 23219590 A 960 971 maprotiline TRIVIAL 23219590 T 13 24 maprotiline TRIVIAL 23219590 T 53 57 Ca2+ FORMULA 23219658 A 185 205 N-methyl-d-Aspartate SYSTEMATIC 23219658 A 207 211 NMDA ABBREVIATION 23219658 A 408 412 NMDA ABBREVIATION 23219658 T 101 110 glutamate TRIVIAL 23219658 T 80 100 N-methyl-d-aspartate SYSTEMATIC 23219696 A 1017 1025 steroids FAMILY 23219696 A 1348 1356 steroids FAMILY 23219696 A 1491 1500 estradiol TRIVIAL 23219696 A 1660 1669 estradiol TRIVIAL 23219696 A 1847 1855 steroids FAMILY 23219696 A 412 420 steroids FAMILY 23219696 A 485 493 steroids FAMILY 23219696 A 512 520 steroids FAMILY 23219696 A 55 63 steroids FAMILY 23219696 A 573 584 Bisphenol-A TRIVIAL 23219696 A 586 597 nonylphenol SYSTEMATIC 23219696 A 70 82 testosterone TRIVIAL 23219696 A 755 762 steroid FAMILY 23219696 A 84 93 estradiol TRIVIAL 23219696 A 95 107 progesterone TRIVIAL 23219696 T 107 115 steroids FAMILY 23219696 T 31 39 steroids FAMILY 23219778 A 1080 1084 MeOH FORMULA 23219778 A 738 746 methanol SYSTEMATIC 23219778 A 748 752 MeOH FORMULA 23219778 A 884 888 MeOH FORMULA 23219778 A 964 976 nitric oxide SYSTEMATIC 23219979 A 25 49 sciryagarol I (1) and II MULTIPLE 23219979 A 77 82 EtOAc FORMULA 23219979 A 8 23 cis-stilbenoids FAMILY 23219979 T 10 25 cis-stilbenoids FAMILY 23220002 A 1430 1437 glucose TRIVIAL 23220002 A 171 187 organophosphorus FAMILY 23220002 A 193 199 esters FAMILY 23220003 A 1005 1016 gallic acid TRIVIAL 23220003 A 1018 1032 methyl gallate SYSTEMATIC 23220003 A 1034 1047 ethyl gallate SYSTEMATIC 23220003 A 1049 1063 propyl gallate SYSTEMATIC 23220003 A 1065 1070 rutin TRIVIAL 23220003 A 1075 1083 curcumin TRIVIAL 23220003 A 1089 1100 polyphenols FAMILY 23220003 A 1132 1135 GSH ABBREVIATION 23220003 A 1162 1173 polyphenols FAMILY 23220003 A 124 131 glyoxal TRIVIAL 23220003 A 1335 1346 polyphenols FAMILY 23220003 A 1357 1362 rutin TRIVIAL 23220003 A 136 149 methylglyoxal SYSTEMATIC 23220003 A 1427 1432 rutin TRIVIAL 23220003 A 1467 1473 oxygen SYSTEMATIC 23220003 A 1504 1509 rutin TRIVIAL 23220003 A 151 159 Fructose TRIVIAL 23220003 A 1533 1538 alkyl FAMILY 23220003 A 1561 1568 gallate TRIVIAL 23220003 A 1607 1617 polyphenol FAMILY 23220003 A 1636 1644 gallates FAMILY 23220003 A 1657 1662 alkyl FAMILY 23220003 A 1706 1712 oxygen SYSTEMATIC 23220003 A 173 186 glycoaldehyde SYSTEMATIC 23220003 A 188 202 glyceraldehyde TRIVIAL 23220003 A 207 222 hydroxypyruvate SYSTEMATIC 23220003 A 289 297 fructose TRIVIAL 23220003 A 415 423 fructose TRIVIAL 23220003 A 43 51 fructose TRIVIAL 23220003 A 459 469 dicarbonyl SYSTEMATIC 23220003 A 559 575 dihydroxyacetone SYSTEMATIC 23220003 A 579 587 fructose TRIVIAL 23220003 A 653 664 dicarbonyls FAMILY 23220003 A 768 779 polyphenols FAMILY 23220003 A 829 836 glyoxal TRIVIAL 23220003 A 842 855 methylglyoxal SYSTEMATIC 23220003 A 887 893 oxygen SYSTEMATIC 23220003 A 975 986 polyphenols FAMILY 23220003 T 0 7 Glyoxal TRIVIAL 23220003 T 12 25 methylglyoxal SYSTEMATIC 23220003 T 45 61 dihydroxyacetone SYSTEMATIC 23220003 T 66 76 polyphenol FAMILY 23220004 A 1019 1026 retinol TRIVIAL 23220004 A 1031 1044 retinaldehyde TRIVIAL 23220004 A 1063 1071 retinoid FAMILY 23220004 A 1313 1321 4-methyl SYSTEMATIC 23220004 A 1337 1350 retinaldehyde TRIVIAL 23220004 A 1577 1586 retinoids FAMILY 23220004 A 1609 1622 retinoic acid TRIVIAL 23220004 A 1643 1651 retinoid FAMILY 23220004 A 1721 1734 retinaldehyde TRIVIAL 23220004 A 1788 1797 retinoids FAMILY 23220004 A 1829 1836 UVI2008 IDENTIFIER 23220004 A 1941 1949 carboxyl SYSTEMATIC 23220004 A 227 234 retinol TRIVIAL 23220004 A 238 251 retinaldehyde TRIVIAL 23220004 A 303 310 retinol TRIVIAL 23220004 A 31 40 retinoids FAMILY 23220004 A 325 328 NAD ABBREVIATION 23220004 A 458 471 Retinaldehyde TRIVIAL 23220004 A 582 590 aldehyde SYSTEMATIC 23220004 A 67 74 retinol TRIVIAL 23220004 A 724 732 retinoid FAMILY 23220004 A 742 750 retinoid FAMILY 23220004 A 769 776 retinol TRIVIAL 23220004 A 78 91 retinoic acid TRIVIAL 23220004 A 850 858 retinoid FAMILY 23220004 T 24 32 retinoid FAMILY 23220291 A 251 259 limonene TRIVIAL 23220291 A 264 269 ozone TRIVIAL 23220291 A 571 579 limonene TRIVIAL 23220291 A 584 589 ozone TRIVIAL 23220291 A 750 758 limonene TRIVIAL 23220291 A 759 764 ozone TRIVIAL 23220291 A 835 843 limonene TRIVIAL 23220291 A 878 886 limonene TRIVIAL 23220291 A 890 898 limonene TRIVIAL 23220291 A 899 904 ozone TRIVIAL 23220291 T 26 34 limonene TRIVIAL 23220293 A 1032 1041 serotonin TRIVIAL 23220293 A 1046 1060 norepinephrine TRIVIAL 23220293 A 1166 1170 5-HT SYSTEMATIC 23220293 A 1210 1214 5-HT SYSTEMATIC 23220293 A 1510 1520 citalopram TRIVIAL 23220293 A 1553 1564 desipramine TRIVIAL 23220293 A 1727 1736 serotonin TRIVIAL 23220293 A 1740 1753 catecholamine TRIVIAL 23220293 A 187 196 monoamine FAMILY 23220293 A 378 387 serotonin TRIVIAL 23220293 A 392 400 dopamine TRIVIAL 23220293 A 501 510 serotonin TRIVIAL 23220293 A 590 599 serotonin TRIVIAL 23220293 A 619 629 citalopram TRIVIAL 23220293 A 668 677 serotonin TRIVIAL 23220293 A 814 818 5-HT SYSTEMATIC 23220293 A 871 881 citalopram TRIVIAL 23220293 A 980 990 citalopram TRIVIAL 23220293 T 6 16 monoamines FAMILY 23220295 A 1028 1036 dopamine TRIVIAL 23220295 A 1117 1128 amphetamine TRIVIAL 23220295 A 1178 1189 amphetamine TRIVIAL 23220295 A 1198 1206 dopamine TRIVIAL 23220295 A 1279 1290 amphetamine TRIVIAL 23220295 A 1308 1316 dopamine TRIVIAL 23220295 A 1371 1379 dopamine TRIVIAL 23220295 A 1402 1413 amphetamine TRIVIAL 23220295 A 1555 1566 amphetamine TRIVIAL 23220295 A 1622 1630 dopamine TRIVIAL 23220295 A 1755 1766 amphetamine TRIVIAL 23220295 A 1798 1809 amphetamine TRIVIAL 23220295 A 1843 1851 dopamine TRIVIAL 23220295 A 1973 1981 dopamine TRIVIAL 23220295 A 283 291 dopamine TRIVIAL 23220295 A 32 40 dopamine TRIVIAL 23220295 A 348 356 dopamine TRIVIAL 23220295 A 391 399 dopamine TRIVIAL 23220295 A 424 435 amphetamine TRIVIAL 23220295 A 451 462 amphetamine TRIVIAL 23220295 A 511 522 amphetamine TRIVIAL 23220295 A 567 578 amphetamine TRIVIAL 23220295 A 601 609 dopamine TRIVIAL 23220295 A 716 724 dopamine TRIVIAL 23220295 A 909 920 amphetamine TRIVIAL 23220295 A 973 984 amphetamine TRIVIAL 23220295 T 45 56 amphetamine TRIVIAL 23220295 T 96 104 dopamine TRIVIAL 23220412 A 0 11 Metolachlor TRIVIAL 23220412 A 1008 1019 metolachlor TRIVIAL 23220412 A 1125 1136 metolachlor TRIVIAL 23220412 A 1468 1479 glutathione TRIVIAL 23220412 A 15 32 chloroacetanilide SYSTEMATIC 23220412 A 1517 1530 chlorophyll a TRIVIAL 23220412 A 1552 1563 metolachlor TRIVIAL 23220412 A 1646 1657 metolachlor TRIVIAL 23220412 A 1858 1869 metolachlor TRIVIAL 23220412 A 303 314 metolachlor TRIVIAL 23220412 A 412 433 chlorophyll a, b or c MULTIPLE 23220412 A 613 624 metolachlor TRIVIAL 23220412 A 685 696 glutathione TRIVIAL 23220412 A 712 723 metolachlor TRIVIAL 23220412 A 755 766 metolachlor TRIVIAL 23220412 T 64 75 metolachlor TRIVIAL 23220413 A 0 37 Tris(1,3-dichloro-2-propyl) phosphate SYSTEMATIC 23220413 A 1227 1232 TDCPP ABBREVIATION 23220413 A 1531 1536 TDCPP ABBREVIATION 23220413 A 1801 1806 TDCPP ABBREVIATION 23220413 A 301 306 TDCPP ABBREVIATION 23220413 A 39 44 TDCPP ABBREVIATION 23220413 A 583 588 TDCPP ABBREVIATION 23220413 A 810 836 3,3',5-triiodo-l-thyronine SYSTEMATIC 23220413 A 877 890 thyroxin (T4) TRIVIAL 23220413 T 40 45 TDCPP ABBREVIATION 23220513 A 0 13 Methyleugenol TRIVIAL 23220513 A 1249 1252 MEG ABBREVIATION 23220513 A 15 18 MEG ABBREVIATION 23220513 A 199 202 MEG ABBREVIATION 23220513 A 326 339 phenobarbital TRIVIAL 23220513 A 488 493 (32)P FORMULA 23220513 A 560 563 MEG ABBREVIATION 23220513 A 711 714 MEG ABBREVIATION 23220513 A 764 775 glutathione TRIVIAL 23220513 A 776 777 S FORMULA 23220513 A 911 914 MEG ABBREVIATION 23220513 T 0 13 Methyleugenol TRIVIAL 23220514 A 1010 1013 DOX ABBREVIATION 23220514 A 1061 1064 DOX ABBREVIATION 23220514 A 1097 1102 Na(+) FORMULA 23220514 A 1113 1123 nucleoside FAMILY 23220514 A 1155 1158 DOX ABBREVIATION 23220514 A 1232 1235 DOX ABBREVIATION 23220514 A 1248 1256 linalool TRIVIAL 23220514 A 1311 1314 DOX ABBREVIATION 23220514 A 278 289 doxorubicin TRIVIAL 23220514 A 291 294 DOX ABBREVIATION 23220514 A 328 331 DOX ABBREVIATION 23220514 A 384 387 DOX ABBREVIATION 23220514 A 422 430 linalool TRIVIAL 23220514 A 479 482 DOX ABBREVIATION 23220514 A 526 534 linalool TRIVIAL 23220514 A 538 541 DOX ABBREVIATION 23220514 A 594 597 DOX ABBREVIATION 23220514 A 603 611 linalool TRIVIAL 23220514 A 671 674 DOX ABBREVIATION 23220514 A 713 716 DOX ABBREVIATION 23220514 A 742 750 linalool TRIVIAL 23220514 A 821 826 Na(+) FORMULA 23220514 A 884 915 S-(4-nitrobenzyl)-6-thioinosine SYSTEMATIC 23220514 A 945 954 phlorizin TRIVIAL 23220514 A 992 1000 linalool TRIVIAL 23220514 T 10 18 linalool TRIVIAL 23220514 T 56 67 doxorubicin TRIVIAL 23220560 A 1066 1070 MeHg FORMULA 23220560 A 1096 1100 MeHg FORMULA 23220560 A 1208 1212 MeHg FORMULA 23220560 A 1395 1399 MeHg FORMULA 23220560 A 1658 1662 MeHg FORMULA 23220560 A 242 246 MeHg FORMULA 23220560 A 48 52 MeHg FORMULA 23220560 A 507 511 MeHg FORMULA 23220560 A 753 757 MeHg FORMULA 23220560 T 31 44 methylmercury SYSTEMATIC 23220562 A 1089 1100 clopidogrel TRIVIAL 23220562 A 1371 1380 SB-203580 IDENTIFIER 23220562 A 1427 1433 U-0126 IDENTIFIER 23220562 A 1456 1465 SP-600125 IDENTIFIER 23220562 A 1501 1512 clopidogrel TRIVIAL 23220562 A 1736 1747 clopidogrel TRIVIAL 23220562 A 221 232 clopidogrel TRIVIAL 23220562 A 413 424 clopidogrel TRIVIAL 23220562 A 478 481 MTT ABBREVIATION 23220562 A 517 521 DAPI ABBREVIATION 23220562 A 83 94 clopidogrel TRIVIAL 23220562 T 68 79 clopidogrel TRIVIAL 23220586 A 1026 1029 PEG ABBREVIATION 23220586 A 1045 1048 PEG ABBREVIATION 23220586 A 1156 1159 PEG ABBREVIATION 23220586 A 132 148 organophosphorus FAMILY 23220586 A 389 394 soman TRIVIAL 23220586 A 565 584 polyethylene glycol SYSTEMATIC 23220586 A 586 589 PEG ABBREVIATION 23220586 A 702 705 PEG ABBREVIATION 23220586 A 712 715 PEG ABBREVIATION 23220586 T 10 29 polyethylene glycol SYSTEMATIC 23220588 A 0 16 Cyclophosphamide TRIVIAL 23220588 A 1065 1073 Acrolein TRIVIAL 23220588 A 1135 1143 acrolein TRIVIAL 23220588 A 1229 1232 CAA ABBREVIATION 23220588 A 1332 1340 Aldehyde SYSTEMATIC 23220588 A 1409 1412 CAA ABBREVIATION 23220588 A 1506 1515 cyanamide SYSTEMATIC 23220588 A 1626 1634 acrolein TRIVIAL 23220588 A 1726 1734 acrolein TRIVIAL 23220588 A 1738 1741 CAA ABBREVIATION 23220588 A 184 192 acrolein TRIVIAL 23220588 A 1858 1876 sodium borohydride SYSTEMATIC 23220588 A 1878 1894 sodium bisulfite SYSTEMATIC 23220588 A 1896 1901 thiol FAMILY 23220588 A 1924 1940 N-acetylcysteine SYSTEMATIC 23220588 A 1942 1950 cysteine TRIVIAL 23220588 A 1952 1963 glutathione TRIVIAL 23220588 A 1965 1991 2-mercaptoethane sulfonate SYSTEMATIC 23220588 A 197 215 chloroacetaldehyde SYSTEMATIC 23220588 A 1993 1998 MESNA ABBREVIATION 23220588 A 2001 2014 penicillamine TRIVIAL 23220588 A 2016 2024 carbonyl FAMILY 23220588 A 2036 2042 amines FAMILY 23220588 A 2044 2058 aminoguanidine SYSTEMATIC 23220588 A 2060 2071 hydralazine SYSTEMATIC 23220588 A 2073 2086 hydroxylamine SYSTEMATIC 23220588 A 21 31 ifosfamide TRIVIAL 23220588 A 2117 2130 ascorbic acid TRIVIAL 23220588 A 2132 2138 Trolox TRIVIAL 23220588 A 217 220 CAA ABBREVIATION 23220588 A 2197 2205 acrolein TRIVIAL 23220588 A 2210 2213 CAA ABBREVIATION 23220588 A 223 231 Acrolein TRIVIAL 23220588 A 236 239 CAA ABBREVIATION 23220588 A 2401 2409 acrolein TRIVIAL 23220588 A 2413 2416 CAA ABBREVIATION 23220588 A 2420 2436 cyclophosphamide TRIVIAL 23220588 A 2440 2450 ifosfamide TRIVIAL 23220588 A 529 537 acrolein TRIVIAL 23220588 A 542 545 CAA ABBREVIATION 23220588 A 651 662 Trypan blue TRIVIAL 23220588 A 693 699 oxygen SYSTEMATIC 23220588 A 729 733 H2O2 FORMULA 23220588 A 936 944 acrolein TRIVIAL 23220588 A 974 977 CAA ABBREVIATION 23220588 T 0 8 Acrolein TRIVIAL 23220588 T 13 31 chloroacetaldehyde SYSTEMATIC 23220589 A 0 16 Organophosphorus FAMILY 23220589 A 1028 1038 dichlorvos TRIVIAL 23220589 A 1040 1048 paraoxon TRIVIAL 23220589 A 1053 1058 tabun TRIVIAL 23220589 A 1105 1113 paraoxon TRIVIAL 23220589 A 1148 1156 BT-07-4M NO CLASS 23220589 A 1158 1167 obidoxime TRIVIAL 23220589 A 1169 1174 TMB-4 IDENTIFIER 23220589 A 1179 1184 BT-08 NO CLASS 23220589 A 1213 1219 oximes FAMILY 23220589 A 1225 1232 Toxidin NO CLASS 23220589 A 1234 1239 BT-05 NO CLASS 23220589 A 1244 1249 BT-03 NO CLASS 23220589 A 1374 1382 BT-07-4M NO CLASS 23220589 A 1384 1389 TMB-4 IDENTIFIER 23220589 A 1394 1403 obidoxime TRIVIAL 23220589 A 1419 1425 oximes FAMILY 23220589 A 1431 1436 BT-05 NO CLASS 23220589 A 1441 1446 BT-03 NO CLASS 23220589 A 1550 1560 dichlorvos TRIVIAL 23220589 A 714 719 tabun TRIVIAL 23220589 A 721 729 paraoxon TRIVIAL 23220589 A 734 744 dichlorvos TRIVIAL 23220589 A 838 844 oximes FAMILY 23220589 A 846 855 obidoxime TRIVIAL 23220589 A 857 861 HI-6 IDENTIFIER 23220589 A 863 868 2-PAM SYSTEMATIC 23220612 A 1030 1038 H(2)O(2) FORMULA 23220612 A 1107 1119 Arachidonate TRIVIAL 23220612 A 1121 1137 docosahexaenoate SYSTEMATIC 23220612 A 1139 1156 eicosapentaenoate SYSTEMATIC 23220612 A 1161 1172 cholesterol TRIVIAL 23220612 A 1208 1216 H(2)O(2) FORMULA 23220612 A 1246 1258 isoprostanes FAMILY 23220612 A 1260 1274 neuroprostanes FAMILY 23220612 A 1275 1284 5(S)-HETE SYSTEMATIC 23220612 A 1286 1293 20-HETE SYSTEMATIC 23220612 A 1295 1312 7-ketocholesterol SYSTEMATIC 23220612 A 1314 1335 27-hydroxycholesterol SYSTEMATIC 23220612 A 1340 1351 resolvin D1 TRIVIAL 23220612 A 1452 1464 isoprostanes FAMILY 23220612 A 289 316 polyunsaturated fatty acids FAMILY 23220612 A 321 332 cholesterol TRIVIAL 23220612 A 365 373 H(2)O(2) FORMULA 23220612 A 41 47 oxygen SYSTEMATIC 23220612 A 456 468 isoprostanes FAMILY 23220612 A 491 503 isoprostanes FAMILY 23220612 A 505 519 neuroprostanes FAMILY 23220612 A 521 538 7-ketocholesterol SYSTEMATIC 23220612 A 540 561 7β-hydroxycholesterol SYSTEMATIC 23220612 A 589 624 5(S)-, 8(S)-, 12(S)- and 15(S)-HETE MULTIPLE 23220612 A 630 641 resolvin D1 TRIVIAL 23220612 A 667 692 9(S)-, 11(S)- and 20-HETE MULTIPLE 23220612 A 698 718 27-hydroxycholestrol SYSTEMATIC 23220612 A 765 777 Arachidonate TRIVIAL 23220612 A 779 795 docosahexaenoate SYSTEMATIC 23220612 A 797 814 eicosapentaenoate SYSTEMATIC 23220612 A 819 830 cholesterol TRIVIAL 23220612 A 891 903 gluthathione TRIVIAL 23220617 A 2183 2194 doxorubicin TRIVIAL 23220617 A 2199 2215 cyclophosphamide TRIVIAL 23220617 A 359 367 carbonyl FAMILY 23220617 A 379 394 3-nitrotyrosine SYSTEMATIC 23220617 A 705 716 doxorubicin TRIVIAL 23220617 A 721 737 cyclophosphamide TRIVIAL 23220635 A 4 20 aryl hydrocarbon FAMILY 23220644 A 120 136 arachidonic acid TRIVIAL 23220644 A 327 334 JMC08-4 IDENTIFIER 23220644 A 498 505 JMC08-4 IDENTIFIER 23220644 A 607 626 5-hydroxytryptamine SYSTEMATIC 23220644 A 742 749 JMC08-4 IDENTIFIER 23220644 T 16 36 5-hydroxytryptamines FAMILY 23220646 A 130 151 isoxazolecarbaldehyde SYSTEMATIC 23220646 A 260 273 benzimidazole SYSTEMATIC 23220646 A 275 288 benzothiazole SYSTEMATIC 23220646 A 290 301 3H-indazole SYSTEMATIC 23220646 A 307 327 5-phenyl-1H-pyrazole SYSTEMATIC 23220646 A 652 656 TLCK ABBREVIATION 23220646 T 30 47 benzoheterocyclic FAMILY 23221006 A 0 10 Phenformin TRIVIAL 23221006 A 1003 1009 oxygen SYSTEMATIC 23221006 A 1157 1167 phenformin TRIVIAL 23221006 A 1337 1347 phenformin TRIVIAL 23221006 A 1449 1459 phenformin TRIVIAL 23221006 A 237 247 phenformin TRIVIAL 23221006 A 252 277 [(14)C]tetraethylammonium SYSTEMATIC 23221006 A 279 282 TEA ABBREVIATION 23221006 A 312 322 phenformin TRIVIAL 23221006 A 389 399 phenformin TRIVIAL 23221006 A 658 661 TEA ABBREVIATION 23221006 A 682 692 phenformin TRIVIAL 23221006 A 729 738 carnitine TRIVIAL 23221006 A 832 835 TEA ABBREVIATION 23221006 A 989 999 phenformin TRIVIAL 23221006 T 23 32 carnitine TRIVIAL 23221006 T 60 70 phenformin TRIVIAL 23221633 A 456 463 phospho SYSTEMATIC 23221633 A 87 93 oxygen SYSTEMATIC 23222689 A 192 205 valproic acid TRIVIAL 23222689 A 277 290 valproic acid TRIVIAL 23222689 A 95 108 valproic acid TRIVIAL 23222689 T 11 24 valproic acid TRIVIAL 23223023 A 44 55 fatty acids FAMILY 23223023 A 72 85 palmitic acid TRIVIAL 23223023 A 884 906 oleic and stearic acid MULTIPLE 23223023 T 12 25 palmitic acid TRIVIAL 23223234 A 605 616 6-azauracil SYSTEMATIC 23223234 A 73 83 nucleotide FAMILY 23223345 A 1062 1069 glucose TRIVIAL 23223345 A 1350 1354 CARB ABBREVIATION 23223345 A 1417 1421 CARB ABBREVIATION 23223345 A 1466 1478 carbohydrate FAMILY 23223345 A 331 343 carbohydrate FAMILY 23223345 A 355 359 CARB ABBREVIATION 23223345 T 15 27 Carbohydrate FAMILY 23223551 A 1166 1172 oxygen SYSTEMATIC 23223551 A 18 25 methane SYSTEMATIC 23223551 A 240 243 C-H FORMULA 23223551 A 327 330 C-H FORMULA 23223551 A 340 347 methane SYSTEMATIC 23223551 A 358 370 hydrocarbons FAMILY 23223551 A 384 400 transition metal FAMILY 23223551 A 471 477 CuO(+) FORMULA 23223551 A 482 489 CuOH(+) FORMULA 23223551 T 54 61 methane SYSTEMATIC 23223551 T 65 77 copper oxide SYSTEMATIC 23223551 T 82 98 copper hydroxide SYSTEMATIC 23223639 A 325 345 polydimethylsiloxane SYSTEMATIC 23223641 A 103 110 zeolite TRIVIAL 23223641 A 266 274 zeolites FAMILY 23223641 A 893 901 zeolites FAMILY 23223641 T 39 46 zeolite TRIVIAL 23223708 A 0 23 Polyvinylidene fluoride SYSTEMATIC 23223708 A 159 163 PVDF ABBREVIATION 23223708 A 25 29 PVDF ABBREVIATION 23223708 A 304 312 vanadium SYSTEMATIC 23223708 A 618 622 PVDF ABBREVIATION 23223708 A 755 761 Nafion TRIVIAL 23223708 A 97 105 vanadium SYSTEMATIC 23223708 T 39 43 PVDF ABBREVIATION 23223801 A 0 20 Trivalent lanthanide FAMILY 23223801 A 22 28 Ln(3+) FORMULA 23223801 A 402 408 Ln(3+) FORMULA 23223801 T 0 10 Lanthanide FAMILY 23223857 A 0 6 Carbon SYSTEMATIC 23223857 T 18 24 carbon SYSTEMATIC 23224291 A 1034 1056 adenosine triphosphate SYSTEMATIC 23224291 A 1092 1103 glutathione TRIVIAL 23224291 A 1104 1105 S FORMULA 23224291 A 1291 1298 glycine TRIVIAL 23224291 A 780 784 (1)H FORMULA 23224291 A 968 975 glucose TRIVIAL 23224291 A 998 1010 thiosulphate SYSTEMATIC 23224775 A 432 461 carboxyl- and hydroxyl oxygen MULTIPLE 23224775 A 471 477 Ti(IV) FORMULA 23224775 A 500 506 TiO(2) FORMULA 23224775 A 596 604 carboxyl SYSTEMATIC 23224775 A 625 631 Ti(IV) FORMULA 23224775 A 860 866 TiO(2) FORMULA 23224942 A 222 230 graphene TRIVIAL 23224942 A 236 241 epoxy SYSTEMATIC 23224942 A 39 53 graphene oxide SYSTEMATIC 23224942 A 664 672 graphene TRIVIAL 23224942 A 77 91 graphene oxide SYSTEMATIC 23224942 T 55 75 epoxy graphene oxide SYSTEMATIC 23225075 A 585 594 manganese SYSTEMATIC 23225075 A 596 605 aluminium SYSTEMATIC 23225075 A 607 614 cadmium SYSTEMATIC 23225075 A 616 622 cobalt SYSTEMATIC 23225075 A 624 630 copper SYSTEMATIC 23225075 A 632 636 zinc SYSTEMATIC 23225075 A 644 652 vanadium SYSTEMATIC 23225075 A 657 664 uranium SYSTEMATIC 23225241 A 1113 1124 cholesterol TRIVIAL 23225241 A 112 127 triacylglycerol FAMILY 23225241 A 1149 1162 biliary acids FAMILY 23225241 A 129 132 TAG ABBREVIATION 23225241 A 1319 1322 TAG ABBREVIATION 23225241 A 138 149 cholesterol TRIVIAL 23225241 A 1505 1516 cholesterol TRIVIAL 23225241 A 41 50 estrogens FAMILY 23225241 A 442 445 TAG ABBREVIATION 23225241 A 591 594 TAG ABBREVIATION 23225241 A 909 920 cholesterol TRIVIAL 23225241 A 992 1003 cholesterol TRIVIAL 23225241 T 39 50 Cholesterol TRIVIAL 23225365 A 1032 1035 MTT ABBREVIATION 23225365 A 1222 1233 resveratrol TRIVIAL 23225365 A 211 222 resveratrol TRIVIAL 23225365 A 477 488 resveratrol TRIVIAL 23225365 A 65 76 resveratrol TRIVIAL 23225365 A 764 775 Resveratrol TRIVIAL 23225365 A 795 797 NO FORMULA 23225365 A 837 839 NO FORMULA 23225365 A 863 883 sodium nitroprusside SYSTEMATIC 23225365 A 926 937 resveratrol TRIVIAL 23225365 T 37 48 resveratrol TRIVIAL 23225366 A 11 27 9,19-cycloartane SYSTEMATIC 23225366 A 28 39 triterpenes FAMILY 23225366 A 366 375 cimigenol TRIVIAL 23225366 A 518 527 cimigenol TRIVIAL 23225366 A 736 745 cimigenol TRIVIAL 23225366 T 10 21 cycloartane TRIVIAL 23225366 T 22 33 triterpenes FAMILY 23225536 A 1018 1022 PAHs ABBREVIATION 23225536 A 1208 1211 GSH ABBREVIATION 23225536 A 204 236 polycyclic aromatic hydrocarbons FAMILY 23225536 A 238 242 PAHs ABBREVIATION 23225536 A 364 368 PAHs ABBREVIATION 23225536 A 369 381 phenanthrene SYSTEMATIC 23225536 A 383 391 fluorene SYSTEMATIC 23225536 A 393 405 fluoranthene SYSTEMATIC 23225536 A 407 413 pyrene SYSTEMATIC 23225536 A 419 433 benzo[a]pyrene SYSTEMATIC 23225536 A 499 505 Cd(2+) FORMULA 23225536 A 528 534 Cu(2+) FORMULA 23225536 A 557 563 Zn(2+) FORMULA 23225536 A 591 597 Ni(2+) FORMULA 23225536 A 645 658 chlorophyll a TRIVIAL 23225536 A 728 732 PAHs ABBREVIATION 23225536 A 855 866 glutathione TRIVIAL 23225536 A 868 871 GSH ABBREVIATION 23225536 A 895 905 superoxide TRIVIAL 23225536 A 967 971 PAHs ABBREVIATION 23225536 T 21 53 polycyclic aromatic hydrocarbons FAMILY 23225542 A 1156 1159 ICG ABBREVIATION 23225542 A 1339 1342 ICG ABBREVIATION 23225542 A 249 266 indocyanine green TRIVIAL 23225542 A 268 271 ICG ABBREVIATION 23225542 A 435 444 Fe(3)O(4) FORMULA 23225542 A 646 676 poly(allylamine hydrochloride) SYSTEMATIC 23225542 A 678 681 PAH ABBREVIATION 23225542 T 35 40 Fe3O4 FORMULA 23225638 A 1002 1038 1-anilinonaphthalene-8-sulfonic acid SYSTEMATIC 23225638 A 140 163 2-azido-1,3-propanediol SYSTEMATIC 23225638 A 165 179 azido glycerol SYSTEMATIC 23225638 A 185 204 polyethylene glycol SYSTEMATIC 23225638 A 206 209 PEG ABBREVIATION 23225638 A 215 227 diethylester SYSTEMATIC 23225638 A 390 403 polyglycerols FAMILY 23225638 A 420 429 octadecyl SYSTEMATIC 23225638 A 991 997 pyrene SYSTEMATIC 23225671 A 149 155 purine TRIVIAL 23225671 A 156 162 purine TRIVIAL 23225671 A 74 87 nucleic acids FAMILY 23225764 A 100 109 L-lysines FAMILY 23225764 A 58 77 poly(methacrylate)s FAMILY 23225764 T 54 73 poly(methacrylate)s FAMILY 23225764 T 96 105 L-lysines FAMILY 23225770 A 244 251 genipin TRIVIAL 23225770 T 86 93 genipin TRIVIAL 23225780 A 24 44 N-Cyano sulfoximines FAMILY 23225780 T 0 20 N-cyano sulfoximines FAMILY 23227887 A 1392 1395 FDV ABBREVIATION 23227887 A 1618 1621 FDV ABBREVIATION 23227887 A 322 325 FDV ABBREVIATION 23227887 A 38 49 Fosdevirine TRIVIAL 23227887 A 458 461 FDV ABBREVIATION 23227887 A 51 54 FDV ABBREVIATION 23227887 A 68 78 nucleoside FAMILY 23227887 A 736 739 FDV ABBREVIATION 23227887 A 809 817 cysteine TRIVIAL 23227887 A 865 876 glutathione TRIVIAL 23227887 A 878 881 GSH ABBREVIATION 23227887 A 907 933 trans-phenyl acrylonitrile SYSTEMATIC 23227887 A 944 947 FDV ABBREVIATION 23227887 T 53 64 Fosdevirine TRIVIAL 23227887 T 66 76 GSK2248761 IDENTIFIER 23227887 T 85 95 nucleoside FAMILY 23228028 A 1296 1305 In(2)O(3) FORMULA 23228028 A 17 26 In(2)O(3) FORMULA 23228028 A 199 208 In(2)O(3) FORMULA 23228028 A 397 406 In(2)O(3) FORMULA 23228028 A 479 481 Mg FORMULA 23228028 A 483 485 Al FORMULA 23228028 A 491 493 Ga FORMULA 23228028 A 616 618 Mg FORMULA 23228028 A 620 622 Ga FORMULA 23228028 A 628 630 Al FORMULA 23228028 A 960 962 Mg FORMULA 23228028 A 969 978 In(2)O(3) FORMULA 23228028 T 50 55 In2O3 FORMULA 23228193 A 33 45 denbinobin B TRIVIAL 23228193 A 6 25 phenanthrenequinone SYSTEMATIC 23228193 A 77 90 phenanthrenes FAMILY 23228193 T 20 39 phenanthrenequinone SYSTEMATIC 23228469 A 18 120 3,5-bis(4-chlorobenzylidene)-1-[4-{2-(4-morpholinyl)ethoxy}phenyl-carbonyl]-4-piperidone hydrochloride SYSTEMATIC 23228469 A 358 369 glutathione TRIVIAL 23228471 A 151 160 chalcones FAMILY 23228471 A 162 179 thiosemicarbazide SYSTEMATIC 23228471 A 18 80 2-(3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles FAMILY 23228471 A 184 200 phenacyl bromide FAMILY 23228471 A 379 382 HCl FORMULA 23228471 A 386 390 EtOH FORMULA 23228471 T 51 71 thiazolyl-pyrazoline FAMILY 23228475 A 0 10 Cyprodinil TRIVIAL 23228475 A 1038 1048 Cyprodinil TRIVIAL 23228475 A 1058 1071 dexamethasone TRIVIAL 23228475 A 1165 1178 dexamethasone TRIVIAL 23228475 A 1340 1343 BaP ABBREVIATION 23228475 A 1345 1349 TCDD ABBREVIATION 23228475 A 1377 1387 cyprodinil TRIVIAL 23228475 A 155 169 Benzo[a]pyrene SYSTEMATIC 23228475 A 1568 1578 cyprodinil TRIVIAL 23228475 A 1591 1594 BaP ABBREVIATION 23228475 A 16 30 pyrimidinamine TRIVIAL 23228475 A 171 174 BaP ABBREVIATION 23228475 A 180 215 2,3,7,8-tetrachlorodibenzo-p-dioxin SYSTEMATIC 23228475 A 217 221 TCDD ABBREVIATION 23228475 A 280 296 aryl hydrocarbon FAMILY 23228475 A 347 357 cyprodinil TRIVIAL 23228475 A 391 394 BaP ABBREVIATION 23228475 A 399 403 TCDD ABBREVIATION 23228475 A 427 437 cyprodinil TRIVIAL 23228475 A 524 540 aryl hydrocarbon FAMILY 23228475 A 566 576 Cyprodinil TRIVIAL 23228475 A 838 848 Cyprodinil TRIVIAL 23228475 A 981 994 Dexamethasone TRIVIAL 23228475 T 0 10 Cyprodinil TRIVIAL 23228475 T 30 46 aryl hydrocarbon FAMILY 23228696 A 0 9 Metformin TRIVIAL 23228696 A 1046 1056 paclitaxel TRIVIAL 23228696 A 1118 1127 metformin TRIVIAL 23228696 A 1162 1172 paclitaxel TRIVIAL 23228696 A 1266 1276 paclitaxel TRIVIAL 23228696 A 1417 1426 metformin TRIVIAL 23228696 A 1431 1441 paclitaxel TRIVIAL 23228696 A 1567 1576 metformin TRIVIAL 23228696 A 1590 1600 paclitaxel TRIVIAL 23228696 A 186 196 paclitaxel TRIVIAL 23228696 A 198 203 Taxol TRIVIAL 23228696 A 509 517 platinum SYSTEMATIC 23228696 A 566 576 paclitaxel TRIVIAL 23228696 A 767 777 paclitaxel TRIVIAL 23228696 A 910 918 SB202190 IDENTIFIER 23228696 T 0 9 Metformin TRIVIAL 23228696 T 194 204 paclitaxel TRIVIAL 23228697 A 0 8 Orlistat TRIVIAL 23228697 A 1001 1009 orlistat TRIVIAL 23228697 A 1047 1050 PPD ABBREVIATION 23228697 A 1382 1390 orlistat TRIVIAL 23228697 A 1405 1413 orlistat TRIVIAL 23228697 A 426 434 orlistat TRIVIAL 23228697 A 678 694 pentyl carbamate SYSTEMATIC 23228697 A 698 721 p-aminobenzyl carbamate SYSTEMATIC 23228697 A 725 737 doxazolidine TRIVIAL 23228697 A 739 742 PPD ABBREVIATION 23228697 A 748 758 irinotecan TRIVIAL 23228697 A 913 921 orlistat TRIVIAL 23228697 T 73 81 orlistat TRIVIAL 23229055 A 158 162 (1)H FORMULA 23229055 A 168 173 (13)C FORMULA 23229055 A 21 52 6-carbethoxy-2-cyclohexen-1-one SYSTEMATIC 23229055 A 295 308 Cyclohexenone SYSTEMATIC 23229055 A 400 409 chalcones FAMILY 23229055 A 428 436 Indazole SYSTEMATIC 23229055 A 57 72 2H-indazol-3-ol SYSTEMATIC 23229055 A 6 14 chalcone FAMILY 23229055 T 126 141 2H-indazol-3-ol SYSTEMATIC 23229055 T 75 83 chalcone FAMILY 23229055 T 90 121 6-carbethoxy-2-cyclohexen-1-one SYSTEMATIC 23229511 A 1086 1092 17-AAG SYSTEMATIC 23229511 A 1212 1218 17-AAG SYSTEMATIC 23229511 A 1233 1239 17-AAG SYSTEMATIC 23229511 A 1369 1376 NAD(P)H ABBREVIATION 23229511 A 1377 1384 quinone FAMILY 23229511 A 1480 1486 17-AAG SYSTEMATIC 23229511 A 1579 1585 17-AAG SYSTEMATIC 23229511 A 1702 1708 17-AAG SYSTEMATIC 23229511 A 1751 1757 17-AAG SYSTEMATIC 23229511 A 183 221 17-Allylamino-17-demethoxygeldanamycin SYSTEMATIC 23229511 A 223 229 17-AAG SYSTEMATIC 23229511 A 26 42 aryl hydrocarbon FAMILY 23229511 A 379 385 17-AAG SYSTEMATIC 23229511 A 676 682 17-AAG SYSTEMATIC 23229511 T 0 16 Aryl hydrocarbon FAMILY 23229511 T 41 79 17-Allylamino-17-demethoxygeldanamycin SYSTEMATIC 23229539 A 1073 1077 iron SYSTEMATIC 23229539 A 1199 1214 malondialdehyde TRIVIAL 23229539 A 1248 1258 superoxide TRIVIAL 23229539 A 207 211 iron SYSTEMATIC 23229539 A 816 820 iron SYSTEMATIC 23229539 A 882 886 iron SYSTEMATIC 23230131 A 0 11 Gemcitabine TRIVIAL 23230131 A 1086 1090 dFdU ABBREVIATION 23230131 A 1205 1209 dFdC ABBREVIATION 23230131 A 1292 1303 gemcitabine TRIVIAL 23230131 A 13 17 dFdC ABBREVIATION 23230131 A 1365 1369 dFdC ABBREVIATION 23230131 A 1409 1413 dFdC ABBREVIATION 23230131 A 19 46 2',2'-difluorodeoxycytidine SYSTEMATIC 23230131 A 485 495 cytarabine TRIVIAL 23230131 A 497 502 Ara-C ABBREVIATION 23230131 A 505 509 dFdC ABBREVIATION 23230131 A 530 556 2',2'-difluorodeoxyuridine SYSTEMATIC 23230131 A 558 562 dFdU ABBREVIATION 23230131 A 637 642 Ara-C ABBREVIATION 23230131 A 647 651 dFdC ABBREVIATION 23230131 A 66 74 cytidine TRIVIAL 23230131 A 746 751 Ara-C ABBREVIATION 23230131 A 829 834 Ara-C ABBREVIATION 23230131 A 839 843 dFdC ABBREVIATION 23230131 A 95 108 deoxycytidine TRIVIAL 23230131 A 979 983 dFdC ABBREVIATION 23230131 T 110 123 deoxycytidine TRIVIAL 23230131 T 20 31 gemcitabine TRIVIAL 23230131 T 87 95 cytidine TRIVIAL 23230274 A 1080 1088 arsenite SYSTEMATIC 23230274 A 376 384 arsenite SYSTEMATIC 23230274 A 686 692 oxygen SYSTEMATIC 23230274 T 55 61 oxygen SYSTEMATIC 23230281 A 1178 1191 peroxynitrite SYSTEMATIC 23230281 A 1416 1429 peroxynitrite SYSTEMATIC 23230281 A 868 881 peroxynitrite SYSTEMATIC 23231350 A 1243 1255 sulfonamides FAMILY 23231350 A 650 664 methyl mercury SYSTEMATIC 23231439 A 112 121 dipeptide FAMILY 23231439 A 256 261 ML188 IDENTIFIER 23231439 A 271 370 (R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide SYSTEMATIC 23231439 A 380 393 CID: 46897844 IDENTIFIER 23231439 T 130 135 ML188 IDENTIFIER 23231439 T 70 128 N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides FAMILY 23231457 A 130 143 poly-L-lysine SYSTEMATIC 23231809 A 14 22 dopamine TRIVIAL 23231809 A 1657 1665 dopamine TRIVIAL 23231809 T 0 8 Dopamine TRIVIAL 23231809 T 112 120 dopamine TRIVIAL 23231967 A 164 173 adenosine TRIVIAL 23231967 A 25 38 methoxyphenyl SYSTEMATIC 23231967 A 339 348 adenosine TRIVIAL 23231967 A 68 105 N-(2,6-diarylpyrimidin-4-yl)acetamide FAMILY 23231967 T 21 30 adenosine TRIVIAL 23231967 T 58 69 methoxyaryl FAMILY 23231967 T 90 127 N-(2,6-diarylpyrimidin-4-yl)acetamide FAMILY 23232056 A 47 66 diphenylpropanamide FAMILY 23232056 T 15 21 amides FAMILY 23232059 A 1054 1066 cynaropicrin TRIVIAL 23232059 A 1215 1227 cynaropicrin TRIVIAL 23232059 A 881 893 cynaropicrin TRIVIAL 23232059 A 906 927 sesquiterpene lactone FAMILY 23232059 T 0 12 Cynaropicrin TRIVIAL 23232150 A 101 109 steroids FAMILY 23232150 A 1483 1490 steroid FAMILY 23232150 A 171 180 estradiol TRIVIAL 23232150 A 518 527 estradiol TRIVIAL 23232150 A 557 566 estradiol TRIVIAL 23232150 A 791 799 glycerol TRIVIAL 23232150 A 823 830 formate SYSTEMATIC 23232150 A 868 888 histidinol-phosphate SYSTEMATIC 23232150 A 995 1002 alcohol FAMILY 23232150 T 39 48 estradiol TRIVIAL 23232150 T 96 103 steroid FAMILY 23232333 A 1017 1031 corticosterone TRIVIAL 23232333 A 1190 1204 corticosterone TRIVIAL 23232333 A 1353 1367 corticosterone TRIVIAL 23232333 A 1490 1504 corticosterone TRIVIAL 23232333 A 1600 1614 corticosterone TRIVIAL 23232333 A 289 303 corticosterone TRIVIAL 23232333 A 50 64 corticosterone TRIVIAL 23232333 A 512 526 corticosterone TRIVIAL 23232333 A 746 760 corticosterone TRIVIAL 23232333 A 820 834 corticosterone TRIVIAL 23232333 A 956 970 corticosterone TRIVIAL 23232333 T 44 58 corticosterone TRIVIAL 23232461 A 1101 1110 organotin FAMILY 23232461 A 1335 1345 organotins FAMILY 23232461 A 159 168 organotin FAMILY 23232461 A 28 37 organotin FAMILY 23232461 A 379 388 organotin FAMILY 23232461 A 607 617 organotins FAMILY 23232461 A 692 701 Organotin FAMILY 23232461 A 912 914 Na FORMULA 23232461 A 915 916 K FORMULA 23232461 T 12 21 organotin FAMILY 23232866 A 1017 1023 Fluo-4 ABBREVIATION 23232866 A 1181 1188 calcium SYSTEMATIC 23232866 A 533 555 poly(dimethylsiloxane) SYSTEMATIC 23232866 A 557 561 PDMS ABBREVIATION 23232866 A 994 1001 calcium SYSTEMATIC 23232941 A 440 445 vinyl FAMILY 23232941 A 447 450 C=C FORMULA 23232941 A 460 465 cyano FAMILY 23232941 A 467 470 C≡N FORMULA 23232941 A 66 79 acrylonitrile SYSTEMATIC 23232941 A 714 717 C=C FORMULA 23232941 A 726 729 C≡N FORMULA 23232941 A 94 101 Cu(100) FORMULA 23232941 T 100 107 Cu(100) FORMULA 23232941 T 74 87 acrylonitrile SYSTEMATIC 23233034 A 1034 1041 citrate FAMILY 23233034 A 1056 1062 silver SYSTEMATIC 23233034 A 1299 1306 citrate FAMILY 23233034 A 490 497 citrate FAMILY 23233034 A 515 521 silver SYSTEMATIC 23233034 A 819 826 citrate FAMILY 23233034 A 841 847 silver SYSTEMATIC 23233456 A 0 25 Dendritic poly(L-lysines) SYSTEMATIC 23233456 A 176 179 DGL ABBREVIATION 23233456 A 27 30 DGL ABBREVIATION 23233456 A 407 410 DGL ABBREVIATION 23233456 A 467 473 jetPEI TRIVIAL 23233456 A 569 572 DGL ABBREVIATION 23233456 A 701 704 DGL ABBREVIATION 23233456 T 46 61 poly(L-lysines) SYSTEMATIC 23234246 A 217 235 benzenesulfonamide SYSTEMATIC 23234246 A 315 323 M(CO)(3) FAMILY 23234246 A 334 336 Re FORMULA 23234246 A 340 347 (99m)Tc FORMULA 23234246 A 417 443 benzenesulfonamide rhenium SYSTEMATIC 23234246 A 617 639 technetium tricarbonyl SYSTEMATIC 23234246 A 641 660 {(99m)Tc(CO)(3)}(+) FORMULA 23234246 A 677 695 (99m)Tc(CO)(3)}(+) FORMULA 23234246 A 740 754 (99m)Tc(CO)(3) FORMULA 23234246 A 902 921 {(99m)Tc(CO)(3)}(+) FORMULA 23234246 T 27 29 Re FORMULA 23234246 T 30 35 99mTc FORMULA 23234246 T 44 62 benzenesulfonamide SYSTEMATIC 23234313 A 433 454 poly(propylene-imine) SYSTEMATIC 23234313 T 31 52 poly(propylene imine) SYSTEMATIC 23234537 A 126 132 carbon SYSTEMATIC 23234537 A 506 512 carbon SYSTEMATIC 23234537 A 56 78 poly(3-hexylthiophene) SYSTEMATIC 23234537 A 657 661 P3HT ABBREVIATION 23234537 A 732 738 carbon SYSTEMATIC 23234537 A 83 87 P3HT ABBREVIATION 23234537 T 7 13 carbon SYSTEMATIC 23234607 A 10 24 2-oxoglutarate SYSTEMATIC 23234607 A 211 214 2OG ABBREVIATION 23234607 A 26 29 2OG ABBREVIATION 23234607 A 315 318 2OG ABBREVIATION 23234607 A 494 497 2OG ABBREVIATION 23234607 T 41 55 2-oxoglutarate SYSTEMATIC 23234812 A 0 18 Strontium Ranelate SYSTEMATIC 23234812 A 1021 1023 NO FORMULA 23234812 A 1035 1041 PGE(2) ABBREVIATION 23234812 A 1093 1098 SrRan FORMULA 23234812 A 1302 1307 SrRan FORMULA 23234812 A 1413 1418 SrRan FORMULA 23234812 A 1513 1518 SrRan FORMULA 23234812 A 1669 1674 SrRan FORMULA 23234812 A 20 25 SrRan FORMULA 23234812 A 275 280 SrRan FORMULA 23234812 A 441 446 SrRan FORMULA 23234812 A 561 573 Nitric oxide SYSTEMATIC 23234812 A 575 577 NO FORMULA 23234812 A 583 601 prostaglandin E(2) TRIVIAL 23234812 A 603 609 PGE(2) ABBREVIATION 23234812 A 874 879 SrRan FORMULA 23234812 A 895 897 NO FORMULA 23234812 A 902 908 PGE(2) ABBREVIATION 23234812 A 958 960 NO FORMULA 23234812 A 972 978 PGE(2) ABBREVIATION 23234812 T 0 18 Strontium Ranelate SYSTEMATIC 23234855 A 111 136 [RuCl(HL)(PPh(3))(2)(CO)] FORMULA 23234855 A 145 171 [RuCl(HL)(AsPh(3))(2)(CO)] FORMULA 23234855 A 182 220 2,2'-bipyridine-4,4'-dicarboxylic acid SYSTEMATIC 23234855 A 26 50 [RuHCl(bpy)(PPh(3))(CO)] FORMULA 23234855 A 56 81 [RuHCl(bpy)(AsPh(3))(CO)] FORMULA 23234855 A 791 795 COOH FORMULA 23234855 A 799 809 bipyridine SYSTEMATIC 23234855 A 843 847 COOH FORMULA 23234855 A 87 90 bpy ABBREVIATION 23234855 A 9 15 Ru(II) FORMULA 23234855 A 93 108 2,2'-bipyridine SYSTEMATIC 23234855 T 13 28 carboxylic acid SYSTEMATIC 23234855 T 48 84 ruthenium (II) polypyridyl complexes FAMILY 23235151 A 1553 1554 C FORMULA 23235151 A 240 249 histamine TRIVIAL 23235151 A 421 428 sulfate SYSTEMATIC 23235151 A 598 599 N FORMULA 23235151 A 668 669 C FORMULA 23235158 A 1008 1016 tyrosine TRIVIAL 23235158 A 1131 1134 Tyr FORMULA 23235158 A 1300 1304 heme FAMILY 23235158 A 377 385 chlorite SYSTEMATIC 23235158 A 487 491 heme FAMILY 23235158 A 513 522 aspartate TRIVIAL 23235158 A 532 535 Asp FORMULA 23235158 A 591 608 hydrogen peroxide SYSTEMATIC 23235158 A 620 624 heme FAMILY 23235158 A 625 629 iron SYSTEMATIC 23235158 A 65 69 heme FAMILY 23235158 A 838 841 Asp FORMULA 23235158 A 905 909 heme FAMILY 23235158 A 96 113 hydrogen peroxide SYSTEMATIC 23235158 A 984 995 amino acids FAMILY 23235435 A 109 126 triazacyclononane SYSTEMATIC 23235435 A 273 279 Co(ii) FORMULA 23235435 A 441 448 Cr(iii) FORMULA 23235435 A 453 459 Co(ii) FORMULA 23235435 A 75 91 transition metal FAMILY 23235435 T 126 142 transition metal FAMILY 23235435 T 69 97 bis(1,4,7-triazacyclononane) SYSTEMATIC 23235742 A 284 286 Pt FORMULA 23235742 A 640 642 Pt FORMULA 23235742 A 71 73 Pt FORMULA 23235742 A 893 907 levulinic acid TRIVIAL 23235742 T 141 143 Pt FORMULA 23237482 A 560 564 GaAs FORMULA 23237482 A 575 577 As FORMULA 23237482 A 578 582 GaAs FORMULA 23237482 T 31 35 GaAs FORMULA 23237546 A 485 492 glucose TRIVIAL 23237546 A 599 601 Au FORMULA 23237546 A 707 714 calcium SYSTEMATIC 23237590 A 27 33 silica TRIVIAL 23237828 A 1151 1164 cycloheximide TRIVIAL 23237828 A 1258 1271 cycloheximide TRIVIAL 23237828 A 201 214 cycloheximide TRIVIAL 23237828 A 305 318 cycloheximide TRIVIAL 23237828 A 407 420 actinomycin D TRIVIAL 23237828 A 431 444 cycloheximide TRIVIAL 23237828 A 510 523 cycloheximide TRIVIAL 23237828 A 559 572 cycloheximide TRIVIAL 23237828 A 710 715 U0126 IDENTIFIER 23237828 A 720 727 PD98059 IDENTIFIER 23237828 A 755 763 SP600125 IDENTIFIER 23237828 A 765 770 U0126 IDENTIFIER 23237828 A 775 782 PD98059 IDENTIFIER 23237828 A 806 819 cycloheximide TRIVIAL 23237828 A 859 867 SP600125 IDENTIFIER 23237828 A 887 900 cycloheximide TRIVIAL 23237828 A 919 932 cycloheximide TRIVIAL 23237828 T 0 13 Cycloheximide TRIVIAL 23237939 A 1208 1214 NU7441 IDENTIFIER 23237939 A 1219 1228 cisplatin TRIVIAL 23237939 A 730 736 NU7441 IDENTIFIER 23237939 A 737 746 cisplatin TRIVIAL 23237974 A 177 191 schisandrin A1 TRIVIAL 23237974 A 222 227 epoxy SYSTEMATIC 23237974 A 30 36 lignan FAMILY 23237974 A 316 330 schisandrin A1 TRIVIAL 23237974 A 339 354 schisantherin A TRIVIAL 23237974 A 44 58 schisandrin A1 TRIVIAL 23237974 A 502 517 schisantherin A TRIVIAL 23237974 A 542 565 6,7-secoschisantherol A SYSTEMATIC 23237974 A 6 24 dibenzocyclooctene SYSTEMATIC 23237974 A 610 617 lignans FAMILY 23237974 A 636 651 schisantherin A TRIVIAL 23237974 T 0 7 Lignans FAMILY 23237974 T 69 84 schisantherin A TRIVIAL 23238233 A 108 129 chikusetsusaponin LM5 TRIVIAL 23238233 A 135 156 chikusetsusaponin LM6 TRIVIAL 23238233 A 179 200 triterpenoid saponins FAMILY 23238233 A 209 224 ginsenoside Rb3 TRIVIAL 23238233 A 230 244 ginsenoside Rc TRIVIAL 23238233 A 24 45 triterpenoid saponins FAMILY 23238233 A 250 264 ginsenoside Rd TRIVIAL 23238233 A 270 284 ginsenoside Re TRIVIAL 23238233 A 290 305 ginsenoside Rg1 TRIVIAL 23238233 A 311 325 ginsenoside F3 TRIVIAL 23238233 A 332 346 ginsenoside F5 TRIVIAL 23238233 A 353 367 ginsenoside F6 TRIVIAL 23238233 A 374 395 chikusetsusaponin IVa TRIVIAL 23238233 A 402 421 chikusetsusaponin V TRIVIAL 23238233 A 428 448 chikusetsusaponin L5 TRIVIAL 23238233 A 455 476 chikusetsusaponin L9a TRIVIAL 23238233 A 483 505 chikusetsusaponin L9bc TRIVIAL 23238233 A 512 533 chikusetsusaponin L10 TRIVIAL 23238233 A 54 75 chikusetsusaponin LM3 TRIVIAL 23238233 A 540 561 chikusetsusaponin FK2 TRIVIAL 23238233 A 568 589 chikusetsusaponin FK6 TRIVIAL 23238233 A 596 617 chikusetsusaponin FK7 TRIVIAL 23238233 A 624 645 chikusetsusaponin FT1 TRIVIAL 23238233 A 652 673 chikusetsusaponin LM1 TRIVIAL 23238233 A 684 705 chikusetsusaponin LM2 TRIVIAL 23238233 A 81 102 chikusetsusaponin LM4 TRIVIAL 23238233 A 836 854 chikusetsusaponins FAMILY 23238233 A 9 18 dammarane TRIVIAL 23238233 T 9 30 triterpenoid saponins FAMILY 23238235 A 1025 1033 acrolein TRIVIAL 23238235 A 1035 1049 crotonaldehyde TRIVIAL 23238235 A 1051 1068 4-hydroxy-hexenal SYSTEMATIC 23238235 A 1070 1075 4-HHE SYSTEMATIC 23238235 A 1081 1096 4-oxo-2-nonenal SYSTEMATIC 23238235 A 1098 1103 4-ONE SYSTEMATIC 23238236 A 556 563 Sterols FAMILY 23238236 A 565 576 triterpenes FAMILY 23238236 A 593 604 fatty acids FAMILY 23238236 A 728 735 DPPH(·) ABBREVIATION 23238236 A 737 747 superoxide TRIVIAL 23238236 A 752 764 nitric oxide SYSTEMATIC 23238352 A 0 10 Zinc oxide SYSTEMATIC 23238352 A 1300 1305 H(2)S FORMULA 23238352 A 1310 1315 H(2)O FORMULA 23238352 A 1354 1357 ZnO FORMULA 23238352 A 1415 1420 H(2)S FORMULA 23238352 A 145 148 ZnO FORMULA 23238352 A 1634 1640 oxygen SYSTEMATIC 23238352 A 1790 1793 ZnO FORMULA 23238352 A 1794 1797 ZnS FORMULA 23238352 A 1943 1946 ZnO FORMULA 23238352 A 1947 1950 ZnS FORMULA 23238352 A 2325 2328 ZnO FORMULA 23238352 A 2329 2332 ZnS FORMULA 23238352 A 303 306 ZnO FORMULA 23238352 A 556 559 ZnS FORMULA 23238352 A 609 617 wurtzite TRIVIAL 23238352 A 693 696 ZnS FORMULA 23238352 A 712 716 zinc SYSTEMATIC 23238352 A 721 727 oxygen SYSTEMATIC 23238352 A 747 750 ZnO FORMULA 23238352 A 751 754 ZnS FORMULA 23238352 A 796 799 ZnS FORMULA 23238352 A 826 829 ZnO FORMULA 23238352 A 845 850 H(2)S FORMULA 23238352 A 984 987 ZnS FORMULA 23238352 T 21 24 ZnO FORMULA 23238352 T 86 89 ZnS FORMULA 23238425 A 1031 1037 SO(3)H FORMULA 23238425 A 1081 1087 Nafion TRIVIAL 23238425 A 1097 1099 Si FORMULA 23238425 A 119 125 SO(3)H FORMULA 23238425 A 1192 1198 SO(3)H FORMULA 23238425 A 1244 1250 oxygen SYSTEMATIC 23238425 A 1289 1295 SO(3)H FORMULA 23238425 A 13 19 Nafion TRIVIAL 23238425 A 1333 1339 Nafion TRIVIAL 23238425 A 1357 1359 Pt FORMULA 23238425 A 1360 1362 Si FORMULA 23238425 A 1449 1455 SO(3)H FORMULA 23238425 A 1524 1532 fluorine SYSTEMATIC 23238425 A 160 167 silicon SYSTEMATIC 23238425 A 1649 1655 Nafion TRIVIAL 23238425 A 169 171 Si FORMULA 23238425 A 1700 1706 Nafion TRIVIAL 23238425 A 174 187 glassy carbon TRIVIAL 23238425 A 197 205 platinum SYSTEMATIC 23238425 A 206 213 silicon SYSTEMATIC 23238425 A 215 217 Pt FORMULA 23238425 A 218 220 Si FORMULA 23238425 A 594 600 Nafion TRIVIAL 23238425 A 611 613 Si FORMULA 23238425 A 680 682 Si FORMULA 23238425 A 693 699 oxygen SYSTEMATIC 23238425 A 734 740 SO(3)H FORMULA 23238425 A 879 885 Nafion TRIVIAL 23238425 A 895 897 Si FORMULA 23238425 T 33 37 SO3H FORMULA 23238425 T 83 89 Nafion TRIVIAL 23238611 A 110 119 magnesium SYSTEMATIC 23238611 A 343 352 magnesium SYSTEMATIC 23238611 A 551 560 magnesium SYSTEMATIC 23238611 A 720 729 magnesium SYSTEMATIC 23238611 T 18 27 magnesium SYSTEMATIC 23238657 A 1099 1106 nitrite SYSTEMATIC 23238657 A 1118 1125 nitrate SYSTEMATIC 23238657 A 1179 1203 N(ε)-carboxymethyllisine SYSTEMATIC 23238657 A 1500 1512 nitric oxide SYSTEMATIC 23238662 A 1252 1259 glucose TRIVIAL 23238662 A 1320 1327 glucose TRIVIAL 23238662 A 204 211 glucose TRIVIAL 23238662 A 550 557 glucose TRIVIAL 23238662 A 903 910 glucose TRIVIAL 23238662 A 931 938 glucose TRIVIAL 23238662 A 972 979 glucose TRIVIAL 23238783 A 1626 1635 bupropion TRIVIAL 23238783 A 1641 1650 bupropion TRIVIAL 23238783 A 1850 1859 bupropion TRIVIAL 23238783 A 403 412 bupropion TRIVIAL 23238783 A 414 427 Wellbutrin SR TRIVIAL 23238783 A 548 557 bupropion TRIVIAL 23238783 A 804 813 bupropion TRIVIAL 23238783 A 823 839 hydroxybupropion SYSTEMATIC 23238783 T 56 65 bupropion TRIVIAL 23238991 A 1154 1158 CFSE ABBREVIATION 23238991 A 354 360 silica TRIVIAL 23238991 A 763 766 MTT ABBREVIATION 23238991 T 44 50 silica TRIVIAL 23239015 A 167 181 graphene oxide SYSTEMATIC 23239015 A 218 224 Pc(8+) FORMULA 23239015 A 38 80 poly-ortho-substituted tetraarylporphycene FAMILY 23239015 A 82 88 Pc(8+) FORMULA 23239015 T 0 47 Poly-Ortho-Functionalizable Tetraarylporphycene FAMILY 23239015 T 142 156 Graphene Oxide SYSTEMATIC 23239015 T 70 82 Octacationic FAMILY 23239601 A 199 207 hydrogen SYSTEMATIC 23239601 A 315 323 hydrogen SYSTEMATIC 23239601 T 63 71 hydrogen SYSTEMATIC 23239639 A 105 109 HPMA ABBREVIATION 23239639 A 184 193 maleimide SYSTEMATIC 23239639 A 209 249 poly(N-(2-hydroxypropyl)-methacrylamide) SYSTEMATIC 23239639 A 251 260 poly-HPMA ABBREVIATION 23239639 A 363 393 pentafluorophenyl methacrylate SYSTEMATIC 23239639 A 436 441 ester FAMILY 23239639 A 719 722 SDS ABBREVIATION 23239639 T 13 22 maleimide SYSTEMATIC 23239639 T 38 42 HPMA ABBREVIATION 23239825 A 311 319 carboxyl SYSTEMATIC 23239825 A 398 404 serine TRIVIAL 23239825 A 558 567 threonine TRIVIAL 23240655 A 416 422 MoS(2) FORMULA 23240655 A 510 518 scandium SYSTEMATIC 23240655 A 554 560 MoS(2) FORMULA 23240655 A 596 605 Al(2)O(3) FORMULA 23240655 A 83 91 graphene TRIVIAL 23240655 T 28 32 MoS2 FORMULA 23240655 T 50 58 scandium SYSTEMATIC 23240993 A 1057 1071 Me(2)DABCO(2+) FORMULA 23240993 A 1105 1107 Ar FORMULA 23240993 A 1108 1113 Ar(l) FORMULA 23240993 A 1132 1139 (129)Xe FORMULA 23240993 A 1241 1248 (129)Xe FORMULA 23240993 A 1341 1348 (129)Xe FORMULA 23240993 A 155 169 Me(2)DABCO(2+) FORMULA 23240993 A 1711 1718 (129)Xe FORMULA 23240993 A 1777 1779 Xe FORMULA 23240993 A 1780 1785 Xe(l) FORMULA 23240993 A 1932 1939 (129)Xe FORMULA 23240993 A 390 397 (129)Xe FORMULA 23240993 A 449 456 (129)Xe FORMULA 23240993 A 466 468 Ar FORMULA 23240993 A 469 474 Ar(l) FORMULA 23240993 A 479 481 Xe FORMULA 23240993 A 482 487 Xe(l) FORMULA 23240993 A 789 793 (1)H FORMULA 23240993 A 795 800 (13)C FORMULA 23240993 A 802 807 (19)F FORMULA 23240993 A 813 819 (29)Si FORMULA 23240993 T 53 58 129Xe FORMULA 23240993 T 80 82 Xe FORMULA 23241030 A 31 66 9-diphenylthiophosphinoylanthracene SYSTEMATIC 23241354 A 105 113 tyrosine TRIVIAL 23241354 A 212 220 tyrosine TRIVIAL 23241354 A 399 407 tyrosine TRIVIAL 23241354 T 82 90 tyrosine TRIVIAL 23243659 A 108 114 nickel SYSTEMATIC 23243659 A 120 126 NH(4)F FORMULA 23243659 A 131 140 H(3)PO(4) FORMULA 23243659 A 19 28 Ni(OH)(2) FORMULA 23243659 A 29 35 NiF(2) FORMULA 23243659 A 450 456 nickel SYSTEMATIC 23243659 T 12 19 Ni(OH)2 FORMULA 23243659 T 20 24 NiF2 FORMULA 23243660 A 123 133 flavonoids FAMILY 23243660 A 134 144 naringenin TRIVIAL 23243660 A 1481 1484 O–H FORMULA 23243660 A 152 161 quercetin TRIVIAL 23243660 A 1652 1656 H(2) FORMULA 23243660 A 171 180 myricetin TRIVIAL 23243660 A 221 229 chromone TRIVIAL 23243660 A 238 245 flavone TRIVIAL 23243660 A 632 642 flavonoids FAMILY 23243660 T 46 56 flavonoids FAMILY 23244178 A 1108 1114 azides FAMILY 23244178 A 1181 1187 azides FAMILY 23244178 A 12 22 aryl azide FAMILY 23244178 A 1239 1252 primary amine FAMILY 23244178 A 1301 1323 oligo(ethylene glycol) SYSTEMATIC 23244178 A 1339 1344 amine SYSTEMATIC 23244178 A 157 171 aluminum oxide SYSTEMATIC 23244178 A 321 330 diazirine SYSTEMATIC 23244178 A 34 40 thiols FAMILY 23244178 A 346 356 aryl thiol FAMILY 23244178 A 45 61 phosphonic acids FAMILY 23244178 A 500 513 primary amine FAMILY 23244178 A 548 559 aryl azides FAMILY 23244178 A 573 582 diazirine SYSTEMATIC 23244178 A 595 609 primary amines FAMILY 23244178 A 649 655 azides FAMILY 23244178 A 841 851 aryl azide FAMILY 23244178 A 909 922 primary amine FAMILY 23244178 A 936 942 amines FAMILY 23244178 T 110 124 primary amines FAMILY 23244178 T 142 153 aryl azides FAMILY 23244178 T 166 180 aluminum oxide SYSTEMATIC 23244521 A 525 532 ethanol SYSTEMATIC 23245188 A 0 7 Silicon SYSTEMATIC 23245188 A 210 218 H(2)O(2) FORMULA 23245188 A 234 240 oxygen SYSTEMATIC 23245188 A 286 304 o-phenylenediamine SYSTEMATIC 23245188 A 306 309 OPD ABBREVIATION 23245188 A 351 359 H(2)O(2) FORMULA 23245188 A 377 379 Si FORMULA 23245188 A 380 381 H FORMULA 23245188 A 524 532 H(2)O(2) FORMULA 23245188 A 593 602 (Si-H)(2) FORMULA 23245188 A 606 607 O FORMULA 23245188 A 618 627 (Si-H)(2) FORMULA 23245188 T 58 65 silicon SYSTEMATIC 23245512 A 115 121 acetyl SYSTEMATIC 23245512 A 123 132 propionyl SYSTEMATIC 23245512 A 134 142 butanoyl SYSTEMATIC 23245512 A 144 153 pentanoyl SYSTEMATIC 23245512 A 155 162 valeryl SYSTEMATIC 23245512 A 167 183 3-methylbutanoyl SYSTEMATIC 23245512 A 18 39 glycopyranosyl azides FAMILY 23245512 A 185 195 isovaleryl TRIVIAL 23245512 A 197 202 ester FAMILY 23245512 A 272 293 glycopyranosyl azides FAMILY 23245512 A 300 306 copper SYSTEMATIC 23245512 A 317 322 azide SYSTEMATIC 23245512 A 323 329 alkyne FAMILY 23245512 A 482 486 acyl FAMILY 23245512 A 534 571 acetyl, propionyl and butanoyl esters MULTIPLE 23245512 A 642 669 mono-, di- and tri-acylated MULTIPLE 23245512 A 69 81 carbohydrate FAMILY 23245512 A 763 800 pentanoyl and 3-methylbutanoyl esters MULTIPLE 23245514 A 103 113 PBI-18-Man TRIVIAL 23245514 A 360 367 mannose TRIVIAL 23245514 A 447 454 mannose TRIVIAL 23245514 A 46 58 α-D-mannoses FAMILY 23245514 A 74 82 perylene SYSTEMATIC 23245514 T 13 30 perylene bisimide FAMILY 23245697 A 1096 1111 ribonucleotides FAMILY 23245697 A 1206 1221 ribonucleotides FAMILY 23245697 A 1262 1277 ribonucleotides FAMILY 23245697 A 1331 1346 ribonucleotides FAMILY 23245697 A 1407 1421 ribonucleotide FAMILY 23245697 A 1554 1568 ribonucleotide FAMILY 23245697 A 1724 1739 ribonucleotides FAMILY 23245697 A 486 501 ribonucleotides FAMILY 23245697 A 53 68 ribonucleotides FAMILY 23245697 A 548 558 nucleotide FAMILY 23245697 A 654 658 rNTP ABBREVIATION 23245697 A 682 687 dNTPs ABBREVIATION 23245697 A 802 817 ribonucleotides FAMILY 23245697 T 0 14 Ribonucleotide FAMILY 23246428 A 0 34 Ergosta-4,6,8(14),22-tetraen-3-one SYSTEMATIC 23246428 A 1143 1152 bile acid FAMILY 23246428 A 1274 1280 ergone TRIVIAL 23246428 A 36 42 ergone TRIVIAL 23246428 A 481 488 adenine TRIVIAL 23246428 A 519 553 ergosta-4,6,8(14),22-tetraen-3-one SYSTEMATIC 23246428 A 555 561 ergone TRIVIAL 23246428 A 689 696 adenine TRIVIAL 23246428 A 719 725 ergone TRIVIAL 23246428 T 133 167 ergosta-4,6,8(14),22-tetraen-3-one SYSTEMATIC 23246428 T 45 52 adenine TRIVIAL 23246436 A 538 539 C FORMULA 23246531 A 1042 1050 diazepam TRIVIAL 23246531 A 1070 1077 KNT-127 IDENTIFIER 23246531 A 1162 1169 ethanol SYSTEMATIC 23246531 A 1293 1300 KNT-127 IDENTIFIER 23246531 A 1406 1421 benzodiazepines FAMILY 23246531 A 187 194 KNT-127 IDENTIFIER 23246531 A 258 265 KNT-127 IDENTIFIER 23246531 A 349 356 KNT-127 IDENTIFIER 23246531 A 519 526 KNT-127 IDENTIFIER 23246531 A 56 61 SNC80 IDENTIFIER 23246531 A 609 617 diazepam TRIVIAL 23246531 A 639 653 benzodiazepine FAMILY 23246531 A 697 704 KNT-127 IDENTIFIER 23246531 A 759 770 naltrindole TRIVIAL 23246531 A 848 855 KNT-127 IDENTIFIER 23246531 T 148 163 benzodiazepines FAMILY 23246531 T 36 43 KNT-127 IDENTIFIER 23246700 A 0 10 Phthalates FAMILY 23246700 A 1084 1088 DEHP ABBREVIATION 23246700 A 1185 1195 phthalates FAMILY 23246700 A 1252 1262 phthalates FAMILY 23246700 A 22 47 di-(2-ethylhexyl) adipate SYSTEMATIC 23246700 A 251 261 phthalates FAMILY 23246700 A 266 270 DEHA ABBREVIATION 23246700 A 408 417 phthalate FAMILY 23246700 A 49 53 DEHA ABBREVIATION 23246700 A 651 676 di-2-ethylhexyl phthalate SYSTEMATIC 23246700 A 678 682 DEHP ABBREVIATION 23246700 A 705 726 di-isobutyl phthalate SYSTEMATIC 23246700 A 728 732 DiBP ABBREVIATION 23246700 A 759 779 di-n-butyl phthalate SYSTEMATIC 23246700 A 781 785 DnBP ABBREVIATION 23246700 A 811 815 DEHA ABBREVIATION 23246700 A 894 898 DEHP ABBREVIATION 23246700 A 919 923 DnBP ABBREVIATION 23246700 A 944 948 DiBP ABBREVIATION 23246700 A 973 994 di-isononyl phthalate SYSTEMATIC 23246700 T 0 9 Phthalate SYSTEMATIC 23246700 T 14 39 di-(2-ethylhexyl) adipate SYSTEMATIC 23246700 T 41 45 DEHA ABBREVIATION 23246701 A 0 25 Perfluorooctane sulfonate SYSTEMATIC 23246701 A 1103 1107 PFOS ABBREVIATION 23246701 A 1159 1167 curcumin TRIVIAL 23246701 A 1217 1221 PFOS ABBREVIATION 23246701 A 27 31 PFOS ABBREVIATION 23246701 A 289 297 Curcumin TRIVIAL 23246701 A 311 323 polyphenolic FAMILY 23246701 A 575 579 PFOS ABBREVIATION 23246701 A 723 731 curcumin TRIVIAL 23246701 A 86 90 PFOS ABBREVIATION 23246701 A 904 908 PFOS ABBREVIATION 23246701 T 23 31 curcumin TRIVIAL 23246701 T 35 60 perfluorooctane sulfonate SYSTEMATIC 23246865 A 1028 1030 Pb FORMULA 23246865 A 1128 1130 Pb FORMULA 23246865 A 1169 1188 amino cupric silver SYSTEMATIC 23246865 A 1279 1282 MUS ABBREVIATION 23246865 A 1317 1321 GABA ABBREVIATION 23246865 A 1337 1348 bicuculline TRIVIAL 23246865 A 1350 1353 BIC ABBREVIATION 23246865 A 1392 1394 Pb FORMULA 23246865 A 1511 1515 GABA ABBREVIATION 23246865 A 183 185 Pb FORMULA 23246865 A 384 391 PbNO(3) FORMULA 23246865 A 56 58 Pb FORMULA 23246865 A 856 858 Pb FORMULA 23246865 A 928 947 γ-aminobutyric acid SYSTEMATIC 23246865 A 961 965 GABA ABBREVIATION 23246865 A 979 987 muscimol TRIVIAL 23246865 A 989 992 MUS ABBREVIATION 23246865 T 81 85 GABA ABBREVIATION 23246867 A 1061 1065 IPA3 ABBREVIATION 23246867 A 1113 1119 ML-141 IDENTIFIER 23246867 A 1133 1140 glucose TRIVIAL 23246867 A 1222 1226 IPA3 ABBREVIATION 23246867 A 1341 1350 PD0325901 IDENTIFIER 23246867 A 1535 1542 glucose TRIVIAL 23246867 A 389 396 glucose TRIVIAL 23246867 A 466 470 IPA3 ABBREVIATION 23246867 A 536 543 glucose TRIVIAL 23246867 A 777 784 glucose TRIVIAL 23246867 A 838 842 IPA3 ABBREVIATION 23246867 A 898 902 IPA3 ABBREVIATION 23246867 A 916 923 glucose TRIVIAL 23247009 A 0 6 Aldose TRIVIAL 23247009 A 170 186 Beta-glucogallin TRIVIAL 23247009 A 188 191 BGG ABBREVIATION 23247009 A 333 336 BGG ABBREVIATION 23247009 A 459 467 sorbitol TRIVIAL 23247009 A 495 498 BGG ABBREVIATION 23247009 A 61 70 aldehydes FAMILY 23247009 A 766 769 BGG ABBREVIATION 23247009 A 80 87 alcohol FAMILY 23247009 A 916 919 BGG ABBREVIATION 23247009 T 0 16 Beta-glucogallin TRIVIAL 23247009 T 108 114 aldose FAMILY 23247010 A 10 18 carbonyl FAMILY 23247010 A 1209 1219 nucleotide FAMILY 23247010 A 151 164 anthracycline FAMILY 23247010 A 184 198 prostaglandins FAMILY 23247010 A 204 210 isatin TRIVIAL 23247010 A 248 257 monoamine FAMILY 23247010 A 473 497 butylated hydroxyanisole SYSTEMATIC 23247010 A 499 502 BHA ABBREVIATION 23247010 A 532 535 BHA ABBREVIATION 23247010 A 809 812 BHA ABBREVIATION 23247010 T 20 28 carbonyl FAMILY 23247040 A 165 196 α-Amino acid-N-carboxyanhydride FAMILY 23247298 A 136 142 serine TRIVIAL 23247298 A 582 584 OH FORMULA 23247298 A 784 790 serine TRIVIAL 23247298 A 973 979 serine TRIVIAL 23247298 T 40 46 serine TRIVIAL 23247504 A 1048 1051 KCl FORMULA 23247504 A 11 21 iron oxide SYSTEMATIC 23247504 A 410 422 carbohydrate FAMILY 23247504 A 430 440 iron oxide SYSTEMATIC 23247504 A 720 729 maghemite TRIVIAL 23247504 A 734 746 ferrihydrite TRIVIAL 23247504 A 919 923 COOH FORMULA 23247504 T 29 39 iron oxide SYSTEMATIC 23247824 A 1141 1149 nicotine TRIVIAL 23247824 A 19 32 acetylcholine SYSTEMATIC 23247824 A 887 895 dopamine TRIVIAL 23248173 A 849 856 glucose TRIVIAL 23248196 A 1090 1102 atorvastatin TRIVIAL 23248196 A 1107 1118 simvastatin TRIVIAL 23248196 A 1228 1234 statin FAMILY 23248196 A 233 239 statin FAMILY 23248196 A 52 59 statins FAMILY 23248196 A 525 532 statins FAMILY 23248196 A 799 805 Statin FAMILY 23248196 T 0 7 Statins FAMILY 23248236 A 1039 1046 Ebselen TRIVIAL 23248236 A 1055 1061 sulfur SYSTEMATIC 23248236 A 1069 1077 ebsulfur TRIVIAL 23248236 A 1100 1103 GSH ABBREVIATION 23248236 A 1124 1132 Ebsulfur TRIVIAL 23248236 A 1358 1374 benzisoselenazol SYSTEMATIC 23248236 A 1379 1393 benzisothiazol SYSTEMATIC 23248236 A 192 197 NADPH ABBREVIATION 23248236 A 367 374 Ebselen TRIVIAL 23248236 A 376 415 2-phenyl-1,2 benzisoselenazol-3(2H)-one SYSTEMATIC 23248236 A 516 527 methicillin TRIVIAL 23248236 A 609 616 ebselen TRIVIAL 23248236 A 736 743 dithiol SYSTEMATIC 23248236 A 776 787 glutathione TRIVIAL 23248236 A 789 792 GSH ABBREVIATION 23248236 T 98 109 glutathione TRIVIAL 23249244 A 242 247 DMABN ABBREVIATION 23249244 A 251 263 acetonitrile SYSTEMATIC 23249244 A 40 45 DMABN ABBREVIATION 23249244 A 876 889 dimethylamino SYSTEMATIC 23249244 T 66 95 4-(dimethylamino)benzonitrile SYSTEMATIC 23249244 T 97 102 DMABN ABBREVIATION 23249338 A 1124 1133 acetylene SYSTEMATIC 23249338 A 1150 1159 porphyrin FAMILY 23249338 A 124 136 chlorophylls FAMILY 23249338 A 1287 1296 porphyrin FAMILY 23249338 A 162 171 porphyrin FAMILY 23249338 A 539 545 Zn(II) FORMULA 23249338 A 546 555 porphyrin FAMILY 23249338 A 563 626 [5,15-dipyridyl-10,20-bis(pentafluorophenyl)porphinato]zinc(II) SYSTEMATIC 23249338 A 631 694 [5,15-bis[4-(pyridyl)ethynyl]-10,20-diphenylporphinato]zinc(II) SYSTEMATIC 23249338 A 881 890 porphyrin FAMILY 23249338 A 99 108 porphyrin FAMILY 23249338 T 51 60 porphyrin FAMILY 23249341 A 302 304 OH FORMULA 23249341 A 339 341 OH FORMULA 23249341 A 401 403 OH FORMULA 23249341 A 44 46 OH FORMULA 23249341 A 554 559 NO(2) FORMULA 23249341 A 624 626 OH FORMULA 23249341 A 896 904 H(2)O(2) FORMULA 23249341 A 909 914 H(2)O FORMULA 23249341 A 965 967 OH FORMULA 23249341 T 15 17 OH FORMULA 23249525 A 1003 1013 quinpirole TRIVIAL 23249525 A 111 120 8-OH-DPAT SYSTEMATIC 23249525 A 1138 1147 8-OH-DPAT SYSTEMATIC 23249525 A 1152 1162 quinpirole TRIVIAL 23249525 A 1304 1314 Quinpirole TRIVIAL 23249525 A 1452 1461 8-OH-DPAT SYSTEMATIC 23249525 A 188 196 dopamine TRIVIAL 23249525 A 220 230 quinpirole TRIVIAL 23249525 A 316 325 8-OH-DPAT SYSTEMATIC 23249525 A 337 347 quinpirole TRIVIAL 23249525 A 36 45 serotonin TRIVIAL 23249525 A 453 462 8-OH-DPAT SYSTEMATIC 23249525 A 466 476 quinpirole TRIVIAL 23249525 A 517 526 8-OH-DPAT SYSTEMATIC 23249525 A 617 627 quinpirole TRIVIAL 23249525 A 679 688 8-OH-DPAT SYSTEMATIC 23249525 A 693 703 quinpirole TRIVIAL 23249525 A 70 109 8-hydroxy-2-(di-n-propylamino) tetralin SYSTEMATIC 23249525 A 812 821 8-OH-DPAT SYSTEMATIC 23249525 A 870 880 quinpirole TRIVIAL 23249525 A 954 964 quinpirole TRIVIAL 23249525 A 989 998 8-OH-DPAT SYSTEMATIC 23249525 T 0 10 Quinpirole TRIVIAL 23249525 T 15 24 8-OH-DPAT SYSTEMATIC 23249745 A 310 321 sparsomycin TRIVIAL 23250357 A 120 127 glucose TRIVIAL 23250357 A 1216 1227 Colesevelam TRIVIAL 23250357 A 1301 1312 Colesevelam TRIVIAL 23250357 A 1428 1435 glucose TRIVIAL 23250357 A 199 210 Colesevelam TRIVIAL 23250357 A 369 378 metformin TRIVIAL 23250357 A 51 60 bile acid FAMILY 23250357 A 520 531 Colesevelam TRIVIAL 23250357 A 645 652 glucose TRIVIAL 23250357 A 675 682 glucose TRIVIAL 23250357 A 80 91 Colesevelam TRIVIAL 23250357 A 843 854 Colesevelam TRIVIAL 23250357 A 958 965 glucose TRIVIAL 23250357 T 16 25 bile acid FAMILY 23250357 T 41 48 glucose TRIVIAL 23250541 A 1003 1005 Fe FORMULA 23250541 A 1202 1204 Cr FORMULA 23250541 A 1237 1244 Cr(III) FORMULA 23250541 A 1420 1439 chromium picolinate SYSTEMATIC 23250541 A 1441 1453 [Cr(pic)(3)] FORMULA 23250541 A 1461 1463 Cr FORMULA 23250541 A 1479 1486 CrCl(3) FORMULA 23250541 A 1493 1495 Cr FORMULA 23250541 A 1515 1557 Cr3 ([Cr(3)O(propionate)(6)(H(2)O)(3)](+)) FORMULA 23250541 A 1574 1576 Cr FORMULA 23250541 A 1662 1669 CrCl(3) FORMULA 23250541 A 1674 1677 Cr3 FORMULA 23250541 A 1687 1699 [Cr(pic)(3)] FORMULA 23250541 A 1709 1711 Cr FORMULA 23250541 A 1771 1773 Cr FORMULA 23250541 A 1878 1880 Cu FORMULA 23250541 A 483 485 Cu FORMULA 23250541 A 487 489 Zn FORMULA 23250541 A 491 493 Fe FORMULA 23250541 A 495 497 Mg FORMULA 23250541 A 503 505 Ca FORMULA 23250541 A 564 566 Cr FORMULA 23250541 A 693 695 Cu FORMULA 23250541 A 697 699 Zn FORMULA 23250541 A 701 703 Fe FORMULA 23250541 A 705 707 Mg FORMULA 23250541 A 895 897 Cu FORMULA 23250541 A 938 940 Ca FORMULA 23250541 T 122 130 chromium SYSTEMATIC 23250541 T 92 102 fatty rats FAMILY 23250811 A 0 8 Curcumin TRIVIAL 23250811 A 1225 1233 curcumin TRIVIAL 23250811 A 1260 1273 sulfasalazine TRIVIAL 23250811 A 1388 1396 curcumin TRIVIAL 23250811 A 1409 1422 sulfasalazine TRIVIAL 23250811 A 1439 1447 Curcumin TRIVIAL 23250811 A 1489 1524 2,4,6-trinitrobenzene sulfonic acid SYSTEMATIC 23250811 A 1564 1577 sulfasalazine TRIVIAL 23250811 A 1612 1620 curcumin TRIVIAL 23250811 A 183 191 curcumin TRIVIAL 23250811 A 354 389 2,4,6-trinitrobenzene sulfonic acid SYSTEMATIC 23250811 A 436 444 curcumin TRIVIAL 23250811 A 448 461 sulfasalazine TRIVIAL 23250811 A 852 860 curcumin TRIVIAL 23250811 T 0 8 Curcumin TRIVIAL 23252421 A 348 358 octylamine SYSTEMATIC 23252481 A 155 164 vindoline TRIVIAL 23252481 A 208 217 vindoline TRIVIAL 23252481 A 46 57 vinblastine TRIVIAL 23252481 A 501 508 Fe(III) FORMULA 23252481 A 532 545 catharanthine TRIVIAL 23252481 A 597 608 vinblastine TRIVIAL 23252481 A 699 708 vindoline TRIVIAL 23252481 A 835 844 vindoline TRIVIAL 23252481 A 998 1009 vinblastine TRIVIAL 23252481 T 111 120 vindoline TRIVIAL 23252481 T 34 45 vinblastine TRIVIAL 23252610 A 1008 1011 HPB ABBREVIATION 23252610 A 1121 1124 HPB ABBREVIATION 23252610 A 270 304 4-hydroxy-1-(3-pyridyl)-1-butanone SYSTEMATIC 23252610 A 306 309 HPB ABBREVIATION 23252610 A 707 710 HPB ABBREVIATION 23252610 A 752 755 HPB ABBREVIATION 23252610 T 12 46 4-Hydroxy-1-(3-pyridyl)-1-butanone SYSTEMATIC 23252610 T 48 51 HPB ABBREVIATION 23252823 A 1140 1149 1-decanol SYSTEMATIC 23252823 A 12 19 glucono TRIVIAL 23252823 A 123 132 methylene SYSTEMATIC 23252823 A 1427 1435 hydrogen SYSTEMATIC 23252823 A 1529 1533 (1)H FORMULA 23252823 A 154 159 amino FAMILY 23252823 A 1573 1581 hydrogen SYSTEMATIC 23252823 A 1598 1605 glucono TRIVIAL 23252823 A 1637 1644 pyrenyl SYSTEMATIC 23252823 A 29 45 1-pyrenesulfonyl SYSTEMATIC 23252823 A 69 86 α,ω-diaminoalkane FAMILY 23252823 A 765 773 naphthyl SYSTEMATIC 23252823 T 0 7 Pyrenyl SYSTEMATIC 23252823 T 15 22 glucono TRIVIAL 23252848 A 25 41 withawrightolide TRIVIAL 23252848 A 261 275 withametelin L TRIVIAL 23252848 A 336 339 MTS ABBREVIATION 23252848 A 358 374 withanolides 1-5 MULTIPLE 23252848 A 6 17 withanolide TRIVIAL 23252848 A 62 74 withanolides FAMILY 23252848 T 18 30 withanolides FAMILY 23253441 A 208 221 oxadiazepines FAMILY 23253441 A 57 67 oxadiazine FAMILY 23253441 T 23 36 oxadiazepines FAMILY 23253856 A 535 546 hydroxyurea SYSTEMATIC 23253856 T 106 117 hydroxyurea SYSTEMATIC 23254196 A 1078 1087 genistein TRIVIAL 23254196 A 1219 1223 cAMP ABBREVIATION 23254196 A 1282 1291 genistein TRIVIAL 23254196 A 1326 1335 genistein TRIVIAL 23254196 A 167 176 genistein TRIVIAL 23254196 A 30 39 genistein TRIVIAL 23254196 A 321 330 Genistein TRIVIAL 23254196 A 466 469 Ser FORMULA 23254196 A 474 477 Thr FORMULA 23254196 A 510 519 Genistein TRIVIAL 23254196 A 560 566 Ca(2+) FORMULA 23254196 A 600 606 Ca(2+) FORMULA 23254196 A 663 675 nitric oxide SYSTEMATIC 23254196 A 688 696 estrogen FAMILY 23254196 A 745 754 genistein TRIVIAL 23254196 A 921 930 genistein TRIVIAL 23254196 T 14 23 genistein TRIVIAL 23255050 A 0 10 Iron oxide SYSTEMATIC 23255050 A 1082 1084 Fe FORMULA 23255050 A 1114 1118 iron SYSTEMATIC 23255050 A 1761 1771 gadolinium SYSTEMATIC 23255050 A 1964 1966 Gd FORMULA 23255050 A 2268 2272 iron SYSTEMATIC 23255050 A 368 388 polyvinylpyrrolidone SYSTEMATIC 23255050 A 863 865 Fe FORMULA 23255050 A 901 912 glutathione TRIVIAL 23255050 A 927 940 acetylcholine SYSTEMATIC 23255050 T 20 30 iron oxide SYSTEMATIC 23255284 A 1013 1023 nucleotide FAMILY 23255284 A 1168 1192 dipeptide-mononucleotide FAMILY 23255284 A 195 207 L-dipeptides FAMILY 23255284 A 221 230 histidine TRIVIAL 23255284 A 250 257 Ser-His FORMULA 23255284 A 532 556 dipeptide-mononucleotide FAMILY 23255284 A 725 734 imidazole SYSTEMATIC 23255284 A 751 760 histidine TRIVIAL 23255284 A 768 776 carboxyl SYSTEMATIC 23255284 A 788 797 dipeptide FAMILY 23255284 T 17 31 phosphodiester SYSTEMATIC 23255284 T 40 49 histidine TRIVIAL 23255284 T 61 71 dipeptides FAMILY 23255384 A 108 127 coniothyrinones A-D MULTIPLE 23255384 A 11 32 hydroxyanthraquinones FAMILY 23255384 A 431 466 coniothyrinones A (5), B (6), and D MULTIPLE 23255384 A 584 600 coniothyrinone C TRIVIAL 23255384 A 614 649 Coniothyrinones A (5), B (6), and D MULTIPLE 23255384 A 754 763 tetralone TRIVIAL 23255384 A 805 819 anthraquinones FAMILY 23255384 A 83 92 tetralone TRIVIAL 23255384 T 41 61 hydroxyanthraquinone SYSTEMATIC 23255471 A 0 16 Tungsten carbide SYSTEMATIC 23255471 A 1037 1039 Na FORMULA 23255471 A 1046 1054 SrTiO(3) FORMULA 23255471 A 1089 1105 tungsten carbide SYSTEMATIC 23255471 A 1176 1184 platinum SYSTEMATIC 23255471 A 145 161 Tungsten carbide SYSTEMATIC 23255471 A 232 240 tungsten SYSTEMATIC 23255471 A 26 34 platinum SYSTEMATIC 23255471 A 278 286 C(3)N(4) FORMULA 23255471 A 292 300 C(3)N(4) FORMULA 23255471 A 557 562 W(2)C FORMULA 23255471 A 566 568 WC FORMULA 23255471 A 630 632 WC FORMULA 23255471 A 709 717 hydrogen SYSTEMATIC 23255471 A 754 756 WC FORMULA 23255471 A 785 793 hydrogen SYSTEMATIC 23255471 A 838 844 oxygen SYSTEMATIC 23255471 A 870 887 tungsten carbides FAMILY 23255471 A 952 956 H(2) FORMULA 23255471 A 961 965 O(2) FORMULA 23255471 A 997 1002 H(2)O FORMULA 23255471 T 0 16 Tungsten carbide SYSTEMATIC 23256442 A 1046 1057 reduced GSH ABBREVIATION 23256442 A 107 117 methionine TRIVIAL 23256442 A 123 130 choline FAMILY 23256442 A 557 564 alanine TRIVIAL 23256442 A 589 601 triglyceride FAMILY 23256442 A 608 623 malondialdehyde TRIVIAL 23256442 A 625 628 MDA ABBREVIATION 23256442 A 635 654 reduced glutathione TRIVIAL 23256442 A 656 659 GSH ABBREVIATION 23256442 A 961 964 MDA ABBREVIATION 23256442 T 64 74 methionine TRIVIAL 23256442 T 80 87 choline FAMILY 23256445 A 1047 1050 TRG ABBREVIATION 23256445 A 149 168 thiobarbituric acid SYSTEMATIC 23256445 A 201 224 8-hydroxydeoxyguanosine SYSTEMATIC 23256445 A 27 39 trigonelline TRIVIAL 23256445 A 318 321 TRG ABBREVIATION 23256445 A 41 44 TRG ABBREVIATION 23256445 A 416 419 TRG ABBREVIATION 23256445 A 583 589 oxygen SYSTEMATIC 23256445 A 614 626 carbohydrate FAMILY 23256445 A 690 701 glutathione TRIVIAL 23256445 A 768 771 TRG ABBREVIATION 23256445 A 832 835 TRG ABBREVIATION 23256445 A 885 890 NADPH ABBREVIATION 23256445 T 0 12 Trigonelline TRIVIAL 23256446 A 1289 1296 glucose TRIVIAL 23256446 A 607 614 glucose TRIVIAL 23256446 A 833 840 glucose TRIVIAL 23256446 A 862 873 cholesterol TRIVIAL 23256446 A 891 904 triglycerides FAMILY 23256510 A 1067 1071 F8BT ABBREVIATION 23256510 A 304 316 polyfluorene SYSTEMATIC 23256510 A 328 419 poly(9,9'-dioctylfluorene-co-bis-N,N'-(4-butylphenyl)-bis-N,N'-phenyl-1,4-phenylene-diamine SYSTEMATIC 23256510 A 422 425 PFB ABBREVIATION 23256510 A 431 476 poly(9,9'-dioctylfluorene-co-benzothiadiazole SYSTEMATIC 23256510 A 479 483 F8BT ABBREVIATION 23256510 A 747 751 F8BT ABBREVIATION 23256510 A 778 781 PFB ABBREVIATION 23256510 A 869 873 F8BT ABBREVIATION 23256510 A 943 946 PFB ABBREVIATION 23256510 A 978 982 F8BT ABBREVIATION 23256609 A 1247 1259 benzoic acid SYSTEMATIC 23256609 A 180 192 Benzoic acid SYSTEMATIC 23256609 A 251 259 hydrogen SYSTEMATIC 23256609 A 481 501 mono- and dihydrates MULTIPLE 23256609 A 83 98 carboxylic acid SYSTEMATIC 23256609 A 852 860 hydrogen SYSTEMATIC 23256609 T 103 115 benzoic acid SYSTEMATIC 23256621 A 0 21 Poly(ethylene glycol) SYSTEMATIC 23256621 A 1005 1009 mPEG ABBREVIATION 23256621 A 1069 1073 PEGs ABBREVIATION 23256621 A 1079 1088 polyether SYSTEMATIC 23256621 A 1241 1262 dibenzylamino ethanol SYSTEMATIC 23256621 A 1287 1291 PEGs ABBREVIATION 23256621 A 1336 1341 amino FAMILY 23256621 A 1392 1397 amino FAMILY 23256621 A 1435 1459 squaric acid ester amide SYSTEMATIC 23256621 A 1543 1546 PEG ABBREVIATION 23256621 A 159 162 PEG ABBREVIATION 23256621 A 1669 1673 mPEG ABBREVIATION 23256621 A 1713 1721 hydroxyl SYSTEMATIC 23256621 A 1761 1782 poly(ethylene glycol) SYSTEMATIC 23256621 A 1857 1863 acetal SYSTEMATIC 23256621 A 1875 1879 PEGs ABBREVIATION 23256621 A 1884 1887 PEG ABBREVIATION 23256621 A 23 26 PEG ABBREVIATION 23256621 A 302 306 PEGs ABBREVIATION 23256621 A 468 474 acetal SYSTEMATIC 23256621 A 486 490 PEGs ABBREVIATION 23256621 A 691 710 acetaldehyde acetal SYSTEMATIC 23256621 A 727 768 (hetero)functional poly(ethylene glycol)s FAMILY 23256621 A 909 923 ethylene oxide SYSTEMATIC 23256621 A 925 936 cholesterol TRIVIAL 23256621 A 938 959 dibenzylamino ethanol SYSTEMATIC 23256621 A 965 1003 poly(ethylene glycol) monomethyl ether SYSTEMATIC 23256621 T 102 124 poly(ethylene glycol)s FAMILY 23256643 A 138 146 pyridine SYSTEMATIC 23256643 A 1483 1491 pyridine SYSTEMATIC 23256643 A 1956 1964 pyridine SYSTEMATIC 23256643 A 2002 2004 Mn FORMULA 23256643 A 2005 2013 pyridine SYSTEMATIC 23256643 A 2125 2131 Mn(II) FORMULA 23256643 A 2177 2185 pyridine SYSTEMATIC 23256643 A 333 350 pyridine nitrogen SYSTEMATIC 23256643 A 39 102 manganese(II) diacetylacetonate and dihexafluoroacetylacetonate MULTIPLE 23256643 A 744 750 m-PyNO FORMULA 23256643 A 811 827 acetyl acetonate SYSTEMATIC 23256643 A 960 976 acetyl acetonate SYSTEMATIC 23256643 T 53 59 Mn(II) FORMULA 23256719 A 1045 1056 glutathione TRIVIAL 23256719 A 1087 1089 NO FORMULA 23256719 A 510 515 Thiol SYSTEMATIC 23256719 A 534 553 N-acetyl-L-cysteine SYSTEMATIC 23256719 A 555 558 NAC ABBREVIATION 23256719 A 561 574 carbocysteine TRIVIAL 23256719 A 576 586 erdosteine TRIVIAL 23256719 A 592 602 fudosteine TRIVIAL 23256719 A 678 681 NAC ABBREVIATION 23256719 A 686 699 carbocysteine TRIVIAL 23256719 A 765 780 corticosteroids FAMILY 23256719 A 858 868 superoxide TRIVIAL 23256724 A 0 10 Clonazepam TRIVIAL 23256724 A 224 234 clonazepam TRIVIAL 23256724 A 373 383 clonazepam TRIVIAL 23256724 A 553 563 clonazepam TRIVIAL 23256724 A 623 626 CO2 FORMULA 23256724 A 780 783 CO2 FORMULA 23256724 A 942 952 clonazepam TRIVIAL 23256724 A 987 996 serotonin TRIVIAL 23256724 T 0 10 Clonazepam TRIVIAL 23256769 A 1008 1016 hematite TRIVIAL 23256769 A 1134 1144 iron oxide SYSTEMATIC 23256769 A 14 22 hematite TRIVIAL 23256769 A 147 155 hematite TRIVIAL 23256769 A 292 299 Fe(III) FORMULA 23256769 A 343 351 hematite TRIVIAL 23256769 A 363 375 ferrihydrite TRIVIAL 23256769 A 455 460 As(V) FORMULA 23256769 A 524 534 iron oxide SYSTEMATIC 23256769 A 62 74 ferrihydrite TRIVIAL 23256769 A 677 689 ferrihydrite TRIVIAL 23256769 A 704 714 iron oxide SYSTEMATIC 23256769 A 812 824 ferrihydrite TRIVIAL 23256769 A 828 836 hematite TRIVIAL 23256769 A 941 946 As(V) FORMULA 23256769 A 991 1003 ferrihydrite TRIVIAL 23256769 T 108 118 iron oxide SYSTEMATIC 23256816 A 121 128 calcium SYSTEMATIC 23256816 A 787 798 pentamidine TRIVIAL 23256819 A 1184 1195 amino acids FAMILY 23256819 A 1322 1331 histidine TRIVIAL 23256819 A 1333 1343 methionine TRIVIAL 23256819 A 1349 1357 cysteine TRIVIAL 23256819 A 1432 1438 lysine TRIVIAL 23256819 A 1498 1503 amino FAMILY 23256819 A 1656 1667 amino acids FAMILY 23256819 A 515 526 amino acids FAMILY 23256819 A 852 882 ((13)C)methyldodecanesulfonate SYSTEMATIC 23256819 T 167 178 Amino Acids FAMILY 23258537 A 1057 1064 ferrous SYSTEMATIC 23258537 A 1144 1159 ribonucleotides FAMILY 23258537 A 847 856 potassium SYSTEMATIC 23258537 A 981 990 Magnesium SYSTEMATIC 23258671 A 10 18 tungsten SYSTEMATIC 23258671 A 116 117 W FORMULA 23258671 A 159 167 tungsten SYSTEMATIC 23258671 A 178 186 nitrogen SYSTEMATIC 23258671 A 487 488 W FORMULA 23258671 A 729 730 W FORMULA 23258671 A 80 93 beta-tungsten SYSTEMATIC 23258671 T 23 36 beta-tungsten SYSTEMATIC 23258742 A 1038 1042 PBDE ABBREVIATION 23258742 A 1171 1175 PBDE ABBREVIATION 23258742 A 1558 1564 BDE-99 ABBREVIATION 23258742 A 185 221 2,2',4,4',5-pentabromodiphenyl ether SYSTEMATIC 23258742 A 223 229 BDE-99 ABBREVIATION 23258742 A 251 268 dimethylsulfoxide SYSTEMATIC 23258742 A 270 274 DMSO ABBREVIATION 23258742 A 47 77 polybrominated diphenyl ethers FAMILY 23258742 A 475 479 PBDE ABBREVIATION 23258742 A 681 687 BDE-99 ABBREVIATION 23258742 A 79 84 PBDEs ABBREVIATION 23258742 A 821 825 PBDE ABBREVIATION 23258742 A 939 943 PBDE ABBREVIATION 23258742 T 49 56 PBDE-99 ABBREVIATION 23258773 A 1040 1044 PCBs ABBREVIATION 23258773 A 1090 1093 PCB ABBREVIATION 23258773 A 1155 1158 PCB ABBREVIATION 23258773 A 1173 1176 PCB ABBREVIATION 23258773 A 1340 1343 PCB ABBREVIATION 23258773 A 1439 1443 PCBs ABBREVIATION 23258773 A 1491 1494 PCB ABBREVIATION 23258773 A 244 256 polyethylene SYSTEMATIC 23258773 A 289 292 PCB ABBREVIATION 23258773 A 460 463 PCB ABBREVIATION 23258773 A 63 88 polychlorinated biphenyls FAMILY 23258773 A 742 746 PCBs ABBREVIATION 23258773 A 879 901 Aroclors 1016 and 1254 MULTIPLE 23258773 A 90 94 PCBs ABBREVIATION 23258773 T 45 70 polychlorinated biphenyls FAMILY 23259536 A 277 286 porphyrin FAMILY 23259536 A 319 328 fullerene TRIVIAL 23259536 A 350 359 quinoline SYSTEMATIC 23259536 A 368 385 dihydroindolizine SYSTEMATIC 23259536 A 405 420 dithienylethene SYSTEMATIC 23259536 A 438 447 porphyrin FAMILY 23259536 A 524 533 fullerene TRIVIAL 23259536 A 681 690 porphyrin FAMILY 23259666 A 0 10 Vancomycin TRIVIAL 23259666 A 1076 1086 vancomycin TRIVIAL 23259666 A 119 129 vancomycin TRIVIAL 23259666 A 1197 1207 vancomycin TRIVIAL 23259666 A 1259 1269 iron oxide SYSTEMATIC 23259666 A 1563 1573 vancomycin TRIVIAL 23259666 A 408 424 poly(amidoamine) SYSTEMATIC 23259666 A 426 431 PAMAM ABBREVIATION 23259666 A 458 468 vancomycin TRIVIAL 23259666 A 476 477 C FORMULA 23259666 A 648 658 vancomycin TRIVIAL 23259666 A 671 686 (D)-Ala-(D)-Ala FORMULA 23259666 A 690 700 vancomycin TRIVIAL 23259666 A 711 726 (D)-Ala-(D)-Lac FORMULA 23259666 A 852 862 vancomycin TRIVIAL 23259666 A 967 977 vancomycin TRIVIAL 23259666 T 28 38 vancomycin TRIVIAL 23259742 A 564 570 oxygen SYSTEMATIC 23259742 A 76 82 carbon SYSTEMATIC 23259742 A 781 787 ZrO(2) FORMULA 23259742 T 62 68 carbon SYSTEMATIC 23259773 A 285 292 silicon SYSTEMATIC 23259773 A 595 601 carbon SYSTEMATIC 23259773 A 623 631 platinum SYSTEMATIC 23259773 A 88 90 Si FORMULA 23259773 T 101 108 silicon SYSTEMATIC 23259865 A 137 149 camptothecin TRIVIAL 23259865 A 272 291 indenoisoquinolines FAMILY 23259865 A 495 514 indenoisoquinolines FAMILY 23259865 T 39 58 indenoisoquinolines FAMILY 23259866 A 214 225 polystyrene SYSTEMATIC 23259866 A 232 245 polybutadiene SYSTEMATIC 23259866 A 256 268 polyisoprene SYSTEMATIC 23259866 A 360 384 poly(1,3-cyclohexadiene) SYSTEMATIC 23259866 A 63 87 poly(1,3-cyclohexadiene) SYSTEMATIC 23259866 A 747 751 PCHD ABBREVIATION 23259866 A 89 93 PCHD ABBREVIATION 23259866 T 57 77 poly(cyclohexadiene) SYSTEMATIC 23259985 A 0 8 Polyplex TRIVIAL 23259985 A 1147 1157 polyplexes FAMILY 23259985 A 1222 1232 polyplexes FAMILY 23259985 A 1335 1345 polyplexes FAMILY 23259985 A 1630 1640 polyplexes FAMILY 23259985 A 264 280 poly((L)-lysine) SYSTEMATIC 23259985 A 282 285 PLL ABBREVIATION 23259985 A 314 317 PLL ABBREVIATION 23259985 A 382 385 PLL ABBREVIATION 23259985 A 423 433 polyplexes FAMILY 23259985 A 580 590 polyplexes FAMILY 23259985 A 60 70 polyplexes FAMILY 23259985 A 722 730 polyplex TRIVIAL 23259985 A 783 786 PLL ABBREVIATION 23259985 A 795 805 polyplexes FAMILY 23259985 A 871 879 polyplex TRIVIAL 23259985 A 945 948 PLL ABBREVIATION 23259985 A 957 967 polyplexes FAMILY 23259985 T 50 58 polyplex TRIVIAL 23260032 A 1028 1035 bismuth SYSTEMATIC 23260032 A 117 124 bismuth SYSTEMATIC 23260032 A 125 135 asparagine TRIVIAL 23260032 T 28 35 Bismuth SYSTEMATIC 23260032 T 36 46 Asparagine TRIVIAL 23260347 A 0 25 Diphenylphosphinic amides FAMILY 23260347 A 115 124 potassium SYSTEMATIC 23260347 A 30 54 diphenylphosphine oxides FAMILY 23260347 T 28 53 diphenylphosphinic amides FAMILY 23260347 T 58 82 diphenylphosphine oxides FAMILY 23260352 A 167 186 hydroxy-ethyl-amine SYSTEMATIC 23260352 A 230 242 Mannich base FAMILY 23260352 A 260 271 amodiaquine TRIVIAL 23260352 A 45 64 hydroxy-ethyl-amine SYSTEMATIC 23260352 T 47 66 hydroxy-ethyl-amine SYSTEMATIC 23261524 A 1015 1023 nutlin-3 TRIVIAL 23261524 A 874 882 nutlin-3 TRIVIAL 23261527 A 11 25 prostaglandins FAMILY 23261528 A 1060 1067 icariin TRIVIAL 23261528 A 1267 1274 icariin TRIVIAL 23261528 A 273 280 steroid FAMILY 23261528 A 445 452 icariin TRIVIAL 23261528 A 594 601 sulfate SYSTEMATIC 23261528 A 602 608 sodium SYSTEMATIC 23261528 A 633 640 icariin TRIVIAL 23261528 A 894 901 icariin TRIVIAL 23261528 T 155 164 flavonoid FAMILY 23261528 T 175 182 icariin TRIVIAL 23261588 A 1409 1414 BPA-f ABBREVIATION 23261588 A 1504 1509 BPA-f ABBREVIATION 23261588 A 1646 1651 BPA-f ABBREVIATION 23261588 A 237 242 BPA-f ABBREVIATION 23261588 A 36 55 boronophenylalanine SYSTEMATIC 23261588 A 415 418 MTT ABBREVIATION 23261588 A 426 436 calcein-AM TRIVIAL 23261588 A 437 453 Propidium Iodide SYSTEMATIC 23261588 A 56 64 fructose TRIVIAL 23261588 A 570 573 MTT ABBREVIATION 23261588 A 653 658 BPA-f ABBREVIATION 23261588 A 66 71 BPA-f ABBREVIATION 23261588 A 882 887 BPA-f ABBREVIATION 23261588 A 905 915 Calcein-AM TRIVIAL 23261588 A 929 934 BPA-f ABBREVIATION 23261588 T 78 83 Boron SYSTEMATIC 23261590 A 1180 1194 neoechinulin A TRIVIAL 23261590 A 1243 1257 neoechinulin A TRIVIAL 23261590 A 1575 1589 neoechinulin A TRIVIAL 23261590 A 1653 1667 neoechinulin A TRIVIAL 23261590 A 358 372 neoechinulin A TRIVIAL 23261590 A 377 383 indole SYSTEMATIC 23261590 A 511 525 Neoechinulin A TRIVIAL 23261590 A 587 593 oxygen SYSTEMATIC 23261590 A 598 606 nitrogen SYSTEMATIC 23261590 A 682 696 neoechinulin A TRIVIAL 23261590 A 857 873 prostaglandin E2 TRIVIAL 23261590 A 875 879 PGE2 ABBREVIATION 23261590 A 990 1002 nitric oxide SYSTEMATIC 23261590 T 0 14 Neoechinulin A TRIVIAL 23261644 A 520 543 methylmethanesulphonate SYSTEMATIC 23261644 A 545 548 MMS ABBREVIATION 23261644 A 612 615 MMS ABBREVIATION 23261644 A 734 737 MMS ABBREVIATION 23261645 A 0 9 Jaspamide TRIVIAL 23261645 A 11 25 jasplakinolide TRIVIAL 23261645 A 1133 1142 jaspamide TRIVIAL 23261645 A 1195 1207 mitoxantrone TRIVIAL 23261645 A 1380 1389 jaspamide TRIVIAL 23261645 A 27 37 NSC-613009 IDENTIFIER 23261645 A 331 340 Jaspamide TRIVIAL 23261645 A 433 442 Jaspamide TRIVIAL 23261645 A 44 61 cyclodepsipeptide FAMILY 23261645 A 486 495 Jaspamide TRIVIAL 23261645 A 790 799 Jaspamide TRIVIAL 23261645 T 15 24 jaspamide TRIVIAL 23261667 A 113 119 copper SYSTEMATIC 23261667 A 1200 1206 copper SYSTEMATIC 23261667 A 191 197 copper SYSTEMATIC 23261667 T 70 76 copper SYSTEMATIC 23261676 A 1086 1096 superoxide TRIVIAL 23261676 A 1101 1109 hydroxyl SYSTEMATIC 23261676 A 1141 1156 (-) epicatechin TRIVIAL 23261676 A 1212 1227 (-) epicatechin TRIVIAL 23261676 A 122 137 (-) epicatechin TRIVIAL 23261676 A 1315 1322 calcium SYSTEMATIC 23261676 A 1363 1381 tricarboxylic acid SYSTEMATIC 23261676 A 1428 1439 glutathione TRIVIAL 23261676 A 1444 1466 adenosine triphosphate SYSTEMATIC 23261676 A 1474 1489 (-) epicatechin TRIVIAL 23261676 A 1525 1538 isoproterenol TRIVIAL 23261676 A 173 186 isoproterenol TRIVIAL 23261676 A 267 282 (-) epicatechin TRIVIAL 23261676 A 368 381 isoproterenol TRIVIAL 23261676 A 506 519 Isoproterenol TRIVIAL 23261676 A 669 676 calcium SYSTEMATIC 23261676 A 753 764 glutathione TRIVIAL 23261676 A 777 788 glutathione TRIVIAL 23261676 A 800 819 reduced glutathione TRIVIAL 23261676 A 821 831 isocitrate TRIVIAL 23261676 A 833 842 succinate TRIVIAL 23261676 A 844 850 malate TRIVIAL 23261676 A 852 867 α-ketoglutarate TRIVIAL 23261676 A 872 876 NADH ABBREVIATION 23261676 A 918 940 adenosine triphosphate SYSTEMATIC 23261676 A 942 957 (-) Epicatechin TRIVIAL 23261676 T 0 15 (-) Epicatechin TRIVIAL 23261676 T 133 140 calcium SYSTEMATIC 23261676 T 144 157 isoproterenol TRIVIAL 23261676 T 97 119 adenosine triphosphate SYSTEMATIC 23261705 A 1029 1038 rapamycin TRIVIAL 23261705 A 629 638 rapamycin TRIVIAL 23261705 A 96 105 rapamycin TRIVIAL 23261715 A 1067 1082 4-oxo-2-nonenal SYSTEMATIC 23261715 A 1176 1180 GSSG ABBREVIATION 23261715 A 1181 1192 glutathione TRIVIAL 23261715 A 121 131 amino acid FAMILY 23261715 A 1260 1268 aldehyde SYSTEMATIC 23261715 A 1352 1356 GSSG ABBREVIATION 23261715 A 1429 1433 GSSG ABBREVIATION 23261715 A 1452 1455 Cys FORMULA 23261715 A 205 220 4-oxo-2-nonenal SYSTEMATIC 23261715 A 298 306 aldehyde SYSTEMATIC 23261715 A 441 443 SH FORMULA 23261715 A 454 488 p-chloromercuriphenylsulfonic acid SYSTEMATIC 23261715 A 493 520 p-chloromercuribenzoic acid SYSTEMATIC 23261715 A 552 557 NADPH ABBREVIATION 23261715 A 62 68 aldose FAMILY 23261715 A 645 666 glutathione disulfide SYSTEMATIC 23261715 A 668 672 GSSG ABBREVIATION 23261715 A 767 781 dithiothreitol SYSTEMATIC 23261715 A 786 797 glutathione TRIVIAL 23261715 A 887 890 Cys FORMULA 23261715 A 944 947 Cys FORMULA 23261715 T 102 122 oxidized glutathione TRIVIAL 23261715 T 127 129 SH FORMULA 23261715 T 59 65 aldose FAMILY 23261820 A 0 9 Triclosan TRIVIAL 23261820 A 11 14 TCS ABBREVIATION 23261820 A 119 122 TCS ABBREVIATION 23261820 A 160 177 ethinyl estradiol TRIVIAL 23261820 A 227 230 TCS ABBREVIATION 23261820 A 266 269 TCS ABBREVIATION 23261820 A 595 603 estrogen FAMILY 23261820 A 645 648 TCS ABBREVIATION 23261820 A 757 760 TCS ABBREVIATION 23261820 A 877 885 estrogen FAMILY 23261820 A 980 983 TCS ABBREVIATION 23261820 T 14 23 triclosan TRIVIAL 23261820 T 74 91 ethinyl estradiol TRIVIAL 23262162 A 0 11 Resveratrol TRIVIAL 23262162 A 1240 1251 resveratrol TRIVIAL 23262162 A 1281 1290 polyamide FAMILY 23262162 A 1380 1391 resveratrol TRIVIAL 23262162 A 1708 1712 DPPH ABBREVIATION 23262162 A 1741 1752 resveratrol TRIVIAL 23262162 A 1978 1989 resveratrol TRIVIAL 23262162 A 2345 2356 resveratrol TRIVIAL 23262162 A 262 273 resveratrol TRIVIAL 23262162 A 277 284 ethanol SYSTEMATIC 23262162 A 388 399 resveratrol TRIVIAL 23262162 A 431 437 trolox TRIVIAL 23262162 A 455 464 Vitamin E FAMILY 23262162 A 607 618 resveratrol TRIVIAL 23262162 A 623 629 trolox TRIVIAL 23262162 A 655 659 DPPH ABBREVIATION 23262162 A 711 715 DPPH ABBREVIATION 23262162 A 842 853 resveratrol TRIVIAL 23262162 A 877 883 trolox TRIVIAL 23262203 A 1022 1026 HPMA ABBREVIATION 23262203 A 255 288 N-(2-hydroxypropyl)methacrylamide SYSTEMATIC 23262203 A 290 294 HPMA ABBREVIATION 23262203 A 456 466 Gadolinium SYSTEMATIC 23262203 A 475 479 HPMA ABBREVIATION 23262203 A 774 778 HPMA ABBREVIATION 23262203 T 71 75 HPMA ABBREVIATION 23262279 A 1019 1107 4-{(Z)-[(2Z)-2-(2-fluorobenzylidene)-4-oxo-1,3-thiazolidin-5-ylidene]methyl}benzoic acid SYSTEMATIC 23262279 A 1464 1470 ML-145 IDENTIFIER 23262279 A 1472 1603 2-hydroxy-4-[4-(5Z)-5-[(E)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]butanoylamino]benzoic acid SYSTEMATIC 23262390 A 1038 1040 Mn FORMULA 23262390 A 1237 1239 Mn FORMULA 23262390 A 297 306 manganese SYSTEMATIC 23262390 A 308 310 Mn FORMULA 23262390 A 638 640 Mn FORMULA 23262390 A 704 706 Mn FORMULA 23262390 T 0 9 Manganese SYSTEMATIC 23263987 A 110 117 glucose TRIVIAL 23263987 A 200 204 cAMP ABBREVIATION 23263987 A 280 284 cAMP ABBREVIATION 23263987 A 32 42 cyclic AMP TRIVIAL 23263987 A 44 48 cAMP ABBREVIATION 23263987 A 621 628 glucose TRIVIAL 23263987 T 136 146 cyclic AMP TRIVIAL 23263987 T 61 68 glucose TRIVIAL 23264030 A 1135 1145 fluoxetine TRIVIAL 23264030 A 119 129 Fluoxetine TRIVIAL 23264030 A 1259 1269 fluoxetine TRIVIAL 23264030 A 14 23 serotonin TRIVIAL 23264030 A 1459 1469 fluoxetine TRIVIAL 23264030 A 150 159 serotonin TRIVIAL 23264030 A 1519 1529 fluoxetine TRIVIAL 23264030 A 43 53 fluoxetine TRIVIAL 23264030 A 434 444 fluoxetine TRIVIAL 23264030 A 445 458 hydrochloride FAMILY 23264030 A 901 911 fluoxetine TRIVIAL 23264030 T 11 21 fluoxetine TRIVIAL 23264615 A 1211 1219 cortisol TRIVIAL 23264615 A 1295 1304 PF 915275 IDENTIFIER 23264615 A 146 160 prostaglandins FAMILY 23264615 A 1564 1572 cortisol TRIVIAL 23264615 A 1611 1623 progesterone TRIVIAL 23264615 A 1712 1720 cortisol TRIVIAL 23264615 A 196 204 cortisol TRIVIAL 23264615 A 209 223 hydroxysteroid FAMILY 23264615 A 266 278 progesterone TRIVIAL 23264615 A 349 353 keto SYSTEMATIC 23264615 A 573 581 cortisol TRIVIAL 23264615 A 729 737 cortisol TRIVIAL 23264615 A 739 748 PF 915275 IDENTIFIER 23264615 A 789 797 cortisol TRIVIAL 23264615 A 806 815 meloxicam TRIVIAL 23264615 A 850 858 cortisol TRIVIAL 23264615 A 863 872 meloxicam TRIVIAL 23264615 A 964 972 Cortisol TRIVIAL 23264615 T 0 8 Cortisol TRIVIAL 23265282 A 1109 1121 α-thioesters FAMILY 23265282 A 346 357 α-thioester FAMILY 23265282 A 375 376 N FORMULA 23265282 A 386 389 Cys FORMULA 23265282 A 510 522 α-thioesters FAMILY 23265282 A 633 645 α-thioesters FAMILY 23265282 A 804 815 α-thioester FAMILY 23265296 A 1021 1025 PGMA ABBREVIATION 23265296 A 105 132 poly(glycidyl methacrylate) SYSTEMATIC 23265296 A 1173 1179 biotin TRIVIAL 23265296 A 134 138 PGMA ABBREVIATION 23265296 A 155 162 silicon SYSTEMATIC 23265296 A 351 355 PGMA ABBREVIATION 23265296 A 356 363 epoxide SYSTEMATIC 23265296 A 376 381 amino FAMILY 23265296 A 415 421 POEGMA ABBREVIATION 23265296 A 50 91 poly(oligo(ethylene glycol) methacrylate) SYSTEMATIC 23265296 A 873 879 POEGMA ABBREVIATION 23265296 A 93 99 POEGMA ABBREVIATION 23265429 A 1112 1114 as FORMULA 23265429 A 1181 1190 As(2)O(3) FORMULA 23265429 A 12 16 GaAs FORMULA 23265429 A 1206 1210 GaAs FORMULA 23265429 A 1365 1369 GaAs FORMULA 23265429 A 145 152 gallium SYSTEMATIC 23265429 A 154 159 Ga(l) FORMULA 23265429 A 1871 1875 GaAs FORMULA 23265429 A 20 24 GaAs FORMULA 23265429 A 207 212 Ga(l) FORMULA 23265429 A 395 404 As(2)O(3) FORMULA 23265429 A 474 478 GaAs FORMULA 23265429 A 641 650 As(2)O(3) FORMULA 23265429 A 791 800 As(2)O(3) FORMULA 23265429 A 81 90 As(2)O(3) FORMULA 23265429 A 877 879 As FORMULA 23265429 A 908 910 As FORMULA 23265429 T 33 37 GaAs FORMULA 23265429 T 48 55 gallium SYSTEMATIC 23265452 A 0 12 Polyphenolic FAMILY 23265452 A 1079 1087 apigenin TRIVIAL 23265452 A 1393 1407 phenolic acids FAMILY 23265452 A 1432 1441 flavonoid FAMILY 23265452 A 675 685 flavonoids FAMILY 23265452 A 810 817 chrysin TRIVIAL 23265452 A 819 830 pinocembrin TRIVIAL 23265452 A 835 843 galangin TRIVIAL 23265452 A 883 898 p-Coumaric acid TRIVIAL 23265452 A 985 996 gallic acid TRIVIAL 23265456 A 109 120 polyphenols FAMILY 23265456 A 414 425 polyphenols FAMILY 23265456 A 747 758 polyphenols FAMILY 23265456 T 37 48 polyphenols FAMILY 23265458 A 353 360 ABTS(+) ABBREVIATION 23265458 A 879 882 ADP ABBREVIATION 23265462 A 1012 1021 sophorose TRIVIAL 23265462 A 110 115 sugar FAMILY 23265462 A 124 145 6-O-caffeoylsophorose SYSTEMATIC 23265462 A 669 678 phloretin TRIVIAL 23265462 A 696 715 monocarboxylic acid SYSTEMATIC 23265462 A 735 747 Benzoic acid SYSTEMATIC 23265462 A 78 90 caffeic acid TRIVIAL 23265462 A 895 904 quercetin TRIVIAL 23265462 A 982 994 caffeic acid TRIVIAL 23265462 T 29 50 6-O-caffeoylsophorose SYSTEMATIC 23265467 A 125 128 HFO ABBREVIATION 23265467 A 17 22 As(V) FORMULA 23265467 A 234 241 arsenic SYSTEMATIC 23265467 A 315 320 As(V) FORMULA 23265467 A 377 380 HFO ABBREVIATION 23265467 A 385 390 As(V) FORMULA 23265467 A 498 503 As(V) FORMULA 23265467 A 559 562 HFO ABBREVIATION 23265467 A 582 587 As(V) FORMULA 23265467 A 630 633 HCl FORMULA 23265467 A 650 654 NaOH FORMULA 23265467 A 66 87 hydrated ferric oxide SYSTEMATIC 23265467 A 733 741 carboxyl SYSTEMATIC 23265467 A 746 754 hydroxyl SYSTEMATIC 23265467 A 788 793 As(V) FORMULA 23265467 A 89 92 HFO ABBREVIATION 23265467 A 907 912 As(V) FORMULA 23265467 A 969 972 HFO ABBREVIATION 23265467 T 31 51 hydrous ferric oxide SYSTEMATIC 23265467 T 96 101 As(V) FORMULA 23265469 A 324 331 propane SYSTEMATIC 23265469 A 333 341 n-butane SYSTEMATIC 23265469 A 343 348 CO(2) FORMULA 23265469 A 678 685 kestose TRIVIAL 23265469 A 703 710 nystose TRIVIAL 23265469 A 730 747 fructosyl nystose TRIVIAL 23265469 A 769 776 sucrose TRIVIAL 23265469 A 79 86 sucrose TRIVIAL 23265483 A 27 35 selenium SYSTEMATIC 23265483 A 340 342 Se FORMULA 23265483 A 444 446 Se FORMULA 23265483 A 618 620 Se FORMULA 23265483 A 912 920 selenium SYSTEMATIC 23265483 T 42 50 selenium SYSTEMATIC 23265488 A 662 665 ser FORMULA 23265491 A 1032 1042 isoflavone FAMILY 23265491 A 1104 1115 isoflavones FAMILY 23265491 A 158 165 alcohol FAMILY 23265491 A 198 225 genistein-7-O-gentiobioside SYSTEMATIC 23265491 A 470 480 isoflavone FAMILY 23265491 A 51 61 isoflavone FAMILY 23265491 A 63 90 genistein-7-O-gentiobioside SYSTEMATIC 23265491 A 778 789 glutathione TRIVIAL 23265491 A 861 871 isoflavone FAMILY 23265491 A 915 926 glutathione TRIVIAL 23265491 T 102 112 isoflavone FAMILY 23265492 A 151 155 DEAE ABBREVIATION 23265492 A 339 346 mannose TRIVIAL 23265492 A 479 488 arabinose TRIVIAL 23265492 A 563 570 mannose TRIVIAL 23265492 A 698 706 sulphate SYSTEMATIC 23265492 A 779 786 mannose TRIVIAL 23265492 A 794 802 sulphate SYSTEMATIC 23265492 A 867 874 mannose TRIVIAL 23265501 A 377 385 Fructose TRIVIAL 23265501 A 387 394 glucose TRIVIAL 23265501 A 400 407 sucrose TRIVIAL 23265501 A 461 467 sugars FAMILY 23265501 A 510 543 Citric, malic, and ascorbic acids MULTIPLE 23265501 A 707 719 anthocyanins FAMILY 23265501 A 882 893 gallic acid TRIVIAL 23265502 A 0 7 Nitrate SYSTEMATIC 23265502 A 21 34 ascorbic acid TRIVIAL 23265502 A 250 257 Nitrate SYSTEMATIC 23265502 A 259 266 nitrate SYSTEMATIC 23265502 A 271 284 ascorbic acid TRIVIAL 23265502 A 36 45 vitamin C TRIVIAL 23265502 A 551 558 nitrate SYSTEMATIC 23265502 A 563 570 nitrite SYSTEMATIC 23265502 A 667 674 nitrate SYSTEMATIC 23265502 A 768 781 Ascorbic acid TRIVIAL 23265502 A 9 16 nitrite SYSTEMATIC 23265502 T 0 13 Ascorbic acid TRIVIAL 23265502 T 15 22 nitrate SYSTEMATIC 23265502 T 28 35 nitrite SYSTEMATIC 23265504 A 268 275 phenols FAMILY 23265504 A 277 292 ρ-coumaric acid TRIVIAL 23265504 A 294 306 sinapic acid TRIVIAL 23265504 A 308 317 quercetin TRIVIAL 23265504 A 339 350 citric acid TRIVIAL 23265504 A 352 362 malic acid TRIVIAL 23265504 A 364 372 fructose TRIVIAL 23265504 A 405 409 DPPH ABBREVIATION 23265504 A 536 546 β-carotene TRIVIAL 23265504 A 548 569 ρ-hydroxybenzoic acid SYSTEMATIC 23265504 A 571 578 sucrose TRIVIAL 23265504 A 586 591 sugar FAMILY 23265504 A 614 622 catechin TRIVIAL 23265504 A 624 637 succinic acid TRIVIAL 23265504 A 787 794 phenols FAMILY 23265504 A 796 806 β-carotene TRIVIAL 23265506 A 0 7 DPPH(·) ABBREVIATION 23265506 A 103 110 DPPH(·) ABBREVIATION 23265506 A 752 761 quercetin TRIVIAL 23265506 A 763 771 catechin TRIVIAL 23265506 A 773 786 ascorbic acid TRIVIAL 23265506 A 788 800 caffeic acid TRIVIAL 23265506 A 802 818 chlorogenic acid TRIVIAL 23265506 A 823 837 acetylcysteine SYSTEMATIC 23265506 A 882 889 DPPH(·) ABBREVIATION 23265506 T 43 48 DPPH· ABBREVIATION 23265507 A 0 17 Trans fatty acids FAMILY 23265507 A 1045 1048 TFA ABBREVIATION 23265507 A 19 22 TFA ABBREVIATION 23265507 A 252 255 TFA ABBREVIATION 23265507 A 413 416 TFA ABBREVIATION 23265507 A 522 525 TFA ABBREVIATION 23265507 A 592 595 TFA ABBREVIATION 23265507 A 707 718 fatty acids FAMILY 23265507 A 755 766 fatty acids FAMILY 23265507 T 9 26 trans fatty acids FAMILY 23265517 A 258 272 streptozotocin TRIVIAL 23265517 A 746 761 malondialdehyde TRIVIAL 23265517 A 775 785 superoxide TRIVIAL 23265517 A 807 818 glutathione TRIVIAL 23265517 T 140 154 streptozotocin TRIVIAL 23265526 A 592 598 Fe(2+) FORMULA 23265529 A 261 274 ethyl acetate SYSTEMATIC 23265529 A 282 297 sodium sulphate SYSTEMATIC 23265529 A 441 464 primary secondary amine MULTIPLE 23265529 A 489 500 formic acid SYSTEMATIC 23265533 A 307 313 sodium SYSTEMATIC 23265533 A 54 60 sodium SYSTEMATIC 23265533 A 984 990 sodium SYSTEMATIC 23265533 T 32 38 sodium SYSTEMATIC 23265542 A 202 218 artemisia ketone TRIVIAL 23265542 A 228 240 germacrene B TRIVIAL 23265542 A 249 256 borneol TRIVIAL 23265542 A 268 293 cis-chrysanthenyl acetate SYSTEMATIC 23265546 A 563 571 lactones FAMILY 23265843 A 1107 1115 lucidone TRIVIAL 23265843 A 1202 1210 lucidone TRIVIAL 23265843 A 212 220 lucidone TRIVIAL 23265843 A 347 355 Lucidone TRIVIAL 23265843 A 620 628 lucidone TRIVIAL 23265843 A 857 868 cholesterol TRIVIAL 23265843 A 870 882 triglyceride FAMILY 23265843 A 884 891 glucose TRIVIAL 23265843 A 947 955 lucidone TRIVIAL 23265843 T 0 8 Lucidone TRIVIAL 23265880 A 192 205 biphenylthiol SYSTEMATIC 23265880 A 207 216 FLIP-IDAM ABBREVIATION 23265880 A 255 264 FLIP-IDAM ABBREVIATION 23265880 A 325 338 [(125)I]-IDAM SYSTEMATIC 23265880 A 408 425 [(125)I]Flip-IDAM SYSTEMATIC 23265880 A 41 50 serotonin TRIVIAL 23265880 A 730 736 (123)I FORMULA 23265880 T 118 182 (2-((2-((dimethylamino)methyl)-4-iodophenyl)thio)phenyl)methanol SYSTEMATIC 23265880 T 75 84 serotonin TRIVIAL 23265880 T 99 116 [(125)I]Flip-IDAM SYSTEMATIC 23265892 A 122 132 SCH 900229 IDENTIFIER 23265892 A 260 267 4-CF(3) FORMULA 23265892 A 272 276 4-Br FORMULA 23265892 A 289 300 arylsulfone FAMILY 23265892 A 447 454 sulfone SYSTEMATIC 23265892 A 82 89 sulfone SYSTEMATIC 23265892 T 43 69 tricyclic bispyran sulfone FAMILY 23265896 A 119 126 ZSTK474 IDENTIFIER 23265896 A 310 323 benzimidazole SYSTEMATIC 23265896 A 579 620 5- and 6-methoxysubstituted benzimidazole MULTIPLE 23265896 A 636 643 ZSTK474 IDENTIFIER 23265896 A 651 660 5-methoxy SYSTEMATIC 23265896 A 714 723 6-methoxy SYSTEMATIC 23265896 A 925 932 ZSTK474 IDENTIFIER 23265896 T 28 73 5- and 6-methoxybenzimidazole-1,3,5-triazines MULTIPLE 23265899 A 0 48 C5-Ethynylbenzenesulfonamide-modified nucleotide FAMILY 23265899 A 206 210 EBNA ABBREVIATION 23265899 A 213 223 nucleotide FAMILY 23265899 A 347 351 EBNA ABBREVIATION 23265899 A 454 458 EBNA ABBREVIATION 23265899 A 461 472 nucleotides FAMILY 23265899 A 50 54 EBNA ABBREVIATION 23265899 T 45 94 C5-ethynylbenzenesulfonamide-modified nucleotides FAMILY 23265899 T 96 100 EBNA ABBREVIATION 23265901 A 141 156 tertiary amines FAMILY 23265901 A 166 167 N FORMULA 23265901 A 187 194 adenine TRIVIAL 23265901 A 227 232 amino FAMILY 23265901 A 356 364 DSR-6434 IDENTIFIER 23265901 A 80 93 8-oxoadenines FAMILY 23265901 T 28 40 8-oxoadenine FAMILY 23265902 A 130 141 Selectfluor TRIVIAL 23265902 A 196 211 difluoroquinone FAMILY 23265902 A 306 321 difluoroquinone FAMILY 23265902 A 357 364 quinone FAMILY 23265902 A 48 56 9-fluoro SYSTEMATIC 23265902 A 98 108 SCH 900229 IDENTIFIER 23265902 T 23 33 SCH 900229 IDENTIFIER 23265902 T 55 62 sulfone SYSTEMATIC 23265903 A 18 39 C-cinnamoyl glycoside FAMILY 23265903 A 361 448 (E)-1-(2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl)-4-(3-hydroxyphenyl)but-3-en-2-one SYSTEMATIC 23265903 A 55 61 phenol SYSTEMATIC 23265903 T 77 99 C-cinnamoyl glycosides FAMILY 23265904 A 1001 1023 spirocyclic piperidine FAMILY 23265904 A 106 109 CoA ABBREVIATION 23265904 A 22 55 benzo-fused spirocyclic oxazepine FAMILY 23265904 A 350 359 oxazepine TRIVIAL 23265904 A 369 377 benzylic TRIVIAL 23265904 A 415 425 piperidine SYSTEMATIC 23265904 A 576 586 piperidine SYSTEMATIC 23265904 A 587 595 nitrogen SYSTEMATIC 23265904 A 675 689 glycine amides FAMILY 23265904 A 710 716 amides FAMILY 23265904 A 722 731 thiazoles FAMILY 23265904 A 85 104 stearoyl-coenzyme A TRIVIAL 23265904 A 951 971 5-carboxy-2-thiazole SYSTEMATIC 23265904 T 42 54 stearoyl-CoA TRIVIAL 23266447 A 472 481 rhodamine TRIVIAL 23266452 A 373 394 N-acetylgalactosamine SYSTEMATIC 23266452 A 629 650 N-acetylgalactosamine SYSTEMATIC 23266452 A 666 710 poly(ethylene glycol)-b-poly(ε-caprolactone) SYSTEMATIC 23266452 A 724 784 poly(ε-caprolactone)-b-poly(2-aminoethyl ethylene phosphate) SYSTEMATIC 23266452 A 786 797 PCL-b-PPEEA ABBREVIATION 23266452 A 892 913 poly(ethylene glycol) SYSTEMATIC 23266452 T 0 21 N-acetylgalactosamine SYSTEMATIC 23266453 A 610 629 polyethylene glycol SYSTEMATIC 23266501 A 187 195 Apigenin TRIVIAL 23266501 A 197 221 4',5,7-trihydroxyflavone SYSTEMATIC 23266501 A 406 414 apigenin TRIVIAL 23266501 A 545 551 oxygen SYSTEMATIC 23266501 A 649 657 Apigenin TRIVIAL 23266501 A 957 965 apigenin TRIVIAL 23266501 A 979 987 apigenin TRIVIAL 23266501 T 37 45 apigenin TRIVIAL 23266502 A 0 9 Carbamate SYSTEMATIC 23266502 A 1083 1091 methomyl TRIVIAL 23266502 A 1240 1244 Urea TRIVIAL 23266502 A 1293 1301 methomyl TRIVIAL 23266502 A 150 158 methomyl TRIVIAL 23266502 A 22 30 methomyl TRIVIAL 23266502 A 284 292 methomyl TRIVIAL 23266502 A 614 622 methomyl TRIVIAL 23266502 A 637 645 methomyl TRIVIAL 23266502 A 997 1005 methomyl TRIVIAL 23266502 T 0 9 Carbamate SYSTEMATIC 23266502 T 22 30 methomyl TRIVIAL 23266674 A 1073 1081 androgen FAMILY 23266674 A 1116 1124 androgen FAMILY 23266674 A 1185 1193 androgen FAMILY 23266674 A 1207 1215 androgen FAMILY 23266674 A 1465 1473 androgen FAMILY 23266674 A 1568 1576 androgen FAMILY 23266674 A 167 192 polyaromatic hydrocarbons FAMILY 23266674 A 1676 1684 androgen FAMILY 23266674 A 201 238 2,3,7,8,-tetrachloro-dibenzo-p-dioxin SYSTEMATIC 23266674 A 240 244 TCDD ABBREVIATION 23266674 A 4 20 aryl hydrocarbon FAMILY 23266674 A 620 628 androgen FAMILY 23266674 A 735 743 androgen FAMILY 23266674 A 802 810 androgen FAMILY 23266674 T 27 43 aryl hydrocarbon FAMILY 23266674 T 80 88 androgen FAMILY 23266719 A 84 90 carbon SYSTEMATIC 23266719 T 44 50 carbon SYSTEMATIC 23266722 A 1050 1063 phorbol ester FAMILY 23266722 A 1239 1252 phorbol ester FAMILY 23266722 A 158 189 7,12-dimethylbenz[a]anthrancene SYSTEMATIC 23266722 A 191 195 DMBA ABBREVIATION 23266722 A 205 218 phorbol ester FAMILY 23266722 A 219 255 12-O-tetradecanoylphorbol-13-acetate SYSTEMATIC 23266722 A 257 260 TPA ABBREVIATION 23266722 A 373 377 DMBA ABBREVIATION 23266722 A 382 385 TPA ABBREVIATION 23266731 A 1063 1070 paeonol TRIVIAL 23266731 A 1078 1090 flavan-3-ols FAMILY 23266731 A 1091 1099 catechin TRIVIAL 23266731 A 1106 1129 epicatechin-3-O-gallate SYSTEMATIC 23266731 A 1145 1161 proanthocyanidin FAMILY 23266731 A 1162 1189 epicatechin-(4β→8)-catechin SYSTEMATIC 23266731 A 1206 1225 trigalloyl-glucoses FAMILY 23266731 A 1232 1269 1,2,3,4,6-penta-O-galloyl-β-d-glucose SYSTEMATIC 23266731 A 1271 1274 PGG ABBREVIATION 23266731 A 1283 1299 proanthocyanidin FAMILY 23266731 A 1332 1335 PGG ABBREVIATION 23266731 A 1422 1425 PGG ABBREVIATION 23266731 A 1830 1840 polyphenol FAMILY 23266731 A 229 233 EtOH FORMULA 23266731 A 407 410 MTT ABBREVIATION 23266732 A 1002 1004 NO FORMULA 23266732 A 1010 1036 6-keto prostaglandin F(1α) SYSTEMATIC 23266732 A 1038 1052 6-keto-PGF(1α) SYSTEMATIC 23266732 A 941 957 thromboxane B(2) TRIVIAL 23266732 A 959 965 TXB(2) ABBREVIATION 23266732 A 988 1000 nitric oxide SYSTEMATIC 23266737 A 104 125 triterpenoid saponins FAMILY 23266737 A 158 166 saponins FAMILY 23266737 A 411 419 saponins FAMILY 23266737 A 483 491 creatine TRIVIAL 23266737 A 514 521 lactate FAMILY 23266737 T 0 21 Triterpenoid saponins FAMILY 23267837 A 473 485 somatostatin TRIVIAL 23267837 A 694 706 somatostatin TRIVIAL 23267837 A 755 765 Cetrorelix TRIVIAL 23267855 A 1104 1113 metformin TRIVIAL 23267855 A 152 161 metformin TRIVIAL 23267855 A 357 366 metformin TRIVIAL 23267855 A 41 50 metformin TRIVIAL 23267855 A 418 425 glucose TRIVIAL 23267855 A 446 455 metformin TRIVIAL 23267855 A 511 520 metformin TRIVIAL 23267855 A 560 569 metformin TRIVIAL 23267855 A 735 744 metformin TRIVIAL 23267855 A 745 752 glucose TRIVIAL 23267855 A 989 998 metformin TRIVIAL 23267855 T 105 114 metformin TRIVIAL 23267862 A 1126 1132 Ca(2+) FORMULA 23267862 A 1138 1144 Mg(2+) FORMULA 23267862 A 1355 1361 Ca(2+) FORMULA 23267862 A 1451 1457 Mg(2+) FORMULA 23267862 A 1608 1614 Ca(2+) FORMULA 23267862 A 1658 1664 Mg(2+) FORMULA 23267862 A 364 370 Ca(2+) FORMULA 23267862 A 399 405 Mg(2+) FORMULA 23267862 A 924 930 Ca(2+) FORMULA 23267862 A 935 941 Mg(2+) FORMULA 23268927 A 481 488 glucose TRIVIAL 23268927 A 856 863 glucose TRIVIAL 23270527 A 1158 1166 aminooxy SYSTEMATIC 23270527 A 1265 1271 sugars FAMILY 23270527 A 1369 1374 NIPAm ABBREVIATION 23270527 A 1546 1559 carbohydrates FAMILY 23270527 A 1685 1691 sugars FAMILY 23270527 A 342 350 aminooxy SYSTEMATIC 23270527 A 359 373 methacrylamide SYSTEMATIC 23270527 A 379 400 N-isopropylacrylamide SYSTEMATIC 23270527 A 402 407 NIPAm ABBREVIATION 23270527 A 412 437 N-isopropylmethacrylamide SYSTEMATIC 23270527 A 439 444 NIPMa ABBREVIATION 23270527 A 451 459 aminooxy SYSTEMATIC 23270527 A 769 791 pyridoxal-5'-phosphate SYSTEMATIC 23270527 A 805 811 ketone SYSTEMATIC 23270527 A 878 883 oxime SYSTEMATIC 23270527 A 897 914 benzylalkoxyamine FAMILY 23270527 A 924 945 poly(ethylene glycol) SYSTEMATIC 23270527 A 946 957 alkoxyamine FAMILY 23270704 A 115 118 APO ABBREVIATION 23270704 A 120 128 apocynin TRIVIAL 23270704 A 154 166 raisanberine TRIVIAL 23270704 A 175 182 calcium SYSTEMATIC 23270704 A 358 361 APO ABBREVIATION 23270704 A 524 528 H2O2 FORMULA 23270704 A 592 604 testosterone TRIVIAL 23270704 A 83 88 NADPH ABBREVIATION 23270704 A 840 843 APO ABBREVIATION 23270704 T 0 8 Apocynin TRIVIAL 23270704 T 13 25 raisanberine TRIVIAL 23270704 T 98 110 testosterone TRIVIAL 23270993 A 0 14 Kynurenic acid TRIVIAL 23270993 A 137 150 acetylcholine SYSTEMATIC 23270993 A 16 20 KYNA ABBREVIATION 23270993 A 267 271 KYNA ABBREVIATION 23270993 A 31 41 tryptophan TRIVIAL 23270993 A 350 354 KYNA ABBREVIATION 23270993 A 423 427 KYNA ABBREVIATION 23270993 A 59 68 glutamate TRIVIAL 23270993 A 615 619 KYNA ABBREVIATION 23270993 T 0 14 Kynurenic acid TRIVIAL 23270993 T 48 61 acetylcholine SYSTEMATIC 23271737 A 256 271 acylsulfonamide FAMILY 23271742 A 1009 1016 arsenic SYSTEMATIC 23271742 A 1189 1196 arsenic SYSTEMATIC 23271742 A 1232 1239 arsenic SYSTEMATIC 23271742 A 1379 1386 arsenic SYSTEMATIC 23271742 A 459 475 arsenic trioxide SYSTEMATIC 23271742 A 633 649 arsenic trioxide SYSTEMATIC 23271742 A 809 825 arsenic trioxide SYSTEMATIC 23271742 T 0 7 Arsenic SYSTEMATIC 23273150 A 1011 1019 carbonyl FAMILY 23273150 A 1020 1021 O FORMULA 23273150 A 1037 1040 C=O FORMULA 23273150 A 1059 1064 amide FAMILY 23273150 A 146 148 NH FORMULA 23273150 A 151 154 O H FORMULA 23273150 A 224 241 N-methylacetamide SYSTEMATIC 23273150 A 243 246 NMA ABBREVIATION 23273150 A 319 320 H FORMULA 23273150 A 383 385 NH FORMULA 23273150 A 443 448 amide FAMILY 23273150 A 532 534 CO FORMULA 23273150 A 549 551 NH FORMULA 23273150 A 689 691 NH FORMULA 23273150 A 694 697 O H FORMULA 23273150 A 756 758 CH FORMULA 23273150 A 761 764 O H FORMULA 23273150 A 809 811 CO FORMULA 23273150 A 879 880 O FORMULA 23273150 A 888 890 CO FORMULA 23273150 A 971 972 O FORMULA 23273225 A 141 150 porphyrin FAMILY 23273225 A 162 211 tetrakis(3,5-di-t-butyl-4-hydroxyphenyl)porphyrin SYSTEMATIC 23273225 A 220 248 tetrakis(4-pyridyl)porphyrin SYSTEMATIC 23273225 A 30 39 porphyrin FAMILY 23273225 T 12 21 Porphyrin FAMILY 23273412 A 0 6 Thymol TRIVIAL 23273412 A 106 118 Schiff bases FAMILY 23273412 A 11 20 carvacrol TRIVIAL 23273412 A 122 150 2-iso-propyl-5-methyl-phenol SYSTEMATIC 23273412 A 152 158 thymol TRIVIAL 23273412 A 164 192 2-tert-butyl-5-methyl-phenol SYSTEMATIC 23273412 A 202 230 5-iso-propyl-2-methyl-phenol SYSTEMATIC 23273412 A 232 241 carvacrol TRIVIAL 23273412 A 294 300 thymol TRIVIAL 23273412 A 305 314 carvacrol TRIVIAL 23273412 A 318 322 DPPH ABBREVIATION 23273412 A 460 473 ascorbic acid TRIVIAL 23273412 A 531 535 ABTS ABBREVIATION 23273412 T 38 44 thymol TRIVIAL 23273412 T 49 58 carvacrol TRIVIAL 23273412 T 65 77 Schiff bases FAMILY 23274352 A 1137 1139 Pb FORMULA 23274352 A 128 130 Co FORMULA 23274352 A 132 134 Cu FORMULA 23274352 A 136 138 Pb FORMULA 23274352 A 140 142 Ni FORMULA 23274353 A 1009 1017 peroxide SYSTEMATIC 23274353 A 1030 1038 carbonyl FAMILY 23274353 A 1142 1146 PBDE ABBREVIATION 23274353 A 1375 1386 glutathione TRIVIAL 23274353 A 1387 1388 S FORMULA 23274353 A 1453 1468 ethoxyresorufin SYSTEMATIC 23274353 A 1469 1470 O FORMULA 23274353 A 1535 1539 PBDE ABBREVIATION 23274353 A 1673 1681 carbonyl FAMILY 23274353 A 1780 1784 PBDE ABBREVIATION 23274353 A 1870 1875 PBDEs ABBREVIATION 23274353 A 41 46 PBDEs ABBREVIATION 23274353 A 644 648 PBDE ABBREVIATION 23274353 A 9 39 polybrominated diphenyl ethers FAMILY 23274353 T 125 155 polybrominated diphenyl ethers FAMILY 23274353 T 157 162 PBDEs ABBREVIATION 23274746 A 1108 1118 flavonoids FAMILY 23274746 A 1123 1140 chlorogenic acids FAMILY 23274768 A 0 4 Zinc SYSTEMATIC 23274768 A 1031 1033 Zn FORMULA 23274768 A 1035 1040 ZnSO4 FORMULA 23274768 A 1188 1193 ZnSO4 FORMULA 23274768 A 1317 1321 zinc SYSTEMATIC 23274768 A 170 174 zinc SYSTEMATIC 23274768 A 401 413 zinc sulfate SYSTEMATIC 23274768 A 415 420 ZnSO4 FORMULA 23274768 A 704 716 zinc sulfate SYSTEMATIC 23274768 A 837 844 lactate FAMILY 23274768 A 877 880 ATP ABBREVIATION 23274768 A 988 993 ZnSO4 FORMULA 23274768 T 11 15 zinc SYSTEMATIC 23274903 A 702 708 oxygen SYSTEMATIC 23274903 A 822 829 glucose TRIVIAL 23274903 A 977 984 glucose TRIVIAL 23274917 A 1012 1015 EMS ABBREVIATION 23274917 A 1072 1080 formalin TRIVIAL 23274917 A 1160 1163 EMS ABBREVIATION 23274917 A 1168 1176 formalin TRIVIAL 23274917 A 563 586 ethyl methane sulfonate SYSTEMATIC 23274917 A 588 591 EMS ABBREVIATION 23274917 A 609 617 formalin TRIVIAL 23274917 A 840 843 EMS ABBREVIATION 23275110 A 1000 1007 calcium SYSTEMATIC 23275110 A 1065 1072 calcium SYSTEMATIC 23275110 A 1229 1236 calcium SYSTEMATIC 23275110 A 1528 1546 PHEA-IB-p(MANa(+)) FORMULA 23275110 A 199 217 PHEA-IB-p(MANa(+)) FORMULA 23275110 A 374 392 PHEA-IB-p(MANa(+)) FORMULA 23275110 A 517 535 PHEA-IB-p(MANa(+)) FORMULA 23275110 A 814 821 calcium SYSTEMATIC 23275110 A 87 197 β-poly(N-2-hydroxyethyl)-graft-{N-2-ethylene[2-poly(methacrylic acid sodium salt)isobutyrate]}-d,l-aspartamide SYSTEMATIC 23275110 A 900 918 PHEA-IB-p(MANa(+)) FORMULA 23275110 T 0 27 PHEA-graft-polymethacrylate SYSTEMATIC 23275111 A 1005 1012 lactide TRIVIAL 23275111 A 1070 1073 PTX ABBREVIATION 23275111 A 1102 1109 lactide TRIVIAL 23275111 A 1116 1119 PLA ABBREVIATION 23275111 A 1214 1217 PLA ABBREVIATION 23275111 A 1355 1358 PLA ABBREVIATION 23275111 A 1412 1415 DOX ABBREVIATION 23275111 A 1423 1426 PLA ABBREVIATION 23275111 A 1548 1551 DOX ABBREVIATION 23275111 A 1553 1556 DOX ABBREVIATION 23275111 A 1560 1563 PTX ABBREVIATION 23275111 A 1580 1583 PLA ABBREVIATION 23275111 A 1686 1689 PLA ABBREVIATION 23275111 A 1733 1736 DOX ABBREVIATION 23275111 A 1740 1743 PLA ABBREVIATION 23275111 A 1753 1756 PLA ABBREVIATION 23275111 A 1810 1813 PTX ABBREVIATION 23275111 A 1846 1849 DOX ABBREVIATION 23275111 A 1853 1856 PLA ABBREVIATION 23275111 A 1908 1911 DOX ABBREVIATION 23275111 A 1916 1919 PLA ABBREVIATION 23275111 A 1942 1945 DOX ABBREVIATION 23275111 A 1953 1956 PLA ABBREVIATION 23275111 A 198 209 polylactide FAMILY 23275111 A 2081 2084 PLA ABBREVIATION 23275111 A 2130 2133 DOX ABBREVIATION 23275111 A 2144 2147 PLA ABBREVIATION 23275111 A 2193 2196 PLA ABBREVIATION 23275111 A 369 380 Doxorubicin TRIVIAL 23275111 A 382 385 DOX ABBREVIATION 23275111 A 390 400 paclitaxel TRIVIAL 23275111 A 402 405 PTX ABBREVIATION 23275111 A 424 427 PLA ABBREVIATION 23275111 A 480 499 polyethylene glycol SYSTEMATIC 23275111 A 511 514 PLA ABBREVIATION 23275111 A 516 519 PLA ABBREVIATION 23275111 A 541 544 PLA ABBREVIATION 23275111 A 554 557 PLA ABBREVIATION 23275111 A 680 683 DOX ABBREVIATION 23275111 A 687 690 PLA ABBREVIATION 23275111 A 700 703 PLA ABBREVIATION 23275111 A 758 761 PTX ABBREVIATION 23275111 A 804 807 DOX ABBREVIATION 23275111 A 812 815 PTX ABBREVIATION 23275111 A 821 824 PLA ABBREVIATION 23275111 A 854 857 PLA ABBREVIATION 23275111 A 978 981 DOX ABBREVIATION 23275111 T 92 103 polylactide FAMILY 23275113 A 1242 1250 Neusilin TRIVIAL 23275113 A 340 349 Fujicalin TRIVIAL 23275113 A 355 363 Neusilin TRIVIAL 23275113 A 615 623 Neusilin TRIVIAL 23276135 A 174 176 Au FORMULA 23276135 A 618 630 carbohydrate FAMILY 23276161 A 463 472 silicates FAMILY 23276161 A 474 484 aluminates FAMILY 23276161 A 494 500 oxides FAMILY 23276161 A 502 510 sulfates FAMILY 23276161 A 516 524 apatites FAMILY 23276627 A 10 25 1-methyladenine SYSTEMATIC 23276627 A 1102 1105 MMS ABBREVIATION 23276627 A 27 32 1-meA SYSTEMATIC 23276627 A 38 54 3-methylcytosine SYSTEMATIC 23276627 A 56 61 3-meC SYSTEMATIC 23276627 A 667 690 methyl methanesulfonate SYSTEMATIC 23276627 A 692 695 MMS ABBREVIATION 23276627 A 863 874 nucleotides FAMILY 23276633 A 1007 1019 testosterone TRIVIAL 23276633 A 104 116 testosterone TRIVIAL 23276633 A 1163 1175 testosterone TRIVIAL 23276633 A 12 24 testosterone TRIVIAL 23276633 A 1561 1573 testosterone TRIVIAL 23276633 A 1672 1684 testosterone TRIVIAL 23276633 A 172 184 Testosterone TRIVIAL 23276633 A 218 231 17β-estradiol SYSTEMATIC 23276633 A 257 276 dihydrotestosterone SYSTEMATIC 23276633 A 278 281 DHT ABBREVIATION 23276633 A 415 427 testosterone TRIVIAL 23276633 A 474 486 testosterone TRIVIAL 23276633 A 906 918 testosterone TRIVIAL 23276633 T 0 12 Testosterone TRIVIAL 23277104 A 1026 1030 FICZ ABBREVIATION 23277104 A 1053 1065 Aroclor 1254 TRIVIAL 23277104 A 1080 1084 PCBs ABBREVIATION 23277104 A 1338 1341 BNF ABBREVIATION 23277104 A 1422 1428 PCB126 TRIVIAL 23277104 A 421 437 aryl hydrocarbon FAMILY 23277104 A 895 911 β-naphthoflavone TRIVIAL 23277104 A 913 916 BNF ABBREVIATION 23277104 A 932 968 3,3',4,4',5-polychlorinated biphenyl SYSTEMATIC 23277104 A 970 976 PCB126 TRIVIAL 23277104 A 994 1024 6-formylindolo[3,2-b]carbazole SYSTEMATIC 23277230 A 1119 1126 Fisetin TRIVIAL 23277230 A 1189 1196 glucose TRIVIAL 23277230 A 1286 1298 nitric oxide SYSTEMATIC 23277230 A 1300 1302 NO FORMULA 23277230 A 1479 1486 fisetin TRIVIAL 23277230 A 1516 1520 DPPH ABBREVIATION 23277230 A 1525 1529 ABTS ABBREVIATION 23277230 A 1590 1597 fisetin TRIVIAL 23277230 A 1683 1690 fisetin TRIVIAL 23277230 A 1714 1721 fisetin TRIVIAL 23277230 A 486 493 fisetin TRIVIAL 23277230 A 513 525 bioflavonoid FAMILY 23277230 A 577 580 STZ ABBREVIATION 23277230 A 723 730 fisetin TRIVIAL 23277230 A 821 835 streptozotocin TRIVIAL 23277230 A 860 867 Fisetin TRIVIAL 23277230 T 0 7 Fisetin TRIVIAL 23277230 T 57 71 streptozotocin TRIVIAL 23278398 A 267 269 Cu FORMULA 23278398 A 270 272 Zn FORMULA 23278398 A 273 283 superoxide TRIVIAL 23278398 A 756 759 Trp FORMULA 23278398 A 791 802 quinazoline SYSTEMATIC 23278398 A 887 901 catecholamines FAMILY 23278633 A 257 258 H FORMULA 23278633 A 308 309 H FORMULA 23278633 A 411 422 nucleobases FAMILY 23278633 A 463 464 H FORMULA 23278633 A 497 505 xanthine TRIVIAL 23278633 A 594 595 H FORMULA 23278633 A 621 622 H FORMULA 23278633 A 678 687 xanthines FAMILY 23278633 A 708 709 H FORMULA 23278633 A 838 846 graphite TRIVIAL 23278633 T 17 43 N(3)-Substituted Xanthines FAMILY 23279802 A 11 29 4-aminoquinazoline SYSTEMATIC 23279802 T 46 64 4-aminoquinazoline SYSTEMATIC 23279841 A 593 600 ethanol SYSTEMATIC 23279841 A 849 856 nitrite SYSTEMATIC 23279841 A 861 868 nitrate SYSTEMATIC 23279841 T 107 114 ethanol SYSTEMATIC 23279844 A 110 114 CCl4 FORMULA 23279844 A 1303 1307 CCl4 FORMULA 23279844 A 211 215 CCl4 FORMULA 23279844 A 243 252 aspartate TRIVIAL 23279844 A 276 283 alanine TRIVIAL 23279844 A 31 41 flavonoids FAMILY 23279844 A 572 582 superoxide TRIVIAL 23279844 A 607 618 glutathione TRIVIAL 23279844 A 657 668 glutathione TRIVIAL 23279844 A 698 713 malondialdehyde TRIVIAL 23279844 A 839 843 CCl4 FORMULA 23279844 A 88 108 carbon tetrachloride SYSTEMATIC 23279844 T 18 27 flavonoid FAMILY 23279844 T 77 97 carbon tetrachloride SYSTEMATIC 23279943 A 1153 1156 GSH ABBREVIATION 23279943 A 1191 1194 MDA ABBREVIATION 23279943 A 1230 1232 Al FORMULA 23279943 A 1234 1236 Fe FORMULA 23279943 A 1242 1244 Cu FORMULA 23279943 A 1271 1273 Mn FORMULA 23279943 A 1275 1277 Zn FORMULA 23279943 A 1283 1285 Se FORMULA 23279943 A 1306 1309 GSH ABBREVIATION 23279943 A 1358 1361 MDA ABBREVIATION 23279943 A 1387 1389 Mn FORMULA 23279943 A 1391 1393 Zn FORMULA 23279943 A 1399 1401 Se FORMULA 23279943 A 1427 1429 Al FORMULA 23279943 A 1431 1433 Fe FORMULA 23279943 A 1439 1441 Cu FORMULA 23279943 A 276 285 donepezil TRIVIAL 23279943 A 660 670 superoxide TRIVIAL 23279943 A 688 699 glutathione TRIVIAL 23279943 A 712 715 GSH ABBREVIATION 23279943 A 725 740 malondialdehyde TRIVIAL 23279943 A 742 745 MDA ABBREVIATION 23279943 A 789 791 Al FORMULA 23279943 A 793 795 Fe FORMULA 23279943 A 797 799 Cu FORMULA 23279943 A 801 803 Zn FORMULA 23279943 A 805 807 Se FORMULA 23279943 A 813 815 Mn FORMULA 23280101 A 1079 1085 oxygen SYSTEMATIC 23280101 A 207 224 protoporphyrin IX TRIVIAL 23280101 A 226 230 PpIX ABBREVIATION 23280620 A 1146 1148 Hg FORMULA 23280620 A 133 135 Hg FORMULA 23280620 A 1384 1386 Hg FORMULA 23280620 A 262 264 Hg FORMULA 23280620 A 388 390 Hg FORMULA 23280620 A 441 443 Hg FORMULA 23280620 A 45 52 mercury SYSTEMATIC 23280620 A 54 56 Hg FORMULA 23280620 A 864 866 Hg FORMULA 23280620 A 983 985 Hg FORMULA 23280620 T 81 88 mercury SYSTEMATIC 23280766 A 1184 1194 pyrethroid FAMILY 23280766 A 1491 1501 pyrethroid FAMILY 23280766 A 687 702 organophosphate FAMILY 23280766 A 716 726 pyrethroid FAMILY 23280951 A 137 183 1-(2'-deoxy-β-D-threo-pentofuranosyl)thymidine SYSTEMATIC 23280951 A 32 46 C3'-thymidinyl SYSTEMATIC 23280951 T 88 102 C3'-thymidinyl SYSTEMATIC 23280958 A 196 204 methanol SYSTEMATIC 23280958 A 256 264 hydrogen SYSTEMATIC 23280958 A 56 64 hydrogen SYSTEMATIC 23280958 A 619 636 hydroxyl hydrogen SYSTEMATIC 23280997 A 303 307 CdSe FORMULA 23280997 A 308 311 ZnS FORMULA 23280997 T 30 34 CdSe FORMULA 23280997 T 35 38 ZnS FORMULA 23281069 A 0 49 Diaromatic-substituted ortho- and meta-carboranes MULTIPLE 23281069 A 105 115 carboranes FAMILY 23281069 A 80 93 manassantin A TRIVIAL 23281069 T 39 68 diaryl-substituted carboranes FAMILY 23281101 A 255 264 Organotin FAMILY 23281101 A 443 482 di- and tri-n-butyltin(IV) carboxylates MULTIPLE 23281101 A 731 738 tin(IV) SYSTEMATIC 23281101 A 979 996 di-n-butyltin(IV) SYSTEMATIC 23281101 T 0 22 Butyltin(IV) benzoates FAMILY 23281242 A 177 183 silica TRIVIAL 23281242 A 33 35 Pt FORMULA 23281242 A 36 38 Ru FORMULA 23281242 A 43 45 Pt FORMULA 23281242 T 71 73 pt FORMULA 23281242 T 74 76 ru FORMULA 23281330 A 100 103 HMF ABBREVIATION 23281330 A 1001 1008 glucose TRIVIAL 23281330 A 1136 1153 hydrogen chloride SYSTEMATIC 23281330 A 1154 1165 formic acid SYSTEMATIC 23281330 A 1187 1207 chloromethylfurfural SYSTEMATIC 23281330 A 150 157 FeCl(3) FORMULA 23281330 A 173 176 HMF ABBREVIATION 23281330 A 198 205 toluene TRIVIAL 23281330 A 207 213 xylene FAMILY 23281330 A 219 229 mesitylene TRIVIAL 23281330 A 248 258 CH(2)Cl(2) FORMULA 23281330 A 263 270 MeNO(2) FORMULA 23281330 A 359 364 ether SYSTEMATIC 23281330 A 36 46 mesitylene TRIVIAL 23281330 A 421 427 p-TsOH FORMULA 23281330 A 466 477 formic acid SYSTEMATIC 23281330 A 501 511 mesitylene TRIVIAL 23281330 A 52 64 carbohydrate FAMILY 23281330 A 539 560 mesitylmethylfurfural SYSTEMATIC 23281330 A 562 565 MMF ABBREVIATION 23281330 A 581 589 fructose TRIVIAL 23281330 A 644 652 fructose TRIVIAL 23281330 A 658 669 formic acid SYSTEMATIC 23281330 A 688 698 mesitylene TRIVIAL 23281330 A 73 98 5-(hydroxymethyl)furfural SYSTEMATIC 23281330 A 730 743 formate ester SYSTEMATIC 23281330 A 747 750 HMF ABBREVIATION 23281330 A 808 816 hydroxyl SYSTEMATIC 23281330 A 834 841 mesityl TRIVIAL 23281330 A 847 852 arene FAMILY 23281330 A 934 945 formic acid SYSTEMATIC 23281330 T 49 62 carbohydrates FAMILY 23281330 T 88 99 formic acid SYSTEMATIC 23281578 A 177 190 carbohydrates FAMILY 23281578 A 341 356 glycofullerenes FAMILY 23281578 A 388 396 mannoses FAMILY 23281578 A 41 72 hexakis-adduct of [60]fullerene TRIVIAL 23281578 T 0 15 Glycofullerenes FAMILY 23281613 A 368 388 ent-3,4-seco-labdane SYSTEMATIC 23281613 A 394 404 diterpenes FAMILY 23281613 A 43 61 methylcallicarpate SYSTEMATIC 23281613 A 70 86 callicarpic acid TRIVIAL 23281613 A 8 41 ent-3,4-seco-labdane diterpenoids FAMILY 23281613 T 8 41 ent-3,4-seco-labdane diterpenoids FAMILY 23281636 A 0 12 Paeoniflorin TRIVIAL 23281636 A 385 397 paeoniflorin TRIVIAL 23281636 A 520 532 paeoniflorin TRIVIAL 23281636 A 558 569 cholesterol TRIVIAL 23281636 A 622 625 ATP ABBREVIATION 23281636 A 736 748 paeoniflorin TRIVIAL 23281636 A 815 823 GSK 3987 IDENTIFIER 23281636 A 875 887 paeoniflorin TRIVIAL 23281636 T 0 12 Paeoniflorin TRIVIAL 23281847 A 445 453 hydrogen SYSTEMATIC 23281917 A 1293 1302 acyclovir TRIVIAL 23281917 A 137 146 acyclovir TRIVIAL 23281917 A 246 253 Span-80 TRIVIAL 23281917 A 258 265 Span-83 TRIVIAL 23281917 A 295 302 Brij-35 TRIVIAL 23281917 T 87 96 acyclovir TRIVIAL 23281937 A 1122 1127 (31)P FORMULA 23281937 A 1209 1215 sodium SYSTEMATIC 23281937 A 1322 1332 phosphorus SYSTEMATIC 23281937 A 1337 1342 boron SYSTEMATIC 23281937 A 1360 1367 oxygens FAMILY 23281937 A 1375 1380 P-O-B FAMILY 23281937 A 1704 1709 boron SYSTEMATIC 23281937 A 1718 1719 B FORMULA 23281937 A 1743 1744 B FORMULA 23281937 A 1753 1754 P FORMULA 23281937 A 1773 1774 B FORMULA 23281937 A 1782 1783 P FORMULA 23281937 A 1911 1912 B FORMULA 23281937 A 206 226 sodium borophosphate SYSTEMATIC 23281937 A 231 237 Na(2)O FORMULA 23281937 A 244 273 [xB(2)O(3) + (1 - x)P(2)O(5)] FAMILY 23281937 A 391 396 (11)B FORMULA 23281937 A 401 406 (31)P FORMULA 23281937 A 623 624 B FORMULA 23281937 A 647 648 P FORMULA 23281937 A 704 709 Na(+) FORMULA 23281937 A 778 791 sodium borate SYSTEMATIC 23281937 A 804 820 sodium phosphate SYSTEMATIC 23281937 T 107 110 31P FORMULA 23281937 T 45 49 Na2O FORMULA 23281937 T 56 77 [xB2O3 + (1 - x)P2O5] FAMILY 23281937 T 99 102 11B FORMULA 23282017 A 0 60 Indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] SYSTEMATIC 23282017 A 151 157 KP1339 IDENTIFIER 23282017 A 361 370 ruthenium SYSTEMATIC 23282017 A 475 482 citrate FAMILY 23282017 A 513 522 carbonate FAMILY 23282017 A 608 619 glutathione TRIVIAL 23282017 A 65 71 KP1019 IDENTIFIER 23282017 A 660 669 carbonate FAMILY 23282017 A 90 146 sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] SYSTEMATIC 23282017 A 965 974 ruthenium SYSTEMATIC 23282017 T 103 163 indazolium trans-[Tetrachlorobis(1H-indazole)ruthenate(III)] SYSTEMATIC 23282017 T 165 171 KP1019 IDENTIFIER 23282066 A 1020 1023 MDZ ABBREVIATION 23282066 A 1092 1095 TRZ ABBREVIATION 23282066 A 222 231 midazolam TRIVIAL 23282066 A 233 236 MDZ ABBREVIATION 23282066 A 241 250 triazolam TRIVIAL 23282066 A 252 255 TRZ ABBREVIATION 23282066 A 445 448 TRZ ABBREVIATION 23282066 A 625 628 MDZ ABBREVIATION 23282066 A 644 647 TRZ ABBREVIATION 23282066 A 673 676 MDZ ABBREVIATION 23282066 A 815 818 MDZ ABBREVIATION 23282066 T 157 166 midazolam TRIVIAL 23282066 T 171 180 triazolam TRIVIAL 23282101 A 0 23 (Xylyl-phanephos)Pt(2+) FORMULA 23282101 A 102 108 olefin FAMILY 23282101 A 137 144 polyene SYSTEMATIC 23282101 A 324 336 P(2)Pt-alkyl FAMILY 23282101 A 44 50 XeF(2) FORMULA 23282101 T 62 70 polyenes FAMILY 23282576 A 998 1009 metal-oxide FAMILY 23282999 A 1130 1132 Al FORMULA 23282999 A 1214 1225 cholesterol TRIVIAL 23282999 A 1250 1252 Al FORMULA 23282999 A 1345 1357 testosterone TRIVIAL 23282999 A 136 149 zinc sulphate SYSTEMATIC 23282999 A 1472 1474 Al FORMULA 23282999 A 154 163 vitamin E FAMILY 23282999 A 1540 1558 aluminium sulphate SYSTEMATIC 23282999 A 1654 1667 zinc sulphate SYSTEMATIC 23282999 A 1672 1681 vitamin E FAMILY 23282999 A 1748 1750 Al FORMULA 23282999 A 1886 1904 aluminium sulphate SYSTEMATIC 23282999 A 1996 2009 zinc sulphate SYSTEMATIC 23282999 A 2017 2026 vitamin E FAMILY 23282999 A 2074 2083 vitamin E FAMILY 23282999 A 2173 2186 zinc sulphate SYSTEMATIC 23282999 A 230 239 aluminium SYSTEMATIC 23282999 A 241 243 Al FORMULA 23282999 A 387 405 aluminium sulphate SYSTEMATIC 23282999 A 454 472 aluminium sulphate SYSTEMATIC 23282999 A 494 507 zinc sulphate SYSTEMATIC 23282999 A 542 560 aluminium sulphate SYSTEMATIC 23282999 A 581 590 vitamin E FAMILY 23282999 A 625 643 aluminium sulphate SYSTEMATIC 23282999 A 666 679 zinc sulphate SYSTEMATIC 23282999 A 68 86 aluminium sulphate SYSTEMATIC 23282999 A 684 693 vitamin E FAMILY 23282999 A 814 832 aluminium sulphate SYSTEMATIC 23282999 A 928 930 Al FORMULA 23282999 T 0 13 Zinc sulphate SYSTEMATIC 23282999 T 18 27 vitamin E FAMILY 23282999 T 70 88 aluminium sulphate SYSTEMATIC 23284002 A 0 14 Trichostatin A TRIVIAL 23284002 A 1067 1070 DPI ABBREVIATION 23284002 A 1074 1077 NAC ABBREVIATION 23284002 A 1092 1095 TSA ABBREVIATION 23284002 A 1128 1136 H(2)O(2) FORMULA 23284002 A 1202 1205 GSH ABBREVIATION 23284002 A 1266 1269 TSA ABBREVIATION 23284002 A 140 146 oxygen SYSTEMATIC 23284002 A 1448 1451 TSA ABBREVIATION 23284002 A 1557 1560 TSA ABBREVIATION 23284002 A 16 19 TSA ABBREVIATION 23284002 A 175 178 TSA ABBREVIATION 23284002 A 372 375 TSA ABBREVIATION 23284002 A 381 388 NAD(P)H ABBREVIATION 23284002 A 407 426 diphenyleneiodonium TRIVIAL 23284002 A 428 431 DPI ABBREVIATION 23284002 A 450 467 N-acetyl-cysteine SYSTEMATIC 23284002 A 469 472 NAC ABBREVIATION 23284002 A 552 564 sulforaphane TRIVIAL 23284002 A 741 749 H(2)O(2) FORMULA 23284002 A 765 776 glutathione TRIVIAL 23284002 A 778 781 GSH ABBREVIATION 23284002 A 920 923 TSA ABBREVIATION 23284002 T 0 14 Trichostatin A TRIVIAL 23284002 T 70 76 oxygen SYSTEMATIC 23284082 A 1149 1154 amide FAMILY 23284082 A 19 34 prostaglandin E FAMILY 23284082 A 329 333 urea TRIVIAL 23284082 A 338 348 creatinine TRIVIAL 23284082 A 429 444 bis-sulfonamide SYSTEMATIC 23284082 A 482 487 amide FAMILY 23284082 A 683 688 amide FAMILY 23284082 A 822 827 amide FAMILY 23284082 T 0 5 Amide SYSTEMATIC 23284082 T 58 73 prostaglandin E FAMILY 23286198 A 123 157 hexadecyltrimethylammonium bromide SYSTEMATIC 23286198 A 159 163 CTAB ABBREVIATION 23286198 A 169 182 sodium oleate SYSTEMATIC 23286198 A 184 188 NaOL ABBREVIATION 23286198 A 399 403 CTAB ABBREVIATION 23286198 A 444 448 CTAB ABBREVIATION 23286198 A 449 453 NaOL ABBREVIATION 23286198 A 582 586 CTAB ABBREVIATION 23286240 A 181 204 dimeric phloroglucinols FAMILY 23286240 A 205 236 mallotojaponins B (1) and C (2) MULTIPLE 23286240 A 262 276 mallotophenone TRIVIAL 23286240 A 36 43 ethanol SYSTEMATIC 23286240 A 527 538 chloroquine TRIVIAL 23286240 T 37 60 dimeric phloroglucinols FAMILY 23287045 A 0 6 Copper SYSTEMATIC 23287045 A 1051 1053 Cu FORMULA 23287045 A 1224 1226 Cu FORMULA 23287045 A 269 271 Cu FORMULA 23287045 A 484 498 copper sulfate SYSTEMATIC 23287045 A 500 505 CuSO4 FORMULA 23287045 A 510 527 copper (II) oxide SYSTEMATIC 23287045 A 529 532 CuO FORMULA 23287045 A 541 543 Cu FORMULA 23287045 A 562 578 transition metal FAMILY 23287045 A 741 747 oxygen SYSTEMATIC 23287045 A 8 10 Cu FORMULA 23287045 A 834 842 Cu salts FAMILY 23287045 A 847 850 CuO FORMULA 23287045 A 878 883 CuSO4 FORMULA 23287045 A 90 92 Cu FORMULA 23287045 T 12 24 copper salts FAMILY 23287056 A 1100 1116 N-alkylcarbazole FAMILY 23287056 A 32 40 tyrosine TRIVIAL 23287056 A 950 960 carbazoles FAMILY 23287056 T 43 59 N-alkylcarbazole FAMILY 23287389 A 0 20 Perfluoroalkyl acids FAMILY 23287389 A 1041 1045 PFOS ABBREVIATION 23287389 A 1050 1054 PFOA ABBREVIATION 23287389 A 1087 1092 PFHxS ABBREVIATION 23287389 A 1110 1129 perfluoroalkyl acid FAMILY 23287389 A 1346 1357 bisphenol A TRIVIAL 23287389 A 1359 1364 PBDEs ABBREVIATION 23287389 A 1369 1373 PCBs ABBREVIATION 23287389 A 257 262 PFHxS ABBREVIATION 23287389 A 32 57 perfluorohexane sulfonate SYSTEMATIC 23287389 A 409 429 perfluoroalkyl acids FAMILY 23287389 A 431 435 PFOS ABBREVIATION 23287389 A 440 444 PFOA ABBREVIATION 23287389 A 59 64 PFHxS ABBREVIATION 23287389 A 625 630 PFHxS ABBREVIATION 23287389 A 865 870 PFHxS ABBREVIATION 23287389 A 926 934 nicotine TRIVIAL 23287389 T 83 88 PFHxS ABBREVIATION 23287538 A 1024 1031 ethanol SYSTEMATIC 23287538 A 1069 1076 ethanol SYSTEMATIC 23287538 A 1140 1147 ethanol SYSTEMATIC 23287538 A 1211 1218 sucrose TRIVIAL 23287538 A 1242 1253 amphetamine TRIVIAL 23287538 A 1525 1532 ethanol SYSTEMATIC 23287538 A 1771 1778 ethanol SYSTEMATIC 23287538 A 214 221 ethanol SYSTEMATIC 23287538 A 313 320 ethanol SYSTEMATIC 23287538 A 366 373 ethanol SYSTEMATIC 23287538 A 582 589 ethanol SYSTEMATIC 23287538 A 652 659 ethanol SYSTEMATIC 23287538 A 709 716 ethanol SYSTEMATIC 23287538 A 850 857 ethanol SYSTEMATIC 23287538 A 935 942 ethanol SYSTEMATIC 23287700 A 0 11 Cannabinoid FAMILY 23287700 A 1008 1014 AM4113 IDENTIFIER 23287700 A 1060 1066 AM4054 IDENTIFIER 23287700 A 1176 1182 AM4054 IDENTIFIER 23287700 A 1218 1228 rimonabant TRIVIAL 23287700 A 1233 1239 AM4113 IDENTIFIER 23287700 A 506 515 SR141716A IDENTIFIER 23287700 A 517 527 rimonabant TRIVIAL 23287700 A 55 65 rimonabant TRIVIAL 23287700 A 562 568 AM4113 IDENTIFIER 23287700 A 741 747 AM4054 IDENTIFIER 23287700 A 771 777 AM4054 IDENTIFIER 23287700 A 914 939 Δ(9)-tetrahydrocannabinol SYSTEMATIC 23287700 A 970 980 rimonabant TRIVIAL 23287700 T 0 11 Cannabinoid FAMILY 23287710 A 193 203 acrylamide TRIVIAL 23287710 A 329 339 acrylamide TRIVIAL 23287710 A 631 641 acrylamide TRIVIAL 23287710 A 661 672 glycidamide TRIVIAL 23287710 A 752 763 glycidamide TRIVIAL 23287710 A 764 774 acrylamide TRIVIAL 23287710 A 89 99 acrylamide TRIVIAL 23287710 T 36 46 acrylamide TRIVIAL 23287710 T 51 62 glycidamide TRIVIAL 23287728 A 3 15 L-amino acid FAMILY 23287728 A 304 314 amino-acid FAMILY 23287728 A 393 398 L-Leu FORMULA 23287728 T 49 61 L-amino acid FAMILY 23288049 A 0 30 Polybrominated diphenyl ethers FAMILY 23288049 A 1196 1202 BDE-49 ABBREVIATION 23288049 A 1236 1241 PBDEs ABBREVIATION 23288049 A 1534 1538 PBDE ABBREVIATION 23288049 A 195 200 PBDEs ABBREVIATION 23288049 A 319 324 PBDEs ABBREVIATION 23288049 A 32 37 PBDEs ABBREVIATION 23288049 A 334 336 Br FORMULA 23288049 A 358 392 2,2',4,4'-tetrabromodiphenyl ether SYSTEMATIC 23288049 A 394 400 BDE-47 ABBREVIATION 23288049 A 406 440 2,2',4,5'-tetrabromodiphenyl ether SYSTEMATIC 23288049 A 442 448 BDE-49 ABBREVIATION 23288049 A 544 550 BDE-49 ABBREVIATION 23288049 A 657 663 BDE-47 ABBREVIATION 23288049 A 801 807 BDE-49 ABBREVIATION 23288049 A 888 894 BDE-49 ABBREVIATION 23288049 T 32 38 BDE-49 ABBREVIATION 23288052 A 1016 1019 DEN ABBREVIATION 23288052 A 1156 1162 CCl(4) FORMULA 23288052 A 348 366 diethylnitrosamine SYSTEMATIC 23288052 A 368 371 DEN ABBREVIATION 23288052 A 431 451 carbon tetrachloride SYSTEMATIC 23288052 A 453 459 CCl(4) FORMULA 23288052 A 604 607 DEN ABBREVIATION 23288091 A 1423 1436 carbamazepine TRIVIAL 23288091 A 1438 1446 clobazam TRIVIAL 23288091 A 1448 1460 ethosuximide TRIVIAL 23288091 A 1462 1472 gabapentin TRIVIAL 23288091 A 1474 1484 lacosamide TRIVIAL 23288091 A 1486 1497 lamotrigine TRIVIAL 23288091 A 1499 1512 levetiracetam TRIVIAL 23288091 A 1514 1527 oxcarbazepine SYSTEMATIC 23288091 A 1529 1542 phenobarbital TRIVIAL 23288091 A 1544 1553 phenytoin TRIVIAL 23288091 A 1555 1564 primidone TRIVIAL 23288091 A 1566 1576 topiramate TRIVIAL 23288091 A 1582 1592 zonisamide TRIVIAL 23288091 A 1610 1623 valproic acid TRIVIAL 23288091 A 1661 1671 clonazepam TRIVIAL 23288091 A 1673 1696 eslicarbazepine acetate SYSTEMATIC 23288091 A 1698 1707 felbamate TRIVIAL 23288091 A 1709 1719 pregabalin TRIVIAL 23288091 A 1721 1731 retigabine TRIVIAL 23288091 A 1733 1743 rufinamide TRIVIAL 23288091 A 1745 1756 stiripentol TRIVIAL 23288091 A 1758 1767 tiagabine TRIVIAL 23288091 A 1773 1783 vigabatrin TRIVIAL 23288103 A 230 232 Sn FORMULA 23288103 A 234 236 Ti FORMULA 23288103 A 242 244 Si FORMULA 23288103 A 377 383 oxygen SYSTEMATIC 23288103 A 523 529 oxygen SYSTEMATIC 23288103 A 554 556 Sn FORMULA 23288103 A 669 675 oxygen SYSTEMATIC 23288103 A 725 733 hematite TRIVIAL 23288103 A 73 81 hematite TRIVIAL 23288103 A 769 771 Sn FORMULA 23288103 A 83 94 α-Fe(2)O(3) FORMULA 23288103 A 844 850 oxygen SYSTEMATIC 23288103 A 865 867 Sn FORMULA 23288103 T 6 14 hematite TRIVIAL 23288103 T 69 75 oxygen SYSTEMATIC 23288866 A 1013 1023 loperamide TRIVIAL 23288866 A 1305 1315 loperamide TRIVIAL 23288866 A 1504 1522 aminobenzotriazole SYSTEMATIC 23288866 A 1710 1720 loperamide TRIVIAL 23288866 A 531 541 loperamide TRIVIAL 23288866 A 650 660 loperamide TRIVIAL 23288866 A 894 904 loperamide TRIVIAL 23288866 A 953 963 loperamide TRIVIAL 23288866 T 51 61 loperamide TRIVIAL 23289403 A 138 152 poly(l-lysine) SYSTEMATIC 23289403 A 154 157 PLL ABBREVIATION 23289403 A 215 226 vinylbenzyl SYSTEMATIC 23289412 A 1053 1062 triazoles FAMILY 23289412 A 1306 1359 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole MULTIPLE 23289412 A 1628 1681 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole MULTIPLE 23289412 A 1793 1802 triazoles FAMILY 23289412 A 18 27 triazoles FAMILY 23289412 A 254 260 carbon SYSTEMATIC 23289412 A 265 273 nitrogen SYSTEMATIC 23289412 A 311 320 triazoles FAMILY 23289412 A 622 675 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole MULTIPLE 23289412 A 786 795 triazoles FAMILY 23289412 T 6 59 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole MULTIPLE 23289585 A 1042 1052 nucleobase FAMILY 23289585 A 115 120 dA5'p SYSTEMATIC 23289585 A 1152 1157 dG5'p SYSTEMATIC 23289585 A 1229 1239 nucleobase FAMILY 23289585 A 123 156 2'-deoxycytidine-5'-monophosphate SYSTEMATIC 23289585 A 1402 1417 phosphate ester SYSTEMATIC 23289585 A 158 163 dC5'p SYSTEMATIC 23289585 A 166 200 2'-deoxyguanosine-5'-monophosphate SYSTEMATIC 23289585 A 202 207 dG5'p SYSTEMATIC 23289585 A 214 240 thymidine-5'-monophosphate SYSTEMATIC 23289585 A 242 246 T5'p SYSTEMATIC 23289585 A 445 460 mononucleotides FAMILY 23289585 A 45 68 2'-deoxymononucleotides FAMILY 23289585 A 79 113 2'-deoxyadenosine-5'-monophosphate SYSTEMATIC 23289585 A 941 946 dA5'p SYSTEMATIC 23289585 A 948 953 dC5'p SYSTEMATIC 23289585 A 959 963 T5'p SYSTEMATIC 23289585 A 989 995 ribose TRIVIAL 23289585 T 78 93 mononucleotides FAMILY 23289615 A 279 289 2-propanol SYSTEMATIC 23289615 A 870 877 alcohol FAMILY 23289624 A 205 210 amide FAMILY 23289624 A 324 329 amide FAMILY 23289624 T 55 60 amide FAMILY 23289646 A 405 426 poly(ethylene glycol) SYSTEMATIC 23289710 A 144 147 Ser FORMULA 23289710 A 148 151 Sec FORMULA 23289710 A 225 238 dimethylallyl SYSTEMATIC 23289710 A 245 248 Ser FORMULA 23289710 A 249 252 Sec FORMULA 23289710 A 364 367 Ser FORMULA 23289710 A 368 371 Sec FORMULA 23289710 A 405 439 [(14)C]dimethylallyl pyrophosphate SYSTEMATIC 23289710 A 449 452 Ser FORMULA 23289710 A 453 456 Sec FORMULA 23289710 A 46 56 amino acid FAMILY 23289710 A 471 474 Ser FORMULA 23289710 A 475 478 Sec FORMULA 23289710 A 57 60 Sec FORMULA 23289710 A 62 76 selenocysteine TRIVIAL 23289710 T 27 30 Ser FORMULA 23289710 T 31 34 Sec FORMULA 23289710 T 36 47 isopentenyl SYSTEMATIC 23289872 A 1097 1105 fluorine SYSTEMATIC 23289872 A 1132 1140 hydrogen SYSTEMATIC 23289872 A 1220 1228 hydrogen SYSTEMATIC 23289872 A 283 287 (1)H FORMULA 23289872 A 289 294 (19)F FORMULA 23289872 A 317 322 (15)N FORMULA 23289872 A 43 48 CF(3) FORMULA 23289872 A 454 456 FH FORMULA 23289872 A 465 467 FN FORMULA 23289872 A 480 482 FF FORMULA 23289872 A 536 544 hydrogen SYSTEMATIC 23289872 A 58 61 N-H FORMULA 23289872 A 606 611 CF(3) FORMULA 23289872 A 64 67 F-C FORMULA 23289872 A 654 662 hydrogen SYSTEMATIC 23289872 A 675 683 hydrogen SYSTEMATIC 23289872 A 68 76 hydrogen SYSTEMATIC 23289872 A 747 752 (19)F FORMULA 23289872 A 753 758 (19)F FORMULA 23289872 A 855 857 NH FORMULA 23289872 T 14 17 CF3 FORMULA 23289872 T 27 30 N-H FORMULA 23289872 T 33 36 F-C FORMULA 23289872 T 37 45 hydrogen SYSTEMATIC 23290050 A 188 194 silica TRIVIAL 23290050 A 259 270 indoxyl red TRIVIAL 23290050 A 298 303 (13)C FORMULA 23290050 A 3 9 indole SYSTEMATIC 23290050 A 309 313 (1)H FORMULA 23290050 A 364 375 indoxyl red TRIVIAL 23290050 T 22 33 indoxyl red TRIVIAL 23290262 A 314 326 Alkyladenine FAMILY 23290262 A 973 996 methyl methanesulfonate SYSTEMATIC 23290262 A 998 1001 MMS ABBREVIATION 23290262 T 0 12 Alkyladenine FAMILY 23290724 A 111 117 copper SYSTEMATIC 23290724 A 122 126 zinc SYSTEMATIC 23290724 A 161 162 C FORMULA 23290724 A 485 489 Zn²⁺ FORMULA 23290724 A 497 498 N FORMULA 23290724 A 511 512 C FORMULA 23290724 A 558 559 C FORMULA 23290724 A 70 71 N FORMULA 23290724 T 0 4 Zinc SYSTEMATIC 23291118 A 12 36 5- and 8-methoxypsoralen MULTIPLE 23291118 A 211 215 MOPs ABBREVIATION 23291118 A 221 237 N-bromosaccharin SYSTEMATIC 23291118 A 367 375 acrylate SYSTEMATIC 23291118 A 38 41 MOP ABBREVIATION 23291118 A 380 388 benzoate SYSTEMATIC 23291118 A 393 402 cinnamate SYSTEMATIC 23291118 A 427 432 8-MOP SYSTEMATIC 23291118 A 487 495 psoralen TRIVIAL 23291118 A 506 520 butyl acrylate SYSTEMATIC 23291118 A 526 546 tert-butyl cinnamate SYSTEMATIC 23291118 A 730 742 indomethacin TRIVIAL 23291118 A 782 787 8-MOP SYSTEMATIC 23291118 A 850 862 indomethacin TRIVIAL 23291118 A 901 906 8-MOP SYSTEMATIC 23291118 T 62 77 methoxypsoralen SYSTEMATIC 23291264 A 1085 1094 cisplatin TRIVIAL 23291264 A 1157 1167 creatinine TRIVIAL 23291264 A 1178 1182 urea TRIVIAL 23291264 A 1183 1191 nitrogen SYSTEMATIC 23291264 A 1252 1261 cisplatin TRIVIAL 23291264 A 1395 1404 cisplatin TRIVIAL 23291264 A 1462 1471 cisplatin TRIVIAL 23291264 A 1670 1679 cisplatin TRIVIAL 23291264 A 1836 1845 cisplatin TRIVIAL 23291264 A 185 194 cisplatin TRIVIAL 23291264 A 196 227 cis-diamminedichloroplatinum II SYSTEMATIC 23291264 A 495 504 cisplatin TRIVIAL 23291264 A 628 637 cisplatin TRIVIAL 23291264 A 824 833 cisplatin TRIVIAL 23291264 T 122 131 cisplatin TRIVIAL 23292343 A 1051 1062 amino acids FAMILY 23292343 A 502 528 ribulose-1, 5-bisphosphate SYSTEMATIC 23292343 A 840 850 amino acid FAMILY 23292752 A 1059 1070 rivaroxaban TRIVIAL 23292752 A 1075 1083 apixaban TRIVIAL 23292752 A 1449 1460 rivaroxaban TRIVIAL 23292752 A 1465 1473 apixaban TRIVIAL 23292752 A 1873 1883 argatroban TRIVIAL 23292752 A 1949 1959 dabigatran TRIVIAL 23292752 A 2002 2022 Dabigatran etexilate TRIVIAL 23292752 A 2139 2149 dabigatran TRIVIAL 23292752 A 215 224 vitamin K FAMILY 23292752 A 2193 2203 Dabigatran TRIVIAL 23292752 A 2395 2405 dabigatran TRIVIAL 23292752 A 2546 2556 Dabigatran TRIVIAL 23292752 A 2642 2662 dabigatran etexilate TRIVIAL 23292752 A 2990 3000 dabigatran TRIVIAL 23292752 A 3015 3026 rivaroxaban TRIVIAL 23292752 A 3031 3039 apixaban TRIVIAL 23292752 A 3052 3062 dabigatran TRIVIAL 23292752 A 3115 3125 dabigatran TRIVIAL 23292752 A 3264 3275 rivaroxaban TRIVIAL 23292752 A 3278 3286 apixaban TRIVIAL 23292752 A 3289 3299 dabigatran TRIVIAL 23292752 T 55 64 vitamin K FAMILY 23292753 A 0 5 Sugar FAMILY 23292753 A 135 154 methylcyclopropenes FAMILY 23292753 A 237 249 mannosamines FAMILY 23292753 A 282 287 azide SYSTEMATIC 23292753 A 288 294 alkyne FAMILY 23292753 A 36 55 methylcyclopropenes FAMILY 23292753 A 399 405 sugars FAMILY 23292753 A 80 89 tetrazine FAMILY 23292753 T 70 82 cyclopropene SYSTEMATIC 23292753 T 83 94 mannosamine FAMILY 23292768 A 1002 1003 C FORMULA 23292768 A 1013 1018 CH2OH FORMULA 23292768 A 1030 1033 O-H FORMULA 23292768 A 1132 1140 methanol SYSTEMATIC 23292768 A 179 180 D FORMULA 23292768 A 181 183 OD FORMULA 23292768 A 197 198 D FORMULA 23292768 A 199 201 CD FORMULA 23292768 A 26 43 propargyl alcohol SYSTEMATIC 23292768 A 301 303 OH FORMULA 23292768 A 309 314 C≡C-H FORMULA 23292768 A 428 432 C-OH FORMULA 23292768 A 660 661 D FORMULA 23292768 A 662 664 CD FORMULA 23292768 A 674 675 D FORMULA 23292768 A 676 678 OD FORMULA 23292768 A 923 926 O-H FORMULA 23292768 T 118 121 H-O FORMULA 23292768 T 140 141 C FORMULA 23292768 T 86 103 propargyl alcohol SYSTEMATIC 23292797 A 1177 1185 adenylyl TRIVIAL 23292797 A 1229 1233 cAMP ABBREVIATION 23292797 A 544 563 5-hydroxytryptamine SYSTEMATIC 23292797 A 569 573 5-HT SYSTEMATIC 23292797 A 654 696 [(35)S]guanosine 5'-(3-O-thio)triphosphate SYSTEMATIC 23292797 A 929 933 5-HT SYSTEMATIC 23292881 A 139 147 aluminum SYSTEMATIC 23292881 A 171 179 zeolites FAMILY 23292881 A 271 279 aluminum SYSTEMATIC 23292881 A 347 354 zeolite TRIVIAL 23292881 T 53 61 aluminum SYSTEMATIC 23292881 T 91 99 zeolites FAMILY 23292988 A 199 207 Sm2 CuO4 FORMULA 23292988 A 212 218 LaFeO3 FORMULA 23292988 A 277 285 Sm2 CuO4 FORMULA 23292988 A 329 337 Sm2 CuO4 FORMULA 23292988 A 339 345 LaFeO3 FORMULA 23292988 T 38 44 LaFeO3 FORMULA 23292988 T 45 52 Sm2CuO4 FORMULA 23293000 A 1123 1128 sugar FAMILY 23293000 A 1129 1138 phosphate SYSTEMATIC 23293094 A 73 97 polychlorinated biphenyl FAMILY 23293094 A 99 102 PCB ABBREVIATION 23293950 T 28 34 pyrene SYSTEMATIC 23293962 A 1217 1221 iron SYSTEMATIC 23293962 A 1280 1284 iron SYSTEMATIC 23293962 A 80 84 iron SYSTEMATIC 23293966 A 249 263 quarteranthene TRIVIAL 23293966 A 593 601 peroxide SYSTEMATIC 23293966 A 90 98 graphene TRIVIAL 23293966 T 103 111 graphene TRIVIAL 23293966 T 34 48 quarteranthene TRIVIAL 23293970 A 1027 1029 O₃ FORMULA 23293970 A 1059 1061 O₃ FORMULA 23293970 A 1221 1229 dopamine TRIVIAL 23293970 A 126 128 O₃ FORMULA 23293970 A 1277 1279 O₃ FORMULA 23293970 A 1399 1401 O₃ FORMULA 23293970 A 1459 1461 O₃ FORMULA 23293970 A 1628 1630 O₃ FORMULA 23293970 A 341 343 O₃ FORMULA 23293970 A 570 572 O₃ FORMULA 23293970 A 709 711 O₃ FORMULA 23293970 A 803 805 O₃ FORMULA 23293970 A 81 86 ozone TRIVIAL 23293970 A 88 90 O₃ FORMULA 23293970 A 95 97 O₃ FORMULA 23293970 A 952 962 superoxide TRIVIAL 23293970 A 989 991 O₃ FORMULA 23293970 A 995 997 O₃ FORMULA 23293970 T 24 29 ozone TRIVIAL 23293971 A 1161 1164 NiO FORMULA 23293971 A 200 212 nickel oxide SYSTEMATIC 23293971 A 214 217 NiO FORMULA 23293971 A 620 623 NiO FORMULA 23293971 A 988 991 NiO FORMULA 23293971 T 98 101 NiO FORMULA 23294326 A 1002 1013 ganglioside TRIVIAL 23294326 A 126 137 ganglioside TRIVIAL 23294326 A 161 172 ganglioside TRIVIAL 23294326 A 296 307 ganglioside TRIVIAL 23294326 A 740 751 ganglioside TRIVIAL 23294566 A 0 9 Androgens FAMILY 23294566 A 1005 1013 androgen FAMILY 23294566 A 1031 1040 oestrogen FAMILY 23294566 A 1085 1093 androgen FAMILY 23294566 A 1098 1107 oestrogen FAMILY 23294566 A 1136 1144 androgen FAMILY 23294566 A 1149 1158 oestrogen FAMILY 23294566 A 122 131 androgens FAMILY 23294566 A 1252 1260 androgen FAMILY 23294566 A 1367 1375 androgen FAMILY 23294566 A 14 24 oestrogens FAMILY 23294566 A 1497 1505 androgen FAMILY 23294566 A 1628 1636 Androgen FAMILY 23294566 A 1695 1703 androgen FAMILY 23294566 A 1816 1824 androgen FAMILY 23294566 A 189 198 oestrogen FAMILY 23294566 A 303 312 androgens FAMILY 23294566 A 317 327 oestrogens FAMILY 23294566 A 650 658 androgen FAMILY 23294566 A 695 703 androgen FAMILY 23294566 A 835 845 oestradiol TRIVIAL 23294566 A 891 900 oestrogen FAMILY 23294566 A 973 981 androgen FAMILY 23294566 T 100 109 androgens FAMILY 23294566 T 117 127 oestrogens FAMILY 23294566 T 41 49 androgen FAMILY 23294699 A 129 135 sterol FAMILY 23294699 A 16 45 pentacyclic hemiacetal sterol FAMILY 23294699 A 162 168 acetyl SYSTEMATIC 23294699 A 349 355 sterol FAMILY 23294699 A 46 59 nephthoacetal TRIVIAL 23294699 T 0 29 Pentacyclic hemiacetal sterol FAMILY 23294895 A 0 7 Aspirin TRIVIAL 23294895 A 185 192 aspirin TRIVIAL 23294895 A 222 229 aspirin TRIVIAL 23294895 A 371 378 aspirin TRIVIAL 23294895 A 568 575 aspirin TRIVIAL 23294895 A 699 706 aspirin TRIVIAL 23294895 A 805 812 aspirin TRIVIAL 23294895 T 0 7 Aspirin TRIVIAL 23294895 T 12 19 aspirin TRIVIAL 23295156 A 1046 1052 l-NAME ABBREVIATION 23295156 A 196 207 l-Carnitine TRIVIAL 23295156 A 270 281 fatty acids FAMILY 23295156 A 670 676 l-NAME ABBREVIATION 23295156 A 728 734 l-NAME ABBREVIATION 23295156 A 877 882 NADPH ABBREVIATION 23295156 T 0 11 L-Carnitine TRIVIAL 23295223 A 1147 1155 steroids FAMILY 23295223 A 1159 1165 carbon SYSTEMATIC 23295223 A 1216 1225 estradiol TRIVIAL 23295223 A 1230 1241 cholesterol TRIVIAL 23295223 A 1413 1420 steroid FAMILY 23295223 A 174 194 3,17β-Hydroxysteroid FAMILY 23295223 A 1923 1935 testosterone TRIVIAL 23295223 A 2029 2041 testosterone TRIVIAL 23295223 A 2113 2121 steroids FAMILY 23295223 A 335 342 steroid FAMILY 23295223 A 58 66 steroids FAMILY 23295223 A 71 103 polycyclic aromatic hydrocarbons FAMILY 23295223 A 731 743 testosterone TRIVIAL 23295223 A 752 761 estradiol TRIVIAL 23295223 A 772 783 cholesterol TRIVIAL 23295223 A 865 877 testosterone TRIVIAL 23295223 T 47 54 steroid FAMILY 23295223 T 83 103 3,17β-hydroxysteroid FAMILY 23295224 A 1072 1076 keto SYSTEMATIC 23295224 A 1135 1152 α-hydroxy ketones FAMILY 23295224 A 1206 1210 keto SYSTEMATIC 23295224 A 1327 1341 2,3-butanediol SYSTEMATIC 23295224 A 1347 1354 acetoin TRIVIAL 23295224 A 1477 1486 diketones FAMILY 23295224 A 1491 1498 acetoin TRIVIAL 23295224 A 1589 1606 α-hydroxy ketones FAMILY 23295224 A 1611 1616 diols FAMILY 23295224 A 253 262 diketones FAMILY 23295224 A 4 21 α-hydroxy ketones FAMILY 23295224 A 422 439 α-hydroxy ketones FAMILY 23295224 A 444 449 diols FAMILY 23295224 A 455 472 vicinal diketones FAMILY 23295224 A 540 545 NADPH ABBREVIATION 23295224 A 580 599 glucose-6-phosphate SYSTEMATIC 23295224 A 604 623 glucose-6-phosphate SYSTEMATIC 23295224 T 27 48 alpha-hydroxy ketones FAMILY 23295224 T 53 66 vicinal diols FAMILY 23295229 A 0 8 Aldehyde SYSTEMATIC 23295229 A 1048 1054 NAD(+) ABBREVIATION 23295229 A 1059 1072 butyraldehyde SYSTEMATIC 23295229 A 1109 1113 NADH ABBREVIATION 23295229 A 1158 1162 NADH ABBREVIATION 23295229 A 121 127 Mg(2+) FORMULA 23295229 A 1230 1234 NADH ABBREVIATION 23295229 A 1243 1249 Mg(2+) FORMULA 23295229 A 1370 1376 Mg(2+) FORMULA 23295229 A 1402 1408 Mg(2+) FORMULA 23295229 A 1504 1508 NADH ABBREVIATION 23295229 A 1587 1596 magnesium SYSTEMATIC 23295229 A 1630 1634 NADH ABBREVIATION 23295229 A 1705 1711 Mg(2+) FORMULA 23295229 A 1763 1769 Mg(2+) FORMULA 23295229 A 179 183 NADH ABBREVIATION 23295229 A 1861 1865 NADH ABBREVIATION 23295229 A 1950 1959 magnesium SYSTEMATIC 23295229 A 1984 1988 NADH ABBREVIATION 23295229 A 321 325 NADH ABBREVIATION 23295229 A 370 374 NADH ABBREVIATION 23295229 A 460 466 Mg(2+) FORMULA 23295229 A 487 491 NADH ABBREVIATION 23295229 A 571 575 NADH ABBREVIATION 23295229 A 624 628 NADH ABBREVIATION 23295229 A 68 77 aldehydes FAMILY 23295229 A 690 696 Mg(2+) FORMULA 23295229 A 794 798 NADH ABBREVIATION 23295229 A 81 97 carboxylic acids FAMILY 23295229 A 839 845 Mg(2+) FORMULA 23295229 A 866 872 Mg(2+) FORMULA 23295229 A 910 916 NAD(+) ABBREVIATION 23295229 A 946 950 NADH ABBREVIATION 23295229 A 979 983 NADH ABBREVIATION 23295229 T 45 54 magnesium SYSTEMATIC 23295229 T 74 78 NADH ABBREVIATION 23295229 T 88 96 aldehyde SYSTEMATIC 23295582 A 0 25 Terbinafine hydrochloride TRIVIAL 23295582 A 27 30 TBF ABBREVIATION 23295582 A 296 299 TBF ABBREVIATION 23295582 A 300 303 HCl FORMULA 23295582 A 31 34 HCl FORMULA 23295582 A 719 722 TBF ABBREVIATION 23295582 A 723 726 HCl FORMULA 23295582 A 804 817 poloxamer gel TRIVIAL 23295582 T 30 41 Terbinafine TRIVIAL 23295582 T 42 45 HCl FORMULA 23295739 A 1061 1079 Methylprednisolone SYSTEMATIC 23295739 A 1111 1125 corticosterone TRIVIAL 23295739 A 255 269 corticosterone TRIVIAL 23295739 A 648 662 corticosterone TRIVIAL 23295739 A 918 936 methylprednisolone SYSTEMATIC 23295740 A 1043 1046 TAM ABBREVIATION 23295740 A 1078 1081 TAM ABBREVIATION 23295740 A 1252 1255 TAM ABBREVIATION 23295740 A 1388 1391 TAM ABBREVIATION 23295740 A 146 154 estrogen FAMILY 23295740 A 1546 1549 TAM ABBREVIATION 23295740 A 20 23 TAM ABBREVIATION 23295740 A 246 249 TAM ABBREVIATION 23295740 A 364 367 TAM ABBREVIATION 23295740 A 38 46 estrogen FAMILY 23295740 A 561 564 TAM ABBREVIATION 23295740 A 783 786 TAM ABBREVIATION 23295740 A 814 818 zinc SYSTEMATIC 23295740 A 9 18 tamoxifen TRIVIAL 23295740 T 0 9 Tamoxifen TRIVIAL 23296019 A 522 525 GDP ABBREVIATION 23296019 A 547 550 GTP ABBREVIATION 23296100 A 0 9 Manganese SYSTEMATIC 23296100 A 11 13 Mn FORMULA 23296100 A 1136 1143 thymine TRIVIAL 23296100 A 1276 1292 N-acetylcysteine SYSTEMATIC 23296100 A 1294 1297 NAC ABBREVIATION 23296100 A 1306 1317 glutathione TRIVIAL 23296100 A 1319 1322 GSH ABBREVIATION 23296100 A 1384 1391 thymine TRIVIAL 23296100 A 1523 1525 Mn FORMULA 23296100 A 1838 1844 Mn(2+) FORMULA 23296100 A 1885 1892 thymine TRIVIAL 23296100 A 2045 2051 Mn(2+) FORMULA 23296100 A 305 307 Mn FORMULA 23296100 A 476 478 Mn FORMULA 23296100 A 590 596 Mn(2+) FORMULA 23296100 A 635 641 Mn(2+) FORMULA 23296100 A 764 770 Mn(2+) FORMULA 23296100 A 800 802 Mn FORMULA 23296100 A 840 856 propidium iodide TRIVIAL 23296100 A 951 957 Mn(2+) FORMULA 23296100 A 996 1002 Mn(2+) FORMULA 23296100 T 0 9 Manganese SYSTEMATIC 23296100 T 105 116 glutathione TRIVIAL 23296100 T 121 137 N-acetylcysteine SYSTEMATIC 23296100 T 81 88 thymine TRIVIAL 23296102 A 1188 1196 Acrolein TRIVIAL 23296102 A 1256 1264 Acrolein TRIVIAL 23296102 A 289 297 Acrolein TRIVIAL 23296102 A 351 359 Acrolein TRIVIAL 23296102 A 446 454 Acrolein TRIVIAL 23296102 A 723 731 Acrolein TRIVIAL 23296102 A 85 93 Acrolein TRIVIAL 23296102 A 879 889 superoxide TRIVIAL 23296102 A 938 953 malondialdehyde TRIVIAL 23296102 A 995 1003 Acrolein TRIVIAL 23296102 T 0 8 Acrolein TRIVIAL 23296105 A 0 7 Uranium SYSTEMATIC 23296105 A 1223 1230 uranium SYSTEMATIC 23296105 A 272 279 uranium SYSTEMATIC 23296105 A 349 356 uranium SYSTEMATIC 23296105 A 535 542 uranium SYSTEMATIC 23296105 A 677 684 uranium SYSTEMATIC 23296105 A 755 762 Uranium SYSTEMATIC 23296105 A 920 927 uranium SYSTEMATIC 23296105 A 995 998 UO₂ FORMULA 23296105 T 14 21 uranium SYSTEMATIC 23296122 A 125 142 metalloporphyrins FAMILY 23296122 A 166 175 magnesium SYSTEMATIC 23296122 A 180 184 zinc SYSTEMATIC 23296122 T 29 58 magnesium and zinc porphyrins MULTIPLE 23296156 A 424 435 chromium-51 SYSTEMATIC 23296368 A 1010 1028 3-methylglutaconic SYSTEMATIC 23296368 A 1065 1087 3-methylglutaconyl-CoA SYSTEMATIC 23296368 A 1139 1146 leucine TRIVIAL 23296368 A 1209 1227 3-methylglutaconic SYSTEMATIC 23296368 A 160 183 3-methylglutaconic acid SYSTEMATIC 23296368 A 1644 1662 3-methylglutaconic SYSTEMATIC 23296368 A 1786 1791 3-MGA SYSTEMATIC 23296368 A 18 40 3-methylglutaconic aci SYSTEMATIC 23296368 A 353 376 3-methylglutaconic acid SYSTEMATIC 23296368 A 398 416 3-methylglutaconic SYSTEMATIC 23296368 A 642 660 3-methylglutaconic SYSTEMATIC 23296368 A 914 932 3-methylglutaconic SYSTEMATIC 23296368 T 33 51 3-methylglutaconic SYSTEMATIC 23296837 A 1039 1042 EHT ABBREVIATION 23296837 A 1175 1187 nitric oxide SYSTEMATIC 23296837 A 1200 1203 EHT ABBREVIATION 23296837 A 1292 1298 MPP(+) ABBREVIATION 23296837 A 1463 1466 EHT ABBREVIATION 23296837 A 1527 1530 EHT ABBREVIATION 23296837 A 1539 1543 MPTP ABBREVIATION 23296837 A 244 274 eicosanoyl-5-hydroxytryptamide SYSTEMATIC 23296837 A 276 279 EHT ABBREVIATION 23296837 A 505 508 EHT ABBREVIATION 23296837 A 530 534 MPTP ABBREVIATION 23296837 A 575 578 EHT ABBREVIATION 23296837 A 673 677 MPTP ABBREVIATION 23296837 A 751 759 dopamine TRIVIAL 23296837 A 764 772 tyrosine TRIVIAL 23296837 A 824 827 EHT ABBREVIATION 23296837 A 873 877 MPTP ABBREVIATION 23296837 A 988 991 EHT ABBREVIATION 23296837 T 78 82 MPTP ABBREVIATION 23296902 A 1032 1039 glucose TRIVIAL 23296902 A 1094 1096 Cr FORMULA 23296902 A 1159 1167 graphite TRIVIAL 23296902 A 1215 1217 Cr FORMULA 23296902 A 1231 1238 glucose TRIVIAL 23296902 A 1297 1299 Cr FORMULA 23296902 A 1334 1338 iron SYSTEMATIC 23296902 A 1409 1411 Cr FORMULA 23296902 A 1432 1436 iron SYSTEMATIC 23296902 A 1449 1451 Cr FORMULA 23296902 A 1509 1513 iron SYSTEMATIC 23296902 A 1586 1588 Cr FORMULA 23296902 A 1633 1635 Cr FORMULA 23296902 A 166 168 Cr FORMULA 23296902 A 19 27 chromium SYSTEMATIC 23296902 A 269 271 Cr FORMULA 23296902 A 29 31 Cr FORMULA 23296902 A 353 355 Cr FORMULA 23296902 A 419 421 Cr FORMULA 23296902 A 519 526 glucose TRIVIAL 23296902 A 575 577 Cr FORMULA 23296902 A 626 628 Cr FORMULA 23296902 A 659 661 Cr FORMULA 23296902 A 709 711 Cr FORMULA 23296902 A 844 846 Cr FORMULA 23296902 A 939 941 Cr FORMULA 23296902 T 8 16 chromium SYSTEMATIC 23296902 T 86 94 chromium SYSTEMATIC 23296950 A 0 7 Chrysin TRIVIAL 23296950 A 1064 1067 TGs ABBREVIATION 23296950 A 1083 1094 cholesterol TRIVIAL 23296950 A 1107 1114 chrysin TRIVIAL 23296950 A 1119 1127 luteolin TRIVIAL 23296950 A 1170 1177 chrysin TRIVIAL 23296950 A 12 20 luteolin TRIVIAL 23296950 A 1248 1256 luteolin TRIVIAL 23296950 A 1280 1282 NO FORMULA 23296950 A 1327 1334 chrysin TRIVIAL 23296950 A 1339 1347 luteolin TRIVIAL 23296950 A 1494 1496 NO FORMULA 23296950 A 195 209 streptozotocin TRIVIAL 23296950 A 211 214 STZ ABBREVIATION 23296950 A 233 240 chrysin TRIVIAL 23296950 A 245 253 luteolin TRIVIAL 23296950 A 288 291 STZ ABBREVIATION 23296950 A 366 373 glucose TRIVIAL 23296950 A 415 428 triglycerides FAMILY 23296950 A 430 433 TGs ABBREVIATION 23296950 A 442 453 cholesterol TRIVIAL 23296950 A 45 55 flavonoids FAMILY 23296950 A 482 493 cholesterol TRIVIAL 23296950 A 553 556 KCl FORMULA 23296950 A 558 571 phenylephrine TRIVIAL 23296950 A 578 591 acetylcholine SYSTEMATIC 23296950 A 593 596 ACh ABBREVIATION 23296950 A 602 605 ACh ABBREVIATION 23296950 A 614 616 NO FORMULA 23296950 A 736 743 chrysin TRIVIAL 23296950 A 748 756 luteolin TRIVIAL 23296950 A 890 893 KCl FORMULA 23296950 A 932 935 ACh ABBREVIATION 23296950 A 943 950 chrysin TRIVIAL 23296950 A 955 963 luteolin TRIVIAL 23296950 A 999 1002 ACh ABBREVIATION 23296950 T 0 7 Chrysin TRIVIAL 23296950 T 12 20 Luteolin TRIVIAL 23296950 T 130 132 NO FORMULA 23296979 A 1074 1078 EATN ABBREVIATION 23296979 A 1116 1120 cAMP ABBREVIATION 23296979 A 1167 1173 Ca(2+) FORMULA 23296979 A 1378 1382 EATN ABBREVIATION 23296979 A 251 316 erythro-(7S,8R)-7-acetoxy-3,4,3`,5`-tetramethoxy-8-O-4`-neolignan SYSTEMATIC 23296979 A 318 322 EATN ABBREVIATION 23296979 A 327 336 neolignan FAMILY 23296979 A 394 398 EATN ABBREVIATION 23296979 A 673 677 EATN ABBREVIATION 23296979 A 735 751 arachidonic acid TRIVIAL 23296979 A 753 757 EATN ABBREVIATION 23296979 A 790 799 serotonin TRIVIAL 23296979 A 804 807 ATP ABBREVIATION 23296979 A 821 837 thromboxane B(2) TRIVIAL 23296979 A 878 882 EATN ABBREVIATION 23296979 A 905 915 cyclic AMP TRIVIAL 23296979 A 917 921 cAMP ABBREVIATION 23296979 A 959 965 Ca(2+) FORMULA 23296979 T 26 91 Erythro-(7S,8R)-7-acetoxy-3,4,3`,5`-tetramethoxy-8-O-4`-neolignan SYSTEMATIC 23297346 A 0 16 Hydrogen sulfide SYSTEMATIC 23297346 A 103 118 carbon monoxide SYSTEMATIC 23297346 A 155 168 cystathionine TRIVIAL 23297346 A 178 191 cystathionine TRIVIAL 23297346 A 18 23 H(2)S FORMULA 23297346 A 208 226 3-mercaptopyruvate SYSTEMATIC 23297346 A 246 251 H(2)S FORMULA 23297346 A 446 451 H(2)S FORMULA 23297346 A 598 603 H(2)S FORMULA 23297346 A 757 762 H(2)S FORMULA 23297346 A 86 98 nitric oxide SYSTEMATIC 23297346 A 863 868 H(2)S FORMULA 23297346 T 0 16 Hydrogen sulfide SYSTEMATIC 23297689 A 459 467 sabinene TRIVIAL 23297712 A 216 230 sesquiterpenes FAMILY 23297712 A 240 247 hinesol TRIVIAL 23297712 A 249 264 z-caryophyllene TRIVIAL 23297712 A 266 276 β-maaliene TRIVIAL 23297712 A 278 289 γ-gurjunene TRIVIAL 23297712 A 291 313 silphiperfol-5-en-3-ol SYSTEMATIC 23297712 A 315 320 ledol TRIVIAL 23297712 A 322 335 cubecol-1-epi SYSTEMATIC 23297712 A 341 358 muurola-3,5-diene SYSTEMATIC 23297712 A 441 454 dexamethasone TRIVIAL 23297713 A 559 573 carbon dioxide SYSTEMATIC 23297713 A 742 756 hydroxyproline SYSTEMATIC 23297713 A 884 895 acetic acid SYSTEMATIC 23297755 A 101 111 CH(2)Cl(2) FORMULA 23297755 A 1036 1098 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide SYSTEMATIC 23297755 A 227 249 sesquiterpene lactones FAMILY 23297755 A 257 279 cis-fused guaianolides FAMILY 23297755 A 308 391 1α-hydroxy-3βH-3α,4α-epoxy-4,10-dimethyl-5αH,7αH,8βH,10αH-guai-11(13)-ene-7,8-olide SYSTEMATIC 23297755 A 421 492 1αH-4α-hydroxy-4,10-dimethyl-5αH,7αH,8βH,10αH-guai-11(13)-ene-7,8-olide SYSTEMATIC 23297755 A 935 944 Efavirenz TRIVIAL 23297755 A 946 949 EFV ABBREVIATION 23297755 T 43 64 sesquiterpene lactone FAMILY 23297817 A 103 119 Au(0.75)Pd(0.25) FORMULA 23297817 A 1095 1106 metal oxide FAMILY 23297817 A 1150 1152 Pd FORMULA 23297817 A 1209 1225 Au(0.75)Pd(0.25) FORMULA 23297817 A 1239 1241 Au FORMULA 23297817 A 127 138 metal oxide FAMILY 23297817 A 1300 1316 Au(0.75)Pd(0.25) FORMULA 23297817 A 217 219 CO FORMULA 23297817 A 240 242 CO FORMULA 23297817 A 245 252 1/2O(2) FORMULA 23297817 A 255 260 CO(2) FORMULA 23297817 A 299 306 alumina TRIVIAL 23297817 A 35 61 Au(0.80)Pd(0.20)-Fe(x)O(y) FAMILY 23297817 A 529 555 Au(0.80)Pd(0.20)-Fe(x)O(y) FAMILY 23297817 A 591 607 Au(0.75)Pd(0.25) FORMULA 23297817 A 688 697 Fe(x)O(y) FAMILY 23297817 A 706 722 Au(0.80)Pd(0.20) FORMULA 23297817 A 812 823 metal oxide FAMILY 23297817 A 825 834 Fe(x)O(y) FAMILY 23297817 A 863 879 Au(0.80)Pd(0.20) FORMULA 23297817 T 0 2 CO FORMULA 23297817 T 26 52 Au(0.80)Pd(0.20)-Fe(x)O(y) FAMILY 23298140 A 1245 1252 glucose TRIVIAL 23298140 A 1260 1272 fructosamine SYSTEMATIC 23298140 A 1386 1403 hydrogen peroxide SYSTEMATIC 23298140 A 1412 1420 peroxide SYSTEMATIC 23298140 A 1432 1442 flavonoids FAMILY 23298140 A 1444 1457 methylglyoxal SYSTEMATIC 23298140 A 424 430 sugars FAMILY 23298140 A 451 459 fructose TRIVIAL 23298140 A 470 477 glucose TRIVIAL 23298140 A 521 537 free amino acids FAMILY 23298140 A 561 572 polyphenols FAMILY 23298140 A 580 591 polyphenols FAMILY 23298140 A 593 603 flavonoids FAMILY 23298140 A 967 978 polyphenols FAMILY 23298158 A 133 140 F4-TCNQ FORMULA 23298158 A 186 200 aluminum oxide SYSTEMATIC 23298158 A 332 339 F4-TCNQ FORMULA 23298158 A 377 381 P3HT ABBREVIATION 23298158 A 468 475 F4-TCNQ FORMULA 23298158 A 49 71 poly(3-hexylthiophene) SYSTEMATIC 23298158 A 580 584 P3HT ABBREVIATION 23298158 A 585 592 F4-TNCQ FORMULA 23298158 A 73 77 P3HT ABBREVIATION 23298158 A 79 131 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane SYSTEMATIC 23298158 T 126 133 Alumina TRIVIAL 23298158 T 36 58 Poly(3-hexylthiophene) SYSTEMATIC 23298158 T 59 95 Fluorinated Tetracyanoquinodimethane FAMILY 23298322 A 812 843 2-(dimethylamino)ethyl acrylate SYSTEMATIC 23298322 A 845 850 DMAEA ABBREVIATION 23298322 A 880 892 acrylic acid TRIVIAL 23298810 A 11 29 prostaglandin E(2) TRIVIAL 23298810 A 198 209 PF-04693627 IDENTIFIER 23298810 A 257 268 benzoxazole SYSTEMATIC 23298810 A 286 297 PF-04693627 IDENTIFIER 23298810 A 426 437 PF-04693627 IDENTIFIER 23298810 A 524 536 benzoxazoles FAMILY 23298810 A 673 684 cyclohexane SYSTEMATIC 23298810 T 51 63 benzoxazoles FAMILY 23299191 A 415 430 sodium chloride SYSTEMATIC 23299191 A 78 94 dimethylarginine SYSTEMATIC 23299191 T 22 38 dimethylarginine SYSTEMATIC 23299194 A 1164 1177 nitrofurazone SYSTEMATIC 23299194 A 1355 1369 hydroxyproline SYSTEMATIC 23299194 A 1697 1711 hydroxyproline SYSTEMATIC 23299909 A 817 818 N FORMULA 23299909 A 847 848 N FORMULA 23300000 A 290 299 flavonoid FAMILY 23300000 A 354 360 La(3+) FORMULA 23300000 A 362 368 Ce(3+) FORMULA 23300000 A 374 380 Nd(3+) FORMULA 23300000 A 507 513 Ce(3+) FORMULA 23300000 A 517 523 Nd(3+) FORMULA 23300000 A 640 649 flavonoid FAMILY 23300000 A 70 79 flavonoid FAMILY 23300000 A 730 743 phenylalanine TRIVIAL 23300000 A 744 751 ammonia SYSTEMATIC 23300000 A 919 929 superoxide TRIVIAL 23300056 A 207 215 dopamine TRIVIAL 23300056 A 470 478 dopamine TRIVIAL 23300056 A 629 643 arylpiperazine FAMILY 23300056 T 66 81 arylpiperazines FAMILY 23300056 T 90 98 dopamine TRIVIAL 23300227 A 1191 1197 TRV130 IDENTIFIER 23300227 A 184 192 Morphine TRIVIAL 23300227 A 466 474 morphine TRIVIAL 23300227 A 508 514 TRV130 IDENTIFIER 23300227 A 516 613 [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethyl})amine SYSTEMATIC 23300227 A 675 681 TRV130 IDENTIFIER 23300227 A 755 763 morphine TRIVIAL 23300227 A 854 860 TRV130 IDENTIFIER 23300227 A 964 972 morphine TRIVIAL 23300227 A 997 1003 TRV130 IDENTIFIER 23300227 T 145 153 morphine TRIVIAL 23300338 A 328 331 Lys FORMULA 23300338 A 79 88 rapamycin TRIVIAL 23301246 A 1097 1100 NiO FORMULA 23301246 A 12 15 NiO FORMULA 23301246 A 1434 1437 NiO FORMULA 23301246 A 1532 1535 NiO FORMULA 23301246 A 1628 1631 NiO FORMULA 23301246 A 174 177 NiO FORMULA 23301246 A 1761 1770 triiodide SYSTEMATIC 23301246 A 1771 1777 iodide SYSTEMATIC 23301246 A 195 203 fluorine SYSTEMATIC 23301246 A 210 219 tin oxide SYSTEMATIC 23301246 A 221 224 FTO ABBREVIATION 23301246 A 652 655 NiO FORMULA 23301246 T 32 44 nickel oxide SYSTEMATIC 23301495 A 116 123 cyanide SYSTEMATIC 23301495 A 253 263 sulfanegen TRIVIAL 23301495 A 264 279 triethanolamine SYSTEMATIC 23301495 A 336 343 cyanide SYSTEMATIC 23301495 T 0 7 Cyanide SYSTEMATIC 23301495 T 66 74 dithiane SYSTEMATIC 23301495 T 76 86 sulfanegen TRIVIAL 23301495 T 93 111 3-mercaptopyruvate SYSTEMATIC 23301701 A 1024 1032 hydrogen SYSTEMATIC 23301701 A 110 146 1-butyl-3-methylimidazolium chloride SYSTEMATIC 23301701 A 148 156 [bmim]Cl FORMULA 23301701 A 159 194 1-ethyl-3-methylimidazolium acetate SYSTEMATIC 23301701 A 1645 1653 [bmim]Cl FORMULA 23301701 A 1658 1669 [dmim][DMP] ABBREVIATION 23301701 A 196 206 [emim][Ac] ABBREVIATION 23301701 A 213 254 1,3-dimethylimidazolium dimethylphosphate SYSTEMATIC 23301701 A 256 267 [dmim][DMP] ABBREVIATION 23301701 T 77 88 imidazolium SYSTEMATIC 23301853 A 254 267 benzoquinones FAMILY 23301853 A 269 280 betulinan A TRIVIAL 23301853 A 289 300 betulinan C TRIVIAL 23301853 A 327 336 terphenyl FAMILY 23301853 A 347 363 BTH-II0204-207:A IDENTIFIER 23301853 T 0 13 Benzoquinones FAMILY 23301853 T 18 27 terphenyl FAMILY 23301948 A 287 292 amide FAMILY 23302583 A 108 126 7-mercaptocoumarin SYSTEMATIC 23302583 A 415 423 prazosin TRIVIAL 23302583 A 582 598 phenylpiperazine SYSTEMATIC 23302583 A 815 833 7-mercaptocoumarin SYSTEMATIC 23302583 T 53 71 7-mercaptocoumarin SYSTEMATIC 23302594 A 10 26 himeic acids E-G MULTIPLE 23302594 A 161 174 himeic acid A TRIVIAL 23302594 T 0 16 Himeic acids E-G MULTIPLE 23302594 T 22 32 4-pyridone SYSTEMATIC 23303191 A 1006 1009 UDP ABBREVIATION 23303191 A 1010 1015 sugar FAMILY 23303191 A 1053 1056 UDP ABBREVIATION 23303191 A 1057 1063 sugars FAMILY 23303191 A 1200 1203 UDP ABBREVIATION 23303191 A 1204 1210 sugars FAMILY 23303191 A 1340 1343 UDP ABBREVIATION 23303191 A 1344 1363 N-acetylhexosamines FAMILY 23303191 A 1368 1371 UDP ABBREVIATION 23303191 A 1372 1387 glucuronic acid TRIVIAL 23303191 A 138 141 UDP ABBREVIATION 23303191 A 142 161 N-acetylglucosamine SYSTEMATIC 23303191 A 1512 1515 UDP ABBREVIATION 23303191 A 1516 1522 sugars FAMILY 23303191 A 166 169 UDP ABBREVIATION 23303191 A 170 185 glucuronic acid TRIVIAL 23303191 A 540 543 UDP ABBREVIATION 23303191 A 544 564 N-acetyl glucosamine SYSTEMATIC 23303191 A 587 598 glucosamine TRIVIAL 23303191 A 678 689 glucosamine TRIVIAL 23303191 A 734 741 Glucose TRIVIAL 23303191 A 783 786 UDP ABBREVIATION 23303191 A 787 793 sugars FAMILY 23303191 T 54 57 UDP ABBREVIATION 23303191 T 58 64 GlcNAc FORMULA 23303198 A 1076 1086 olmesartan TRIVIAL 23303198 A 116 127 telmisartan TRIVIAL 23303198 A 1177 1187 olmesartan TRIVIAL 23303198 A 1298 1308 olmesartan TRIVIAL 23303198 A 1319 1330 telmisartan TRIVIAL 23303198 A 1418 1428 olmesartan TRIVIAL 23303198 A 1536 1546 olmesartan TRIVIAL 23303198 A 346 356 olmesartan TRIVIAL 23303198 A 373 384 telmisartan TRIVIAL 23303198 A 533 540 glucose TRIVIAL 23303198 A 88 98 olmesartan TRIVIAL 23303198 A 941 951 olmesartan TRIVIAL 23303198 A 997 1007 olmesartan TRIVIAL 23303198 T 52 62 olmesartan TRIVIAL 23303198 T 67 78 telmisartan TRIVIAL 23303441 A 0 10 Paroxetine TRIVIAL 23303441 A 1017 1024 sulfate SYSTEMATIC 23303441 A 1113 1123 paroxetine TRIVIAL 23303441 A 1316 1319 ATP ABBREVIATION 23303441 A 298 305 sulfate SYSTEMATIC 23303441 A 358 368 paroxetine TRIVIAL 23303441 A 604 614 paroxetine TRIVIAL 23303441 A 666 682 [(3)H]paroxetine SYSTEMATIC 23303441 T 37 47 paroxetine TRIVIAL 23303486 A 1050 1059 thioether SYSTEMATIC 23303486 A 45 51 biotin TRIVIAL 23303486 A 937 943 biotin TRIVIAL 23303486 A 955 960 amide FAMILY 23303710 A 0 15 Myriaporone 3/4 MULTIPLE 23303710 A 195 210 myriaporone 3/4 MULTIPLE 23303710 A 374 389 myriaporone 3/4 MULTIPLE 23303710 A 458 473 myriaporone 3/4 MULTIPLE 23303710 A 588 603 myriaporone 3/4 MULTIPLE 23303710 T 22 37 myriaporone 3/4 MULTIPLE 23305110 A 207 215 LaAlO(3) FORMULA 23305110 A 216 224 SrTiO(3) FORMULA 23305110 A 337 345 SrTiO(3) FORMULA 23305110 A 377 379 Si FORMULA 23305110 A 77 85 LaAlO(3) FORMULA 23305110 A 90 98 SrTiO(3) FORMULA 23305110 T 27 33 LaAlO3 FORMULA 23305110 T 34 40 SrTiO3 FORMULA 23305294 A 0 7 Lithium SYSTEMATIC 23305294 A 148 155 lithium SYSTEMATIC 23305294 A 392 399 lithium SYSTEMATIC 23305294 A 481 491 Li(3)PS(4) FORMULA 23305294 A 587 594 lithium SYSTEMATIC 23305294 A 630 640 Li(3)PS(4) FORMULA 23305294 A 906 916 Li(3)PS(4) FORMULA 23305444 A 374 399 benzofuran salicylic acid SYSTEMATIC 23305444 A 921 935 salicylic acid TRIVIAL 23305444 T 102 140 6-Hydroxy-benzofuran-5-carboxylic acid SYSTEMATIC 23305444 T 70 78 tyrosine TRIVIAL 23305465 A 101 114 meroterpenoid FAMILY 23305465 A 126 141 albatrelins D-F MULTIPLE 23305465 A 169 268 6a,7,8,9,10,10a-hexahydro-3,6,9-trimethyl-6-(4-methyl-3-penten-1-yl)-1,9-epoxy-6H-dibenzo[b,d]pyran SYSTEMATIC 23305465 A 277 288 confluentin TRIVIAL 23305465 A 546 558 Albatrelin F TRIVIAL 23305465 A 58 73 albatrelins A-C MULTIPLE 23305465 A 6 14 grifolin TRIVIAL 23305465 A 627 638 Confluentin TRIVIAL 23305465 T 0 13 Meroterpenoid FAMILY 23305777 A 101 112 miliumollin TRIVIAL 23305777 A 114 134 7-methoxymiliumollin SYSTEMATIC 23305777 A 136 157 3'-methoxymiliumollin SYSTEMATIC 23305777 A 159 181 4'-O-methylmiliumollin SYSTEMATIC 23305777 A 186 200 miliumollinone TRIVIAL 23305777 A 212 228 8-O-4' neolignan SYSTEMATIC 23305777 A 235 248 miliusamollin TRIVIAL 23305777 A 341 352 Miliumollin TRIVIAL 23305777 A 354 375 3'-methoxymiliumollin SYSTEMATIC 23305777 A 377 391 miliumollinone TRIVIAL 23305777 A 472 486 Miliumollinone TRIVIAL 23305777 A 64 92 dihydrobenzofuran neolignans FAMILY 23305777 T 0 10 Neolignans FAMILY 23305807 A 0 9 Estrogens FAMILY 23305807 A 1027 1038 glutathione TRIVIAL 23305807 A 1119 1131 nitric oxide SYSTEMATIC 23305807 A 1145 1160 malondialdehyde TRIVIAL 23305807 A 1226 1229 RES ABBREVIATION 23305807 A 1311 1314 RES ABBREVIATION 23305807 A 140 149 bile acid FAMILY 23305807 A 1475 1483 estrogen FAMILY 23305807 A 251 262 resveratrol TRIVIAL 23305807 A 264 267 RES ABBREVIATION 23305807 A 368 371 RES ABBREVIATION 23305807 A 49 65 ethinylestradiol SYSTEMATIC 23305807 A 581 590 bile acid FAMILY 23305807 A 638 647 bilirubin TRIVIAL 23305807 A 728 738 superoxide TRIVIAL 23305807 A 750 761 glutathione TRIVIAL 23305807 A 774 785 glutathione TRIVIAL 23305807 A 869 879 sulfhydryl FAMILY 23305807 A 888 891 RES ABBREVIATION 23305807 A 930 937 alanine TRIVIAL 23305807 A 959 970 glutathione TRIVIAL 23305807 A 971 972 S FORMULA 23305807 A 992 1000 glutamyl TRIVIAL 23305807 T 23 34 resveratrol TRIVIAL 23305807 T 43 59 ethinylestradiol SYSTEMATIC 23305918 A 131 150 pyrazine-2-(1H)-one SYSTEMATIC 23305918 A 269 288 ma'edamines A and B MULTIPLE 23305918 A 583 594 ma'edamines FAMILY 23305918 A 631 642 ma'edamines FAMILY 23305918 A 71 95 ma'edamines A (18) and B MULTIPLE 23305918 T 79 98 ma'edamines A and B MULTIPLE 23305993 A 1000 1006 GW9962 IDENTIFIER 23305993 A 1207 1213 LYSO-7 ABBREVIATION 23305993 A 13 96 (5Z)-5-[(5-bromo-1H-indol-3-yl)methylene]-3-(4-chlorobenzyl)-thiazolidine-2,4-dione SYSTEMATIC 23305993 A 490 496 LYSO-7 ABBREVIATION 23305993 A 644 651 LYSO-07 ABBREVIATION 23305993 A 935 947 nitric oxide SYSTEMATIC 23305993 A 949 951 NO FORMULA 23305993 A 98 104 LYSO-7 ABBREVIATION 23306171 A 101 111 diterpenes FAMILY 23306171 A 14 25 diterpenoid FAMILY 23306171 A 27 40 leptoclalin A TRIVIAL 23306171 A 6 13 spatane TRIVIAL 23306171 A 87 100 norcembranoid FAMILY 23306171 T 14 25 diterpenoid FAMILY 23306171 T 6 13 spatane TRIVIAL 23306172 A 16 90 2-hydroxy-5-((6-hydroxy-4-oxo-4H-pyran-2-yl)methyl)-2- propylchroman-4-one SYSTEMATIC 23306172 A 463 470 CD(3)OD FORMULA 23306172 A 509 518 deuterium SYSTEMATIC 23306172 A 572 590 2-hydroxy-γ-pyrone SYSTEMATIC 23306172 A 748 766 4-hydroxy-α-pyrone SYSTEMATIC 23306172 A 771 789 2-hydroxy-γ-pyrone SYSTEMATIC 23306172 A 952 963 methicillin TRIVIAL 23306172 T 107 120 hydroxypyrone SYSTEMATIC 23306790 A 24 36 verrucarin A TRIVIAL 23306790 A 741 752 glutathione TRIVIAL 23306790 A 757 776 N-acetyl-l-cysteine SYSTEMATIC 23306790 A 805 810 MG132 IDENTIFIER 23306790 T 0 12 Verrucarin A TRIVIAL 23306791 A 0 19 Polyethylene glycol SYSTEMATIC 23306791 A 22 39 polyvinyl alcohol SYSTEMATIC 23306791 A 41 48 PEG-PVA ABBREVIATION 23306791 A 578 585 PEG-PVA ABBREVIATION 23306791 A 891 898 PEG-PVA ABBREVIATION 23306791 T 0 19 Polyethylene glycol SYSTEMATIC 23306791 T 22 39 polyvinyl alcohol SYSTEMATIC 23307185 A 804 810 serine TRIVIAL 23307185 A 818 827 threonine TRIVIAL 23307790 A 664 671 glucose TRIVIAL 23311296 A 216 222 carbon SYSTEMATIC 23311296 A 309 315 carbon SYSTEMATIC 23311296 A 69 75 carbon SYSTEMATIC 23311296 A 838 844 carbon SYSTEMATIC 23311296 T 57 63 carbon SYSTEMATIC 23311700 A 1026 1029 RAI ABBREVIATION 23311700 A 937 940 RAI ABBREVIATION 23311718 A 1230 1244 [C(4)mim][AOT] FORMULA 23311718 A 1285 1302 [C(2)mim][TF(2)N] FORMULA 23311718 A 1303 1317 [C(4)mim][AOT] FORMULA 23311718 A 1318 1325 benzene SYSTEMATIC 23311718 A 1363 1380 [C(2)mim][TF(2)N] FORMULA 23311718 A 1383 1400 [C(4)mim][TF(2)N] FORMULA 23311718 A 1403 1420 [C(6)mim][TF(2)N] FORMULA 23311718 A 2423 2427 (1)H FORMULA 23311718 A 2584 2598 [C(4)mim][AOT] FORMULA 23311718 A 2599 2606 benzene SYSTEMATIC 23311718 A 444 458 [C(4)mim][AOT] FORMULA 23311718 A 459 466 benzene SYSTEMATIC 23311718 A 569 573 (1)H FORMULA 23311718 A 753 770 [C(6)mim][TF(2)N] FORMULA 23311718 A 773 790 [C(4)mim][TF(2)N] FORMULA 23311718 A 793 810 [C(2)mim][TF(2)N] FORMULA 23311718 A 913 930 [C(4)mim][TF(2)N] FORMULA 23311718 A 933 949 [C(4)mim][PF(6)] FORMULA 23311718 A 952 968 [C(4)mim][BF(4)] FORMULA 23311754 A 180 185 PEDOT ABBREVIATION 23311754 A 203 209 MnO(2) FORMULA 23311754 A 284 290 MnO(2) FORMULA 23311754 A 314 332 vanadium pentoxide SYSTEMATIC 23311754 A 333 365 poly(3,4-ethylenedioxythiophene) SYSTEMATIC 23311754 A 367 372 PEDOT ABBREVIATION 23311754 A 564 572 V(2)O(5) FORMULA 23311754 A 816 823 lithium SYSTEMATIC 23311754 T 14 18 V2O5 FORMULA 23311754 T 19 51 poly(3,4-ethylenedioxythiophene) SYSTEMATIC 23311754 T 52 56 MnO2 FORMULA 23312946 A 18 24 flavin FAMILY 23312946 A 276 289 monocillin II TRIVIAL 23312946 A 328 349 4-hydroxyisoquinoline SYSTEMATIC 23312946 A 358 379 6-hydroxyisoquinoline SYSTEMATIC 23312946 A 502 510 hydroxyl SYSTEMATIC 23312946 A 562 575 isoquinolines FAMILY 23312946 T 25 38 isoquinolines FAMILY 23312946 T 51 57 flavin FAMILY 23313176 A 1052 1058 carbon SYSTEMATIC 23313176 A 999 1009 dendrimers FAMILY 23313245 A 50 62 diaryl ureas FAMILY 23313245 T 6 18 diaryl ureas FAMILY 23313376 A 1063 1066 PTE ABBREVIATION 23313376 A 108 119 resveratrol TRIVIAL 23313376 A 1127 1130 Tyr FORMULA 23313376 A 1176 1179 PTE ABBREVIATION 23313376 A 1492 1495 PTE ABBREVIATION 23313376 A 155 158 PTE ABBREVIATION 23313376 A 1552 1557 AG490 TRIVIAL 23313376 A 1630 1633 PTE ABBREVIATION 23313376 A 1825 1828 PTE ABBREVIATION 23313376 A 292 295 PTE ABBREVIATION 23313376 A 51 64 Pterostilbene TRIVIAL 23313376 A 536 539 PTE ABBREVIATION 23313376 A 66 69 PTE ABBREVIATION 23313376 A 669 672 PTE ABBREVIATION 23313376 A 674 677 PTE ABBREVIATION 23313376 A 784 787 PTE ABBREVIATION 23313376 A 993 999 oxygen SYSTEMATIC 23313376 T 0 13 Pterostilbene TRIVIAL 23313448 A 1510 1513 ADP ABBREVIATION 23313448 A 368 379 amino acids FAMILY 23313621 A 1076 1094 phorbol dibutyrate SYSTEMATIC 23313621 A 154 176 1-nitro-2-phenylethane SYSTEMATIC 23313621 A 347 350 KCl FORMULA 23313621 A 495 508 phenylephrine TRIVIAL 23313621 A 510 513 PHE ABBREVIATION 23313621 A 710 716 Ca(2+) FORMULA 23313621 A 796 804 caffeine TRIVIAL 23313621 A 829 835 Ca(2+) FORMULA 23313621 A 850 854 K(+) FORMULA 23313621 A 900 907 CaCl(2) FORMULA 23313621 A 911 918 BaCl(2) FORMULA 23313621 T 24 46 1-nitro-2-phenylethane SYSTEMATIC 23313638 A 191 196 amide FAMILY 23313638 A 211 231 D-leucine-D-cysteine TRIVIAL 23313638 A 236 255 D-valine-D-cysteine TRIVIAL 23313638 A 282 291 D-alanine TRIVIAL 23313638 A 296 304 D-valine TRIVIAL 23313638 A 543 562 spiruchostatins A-D MULTIPLE 23313638 A 619 624 FK228 IDENTIFIER 23313638 A 626 636 romidepsin TRIVIAL 23313638 A 64 87 spiruchostatins C and D MULTIPLE 23313638 T 42 65 spiruchostatins C and D MULTIPLE 23313639 A 202 242 4,5,6-trimethoxybiphenyl-2-carbaldehydes FAMILY 23313639 A 28 64 E-2,3,4-trimethoxy-6-styrylbiphenyls FAMILY 23313639 A 370 389 3,4-(1,3-dioxolane) SYSTEMATIC 23313639 A 394 406 3,4-difluoro SYSTEMATIC 23313639 A 69 112 2,3,4-trimethoxy-6-(1-phenylvinyl)biphenyls FAMILY 23313639 A 769 779 colchicine TRIVIAL 23313639 T 24 45 biaryl aryl stilbenes FAMILY 23313639 T 46 55 ethylenes FAMILY 23313712 A 102 143 polyhexamethylene biguanide hydrochloride SYSTEMATIC 23313712 A 145 149 PHMB ABBREVIATION 23313712 A 156 160 PHMB ABBREVIATION 23313712 A 265 269 PHMB ABBREVIATION 23313712 A 328 339 neutral red TRIVIAL 23313712 A 49 68 phosphatidylcholine FAMILY 23313712 A 606 610 PHMB ABBREVIATION 23313712 A 673 677 PHMB ABBREVIATION 23313712 A 760 764 PHMB ABBREVIATION 23313712 A 836 840 PHMB ABBREVIATION 23313712 T 15 56 polyhexamethylene biguanide hydrochloride SYSTEMATIC 23313712 T 58 62 PHMB ABBREVIATION 23313712 T 69 88 phosphatidylcholine FAMILY 23313797 A 1011 1023 nicotinamide TRIVIAL 23313797 A 1110 1116 oxygen SYSTEMATIC 23313797 A 1126 1141 malondialdehyde TRIVIAL 23313797 A 1143 1150 nitrite SYSTEMATIC 23313797 A 1152 1163 glutathione TRIVIAL 23313797 A 1168 1178 superoxide TRIVIAL 23313797 A 1222 1225 Res ABBREVIATION 23313797 A 1273 1276 Res ABBREVIATION 23313797 A 1303 1307 EtOH FORMULA 23313797 A 1331 1334 Res ABBREVIATION 23313797 A 1456 1460 EtOH FORMULA 23313797 A 222 226 EtOH FORMULA 23313797 A 258 269 resveratrol TRIVIAL 23313797 A 271 274 Res ABBREVIATION 23313797 A 30 37 ethanol SYSTEMATIC 23313797 A 39 43 EtOH FORMULA 23313797 A 395 398 Res ABBREVIATION 23313797 A 402 409 ethanol SYSTEMATIC 23313797 A 570 573 Res ABBREVIATION 23313797 A 577 581 EtOH FORMULA 23313797 A 605 608 Res ABBREVIATION 23313797 A 704 717 Hoechst 33342 TRIVIAL 23313797 A 778 782 dUTP ABBREVIATION 23313797 A 826 830 EtOH FORMULA 23313797 A 866 869 Res ABBREVIATION 23313797 A 886 889 Res ABBREVIATION 23313797 A 910 936 5'-adenosine monophosphate SYSTEMATIC 23313797 T 111 118 ethanol SYSTEMATIC 23313797 T 27 38 resveratrol TRIVIAL 23313961 A 1258 1272 benzyl alcohol SYSTEMATIC 23313961 A 1322 1328 folate TRIVIAL 23313961 A 1476 1482 folate TRIVIAL 23313961 A 1483 1486 PEG ABBREVIATION 23313961 A 1487 1490 PCL ABBREVIATION 23313961 A 17 23 folate TRIVIAL 23313961 A 435 441 folate TRIVIAL 23313961 A 457 478 poly(ethylene glycol) SYSTEMATIC 23313961 A 481 497 polycaprolactone SYSTEMATIC 23313961 A 499 505 folate TRIVIAL 23313961 A 506 509 PEG ABBREVIATION 23313961 A 512 515 PCL ABBREVIATION 23313961 A 759 765 folate TRIVIAL 23313961 A 780 803 Triamcinolone acetonide SYSTEMATIC 23313961 A 854 860 folate TRIVIAL 23313961 T 19 25 folate TRIVIAL 23313961 T 36 49 triamcinolone TRIVIAL 23313962 A 1179 1189 temoporfin TRIVIAL 23313962 A 1242 1252 temoporfin TRIVIAL 23313962 A 1326 1336 temoporfin TRIVIAL 23313962 A 1460 1470 temoporfin TRIVIAL 23313962 A 1581 1591 temoporfin TRIVIAL 23313962 A 1685 1695 temoporfin TRIVIAL 23313962 A 205 215 temoporfin TRIVIAL 23313962 A 2052 2062 temoporfin TRIVIAL 23313962 A 2206 2215 glycerols FAMILY 23313962 A 264 275 cholesterol TRIVIAL 23313962 A 366 378 PEG2000-DSPE ABBREVIATION 23313962 A 562 572 temoporfin TRIVIAL 23313962 A 628 644 (14)C-temoporfin SYSTEMATIC 23313962 A 65 75 temoporfin TRIVIAL 23313962 A 688 698 temoporfin TRIVIAL 23313962 A 879 889 temoporfin TRIVIAL 23313962 A 941 951 temoporfin TRIVIAL 23313962 T 20 30 temoporfin TRIVIAL 23313962 T 89 99 temoporfin TRIVIAL 23314045 A 29 33 urea TRIVIAL 23314045 A 34 42 thiourea SYSTEMATIC 23314045 A 341 346 rutin TRIVIAL 23314045 A 415 422 methoxy SYSTEMATIC 23314045 A 427 434 bromine SYSTEMATIC 23314045 A 58 61 Gly FORMULA 23314045 A 62 65 Pro FORMULA 23314045 A 77 90 benzisoxazole SYSTEMATIC 23314045 T 35 39 urea TRIVIAL 23314045 T 44 52 thiourea SYSTEMATIC 23314045 T 68 75 glycine TRIVIAL 23314045 T 76 83 proline TRIVIAL 23314045 T 95 108 benzisoxazole SYSTEMATIC 23314276 A 1081 1089 androgen FAMILY 23314276 A 1090 1104 17β-trenbolone SYSTEMATIC 23314276 A 2165 2173 androgen FAMILY 23314276 A 255 264 androgens FAMILY 23314276 A 762 770 androgen FAMILY 23314276 A 925 933 androgen FAMILY 23314276 T 11 25 17β-trenbolone SYSTEMATIC 23314277 A 115 123 TiSiO(4) FORMULA 23314277 A 207 215 TiSiO(4) FORMULA 23314277 A 319 330 glutathione TRIVIAL 23314277 A 331 332 S FORMULA 23314277 A 347 354 lactate FAMILY 23314277 A 399 406 alanine TRIVIAL 23314277 A 411 418 lactate FAMILY 23314277 A 488 496 TiSiO(4) FORMULA 23314277 A 624 632 TiSiO(4) FORMULA 23314277 A 82 99 titanium silicate SYSTEMATIC 23314277 A 923 931 TiSiO(4) FORMULA 23314277 A 983 991 TiSiO(4) FORMULA 23314277 T 79 96 titanium silicate SYSTEMATIC 23314331 A 0 6 Copper SYSTEMATIC 23314331 A 1275 1277 Cu FORMULA 23314331 A 138 140 Cu FORMULA 23314331 A 354 356 Cu FORMULA 23314331 A 476 478 Cu FORMULA 23314331 A 8 10 Cu FORMULA 23314331 A 841 843 Cu FORMULA 23314331 A 934 936 Cu FORMULA 23314331 T 0 6 Copper SYSTEMATIC 23314757 A 1069 1073 COOH FORMULA 23314757 A 1103 1109 folate TRIVIAL 23314757 A 1250 1256 folate TRIVIAL 23314757 A 1339 1345 folate TRIVIAL 23314757 A 220 228 AgInS(2) FORMULA 23314757 A 229 232 ZnS FORMULA 23314757 A 466 474 carboxyl SYSTEMATIC 23314757 A 476 481 amine SYSTEMATIC 23314757 A 483 491 hydroxyl SYSTEMATIC 23314757 A 497 502 thiol FAMILY 23314757 A 813 821 carboxyl SYSTEMATIC 23314757 A 839 843 COOH FORMULA 23315090 A 1074 1085 cholesterol TRIVIAL 23315090 A 1090 1102 triglyceride FAMILY 23315090 A 706 717 cholesterol TRIVIAL 23315090 A 743 754 cholesterol TRIVIAL 23315090 A 822 833 cholesterol TRIVIAL 23315090 A 962 973 cholesterol TRIVIAL 23315216 A 74 91 pentose phosphate FAMILY 23315496 A 1040 1044 oATP ABBREVIATION 23315496 A 1310 1314 oATP ABBREVIATION 23315496 A 623 626 ATP ABBREVIATION 23315496 A 628 632 oATP ABBREVIATION 23315496 A 764 768 oATP ABBREVIATION 23315496 A 82 85 ATP ABBREVIATION 23315496 A 865 874 rapamycin TRIVIAL 23315496 T 44 47 ATP ABBREVIATION 23315585 A 0 11 Domoic acid TRIVIAL 23315585 A 118 125 kainate TRIVIAL 23315585 A 1256 1260 DomA ABBREVIATION 23315585 A 13 17 DomA ABBREVIATION 23315585 A 137 141 DomA ABBREVIATION 23315585 A 1426 1430 DomA ABBREVIATION 23315585 A 1472 1475 GSH ABBREVIATION 23315585 A 1611 1615 DomA ABBREVIATION 23315585 A 294 298 DomA ABBREVIATION 23315585 A 460 469 glutamate TRIVIAL 23315585 A 470 478 cysteine TRIVIAL 23315585 A 559 570 glutathione TRIVIAL 23315585 A 572 575 GSH ABBREVIATION 23315585 A 610 614 DomA ABBREVIATION 23315585 A 64 117 α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid SYSTEMATIC 23315585 A 680 684 DomA ABBREVIATION 23315585 A 849 853 DomA ABBREVIATION 23315585 A 926 930 DomA ABBREVIATION 23315585 A 950 953 GSH ABBREVIATION 23315585 T 10 21 domoic acid TRIVIAL 23315585 T 98 109 glutathione TRIVIAL 23315601 A 1075 1082 glucose TRIVIAL 23315601 A 1183 1190 glucose TRIVIAL 23315601 A 1276 1283 glucose TRIVIAL 23315601 A 1313 1320 glucose TRIVIAL 23315601 A 1510 1517 glucose TRIVIAL 23315601 A 152 159 glucose TRIVIAL 23315601 A 24 31 glucose TRIVIAL 23315601 A 260 267 glucose TRIVIAL 23315601 A 47 54 glucose TRIVIAL 23315601 A 598 605 glucose TRIVIAL 23315601 A 740 747 glucose TRIVIAL 23315601 A 921 928 glucose TRIVIAL 23315601 T 32 39 Glucose TRIVIAL 23315601 T 9 16 Glucose TRIVIAL 23315683 A 118 140 poly(3-hexylthiophene) SYSTEMATIC 23315683 A 141 147 indene TRIVIAL 23315683 A 148 151 C60 TRIVIAL 23315683 A 152 161 bisadduct FAMILY 23315683 A 163 167 P3HT ABBREVIATION 23315683 A 168 172 ICBA ABBREVIATION 23315683 A 21 24 InP FORMULA 23315683 A 37 38 N FORMULA 23315683 A 57 63 carbon SYSTEMATIC 23315791 A 15 33 poly(benzyl ether) SYSTEMATIC 23315791 A 314 331 (R,R)-G(2)DPENBoc FORMULA 23315791 A 433 437 (1)H FORMULA 23315791 A 666 674 hydrogen SYSTEMATIC 23315791 A 76 119 N-Boc-protected 1,2-diphenylethylenediamine FAMILY 23315791 T 0 43 N-Boc-protected 1,2-diphenylethylenediamine FAMILY 23315938 A 272 279 steroid FAMILY 23315938 A 452 462 fatty acid FAMILY 23315938 A 670 677 glucose TRIVIAL 23315938 A 679 689 fatty acid FAMILY 23315938 A 695 705 amino acid FAMILY 23315938 A 792 803 amino acids FAMILY 23315938 A 805 820 acyl carnitines FAMILY 23315938 T 76 83 steroid FAMILY 23315996 A 157 174 hydrogen peroxide SYSTEMATIC 23315996 A 2 4 Pd FORMULA 23316021 A 225 240 gadolinium(III) SYSTEMATIC 23316021 A 261 275 β-cyclodextrin TRIVIAL 23316021 A 277 285 Gd-F-βCD FORMULA 23316021 A 299 315 titanium dioxide SYSTEMATIC 23316021 A 317 321 TiO2 FORMULA 23316021 A 421 432 Fluorescein TRIVIAL 23316021 A 436 445 rhodamine TRIVIAL 23316021 A 522 537 gadolinium(III) SYSTEMATIC 23316021 T 0 10 Gadolinium SYSTEMATIC 23316913 A 1188 1193 TiCl₄ FORMULA 23316913 A 1232 1235 BSO ABBREVIATION 23316913 A 1334 1337 BSO ABBREVIATION 23316913 A 1394 1398 TiO₂ FORMULA 23316913 A 302 312 perovskite TRIVIAL 23316913 A 313 319 BaSnO₃ FORMULA 23316913 A 321 324 BSO ABBREVIATION 23316913 A 371 376 TiCl₄ FORMULA 23316913 A 449 452 BSO ABBREVIATION 23316913 A 487 492 TiCl₄ FORMULA 23316913 A 534 538 TiO₂ FORMULA 23316913 A 552 555 BSO ABBREVIATION 23316913 A 644 648 TiO₂ FORMULA 23316913 A 8 14 oxides FAMILY 23316913 A 806 811 TiCl₄ FORMULA 23316913 A 866 868 OH FORMULA 23316913 A 94 98 TiO₂ FORMULA 23316913 T 48 58 perovskite TRIVIAL 23316913 T 59 65 BaSnO₃ FORMULA 23316965 A 1343 1354 doxycycline TRIVIAL 23316966 A 1073 1084 doxycycline TRIVIAL 23317100 A 1154 1161 SZ-685C IDENTIFIER 23317100 A 1172 1179 SZ-685C IDENTIFIER 23317100 A 1308 1315 SZ-685C IDENTIFIER 23317100 A 1524 1531 SZ-685C IDENTIFIER 23317100 A 1763 1770 SZ-685C IDENTIFIER 23317100 A 1857 1864 SZ-685C IDENTIFIER 23317100 A 1935 1942 SZ-685C IDENTIFIER 23317100 A 2013 2020 SZ-685C IDENTIFIER 23317100 A 366 373 SZ-685C IDENTIFIER 23317100 A 41 48 SZ-685C IDENTIFIER 23317100 A 541 548 SZ-685C IDENTIFIER 23317100 A 623 626 MTT ABBREVIATION 23317100 A 659 663 FITC ABBREVIATION 23317100 A 773 780 SZ-685C IDENTIFIER 23317100 A 796 803 SZ-685C IDENTIFIER 23317100 A 949 956 SZ-685C IDENTIFIER 23317100 T 21 28 SZ-685C IDENTIFIER 23317159 A 1348 1359 Ruxolitinib TRIVIAL 23317159 A 1514 1522 TG101348 IDENTIFIER 23317159 A 1526 1535 SAR302503 IDENTIFIER 23317159 A 1537 1543 SB1518 IDENTIFIER 23317159 A 1545 1551 CEP701 IDENTIFIER 23317159 A 1556 1565 LY2784544 IDENTIFIER 23317159 A 1627 1638 tasocitinib TRIVIAL 23317159 A 256 264 tyrosine TRIVIAL 23317159 A 945 948 ATP ABBREVIATION 23317163 A 1318 1331 acetylcholine SYSTEMATIC 23317450 A 1094 1125 benzylic and aliphatic alcohols MULTIPLE 23317450 A 1188 1192 O(2) FORMULA 23317450 A 12 14 Cu FORMULA 23317450 A 1219 1236 benzylic alcohols FAMILY 23317450 A 1311 1329 aliphatic alcohols FAMILY 23317450 A 15 20 TEMPO ABBREVIATION 23317450 A 164 171 alcohol FAMILY 23317450 A 213 218 Cu(I) FORMULA 23317450 A 219 224 TEMPO ABBREVIATION 23317450 A 225 228 NMI ABBREVIATION 23317450 A 246 249 NMI ABBREVIATION 23317450 A 252 269 N-methylimidazole SYSTEMATIC 23317450 A 352 360 alcohols FAMILY 23317450 A 39 44 TEMPO ABBREVIATION 23317450 A 47 83 2,2,6,6-tetramethylpiperidine-N-oxyl SYSTEMATIC 23317450 A 470 501 benzylic and aliphatic alcohols MULTIPLE 23317450 A 805 810 Cu(I) FORMULA 23317450 A 815 820 TEMPO ABBREVIATION 23317450 A 821 822 H FORMULA 23317450 A 839 843 O(2) FORMULA 23317450 A 860 869 Cu(2)O(2) FORMULA 23317450 A 925 931 Cu(II) FORMULA 23317450 A 940 948 nitroxyl SYSTEMATIC 23317450 A 972 978 Cu(II) FORMULA 23317450 A 979 987 alkoxide FAMILY 23317450 T 13 22 copper(I) SYSTEMATIC 23317450 T 47 54 alcohol FAMILY 23317497 A 0 19 Pyrroloquinoxalines FAMILY 23317497 A 372 391 pyrroloquinoxalines FAMILY 23317497 A 562 581 pyrroloquinoxalines FAMILY 23317497 T 72 91 pyrroloquinoxalines FAMILY 23317498 A 1040 1051 nucleosides FAMILY 23317498 A 161 171 nucleoside FAMILY 23317498 A 762 772 nucleoside FAMILY 23317498 A 801 812 nucleosides FAMILY 23317498 A 822 833 nucleosides FAMILY 23317572 A 114 127 rotenoisins A FAMILY 23317572 A 171 179 rotenone TRIVIAL 23317572 A 33 54 isoflavonoid rotenone TRIVIAL 23317572 A 423 431 rotenone TRIVIAL 23317572 T 29 37 rotenone TRIVIAL 23318226 A 1141 1146 NADPH ABBREVIATION 23318226 A 1180 1185 NADPH ABBREVIATION 23318226 A 1272 1281 Ro-318220 IDENTIFIER 23318226 A 1283 1289 Gö6983 IDENTIFIER 23318226 A 1294 1303 Rottlerin TRIVIAL 23318226 A 133 144 nucleotides FAMILY 23318226 A 1444 1447 NAC ABBREVIATION 23318226 A 1449 1452 APO ABBREVIATION 23318226 A 1454 1457 DPI ABBREVIATION 23318226 A 1459 1468 Ro-318220 IDENTIFIER 23318226 A 1470 1476 Gö6983 IDENTIFIER 23318226 A 1478 1487 Rottlerin TRIVIAL 23318226 A 154 157 ATP ABBREVIATION 23318226 A 1615 1619 PGE2 ABBREVIATION 23318226 A 1709 1713 PGE2 ABBREVIATION 23318226 A 1750 1755 NADPH ABBREVIATION 23318226 A 297 308 nucleotides FAMILY 23318226 A 496 499 ATP ABBREVIATION 23318226 A 539 543 PGE2 ABBREVIATION 23318226 A 642 647 NADPH ABBREVIATION 23318226 A 657 685 diphenyleneiodonium chloride SYSTEMATIC 23318226 A 687 690 DPI ABBREVIATION 23318226 A 695 703 apocynin TRIVIAL 23318226 A 705 708 APO ABBREVIATION 23318226 A 717 736 N-acetyl-l-cysteine SYSTEMATIC 23318226 A 738 741 NAC ABBREVIATION 23318226 A 754 763 Ro-318220 IDENTIFIER 23318226 A 765 771 Gö6983 IDENTIFIER 23318226 A 776 785 Rottlerin TRIVIAL 23318226 A 937 941 PGE2 ABBREVIATION 23318226 T 0 3 ATP ABBREVIATION 23318226 T 107 112 NADPH ABBREVIATION 23318226 T 15 21 PGE(2) ABBREVIATION 23318425 A 399 405 acetyl SYSTEMATIC 23318425 A 464 470 lysine TRIVIAL 23318445 A 1150 1160 superoxide TRIVIAL 23318445 A 1224 1230 oxygen SYSTEMATIC 23318445 A 919 925 oxygen SYSTEMATIC 23318645 A 779 785 iodine SYSTEMATIC 23318729 A 0 12 Isotretinoin TRIVIAL 23318729 A 1028 1040 isotretinoin TRIVIAL 23318729 A 1191 1203 isotretinoin TRIVIAL 23318729 A 1248 1260 isotretinoin TRIVIAL 23318729 A 18 31 retinoic acid TRIVIAL 23318729 A 286 295 retinoids FAMILY 23318729 A 361 373 isotretinoin TRIVIAL 23318729 A 540 552 isotretinoin TRIVIAL 23318729 A 809 821 isotretinoin TRIVIAL 23318729 A 882 894 isotretinoin TRIVIAL 23318729 T 41 53 isotretinoin TRIVIAL 23318730 A 1056 1071 platinum folate SYSTEMATIC 23318730 A 1555 1565 folic acid TRIVIAL 23318730 A 1601 1611 folic acid TRIVIAL 23318730 A 1727 1737 folic acid TRIVIAL 23318730 A 465 475 folic acid TRIVIAL 23318730 A 612 620 platinum SYSTEMATIC 23318730 A 641 651 folic acid TRIVIAL 23318730 T 0 15 Platinum folate SYSTEMATIC 23318905 A 101 133 benzofuran-3-yl(phenyl)methanone SYSTEMATIC 23318905 A 11 17 NAD(+) ABBREVIATION 23318905 A 233 236 Phe FORMULA 23318905 A 241 244 Phe FORMULA 23318905 A 252 255 Ile FORMULA 23318905 A 272 280 hydroxyl SYSTEMATIC 23318905 A 301 307 phenyl SYSTEMATIC 23318905 A 317 318 H FORMULA 23318905 A 329 332 Asn FORMULA 23318905 A 345 404 (2,5-dihydroxyphenyl)(5-hydroxy-1-benzofuran-3-yl)methanone SYSTEMATIC 23318905 A 428 437 hydroxyls FAMILY 23318905 A 611 623 nicotinamide TRIVIAL 23318905 A 634 640 NAD(+) ABBREVIATION 23318905 A 739 745 NAD(+) ABBREVIATION 23318905 T 18 51 benzofuran-3-yl(phenyl)methanones FAMILY 23319584 A 0 7 Calcium SYSTEMATIC 23319584 A 161 167 Ca(2+) FORMULA 23319584 A 1686 1692 Ca(2+) FORMULA 23319584 A 391 401 nucleotide FAMILY 23319591 T 29 35 lysine TRIVIAL 23319591 T 45 51 lysine TRIVIAL 23320385 A 1095 1106 Delphinidin TRIVIAL 23320385 A 12 24 Anthocyanins FAMILY 23320385 A 1250 1264 anthocyanidins FAMILY 23320385 A 1317 1331 Anthocyanidins FAMILY 23320385 A 1399 1413 anthocyanidins FAMILY 23320385 A 233 247 anthocyanidins FAMILY 23320385 A 249 260 delphinidin TRIVIAL 23320385 A 262 270 cyanidin TRIVIAL 23320385 A 272 280 malvidin TRIVIAL 23320385 A 285 297 pelargonidin TRIVIAL 23320385 A 357 365 carbonyl FAMILY 23320385 A 385 396 glutathione TRIVIAL 23320385 A 397 398 S FORMULA 23320385 A 423 426 UDP ABBREVIATION 23320385 A 44 58 anthocyanidins FAMILY 23320385 A 541 555 anthocyanidins FAMILY 23320385 A 623 632 menadione TRIVIAL 23320385 A 634 661 1-chloro-2,4-dinitrobenzene SYSTEMATIC 23320385 A 666 679 p-nitrophenol SYSTEMATIC 23320385 A 857 871 Anthocyanidins FAMILY 23320385 A 87 97 flavonoids FAMILY 23320385 A 955 963 Cyanidin TRIVIAL 23320385 T 106 114 carbonyl FAMILY 23320385 T 21 35 anthocyanidins FAMILY 23320385 T 47 58 glutathione TRIVIAL 23320385 T 59 60 S FORMULA 23320385 T 74 77 UDP ABBREVIATION 23320412 A 14 21 sulfate SYSTEMATIC 23320521 A 0 38 Dideoxy bicyclic pyrimidine nucleoside FAMILY 23320521 A 382 387 ether SYSTEMATIC 23320521 A 418 443 n-C(9)H(18)-O-n-C(5)H(11) FORMULA 23320521 A 50 57 ddBCNAs ABBREVIATION 23320521 A 530 539 cidofovir TRIVIAL 23320521 A 558 565 ddBCNAs ABBREVIATION 23320521 A 689 696 ddBCNAs ABBREVIATION 23320521 T 28 57 l-dideoxy bicyclic nucleoside FAMILY 23320931 A 266 274 europium SYSTEMATIC 23320931 A 279 286 terbium SYSTEMATIC 23320931 A 32 42 lanthanide FAMILY 23320931 A 334 344 lanthanide FAMILY 23320931 A 453 463 lanthanide FAMILY 23320931 A 501 509 catechol TRIVIAL 23320931 A 68 84 isophthalic acid TRIVIAL 23320931 A 89 97 catechol TRIVIAL 23320931 T 52 62 lanthanide FAMILY 23320940 A 43 64 perdeuterated tempone TRIVIAL 23320940 A 66 69 PDT ABBREVIATION 23320940 A 664 667 PDT ABBREVIATION 23321054 A 0 19 5-Hydroxytryptamine SYSTEMATIC 23321054 A 1097 1105 zolpidem TRIVIAL 23321054 A 1184 1196 eplivanserin TRIVIAL 23321054 A 1222 1230 zolpidem TRIVIAL 23321054 A 21 25 5-HT SYSTEMATIC 23321054 A 257 269 eplivanserin TRIVIAL 23321054 A 271 283 volinanserin TRIVIAL 23321054 A 288 295 AVE8488 NO CLASS 23321054 A 357 365 zolpidem TRIVIAL 23321054 A 461 473 eplivanserin TRIVIAL 23321054 A 506 518 volinanserin TRIVIAL 23321054 A 540 547 AVE8488 NO CLASS 23321054 A 572 580 zolpidem TRIVIAL 23321054 A 652 664 eplivanserin TRIVIAL 23321054 A 685 693 zolpidem TRIVIAL 23321054 A 775 787 Eplivanserin TRIVIAL 23321054 A 863 871 zolpidem TRIVIAL 23321054 A 931 943 Volinanserin TRIVIAL 23321054 A 964 971 AVE8488 NO CLASS 23321054 T 140 148 zolpidem TRIVIAL 23321916 A 181 200 decamethylferrocene SYSTEMATIC 23321916 A 202 206 DmFc ABBREVIATION 23321916 A 289 319 permethylated transition-metal FAMILY 23321916 A 463 472 ferrocene TRIVIAL 23321916 A 477 490 cobaltocenium SYSTEMATIC 23321916 A 48 71 decamethylcobaltocenium SYSTEMATIC 23321916 A 511 515 DmFc ABBREVIATION 23321916 A 599 608 DmFc(0/+) ABBREVIATION 23321916 A 613 622 DmCc(+/0) ABBREVIATION 23321916 A 73 80 DmCc(+) ABBREVIATION 23321916 A 743 747 DmFc ABBREVIATION 23321916 A 845 849 DmFc ABBREVIATION 23321916 T 14 44 permethylated transition-metal FAMILY 23322164 A 0 14 Acylcarnitines FAMILY 23322164 A 1035 1052 octanoylcarnitine SYSTEMATIC 23322164 A 1112 1126 acylcarnitines FAMILY 23322164 A 1221 1238 octanoylcarnitine SYSTEMATIC 23322164 A 1486 1499 acylcarnitine SYSTEMATIC 23322164 A 151 164 acylcarnitine SYSTEMATIC 23322164 A 1672 1681 Carnitine TRIVIAL 23322164 A 1709 1718 carnitine TRIVIAL 23322164 A 1719 1732 acylcarnitine SYSTEMATIC 23322164 A 1803 1817 acylcarnitines FAMILY 23322164 A 216 225 acyl-CoAs FAMILY 23322164 A 460 468 acyl-CoA ABBREVIATION 23322164 A 505 514 carnitine TRIVIAL 23322164 A 547 556 carnitine TRIVIAL 23322164 A 557 570 acylcarnitine SYSTEMATIC 23322164 A 609 618 carnitine TRIVIAL 23322164 A 67 77 fatty acid FAMILY 23322164 A 739 752 decanoic acid SYSTEMATIC 23322164 A 757 766 carnitine TRIVIAL 23322164 A 803 816 acylcarnitine SYSTEMATIC 23322164 A 930 947 octanoylcarnitine SYSTEMATIC 23322164 T 0 9 Carnitine TRIVIAL 23322164 T 131 145 acylcarnitines FAMILY 23322164 T 37 46 carnitine TRIVIAL 23322164 T 47 60 acylcarnitine SYSTEMATIC 23322347 A 1219 1226 calcium SYSTEMATIC 23322347 A 1285 1289 iron SYSTEMATIC 23322347 A 1424 1428 iron SYSTEMATIC 23322347 A 1811 1815 iron SYSTEMATIC 23322347 A 940 946 Ca(++) FORMULA 23322508 A 394 400 copper SYSTEMATIC 23322508 T 0 6 Copper SYSTEMATIC 23322559 A 10 30 monoterpene lactones FAMILY 23322559 A 32 51 cimicifugolides A-C MULTIPLE 23322559 T 4 24 monoterpene lactones FAMILY 23322648 A 33 112 1-O-hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol SYSTEMATIC 23322648 A 533 612 1-O-Hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-α-D-glucopyranosyl)-sn-glycerol SYSTEMATIC 23322648 A 765 766 O FORMULA 23322648 A 791 805 thioglycosidic FAMILY 23322648 A 836 841 amino FAMILY 23322648 A 854 859 azide SYSTEMATIC 23322648 A 863 872 guanidino SYSTEMATIC 23322648 A 936 943 glycero SYSTEMATIC 23322648 T 133 140 glycero SYSTEMATIC 23322648 T 36 47 glucosamine TRIVIAL 23322709 A 13 15 CO FORMULA 23322709 A 143 158 carbon monoxide SYSTEMATIC 23322709 A 223 230 olefins FAMILY 23322709 A 248 262 alkyl formates FAMILY 23322709 A 293 302 palladium SYSTEMATIC 23322709 A 356 363 olefins FAMILY 23322709 A 419 425 esters FAMILY 23322709 T 79 86 olefins FAMILY 23322709 T 9 18 palladium SYSTEMATIC 23322709 T 92 100 formates FAMILY 23323677 A 1067 1081 cyanate esters FAMILY 23323677 A 108 132 2-methoxy-4-methylphenol SYSTEMATIC 23323677 A 134 141 creosol TRIVIAL 23323677 A 148 160 formaldehyde SYSTEMATIC 23323677 A 1553 1560 phenols FAMILY 23323677 A 1562 1576 isocyanic acid TRIVIAL 23323677 A 162 174 acetaldehyde SYSTEMATIC 23323677 A 1626 1629 CO2 FORMULA 23323677 A 1665 1667 N2 FORMULA 23323677 A 180 195 propionaldehyde SYSTEMATIC 23323677 A 1820 1827 phenols FAMILY 23323677 A 1829 1836 creosol TRIVIAL 23323677 A 1848 1866 alkylated creosols FAMILY 23323677 A 1982 1988 phenol SYSTEMATIC 23323677 A 1990 1997 creosol TRIVIAL 23323677 A 201 215 cyanate esters FAMILY 23323677 A 22 41 bis(cyanate) esters FAMILY 23323677 A 272 276 (1)H FORMULA 23323677 A 281 286 (13)C FORMULA 23323677 A 610 617 creosol TRIVIAL 23323677 A 626 640 cyanate esters FAMILY 23323677 A 66 76 bisphenols FAMILY 23323677 A 741 755 cyanate esters FAMILY 23323677 A 857 871 cyanate esters FAMILY 23323677 A 989 998 methylene SYSTEMATIC 23323677 T 61 80 bis(cyanate) esters FAMILY 23323677 T 94 118 2-methoxy-4-methylphenol SYSTEMATIC 23323680 A 1109 1111 Si FORMULA 23323680 A 125 130 Li-Si FORMULA 23323680 A 25 27 Si FORMULA 23323680 A 274 276 Si FORMULA 23323680 A 300 302 Si FORMULA 23323680 A 378 380 Si FORMULA 23323680 A 54 56 Li FORMULA 23323680 A 712 717 Si-Si FORMULA 23323680 A 778 780 Si FORMULA 23323680 A 850 852 Li FORMULA 23323680 A 875 877 Si FORMULA 23323680 T 49 56 silicon SYSTEMATIC 23323691 A 235 251 carboxylic acids FAMILY 23323691 A 326 332 aldose FAMILY 23323691 A 8 24 carboxylic acids FAMILY 23323691 T 10 26 carboxylic acids FAMILY 23323763 A 63 82 tuberostemonoxirine TRIVIAL 23323763 A 8 29 pyrrolo[1,2-α]azepine SYSTEMATIC 23323763 A 91 113 9α-epi-tuberospironine TRIVIAL 23323829 A 333 343 anthracene SYSTEMATIC 23323829 A 364 426 9,10-bis[4-(3-sulfonatopropoxyl)-styryl]anthracene sodium salt SYSTEMATIC 23323829 A 428 433 BSPSA ABBREVIATION 23323829 A 643 648 BSPSA ABBREVIATION 23323829 A 685 708 guanidine hydrochloride SYSTEMATIC 23323829 A 855 860 BSPSA ABBREVIATION 23323829 A 964 969 BSPSA ABBREVIATION 23323829 T 26 36 anthracene SYSTEMATIC 23323854 A 1052 1059 adenine TRIVIAL 23323854 A 1061 1069 cytosine TRIVIAL 23323854 A 1075 1082 guanine TRIVIAL 23323854 A 1097 1101 DOPC ABBREVIATION 23323854 A 1102 1107 DOTAP ABBREVIATION 23323854 A 1120 1124 DOPC ABBREVIATION 23323854 A 1125 1130 DC-Ch ABBREVIATION 23323854 A 1152 1156 DOPC ABBREVIATION 23323854 A 1192 1196 DOPC ABBREVIATION 23323854 A 1197 1202 DOTAP ABBREVIATION 23323854 A 1270 1274 DOPC ABBREVIATION 23323854 A 1275 1280 DC-Ch ABBREVIATION 23323854 A 157 198 1,2-dioleoyl-sn-glycerol-3-phosphocholine SYSTEMATIC 23323854 A 199 238 1,2-dioleoyl-3-timethylammonium propane SYSTEMATIC 23323854 A 240 244 DOPC ABBREVIATION 23323854 A 245 250 DOTAP ABBREVIATION 23323854 A 256 260 DOPC ABBREVIATION 23323854 A 261 316 3β-{N-[(N',N'-dimethylamino)ethyl]carbamoyl}cholesterol SYSTEMATIC 23323854 A 318 322 DOPC ABBREVIATION 23323854 A 323 328 DC-Ch ABBREVIATION 23323854 A 484 488 DOPC ABBREVIATION 23323854 A 489 494 DC-Ch ABBREVIATION 23323854 A 592 596 DOPC ABBREVIATION 23323854 A 597 602 DC-Ch ABBREVIATION 23323854 A 650 654 DOPC ABBREVIATION 23323854 A 655 660 DOTAP ABBREVIATION 23323854 A 761 765 DOPC ABBREVIATION 23323854 A 766 771 DOTAP ABBREVIATION 23323854 A 784 788 DOPC ABBREVIATION 23323854 A 789 794 DC-Ch ABBREVIATION 23323854 A 876 880 DOPC ABBREVIATION 23323854 A 942 951 phosphate SYSTEMATIC 23323854 A 954 962 PO(2)(-) FORMULA 23323854 A 969 977 carbonyl FAMILY 23323854 A 980 983 C=O FORMULA 23323854 T 47 102 3β-{N-[(N',N'-dimethylamino)ethyl]carbamoyl}cholesterol SYSTEMATIC 23323987 A 15 26 diterpenoid FAMILY 23323987 A 28 40 acerifolin A TRIVIAL 23323987 A 385 395 cisplantin TRIVIAL 23323987 A 56 67 isopimarane TRIVIAL 23323987 A 6 14 tigliane TRIVIAL 23323987 A 68 79 diterpenoid FAMILY 23323987 A 81 93 acerifolin B TRIVIAL 23323987 T 8 20 diterpenoids FAMILY 23324400 A 1209 1212 LT4 ABBREVIATION 23324400 A 1489 1492 LT4 ABBREVIATION 23324400 A 1830 1833 LT4 ABBREVIATION 23324400 A 254 267 levothyroxine TRIVIAL 23324400 A 269 272 LT4 ABBREVIATION 23324400 T 16 29 LEVOTHYROXINE TRIVIAL 23324437 A 1096 1107 Nateglinide TRIVIAL 23324437 A 1268 1279 Nateglinide TRIVIAL 23324437 A 1395 1402 glucose TRIVIAL 23324437 A 1422 1429 glucose TRIVIAL 23324437 A 143 150 glucose TRIVIAL 23324437 A 1458 1469 Nateglinide TRIVIAL 23324437 A 1473 1481 Acarbose TRIVIAL 23324437 A 1520 1530 Natelinide TRIVIAL 23324437 A 1535 1543 Acarbose TRIVIAL 23324437 A 1648 1655 glucose TRIVIAL 23324437 A 1688 1698 Natelinide TRIVIAL 23324437 A 1702 1710 Acarbose TRIVIAL 23324437 A 319 326 glucose TRIVIAL 23324437 A 466 477 Nateglinide TRIVIAL 23324437 A 481 489 Acarbose TRIVIAL 23324437 A 568 575 glucose TRIVIAL 23324437 A 601 608 glucose TRIVIAL 23324437 A 650 657 glucose TRIVIAL 23324437 A 69 76 glucose TRIVIAL 23324437 A 943 954 Nateglinide TRIVIAL 23324437 A 959 967 Acarbose TRIVIAL 23324437 T 42 53 Nateglinide TRIVIAL 23324437 T 57 65 Acarbose TRIVIAL 23324437 T 89 96 Glucose TRIVIAL 23325046 A 104 110 hexane SYSTEMATIC 23325046 A 1058 1064 oxygen SYSTEMATIC 23325046 A 977 981 DPPH ABBREVIATION 23325046 A 983 1012 α,α-diphenyl-β-picrylhydrazyl SYSTEMATIC 23325050 A 129 135 indole SYSTEMATIC 23325050 A 141 159 aromatic aldehydes FAMILY 23325050 A 18 35 dichlorophosphate SYSTEMATIC 23325050 A 212 233 bis(indolyl) methanes FAMILY 23325050 A 37 49 PEG-OPOCl(2) FORMULA 23325050 T 13 31 bisindolylmethanes FAMILY 23325373 A 1015 1022 glucose TRIVIAL 23325373 A 1027 1035 fructose TRIVIAL 23325373 A 138 145 glucose TRIVIAL 23325373 A 19 26 glucose TRIVIAL 23325373 A 237 244 glucose TRIVIAL 23325373 A 277 284 glucose TRIVIAL 23325373 A 494 502 fructose TRIVIAL 23325373 A 504 511 glucose TRIVIAL 23325373 A 566 574 Fructose TRIVIAL 23325373 A 617 624 glucose TRIVIAL 23325373 A 743 751 fructose TRIVIAL 23325373 A 765 772 glucose TRIVIAL 23325373 A 77 84 glucose TRIVIAL 23325373 A 873 881 fructose TRIVIAL 23325373 A 886 893 glucose TRIVIAL 23325373 T 42 49 glucose TRIVIAL 23325373 T 66 74 fructose TRIVIAL 23325486 A 1207 1210 Glu FORMULA 23325486 A 1250 1260 amino acid FAMILY 23325486 A 1271 1274 Tyr FORMULA 23325486 A 1281 1284 Thr FORMULA 23325489 A 1007 1014 linarin TRIVIAL 23325489 A 1100 1108 acacetin TRIVIAL 23325489 A 210 223 pentobarbital TRIVIAL 23325489 A 251 269 pentylenetetrazole SYSTEMATIC 23325489 A 271 274 PTZ ABBREVIATION 23325489 A 454 462 acacetin TRIVIAL 23325489 A 464 471 linarin TRIVIAL 23325489 A 473 561 acacetin 7-O-β-D-glucopyranosyl-(1 → 2)[α-L-rhamnopyranosyl-(1 → 6)]-β-D-glucopyranoside SYSTEMATIC 23325489 A 563 579 chlorogenic acid TRIVIAL 23325489 A 585 613 3,5-di-O-caffeoylquinic acid SYSTEMATIC 23325489 A 715 722 linarin TRIVIAL 23325489 A 865 872 Linarin TRIVIAL 23325489 A 891 899 acacetin TRIVIAL 23325489 T 69 86 flavone glycoside FAMILY 23325492 A 1146 1153 citrate FAMILY 23325492 A 17 24 citrate FAMILY 23325492 A 32 38 silver SYSTEMATIC 23325492 T 13 20 citrate FAMILY 23325492 T 28 34 silver SYSTEMATIC 23325530 A 0 10 Diclofenac TRIVIAL 23325530 A 1155 1158 DCF ABBREVIATION 23325530 A 1195 1198 DCF ABBREVIATION 23325530 A 12 15 DCF ABBREVIATION 23325530 A 1377 1380 DCF ABBREVIATION 23325530 A 534 537 DCF ABBREVIATION 23325530 A 742 745 DCF ABBREVIATION 23325530 A 883 886 DCF ABBREVIATION 23325530 T 0 10 Diclofenac TRIVIAL 23325631 A 0 5 CO(2) FORMULA 23325631 A 223 228 CO(2) FORMULA 23325631 A 292 303 bicarbonate SYSTEMATIC 23325631 A 481 505 3-nitrophenylacetic acid SYSTEMATIC 23325631 A 535 540 CO(2) FORMULA 23325631 A 705 710 CO(2) FORMULA 23325631 A 762 767 CO(2) FORMULA 23325631 T 42 47 CO(2) FORMULA 23325631 T 6 11 CO(2) FORMULA 23327112 A 19 49 clauexcavatins A (1) and B (2) MULTIPLE 23327112 A 8 17 coumarins FAMILY 23327112 T 0 9 Coumarins FAMILY 23327360 A 1065 1071 TiO(2) FORMULA 23327360 A 1364 1374 amino acid FAMILY 23327360 A 1444 1455 amino acids FAMILY 23327360 A 1512 1522 phosphoryl FAMILY 23327360 A 1597 1603 TiO(2) FORMULA 23327360 A 1793 1799 TiO(2) FORMULA 23327360 A 279 289 phosphoryl FAMILY 23327360 A 301 317 titanium dioxide SYSTEMATIC 23327360 A 319 325 TiO(2) FORMULA 23327360 A 636 642 TiO(2) FORMULA 23327360 A 692 698 quartz TRIVIAL 23327360 A 877 887 amino acid FAMILY 23327360 T 51 67 titanium dioxide SYSTEMATIC 23327360 T 95 101 quartz TRIVIAL 23327494 A 810 824 speciophylline TRIVIAL 23327494 A 826 836 uncarine F TRIVIAL 23327494 A 841 851 uncarine E TRIVIAL 23327494 A 857 866 flavanols FAMILY 23327494 A 868 876 catechin TRIVIAL 23327494 A 881 897 epigallocatechin TRIVIAL 23327532 A 1013 1020 styrene TRIVIAL 23327532 A 1026 1039 4-vinylphenol SYSTEMATIC 23327532 A 1083 1097 Styrene glycol TRIVIAL 23327532 A 331 338 styrene TRIVIAL 23327532 A 376 383 styrene TRIVIAL 23327532 A 549 556 styrene TRIVIAL 23327532 A 597 610 4-nitrophenol SYSTEMATIC 23327532 A 667 674 Styrene TRIVIAL 23327532 A 901 914 Styrene oxide SYSTEMATIC 23327532 A 919 932 4-vinylphenol SYSTEMATIC 23327532 A 972 985 Styrene oxide SYSTEMATIC 23327532 T 46 53 styrene TRIVIAL 23327534 A 551 563 germacrene B TRIVIAL 23327534 A 577 590 viridiflorene TRIVIAL 23327534 A 609 617 globulol TRIVIAL 23327534 A 631 640 α-cadinol TRIVIAL 23327534 A 656 665 τ-cadinol TRIVIAL 23327557 A 1111 1122 procyanidin FAMILY 23327557 A 25 37 procyanidins FAMILY 23327557 A 412 429 galacturonic acid TRIVIAL 23327557 A 469 480 procyanidin FAMILY 23327557 A 501 516 (-)-epicatechin SYSTEMATIC 23327557 A 685 697 procyanidins FAMILY 23327557 A 787 799 procyanidins FAMILY 23327557 A 96 108 Procyanidins FAMILY 23327557 A 998 1010 procyanidins FAMILY 23327557 T 42 54 procyanidins FAMILY 23327580 A 86 97 doxorubicin TRIVIAL 23327668 A 10 18 abietane TRIVIAL 23327668 A 19 31 diterpenoids FAMILY 23327668 A 33 50 isoabietenins A-C MULTIPLE 23327668 A 630 642 nitric oxide SYSTEMATIC 23327668 A 69 83 ent-kauranoids FAMILY 23327668 A 85 100 tenuifolins A-M MULTIPLE 23327668 T 10 18 abietane TRIVIAL 23327668 T 23 34 ent-kaurane TRIVIAL 23327668 T 35 47 diterpenoids FAMILY 23327794 A 144 164 piperidine alkaloids FAMILY 23327794 A 166 186 microgrewiapines A-C MULTIPLE 23327794 A 241 256 microcosamine A TRIVIAL 23327794 A 262 325 7'-(3',4'-dihydroxyphenyl)-N-[4-methoxyphenyl)ethyl]propenamide SYSTEMATIC 23327794 A 335 346 liriodenine TRIVIAL 23327794 A 407 417 chloroform TRIVIAL 23327794 A 514 541 microgrewiapine A 3-acetate SYSTEMATIC 23327794 A 694 707 acetylcholine SYSTEMATIC 23327794 A 828 845 microgrewiapine A TRIVIAL 23327993 A 1128 1131 NAC ABBREVIATION 23327993 A 1133 1136 AD4 IDENTIFIER 23327993 A 1141 1154 ascorbic acid TRIVIAL 23327993 A 1207 1228 NAc-Cys-Pro-Cys amide SYSTEMATIC 23327993 A 590 599 auranofin TRIVIAL 23327993 A 601 604 AuF ABBREVIATION 23327993 A 624 627 AuF ABBREVIATION 23327993 A 735 738 AuF ABBREVIATION 23327993 A 893 902 disulfide SYSTEMATIC 23327993 T 43 52 auranofin TRIVIAL 23328072 A 1544 1555 1,25(OH)₂D₃ SYSTEMATIC 23328072 A 371 381 vitamin D₃ TRIVIAL 23328072 A 383 407 1,25-dihydroxyvitamin D₃ SYSTEMATIC 23328072 A 409 420 1,25(OH)₂D₃ SYSTEMATIC 23328072 A 65 74 vitamin D FAMILY 23328072 A 681 692 1,25(OH)₂D₃ SYSTEMATIC 23328072 A 966 977 1,25(OH)₂D3 SYSTEMATIC 23328072 T 26 35 vitamin D FAMILY 23328126 A 1037 1052 ω-3 fatty acids FAMILY 23328126 A 201 216 ω-3 fatty acids FAMILY 23328126 A 315 340 Omega-3-Acid Ethyl Esters FAMILY 23328126 A 757 771 ω-3 fatty acid FAMILY 23328126 A 958 973 ω-3 fatty acids FAMILY 23328126 T 0 19 Omega-3 Fatty acids FAMILY 23328252 A 0 25 2,4-Dihydroxybenzophenone SYSTEMATIC 23328252 A 1176 1180 BP-1 ABBREVIATION 23328252 A 1273 1277 BP-1 ABBREVIATION 23328252 A 1451 1455 BP-1 ABBREVIATION 23328252 A 1704 1708 BP-1 ABBREVIATION 23328252 A 177 181 BP-1 ABBREVIATION 23328252 A 27 41 benzophenone-1 SYSTEMATIC 23328252 A 407 411 BP-1 ABBREVIATION 23328252 A 43 47 BP-1 ABBREVIATION 23328252 A 458 466 estrogen FAMILY 23328252 A 541 555 17-β estradiol SYSTEMATIC 23328252 A 596 600 BP-1 ABBREVIATION 23328252 A 824 828 BP-1 ABBREVIATION 23328252 A 835 839 BP-1 ABBREVIATION 23328252 A 933 944 ICI 182,780 IDENTIFIER 23328252 A 980 984 BP-1 ABBREVIATION 23328252 T 0 14 Benzophenone-1 SYSTEMATIC 23328252 T 98 106 estrogen FAMILY 23329065 A 1060 1070 quinpirole TRIVIAL 23329065 A 1418 1428 quinpirole TRIVIAL 23329065 A 1544 1554 quinpirole TRIVIAL 23329065 A 1631 1641 quinpirole TRIVIAL 23329065 A 1700 1710 quinpirole TRIVIAL 23329065 A 311 321 quinpirole TRIVIAL 23329065 A 45 55 quinpirole TRIVIAL 23329065 A 484 494 quinpirole TRIVIAL 23329065 A 626 634 urethane TRIVIAL 23329065 A 705 715 quinpirole TRIVIAL 23329065 A 766 776 quinpirole TRIVIAL 23329065 T 11 19 dopamine TRIVIAL 23329065 T 31 41 quinpirole TRIVIAL 23329125 A 1005 1008 PCB ABBREVIATION 23329125 A 1078 1082 tBHQ ABBREVIATION 23329125 A 1206 1210 tBHQ ABBREVIATION 23329125 A 126 142 aryl hydrocarbon FAMILY 23329125 A 1430 1441 glutathione TRIVIAL 23329125 A 1442 1443 S FORMULA 23329125 A 1491 1495 tBHQ ABBREVIATION 23329125 A 1557 1567 superoxide TRIVIAL 23329125 A 1649 1653 PCBs ABBREVIATION 23329125 A 1772 1775 PCB ABBREVIATION 23329125 A 205 230 polychlorinated biphenyls FAMILY 23329125 A 232 236 PCBs ABBREVIATION 23329125 A 242 277 2,3,7,8-tetrachlorodibenzo-p-dioxin SYSTEMATIC 23329125 A 279 283 TCDD ABBREVIATION 23329125 A 529 532 PCB ABBREVIATION 23329125 A 747 769 tert-butylhydroquinone SYSTEMATIC 23329125 A 771 775 tBHQ ABBREVIATION 23329180 A 1054 1065 theaflavins FAMILY 23329180 A 1181 1191 theaflavin TRIVIAL 23329180 A 1548 1558 theaflavin TRIVIAL 23329180 A 348 359 theaflavins FAMILY 23329180 A 59 67 tyrosine TRIVIAL 23330542 A 1059 1065 azoles FAMILY 23330542 A 1326 1331 azole FAMILY 23330542 A 38 46 pregnane TRIVIAL 23330542 A 464 477 acetaminophen TRIVIAL 23330542 A 939 951 sulforaphane TRIVIAL 23330549 A 103 108 Pt(6) FORMULA 23330549 T 12 20 platinum SYSTEMATIC 23330613 A 1308 1317 ornithine TRIVIAL 23330613 A 1480 1490 spermidine TRIVIAL 23330613 A 412 421 polyamine FAMILY 23330613 A 453 474 5-methylthioadenosine SYSTEMATIC 23330613 A 476 486 putrescine TRIVIAL 23330613 A 491 501 spermidine TRIVIAL 23330613 A 571 580 polyamine FAMILY 23330613 A 6 22 phosphoinositide FAMILY 23330613 A 668 678 spermidine TRIVIAL 23330613 A 777 786 polyamine FAMILY 23330613 A 803 812 ornithine TRIVIAL 23330613 A 928 938 spermidine TRIVIAL 23330613 T 0 9 Polyamine SYSTEMATIC 23330789 A 490 497 silanes FAMILY 23330847 A 1040 1061 carbonyl di-imidazole SYSTEMATIC 23330847 A 1066 1073 hydroxy SYSTEMATIC 23330847 A 1355 1362 hydroxy SYSTEMATIC 23330847 A 1484 1495 cholesterol TRIVIAL 23330847 A 1651 1658 hydroxy SYSTEMATIC 23330847 A 892 899 hydroxy SYSTEMATIC 23330847 A 911 930 polyethylene glycol SYSTEMATIC 23330847 T 0 7 Hydroxy SYSTEMATIC 23330847 T 95 106 cholesterol TRIVIAL 23330848 A 404 411 choline FAMILY 23330848 A 433 434 H FORMULA 23330848 A 470 476 C2H3OH FORMULA 23330848 A 485 486 H FORMULA 23330848 A 567 574 tacrine TRIVIAL 23330848 A 579 591 galanthamine TRIVIAL 23330848 A 633 641 coumarin TRIVIAL 23330848 A 802 810 coumarin TRIVIAL 23330848 A 843 850 tacrine TRIVIAL 23330908 A 100 101 C FORMULA 23330908 A 108 109 C FORMULA 23330908 A 402 411 zanamivir TRIVIAL 23330908 A 594 603 zanamivir TRIVIAL 23330908 A 77 86 zanamivir TRIVIAL 23330908 T 40 41 C FORMULA 23330908 T 49 50 C FORMULA 23330908 T 73 82 zanamivir TRIVIAL 23330971 A 110 113 ZnO FORMULA 23330971 A 14 20 indium SYSTEMATIC 23330971 A 189 192 ZnO FORMULA 23330971 A 239 242 ZnO FORMULA 23330971 A 248 251 ZnO FORMULA 23330971 A 514 530 Cu(In,Ga)(S,Se)₂ FORMULA 23330971 A 532 538 CIGSSe ABBREVIATION 23330971 A 709 714 oxide SYSTEMATIC 23330971 A 721 727 CIGSSe ABBREVIATION 23330971 A 744 747 ZnO FORMULA 23330971 A 753 756 ZnO FORMULA 23330971 A 81 87 silver SYSTEMATIC 23330971 T 34 37 ZnO FORMULA 23330971 T 38 40 Ag FORMULA 23330971 T 50 53 ZnO FORMULA 23331178 A 1027 1035 carbonyl FAMILY 23331178 A 1040 1049 phosphate SYSTEMATIC 23331178 A 1106 1110 DMPE ABBREVIATION 23331178 A 113 149 dimyristoyl phosphatidylethanolamine SYSTEMATIC 23331178 A 151 155 DMPE ABBREVIATION 23331178 A 174 181 Au(111) FORMULA 23331178 A 560 564 DMPE ABBREVIATION 23331178 A 645 676 dimyristoyl phosphatidylcholine SYSTEMATIC 23331178 A 678 682 DMPC ABBREVIATION 23331178 A 818 822 DMPE ABBREVIATION 23331178 A 852 863 hydrocarbon FAMILY 23331178 A 957 968 hydrocarbon FAMILY 23331539 A 133 145 quinazolinon FAMILY 23331539 A 447 459 quinazolinon FAMILY 23331539 A 516 524 hydrogen SYSTEMATIC 23331539 A 647 659 quinazolinon FAMILY 23331539 T 31 43 quinazolinon FAMILY 23331618 A 102 128 4-amino-7-chloroquinolines FAMILY 23331618 A 153 187 7-chloro-4-aminoquinoline-triazine FAMILY 23331618 A 242 253 chloroquine TRIVIAL 23331618 A 273 284 chloroquine TRIVIAL 23331618 A 42 50 triazine FAMILY 23331618 A 501 512 chloroquine TRIVIAL 23331618 A 639 650 chloroquine TRIVIAL 23331618 A 663 674 chloroquine TRIVIAL 23331618 T 0 25 4-Aminoquinoline-Triazine FAMILY 23332347 A 355 366 sibutramine TRIVIAL 23332347 A 418 426 orlistat TRIVIAL 23332347 A 539 545 Belviq TRIVIAL 23332347 A 550 556 Qsymia TRIVIAL 23332762 A 632 638 serine TRIVIAL 23332762 A 643 646 Ser FORMULA 23332762 A 697 700 Ser FORMULA 23333093 A 273 281 catechin TRIVIAL 23333093 A 861 872 cholesterol TRIVIAL 23333093 A 901 912 cholesterol TRIVIAL 23333093 A 960 971 cholesterol TRIVIAL 23333093 T 10 18 catechin TRIVIAL 23333261 A 1011 1019 curcumin TRIVIAL 23333261 A 208 215 glucose TRIVIAL 23333261 A 592 606 streptozotocin TRIVIAL 23333261 A 847 854 glucose TRIVIAL 23333261 A 916 924 Curcumin TRIVIAL 23333575 A 1000 1011 glutathione TRIVIAL 23333575 A 1055 1064 genistein TRIVIAL 23333575 A 1116 1125 genistein TRIVIAL 23333575 A 113 132 uridine diphosphate SYSTEMATIC 23333575 A 1168 1177 genistein TRIVIAL 23333575 A 1210 1214 APAP ABBREVIATION 23333575 A 1263 1267 APAP ABBREVIATION 23333575 A 191 204 acetaminophen TRIVIAL 23333575 A 271 280 genistein TRIVIAL 23333575 A 346 353 alanine TRIVIAL 23333575 A 372 379 alanine TRIVIAL 23333575 A 398 405 lactate FAMILY 23333575 A 424 439 malondialdehyde TRIVIAL 23333575 A 45 54 genistein TRIVIAL 23333575 A 487 491 APAP ABBREVIATION 23333575 A 519 522 GSH ABBREVIATION 23333575 A 561 565 APAP ABBREVIATION 23333575 A 621 630 genistein TRIVIAL 23333575 A 709 718 Genistein TRIVIAL 23333575 A 746 750 APAP ABBREVIATION 23333575 A 794 798 APAP ABBREVIATION 23333575 A 799 810 glucuronide TRIVIAL 23333575 A 876 885 genistein TRIVIAL 23333575 A 952 956 APAP ABBREVIATION 23333575 T 0 9 Genistein TRIVIAL 23333575 T 110 113 UDP ABBREVIATION 23333575 T 29 42 acetaminophen TRIVIAL 23333639 A 463 482 formamidopyrimidine SYSTEMATIC 23333639 A 694 706 8-oxoguanine SYSTEMATIC 23333639 A 708 714 8-oxoG SYSTEMATIC 23333639 A 842 848 oxygen SYSTEMATIC 23333639 A 932 944 α-tocopherol TRIVIAL 23333641 A 0 12 Methoxychlor TRIVIAL 23333641 A 14 17 MXC ABBREVIATION 23333641 A 166 169 MXC ABBREVIATION 23333641 A 189 233 2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane SYSTEMATIC 23333641 A 235 239 HPTE ABBREVIATION 23333641 A 260 278 11β-hydroxysteroid FAMILY 23333641 A 560 563 MXC ABBREVIATION 23333641 A 568 572 HPTE ABBREVIATION 23333641 A 622 626 HPTE ABBREVIATION 23333641 A 684 687 MXC ABBREVIATION 23333641 A 716 719 MXC ABBREVIATION 23333641 A 724 728 HPTE ABBREVIATION 23333641 A 770 774 HPTE ABBREVIATION 23333641 A 889 892 MXC ABBREVIATION 23333641 A 955 958 MXC ABBREVIATION 23333641 A 978 982 HPTE ABBREVIATION 23333641 T 11 23 methoxychlor TRIVIAL 23333641 T 43 89 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane SYSTEMATIC 23333641 T 93 111 11β-hydroxysteroid FAMILY 23333716 A 117 125 phenolic FAMILY 23333716 A 136 155 protocatechuic acid TRIVIAL 23333716 A 405 424 protocatechuic acid TRIVIAL 23333716 T 61 80 protocatechuic acid TRIVIAL 23333834 A 1011 1016 YR-11 IDENTIFIER 23333834 A 1067 1075 cysteine TRIVIAL 23333834 A 1083 1089 serine TRIVIAL 23333834 A 1297 1302 YR-11 IDENTIFIER 23333834 A 1593 1598 YR-11 IDENTIFIER 23333834 A 391 394 Tyr FORMULA 23333834 A 397 400 Asp FORMULA 23333834 A 404 407 Tyr FORMULA 23333834 A 410 413 Glu FORMULA 23333834 A 421 424 Leu FORMULA 23333834 A 428 431 Arg FORMULA 23333834 A 472 475 Leu FORMULA 23333834 A 479 482 Arg FORMULA 23333834 A 988 997 celecoxib TRIVIAL 23333899 A 0 11 Doxorubicin TRIVIAL 23333899 A 1001 1004 Dox ABBREVIATION 23333899 A 1024 1035 Doxorubicin TRIVIAL 23333899 A 1296 1299 Dox ABBREVIATION 23333899 A 1385 1388 Dox ABBREVIATION 23333899 A 1415 1418 Dox ABBREVIATION 23333899 A 1424 1427 Dox ABBREVIATION 23333899 A 147 160 octa-arginine TRIVIAL 23333899 A 1540 1543 Dox ABBREVIATION 23333899 A 1575 1578 Dox ABBREVIATION 23333899 A 1612 1615 Dox ABBREVIATION 23333899 A 1714 1725 doxorubicin TRIVIAL 23333899 A 218 271 polyethylene glycol-dioleoyl phosphatidylethanolamine SYSTEMATIC 23333899 A 273 281 PEG-DOPE ABBREVIATION 23333899 A 321 330 R8-PEG-PE FORMULA 23333899 A 66 71 DOXIL TRIVIAL 23333899 A 751 754 Dox ABBREVIATION 23333899 A 76 83 Lipodox TRIVIAL 23333899 A 824 835 doxorubicin TRIVIAL 23333899 A 950 961 Doxorubicin TRIVIAL 23333899 A 990 993 Dox ABBREVIATION 23333899 T 29 40 doxorubicin TRIVIAL 23333899 T 63 76 octa-arginine TRIVIAL 23333900 A 1032 1045 carbamazepine TRIVIAL 23333900 A 1050 1058 Soluplus TRIVIAL 23333900 A 1248 1251 CBZ ABBREVIATION 23333900 A 1289 1292 CBZ ABBREVIATION 23333900 A 1345 1348 CBZ ABBREVIATION 23333900 A 1517 1520 CBZ ABBREVIATION 23333900 A 1637 1650 carbamazepine TRIVIAL 23333900 A 1654 1662 Soluplus TRIVIAL 23333900 A 382 395 carbamazepine TRIVIAL 23333900 A 397 400 CBZ ABBREVIATION 23333900 A 407 425 polyethyleneglycol SYSTEMATIC 23333900 A 426 447 polyvinyl caprolactam SYSTEMATIC 23333900 A 448 465 polyvinyl acetate SYSTEMATIC 23333900 A 485 493 Soluplus TRIVIAL 23333900 A 849 852 CBZ ABBREVIATION 23333900 A 857 865 Soluplus TRIVIAL 23333900 T 15 28 carbamazepine TRIVIAL 23333900 T 29 37 Soluplus TRIVIAL 23333908 A 1416 1426 Captropril TRIVIAL 23333908 A 1452 1462 Lisinopril TRIVIAL 23333908 A 1470 1481 cholesterol TRIVIAL 23333908 A 1507 1518 cholesterol TRIVIAL 23333908 A 1532 1545 triglycerides FAMILY 23333908 A 1671 1682 cholesterol TRIVIAL 23333908 A 1892 1903 cholesterol TRIVIAL 23333908 A 1912 1925 triglycerides FAMILY 23333908 A 1955 1967 Anthocyanins FAMILY 23333908 A 2171 2182 polyphenols FAMILY 23333908 A 2187 2200 hibiscus acid TRIVIAL 23333908 A 2376 2388 anthocyanins FAMILY 23334176 A 558 563 sugar FAMILY 23334176 A 574 581 glucose TRIVIAL 23334176 A 700 707 glucose TRIVIAL 23334176 A 831 836 sugar FAMILY 23334176 A 847 854 glucose TRIVIAL 23334322 A 0 22 Pyridoxal-5'-phosphate SYSTEMATIC 23334322 A 1033 1043 vitamin B6 TRIVIAL 23334322 A 1105 1117 homocysteine TRIVIAL 23334322 A 1275 1285 vitamin B6 TRIVIAL 23334322 A 1448 1457 pyridoxal TRIVIAL 23334322 A 1498 1508 pyridoxine TRIVIAL 23334322 A 1519 1529 vitamin B6 TRIVIAL 23334322 A 1546 1549 PLP ABBREVIATION 23334322 A 1738 1748 vitamin B6 TRIVIAL 23334322 A 214 224 vitamin B6 TRIVIAL 23334322 A 24 27 PLP ABBREVIATION 23334322 A 375 383 aldehyde SYSTEMATIC 23334322 A 409 419 pyridoxine TRIVIAL 23334322 A 511 514 PLP ABBREVIATION 23334322 A 52 62 vitamin B6 TRIVIAL 23334322 A 529 532 PLP ABBREVIATION 23334322 A 567 579 homocysteine TRIVIAL 23334322 A 638 640 B6 TRIVIAL 23334322 A 661 664 PLP ABBREVIATION 23334322 A 696 706 pyridoxine TRIVIAL 23334322 A 977 987 vitamin B6 TRIVIAL 23334322 T 11 21 vitamin B6 TRIVIAL 23334583 A 1179 1185 Ca(+2) FORMULA 23335034 A 0 6 Carbon SYSTEMATIC 23335034 A 188 194 carbon SYSTEMATIC 23335034 A 258 264 (14) C FORMULA 23335034 A 287 299 phenanthrene SYSTEMATIC 23335034 A 342 348 carbon SYSTEMATIC 23335034 A 413 425 phenanthrene SYSTEMATIC 23335034 A 491 503 phenanthrene SYSTEMATIC 23335034 A 703 715 phenanthrene SYSTEMATIC 23335034 A 969 981 phenanthrene SYSTEMATIC 23335034 T 18 30 phenanthrene SYSTEMATIC 23335034 T 53 59 carbon SYSTEMATIC 23335220 A 247 250 ATP ABBREVIATION 23335220 A 251 257 biotin TRIVIAL 23335220 A 332 338 biotin TRIVIAL 23335220 A 486 492 biotin TRIVIAL 23335220 A 550 566 phosphorylbiotin SYSTEMATIC 23335220 A 900 903 ATP ABBREVIATION 23335220 A 904 910 biotin TRIVIAL 23335220 A 983 986 ATP ABBREVIATION 23335243 A 20 28 terpenes FAMILY 23335243 A 249 263 sesquiterpenes FAMILY 23335243 A 57 70 sesquiterpene FAMILY 23335243 T 22 35 sesquiterpene FAMILY 23335320 A 161 169 pyridine SYSTEMATIC 23335320 A 185 207 N-heterocyclic carbene FAMILY 23335320 A 208 221 palladacycles FAMILY 23335320 A 339 349 amino acid FAMILY 23335320 A 514 516 Pd FORMULA 23335320 A 517 518 N FORMULA 23335320 A 574 582 α-carbon SYSTEMATIC 23335320 A 77 84 carbene FAMILY 23335320 A 91 104 palladacycles FAMILY 23335320 T 102 115 palladacycles FAMILY 23335320 T 135 137 Pd FORMULA 23335320 T 138 139 N FORMULA 23335320 T 64 72 pyridine SYSTEMATIC 23335320 T 73 95 N-heterocyclic carbene FAMILY 23335450 A 205 213 cysteine TRIVIAL 23335450 A 968 972 S-Au FORMULA 23335565 A 389 402 5-azacytidine SYSTEMATIC 23335565 A 461 467 oxygen SYSTEMATIC 23335565 A 740 751 phytic acid TRIVIAL 23335565 T 43 54 phytic Acid TRIVIAL 23335833 A 138 142 DPPC ABBREVIATION 23335833 A 211 236 poly(methyl methacrylate) SYSTEMATIC 23335833 A 316 320 DPPC ABBREVIATION 23335833 A 374 378 DPPC ABBREVIATION 23335833 A 48 57 formamide SYSTEMATIC 23335833 A 62 75 diiodomethane SYSTEMATIC 23335833 A 620 624 DPPC ABBREVIATION 23335833 A 93 136 1,2-dipalmitoyl-sn-glycero-3-phosphocholine SYSTEMATIC 23336337 A 127 132 ester FAMILY 23336337 A 403 413 jolkinol D TRIVIAL 23336337 A 532 551 lathyrane diterpene FAMILY 23336337 A 56 66 jolkinol D TRIVIAL 23336337 A 762 769 octanol SYSTEMATIC 23336337 T 22 32 diterpenes FAMILY 23336337 T 98 108 jolkinol D TRIVIAL 23336368 A 100 110 kaempferol TRIVIAL 23336368 A 119 128 quercetin TRIVIAL 23336368 A 8 20 homoflavanol FAMILY 23336368 A 89 99 flavonoids FAMILY 23336368 T 46 58 homoflavanol FAMILY 23336729 A 194 206 methacrylate TRIVIAL 23336729 A 260 273 acetylcholine SYSTEMATIC 23336729 A 305 336 dimethylaminoethyl methacrylate SYSTEMATIC 23336729 A 345 353 hydroxyl SYSTEMATIC 23336729 A 365 386 poly(ethylene glycol) SYSTEMATIC 23336729 A 775 788 poly-l-lysine SYSTEMATIC 23336729 T 47 60 acetylcholine SYSTEMATIC 23337202 A 567 579 [Au(CN)(2)]- FORMULA 23337202 A 763 775 [Au(CN)(2)]- FORMULA 23337397 A 121 132 Trypan blue TRIVIAL 23337397 A 188 191 MTT ABBREVIATION 23337599 A 134 140 indole SYSTEMATIC 23337599 A 362 370 zileuton TRIVIAL 23337599 A 565 570 tosyl TRIVIAL 23337599 A 588 609 pyrolidinyl-1,2-dione SYSTEMATIC 23337599 A 632 638 indole SYSTEMATIC 23337599 T 21 28 indoles FAMILY 23337600 A 0 15 (Me)FGC(Bz)DEVD FORMULA 23337600 A 191 200 cisplatin TRIVIAL 23337600 A 298 317 (99m)Tc-(Me)FGCDEVD SYSTEMATIC 23337600 A 38 52 technetium-99m SYSTEMATIC 23337600 T 0 17 ⁹⁹mTc-(Me)FGCDEVD SYSTEMATIC 23337925 A 720 729 acetylene SYSTEMATIC 23337941 A 1015 1039 quinoidal oligothiophene TRIVIAL 23337941 A 136 161 quinoidal quaterthiophene SYSTEMATIC 23337941 A 163 171 QQT(CN)4 FORMULA 23337941 A 498 506 QQT(CN)4 FORMULA 23337941 A 658 666 QQT(CN)4 FORMULA 23337941 A 877 885 QQT(CN)4 FORMULA 23338525 A 1036 1038 Ir FORMULA 23338525 A 1231 1237 oxygen SYSTEMATIC 23338525 A 1513 1519 IrO(2) FORMULA 23338525 A 1520 1526 SnO(2) FORMULA 23338525 A 1604 1606 Ir FORMULA 23338525 A 1636 1644 hydrogen SYSTEMATIC 23338525 A 328 330 Ir FORMULA 23338525 A 333 335 Sn FORMULA 23338525 A 340 344 O(2) FORMULA 23338525 A 485 487 Ir FORMULA 23338525 A 505 520 bi-metal oxides FAMILY 23338525 A 566 568 Ir FORMULA 23338525 A 574 576 Sn FORMULA 23338525 A 61 63 Ir FORMULA 23338525 A 66 68 Sn FORMULA 23338525 A 664 670 SnO(2) FORMULA 23338525 A 689 695 IrO(2) FORMULA 23338525 A 73 77 O(2) FORMULA 23338525 A 749 755 IrO(2) FORMULA 23338525 A 797 799 Ir FORMULA 23338525 A 851 853 Ir FORMULA 23338525 A 895 897 Sn FORMULA 23338525 A 918 920 Ir FORMULA 23338525 A 926 928 Sn FORMULA 23338525 A 934 938 O(2) FORMULA 23338525 A 968 974 Nafion TRIVIAL 23338525 T 17 19 Ir FORMULA 23338525 T 22 24 Sn FORMULA 23338525 T 29 31 O2 FORMULA 23338525 T 53 59 oxygen SYSTEMATIC 23338537 A 168 178 cefuroxime TRIVIAL 23338537 A 275 285 cefuroxime TRIVIAL 23338537 A 419 429 cefuroxime TRIVIAL 23338537 A 580 587 Aprokam TRIVIAL 23338537 A 603 613 cefuroxime TRIVIAL 23338537 A 744 751 Aprokam TRIVIAL 23338537 T 13 23 cefuroxime TRIVIAL 23339036 A 250 259 estrogens FAMILY 23339036 A 298 307 tamoxifen TRIVIAL 23339036 A 653 662 estrogens FAMILY 23339547 A 1192 1202 rasagiline TRIVIAL 23339547 A 1305 1315 rasagiline TRIVIAL 23339547 A 1378 1388 rasagiline TRIVIAL 23339547 A 14 24 rasagiline TRIVIAL 23339547 A 157 167 rasagiline TRIVIAL 23339547 A 250 260 rasagiline TRIVIAL 23339547 A 406 416 rasagiline TRIVIAL 23339547 A 521 531 rasagiline TRIVIAL 23339547 A 915 925 rasagiline TRIVIAL 23339547 T 44 54 rasagiline TRIVIAL 23339572 A 1019 1031 sulforaphane TRIVIAL 23339572 A 1033 1049 dimethylfumarate SYSTEMATIC 23339572 A 1051 1059 chalcone FAMILY 23339572 A 1063 1108 (2E)-1-phenyl-3-pyrimidin-2-ylprop-2-en-1-one SYSTEMATIC 23339572 A 1114 1122 chalcone FAMILY 23339572 A 1126 1153 1,3-diphenylprop-2-yn-1-one SYSTEMATIC 23339572 A 1186 1210 α,β-unsaturated carbonyl FAMILY 23339572 A 12 21 Chalcones FAMILY 23339572 A 1234 1240 thiols FAMILY 23339572 A 1514 1517 BAP ABBREVIATION 23339572 A 1519 1535 4-hydroxynonenal SYSTEMATIC 23339572 A 1540 1548 chalcone FAMILY 23339572 A 1552 1601 4-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]benzonitrile SYSTEMATIC 23339572 A 1604 1612 chalcone FAMILY 23339572 A 1616 1675 (2E)-1-phenyl-3-[4-(trifluoromethyl)-phenyl]prop-2-en-1-one SYSTEMATIC 23339572 A 1681 1689 chalcone FAMILY 23339572 A 465 474 chalcones FAMILY 23339572 A 478 483 thiol FAMILY 23339572 A 50 68 benzalacetophenone SYSTEMATIC 23339572 A 617 626 chalcones FAMILY 23339572 A 637 661 α,β-unsaturated carbonyl FAMILY 23339572 A 677 683 thiols FAMILY 23339572 A 70 73 BAP ABBREVIATION 23339572 A 840 845 thiol FAMILY 23339572 A 855 871 N-acetylcysteine SYSTEMATIC 23339572 A 892 928 5,5'-dithiobis-(2-nitrobenzoic acid) SYSTEMATIC 23339572 T 47 56 chalcones FAMILY 23339572 T 67 91 α,β-unsaturated carbonyl FAMILY 23339577 A 105 115 ferrocenyl TRIVIAL 23339577 A 122 128 acetyl SYSTEMATIC 23339577 A 1290 1300 ferrocenyl TRIVIAL 23339577 A 134 165 AcS-C6H4-C≡C-(fc)n-C≡C-C6H4-SAc FORMULA 23339577 A 214 224 ferrocenyl TRIVIAL 23339577 A 292 294 Au FORMULA 23339577 A 508 522 organometallic FAMILY 23339577 A 583 593 ferrocenyl TRIVIAL 23339577 A 772 782 ferrocenyl TRIVIAL 23339577 A 83 98 fc-C≡C-C6H4-SAc FORMULA 23339577 A 982 989 Au(111) FORMULA 23339577 T 26 40 organometallic FAMILY 23339604 A 1230 1245 dodecamanganese SYSTEMATIC 23339604 A 419 470 Mn(III)(8)Mn(IV)(4)O(12)(L(x,y,z-CB))(16)(H(2)O)(4) FAMILY 23339604 T 122 161 Mn(III)8Mn(IV)4O12(L(x,y,z-CB))16(H2O)4 FAMILY 23339604 T 87 96 manganese SYSTEMATIC 23339678 A 1009 1018 ketorolac TRIVIAL 23339678 A 1164 1173 ketorolac TRIVIAL 23339678 A 1306 1315 ketorolac TRIVIAL 23339678 A 250 259 ketorolac TRIVIAL 23339678 A 62 71 ketorolac TRIVIAL 23339678 A 791 800 ketorolac TRIVIAL 23339678 T 10 19 ketorolac TRIVIAL 23339974 A 516 527 gly-gly-lys FORMULA 23340331 A 106 115 hydroxide SYSTEMATIC 23340331 A 120 129 carbonate FAMILY 23340331 A 421 435 carbon dioxide SYSTEMATIC 23340331 A 488 490 Pb FORMULA 23340331 A 592 594 Pb FORMULA 23340331 A 599 605 Pb(2+) FORMULA 23340331 A 700 703 HCl FORMULA 23340332 A 1035 1040 Na(+) FORMULA 23340332 A 1041 1045 K(+) FORMULA 23340332 A 1069 1074 Na(+) FORMULA 23340332 A 1079 1084 Cl(-) FORMULA 23340332 A 1257 1263 Cu(2+) FORMULA 23340332 A 1313 1318 Cl(-) FORMULA 23340332 A 1376 1381 Na(+) FORMULA 23340332 A 1703 1709 copper SYSTEMATIC 23340332 A 489 495 copper SYSTEMATIC 23340332 A 880 886 Cu(2+) FORMULA 23340332 T 35 41 copper SYSTEMATIC 23340333 A 1055 1064 disulfide SYSTEMATIC 23340334 A 379 386 Toluene TRIVIAL 23340334 A 702 708 oxygen SYSTEMATIC 23340334 A 840 847 toluene TRIVIAL 23340334 A 915 922 toluene TRIVIAL 23340334 A 927 933 oxygen SYSTEMATIC 23340646 A 1254 1261 lithium SYSTEMATIC 23340646 A 1373 1382 Fe(3)O(4) FORMULA 23340646 A 1392 1399 lithium SYSTEMATIC 23340646 A 1467 1473 sodium SYSTEMATIC 23340646 A 191 198 lithium SYSTEMATIC 23340646 A 203 209 sodium SYSTEMATIC 23340646 A 295 304 Fe(3)O(4) FORMULA 23340646 A 66 73 lithium SYSTEMATIC 23340646 A 78 84 sodium SYSTEMATIC 23340646 A 819 826 lithium SYSTEMATIC 23340646 A 850 859 Fe(3)O(4) FORMULA 23340646 A 947 955 graphite TRIVIAL 23340646 A 982 997 Li(4)Ti(5)O(12) FORMULA 23340646 T 116 121 Fe3O4 FORMULA 23340646 T 51 58 lithium SYSTEMATIC 23340646 T 67 73 sodium SYSTEMATIC 23340858 A 229 237 GaZnSeAs FORMULA 23340858 T 24 32 GaZnSeAs FORMULA 23340977 A 123 125 Mn FORMULA 23340977 A 130 132 Fe FORMULA 23340977 A 196 198 Mn FORMULA 23340977 A 203 205 Fe FORMULA 23340977 A 329 336 ammonia SYSTEMATIC 23340977 A 338 341 NH3 FORMULA 23340981 A 1050 1058 nicotine TRIVIAL 23340981 A 1204 1212 nicotine TRIVIAL 23340981 A 1308 1316 nicotine TRIVIAL 23340981 A 1455 1463 nicotine TRIVIAL 23340981 A 1619 1627 nicotine TRIVIAL 23340981 A 181 189 nicotine TRIVIAL 23340981 A 435 443 nicotine TRIVIAL 23340981 A 893 901 nicotine TRIVIAL 23340981 T 33 41 nicotine TRIVIAL 23341175 A 11 21 pyrethroid FAMILY 23341175 A 124 137 organophorous FAMILY 23341175 A 139 148 carbamate FAMILY 23341175 A 1500 1511 pyrethroids FAMILY 23341175 A 154 168 organochlorine FAMILY 23341175 A 203 214 Pyrethroids FAMILY 23341175 A 355 366 Pyrethroids FAMILY 23341175 A 765 775 permethrin TRIVIAL 23341175 A 838 848 permethrin TRIVIAL 23341175 A 936 947 pyrethroids FAMILY 23341175 T 51 61 pyrethroid FAMILY 23341248 A 1075 1077 Ag FORMULA 23341248 A 1179 1181 Ag FORMULA 23341248 A 23 29 silver SYSTEMATIC 23341248 A 524 530 oxygen SYSTEMATIC 23341248 A 693 695 Ag FORMULA 23341248 A 984 986 Ag FORMULA 23341248 T 0 6 Silver SYSTEMATIC 23341258 A 0 10 Nonivamide TRIVIAL 23341258 A 1030 1040 nonivamide TRIVIAL 23341258 A 1093 1099 Ca(2+) FORMULA 23341258 A 1209 1219 nonivamide TRIVIAL 23341258 A 178 188 nonivamide TRIVIAL 23341258 A 292 302 nonivamide TRIVIAL 23341258 A 44 53 capsaicin TRIVIAL 23341258 A 473 483 nonivamide TRIVIAL 23341258 A 507 513 oxygen SYSTEMATIC 23341258 A 565 575 nonivamide TRIVIAL 23341258 A 657 667 superoxide TRIVIAL 23341258 A 690 701 glutathione TRIVIAL 23341258 A 703 706 GSH ABBREVIATION 23341258 T 50 60 nonivamide TRIVIAL 23343117 A 1040 1045 OH(-) FORMULA 23343117 A 1058 1060 Zn FORMULA 23343117 A 1090 1098 coumarin TRIVIAL 23343117 A 11 16 amide FAMILY 23343117 A 1146 1154 coumarin TRIVIAL 23343117 A 17 31 dipicolylamine FAMILY 23343117 A 2 10 coumarin TRIVIAL 23343117 A 257 282 amide and amine nitrogens MULTIPLE 23343117 A 304 312 coumarin TRIVIAL 23343117 A 337 343 Zn(2+) FORMULA 23343117 A 347 353 Cd(2+) FORMULA 23343117 A 581 587 Zn(2+) FORMULA 23343117 A 592 598 Cd(2+) FORMULA 23343117 A 624 632 pyridine SYSTEMATIC 23343117 A 633 634 N FORMULA 23343117 A 636 641 amine SYSTEMATIC 23343117 A 642 643 N FORMULA 23343117 A 649 654 amide FAMILY 23343117 A 655 656 O FORMULA 23343117 A 671 677 Zn(2+) FORMULA 23343117 A 712 721 hydroxide SYSTEMATIC 23343117 A 729 734 OH(-) FORMULA 23343117 A 766 768 Zn FORMULA 23343117 A 773 775 Cd FORMULA 23343117 A 912 914 Cd FORMULA 23343117 A 966 968 Cd FORMULA 23343117 T 103 109 Cd(II) FORMULA 23343117 T 51 59 coumarin TRIVIAL 23343117 T 60 65 amide FAMILY 23343117 T 66 80 dipicolylamine FAMILY 23343117 T 92 98 Zn(II) FORMULA 23343172 A 151 161 porphyrins FAMILY 23343172 A 814 823 porphyrin FAMILY 23343324 A 131 138 3 μ-ISF ABBREVIATION 23343324 A 256 263 3 μ-ISF ABBREVIATION 23343324 A 65 77 polyisoprene SYSTEMATIC 23343324 A 82 93 polystyrene SYSTEMATIC 23343324 A 98 129 polyferrocenylethylmethylsilane SYSTEMATIC 23343325 A 207 210 EuS FORMULA 23343325 A 252 255 EuS FORMULA 23343325 A 310 317 Eu(III) FORMULA 23343325 A 318 333 dithiocarbamate SYSTEMATIC 23343325 A 342 410 tetraphenylphosphonium tetrakis(diethyldithiocarbamate)europium(III) SYSTEMATIC 23343325 A 416 432 transition-metal FAMILY 23343325 A 458 461 EuS FORMULA 23343325 A 47 53 Mn(II) FORMULA 23343325 A 55 61 Co(II) FORMULA 23343325 A 6 9 EuS FORMULA 23343325 A 66 72 Fe(II) FORMULA 23343325 A 757 760 EuS FORMULA 23343325 T 53 56 EuS FORMULA 23343325 T 88 104 transition-metal FAMILY 23343474 A 0 32 Penta(tert-butylthio)corannulene SYSTEMATIC 23343474 A 273 279 sulfur SYSTEMATIC 23343474 A 37 80 penta(4-dimethylaminophenylthio)corannulene SYSTEMATIC 23343474 A 392 395 C-S FORMULA 23343474 A 522 531 thioether SYSTEMATIC 23343474 A 708 717 thiolates FAMILY 23343474 T 26 54 corannulene penta-thioethers FAMILY 23343595 A 703 713 olanzapine TRIVIAL 23344429 A 1078 1094 L-pipecolic acid TRIVIAL 23344429 A 1100 1108 L-lysine TRIVIAL 23344429 A 1134 1138 NADH ABBREVIATION 23344429 A 702 706 NADH ABBREVIATION 23344429 A 709 712 FAD ABBREVIATION 23344429 A 718 722 haem TRIVIAL 23344429 A 916 921 amine SYSTEMATIC 23344820 A 1051 1066 malondialdehyde TRIVIAL 23344820 A 1068 1071 MDA ABBREVIATION 23344820 A 1077 1089 nitric oxide SYSTEMATIC 23344820 A 1310 1313 MDA ABBREVIATION 23344820 A 1318 1320 NO FORMULA 23344820 A 138 163 adenosine-5'-triphosphate SYSTEMATIC 23344820 A 1492 1496 DMBA ABBREVIATION 23344820 A 1586 1588 NO FORMULA 23344820 A 1643 1647 2-DG ABBREVIATION 23344820 A 1652 1660 malonate TRIVIAL 23344820 A 189 219 7,12-dimethylbenz(a)anthracene SYSTEMATIC 23344820 A 221 225 DMBA ABBREVIATION 23344820 A 509 513 DMBA ABBREVIATION 23344820 A 52 65 2-deoxglucose SYSTEMATIC 23344820 A 527 531 DMBA ABBREVIATION 23344820 A 615 629 2-deoxyglucose SYSTEMATIC 23344820 A 631 635 2-DG ABBREVIATION 23344820 A 69 77 malonate TRIVIAL 23344820 A 695 710 sodium malonate SYSTEMATIC 23344820 A 790 805 sodium malonate SYSTEMATIC 23344820 A 870 874 DMBA ABBREVIATION 23344820 A 932 943 glutathione TRIVIAL 23344820 A 966 976 superoxide TRIVIAL 23344820 A 994 1005 glutathione TRIVIAL 23344820 T 41 55 2-deoxyglucose SYSTEMATIC 23344820 T 60 68 malonate TRIVIAL 23344820 T 72 102 7,12-dimethylbenz(a)anthracene SYSTEMATIC 23344824 A 1100 1108 saponins FAMILY 23344824 A 1113 1123 terpenoids FAMILY 23344824 A 1171 1178 tannins FAMILY 23344824 A 1180 1190 terpenoids FAMILY 23344825 A 102 104 Cr FORMULA 23344825 A 453 455 Pb FORMULA 23344825 A 47 49 Pb FORMULA 23344825 A 52 56 iron SYSTEMATIC 23344825 A 58 60 Fe FORMULA 23344825 A 63 67 zinc SYSTEMATIC 23344825 A 69 71 Zn FORMULA 23344825 A 74 81 cadmium SYSTEMATIC 23344825 A 83 85 Cd FORMULA 23344825 A 92 100 chromium SYSTEMATIC 23344975 A 0 6 Copper SYSTEMATIC 23344975 A 1105 1110 Cu(+) FORMULA 23344975 A 1182 1188 copper SYSTEMATIC 23344975 A 119 125 copper SYSTEMATIC 23344975 A 1226 1232 copper SYSTEMATIC 23344975 A 1291 1297 copper SYSTEMATIC 23344975 A 166 172 Copper SYSTEMATIC 23344975 A 242 248 copper SYSTEMATIC 23344975 A 575 581 copper SYSTEMATIC 23344975 A 659 665 copper SYSTEMATIC 23344975 A 734 740 copper SYSTEMATIC 23344975 A 80 86 copper SYSTEMATIC 23344975 A 901 906 Cu(+) FORMULA 23344975 T 60 66 copper SYSTEMATIC 23345132 A 1329 1336 steroid FAMILY 23345132 A 1431 1439 androgen FAMILY 23345132 A 1583 1591 androgen FAMILY 23345132 A 189 212 17α-hydroxyprogesterone SYSTEMATIC 23345132 A 254 262 androgen FAMILY 23345132 A 280 299 dihydrotestosterone SYSTEMATIC 23345132 A 301 324 17α-Hydroxyprogesterone SYSTEMATIC 23345132 A 347 366 dihydrotestosterone SYSTEMATIC 23345132 A 371 388 4-androstenedione SYSTEMATIC 23345132 A 429 452 17α-hydroxypregnenolone SYSTEMATIC 23345132 A 457 479 dehydroepiandrosterone TRIVIAL 23345132 A 600 622 dehydroepiandrosterone TRIVIAL 23345132 A 624 641 4-androstenedione SYSTEMATIC 23345132 A 647 659 testosterone TRIVIAL 23345132 A 771 779 androgen FAMILY 23345132 A 862 869 steroid FAMILY 23345132 T 0 8 Androgen FAMILY 23346898 A 113 138 [Ni(Me(6)tren)Cl](ClO(4)) FORMULA 23346898 A 147 168 [Ni(Me(6)tren)Br](Br) FORMULA 23346898 A 561 567 Ni(II) FORMULA 23346898 A 74 101 trigonal bipyramidal Ni(II) FAMILY 23346898 T 40 67 trigonal bipyramidal Ni(II) FAMILY 23347052 A 231 235 DOPA ABBREVIATION 23347052 A 242 247 amine SYSTEMATIC 23347052 A 326 330 iron SYSTEMATIC 23347052 A 410 414 DOPA ABBREVIATION 23347052 A 415 419 iron SYSTEMATIC 23347151 A 1312 1315 C-C FORMULA 23347151 A 390 395 CH3CN FORMULA 23347151 A 44 52 hydrogen SYSTEMATIC 23347151 A 509 512 C═C FORMULA 23347151 A 784 789 CH3CN FORMULA 23347151 A 828 833 CH3OH FORMULA 23347151 A 838 846 CF3CH2OH FORMULA 23347151 T 11 19 hydrogen SYSTEMATIC 23347151 T 84 94 para-amino SYSTEMATIC 23347422 A 1029 1036 DiynePE ABBREVIATION 23347422 A 1100 1119 polydimethylsiloxan SYSTEMATIC 23347422 A 1121 1125 PDMS ABBREVIATION 23347422 A 1427 1434 DiynePC ABBREVIATION 23347422 A 1435 1442 DiynePE ABBREVIATION 23347422 A 196 207 diacetylene SYSTEMATIC 23347422 A 234 291 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine SYSTEMATIC 23347422 A 293 300 DiynePC ABBREVIATION 23347422 A 306 368 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphoethanolamine SYSTEMATIC 23347422 A 370 377 DiynePE ABBREVIATION 23347422 A 380 387 DiynePC ABBREVIATION 23347422 A 435 447 ethanolamine SYSTEMATIC 23347422 A 461 468 DiynePE ABBREVIATION 23347422 A 559 566 DiynePC ABBREVIATION 23347422 A 571 578 DiynePE ABBREVIATION 23347547 A 0 9 Quercetin TRIVIAL 23347547 A 1138 1147 quercetin TRIVIAL 23347547 A 476 487 acetic acid SYSTEMATIC 23347547 A 54 63 flavonoid FAMILY 23347547 T 0 9 Quercetin TRIVIAL 23347683 A 102 116 norepinephrine TRIVIAL 23347683 A 12 49 3-(phenoxy-phenyl-methyl)-pyrrolidine SYSTEMATIC 23347683 A 126 135 serotonin TRIVIAL 23347683 A 137 156 5-hydroxytryptamine SYSTEMATIC 23347683 A 158 162 5-HT SYSTEMATIC 23347683 T 17 55 3-(phenoxy-phenyl-methyl)-pyrrolidines FAMILY 23347683 T 79 93 norepinephrine TRIVIAL 23347683 T 98 107 serotonin TRIVIAL 23347684 A 0 44 2-(4-Chloro-2-cyano-2-phenylbutyl)aziridines FAMILY 23347684 A 113 177 endo- and exo-2-aminomethyl-4-phenyl-1-azabicyclo[2.2.1]heptanes MULTIPLE 23347684 A 185 202 azaheterobicyclic FAMILY 23347684 A 226 234 LiAlH(4) FORMULA 23347684 A 310 337 1-azabicyclo[2.2.1]heptanes FAMILY 23347684 T 108 152 2-(4-chloro-2-cyano-2-phenylbutyl)aziridines FAMILY 23347684 T 13 63 2-aminomethyl-4-phenyl-1-azabicyclo[2.2.1]heptanes FAMILY 23347684 T 68 74 LiAlH₄ FORMULA 23347875 A 0 22 Hexabromocyclododecane SYSTEMATIC 23347875 A 1010 1015 HBCDD ABBREVIATION 23347875 A 1161 1166 HBCDD ABBREVIATION 23347875 A 1261 1265 cAMP ABBREVIATION 23347875 A 1291 1295 cAMP ABBREVIATION 23347875 A 1306 1317 cholesterol TRIVIAL 23347875 A 1373 1377 cAMP ABBREVIATION 23347875 A 1422 1427 HBCDD ABBREVIATION 23347875 A 237 242 HBCDD ABBREVIATION 23347875 A 24 29 HBCDD ABBREVIATION 23347875 A 316 321 HBCDD ABBREVIATION 23347875 A 366 375 forskolin TRIVIAL 23347875 A 386 390 cAMP ABBREVIATION 23347875 A 449 453 cAMP ABBREVIATION 23347875 A 528 532 cAMP ABBREVIATION 23347875 A 600 611 cholesterol TRIVIAL 23347875 A 644 661 3β-hydroxysteroid FAMILY 23347875 A 699 704 HBCDD ABBREVIATION 23347875 A 975 999 22(R)-hydroxycholesterol SYSTEMATIC 23347875 T 17 39 hexabromocyclododecane SYSTEMATIC 23347875 T 62 72 nucleotide FAMILY 23348152 A 1059 1066 selenol FAMILY 23348152 A 1082 1086 RSeH FORMULA 23348152 A 1132 1138 thiols FAMILY 23348152 A 1197 1202 NADPH ABBREVIATION 23348152 A 301 319 diaryl diselenides FAMILY 23348152 A 321 351 p-methoxyl-diphenyl diselenide SYSTEMATIC 23348152 A 352 376 (p-CH(3)O-C(6)H(4)Se)(2) FORMULA 23348152 A 386 414 p-chloro-diphenyl diselenide SYSTEMATIC 23348152 A 415 435 (p-Cl-C(6)H(4)Se)(2) SYSTEMATIC 23348152 A 445 451 Cu(2+) FORMULA 23348152 A 747 753 Cu(2+) FORMULA 23348152 A 801 819 diaryl diselenides FAMILY 23348152 T 14 32 diaryl diselenides FAMILY 23348499 A 132 139 glucose TRIVIAL 23348501 A 100 109 disulfide SYSTEMATIC 23348501 A 1017 1026 disulfide SYSTEMATIC 23348501 A 1041 1044 CPT ABBREVIATION 23348501 A 1049 1052 NPT ABBREVIATION 23348501 A 1131 1134 GSH ABBREVIATION 23348501 A 1207 1218 clopidogrel TRIVIAL 23348501 A 124 135 clopidogrel TRIVIAL 23348501 A 1404 1409 thiol FAMILY 23348501 A 1410 1419 disulfide SYSTEMATIC 23348501 A 1442 1445 GSH ABBREVIATION 23348501 A 1504 1513 disulfide SYSTEMATIC 23348501 A 1750 1761 clopidogrel TRIVIAL 23348501 A 211 227 2-oxoclopidogrel SYSTEMATIC 23348501 A 288 293 thiol FAMILY 23348501 A 324 329 thiol FAMILY 23348501 A 348 359 glutathione TRIVIAL 23348501 A 361 364 GSH ABBREVIATION 23348501 A 483 492 disulfide SYSTEMATIC 23348501 A 535 561 6-chloropyridazine-3-thiol SYSTEMATIC 23348501 A 563 566 CPT ABBREVIATION 23348501 A 569 594 2,5-dimethylfuran-3-thiol SYSTEMATIC 23348501 A 600 623 3-nitropyridine-2-thiol SYSTEMATIC 23348501 A 625 628 NPT ABBREVIATION 23348501 A 753 762 disulfide SYSTEMATIC 23348501 A 799 804 thiol FAMILY 23348501 A 857 866 disulfide SYSTEMATIC 23348501 A 905 911 thiols FAMILY 23348501 A 917 920 GSH ABBREVIATION 23348501 T 58 67 disulfide SYSTEMATIC 23348501 T 82 93 clopidogrel TRIVIAL 23348514 A 1044 1053 metformin TRIVIAL 23348514 A 1152 1161 metformin TRIVIAL 23348514 A 1232 1242 fatty acid FAMILY 23348514 A 1304 1313 metformin TRIVIAL 23348514 A 1425 1434 metformin TRIVIAL 23348514 A 393 400 glucose TRIVIAL 23348514 A 414 423 Metformin TRIVIAL 23348514 A 542 551 metformin TRIVIAL 23348514 A 663 672 metformin TRIVIAL 23348514 A 794 803 metformin TRIVIAL 23348514 A 977 984 alanine TRIVIAL 23348514 T 11 20 metformin TRIVIAL 23348754 A 1035 1043 oxytocin TRIVIAL 23348754 A 1072 1105 3,4-methylenedioxymethamphetamine SYSTEMATIC 23348754 A 1107 1111 MDMA ABBREVIATION 23348754 A 1113 1120 Ecstasy TRIVIAL 23348754 A 1210 1218 oxytocin TRIVIAL 23348754 A 1352 1356 MDMA ABBREVIATION 23348754 A 204 212 Oxytocin TRIVIAL 23348754 A 39 47 oxytocin TRIVIAL 23348754 A 509 517 oxytocin TRIVIAL 23348754 A 681 689 oxytocin TRIVIAL 23348754 A 797 805 oxytocin TRIVIAL 23348754 A 872 880 oxytocin TRIVIAL 23348754 A 910 917 cocaine TRIVIAL 23348754 A 922 937 methamphetamine TRIVIAL 23348754 T 19 27 oxytocin TRIVIAL 23349486 A 1034 1046 pioglitazone TRIVIAL 23349486 A 324 342 thiazolidinediones FAMILY 23349486 A 470 482 pioglitazone TRIVIAL 23349486 A 540 552 pioglitazone TRIVIAL 23349486 A 934 946 pioglitazone TRIVIAL 23349486 T 93 110 Thiazolidinedione SYSTEMATIC 23349498 A 204 211 glucose TRIVIAL 23349500 A 1051 1058 calcium SYSTEMATIC 23349500 A 142 149 glucose TRIVIAL 23349500 A 1426 1433 glucose TRIVIAL 23349500 A 225 229 cAMP ABBREVIATION 23349500 A 281 288 glucose TRIVIAL 23349500 A 341 345 cAMP ABBREVIATION 23349500 A 53 60 glucose TRIVIAL 23349500 A 593 600 glucose TRIVIAL 23349500 A 728 735 glucose TRIVIAL 23349500 T 71 78 Glucose TRIVIAL 23349501 A 1090 1097 17-HDHA SYSTEMATIC 23349501 A 1215 1222 glucose TRIVIAL 23349501 A 1375 1382 17-HDHA SYSTEMATIC 23349501 A 1387 1399 protectin D1 TRIVIAL 23349501 A 1466 1473 17-HDHA SYSTEMATIC 23349501 A 367 376 resolvins FAMILY 23349501 A 419 446 polyunsaturated fatty acids FAMILY 23349501 A 447 468 eicosapentaenoic acid SYSTEMATIC 23349501 A 470 473 EPA ABBREVIATION 23349501 A 479 499 docosahexaenoic acid SYSTEMATIC 23349501 A 501 504 DHA ABBREVIATION 23349501 A 603 606 EPA ABBREVIATION 23349501 A 607 610 DHA ABBREVIATION 23349501 A 773 776 DHA ABBREVIATION 23349501 A 785 815 17-hydroxydocosahexaenoic acid SYSTEMATIC 23349501 A 817 824 17-HDHA SYSTEMATIC 23349501 A 826 837 resolvin D1 TRIVIAL 23349501 A 853 865 protectin D1 TRIVIAL 23349501 A 907 910 EPA ABBREVIATION 23349501 A 911 914 DHA ABBREVIATION 23349501 T 74 81 17-HDHA SYSTEMATIC 23350730 A 227 234 calcium SYSTEMATIC 23350730 A 374 381 calcium SYSTEMATIC 23350730 A 506 513 calcium SYSTEMATIC 23350730 A 593 600 calcium SYSTEMATIC 23350730 A 605 614 vitamin D FAMILY 23350730 T 16 23 calcium SYSTEMATIC 23350797 A 438 450 nitric oxide SYSTEMATIC 23350797 A 65 96 7-chloro-4-quinolinyl hydrazone FAMILY 23350797 T 0 32 7-Chloro-4-quinolinyl Hydrazones FAMILY 23350945 A 1025 1029 DMMP ABBREVIATION 23350945 A 111 120 Al(2)O(3) FORMULA 23350945 A 263 267 DMMP ABBREVIATION 23350945 A 293 298 H(2)O FORMULA 23350945 A 318 322 DMMP ABBREVIATION 23350945 A 375 383 hydrogen SYSTEMATIC 23350945 A 39 65 dimethyl methylphosphonate SYSTEMATIC 23350945 A 391 396 H(2)O FORMULA 23350945 A 451 460 Al(2)O(3) FORMULA 23350945 A 469 478 Al(OH)(3) FORMULA 23350945 A 486 493 AlO(OH) FORMULA 23350945 A 499 502 P═O FORMULA 23350945 A 512 516 DMMP ABBREVIATION 23350945 A 546 551 H(2)O FORMULA 23350945 A 600 605 oxide SYSTEMATIC 23350945 A 67 71 DMMP ABBREVIATION 23350945 A 689 694 H(2)O FORMULA 23350945 A 734 739 Al-OH FORMULA 23350945 A 755 762 methoxy SYSTEMATIC 23350945 A 76 81 H(2)O FORMULA 23350945 A 763 764 O FORMULA 23350945 A 774 778 DMMP ABBREVIATION 23350945 A 801 805 DMMP ABBREVIATION 23350945 A 849 854 oxide SYSTEMATIC 23350945 T 38 43 Al2O3 FORMULA 23350945 T 70 96 dimethyl methylphosphonate SYSTEMATIC 23351082 A 332 358 10-hydroxy-2-decenoic acid SYSTEMATIC 23351082 A 523 534 fatty acids FAMILY 23351082 A 576 587 fatty acids FAMILY 23351082 A 608 614 esters FAMILY 23351082 A 621 632 fatty acids FAMILY 23351082 A 643 667 medium-chain fatty acids FAMILY 23351082 A 745 771 mono- or dicarboxylic acid MULTIPLE 23351082 A 846 857 fatty acids FAMILY 23351096 A 250 260 iron oxide SYSTEMATIC 23351096 A 752 820 poly(N-isopropylacrylamide-co-acrylamide)-block-poly(ε-caprolactone) SYSTEMATIC 23351096 A 972 983 doxorubicin TRIVIAL 23351139 A 114 120 AZT-TP ABBREVIATION 23351139 A 23 45 adenosine triphosphate SYSTEMATIC 23351139 A 433 436 ATP ABBREVIATION 23351139 A 437 443 AZT-TP ABBREVIATION 23351139 A 47 50 ATP ABBREVIATION 23351139 A 56 66 nucleotide FAMILY 23351139 A 674 684 nucleotide FAMILY 23351139 A 689 699 nucleotide FAMILY 23351139 A 796 799 ATP ABBREVIATION 23351139 A 804 810 AZT-TP ABBREVIATION 23351139 A 85 112 azidothymidine triphosphate SYSTEMATIC 23351139 A 863 866 ATP ABBREVIATION 23351139 A 874 880 AZT-TP ABBREVIATION 23351139 A 986 989 ATP ABBREVIATION 23351139 A 994 1000 AZT-TP ABBREVIATION 23351139 T 77 88 nucleotides FAMILY 23351139 T 93 103 nucleotide FAMILY 23351961 A 0 8 Curcumin TRIVIAL 23351961 A 1186 1189 SDS ABBREVIATION 23351961 A 1295 1303 curcumin TRIVIAL 23351961 A 1446 1454 curcumin TRIVIAL 23351961 A 157 165 curcumin TRIVIAL 23351961 A 1986 1994 curcumin TRIVIAL 23351961 A 2094 2102 curcumin TRIVIAL 23351961 A 289 350 3-(4,5-dimethyl-thiazol-2-yl)-2-5-diphenyltetrazolium-bromide SYSTEMATIC 23351961 A 352 355 MTT ABBREVIATION 23351961 A 375 383 curcumin TRIVIAL 23351961 A 528 536 curcumin TRIVIAL 23351961 A 734 742 curcumin TRIVIAL 23351961 A 862 870 curcumin TRIVIAL 23351961 T 22 30 curcumin TRIVIAL 23352141 A 501 510 γ-pyrones FAMILY 23352141 A 520 531 nocapyrones FAMILY 23352141 A 758 769 nocapyrones FAMILY 23352141 T 31 49 pyrone polyketides FAMILY 23352430 A 149 157 cytidine TRIVIAL 23352430 A 496 499 CpG ABBREVIATION 23352430 A 500 513 dinucleotides FAMILY 23352430 A 767 778 hydroxyurea SYSTEMATIC 23352650 A 1184 1192 hydrogen SYSTEMATIC 23352650 A 1346 1356 PNU-120596 IDENTIFIER 23352650 A 1573 1574 H FORMULA 23352650 A 254 260 GTS-21 IDENTIFIER 23352650 A 262 272 2,4diMeOBA SYSTEMATIC 23352650 A 27 40 acetylcholine SYSTEMATIC 23352650 A 324 346 benzylidene anabaseine FAMILY 23352650 A 558 564 GTS-21 IDENTIFIER 23352650 A 567 576 dihydroxy SYSTEMATIC 23352650 A 589 598 2,4diOHBA SYSTEMATIC 23352650 A 779 787 hydroxyl SYSTEMATIC 23352650 A 804 815 benzylidene SYSTEMATIC 23352650 A 893 899 serine TRIVIAL 23352650 T 158 181 benzylidene anabaseines FAMILY 23352910 A 202 217 poly-l-arginine SYSTEMATIC 23352910 A 592 655 1, 1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine iodide SYSTEMATIC 23352910 A 656 659 DiR ABBREVIATION 23352929 A 1115 1123 phenolic FAMILY 23352929 A 1182 1196 salicylic acid TRIVIAL 23352929 A 372 384 nitric oxide SYSTEMATIC 23352929 A 386 388 NO FORMULA 23352929 A 429 441 nitric oxide SYSTEMATIC 23352929 A 940 942 NO FORMULA 23353026 A 1136 1138 Mn FORMULA 23353026 A 124 130 oxygen SYSTEMATIC 23353026 A 1256 1259 GSH ABBREVIATION 23353026 A 1278 1282 H2O2 FORMULA 23353026 A 1319 1321 Mn FORMULA 23353026 A 16 25 manganese SYSTEMATIC 23353026 A 188 190 Mn FORMULA 23353026 A 27 29 Mn FORMULA 23353026 A 272 281 manganese SYSTEMATIC 23353026 A 372 374 Mn FORMULA 23353026 A 455 471 propidium iodide TRIVIAL 23353026 A 520 527 lactate FAMILY 23353026 A 600 602 Mn FORMULA 23353026 A 692 702 superoxide TRIVIAL 23353026 A 729 731 Mn FORMULA 23353026 A 822 824 Mn FORMULA 23353026 A 957 959 Mn FORMULA 23353026 T 32 41 manganese SYSTEMATIC 23353027 A 10 17 arsenic SYSTEMATIC 23353027 A 1007 1015 arsenite SYSTEMATIC 23353027 A 1020 1028 thio-DMA SYSTEMATIC 23353027 A 1058 1061 GSH ABBREVIATION 23353027 A 1066 1070 GSSG ABBREVIATION 23353027 A 1162 1166 H2O2 FORMULA 23353027 A 1347 1355 arsenite SYSTEMATIC 23353027 A 1360 1368 thio-DMA SYSTEMATIC 23353027 A 1417 1424 arsenic SYSTEMATIC 23353027 A 157 164 arsenic SYSTEMATIC 23353027 A 253 260 arsenic SYSTEMATIC 23353027 A 334 335 S FORMULA 23353027 A 347 354 arsenic SYSTEMATIC 23353027 A 452 460 arsenite SYSTEMATIC 23353027 A 462 487 thio-dimethylarsinic acid SYSTEMATIC 23353027 A 489 497 thio-DMA SYSTEMATIC 23353027 A 506 533 dimethylarsinic glutathione SYSTEMATIC 23353027 A 535 539 DMAG ABBREVIATION 23353027 A 789 795 oxygen SYSTEMATIC 23353027 A 800 808 nitrogen SYSTEMATIC 23353027 T 110 137 dimethylarsinic glutathione SYSTEMATIC 23353027 T 47 48 S FORMULA 23353027 T 60 67 arsenic SYSTEMATIC 23353027 T 80 105 thio-dimethylarsinic acid SYSTEMATIC 23353058 A 1021 1023 Cu FORMULA 23353058 A 1050 1052 Na FORMULA 23353058 A 1076 1078 Cu FORMULA 23353058 A 1204 1210 copper SYSTEMATIC 23353058 A 1377 1379 Cu FORMULA 23353058 A 1411 1413 Cu FORMULA 23353058 A 1455 1457 Cu FORMULA 23353058 A 1483 1485 Cu FORMULA 23353058 A 1500 1502 Na FORMULA 23353058 A 1503 1504 K FORMULA 23353058 A 1613 1615 Cu FORMULA 23353058 A 1642 1644 Cu FORMULA 23353058 A 1697 1699 Cu FORMULA 23353058 A 1756 1758 Cu FORMULA 23353058 A 1809 1811 Cu FORMULA 23353058 A 1847 1849 Cu FORMULA 23353058 A 1986 1988 Cu FORMULA 23353058 A 2132 2134 Na FORMULA 23353058 A 2135 2136 K FORMULA 23353058 A 2275 2277 Cu FORMULA 23353058 A 2492 2494 Cu FORMULA 23353058 A 301 303 Cu FORMULA 23353058 A 324 326 Cu FORMULA 23353058 A 34 40 copper SYSTEMATIC 23353058 A 379 381 Cu FORMULA 23353058 A 398 400 Cu FORMULA 23353058 A 557 559 Na FORMULA 23353058 A 619 621 Cu FORMULA 23353058 A 652 658 copper SYSTEMATIC 23353058 A 757 759 Na FORMULA 23353058 A 783 785 Cu FORMULA 23353058 A 845 847 Cu FORMULA 23353058 T 14 20 copper SYSTEMATIC 23353658 A 0 9 Coumarins FAMILY 23353658 A 1289 1300 imperatorin TRIVIAL 23353658 A 1302 1316 isoimperatorin TRIVIAL 23353658 A 1321 1329 cnidilin TRIVIAL 23353658 A 1371 1380 coumarins FAMILY 23353658 A 1479 1490 imperatorin TRIVIAL 23353658 A 1495 1509 isoimperatorin TRIVIAL 23353658 A 1599 1607 cnidilin TRIVIAL 23353658 A 1653 1662 coumarins FAMILY 23353658 A 327 336 coumarins FAMILY 23353658 A 348 359 imperatorin TRIVIAL 23353658 A 361 375 isoimperatorin TRIVIAL 23353658 A 380 388 cnidilin TRIVIAL 23353658 A 501 513 acetonitrile SYSTEMATIC 23353658 A 951 962 imperatorin TRIVIAL 23353658 A 964 978 isoimperatorin TRIVIAL 23353658 A 983 991 cnidilin TRIVIAL 23353658 T 101 115 isoimperatorin TRIVIAL 23353658 T 120 128 cnidilin TRIVIAL 23353658 T 88 99 imperatorin TRIVIAL 23353659 A 112 125 curculigine I TRIVIAL 23353659 A 142 160 phenolic glycoside FAMILY 23353659 A 162 174 orcinoside H TRIVIAL 23353659 A 206 225 phenolic glycosides FAMILY 23353659 A 36 49 curculigine E TRIVIAL 23353659 A 389 408 phenolic glycosides FAMILY 23353659 A 487 490 MTT ABBREVIATION 23353659 A 55 68 curculigine F TRIVIAL 23353659 A 74 87 curculigine G TRIVIAL 23353659 A 9 34 chlorophenolic glucosides FAMILY 23353659 A 93 106 curculigine H TRIVIAL 23353659 T 0 19 Phenolic glycosides FAMILY 23353698 A 1050 1059 quercetin TRIVIAL 23353698 A 1149 1156 ABT-737 IDENTIFIER 23353698 A 1161 1170 quercetin TRIVIAL 23353698 A 1268 1277 quercetin TRIVIAL 23353698 A 288 295 ABT-737 IDENTIFIER 23353698 A 345 352 ABT-737 IDENTIFIER 23353698 A 512 521 quercetin TRIVIAL 23353698 A 525 534 flavonoid FAMILY 23353698 A 795 802 ABT-737 IDENTIFIER 23353698 A 807 816 quercetin TRIVIAL 23353698 A 993 1002 quercetin TRIVIAL 23353698 T 0 7 ABT-737 IDENTIFIER 23353698 T 154 163 quercetin TRIVIAL 23353699 A 1050 1053 PP1 IDENTIFIER 23353699 A 1122 1125 PP1 IDENTIFIER 23353699 A 1127 1133 AG1478 IDENTIFIER 23353699 A 1135 1141 AG1296 IDENTIFIER 23353699 A 1146 1154 LY294002 IDENTIFIER 23353699 A 1453 1456 PP1 IDENTIFIER 23353699 A 1458 1464 AG1478 IDENTIFIER 23353699 A 1466 1472 AG1296 IDENTIFIER 23353699 A 1474 1482 LY294002 IDENTIFIER 23353699 A 1484 1492 SB202190 IDENTIFIER 23353699 A 1494 1502 SP600125 IDENTIFIER 23353699 A 1507 1512 U0126 IDENTIFIER 23353699 A 752 755 PP1 IDENTIFIER 23353699 A 764 770 AG1478 IDENTIFIER 23353699 A 780 786 AG1296 IDENTIFIER 23353699 A 795 803 LY294002 IDENTIFIER 23353699 A 811 815 SH-5 IDENTIFIER 23353699 A 826 831 U0126 IDENTIFIER 23353699 A 844 852 SB202190 IDENTIFIER 23353699 A 863 871 SP600125 IDENTIFIER 23353699 A 883 897 Tanshinone IIA TRIVIAL 23353733 A 143 178 1,4-di-substituted 2-aminoimidazole FAMILY 23353733 A 179 188 triazoles FAMILY 23353733 A 190 196 2-AITs FAMILY 23353733 A 373 379 2-AITs FAMILY 23353733 A 38 55 2-aminoimidazoles FAMILY 23353733 A 4 31 pyrrole-imidazole alkaloids FAMILY 23353733 T 125 134 β-lactams FAMILY 23353733 T 23 59 1,4-di-substituted 2-aminoimidazoles FAMILY 23353741 A 171 175 (1)H FORMULA 23353741 A 181 186 (13)C FORMULA 23353741 A 22 39 resveratrol amide SYSTEMATIC 23353741 A 449 465 prostaglandin E2 TRIVIAL 23353741 A 467 471 PGE2 ABBREVIATION 23353741 T 50 67 resveratrol amide SYSTEMATIC 23353743 A 18 48 1,2,3-triazole-dithiocarbamate SYSTEMATIC 23353743 A 513 527 5-fluorouracil SYSTEMATIC 23353743 T 30 60 1,2,3-triazole-dithiocarbamate SYSTEMATIC 23353815 A 1032 1034 Zn FORMULA 23353815 A 1091 1093 Cd FORMULA 23353815 A 218 225 cadmium SYSTEMATIC 23353815 A 227 229 Cd FORMULA 23353815 A 329 337 n-hexane SYSTEMATIC 23353815 A 339 342 Hex ABBREVIATION 23353815 A 378 380 Zn FORMULA 23353815 A 385 387 Fe FORMULA 23353815 A 45 49 zinc SYSTEMATIC 23353815 A 51 53 Zn FORMULA 23353815 A 585 588 Hex ABBREVIATION 23353815 A 597 600 Hex ABBREVIATION 23353815 A 752 754 Cd FORMULA 23353815 A 759 761 Zn FORMULA 23353815 A 81 85 iron SYSTEMATIC 23353815 A 830 832 Cd FORMULA 23353815 A 844 847 Hex ABBREVIATION 23353815 A 87 89 Fe FORMULA 23353815 A 903 906 Hex ABBREVIATION 23353815 A 938 940 Cd FORMULA 23353815 A 957 959 Zn FORMULA 23353815 A 986 988 Fe FORMULA 23353815 T 64 66 Cd FORMULA 23353816 A 10 17 arsenic SYSTEMATIC 23353816 A 1000 1008 DMA(III) FORMULA 23353816 A 1097 1103 oxygen SYSTEMATIC 23353816 A 112 120 MMA(III) ABBREVIATION 23353816 A 1157 1160 GSH ABBREVIATION 23353816 A 126 147 dimethylarsinous acid SYSTEMATIC 23353816 A 1286 1297 glutathione TRIVIAL 23353816 A 1434 1441 arsenic SYSTEMATIC 23353816 A 149 157 DMA(III) FORMULA 23353816 A 188 195 arsenic SYSTEMATIC 23353816 A 19 24 As(V) FORMULA 23353816 A 25 32 As(III) FORMULA 23353816 A 347 354 arsenic SYSTEMATIC 23353816 A 553 575 monomethylarsonic acid SYSTEMATIC 23353816 A 577 583 MMA(V) ABBREVIATION 23353816 A 585 605 dimethylarsinic acid SYSTEMATIC 23353816 A 607 613 DMA(V) FORMULA 23353816 A 615 623 MMA(III) ABBREVIATION 23353816 A 628 636 DMA(III) FORMULA 23353816 A 87 110 monomethylarsonous acid SYSTEMATIC 23353816 A 880 887 As(III) FORMULA 23353816 A 982 990 MMA(III) ABBREVIATION 23353816 T 69 76 arsenic SYSTEMATIC 23354070 A 1050 1059 palinurin TRIVIAL 23354070 A 470 483 sesquiterpene FAMILY 23354070 A 484 493 palinurin TRIVIAL 23354070 A 627 636 palinurin TRIVIAL 23354070 A 663 666 ATP ABBREVIATION 23354070 A 891 900 palinurin TRIVIAL 23354070 T 87 96 palinurin TRIVIAL 23354072 A 117 135 phenolic glycoside FAMILY 23354072 A 137 242 2-(2-benzoyl-β-D-glucopyranosyloxy)-7-(1α,2α,6α-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol SYSTEMATIC 23354072 A 261 276 poliothrysoside TRIVIAL 23354072 A 282 345 catechin-[5,6-e]-4β-(3,4-dihydroxyphenyl)dihydro-2(3H)-pyranone SYSTEMATIC 23354072 A 351 456 2-(6-benzoyl-β-D-glucopyranosyloxy)-7-(1α,2α,6α-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol SYSTEMATIC 23354072 A 462 497 chrysoeriol-7-O-β-D-glucopyranoside SYSTEMATIC 23354072 A 507 516 mururin A TRIVIAL 23354072 A 587 598 chloroquine TRIVIAL 23354072 A 621 632 chloroquine TRIVIAL 23354072 A 705 712 hematin TRIVIAL 23354072 A 726 735 β-hematin TRIVIAL 23354072 A 786 790 heme FAMILY 23354072 T 32 41 β-hematin TRIVIAL 23354391 A 0 8 Daidzein TRIVIAL 23354391 A 1068 1076 daidzein TRIVIAL 23354391 A 1122 1124 Ca FORMULA 23354391 A 1165 1173 daidzein TRIVIAL 23354391 A 1229 1237 daidzein TRIVIAL 23354391 A 1273 1280 calcium SYSTEMATIC 23354391 A 13 21 estrogen FAMILY 23354391 A 1341 1348 calcium SYSTEMATIC 23354391 A 187 195 estrogen FAMILY 23354391 A 360 368 daidzein TRIVIAL 23354391 A 382 389 calcium SYSTEMATIC 23354391 A 682 690 daidzein TRIVIAL 23354391 A 775 777 Ca FORMULA 23354391 A 839 847 daidzein TRIVIAL 23354391 A 925 927 Ca FORMULA 23354391 A 970 978 daidzein TRIVIAL 23354391 T 21 29 daidzein TRIVIAL 23354391 T 66 73 calcium SYSTEMATIC 23354727 A 511 519 steroids FAMILY 23354755 A 127 131 coal TRIVIAL 23354755 T 40 44 coal TRIVIAL 23355287 A 119 125 carbon SYSTEMATIC 23355287 A 145 149 TiO2 FORMULA 23355287 T 12 16 TiO2 FORMULA 23355287 T 31 37 carbon SYSTEMATIC 23355467 A 1117 1122 sugar FAMILY 23355467 A 1200 1212 carbohydrate FAMILY 23355467 A 170 175 sugar FAMILY 23355467 A 209 216 glucose TRIVIAL 23355467 A 369 374 sugar FAMILY 23355467 A 418 429 fatty acids FAMILY 23355467 A 443 450 glucose TRIVIAL 23355467 A 502 508 carbon SYSTEMATIC 23355467 A 552 562 fatty acid FAMILY 23355467 A 600 613 triglycerides FAMILY 23355467 A 778 783 sugar FAMILY 23355467 A 832 844 carbohydrate FAMILY 23355467 A 881 893 stearoyl-CoA TRIVIAL 23355467 A 937 942 sugar FAMILY 23355488 A 286 296 vancomycin TRIVIAL 23355488 A 319 332 actinomycin D TRIVIAL 23355488 A 337 347 romidepsin TRIVIAL 23355488 A 501 511 vancomycin TRIVIAL 23355488 A 513 526 actinomycin D TRIVIAL 23355488 A 531 541 romidepsin TRIVIAL 23355488 A 875 882 cystine TRIVIAL 23355489 A 1225 1241 poly(ADP-ribose) SYSTEMATIC 23355489 A 163 169 serine TRIVIAL 23355489 A 175 178 Ser FORMULA 23355489 A 297 300 Ser FORMULA 23355489 A 767 783 poly(ADP-ribose) SYSTEMATIC 23355489 A 948 951 Ser FORMULA 23355616 A 1115 1118 CpG ABBREVIATION 23355616 A 22 25 CpG ABBREVIATION 23355616 A 26 39 dinucleotides FAMILY 23355616 A 545 555 nucleotide FAMILY 23355616 A 828 831 CpG ABBREVIATION 23355616 A 832 845 dinucleotides FAMILY 23355616 A 885 889 CpGs ABBREVIATION 23356207 A 475 486 triterpenes FAMILY 23356207 A 737 748 triterpenes FAMILY 23356207 A 900 914 monoglycerides FAMILY 23356207 A 989 999 triterpene FAMILY 23356207 T 101 112 triterpenes FAMILY 23356740 A 1030 1040 cyclic AMP TRIVIAL 23356740 A 119 133 catecholamines FAMILY 23356740 A 135 148 noradrenaline TRIVIAL 23356740 A 1393 1401 tyramine TRIVIAL 23356740 A 1442 1450 Tyramine TRIVIAL 23356740 A 153 163 adrenaline TRIVIAL 23356740 A 22 34 phenolamines FAMILY 23356740 A 223 233 octopamine TRIVIAL 23356740 A 267 277 octopamine TRIVIAL 23356740 A 283 291 tyramine TRIVIAL 23356740 A 308 316 Tyramine TRIVIAL 23356740 A 345 355 Octopamine TRIVIAL 23356740 A 356 364 Tyramine TRIVIAL 23356740 A 36 44 tyramine TRIVIAL 23356740 A 400 408 tyramine TRIVIAL 23356740 A 414 424 octopamine TRIVIAL 23356740 A 451 459 Tyramine TRIVIAL 23356740 A 49 59 octopamine TRIVIAL 23356740 A 555 563 tyramine TRIVIAL 23356740 A 824 832 tyramine TRIVIAL 23356740 A 931 937 amines FAMILY 23356740 A 949 959 octopamine TRIVIAL 23356740 A 961 969 dopamine TRIVIAL 23356740 A 971 984 noradrenaline TRIVIAL 23356740 A 986 996 adrenaline TRIVIAL 23356740 T 49 57 tyramine TRIVIAL 23356791 A 0 12 Formaldehyde SYSTEMATIC 23356791 A 1000 1011 glutathione TRIVIAL 23356791 A 1084 1095 glutathione TRIVIAL 23356791 A 1217 1229 formaldehyde SYSTEMATIC 23356791 A 1267 1278 glutathione TRIVIAL 23356791 A 1327 1339 formaldehyde SYSTEMATIC 23356791 A 181 193 formaldehyde SYSTEMATIC 23356791 A 336 348 formaldehyde SYSTEMATIC 23356791 A 509 521 formaldehyde SYSTEMATIC 23356791 A 576 588 formaldehyde SYSTEMATIC 23356791 A 638 650 formaldehyde SYSTEMATIC 23356791 A 790 797 formate SYSTEMATIC 23356791 A 812 824 formaldehyde SYSTEMATIC 23356791 A 861 868 glucose TRIVIAL 23356791 A 909 916 lactate FAMILY 23356791 T 0 12 Formaldehyde SYSTEMATIC 23356791 T 28 40 formaldehyde SYSTEMATIC 23356791 T 64 71 lactate FAMILY 23356791 T 87 98 glutathione TRIVIAL 23356859 A 844 855 tetrazolium SYSTEMATIC 23356859 A 861 921 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide SYSTEMATIC 23356859 A 923 926 MTT ABBREVIATION 23356867 A 33 45 carbohydrate FAMILY 23356867 A 730 740 saccharide FAMILY 23356867 A 793 805 cellohexaose TRIVIAL 23356867 A 818 831 cellotetraose TRIVIAL 23356867 T 64 76 carbohydrate FAMILY 23356907 A 240 259 zinc phthalocyanine SYSTEMATIC 23356907 A 265 284 acetylenic bombesin SYSTEMATIC 23356907 A 288 296 arginine TRIVIAL 23356907 A 297 304 glycine TRIVIAL 23356907 A 305 318 aspartic acid TRIVIAL 23356907 A 33 52 zinc phthalocyanine SYSTEMATIC 23356907 A 807 821 phthalocyanine TRIVIAL 23356907 A 822 830 bombesin TRIVIAL 23356907 T 0 14 Phthalocyanine TRIVIAL 23356946 A 237 249 glucuronides FAMILY 23356946 A 25 33 sulfates FAMILY 23356946 A 254 262 sulfates FAMILY 23356946 A 293 330 epicatechin glucuronides and sulfates MULTIPLE 23356946 A 4 20 monoglucuronides FAMILY 23356946 A 50 72 3'-O-methylepicatechin SYSTEMATIC 23356946 A 615 626 epicatechin TRIVIAL 23356946 A 78 100 4'-O-methylepicatechin SYSTEMATIC 23356946 T 43 80 epicatechin glucuronides and sulfates MULTIPLE 23356964 A 108 133 benzyl alcohol glycosides FAMILY 23356964 A 203 303 7-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)]-β-d-glucopyranosyl SYSTEMATIC 23356964 A 316 341 benzyl alcohol glycosides FAMILY 23356964 A 346 350 acyl FAMILY 23356964 A 367 375 glycosyl SYSTEMATIC 23356964 A 455 459 DPPH ABBREVIATION 23356964 A 505 531 phenylpropanoylquinic acid SYSTEMATIC 23356964 A 75 97 lavone tetraglycosides FAMILY 23356964 T 0 23 Flavone tetraglycosides FAMILY 23356964 T 28 53 benzyl alcohol glycosides FAMILY 23357308 A 435 474 5-acetyl-4-methyl-2-(3-pyridyl)thiazole SYSTEMATIC 23357308 A 523 533 ampicillin TRIVIAL 23357308 A 658 671 amphotricin B TRIVIAL 23357308 A 849 857 thiazole SYSTEMATIC 23357308 A 94 135 2-(3-pyridyl)-4,5-disubstituted thiazoles FAMILY 23357308 T 22 63 2-(3-pyridyl)-4,5-disubstituted thiazoles FAMILY 23357312 A 0 7 Paeonol TRIVIAL 23357312 A 1246 1253 paeonol TRIVIAL 23357312 A 1558 1565 Paeonol TRIVIAL 23357312 A 1635 1642 paeonol TRIVIAL 23357312 A 1765 1772 paeonol TRIVIAL 23357312 A 244 251 paeonol TRIVIAL 23357312 A 429 436 lactate FAMILY 23357312 A 529 542 Hoechst 33342 TRIVIAL 23357312 A 595 601 oxygen SYSTEMATIC 23357312 A 643 678 2',7'-dichlorofluorescein diacetate SYSTEMATIC 23357312 A 680 687 DCFH-DA ABBREVIATION 23357312 T 0 7 Paeonol TRIVIAL 23357362 A 196 209 acetylcholine SYSTEMATIC 23357362 A 213 219 Ba(2+) FORMULA 23357362 A 279 292 acetylcholine SYSTEMATIC 23357362 A 297 303 Ba(2+) FORMULA 23357362 A 98 107 Vicenin 2 TRIVIAL 23357362 T 42 51 Vicenin 2 TRIVIAL 23357565 A 0 9 Silymarin FAMILY 23357565 A 1049 1058 silymarin FAMILY 23357565 A 1113 1115 NO FORMULA 23357565 A 1123 1125 SH FORMULA 23357565 A 1148 1157 capsaicin TRIVIAL 23357565 A 137 146 silymarin FAMILY 23357565 A 192 201 silymarin FAMILY 23357565 A 248 255 ethanol SYSTEMATIC 23357565 A 281 290 Silymarin FAMILY 23357565 A 359 366 aspirin TRIVIAL 23357565 A 493 502 silymarin FAMILY 23357565 A 518 530 nitric oxide SYSTEMATIC 23357565 A 532 534 NO FORMULA 23357565 A 555 561 l-NAME ABBREVIATION 23357565 A 563 565 SH FORMULA 23357565 A 574 590 N-ethylmaleimide SYSTEMATIC 23357565 A 611 622 capsazepine TRIVIAL 23357565 A 626 633 ethanol SYSTEMATIC 23357565 A 703 710 ethanol SYSTEMATIC 23357565 A 761 771 sulfhydryl FAMILY 23357565 A 816 825 silymarin FAMILY 23357565 A 882 891 silymarin FAMILY 23357565 A 895 902 ethanol SYSTEMATIC 23357565 A 971 980 silymarin FAMILY 23357565 T 21 30 silymarin FAMILY 23357565 T 39 46 ethanol SYSTEMATIC 23357565 T 82 93 sulfhydryls FAMILY 23357565 T 95 107 nitric oxide SYSTEMATIC 23357626 A 0 12 Aplyronine A TRIVIAL 23357626 A 21 33 mycalolide B TRIVIAL 23357626 A 410 422 aplyronine A TRIVIAL 23357626 T 62 74 aplyronine A TRIVIAL 23357627 A 438 462 phosphonic glutamic acid SYSTEMATIC 23357627 A 494 526 Boc-Phe-Leu-Glu(P)(OC(6)H(4))(2) FORMULA 23357627 A 608 640 Boc-Phe-Leu-Glu(P)(OC(6)H(4))(2) FORMULA 23357627 T 0 10 Phosphonic SYSTEMATIC 23357627 T 24 37 glutamic acid TRIVIAL 23357628 A 12 52 dimethylaminomethyl-substituted curcumin FAMILY 23357628 A 210 213 MTT ABBREVIATION 23357628 A 288 296 curcumin TRIVIAL 23357628 A 457 461 DPPH ABBREVIATION 23357628 A 466 476 galvinoxyl TRIVIAL 23357628 A 608 616 curcumin TRIVIAL 23357628 T 187 195 curcumin TRIVIAL 23357628 T 24 64 dimethylaminomethyl-substituted curcumin FAMILY 23357629 A 18 26 pyrazole SYSTEMATIC 23357629 A 198 202 (1)H FORMULA 23357629 A 203 207 (1)H FORMULA 23357629 A 214 218 (1)H FORMULA 23357629 A 219 224 (13)C FORMULA 23357629 A 234 238 (1)H FORMULA 23357629 A 239 244 (13)C FORMULA 23357629 A 39 47 flavones FAMILY 23357629 A 400 411 acetic acid SYSTEMATIC 23357629 A 801 805 keto SYSTEMATIC 23357629 A 810 818 phenolic FAMILY 23357629 A 820 822 OH FORMULA 23357629 A 87 135 1-methyl-5-(2,4,6-trimethoxy-phenyl)-1H-pyrazole SYSTEMATIC 23357629 T 78 86 pyrazole SYSTEMATIC 23357629 T 99 107 flavones FAMILY 23357633 A 12 52 C-(3-aminomethyl-cyclohexyl)-methylamine SYSTEMATIC 23357633 A 248 255 t-butyl SYSTEMATIC 23357633 A 280 287 benzene SYSTEMATIC 23357633 A 354 364 ethambutol TRIVIAL 23357633 T 78 118 C-(3-aminomethyl-cyclohexyl)-methylamine SYSTEMATIC 23357976 A 164 171 glucose TRIVIAL 23357976 A 315 322 glucose TRIVIAL 23357976 A 357 364 glucose TRIVIAL 23357976 A 393 400 glucose TRIVIAL 23357976 A 611 618 glucose TRIVIAL 23357976 A 7 25 11β-hydroxysteroid FAMILY 23357976 A 77 85 cortisol TRIVIAL 23357976 A 98 107 cortisone TRIVIAL 23357976 A 980 987 glucose TRIVIAL 23357976 T 37 44 glucose TRIVIAL 23359435 A 18 31 triscarbazole SYSTEMATIC 23359435 A 60 67 oxetane SYSTEMATIC 23359435 A 71 87 benzocyclobutene SYSTEMATIC 23359520 A 303 316 triglycerides FAMILY 23359520 A 331 342 cholesterol TRIVIAL 23359520 A 382 389 glucose TRIVIAL 23359520 A 756 767 cholesterol TRIVIAL 23359520 A 815 822 glucose TRIVIAL 23359538 A 106 113 mercury SYSTEMATIC 23359538 A 115 121 copper SYSTEMATIC 23359538 A 127 134 cadmium SYSTEMATIC 23359538 A 350 363 aluminosilica TRIVIAL 23359538 A 554 560 Cu(2+) FORMULA 23359538 A 563 569 Cd(2+) FORMULA 23359538 A 576 582 Hg(2+) FORMULA 23359555 A 169 174 C(60) TRIVIAL 23359555 A 278 283 C(60) TRIVIAL 23359555 A 355 364 fullerene TRIVIAL 23359555 A 91 107 N-alkylcarbazole FAMILY 23359555 T 53 58 C(60) TRIVIAL 23359587 A 223 237 hydroxyapatite TRIVIAL 23359587 A 242 262 tricalcium phosphate SYSTEMATIC 23360142 A 203 205 CO FORMULA 23360142 A 25 27 CO FORMULA 23360142 A 354 356 CO FORMULA 23360142 A 562 564 CO FORMULA 23360142 A 586 588 CO FORMULA 23360142 A 620 622 CO FORMULA 23360142 A 690 705 carbon monoxide SYSTEMATIC 23360142 A 800 802 CO FORMULA 23360142 A 831 833 CO FORMULA 23360142 A 838 840 CO FORMULA 23360142 A 899 901 CO FORMULA 23360142 T 0 2 CO FORMULA 23360142 T 7 9 CO FORMULA 23360180 A 1020 1026 Oxygen SYSTEMATIC 23360180 A 1035 1039 PLGA ABBREVIATION 23360180 A 1040 1042 Ag FORMULA 23360180 A 1150 1154 PLGA ABBREVIATION 23360180 A 1175 1177 Ag FORMULA 23360180 A 119 121 Ag FORMULA 23360180 A 1201 1207 oxygen SYSTEMATIC 23360180 A 126 130 PLGA ABBREVIATION 23360180 A 235 239 PLGA ABBREVIATION 23360180 A 315 317 Ag FORMULA 23360180 A 355 359 PLGA ABBREVIATION 23360180 A 364 368 PLGA ABBREVIATION 23360180 A 369 371 Ag FORMULA 23360180 A 413 419 oxygen SYSTEMATIC 23360180 A 450 454 PLGA ABBREVIATION 23360180 A 68 74 oxygen SYSTEMATIC 23360180 A 785 789 PLGA ABBREVIATION 23360180 A 828 834 oxygen SYSTEMATIC 23360180 A 928 930 Ag FORMULA 23360180 A 97 103 silver SYSTEMATIC 23360180 T 20 22 Ag FORMULA 23360180 T 41 47 oxygen SYSTEMATIC 23360230 A 553 556 PEG ABBREVIATION 23360230 A 605 607 Au FORMULA 23360230 A 868 871 PEG ABBREVIATION 23360230 T 46 48 Au FORMULA 23360232 A 1162 1165 PEG ABBREVIATION 23360232 A 131 134 PEG ABBREVIATION 23360232 A 78 87 histidine TRIVIAL 23360232 A 88 94 lysine TRIVIAL 23360361 A 1255 1262 DMAPODA ABBREVIATION 23360361 A 1479 1486 DMAPODA ABBREVIATION 23360361 A 1678 1685 DMAPODA ABBREVIATION 23360361 A 168 178 carboxylic SYSTEMATIC 23360361 A 189 200 fatty acids FAMILY 23360361 A 215 220 amino FAMILY 23360361 A 231 273 N-[3-(Dimethylamino)propyl]-Octadecanamide SYSTEMATIC 23360361 A 275 282 DMAPODA ABBREVIATION 23360361 A 394 407 Decanoic acid SYSTEMATIC 23360361 A 414 427 myristic acid TRIVIAL 23360361 A 434 446 stearic acid TRIVIAL 23360361 A 456 468 behenic acid TRIVIAL 23360361 A 522 529 DMAPODA ABBREVIATION 23360361 A 699 706 DMAPODA ABBREVIATION 23360361 A 743 750 DMAPODA ABBREVIATION 23360361 A 833 840 DMAPODA ABBREVIATION 23360361 T 21 31 fatty acid FAMILY 23360361 T 36 78 N-[3-(dimethylamino)propyl]-octadecanamide SYSTEMATIC 23360361 T 90 100 fatty acid FAMILY 23360392 A 1021 1030 flavonols FAMILY 23360392 A 1036 1045 cisplatin TRIVIAL 23360392 A 104 113 cisplatin TRIVIAL 23360392 A 203 212 cisplatin TRIVIAL 23360392 A 217 226 flavonols FAMILY 23360392 A 23 32 cisplatin TRIVIAL 23360392 A 344 352 hydroxyl SYSTEMATIC 23360392 A 377 386 flavonols FAMILY 23360392 A 38 47 flavonols FAMILY 23360392 A 421 430 cisplatin TRIVIAL 23360392 A 445 451 quartz TRIVIAL 23360392 A 562 571 hydroxyls FAMILY 23360392 A 601 610 cisplatin TRIVIAL 23360392 A 675 683 hydroxyl SYSTEMATIC 23360392 A 708 717 flavonols FAMILY 23360392 A 770 779 cisplatin TRIVIAL 23360392 A 913 922 hydroxyls FAMILY 23360392 A 926 935 cisplatin TRIVIAL 23360392 T 49 58 Cisplatin TRIVIAL 23360392 T 63 71 Flavonol FAMILY 23360412 A 1034 1038 DCBN ABBREVIATION 23360412 A 1099 1103 DCBN ABBREVIATION 23360412 A 1161 1165 DCBN ABBREVIATION 23360412 A 118 122 DCBN ABBREVIATION 23360412 A 1245 1249 DCBN ABBREVIATION 23360412 A 14 38 2,6-dichlorobenzonitrile SYSTEMATIC 23360412 A 1454 1458 DCBN ABBREVIATION 23360412 A 1471 1475 DCBN ABBREVIATION 23360412 A 1556 1560 DCBN ABBREVIATION 23360412 A 197 201 DCBN ABBREVIATION 23360412 A 40 44 DCBN ABBREVIATION 23360412 A 405 409 DCBN ABBREVIATION 23360412 A 498 502 DCBN ABBREVIATION 23360412 A 540 551 glutathione TRIVIAL 23360412 A 565 569 DCBN ABBREVIATION 23360412 A 574 578 DCBN ABBREVIATION 23360412 A 616 620 DCBN ABBREVIATION 23360412 A 745 749 DCBN ABBREVIATION 23360412 A 893 910 8-methoxypsoralen SYSTEMATIC 23360412 A 940 944 DCBN ABBREVIATION 23360412 T 36 60 2,6-dichlorobenzonitrile SYSTEMATIC 23360619 A 106 109 UDP ABBREVIATION 23360619 A 327 342 glucuronic acid TRIVIAL 23360619 A 943 985 7-ethyl-10-hydroxycamptothecin glucuronide SYSTEMATIC 23361101 A 502 510 Caffeine TRIVIAL 23361101 A 546 554 caffeine TRIVIAL 23361383 A 1099 1115 N-acetylcysteine SYSTEMATIC 23361383 A 120 134 amphotericin B TRIVIAL 23361383 A 136 139 AmB ABBREVIATION 23361383 A 425 433 mannitol TRIVIAL 23361383 A 503 512 Potassium SYSTEMATIC 23361383 A 540 549 amiloride TRIVIAL 23361383 A 554 568 spironolactone TRIVIAL 23361383 A 661 670 potassium SYSTEMATIC 23361383 A 716 719 AmB ABBREVIATION 23361383 A 749 752 AmB ABBREVIATION 23361383 A 962 965 AmB ABBREVIATION 23361383 T 62 76 amphotericin B TRIVIAL 23361517 A 0 13 Y(2)Ti(2)O(7) FORMULA 23361517 A 144 147 YTO FORMULA 23361517 A 15 18 YTO FORMULA 23361517 A 152 157 EYYTO FORMULA 23361517 A 24 30 Er(3+) FORMULA 23361517 A 253 258 EYYTO FORMULA 23361517 A 31 37 Yb(3+) FORMULA 23361517 A 47 60 Y(2)Ti(2)O(7) FORMULA 23361517 A 477 483 Er(3+) FORMULA 23361517 A 62 67 EYYTO FORMULA 23361517 A 671 676 EYYTO FORMULA 23361517 T 43 47 Er3+ FORMULA 23361517 T 52 56 Yb3+ FORMULA 23361517 T 66 73 Y2Ti2O7 FORMULA 23361587 A 180 186 NAD(+) ABBREVIATION 23361587 A 385 391 NAD(+) ABBREVIATION 23361914 A 121 137 (S)-argininamide TRIVIAL 23361914 A 36 55 [2,3-(3)H]propionyl SYSTEMATIC 23361914 A 99 108 guanidine TRIVIAL 23361914 T 0 15 [(3)H]UR-PLN196 SYSTEMATIC 23362105 A 0 10 Nucleotide FAMILY 23362105 A 173 190 muramyl dipeptide TRIVIAL 23362105 A 192 195 MDP ABBREVIATION 23362105 A 399 417 GlcNAcβ(1→4)MurNAc ABBREVIATION 23362105 A 421 439 MurNAcβ(1→4)GlcNAc ABBREVIATION 23362105 A 468 480 disaccharide FAMILY 23362105 A 484 499 tetrasaccharide FAMILY 23362105 A 798 816 MurNAcβ(1→4)GlcNAc ABBREVIATION 23362105 A 895 913 GlcNAcβ(1→4)MurNAc ABBREVIATION 23362239 A 1025 1029 Ca²⁺ FORMULA 23362239 A 1105 1109 Ca²⁺ FORMULA 23362239 A 1196 1200 Ca²⁺ FORMULA 23362239 A 1330 1334 Ca²⁺ FORMULA 23362239 A 1384 1388 Ca²⁺ FORMULA 23362239 A 1509 1513 Ca²⁺ FORMULA 23362239 A 1557 1561 Ca²⁺ FORMULA 23362239 A 1591 1595 Ca²⁺ FORMULA 23362239 A 1713 1717 Ca²⁺ FORMULA 23362239 A 313 317 Ca²⁺ FORMULA 23362239 A 335 344 ryanodine TRIVIAL 23362239 A 418 422 Ca²⁺ FORMULA 23362239 A 525 529 Ca²⁺ FORMULA 23362239 A 579 583 Ca²⁺ FORMULA 23362239 A 606 610 Ca²⁺ FORMULA 23362239 A 806 810 Ca²⁺ FORMULA 23362239 A 916 920 Ca²⁺ FORMULA 23362239 T 0 4 Ca²⁺ FORMULA 23362239 T 34 38 Ca²⁺ FORMULA 23362239 T 88 92 Ca²⁺ FORMULA 23362923 A 306 326 cyclic pentapeptides FAMILY 23362923 A 566 577 amino acids FAMILY 23362923 T 130 141 Amino Acids FAMILY 23362942 A 17 42 pillar[n]arene (n = 5, 6) SYSTEMATIC 23362942 A 350 361 amino acids FAMILY 23362942 A 487 497 amino acid FAMILY 23362942 A 569 579 amino acid FAMILY 23362942 A 78 82 (1)H FORMULA 23362942 T 44 55 amino acids FAMILY 23362960 A 314 321 biotins FAMILY 23363072 A 0 8 Hydrogen SYSTEMATIC 23363072 A 105 113 hydrogen SYSTEMATIC 23363072 A 128 141 LiNMe(2)BH(3) FORMULA 23363072 A 146 158 KNMe(2)BH(3) FORMULA 23363072 A 201 204 H-B FORMULA 23363072 A 261 262 H FORMULA 23363072 A 265 266 H FORMULA 23363072 T 10 20 dihydrogen SYSTEMATIC 23363072 T 32 57 alkali metal amidoboranes FAMILY 23363335 A 1182 1191 cytosines FAMILY 23363335 A 1389 1392 CpG ABBREVIATION 23363335 A 1525 1535 pyrimidine SYSTEMATIC 23363335 A 1587 1595 cytosine TRIVIAL 23363335 A 167 170 CpG ABBREVIATION 23363335 A 1703 1711 cytosine TRIVIAL 23363335 A 1755 1764 cytosines FAMILY 23363335 A 1783 1792 cytosines FAMILY 23363335 A 1806 1814 cytosine TRIVIAL 23363335 A 1919 1927 hydrogen SYSTEMATIC 23363335 A 1950 1957 guanine TRIVIAL 23363335 A 21 30 cytosines FAMILY 23363335 A 304 312 cytosine TRIVIAL 23363335 A 34 50 CpG dinucleotide FAMILY 23363335 A 442 445 CpG ABBREVIATION 23363335 A 524 533 cytosines FAMILY 23363335 A 541 550 cytosines FAMILY 23363335 A 759 768 cytosines FAMILY 23363335 A 830 839 cytosines FAMILY 23363335 A 947 956 cytosines FAMILY 23363335 T 81 84 CpG ABBREVIATION 23363407 A 182 188 silica TRIVIAL 23363407 A 220 237 6-mercaptohexanol SYSTEMATIC 23363407 A 437 443 silica TRIVIAL 23363407 A 477 483 oxygen SYSTEMATIC 23363407 T 47 53 silica TRIVIAL 23363425 A 1006 1015 phosphate SYSTEMATIC 23363425 A 1093 1099 silica TRIVIAL 23363425 A 11 22 Pro-Hyp-Gly FORMULA 23363425 A 122 128 silica TRIVIAL 23363425 A 158 161 Hyp ABBREVIATION 23363425 A 164 185 (2S,4R)hydroxyproline SYSTEMATIC 23363425 A 332 338 silica TRIVIAL 23363425 A 353 365 silicic acid TRIVIAL 23363425 A 470 482 silicic acid TRIVIAL 23363425 A 94 95 C FORMULA 23363425 A 989 1002 (poly-)amines FAMILY 23363425 T 0 6 Silica TRIVIAL 23363574 A 0 19 Glucose 6-phosphate SYSTEMATIC 23363574 A 1202 1207 Tl(+) FORMULA 23363574 A 239 256 pentose phosphate FAMILY 23363574 A 35 65 d-glucose 6-phosphate SYSTEMATIC 23363574 A 377 399 2',5'-ADP-sepharose-4B SYSTEMATIC 23363574 A 483 505 sodium dodecyl sulfate SYSTEMATIC 23363574 A 506 520 polyacrylamide SYSTEMATIC 23363574 A 67 74 NADP(+) ABBREVIATION 23363574 A 738 752 silver nitrate SYSTEMATIC 23363574 A 754 759 Ag(+) FORMULA 23363574 A 762 779 thallium sulphate SYSTEMATIC 23363574 A 781 786 TI(+) FORMULA 23363574 A 789 808 cobalt (II) nitrate SYSTEMATIC 23363574 A 810 816 Co(2+) FORMULA 23363574 A 822 839 arsenic (V) oxide SYSTEMATIC 23363574 A 841 847 As(5+) FORMULA 23363574 A 942 947 Ag(+) FORMULA 23363574 A 949 955 Co(2+) FORMULA 23363574 A 960 966 As(5+) FORMULA 23363574 T 37 56 glucose 6-phosphate SYSTEMATIC 23363576 A 1120 1137 hydrogen peroxide SYSTEMATIC 23363576 A 1192 1196 EtOH FORMULA 23363576 A 1342 1346 EtOH FORMULA 23363576 A 1533 1537 EtOH FORMULA 23363576 A 156 163 ethanol SYSTEMATIC 23363576 A 165 169 EtOH FORMULA 23363576 A 265 269 EtOH FORMULA 23363576 A 274 278 EtOH FORMULA 23363576 A 443 447 EtOH FORMULA 23363576 A 529 533 EtOH FORMULA 23363576 A 619 628 aspartate TRIVIAL 23363576 A 650 657 alanine TRIVIAL 23363576 A 709 713 EtOH FORMULA 23363576 A 746 761 malondialdehyde TRIVIAL 23363576 A 871 881 superoxide TRIVIAL 23363576 A 906 917 glutathione TRIVIAL 23363576 A 999 1003 EtOH FORMULA 23363576 T 47 54 ethanol SYSTEMATIC 23363577 A 326 328 Se FORMULA 23363577 A 533 535 Se FORMULA 23363577 A 551 585 diethylenetriaminepentaacetic acid SYSTEMATIC 23363577 A 640 642 Se FORMULA 23363577 A 673 675 Se FORMULA 23363577 A 78 86 selenium SYSTEMATIC 23363577 A 88 90 Se FORMULA 23364612 A 1020 1022 1H FORMULA 23364612 A 1024 1027 11B FORMULA 23364612 A 1033 1036 13C FORMULA 23364612 A 1139 1151 thioglycerol SYSTEMATIC 23364612 A 223 228 boron SYSTEMATIC 23364612 A 264 284 1,4-dihydropyridines FAMILY 23364612 A 295 319 3,4-dihydropyrimidinones FAMILY 23364612 A 334 359 formylphenylboronic acids FAMILY 23364612 A 478 485 ethanol SYSTEMATIC 23364612 T 50 55 boron SYSTEMATIC 23364615 A 0 16 Titanium dioxide SYSTEMATIC 23364615 A 1253 1269 titanium dioxide SYSTEMATIC 23364615 A 480 496 titanium dioxide SYSTEMATIC 23364615 A 55 67 metal oxides FAMILY 23364615 T 78 82 TiO2 FORMULA 23364884 A 306 314 cysteine TRIVIAL 23364884 A 491 499 cysteine TRIVIAL 23364884 A 634 644 serotonine TRIVIAL 23364884 A 920 924 E-64 TRIVIAL 23368510 A 135 144 metformin TRIVIAL 23368510 A 493 500 glucose TRIVIAL 23368510 T 151 160 metformin TRIVIAL 23368777 A 1033 1042 aspartate TRIVIAL 23368777 A 1062 1065 Ser FORMULA 23368777 A 1227 1234 sucrose TRIVIAL 23368777 A 164 170 lysine TRIVIAL 23368777 A 511 514 Ser FORMULA 23368777 A 604 607 Tyr FORMULA 23368777 A 880 883 Ser FORMULA 23368777 A 902 911 aspartate TRIVIAL 23368777 A 932 939 alanine TRIVIAL 23368884 A 0 16 Hydroxamic acids FAMILY 23368884 A 180 187 BRD9757 IDENTIFIER 23369033 A 13 28 (-)-tylophorine TRIVIAL 23369033 A 372 396 levorotatory tylophorine TRIVIAL 23369033 T 50 81 phenanthroindolizidine alkaloid FAMILY 23369343 A 1019 1029 sulfhydryl FAMILY 23369343 A 1039 1047 carbonyl FAMILY 23369343 A 1049 1061 nitric oxide SYSTEMATIC 23369343 A 1075 1083 peroxide SYSTEMATIC 23369343 A 1122 1133 d-galactose TRIVIAL 23369343 A 1230 1240 α-santalol TRIVIAL 23369343 A 243 253 α-santalol TRIVIAL 23369343 A 314 321 alloxan TRIVIAL 23369343 A 422 433 d-galactose TRIVIAL 23369343 A 533 543 α-santalol TRIVIAL 23369343 A 648 655 glucose TRIVIAL 23369343 A 663 672 bilirubin TRIVIAL 23369343 A 700 709 peroxides FAMILY 23369343 A 750 757 alloxan TRIVIAL 23369343 A 826 836 α-santalol TRIVIAL 23369343 A 971 980 bilirubin TRIVIAL 23369343 A 982 992 superoxide TRIVIAL 23369343 T 71 81 α-santalol TRIVIAL 23369344 A 1121 1125 cGMP ABBREVIATION 23369344 A 1147 1159 prostacyclin TRIVIAL 23369344 A 592 604 nitric oxide SYSTEMATIC 23369344 A 624 630 l-NAME ABBREVIATION 23369344 A 655 664 guanylate TRIVIAL 23369344 A 888 900 indomethacin TRIVIAL 23369344 A 902 906 Indo ABBREVIATION 23369344 A 941 952 propranolol TRIVIAL 23369344 A 954 958 Prop ABBREVIATION 23369537 T 24 33 chalcones FAMILY 23369833 A 1345 1346 N FORMULA 23369833 A 1390 1420 carbamate and N-sulfocarbamoyl MULTIPLE 23369833 A 1634 1635 N FORMULA 23369833 A 1768 1777 carbamate FAMILY 23369833 A 700 716 N-sulfocarbamoyl SYSTEMATIC 23369833 A 754 763 carbamate FAMILY 23369933 A 0 7 Mercury SYSTEMATIC 23369933 A 1043 1060 mercuric chloride SYSTEMATIC 23369933 A 1149 1164 sodium selenite SYSTEMATIC 23369933 A 1172 1181 vitamin E FAMILY 23369933 A 1201 1218 mercuric chloride SYSTEMATIC 23369933 A 1246 1263 mercuric chloride SYSTEMATIC 23369933 A 1306 1321 sodium selenite SYSTEMATIC 23369933 A 1329 1338 vitamin E FAMILY 23369933 A 154 171 mercuric chloride SYSTEMATIC 23369933 A 275 290 sodium selenite SYSTEMATIC 23369933 A 298 307 vitamin E FAMILY 23369933 A 426 443 mercuric chloride SYSTEMATIC 23369933 A 463 478 sodium selenite SYSTEMATIC 23369933 A 494 503 vitamin E FAMILY 23369933 A 566 583 mercuric chloride SYSTEMATIC 23369933 A 768 775 mercury SYSTEMATIC 23369933 A 865 880 sodium selenite SYSTEMATIC 23369933 A 888 897 vitamin E FAMILY 23369933 A 901 908 mercury SYSTEMATIC 23369933 T 0 17 Mercuric chloride SYSTEMATIC 23369933 T 101 110 vitamin E FAMILY 23369933 T 81 96 sodium selenite SYSTEMATIC 23370006 A 1023 1030 Uranium SYSTEMATIC 23370006 A 1035 1044 manganese SYSTEMATIC 23370006 A 1137 1141 zinc SYSTEMATIC 23370006 A 26 33 uranium SYSTEMATIC 23370006 A 455 462 uranium SYSTEMATIC 23370006 T 65 72 uranium SYSTEMATIC 23370180 A 223 235 testosterone TRIVIAL 23370180 A 667 686 dihydrotestosterone SYSTEMATIC 23370180 A 688 691 DHT ABBREVIATION 23370180 A 696 714 diethylstilbestrol SYSTEMATIC 23370180 A 716 719 DES ABBREVIATION 23370306 A 1009 1021 crotofolanes FAMILY 23370306 A 106 117 crotofolane TRIVIAL 23370306 A 160 176 nor-diterpenoids FAMILY 23370306 A 256 267 crotofolane TRIVIAL 23370306 A 434 443 diterpene FAMILY 23370306 A 51 63 diterpenoids FAMILY 23370306 A 526 535 γ-lactone SYSTEMATIC 23370306 A 577 589 crotofolanes FAMILY 23370306 A 71 89 crotocascarins A-H MULTIPLE 23370306 A 714 734 2-methylbutyric acid SYSTEMATIC 23370306 A 923 937 crotocascarins FAMILY 23370306 T 10 22 Diterpenoids FAMILY 23370306 T 35 51 Nor-Diterpenoids FAMILY 23370795 A 1127 1140 buprenorphine TRIVIAL 23370795 A 478 491 buprenorphine TRIVIAL 23370795 A 624 637 buprenorphine TRIVIAL 23370795 A 718 731 buprenorphine TRIVIAL 23370795 A 781 794 buprenorphine TRIVIAL 23370795 T 9 22 buprenorphine TRIVIAL 23371032 A 301 315 organochlorine FAMILY 23371032 A 317 332 organophosphate FAMILY 23371032 A 334 343 carbamate FAMILY 23371032 A 348 358 pyrethroid FAMILY 23371032 A 374 390 chlorocyclodiene FAMILY 23371032 A 399 415 organophosphates FAMILY 23371032 A 500 510 endosulfan TRIVIAL 23371032 A 566 578 chlorpyrifos TRIVIAL 23371032 A 588 599 pyrethroids FAMILY 23371032 A 608 617 carbamate FAMILY 23371032 A 662 674 cypermethrin TRIVIAL 23371032 A 691 703 deltamethrin TRIVIAL 23371032 A 724 732 methomyl TRIVIAL 23371303 A 0 9 Avibactam TRIVIAL 23371303 A 1039 1050 ceftazidime TRIVIAL 23371303 A 1120 1129 avibactam TRIVIAL 23371303 A 1163 1174 ceftazidime TRIVIAL 23371303 A 1356 1365 avibactam TRIVIAL 23371303 A 1457 1468 ceftazidime TRIVIAL 23371303 A 1577 1586 avibactam TRIVIAL 23371303 A 1757 1768 ceftazidime TRIVIAL 23371303 A 1775 1786 ceftazidime TRIVIAL 23371303 A 1788 1797 avibactam TRIVIAL 23371303 A 1859 1869 creatinine TRIVIAL 23371303 A 1915 1926 ceftazidime TRIVIAL 23371303 A 1927 1936 avibactam TRIVIAL 23371303 A 20 26 NXL104 IDENTIFIER 23371303 A 2038 2049 ceftazidime TRIVIAL 23371303 A 2099 2110 ceftazidime TRIVIAL 23371303 A 2111 2120 avibactam TRIVIAL 23371303 A 2149 2159 carbapenem FAMILY 23371303 A 2280 2293 cephalosporin FAMILY 23371303 A 2359 2370 ceftazidime TRIVIAL 23371303 A 2371 2380 avibactam TRIVIAL 23371303 A 243 254 ceftazidime TRIVIAL 23371303 A 2475 2486 Ceftazidime TRIVIAL 23371303 A 2487 2496 avibactam TRIVIAL 23371303 A 255 264 avibactam TRIVIAL 23371303 A 2669 2678 avibactam TRIVIAL 23371303 A 2713 2724 ceftazidime TRIVIAL 23371303 A 2797 2808 ceftazidime TRIVIAL 23371303 A 28 36 AVE1330A IDENTIFIER 23371303 A 2809 2818 avibactam TRIVIAL 23371303 A 2920 2931 ceftazidime TRIVIAL 23371303 A 2932 2941 avibactam TRIVIAL 23371303 A 3175 3186 ceftazidime TRIVIAL 23371303 A 3187 3196 avibactam TRIVIAL 23371303 A 3230 3243 metronidazole TRIVIAL 23371303 A 3320 3331 ceftazidime TRIVIAL 23371303 A 3332 3341 avibactam TRIVIAL 23371303 A 457 465 β-lactam TRIVIAL 23371303 A 493 502 avibactam TRIVIAL 23371303 A 537 543 cephem TRIVIAL 23371303 A 57 65 β-lactam TRIVIAL 23371303 A 570 579 avibactam TRIVIAL 23371303 A 676 685 avibactam TRIVIAL 23371303 A 728 737 avibactam TRIVIAL 23371303 A 834 845 ceftazidime TRIVIAL 23371303 A 999 1008 avibactam TRIVIAL 23371303 T 0 11 Ceftazidime TRIVIAL 23371303 T 12 21 avibactam TRIVIAL 23371303 T 31 44 cephalosporin FAMILY 23371451 A 1021 1024 GSH ABBREVIATION 23371451 A 1113 1123 cysteamine TRIVIAL 23371451 A 117 127 cysteamine TRIVIAL 23371451 A 1263 1273 cysteamine TRIVIAL 23371451 A 1333 1343 cysteamine TRIVIAL 23371451 A 1394 1397 GSH ABBREVIATION 23371451 A 1448 1458 cysteamine TRIVIAL 23371451 A 1545 1548 GSH ABBREVIATION 23371451 A 1584 1594 Cysteamine TRIVIAL 23371451 A 162 172 cysteamine TRIVIAL 23371451 A 1744 1747 GSH ABBREVIATION 23371451 A 1839 1849 cysteamine TRIVIAL 23371451 A 330 340 cysteamine TRIVIAL 23371451 A 377 387 cysteamine TRIVIAL 23371451 A 461 471 cysteamine TRIVIAL 23371451 A 559 577 tetrazolium salt-1 FAMILY 23371451 A 691 708 bromodeoxyuridine TRIVIAL 23371451 A 710 714 BrdU ABBREVIATION 23371451 A 796 807 glutathione TRIVIAL 23371451 A 809 812 GSH ABBREVIATION 23371451 A 843 853 cysteamine TRIVIAL 23371451 A 895 905 cysteamine TRIVIAL 23371451 T 74 84 cysteamine TRIVIAL 23371488 A 1269 1277 nicotine TRIVIAL 23371488 A 1445 1453 Nicotine TRIVIAL 23371488 A 1701 1709 nicotine TRIVIAL 23371488 A 372 380 nicotine TRIVIAL 23371488 A 502 510 nicotine TRIVIAL 23371488 A 792 805 polycarbonate FAMILY 23371488 A 80 88 nicotine TRIVIAL 23371488 A 923 931 Nicotine TRIVIAL 23371488 T 56 64 nicotine TRIVIAL 23371489 A 1010 1017 cocaine TRIVIAL 23371489 A 186 195 cathinone TRIVIAL 23371489 A 205 215 mephedrone TRIVIAL 23371489 A 220 246 methylenedioxypyrovalerone SYSTEMATIC 23371489 A 248 252 MDPV ABBREVIATION 23371489 A 298 307 cathinone TRIVIAL 23371489 A 379 388 cathinone TRIVIAL 23371489 A 393 406 methcathinone TRIVIAL 23371489 A 457 465 dopamine TRIVIAL 23371489 A 486 496 mephedrone TRIVIAL 23371489 A 501 505 MDPV ABBREVIATION 23371489 A 579 589 mephedrone TRIVIAL 23371489 A 627 635 dopamine TRIVIAL 23371489 A 663 678 methamphetamine TRIVIAL 23371489 A 682 695 methcathinone TRIVIAL 23371489 A 697 701 MDPV ABBREVIATION 23371489 A 715 722 cocaine TRIVIAL 23371489 A 750 758 dopamine TRIVIAL 23371489 A 773 783 Mephedrone TRIVIAL 23371489 A 788 792 MDPV ABBREVIATION 23371489 A 990 1005 methamphetamine TRIVIAL 23371489 T 0 10 Mephedrone TRIVIAL 23371489 T 124 132 dopamine TRIVIAL 23371489 T 15 41 methylenedioxypyrovalerone SYSTEMATIC 23371489 T 43 47 MDPV ABBREVIATION 23371760 A 1035 1046 resin acids FAMILY 23371760 A 147 150 CH FORMULA 23371760 A 240 252 sulfonylurea FAMILY 23371760 A 322 334 vitamin D(3) TRIVIAL 23371760 A 422 433 diterpenoid FAMILY 23371760 A 499 510 resin acids FAMILY 23371760 A 523 535 abietic acid TRIVIAL 23371760 A 537 556 dehydroabietic acid SYSTEMATIC 23371760 A 562 577 isopimaric acid TRIVIAL 23371760 A 719 741 15-hydroxyabietic acid SYSTEMATIC 23371760 A 743 772 15-hydroxydehydroabietic acid SYSTEMATIC 23371760 A 778 804 15,16-epoxyisopimaric acid SYSTEMATIC 23371760 T 0 10 Resin acid FAMILY 23371760 T 110 122 diterpenoids FAMILY 23371763 A 190 196 carbon SYSTEMATIC 23371763 A 42 49 Eu(III) FORMULA 23371763 T 77 84 Eu(III) FORMULA 23371965 A 0 23 Phenethylisothiocyanate SYSTEMATIC 23371965 A 1064 1069 PEITC ABBREVIATION 23371965 A 1085 1088 PIC ABBREVIATION 23371965 A 1287 1293 sulfur SYSTEMATIC 23371965 A 1335 1340 PEITC ABBREVIATION 23371965 A 1424 1429 PEITC ABBREVIATION 23371965 A 1544 1550 sulfur SYSTEMATIC 23371965 A 1581 1590 parathion TRIVIAL 23371965 A 1664 1667 Cys FORMULA 23371965 A 1703 1706 PIC ABBREVIATION 23371965 A 25 30 PEITC ABBREVIATION 23371965 A 272 277 PEITC ABBREVIATION 23371965 A 427 432 PEITC ABBREVIATION 23371965 A 518 523 PEITC ABBREVIATION 23371965 A 525 530 PEITC ABBREVIATION 23371965 A 55 69 isothiocyanate FAMILY 23371965 A 650 661 glutathione TRIVIAL 23371965 A 663 666 GSH ABBREVIATION 23371965 A 735 740 PEITC ABBREVIATION 23371965 A 857 860 GSH ABBREVIATION 23371965 A 872 892 phenethyl isocyanate SYSTEMATIC 23371965 A 894 897 PIC ABBREVIATION 23371965 A 903 917 phenethylamine SYSTEMATIC 23371965 A 989 992 PIC ABBREVIATION 23371965 T 36 60 phenethyl isothiocyanate SYSTEMATIC 23373444 A 1006 1010 H(I) FORMULA 23373444 A 1082 1087 α-ZrP SYSTEMATIC 23373444 A 1230 1236 Zr(IV) FORMULA 23373444 A 1237 1242 α-ZrP SYSTEMATIC 23373444 A 1250 1256 Zr(IV) FORMULA 23373444 A 1257 1262 α-ZrP SYSTEMATIC 23373444 A 1377 1382 α-ZrP SYSTEMATIC 23373444 A 140 158 α-Zr(IV) phosphate SYSTEMATIC 23373444 A 1427 1432 α-ZrP SYSTEMATIC 23373444 A 1452 1458 Mg(II) FORMULA 23373444 A 1461 1466 Na(I) FORMULA 23373444 A 1469 1473 H(I) FORMULA 23373444 A 1476 1483 Cr(III) FORMULA 23373444 A 1486 1492 Ca(II) FORMULA 23373444 A 1495 1501 Zr(IV) FORMULA 23373444 A 160 165 α-ZrP SYSTEMATIC 23373444 A 200 207 glucose TRIVIAL 23373444 A 266 272 Zr(IV) FORMULA 23373444 A 274 281 Cr(III) FORMULA 23373444 A 283 290 Au(III) FORMULA 23373444 A 292 299 Al(III) FORMULA 23373444 A 301 307 Ca(II) FORMULA 23373444 A 309 315 Mg(II) FORMULA 23373444 A 317 323 Zn(II) FORMULA 23373444 A 325 331 Ni(II) FORMULA 23373444 A 333 338 Na(I) FORMULA 23373444 A 344 348 H(I) FORMULA 23373444 A 383 388 α-ZrP SYSTEMATIC 23373444 A 444 450 Zr(IV) FORMULA 23373444 A 459 465 Ca(II) FORMULA 23373444 A 501 507 Zr(IV) FORMULA 23373444 A 510 516 Ca(II) FORMULA 23373444 A 519 526 Cr(III) FORMULA 23373444 A 529 535 Mg(II) FORMULA 23373444 A 538 542 H(I) FORMULA 23373444 A 545 550 Na(I) FORMULA 23373444 A 596 603 Au(III) FORMULA 23373444 A 605 612 Al(III) FORMULA 23373444 A 614 620 Zn(II) FORMULA 23373444 A 622 628 Cu(II) FORMULA 23373444 A 634 640 Ni(II) FORMULA 23373444 A 679 685 Zr(IV) FORMULA 23373444 A 719 724 α-ZrP SYSTEMATIC 23373444 A 782 788 Zr(IV) FORMULA 23373444 A 791 795 H(I) FORMULA 23373444 A 798 804 Mg(II) FORMULA 23373444 A 807 812 Na(I) FORMULA 23373444 A 815 821 Ca(II) FORMULA 23373444 A 824 831 Cr(III) FORMULA 23373444 A 892 897 α-ZrP SYSTEMATIC 23373444 A 933 939 Zr(IV) FORMULA 23373444 A 942 949 Cr(III) FORMULA 23373444 A 952 958 Zn(II) FORMULA 23373444 A 961 967 Ni(II) FORMULA 23373444 A 970 976 Mg(II) FORMULA 23373444 A 979 985 Ca(II) FORMULA 23373444 A 988 995 Au(III) FORMULA 23373444 A 998 1003 Na(I) FORMULA 23373444 T 81 106 α-zirconium(IV) phosphate SYSTEMATIC 23373463 A 149 158 α-Co(OH)2 FORMULA 23373463 A 204 213 β-Co(OH)2 FORMULA 23373463 A 265 274 hydroxide SYSTEMATIC 23373463 A 311 317 cobalt SYSTEMATIC 23373463 A 527 536 α-Co(OH)2 FORMULA 23373463 A 848 857 α-Co(OH)2 FORMULA 23373463 T 77 101 α- to β-cobalt hydroxide MULTIPLE 23373530 A 148 175 poly(2-phenyl-1,4-xylylene) SYSTEMATIC 23373530 A 177 181 PPPX ABBREVIATION 23373530 A 249 253 PPPX ABBREVIATION 23373544 A 12 19 lignans FAMILY 23373544 A 156 172 Deoxyschisandrin TRIVIAL 23373544 A 182 197 schisantherin A TRIVIAL 23373544 A 327 334 lignans FAMILY 23373544 A 518 525 lignans FAMILY 23373544 A 526 534 Eudragit TRIVIAL 23373544 A 581 594 poloxamer 188 TRIVIAL 23373544 T 11 18 lignans FAMILY 23373590 A 1019 1029 iron oxide SYSTEMATIC 23373590 A 1095 1111 poly(AMPS-co-AA) SYSTEMATIC 23373590 A 208 212 NaCl FORMULA 23373590 A 221 226 CaCl2 FORMULA 23373590 A 245 249 NaCl FORMULA 23373590 A 258 263 CaCl2 FORMULA 23373590 A 336 342 Ca(2+) FORMULA 23373590 A 374 386 acrylic acid TRIVIAL 23373590 A 431 438 citrate FAMILY 23373590 A 554 613 poly(2-methyl-2-acrylamidopropanesulfonate-co-acrylic acid) SYSTEMATIC 23373590 A 615 631 poly(AMPS-co-AA) SYSTEMATIC 23373590 A 655 696 poly(styrenesulfonate-block-acrylic acid) SYSTEMATIC 23373590 A 718 756 poly(styrenesulfonate-alt-maleic acid) SYSTEMATIC 23373590 A 847 851 AMPS ABBREVIATION 23373590 A 91 101 iron oxide SYSTEMATIC 23373590 A 959 963 AMPS ABBREVIATION 23373590 T 17 27 iron oxide SYSTEMATIC 23373590 T 50 56 sodium SYSTEMATIC 23373590 T 61 68 calcium SYSTEMATIC 23373613 T 48 58 iron oxide SYSTEMATIC 23373648 A 360 368 tyrosine TRIVIAL 23373648 A 522 530 tyrosine TRIVIAL 23373648 A 847 865 steroidal hormones FAMILY 23373648 T 99 107 tyrosine TRIVIAL 23373724 A 0 29 1β-d-Arabinofuranosylcytosine SYSTEMATIC 23373724 A 108 113 Ara-C ABBREVIATION 23373724 A 1146 1149 PEG ABBREVIATION 23373724 A 1150 1155 Ara-C ABBREVIATION 23373724 A 1295 1300 Ara-C ABBREVIATION 23373724 A 1302 1307 Ara-U ABBREVIATION 23373724 A 1341 1346 Ara-C ABBREVIATION 23373724 A 1413 1418 Ara-C ABBREVIATION 23373724 A 1423 1426 PEG ABBREVIATION 23373724 A 1427 1432 Ara-C ABBREVIATION 23373724 A 1525 1528 PEG ABBREVIATION 23373724 A 1529 1534 Ara-C ABBREVIATION 23373724 A 1618 1623 Ara-C ABBREVIATION 23373724 A 174 182 cytidine TRIVIAL 23373724 A 257 262 Ara-U ABBREVIATION 23373724 A 264 291 1β-d-arabinofuranosyluracil SYSTEMATIC 23373724 A 31 41 Cytarabine TRIVIAL 23373724 A 410 418 hydroxyl SYSTEMATIC 23373724 A 43 48 Ara-C ABBREVIATION 23373724 A 430 435 PAMAM ABBREVIATION 23373724 A 450 452 OH FORMULA 23373724 A 463 466 PEG ABBREVIATION 23373724 A 503 508 Ara-C ABBREVIATION 23373724 A 669 677 hydroxyl SYSTEMATIC 23373724 A 687 692 Ara-C ABBREVIATION 23373724 A 707 710 PEG ABBREVIATION 23373724 A 813 817 (1)H FORMULA 23373724 A 890 895 Ara-C ABBREVIATION 23373724 A 947 952 Ara-C ABBREVIATION 23373724 T 26 31 Ara-C ABBREVIATION 23373724 T 57 62 PAMAM ABBREVIATION 23373724 T 84 87 PEG ABBREVIATION 23373772 A 111 116 CF(3) FORMULA 23373772 A 128 132 MeOH FORMULA 23373772 A 250 265 Ru(bpy)(3)Cl(2) FORMULA 23373772 A 66 73 alkenes FAMILY 23373772 T 51 58 alkenes FAMILY 23373965 A 157 167 1-en-3-one SYSTEMATIC 23373965 A 172 186 9(11),12-diene SYSTEMATIC 23373965 A 191 205 2,20-dinitrile SYSTEMATIC 23373965 A 29 48 glycyrrhetinic acid TRIVIAL 23373965 A 319 321 NO FORMULA 23373965 A 417 419 NO FORMULA 23373965 A 876 878 NO FORMULA 23373965 T 50 105 3-oxo-29-noroleana-1,9(11),12-trien-2,20-dicarbonitrile SYSTEMATIC 23374865 A 15 24 bile acid FAMILY 23374865 A 165 182 cresol red sodium TRIVIAL 23374865 A 192 198 pyrene SYSTEMATIC 23374865 A 437 444 acetone SYSTEMATIC 23374865 A 484 493 bile acid FAMILY 23374865 A 59 64 Cu(I) FORMULA 23374865 A 75 87 azide-alkyne FAMILY 23374865 T 43 52 bile acid FAMILY 23374868 A 323 336 [(125)I]-CCL3 SYSTEMATIC 23374868 A 48 102 1-(4-phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanone SYSTEMATIC 23374868 T 0 55 1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones FAMILY 23374869 A 1049 1050 C FORMULA 23374869 A 1064 1074 phthalides FAMILY 23374869 A 128 137 monoamine FAMILY 23374869 A 236 245 phthalide TRIVIAL 23374869 A 247 269 2-benzofuran-1(3H)-one SYSTEMATIC 23374869 A 282 291 Phthalide TRIVIAL 23374869 A 319 325 isatin TRIVIAL 23374869 A 330 341 phthalimide TRIVIAL 23374869 A 401 410 phthalide TRIVIAL 23374869 A 50 56 isatin TRIVIAL 23374869 A 61 72 phthalimide TRIVIAL 23374869 A 684 694 phthalides FAMILY 23374869 A 748 769 6-benzyloxyphthalides FAMILY 23374869 A 819 825 phenyl SYSTEMATIC 23374869 A 864 869 CF(3) FORMULA 23374869 A 872 873 I FORMULA 23374869 A 876 878 Br FORMULA 23374869 A 881 883 Cl FORMULA 23374869 A 886 887 F FORMULA 23374869 A 890 895 CH(3) FORMULA 23374869 A 898 899 H FORMULA 23374869 A 964 974 phthalides FAMILY 23374869 T 14 23 monoamine FAMILY 23374869 T 35 44 phthalide TRIVIAL 23374871 A 116 125 imidazole SYSTEMATIC 23374871 A 127 144 1-methylimidazole SYSTEMATIC 23374871 A 149 175 2-phenyl-1-methylimidazole SYSTEMATIC 23374871 A 34 45 imidazolium SYSTEMATIC 23374871 T 114 123 imidazole SYSTEMATIC 23374872 A 218 223 (11)C FORMULA 23374872 A 228 233 (18)F FORMULA 23374872 A 52 62 tariquidar TRIVIAL 23374872 T 21 31 tariquidar TRIVIAL 23375260 A 22 40 guanine nucleotide TRIVIAL 23375260 T 43 61 guanine nucleotide TRIVIAL 23375851 A 1091 1094 ACE ABBREVIATION 23375851 A 1099 1102 GEM ABBREVIATION 23375851 A 1274 1277 ACE ABBREVIATION 23375851 A 1398 1401 CBZ ABBREVIATION 23375851 A 1419 1438 11-ketotestosterone SYSTEMATIC 23375851 A 273 286 acetaminophen TRIVIAL 23375851 A 288 291 ACE ABBREVIATION 23375851 A 294 306 venlafaxaine TRIVIAL 23375851 A 308 311 VEN ABBREVIATION 23375851 A 326 339 carbamazepine TRIVIAL 23375851 A 341 344 CBZ ABBREVIATION 23375851 A 350 361 gemfibrozil TRIVIAL 23375851 A 363 366 GEM ABBREVIATION 23375851 A 506 509 CBZ ABBREVIATION 23375851 A 514 517 GEM ABBREVIATION 23376090 A 0 11 Chlordecone TRIVIAL 23376090 A 1070 1081 chlordecone TRIVIAL 23376090 A 1308 1319 chlordecone TRIVIAL 23376090 A 1441 1455 organochlorine FAMILY 23376090 A 28 42 organochlorine FAMILY 23376090 A 510 521 chlordecone TRIVIAL 23376090 A 622 633 chlordecone TRIVIAL 23376090 A 828 839 chlordecone TRIVIAL 23376090 T 15 29 organochlorine FAMILY 23376090 T 41 52 chlordecone TRIVIAL 23376110 A 116 148 1,3-thiazolane-4-carboxylic acid SYSTEMATIC 23376110 A 202 220 trans-androsterone SYSTEMATIC 23376110 A 225 250 trans-dehydroandrosterone SYSTEMATIC 23376110 A 279 397 spiro[5'.2″]acenaphthylene-1″-one-spiro[16.6']-(7'-aryl)-tetrahydro-1H-pyrrolo [1,2-c][1,3]thiazolo-trans-androsterone FAMILY 23376110 A 33 43 azomethine SYSTEMATIC 23376110 A 398 417 dehydroandrosterone SYSTEMATIC 23376110 A 531 548 16-spiro steroids FAMILY 23376110 A 87 111 acenaphthylene-1,2-dione SYSTEMATIC 23376110 T 19 36 16-spiro steroids FAMILY 23376110 T 38 113 Spiro-7'-(aryl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazolo-trans-androsterone FAMILY 23376119 A 0 16 Poly(ADP-ribose) SYSTEMATIC 23376119 A 1082 1085 TPT ABBREVIATION 23376119 A 1163 1167 PJ34 IDENTIFIER 23376119 A 1352 1355 TPT ABBREVIATION 23376119 A 1356 1360 PJ34 IDENTIFIER 23376119 A 1500 1503 TPT ABBREVIATION 23376119 A 1504 1508 PJ34 IDENTIFIER 23376119 A 444 456 camptothecin TRIVIAL 23376119 A 489 498 topotecan TRIVIAL 23376119 A 504 508 PJ34 IDENTIFIER 23376119 A 708 711 TPT ABBREVIATION 23376119 A 712 716 PJ34 IDENTIFIER 23376119 A 868 872 PJ34 IDENTIFIER 23376119 A 893 896 TPT ABBREVIATION 23376119 A 965 969 PJ34 IDENTIFIER 23376119 A 987 990 TPT ABBREVIATION 23376119 T 19 35 poly(ADP-ribose) SYSTEMATIC 23376162 A 356 370 [Rh2(OCOCF3)4] FORMULA 23376162 A 40 51 bisabolenes FAMILY 23376162 A 420 432 nitric oxide SYSTEMATIC 23376162 A 52 66 sesquiterpenes FAMILY 23376162 T 0 14 Sesquiterpenes FAMILY 23376162 T 85 97 nitric oxide SYSTEMATIC 23376242 A 1089 1092 MAN ABBREVIATION 23376242 A 230 263 P-aminophenyl-α-d-mannopyranoside SYSTEMATIC 23376242 A 265 268 MAN ABBREVIATION 23376242 A 393 396 MAN ABBREVIATION 23376242 A 398 401 MAN ABBREVIATION 23376242 A 540 543 MAN ABBREVIATION 23376242 A 717 720 MAN ABBREVIATION 23376242 A 844 847 MAN ABBREVIATION 23376242 T 24 57 P-aminophenyl-α-d-mannopyranoside SYSTEMATIC 23376245 A 0 8 Tyrosine TRIVIAL 23376245 A 1057 1061 NMDA ABBREVIATION 23376245 A 106 114 tyrosine TRIVIAL 23376245 A 1175 1178 Tyr FORMULA 23376245 A 1265 1269 NMDA ABBREVIATION 23376245 A 195 203 tyrosine TRIVIAL 23376245 A 270 278 tyrosine TRIVIAL 23376245 A 28 48 N-methyl-d-aspartate SYSTEMATIC 23376245 A 475 488 orthovanadate SYSTEMATIC 23376245 A 492 502 Bpv (phen) ABBREVIATION 23376245 A 50 54 NMDA ABBREVIATION 23376245 A 64 73 glutamate TRIVIAL 23376245 A 747 751 NMDA ABBREVIATION 23376245 A 778 791 orthovanadate SYSTEMATIC 23376245 A 796 806 Bpv (phen) ABBREVIATION 23376245 A 858 862 NMDA ABBREVIATION 23376245 T 22 30 tyrosine TRIVIAL 23376249 A 112 118 acetyl SYSTEMATIC 23376249 A 30 47 1,3,4-thiadiazole SYSTEMATIC 23376249 T 39 56 1,3,4-thiadiazole SYSTEMATIC 23376353 A 195 206 doxorubicin TRIVIAL 23376353 A 231 240 verapamil TRIVIAL 23376353 A 388 392 PLGA ABBREVIATION 23376353 A 482 510 cyclo(Arg-Gly-Asp-D-Phe-Lys) SYSTEMATIC 23376353 A 544 552 carboxyl SYSTEMATIC 23376353 A 567 571 PLGA ABBREVIATION 23376353 A 608 611 DOX ABBREVIATION 23376353 A 612 615 VER ABBREVIATION 23376353 A 620 624 PLGA ABBREVIATION 23376353 A 762 765 DOX ABBREVIATION 23376353 A 770 773 VER ABBREVIATION 23376353 A 819 822 DOX ABBREVIATION 23376353 A 823 826 VER ABBREVIATION 23376353 A 831 835 PLGA ABBREVIATION 23376354 A 208 214 Ca(2+) FORMULA 23376354 A 219 223 K(+) FORMULA 23376354 A 469 475 Ca(2+) FORMULA 23376354 A 480 484 K(+) FORMULA 23376354 A 606 612 Ca(2+) FORMULA 23376354 A 650 654 K(+) FORMULA 23376354 A 696 702 Ca(2+) FORMULA 23376354 A 713 717 K(+) FORMULA 23376412 A 334 350 indole alkaloids FAMILY 23376412 A 448 464 indole alkaloids FAMILY 23376412 T 12 28 indole alkaloids FAMILY 23376437 A 1143 1146 CPZ ABBREVIATION 23376437 A 1489 1492 CPZ ABBREVIATION 23376437 A 280 294 chlorpromazine TRIVIAL 23376437 A 296 299 CPZ ABBREVIATION 23376437 A 452 455 CPZ ABBREVIATION 23376437 A 476 479 CPZ ABBREVIATION 23376437 A 692 695 CPZ ABBREVIATION 23376437 A 719 722 CPZ ABBREVIATION 23376437 A 838 841 CPZ ABBREVIATION 23376437 T 24 38 chlorpromazine TRIVIAL 23376439 A 1096 1103 alkanes FAMILY 23376439 A 1108 1119 hydrocarbon FAMILY 23376439 A 1227 1233 hexane SYSTEMATIC 23376439 A 1241 1247 decane SYSTEMATIC 23376439 A 1256 1266 hexadecane SYSTEMATIC 23376439 A 146 158 hydrocarbons FAMILY 23376439 A 167 180 methyl esters FAMILY 23376439 A 232 239 alkanes FAMILY 23376439 T 25 37 hydrocarbons FAMILY 23376477 A 149 161 xenoestrogen FAMILY 23376477 A 168 179 nonylphenol SYSTEMATIC 23376477 A 336 340 K(+) FORMULA 23376477 A 377 383 Ca(2+) FORMULA 23376477 A 58 62 K(+) FORMULA 23376477 A 83 89 Ca(2+) FORMULA 23376477 T 0 11 Nonylphenol SYSTEMATIC 23376477 T 30 38 estrogen FAMILY 23376477 T 62 64 K⁺ FORMULA 23376477 T 85 89 Ca²⁺ FORMULA 23376608 A 0 8 Apigenin TRIVIAL 23376608 A 166 174 Apigenin TRIVIAL 23376608 A 317 325 apigenin TRIVIAL 23376608 A 359 367 apigenin TRIVIAL 23376608 A 473 481 apigenin TRIVIAL 23376608 A 547 555 apigenin TRIVIAL 23376608 A 670 678 apigenin TRIVIAL 23376608 A 70 78 apigenin TRIVIAL 23376608 A 872 880 apigenin TRIVIAL 23376608 T 0 8 Apigenin TRIVIAL 23376696 A 1007 1015 fluoride SYSTEMATIC 23376696 A 1118 1126 chloride SYSTEMATIC 23376696 A 1276 1284 fluoride SYSTEMATIC 23376696 A 165 173 fluoride SYSTEMATIC 23376696 A 264 272 fluoride SYSTEMATIC 23376696 A 314 322 fluoride SYSTEMATIC 23376696 A 392 400 fluoride SYSTEMATIC 23376696 A 576 584 fluoride SYSTEMATIC 23376696 A 65 73 fluoride SYSTEMATIC 23376696 A 708 713 Na(+) FORMULA 23376696 A 714 718 K(+) FORMULA 23376696 A 730 736 Ca(2+) FORMULA 23376696 A 820 828 fluoride SYSTEMATIC 23376696 A 867 877 superoxide TRIVIAL 23376696 A 941 956 malondialdehyde TRIVIAL 23376696 A 958 961 MDA ABBREVIATION 23376696 T 24 32 fluoride SYSTEMATIC 23376697 A 1005 1019 titanium oxide SYSTEMATIC 23376697 A 1024 1030 cobalt SYSTEMATIC 23376712 A 0 19 γ-Aminobutyric acid SYSTEMATIC 23376712 A 1116 1124 baclofen TRIVIAL 23376712 A 1166 1174 baclofen TRIVIAL 23376712 A 1289 1295 BHF177 IDENTIFIER 23376712 A 1345 1351 BHF177 IDENTIFIER 23376712 A 1523 1531 baclofen TRIVIAL 23376712 A 1536 1542 BHF177 IDENTIFIER 23376712 A 1709 1715 BHF177 IDENTIFIER 23376712 A 479 573 N-([1R,2R,4S]-bicyclo[2.2.1]hept-2-yl)-2-methyl-5-(4-[trifluoromethyl]phenyl)-4-pyrimidinamine SYSTEMATIC 23376712 A 575 581 BHF177 IDENTIFIER 23376712 A 697 703 BHF177 IDENTIFIER 23376712 A 735 743 baclofen TRIVIAL 23376712 A 767 783 chlordiazepoxide TRIVIAL 23376712 A 785 793 baclofen TRIVIAL 23376712 A 843 849 BHF177 IDENTIFIER 23376712 A 987 995 Baclofen TRIVIAL 23376712 T 105 113 baclofen TRIVIAL 23376712 T 67 73 BHF177 IDENTIFIER 23376780 A 1297 1306 β-asarone TRIVIAL 23376780 A 296 303 eugenol TRIVIAL 23376780 A 305 313 rotenone TRIVIAL 23376780 A 315 324 β-asarone TRIVIAL 23376780 A 329 339 pyrethrins FAMILY 23376780 A 473 482 β-asarone TRIVIAL 23376780 A 884 892 rotenone TRIVIAL 23376817 A 1004 1008 BrdU ABBREVIATION 23376817 A 1036 1040 BrdU ABBREVIATION 23376817 A 1157 1165 DMA(III) FORMULA 23376817 A 1435 1443 DMA(III) FORMULA 23376817 A 1551 1558 arsenic SYSTEMATIC 23376817 A 1596 1602 DMA(V) FORMULA 23376817 A 162 168 DMA(V) FORMULA 23376817 A 1682 1690 DMA(III) FORMULA 23376817 A 1724 1730 DMA(V) FORMULA 23376817 A 290 298 DMA(III) FORMULA 23376817 A 30 37 arsenic SYSTEMATIC 23376817 A 348 354 DMA(V) FORMULA 23376817 A 472 480 DMA(III) FORMULA 23376817 A 565 585 methylate arsenicals FAMILY 23376817 A 665 673 DMA(III) FORMULA 23376817 A 826 843 bromodeoxyuridine TRIVIAL 23376817 A 845 849 BrdU ABBREVIATION 23376817 A 967 975 DMA(III) FORMULA 23376817 T 103 110 arsenic SYSTEMATIC 23376817 T 33 54 dimethylarsinous acid SYSTEMATIC 23376817 T 56 64 DMA(III) FORMULA 23376997 A 391 406 arylsulfonamido FAMILY 23376997 A 413 425 hydroxamates FAMILY 23376997 T 0 15 Arylsulfonamide FAMILY 23377100 A 1246 1248 Cd FORMULA 23377100 A 1283 1292 ascorbate TRIVIAL 23377100 A 1343 1349 oxygen SYSTEMATIC 23377100 A 1445 1454 ascorbate TRIVIAL 23377100 A 321 328 cadmium SYSTEMATIC 23377100 A 335 341 Cd(2+) FORMULA 23377100 A 376 399 polytetrafluoroethylene TRIVIAL 23377100 A 401 405 PTFE ABBREVIATION 23377100 A 603 607 PTFE ABBREVIATION 23377100 A 695 701 Cd(2+) FORMULA 23377100 A 894 896 Cd FORMULA 23377100 A 957 963 Cd(2+) FORMULA 23377100 T 27 36 ascorbate TRIVIAL 23377115 A 106 125 calcium diglutamate SYSTEMATIC 23377115 A 127 149 monoammonium glutamate SYSTEMATIC 23377115 A 155 176 magnesium diglutamate SYSTEMATIC 23377115 A 59 79 monosodium glutamate SYSTEMATIC 23377115 A 81 104 monopotassium glutamate SYSTEMATIC 23377115 T 59 69 glutamates FAMILY 23377609 A 1038 1042 EDTA ABBREVIATION 23377609 A 1046 1053 cadmium SYSTEMATIC 23377609 A 133 140 cadmium SYSTEMATIC 23377609 A 1532 1539 cadmium SYSTEMATIC 23377609 A 17 24 cadmium SYSTEMATIC 23377609 A 228 235 cadmium SYSTEMATIC 23377609 A 395 462 1-(4-isothiocyanobenzyl) ethylenediamine N,N,N',N'-tetraacetic acid SYSTEMATIC 23377609 A 464 469 ITCBE ABBREVIATION 23377609 A 494 499 ITCBE ABBREVIATION 23377609 A 566 626 1-(4-aminobenzyl) ethylenediamine N,N,N',N'-tetraacetic acid SYSTEMATIC 23377609 A 628 644 aminobenzyl-EDTA SYSTEMATIC 23377609 A 653 660 cadmium SYSTEMATIC 23377609 A 708 724 aminobenzyl-EDTA SYSTEMATIC 23377609 A 847 854 cadmium SYSTEMATIC 23377609 T 60 67 cadmium SYSTEMATIC 23377617 A 1122 1124 Zn FORMULA 23377617 A 1263 1266 GSH ABBREVIATION 23377617 A 1291 1293 Zn FORMULA 23377617 A 13 17 zinc SYSTEMATIC 23377617 A 1367 1370 GSH ABBREVIATION 23377617 A 1429 1431 Zn FORMULA 23377617 A 1457 1460 GSH ABBREVIATION 23377617 A 1597 1600 GSH ABBREVIATION 23377617 A 1658 1660 Zn FORMULA 23377617 A 19 21 Zn FORMULA 23377617 A 219 221 Zn FORMULA 23377617 A 246 257 glutathione TRIVIAL 23377617 A 259 262 GSH ABBREVIATION 23377617 A 411 414 GSH ABBREVIATION 23377617 A 436 444 dopamine TRIVIAL 23377617 A 451 454 GSH ABBREVIATION 23377617 A 542 544 Zn FORMULA 23377617 A 579 581 Zn FORMULA 23377617 A 606 624 γ-Glutamylcysteine SYSTEMATIC 23377617 A 667 670 GSH ABBREVIATION 23377617 A 705 707 Zn FORMULA 23377617 A 828 830 Zn FORMULA 23377617 T 10 14 zinc SYSTEMATIC 23377617 T 36 47 glutathione TRIVIAL 23378200 A 114 122 Baicalin TRIVIAL 23378200 A 1542 1550 Baicalin TRIVIAL 23378200 A 1626 1634 baicalin TRIVIAL 23378200 A 211 219 baicalin TRIVIAL 23378200 A 323 331 baicalin TRIVIAL 23378200 A 631 639 baicalin TRIVIAL 23378200 T 11 19 baicalin TRIVIAL 23378608 A 1138 1147 celecoxib TRIVIAL 23378608 A 859 870 Fatty acids FAMILY 23378626 A 1098 1105 CS-1036 IDENTIFIER 23378626 A 1118 1125 CS-1036 IDENTIFIER 23378626 A 1333 1340 CS-1036 IDENTIFIER 23378626 A 1379 1386 glucose TRIVIAL 23378626 A 1472 1479 CS-1036 IDENTIFIER 23378626 A 153 160 CS-1036 IDENTIFIER 23378626 A 344 351 CS-1036 IDENTIFIER 23378626 A 45 151 (2R,3R,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-3-yl 4-O-(6-deoxy-β-d-glucopyranosyl)-α-d-glucopyranoside SYSTEMATIC 23378626 A 507 521 [(14)C]CS-1036 IDENTIFIER 23378626 T 179 186 glucose TRIVIAL 23378626 T 43 50 CS-1036 IDENTIFIER 23378627 A 19 29 androstane TRIVIAL 23378627 T 95 105 androstane TRIVIAL 23378820 A 11 19 selenate SYSTEMATIC 23378820 A 140 151 bicarbonate SYSTEMATIC 23378820 A 160 164 Iron SYSTEMATIC 23378820 A 180 197 ferrous hydroxide SYSTEMATIC 23378820 A 241 249 selenate SYSTEMATIC 23378820 A 265 269 Iron SYSTEMATIC 23378820 A 407 413 oxygen SYSTEMATIC 23378820 A 526 534 selenate SYSTEMATIC 23378820 A 572 580 selenate SYSTEMATIC 23378820 A 684 691 ferrous SYSTEMATIC 23378820 A 696 705 hydroxide SYSTEMATIC 23378820 A 842 848 oxygen SYSTEMATIC 23378820 A 903 911 selenate SYSTEMATIC 23378820 A 98 102 iron SYSTEMATIC 23378820 T 27 35 Selenate SYSTEMATIC 23379362 A 19 32 polyacetylene SYSTEMATIC 23379362 A 297 311 Petroacetylene TRIVIAL 23379362 A 53 67 petroacetylene TRIVIAL 23379362 T 0 14 Petroacetylene TRIVIAL 23379362 T 22 35 polyacetylene SYSTEMATIC 23379369 A 33 52 2-fluoroethyl azide SYSTEMATIC 23379369 A 54 63 FCH2CH2N3 FORMULA 23379369 A 619 626 F-C-C-N FORMULA 23379369 A 631 638 C-C-N-N FORMULA 23379369 A 668 676 fluorine SYSTEMATIC 23379369 A 690 695 azido SYSTEMATIC 23379369 T 64 83 2-fluoroethyl azide SYSTEMATIC 23379369 T 85 94 FCH2CH2N3 FORMULA 23379686 A 112 125 [C10C10mim]Cl FORMULA 23379686 A 1401 1414 [C10C10mim]Cl FORMULA 23379686 A 1505 1538 4-methoxybenzenesulfonyl chloride SYSTEMATIC 23379686 A 1540 1544 MBSC ABBREVIATION 23379686 A 545 551 pyrene SYSTEMATIC 23379686 A 556 564 Nile red TRIVIAL 23379686 A 617 628 rhodamine B TRIVIAL 23379686 A 659 663 (1)H FORMULA 23379686 A 672 675 D2O FORMULA 23379686 A 70 110 1,3-didecyl-2-methylimidazolium chloride SYSTEMATIC 23379686 T 44 84 1,3-didecyl-2-methylimidazolium chloride SYSTEMATIC 23379723 A 169 179 spiropyran FAMILY 23379723 A 400 407 toluene TRIVIAL 23379723 A 409 424 tetrahydrofuran SYSTEMATIC 23379723 A 426 433 acetone SYSTEMATIC 23379723 A 435 447 acetonitrile SYSTEMATIC 23379723 A 449 456 ethanol SYSTEMATIC 23379723 A 462 470 methanol SYSTEMATIC 23379723 A 55 65 spiropyran FAMILY 23379723 A 6 12 silica TRIVIAL 23379723 A 632 642 spiropyran FAMILY 23379723 A 662 673 merocyanine FAMILY 23379723 A 840 850 spiropyran FAMILY 23379723 T 0 10 Spiropyran FAMILY 23379784 A 0 11 Polystyrene SYSTEMATIC 23379784 A 830 831 H FORMULA 23379784 A 959 970 polystyrene SYSTEMATIC 23379784 A 973 993 poly(ethylene oxide) SYSTEMATIC 23379784 T 27 38 polystyrene SYSTEMATIC 23379962 A 1032 1037 PFH-A ABBREVIATION 23379962 A 187 193 carbon SYSTEMATIC 23379962 A 287 356 poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(6,6'-{2,2'-bipyridine})] SYSTEMATIC 23379962 A 358 365 PFO-BPy ABBREVIATION 23379962 A 371 429 poly[(9,9-dihexylfluorenyl-2,7-diyl)-co-(9,10-anthracene)] SYSTEMATIC 23379962 A 431 436 PFH-A ABBREVIATION 23379962 A 51 59 fluorene SYSTEMATIC 23379962 T 70 76 carbon SYSTEMATIC 23380082 A 278 292 phenolic acids FAMILY 23380082 A 294 309 rosmarinic acid TRIVIAL 23380082 A 316 328 caffeic acid TRIVIAL 23380082 A 338 350 ferulic acid TRIVIAL 23380082 A 564 578 phenolic acids FAMILY 23380082 A 689 703 phenolic acids FAMILY 23380082 T 77 91 phenolic acids FAMILY 23380243 A 930 937 arsenic SYSTEMATIC 23380305 A 0 9 Histamine TRIVIAL 23380305 A 1047 1054 ABT-239 IDENTIFIER 23380305 A 1073 1082 histamine TRIVIAL 23380305 A 1184 1191 ABT-239 IDENTIFIER 23380305 A 1202 1211 histamine TRIVIAL 23380305 A 1305 1312 ABT-239 IDENTIFIER 23380305 A 1438 1445 ABT-239 IDENTIFIER 23380305 A 158 167 histamine TRIVIAL 23380305 A 1679 1688 histamine TRIVIAL 23380305 A 1835 1844 histamine TRIVIAL 23380305 A 510 519 histamine TRIVIAL 23380305 A 543 613 4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile SYSTEMATIC 23380305 A 615 622 ABT-239 IDENTIFIER 23380305 A 801 814 acetylcholine SYSTEMATIC 23380305 A 819 828 histamine TRIVIAL 23380305 T 103 116 acetylcholine SYSTEMATIC 23380305 T 121 130 histamine TRIVIAL 23380305 T 37 46 histamine TRIVIAL 23380305 T 86 93 ABT-239 IDENTIFIER 23380477 A 459 474 cobalt chloride SYSTEMATIC 23380477 A 561 567 oxygen SYSTEMATIC 23380477 A 597 602 CoCl2 FORMULA 23380477 A 831 836 CoCl2 FORMULA 23380477 T 88 95 CoCl(2) FORMULA 23380917 A 1064 1067 PCP ABBREVIATION 23380917 A 1262 1265 PCP ABBREVIATION 23380917 A 1439 1442 PCP ABBREVIATION 23380917 A 1596 1599 PCP ABBREVIATION 23380917 A 21 34 phencyclidine TRIVIAL 23380917 A 227 246 γ-aminobutyric acid SYSTEMATIC 23380917 A 248 252 GABA ABBREVIATION 23380917 A 36 39 PCP ABBREVIATION 23380917 A 430 434 GABA ABBREVIATION 23380917 A 531 534 PCP ABBREVIATION 23380917 A 726 729 PCP ABBREVIATION 23380917 A 74 94 N-methyl D-aspartate SYSTEMATIC 23380917 T 10 23 phencyclidine TRIVIAL 23381681 A 1128 1130 Se FORMULA 23381681 A 1188 1190 Se FORMULA 23381681 A 1216 1222 seleno SYSTEMATIC 23381681 A 1261 1264 GSH ABBREVIATION 23381681 A 1294 1309 sodium selenite SYSTEMATIC 23381681 A 1311 1320 Thyroxine TRIVIAL 23381681 A 1327 1343 triiodothyronine TRIVIAL 23381681 A 1538 1540 Se FORMULA 23381681 A 1572 1574 Se FORMULA 23381681 A 1617 1632 sodium selenite SYSTEMATIC 23381681 A 1697 1703 seleno SYSTEMATIC 23381681 A 1711 1719 Selenium SYSTEMATIC 23381681 A 1808 1811 GSH ABBREVIATION 23381681 A 1827 1833 seleno SYSTEMATIC 23381681 A 1845 1847 Se FORMULA 23381681 A 1871 1886 sodium selenite SYSTEMATIC 23381681 A 374 382 selenium SYSTEMATIC 23381681 A 384 386 Se FORMULA 23381681 A 415 417 Se FORMULA 23381681 A 423 438 sodium selenite SYSTEMATIC 23381681 A 483 485 Se FORMULA 23381681 A 491 497 seleno SYSTEMATIC 23381681 A 756 758 Se FORMULA 23381681 A 794 796 Se FORMULA 23381681 A 822 833 glutathione TRIVIAL 23381681 A 857 860 GSH ABBREVIATION 23381681 A 901 903 Se FORMULA 23381681 A 914 920 seleno SYSTEMATIC 23381681 A 969 984 sodium selenite SYSTEMATIC 23381681 A 990 993 GSH ABBREVIATION 23381681 T 25 33 selenium SYSTEMATIC 23381882 A 1048 1058 saquinavir TRIVIAL 23381882 A 143 152 midazolam TRIVIAL 23381882 A 171 183 fexofenadine TRIVIAL 23381882 A 199 210 pravastatin TRIVIAL 23381882 A 280 290 saquinavir TRIVIAL 23381882 A 34 43 ritonavir TRIVIAL 23381882 A 439 448 ritonavir TRIVIAL 23381882 A 572 582 saquinavir TRIVIAL 23381882 A 739 748 midazolam TRIVIAL 23381882 A 753 765 fexofenadine TRIVIAL 23381882 A 922 933 pravastatin TRIVIAL 23381882 A 99 109 saquinavir TRIVIAL 23381882 T 107 116 Midazolam TRIVIAL 23381882 T 127 139 Fexofenadine TRIVIAL 23381882 T 162 173 Pravastatin TRIVIAL 23381882 T 50 59 Ritonavir TRIVIAL 23381882 T 64 74 Saquinavir TRIVIAL 23381951 A 0 11 Allopurinol TRIVIAL 23381951 A 571 582 allopurinol TRIVIAL 23381951 A 701 709 abacavir TRIVIAL 23381951 A 714 727 carbamazepine TRIVIAL 23381951 A 844 855 allopurinol TRIVIAL 23381951 T 20 31 Allopurinol TRIVIAL 23382013 A 1017 1024 octanol SYSTEMATIC 23382105 A 1051 1054 MMF ABBREVIATION 23382105 A 1089 1101 cyclosporine TRIVIAL 23382105 A 1119 1122 MPA ABBREVIATION 23382105 A 1238 1259 mycophenolate mofetil TRIVIAL 23382105 A 1276 1279 MPA ABBREVIATION 23382105 A 138 141 MPA ABBREVIATION 23382105 A 220 223 MPA ABBREVIATION 23382105 A 465 468 MPA ABBREVIATION 23382105 A 600 603 MPA ABBREVIATION 23382105 A 65 82 mycophenolic acid TRIVIAL 23382105 A 759 771 cyclosporine TRIVIAL 23382105 A 830 833 MPA ABBREVIATION 23382105 A 84 87 MPA ABBREVIATION 23382105 A 960 970 tacrolimus TRIVIAL 23382105 T 104 125 mycophenolate mofetil TRIVIAL 23382105 T 53 70 mycophenolic acid TRIVIAL 23382380 A 0 4 AMPA ABBREVIATION 23382380 A 28 37 glutamate TRIVIAL 23383423 A 121 131 amino acid FAMILY 23383594 A 430 444 carbon dioxide SYSTEMATIC 23383594 A 449 456 methane SYSTEMATIC 23383594 A 520 527 zeolite TRIVIAL 23383594 A 550 556 carbon SYSTEMATIC 23383594 A 598 601 CO2 FORMULA 23383594 A 602 605 CH4 FORMULA 23383710 A 137 143 DMAAPS ABBREVIATION 23383710 A 157 173 polyethylenimine SYSTEMATIC 23383710 A 175 178 PEI ABBREVIATION 23383710 A 315 318 PEI ABBREVIATION 23383710 A 338 341 PEI ABBREVIATION 23383710 A 342 348 DMAAPS ABBREVIATION 23383710 A 353 356 PEI ABBREVIATION 23383710 A 357 363 DMAAPS ABBREVIATION 23383710 A 372 375 PEI ABBREVIATION 23383710 A 376 382 DMAAPS ABBREVIATION 23383710 A 462 465 PEI ABBREVIATION 23383710 A 558 561 PEI ABBREVIATION 23383710 A 633 636 PEI ABBREVIATION 23383710 A 748 751 PEI ABBREVIATION 23383710 A 752 758 DMAAPS ABBREVIATION 23383710 A 772 775 PEI ABBREVIATION 23383710 A 776 782 DMAAPS ABBREVIATION 23383710 A 79 135 N,N-dimethyl(acrylamidopropyl)ammonium propane sulfonate SYSTEMATIC 23383710 A 939 942 PEI ABBREVIATION 23383710 A 985 988 PEI ABBREVIATION 23383723 A 0 9 Pluronics FAMILY 23383723 A 1034 1043 bile salt FAMILY 23383723 A 1057 1070 Pluronic F127 TRIVIAL 23383723 A 1112 1121 bile salt FAMILY 23383723 A 1214 1227 Pluronic F127 TRIVIAL 23383723 A 1270 1279 bile salt FAMILY 23383723 A 200 210 bile salts FAMILY 23383723 A 323 343 Pluronic F127 or F68 MULTIPLE 23383723 A 352 361 bile salt FAMILY 23383723 A 362 367 NaTDC ABBREVIATION 23383723 A 464 472 Pluronic FAMILY 23383723 A 529 537 Pluronic FAMILY 23383723 A 741 754 Pluronic F127 TRIVIAL 23383723 A 805 814 bile salt FAMILY 23383723 A 820 823 F68 IDENTIFIER 23383723 A 934 943 Pluronics FAMILY 23383723 T 21 45 Pluronics (F127 and F68) MULTIPLE 23383723 T 50 60 bile salts FAMILY 23383723 T 62 67 NaTDC ABBREVIATION 23383746 A 102 108 LA-Tam ABBREVIATION 23383746 A 1034 1040 Prodan ABBREVIATION 23383746 A 1118 1124 LA-Tam ABBREVIATION 23383746 A 1135 1142 DCA-Tam ABBREVIATION 23383746 A 117 133 deoxycholic acid TRIVIAL 23383746 A 134 143 tamoxifen TRIVIAL 23383746 A 1415 1422 TamNHMe FORMULA 23383746 A 1427 1433 CA-Tam ABBREVIATION 23383746 A 1449 1455 LA-Tam ABBREVIATION 23383746 A 145 152 DCA-Tam ABBREVIATION 23383746 A 1466 1473 DCA-Tam ABBREVIATION 23383746 A 1554 1558 DPPC ABBREVIATION 23383746 A 1620 1629 bile acid FAMILY 23383746 A 1630 1639 tamoxifen TRIVIAL 23383746 A 165 176 cholic acid TRIVIAL 23383746 A 177 186 tamoxifen TRIVIAL 23383746 A 1780 1789 tamoxifen TRIVIAL 23383746 A 1805 1815 bile acids FAMILY 23383746 A 188 194 CA-Tam ABBREVIATION 23383746 A 218 227 tamoxifen TRIVIAL 23383746 A 248 253 amine SYSTEMATIC 23383746 A 275 279 DPPC ABBREVIATION 23383746 A 308 333 N-desmethylated tamoxifen TRIVIAL 23383746 A 335 342 TamNHMe FORMULA 23383746 A 350 353 DPH ABBREVIATION 23383746 A 385 391 Prodan ABBREVIATION 23383746 A 42 51 bile acid FAMILY 23383746 A 456 459 DPH ABBREVIATION 23383746 A 497 506 bile acid FAMILY 23383746 A 507 516 tamoxifen TRIVIAL 23383746 A 52 61 tamoxifen TRIVIAL 23383746 A 596 605 tamoxifen TRIVIAL 23383746 A 630 639 bile acid FAMILY 23383746 A 672 681 bile acid FAMILY 23383746 A 682 691 tamoxifen TRIVIAL 23383746 A 710 714 DPPC ABBREVIATION 23383746 A 74 90 lithocholic acid TRIVIAL 23383746 A 781 790 bile acid FAMILY 23383746 A 791 800 tamoxifen TRIVIAL 23383746 A 816 820 DPPC ABBREVIATION 23383746 A 857 863 CA-Tam ABBREVIATION 23383746 A 872 879 DCA-Tam ABBREVIATION 23383746 A 888 894 LA-Tam ABBREVIATION 23383746 A 903 910 TamNHMe FORMULA 23383746 A 91 100 tamoxifen TRIVIAL 23383746 A 929 938 bile acid FAMILY 23383746 A 939 948 tamoxifen TRIVIAL 23383746 T 78 87 bile acid FAMILY 23383750 A 1302 1309 PS-P4VP ABBREVIATION 23383750 A 1310 1313 PDP ABBREVIATION 23383750 A 1398 1405 PS-P4VP ABBREVIATION 23383750 A 241 275 polystyrene-poly(4-vinyl pyridine) SYSTEMATIC 23383750 A 277 284 PS-P4VP ABBREVIATION 23383750 A 530 550 3-n-pentadecylphenol SYSTEMATIC 23383750 A 552 555 PDP ABBREVIATION 23383750 A 598 606 hydrogen SYSTEMATIC 23383750 T 100 107 PS-P4VP ABBREVIATION 23383750 T 112 119 PS-P4VP ABBREVIATION 23383750 T 120 123 PDP ABBREVIATION 23383871 A 1829 1836 steroid FAMILY 23383871 A 1911 1922 cyclohexene SYSTEMATIC 23383871 A 88 96 estrogen FAMILY 23383871 A 908 916 estrogen FAMILY 23384042 A 233 241 perylene SYSTEMATIC 23384042 A 242 248 CH2Cl2 FORMULA 23384042 T 40 48 perylene SYSTEMATIC 23384363 A 253 261 nitrogen SYSTEMATIC 23384363 T 67 75 nitrogen SYSTEMATIC 23384387 A 101 124 elaidoyl-L-valinolamide SYSTEMATIC 23384387 A 130 153 elaidoyl-D-valinolamide SYSTEMATIC 23384387 A 158 181 stearoyl-L-valinolamide SYSTEMATIC 23384387 A 18 34 acylethanolamide FAMILY 23384387 A 191 215 palmitoyl-L-valinolamide SYSTEMATIC 23384387 A 47 68 oleoyl-L-valinolamide SYSTEMATIC 23384387 A 74 95 oleoyl-D-valinolamide SYSTEMATIC 23384387 A 785 806 Oleoyl-L-valinolamide SYSTEMATIC 23384387 A 857 864 glucose TRIVIAL 23384387 A 937 958 oleoyl-L-valinolamide SYSTEMATIC 23384387 T 6 22 acylethanolamide FAMILY 23384446 A 1012 1017 NADPH ABBREVIATION 23384446 A 1036 1044 apocynin TRIVIAL 23384446 A 1144 1146 NO FORMULA 23384446 A 1178 1181 CPA ABBREVIATION 23384446 A 1186 1189 ACh ABBREVIATION 23384446 A 1209 1217 arsenite SYSTEMATIC 23384446 A 1219 1227 Arsenite SYSTEMATIC 23384446 A 1236 1244 apocynin TRIVIAL 23384446 A 1408 1416 arsenite SYSTEMATIC 23384446 A 1491 1508 hydrogen peroxide SYSTEMATIC 23384446 A 1553 1563 superoxide TRIVIAL 23384446 A 1583 1588 NADPH ABBREVIATION 23384446 A 1628 1630 NO FORMULA 23384446 A 172 180 arsenite SYSTEMATIC 23384446 A 1775 1783 arsenite SYSTEMATIC 23384446 A 1836 1838 NO FORMULA 23384446 A 284 296 nitric oxide SYSTEMATIC 23384446 A 298 300 NO FORMULA 23384446 A 460 473 acetylcholine SYSTEMATIC 23384446 A 475 478 ACh ABBREVIATION 23384446 A 487 505 cyclopiazonic acid TRIVIAL 23384446 A 507 510 CPA ABBREVIATION 23384446 A 543 549 Ca(2+) FORMULA 23384446 A 621 627 oxygen SYSTEMATIC 23384446 A 765 780 dihydroethidium SYSTEMATIC 23384446 A 8 15 arsenic SYSTEMATIC 23384446 A 821 829 arsenite SYSTEMATIC 23384446 A 889 892 CPA ABBREVIATION 23384446 A 897 900 ACh ABBREVIATION 23384446 A 955 965 superoxide TRIVIAL 23384446 A 984 1003 manganese porphyrin SYSTEMATIC 23384446 T 24 31 arsenic SYSTEMATIC 23384446 T 77 82 NADPH ABBREVIATION 23384446 T 95 112 hydrogen peroxide SYSTEMATIC 23384967 A 0 11 Bisphenol A TRIVIAL 23384967 A 13 16 BPA ABBREVIATION 23384967 A 189 196 steroid FAMILY 23384967 A 22 40 diethylstilbestrol SYSTEMATIC 23384967 A 321 324 BPA ABBREVIATION 23384967 A 329 332 DES ABBREVIATION 23384967 A 42 45 DES ABBREVIATION 23384967 A 483 486 BPA ABBREVIATION 23384967 A 491 494 DES ABBREVIATION 23384967 A 607 610 BPA ABBREVIATION 23384967 A 783 786 BPA ABBREVIATION 23384967 A 847 850 DES ABBREVIATION 23384967 T 110 128 diethylstilbestrol SYSTEMATIC 23384967 T 94 105 bisphenol A TRIVIAL 23384996 A 1045 1052 ammonia SYSTEMATIC 23384996 A 1153 1160 ammonia SYSTEMATIC 23384996 A 121 128 ammonia SYSTEMATIC 23384996 A 1289 1298 glutamine TRIVIAL 23384996 A 1344 1353 glutamine TRIVIAL 23384996 A 1429 1438 glutamine TRIVIAL 23384996 A 1504 1513 glutamate TRIVIAL 23384996 A 1545 1554 glutamate TRIVIAL 23384996 A 1642 1651 glutamate TRIVIAL 23384996 A 1690 1699 glutamine TRIVIAL 23384996 A 2009 2018 aspartate TRIVIAL 23384996 A 2023 2030 alanine TRIVIAL 23384996 A 205 212 ammonia SYSTEMATIC 23384996 A 2069 2076 alanine TRIVIAL 23384996 A 2105 2112 ammonia SYSTEMATIC 23384996 A 216 225 glutamine TRIVIAL 23384996 A 2171 2182 amino acids FAMILY 23384996 A 2239 2246 ammonia SYSTEMATIC 23384996 A 2315 2322 ammonia SYSTEMATIC 23384996 A 241 252 amino acids FAMILY 23384996 A 331 338 ammonia SYSTEMATIC 23384996 A 384 391 ammonia SYSTEMATIC 23384996 A 441 450 glutamate TRIVIAL 23384996 A 454 463 glutamine TRIVIAL 23384996 A 493 502 glutamate TRIVIAL 23384996 A 51 58 ammonia SYSTEMATIC 23384996 A 538 547 aspartate TRIVIAL 23384996 A 576 583 alanine TRIVIAL 23384996 A 613 622 glutamine TRIVIAL 23384996 A 685 696 amino acids FAMILY 23384996 A 917 924 ammonia SYSTEMATIC 23384996 A 929 936 NH4HCO3 FORMULA 23384996 T 136 143 ammonia SYSTEMATIC 23384996 T 14 24 amino acid FAMILY 23385211 A 133 144 desipramine TRIVIAL 23385211 A 203 228 lithium aluminium hydride SYSTEMATIC 23385211 A 32 47 ethylene glycol SYSTEMATIC 23385211 A 456 461 amine SYSTEMATIC 23385211 A 48 49 N FORMULA 23385211 A 522 532 Imipramine TRIVIAL 23385211 A 537 548 desipramine TRIVIAL 23385211 A 62 72 imipramine TRIVIAL 23385211 A 661 671 Imipramine TRIVIAL 23385211 A 734 743 serotonin TRIVIAL 23385211 A 963 974 imipramines FAMILY 23385211 T 20 31 imipramines FAMILY 23385211 T 6 7 N FORMULA 23385214 A 244 246 OH FORMULA 23385214 A 259 260 H FORMULA 23385214 A 268 270 OH FORMULA 23385214 A 523 525 OH FORMULA 23385214 A 651 653 OH FORMULA 23386250 A 1071 1077 FK-506 IDENTIFIER 23386250 A 1079 1089 tacrolimus TRIVIAL 23386250 A 1207 1213 FK-506 IDENTIFIER 23386250 A 1310 1316 Ca(2+) FORMULA 23386250 A 1327 1331 K(+) FORMULA 23386250 A 308 314 Ca(2+) FORMULA 23386468 A 0 27 2'-Fluoro-2'-deoxyguanosine SYSTEMATIC 23386468 A 1047 1054 guanine TRIVIAL 23386468 A 1099 1108 adenosine TRIVIAL 23386468 A 1153 1181 nucleoside 5'-monophosphates FAMILY 23386468 A 186 213 2'-fluoro-2'-deoxyguanosine SYSTEMATIC 23386468 A 248 263 phosphoramidate SYSTEMATIC 23386468 A 334 345 nucleosides FAMILY 23386468 A 418 451 5'-O-naphthyl(methoxy-L-alaninyl) SYSTEMATIC 23386468 A 475 513 6-O-methyl-2'-fluoro-2'-deoxyguanosine SYSTEMATIC 23386468 A 515 552 6-O-ethyl-2'-fluoro-2'-deoxyguanosine SYSTEMATIC 23386468 A 558 594 2'-deoxy-2'-fluoro-6-chloroguanosine SYSTEMATIC 23386468 A 604 636 5'-O-naphthyl(ethoxy-L-alaninyl) SYSTEMATIC 23386468 A 648 685 6-O-ethyl-2'-fluoro-2'-deoxyguanosine SYSTEMATIC 23386468 A 816 826 L-alaninyl TRIVIAL 23386468 A 858 902 2'-fluoro-2'-deoxyguanosine 5'-monophosphate SYSTEMATIC 23386468 T 39 72 purine 2'-fluoro-2'-deoxyriboside SYSTEMATIC 23386597 A 1040 1049 ezogabine TRIVIAL 23386597 A 1230 1239 ezogabine TRIVIAL 23386597 A 332 341 Ezogabine TRIVIAL 23386597 A 352 362 retigabine TRIVIAL 23386597 A 380 441 ethyl N-(2-amino-4-[{fluorophenyl}methlamino]phenylcarbamate) SYSTEMATIC 23386597 A 618 627 Ezogabine TRIVIAL 23386597 A 685 694 potassium SYSTEMATIC 23386597 A 847 856 ezogabine TRIVIAL 23386597 T 0 9 Ezogabine TRIVIAL 23386599 A 133 139 esters FAMILY 23386599 A 1358 1365 statins FAMILY 23386599 A 141 147 amides FAMILY 23386599 A 149 159 thioesters FAMILY 23386599 A 165 175 carbamates FAMILY 23386599 A 448 453 ester FAMILY 23386599 A 545 560 carboxylic acid SYSTEMATIC 23386616 A 33 38 NADPH ABBREVIATION 23386616 A 948 954 oxygen SYSTEMATIC 23386616 T 62 67 NADPH ABBREVIATION 23386704 A 1002 1011 vitamin D FAMILY 23386704 A 105 126 4β-hydroxycholesterol SYSTEMATIC 23386704 A 1099 1118 25-hydroxyvitamin D SYSTEMATIC 23386704 A 1123 1144 4β-hydroxycholesterol SYSTEMATIC 23386704 A 1235 1256 4β-hydroxycholesterol SYSTEMATIC 23386704 A 1338 1357 25-hydroxyvitamin D SYSTEMATIC 23386704 A 1400 1409 vitamin D FAMILY 23386704 A 1414 1435 4β-hydroxycholesterol SYSTEMATIC 23386704 A 1530 1551 4β-hydroxycholesterol SYSTEMATIC 23386704 A 556 565 vitamin D FAMILY 23386704 A 737 756 25-hydroxyvitamin D SYSTEMATIC 23386704 A 81 100 25-hydroxyvitamin D SYSTEMATIC 23386704 A 828 847 25-hydroxyvitamin D SYSTEMATIC 23386704 A 882 903 4β-hydroxycholesterol SYSTEMATIC 23386704 T 16 35 25-hydroxyvitamin D SYSTEMATIC 23386704 T 60 81 4β-hydroxycholesterol SYSTEMATIC 23386704 T 97 106 vitamin D FAMILY 23386780 A 0 15 Epichlorohydrin TRIVIAL 23386780 A 17 20 ECH ABBREVIATION 23386780 A 302 305 ECH ABBREVIATION 23386780 A 318 321 ECH ABBREVIATION 23386780 A 404 408 dUTP ABBREVIATION 23386780 A 934 939 amino FAMILY 23386780 T 49 64 epichlorohydrin TRIVIAL 23387796 A 1029 1039 geralcin C TRIVIAL 23387796 A 115 132 geralcins A and B MULTIPLE 23387796 A 12 22 hydrazides FAMILY 23387796 A 236 252 Amberlite XAD-16 TRIVIAL 23387796 A 24 37 geralcins C-E MULTIPLE 23387796 A 577 585 methanol SYSTEMATIC 23387796 A 625 629 (1)H FORMULA 23387796 A 631 636 (13)C FORMULA 23387796 A 642 647 (15)N FORMULA 23387796 A 881 898 geralcins D and E MULTIPLE 23387796 A 900 910 Geralcin C TRIVIAL 23387796 T 42 52 hydrazides FAMILY 23387851 A 1211 1217 SA4503 IDENTIFIER 23387851 A 1222 1233 ANAVEX 2-73 IDENTIFIER 23387851 A 1256 1263 E-52862 IDENTIFIER 23387865 A 0 23 Hydroxysafflor yellow A SYSTEMATIC 23387865 A 25 29 HSYA ABBREVIATION 23387865 A 356 365 DMSO-d(6) ABBREVIATION 23387865 A 367 380 pyridine-d(5) SYSTEMATIC 23387865 A 386 393 CD(3)OH FORMULA 23387865 A 438 442 HSYA ABBREVIATION 23387865 A 495 512 3-enol-1,7-diketo SYSTEMATIC 23387865 A 541 550 keto-enol SYSTEMATIC 23387865 A 591 608 1-enol-3,7-diketo SYSTEMATIC 23387865 A 688 713 quinochalcone C-glycoside FAMILY 23387865 A 767 772 (13)C FORMULA 23387865 A 789 809 (E)-olefinic carbons FAMILY 23387865 A 813 839 quinochalcone C-glycosides FAMILY 23387865 A 971 980 keto-enol SYSTEMATIC 23387865 T 61 84 hydroxysafflor yellow A SYSTEMATIC 23387865 T 95 121 quinochalcone C-glycosides FAMILY 23389039 A 1124 1132 curcumin TRIVIAL 23389039 A 1273 1281 curcumin TRIVIAL 23389045 A 0 7 Pyridyl SYSTEMATIC 23389045 A 1211 1220 4-pyridyl SYSTEMATIC 23389045 A 1225 1245 bis(2-hydroxy-ethyl) SYSTEMATIC 23389045 A 1261 1272 lipoic acid TRIVIAL 23389045 A 176 183 ethanol SYSTEMATIC 23389045 A 537 546 4-pyridyl SYSTEMATIC 23389045 A 553 572 bis(2-hydroxyethyl) SYSTEMATIC 23389045 A 587 598 lipoic acid TRIVIAL 23389045 A 98 112 thyroxine (T4) TRIVIAL 23389045 T 17 25 pyridine SYSTEMATIC 23389045 T 35 46 lipoic Acid TRIVIAL 23389045 T 94 108 thyroxine (t4) TRIVIAL 23389625 A 101 110 LiFePO(4) FORMULA 23389625 A 152 159 lithium SYSTEMATIC 23389625 A 179 188 LiFePO(4) FORMULA 23389625 A 271 277 carbon SYSTEMATIC 23389625 A 330 336 carbon SYSTEMATIC 23389625 A 359 366 sucrose TRIVIAL 23389625 A 372 373 C FORMULA 23389625 A 374 383 LiFePO(4) FORMULA 23389625 A 60 66 carbon SYSTEMATIC 23389625 A 640 641 C FORMULA 23389625 A 642 651 LiFePO(4) FORMULA 23389625 A 74 83 LiFePO(4) FORMULA 23389625 A 752 758 carbon SYSTEMATIC 23389625 A 774 780 carbon SYSTEMATIC 23389625 A 825 831 carbon SYSTEMATIC 23389625 A 91 97 carbon SYSTEMATIC 23389625 A 916 925 LiFePO(4) FORMULA 23389625 A 99 100 C FORMULA 23389625 T 0 6 Carbon SYSTEMATIC 23389625 T 14 21 LiFePO4 FORMULA 23389625 T 29 35 carbon SYSTEMATIC 23389625 T 72 79 lithium SYSTEMATIC 23389738 A 1139 1143 ETBE ABBREVIATION 23389738 A 19 45 ethyl tertiary-butyl ether SYSTEMATIC 23389738 A 200 204 ETBE ABBREVIATION 23389738 A 47 51 ETBE ABBREVIATION 23389738 T 24 50 ethyl tertiary-butyl ether SYSTEMATIC 23389956 A 271 274 sGC ABBREVIATION 23389956 A 41 49 cortisol TRIVIAL 23389956 A 449 457 cortisol TRIVIAL 23389956 A 663 671 cortisol TRIVIAL 23389956 A 777 790 betamethasone TRIVIAL 23389956 A 941 949 cortisol TRIVIAL 23391096 A 0 10 Paclitaxel TRIVIAL 23391096 A 1098 1108 paclitaxel TRIVIAL 23391096 A 1120 1125 PAMAM ABBREVIATION 23391096 A 12 17 Taxol TRIVIAL 23391096 A 221 231 paclitaxel TRIVIAL 23391096 A 243 257 polyamidoamine FAMILY 23391096 A 259 264 PAMAM ABBREVIATION 23391096 A 437 447 paclitaxel TRIVIAL 23391096 A 493 503 paclitaxel TRIVIAL 23391096 A 588 598 paclitaxel TRIVIAL 23391096 A 850 860 paclitaxel TRIVIAL 23391096 A 924 934 paclitaxel TRIVIAL 23391096 A 989 1004 tertiary amines FAMILY 23391096 T 0 10 Paclitaxel TRIVIAL 23391096 T 22 27 PAMAM ABBREVIATION 23391133 A 298 303 ester FAMILY 23391133 A 305 318 monophosphate SYSTEMATIC 23391133 A 329 334 amide FAMILY 23391162 A 23 47 DO3A-N-α-aminopropionate SYSTEMATIC 23391162 A 246 248 Gd FORMULA 23391162 A 4 11 Gd(III) FORMULA 23391162 A 49 59 Gd(DOTAla) FORMULA 23391162 T 101 103 Gd FORMULA 23391162 T 90 100 Amino Acid FAMILY 23391254 A 231 236 taxol TRIVIAL 23391254 A 577 580 ATP ABBREVIATION 23391441 A 1081 1096 Alexa Fluor 488 TRIVIAL 23391441 A 1108 1118 phalloidin TRIVIAL 23391441 A 388 421 biotin-fluorescein isothiocyanate FAMILY 23391441 A 434 440 biotin TRIVIAL 23391441 A 441 445 FITC ABBREVIATION 23391441 A 574 580 biotin TRIVIAL 23391441 A 581 585 FITC ABBREVIATION 23391441 A 663 669 biotin TRIVIAL 23391441 A 670 674 FITC ABBREVIATION 23391441 A 794 804 gentamicin FAMILY 23391441 A 864 874 gentamicin FAMILY 23391441 A 875 884 Texas Red TRIVIAL 23391441 A 888 898 gentamicin FAMILY 23391442 A 47 53 oxygen SYSTEMATIC 23391443 A 783 787 cAMP ABBREVIATION 23391484 A 0 22 Perfluorooctanoic acid SYSTEMATIC 23391484 A 1099 1103 PFOA ABBREVIATION 23391484 A 1295 1299 PFCA ABBREVIATION 23391484 A 1315 1321 carbon SYSTEMATIC 23391484 A 1362 1366 PFOA ABBREVIATION 23391484 A 221 227 carbon SYSTEMATIC 23391484 A 24 28 PFOA ABBREVIATION 23391484 A 289 293 PFOA ABBREVIATION 23391484 A 316 320 PFOA ABBREVIATION 23391484 A 437 468 perfluorinated carboxylic acids FAMILY 23391484 A 470 474 PFCA ABBREVIATION 23391484 A 483 489 carbon SYSTEMATIC 23391484 A 531 537 carbon SYSTEMATIC 23391484 A 62 76 fluoropolymers FAMILY 23391484 A 688 694 carbon SYSTEMATIC 23391484 A 726 730 PFCA ABBREVIATION 23391484 A 78 81 PFT ABBREVIATION 23391484 A 835 839 PFCA ABBREVIATION 23391484 A 917 921 PFOA ABBREVIATION 23391484 A 977 981 PFCA ABBREVIATION 23391484 T 43 74 perfluorinated carboxylic acids FAMILY 23391484 T 90 96 carbon SYSTEMATIC 23391485 A 1094 1097 BPA ABBREVIATION 23391485 A 1234 1237 BPA ABBREVIATION 23391485 A 1382 1385 BPA ABBREVIATION 23391485 A 333 336 BPA ABBREVIATION 23391485 A 37 48 Bisphenol A TRIVIAL 23391485 A 50 53 BPA ABBREVIATION 23391485 A 776 779 BPA ABBREVIATION 23391485 A 842 846 DMSO ABBREVIATION 23391485 A 874 888 17-β-estrodiol SYSTEMATIC 23391485 A 961 964 BPA ABBREVIATION 23391485 T 19 30 Bisphenol A TRIVIAL 23391598 A 1099 1101 As FORMULA 23391598 A 1112 1114 Fe FORMULA 23391598 A 239 241 Co FORMULA 23391598 A 243 245 Cr FORMULA 23391598 A 247 249 Cu FORMULA 23391598 A 251 253 Fe FORMULA 23391598 A 255 256 I FORMULA 23391598 A 258 260 Mn FORMULA 23391598 A 262 264 Mo FORMULA 23391598 A 266 268 Ni FORMULA 23391598 A 270 272 Se FORMULA 23391598 A 277 279 Zn FORMULA 23391598 A 292 294 As FORMULA 23391598 A 296 298 Cd FORMULA 23391598 A 300 302 Hg FORMULA 23391598 A 307 309 Pb FORMULA 23391598 A 699 701 Cu FORMULA 23391598 A 770 772 Zn FORMULA 23391598 A 794 795 I FORMULA 23391598 A 817 819 Se FORMULA 23391631 A 1230 1236 Pb(2+) FORMULA 23391631 A 1334 1341 lactate FAMILY 23391631 A 1360 1368 creatine TRIVIAL 23391631 A 1428 1434 Pb(2+) FORMULA 23391631 A 1587 1593 Pb(2+) FORMULA 23391631 A 176 182 Pb(2+) FORMULA 23391631 A 1958 1964 Pb(2+) FORMULA 23391631 A 2013 2024 resveratrol TRIVIAL 23391631 A 2055 2061 Pb(2+) FORMULA 23391631 A 265 271 Pb(2+) FORMULA 23391631 A 390 396 Pb(2+) FORMULA 23391631 A 509 525 aryl hydrocarbon FAMILY 23391631 A 593 599 Pb(2+) FORMULA 23391631 A 6 12 Pb(2+) FORMULA 23391631 A 682 688 Pb(2+) FORMULA 23391631 A 938 944 Pb(2+) FORMULA 23391631 T 12 28 aryl hydrocarbon FAMILY 23391632 A 1005 1023 11β-hydroxysteroid FAMILY 23391632 A 1259 1262 EDS ABBREVIATION 23391632 A 1415 1419 DEHP ABBREVIATION 23391632 A 1648 1651 EDS ABBREVIATION 23391632 A 1668 1672 DEHP ABBREVIATION 23391632 A 1794 1798 DEHP ABBREVIATION 23391632 A 1847 1851 DEHP ABBREVIATION 23391632 A 318 322 DEHP ABBREVIATION 23391632 A 399 424 ethane dimethanesulfonate SYSTEMATIC 23391632 A 426 429 EDS ABBREVIATION 23391632 A 464 476 testosterone TRIVIAL 23391632 A 578 581 EDS ABBREVIATION 23391632 A 59 85 di(2-ethylhexyl) phthalate SYSTEMATIC 23391632 A 646 649 EDS ABBREVIATION 23391632 A 683 695 testosterone TRIVIAL 23391632 A 709 726 3β-hydroxysteroid FAMILY 23391632 A 803 807 DEHP ABBREVIATION 23391632 A 852 864 testosterone TRIVIAL 23391632 A 87 91 DEHP ABBREVIATION 23391632 T 40 66 di(2-ethylhexyl) phthalate SYSTEMATIC 23391637 A 593 598 Na(+) FORMULA 23391637 A 600 604 K(+) FORMULA 23391637 A 609 615 Ca(2+) FORMULA 23391637 A 746 751 Na(+) FORMULA 23391637 A 763 769 Ca(2+) FORMULA 23392568 A 1157 1159 Hg FORMULA 23392568 A 121 123 Hg FORMULA 23392568 A 1264 1266 Hg FORMULA 23392568 A 1355 1357 Hg FORMULA 23392568 A 14 19 HgCl2 FORMULA 23392568 A 1635 1637 Hg FORMULA 23392568 A 233 235 Hg FORMULA 23392568 A 284 286 Hg FORMULA 23392568 A 555 557 Hg FORMULA 23392568 A 621 623 Hg FORMULA 23392568 A 818 820 Hg FORMULA 23392568 A 920 922 Hg FORMULA 23392568 T 21 37 mercury chloride SYSTEMATIC 23392606 A 1074 1077 PVP ABBREVIATION 23392606 A 1087 1091 PLLA ABBREVIATION 23392606 A 1092 1095 PVP ABBREVIATION 23392606 A 1135 1138 PVP ABBREVIATION 23392606 A 1162 1166 PLLA ABBREVIATION 23392606 A 1362 1365 PVP ABBREVIATION 23392606 A 1370 1374 PLLA ABBREVIATION 23392606 A 1532 1535 PVP ABBREVIATION 23392606 A 1597 1601 PLLA ABBREVIATION 23392606 A 1704 1708 PLLA ABBREVIATION 23392606 A 578 598 polyvinylpyrrolidone SYSTEMATIC 23392606 A 600 603 PVP ABBREVIATION 23392606 A 609 628 poly(l-lactic acid) SYSTEMATIC 23392606 A 630 634 PLLA ABBREVIATION 23393163 A 0 11 Vesnarinone TRIVIAL 23393163 A 27 38 quinolinone SYSTEMATIC 23393163 A 281 292 vesnarinone TRIVIAL 23393163 A 477 488 vesnarinone TRIVIAL 23393163 A 662 673 vesnarinone TRIVIAL 23393163 A 702 713 vesnarinone TRIVIAL 23393163 T 0 11 Vesnarinone TRIVIAL 23393209 A 1137 1150 triglycerides FAMILY 23393209 A 1285 1298 triglycerides FAMILY 23393209 A 1353 1362 metformin TRIVIAL 23393209 A 1442 1455 triglycerides FAMILY 23393209 A 1472 1479 glucose TRIVIAL 23393209 A 1554 1563 metformin TRIVIAL 23393209 A 159 166 glucose TRIVIAL 23393209 A 1635 1644 metformin TRIVIAL 23393209 A 1690 1697 glucose TRIVIAL 23393209 A 1710 1723 triglycerides FAMILY 23393209 A 209 218 Metformin TRIVIAL 23393209 A 272 285 triglycerides FAMILY 23393209 A 366 375 metformin TRIVIAL 23393209 A 493 506 triglycerides FAMILY 23393209 A 53 65 triglyceride FAMILY 23393209 A 580 589 metformin TRIVIAL 23393209 A 628 637 metformin TRIVIAL 23393209 A 674 687 triglycerides FAMILY 23393209 A 761 774 triglycerides FAMILY 23393209 A 838 850 triglyceride FAMILY 23393209 A 917 930 Triglycerides FAMILY 23393209 A 978 987 metformin TRIVIAL 23393209 T 25 38 Triglycerides FAMILY 23393209 T 90 99 Metformin TRIVIAL 23393216 A 1017 1028 cholesterol TRIVIAL 23393216 A 102 109 glucose TRIVIAL 23393216 A 1030 1043 triglycerides FAMILY 23393216 A 1236 1242 25-OHD SYSTEMATIC 23393216 A 1421 1427 25-OHD SYSTEMATIC 23393216 A 1488 1494 25-OHD SYSTEMATIC 23393216 A 1616 1625 Vitamin D FAMILY 23393216 A 414 439 25-hydroxycholecalciferol SYSTEMATIC 23393216 A 43 52 vitamin D FAMILY 23393216 A 441 447 25-OHD SYSTEMATIC 23393216 A 552 558 25-OHD SYSTEMATIC 23393216 A 982 991 vitamin D FAMILY 23393216 T 130 137 glucose TRIVIAL 23393216 T 34 59 25-hydroxycholecalciferol SYSTEMATIC 23393219 A 0 11 Repaglinide TRIVIAL 23393219 A 1048 1059 repaglinide TRIVIAL 23393219 A 1087 1097 rifampicin TRIVIAL 23393219 A 1375 1386 repaglinide TRIVIAL 23393219 A 1417 1428 repaglinide TRIVIAL 23393219 A 1473 1483 rifampicin TRIVIAL 23393219 A 1636 1647 repaglinide TRIVIAL 23393219 A 1844 1855 repaglinide TRIVIAL 23393219 A 1856 1866 rifampicin TRIVIAL 23393219 A 288 299 repaglinide TRIVIAL 23393219 A 305 315 rifampicin TRIVIAL 23393219 A 373 384 repaglinide TRIVIAL 23393219 A 606 617 repaglinide TRIVIAL 23393219 A 737 748 repaglinide TRIVIAL 23393219 A 806 816 rifampicin TRIVIAL 23393219 A 914 924 rifampicin TRIVIAL 23393219 T 199 209 Rifampicin TRIVIAL 23393219 T 27 38 Repaglinide TRIVIAL 23393219 T 39 49 Rifampicin TRIVIAL 23394218 A 138 145 AZD5363 IDENTIFIER 23394218 T 126 133 AZD5363 IDENTIFIER 23394218 T 13 124 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide SYSTEMATIC 23394309 A 1026 1027 O FORMULA 23394309 A 1032 1033 O FORMULA 23394309 A 160 172 Hydrocarbons FAMILY 23394309 A 252 270 [Nb6O19Hx]((8-x)-) FAMILY 23394309 A 586 590 H(+) FORMULA 23394309 A 595 600 OH(-) FORMULA 23394309 A 656 674 [Nb6O19Hx]((8-x)-) FAMILY 23394309 A 765 766 H FORMULA 23394309 A 852 858 oxygen SYSTEMATIC 23394309 A 881 882 H FORMULA 23394309 T 58 76 [Nb6O19Hx]((8-x)-) FAMILY 23394318 A 150 165 petroleum ether TRIVIAL 23394318 A 17 29 diterpenoids FAMILY 23394318 A 170 177 ethanol SYSTEMATIC 23394318 A 31 55 aquilarabietic acids A-J MULTIPLE 23394318 A 479 493 norepinephrine TRIVIAL 23394318 A 74 85 podocarpane TRIVIAL 23394318 A 8 16 abietane TRIVIAL 23394318 A 86 97 diterpenoid FAMILY 23394318 A 99 120 aquilarabietic acid K TRIVIAL 23394318 T 15 23 abietane TRIVIAL 23394318 T 24 36 diterpenoids FAMILY 23394432 A 831 846 cadmium sulfide SYSTEMATIC 23394432 A 848 851 CdS FORMULA 23394469 A 1059 1067 graphite TRIVIAL 23394469 A 610 624 met-enkephalin TRIVIAL 23394469 A 625 637 pentapeptide FAMILY 23394469 A 649 657 graphite TRIVIAL 23394480 A 1112 1114 Ge FORMULA 23394480 A 116 118 Ge FORMULA 23394480 A 164 166 Ge FORMULA 23394480 A 279 281 Si FORMULA 23394480 A 84 86 Ge FORMULA 23394480 A 87 89 Si FORMULA 23394480 A 916 918 Ge FORMULA 23394480 A 983 985 Ge FORMULA 23394480 T 58 60 Ge FORMULA 23394480 T 61 63 Si FORMULA 23394542 A 244 249 (31)P FORMULA 23394542 A 394 402 chlorine SYSTEMATIC 23394542 A 504 508 CdSe FORMULA 23394542 A 516 522 carbon SYSTEMATIC 23394542 T 53 61 chlorine SYSTEMATIC 23395165 A 107 113 serine TRIVIAL 23395165 A 194 200 purine TRIVIAL 23395165 A 217 228 glutathione TRIVIAL 23395165 T 48 54 serine TRIVIAL 23395652 A 232 247 (-)-huperzine A TRIVIAL 23395652 A 393 417 (+)- and (-)-huperzine A MULTIPLE 23395652 A 460 464 NMDA ABBREVIATION 23395652 A 610 621 huperzine A TRIVIAL 23395652 T 22 33 huperzine A TRIVIAL 23395656 A 12 43 indazolo[4,3-gh]isoquinolinones FAMILY 23395656 A 132 144 Mitoxantrone TRIVIAL 23395656 T 53 83 indazolo[4,3-gh]isoquinolinone SYSTEMATIC 23395663 A 36 43 lactose TRIVIAL 23395663 A 505 512 lactose TRIVIAL 23395663 A 525 544 zinc phthalocyanine SYSTEMATIC 23395663 A 56 75 zinc phthalocyanine SYSTEMATIC 23395663 A 77 188 [2,9(10),16(17),23(24)-tetrakis((1-(β-d-lactose-2-yl)-1H-1,2,3-triazol-4-yl)methoxyl)phthalocyaninato] zinc(II) SYSTEMATIC 23395663 T 0 7 Lactose TRIVIAL 23395663 T 20 39 zinc phthalocyanine SYSTEMATIC 23395665 A 108 118 azomethine SYSTEMATIC 23395665 A 140 146 isatin TRIVIAL 23395665 A 151 160 sarcosine TRIVIAL 23395665 A 184 248 3-(1H-indol-3-yl)-3-oxo-2-(2-oxoindolin-3-ylidene)propanenitrile SYSTEMATIC 23395665 A 277 296 acenaphthenequinone SYSTEMATIC 23395665 A 6 33 dispirooxindole-pyrrolidine SYSTEMATIC 23395665 T 34 61 dispirooxindole-pyrrolidine SYSTEMATIC 23395689 A 0 10 Gadolinium SYSTEMATIC 23395689 A 106 112 Gd(3+) FORMULA 23395689 A 12 14 Gd FORMULA 23395689 A 1267 1278 doxorubicin TRIVIAL 23395689 A 247 256 manganese SYSTEMATIC 23395689 A 258 260 Mn FORMULA 23395689 A 423 425 Mn FORMULA 23395689 A 611 619 Mn oxide SYSTEMATIC 23395689 A 686 696 Oleic acid TRIVIAL 23395689 A 704 707 MnO FORMULA 23395689 A 764 783 polyethylene glycol SYSTEMATIC 23395689 A 785 793 PEG-2000 ABBREVIATION 23395689 A 796 820 phosphatidylethanolamine SYSTEMATIC 23395689 A 830 841 cholesterol TRIVIAL 23395689 A 847 880 dioleoyl-phosphatidylethanolamine SYSTEMATIC 23395689 A 882 886 DOPE ABBREVIATION 23395689 T 0 9 Manganese SYSTEMATIC 23395717 A 0 14 Xestospongin C TRIVIAL 23395717 A 1150 1157 PD98059 IDENTIFIER 23395717 A 53 76 bis-1-oxaquinolizidines FAMILY 23395717 A 632 653 nitroblue tetrazolium TRIVIAL 23395717 T 0 14 Xestospongin C TRIVIAL 23395719 A 104 112 phenolic FAMILY 23395719 A 370 378 phenolic FAMILY 23395719 A 681 697 coumaroyl hexose FAMILY 23395719 A 716 737 dihydroxybenzoic acid SYSTEMATIC 23395719 A 739 755 caffeoyl glucose TRIVIAL 23395719 A 757 796 dihydroferulic acid 4-O-β-d-glucuronide SYSTEMATIC 23395719 A 798 830 methoxyquercetin 3-O-galactoside SYSTEMATIC 23395719 A 832 842 scopoletin TRIVIAL 23395719 A 844 853 myricetin TRIVIAL 23395719 A 858 867 quercetin TRIVIAL 23395719 T 18 29 polyphenols FAMILY 23395783 A 0 7 Cadmium SYSTEMATIC 23395783 A 1020 1025 δ-ALA SYSTEMATIC 23395783 A 1050 1057 cadmium SYSTEMATIC 23395783 A 1131 1134 ORY ABBREVIATION 23395783 A 1157 1164 cadmium SYSTEMATIC 23395783 A 185 192 cadmium SYSTEMATIC 23395783 A 238 248 γ-oryzanol TRIVIAL 23395783 A 250 253 ORY ABBREVIATION 23395783 A 314 319 CdCl2 FORMULA 23395783 A 343 346 ORY ABBREVIATION 23395783 A 487 500 ascorbic acid TRIVIAL 23395783 A 502 509 cadmium SYSTEMATIC 23395783 A 526 532 thiols FAMILY 23395783 A 569 579 superoxide TRIVIAL 23395783 A 613 624 glutathione TRIVIAL 23395783 A 643 654 glutathione TRIVIAL 23395783 A 655 656 S FORMULA 23395783 A 679 698 δ-aminolevulic acid SYSTEMATIC 23395783 A 712 717 δ-ALA SYSTEMATIC 23395783 A 722 729 Cadmium SYSTEMATIC 23395783 A 850 857 cadmium SYSTEMATIC 23395783 A 896 899 ORY ABBREVIATION 23395783 A 996 999 ORY ABBREVIATION 23395783 T 0 10 γ-Oryzanol TRIVIAL 23395783 T 34 41 cadmium SYSTEMATIC 23395914 A 1151 1160 darunavir TRIVIAL 23395914 A 1249 1258 darunavir TRIVIAL 23395914 A 1264 1276 ketoconazole TRIVIAL 23395914 A 1327 1339 ketoconazole TRIVIAL 23395914 A 1401 1410 darunavir TRIVIAL 23395914 A 378 387 darunavir TRIVIAL 23395914 A 495 507 ketoconazole TRIVIAL 23395914 A 540 549 darunavir TRIVIAL 23395914 A 758 767 darunavir TRIVIAL 23395914 A 851 860 darunavir TRIVIAL 23395914 A 897 906 darunavir TRIVIAL 23395914 A 931 941 zosuquidar TRIVIAL 23395914 A 958 968 zosuquidar TRIVIAL 23395914 T 40 49 darunavir TRIVIAL 23395914 T 75 87 ketoconazole TRIVIAL 23396041 A 1077 1081 AZAs ABBREVIATION 23396041 A 1252 1256 AZAs ABBREVIATION 23396041 A 1379 1383 AZA1 ABBREVIATION 23396041 A 1409 1414 AZA17 ABBREVIATION 23396041 A 1427 1431 AZA3 ABBREVIATION 23396041 A 152 163 AZA1 and -2 MULTIPLE 23396041 A 171 175 AZA3 ABBREVIATION 23396041 A 25 36 azaspiracid TRIVIAL 23396041 A 308 319 AZA1 and -2 MULTIPLE 23396041 A 501 504 AZA ABBREVIATION 23396041 A 554 558 AZA1 ABBREVIATION 23396041 A 607 611 AZAs ABBREVIATION 23396041 A 623 631 AZA1 + 2 MULTIPLE 23396041 A 684 690 AZA1+2 MULTIPLE 23396041 A 864 872 AZA1 + 2 MULTIPLE 23396041 A 994 998 AZAs ABBREVIATION 23396041 T 10 22 azaspiracids FAMILY 23396116 A 112 115 TTX ABBREVIATION 23396116 A 1295 1298 TTX ABBREVIATION 23396116 A 1377 1380 TTX ABBREVIATION 23396116 A 1592 1595 TTX ABBREVIATION 23396116 A 463 466 TTX ABBREVIATION 23396116 A 571 574 TTX ABBREVIATION 23396116 A 60 72 tetrodotoxin TRIVIAL 23396116 A 614 617 TTX ABBREVIATION 23396116 A 683 686 TTX ABBREVIATION 23396116 A 74 77 TTX ABBREVIATION 23396116 A 801 804 TTX ABBREVIATION 23396116 T 54 66 tetrodotoxin TRIVIAL 23396441 A 141 148 sucrose TRIVIAL 23396441 A 177 180 ATP ABBREVIATION 23396442 A 864 882 dimethyl sulfoxide SYSTEMATIC 23396442 A 884 888 DMSO ABBREVIATION 23396442 A 893 905 acetonitrile SYSTEMATIC 23396442 A 907 910 ACN ABBREVIATION 23397032 A 1163 1176 Dexamethasone TRIVIAL 23397032 A 1300 1313 dexamethasone TRIVIAL 23397032 A 1441 1454 dexamethasone TRIVIAL 23397032 A 1740 1753 dexamethasone TRIVIAL 23397049 A 1011 1023 paliperidone TRIVIAL 23397049 A 1109 1121 paliperidone TRIVIAL 23397049 A 1249 1261 Paliperidone TRIVIAL 23397049 A 1385 1397 paliperidone TRIVIAL 23397049 A 151 163 paliperidone TRIVIAL 23397049 A 1610 1622 paliperidone TRIVIAL 23397049 A 314 326 paliperidone TRIVIAL 23397049 T 34 46 paliperidone TRIVIAL 23398290 A 0 9 Vitamin A FAMILY 23398290 A 1067 1070 Dex ABBREVIATION 23398290 A 21 34 retinoic acid TRIVIAL 23398290 A 610 623 dexamethasone TRIVIAL 23398290 A 625 628 Dex ABBREVIATION 23398290 T 0 9 Retinoids FAMILY 23399323 A 259 260 O FORMULA 23399323 T 22 23 O FORMULA 23399639 A 1088 1104 taccalonolide AJ TRIVIAL 23399639 A 1230 1246 taccalonolide AJ TRIVIAL 23399639 A 1350 1361 Laulimalide TRIVIAL 23399639 A 1366 1376 paclitaxel TRIVIAL 23399639 A 300 316 taccalonolide AJ TRIVIAL 23399639 A 318 329 laulimalide TRIVIAL 23399639 A 330 343 fijianolide B TRIVIAL 23399639 A 348 358 paclitaxel TRIVIAL 23399639 A 662 678 Taccalonolide AJ TRIVIAL 23399639 A 762 772 paclitaxel TRIVIAL 23399639 A 776 787 laulimalide TRIVIAL 23399641 A 1058 1064 CB1954 IDENTIFIER 23399641 A 605 611 CB1954 IDENTIFIER 23399641 A 616 623 PR-104A IDENTIFIER 23399641 T 160 166 CB1954 IDENTIFIER 23399641 T 171 178 PR-104A IDENTIFIER 23400262 A 254 260 TiO(2) FORMULA 23400262 A 821 827 TiO(2) FORMULA 23400262 A 884 890 TiO(2) FORMULA 23400262 A 941 944 MgO FORMULA 23400262 T 22 26 TiO2 FORMULA 23400270 A 166 172 silica TRIVIAL 23400270 A 18 24 silica TRIVIAL 23400270 A 282 288 silica TRIVIAL 23400270 A 578 584 silica TRIVIAL 23400270 A 854 861 silicas TRIVIAL 23400270 T 47 53 silica TRIVIAL 23400782 A 122 123 C FORMULA 23400782 A 410 413 ATP ABBREVIATION 23400782 A 55 58 ATP ABBREVIATION 23400782 A 594 597 ADP ABBREVIATION 23400782 A 697 698 N FORMULA 23400782 A 80 83 ATP ABBREVIATION 23400782 A 814 815 C FORMULA 23400782 A 861 862 N FORMULA 23400782 A 898 901 ADP ABBREVIATION 23400782 T 103 106 ADP ABBREVIATION 23400782 T 66 69 ATP ABBREVIATION 23400795 A 1041 1052 tributyltin SYSTEMATIC 23400795 A 191 200 organotin FAMILY 23400795 A 43 52 organotin FAMILY 23400795 A 947 968 triphenyltin chloride SYSTEMATIC 23400796 A 1030 1032 Mn FORMULA 23400796 A 1037 1039 Zn FORMULA 23400796 A 105 107 Zn FORMULA 23400796 A 1060 1062 Co FORMULA 23400796 A 1294 1296 Mn FORMULA 23400796 A 1301 1303 Cr FORMULA 23400796 A 643 645 Mn FORMULA 23400796 A 648 650 Zn FORMULA 23400796 A 653 655 Cr FORMULA 23400796 A 658 660 Cu FORMULA 23400796 A 663 665 Co FORMULA 23400796 A 670 672 Mn FORMULA 23400796 A 675 677 Cr FORMULA 23400796 A 680 682 Zn FORMULA 23400796 A 685 687 Cu FORMULA 23400796 A 690 692 Co FORMULA 23400796 A 779 781 Mn FORMULA 23400796 A 86 88 Co FORMULA 23400796 A 90 92 Cr FORMULA 23400796 A 94 96 Cu FORMULA 23400796 A 98 100 Mn FORMULA 23400796 T 27 29 Co FORMULA 23400796 T 31 33 Cr FORMULA 23400796 T 35 37 Cu FORMULA 23400796 T 39 41 Mn FORMULA 23400796 T 46 48 Zn FORMULA 23400888 A 34 47 acetylcholine SYSTEMATIC 23400925 A 1157 1159 Hg FORMULA 23400925 A 123 125 Hg FORMULA 23400925 A 1345 1347 Hg FORMULA 23400925 A 1385 1387 Hg FORMULA 23400925 A 205 212 mercury SYSTEMATIC 23400925 A 220 237 monomethylmercury SYSTEMATIC 23400925 A 239 243 MMHg FORMULA 23400925 A 256 264 selenium SYSTEMATIC 23400925 A 331 333 Hg FORMULA 23400925 A 44 46 Hg FORMULA 23400925 A 468 474 carbon SYSTEMATIC 23400925 A 477 483 (13) C FORMULA 23400925 A 489 497 nitrogen SYSTEMATIC 23400925 A 500 506 (15) N FORMULA 23400925 A 51 53 Se FORMULA 23400925 A 535 537 Hg FORMULA 23400925 A 620 626 (15) N FORMULA 23400925 A 688 694 (15) N FORMULA 23400925 A 724 728 MMHg FORMULA 23400925 A 737 739 Hg FORMULA 23400925 A 908 914 (15) N FORMULA 23400925 T 40 47 mercury SYSTEMATIC 23400925 T 52 60 selenium SYSTEMATIC 23400943 A 795 808 valproic acid TRIVIAL 23400943 A 814 824 clonazepam TRIVIAL 23400943 A 862 875 valproic acid TRIVIAL 23400943 A 877 888 stiripentol TRIVIAL 23400943 A 894 902 clobazam TRIVIAL 23400943 A 971 981 vigabatrin TRIVIAL 23401139 A 0 22 Petroleum hydrocarbons FAMILY 23401139 A 164 167 PHC ABBREVIATION 23401139 A 24 28 PHCs ABBREVIATION 23401139 A 359 366 C10-C16 MULTIPLE 23401139 A 375 382 C16-C23 MULTIPLE 23401139 A 395 402 C23-C34 MULTIPLE 23401139 T 54 75 petroleum hydrocarbon FAMILY 23401211 A 1017 1019 Hg FORMULA 23401211 A 129 131 Hg FORMULA 23401211 A 18 20 Hg FORMULA 23401211 A 470 472 Hg FORMULA 23401211 A 69 71 Hg FORMULA 23401211 A 858 866 nitrogen SYSTEMATIC 23401211 A 9 16 mercury SYSTEMATIC 23401211 T 38 45 mercury SYSTEMATIC 23401217 A 561 568 alloxan TRIVIAL 23401244 A 1025 1028 C60 TRIVIAL 23401244 A 1050 1053 DDE ABBREVIATION 23401244 A 1093 1096 DDE ABBREVIATION 23401244 A 1119 1128 fullerene TRIVIAL 23401244 A 1217 1226 fullerene TRIVIAL 23401244 A 1241 1244 DDE ABBREVIATION 23401244 A 1358 1361 C60 TRIVIAL 23401244 A 1396 1399 DDE ABBREVIATION 23401244 A 1473 1476 DDE ABBREVIATION 23401244 A 1519 1529 fullerenes FAMILY 23401244 A 1606 1609 DDE ABBREVIATION 23401244 A 1714 1717 DDE ABBREVIATION 23401244 A 1745 1748 C60 TRIVIAL 23401244 A 352 355 C60 TRIVIAL 23401244 A 356 366 fullerenes FAMILY 23401244 A 400 432 dichlorodiphenyldichloroethylene SYSTEMATIC 23401244 A 434 442 p,p'-DDE SYSTEMATIC 23401244 A 444 447 DDT ABBREVIATION 23401244 A 670 673 DDE ABBREVIATION 23401244 A 706 709 C60 TRIVIAL 23401244 A 710 720 fullerenes FAMILY 23401244 A 828 831 DDE ABBREVIATION 23401244 A 836 839 C60 TRIVIAL 23401244 A 912 922 fullerenes FAMILY 23401244 T 10 13 C60 TRIVIAL 23401244 T 14 24 FULLERENES FAMILY 23401244 T 58 66 p,p'-DDE SYSTEMATIC 23401262 A 1152 1161 phenytoin TRIVIAL 23401262 A 211 220 phenytoin TRIVIAL 23401262 A 263 272 Phenytoin TRIVIAL 23401262 A 630 639 phenytoin TRIVIAL 23401262 T 77 86 Phenytoin TRIVIAL 23401281 A 125 127 Cd FORMULA 23401281 A 1268 1270 Al FORMULA 23401281 A 1272 1274 Fe FORMULA 23401281 A 1280 1282 Mn FORMULA 23401281 A 129 131 Cu FORMULA 23401281 A 133 135 Pb FORMULA 23401281 A 141 143 Zn FORMULA 23401281 A 373 379 carbon SYSTEMATIC 23401281 A 525 527 Pb FORMULA 23401281 A 530 532 Cu FORMULA 23401281 A 535 537 Zn FORMULA 23401281 A 540 542 Cd FORMULA 23401281 A 737 739 Al FORMULA 23401291 A 0 10 Fatty acid FAMILY 23401291 A 247 257 β-ketoacyl SYSTEMATIC 23401291 A 258 262 acyl FAMILY 23401291 A 372 382 fatty acid FAMILY 23401291 A 683 694 Schiff base FAMILY 23401291 A 838 915 (E)-N-((3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)methylene)hexadecan-1-amine SYSTEMATIC 23401291 T 6 17 Schiff-base FAMILY 23401303 A 1132 1138 carbon SYSTEMATIC 23401303 A 1168 1178 carboxylic SYSTEMATIC 23401303 A 1182 1190 phenolic FAMILY 23401303 A 357 363 carbon SYSTEMATIC 23401303 A 386 392 carbon SYSTEMATIC 23401303 A 433 443 pyrethroid FAMILY 23401303 A 621 632 pyrethroids FAMILY 23401303 T 31 42 pyrethroids FAMILY 23401323 A 163 166 MNG ABBREVIATION 23401323 T 16 40 maltose-neopentyl glycol SYSTEMATIC 23401323 T 45 48 MNG ABBREVIATION 23401324 A 343 368 polychlorinated biphenyls FAMILY 23401324 A 370 374 PCBs ABBREVIATION 23401324 A 396 426 polybrominated diphenyl ethers FAMILY 23401324 A 721 725 PCBs ABBREVIATION 23401324 A 730 744 organochlorine FAMILY 23401324 T 105 135 polybrominated diphenyl ethers FAMILY 23401324 T 141 155 organochlorine FAMILY 23401324 T 78 103 polychlorinated biphenyls FAMILY 23401355 A 11 14 MnO FORMULA 23401355 A 131 134 MnO FORMULA 23401355 A 167 169 Co FORMULA 23401355 A 233 235 Li FORMULA 23401355 A 391 394 MnO FORMULA 23401355 A 396 398 Mn FORMULA 23401355 A 404 408 Li2O FORMULA 23401355 A 476 478 Co FORMULA 23401355 A 48 50 Co FORMULA 23401355 A 526 528 Li FORMULA 23401355 A 602 605 MnO FORMULA 23401355 A 626 628 Co FORMULA 23401355 A 708 710 Li FORMULA 23401355 A 84 89 MnCO3 FORMULA 23401355 T 115 122 lithium SYSTEMATIC 23401355 T 28 31 MnO FORMULA 23401355 T 32 34 Co FORMULA 23401470 A 653 654 N FORMULA 23401472 A 1024 1046 5-aza-2'-deoxycytidine SYSTEMATIC 23401472 A 1048 1056 5-Aza-dC SYSTEMATIC 23401472 A 1361 1369 5-Aza-dC SYSTEMATIC 23401472 A 142 151 bilirubin TRIVIAL 23401472 A 156 161 SN-38 IDENTIFIER 23401472 A 387 396 Bisulfite SYSTEMATIC 23401472 A 433 436 CpG ABBREVIATION 23401472 A 6 9 UDP ABBREVIATION 23401602 A 162 173 fatty acids FAMILY 23401602 A 274 285 fatty acids FAMILY 23401602 A 291 304 linoleic acid TRIVIAL 23401602 A 370 383 linoleic acid TRIVIAL 23401602 A 511 524 linoleic acid TRIVIAL 23401602 A 77 90 linoleic acid TRIVIAL 23401602 T 11 24 linoleic acid TRIVIAL 23402270 A 116 127 polystyrene SYSTEMATIC 23402270 A 168 212 poly(2-aminoethylmethacrylate hydrochloride) SYSTEMATIC 23402270 A 214 219 PAEMH ABBREVIATION 23402341 A 0 14 Mefenamic acid TRIVIAL 23402341 A 1034 1041 MFA-CoA ABBREVIATION 23402341 A 1177 1186 MFA-1-O-G SYSTEMATIC 23402341 A 1331 1342 glutathione TRIVIAL 23402341 A 1344 1347 GSH ABBREVIATION 23402341 A 1387 1394 MFA-AMP ABBREVIATION 23402341 A 1417 1420 GSH ABBREVIATION 23402341 A 1453 1460 MFA-CoA ABBREVIATION 23402341 A 1468 1477 MFA-1-O-G SYSTEMATIC 23402341 A 152 176 MFA-1-O-acyl-glucuronide FAMILY 23402341 A 1535 1546 glutathione TRIVIAL 23402341 A 1547 1548 S FORMULA 23402341 A 1568 1575 MFA-AMP ABBREVIATION 23402341 A 1598 1605 MFA-GSH ABBREVIATION 23402341 A 1630 1637 MFA-CoA ABBREVIATION 23402341 A 1660 1667 MFA-GSH ABBREVIATION 23402341 A 17 20 MFA ABBREVIATION 23402341 A 1726 1735 MFA-1-O-G SYSTEMATIC 23402341 A 1768 1782 mefenamic acid TRIVIAL 23402341 A 178 187 MFA-1-O-G SYSTEMATIC 23402341 A 1811 1819 acyl-CoA ABBREVIATION 23402341 A 1914 1921 MFA-AMP ABBREVIATION 23402341 A 1926 1933 MFA-CoA ABBREVIATION 23402341 A 193 207 MFA-S-acyl-CoA FAMILY 23402341 A 1985 1988 GSH ABBREVIATION 23402341 A 209 216 MFA-CoA ABBREVIATION 23402341 A 25 40 carboxylic acid SYSTEMATIC 23402341 A 265 287 MFA-S-acyl-glutathione FAMILY 23402341 A 289 296 MFA-GSH ABBREVIATION 23402341 A 433 437 acyl FAMILY 23402341 A 494 501 MFA-GSH ABBREVIATION 23402341 A 556 559 MFA ABBREVIATION 23402341 A 592 596 acyl FAMILY 23402341 A 616 625 mefenamyl TRIVIAL 23402341 A 626 635 adenylate TRIVIAL 23402341 A 637 644 MFA-AMP ABBREVIATION 23402341 A 692 695 MFA ABBREVIATION 23402341 A 773 780 MFA-AMP ABBREVIATION 23402341 A 824 831 MFA-AMP ABBREVIATION 23402341 A 918 925 MFA-GSH ABBREVIATION 23402341 T 24 28 acyl FAMILY 23402341 T 29 38 adenylate TRIVIAL 23402341 T 60 74 mefenamic Acid TRIVIAL 23402364 A 1015 1027 Nitric oxide SYSTEMATIC 23402364 A 1040 1045 VP-16 IDENTIFIER 23402364 A 1198 1210 nitric oxide SYSTEMATIC 23402364 A 1254 1259 VP-16 IDENTIFIER 23402364 A 1307 1312 (·)NO FORMULA 23402364 A 1361 1366 VP-16 IDENTIFIER 23402364 A 1476 1481 (·)NO FORMULA 23402364 A 1535 1540 VP-16 IDENTIFIER 23402364 A 1578 1583 VP-16 IDENTIFIER 23402364 A 187 192 (·)NO FORMULA 23402364 A 286 295 Etoposide TRIVIAL 23402364 A 297 302 VP-16 IDENTIFIER 23402364 A 328 333 VP-16 IDENTIFIER 23402364 A 365 370 VP-16 IDENTIFIER 23402364 A 374 379 (·)NO FORMULA 23402364 A 457 485 o-quinone- and nitroso-VP-16 MULTIPLE 23402364 A 46 58 nitric oxide SYSTEMATIC 23402364 A 534 544 chloroform TRIVIAL 23402364 A 552 558 oxygen SYSTEMATIC 23402364 A 60 65 (·)NO FORMULA 23402364 A 620 625 VP-16 IDENTIFIER 23402364 A 650 655 VP-16 IDENTIFIER 23402364 A 683 687 H2O2 FORMULA 23402364 A 713 718 (·)NO FORMULA 23402364 A 722 732 chloroform TRIVIAL 23402364 A 752 758 oxygen SYSTEMATIC 23402364 A 796 801 VP-16 IDENTIFIER 23402364 A 890 897 phenoxy SYSTEMATIC 23402364 A 914 923 o-quinone SYSTEMATIC 23402364 A 927 932 VP-16 IDENTIFIER 23402364 A 954 963 nitroxide SYSTEMATIC 23402364 A 965 973 iminoxyl SYSTEMATIC 23402364 A 985 999 nitrogen oxide SYSTEMATIC 23402364 T 65 74 etoposide TRIVIAL 23402364 T 76 85 VP-16,213 IDENTIFIER 23402364 T 8 20 nitric oxide SYSTEMATIC 23402423 A 288 292 CdTe FORMULA 23402423 A 378 382 CdTe FORMULA 23402423 A 466 470 CdTe FORMULA 23402423 A 678 682 CdTe FORMULA 23402423 A 794 803 monothiol FAMILY 23402636 A 216 232 γ-linolenic acid TRIVIAL 23402636 A 252 259 sterols FAMILY 23402636 A 401 412 cholesterol TRIVIAL 23402636 A 417 429 triglyceride FAMILY 23402636 A 488 499 cholesterol TRIVIAL 23402638 A 107 115 iron(II) SYSTEMATIC 23402638 A 202 216 amino alcohols FAMILY 23402638 A 296 304 iron(II) SYSTEMATIC 23402638 A 361 375 iron nitrenoid FAMILY 23402638 A 43 50 olefins FAMILY 23402638 A 73 86 hydroxylamine SYSTEMATIC 23402638 T 0 8 Iron(II) SYSTEMATIC 23402638 T 56 63 olefins FAMILY 23402638 T 84 98 hydroxylamines FAMILY 23402647 A 185 202 diethylene glycol SYSTEMATIC 23402647 A 224 244 lanthanide chlorides FAMILY 23402647 A 266 273 1-Butyl SYSTEMATIC 23402647 A 275 312 2-methylimidazolium tetrafluoroborate SYSTEMATIC 23402647 A 317 325 fluoride SYSTEMATIC 23402647 A 460 464 GdF3 FORMULA 23402647 A 49 62 europium(III) SYSTEMATIC 23402647 A 628 630 Eu FORMULA 23402647 A 631 635 GdF3 FORMULA 23402647 A 69 93 gadolinium(III) fluoride SYSTEMATIC 23402647 A 913 915 Eu FORMULA 23402647 A 916 920 GdF3 FORMULA 23402647 A 95 97 Eu FORMULA 23402647 A 98 102 GdF3 FORMULA 23402647 T 87 89 Eu FORMULA 23402647 T 90 94 GdF3 FORMULA 23402855 A 1214 1228 pheophorbide a TRIVIAL 23402855 A 1233 1245 pheophytin a TRIVIAL 23402855 A 1354 1356 NO FORMULA 23402855 A 166 178 nitric oxide SYSTEMATIC 23402855 A 180 182 NO FORMULA 23402855 A 206 218 nitric oxide SYSTEMATIC 23402855 A 542 544 NO FORMULA 23402855 A 591 597 CH2Cl2 FORMULA 23402855 A 694 700 CH2Cl2 FORMULA 23402855 A 774 783 porphyrin FAMILY 23402855 A 797 811 pheophorbide a TRIVIAL 23402855 A 816 828 pheophytin a TRIVIAL 23402855 A 856 867 fucoxanthin TRIVIAL 23402855 A 884 895 fucoxanthin TRIVIAL 23402855 A 897 911 pheophorbide a TRIVIAL 23402855 A 916 928 pheophytin a TRIVIAL 23402855 A 982 984 NO FORMULA 23402855 T 108 120 pheophytin a TRIVIAL 23402855 T 89 103 pheophorbide a TRIVIAL 23402859 A 0 12 Chlorpyrifos TRIVIAL 23402859 A 1008 1023 malondialdehyde TRIVIAL 23402859 A 1034 1046 chlorpyrifos TRIVIAL 23402859 A 1091 1099 catechin TRIVIAL 23402859 A 1100 1112 chlorpyrifos TRIVIAL 23402859 A 1131 1140 quercetin TRIVIAL 23402859 A 1141 1153 chlorpyrifos TRIVIAL 23402859 A 1206 1214 catechin TRIVIAL 23402859 A 1219 1228 quercetin TRIVIAL 23402859 A 1339 1351 chlorpyrifos TRIVIAL 23402859 A 1415 1423 catechin TRIVIAL 23402859 A 1424 1436 chlorpyrifos TRIVIAL 23402859 A 1441 1450 quercetin TRIVIAL 23402859 A 1451 1463 chlorpyrifos TRIVIAL 23402859 A 1519 1527 catechin TRIVIAL 23402859 A 1532 1541 quercetin TRIVIAL 23402859 A 1563 1575 chlorpyrifos TRIVIAL 23402859 A 188 196 catechin TRIVIAL 23402859 A 19 35 organophosphorus FAMILY 23402859 A 198 207 quercetin TRIVIAL 23402859 A 209 221 chlorpyrifos TRIVIAL 23402859 A 223 231 catechin TRIVIAL 23402859 A 232 244 chlorpyrifos TRIVIAL 23402859 A 246 255 quercetin TRIVIAL 23402859 A 256 268 chlorpyrifos TRIVIAL 23402859 A 350 359 aspartate TRIVIAL 23402859 A 378 385 alanine TRIVIAL 23402859 A 426 433 lactate FAMILY 23402859 A 449 461 trigliceride FAMILY 23402859 A 469 480 cholesterol TRIVIAL 23402859 A 512 522 superoxide TRIVIAL 23402859 A 544 555 glutathione TRIVIAL 23402859 A 568 579 glutathione TRIVIAL 23402859 A 609 624 malondialdehyde TRIVIAL 23402859 A 840 848 catechin TRIVIAL 23402859 A 853 862 quercetin TRIVIAL 23402859 T 0 12 Chlorpyrifos TRIVIAL 23402859 T 78 87 quercetin TRIVIAL 23402859 T 92 100 catechin TRIVIAL 23402860 A 0 11 (-)-Cubebin TRIVIAL 23402860 A 1016 1019 CUB ABBREVIATION 23402860 A 1209 1212 DXR ABBREVIATION 23402860 A 1216 1219 URE ABBREVIATION 23402860 A 13 16 CUB ABBREVIATION 23402860 A 193 204 doxorubicin TRIVIAL 23402860 A 206 209 DXR ABBREVIATION 23402860 A 23 29 lignan FAMILY 23402860 A 231 239 urethane TRIVIAL 23402860 A 241 244 URE ABBREVIATION 23402860 A 326 329 CUB ABBREVIATION 23402860 A 417 420 CUB ABBREVIATION 23402860 A 474 477 DXR ABBREVIATION 23402860 A 579 582 CUB ABBREVIATION 23402860 A 819 822 CUB ABBREVIATION 23402860 A 839 842 URE ABBREVIATION 23402860 T 49 60 (-)-cubebin TRIVIAL 23402938 A 1162 1168 IR3535 IDENTIFIER 23402938 A 1176 1182 IR3535 IDENTIFIER 23402938 A 1279 1285 IR3535 IDENTIFIER 23402938 A 1333 1339 IR3535 IDENTIFIER 23402938 A 1448 1454 IR3535 IDENTIFIER 23402938 A 1472 1478 IR3535 IDENTIFIER 23402938 A 1527 1533 IR3535 IDENTIFIER 23402938 A 1613 1619 IR3535 IDENTIFIER 23402938 A 194 200 IR3535 IDENTIFIER 23402938 A 225 231 IR3535 IDENTIFIER 23402938 A 338 344 IR3535 IDENTIFIER 23402938 A 373 379 IR3535 IDENTIFIER 23402938 A 470 476 IR3535 IDENTIFIER 23402938 A 53 59 IR3535 IDENTIFIER 23402938 A 541 547 IR3535 IDENTIFIER 23402938 A 865 871 IR3535 IDENTIFIER 23402938 A 879 885 IR3535 IDENTIFIER 23402938 A 952 958 IR3535 IDENTIFIER 23402938 A 992 998 IR3535 IDENTIFIER 23402938 T 61 67 IR3535 IDENTIFIER 23402971 A 113 125 benztriazole SYSTEMATIC 23402971 A 99 112 benzimidazole SYSTEMATIC 23402971 T 80 93 benzimidazole SYSTEMATIC 23402971 T 98 110 benztriazole SYSTEMATIC 23402972 A 1043 1052 ritonavir TRIVIAL 23402972 A 1117 1126 indinavir TRIVIAL 23402972 A 504 513 indinavir TRIVIAL 23402972 A 640 649 indinavir TRIVIAL 23402972 A 783 792 indinavir TRIVIAL 23402972 A 900 909 indinavir TRIVIAL 23402972 T 26 35 indinavir TRIVIAL 23403080 A 13 35 hydrazino-1,3-thiazole SYSTEMATIC 23403080 A 132 139 indolyl SYSTEMATIC 23403080 A 161 170 hydrazone FAMILY 23403080 A 303 319 (S)-2-aminoethyl SYSTEMATIC 23403080 A 333 341 thiazole SYSTEMATIC 23403080 T 45 69 2-hydrazino-1,3-thiazole SYSTEMATIC 23403395 A 1118 1127 docetaxel TRIVIAL 23403395 A 1128 1137 cisplatin TRIVIAL 23403395 A 135 139 TPGS ABBREVIATION 23403395 A 141 150 cisplatin TRIVIAL 23403395 A 198 207 cisplatin TRIVIAL 23403395 A 209 218 docetaxel TRIVIAL 23403395 A 362 384 poly(lactic acid)-TPGS SYSTEMATIC 23403395 A 386 394 PLA-TPGS ABBREVIATION 23403395 A 400 408 carboxyl SYSTEMATIC 23403395 A 426 430 TPGS ABBREVIATION 23403395 A 432 436 TPGS ABBREVIATION 23403395 A 437 441 COOH FORMULA 23403395 A 602 611 docetaxel TRIVIAL 23403395 A 619 628 cisplatin TRIVIAL 23403395 A 75 133 d-alpha-tocopheryl-co-poly(ethylene glycol) 1000 succinate SYSTEMATIC 23403395 A 823 831 Taxotere TRIVIAL 23403395 A 837 846 cisplatin TRIVIAL 23403395 A 869 878 docetaxel TRIVIAL 23403395 A 886 895 cisplatin TRIVIAL 23403395 A 968 977 docetaxel TRIVIAL 23403395 A 985 994 cisplatin TRIVIAL 23403395 T 24 33 docetaxel TRIVIAL 23403395 T 35 44 cisplatin TRIVIAL 23403395 T 62 71 vitamin E FAMILY 23403395 T 72 76 TPGS ABBREVIATION 23403395 T 77 86 cisplatin TRIVIAL 23403537 A 103 116 tetrapeptides FAMILY 23403537 T 39 51 tetrapeptide FAMILY 23404062 A 1211 1219 SCH23390 IDENTIFIER 23404062 A 1240 1249 sulpiride TRIVIAL 23404062 A 1271 1279 naloxone TRIVIAL 23404062 A 1377 1386 sulpiride TRIVIAL 23404062 A 1392 1400 naloxone TRIVIAL 23404062 A 362 370 dopamine TRIVIAL 23404062 A 700 708 SCH23390 IDENTIFIER 23404062 A 795 803 naloxone TRIVIAL 23404062 A 874 883 sulpiride TRIVIAL 23404062 T 46 54 dopamine TRIVIAL 23404443 A 1384 1392 arginine TRIVIAL 23404443 A 1534 1542 arginine TRIVIAL 23404443 A 888 895 glucose TRIVIAL 23404443 A 897 904 glucose TRIVIAL 23404443 A 911 918 glucose TRIVIAL 23404443 A 934 941 glucose TRIVIAL 23404443 A 966 974 arginine TRIVIAL 23404458 A 1001 1003 Ca FORMULA 23404458 A 1004 1006 Zn FORMULA 23404458 A 1011 1013 Ca FORMULA 23404458 A 1014 1016 Cu FORMULA 23404458 A 1053 1060 calcium SYSTEMATIC 23404458 A 1320 1342 calcium hydroxyapatite SYSTEMATIC 23404458 A 1347 1358 cholesterol TRIVIAL 23404458 A 1572 1574 Mg FORMULA 23404458 A 1576 1577 P FORMULA 23404458 A 1582 1584 Ca FORMULA 23404458 A 1702 1724 calcium hydroxyapatite SYSTEMATIC 23404458 A 1729 1740 cholesterol TRIVIAL 23404458 A 686 688 Ni FORMULA 23404458 A 690 692 Pt FORMULA 23404458 A 694 696 Hg FORMULA 23404458 A 698 700 Sn FORMULA 23404458 A 702 704 Pb FORMULA 23404458 A 706 707 W FORMULA 23404458 A 709 711 Au FORMULA 23404458 A 713 715 Al FORMULA 23404458 A 717 719 Si FORMULA 23404458 A 757 759 Ca FORMULA 23404458 A 761 763 Sr FORMULA 23404458 A 765 767 Cr FORMULA 23404458 A 769 770 P FORMULA 23404458 A 859 861 Mg FORMULA 23404458 A 863 865 Ca FORMULA 23404458 A 869 870 P FORMULA 23404739 A 0 12 Sipholenol A TRIVIAL 23404739 A 1063 1072 carbamate FAMILY 23404739 A 1100 1143 19,20-anhydrosipholenol A 4β-benzoate ester SYSTEMATIC 23404739 A 1197 1205 tyrosine TRIVIAL 23404739 A 1351 1361 sipholanes FAMILY 23404739 A 1498 1530 sipholenol A 4β-4-chlorobenzoate SYSTEMATIC 23404739 A 1535 1580 19,20-anhydrosipholenol A 4β-4-chlorobenzoate SYSTEMATIC 23404739 A 1581 1587 esters FAMILY 23404739 A 16 36 sipholane triterpene FAMILY 23404739 A 1823 1845 sipholenol A succinate TRIVIAL 23404739 A 1924 1947 sipholane triterpenoids FAMILY 23404739 A 235 247 sipholenol A TRIVIAL 23404739 A 372 384 Sipholenol A TRIVIAL 23404739 A 389 402 sipholenone A TRIVIAL 23404739 A 593 598 ester FAMILY 23404739 A 600 605 ether SYSTEMATIC 23404739 A 607 612 oxime SYSTEMATIC 23404739 A 618 627 carbamate FAMILY 23404739 A 771 803 Sipholenol A 4β-4-chlorobenzoate SYSTEMATIC 23404739 A 808 853 19,20-anhydrosipholenol A 4β-4-chlorobenzoate SYSTEMATIC 23404739 A 854 860 esters FAMILY 23404739 T 23 33 triterpene FAMILY 23404739 T 34 45 sipholenols FAMILY 23404750 A 991 994 Phe FORMULA 23404750 T 74 77 Phe FORMULA 23405943 A 147 160 4-aminophenol SYSTEMATIC 23405943 A 165 175 salicylate SYSTEMATIC 23405943 A 319 348 1,1-diphenyl-2-picrylhydrazyl SYSTEMATIC 23405943 A 365 384 thiobarbituric acid SYSTEMATIC 23405943 A 444 450 Fe(2+) FORMULA 23405943 A 455 468 ascorbic acid TRIVIAL 23405943 A 562 576 salicylic acid TRIVIAL 23405943 A 588 595 benzoyl SYSTEMATIC 23405943 A 645 656 paracetamol TRIVIAL 23405943 T 25 38 4-aminophenol SYSTEMATIC 23405943 T 43 53 salicylate SYSTEMATIC 23406166 A 120 152 2'-hydroxy-3,4-dimethoxychalcone SYSTEMATIC 23406166 A 158 169 biochanin A TRIVIAL 23406166 A 178 212 kaempferol-3-O-β-d-glucopyranoside SYSTEMATIC 23406166 A 29 77 3',4'-dimethoxy-7-(γ,γ-dimethylallyloxy)flavonol SYSTEMATIC 23406166 A 6 27 O-prenylated flavonol FAMILY 23406166 T 6 27 O-prenylated flavonol FAMILY 23406277 A 1152 1161 ruthenium SYSTEMATIC 23406277 A 12 31 poly(vinyl alcohol) SYSTEMATIC 23406277 A 33 36 PVA ABBREVIATION 23406277 A 450 453 PVA ABBREVIATION 23406277 A 541 544 PVA ABBREVIATION 23406277 A 627 660 [μ-(11,11'-bidppz)(phen)4Ru2](4+) FORMULA 23406277 A 765 774 ruthenium SYSTEMATIC 23406277 T 26 39 ruthenium(II) SYSTEMATIC 23406348 A 1004 1013 methylene SYSTEMATIC 23406348 A 1024 1040 n-butyl acrylate SYSTEMATIC 23406348 A 1370 1378 hydrogen SYSTEMATIC 23406348 A 146 161 alkyl acrylates FAMILY 23406348 A 163 198 methyl, ethyl, and n-butyl acrylate MULTIPLE 23406348 A 1702 1710 hydrogen SYSTEMATIC 23406348 A 1755 1761 methyl SYSTEMATIC 23406348 A 1771 1786 methyl acrylate SYSTEMATIC 23406348 A 1791 1800 methylene SYSTEMATIC 23406348 A 1813 1837 ethyl (n-butyl) acrylate SYSTEMATIC 23406348 A 880 888 hydrogen SYSTEMATIC 23406348 A 928 934 methyl SYSTEMATIC 23406348 A 944 959 methyl acrylate SYSTEMATIC 23406348 A 965 974 methylene SYSTEMATIC 23406348 A 984 998 ethyl acrylate SYSTEMATIC 23406348 T 97 112 alkyl acrylates FAMILY 23406429 A 167 187 triaryl sulfonamides FAMILY 23406429 A 281 288 triaryl FAMILY 23406429 T 6 25 triaryl sulfonamide FAMILY 23406469 A 137 143 silica TRIVIAL 23406469 A 287 304 protoporphyrin IX TRIVIAL 23406469 A 306 310 PpIX ABBREVIATION 23406469 A 890 894 PpIX ABBREVIATION 23406469 T 95 101 silica TRIVIAL 23407893 A 0 9 Imogolite TRIVIAL 23407893 A 1093 1102 imogolite TRIVIAL 23407893 A 1279 1287 silicate FAMILY 23407893 A 1291 1300 phosphate SYSTEMATIC 23407893 A 1302 1311 phosphite SYSTEMATIC 23407893 A 131 147 aluminogermanate TRIVIAL 23407893 A 1313 1321 arsenate SYSTEMATIC 23407893 A 1326 1334 arsenite SYSTEMATIC 23407893 A 217 222 H3PO4 FORMULA 23407893 A 224 229 H3PO3 FORMULA 23407893 A 231 237 H3AsO3 FORMULA 23407893 A 239 245 H3AsO4 FORMULA 23407893 A 279 288 imogolite TRIVIAL 23407893 A 29 44 aluminosilicate TRIVIAL 23407893 A 429 438 imogolite TRIVIAL 23407893 A 548 564 aluminogermanate TRIVIAL 23407893 A 588 596 silicate FAMILY 23407893 A 620 629 germanate SYSTEMATIC 23407893 A 656 664 silicate FAMILY 23407893 A 691 700 phosphate SYSTEMATIC 23407893 A 702 711 phosphite SYSTEMATIC 23407893 A 713 721 arsenate SYSTEMATIC 23407893 A 726 734 arsenite SYSTEMATIC 23407893 A 748 757 imogolite TRIVIAL 23407893 A 942 951 imogolite TRIVIAL 23407893 T 0 9 Imogolite TRIVIAL 23407893 T 108 115 arsenic SYSTEMATIC 23407893 T 92 103 phosphorous SYSTEMATIC 23408116 A 0 13 Acetaminophen TRIVIAL 23408116 A 113 116 UDP ABBREVIATION 23408116 A 1254 1267 acetaminophen TRIVIAL 23408116 A 1618 1631 acetaminophen TRIVIAL 23408116 A 1827 1840 acetaminophen TRIVIAL 23408116 A 1899 1912 acetaminophen TRIVIAL 23408116 A 200 213 acetaminophen TRIVIAL 23408116 A 271 284 acetaminophen TRIVIAL 23408116 A 355 368 acetaminophen TRIVIAL 23408116 A 422 435 acetaminophen TRIVIAL 23408116 A 653 666 acetaminophen TRIVIAL 23408116 A 733 746 acetaminophen TRIVIAL 23408116 A 799 812 acetaminophen TRIVIAL 23408116 A 99 112 acetaminophen TRIVIAL 23408116 T 114 127 Acetaminophen TRIVIAL 23408116 T 235 248 Acetaminophen TRIVIAL 23408116 T 4 7 UDP ABBREVIATION 23408270 A 1070 1090 (+)-limonene epoxide SYSTEMATIC 23408270 A 1205 1225 (+)-limonene epoxide SYSTEMATIC 23408270 A 243 255 praziquantel TRIVIAL 23408270 A 275 287 praziquantel TRIVIAL 23408270 A 490 510 (+)-Limonene epoxide SYSTEMATIC 23408270 A 837 857 (+)-limonene epoxide SYSTEMATIC 23408270 A 943 955 praziquantel TRIVIAL 23408270 T 46 66 (+)-limonene epoxide SYSTEMATIC 23408434 A 1183 1189 Ca(2+) FORMULA 23408434 A 1361 1367 Ca(2+) FORMULA 23408434 T 29 36 calcium SYSTEMATIC 23408851 A 1285 1286 N FORMULA 23408851 A 1337 1338 C FORMULA 23408851 A 291 301 amino acid FAMILY 23409716 A 507 516 capsaicin TRIVIAL 23409716 A 520 527 menthol TRIVIAL 23409716 A 605 613 SB705498 IDENTIFIER 23409716 A 615 621 JTS653 IDENTIFIER 23409716 A 623 634 JNJ17203212 IDENTIFIER 23409716 A 636 640 AP18 IDENTIFIER 23409716 A 642 649 A967079 IDENTIFIER 23409716 A 651 669 Chembridge-5861528 IDENTIFIER 23409719 A 0 20 Farnesyl diphosphate SYSTEMATIC 23409719 A 122 136 sesquiterpenes FAMILY 23409719 A 183 186 FPP ABBREVIATION 23409719 A 209 219 isoprenoid FAMILY 23409719 A 22 25 FPP ABBREVIATION 23409719 A 280 283 FPP ABBREVIATION 23409719 A 430 433 FPP ABBREVIATION 23409719 A 582 585 FPP ABBREVIATION 23409719 A 632 643 aryl azides FAMILY 23409719 A 645 670 diazotrifluoropropionates FAMILY 23409719 A 675 688 benzophenones FAMILY 23409719 T 129 139 isoprenoid FAMILY 23409719 T 23 43 farnesyl diphosphate SYSTEMATIC 23409719 T 56 67 isoprenoids FAMILY 23409765 A 1007 1020 phenylalanine TRIVIAL 23409765 A 1049 1057 pyruvate TRIVIAL 23409765 A 443 458 porphobilinogen TRIVIAL 23409842 A 1230 1233 Arg FORMULA 23409842 A 394 399 (13)C FORMULA 23409842 A 401 406 (15)N FORMULA 23409842 A 429 448 polyethylene glycol SYSTEMATIC 23409842 A 577 581 (1)H FORMULA 23409842 A 582 587 (15)N FORMULA 23409842 A 711 715 (1)H FORMULA 23409842 A 773 787 amide nitrogen SYSTEMATIC 23409842 A 810 814 (1)H FORMULA 23409925 A 253 266 carboxymethyl SYSTEMATIC 23409925 A 441 447 folate TRIVIAL 23409925 A 500 506 folate TRIVIAL 23409925 A 548 552 5-FU SYSTEMATIC 23409925 A 665 669 5-FU SYSTEMATIC 23409925 A 701 705 FITC ABBREVIATION 23409925 A 78 91 carboxymethyl SYSTEMATIC 23409925 T 16 29 carboxymethyl SYSTEMATIC 23409925 T 95 101 folate TRIVIAL 23409952 A 0 5 Azide SYSTEMATIC 23409952 A 1034 1045 metal azide FAMILY 23409952 A 1239 1243 DMSO ABBREVIATION 23409952 A 185 190 azide SYSTEMATIC 23409952 A 235 252 dimethylsulfoxide SYSTEMATIC 23409952 A 254 258 DMSO ABBREVIATION 23409952 A 266 271 azide SYSTEMATIC 23409952 A 465 470 azide SYSTEMATIC 23409952 A 498 502 LiN3 FORMULA 23409952 A 504 508 NaN3 FORMULA 23409952 A 510 515 NH4N3 FORMULA 23409952 A 517 524 MgN3(+) FORMULA 23409952 A 530 537 CaN3(+) FORMULA 23409952 A 542 546 DMSO ABBREVIATION 23409952 A 582 593 metal azide FAMILY 23409952 A 661 666 azide SYSTEMATIC 23409952 A 824 829 azide SYSTEMATIC 23409952 A 894 899 azide SYSTEMATIC 23409952 A 924 935 metal azide FAMILY 23409952 T 23 34 metal azide FAMILY 23409952 T 48 65 dimethylsulfoxide SYSTEMATIC 23410078 A 198 208 pyrimidine SYSTEMATIC 23410078 A 209 219 diterpenes FAMILY 23410078 A 231 265 axistatins 1 (1), 2 (2), and 3 (3) MULTIPLE 23410078 A 305 315 formamides FAMILY 23410078 A 326 337 agelasine F TRIVIAL 23410078 A 507 521 Axistatins 1-3 MULTIPLE 23410078 A 529 538 formamide SYSTEMATIC 23410078 A 546 557 agelasine F TRIVIAL 23410078 T 28 42 axistatins 1-3 MULTIPLE 23410105 A 388 393 X-NO2 FAMILY 23410105 A 693 698 nitro SYSTEMATIC 23410105 A 77 82 nitro SYSTEMATIC 23410168 A 668 689 phenylaminopyrimidine SYSTEMATIC 23410168 A 691 704 anthracycline FAMILY 23410168 A 709 722 naphthalimide FAMILY 23410172 A 0 16 Arachidonic acid TRIVIAL 23410172 A 1068 1071 ARA ABBREVIATION 23410172 A 1250 1260 eicosanoid FAMILY 23410172 A 18 21 ARA ABBREVIATION 23410172 A 640 648 oxylipin FAMILY 23410172 A 699 702 ARA ABBREVIATION 23410172 A 812 815 ARA ABBREVIATION 23410634 A 1085 1096 glutathione TRIVIAL 23410634 A 136 142 oxygen SYSTEMATIC 23410634 A 603 612 menadione TRIVIAL 23410634 A 614 631 hydrogen peroxide SYSTEMATIC 23410634 A 636 660 tert-butyl hydroperoxide SYSTEMATIC 23410634 A 738 746 carbonyl FAMILY 23410745 A 712 723 Cholesterol TRIVIAL 23410745 A 947 957 creatinine TRIVIAL 23410745 A 962 971 uric acid TRIVIAL 23411075 A 12 23 arylglycine FAMILY 23411075 A 317 323 icilin TRIVIAL 23411075 T 0 11 Arylglycine FAMILY 23411076 A 1083 1090 (99m)Tc FORMULA 23411076 A 117 119 Re FORMULA 23411076 A 139 146 (99m)Tc FORMULA 23411076 A 148 168 2-arylbenzothiazoles FAMILY 23411076 A 258 260 Re FORMULA 23411076 A 339 346 (99m)Tc FORMULA 23411076 A 475 498 Re 2-arylbenzothiazoles FAMILY 23411076 A 50 57 (99m)Tc FORMULA 23411076 A 683 704 2-phenylbenzothiazole FAMILY 23411076 A 786 809 Re 2-arylbenzothiazoles FAMILY 23411076 A 954 977 Re 2-arylbenzothiazoles FAMILY 23411076 T 57 85 rhenium 2-arylbenzothiazoles FAMILY 23411079 A 1013 1015 NO FORMULA 23411079 A 358 367 steroidal FAMILY 23411079 A 379 390 longipenane TRIVIAL 23411079 A 396 432 longipenane 26-O-β-d-glucopyranoside SYSTEMATIC 23411079 A 441 534 neogitogenin 3-O-α-l-rhamnopyranosyl-(1→2)-O-[β-d-glucopyranosyl-(1→4)]-β-d-galactopyranoside SYSTEMATIC 23411079 A 561 579 steroidal saponins FAMILY 23411079 A 799 811 nitric oxide SYSTEMATIC 23411079 A 813 815 NO FORMULA 23411079 T 0 9 Steroidal FAMILY 23411079 T 89 101 nitric oxide SYSTEMATIC 23411082 A 15 28 Hypocrellin A TRIVIAL 23411082 A 168 174 Al(3+) FORMULA 23411082 A 236 242 oxygen SYSTEMATIC 23411082 A 244 249 (1)O2 FORMULA 23411082 A 339 345 Al(3+) FORMULA 23411082 A 34 40 Al(3+) FORMULA 23411082 T 16 29 Hypocrellin A TRIVIAL 23411082 T 35 39 Al3+ FORMULA 23411168 A 439 444 diene SYSTEMATIC 23411168 A 494 497 AOT ABBREVIATION 23411168 A 502 511 isooctane SYSTEMATIC 23411168 A 557 570 linoleic acid TRIVIAL 23411168 A 618 621 AOT ABBREVIATION 23411168 A 693 696 AOT ABBREVIATION 23411168 A 697 706 isooctane SYSTEMATIC 23411168 A 792 795 AOT ABBREVIATION 23411168 A 809 812 AOT ABBREVIATION 23411168 T 73 76 AOT ABBREVIATION 23411168 T 77 86 isooctane SYSTEMATIC 23411173 A 1045 1052 phytate TRIVIAL 23411173 A 1054 1061 oxalate SYSTEMATIC 23411173 A 1066 1073 saponin FAMILY 23411173 A 271 284 carbohydrates FAMILY 23411173 A 366 374 Palmitic TRIVIAL 23411173 A 383 390 stearic TRIVIAL 23411173 A 399 404 oleic TRIVIAL 23411173 A 417 425 linoleic TRIVIAL 23411173 A 511 518 oxalate SYSTEMATIC 23411173 A 534 541 saponin FAMILY 23411173 A 580 587 phytate TRIVIAL 23411175 A 252 262 polyphenol FAMILY 23411175 A 306 320 polyacrylamide SYSTEMATIC 23411175 A 351 362 polyphenols FAMILY 23411175 A 4 15 polyphenols FAMILY 23411175 A 623 634 polyphenols FAMILY 23411175 T 43 53 polyphenol FAMILY 23411177 A 533 570 eicosapentaenoic-docosahexaenoic acid MULTIPLE 23411177 A 602 629 polyunsaturated fatty acids FAMILY 23411177 A 669 690 saturated fatty acids FAMILY 23411177 A 755 773 cholesterol oxides FAMILY 23411177 A 789 807 cholesterol oxides FAMILY 23411178 A 111 116 2-NAP SYSTEMATIC 23411178 A 260 263 KOH FORMULA 23411178 A 590 595 2-NAP SYSTEMATIC 23411178 A 600 605 1-HOP SYSTEMATIC 23411178 A 701 706 2-NAP SYSTEMATIC 23411178 A 71 86 l-hydroxypyrene SYSTEMATIC 23411178 A 878 883 2-NAP SYSTEMATIC 23411178 A 88 93 1-HOP SYSTEMATIC 23411178 A 99 109 2-naphthol SYSTEMATIC 23411178 T 30 40 2-naphthol SYSTEMATIC 23411178 T 45 60 1-hydroxypyrene SYSTEMATIC 23411181 A 397 417 furanosesquiterpenes FAMILY 23411181 A 513 516 MTT ABBREVIATION 23411181 A 553 557 DPPH ABBREVIATION 23411181 A 559 563 ABTS ABBREVIATION 23411181 A 904 918 Isofuranodiene SYSTEMATIC 23411181 A 923 955 1β-acetoxyfuranoeudesm-4(15)-ene SYSTEMATIC 23411181 T 60 80 furanosesquiterpenes FAMILY 23411182 A 422 454 ascorbic, citric and malic acids MULTIPLE 23411182 A 561 574 ascorbic acid TRIVIAL 23411182 A 591 593 Ni FORMULA 23411182 A 598 600 Ag FORMULA 23411182 A 613 615 Ag FORMULA 23411182 A 620 622 Ir FORMULA 23411182 A 709 731 citric and malic acids MULTIPLE 23411182 A 765 767 Ir FORMULA 23411182 A 769 771 Rh FORMULA 23411182 A 773 775 Pt FORMULA 23411182 A 777 779 Ag FORMULA 23411182 A 784 786 Cu FORMULA 23411183 A 92 103 polyphenols FAMILY 23411184 A 201 213 acetonitrile SYSTEMATIC 23411184 A 472 484 acetonitrile SYSTEMATIC 23411184 A 656 667 avermectins FAMILY 23411185 A 0 4 Iron SYSTEMATIC 23411185 A 101 105 iron SYSTEMATIC 23411185 A 122 126 iron SYSTEMATIC 23411185 A 614 618 iron SYSTEMATIC 23411185 A 623 627 zinc SYSTEMATIC 23411185 T 68 72 iron SYSTEMATIC 23411189 A 185 192 Fe(III) FORMULA 23411189 A 220 227 Fe(III) FORMULA 23411189 A 234 238 EDTA ABBREVIATION 23411189 A 334 341 Citrate TRIVIAL 23411189 A 346 352 malate TRIVIAL 23411189 A 399 406 Fe(III) FORMULA 23411189 A 477 481 EDTA ABBREVIATION 23411189 A 519 523 EDTA ABBREVIATION 23411189 A 63 67 EDTA ABBREVIATION 23411189 A 761 765 EDTA ABBREVIATION 23411189 A 92 96 EDTA ABBREVIATION 23411189 T 17 48 ethylenediaminetetraacetic acid SYSTEMATIC 23411191 A 0 12 Ginsenosides FAMILY 23411191 A 1019 1033 ginsenoside Re TRIVIAL 23411191 A 1034 1040 lysine TRIVIAL 23411191 A 1123 1135 ginsenosides FAMILY 23411191 A 241 255 Ginsenoside Re TRIVIAL 23411191 A 274 279 triol SYSTEMATIC 23411191 A 285 297 ginsenosides FAMILY 23411191 A 387 392 sugar FAMILY 23411191 A 405 412 carbons FAMILY 23411191 A 533 547 ginsenoside Re TRIVIAL 23411191 A 572 586 Ginsenoside Re TRIVIAL 23411191 A 619 661 ginsenosides, namely Rg(2), Rg(6) and F(4) MULTIPLE 23411191 A 722 736 ginsenoside Re TRIVIAL 23411191 A 737 743 lysine TRIVIAL 23411191 A 84 88 diol SYSTEMATIC 23411191 A 913 921 glucosyl TRIVIAL 23411191 A 94 106 ginsenosides FAMILY 23411191 A 944 950 carbon SYSTEMATIC 23411191 A 957 971 ginsenoside Re TRIVIAL 23411191 A 976 982 lysine TRIVIAL 23411191 T 50 64 ginsenoside Re TRIVIAL 23411191 T 65 71 lysine TRIVIAL 23411194 A 19 30 quinic acid TRIVIAL 23411194 A 917 928 quinic acid TRIVIAL 23411195 A 184 210 polyunsaturated fatty acid FAMILY 23411195 A 212 216 PUFA ABBREVIATION 23411195 A 544 548 PUFA ABBREVIATION 23411199 A 101 112 polyphenols FAMILY 23411199 A 1196 1207 polyphenols FAMILY 23411199 A 241 253 anthocyanins FAMILY 23411199 A 426 437 polyphenols FAMILY 23411199 A 442 454 anthocyanins FAMILY 23411199 A 459 468 flavonols FAMILY 23411199 A 472 492 hydroxybenzoic acids FAMILY 23411199 A 497 518 hydroxycinnamic acids FAMILY 23411199 A 522 532 flavanones FAMILY 23411199 A 536 552 dihydrochalcones FAMILY 23411199 A 556 568 flavan-3-ols FAMILY 23411199 A 575 584 stilbenes FAMILY 23411199 A 600 610 polyphenol FAMILY 23411199 A 658 668 polyphenol FAMILY 23411199 A 720 731 polyphenols FAMILY 23411199 A 783 794 polyphenols FAMILY 23411199 A 881 892 polyphenols FAMILY 23411199 T 44 55 polyphenols FAMILY 23411206 A 165 182 ammonium sulphate SYSTEMATIC 23411206 A 184 197 dicyandiamide SYSTEMATIC 23411206 A 199 207 melamine TRIVIAL 23411206 A 213 217 urea TRIVIAL 23411208 A 179 191 α-tocopherol TRIVIAL 23411208 A 234 243 vitamin E FAMILY 23411208 A 245 257 α-Tocopherol TRIVIAL 23411208 A 316 328 α-tocopherol TRIVIAL 23411208 A 691 713 α-tocopheryl succinate SYSTEMATIC 23411208 A 715 720 α-TOS ABBREVIATION 23411208 A 749 761 α-tocopherol TRIVIAL 23411208 A 798 809 doxorubicin TRIVIAL 23411208 A 926 935 vitamin E FAMILY 23411208 T 14 26 α-tocopherol TRIVIAL 23411210 A 1009 1015 6-OHDA SYSTEMATIC 23411210 A 170 181 gallic acid TRIVIAL 23411210 A 286 303 6-hydroxydopamine SYSTEMATIC 23411210 A 305 311 6-OHDA SYSTEMATIC 23411210 A 464 470 6-OHDA SYSTEMATIC 23411210 A 556 561 thiol FAMILY 23411210 A 578 589 glutathione TRIVIAL 23411210 A 656 671 malondialdehyde TRIVIAL 23411210 A 673 676 MDA ABBREVIATION 23411210 A 869 874 thiol FAMILY 23411210 A 911 914 MDA ABBREVIATION 23411210 T 32 43 gallic acid TRIVIAL 23411210 T 80 97 6-hydroxydopamine SYSTEMATIC 23411211 A 159 171 cannabisin B TRIVIAL 23411211 A 361 373 cannabisin B TRIVIAL 23411211 A 430 442 Cannabisin B TRIVIAL 23411211 A 525 540 3-methyladenine SYSTEMATIC 23411211 A 53 65 cannabisin B TRIVIAL 23411211 A 542 546 3-MA SYSTEMATIC 23411211 A 595 607 cannabisin B TRIVIAL 23411211 A 641 653 cannabisin B TRIVIAL 23411211 A 726 738 cannabisin B TRIVIAL 23411211 A 864 873 rapamycin TRIVIAL 23411211 A 910 922 cannabisin B TRIVIAL 23411211 T 0 12 Cannabisin B TRIVIAL 23411212 A 104 123 25-hydroxyvitamin D SYSTEMATIC 23411212 A 125 135 25OH-Vit D SYSTEMATIC 23411212 A 434 439 Vit D ABBREVIATION 23411212 A 444 454 25OH-Vit D SYSTEMATIC 23411212 A 496 505 Deuterium SYSTEMATIC 23411212 A 515 520 Vit D ABBREVIATION 23411212 A 525 535 25OH-Vit D SYSTEMATIC 23411212 A 82 91 vitamin D FAMILY 23411212 A 93 98 Vit D ABBREVIATION 23411212 T 0 9 Vitamin D FAMILY 23411212 T 14 33 25-hydroxyvitamin D SYSTEMATIC 23411213 A 105 119 aflatoxin B(1) TRIVIAL 23411213 A 124 136 ochratoxin A TRIVIAL 23411213 A 438 450 acetonitrile SYSTEMATIC 23411213 A 474 490 ammonium acetate SYSTEMATIC 23411213 T 30 44 aflatoxin B(1) TRIVIAL 23411213 T 49 61 ochratoxin A TRIVIAL 23411217 A 144 148 GalA ABBREVIATION 23411217 A 150 154 GlcA ABBREVIATION 23411217 A 156 159 Ara ABBREVIATION 23411217 A 161 164 Gal ABBREVIATION 23411217 A 169 172 Rha ABBREVIATION 23411217 A 203 207 GalA ABBREVIATION 23411217 A 218 222 Araf ABBREVIATION 23411217 A 260 263 Ara ABBREVIATION 23411217 A 274 277 Gal ABBREVIATION 23411217 A 305 308 Rha ABBREVIATION 23411219 A 20 36 triacylglycerols FAMILY 23411219 A 261 271 fatty acid FAMILY 23411219 A 289 306 hexacosanoic acid SYSTEMATIC 23411219 A 321 339 heneicosanoic acid SYSTEMATIC 23411219 A 360 376 triacylglycerols FAMILY 23411219 A 457 472 triacylglycerol FAMILY 23411219 A 517 535 dioleoyl linoleoyl TRIVIAL 23411219 A 537 540 OOL ABBREVIATION 23411219 A 543 557 1,2,3-trioleyl SYSTEMATIC 23411219 A 559 562 OOO ABBREVIATION 23411219 A 565 588 1,2-dioleyl-3-palmitoyl SYSTEMATIC 23411219 A 590 593 POO ABBREVIATION 23411219 A 596 619 1,2-dilinoleoyl-3-oleyl SYSTEMATIC 23411219 A 621 624 OLL ABBREVIATION 23411219 A 630 663 1-oleoyl-2-linoleoyl-3-linolenoyl SYSTEMATIC 23411219 A 665 669 OLLn ABBREVIATION 23411219 A 806 809 OOO ABBREVIATION 23411219 A 844 847 OOL ABBREVIATION 23411219 A 857 860 OOO ABBREVIATION 23411219 A 873 876 POO ABBREVIATION 23411219 A 905 908 OLL ABBREVIATION 23411219 A 918 921 OOO ABBREVIATION 23411219 A 934 937 OLL ABBREVIATION 23411219 T 58 74 triacylglycerols FAMILY 23411220 A 105 113 H(2)O(2) FORMULA 23411220 A 1058 1066 H(2)O(2) FORMULA 23411220 A 322 330 H(2)O(2) FORMULA 23411220 A 394 402 H(2)O(2) FORMULA 23411220 A 568 576 H(2)O(2) FORMULA 23411220 A 739 747 H(2)O(2) FORMULA 23411220 A 86 103 hydrogen peroxide SYSTEMATIC 23411220 A 892 900 H(2)O(2) FORMULA 23411220 A 996 1004 H(2)O(2) FORMULA 23411220 T 91 108 hydrogen peroxide SYSTEMATIC 23411223 A 1002 1004 Co FORMULA 23411223 A 1010 1011 V FORMULA 23411223 A 913 915 Ni FORMULA 23411223 A 917 919 Ag FORMULA 23411223 A 921 923 Cr FORMULA 23411223 A 925 927 Sr FORMULA 23411223 A 929 931 Zn FORMULA 23411223 A 937 939 Cu FORMULA 23411223 A 964 966 Rb FORMULA 23411223 A 968 970 Zn FORMULA 23411223 A 976 978 Mn FORMULA 23411223 A 998 1000 Pb FORMULA 23411232 A 11 23 vitamin D(3) TRIVIAL 23411232 A 377 389 Vitamin D(3) TRIVIAL 23411232 A 394 417 25-hydroxy vitamin D(3) SYSTEMATIC 23411232 A 527 539 vitamin D(3) TRIVIAL 23411232 A 563 586 25-hydroxy vitamin D(3) SYSTEMATIC 23411232 A 644 671 1,25 dihydroxy vitamin D(3) SYSTEMATIC 23411232 T 18 28 vitamin D3 TRIVIAL 23411236 A 540 551 chitotriose TRIVIAL 23411236 A 553 563 chitobiose TRIVIAL 23411236 A 585 604 N-acetylglucosamine SYSTEMATIC 23411239 A 134 150 Organophosphorus FAMILY 23411239 A 155 165 pyrethroid FAMILY 23411239 A 881 889 diazinon TRIVIAL 23411239 A 913 925 fenitrothion TRIVIAL 23411239 A 949 961 cypermethrin TRIVIAL 23411239 A 989 999 permethrin TRIVIAL 23411239 T 72 88 organophosphorus FAMILY 23411239 T 93 103 pyrethroid FAMILY 23411248 A 280 284 zinc SYSTEMATIC 23411248 A 380 384 zinc SYSTEMATIC 23411248 A 495 499 zinc SYSTEMATIC 23411248 T 62 66 zinc SYSTEMATIC 23411250 A 139 150 polyphenols FAMILY 23411250 A 203 218 pyrogallic acid TRIVIAL 23411250 A 287 294 Fe(III) FORMULA 23411250 A 298 304 Fe(II) FORMULA 23411250 A 332 335 NRS ABBREVIATION 23411250 A 35 42 Fe(III) FORMULA 23411250 A 390 396 Fe(II) FORMULA 23411250 A 397 400 NRS ABBREVIATION 23411250 A 43 93 3-hydroxy-4-nitroso-2,7-naphthalenedisulfonic acid SYSTEMATIC 23411250 A 830 837 Fe(III) FORMULA 23411250 A 838 841 NRS ABBREVIATION 23411250 A 95 98 NRS ABBREVIATION 23411250 T 124 135 polyphenols FAMILY 23411250 T 31 37 Fe(II) FORMULA 23411250 T 38 88 3-hydroxy-4-nitroso-2,7-naphthalenedisulfonic acid SYSTEMATIC 23411252 A 115 124 vitamin A FAMILY 23411252 A 447 455 phytoene TRIVIAL 23411252 A 457 468 phytofluene TRIVIAL 23411252 A 470 476 lutein TRIVIAL 23411252 A 478 488 zeaxanthin TRIVIAL 23411252 A 490 505 β-cryptoxanthin TRIVIAL 23411252 A 507 517 α-carotene TRIVIAL 23411252 A 519 529 β-carotene TRIVIAL 23411252 A 534 542 lycopene TRIVIAL 23411255 A 1017 1026 ascorbate TRIVIAL 23411255 A 1027 1038 glutathione TRIVIAL 23411255 A 1167 1180 ascorbic acid TRIVIAL 23411255 A 1185 1196 glutathione TRIVIAL 23411255 A 1313 1326 ascorbic acid TRIVIAL 23411255 A 1342 1353 glutathione TRIVIAL 23411255 A 1464 1477 ascorbic acid TRIVIAL 23411255 A 1482 1493 glutathione TRIVIAL 23411255 A 1683 1692 peroxides FAMILY 23411255 A 1702 1711 carbonyls FAMILY 23411255 A 1794 1807 ascorbic acid TRIVIAL 23411255 A 1812 1823 glutathione TRIVIAL 23411255 A 260 273 ascorbic acid TRIVIAL 23411255 A 278 289 glutathione TRIVIAL 23411255 A 420 433 ascorbic acid TRIVIAL 23411255 A 438 449 glutathione TRIVIAL 23411255 A 637 650 ascorbic acid TRIVIAL 23411255 A 655 666 glutathione TRIVIAL 23411255 A 66 79 ascorbic acid TRIVIAL 23411255 A 799 812 ascorbic acid TRIVIAL 23411255 A 84 95 glutathione TRIVIAL 23411255 A 848 859 glutathione TRIVIAL 23411255 A 919 932 ascorbic acid TRIVIAL 23411255 A 937 948 glutathione TRIVIAL 23411255 T 33 46 ascorbic acid TRIVIAL 23411255 T 51 62 glutathione TRIVIAL 23411265 A 0 12 Phytosterols FAMILY 23411265 A 1045 1066 phytosteryl sinapates FAMILY 23411265 A 1105 1118 vanillic acid SYSTEMATIC 23411265 A 1123 1138 vinyl vanillate SYSTEMATIC 23411265 A 1179 1191 phytosterols FAMILY 23411265 A 1197 1221 sinapic or vanillic acid MULTIPLE 23411265 A 1298 1319 phytosteryl sinapates FAMILY 23411265 A 1324 1334 vanillates FAMILY 23411265 A 236 248 phytosterols FAMILY 23411265 A 253 286 phytosteryl esters of fatty acids FAMILY 23411265 A 315 337 phytosteryl phenolates FAMILY 23411265 A 353 365 phytosterols FAMILY 23411265 A 371 385 phenolic acids FAMILY 23411265 A 403 425 phytosteryl phenolates FAMILY 23411265 A 434 455 phytosteryl sinapates FAMILY 23411265 A 460 470 vanillates FAMILY 23411265 A 843 864 phytosteryl sinapates FAMILY 23411265 A 889 895 oxygen SYSTEMATIC 23411265 A 983 1005 phytosteryl vanillates FAMILY 23411265 T 0 21 Phytosteryl sinapates FAMILY 23411265 T 26 36 vanillates FAMILY 23411268 A 151 155 (1)H FORMULA 23411268 T 37 39 1H FORMULA 23411271 A 1014 1019 thiol FAMILY 23411271 A 1031 1053 methyl dihydrocaffeate SYSTEMATIC 23411271 A 1119 1128 caffeates FAMILY 23411271 A 123 126 azo SYSTEMATIC 23411271 A 192 197 thiol FAMILY 23411271 A 24 39 methyl caffeate SYSTEMATIC 23411271 A 279 288 caffeates FAMILY 23411271 A 437 452 methyl caffeate SYSTEMATIC 23411271 A 44 66 methyl dihydrocaffeate SYSTEMATIC 23411271 A 566 571 thiol FAMILY 23411271 A 619 641 methyl dihydrocaffeate SYSTEMATIC 23411271 A 709 714 thiol FAMILY 23411271 A 88 103 cysteinyl thiol SYSTEMATIC 23411271 A 961 966 thiol FAMILY 23411271 A 977 992 methyl caffeate SYSTEMATIC 23411271 T 50 65 cysteinyl thiol SYSTEMATIC 23411271 T 97 130 caffeic and dihydrocaffeic esters MULTIPLE 23411272 A 297 304 glucose TRIVIAL 23411272 A 37 49 procyanidins FAMILY 23411272 A 627 635 catechin TRIVIAL 23411272 A 697 710 methylglyoxal SYSTEMATIC 23411272 A 736 744 carbonyl FAMILY 23411272 A 826 839 methylglyoxal SYSTEMATIC 23411272 A 850 858 carbonyl FAMILY 23411272 T 11 23 procyanidins FAMILY 23411272 T 122 131 carbonyls FAMILY 23411283 A 0 10 Biguanides FAMILY 23411283 A 115 124 guanidine TRIVIAL 23411283 A 19 28 metformin TRIVIAL 23411283 A 219 229 biguanides FAMILY 23411283 A 262 272 biguanides FAMILY 23411283 A 351 360 biguanide TRIVIAL 23411283 A 960 969 biguanide TRIVIAL 23411283 T 0 9 Biguanide TRIVIAL 23411284 A 0 10 β-Carotene TRIVIAL 23411284 A 111 121 β-Carotene TRIVIAL 23411284 A 178 184 oxygen SYSTEMATIC 23411284 A 268 278 β-carotene TRIVIAL 23411284 A 408 418 β-carotene TRIVIAL 23411284 A 637 647 β-carotene TRIVIAL 23411284 A 82 91 vitamin A FAMILY 23411284 T 22 32 β-carotene TRIVIAL 23411306 A 102 111 sulfonate SYSTEMATIC 23411306 A 118 129 Ponceau 4RC TRIVIAL 23411306 A 131 144 Sunset yellow TRIVIAL 23411306 A 146 156 Allura red TRIVIAL 23411306 A 158 169 Azophloxine TRIVIAL 23411306 A 171 187 Ponceau xylidine TRIVIAL 23411306 A 189 200 Erythrosine TRIVIAL 23411306 A 205 214 Orange II TRIVIAL 23411306 A 339 346 Ethanol SYSTEMATIC 23411306 A 347 354 ammonia SYSTEMATIC 23411307 A 321 324 SFA ABBREVIATION 23411307 A 326 330 MUFA ABBREVIATION 23411307 A 335 339 PUFA ABBREVIATION 23411307 A 39 49 fatty acid FAMILY 23411307 A 476 486 fatty acid FAMILY 23411307 A 789 800 fatty acids FAMILY 23411307 A 973 983 fatty acid FAMILY 23411307 T 0 10 Fatty acid FAMILY 23411311 A 221 233 dienoic acid SYSTEMATIC 23411311 A 247 258 p-anisidine SYSTEMATIC 23411311 A 358 363 C11:0 FORMULA 23411311 A 374 397 unsaturated fatty acids FAMILY 23411311 A 399 403 UFAs ABBREVIATION 23411311 A 409 430 saturated fatty acids FAMILY 23411311 A 432 436 SFAs ABBREVIATION 23411311 A 525 528 SFA ABBREVIATION 23411311 A 552 555 UFA ABBREVIATION 23411311 A 605 618 caprylic acid TRIVIAL 23411311 A 620 624 C8:0 FORMULA 23411311 A 736 759 unsaturated fatty acids FAMILY 23411311 A 761 765 SFAs ABBREVIATION 23411311 A 766 770 UFAs ABBREVIATION 23411311 A 775 788 caprylic acid TRIVIAL 23411311 A 790 794 C8:0 FORMULA 23411311 A 801 805 UFAs ABBREVIATION 23411311 A 892 899 sesamol TRIVIAL 23411311 A 961 972 fatty acids FAMILY 23411311 A 98 109 fatty acids FAMILY 23411311 T 92 103 fatty acids FAMILY 23411312 A 1389 1395 sugars FAMILY 23411312 A 1565 1576 polyphenols FAMILY 23411312 A 1669 1672 HMF ABBREVIATION 23411312 A 287 290 ACs ABBREVIATION 23411312 A 724 747 5-hydroxymethylfurfural SYSTEMATIC 23411312 A 749 752 HMF ABBREVIATION 23411312 A 82 93 anthocyanin FAMILY 23411312 T 21 33 anthocyanins FAMILY 23411314 A 205 212 proline TRIVIAL 23411314 A 214 228 phloroglucinol TRIVIAL 23411314 A 230 238 mannitol TRIVIAL 23411314 A 242 253 fatty acids FAMILY 23411314 A 260 267 sterols FAMILY 23411314 A 423 427 DPPH ABBREVIATION 23411314 A 429 441 nitric oxide SYSTEMATIC 23411314 A 443 453 superoxide TRIVIAL 23411314 A 458 466 hydroxyl SYSTEMATIC 23411314 A 917 931 phloroglucinol TRIVIAL 23411314 A 933 941 mannitol TRIVIAL 23411314 A 943 988 oleic, arachidonic and eicosapentaenoic acids MULTIPLE 23411314 A 994 1004 fucosterol TRIVIAL 23411334 A 1075 1083 l-5-MTHF SYSTEMATIC 23411334 A 1169 1177 l-5-MTHF SYSTEMATIC 23411334 A 130 156 l-5-methyltetrahydrofolate SYSTEMATIC 23411334 A 158 166 l-5-MTHF SYSTEMATIC 23411334 A 188 212 epigallocatechin-gallate TRIVIAL 23411334 A 303 311 l-5-MTHF SYSTEMATIC 23411334 A 326 334 catechin TRIVIAL 23411334 A 375 383 l-5-MTHF SYSTEMATIC 23411334 A 599 607 l-5-MTHF SYSTEMATIC 23411334 A 634 642 l-5-MTHF SYSTEMATIC 23411334 A 763 772 catechins FAMILY 23411334 A 812 816 EGCG ABBREVIATION 23411334 A 892 900 hydrogen SYSTEMATIC 23411334 A 930 939 catechins FAMILY 23411334 A 983 991 l-5-MTHF SYSTEMATIC 23411334 T 20 29 catechins FAMILY 23411334 T 83 109 L-5-methyltetrahydrofolate SYSTEMATIC 23411335 A 136 145 natamycin TRIVIAL 23411335 A 245 250 sugar FAMILY 23411335 A 261 266 sugar FAMILY 23411335 A 268 281 ascorbic acid TRIVIAL 23411335 A 364 373 natamycin TRIVIAL 23411335 A 589 594 sugar FAMILY 23411335 A 599 612 ascorbic acid TRIVIAL 23411335 T 131 140 natamycin TRIVIAL 23411340 A 174 187 ascorbic acid TRIVIAL 23411340 A 200 214 manganese(III) SYSTEMATIC 23411340 A 248 262 manganese(III) SYSTEMATIC 23411340 A 268 281 diphenylamine SYSTEMATIC 23411340 A 285 316 barium diphenylamine sulphonate SYSTEMATIC 23411340 A 46 59 ascorbic acid TRIVIAL 23411340 A 462 471 vitamin C TRIVIAL 23411340 A 736 750 manganese(III) SYSTEMATIC 23411340 A 755 768 diphenylamine SYSTEMATIC 23411340 A 774 787 ascorbic acid TRIVIAL 23411340 T 137 150 ascorbic acid TRIVIAL 23411340 T 69 92 manganese(III) sulphate SYSTEMATIC 23411340 T 98 111 diphenylamine SYSTEMATIC 23411342 A 1084 1090 Pb(II) FORMULA 23411342 A 128 158 ethylene glycol dimethacrylate SYSTEMATIC 23411342 A 180 208 2,2'- azobisisobutyronitrile SYSTEMATIC 23411342 A 227 244 diphenylcarbazone SYSTEMATIC 23411342 A 260 271 acetonitril SYSTEMATIC 23411342 A 292 304 Pb(NO(3))(2) FORMULA 23411342 A 44 50 Pb(II) FORMULA 23411342 A 442 445 HCl FORMULA 23411342 A 647 653 Pb(II) FORMULA 23411342 A 87 102 2-vinylpyridine SYSTEMATIC 23411351 A 1176 1184 carbaryl TRIVIAL 23411351 A 1444 1456 carbohydrate FAMILY 23411351 A 1618 1626 carbaryl TRIVIAL 23411351 A 1774 1782 carbaryl TRIVIAL 23411351 A 605 613 carbaryl TRIVIAL 23411351 A 732 740 carbaryl TRIVIAL 23411351 A 969 977 carbaryl TRIVIAL 23411351 T 145 153 carbaryl TRIVIAL 23411351 T 64 72 carbaryl TRIVIAL 23412078 A 1046 1053 glucose TRIVIAL 23412078 A 1129 1142 Canagliflozin TRIVIAL 23412078 A 1302 1315 canagliflozin TRIVIAL 23412078 A 1464 1477 acetaminophen TRIVIAL 23412078 A 1602 1609 glucose TRIVIAL 23412078 A 164 177 canagliflozin TRIVIAL 23412078 A 1670 1683 Canagliflozin TRIVIAL 23412078 A 1712 1719 glucose TRIVIAL 23412078 A 26 32 sodium SYSTEMATIC 23412078 A 285 292 glucose TRIVIAL 23412078 A 33 40 glucose TRIVIAL 23412078 A 385 398 canagliflozin TRIVIAL 23412078 A 413 420 glucose TRIVIAL 23412078 A 494 507 canagliflozin TRIVIAL 23412078 A 584 591 glucose TRIVIAL 23412078 A 593 605 (3)H-glucose SYSTEMATIC 23412078 A 607 620 (14)C-glucose SYSTEMATIC 23412078 A 708 715 glucose TRIVIAL 23412078 A 746 753 glucose TRIVIAL 23412078 A 770 777 glucose TRIVIAL 23412078 A 817 830 canagliflozin TRIVIAL 23412078 A 869 876 glucose TRIVIAL 23412078 A 9 22 Canagliflozin TRIVIAL 23412078 T 0 13 Canagliflozin TRIVIAL 23412078 T 130 137 Glucose TRIVIAL 23412078 T 34 41 Glucose TRIVIAL 23412078 T 77 84 Glucose TRIVIAL 23412396 A 1120 1126 JZL184 IDENTIFIER 23412396 A 1211 1217 JZL184 IDENTIFIER 23412396 A 1335 1341 JZL184 IDENTIFIER 23412396 A 1408 1414 JZL184 IDENTIFIER 23412396 A 1442 1448 JZL184 IDENTIFIER 23412396 A 1516 1541 Δ(9)-tetrahydrocannabinol SYSTEMATIC 23412396 A 154 160 JZL184 IDENTIFIER 23412396 A 1543 1546 THC ABBREVIATION 23412396 A 1593 1603 rimonabant TRIVIAL 23412396 A 4 20 monoacylglycerol SYSTEMATIC 23412396 A 45 51 JZL184 IDENTIFIER 23412396 A 552 558 JZL184 IDENTIFIER 23412396 A 795 801 JZL184 IDENTIFIER 23412396 A 908 923 [(3)H]SR141716A SYSTEMATIC 23412396 A 936 944 CP55,940 IDENTIFIER 23412396 A 957 962 (35)S FORMULA 23412396 T 40 56 Monoacylglycerol SYSTEMATIC 23412396 T 74 80 JZL184 IDENTIFIER 23412992 A 1253 1256 ATP ABBREVIATION 23412992 A 1393 1396 NaK FORMULA 23412992 A 271 277 sodium SYSTEMATIC 23412992 A 278 287 potassium SYSTEMATIC 23412992 A 298 301 Na+ FORMULA 23412992 A 302 304 K+ FORMULA 23412992 A 319 322 NaK FORMULA 23412992 A 376 384 steroids FAMILY 23412992 A 588 591 Na+ FORMULA 23412992 A 592 594 K+ FORMULA 23412992 A 712 715 Na+ FORMULA 23412992 A 716 718 K+ FORMULA 23412992 A 762 765 Na+ FORMULA 23412992 A 766 768 K+ FORMULA 23412992 A 833 840 steroid FAMILY 23412992 T 30 33 Na+ FORMULA 23412992 T 34 36 K+ FORMULA 23413033 A 887 896 potassium SYSTEMATIC 23413033 T 48 57 Potassium SYSTEMATIC 23413101 A 516 528 nitric oxide SYSTEMATIC 23414252 A 648 654 methyl SYSTEMATIC 23414252 A 992 1000 hydrogen SYSTEMATIC 23414433 A 1175 1179 METH ABBREVIATION 23414433 A 1181 1185 METH ABBREVIATION 23414433 A 1186 1190 METH ABBREVIATION 23414433 A 1263 1267 METH ABBREVIATION 23414433 A 1361 1365 METH ABBREVIATION 23414433 A 146 154 dopamine TRIVIAL 23414433 A 198 202 METH ABBREVIATION 23414433 A 23 38 methamphetamine TRIVIAL 23414433 A 272 276 METH ABBREVIATION 23414433 A 40 44 METH ABBREVIATION 23414433 A 422 426 METH ABBREVIATION 23414433 A 687 691 METH ABBREVIATION 23414433 A 747 751 METH ABBREVIATION 23414433 A 753 757 METH ABBREVIATION 23414433 A 766 770 METH ABBREVIATION 23414433 A 771 775 METH ABBREVIATION 23414433 A 853 857 METH ABBREVIATION 23414433 A 953 957 METH ABBREVIATION 23414433 A 958 962 METH ABBREVIATION 23414433 T 34 49 methamphetamine TRIVIAL 23414802 A 169 189 2-hydroxydiarylamide FAMILY 23414802 A 256 262 serine TRIVIAL 23414802 A 391 397 serine TRIVIAL 23414802 T 19 39 2-hydroxydiarylamide FAMILY 23414841 A 13 24 Arg-Gly-Asp FORMULA 23414841 A 349 356 (99m)Tc FORMULA 23414841 A 412 426 [(99m)TcN](+2) FORMULA 23414841 A 445 460 dithiocarbamate SYSTEMATIC 23414841 A 494 505 G3-c(RGDfK) FORMULA 23414841 A 507 521 G3=Gly-Gly-Gly FORMULA 23414841 A 523 528 f=Phe FORMULA 23414841 A 530 535 K=Lys FORMULA 23414841 A 575 589 [(99m)TcN](+2) FORMULA 23414841 A 615 638 (99m)TcN-[G3-c(RGDfK)]2 FORMULA 23414841 T 39 46 (99m)Tc FORMULA 23415714 A 1025 1034 flutamide TRIVIAL 23415714 A 1069 1072 DHT ABBREVIATION 23415714 A 1257 1265 androgen FAMILY 23415714 A 1339 1347 androgen FAMILY 23415714 A 1454 1462 androgen FAMILY 23415714 A 26 34 androgen FAMILY 23415714 A 303 311 androgen FAMILY 23415714 A 35 43 androgen FAMILY 23415714 A 554 562 androgen FAMILY 23415714 A 710 718 androgen FAMILY 23415714 A 720 742 5α-dihydrotestosterone SYSTEMATIC 23415714 A 744 747 DHT ABBREVIATION 23415714 A 750 753 DHT ABBREVIATION 23415714 A 831 844 prostaglandin FAMILY 23415714 T 0 8 Androgen FAMILY 23415714 T 9 17 androgen FAMILY 23415893 A 104 115 glucosamine TRIVIAL 23415893 A 138 151 2-glucosamine SYSTEMATIC 23415893 A 81 103 prednisolone carbamate SYSTEMATIC 23415893 A 822 834 prednisolone TRIVIAL 23415893 A 892 905 2-glucosamine SYSTEMATIC 23415893 A 966 978 prednisolone TRIVIAL 23415893 T 77 90 2-glucosamine SYSTEMATIC 23416001 A 128 139 spirocycles FAMILY 23416001 A 156 162 isatin TRIVIAL 23416001 A 163 169 ketone SYSTEMATIC 23416001 T 33 39 isatin TRIVIAL 23416011 A 0 9 Celecoxib TRIVIAL 23416011 A 357 390 nitro-substituted acylsulfonamide FAMILY 23416011 A 412 421 celecoxib TRIVIAL 23416011 A 428 454 nitro-substituted 21-ester FAMILY 23416011 A 513 518 nitro SYSTEMATIC 23416011 T 2 12 nitropheny SYSTEMATIC 23416011 T 61 73 prednisolone TRIVIAL 23416011 T 75 85 budesonide TRIVIAL 23416011 T 90 99 celecoxib TRIVIAL 23416070 A 143 150 glucose TRIVIAL 23416070 A 934 944 fatty acid FAMILY 23416115 A 0 16 Chlorogenic acid TRIVIAL 23416115 A 1011 1014 CGA ABBREVIATION 23416115 A 1115 1122 glucose TRIVIAL 23416115 A 1138 1148 fatty acid FAMILY 23416115 A 1247 1250 CGA ABBREVIATION 23416115 A 1260 1267 glucose TRIVIAL 23416115 A 18 21 CGA ABBREVIATION 23416115 A 276 279 CGA ABBREVIATION 23416115 A 283 290 glucose TRIVIAL 23416115 A 385 392 glucose TRIVIAL 23416115 A 460 463 CGA ABBREVIATION 23416115 A 484 491 glucose TRIVIAL 23416115 A 507 517 fatty acid FAMILY 23416115 A 51 58 glucose TRIVIAL 23416115 A 593 596 CGA ABBREVIATION 23416115 A 683 686 CGA ABBREVIATION 23416115 A 698 705 glucose TRIVIAL 23416115 A 744 747 CGA ABBREVIATION 23416115 A 872 879 glucose TRIVIAL 23416115 A 919 926 glucose TRIVIAL 23416115 A 934 941 glucose TRIVIAL 23416115 T 44 60 chlorogenic acid TRIVIAL 23416191 A 552 559 HJC0123 IDENTIFIER 23416191 A 885 893 estrogen FAMILY 23416191 T 49 56 HJC0123 IDENTIFIER 23416192 A 136 162 3-(2-bromoacetyl)coumarins FAMILY 23416192 A 18 100 2-(5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles FAMILY 23416192 A 180 245 5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-thiocarboxamides FAMILY 23416192 A 279 296 thiosemicarbazide SYSTEMATIC 23416192 A 302 329 trifluoromethyl-β-diketones FAMILY 23416192 A 460 472 indomethacin TRIVIAL 23416192 A 609 617 cefixime TRIVIAL 23416192 T 55 137 2-(5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles FAMILY 23416229 A 271 284 acetylcholine SYSTEMATIC 23416262 A 390 396 oxygen SYSTEMATIC 23416264 A 1013 1025 hydroquinone SYSTEMATIC 23416264 A 1041 1049 nicotine TRIVIAL 23416264 A 1065 1073 acrolein TRIVIAL 23416264 A 1202 1219 2,5-dimethylfuran SYSTEMATIC 23416264 A 122 131 aldehydes FAMILY 23416264 A 1230 1238 aldehyde SYSTEMATIC 23416264 A 147 159 formaldehyde SYSTEMATIC 23416264 A 1507 1516 aldehydes FAMILY 23416264 A 161 173 acetaldehyde SYSTEMATIC 23416264 A 178 186 acrolein TRIVIAL 23416264 A 304 316 formaldehyde SYSTEMATIC 23416264 A 318 326 acrolein TRIVIAL 23416264 A 331 343 acetaldehyde SYSTEMATIC 23416264 A 403 412 aldehydes FAMILY 23416264 A 421 429 aldehyde SYSTEMATIC 23416264 A 441 449 nicotine TRIVIAL 23416264 A 451 463 hydroquinone SYSTEMATIC 23416264 A 468 485 2,5-dimethylfuran SYSTEMATIC 23416264 A 630 639 aldehydes FAMILY 23416264 A 661 670 aldehydes FAMILY 23416264 A 708 717 aldehydes FAMILY 23416264 A 802 814 Formaldehyde SYSTEMATIC 23416264 A 988 1000 acetaldehyde SYSTEMATIC 23416264 T 20 29 aldehydes FAMILY 23416326 A 115 120 (32)P FORMULA 23416326 A 235 238 PAH ABBREVIATION 23416326 A 265 269 PAHs ABBREVIATION 23416326 A 37 40 PAH ABBREVIATION 23416326 A 439 442 PAH ABBREVIATION 23416326 A 499 510 nucleotides FAMILY 23416326 A 549 560 nucleotides FAMILY 23416326 A 563 566 PAH ABBREVIATION 23416326 A 676 679 PAH ABBREVIATION 23416326 A 730 733 PAH ABBREVIATION 23416326 A 841 844 PAH ABBREVIATION 23416326 A 995 998 PAH ABBREVIATION 23416326 T 10 13 PAH ABBREVIATION 23416409 A 0 7 Mercury SYSTEMATIC 23416409 A 1193 1195 Hg FORMULA 23416409 A 1319 1321 Hg FORMULA 23416409 A 1447 1449 Hg FORMULA 23416409 A 180 197 mercuric chloride SYSTEMATIC 23416409 A 199 204 HgCl2 FORMULA 23416409 A 344 346 Hg FORMULA 23416409 A 411 413 Hg FORMULA 23416409 A 690 692 Hg FORMULA 23416409 A 9 11 Hg FORMULA 23416409 T 71 78 mercury SYSTEMATIC 23416650 A 57 65 urushiol TRIVIAL 23416930 A 607 616 rapamycin TRIVIAL 23416930 A 618 629 resveratrol TRIVIAL 23416930 A 633 643 spermidine TRIVIAL 23417420 A 1010 1013 DHT ABBREVIATION 23417420 A 1094 1097 DHT ABBREVIATION 23417420 A 1423 1426 DHT ABBREVIATION 23417420 A 1615 1623 androgen FAMILY 23417420 A 534 542 androgen FAMILY 23417420 A 699 707 androgen FAMILY 23417420 A 786 794 androgen FAMILY 23417420 A 976 984 androgen FAMILY 23417420 A 986 1008 5α-dihydrotestosterone SYSTEMATIC 23417420 T 7 15 androgen FAMILY 23417717 A 331 337 copper SYSTEMATIC 23417717 A 373 379 copper SYSTEMATIC 23417717 A 630 636 copper SYSTEMATIC 23417717 T 36 42 copper SYSTEMATIC 23417790 A 1070 1072 Hg FORMULA 23417790 A 111 113 Hg FORMULA 23417790 A 1156 1169 methylmercury SYSTEMATIC 23417790 A 1204 1206 Hg FORMULA 23417790 A 1239 1241 Hg FORMULA 23417790 A 1256 1258 Hg FORMULA 23417790 A 13 15 Hg FORMULA 23417790 A 1330 1332 Hg FORMULA 23417790 A 1444 1446 Hg FORMULA 23417790 A 1526 1528 Hg FORMULA 23417790 A 1600 1602 Hg FORMULA 23417790 A 249 251 Hg FORMULA 23417790 A 471 473 Hg FORMULA 23417790 A 571 573 Hg FORMULA 23417790 A 603 605 Hg FORMULA 23417790 A 791 793 Hg FORMULA 23417790 A 898 900 Hg FORMULA 23417790 A 988 1001 methylmercury SYSTEMATIC 23417790 T 17 24 mercury SYSTEMATIC 23417790 T 65 72 mercury SYSTEMATIC 23418006 A 135 143 catechol TRIVIAL 23418006 A 308 316 catechol TRIVIAL 23418006 A 505 513 catechol TRIVIAL 23418006 A 71 79 catechol TRIVIAL 23418006 T 73 82 Catechols FAMILY 23418011 A 1036 1048 γ-thialysine SYSTEMATIC 23418011 A 1088 1096 pyruvate TRIVIAL 23418011 A 1127 1139 γ-thialysine SYSTEMATIC 23418011 A 1183 1189 lysine TRIVIAL 23418011 A 1237 1247 thialysine SYSTEMATIC 23418011 A 127 130 Lys FORMULA 23418011 A 1344 1354 thialysine SYSTEMATIC 23418011 A 148 171 N-acetylneuraminic acid SYSTEMATIC 23418011 A 1512 1522 amino acid FAMILY 23418011 A 1714 1726 γ-thialysine SYSTEMATIC 23418011 A 404 412 cysteine TRIVIAL 23418011 A 480 488 cysteine TRIVIAL 23418011 A 501 504 Lys FORMULA 23418011 A 594 602 cysteine TRIVIAL 23418011 A 608 620 γ-thialysine SYSTEMATIC 23418011 A 629 643 dehydroalanine SYSTEMATIC 23418011 A 63 73 amino acid FAMILY 23418011 A 645 648 Dha ABBREVIATION 23418011 A 74 86 γ-thialysine SYSTEMATIC 23418011 A 745 757 γ-thialysine SYSTEMATIC 23418011 A 961 969 pyruvate TRIVIAL 23418011 T 135 141 lysine TRIVIAL 23418011 T 147 159 γ-thialysine SYSTEMATIC 23418011 T 62 85 N-acetylneuraminic acid SYSTEMATIC 23418059 A 1317 1342 polychlorinated biphenyls FAMILY 23418059 A 1432 1460 polybrominated diphenylether FAMILY 23418087 A 0 11 Bisphenol A TRIVIAL 23418087 A 1016 1023 phospho SYSTEMATIC 23418087 A 1141 1148 calcium SYSTEMATIC 23418087 A 1179 1186 calcium SYSTEMATIC 23418087 A 122 125 BPA ABBREVIATION 23418087 A 13 16 BPA ABBREVIATION 23418087 A 1305 1308 BPA ABBREVIATION 23418087 A 1319 1322 BPA ABBREVIATION 23418087 A 1350 1353 BPA ABBREVIATION 23418087 A 1407 1410 BPA ABBREVIATION 23418087 A 1436 1439 BPA ABBREVIATION 23418087 A 1453 1456 BPA ABBREVIATION 23418087 A 1514 1517 CpG ABBREVIATION 23418087 A 1608 1611 BPA ABBREVIATION 23418087 A 167 174 calcium SYSTEMATIC 23418087 A 284 287 BPA ABBREVIATION 23418087 A 419 422 BPA ABBREVIATION 23418087 A 580 583 BPA ABBREVIATION 23418087 A 679 682 BPA ABBREVIATION 23418087 A 873 876 BPA ABBREVIATION 23418087 A 890 897 calcium SYSTEMATIC 23418087 A 967 973 sodium SYSTEMATIC 23418087 A 974 981 calcium SYSTEMATIC 23418087 T 21 32 bisphenol a TRIVIAL 23418674 A 773 782 berberine TRIVIAL 23418674 A 856 861 EtOAc FORMULA 23418674 A 874 883 berberine TRIVIAL 23418674 A 989 998 berberine TRIVIAL 23418859 A 1136 1147 salidroside TRIVIAL 23418859 A 1165 1173 LY294002 IDENTIFIER 23418859 A 1273 1284 salidroside TRIVIAL 23418859 A 375 386 Salidroside TRIVIAL 23418859 A 390 401 salidroside TRIVIAL 23418859 A 418 426 LY294002 IDENTIFIER 23418859 A 47 58 salidroside TRIVIAL 23418859 A 556 560 dUTP ABBREVIATION 23418859 A 824 835 salidroside TRIVIAL 23418859 T 0 11 Salidroside TRIVIAL 23418880 A 117 143 (-)-sukhodianine-β-N-oxide SYSTEMATIC 23418880 A 149 158 palmatine TRIVIAL 23418880 A 164 175 corydalmine TRIVIAL 23418880 A 181 199 dehydrocorydalmine SYSTEMATIC 23418880 A 209 221 corynoxidine TRIVIAL 23418880 A 297 318 demethylaristofolin C SYSTEMATIC 23418880 A 32 53 demethylaristofolin C SYSTEMATIC 23418880 A 496 507 methicillin TRIVIAL 23418880 A 6 30 denitroaristolochic acid TRIVIAL 23418880 A 94 111 crebanine N-oxide SYSTEMATIC 23418880 T 20 44 denitroaristolochic acid TRIVIAL 23418960 A 1096 1099 PGN ABBREVIATION 23418960 A 1116 1121 CO(2) FORMULA 23418960 A 1152 1155 PGN ABBREVIATION 23418960 A 1214 1217 PGN ABBREVIATION 23418960 A 1234 1237 PGN ABBREVIATION 23418960 A 1301 1304 PGN ABBREVIATION 23418960 A 1376 1379 PGN ABBREVIATION 23418960 A 1466 1469 PGN ABBREVIATION 23418960 A 1523 1526 PGN ABBREVIATION 23418960 A 1604 1607 PGN ABBREVIATION 23418960 A 326 338 progesterone TRIVIAL 23418960 A 340 343 PGN ABBREVIATION 23418960 A 373 378 CO(2) FORMULA 23418960 A 407 410 PGN ABBREVIATION 23418960 A 474 493 polyethylene glycol SYSTEMATIC 23418960 A 495 498 PEG ABBREVIATION 23418960 A 518 526 Gelucire TRIVIAL 23418960 A 537 570 D-α-tocopheryl PEG 1000 succinate SYSTEMATIC 23418960 A 572 576 TPGS ABBREVIATION 23418960 A 604 607 PGN ABBREVIATION 23418960 A 911 914 PGN ABBREVIATION 23418960 T 36 48 progesterone TRIVIAL 23418960 T 81 95 carbon dioxide SYSTEMATIC 23419007 A 498 509 ketosteroid FAMILY 23419139 A 106 115 midazolam TRIVIAL 23419139 A 182 191 midazolam TRIVIAL 23419139 A 291 302 thalidomide TRIVIAL 23419139 A 374 393 1'-hydroxymidazolam SYSTEMATIC 23419139 A 423 434 thalidomide TRIVIAL 23419139 A 43 54 thalidomide TRIVIAL 23419139 A 557 575 4-hydroxymidazolam SYSTEMATIC 23419139 A 625 636 thalidomide TRIVIAL 23419139 A 781 792 thalidomide TRIVIAL 23419139 A 862 873 thalidomide TRIVIAL 23419139 T 43 54 thalidomide TRIVIAL 23419139 T 60 69 midazolam TRIVIAL 23419143 A 1031 1037 copper SYSTEMATIC 23419143 A 118 124 copper SYSTEMATIC 23419143 A 143 145 Si FORMULA 23419143 A 208 210 Pd FORMULA 23419143 A 440 442 Pd FORMULA 23419143 A 581 583 Au FORMULA 23419143 A 589 591 Cu FORMULA 23419143 A 774 780 copper SYSTEMATIC 23419143 A 921 923 Cu FORMULA 23419143 T 34 40 copper SYSTEMATIC 23419593 A 1511 1515 K(+) FORMULA 23419638 A 1044 1055 delphinidin TRIVIAL 23419638 A 1073 1085 pelargonidin TRIVIAL 23419638 A 1123 1137 anthocyanidins FAMILY 23419638 A 1178 1190 pelargonidin TRIVIAL 23419638 A 118 134 aryl hydrocarbon FAMILY 23419638 A 1263 1275 pelargonidin TRIVIAL 23419638 A 1280 1291 delphinidin TRIVIAL 23419638 A 27 41 anthocyanidins FAMILY 23419638 A 330 342 pelargonidin TRIVIAL 23419638 A 398 410 pelargonidin TRIVIAL 23419638 A 43 51 cyanidin TRIVIAL 23419638 A 522 554 2,3,7,8-tetrachlorodibenzodioxin SYSTEMATIC 23419638 A 53 64 delphinidin TRIVIAL 23419638 A 556 560 TCDD ABBREVIATION 23419638 A 644 656 pelargonidin TRIVIAL 23419638 A 66 74 malvidin TRIVIAL 23419638 A 722 726 TCDD ABBREVIATION 23419638 A 76 84 peonidin TRIVIAL 23419638 A 86 95 petunidin TRIVIAL 23419638 A 910 922 pelargonidin TRIVIAL 23419638 A 97 109 pelargonidin TRIVIAL 23419638 T 0 12 Pelargonidin TRIVIAL 23419783 A 1144 1156 sulfonylurea FAMILY 23419783 A 1199 1211 sulfonylurea FAMILY 23419783 A 1550 1559 metformin TRIVIAL 23419783 A 1579 1591 sulfonylurea FAMILY 23419783 A 217 226 metformin TRIVIAL 23419783 A 258 271 sulfonylureas FAMILY 23419783 A 528 537 metformin TRIVIAL 23419783 A 545 557 sulfonylurea FAMILY 23419783 A 558 571 sulfonylureas FAMILY 23419783 A 831 840 metformin TRIVIAL 23419783 A 883 892 metformin TRIVIAL 23419783 T 0 9 Metformin TRIVIAL 23419783 T 14 27 Sulfonylureas FAMILY 23419813 A 0 19 Polyethylene glycol SYSTEMATIC 23419813 A 262 274 ketoconazole TRIVIAL 23419813 A 57 64 acrylic SYSTEMATIC 23419813 A 850 853 PEG ABBREVIATION 23419813 A 86 95 6-carboxy SYSTEMATIC 23419814 A 310 318 fentanyl TRIVIAL 23419814 A 4 12 fentanyl TRIVIAL 23419814 A 568 576 fentanyl TRIVIAL 23419814 A 634 642 fentanyl TRIVIAL 23419814 T 28 36 fentanyl TRIVIAL 23419950 A 1004 1011 methoxy SYSTEMATIC 23419950 A 1023 1026 PEG ABBREVIATION 23419950 A 1161 1170 mannoside FAMILY 23419950 A 1182 1185 PEG ABBREVIATION 23419950 A 1200 1203 PEG ABBREVIATION 23419950 A 1237 1244 mannose TRIVIAL 23419950 A 1341 1350 mannoside FAMILY 23419950 A 1362 1365 PEG ABBREVIATION 23419950 A 1465 1472 methoxy SYSTEMATIC 23419950 A 1484 1487 PEG ABBREVIATION 23419950 A 1515 1522 methoxy SYSTEMATIC 23419950 A 1534 1537 PEG ABBREVIATION 23419950 A 1590 1597 methoxy SYSTEMATIC 23419950 A 1609 1612 PEG ABBREVIATION 23419950 A 166 173 mannose TRIVIAL 23419950 A 375 382 mannose TRIVIAL 23419950 A 650 653 PEG ABBREVIATION 23419950 A 731 739 hydroxyl SYSTEMATIC 23419950 A 741 748 methoxy SYSTEMATIC 23419950 A 753 762 mannoside FAMILY 23419950 A 914 922 hydroxyl SYSTEMATIC 23419950 A 934 937 PEG ABBREVIATION 23420115 A 12 23 Theobromine TRIVIAL 23420115 A 27 41 methylxanthine SYSTEMATIC 23420115 A 281 292 theobromine TRIVIAL 23420115 A 356 364 caffeine TRIVIAL 23420115 A 411 419 Caffeine TRIVIAL 23420115 A 516 527 Theobromine TRIVIAL 23420115 A 53 61 caffeine TRIVIAL 23420115 A 935 946 theobromine TRIVIAL 23420115 A 983 994 theobromine TRIVIAL 23420115 T 22 33 theobromine TRIVIAL 23420400 A 0 42 Trinitromethyl-substituted aminotetrazoles FAMILY 23420400 A 373 378 nitro SYSTEMATIC 23420400 A 402 411 tetrazole FAMILY 23420400 A 49 54 NH(2) FORMULA 23420400 A 57 62 NO(2) FORMULA 23420400 A 65 69 N(3) FORMULA 23420400 A 76 89 NHC(NO(2))(3) FORMULA 23420400 A 783 786 HMX ABBREVIATION 23420400 A 788 826 1,3,5,7-tetranitro-1,3,5,7-tetrazocine SYSTEMATIC 23420400 A 949 956 C-NO(2) FORMULA 23420400 T 115 156 trinitromethyl-substituted aminotetrazole FAMILY 23420471 A 1014 1018 TiO2 FORMULA 23420471 A 384 388 TiO2 FORMULA 23420471 A 584 588 P3HT ABBREVIATION 23420471 A 589 593 PCBM ABBREVIATION 23420471 A 636 640 TiO2 FORMULA 23420471 A 679 683 TiO2 FORMULA 23420471 A 952 956 TiO2 FORMULA 23420471 T 0 4 TiO2 FORMULA 23421331 A 1584 1593 metformin TRIVIAL 23421331 A 164 173 metformin TRIVIAL 23421331 A 370 379 metformin TRIVIAL 23421331 A 483 490 glucose TRIVIAL 23421331 T 52 61 metformin TRIVIAL 23421617 A 1071 1076 LAS-6 ABBREVIATION 23421617 A 1077 1085 linalool TRIVIAL 23421617 A 108 121 phenylethanol SYSTEMATIC 23421617 A 1104 1109 LAS-6 ABBREVIATION 23421617 A 1110 1118 linalool TRIVIAL 23421617 A 176 210 sodium dodecyl 6-benzene sulfonate SYSTEMATIC 23421617 A 212 217 LAS-6 ABBREVIATION 23421617 A 795 800 LAS-6 ABBREVIATION 23421617 A 865 873 linalool TRIVIAL 23421617 A 90 98 linalool TRIVIAL 23421617 A 962 967 LAS-6 ABBREVIATION 23421617 T 77 111 sodium dodecyl 6-benzene sulfonate SYSTEMATIC 23421714 A 0 18 (M)-Bicelaphanol A TRIVIAL 23421714 A 148 160 celaphanol A TRIVIAL 23421714 A 27 45 (P)-bicelaphanol A TRIVIAL 23421714 A 436 453 hydrogen peroxide SYSTEMATIC 23421714 T 0 27 (M)- and (P)-Bicelaphanol A MULTIPLE 23421714 T 37 53 Trinorditerpenes FAMILY 23421737 A 178 206 3-keton-desacetylcinobufagin SYSTEMATIC 23421737 A 212 238 3-epi-desacetylcinobufagin SYSTEMATIC 23421737 A 244 259 bufadienolide A TRIVIAL 23421737 A 269 300 15β,16α-dihydroxyl-17βH-bufalin SYSTEMATIC 23421737 A 47 67 desacetylcinobufagin TRIVIAL 23421737 T 34 54 desacetylcinobufagin TRIVIAL 23421743 A 239 246 CHCl(3) FORMULA 23421743 A 337 382 dorsamin-A763, -A737, -A765, -A739, and -A767 MULTIPLE 23421743 A 395 445 1,2-diacyl-sn-glycero-3-dehydrophenylalanine ester SYSTEMATIC 23421743 A 468 472 ABTS ABBREVIATION 23421743 A 508 518 dorsamin-A FAMILY 23421743 A 566 572 Trolox TRIVIAL 23421743 A 71 75 ABTS ABBREVIATION 23421743 T 0 10 Dorsamin-A FAMILY 23421743 T 39 59 Dehydrophenylalanine SYSTEMATIC 23421743 T 60 65 Ester SYSTEMATIC 23421877 A 210 230 sodium phenobarbital SYSTEMATIC 23421877 A 25 43 atractylenolide II TRIVIAL 23421877 A 533 565 4(R),15-epoxy-atractylenolide II SYSTEMATIC 23421877 A 573 615 4(R),15-epoxy-13-hydroxyatractylenolide II SYSTEMATIC 23421877 A 623 665 4(R),15-epoxy-1β-hydroxyatractylenolide II SYSTEMATIC 23421877 A 677 712 4(R),15-dihydroxyatractylenolide II SYSTEMATIC 23421877 A 753 771 atractylenolide II TRIVIAL 23421877 T 24 48 sesquiterpenoid lactones FAMILY 23421877 T 54 72 atractylenolide II TRIVIAL 23421877 T 9 18 eudesmane TRIVIAL 23422033 A 1132 1143 resveratrol TRIVIAL 23422033 A 203 214 resveratrol TRIVIAL 23422033 A 307 318 resveratrol TRIVIAL 23422033 A 420 431 resveratrol TRIVIAL 23422033 A 472 483 resveratrol TRIVIAL 23422033 A 586 597 resveratrol TRIVIAL 23422033 A 612 615 AMP ABBREVIATION 23422033 A 895 906 resveratrol TRIVIAL 23422033 T 0 11 Resveratrol TRIVIAL 23422034 A 386 392 phenol SYSTEMATIC 23422034 A 764 771 phenols FAMILY 23422226 A 121 128 steroid FAMILY 23422226 A 130 164 6-O-acyl-β-d-glucosyl-β-sitosterol SYSTEMATIC 23422226 A 171 187 klainedoxasterol TRIVIAL 23422226 A 240 253 triterpenoids FAMILY 23422226 A 265 273 steroids FAMILY 23422226 A 290 296 tanins FAMILY 23422226 A 30 75 2-hydroxy-24-methylenelanostan-1,8-dien-3-one SYSTEMATIC 23422226 A 423 432 lanostane TRIVIAL 23422226 A 438 451 triterpenoids FAMILY 23422226 A 6 28 lanostane triterpenoid FAMILY 23422226 A 610 618 xanthine TRIVIAL 23422226 A 726 734 xanthine TRIVIAL 23422226 A 82 103 klainedoxalanostenone TRIVIAL 23422226 T 0 9 Lanostane TRIVIAL 23422226 T 15 27 triterpenoid FAMILY 23422226 T 32 39 steroid FAMILY 23422227 A 123 137 sesquiterpenes FAMILY 23422227 A 31 41 chloroform TRIVIAL 23422227 T 10 24 sesquiterpenes FAMILY 23422263 A 1091 1099 E2-3,4-Q SYSTEMATIC 23422263 A 111 119 estrogen FAMILY 23422263 A 1242 1250 estrogen FAMILY 23422263 A 1321 1329 E2-3,4-Q SYSTEMATIC 23422263 A 134 142 E2-3,4-Q SYSTEMATIC 23422263 A 146 154 E2-2,3-Q SYSTEMATIC 23422263 A 204 212 estrogen FAMILY 23422263 A 300 317 estrogen quinones FAMILY 23422263 A 32 40 E2-2,3-Q SYSTEMATIC 23422263 A 46 71 17β-estradiol-3,4-quinone SYSTEMATIC 23422263 A 5 30 17β-estradiol-2,3-quinone SYSTEMATIC 23422263 A 507 516 cysteinyl TRIVIAL 23422263 A 528 536 E2-2,3-Q SYSTEMATIC 23422263 A 549 557 E2-3,4-Q SYSTEMATIC 23422263 A 691 699 E2-2,3-Q SYSTEMATIC 23422263 A 712 720 E2-3,4-Q SYSTEMATIC 23422263 A 73 81 E2-3,4-Q SYSTEMATIC 23422263 A 909 917 E2-3,4-Q SYSTEMATIC 23422263 A 987 995 E2-3,4-Q SYSTEMATIC 23422263 T 47 67 estrogen-3,4-quinone FAMILY 23422733 A 1086 1094 Soluplus TRIVIAL 23422733 A 1097 1113 polycaprolactone SYSTEMATIC 23422733 A 1119 1122 PEO ABBREVIATION 23422733 A 1128 1144 polycaprolactone SYSTEMATIC 23422733 A 1145 1148 PEO ABBREVIATION 23422733 A 1240 1248 Soluplus TRIVIAL 23422733 A 284 301 Diclofenac sodium SYSTEMATIC 23422733 A 896 904 Soluplus TRIVIAL 23422733 A 917 933 polycaprolactone SYSTEMATIC 23422733 A 946 949 PEO ABBREVIATION 23422872 A 205 214 peramivir TRIVIAL 23422872 T 69 78 peramivir TRIVIAL 23423243 A 1093 1113 acetylsalicylic acid SYSTEMATIC 23423243 A 1421 1429 warfarin TRIVIAL 23423243 A 1700 1720 acetylsalicylic acid SYSTEMATIC 23423243 A 51 59 warfarin TRIVIAL 23423243 A 612 620 warfarin TRIVIAL 23423243 T 24 32 warfarin TRIVIAL 23423353 A 384 397 Hoechst 33258 TRIVIAL 23423468 A 1019 1023 DAPI ABBREVIATION 23423468 A 22 51 4',6-diamidino-2-phenylindole SYSTEMATIC 23423468 A 53 57 DAPI ABBREVIATION 23423468 A 818 825 amidine SYSTEMATIC 23423468 T 88 92 DAPI ABBREVIATION 23423695 A 1042 1049 glucose TRIVIAL 23423695 A 1099 1106 glucose TRIVIAL 23423695 A 1196 1209 triglycerides FAMILY 23423695 A 1521 1528 glucose TRIVIAL 23423695 A 813 820 glucose TRIVIAL 23423710 A 1376 1383 Aza-CdR SYSTEMATIC 23423710 A 1635 1642 Aza-CdR SYSTEMATIC 23423710 A 362 384 5-Aza-2'-deoxycytidine SYSTEMATIC 23423710 A 386 393 Aza-CdR SYSTEMATIC 23423710 A 638 641 MTT ABBREVIATION 23423710 A 828 835 Aza-CdR SYSTEMATIC 23423710 A 946 953 Aza-CdR SYSTEMATIC 23423710 T 0 22 5-Aza-2'-deoxycytidine SYSTEMATIC 23423942 A 763 776 17β-estradiol SYSTEMATIC 23423942 A 780 794 17β-trenbolone SYSTEMATIC 23423942 T 105 115 trenbolone TRIVIAL 23423942 T 119 128 estradiol TRIVIAL 23423972 A 1227 1246 γ-aminobutyric acid SYSTEMATIC 23423972 A 1288 1297 N-nitroso SYSTEMATIC 23423972 A 1890 1899 N-nitroso SYSTEMATIC 23423972 A 233 272 hexahydro-1,3,5-trinitro-1,3,5-triazine SYSTEMATIC 23423972 A 418 464 hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine SYSTEMATIC 23423972 A 472 518 hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine SYSTEMATIC 23423972 A 530 571 hexahydro-1,3,5-trinitroso-1,3,5-triazine SYSTEMATIC 23423972 T 51 90 hexahydro-1,3,5-trinitro-1,3,5-triazine SYSTEMATIC 23424012 A 183 191 saponins FAMILY 23424012 A 325 333 oleanane TRIVIAL 23424012 A 339 347 saponins FAMILY 23424012 A 353 358 sugar FAMILY 23424012 A 37 56 longicarposides A-I MULTIPLE 23424012 A 429 437 saponins FAMILY 23424012 A 546 549 MTT ABBREVIATION 23424012 A 9 30 triterpenoid saponins FAMILY 23424012 A 90 98 saponins FAMILY 23424012 T 10 31 triterpenoid saponins FAMILY 23424028 A 1095 1105 permethrin TRIVIAL 23424028 A 1198 1208 permethrin TRIVIAL 23424028 A 190 210 pyrethoid permethrin TRIVIAL 23424028 A 376 386 Permethrin TRIVIAL 23424028 A 450 456 carbon SYSTEMATIC 23424028 T 55 65 permethrin TRIVIAL 23424207 A 0 7 Cadmium SYSTEMATIC 23424207 A 1027 1030 RUT ABBREVIATION 23424207 A 1035 1037 Se FORMULA 23424207 A 1047 1049 Cd FORMULA 23424207 A 1128 1130 Cd FORMULA 23424207 A 1192 1194 Se FORMULA 23424207 A 1203 1206 RUT ABBREVIATION 23424207 A 1211 1213 Se FORMULA 23424207 A 1291 1293 Cd FORMULA 23424207 A 1332 1334 Se FORMULA 23424207 A 135 140 rutin TRIVIAL 23424207 A 1356 1359 RUT ABBREVIATION 23424207 A 1379 1391 testosterone TRIVIAL 23424207 A 142 145 RUT ABBREVIATION 23424207 A 1432 1435 RUT ABBREVIATION 23424207 A 1440 1442 Se FORMULA 23424207 A 1480 1482 Cd FORMULA 23424207 A 161 169 selenium SYSTEMATIC 23424207 A 171 173 Se FORMULA 23424207 A 217 219 Cd FORMULA 23424207 A 368 370 Cd FORMULA 23424207 A 446 458 testosterone TRIVIAL 23424207 A 460 467 lactate FAMILY 23424207 A 560 577 3β-hydroxysteroid FAMILY 23424207 A 673 676 RUT ABBREVIATION 23424207 A 681 683 Se FORMULA 23424207 A 758 760 Cd FORMULA 23424207 A 850 860 superoxide TRIVIAL 23424207 A 894 905 glutathione TRIVIAL 23424207 A 9 11 Cd FORMULA 23424207 A 918 921 GSH ABBREVIATION 23424207 A 927 938 glutathione TRIVIAL 23424207 A 955 966 glutathione TRIVIAL 23424207 A 968 971 GSH ABBREVIATION 23424207 A 978 989 glutathione TRIVIAL 23424207 A 990 991 S FORMULA 23424207 T 0 5 Rutin TRIVIAL 23424207 T 11 19 Selenium SYSTEMATIC 23424207 T 31 38 cadmium SYSTEMATIC 23424208 A 1064 1074 Triparanol TRIVIAL 23424208 A 1085 1096 cholesterol TRIVIAL 23424208 A 1250 1258 probucol TRIVIAL 23424208 A 1312 1323 cholesterol TRIVIAL 23424208 A 1423 1434 cholesterol TRIVIAL 23424208 A 1446 1457 simvastatin TRIVIAL 23424208 A 1462 1472 triparanol TRIVIAL 23424208 A 265 273 probucol TRIVIAL 23424208 A 407 418 cholesterol TRIVIAL 23424208 A 436 444 probucol TRIVIAL 23424208 A 461 472 cholesterol TRIVIAL 23424208 A 481 492 simvastatin TRIVIAL 23424208 A 496 522 3-hydroxy-3-methylglutaryl SYSTEMATIC 23424208 A 559 569 triparanol TRIVIAL 23424208 A 573 589 3β-hydroxysterol FAMILY 23424208 A 61 70 potassium SYSTEMATIC 23424208 A 618 629 cholesterol TRIVIAL 23424208 A 765 773 Probucol TRIVIAL 23424208 A 790 801 cholesterol TRIVIAL 23424208 A 887 898 Simvastatin TRIVIAL 23424208 A 909 920 cholesterol TRIVIAL 23424208 T 0 8 Probucol TRIVIAL 23424208 T 17 28 cholesterol TRIVIAL 23424208 T 50 61 simvastatin TRIVIAL 23424208 T 66 76 triparanol TRIVIAL 23424212 A 1067 1070 MTX ABBREVIATION 23424212 A 1207 1210 MTX ABBREVIATION 23424212 A 1227 1230 RVT ABBREVIATION 23424212 A 1265 1268 MTX ABBREVIATION 23424212 A 1388 1391 RVT ABBREVIATION 23424212 A 1500 1503 MTX ABBREVIATION 23424212 A 153 164 resveratrol TRIVIAL 23424212 A 1547 1550 RVT ABBREVIATION 23424212 A 1588 1591 MTX ABBREVIATION 23424212 A 166 197 trans-3,5,4'-trihydroxystilbene SYSTEMATIC 23424212 A 1689 1692 RVT ABBREVIATION 23424212 A 1741 1744 MTX ABBREVIATION 23424212 A 199 202 RVT ABBREVIATION 23424212 A 212 215 MTX ABBREVIATION 23424212 A 296 299 MTX ABBREVIATION 23424212 A 384 387 MTX ABBREVIATION 23424212 A 390 393 RVT ABBREVIATION 23424212 A 428 431 RVT ABBREVIATION 23424212 A 455 458 RVT ABBREVIATION 23424212 A 495 498 MTX ABBREVIATION 23424212 A 52 64 methotrexate TRIVIAL 23424212 A 594 603 Aspartate TRIVIAL 23424212 A 628 635 alanine TRIVIAL 23424212 A 66 69 MTX ABBREVIATION 23424212 A 727 730 MTX ABBREVIATION 23424212 A 769 788 thiobarbituric acid SYSTEMATIC 23424212 A 922 933 glutathione TRIVIAL 23424212 A 934 935 S FORMULA 23424212 T 0 11 Resveratrol TRIVIAL 23424212 T 24 36 methotrexate TRIVIAL 23424213 A 1055 1058 GSH ABBREVIATION 23424213 A 1167 1170 MDA ABBREVIATION 23424213 A 1175 1177 NO FORMULA 23424213 A 433 440 alanine TRIVIAL 23424213 A 465 474 aspartate TRIVIAL 23424213 A 505 514 bilirubin TRIVIAL 23424213 A 529 533 urea TRIVIAL 23424213 A 534 542 nitrogen SYSTEMATIC 23424213 A 615 630 malondialdehyde TRIVIAL 23424213 A 632 635 MDA ABBREVIATION 23424213 A 638 649 glutathione TRIVIAL 23424213 A 651 654 GSH ABBREVIATION 23424213 A 663 673 superoxide TRIVIAL 23424213 A 694 706 nitric oxide SYSTEMATIC 23424213 A 708 710 NO FORMULA 23424213 A 823 834 hematoxylin TRIVIAL 23424213 A 839 844 eosin FAMILY 23425339 A 104 108 iron SYSTEMATIC 23425339 A 117 124 acetone SYSTEMATIC 23425339 A 144 149 FeCl2 FORMULA 23425339 A 180 186 Fe(II) FORMULA 23425339 A 269 281 Fe(H2O)6(2+) FORMULA 23425339 A 297 307 [FeCl4](-) FORMULA 23425339 A 317 324 acetone SYSTEMATIC 23425339 A 354 360 Fe(II) FORMULA 23425339 A 361 368 Fe(III) FORMULA 23425339 A 527 537 [FeCl4](-) FORMULA 23425339 A 549 556 acetone SYSTEMATIC 23425339 T 13 17 iron SYSTEMATIC 23425339 T 31 38 acetone SYSTEMATIC 23425601 A 176 220 3β, 7β, 21β-trihydroxy-urs-12-en-28-oic acid SYSTEMATIC 23425601 A 226 276 3β, 21β-dihydroxy-urs-11-en-28-oic acid-13-lactone SYSTEMATIC 23425601 A 28 40 ursolic acid TRIVIAL 23425601 A 282 326 1β, 3β, 21β-trihydroxy-urs-12-en-28-oic acid SYSTEMATIC 23425601 A 332 386 3β, 7β, 21β-trihydroxy-urs-1-en-28-oic acid-13-lactone SYSTEMATIC 23425601 A 396 441 21-oxo-1β, 3β-dihydroxy-urs-12-en-28-oic acid SYSTEMATIC 23425601 A 46 78 3β-hydroxy-urs-12-en-28-oic acid SYSTEMATIC 23425601 T 21 33 ursolic acid TRIVIAL 23425604 A 1131 1143 acetaldehyde SYSTEMATIC 23425604 A 1269 1281 acetaldehyde SYSTEMATIC 23425604 A 1381 1393 acetaldehyde SYSTEMATIC 23425604 A 204 225 [(13)C2]-acetaldehyde SYSTEMATIC 23425604 A 319 338 N (2)-ethylidene-dG SYSTEMATIC 23425604 A 59 77 N(2)-ethylidene-dG SYSTEMATIC 23425604 T 78 97 [13C2]-Acetaldehyde SYSTEMATIC 23425605 A 1003 1007 MeHg FORMULA 23425605 A 1032 1040 tyrosine TRIVIAL 23425605 A 1063 1079 α-methyltyrosine SYSTEMATIC 23425605 A 1114 1118 MeHg FORMULA 23425605 A 1139 1143 MeHg FORMULA 23425605 A 1216 1240 3-hydroxybenzylhydrazine SYSTEMATIC 23425605 A 1264 1268 MeHg FORMULA 23425605 A 1279 1287 tyrosine TRIVIAL 23425605 A 1347 1351 MeHg FORMULA 23425605 A 217 221 MeHg FORMULA 23425605 A 361 365 MeHg FORMULA 23425605 A 386 390 MeHg FORMULA 23425605 A 405 409 MeHg FORMULA 23425605 A 46 59 methylmercury SYSTEMATIC 23425605 A 464 468 MeHg FORMULA 23425605 A 550 554 MeHg FORMULA 23425605 A 61 65 MeHg FORMULA 23425605 A 618 622 MeHg FORMULA 23425605 A 707 714 calcium SYSTEMATIC 23425605 A 75 83 dopamine TRIVIAL 23425605 A 803 807 MeHg FORMULA 23425605 A 879 886 calcium SYSTEMATIC 23425605 A 888 892 MeHg FORMULA 23425605 T 20 33 catecholamine TRIVIAL 23425605 T 57 70 methylmercury SYSTEMATIC 23425605 T 89 97 dopamine TRIVIAL 23426609 A 456 469 phenobarbital TRIVIAL 23426609 A 471 480 phenytoin TRIVIAL 23426609 A 482 494 ethosuximide TRIVIAL 23426609 A 496 509 valproic acid TRIVIAL 23426609 A 511 521 vigabatrin TRIVIAL 23426609 A 523 531 tiagabin TRIVIAL 23426609 A 533 546 levitiracetam TRIVIAL 23426609 A 548 558 zonisamide TRIVIAL 23426609 A 564 574 lacosamide TRIVIAL 23426718 A 103 115 Paricalcitol TRIVIAL 23426718 A 1239 1251 paricalcitol TRIVIAL 23426718 A 129 138 vitamin D FAMILY 23426718 A 1448 1460 paricalcitol TRIVIAL 23426718 A 428 438 calcitriol TRIVIAL 23426718 A 480 492 paricalcitol TRIVIAL 23426718 T 29 41 paricalcitol TRIVIAL 23426954 A 1087 1095 CP55,940 IDENTIFIER 23426954 A 1188 1196 CP55,940 IDENTIFIER 23426954 A 1276 1284 CP55,940 IDENTIFIER 23426954 A 1290 1419 (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]-pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthalenyl)-methanone mesylate SYSTEMATIC 23426954 A 1421 1432 WIN55,212-2 IDENTIFIER 23426954 A 1487 1494 alanine TRIVIAL 23426954 A 1584 1592 CP55,940 IDENTIFIER 23426954 A 1597 1608 WIN55,212-2 IDENTIFIER 23426954 A 65 74 aspartate TRIVIAL 23426954 A 725 760 guanosine 5'-3-O-(thio)triphosphate TRIVIAL 23426954 A 862 973 N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride SYSTEMATIC 23426954 A 975 984 SR141716A IDENTIFIER 23426954 A 989 1085 (-)-3cis -[2-hydroxyl-4-(1,1-dimethyl-heptyl)phenyl]-trans-4-[3-hydroxyl-propyl] cyclohexan-1-ol SYSTEMATIC 23426982 A 0 30 Polybrominated diphenyl ethers FAMILY 23426982 A 1053 1061 nona-BDE ABBREVIATION 23426982 A 1097 1105 octa-BDE ABBREVIATION 23426982 A 1128 1130 Br FORMULA 23426982 A 1164 1173 octa-BDEs ABBREVIATION 23426982 A 1201 1203 Br FORMULA 23426982 A 32 37 PBDEs ABBREVIATION 23426982 A 337 346 nona-BDEs ABBREVIATION 23426982 A 350 358 methanol SYSTEMATIC 23426982 A 573 581 octa-BDE ABBREVIATION 23426982 A 625 634 nona-BDEs ABBREVIATION 23426982 A 759 768 nona-BDEs ABBREVIATION 23426982 A 874 882 nona-BDE ABBREVIATION 23426982 A 892 894 Br FORMULA 23426982 A 905 907 Br FORMULA 23426982 A 960 968 penta-Br FORMULA 23426982 A 973 981 tetra-Br FORMULA 23426982 A 994 1001 phenyls FAMILY 23426982 T 55 64 Nona-BDEs ABBREVIATION 23426982 T 68 76 Methanol SYSTEMATIC 23427007 A 1293 1298 25OHD SYSTEMATIC 23427007 A 138 147 vitamin D FAMILY 23427007 A 1440 1449 vitamin D FAMILY 23427007 A 1587 1592 25OHD SYSTEMATIC 23427007 A 291 300 vitamin D FAMILY 23427007 A 319 338 25-hydroxyvitamin D SYSTEMATIC 23427007 A 340 345 25OHD SYSTEMATIC 23427007 A 372 384 vitamin D(3) TRIVIAL 23427007 A 57 66 vitamin D FAMILY 23427007 A 660 672 vitamin D(3) TRIVIAL 23427007 A 786 798 vitamin D(3) TRIVIAL 23427007 A 868 873 25OHD SYSTEMATIC 23427007 A 974 986 vitamin D(3) TRIVIAL 23427007 T 54 66 vitamin D(3) TRIVIAL 23427007 T 86 105 25-hydroxyvitamin D SYSTEMATIC 23427056 A 1101 1111 creatinine TRIVIAL 23427056 A 129 136 glucose TRIVIAL 23427063 A 201 228 poly(methyl metha-acrylate) SYSTEMATIC 23427063 A 232 246 Disperse Red 1 TRIVIAL 23427064 A 227 234 cadmium SYSTEMATIC 23427064 A 385 387 Cd FORMULA 23427064 A 561 563 Cd FORMULA 23427064 A 744 746 Cd FORMULA 23427064 A 879 881 Cd FORMULA 23427064 A 953 955 Cd FORMULA 23427064 T 109 116 cadmium SYSTEMATIC 23427074 A 191 206 1,3- and 1,5-DP MULTIPLE 23427074 A 64 79 Dechlorane Plus TRIVIAL 23427074 A 847 853 carbon SYSTEMATIC 23427074 T 0 15 Dechlorane plus TRIVIAL 23427076 A 230 234 SiO2 FORMULA 23427076 A 250 252 Au FORMULA 23427088 A 1649 1665 Titanium dioxide SYSTEMATIC 23427088 A 211 224 pyrophosphate SYSTEMATIC 23427137 A 154 171 4-cyanoresorcinol SYSTEMATIC 23427137 A 186 196 azobenzene SYSTEMATIC 23427850 A 272 276 PDMS ABBREVIATION 23428155 A 1036 1045 linezolid TRIVIAL 23428155 A 159 185 benzoxazinyl-oxazolidinone SYSTEMATIC 23428155 A 285 294 linezolid TRIVIAL 23428155 A 436 443 pyridyl SYSTEMATIC 23428155 A 49 91 (pyridin-3-yl) benzoxazinyl-oxazolidinones FAMILY 23428155 A 556 569 Oxazolidinone SYSTEMATIC 23428155 A 595 602 pyridyl SYSTEMATIC 23428155 A 668 683 imidazolidinone SYSTEMATIC 23428155 T 34 76 (pyridin-3-yl) benzoxazinyl-oxazolidinones FAMILY 23428212 A 117 123 carbon SYSTEMATIC 23428212 A 146 182 2,2,6,6-tetramethylpiperidine-1-oxyl SYSTEMATIC 23428212 A 184 189 TEMPO ABBREVIATION 23428212 A 244 259 sodium carboxyl SYSTEMATIC 23428212 A 763 771 graphene TRIVIAL 23428212 T 64 69 TEMPO ABBREVIATION 23428212 T 97 103 Carbon SYSTEMATIC 23428325 A 172 187 brassinosteroid FAMILY 23428325 T 19 35 brassinosteroids FAMILY 23428347 A 1043 1053 bortezomib TRIVIAL 23428347 A 1217 1227 bortezomib TRIVIAL 23428347 A 1576 1586 bortezomib TRIVIAL 23428347 A 336 346 bortezomib TRIVIAL 23428347 A 718 728 bortezomib TRIVIAL 23428347 A 948 958 bortezomib TRIVIAL 23428347 T 0 10 Bortezomib TRIVIAL 23428841 A 0 17 Tamoxifen citrate SYSTEMATIC 23428841 A 1212 1221 Tamoxifen TRIVIAL 23428841 A 1316 1333 tamoxifen citrate SYSTEMATIC 23428841 A 1495 1498 TAM ABBREVIATION 23428841 A 178 187 tamoxifen TRIVIAL 23428841 A 19 22 TAM ABBREVIATION 23428841 A 314 323 tamoxifen TRIVIAL 23428841 A 350 353 TAM ABBREVIATION 23428841 A 390 399 tamoxifen TRIVIAL 23428841 A 418 421 TAM ABBREVIATION 23428841 A 583 586 TAM ABBREVIATION 23428841 A 644 653 tamoxifen TRIVIAL 23428841 A 674 682 lecithin FAMILY 23428841 A 810 819 tamoxifen TRIVIAL 23428841 A 87 95 lecithin FAMILY 23428841 A 902 905 TAM ABBREVIATION 23428841 A 954 971 tamoxifen citrate SYSTEMATIC 23428841 T 0 8 Lecithin FAMILY 23428841 T 57 74 tamoxifen citrate SYSTEMATIC 23429043 A 0 26 1,2-Benzisothiazolin-3-one SYSTEMATIC 23429043 A 1005 1008 BIT ABBREVIATION 23429043 A 1020 1023 BIT ABBREVIATION 23429043 A 1105 1108 BIT ABBREVIATION 23429043 A 114 117 BIT ABBREVIATION 23429043 A 1375 1378 BIT ABBREVIATION 23429043 A 28 31 BIT ABBREVIATION 23429043 A 313 316 BIT ABBREVIATION 23429043 A 39 48 2634-33-5 IDENTIFIER 23429043 A 662 665 BIT ABBREVIATION 23429043 T 62 88 1,2-benzisothiazolin-3-one SYSTEMATIC 23429043 T 90 93 BIT ABBREVIATION 23429184 A 518 519 N FORMULA 23429184 A 792 798 Ca(2+) FORMULA 23429184 A 816 820 PMSF ABBREVIATION 23429184 A 824 831 lactose TRIVIAL 23429184 A 868 874 serine TRIVIAL 23429231 A 1056 1059 NVP ABBREVIATION 23429231 A 1384 1393 RhodaminB TRIVIAL 23429231 A 1420 1423 NVP ABBREVIATION 23429231 A 322 365 poly[acrylonitrile-co-(N-vinylpyrrolidone)] SYSTEMATIC 23429231 A 471 489 N-vinylpyrrolidone SYSTEMATIC 23429231 A 491 494 NVP ABBREVIATION 23429231 A 570 573 NVP ABBREVIATION 23429231 A 791 794 NVP ABBREVIATION 23429282 A 263 279 sesquiterpenoids FAMILY 23429282 A 281 287 avarol TRIVIAL 23429282 A 822 848 avarol and its monoacetate MULTIPLE 23429889 A 1130 1142 rosuvastatin TRIVIAL 23429889 A 1301 1313 Rosuvastatin TRIVIAL 23429889 A 131 143 rosuvastatin TRIVIAL 23429889 A 1459 1471 rosuvastatin TRIVIAL 23429889 A 147 158 cholesterol TRIVIAL 23429889 A 1549 1561 rosuvastatin TRIVIAL 23429889 A 1793 1805 rosuvastatin TRIVIAL 23429889 A 1854 1866 rosuvastatin TRIVIAL 23429889 A 372 384 rosuvastatin TRIVIAL 23429889 A 489 501 rosuvastatin TRIVIAL 23429889 T 45 57 rosuvastatin TRIVIAL 23429911 A 1149 1187 7-hydroxy-N,N-dipropyl-2-aminotetralin SYSTEMATIC 23429911 A 1189 1198 7-OH-DPAT SYSTEMATIC 23429911 A 4 12 dopamine TRIVIAL 23429911 A 467 480 retinoic acid TRIVIAL 23429911 A 628 641 dexamethasone TRIVIAL 23429911 T 49 57 dopamine TRIVIAL 23430408 A 1020 1032 thiamethoxam TRIVIAL 23430408 A 1273 1285 thiamethoxam TRIVIAL 23430408 A 544 556 thiamethoxam TRIVIAL 23430408 A 872 877 (14)C FORMULA 23430408 T 26 38 thiamethoxam TRIVIAL 23430761 A 1021 1032 ondansetron TRIVIAL 23430761 A 311 321 poloxamers FAMILY 23430761 A 323 327 P407 IDENTIFIER 23430761 A 33 44 ondansetron TRIVIAL 23430761 A 332 336 P188 IDENTIFIER 23430761 A 342 361 hydroxypropylmethyl SYSTEMATIC 23430761 A 755 766 ondansetron TRIVIAL 23430761 A 844 848 P407 IDENTIFIER 23430761 A 850 854 P188 IDENTIFIER 23430761 T 25 36 ondansetron TRIVIAL 23432004 A 497 507 gadolinium SYSTEMATIC 23432004 A 509 511 Gd FORMULA 23432004 A 576 578 Gd FORMULA 23432004 A 778 780 Gd FORMULA 23432004 A 975 977 Gd FORMULA 23432004 T 0 2 Gd FORMULA 23432007 A 200 206 (89)Zr FORMULA 23432007 A 277 283 (89)Zr FORMULA 23432007 A 300 315 desferrioxamine TRIVIAL 23432007 A 317 320 DFO ABBREVIATION 23432007 A 34 40 (89)Zr FORMULA 23432007 A 488 494 lysine TRIVIAL 23432007 A 589 595 lysine TRIVIAL 23432007 A 614 623 N-suc-DFO FORMULA 23432007 A 627 637 DFO-Bz-NCS FORMULA 23432007 A 758 764 (89)Zr FORMULA 23432007 A 913 919 (89)Zr FORMULA 23432007 T 0 6 (89)Zr FORMULA 23432061 A 154 158 Ca2+ FORMULA 23432061 A 303 307 Ca2+ FORMULA 23432095 A 135 143 androgen FAMILY 23432095 A 167 175 androgen FAMILY 23432095 A 224 232 androgen FAMILY 23432095 A 320 329 androgens FAMILY 23432095 A 454 476 5α-dihydrotestosterone SYSTEMATIC 23432095 A 478 490 Indomethacin TRIVIAL 23432095 A 655 667 indomethacin TRIVIAL 23432095 A 914 926 testosterone TRIVIAL 23432095 A 971 978 NADP(+) ABBREVIATION 23432095 A 979 1005 2'-des-methyl-indomethacin SYSTEMATIC 23432095 T 36 48 indomethacin TRIVIAL 23432095 T 96 114 17β-hydroxysteroid SYSTEMATIC 23432151 A 271 281 Silica gel TRIVIAL 23432151 A 353 366 ethyl acetate SYSTEMATIC 23432151 A 368 380 acetonitrile SYSTEMATIC 23432151 A 385 405 carbon tetrachloride SYSTEMATIC 23432151 A 447 467 benzopranyl capriate TRIVIAL 23432151 A 469 533 9H-1-isoprenyl-benzopyran-5-isopropanoic acid-6-ol-6-n-decanoate SYSTEMATIC 23432151 A 536 552 shorghumoic acid TRIVIAL 23432151 A 554 590 n-octadec-8,11-dien-7α-ol-1-oic acid SYSTEMATIC 23432151 A 596 611 sorghumflavin A TRIVIAL 23432151 A 613 662 2-n-butyloxo-6-β-hydroxy-7-β-isoprenyl ankaflavin SYSTEMATIC 23432151 A 706 721 hordeumflavin B TRIVIAL 23432151 A 723 764 2-n-undecanyloxo-7-β-isoprenyl ankaflavin SYSTEMATIC 23432151 A 770 783 vulgaredilone TRIVIAL 23432151 A 785 824 2-dodecanyl-7-β isopranyl monoscodilone SYSTEMATIC 23432203 A 330 337 α-amino SYSTEMATIC 23432203 A 36 37 N FORMULA 23432203 A 47 58 amino acids FAMILY 23432203 A 912 931 p-chloroamphetamine SYSTEMATIC 23432335 A 119 155 (Z)-13,15-hexadecadien-2,4-diyn-1-ol SYSTEMATIC 23432335 A 42 59 montiporic acid D TRIVIAL 23432335 A 6 35 polyacetylene carboxylic acid FAMILY 23432335 A 96 117 polyacetylene alcohol FAMILY 23432335 T 0 17 Montiporic acid D TRIVIAL 23432335 T 25 54 polyacetylene carboxylic acid FAMILY 23432582 A 0 27 Bisacylimidoselenocarbamate SYSTEMATIC 23432582 A 1074 1077 BSC ABBREVIATION 23432582 A 1122 1125 BSC ABBREVIATION 23432582 A 158 176 phosphatidylserine FAMILY 23432582 A 221 224 BSC ABBREVIATION 23432582 A 373 376 BSC ABBREVIATION 23432582 A 41 44 BSC ABBREVIATION 23432582 A 477 480 BSC ABBREVIATION 23432582 A 824 827 BSC ABBREVIATION 23432582 A 936 945 z-VAD-fmk ABBREVIATION 23432582 T 0 28 Bisacylimidoselenocarbamates FAMILY 23432586 A 1410 1416 Ca(2+) FORMULA 23432586 A 179 183 Ca2+ FORMULA 23432586 A 348 352 Ca2+ FORMULA 23432586 A 440 450 tacrolimus TRIVIAL 23432586 A 452 457 FK506 IDENTIFIER 23432586 A 463 472 sirolimus TRIVIAL 23432586 A 474 483 rapamycin TRIVIAL 23432586 A 493 497 Ca2+ FORMULA 23432586 A 920 925 FK506 IDENTIFIER 23432586 A 970 976 Ca(2+) FORMULA 23432587 A 1002 1012 technetium SYSTEMATIC 23432587 A 1014 1021 rhenium SYSTEMATIC 23432587 A 1023 1031 samarium SYSTEMATIC 23432587 A 1036 1046 gadolinium SYSTEMATIC 23432587 A 1198 1209 phosphonate SYSTEMATIC 23432587 A 1462 1478 aminophosphonate SYSTEMATIC 23432587 A 562 583 aminophosphonic acids FAMILY 23432587 A 825 841 aminophosphonate SYSTEMATIC 23432587 A 855 863 platinum SYSTEMATIC 23432587 T 0 16 Aminophosphonate SYSTEMATIC 23432708 A 0 18 Carbon monosulfide SYSTEMATIC 23432708 A 1290 1292 CS FORMULA 23432708 A 20 22 CS FORMULA 23432708 A 207 209 CS FORMULA 23432708 A 386 388 CS FORMULA 23432708 A 814 816 CS FORMULA 23433812 A 0 3 ATP ABBREVIATION 23433812 A 226 234 arsenate SYSTEMATIC 23433812 A 271 274 ATP ABBREVIATION 23433812 A 563 567 dNTP ABBREVIATION 23433812 A 611 619 arsenate SYSTEMATIC 23433812 A 658 662 dNTP ABBREVIATION 23433812 A 863 867 dNTP ABBREVIATION 23433812 T 13 17 dNTP ABBREVIATION 23434226 A 500 503 Tyr FORMULA 23434226 A 570 578 tyrosine TRIVIAL 23434228 A 105 110 DEACM ABBREVIATION 23434228 A 113 138 6-bromo-7-hydroxycoumarin SYSTEMATIC 23434228 A 140 143 BHC ABBREVIATION 23434228 A 149 174 6-bromo-7-methoxycoumarin SYSTEMATIC 23434228 A 176 180 BMCM ABBREVIATION 23434228 A 23 31 coumarin TRIVIAL 23434228 A 264 267 BHC ABBREVIATION 23434228 A 268 279 cholesterol TRIVIAL 23434228 A 38 50 cholesterols FAMILY 23434228 A 81 103 6-diethylaminocoumarin SYSTEMATIC 23434228 T 40 48 coumarin TRIVIAL 23434228 T 55 66 cholesterol TRIVIAL 23434322 A 117 120 caC ABBREVIATION 23434322 A 161 169 cytosine TRIVIAL 23434322 A 21 37 5-methylcytosine SYSTEMATIC 23434322 A 283 286 hmC ABBREVIATION 23434322 A 55 70 5-hydroxymethyl SYSTEMATIC 23434322 A 678 681 hmC ABBREVIATION 23434322 A 72 75 hmC ABBREVIATION 23434322 A 731 734 hmC ABBREVIATION 23434322 A 78 86 5-formyl SYSTEMATIC 23434322 A 97 115 5-carboxylcytosine SYSTEMATIC 23434322 T 20 45 5-(hydroxy)methylcytosine SYSTEMATIC 23434422 A 17 31 sesquiterpenes FAMILY 23434422 A 177 205 bicyclic furanosesquiterpene SYSTEMATIC 23434422 A 285 310 α,β-unsaturated-γ-lactone SYSTEMATIC 23434422 A 33 49 euryspongins A-C MULTIPLE 23434422 A 331 336 furan SYSTEMATIC 23434422 A 625 645 dehydroeuryspongin A SYSTEMATIC 23434422 T 0 16 Euryspongins A-C MULTIPLE 23434422 T 35 49 sesquiterpenes FAMILY 23434491 A 1012 1014 E2 FORMULA 23434491 A 1061 1068 steroid FAMILY 23434491 A 1212 1215 KTC ABBREVIATION 23434491 A 1277 1280 KTC ABBREVIATION 23434491 A 1392 1395 KTC ABBREVIATION 23434491 A 1477 1480 KTC ABBREVIATION 23434491 A 1501 1503 E2 FORMULA 23434491 A 306 319 17β-estradiol SYSTEMATIC 23434491 A 321 323 E2 FORMULA 23434491 A 329 341 ketoconazole TRIVIAL 23434491 A 343 346 KTC ABBREVIATION 23434491 A 536 553 7-ethoxyresorufin SYSTEMATIC 23434491 A 554 555 O FORMULA 23434491 A 605 607 E2 FORMULA 23434491 A 749 751 E2 FORMULA 23434491 A 859 867 estrogen FAMILY 23434491 A 947 949 E2 FORMULA 23434491 A 954 957 KTC ABBREVIATION 23434491 T 15 28 17β-estradiol SYSTEMATIC 23434491 T 33 45 ketoconazole TRIVIAL 23434641 A 1023 1033 rifampicin TRIVIAL 23434641 A 139 202 5-(2-benzylsulfanyl-pyridin-3-yl)-3H-[1,3,4]oxadiazole-2-thione SYSTEMATIC 23434641 A 18 94 5-(2-benzylsulfanyl-pyridin-3-yl)-2-(substituted)-sulfanyl-1,3,4-oxadiazoles FAMILY 23434641 A 285 296 haloacetate FAMILY 23434641 A 301 310 haloalkyl FAMILY 23434641 A 422 423 C FORMULA 23434641 A 425 426 H FORMULA 23434641 A 428 429 N FORMULA 23434641 A 779 792 benzothiazole SYSTEMATIC 23434641 A 883 893 ampicillin TRIVIAL 23434641 A 920 928 triazole FAMILY 23434641 A 933 943 morpholine SYSTEMATIC 23434641 T 4 35 2-benzylsulfanyl-nicotinic acid SYSTEMATIC 23434641 T 42 59 1,3,4-oxadiazoles FAMILY 23434648 A 1052 1053 C FORMULA 23434648 A 1137 1140 LPA ABBREVIATION 23434648 A 1292 1295 LPA ABBREVIATION 23434648 A 427 430 LPA ABBREVIATION 23434648 A 632 635 LPA ABBREVIATION 23434648 A 786 789 LPA ABBREVIATION 23434669 A 24 33 rapamycin TRIVIAL 23434669 A 506 515 Rapamycin TRIVIAL 23434669 A 842 845 ATP ABBREVIATION 23434669 T 76 85 Rapamycin TRIVIAL 23434929 A 1097 1111 Corticosterone TRIVIAL 23434929 A 1215 1228 Catecholamine FAMILY 23434929 A 1354 1368 corticosterone TRIVIAL 23434929 A 24 36 somatostatin TRIVIAL 23434929 A 344 358 Streptozotocin TRIVIAL 23434929 A 86 100 corticosterone TRIVIAL 23434929 T 33 45 Somatostatin TRIVIAL 23434931 A 601 612 tunicamycin TRIVIAL 23434931 A 932 938 oxygen SYSTEMATIC 23434934 A 122 132 nucleotide FAMILY 23435179 A 483 492 disulfide SYSTEMATIC 23435179 A 925 938 acetylcholine SYSTEMATIC 23435356 A 0 9 Serotonin TRIVIAL 23435356 A 1008 1012 5-HT SYSTEMATIC 23435356 A 1057 1061 5-HT SYSTEMATIC 23435356 A 11 15 5-HT SYSTEMATIC 23435356 A 166 170 5-HT SYSTEMATIC 23435356 A 235 245 Tryptophan TRIVIAL 23435356 A 295 299 5-HT SYSTEMATIC 23435356 A 94 98 5-HT SYSTEMATIC 23435356 T 0 10 Tryptophan TRIVIAL 23435615 A 1008 1026 omeprazole sulfone TRIVIAL 23435615 A 1105 1128 (R)-5-hydroxyomeprazole SYSTEMATIC 23435615 A 1220 1243 (S)-5-hydroxyomeprazole SYSTEMATIC 23435615 A 1256 1270 (R)-omeprazole TRIVIAL 23435615 A 1422 1436 (S)-omeprazole TRIVIAL 23435615 A 1483 1497 (R)-omeprazole TRIVIAL 23435615 A 1553 1571 racemic-omeprazole SYSTEMATIC 23435615 A 235 249 (R)-omeprazole TRIVIAL 23435615 A 278 296 racemic omeprazole SYSTEMATIC 23435615 A 676 686 omeprazole TRIVIAL 23435615 A 715 725 omeprazole TRIVIAL 23435615 A 871 894 (R)- and (S)-omeprazole MULTIPLE 23435615 A 9 19 Omeprazole TRIVIAL 23435615 T 4 18 (R)-omeprazole TRIVIAL 23435910 A 0 12 Sinapic acid TRIVIAL 23435910 A 1006 1018 sinapic acid TRIVIAL 23435910 A 1078 1081 DMN ABBREVIATION 23435910 A 1292 1304 sinapic acid TRIVIAL 23435910 A 249 261 sinapic acid TRIVIAL 23435910 A 265 284 dimethylnitrosamine SYSTEMATIC 23435910 A 286 289 DMN ABBREVIATION 23435910 A 32 47 phenylpropanoid SYSTEMATIC 23435910 A 329 341 Sinapic acid TRIVIAL 23435910 A 363 366 DMN ABBREVIATION 23435910 A 462 469 alanine TRIVIAL 23435910 A 484 493 aspartate TRIVIAL 23435910 A 518 533 malondialdehyde TRIVIAL 23435910 A 556 568 sinapic acid TRIVIAL 23435910 A 585 599 hydroxyproline SYSTEMATIC 23435910 A 913 925 sinapic acid TRIVIAL 23435910 A 927 939 Sinapic acid TRIVIAL 23435910 T 10 22 sinapic acid TRIVIAL 23435910 T 31 50 dimethylnitrosamine SYSTEMATIC 23435913 A 1094 1103 tadalafil TRIVIAL 23435913 A 141 150 tadalafil TRIVIAL 23435913 A 204 213 Tadalafil TRIVIAL 23435913 A 218 228 acebutolol TRIVIAL 23435913 A 297 320 tert-butyl methyl ether SYSTEMATIC 23435913 A 437 448 formic acid SYSTEMATIC 23435913 A 453 465 acetonitrile SYSTEMATIC 23435913 A 918 927 Tadalafil TRIVIAL 23435913 T 98 107 tadalafil TRIVIAL 23435916 A 0 11 Pristimerin TRIVIAL 23435916 A 15 42 quinonemethide triterpenoid FAMILY 23435916 A 243 254 pristimerin TRIVIAL 23435916 A 281 292 Pristimerin TRIVIAL 23435916 A 331 343 nitric oxide SYSTEMATIC 23435916 A 345 347 NO FORMULA 23435916 A 353 369 prostaglandin E2 TRIVIAL 23435916 A 408 410 NO FORMULA 23435916 A 524 535 pristimerin TRIVIAL 23435916 A 716 727 pristimerin TRIVIAL 23435916 T 28 39 pristimerin TRIVIAL 23435942 A 1049 1056 tacrine TRIVIAL 23435942 A 1058 1067 donepezil TRIVIAL 23435942 A 1069 1081 rivastigmine TRIVIAL 23435942 A 1083 1094 galantamine TRIVIAL 23435942 A 1096 1110 xanthostigmine TRIVIAL 23435942 A 1112 1134 para-aminobenzoic acid SYSTEMATIC 23435942 A 1136 1144 coumarin TRIVIAL 23435942 A 1146 1155 flavonoid FAMILY 23435942 A 1161 1178 pyrrolo-isoxazole SYSTEMATIC 23435942 A 530 543 acetylcholine SYSTEMATIC 23435942 A 896 909 acetylcholine SYSTEMATIC 23435948 A 1024 1049 3,5-dicaffeoylquinic acid SYSTEMATIC 23435948 A 1051 1089 3,5-dicaffeoylquinic acid methyl ester SYSTEMATIC 23435948 A 1091 1116 4,5-dicaffeoylquinic acid SYSTEMATIC 23435948 A 1118 1139 3-caffeoylquinic acid SYSTEMATIC 23435948 A 1150 1158 chromone TRIVIAL 23435948 A 1160 1172 capillarisin TRIVIAL 23435948 A 1198 1207 esculetin TRIVIAL 23435948 A 1209 1219 scopoletin TRIVIAL 23435948 A 1221 1230 quercetin TRIVIAL 23435948 A 1232 1242 hyperoside TRIVIAL 23435948 A 1244 1256 isorhamnetin TRIVIAL 23435948 A 1258 1296 3,5-dicaffeoylquinic acid methyl ester SYSTEMATIC 23435948 A 1298 1323 3,4-dicaffeoylquinic acid SYSTEMATIC 23435948 A 1329 1354 1,5-dicaffeoylquinic acid SYSTEMATIC 23435948 A 136 144 methanol SYSTEMATIC 23435948 A 1444 1452 acarbose TRIVIAL 23435948 A 1467 1476 esculetin TRIVIAL 23435948 A 1481 1504 6-methoxy artemicapin C SYSTEMATIC 23435948 A 1570 1592 dicaffeoylquinic acids FAMILY 23435948 A 1897 1906 coumarins FAMILY 23435948 A 1908 1918 flavonoids FAMILY 23435948 A 1924 1946 dicaffeoylquinic acids FAMILY 23435948 A 226 234 tyrosine TRIVIAL 23435948 A 263 271 methanol SYSTEMATIC 23435948 A 379 387 methanol SYSTEMATIC 23435948 A 656 665 coumarins FAMILY 23435948 A 667 676 esculetin TRIVIAL 23435948 A 678 685 esculin TRIVIAL 23435948 A 687 695 scopolin TRIVIAL 23435948 A 697 708 isoscopolin TRIVIAL 23435948 A 710 719 daphnetin TRIVIAL 23435948 A 721 734 umbelliferone TRIVIAL 23435948 A 736 754 7-methoxy coumarin SYSTEMATIC 23435948 A 756 765 scoparone TRIVIAL 23435948 A 767 777 scopoletin TRIVIAL 23435948 A 779 802 6-methoxy artemicapin C SYSTEMATIC 23435948 A 807 817 flavonoids FAMILY 23435948 A 819 829 hyperoside TRIVIAL 23435948 A 831 840 quercetin TRIVIAL 23435948 A 842 854 isorhamnetin TRIVIAL 23435948 A 856 867 cirsilineol TRIVIAL 23435948 A 869 879 arcapillin TRIVIAL 23435948 A 881 909 isorhamnetin 3-robinobioside SYSTEMATIC 23435948 A 911 918 linarin TRIVIAL 23435948 A 920 945 isorhamnetin 3-glucoiside SYSTEMATIC 23435948 A 950 958 phenolic FAMILY 23435948 A 970 995 1,5-dicaffeoylquinic acid SYSTEMATIC 23435948 A 997 1022 3,4-dicaffeoylquinic acid SYSTEMATIC 23435948 T 33 41 tyrosine TRIVIAL 23436129 A 1101 1112 acamprosate TRIVIAL 23436129 A 1396 1407 Acamprosate TRIVIAL 23436129 A 1660 1671 acamprosate TRIVIAL 23436129 A 1747 1758 acamprosate TRIVIAL 23436129 A 391 400 glutamate TRIVIAL 23436129 A 415 438 gamma-aminobutyric acid SYSTEMATIC 23436129 A 440 444 GABA ABBREVIATION 23436129 A 529 540 acamprosate TRIVIAL 23436129 A 611 622 Acamprosate TRIVIAL 23436129 T 10 21 acamprosate TRIVIAL 23436266 A 0 11 Allopurinol TRIVIAL 23436266 A 1076 1083 statins FAMILY 23436266 A 1172 1183 allopurinol TRIVIAL 23436266 A 1223 1233 colchicine TRIVIAL 23436266 A 1237 1244 statins FAMILY 23436266 A 1284 1295 allopurinol TRIVIAL 23436266 A 140 151 allopurinol TRIVIAL 23436266 A 223 234 allopurinol TRIVIAL 23436266 A 328 339 allopurinol TRIVIAL 23436266 A 43 52 uric acid TRIVIAL 23436266 A 476 487 allopurinol TRIVIAL 23436266 A 654 665 cholesterol TRIVIAL 23436266 A 688 697 aspartate TRIVIAL 23436266 A 730 737 alanine TRIVIAL 23436266 A 850 861 colchicines FAMILY 23436266 A 888 895 statins FAMILY 23436266 A 995 1006 colchicines FAMILY 23436266 T 44 55 allopurinol TRIVIAL 23436544 A 0 11 Vemurafenib TRIVIAL 23436544 A 136 147 vemurafenib TRIVIAL 23436544 A 203 214 vemurafenib TRIVIAL 23436544 A 412 423 Vemurafenib TRIVIAL 23436544 A 774 785 vemurafenib TRIVIAL 23436544 T 0 11 Vemurafenib TRIVIAL 23436791 A 1049 1052 ATP ABBREVIATION 23436791 A 1069 1072 ATP ABBREVIATION 23436791 A 11 17 serine TRIVIAL 23436791 A 1240 1250 paclitaxel TRIVIAL 23436791 A 18 27 threonine TRIVIAL 23436791 A 351 354 ATP ABBREVIATION 23436791 A 367 384 indolyl-pyrrolone SYSTEMATIC 23436791 A 545 548 ATP ABBREVIATION 23436791 A 595 610 2-aminothiazole SYSTEMATIC 23436791 A 670 673 ATP ABBREVIATION 23436791 A 846 862 2-aminothiazoles FAMILY 23436791 A 957 960 ATP ABBREVIATION 23436791 T 78 81 ATP ABBREVIATION 23437766 A 189 199 amantadine TRIVIAL 23437766 A 22 32 amantadine TRIVIAL 23437766 A 37 48 rimantadine TRIVIAL 23437766 A 715 721 benzyl SYSTEMATIC 23437766 A 734 744 amantadine TRIVIAL 23437766 A 809 855 4-(adamantan-1-ylaminomethyl)-benzene-1,3-diol SYSTEMATIC 23437926 A 0 9 Hecogenin TRIVIAL 23437926 A 1012 1023 naltrindole TRIVIAL 23437926 A 1068 1081 glibenclamide TRIVIAL 23437926 A 1083 1086 ATP ABBREVIATION 23437926 A 1097 1101 K(+) FORMULA 23437926 A 194 211 hecogenin acetate SYSTEMATIC 23437926 A 854 862 naloxone TRIVIAL 23437926 A 915 919 CTOP ABBREVIATION 23437926 A 961 968 nor-BNI ABBREVIATION 23437926 T 103 120 Hecogenin Acetate SYSTEMATIC 23438500 A 178 183 Br(-) FORMULA 23438500 A 209 211 Pd FORMULA 23438500 A 230 235 Br(-) FORMULA 23438500 A 267 269 Pd FORMULA 23438500 A 345 347 Pd FORMULA 23438500 A 370 375 Br(-) FORMULA 23438500 A 528 530 Pd FORMULA 23438500 A 694 699 Br(-) FORMULA 23438500 A 733 735 Pd FORMULA 23438500 A 792 797 Br(-) FORMULA 23438500 T 117 119 Pd FORMULA 23438500 T 49 52 Br- FORMULA 23438500 T 61 63 Pd FORMULA 23438503 A 1077 1088 atomoxetine TRIVIAL 23438503 A 1125 1140 methylphenidate SYSTEMATIC 23438503 A 1386 1401 methylphenidate SYSTEMATIC 23438503 A 1443 1454 atomoxetine TRIVIAL 23438503 A 160 171 atomoxetine TRIVIAL 23438503 A 254 265 atomoxetine TRIVIAL 23438503 A 417 428 atomoxetine TRIVIAL 23438503 A 493 504 atomoxetine TRIVIAL 23438503 A 579 590 atomoxetine TRIVIAL 23438503 A 793 804 Atomoxetine TRIVIAL 23438503 T 21 32 atomoxetine TRIVIAL 23439033 A 565 581 hydrofluoroether SYSTEMATIC 23439131 A 133 154 poly(ethylene glycol) SYSTEMATIC 23439131 A 156 159 PEG ABBREVIATION 23439131 A 312 315 PEG ABBREVIATION 23439223 A 257 264 steroid FAMILY 23439223 A 486 498 testosterone TRIVIAL 23439223 A 500 509 estradiol TRIVIAL 23439223 A 515 523 cortisol TRIVIAL 23439223 T 81 88 steroid FAMILY 23439241 A 974 984 phenacetin TRIVIAL 23439241 A 989 998 bupropion TRIVIAL 23439561 A 1265 1274 thymidine TRIVIAL 23439561 A 1294 1298 PGE2 ABBREVIATION 23439561 A 141 157 prostaglandin E2 TRIVIAL 23439561 A 1475 1479 PGE2 ABBREVIATION 23439561 A 159 163 PGE2 ABBREVIATION 23439561 A 272 276 PGE2 ABBREVIATION 23439561 A 293 308 prostaglandin E FAMILY 23439561 A 354 358 PGE2 ABBREVIATION 23439561 A 729 733 PGE2 ABBREVIATION 23439561 A 749 758 thymidine TRIVIAL 23439561 A 787 792 NADPH ABBREVIATION 23439561 A 828 835 calcium SYSTEMATIC 23439561 A 935 944 thymidine TRIVIAL 23439561 A 964 968 PGE2 ABBREVIATION 23439561 T 0 5 NADPH ABBREVIATION 23439561 T 76 91 Prostaglandin E FAMILY 23439649 A 1129 1138 thioester SYSTEMATIC 23439649 A 1346 1349 Phe FORMULA 23439649 A 14 20 (125)I FORMULA 23439649 A 680 688 oxyester SYSTEMATIC 23439660 A 1291 1300 oxycodone TRIVIAL 23439660 A 1327 1339 noroxycodone TRIVIAL 23439660 A 1344 1355 oxymorphone TRIVIAL 23439660 A 1366 1375 oxycodone TRIVIAL 23439660 A 1522 1531 oxycodone TRIVIAL 23439660 A 1576 1585 oxycodone TRIVIAL 23439660 A 1794 1803 oxycodone TRIVIAL 23439660 A 276 286 androstane TRIVIAL 23439660 A 307 323 Aryl hydrocarbon FAMILY 23439660 A 489 498 oxycodone TRIVIAL 23439660 T 82 91 oxycodone TRIVIAL 23440404 A 1008 1011 BDT ABBREVIATION 23440404 A 1294 1300 Au-S-C FORMULA 23440404 A 1315 1323 Au-S-C-C FORMULA 23440404 A 275 277 Au FORMULA 23440404 A 292 304 thiol sulfur SYSTEMATIC 23440404 A 66 89 gold-1,4-benzenedithiol SYSTEMATIC 23440404 A 91 94 BDT ABBREVIATION 23440404 A 974 977 C=C FORMULA 23440664 A 300 304 cGMP ABBREVIATION 23440664 A 481 493 Nikkomycin Z TRIVIAL 23440664 A 50 62 Nikkomycin Z TRIVIAL 23440664 A 63 66 HCl FORMULA 23440664 T 73 85 Nikkomycin Z TRIVIAL 23440956 A 0 7 Silicon SYSTEMATIC 23440956 A 1008 1016 graphene TRIVIAL 23440956 A 1121 1123 Si FORMULA 23440956 A 1145 1153 graphene TRIVIAL 23440956 A 1202 1204 Si FORMULA 23440956 A 1305 1307 Si FORMULA 23440956 A 1324 1332 graphene TRIVIAL 23440956 A 1406 1414 graphene TRIVIAL 23440956 A 1419 1421 Si FORMULA 23440956 A 152 154 Si FORMULA 23440956 A 1569 1577 graphene TRIVIAL 23440956 A 1591 1593 Si FORMULA 23440956 A 1708 1715 lithium SYSTEMATIC 23440956 A 357 359 Si FORMULA 23440956 A 396 404 graphene TRIVIAL 23440956 A 471 473 Si FORMULA 23440956 A 492 506 graphene oxide SYSTEMATIC 23440956 A 559 561 Si FORMULA 23440956 A 608 622 graphene oxide SYSTEMATIC 23440956 A 632 634 Si FORMULA 23440956 A 656 670 graphene oxide SYSTEMATIC 23440956 A 69 76 lithium SYSTEMATIC 23440956 A 695 697 Si FORMULA 23440956 A 761 763 Si FORMULA 23440956 A 790 798 graphene TRIVIAL 23440956 A 812 814 Si FORMULA 23440956 A 897 905 graphene TRIVIAL 23440956 A 9 11 Si FORMULA 23440956 T 0 8 Graphene TRIVIAL 23440956 T 34 36 Si FORMULA 23440956 T 55 62 Lithium SYSTEMATIC 23441753 A 1030 1037 pNIPAAm ABBREVIATION 23441753 A 19 55 hydrated poly(N-isopropylacrylamide) SYSTEMATIC 23441753 A 226 235 Isoniazid TRIVIAL 23441753 A 390 399 Isoniazid TRIVIAL 23441753 A 577 586 Isoniazid TRIVIAL 23441753 A 82 91 Isoniazid TRIVIAL 23441753 T 59 86 poly(N-isopropylacrylamide) SYSTEMATIC 23441816 A 299 305 Ca(2+) FORMULA 23441816 A 4 10 Ca(2+) FORMULA 23441816 A 537 543 Ca(2+) FORMULA 23441816 T 0 6 Ca(2+) FORMULA 23441829 A 195 199 V2O5 FORMULA 23441829 A 20 24 V2O5 FORMULA 23441829 A 215 223 n-butane SYSTEMATIC 23441829 A 225 230 C4H10 FORMULA 23441829 A 244 250 V2O5H2 FORMULA 23441829 A 270 278 hydrogen SYSTEMATIC 23441829 A 298 303 C4H10 FORMULA 23441829 A 307 311 V2O5 FORMULA 23441829 A 323 327 C4H8 FORMULA 23441829 A 374 378 V2O5 FORMULA 23441829 A 441 446 C4H10 FORMULA 23441829 A 533 537 V2O5 FORMULA 23441829 A 557 562 C4H10 FORMULA 23441829 A 597 601 V2O5 FORMULA 23441829 A 736 742 V2O5H2 FORMULA 23441829 A 825 829 V2O5 FORMULA 23441829 A 842 846 V2O5 FORMULA 23441829 A 867 871 C2H6 FORMULA 23441829 A 880 886 V2O5H2 FORMULA 23441829 A 891 895 C2H4 FORMULA 23441829 A 979 983 V2O5 FORMULA 23441829 A 984 988 C2H6 FORMULA 23441829 T 30 42 hydrocarbons FAMILY 23441829 T 66 71 oxide SYSTEMATIC 23441829 T 7 10 C-H FORMULA 23441843 A 1070 1073 Lig ABBREVIATION 23441843 A 1178 1181 Lig ABBREVIATION 23441843 A 1287 1290 Lig ABBREVIATION 23441843 A 1592 1595 Lig ABBREVIATION 23441843 A 535 548 Z-Ligustilide SYSTEMATIC 23441843 A 550 553 Lig ABBREVIATION 23441843 A 631 634 Lig ABBREVIATION 23441843 A 726 729 Lig ABBREVIATION 23441843 A 863 872 Bisulfite SYSTEMATIC 23441843 A 906 909 Lig ABBREVIATION 23441843 T 99 112 Z-ligustilide SYSTEMATIC 23441878 A 104 109 CHBr3 FORMULA 23441878 A 1140 1142 Br FORMULA 23441878 A 1165 1170 CHBr3 FORMULA 23441878 A 120 124 CHI3 FORMULA 23441878 A 1270 1275 CHBr2 FORMULA 23441878 A 1276 1278 Br FORMULA 23441878 A 135 139 CCl4 FORMULA 23441878 A 205 206 C FORMULA 23441878 A 207 208 H FORMULA 23441878 A 243 259 polyhalomethanes FAMILY 23441878 A 308 309 C FORMULA 23441878 A 310 311 H FORMULA 23441878 A 375 382 halogen FAMILY 23441878 A 406 407 C FORMULA 23441878 A 470 475 CHBr2 FORMULA 23441878 A 476 478 Br FORMULA 23441878 A 506 510 CHI2 FORMULA 23441878 A 511 512 I FORMULA 23441878 A 929 934 CHBr3 FORMULA 23441878 T 34 39 CHBr3 FORMULA 23441878 T 44 48 CHI3 FORMULA 23442005 A 1022 1039 amino sulfonamide SYSTEMATIC 23442005 A 1044 1051 proline TRIVIAL 23442005 A 153 162 aldehydes FAMILY 23442005 A 308 315 enamine SYSTEMATIC 23442005 A 339 357 aliphatic aldehyde FAMILY 23442005 A 449 464 3-methylbutanal SYSTEMATIC 23442005 A 471 478 enamine SYSTEMATIC 23442005 A 493 510 α-chloroaldehydes FAMILY 23442005 A 516 524 carbonyl FAMILY 23442005 A 52 59 proline TRIVIAL 23442005 A 602 603 C FORMULA 23442005 A 604 605 C FORMULA 23442005 A 633 640 enamine SYSTEMATIC 23442005 A 670 678 aldehyde SYSTEMATIC 23442005 A 692 699 proline TRIVIAL 23442005 A 711 728 amino sulfonamide SYSTEMATIC 23442005 A 79 96 amino sulfonamide SYSTEMATIC 23442005 A 883 902 aliphatic aldehydes FAMILY 23442005 A 916 927 α-methylene SYSTEMATIC 23442005 T 78 97 Aliphatic Aldehydes FAMILY 23442025 A 136 141 argon SYSTEMATIC 23442025 A 319 332 Fe(CN)(6)(3–) FORMULA 23442025 A 337 343 methyl SYSTEMATIC 23442025 A 71 72 H FORMULA 23442025 A 75 80 OH(–) FORMULA 23442025 A 83 88 H(2)O FORMULA 23442151 A 0 6 Phenol SYSTEMATIC 23442151 A 1031 1038 benzene SYSTEMATIC 23442151 A 1139 1145 phenol SYSTEMATIC 23442151 A 1165 1171 phenol SYSTEMATIC 23442151 A 138 145 benzene SYSTEMATIC 23442151 A 166 185 sodium hypochlorite SYSTEMATIC 23442151 A 260 279 sodium hypochlorite SYSTEMATIC 23442151 A 296 315 sodium hypochlorite SYSTEMATIC 23442151 A 342 348 phenol SYSTEMATIC 23442151 A 412 431 sodium hypochlorite SYSTEMATIC 23442151 A 445 451 phenol SYSTEMATIC 23442151 A 51 58 benzene SYSTEMATIC 23442151 A 521 540 sodium hypochlorite SYSTEMATIC 23442151 A 555 561 phenol SYSTEMATIC 23442151 A 567 586 sodium hypochlorite SYSTEMATIC 23442151 A 672 678 oxygen SYSTEMATIC 23442151 A 715 718 •OH FORMULA 23442151 A 726 727 H FORMULA 23442151 A 729 731 H2 FORMULA 23442151 A 737 741 H2O2 FORMULA 23442151 A 760 766 phenol SYSTEMATIC 23442151 A 772 791 sodium hypochlorite SYSTEMATIC 23442151 A 79 98 sodium hypochlorite SYSTEMATIC 23442151 A 807 811 NaCl FORMULA 23442151 A 862 868 phenol SYSTEMATIC 23442151 A 874 881 benzene SYSTEMATIC 23442151 A 896 915 sodium hypochlorite SYSTEMATIC 23442151 A 958 966 chlorine SYSTEMATIC 23442151 A 974 993 Sodium hypochlorite SYSTEMATIC 23442151 T 0 6 Phenol SYSTEMATIC 23442151 T 48 55 benzene SYSTEMATIC 23442151 T 70 89 sodium hypochlorite SYSTEMATIC 23442197 A 0 7 A-74528 IDENTIFIER 23442197 A 13 27 C30 polyketide FAMILY 23442197 A 322 329 A-74528 IDENTIFIER 23442197 A 471 485 fredericamycin TRIVIAL 23442197 A 592 599 A-74528 IDENTIFIER 23442197 A 709 716 A-74528 IDENTIFIER 23442197 A 965 972 A-74528 IDENTIFIER 23442197 A 991 1005 fredericamycin TRIVIAL 23442197 T 32 39 A-74528 IDENTIFIER 23443405 A 1104 1111 silicon SYSTEMATIC 23443405 A 201 204 ZnO FORMULA 23443405 A 45 52 silicon SYSTEMATIC 23443405 A 668 675 silicon SYSTEMATIC 23443405 A 676 679 ZnO FORMULA 23443405 A 77 87 zinc oxide SYSTEMATIC 23443405 A 89 92 ZnO FORMULA 23443405 A 939 942 ZnO FORMULA 23443405 T 72 74 Si FORMULA 23443405 T 75 78 ZnO FORMULA 23443408 A 0 16 Titanium dioxide SYSTEMATIC 23443408 A 265 269 TiO2 FORMULA 23443408 A 32 36 TiO2 FORMULA 23443408 A 335 339 TiO2 FORMULA 23443408 A 576 580 TiO2 FORMULA 23443408 A 748 758 nucleotide FAMILY 23443408 A 765 771 O-Ti-O FORMULA 23443408 A 987 993 oxygen SYSTEMATIC 23443408 T 46 62 titanium dioxide SYSTEMATIC 23443628 A 1172 1181 donepezil TRIVIAL 23443628 A 1186 1195 memantine TRIVIAL 23443628 A 1393 1402 donepezil TRIVIAL 23443628 A 1407 1416 memantine TRIVIAL 23443628 A 1664 1676 rivastigmine TRIVIAL 23443628 A 1681 1690 donepezil TRIVIAL 23443628 A 2025 2034 memantine TRIVIAL 23443628 A 2058 2067 donepezil TRIVIAL 23443628 A 39 48 memantine TRIVIAL 23443628 A 585 594 donepezil TRIVIAL 23443628 A 596 608 rivastigmine TRIVIAL 23443628 A 610 621 galantamine TRIVIAL 23443628 A 626 635 memantine TRIVIAL 23443957 A 1168 1174 oxygen SYSTEMATIC 23443957 A 1240 1246 oxygen SYSTEMATIC 23443957 A 292 298 oxygen SYSTEMATIC 23443957 A 42 48 oxygen SYSTEMATIC 23443957 A 544 550 oxygen SYSTEMATIC 23443957 A 573 644 platinum(ii)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorphenyl)-porphyrin SYSTEMATIC 23443957 A 646 652 PtTFPP ABBREVIATION 23443957 A 817 823 oxygen SYSTEMATIC 23443957 A 97 103 oxygen SYSTEMATIC 23443957 T 13 19 oxygen SYSTEMATIC 23444256 A 105 112 Truvada TRIVIAL 23444256 A 1169 1172 FTC ABBREVIATION 23444256 A 1173 1176 TDF ABBREVIATION 23444256 A 1482 1485 FTC ABBREVIATION 23444256 A 1486 1489 TDF ABBREVIATION 23444256 A 1707 1710 FTC ABBREVIATION 23444256 A 1711 1714 TDF ABBREVIATION 23444256 A 1831 1834 FTC ABBREVIATION 23444256 A 1835 1838 TDF ABBREVIATION 23444256 A 273 276 FTC ABBREVIATION 23444256 A 277 280 TDF ABBREVIATION 23444256 A 30 43 emtricitabine TRIVIAL 23444256 A 45 48 FTC ABBREVIATION 23444256 A 564 567 FTC ABBREVIATION 23444256 A 568 571 TDF ABBREVIATION 23444256 A 61 90 tenofovir disoproxil fumarate TRIVIAL 23444256 A 743 746 FTC ABBREVIATION 23444256 A 747 750 TDF ABBREVIATION 23444256 A 92 95 TDF ABBREVIATION 23444256 T 0 13 Emtricitabine TRIVIAL 23444256 T 14 43 tenofovir disoproxil fumarate TRIVIAL 23444284 A 1090 1100 nevirapine TRIVIAL 23444284 A 1143 1153 nevirapine TRIVIAL 23444284 A 12 22 nevirapine TRIVIAL 23444284 A 1277 1287 nevirapine TRIVIAL 23444284 A 1370 1380 nevirapine TRIVIAL 23444284 A 241 251 nevirapine TRIVIAL 23444284 A 573 583 nevirapine TRIVIAL 23444284 A 837 847 nevirapine TRIVIAL 23444284 T 41 51 nevirapine TRIVIAL 23444335 A 302 306 iron SYSTEMATIC 23444335 A 587 591 zinc SYSTEMATIC 23444335 A 596 604 selenium SYSTEMATIC 23444335 A 766 774 selenium SYSTEMATIC 23444335 A 779 783 zinc SYSTEMATIC 23444335 T 35 39 iron SYSTEMATIC 23444387 A 1014 1023 menadione TRIVIAL 23444387 A 1050 1058 carbonyl FAMILY 23444387 A 482 493 haloperidol TRIVIAL 23444387 A 495 506 mebendazole TRIVIAL 23444387 A 512 523 ziprasidone TRIVIAL 23444387 A 821 832 haloperidol TRIVIAL 23444387 A 837 848 mebendazole TRIVIAL 23444387 A 889 894 NADPH ABBREVIATION 23444387 A 903 907 NADH ABBREVIATION 23444389 A 1084 1087 Rb1 ABBREVIATION 23444389 A 1134 1137 Rb1 ABBREVIATION 23444389 A 1175 1178 ATP ABBREVIATION 23444389 A 1182 1185 ADP ABBREVIATION 23444389 A 1218 1226 Ca(2)(+) FORMULA 23444389 A 1266 1271 azide SYSTEMATIC 23444389 A 1304 1313 diazoxide SYSTEMATIC 23444389 A 1332 1340 Ca(2)(+) FORMULA 23444389 A 1357 1367 nifedipine TRIVIAL 23444389 A 1399 1402 Rb1 ABBREVIATION 23444389 A 1469 1481 ginsenosides FAMILY 23444389 A 1563 1575 ginsenosides FAMILY 23444389 A 296 303 glucose TRIVIAL 23444389 A 422 430 saponins FAMILY 23444389 A 498 513 Ginsenoside Rb1 TRIVIAL 23444389 A 515 518 Rb1 ABBREVIATION 23444389 A 58 70 Ginsenosides FAMILY 23444389 A 721 735 streptozotocin TRIVIAL 23444389 A 954 961 glucose TRIVIAL 23444389 T 87 99 ginsenosides FAMILY 23444429 A 1055 1071 poly(ADP-ribose) SYSTEMATIC 23444773 A 334 345 mitomycin C TRIVIAL 23444773 A 347 350 MMC ABBREVIATION 23444773 A 353 362 cisplatin TRIVIAL 23444782 A 588 598 sibutramin TRIVIAL 23444782 A 672 679 alanine TRIVIAL 23444782 A 707 716 aspartate TRIVIAL 23444783 A 1175 1178 Glu FORMULA 23444783 A 1309 1312 Glu FORMULA 23444783 A 518 527 glutamate TRIVIAL 23444783 A 529 532 Glu FORMULA 23444783 A 629 632 Glu FORMULA 23444783 A 647 650 Glu FORMULA 23444783 T 140 149 glutamate TRIVIAL 23444785 A 429 444 Malondialdehyde TRIVIAL 23444785 A 446 449 MDA ABBREVIATION 23444785 A 452 462 superoxide TRIVIAL 23444785 A 658 661 MDA ABBREVIATION 23444785 A 724 727 MDA ABBREVIATION 23444833 A 141 165 lystabactins A, B, and C MULTIPLE 23444833 A 255 265 amino acid FAMILY 23444833 A 289 301 lystabactins FAMILY 23444833 A 318 324 serine TRIVIAL 23444833 A 326 329 Ser FORMULA 23444833 A 332 342 asparagine TRIVIAL 23444833 A 344 347 Asn FORMULA 23444833 A 354 388 formylated/hydroxylated ornithines MULTIPLE 23444833 A 390 396 FOHOrn ABBREVIATION 23444833 A 399 421 dihydroxy benzoic acid SYSTEMATIC 23444833 A 423 426 Dhb ABBREVIATION 23444833 A 448 475 nonproteinogenic amino acid NO CLASS 23444833 A 477 511 4,8-diamino-3-hydroxyoctanoic acid SYSTEMATIC 23444833 A 513 518 LySta ABBREVIATION 23444833 T 38 42 Iron SYSTEMATIC 23444833 T 65 77 Lystabactins FAMILY 23445125 A 499 511 erythromycin TRIVIAL 23445125 A 662 668 amines FAMILY 23445125 A 763 775 erythromycin TRIVIAL 23445362 A 101 103 Zn FORMULA 23445362 A 104 114 superoxide TRIVIAL 23445362 A 31 51 aryloxanylpyrazolone FAMILY 23445362 A 4 26 arylsulfanylpyrazolone FAMILY 23445362 A 403 424 arylazanylpyrazolones FAMILY 23445362 A 534 544 pyrazolone SYSTEMATIC 23445362 A 639 645 phenol SYSTEMATIC 23445362 A 668 678 pyrazolone SYSTEMATIC 23445362 A 722 742 arylazanylpyrazolone FAMILY 23445362 A 98 100 Cu FORMULA 23445362 T 0 20 Arylazanylpyrazolone FAMILY 23445362 T 57 67 superoxide TRIVIAL 23445497 A 131 143 camptothecin TRIVIAL 23445497 A 145 155 paclitaxel TRIVIAL 23445497 A 157 168 doxorubicin TRIVIAL 23445497 A 173 182 docetaxel TRIVIAL 23445497 A 226 251 phenyl O-carboxyanhydride SYSTEMATIC 23445497 A 253 260 Phe-OCA ABBREVIATION 23445497 A 282 289 Phe-OCA ABBREVIATION 23445497 A 329 334 PheLA ABBREVIATION 23445497 A 695 706 polylactide FAMILY 23445497 A 716 721 PheLA ABBREVIATION 23445497 A 99 107 hydroxyl SYSTEMATIC 23445497 T 105 129 poly(O-carboxyanhydride) FAMILY 23445497 T 46 65 O-carboxyanhydrides FAMILY 23446230 A 1012 1016 EETs ABBREVIATION 23446230 A 106 110 EETs ABBREVIATION 23446230 A 1440 1444 EETs ABBREVIATION 23446230 A 212 216 EETs ABBREVIATION 23446230 A 53 70 arachidonic acids FAMILY 23446230 A 572 576 EETs ABBREVIATION 23446230 A 79 104 epoxyeicosatrienoic acids FAMILY 23446230 A 903 907 EETs ABBREVIATION 23446230 T 32 36 EETs ABBREVIATION 23446276 A 1051 1057 Mg(2+) FORMULA 23446276 A 1281 1285 urea TRIVIAL 23446276 A 533 540 adenine TRIVIAL 23446276 A 948 955 adenine TRIVIAL 23447132 A 1108 1112 cAMP ABBREVIATION 23447132 A 1182 1186 cAMP ABBREVIATION 23447132 A 148 152 cAMP ABBREVIATION 23447132 A 1656 1660 cAMP ABBREVIATION 23447132 A 220 227 calcium SYSTEMATIC 23447132 A 41 45 cAMP ABBREVIATION 23447132 A 429 433 cAMP ABBREVIATION 23447132 A 462 466 cAMP ABBREVIATION 23447132 A 507 511 cAMP ABBREVIATION 23447132 A 566 576 nucleotide FAMILY 23447132 A 827 831 cAMP ABBREVIATION 23447132 A 857 861 cAMP ABBREVIATION 23447132 T 39 43 cAMP ABBREVIATION 23447132 T 66 70 cAMP ABBREVIATION 23447427 A 192 198 Cu(2+) FORMULA 23447427 A 206 214 ZnIn2 S4 FORMULA 23447427 A 329 331 H2 FORMULA 23447427 A 38 46 sulphide SYSTEMATIC 23447427 A 95 101 copper SYSTEMATIC 23447427 T 140 148 hydrogen SYSTEMATIC 23447427 T 52 60 sulphide SYSTEMATIC 23447538 A 1538 1545 tryptic FAMILY 23447538 A 1915 1921 serine TRIVIAL 23447538 A 39 45 serine TRIVIAL 23447538 T 92 98 serine TRIVIAL 23448196 A 267 274 glucose TRIVIAL 23448196 A 288 295 glucose TRIVIAL 23448202 T 112 129 cadmium telluride SYSTEMATIC 23448384 A 1042 1049 ethanol SYSTEMATIC 23448384 A 1059 1067 methanol SYSTEMATIC 23448384 A 1069 1073 MeOH FORMULA 23448384 A 1122 1128 Hfa(-) ABBREVIATION 23448384 A 1189 1201 [dppz][H2fa] ABBREVIATION 23448384 A 1222 1246 [H-dppz(+)][Hfa(-)]·MeOH FORMULA 23448384 A 133 141 hydrogen SYSTEMATIC 23448384 A 1393 1412 [H-dppz(+)][Hfa(-)] FORMULA 23448384 A 1486 1498 [dppz][H2fa] ABBREVIATION 23448384 A 21 33 anilic acids FAMILY 23448384 A 213 226 [H-dppz][Hca] ABBREVIATION 23448384 A 231 244 [H-dppz][Hba] ABBREVIATION 23448384 A 246 250 H2ca ABBREVIATION 23448384 A 253 269 chloranilic acid TRIVIAL 23448384 A 271 275 H2ba ABBREVIATION 23448384 A 278 293 bromanilic acid TRIVIAL 23448384 A 35 39 H2xa ABBREVIATION 23448384 A 406 414 hydrogen SYSTEMATIC 23448384 A 45 72 2,3-di(2-pyridinyl)pyrazine SYSTEMATIC 23448384 A 598 606 hydrogen SYSTEMATIC 23448384 A 731 735 dppz ABBREVIATION 23448384 A 74 78 dppz ABBREVIATION 23448384 A 740 744 H2ba ABBREVIATION 23448384 A 816 836 [H(1.5)-dppz]2[Hba]3 FORMULA 23448384 A 868 889 [H-dppz]2[Hba]2[H2ba] FORMULA 23448384 A 910 914 dppz ABBREVIATION 23448384 A 936 952 fluoranilic acid TRIVIAL 23448384 A 954 958 H2fa ABBREVIATION 23448384 A 993 997 H2fa ABBREVIATION 23448384 T 101 113 anilic acids FAMILY 23448384 T 118 145 2,3-di(2-pyridinyl)pyrazine SYSTEMATIC 23448384 T 58 66 hydrogen SYSTEMATIC 23448620 A 527 557 carbazochrome sodium sulfonate SYSTEMATIC 23448620 A 690 700 tinidazole TRIVIAL 23448682 A 284 293 tetrazine FAMILY 23448682 A 294 304 norbornene TRIVIAL 23448682 A 565 568 PEG ABBREVIATION 23448682 A 569 578 tetrazine FAMILY 23448682 A 607 619 dinorbornene TRIVIAL 23448682 A 786 795 tetrazine FAMILY 23448682 A 796 806 norbornene TRIVIAL 23448682 A 877 882 thiol FAMILY 23448682 A 883 886 ene SYSTEMATIC 23448682 A 970 979 tetrazine FAMILY 23448682 T 88 97 tetrazine FAMILY 23448682 T 98 108 norbornene TRIVIAL 23448860 A 1016 1025 manganese SYSTEMATIC 23448860 A 128 137 manganese SYSTEMATIC 23448860 A 139 141 Mn FORMULA 23448860 A 294 296 Mn FORMULA 23448860 A 421 423 Mn FORMULA 23448860 A 619 621 Mn FORMULA 23448860 A 758 760 Mn FORMULA 23448860 A 810 812 Mn FORMULA 23448860 A 844 846 Mn FORMULA 23448860 A 901 903 Mn FORMULA 23448860 A 931 933 Mn FORMULA 23448860 T 47 56 manganese SYSTEMATIC 23448861 A 1124 1132 ethenone SYSTEMATIC 23448861 A 1137 1151 crotonaldehyde TRIVIAL 23448861 A 248 256 ethenone SYSTEMATIC 23448861 A 261 275 crotonaldehyde TRIVIAL 23448861 A 385 393 ethenone SYSTEMATIC 23448861 A 398 412 crotonaldehyde TRIVIAL 23448861 A 688 694 oxygen SYSTEMATIC 23448861 A 782 788 oxygen SYSTEMATIC 23448861 T 85 93 ethenone SYSTEMATIC 23448861 T 98 112 crotonaldehyde TRIVIAL 23449201 A 1057 1064 lactose TRIVIAL 23449201 A 124 131 Lactose TRIVIAL 23449201 A 1258 1265 lactose TRIVIAL 23449201 A 213 226 hydroxypropyl SYSTEMATIC 23449201 A 238 258 hydroxypropyl methyl SYSTEMATIC 23449201 A 274 294 polyvinylpyrrolidone SYSTEMATIC 23449201 A 449 456 lactose TRIVIAL 23449205 A 124 156 (3R),(5S)-5-hydroxylasiodiplodin SYSTEMATIC 23449205 A 184 188 EtOH FORMULA 23449205 A 23 30 lactone FAMILY 23449205 A 32 64 (3S),(6R)-6-hydroxylasiodiplodin SYSTEMATIC 23449205 A 96 114 (3R)-lasiodiplodin TRIVIAL 23449205 T 0 13 Lasiodiplodin TRIVIAL 23449220 A 1034 1037 FdU ABBREVIATION 23449220 A 1050 1055 FdUMP ABBREVIATION 23449220 A 316 330 deoxythymidine SYSTEMATIC 23449220 A 649 673 5-fluoro-2'-deoxyuridine SYSTEMATIC 23449220 A 675 678 FdU ABBREVIATION 23449220 A 873 876 FdU ABBREVIATION 23449220 A 891 894 FdU ABBREVIATION 23449220 T 54 78 5-fluoro-2'-deoxyuridine SYSTEMATIC 23450151 A 230 237 cadmium SYSTEMATIC 23450151 A 255 257 Zn FORMULA 23450151 A 258 260 Ag FORMULA 23450151 A 261 263 In FORMULA 23450151 A 264 265 S FORMULA 23450151 A 267 271 ZAIS ABBREVIATION 23450151 A 494 498 ZAIS ABBREVIATION 23450151 A 553 560 cadmium SYSTEMATIC 23450151 A 599 607 DHLA-PEG ABBREVIATION 23450151 A 704 710 folate TRIVIAL 23450151 A 839 841 Cd FORMULA 23450151 T 44 46 Zn FORMULA 23450151 T 47 49 Ag FORMULA 23450151 T 50 52 In FORMULA 23450151 T 53 54 S FORMULA 23450752 A 1024 1036 tetraproline FAMILY 23450752 A 1094 1102 hydrogen SYSTEMATIC 23450752 A 136 178 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines FAMILY 23450752 A 204 216 tetraproline FAMILY 23450752 A 272 284 tetraproline FAMILY 23450752 A 350 395 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines FAMILY 23450752 A 408 450 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines FAMILY 23450752 A 41 68 4-aryl-1,4-dihydropyridines FAMILY 23450752 A 499 534 racemic 4-aryl-1,4-dihydropyridines FAMILY 23450752 A 542 554 tetraproline FAMILY 23450752 A 593 605 5,5-dimethyl SYSTEMATIC 23450752 A 674 686 5,5-dimethyl SYSTEMATIC 23450752 A 712 754 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines FAMILY 23450752 A 77 122 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines FAMILY 23450752 A 773 779 sulfur SYSTEMATIC 23450752 A 826 871 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines FAMILY 23450752 A 982 994 tetraproline FAMILY 23450752 T 116 128 tetraproline FAMILY 23450752 T 35 62 4-aryl-1,4-dihydropyridines FAMILY 23450752 T 67 103 4-aryl-1,2,3,4-tetrahydropyrimidines FAMILY 23450777 A 0 24 Graphitic carbon nitride SYSTEMATIC 23450777 A 126 131 C3 N4 FORMULA 23450777 A 187 188 N FORMULA 23450777 A 189 190 C FORMULA 23450777 A 253 267 carbon nitride SYSTEMATIC 23450777 A 345 353 hydrogen SYSTEMATIC 23450777 T 11 35 graphitic carbon nitride SYSTEMATIC 23450777 T 74 82 hydrogen SYSTEMATIC 23450829 A 125 129 TiO2 FORMULA 23450829 A 13 17 TiO2 FORMULA 23450829 A 43 45 Ti FORMULA 23451707 A 178 208 sulfated quinazolin-4(3H)-ones FAMILY 23451707 A 210 214 QAOs ABBREVIATION 23451758 A 1189 1193 C2-D FORMULA 23451758 A 1214 1223 imidazole SYSTEMATIC 23451758 A 1245 1246 H FORMULA 23451758 A 1335 1339 C2-D FORMULA 23451758 A 1374 1375 H FORMULA 23451758 A 1405 1408 His FORMULA 23451758 A 1462 1468 Cu(2+) FORMULA 23451758 A 1483 1487 C2-D FORMULA 23451758 A 15 24 histidine TRIVIAL 23451758 A 1765 1768 His FORMULA 23451758 A 1786 1789 His FORMULA 23451758 A 212 215 His FORMULA 23451758 A 218 241 4-substituted imidazole FAMILY 23451758 A 248 251 His FORMULA 23451758 A 26 29 His FORMULA 23451758 A 319 322 His FORMULA 23451758 A 4 14 amino acid FAMILY 23451758 A 514 517 His FORMULA 23451758 A 562 571 deuterium SYSTEMATIC 23451758 A 605 609 C2-H FORMULA 23451758 A 610 618 hydrogen SYSTEMATIC 23451758 A 631 634 His FORMULA 23451758 A 635 644 imidazole SYSTEMATIC 23451758 A 655 664 deuterium SYSTEMATIC 23451758 A 695 699 C2-D FORMULA 23451758 A 793 802 imidazole SYSTEMATIC 23451758 A 911 915 C2-D FORMULA 23451758 A 966 969 His FORMULA 23451758 A 993 997 C2-D FORMULA 23451797 A 33 53 racemosalactones A-E MULTIPLE 23451797 A 81 102 sesquiterpene latones FAMILY 23451797 A 870 881 alantolides FAMILY 23451797 A 9 31 sesquiterpene lactones FAMILY 23451797 T 52 74 Sesquiterpene Lactones FAMILY 23451803 A 146 148 Au FORMULA 23451803 A 45 53 Fe-PTCDA FORMULA 23451803 A 505 510 PTCDA ABBREVIATION 23451803 A 518 526 Fe-PTCDA FORMULA 23451803 A 55 109 perylene-3,4,9,10-tetracarboxylic-3,4,9,10-dianhydride SYSTEMATIC 23451823 A 17 41 cryptocapsin-5,6-epoxide SYSTEMATIC 23451823 A 178 202 Cryptocapsin-5,6-epoxide SYSTEMATIC 23451823 A 256 268 cryptocapsin TRIVIAL 23451823 A 43 73 3'-deoxycapsanthin-5,6-epoxide SYSTEMATIC 23451823 A 472 496 cryptocapsin-5,8-epoxide SYSTEMATIC 23451823 A 616 641 cryptocapsin-5,8-epoxides FAMILY 23451823 A 79 104 cryptocapsin-5,8-epoxides FAMILY 23451823 T 0 19 Cryptocapsinepoxide FAMILY 23451983 A 101 105 PFCE ABBREVIATION 23451983 A 110 118 fluorine SYSTEMATIC 23451983 A 141 145 PFCE ABBREVIATION 23451983 A 262 266 PFCE ABBREVIATION 23451983 A 74 99 perfluoro-1,5-crown ether SYSTEMATIC 23452042 A 20 26 NAD(+) ABBREVIATION 23452042 A 356 374 N-hydroxyarylamine FAMILY 23452042 A 375 376 O FORMULA 23452042 A 521 527 lysine TRIVIAL 23452042 A 632 638 lysine TRIVIAL 23452042 A 785 791 lysine TRIVIAL 23452042 A 826 827 O FORMULA 23452042 A 850 851 N FORMULA 23452042 A 969 975 lysine TRIVIAL 23452042 T 105 123 N-hydroxyarylamine FAMILY 23452042 T 124 125 O FORMULA 23452042 T 22 28 lysine TRIVIAL 23452147 A 1096 1097 N FORMULA 23452147 A 1155 1156 C FORMULA 23452147 A 1272 1273 N FORMULA 23452147 A 1279 1280 C FORMULA 23452147 A 1423 1424 N FORMULA 23452147 A 1565 1566 C FORMULA 23452147 A 745 746 N FORMULA 23452147 A 774 775 C FORMULA 23452147 A 851 852 N FORMULA 23452147 A 858 859 C FORMULA 23452219 A 191 203 Theophylline TRIVIAL 23452219 A 352 364 theophylline TRIVIAL 23452219 A 387 395 caffeine TRIVIAL 23452219 A 423 429 methyl SYSTEMATIC 23452219 A 478 490 theophylline TRIVIAL 23452219 A 585 591 Purine TRIVIAL 23452219 A 695 702 guanine TRIVIAL 23452219 A 706 713 adenine TRIVIAL 23452219 A 812 818 purine TRIVIAL 23452254 A 102 118 polyoxometalates FAMILY 23452254 A 1020 1026 oxygen SYSTEMATIC 23452254 A 120 124 POMs ABBREVIATION 23452254 A 126 152 (R, R)-[(R*PO3)2M5O15](2-) FAMILY 23452254 A 1319 1335 transition metal FAMILY 23452254 A 1427 1431 POMs ABBREVIATION 23452254 A 159 169 CH3CH(NH3) FORMULA 23452254 A 176 178 Mo FORMULA 23452254 A 180 181 W FORMULA 23452254 A 624 650 (R, R)-[(R*PO3)2W5O15](2-) FAMILY 23452254 A 657 667 CH3CH(NH3) FORMULA 23452855 A 310 317 glycine TRIVIAL 23452855 A 321 330 glutamate TRIVIAL 23452857 A 18 38 N-methyl-D-aspartate SYSTEMATIC 23452857 A 582 588 serine TRIVIAL 23452857 T 65 69 NMDA ABBREVIATION 23453039 A 1024 1031 glucose TRIVIAL 23453039 A 1162 1169 glucose TRIVIAL 23453039 A 1300 1312 triglyceride FAMILY 23453039 A 1320 1331 cholesterol TRIVIAL 23453039 A 136 143 calcium SYSTEMATIC 23453039 A 396 403 calcium SYSTEMATIC 23453039 A 69 76 calcium SYSTEMATIC 23453039 A 873 887 streptozotocin TRIVIAL 23453039 A 963 970 glucose TRIVIAL 23453067 A 1009 1019 nucleotide FAMILY 23453067 A 1066 1073 guanine TRIVIAL 23453067 A 265 275 6-O-methyl SYSTEMATIC 23453067 A 333 352 guanine nucleosides FAMILY 23453067 A 389 420 2'-C-methyl-6-O-methylguanosine SYSTEMATIC 23453067 A 548 571 2'-C-methyl-6-O-methyl- SYSTEMATIC 23453067 A 579 588 guanosine TRIVIAL 23453067 A 659 660 N FORMULA 23453067 A 670 680 nucleobase FAMILY 23453067 A 732 763 2'-C-methyl-6-O-methylguanosine SYSTEMATIC 23453067 A 74 94 2'-C-methylguanosine FAMILY 23453067 A 902 925 2'-C-methyl-6-O-methyl- SYSTEMATIC 23453067 A 933 942 guanosine TRIVIAL 23453067 T 123 155 L-Alanine ester phosphoramidates FAMILY 23453067 T 75 118 2'-C-methyl-6-O-methyl guanosine nucleoside FAMILY 23453068 A 13 20 leucine TRIVIAL 23453068 A 339 376 4-alkylamino-7-aryl-3-cyanoquinolines FAMILY 23453068 A 635 638 Ser FORMULA 23453068 T 13 49 4-alkylamino-7-aryl-3-cyanoquinoline FAMILY 23453303 A 1165 1168 MDA ABBREVIATION 23453303 A 726 729 MDA ABBREVIATION 23453831 A 1604 1622 iridoid glucosides FAMILY 23453831 A 1624 1632 iridoids FAMILY 23453831 A 1637 1649 secoiridoids FAMILY 23453831 A 1652 1661 xanthones FAMILY 23453831 A 1666 1676 flavonoids FAMILY 23453831 A 1678 1696 Iridoid glucosides FAMILY 23453831 A 1744 1756 Loganic acid TRIVIAL 23453831 A 1758 1767 Sweroside TRIVIAL 23453831 A 1769 1781 Swertiamarin TRIVIAL 23453831 A 1783 1798 Gentiopicroside TRIVIAL 23453831 A 1800 1808 Gentisin TRIVIAL 23453831 A 1810 1821 Isogentisin TRIVIAL 23453831 A 1823 1833 Gentioside TRIVIAL 23453831 A 1835 1850 Norswertianolin TRIVIAL 23453831 A 1852 1864 Swertianolin TRIVIAL 23453831 A 1866 1927 4″-O-β-d-glucosyl-6'-O-(4-O-β-d-glucosylcaffeoyl)-linearoside SYSTEMATIC 23453831 A 1932 1941 Swertisin TRIVIAL 23453831 A 1986 1994 methanol SYSTEMATIC 23453831 A 341 345 DPPH ABBREVIATION 23453831 A 347 355 hydroxyl SYSTEMATIC 23453831 A 486 498 α-tocopherol TRIVIAL 23453831 A 500 508 catechin TRIVIAL 23453831 A 513 516 BHT ABBREVIATION 23453831 A 633 642 flavonoid FAMILY 23453831 A 781 798 sulphorhodamine B TRIVIAL 23453831 A 800 803 SRB ABBREVIATION 23454011 A 1042 1050 vitamins FAMILY 23454011 A 1092 1102 vitamin D3 TRIVIAL 23454011 A 1232 1242 vitamin D3 TRIVIAL 23454011 A 149 160 cholesterol TRIVIAL 23454011 A 26 43 aluminum silicate TRIVIAL 23454011 A 325 342 vitamin D3 and K1 MULTIPLE 23454011 A 537 547 vitamin D3 TRIVIAL 23454011 A 559 569 vitamin K1 TRIVIAL 23454011 A 606 616 vitamin D3 TRIVIAL 23454011 A 631 641 vitamin K1 TRIVIAL 23454011 A 67 82 montmorillonite TRIVIAL 23454011 A 726 738 stigmastanol TRIVIAL 23454011 A 768 778 vitamin D3 TRIVIAL 23454011 A 906 916 vitamin K1 TRIVIAL 23454011 T 145 163 vitamins D3 and K1 MULTIPLE 23454011 T 57 74 aluminum silicate TRIVIAL 23454011 T 76 87 cholesterol TRIVIAL 23454052 A 1140 1143 ZnO FORMULA 23454052 A 1315 1318 ZnO FORMULA 23454052 A 173 176 ZnO FORMULA 23454052 A 227 230 ZnO FORMULA 23454052 A 27 37 zinc oxide SYSTEMATIC 23454052 A 338 341 ZnO FORMULA 23454052 A 39 42 ZnO FORMULA 23454052 A 703 706 ZnO FORMULA 23454052 A 839 842 ZnO FORMULA 23454052 A 876 879 ZnO FORMULA 23454052 A 995 998 ZnO FORMULA 23454052 T 68 78 zinc oxide SYSTEMATIC 23454054 A 205 217 indomethacin TRIVIAL 23454054 A 222 231 saccharin TRIVIAL 23454054 A 233 236 IMC ABBREVIATION 23454054 A 237 240 SAC ABBREVIATION 23454054 A 480 488 methanol SYSTEMATIC 23454054 A 564 567 IMC ABBREVIATION 23454054 A 568 571 SAC ABBREVIATION 23454054 A 662 665 IMC ABBREVIATION 23454054 A 666 669 SAC ABBREVIATION 23454054 A 684 687 IMC ABBREVIATION 23454054 T 19 31 indomethacin TRIVIAL 23454054 T 32 41 saccharin TRIVIAL 23454054 T 43 46 IMC ABBREVIATION 23454054 T 47 50 SAC ABBREVIATION 23454133 A 1154 1155 H FORMULA 23454133 A 259 269 olanzapine TRIVIAL 23454133 A 274 285 simvastatin TRIVIAL 23454133 A 945 955 olanzapine TRIVIAL 23454133 A 960 971 simvastatin TRIVIAL 23454148 A 105 119 5-fluorouracil SYSTEMATIC 23454148 A 1279 1295 prostaglandin E2 TRIVIAL 23454148 A 129 140 mitomycin C TRIVIAL 23454148 A 1313 1316 MMC ABBREVIATION 23454148 A 1376 1379 MMC ABBREVIATION 23454148 A 142 145 MMC ABBREVIATION 23454148 A 1516 1519 MMC ABBREVIATION 23454148 A 436 439 MMC ABBREVIATION 23454148 A 442 451 Cisplatin TRIVIAL 23454148 A 456 459 MMC ABBREVIATION 23454148 A 551 565 5-Fluorouracil SYSTEMATIC 23454148 A 677 688 glutathione TRIVIAL 23454148 A 689 690 S FORMULA 23454148 A 719 720 N FORMULA 23454148 A 725 733 cysteine TRIVIAL 23454148 A 734 735 S FORMULA 23454148 A 843 860 dihydropyrimidine SYSTEMATIC 23454148 A 89 98 cisplatin TRIVIAL 23454148 A 919 922 MMC ABBREVIATION 23454148 A 942 949 quinone FAMILY 23454148 A 973 981 xanthine TRIVIAL 23454148 T 65 74 cisplatin TRIVIAL 23454148 T 76 90 5-fluorouracil SYSTEMATIC 23454148 T 95 106 mitomycin C TRIVIAL 23454208 A 1033 1041 luteolin TRIVIAL 23454208 A 1189 1197 luteolin TRIVIAL 23454208 A 1279 1287 luteolin TRIVIAL 23454208 A 160 168 luteolin TRIVIAL 23454208 A 319 327 luteolin TRIVIAL 23454208 A 504 505 N FORMULA 23454208 A 58 66 luteolin TRIVIAL 23454208 A 583 591 luteolin TRIVIAL 23454208 A 617 625 luteolin TRIVIAL 23454208 A 84 93 flavonoid FAMILY 23454208 A 857 871 bafilomycin A1 TRIVIAL 23454208 A 918 926 luteolin TRIVIAL 23454208 T 92 100 luteolin TRIVIAL 23454297 A 1058 1070 caffeic acid TRIVIAL 23454297 A 1178 1190 caffeic acid TRIVIAL 23454297 A 1260 1272 caffeic acid TRIVIAL 23454297 A 152 162 nucleotide FAMILY 23454297 A 219 228 adenosine TRIVIAL 23454297 A 36 48 caffeic acid TRIVIAL 23454297 A 401 413 caffeic acid TRIVIAL 23454297 A 428 440 caffeic acid TRIVIAL 23454297 A 458 470 caffeic acid TRIVIAL 23454297 A 508 520 caffeic acid TRIVIAL 23454297 A 562 574 caffeic acid TRIVIAL 23454297 A 589 592 ATP ABBREVIATION 23454297 A 618 621 ADP ABBREVIATION 23454297 A 837 849 Caffeic acid TRIVIAL 23454297 A 97 120 nucleoside triphosphate FAMILY 23454297 T 0 12 Caffeic acid TRIVIAL 23454297 T 48 66 adenine nucleotide TRIVIAL 23454308 A 1569 1575 Al(3+) FORMULA 23454308 A 170 185 aluminium oxide SYSTEMATIC 23454308 A 461 468 alumina TRIVIAL 23454308 A 48 63 aluminium oxide SYSTEMATIC 23454308 A 616 622 Al(3+) FORMULA 23454308 T 16 31 aluminium oxide SYSTEMATIC 23454309 A 1072 1078 methyl SYSTEMATIC 23454309 A 1079 1081 Hg FORMULA 23454309 A 1349 1351 Hg FORMULA 23454309 A 139 145 methyl SYSTEMATIC 23454309 A 146 148 Hg FORMULA 23454309 A 1477 1479 Hg FORMULA 23454309 A 1513 1515 Hg FORMULA 23454309 A 1689 1691 Hg FORMULA 23454309 A 1812 1814 Hg FORMULA 23454309 A 202 207 (15)N FORMULA 23454309 A 422 424 Hg FORMULA 23454309 A 537 539 Hg FORMULA 23454309 A 545 550 (15)N FORMULA 23454309 A 652 654 Hg FORMULA 23454309 A 715 717 Hg FORMULA 23454309 A 723 728 (15)N FORMULA 23454309 A 766 772 methyl SYSTEMATIC 23454309 A 773 775 Hg FORMULA 23454309 A 81 88 mercury SYSTEMATIC 23454309 A 847 853 methyl SYSTEMATIC 23454309 A 854 856 Hg FORMULA 23454309 A 862 867 (15)N FORMULA 23454309 A 90 92 Hg FORMULA 23454309 A 908 910 Hg FORMULA 23454309 T 43 50 mercury SYSTEMATIC 23454310 A 1425 1431 silver SYSTEMATIC 23454310 A 1725 1731 silver SYSTEMATIC 23454310 A 190 196 silver SYSTEMATIC 23454310 A 44 50 silver SYSTEMATIC 23454310 T 36 42 silver SYSTEMATIC 23454529 A 112 123 quinazoline SYSTEMATIC 23454529 A 223 231 hydrogen SYSTEMATIC 23454529 A 264 275 quinazoline SYSTEMATIC 23454529 A 30 45 indoloquinoline SYSTEMATIC 23454529 A 406 444 N-(2-(quinazolin-2-yl)phenyl)benzamide SYSTEMATIC 23454529 A 446 449 QPB ABBREVIATION 23454529 A 473 484 quinazoline SYSTEMATIC 23454529 A 49 67 benzofuroquinoline SYSTEMATIC 23454529 A 522 528 phenyl SYSTEMATIC 23454529 A 615 618 QPB ABBREVIATION 23454529 A 719 724 LZ-11 IDENTIFIER 23454529 A 766 777 quinazoline SYSTEMATIC 23454529 A 829 832 QPB ABBREVIATION 23454529 T 4 15 quinazoline SYSTEMATIC 23454529 T 80 86 phenyl SYSTEMATIC 23454648 A 0 14 Polyamidoamine SYSTEMATIC 23454648 A 1112 1117 amino FAMILY 23454648 A 1153 1158 PAMAM ABBREVIATION 23454648 A 16 21 PAMAM ABBREVIATION 23454648 A 294 300 oxygen SYSTEMATIC 23454648 A 465 470 PAMAM ABBREVIATION 23454648 A 707 712 amino FAMILY 23454648 A 883 888 amino FAMILY 23454648 T 101 115 polyamidoamine FAMILY 23454648 T 117 122 PAMAM ABBREVIATION 23454648 T 37 43 oxygen SYSTEMATIC 23454829 A 0 106 (2R,3R,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-3-yl 4-O-(6-deoxy-β-D-glucopyranosyl)-α-D-glucopyranoside SYSTEMATIC 23454829 A 1008 1015 alanine TRIVIAL 23454829 A 1021 1028 proline TRIVIAL 23454829 A 1066 1077 amino acids FAMILY 23454829 A 108 115 CS-1036 IDENTIFIER 23454829 A 1108 1119 amino acids FAMILY 23454829 A 1232 1243 fatty acids FAMILY 23454829 A 1314 1325 fatty acids FAMILY 23454829 A 1365 1378 palmitic acid TRIVIAL 23454829 A 1380 1390 oleic acid TRIVIAL 23454829 A 1396 1423 8,11,14-eicosatrienoic acid SYSTEMATIC 23454829 A 1459 1466 CS-1036 IDENTIFIER 23454829 A 1586 1597 amino acids FAMILY 23454829 A 1602 1613 fatty acids FAMILY 23454829 A 1620 1634 [(14)C]CS-1036 IDENTIFIER 23454829 A 1678 1692 [(14)C]CS-1036 IDENTIFIER 23454829 A 1733 1744 amino acids FAMILY 23454829 A 1768 1779 fatty acids FAMILY 23454829 A 206 220 [(14)C]CS-1036 IDENTIFIER 23454829 A 405 412 CS-1036 IDENTIFIER 23454829 A 642 652 amino acid FAMILY 23454829 A 771 785 [(14)C]CS-1036 IDENTIFIER 23454829 A 957 967 amino acid FAMILY 23454829 A 978 991 glutamic acid TRIVIAL 23454829 A 993 1006 aspartic acid TRIVIAL 23454829 T 117 129 [14C]CS-1036 IDENTIFIER 23455056 A 121 130 palladium SYSTEMATIC 23455056 A 159 181 bis(pinacolato)diboron SYSTEMATIC 23455056 A 18 26 oleanane TRIVIAL 23455056 A 187 202 vinyl triflates FAMILY 23455056 A 434 459 oleanolic vinyl boronates FAMILY 23455056 A 44 57 triterpenoids FAMILY 23455056 A 68 82 boronate ester FAMILY 23455056 A 792 797 boron SYSTEMATIC 23455056 A 805 819 oleanolic acid TRIVIAL 23455056 A 855 860 amide FAMILY 23455056 T 6 31 oleanolic vinyl boronates FAMILY 23455057 A 12 31 arene ruthenium(II) FAMILY 23455057 A 130 139 p-NMe2PIP FORMULA 23455057 A 1307 1312 arene FAMILY 23455057 A 1313 1319 Ru(II) FORMULA 23455057 A 148 156 p-MeOPIP FORMULA 23455057 A 165 172 p-HOPIP FORMULA 23455057 A 181 190 p-COOHPIP FORMULA 23455057 A 199 207 p-CF3PIP FORMULA 23455057 A 216 223 p-BrPIP FORMULA 23455057 A 482 485 MTT ABBREVIATION 23455057 A 532 537 arene FAMILY 23455057 A 538 544 Ru(II) FORMULA 23455057 A 57 76 phenanthroimidazole FAMILY 23455057 A 815 820 arene FAMILY 23455057 A 821 827 Ru(II) FORMULA 23455057 A 88 110 [(C6H6)Ru(L)Cl]Cl·2H2O FORMULA 23455057 T 32 51 arene ruthenium(II) FAMILY 23455229 A 104 106 Au FORMULA 23455229 A 306 308 Au FORMULA 23455229 A 868 870 Au FORMULA 23455312 A 1007 1011 HENA ABBREVIATION 23455312 A 1169 1176 steroid FAMILY 23455312 A 1191 1195 HENA ABBREVIATION 23455312 A 1355 1358 LCA ABBREVIATION 23455312 A 1360 1364 HENA ABBREVIATION 23455312 A 1456 1460 HENA ABBREVIATION 23455312 A 1505 1509 HENA ABBREVIATION 23455312 A 1735 1742 steroid FAMILY 23455312 A 25 29 K(+) FORMULA 23455312 A 252 259 steroid FAMILY 23455312 A 260 276 lithocholic acid TRIVIAL 23455312 A 278 281 LCA ABBREVIATION 23455312 A 393 396 Thr FORMULA 23455312 A 4 9 Ca(2+ FORMULA 23455312 A 616 619 LCA ABBREVIATION 23455312 A 678 713 sodium 3-hydroxyolean-12-en-30-oate SYSTEMATIC 23455312 A 715 719 HENA ABBREVIATION 23455312 A 722 726 HENA ABBREVIATION 23455312 A 918 921 LCA ABBREVIATION 23455312 A 928 932 HENA ABBREVIATION 23455312 T 56 63 Cholane TRIVIAL 23455312 T 64 71 Steroid FAMILY 23455314 A 0 20 N-methyl-d-aspartate SYSTEMATIC 23455314 A 1063 1066 CIQ ABBREVIATION 23455314 A 1305 1309 NMDA ABBREVIATION 23455314 A 1385 1389 NMDA ABBREVIATION 23455314 A 1454 1458 NMDA ABBREVIATION 23455314 A 22 26 NMDA ABBREVIATION 23455314 A 231 235 NMDA ABBREVIATION 23455314 A 507 511 NMDA ABBREVIATION 23455314 A 640 741 (3-chlorophenyl)(6,7-dimethoxy-1-((4-methoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone SYSTEMATIC 23455314 A 743 746 CIQ ABBREVIATION 23455314 A 815 818 CIQ ABBREVIATION 23455314 A 840 845 amino FAMILY 23455314 A 869 873 NMDA ABBREVIATION 23455314 T 109 129 N-methyl-d-aspartate SYSTEMATIC 23455373 A 0 36 Polyhedral oligomeric silsesquioxane FAMILY 23455373 A 101 106 T8C18 FORMULA 23455373 A 112 164 octakis(n-octadecyldimethylsiloxy)octasilsesquioxane SYSTEMATIC 23455373 A 1193 1199 OSiMe2 FORMULA 23455373 A 167 172 Q8C18 FORMULA 23455373 A 227 233 C18H37 FORMULA 23455373 A 38 42 POSS ABBREVIATION 23455373 A 64 98 octa-n-octadecyloctasilsesquioxane SYSTEMATIC 23455373 T 122 126 POSS ABBREVIATION 23455373 T 83 120 polyhedral oligomeric silsesquioxanes FAMILY 23455513 A 572 573 O FORMULA 23455513 A 825 837 carbohydrate FAMILY 23455513 A 896 897 O FORMULA 23455995 A 1025 1033 spinosad FAMILY 23455995 A 1146 1159 λ-cyhalothrin FAMILY 23455995 A 1274 1287 λ-cyhalothrin FAMILY 23455995 A 1332 1340 spinosad FAMILY 23455995 A 1416 1424 spinosad FAMILY 23455995 A 1454 1462 spinosad FAMILY 23455995 A 1495 1508 λ-cyhalothrin FAMILY 23455995 A 1528 1536 spinosad FAMILY 23455995 A 1593 1606 λ-cyhalothrin FAMILY 23455995 A 185 193 spinosad FAMILY 23455995 A 198 211 λ-cyhalothrin FAMILY 23455995 A 388 396 spinosad FAMILY 23455995 A 401 414 λ-cyhalothrin FAMILY 23455995 A 740 748 Spinosad FAMILY 23455995 A 848 861 λ-cyhalothrin FAMILY 23455995 T 11 19 spinosad FAMILY 23455995 T 24 37 λ-cyhalothrin FAMILY 23456038 A 1303 1310 phospho SYSTEMATIC 23456038 A 1470 1477 phospho SYSTEMATIC 23456038 A 1565 1574 phosphate SYSTEMATIC 23456038 A 1585 1592 phospho SYSTEMATIC 23456038 A 1620 1627 phospho SYSTEMATIC 23456038 A 433 439 serine TRIVIAL 23456038 A 440 449 threonine TRIVIAL 23456038 A 816 820 (1)H FORMULA 23456038 A 821 826 (15)N FORMULA 23456038 A 827 832 amide FAMILY 23456097 A 1305 1306 N FORMULA 23456248 A 137 145 nitrogen SYSTEMATIC 23456248 A 498 508 amino acid FAMILY 23456248 A 656 676 phosphatidylinositol TRIVIAL 23456735 A 1390 1397 glucose TRIVIAL 23456735 A 1431 1438 glucose TRIVIAL 23456735 A 557 564 glucose TRIVIAL 23456814 A 1089 1092 MDA ABBREVIATION 23456814 A 1142 1145 GSH ABBREVIATION 23456814 A 489 504 malondialdehyde TRIVIAL 23456814 A 506 509 MDA ABBREVIATION 23456814 A 512 522 superoxide TRIVIAL 23456814 A 543 554 glutathione TRIVIAL 23456814 A 556 559 GSH ABBREVIATION 23456814 A 751 776 deoxyuridine triphosphate SYSTEMATIC 23456816 A 414 429 sodium chloride SYSTEMATIC 23456816 A 476 492 sodium hydroxide SYSTEMATIC 23456892 A 0 13 Rosiglitazone TRIVIAL 23456892 A 1034 1037 RSG ABBREVIATION 23456892 A 1062 1079 deoxypyridinoline SYSTEMATIC 23456892 A 1228 1231 RSG ABBREVIATION 23456892 A 1423 1426 RSG ABBREVIATION 23456892 A 1431 1434 ALN ABBREVIATION 23456892 A 1475 1478 RSG ABBREVIATION 23456892 A 15 18 RSG ABBREVIATION 23456892 A 1513 1516 RSG ABBREVIATION 23456892 A 1624 1627 RSG ABBREVIATION 23456892 A 1816 1819 ALN ABBREVIATION 23456892 A 1869 1872 RSG ABBREVIATION 23456892 A 202 205 RSG ABBREVIATION 23456892 A 321 324 RSG ABBREVIATION 23456892 A 607 610 RSG ABBREVIATION 23456892 A 612 623 alendronate TRIVIAL 23456892 A 625 628 ALN ABBREVIATION 23456892 A 633 636 RSG ABBREVIATION 23456892 A 642 645 ALN ABBREVIATION 23456892 A 757 760 RSG ABBREVIATION 23456892 T 14 27 rosiglitazone TRIVIAL 23456892 T 96 107 alendronate TRIVIAL 23457119 A 1123 1129 MK-801 IDENTIFIER 23457119 A 1146 1157 Scopolamine TRIVIAL 23457119 A 1190 1200 [(18)F]FDG SYSTEMATIC 23457119 A 1225 1231 MK-801 IDENTIFIER 23457119 A 1334 1340 MK-801 IDENTIFIER 23457119 A 1369 1379 [(18)F]FDG SYSTEMATIC 23457119 A 1483 1493 [(18)F]FDG SYSTEMATIC 23457119 A 161 192 [(18)F]fluoro-2-deoxy-d-glucose SYSTEMATIC 23457119 A 1634 1638 NMDA ABBREVIATION 23457119 A 1702 1708 MK-801 IDENTIFIER 23457119 A 194 204 [(18)F]FDG SYSTEMATIC 23457119 A 244 251 glucose TRIVIAL 23457119 A 377 397 N-methyl-d-aspartate SYSTEMATIC 23457119 A 399 403 NMDA ABBREVIATION 23457119 A 581 588 glucose TRIVIAL 23457119 A 637 647 [(18)F]FDG SYSTEMATIC 23457119 A 707 711 NMDA ABBREVIATION 23457119 A 733 739 MK-801 IDENTIFIER 23457119 A 747 757 [(18)F]FDG SYSTEMATIC 23457119 A 792 799 glucose TRIVIAL 23457119 A 850 856 MK-801 IDENTIFIER 23457119 A 878 888 [(18)F]FDG SYSTEMATIC 23457119 T 0 8 [18F]FDG SYSTEMATIC 23457119 T 40 44 NMDA ABBREVIATION 23458167 A 39 46 silicon SYSTEMATIC 23458385 A 228 238 saccharide FAMILY 23458385 A 836 859 poly(styrene sulfonate) SYSTEMATIC 23458422 A 1009 1012 PNB ABBREVIATION 23458422 A 1211 1214 PNB ABBREVIATION 23458422 A 1314 1317 PNB ABBREVIATION 23458422 A 15 64 poly(N-isopropylacrylamide-co-butyl methacrylate) SYSTEMATIC 23458422 A 279 282 PNB ABBREVIATION 23458422 A 394 407 sulfuric acid SYSTEMATIC 23458422 A 522 525 PNB ABBREVIATION 23458422 A 562 565 PNB ABBREVIATION 23458422 A 597 600 PNB ABBREVIATION 23458422 A 66 69 PNB ABBREVIATION 23458422 A 664 667 PNB ABBREVIATION 23458422 A 873 876 PNB ABBREVIATION 23458422 A 941 944 PNB ABBREVIATION 23458422 T 45 63 Poly(NIPAM-co-BMA) SYSTEMATIC 23458573 A 156 163 cocaine TRIVIAL 23458573 A 219 226 cocaine TRIVIAL 23458573 A 277 284 cocaine TRIVIAL 23458573 A 425 432 cocaine TRIVIAL 23458573 A 448 455 Cocaine TRIVIAL 23458573 A 629 636 cocaine TRIVIAL 23458573 T 42 49 cocaine TRIVIAL 23458575 A 358 364 oxygen SYSTEMATIC 23458617 A 1148 1163 cis-imidazoline SYSTEMATIC 23458617 A 1173 1181 Nutlin-3 TRIVIAL 23458621 A 606 612 silica TRIVIAL 23458621 A 616 622 silica TRIVIAL 23458621 A 907 913 silica TRIVIAL 23458621 T 12 18 silica TRIVIAL 23458727 A 149 152 A12 ABBREVIATION 23458727 A 37 86 N-(4-carboxy-3-hydroxyphenyl)-2,5-dimethylpyrrole SYSTEMATIC 23458727 A 430 434 NB-2 ABBREVIATION 23458727 A 439 442 A12 ABBREVIATION 23458727 A 88 92 NB-2 ABBREVIATION 23458727 A 98 147 N-(3-carboxy-4-hydroxyphenyl)-2,5-dimethylpyrrole SYSTEMATIC 23458730 A 0 8 Baicalin TRIVIAL 23458730 A 1094 1102 baicalin TRIVIAL 23458730 A 1215 1223 baicalin TRIVIAL 23458730 A 1316 1324 baicalin TRIVIAL 23458730 A 1352 1355 DXM ABBREVIATION 23458730 A 203 211 baicalin TRIVIAL 23458730 A 233 249 dextromethorphan TRIVIAL 23458730 A 251 254 DXM ABBREVIATION 23458730 A 349 357 baicalin TRIVIAL 23458730 A 492 500 baicalin TRIVIAL 23458730 A 522 525 DXM ABBREVIATION 23458730 A 694 697 DXM ABBREVIATION 23458730 A 774 777 DXM ABBREVIATION 23458730 A 832 840 baicalin TRIVIAL 23458730 A 895 903 baicalin TRIVIAL 23458730 A 950 953 DXM ABBREVIATION 23458730 T 46 54 baicalin TRIVIAL 23458730 T 76 92 dextromethorphan TRIVIAL 23458895 A 0 7 NAD(P)H ABBREVIATION 23458895 A 126 140 streptozotocin TRIVIAL 23458895 A 142 145 STZ ABBREVIATION 23458895 A 278 281 STZ ABBREVIATION 23458895 A 374 381 glucose TRIVIAL 23458895 A 617 620 STZ ABBREVIATION 23458895 A 8 15 quinone FAMILY 23458895 T 75 82 NAD(P)H ABBREVIATION 23458895 T 83 90 quinone FAMILY 23459146 A 1173 1176 NaF FORMULA 23459146 A 1265 1268 NaF FORMULA 23459146 A 1290 1293 NaF FORMULA 23459146 A 1340 1343 NaF FORMULA 23459146 A 181 184 NaF FORMULA 23459146 A 299 302 NaF FORMULA 23459146 A 329 332 NaF FORMULA 23459146 A 396 399 NaF FORMULA 23459146 A 56 71 sodium fluoride SYSTEMATIC 23459146 A 569 581 testosterone TRIVIAL 23459146 A 587 599 progesterone TRIVIAL 23459146 A 608 617 estradiol TRIVIAL 23459146 A 73 76 NaF FORMULA 23459146 A 770 781 hematoxylin TRIVIAL 23459146 A 782 787 eosin FAMILY 23459146 A 854 857 NaF FORMULA 23459146 A 990 993 NaF FORMULA 23459146 T 11 26 sodium fluoride SYSTEMATIC 23459233 A 0 10 Phosphorus SYSTEMATIC 23459233 A 1001 1002 P FORMULA 23459233 A 12 13 P FORMULA 23459233 A 1308 1309 P FORMULA 23459233 A 436 437 P FORMULA 23459233 A 570 572 N2 FORMULA 23459233 A 633 634 P FORMULA 23459233 A 724 726 N2 FORMULA 23459233 A 898 900 N2 FORMULA 23459233 A 908 910 H+ FORMULA 23459233 A 944 953 succinate TRIVIAL 23459233 T 98 108 Phosphorus SYSTEMATIC 23460347 A 187 223 poly(ethylene glycol)-dimethacrylate SYSTEMATIC 23460347 A 225 232 PEG-DMA ABBREVIATION 23460347 A 480 487 PEG-DMA ABBREVIATION 23460347 A 582 589 PEG-DMA ABBREVIATION 23460347 T 29 36 PEG-DMA ABBREVIATION 23460383 A 126 140 1,4-butanediol SYSTEMATIC 23460383 A 141 176 4,4'-methylenebis(phenylisocyanate) SYSTEMATIC 23460383 A 23 36 polyurethanes FAMILY 23460383 A 519 523 diol SYSTEMATIC 23460383 A 63 79 undecylenic acid SYSTEMATIC 23460383 A 88 104 telechelic diols FAMILY 23460383 T 14 27 Polyurethanes FAMILY 23460383 T 33 49 Undecylenic Acid SYSTEMATIC 23461617 A 106 121 6-nitrochrysene SYSTEMATIC 23461617 A 1154 1158 6-NC SYSTEMATIC 23461617 A 1163 1175 1,2-DHD-6-NC SYSTEMATIC 23461617 A 123 127 6-NC SYSTEMATIC 23461617 A 1332 1336 6-NC SYSTEMATIC 23461617 A 1345 1357 1,2-DHD-6-NC SYSTEMATIC 23461617 A 1446 1450 6-NC SYSTEMATIC 23461617 A 1506 1510 6-NC SYSTEMATIC 23461617 A 1515 1527 1,2-DHD-6-NC SYSTEMATIC 23461617 A 1603 1607 6-NC SYSTEMATIC 23461617 A 203 207 6-NC SYSTEMATIC 23461617 A 288 339 (±)-trans-1,2-dihydroxy-1,2-dihydro-6-nitrochrysene SYSTEMATIC 23461617 A 341 353 1,2-DHD-6-NC SYSTEMATIC 23461617 A 402 418 (±)-1,2-DHD-6-NC SYSTEMATIC 23461617 A 424 461 (-)-[R,R]- and (+)-[S,S]-1,2-DHD-6-NC MULTIPLE 23461617 A 767 771 6-NC SYSTEMATIC 23461617 A 903 907 6-NC SYSTEMATIC 23461617 A 913 925 1,2-DHD-6-NC SYSTEMATIC 23461617 A 962 966 6-NC SYSTEMATIC 23461617 A 971 983 1,2-DHD-6-NC SYSTEMATIC 23461617 T 124 190 (-)-[R,R]- and (+)-[S,S]-1,2-Dihydroxy-1,2-dihydro-6-nitrochrysene MULTIPLE 23461617 T 88 103 6-Nitrochrysene SYSTEMATIC 23461650 A 19 26 cyanine TRIVIAL 23461784 A 183 190 lithium SYSTEMATIC 23461784 A 272 281 germanium SYSTEMATIC 23461784 A 436 445 germanium SYSTEMATIC 23461784 A 581 588 silicon SYSTEMATIC 23461784 A 675 682 silicon SYSTEMATIC 23461784 A 733 742 germanium SYSTEMATIC 23461784 A 856 865 germanium SYSTEMATIC 23461784 A 989 996 lithium SYSTEMATIC 23461784 T 6 15 Germanium SYSTEMATIC 23461821 A 125 131 Silver SYSTEMATIC 23461821 A 168 196 polyguanidino oxanorbornenes FAMILY 23461821 A 222 246 polyamino oxanorbornenes FAMILY 23461821 A 310 316 silver SYSTEMATIC 23461821 A 327 332 NaBH4 FORMULA 23461821 A 397 403 silver SYSTEMATIC 23461821 A 55 61 silver SYSTEMATIC 23461821 A 661 667 silver SYSTEMATIC 23461821 A 843 856 4-nitrophenol SYSTEMATIC 23461821 A 860 873 4-aminophenol SYSTEMATIC 23461821 A 893 898 NaBH4 FORMULA 23461821 A 90 100 norbornene TRIVIAL 23461821 T 112 125 4-nitrophenol SYSTEMATIC 23461821 T 20 26 silver SYSTEMATIC 23461821 T 64 79 polynorbornenes FAMILY 23461841 A 1045 1059 spironolactone TRIVIAL 23461841 A 1166 1180 spironolactone TRIVIAL 23461841 A 273 288 magnesium oxide SYSTEMATIC 23461841 A 340 354 spironolactone TRIVIAL 23461841 A 378 385 glucose TRIVIAL 23461841 A 411 418 glucose TRIVIAL 23461841 A 45 60 magnesium oxide SYSTEMATIC 23461841 A 512 519 glucose TRIVIAL 23461841 A 529 540 aldosterone TRIVIAL 23461841 A 65 79 spironolactone TRIVIAL 23461841 A 820 835 magnesium oxide SYSTEMATIC 23461841 A 840 854 spironolactone TRIVIAL 23461841 A 959 974 magnesium oxide SYSTEMATIC 23461841 A 97 108 fatty acids FAMILY 23461841 T 11 21 fatty acid FAMILY 23461841 T 71 86 magnesium oxide SYSTEMATIC 23461841 T 91 105 spironolactone TRIVIAL 23461969 A 1004 1007 Pro FORMULA 23461969 A 1012 1015 Ala FORMULA 23461969 A 1020 1023 Asp FORMULA 23461969 A 1028 1031 Arg FORMULA 23461969 A 1036 1039 His FORMULA 23461969 A 1048 1051 Tyr FORMULA 23461969 A 806 812 phenyl SYSTEMATIC 23461969 A 865 871 phenyl SYSTEMATIC 23461969 A 945 948 Gln FORMULA 23461969 A 952 955 Ile FORMULA 23461969 A 959 962 Asp FORMULA 23461969 A 966 969 Trp FORMULA 23461969 A 973 976 His FORMULA 23461969 A 980 983 Ile FORMULA 23461969 A 988 991 Tyr FORMULA 23461969 A 996 999 Glu FORMULA 23462104 A 237 248 Cholesterol TRIVIAL 23462104 A 339 350 cholesterol TRIVIAL 23462104 A 378 389 cholesterol TRIVIAL 23462104 A 549 560 Cholesterol TRIVIAL 23462104 A 575 586 Cholesterol TRIVIAL 23462104 A 600 611 Cholesterol TRIVIAL 23462104 A 626 637 Cholesterol TRIVIAL 23462104 T 64 75 cholesterol TRIVIAL 23462193 A 0 7 Glucose TRIVIAL 23462194 A 1049 1059 nevirapine TRIVIAL 23462194 A 1192 1202 nevirapine TRIVIAL 23462194 A 1338 1348 nevirapine TRIVIAL 23462194 A 1406 1412 iodine SYSTEMATIC 23462194 A 1450 1460 nevirapine TRIVIAL 23462194 A 172 182 Nevirapine TRIVIAL 23462194 A 350 360 nevirapine TRIVIAL 23462194 A 498 508 nevirapine TRIVIAL 23462194 A 598 626 methly thiazolyl tetrazolium SYSTEMATIC 23462194 A 628 631 MTT ABBREVIATION 23462194 A 671 684 Hoechst 33258 TRIVIAL 23462194 A 840 846 Iodine SYSTEMATIC 23462194 A 872 878 (125)I FORMULA 23462194 A 948 958 nevirapine TRIVIAL 23462194 T 52 62 nevirapine TRIVIAL 23462212 A 109 124 chebulinic acid TRIVIAL 23462212 A 182 197 Chebulinic acid TRIVIAL 23462212 A 242 249 aspirin TRIVIAL 23462212 A 256 263 alcohol FAMILY 23462212 A 366 381 chebulinic acid TRIVIAL 23462212 A 497 507 omeprazole TRIVIAL 23462212 A 609 619 Sucralfate TRIVIAL 23462212 A 713 728 Chebulinic acid TRIVIAL 23462212 A 862 877 chebulinic acid TRIVIAL 23462212 A 902 906 H(+) FORMULA 23462212 A 907 911 K(+) FORMULA 23462212 A 994 1004 omeprazole TRIVIAL 23462212 T 46 61 chebulinic acid TRIVIAL 23462213 A 1082 1085 VPA ABBREVIATION 23462213 A 1110 1113 VPA ABBREVIATION 23462213 A 1225 1236 fluorescein TRIVIAL 23462213 A 1330 1333 VPA ABBREVIATION 23462213 A 241 254 Valproic acid TRIVIAL 23462213 A 256 259 VPA ABBREVIATION 23462213 A 407 410 VPA ABBREVIATION 23462213 A 429 444 monocarboxylate SYSTEMATIC 23462213 A 487 490 VPA ABBREVIATION 23462213 A 558 561 VPA ABBREVIATION 23462213 A 577 580 VPA ABBREVIATION 23462213 A 712 715 VPA ABBREVIATION 23462213 A 744 747 VPA ABBREVIATION 23462213 A 870 873 VPA ABBREVIATION 23462213 A 994 997 VPA ABBREVIATION 23462213 T 37 52 monocarboxylate SYSTEMATIC 23462213 T 88 101 valproic acid TRIVIAL 23462281 A 1011 1019 thiamine TRIVIAL 23462281 A 273 281 thiamine TRIVIAL 23462281 A 381 389 thiamine TRIVIAL 23462281 A 395 403 thiamine TRIVIAL 23462281 A 526 534 thiamine TRIVIAL 23462281 A 637 645 tyrosine TRIVIAL 23462281 A 839 882 nicotinamide adenine dinucleotide phosphate SYSTEMATIC 23462281 A 931 939 thiamine TRIVIAL 23462281 T 23 31 Thiamine TRIVIAL 23462379 A 151 152 N FORMULA 23462380 A 2038 2049 neostigmine TRIVIAL 23462505 A 0 8 Estrogen FAMILY 23462505 A 1284 1297 17β-estradiol SYSTEMATIC 23462505 A 1343 1352 tamoxifen TRIVIAL 23462505 A 1354 1364 raloxifene TRIVIAL 23462505 A 1366 1378 bazedoxifene TRIVIAL 23462505 A 1383 1394 fulvestrant TRIVIAL 23462505 A 68 76 estrogen FAMILY 23462505 T 82 90 estrogen FAMILY 23462666 A 1234 1241 glucose TRIVIAL 23462666 A 1395 1402 glucose TRIVIAL 23462666 A 1424 1431 glucose TRIVIAL 23462666 A 227 234 glucose TRIVIAL 23463333 A 1223 1233 robenidine TRIVIAL 23463333 A 296 308 acetonitrile SYSTEMATIC 23463333 A 309 320 formic acid SYSTEMATIC 23463333 A 351 357 hexane SYSTEMATIC 23463333 A 450 458 methanol SYSTEMATIC 23463333 A 485 505 trifluoroacetic acid SYSTEMATIC 23463333 A 71 81 robenidine TRIVIAL 23463333 T 17 27 robenidine TRIVIAL 23463334 A 176 197 polyvinyl pyrrolidone SYSTEMATIC 23463334 A 202 214 stearic acid TRIVIAL 23463334 A 248 258 nifedipine TRIVIAL 23463334 T 86 96 nifedipine TRIVIAL 23463336 A 749 760 acetic acid SYSTEMATIC 23463609 A 48 54 carbon SYSTEMATIC 23463609 T 38 44 carbon SYSTEMATIC 23463634 A 11 19 graphene TRIVIAL 23463634 A 53 61 graphene TRIVIAL 23463634 A 93 101 graphene TRIVIAL 23463634 T 4 12 graphene TRIVIAL 23463732 A 1173 1177 PFBV ABBREVIATION 23463732 A 411 442 polyfluorene-bis-vinylphenylene SYSTEMATIC 23463732 A 444 448 PFBV ABBREVIATION 23463732 A 487 491 PMMA ABBREVIATION 23463732 A 579 583 PFBV ABBREVIATION 23463732 A 708 712 PMMA ABBREVIATION 23463732 A 752 756 PFBV ABBREVIATION 23463732 A 796 800 PMMA ABBREVIATION 23463732 A 904 908 PFBV ABBREVIATION 23463898 A 779 789 daunomycin TRIVIAL 23464618 A 0 6 Carbon SYSTEMATIC 23464618 A 182 188 carbon SYSTEMATIC 23464618 T 51 57 carbon SYSTEMATIC 23464667 A 313 327 Liquiritigenin TRIVIAL 23464667 A 521 535 liquiritigenin TRIVIAL 23464667 A 626 640 liquiritigenin TRIVIAL 23464667 A 757 764 lactate FAMILY 23464667 A 801 815 liquiritigenin TRIVIAL 23464667 T 0 14 Liquiritigenin TRIVIAL 23464789 A 137 156 lithium borohydride SYSTEMATIC 23464789 A 177 205 oligo(hydroxyalkanoate)diols FAMILY 23464789 A 221 265 poly(3-hydroxybutyrate-co-4-hydroxybutyrate) SYSTEMATIC 23464789 A 280 296 poly(3HB-co-4HB) SYSTEMATIC 23464789 A 325 354 poly[(R,S)-3-hydroxybutyrate] SYSTEMATIC 23464789 A 358 361 PHB ABBREVIATION 23464789 A 417 445 oligo(hydroxyalkanoate)diols FAMILY 23464789 A 565 573 hydroxyl SYSTEMATIC 23464789 A 619 624 ester FAMILY 23464789 A 74 95 polyhydroxyalkanoates FAMILY 23464789 A 754 763 polyester FAMILY 23464789 A 826 829 PHA ABBREVIATION 23464789 A 97 100 PHA ABBREVIATION 23464789 T 23 26 PHA ABBREVIATION 23464789 T 88 91 PHA ABBREVIATION 23464859 A 820 827 silicon SYSTEMATIC 23464990 A 1062 1066 SiO2 FORMULA 23464990 A 373 375 O2 FORMULA 23464990 A 430 436 Pt(II) FORMULA 23464990 A 437 448 tetraphenyl SYSTEMATIC 23464990 A 449 468 tetrabenzoporphyrin SYSTEMATIC 23464990 A 470 476 PtTPBP ABBREVIATION 23464990 A 482 488 BODIPY ABBREVIATION 23464990 A 495 500 BDP-G NO CLASS 23464990 A 505 510 BDP-Y NO CLASS 23465066 A 10 13 GaS FORMULA 23465066 A 1073 1076 GaS FORMULA 23465066 A 1225 1228 GaS FORMULA 23465066 A 1321 1328 silicon SYSTEMATIC 23465066 A 145 148 GaS FORMULA 23465066 A 285 288 GaS FORMULA 23465066 A 322 326 SiO2 FORMULA 23465066 A 327 329 Si FORMULA 23465066 A 354 380 polyethylene terephthalate SYSTEMATIC 23465066 A 382 385 PET ABBREVIATION 23465066 A 506 514 graphene TRIVIAL 23465066 A 516 520 MoS2 FORMULA 23465066 A 615 619 SiO2 FORMULA 23465066 A 620 622 Si FORMULA 23465066 A 627 630 PET ABBREVIATION 23465066 A 958 961 GaS FORMULA 23465066 T 28 31 GaS FORMULA 23465072 A 130 140 [(3)H]EBOB SYSTEMATIC 23465072 A 231 235 GABA ABBREVIATION 23465072 A 242 250 chloride SYSTEMATIC 23465072 A 322 328 phenyl SYSTEMATIC 23465072 A 337 348 [(3)H]A1443 SYSTEMATIC 23465072 A 35 46 isoxazoline SYSTEMATIC 23465072 A 516 526 [(3)H]EBOB SYSTEMATIC 23465072 A 552 563 isoxazoline SYSTEMATIC 23465072 A 59 64 A1443 IDENTIFIER 23465072 A 604 614 avermectin FAMILY 23465072 A 615 619 GABA ABBREVIATION 23465072 A 620 629 glutamate TRIVIAL 23465072 A 630 638 chloride SYSTEMATIC 23465072 A 708 712 GABA ABBREVIATION 23465072 A 713 722 glutamate TRIVIAL 23465072 A 95 128 [(3)H]ethynylbicycloorthobenzoate SYSTEMATIC 23465072 T 39 56 [(3)H]Isoxazoline SYSTEMATIC 23465072 T 4 8 GABA ABBREVIATION 23465072 T 9 18 Glutamate TRIVIAL 23465594 A 1013 1016 Ser FORMULA 23465594 A 106 113 ethanol SYSTEMATIC 23465594 A 1063 1066 Thr FORMULA 23465594 A 1113 1116 Ser FORMULA 23465594 A 1144 1151 ethanol SYSTEMATIC 23465594 A 1204 1210 sterol FAMILY 23465594 A 1251 1263 carbohydrate FAMILY 23465594 A 1335 1342 ethanol SYSTEMATIC 23465594 A 1401 1409 acyl-CoA ABBREVIATION 23465594 A 1443 1451 acyl-CoA ABBREVIATION 23465594 A 1493 1501 acyl-CoA ABBREVIATION 23465594 A 1611 1621 fatty acid FAMILY 23465594 A 1641 1648 ethanol SYSTEMATIC 23465594 A 1695 1707 stearoyl CoA TRIVIAL 23465594 A 1725 1735 fatty acid FAMILY 23465594 A 175 178 AMP ABBREVIATION 23465594 A 1851 1858 ethanol SYSTEMATIC 23465594 A 247 254 ethanol SYSTEMATIC 23465594 A 492 499 ethanol SYSTEMATIC 23465594 A 538 545 ethanol SYSTEMATIC 23465594 A 602 609 alanine TRIVIAL 23465594 A 680 693 triglycerides FAMILY 23465594 A 752 759 Ethanol SYSTEMATIC 23465594 A 887 894 ethanol SYSTEMATIC 23465594 A 938 941 Thr FORMULA 23465594 A 956 966 acetyl CoA SYSTEMATIC 23465594 A 994 1001 ethanol SYSTEMATIC 23465594 T 129 136 ethanol SYSTEMATIC 23465612 A 214 229 carboxylic acid SYSTEMATIC 23465612 A 326 334 hydrogen SYSTEMATIC 23465612 A 51 70 dihydroisoquinoline SYSTEMATIC 23465612 T 103 113 aspartates FAMILY 23465612 T 32 51 dihydroisoquinoline SYSTEMATIC 23466228 A 0 10 Olanzapine TRIVIAL 23466228 A 104 127 1-fluoro-2-nitrobenzene SYSTEMATIC 23466228 A 145 155 piperazine SYSTEMATIC 23466228 A 246 263 [(11)C]Olanzapine SYSTEMATIC 23466228 A 308 321 [(11)C]CH3OTf SYSTEMATIC 23466228 A 330 331 N FORMULA 23466228 A 333 338 (11)C FORMULA 23466228 A 454 464 [(11)C]CO2 SYSTEMATIC 23466228 A 599 616 [(11)C]Olanzapine SYSTEMATIC 23466228 A 72 85 malononitrile TRIVIAL 23466228 A 87 102 propionaldehyde SYSTEMATIC 23466228 T 0 15 [11C]olanzapine SYSTEMATIC 23466231 A 154 199 17α-bromo-21-iodo-3β-acetoxypregn-5-en-20-one SYSTEMATIC 23466231 A 20 79 [17(20)Z]- and [17(20)E]-pregna-5,17(20)-dien-21-oyl amides MULTIPLE 23466231 A 298 304 sterol FAMILY 23466231 A 309 321 triglyceride FAMILY 23466231 A 385 406 25-hydroxycholesterol SYSTEMATIC 23466231 A 414 458 [17(20)E]-pregna-5,17(20)-dien-21-oyl amides FAMILY 23466231 A 532 544 triglyceride FAMILY 23466231 A 618 623 amide FAMILY 23466231 A 645 689 [17(20)Z]-pregna-5,17(20)-dien-21-oyl amides FAMILY 23466231 T 0 34 Pregna-5,17(20)-dien-21-oyl amides FAMILY 23466231 T 45 51 sterol FAMILY 23466231 T 56 68 triglyceride FAMILY 23466235 A 598 606 hydrogen SYSTEMATIC 23466235 A 638 641 Asp FORMULA 23466235 A 649 652 Asp FORMULA 23466444 A 632 638 oxygen SYSTEMATIC 23466459 A 100 119 heterocyclic amines FAMILY 23466459 A 1257 1261 PhIP ABBREVIATION 23466459 A 17 64 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine SYSTEMATIC 23466459 A 173 177 PhIP ABBREVIATION 23466459 A 336 340 PhIP ABBREVIATION 23466459 A 410 414 PhIP ABBREVIATION 23466459 A 521 525 PhIP ABBREVIATION 23466459 A 629 633 PhIP ABBREVIATION 23466459 A 66 70 PhIP ABBREVIATION 23466459 A 769 773 PhIP ABBREVIATION 23466459 A 955 959 PhIP ABBREVIATION 23466459 T 151 155 PhIP ABBREVIATION 23466459 T 35 53 heterocyclic amine FAMILY 23466461 A 1080 1083 FB1 ABBREVIATION 23466461 A 1088 1091 FB2 ABBREVIATION 23466461 A 147 157 Fumonisins FAMILY 23466461 A 62 82 fumonisins B1 and B2 MULTIPLE 23466461 A 761 780 fumonisin B1 and B2 MULTIPLE 23466461 A 84 87 FB1 ABBREVIATION 23466461 A 900 903 FB1 ABBREVIATION 23466461 A 916 919 FB2 ABBREVIATION 23466461 A 92 95 FB2 ABBREVIATION 23466461 T 14 24 fumonisins FAMILY 23466488 A 0 11 l-glutamine TRIVIAL 23466488 A 1080 1085 amide FAMILY 23466488 A 1247 1258 glutathione TRIVIAL 23466488 A 1260 1275 malondialdehyde TRIVIAL 23466488 A 1277 1288 glutathione TRIVIAL 23466488 A 1301 1312 glutathione TRIVIAL 23466488 A 1402 1409 glucose TRIVIAL 23466488 A 1432 1443 sitagliptin TRIVIAL 23466488 A 1465 1476 l-glutamine TRIVIAL 23466488 A 1499 1510 l-glutamine TRIVIAL 23466488 A 1535 1546 l-glutamine TRIVIAL 23466488 A 1573 1580 glucose TRIVIAL 23466488 A 1602 1607 amide FAMILY 23466488 A 1661 1668 glucose TRIVIAL 23466488 A 1710 1721 l-glutamine TRIVIAL 23466488 A 1750 1761 l-glutamine TRIVIAL 23466488 A 1779 1786 glucose TRIVIAL 23466488 A 186 197 l-glutamine TRIVIAL 23466488 A 1878 1883 amide FAMILY 23466488 A 1935 1949 streptozotocin TRIVIAL 23466488 A 1950 1962 nicotinamide TRIVIAL 23466488 A 247 252 amide FAMILY 23466488 A 266 280 streptozotocin TRIVIAL 23466488 A 281 293 nicotinamide TRIVIAL 23466488 A 295 298 STZ ABBREVIATION 23466488 A 299 302 NTM ABBREVIATION 23466488 A 31 41 amino acid FAMILY 23466488 A 537 549 nicotinamide TRIVIAL 23466488 A 609 623 streptozotocin TRIVIAL 23466488 A 62 67 sugar FAMILY 23466488 A 715 726 sitagliptin TRIVIAL 23466488 A 747 758 l-glutamine TRIVIAL 23466488 A 780 791 l-glutamine TRIVIAL 23466488 A 817 828 l-glutamine TRIVIAL 23466488 A 852 863 l-glutamine TRIVIAL 23466488 A 868 879 sitagliptin TRIVIAL 23466488 A 908 915 glucose TRIVIAL 23466488 T 111 123 nicotinamide TRIVIAL 23466488 T 47 52 amide FAMILY 23466488 T 5 16 l-glutamine TRIVIAL 23466488 T 96 110 stretpozotocin TRIVIAL 23466874 A 267 280 phlorotannins FAMILY 23466874 A 289 300 polyphenols FAMILY 23466874 A 454 467 phlorotannins FAMILY 23466874 A 602 609 glucose TRIVIAL 23466874 A 652 660 tyrosine TRIVIAL 23466874 A 927 940 phlorotannins FAMILY 23466874 T 45 58 phlorotannins FAMILY 23466874 T 67 78 polyphenols FAMILY 23468099 T 56 63 choline FAMILY 23468099 T 90 97 glucose TRIVIAL 23468310 A 250 259 flavonoid FAMILY 23468310 A 260 269 sarothrin TRIVIAL 23468310 A 271 312 5,7,4'-trihydroxy-3,6,8-trimethoxyflavone SYSTEMATIC 23468310 A 538 547 sarothrin TRIVIAL 23468310 A 717 726 sarothrin TRIVIAL 23468310 T 0 9 Sarothrin TRIVIAL 23468426 A 0 15 Isopenicillin N TRIVIAL 23468426 A 1038 1043 AhCmC ABBREVIATION 23468426 A 106 109 ACV ABBREVIATION 23468426 A 1123 1129 Fe(II) FORMULA 23468426 A 1130 1134 AhCV ABBREVIATION 23468426 A 125 140 isopenicillin N TRIVIAL 23468426 A 1333 1339 Fe(II) FORMULA 23468426 A 1340 1345 AhCmC ABBREVIATION 23468426 A 1368 1377 thioether SYSTEMATIC 23468426 A 1394 1398 iron SYSTEMATIC 23468426 A 1400 1405 AhCmC ABBREVIATION 23468426 A 142 145 IPN ABBREVIATION 23468426 A 1492 1495 ACV ABBREVIATION 23468426 A 1531 1540 methylene SYSTEMATIC 23468426 A 190 200 penicillin FAMILY 23468426 A 205 218 cephalosporin FAMILY 23468426 A 362 369 valinyl TRIVIAL 23468426 A 446 455 cysteinyl TRIVIAL 23468426 A 513 558 δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-valine SYSTEMATIC 23468426 A 560 564 AhCV ABBREVIATION 23468426 A 570 621 δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-allylglycine SYSTEMATIC 23468426 A 623 628 AhCaG ABBREVIATION 23468426 A 63 104 δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine SYSTEMATIC 23468426 A 635 660 monocyclic hydroxy-lactam SYSTEMATIC 23468426 A 705 714 methylene SYSTEMATIC 23468426 A 819 825 lactam SYSTEMATIC 23468426 A 907 949 δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-Xaa FAMILY 23468426 A 972 976 AhCV ABBREVIATION 23468426 A 981 1036 δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-S-methylcysteine SYSTEMATIC 23468426 T 19 34 isopenicillin N TRIVIAL 23468426 T 81 123 δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-Xaa FAMILY 23469688 A 1047 1055 LY294002 IDENTIFIER 23469688 A 1060 1065 U0126 IDENTIFIER 23469688 A 1133 1137 8-TQ SYSTEMATIC 23469688 A 1148 1152 8-TQ SYSTEMATIC 23469688 A 1317 1321 8-TQ SYSTEMATIC 23469688 A 20 43 8-(tosylamino)quinoline SYSTEMATIC 23469688 A 201 205 8-TQ SYSTEMATIC 23469688 A 45 49 8-TQ SYSTEMATIC 23469688 A 487 491 8-TQ SYSTEMATIC 23469688 A 77 88 BAY 11-7082 IDENTIFIER 23469688 A 775 779 8-TQ SYSTEMATIC 23469688 A 998 1002 8-TQ SYSTEMATIC 23469688 T 0 23 8-(Tosylamino)quinoline SYSTEMATIC 23469781 A 34 44 quinolines FAMILY 23469781 A 412 422 quinolines FAMILY 23469781 A 492 501 quinoline SYSTEMATIC 23469781 A 508 521 sitamaquinine TRIVIAL 23469781 A 526 535 Imiquimod TRIVIAL 23469781 T 0 10 Quinolines FAMILY 23469924 A 0 8 Androgen FAMILY 23469924 A 121 129 androgen FAMILY 23469924 A 1400 1408 androgen FAMILY 23469924 A 805 813 androgen FAMILY 23469924 A 916 924 androgen FAMILY 23469924 T 57 65 Androgen FAMILY 23470034 A 133 192 3,7-dioxo-11β-hydroxy-5α-tirucalla-8,24(Z)-dien-26-oic acid SYSTEMATIC 23470034 A 49 68 mastichinoic acid A TRIVIAL 23470034 A 6 30 tetracyclic triterpenoid FAMILY 23470034 T 6 30 tetracyclic triterpenoid FAMILY 23470076 A 200 208 cysteine TRIVIAL 23470076 A 52 62 amino acid FAMILY 23470076 A 695 704 cysteinyl TRIVIAL 23470080 A 289 290 N FORMULA 23470080 A 657 665 arginine TRIVIAL 23470104 A 1202 1215 hydroxymethyl SYSTEMATIC 23470104 A 134 136 CH FORMULA 23470104 A 306 308 CH FORMULA 23470104 A 321 326 CH2OH FORMULA 23470104 A 408 421 hydroxymethyl SYSTEMATIC 23470104 A 518 523 CH3OH FORMULA 23470104 A 532 537 CH2OH FORMULA 23470104 A 563 566 Cl2 FORMULA 23470104 A 591 592 H FORMULA 23470104 A 618 620 Cl FORMULA 23470104 A 623 628 CH3OH FORMULA 23470104 A 631 634 HCl FORMULA 23470104 A 637 642 CH2OH FORMULA 23470104 A 74 87 hydroxymethyl SYSTEMATIC 23470104 A 97 102 CH2OH FORMULA 23470104 T 50 63 Hydroxymethyl SYSTEMATIC 23470104 T 79 81 CH FORMULA 23470105 A 429 436 guanine TRIVIAL 23470105 A 704 711 guanine TRIVIAL 23470152 A 120 139 phenyleneethynylene SYSTEMATIC 23470152 A 168 176 trithiol FAMILY 23470152 A 227 234 Au(111) FORMULA 23470152 A 318 324 sulfur SYSTEMATIC 23470152 A 37 45 trithiol FAMILY 23470152 A 54 64 adamantane TRIVIAL 23470152 A 549 559 ferrocenyl TRIVIAL 23470152 A 85 95 ferrocenyl TRIVIAL 23470152 T 125 134 ferrocene TRIVIAL 23470152 T 93 100 au(111) FORMULA 23470280 A 1108 1111 ISO ABBREVIATION 23470280 A 1171 1184 catecholamine TRIVIAL 23470280 A 1317 1326 glutamate TRIVIAL 23470280 A 1408 1417 glutamate TRIVIAL 23470280 A 272 285 catecholamine TRIVIAL 23470280 A 536 544 dopamine TRIVIAL 23470280 A 588 601 isoproterenol TRIVIAL 23470280 A 603 606 ISO ABBREVIATION 23470280 A 760 769 glutamate TRIVIAL 23470280 A 942 956 catecholamines FAMILY 23470280 T 35 49 catecholamines FAMILY 23470359 A 1061 1066 PFAAs ABBREVIATION 23470359 A 1151 1163 carboxylates FAMILY 23470359 A 1168 1178 sulfonates FAMILY 23470359 A 1397 1402 PFAAs ABBREVIATION 23470359 A 169 189 perfluoroalkyl acids FAMILY 23470359 A 191 196 PFAAs ABBREVIATION 23470359 A 411 416 PFAAs ABBREVIATION 23470359 A 657 662 PFAAs ABBREVIATION 23470359 A 853 858 PFAAs ABBREVIATION 23470359 T 54 74 perfluoroalkyl acids FAMILY 23470359 T 76 81 PFAAs ABBREVIATION 23470418 A 0 11 Bisphenol A TRIVIAL 23470418 A 1166 1169 BPA ABBREVIATION 23470418 A 157 169 para-hydroxy SYSTEMATIC 23470418 A 184 191 benzene SYSTEMATIC 23470418 A 199 210 Bisphenol A TRIVIAL 23470418 A 212 215 BPA ABBREVIATION 23470418 A 475 478 BPA ABBREVIATION 23470418 A 54 70 diphenylmethanes FAMILY 23470418 A 738 749 glutathione TRIVIAL 23470418 A 764 767 BPA ABBREVIATION 23470418 A 785 788 BPF ABBREVIATION 23470418 A 790 794 BPAF ABBREVIATION 23470418 A 796 799 BPZ ABBREVIATION 23470418 A 804 809 DMBPA ABBREVIATION 23470418 A 895 900 NADPH ABBREVIATION 23470418 A 90 97 benzene SYSTEMATIC 23470418 A 905 908 GSH ABBREVIATION 23470418 A 953 956 BPA ABBREVIATION 23470418 T 17 28 bisphenol A TRIVIAL 23470418 T 46 49 BPF ABBREVIATION 23470418 T 51 55 BPAF ABBREVIATION 23470418 T 57 60 BPZ ABBREVIATION 23470418 T 65 70 DMBPA ABBREVIATION 23470922 A 1049 1053 NADH ABBREVIATION 23470922 A 742 785 nicotinamide adenine dinucleotide phosphate SYSTEMATIC 23470922 A 787 792 NADPH ABBREVIATION 23470922 A 812 825 plastoquinone TRIVIAL 23471029 A 0 9 Resolvins FAMILY 23471029 A 1004 1031 cis-1,4,7,10-undecatetraene SYSTEMATIC 23471029 A 126 145 omega-3 fatty acids FAMILY 23471029 A 146 188 all-cis-5,8,11,14,17-eicosapentaenoic acid SYSTEMATIC 23471029 A 190 193 EPA ABBREVIATION 23471029 A 199 243 all-cis-4,7,10,13,16,19-docosahexaenoic acid SYSTEMATIC 23471029 A 245 248 DHA ABBREVIATION 23471029 A 323 331 resolvin FAMILY 23471029 A 359 369 fatty acid FAMILY 23471029 A 477 496 mono- and dihydroxy MULTIPLE 23471029 A 660 690 omega-3 and omega-6 fatty acid MULTIPLE 23471029 A 703 722 Mono- and dihydroxy MULTIPLE 23471029 A 961 988 polyunsaturated fatty acids FAMILY 23471029 T 24 53 mono- and dihydroxy-resolvins FAMILY 23471029 T 59 62 EPA ABBREVIATION 23471029 T 67 70 DHA ABBREVIATION 23471156 A 227 239 metal oxides FAMILY 23471156 A 362 374 metal oxides FAMILY 23471156 A 383 386 ZnO FORMULA 23471156 A 388 391 NiO FORMULA 23471156 A 393 396 CuO FORMULA 23471156 A 398 403 Co3O4 FORMULA 23471156 A 408 412 CeO2 FORMULA 23471156 A 499 510 metal oxide FAMILY 23471156 A 723 735 metal oxides FAMILY 23471156 A 737 740 NiO FORMULA 23471156 A 796 802 silver SYSTEMATIC 23471156 A 897 909 metal oxides FAMILY 23471156 T 11 23 metal oxides FAMILY 23471218 A 1128 1134 oxygen SYSTEMATIC 23471218 A 194 200 oxygen SYSTEMATIC 23471440 A 1338 1348 quinolones FAMILY 23471440 A 1417 1431 propionic acid SYSTEMATIC 23471440 A 1668 1678 quinolones FAMILY 23471440 A 1683 1697 propionic acid SYSTEMATIC 23471440 T 34 44 quinolones FAMILY 23471488 A 1159 1166 glucose TRIVIAL 23471488 A 1565 1572 glucose TRIVIAL 23471488 A 287 298 lauric acid TRIVIAL 23471488 A 505 514 metformin TRIVIAL 23471488 A 965 972 glucose TRIVIAL 23471504 A 0 20 Olmesartan medoxomil TRIVIAL 23471504 A 138 148 olmesartan TRIVIAL 23471504 T 77 97 olmesartan medoxomil TRIVIAL 23471539 A 674 685 amino acids FAMILY 23471561 A 130 143 Anthraquinone SYSTEMATIC 23471561 A 287 304 bis-anthraquinone SYSTEMATIC 23471561 T 19 36 bis-anthraquinone SYSTEMATIC 23471710 A 116 126 omeprazole TRIVIAL 23471710 A 1251 1258 glucose TRIVIAL 23471710 A 252 266 clarithromycin TRIVIAL 23471710 A 268 279 amoxicillin TRIVIAL 23471710 A 285 295 omeprazole TRIVIAL 23471710 A 649 661 carbohydrate FAMILY 23471710 A 710 724 clarithromycin TRIVIAL 23471710 A 743 754 amoxicillin TRIVIAL 23471710 A 777 787 omeprazole TRIVIAL 23471710 A 905 919 clarithromycin TRIVIAL 23471710 A 97 111 clarithromycin TRIVIAL 23471969 A 293 303 amino acid FAMILY 23471969 A 642 653 amino acids FAMILY 23472709 A 101 103 N2 FORMULA 23472709 A 133 149 Iron aminoimides FAMILY 23472709 A 199 201 N2 FORMULA 23472709 A 230 233 E-H FAMILY 23472709 A 245 251 PhSiH3 FORMULA 23472709 A 256 258 H2 FORMULA 23472709 A 336 337 H FORMULA 23472709 A 346 347 B FORMULA 23472709 A 38 58 Fe-diphosphineborane SYSTEMATIC 23472709 A 385 391 Fe-BPh FORMULA 23472709 T 0 3 H-H FORMULA 23472709 T 30 37 Fe≡NNR2 FAMILY 23472709 T 65 67 N2 FORMULA 23472709 T 8 12 Si-H FORMULA 23472738 A 1159 1171 [Au25L18](-) FORMULA 23472738 A 473 506 trialkylacryloylphosphonium salts FAMILY 23472738 A 776 788 [Au25L18](-) FORMULA 23472738 A 794 803 SCH2CH2Ph FORMULA 23472738 A 958 962 Au25 FORMULA 23472745 A 1347 1359 anthocyanins FAMILY 23472745 A 392 445 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid SYSTEMATIC 23472745 A 450 497 N,N-dimethyl-p-phenylenediamine dihydrochloride SYSTEMATIC 23472745 A 58 70 polyphenolic FAMILY 23472745 A 583 612 2,2-diphenyl-1-picrylhydrazyl SYSTEMATIC 23472745 A 642 654 polyphenolic FAMILY 23472745 A 675 687 polyphenolic FAMILY 23472745 A 692 703 anthocyanin FAMILY 23472745 A 75 86 anthocyanin FAMILY 23472745 A 980 992 polyphenolic FAMILY 23472803 A 324 326 Au FORMULA 23472803 A 36 38 Au FORMULA 23472803 A 505 507 Au FORMULA 23472803 A 587 598 polystyrene SYSTEMATIC 23472803 A 605 630 poly(methyl methacrylate) SYSTEMATIC 23472803 A 637 641 PMMA ABBREVIATION 23472803 A 832 834 Au FORMULA 23472803 A 917 919 Au FORMULA 23472803 T 31 33 au FORMULA 23472840 A 13 22 ibuprofen TRIVIAL 23472840 A 24 31 aspirin TRIVIAL 23472840 A 37 49 erythromycin TRIVIAL 23472840 A 81 94 Pluronic F127 TRIVIAL 23472840 T 38 51 Pluronic F127 TRIVIAL 23472886 A 439 458 indenoisoquinolines FAMILY 23472886 A 605 633 indenoisoquinoline rexinoids FAMILY 23472886 A 667 685 indenoisoquinoline SYSTEMATIC 23472886 A 726 734 carboxyl SYSTEMATIC 23472886 T 48 76 indenoisoquinoline rexinoids FAMILY 23473024 A 1027 1029 Au FORMULA 23473024 A 1086 1090 H2O2 FORMULA 23473024 A 123 125 Au FORMULA 23473024 A 1278 1280 Au FORMULA 23473024 A 262 279 hydrogen peroxide SYSTEMATIC 23473024 A 281 285 H2O2 FORMULA 23473024 A 345 352 citrate FAMILY 23473024 A 434 438 H2O2 FORMULA 23473024 A 450 452 Au FORMULA 23473024 A 489 491 Au FORMULA 23473024 A 548 550 Au FORMULA 23473024 A 604 606 Au FORMULA 23473024 A 714 716 Au FORMULA 23473024 A 754 760 thiols FAMILY 23473024 A 837 841 H2O2 FORMULA 23473024 A 858 871 poly-l-lysine SYSTEMATIC 23473024 A 909 911 Au FORMULA 23473024 T 130 147 hydrogen peroxide SYSTEMATIC 23473030 A 0 4 Iron SYSTEMATIC 23473030 A 196 200 iron SYSTEMATIC 23473030 A 228 232 Iron SYSTEMATIC 23473030 A 345 349 Iron SYSTEMATIC 23473030 A 466 470 iron SYSTEMATIC 23473030 A 62 66 iron SYSTEMATIC 23473030 T 0 4 Iron SYSTEMATIC 23473037 A 717 724 leucine TRIVIAL 23473037 A 728 735 proline TRIVIAL 23473037 A 844 856 nitric oxide SYSTEMATIC 23473444 A 100 104 GdIO FORMULA 23473444 A 353 363 gadolinium SYSTEMATIC 23473444 A 391 395 GdIO FORMULA 23473444 A 475 479 GdIO FORMULA 23473444 A 641 659 dopamine sulfonate SYSTEMATIC 23473444 A 68 78 gadolinium SYSTEMATIC 23473444 A 682 686 GdIO FORMULA 23473444 A 88 98 iron oxide SYSTEMATIC 23473444 A 925 935 iron-oxide SYSTEMATIC 23473444 T 11 21 iron-oxide SYSTEMATIC 23473664 A 137 146 glutamate TRIVIAL 23473664 T 14 23 glutamate TRIVIAL 23473681 A 1036 1044 thiourea SYSTEMATIC 23473681 A 306 314 MAC13243 IDENTIFIER 23473681 A 432 440 MAC13243 IDENTIFIER 23473681 A 466 495 S-(4-chlorobenzyl)isothiourea SYSTEMATIC 23473681 A 684 692 MAC13243 IDENTIFIER 23473681 A 701 709 thiourea SYSTEMATIC 23473681 A 935 943 thiourea SYSTEMATIC 23473681 A 967 975 MAC13243 IDENTIFIER 23473681 T 15 23 MAC13243 IDENTIFIER 23473681 T 68 76 thiourea SYSTEMATIC 23473801 A 0 10 Hinokitiol TRIVIAL 23473801 A 1000 1010 hinokitiol TRIVIAL 23473801 A 1059 1069 Hinokitiol TRIVIAL 23473801 A 1190 1193 ODQ ABBREVIATION 23473801 A 1198 1205 SQ22536 IDENTIFIER 23473801 A 1233 1243 hinokitiol TRIVIAL 23473801 A 1304 1314 hinokitiol TRIVIAL 23473801 A 1387 1395 hydroxyl SYSTEMATIC 23473801 A 145 155 hinokitiol TRIVIAL 23473801 A 1496 1506 hinokitiol TRIVIAL 23473801 A 329 339 hinokitiol TRIVIAL 23473801 A 418 428 hinokitiol TRIVIAL 23473801 A 591 607 arachidonic acid TRIVIAL 23473801 A 613 616 ADP ABBREVIATION 23473801 A 618 628 Hinokitiol TRIVIAL 23473801 A 841 848 calcium SYSTEMATIC 23473801 A 866 874 hydroxyl SYSTEMATIC 23473801 A 884 886 OH FORMULA 23473801 A 899 909 Hinokitiol TRIVIAL 23473801 T 0 10 Hinokitiol TRIVIAL 23473802 A 1138 1144 sodium SYSTEMATIC 23473802 A 1226 1232 sodium SYSTEMATIC 23473802 A 274 283 disulfide SYSTEMATIC 23473802 A 466 475 disulfide SYSTEMATIC 23473802 A 511 518 cystine TRIVIAL 23473802 A 547 556 disulfide SYSTEMATIC 23473802 A 843 849 sodium SYSTEMATIC 23473804 A 1002 1005 7KC SYSTEMATIC 23473804 A 1014 1019 7βOHC SYSTEMATIC 23473804 A 1072 1077 27OHC SYSTEMATIC 23473804 A 1136 1148 α-tocopherol TRIVIAL 23473804 A 1158 1170 ellagic acid TRIVIAL 23473804 A 116 121 7βOHC SYSTEMATIC 23473804 A 1175 1186 resveratrol TRIVIAL 23473804 A 1211 1214 7KC SYSTEMATIC 23473804 A 1220 1225 7βOHC SYSTEMATIC 23473804 A 1280 1283 7KC SYSTEMATIC 23473804 A 1288 1293 27OHC SYSTEMATIC 23473804 A 1346 1356 oxysterols FAMILY 23473804 A 1481 1487 Ca(2+) FORMULA 23473804 A 330 340 oxysterols FAMILY 23473804 A 459 462 7KC SYSTEMATIC 23473804 A 466 471 7βOHC SYSTEMATIC 23473804 A 52 63 cholesterol TRIVIAL 23473804 A 65 82 7-ketocholesterol SYSTEMATIC 23473804 A 713 734 27-hydroxycholesterol SYSTEMATIC 23473804 A 805 811 Fura-2 TRIVIAL 23473804 A 828 834 Ca(2+) FORMULA 23473804 A 84 87 7KC SYSTEMATIC 23473804 A 869 879 oxysterols FAMILY 23473804 A 923 932 ionomycin TRIVIAL 23473804 A 93 114 7β-hydroxycholesterol SYSTEMATIC 23473804 T 31 40 oxysterol FAMILY 23473804 T 82 89 calcium SYSTEMATIC 23474013 A 1884 1891 cocaine TRIVIAL 23474013 A 32 39 cocaine TRIVIAL 23474013 A 932 939 cocaine TRIVIAL 23474013 T 109 116 cocaine TRIVIAL 23474217 A 1110 1123 camptothecine TRIVIAL 23474217 A 33 46 camptothecine TRIVIAL 23474217 A 470 483 camptothecine TRIVIAL 23474217 A 590 603 camptothecine TRIVIAL 23474217 A 644 667 10-hydroxycamptothecine SYSTEMATIC 23474217 A 669 691 9-methoxycamptothecine SYSTEMATIC 23474217 A 693 714 20-deoxycamptothecine SYSTEMATIC 23474217 A 989 1002 camptothecine TRIVIAL 23474217 T 47 60 camptothecine TRIVIAL 23474319 A 0 6 Copper SYSTEMATIC 23474319 A 1049 1051 Cu FORMULA 23474319 A 1068 1076 carbonyl FAMILY 23474319 A 1102 1104 Cu FORMULA 23474319 A 1182 1184 Cu FORMULA 23474319 A 1211 1221 superoxide TRIVIAL 23474319 A 1403 1405 Cu FORMULA 23474319 A 1438 1457 reduced glutathione TRIVIAL 23474319 A 1459 1462 GSH ABBREVIATION 23474319 A 1523 1534 glutathione TRIVIAL 23474319 A 1553 1564 glutathione TRIVIAL 23474319 A 1565 1566 S FORMULA 23474319 A 1589 1600 glutathione TRIVIAL 23474319 A 1636 1638 Cu FORMULA 23474319 A 165 177 myo-inositol TRIVIAL 23474319 A 1836 1839 MDA ABBREVIATION 23474319 A 1884 1886 Cu FORMULA 23474319 A 1940 1942 Cu FORMULA 23474319 A 1997 2007 superoxide TRIVIAL 23474319 A 206 208 Cu FORMULA 23474319 A 2246 2248 Cu FORMULA 23474319 A 2283 2294 reduced GSH ABBREVIATION 23474319 A 2425 2427 Cu FORMULA 23474319 A 2523 2525 Cu FORMULA 23474319 A 2634 2636 Cu FORMULA 23474319 A 434 436 Cu FORMULA 23474319 A 580 582 Cu FORMULA 23474319 A 673 675 Cu FORMULA 23474319 A 762 764 Cu FORMULA 23474319 A 8 10 Cu FORMULA 23474319 A 802 809 lactate FAMILY 23474319 A 839 854 malondialdehyde TRIVIAL 23474319 A 856 859 MDA ABBREVIATION 23474319 T 48 60 myo-inositol TRIVIAL 23474319 T 69 75 copper SYSTEMATIC 23474320 A 999 1001 Cu FORMULA 23474321 A 1649 1654 Na(+) FORMULA 23474321 A 1655 1659 K(+) FORMULA 23474321 T 116 121 Na(+) FORMULA 23474321 T 122 126 K(+) FORMULA 23474323 A 1265 1275 creatinine TRIVIAL 23474323 A 696 703 tannins FAMILY 23474323 A 717 728 polyphenols FAMILY 23474323 A 892 903 cholesterol TRIVIAL 23474323 A 909 920 cholesterol TRIVIAL 23474323 A 929 940 cholesterol TRIVIAL 23474356 A 0 10 Macrolones FAMILY 23474356 A 1004 1016 azithromycin TRIVIAL 23474356 A 101 130 4-quinolone-3-carboxylic acid SYSTEMATIC 23474356 A 1065 1075 macrolones FAMILY 23474356 A 1140 1147 octanol SYSTEMATIC 23474356 A 1208 1216 hydrogen SYSTEMATIC 23474356 A 1233 1248 secondary amide FAMILY 23474356 A 1281 1290 macrolone FAMILY 23474356 A 142 143 C FORMULA 23474356 A 162 171 macrolide FAMILY 23474356 A 176 186 macrolides FAMILY 23474356 A 410 419 macrolone FAMILY 23474356 A 548 558 macrolones FAMILY 23474356 A 610 619 macrolide FAMILY 23474356 A 620 632 azithromycin TRIVIAL 23474356 A 70 79 macrolide FAMILY 23474356 A 707 716 macrolide FAMILY 23474356 A 727 736 quinolone FAMILY 23474356 A 822 831 macrolide FAMILY 23474356 A 833 845 azithromycin TRIVIAL 23474356 A 890 904 clarithromycin TRIVIAL 23474356 A 912 922 macrolones FAMILY 23474356 A 927 941 clarithromycin TRIVIAL 23474356 T 61 71 macrolones FAMILY 23474357 A 1059 1069 certramide FAMILY 23474357 A 1074 1077 IPM ABBREVIATION 23474357 A 1220 1231 certramides FAMILY 23474357 A 1244 1247 IPM ABBREVIATION 23474357 A 368 387 isopropyl myristate SYSTEMATIC 23474357 A 389 392 IPM ABBREVIATION 23474357 A 395 406 certramides FAMILY 23474357 A 490 498 caffeine TRIVIAL 23474357 A 500 509 cortisone TRIVIAL 23474357 A 511 528 diclofenac sodium SYSTEMATIC 23474357 A 530 538 mannitol TRIVIAL 23474357 A 540 554 salicylic acid TRIVIAL 23474357 A 559 571 testosterone TRIVIAL 23474357 A 583 599 propylene glycol SYSTEMATIC 23474357 A 611 618 ethanol SYSTEMATIC 23474357 A 894 904 certramide FAMILY 23474357 A 909 912 IPM ABBREVIATION 23474382 A 1057 1068 alcian blue TRIVIAL 23474382 A 299 306 HMG-CoA ABBREVIATION 23474382 A 367 374 statins FAMILY 23474382 A 470 477 statins FAMILY 23474382 T 19 30 simvastatin TRIVIAL 23474386 A 134 140 amides FAMILY 23474386 A 145 160 benzoimidazoles FAMILY 23474386 A 18 49 5-(benzyloxy)pyridin-2(1H)-ones SYSTEMATIC 23474386 T 6 36 5-(benzyloxy)pyridin-2(1H)-one SYSTEMATIC 23474441 A 306 315 estradiol TRIVIAL 23474645 A 108 124 titanium dioxide SYSTEMATIC 23474645 A 126 130 TiO2 FORMULA 23474645 A 253 281 4,4-N,N-dicarbazole-biphenyl SYSTEMATIC 23474645 A 283 286 CBP ABBREVIATION 23474645 A 292 335 4,4',4''-tris(carbazol-9-yl)-triphenylamine SYSTEMATIC 23474645 A 337 341 TCTA ABBREVIATION 23474645 A 44 48 CdSe FORMULA 23474645 A 442 446 TCTA ABBREVIATION 23474645 A 49 52 CdS FORMULA 23474645 A 53 56 ZnS FORMULA 23474645 A 567 571 TCTA ABBREVIATION 23474645 T 14 17 CdS FORMULA 23474645 T 18 21 ZnS FORMULA 23474645 T 62 78 titanium dioxide SYSTEMATIC 23474645 T 9 13 CdSe FORMULA 23474688 A 1048 1050 Pt FORMULA 23474688 A 1051 1052 C FORMULA 23474688 A 143 149 carbon SYSTEMATIC 23474688 A 381 389 nitrogen SYSTEMATIC 23474688 A 419 427 graphene TRIVIAL 23474688 A 452 460 graphene TRIVIAL 23474688 A 566 574 Nitrogen SYSTEMATIC 23474688 A 692 700 graphene TRIVIAL 23474688 A 874 883 hydrazine SYSTEMATIC 23474688 A 958 960 Pt FORMULA 23474688 A 961 962 C FORMULA 23474688 A 977 983 oxygen SYSTEMATIC 23474688 T 0 8 Nitrogen SYSTEMATIC 23474688 T 102 111 hydrazine SYSTEMATIC 23474688 T 126 132 oxygen SYSTEMATIC 23474688 T 21 29 graphene TRIVIAL 23474899 A 26 46 tetrahydroquinolines FAMILY 23474899 A 358 393 tricyclic pyrimido[4,5-b]quinolines FAMILY 23474899 A 48 83 tetrahydropyrimido[4,5-b]quinolines FAMILY 23474899 A 89 131 tetrahydropentaazacyclopenta[a]anthracenes FAMILY 23474899 T 72 92 tetrahydroquinolines FAMILY 23474972 A 253 261 hydrogen SYSTEMATIC 23474972 A 27 31 NaCl FORMULA 23474972 A 454 462 hydrogen SYSTEMATIC 23474972 A 67 73 carbon SYSTEMATIC 23474972 T 104 112 hydrogen SYSTEMATIC 23475901 A 0 7 Calcium SYSTEMATIC 23475901 A 1293 1299 Ca(2+) FORMULA 23475901 A 159 166 calcium SYSTEMATIC 23475901 A 182 189 calcium SYSTEMATIC 23475901 A 208 215 calcium SYSTEMATIC 23475901 A 403 409 Ca(2+) FORMULA 23475901 A 597 603 Ca(2+) FORMULA 23477344 A 58 64 carbon SYSTEMATIC 23477344 A 598 605 proline TRIVIAL 23477344 T 22 28 Carbon SYSTEMATIC 23477344 T 43 50 Proline TRIVIAL 23477419 A 126 160 α-methylene-β-aminopropanoic acids FAMILY 23477419 A 162 165 Map ABBREVIATION 23477419 A 206 210 EM-1 ABBREVIATION 23477419 A 232 235 Dmt ABBREVIATION 23477419 A 240 250 (R/S)-βPro ABBREVIATION 23477419 A 259 266 (ph)Map ABBREVIATION 23477419 A 270 282 (2-furyl)Map SYSTEMATIC 23477419 A 437 440 Dmt ABBREVIATION 23477419 A 444 452 (R)-βPro ABBREVIATION 23477419 A 456 459 Trp FORMULA 23477419 A 463 475 (2-furyl)Map SYSTEMATIC 23477419 A 578 587 Forskolin TRIVIAL 23477419 A 596 600 cAMP ABBREVIATION 23477419 A 67 80 endomorphin-1 TRIVIAL 23477419 A 82 86 EM-1 ABBREVIATION 23477419 A 869 877 morphine TRIVIAL 23477419 T 65 78 Endomorphin-1 TRIVIAL 23477451 A 107 123 penicimarins D-F MULTIPLE 23477451 A 140 151 benzofurans FAMILY 23477451 A 153 169 penicifurans A-D MULTIPLE 23477451 A 204 215 isocoumarin TRIVIAL 23477451 A 44 61 hydroisocoumarins FAMILY 23477451 A 63 79 penicimarins A-C MULTIPLE 23477451 A 711 722 isocoumarin TRIVIAL 23477451 A 900 913 penicifuran A TRIVIAL 23477451 A 93 105 isocoumarins FAMILY 23477451 T 0 11 Isocoumarin TRIVIAL 23477451 T 28 39 Benzofurans FAMILY 23477623 A 100 129 2,2-diphenyl-1-picrylhydrazyl SYSTEMATIC 23477623 A 1006 1011 Sal B ABBREVIATION 23477623 A 131 135 DPPH ABBREVIATION 23477623 A 15 33 salvianolic acid B TRIVIAL 23477623 A 166 172 Fe(2+) FORMULA 23477623 A 219 227 phenolic FAMILY 23477623 A 243 248 Sal B ABBREVIATION 23477623 A 35 40 Sal B ABBREVIATION 23477623 A 363 394 cholesteryl ester hydroperoxide SYSTEMATIC 23477623 A 396 402 CE-OOH FORMULA 23477623 A 439 444 Sal B ABBREVIATION 23477623 A 530 535 Sal B ABBREVIATION 23477623 A 613 619 CE-OOH FORMULA 23477623 A 667 672 Sal B ABBREVIATION 23477623 A 738 743 Sal B ABBREVIATION 23477623 A 923 928 Sal B ABBREVIATION 23477623 T 116 134 salvianolic acid B TRIVIAL 23477623 T 44 50 copper SYSTEMATIC 23478800 A 1223 1237 cucurbitacin I TRIVIAL 23478800 A 1312 1326 cucurbitacin I TRIVIAL 23478800 A 1351 1357 oxygen SYSTEMATIC 23478800 A 1391 1410 N-acetyl l-cysteine SYSTEMATIC 23478800 A 1489 1503 cucurbitacin I TRIVIAL 23478800 A 1719 1733 cucurbitacin I TRIVIAL 23478800 A 226 244 guanine nucleotide TRIVIAL 23478800 A 282 290 tyrosine TRIVIAL 23478800 A 571 585 cucurbitacin I TRIVIAL 23478800 A 822 836 cucurbitacin I TRIVIAL 23478800 A 882 896 Cucurbitacin I TRIVIAL 23478800 A 992 1006 cucurbitacin I TRIVIAL 23478800 T 0 14 Cucurbitacin I TRIVIAL 23478800 T 138 146 tyrosine TRIVIAL 23478800 T 77 83 oxygen SYSTEMATIC 23479193 A 104 117 Mannich bases FAMILY 23479193 A 121 128 S-alkyl FAMILY 23479193 A 25 88 4-phenyl-5-pyridin-4-yl-2,3-dihydro-3H-1,2,4-triazole-3-thiones FAMILY 23479193 A 309 318 celocoxib TRIVIAL 23479193 T 40 54 diaryltriazole FAMILY 23479194 A 1183 1194 Lupinifolin TRIVIAL 23479194 A 171 182 lupinifolin TRIVIAL 23479194 A 188 223 8-methoxy-7,3',4'-trihydroxyflavone SYSTEMATIC 23479194 A 233 262 7,8,3',4'-tetrahydroxyflavone SYSTEMATIC 23479194 A 270 282 triterpenoid FAMILY 23479194 A 283 289 lupeol TRIVIAL 23479194 A 310 317 sterols FAMILY 23479194 A 318 331 β-sitosterone TRIVIAL 23479194 A 337 362 stigmasta-5,22-dien-3-one SYSTEMATIC 23479194 A 368 380 β-sitosterol TRIVIAL 23479194 A 390 402 stigmasterol TRIVIAL 23479194 A 815 826 lupinifolin TRIVIAL 23479194 A 912 923 Lupinifolin TRIVIAL 23479318 A 19 26 cadmium SYSTEMATIC 23479318 A 28 30 Cd FORMULA 23479318 A 378 380 Cd FORMULA 23479318 A 385 387 Pb FORMULA 23479318 A 42 44 Pb FORMULA 23479318 A 529 531 Cd FORMULA 23479318 A 533 535 Pb FORMULA 23479318 A 701 703 Cd FORMULA 23479318 A 708 710 Pb FORMULA 23479318 T 15 22 cadmium SYSTEMATIC 23479389 A 457 469 [6]-Gingerol TRIVIAL 23479389 A 805 817 [6]-gingerol TRIVIAL 23479389 T 0 12 [6]-gingerol TRIVIAL 23479390 A 212 223 ophioglonin TRIVIAL 23479390 A 238 255 2-phenoxychromone SYSTEMATIC 23479390 A 269 287 3'-O-β-D-glucoside SYSTEMATIC 23479390 A 35 50 dichloromethane SYSTEMATIC 23479390 A 405 416 ophioglonin TRIVIAL 23479390 A 820 828 estrogen FAMILY 23479390 T 0 12 Peltogynoids FAMILY 23479390 T 17 35 2-Phenoxychromones FAMILY 23479407 A 0 9 Gefitinib TRIVIAL 23479407 A 1249 1257 afatinib TRIVIAL 23479407 A 1262 1273 dacomitinib TRIVIAL 23479407 A 14 23 erlotinib TRIVIAL 23479407 A 54 62 tyrosine TRIVIAL 23479455 A 1005 1015 EMD 386088 IDENTIFIER 23479455 A 1085 1094 clozapine TRIVIAL 23479455 A 1146 1154 ketamine TRIVIAL 23479455 A 1259 1267 ketamine TRIVIAL 23479455 A 34 53 5-hydroxytryptamine SYSTEMATIC 23479455 A 55 64 serotonin TRIVIAL 23479455 A 588 598 EMD 386088 IDENTIFIER 23479455 A 607 615 ketamine TRIVIAL 23479455 A 782 792 EMD 386088 IDENTIFIER 23479455 A 906 914 ketamine TRIVIAL 23479455 A 945 953 ketamine TRIVIAL 23479455 T 25 34 serotonin TRIVIAL 23479455 T 4 23 5-hydroxytryptamine SYSTEMATIC 23479455 T 55 65 EMD 386088 IDENTIFIER 23479455 T 78 86 ketamine TRIVIAL 23479738 A 0 15 S-Nitrosothiols FAMILY 23479738 A 101 105 H2O2 FORMULA 23479738 A 1120 1122 NO FORMULA 23479738 A 1123 1126 SNO FORMULA 23479738 A 1201 1218 S-nitrosocysteine SYSTEMATIC 23479738 A 129 135 oxygen SYSTEMATIC 23479738 A 1354 1371 S-nitrosocysteine SYSTEMATIC 23479738 A 1425 1442 S-nitrosocysteine SYSTEMATIC 23479738 A 1488 1490 NO FORMULA 23479738 A 1491 1494 SNO FORMULA 23479738 A 17 21 SNOs FAMILY 23479738 A 282 286 SNOs FAMILY 23479738 A 291 295 H2O2 FORMULA 23479738 A 317 322 thiol FAMILY 23479738 A 34 46 nitric oxide SYSTEMATIC 23479738 A 472 474 NO FORMULA 23479738 A 475 478 SNO FORMULA 23479738 A 48 50 NO FORMULA 23479738 A 569 572 Cys FORMULA 23479738 A 61 62 S FORMULA 23479738 A 687 689 NO FORMULA 23479738 A 690 693 SNO FORMULA 23479738 A 709 726 S-nitrosocysteine SYSTEMATIC 23479738 A 731 751 S-nitrosoglutathione SYSTEMATIC 23479738 A 772 773 S FORMULA 23479738 A 82 99 hydrogen peroxide SYSTEMATIC 23479738 A 882 891 disulfide SYSTEMATIC 23479738 A 934 943 cysteines FAMILY 23479738 A 945 948 Cys FORMULA 23479738 A 956 959 Cys FORMULA 23479738 T 27 30 cys FORMULA 23480196 A 1278 1282 COOH FORMULA 23480196 A 1563 1565 Ni FORMULA 23480196 A 1600 1604 COOH FORMULA 23480196 A 199 202 HCl FORMULA 23480196 A 287 293 carbon SYSTEMATIC 23480196 A 361 363 Ni FORMULA 23480196 A 391 397 carbon SYSTEMATIC 23480196 A 489 492 HCl FORMULA 23480196 A 612 615 HCl FORMULA 23480196 A 668 672 COOH FORMULA 23480196 A 683 689 HNO(3) FORMULA 23480196 A 763 767 COOH FORMULA 23480196 A 77 83 carbon SYSTEMATIC 23480196 A 795 799 COOH FORMULA 23480196 T 59 65 carbon SYSTEMATIC 23480279 A 55 65 colchicine TRIVIAL 23480279 A 70 84 thiocolchicine SYSTEMATIC 23480279 T 65 78 colchicinoids FAMILY 23480348 A 0 14 Polyallylamine SYSTEMATIC 23480348 A 142 145 PAH ABBREVIATION 23480348 A 16 19 PAH ABBREVIATION 23480348 A 267 270 PAH ABBREVIATION 23480348 A 275 277 Pd FORMULA 23480348 A 327 329 Pd FORMULA 23480348 A 342 355 Pd icosahedra FORMULA 23480348 A 36 49 Pd icosahedra FORMULA 23480348 A 384 387 PAH ABBREVIATION 23480348 A 434 436 Pd FORMULA 23480348 A 483 496 Pd icosahedra FORMULA 23480348 A 532 535 PAH ABBREVIATION 23480348 A 551 564 Pd icosahedra FORMULA 23480348 A 612 619 ethanol SYSTEMATIC 23480348 A 648 654 oxygen SYSTEMATIC 23480348 A 719 727 Pt black FORMULA 23480348 A 815 828 Pd icosahedra FORMULA 23480348 A 874 882 Pt black FORMULA 23480348 A 950 952 Pd FORMULA 23480348 T 0 14 Polyallylamine SYSTEMATIC 23480348 T 131 138 ethanol SYSTEMATIC 23480348 T 30 50 palladium icosahedra SYSTEMATIC 23480446 A 203 213 amino acid FAMILY 23480446 A 367 378 amino acids FAMILY 23480446 A 424 444 aromatic amino acids FAMILY 23480446 A 445 458 phenylalanine TRIVIAL 23480446 A 460 468 tyrosine TRIVIAL 23480446 A 474 484 tryptophan TRIVIAL 23480446 A 632 640 hydrogen SYSTEMATIC 23480446 A 661 669 hydrogen SYSTEMATIC 23480532 A 1254 1261 lactose TRIVIAL 23480532 A 239 258 lactose monohydrate TRIVIAL 23480597 A 534 543 polyamine FAMILY 23480798 A 104 110 phenol SYSTEMATIC 23480798 A 1095 1103 hydrogen SYSTEMATIC 23480798 A 1112 1132 carbon tetrachloride SYSTEMATIC 23480798 A 116 117 F FORMULA 23480798 A 119 121 Cl FORMULA 23480798 A 1258 1266 hydrogen SYSTEMATIC 23480798 A 1311 1317 phenol SYSTEMATIC 23480798 A 1450 1460 trihydrate SYSTEMATIC 23480798 A 1485 1495 2F-ethanol SYSTEMATIC 23480798 A 1640 1648 hydrogen SYSTEMATIC 23480798 A 1703 1704 F FORMULA 23480798 A 1709 1711 Cl FORMULA 23480798 A 713 733 carbon tetrachloride SYSTEMATIC 23480798 A 89 96 ethanol SYSTEMATIC 23480798 A 919 923 OCCF FORMULA 23480798 A 947 957 2F-ethanol SYSTEMATIC 23480798 T 23 26 o-h FORMULA 23480798 T 29 30 f FORMULA 23480798 T 35 38 o-h FORMULA 23480798 T 41 43 cl FORMULA 23480798 T 44 52 hydrogen SYSTEMATIC 23480848 A 103 106 SNP ABBREVIATION 23480848 A 108 127 Na2[Fe(CN)5NO]·2H2O FORMULA 23480848 A 1118 1120 NO FORMULA 23480848 A 1124 1127 SNP ABBREVIATION 23480848 A 1370 1374 heme FAMILY 23480848 A 1453 1455 NO FORMULA 23480848 A 1459 1462 SNP ABBREVIATION 23480848 A 1566 1574 nitrosyl SYSTEMATIC 23480848 A 1579 1586 cyanide SYSTEMATIC 23480848 A 1645 1653 trans-CN SYSTEMATIC 23480848 A 1717 1722 Fe-NO FORMULA 23480848 A 1731 1734 SNP ABBREVIATION 23480848 A 204 206 NO FORMULA 23480848 A 210 213 SNP ABBREVIATION 23480848 A 245 253 nitrosyl SYSTEMATIC 23480848 A 354 366 nitric oxide SYSTEMATIC 23480848 A 368 370 NO FORMULA 23480848 A 42 50 nitrosyl SYSTEMATIC 23480848 A 439 441 NO FORMULA 23480848 A 476 491 deuterium oxide SYSTEMATIC 23480848 A 493 501 methanol SYSTEMATIC 23480848 A 503 510 ethanol SYSTEMATIC 23480848 A 512 527 ethylene glycol SYSTEMATIC 23480848 A 529 538 formamide SYSTEMATIC 23480848 A 544 562 dimethyl sulfoxide SYSTEMATIC 23480848 A 586 588 NO FORMULA 23480848 A 681 699 dimethyl sulfoxide SYSTEMATIC 23480848 A 74 76 NO FORMULA 23480848 A 763 765 NO FORMULA 23480848 A 81 101 sodium nitroprusside SYSTEMATIC 23480848 A 892 894 NO FORMULA 23480848 A 898 901 SNP ABBREVIATION 23480848 A 984 986 2D FORMULA 23480848 T 72 80 Nitrosyl SYSTEMATIC 23480848 T 95 101 Fe(II) FORMULA 23481139 A 12 26 nicotinic acid TRIVIAL 23481139 A 131 135 TBTU ABBREVIATION 23481139 T 0 14 Nicotinic acid TRIVIAL 23481236 A 1009 1017 tyrosine TRIVIAL 23481236 A 1033 1059 palmitic and stearic acids MULTIPLE 23481236 A 1070 1079 ceramides FAMILY 23481236 A 1142 1145 Ser FORMULA 23481236 A 1312 1322 wortmannin TRIVIAL 23481236 A 1373 1382 ceramides FAMILY 23481236 A 1437 1440 Ser FORMULA 23481236 A 1663 1666 Ser FORMULA 23481236 A 295 303 tyrosine TRIVIAL 23481236 A 417 430 triglycerides FAMILY 23481236 A 432 436 TAGs ABBREVIATION 23481236 A 439 451 diglycerides FAMILY 23481236 A 453 457 DAGs ABBREVIATION 23481236 A 464 473 ceramides FAMILY 23481236 A 656 667 fatty acids FAMILY 23481236 A 7 14 glucose TRIVIAL 23481236 A 730 740 wortmannin TRIVIAL 23481236 A 758 778 phosphatidylinositol TRIVIAL 23481236 A 841 845 DAGs ABBREVIATION 23481236 A 847 851 TAGs ABBREVIATION 23481236 A 89 96 glucose TRIVIAL 23481236 A 980 986 serine TRIVIAL 23481236 A 988 991 Ser FORMULA 23481236 A 997 1000 Ser FORMULA 23481281 A 0 17 Aphanamgrandiol A TRIVIAL 23481281 A 31 43 triterpenoid FAMILY 23481281 A 369 386 Aphanamgrandiol A TRIVIAL 23481281 A 51 71 bicyclo[3,2,1]octane SYSTEMATIC 23481281 T 0 17 Aphanamgrandiol A TRIVIAL 23481281 T 25 37 triterpenoid FAMILY 23481281 T 52 58 carbon SYSTEMATIC 23481650 A 203 209 indole SYSTEMATIC 23481650 A 237 243 indole SYSTEMATIC 23481650 A 248 257 azaindole FAMILY 23481650 A 295 306 5-azaindole SYSTEMATIC 23481650 A 597 608 7-azaindole SYSTEMATIC 23481650 T 0 24 N-substituted azaindoles FAMILY 23481677 A 209 226 chloroazaphilones FAMILY 23481677 A 273 290 chloroazaphilones FAMILY 23481677 A 375 386 helicusin A TRIVIAL 23481677 A 395 415 deacetylsclerotiorin TRIVIAL 23481677 A 432 449 chloroazaphilones FAMILY 23481677 A 451 462 helicusin E TRIVIAL 23481677 A 468 486 isochromophilone X TRIVIAL 23481677 A 495 514 isochromophilone XI TRIVIAL 23481677 A 532 543 pentaketide FAMILY 23481677 A 545 556 bartanolide TRIVIAL 23481677 T 0 11 Helicusin E TRIVIAL 23481677 T 13 31 Isochromophilone X TRIVIAL 23481677 T 36 55 Isochromophilone XI TRIVIAL 23481677 T 61 78 Chloroazaphilones FAMILY 23483327 A 1227 1239 phenanthrene SYSTEMATIC 23483327 A 1541 1548 cadmium SYSTEMATIC 23483327 A 1552 1564 phenanthrene SYSTEMATIC 23483327 A 246 253 cadmium SYSTEMATIC 23483327 A 258 270 phenanthrene SYSTEMATIC 23483327 A 853 860 cadmium SYSTEMATIC 23483327 A 865 877 phenanthrene SYSTEMATIC 23483327 T 121 128 cadmium SYSTEMATIC 23483327 T 133 145 phenanthrene SYSTEMATIC 23484490 A 32 38 carbon SYSTEMATIC 23484490 T 59 65 Carbon SYSTEMATIC 23484546 A 1055 1063 hydrogen SYSTEMATIC 23484546 A 161 169 graphene TRIVIAL 23484546 A 487 495 graphene TRIVIAL 23484546 A 611 619 graphene TRIVIAL 23484546 A 742 751 acetylene SYSTEMATIC 23484546 A 799 807 graphene TRIVIAL 23484546 A 856 867 hydrocarbon FAMILY 23484546 A 94 102 graphene TRIVIAL 23484546 A 977 985 graphene TRIVIAL 23484546 T 70 78 graphene TRIVIAL 23484622 A 1159 1162 ZnO FORMULA 23484622 A 256 270 benzo[a]pyrene SYSTEMATIC 23484622 A 341 355 p-benzoquinone SYSTEMATIC 23484622 A 468 478 zinc oxide SYSTEMATIC 23484622 A 480 483 ZnO FORMULA 23484622 A 56 62 oxygen SYSTEMATIC 23484622 T 73 87 Benzo[a]pyrene SYSTEMATIC 23484851 A 108 121 phenylalanine TRIVIAL 23484851 A 123 126 Phe FORMULA 23484851 A 1486 1492 pyrene SYSTEMATIC 23484851 A 1550 1553 Phe FORMULA 23484851 A 207 210 Asp FORMULA 23484851 A 215 218 Phe FORMULA 23484851 A 517 520 Asp FORMULA 23484851 A 645 648 Asp FORMULA 23484851 A 654 657 Asp FORMULA 23484851 A 72 85 aspartic acid TRIVIAL 23484851 A 87 90 Asp FORMULA 23484851 A 938 941 Asp FORMULA 23484851 A 951 954 Phe FORMULA 23484851 A 993 996 Asp FORMULA 23484974 A 316 322 quartz TRIVIAL 23485065 A 789 797 dopamine TRIVIAL 23485151 A 106 110 LiCl FORMULA 23485151 A 126 130 H(+) FORMULA 23485151 A 2 8 Ca(2+) FORMULA 23485151 A 272 276 H(+) FORMULA 23485151 A 321 326 Li(+) FORMULA 23485151 T 63 67 LiCl FORMULA 23485151 T 79 81 H+ FORMULA 23485441 A 0 16 Poly(ADP-ribose) SYSTEMATIC 23485441 A 1016 1022 NAD(+) ABBREVIATION 23485441 A 176 179 ADP ABBREVIATION 23485441 A 180 186 ribose TRIVIAL 23485441 A 207 217 amino acid FAMILY 23485441 A 254 257 ADP ABBREVIATION 23485441 A 258 264 ribose TRIVIAL 23485441 A 318 321 ADP ABBREVIATION 23485441 A 322 329 ribosyl TRIVIAL 23485441 A 445 448 ADP ABBREVIATION 23485441 A 449 455 ribose TRIVIAL 23485441 A 62 65 ADP ABBREVIATION 23485441 A 66 73 ribosyl TRIVIAL 23485441 T 36 39 ADP ABBREVIATION 23485450 A 1100 1102 Fe FORMULA 23485450 A 244 255 doxorubicin TRIVIAL 23485450 A 257 260 DOX ABBREVIATION 23485450 A 280 301 poly(ethylene glycol) SYSTEMATIC 23485450 A 303 306 PEG ABBREVIATION 23485450 A 329 342 acylhydrazone SYSTEMATIC 23485450 A 462 465 DOX ABBREVIATION 23485450 A 49 59 iron-oxide SYSTEMATIC 23485450 A 625 628 DOX ABBREVIATION 23485450 A 776 779 DOX ABBREVIATION 23485450 A 904 907 DOX ABBREVIATION 23485450 A 913 916 DOX ABBREVIATION 23485450 T 47 57 iron-oxide SYSTEMATIC 23485613 A 0 8 Gossypol TRIVIAL 23485613 A 1033 1041 gossypol TRIVIAL 23485613 A 1120 1128 gossypol TRIVIAL 23485613 A 1171 1179 gossypol TRIVIAL 23485613 A 1296 1304 gossypol TRIVIAL 23485613 A 143 151 gossypol TRIVIAL 23485613 A 253 261 gossypol TRIVIAL 23485613 A 325 333 gossypol TRIVIAL 23485613 A 435 443 gossypol TRIVIAL 23485613 A 594 602 gossypol TRIVIAL 23485613 A 810 818 gossypol TRIVIAL 23485613 T 36 44 gossypol TRIVIAL 23485613 T 72 80 gossypol TRIVIAL 23485991 A 444 453 disulfide SYSTEMATIC 23485991 A 483 484 N FORMULA 23485991 A 642 659 hydrogen peroxide SYSTEMATIC 23485991 A 670 685 methyl viologen SYSTEMATIC 23486187 A 392 395 Trp FORMULA 23487486 A 1357 1369 progesterone TRIVIAL 23487486 A 1392 1395 MPA ABBREVIATION 23487486 A 1633 1645 progesterone TRIVIAL 23487486 A 4 12 steroids FAMILY 23487486 A 493 505 progesterone TRIVIAL 23487486 A 531 540 progestin FAMILY 23487486 A 541 568 medroxyprogesterone acetate TRIVIAL 23487486 A 570 573 MPA ABBREVIATION 23487486 A 717 720 MPA ABBREVIATION 23487486 T 11 23 progesterone TRIVIAL 23487486 T 28 47 medroxyprogesterone TRIVIAL 23488728 A 1113 1120 citrate FAMILY 23488728 A 1158 1171 ascorbic acid TRIVIAL 23488728 A 151 158 silicon SYSTEMATIC 23488728 A 50 57 silicon SYSTEMATIC 23488728 A 58 65 Si(111) FORMULA 23488728 A 596 603 silicon SYSTEMATIC 23488728 A 835 841 carbon SYSTEMATIC 23488728 A 906 911 amine SYSTEMATIC 23488728 A 967 974 Si(111) FORMULA 23488728 T 22 27 oxide SYSTEMATIC 23488728 T 33 40 silicon SYSTEMATIC 23488739 A 102 110 glycidol TRIVIAL 23488739 A 1020 1028 hydrogen SYSTEMATIC 23488739 A 173 188 ethylene glycol SYSTEMATIC 23488739 A 230 244 poly(glycidol) SYSTEMATIC 23488739 A 391 401 oleic acid TRIVIAL 23488739 A 402 408 octane SYSTEMATIC 23488739 A 41 48 diamond TRIVIAL 23488739 A 480 486 octane SYSTEMATIC 23488739 A 496 506 oleic acid TRIVIAL 23488739 A 58 75 dimethylsulfoxide SYSTEMATIC 23488739 A 722 725 H2O FORMULA 23488739 A 741 748 toluene TRIVIAL 23488748 A 1300 1308 hydrogen SYSTEMATIC 23488987 A 101 107 oxygen SYSTEMATIC 23488987 A 1058 1064 oxygen SYSTEMATIC 23488987 A 1112 1121 nitroaryl FAMILY 23488987 A 1153 1158 amino FAMILY 23488987 A 1247 1255 xanthine TRIVIAL 23488987 A 1279 1304 6-nitroquinolin-2(1H)-one SYSTEMATIC 23488987 A 138 147 Nitroaryl FAMILY 23488987 A 1784 1793 nitroaryl FAMILY 23488987 A 1803 1809 oxygen SYSTEMATIC 23488987 A 290 299 nitroaryl FAMILY 23488987 A 309 316 nitroso SYSTEMATIC 23488987 A 318 331 hydroxylamino SYSTEMATIC 23488987 A 337 342 amino FAMILY 23488987 A 377 383 oxygen SYSTEMATIC 23488987 A 481 497 6-nitroquinoline SYSTEMATIC 23488987 A 660 668 xanthine TRIVIAL 23488987 A 669 677 xanthine TRIVIAL 23488987 A 759 775 6-aminoquinoline SYSTEMATIC 23488987 A 871 895 6-hydroxylaminoquinoline SYSTEMATIC 23488987 A 952 960 xanthine TRIVIAL 23488987 A 961 969 xanthine TRIVIAL 23488987 T 24 40 6-Nitroquinoline SYSTEMATIC 23488987 T 60 76 6-Aminoquinoline SYSTEMATIC 23489135 A 111 116 OZ277 IDENTIFIER 23489135 A 121 126 OZ439 IDENTIFIER 23489135 A 193 206 1,2-dioxolane SYSTEMATIC 23489135 A 208 222 1,2,4-trioxane SYSTEMATIC 23489135 A 228 246 1,2,4,5-tetraoxane SYSTEMATIC 23489135 A 294 304 dioxolanes FAMILY 23489135 A 352 357 OZ277 IDENTIFIER 23489135 A 370 378 trioxane FAMILY 23489135 A 485 495 trioxolane FAMILY 23489135 A 499 509 tetraoxane FAMILY 23489135 A 529 534 OZ439 IDENTIFIER 23489135 A 61 77 1,2,4-trioxolane SYSTEMATIC 23489135 A 642 652 trioxolane FAMILY 23489135 A 655 663 trioxane FAMILY 23489135 A 666 676 tetraoxane FAMILY 23489135 A 713 718 OZ439 IDENTIFIER 23489135 A 726 731 OZ277 IDENTIFIER 23489135 A 737 742 OZ439 IDENTIFIER 23489135 A 750 759 peroxides FAMILY 23489135 A 833 838 OZ277 IDENTIFIER 23489135 A 846 855 peroxides FAMILY 23489135 A 94 110 dispiro ozonides FAMILY 23489135 T 110 123 1,2-dioxolane SYSTEMATIC 23489135 T 125 139 1,2,4-trioxane SYSTEMATIC 23489135 T 145 163 1,2,4,5-tetraoxane SYSTEMATIC 23489135 T 57 65 ozonides FAMILY 23489135 T 67 84 1,2,4-trioxolanes FAMILY 23489135 T 86 91 OZ277 IDENTIFIER 23489135 T 93 98 OZ439 IDENTIFIER 23489301 A 1042 1052 alogliptin TRIVIAL 23489301 A 1246 1256 alogliptin TRIVIAL 23489301 A 1360 1370 alogliptin TRIVIAL 23489301 A 1512 1521 aloglipin TRIVIAL 23489301 A 200 210 alogliptin TRIVIAL 23489301 A 286 296 alogliptin TRIVIAL 23489301 A 380 390 alogliptin TRIVIAL 23489301 A 593 603 alogliptin TRIVIAL 23489301 A 774 783 metformin TRIVIAL 23489301 A 785 798 sulfonylureas FAMILY 23489301 A 803 821 thiazolidinediones FAMILY 23489301 T 61 71 alogliptin TRIVIAL 23489623 A 0 12 (R)-Bgugaine TRIVIAL 23489623 A 182 193 norbgugaine TRIVIAL 23489623 A 224 232 bgugaine TRIVIAL 23489623 A 26 46 pyrrolidine alkaloid FAMILY 23489623 A 379 390 norbgugaine TRIVIAL 23489623 A 495 504 pyocyanin TRIVIAL 23489623 T 13 28 (R)-norbgugaine TRIVIAL 23489624 A 252 255 MTT ABBREVIATION 23489629 A 0 33 N-(Pyridin-2-yl) arylsulfonamides FAMILY 23489629 A 199 210 glutathione TRIVIAL 23489629 A 317 326 PF-915275 IDENTIFIER 23489629 A 43 52 PF-915275 IDENTIFIER 23489629 A 545 578 N-(pyridin-2-yl) arylsulfonamides FAMILY 23489629 A 620 638 11β-hydroxysteroid FAMILY 23489629 A 94 112 11β-hydroxysteroid FAMILY 23489629 T 0 32 N-(Pyridin-2-yl) arylsulfonamide FAMILY 23489629 T 47 65 11β-hydroxysteroid FAMILY 23489976 A 1410 1418 cortisol TRIVIAL 23489976 A 1605 1613 cortisol TRIVIAL 23489976 T 40 48 Cortisol TRIVIAL 23490078 A 0 10 Haloalkane FAMILY 23490078 A 1200 1208 tyrosine TRIVIAL 23490078 A 1214 1224 tryptophan TRIVIAL 23490078 A 1234 1240 halide FAMILY 23490078 A 1322 1330 hydrogen SYSTEMATIC 23490078 A 1606 1616 haloalkane FAMILY 23490078 A 1699 1707 hydrogen SYSTEMATIC 23490078 A 172 178 halide FAMILY 23490078 A 290 296 halide FAMILY 23490078 A 313 321 hydrogen SYSTEMATIC 23490078 A 355 365 haloalkane FAMILY 23490078 A 417 428 tryptophans FAMILY 23490078 A 434 444 tryptophan TRIVIAL 23490078 A 445 455 asparagine TRIVIAL 23490078 A 481 491 haloalkane FAMILY 23490078 A 52 58 carbon SYSTEMATIC 23490078 A 577 583 halide FAMILY 23490078 A 59 66 halogen FAMILY 23490078 A 596 604 tyrosine TRIVIAL 23490078 A 649 659 tryptophan TRIVIAL 23490078 A 980 988 hydrogen SYSTEMATIC 23490078 T 23 29 halide FAMILY 23490078 T 81 91 haloalkane FAMILY 23491602 A 782 788 Mn(2+) FORMULA 23491602 A 810 822 5'-phosphate SYSTEMATIC 23491602 A 872 882 amino acid FAMILY 23492810 A 1256 1265 fadrozole TRIVIAL 23492810 A 1374 1377 VTG ABBREVIATION 23492810 A 453 462 fadrozole TRIVIAL 23492810 A 587 596 fadrozole TRIVIAL 23492810 A 712 725 17β-estradiol SYSTEMATIC 23492810 A 735 747 vitellogenin TRIVIAL 23492810 A 749 752 VTG ABBREVIATION 23492810 A 863 872 fadrozole TRIVIAL 23492810 A 911 914 VTG ABBREVIATION 23493317 A 1181 1188 glucose TRIVIAL 23493317 A 243 250 glucose TRIVIAL 23493317 A 308 344 adenosine-3',5'-cyclic monophosphate SYSTEMATIC 23493317 A 346 350 cAMP ABBREVIATION 23493317 A 360 370 nucleotide FAMILY 23493317 A 423 427 cAMP ABBREVIATION 23493317 A 82 89 glucose TRIVIAL 23493374 A 1109 1116 (m)CpGs ABBREVIATION 23493374 A 1310 1316 (m)CpG ABBREVIATION 23493374 A 1370 1392 5-aza-2'-deoxycytidine SYSTEMATIC 23493374 A 1429 1443 trichostatin A TRIVIAL 23493374 A 1452 1458 (m)CpG ABBREVIATION 23493374 A 1591 1598 (m)CpGs ABBREVIATION 23493374 A 1760 1766 (m)CpG ABBREVIATION 23493374 A 1831 1837 (m)CpG ABBREVIATION 23493374 A 199 202 CpG ABBREVIATION 23493374 A 290 299 bisulfite SYSTEMATIC 23493374 A 33 40 glucose TRIVIAL 23493374 A 342 345 CpG ABBREVIATION 23493374 A 347 353 (m)CpG ABBREVIATION 23493374 A 662 669 (m)CpGs ABBREVIATION 23493374 A 779 786 (m)CpGs ABBREVIATION 23493374 A 860 866 methyl SYSTEMATIC 23493374 A 913 920 (m)CpGs ABBREVIATION 23493374 T 12 18 (m)CpG ABBREVIATION 23493374 T 68 75 glucose TRIVIAL 23493449 A 103 109 indole SYSTEMATIC 23493449 A 345 349 SAHA ABBREVIATION 23493449 A 575 579 SAHA ABBREVIATION 23493449 A 59 79 N-hydroxycinnamamide SYSTEMATIC 23493449 A 745 749 SAHA ABBREVIATION 23493449 T 15 35 N-Hydroxycinnamamide SYSTEMATIC 23493449 T 78 84 Indole SYSTEMATIC 23494106 A 1316 1323 JWH-210 IDENTIFIER 23494106 A 1328 1335 JWH-122 IDENTIFIER 23494106 A 30 42 cannabinoids FAMILY 23494106 A 330 345 naphthoylindole FAMILY 23494106 A 357 364 JWH-018 IDENTIFIER 23494106 A 366 373 JWH-073 IDENTIFIER 23494106 A 375 382 JWH-122 IDENTIFIER 23494106 A 387 394 JWH-210 IDENTIFIER 23494106 A 407 420 benzoylindole FAMILY 23494106 A 422 428 AM-694 IDENTIFIER 23494106 A 482 502 tetrahydrocannabinol SYSTEMATIC 23494106 A 842 849 JWH-073 IDENTIFIER 23494106 A 854 861 JWH-122 IDENTIFIER 23494106 A 967 974 JWH-210 IDENTIFIER 23494106 T 45 57 cannabinoids FAMILY 23494106 T 97 108 cannabinoid FAMILY 23494232 A 1114 1122 ketamine TRIVIAL 23494232 A 1143 1151 Ketamine TRIVIAL 23494232 A 1352 1360 SCH23390 IDENTIFIER 23494232 A 1377 1385 Ketamine TRIVIAL 23494232 A 1547 1555 SCH23390 IDENTIFIER 23494232 A 1598 1606 ketamine TRIVIAL 23494232 A 1667 1675 SCH23390 IDENTIFIER 23494232 A 1778 1786 ketamine TRIVIAL 23494232 A 1870 1874 AMPA ABBREVIATION 23494232 A 34 42 ketamine TRIVIAL 23494232 A 377 385 dopamine TRIVIAL 23494232 A 406 462 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid SYSTEMATIC 23494232 A 464 468 AMPA ABBREVIATION 23494232 A 558 566 ketamine TRIVIAL 23494232 A 618 626 ketamine TRIVIAL 23494232 A 790 798 SCH23390 IDENTIFIER 23494232 A 806 810 AMPA ABBREVIATION 23494232 A 918 926 ketamine TRIVIAL 23494232 T 6 14 ketamine TRIVIAL 23494232 T 93 101 dopamine TRIVIAL 23494233 A 1002 1006 TRIM ABBREVIATION 23494233 A 1032 1044 nitric oxide SYSTEMATIC 23494233 A 1071 1135 N-([3-(aminomethyl)phenyl]methyl) ethanimidamide dihydrochloride SYSTEMATIC 23494233 A 11 23 Nitric oxide SYSTEMATIC 23494233 A 1137 1142 1400W IDENTIFIER 23494233 A 1235 1247 Carboxy-PTIO SYSTEMATIC 23494233 A 1258 1264 L-NAME ABBREVIATION 23494233 A 1277 1281 TRIM ABBREVIATION 23494233 A 1297 1302 1400W IDENTIFIER 23494233 A 1361 1368 ethanol SYSTEMATIC 23494233 A 1420 1422 NO FORMULA 23494233 A 1433 1443 L-arginine TRIVIAL 23494233 A 1468 1474 L-NAME ABBREVIATION 23494233 A 1489 1491 NO FORMULA 23494233 A 1553 1560 ethanol SYSTEMATIC 23494233 A 1638 1640 NO FORMULA 23494233 A 169 176 Ethanol SYSTEMATIC 23494233 A 1751 1758 ethanol SYSTEMATIC 23494233 A 25 27 NO FORMULA 23494233 A 329 331 NO FORMULA 23494233 A 378 385 ethanol SYSTEMATIC 23494233 A 555 562 ethanol SYSTEMATIC 23494233 A 655 662 ethanol SYSTEMATIC 23494233 A 724 726 NO FORMULA 23494233 A 737 802 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide SYSTEMATIC 23494233 A 804 816 carboxy-PTIO SYSTEMATIC 23494233 A 832 844 nitric oxide SYSTEMATIC 23494233 A 864 899 N (G)-nitro-L-arginine methyl ester SYSTEMATIC 23494233 A 901 907 L-NAME ABBREVIATION 23494233 A 929 941 nitric oxide SYSTEMATIC 23494233 A 961 1000 1-(2-[trifluoromethyl]phenyl) imidazole SYSTEMATIC 23494233 T 11 23 nitric oxide SYSTEMATIC 23494233 T 94 101 ethanol SYSTEMATIC 23494732 A 0 10 Ascorbigen TRIVIAL 23494732 A 12 15 ABG ABBREVIATION 23494732 A 141 144 ABG ABBREVIATION 23494732 A 324 327 ABG ABBREVIATION 23494732 A 36 42 indole SYSTEMATIC 23494732 A 437 448 hematoxylin TRIVIAL 23494732 A 453 458 eosin FAMILY 23494732 A 531 534 ABG ABBREVIATION 23494732 A 622 625 ABG ABBREVIATION 23494732 A 731 734 ABG ABBREVIATION 23494732 A 832 835 ABG ABBREVIATION 23494732 T 0 10 Ascorbigen TRIVIAL 23494763 A 1013 1021 safranal TRIVIAL 23494763 A 1050 1058 safranal TRIVIAL 23494763 A 1184 1192 safranal TRIVIAL 23494763 A 1194 1202 Safranal TRIVIAL 23494763 A 228 236 safranal TRIVIAL 23494763 A 443 451 safranal TRIVIAL 23494763 A 477 485 safranal TRIVIAL 23494763 A 502 555 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium SYSTEMATIC 23494763 A 557 560 MTT ABBREVIATION 23494763 A 653 669 propidium iodide TRIVIAL 23494763 A 717 720 MTT ABBREVIATION 23494763 A 894 902 safranal TRIVIAL 23494763 T 38 46 Safranal TRIVIAL 23494763 T 65 73 Safranal TRIVIAL 23494802 A 0 12 Curcuminoids FAMILY 23494802 A 1016 1028 curcuminoids FAMILY 23494802 A 203 214 curcuminoid FAMILY 23494802 A 416 428 curcuminoids FAMILY 23494802 A 784 795 Curcuminoid FAMILY 23494802 T 0 12 Curcuminoids FAMILY 23494810 A 1016 1023 pyridyl SYSTEMATIC 23494810 A 1040 1047 pyridyl SYSTEMATIC 23494810 A 1197 1204 pyridyl SYSTEMATIC 23494810 A 1359 1374 (S)-nornicotine TRIVIAL 23494810 A 1398 1410 (S)-nicotine TRIVIAL 23494810 A 1521 1536 (S)-nornicotine TRIVIAL 23494810 A 1580 1592 (S)-nicotine TRIVIAL 23494810 A 337 345 nicotine TRIVIAL 23494810 A 479 491 (S)-nicotine TRIVIAL 23494810 A 69 90 (R)- and (S)-nicotine MULTIPLE 23494810 A 722 729 pyridyl SYSTEMATIC 23494810 A 95 110 (S)-nornicotine TRIVIAL 23494810 A 986 996 pyrrolidyl SYSTEMATIC 23494810 A 997 998 N FORMULA 23494810 T 25 33 Nicotine TRIVIAL 23494810 T 38 49 Nornicotine TRIVIAL 23494831 A 0 6 Ca(2+) FORMULA 23494831 A 122 128 Ca(2+) FORMULA 23494831 A 226 240 coelenterazine TRIVIAL 23494831 A 255 261 oxygen SYSTEMATIC 23494831 A 331 345 coelenterazine TRIVIAL 23494831 A 462 476 coelenterazine TRIVIAL 23494831 A 534 536 N7 FORMULA 23494831 A 552 557 C2(-) FORMULA 23494831 A 58 85 2-hydroperoxycoelenterazine SYSTEMATIC 23494831 A 582 588 oxygen SYSTEMATIC 23494831 A 628 633 C2(-) FORMULA 23494831 A 655 661 peroxy SYSTEMATIC 23494831 A 699 701 N7 FORMULA 23494831 A 729 735 peroxy SYSTEMATIC 23494831 A 773 800 2-hydroperoxycoelenterazine SYSTEMATIC 23494831 A 846 849 His FORMULA 23494831 A 889 892 His FORMULA 23494831 A 971 977 Ca(2+) FORMULA 23494831 T 0 6 Oxygen SYSTEMATIC 23494831 T 32 46 Coelenterazine TRIVIAL 23494834 A 0 8 Graphene TRIVIAL 23494834 A 255 263 graphene TRIVIAL 23494834 A 444 452 Graphene TRIVIAL 23494834 A 821 829 graphene TRIVIAL 23494834 T 28 36 graphene TRIVIAL 23495001 A 247 258 cholesterol TRIVIAL 23495001 A 310 324 Glucosinolates FAMILY 23495001 A 408 423 isothiocyanates FAMILY 23495001 A 522 533 cholesterol TRIVIAL 23495001 A 596 607 cholesterol TRIVIAL 23495001 A 765 779 glucosinolates FAMILY 23495001 A 843 854 cholesterol TRIVIAL 23495001 T 82 93 Cholesterol TRIVIAL 23495151 A 112 117 H(2)O FORMULA 23495151 A 203 204 H FORMULA 23495151 A 217 226 hydronium SYSTEMATIC 23495151 A 244 245 H FORMULA 23495151 A 269 270 H FORMULA 23495151 A 324 325 O FORMULA 23495151 A 371 380 hydronium SYSTEMATIC 23495151 A 38 39 H FORMULA 23495151 A 382 390 H(3)O(+) FORMULA 23495151 A 456 465 hydronium SYSTEMATIC 23495151 A 470 475 H(2)O FORMULA 23495151 A 50 59 hydronium SYSTEMATIC 23495151 A 538 543 H(2)O FORMULA 23495151 A 638 643 H(2)O FORMULA 23495151 A 72 73 H FORMULA 23495151 A 88 89 O FORMULA 23495161 A 284 317 acarviostatins III0(-1) and III23 MULTIPLE 23495161 A 392 406 acarviostatins FAMILY 23495161 A 524 557 acarviostatins III0(-1) and III23 MULTIPLE 23495161 T 57 71 acarviostatins FAMILY 23495163 A 1075 1084 n-alkanes FAMILY 23495163 A 172 178 hexane SYSTEMATIC 23495163 A 366 381 nonacosan-10-ol SYSTEMATIC 23495163 A 597 606 n-alkanes FAMILY 23495163 A 662 663 C FORMULA 23495163 A 671 672 C FORMULA 23495163 A 696 705 n-alkanes FAMILY 23495163 A 70 79 n-alkanes FAMILY 23495163 A 711 712 C FORMULA 23495163 A 718 719 C FORMULA 23495163 A 729 730 C FORMULA 23495163 A 785 791 carbon SYSTEMATIC 23495163 A 820 829 n-alkanes FAMILY 23495163 A 84 99 nonacosan-10-ol SYSTEMATIC 23495163 T 15 24 n-alkanes FAMILY 23495163 T 29 44 nonacosan-10-ol SYSTEMATIC 23495190 A 217 228 artemisinin TRIVIAL 23495190 A 229 240 polypyrrole FAMILY 23495190 A 35 47 Artemisinins FAMILY 23495190 T 0 11 Artemisinin TRIVIAL 23495190 T 12 23 polypyrrole FAMILY 23495719 A 182 190 furfural TRIVIAL 23495719 A 201 223 hydroxymethyl furfural SYSTEMATIC 23495719 A 225 228 HMF ABBREVIATION 23495719 A 719 722 HMF ABBREVIATION 23495769 A 1297 1303 silver SYSTEMATIC 23495769 A 643 645 Ag FORMULA 23495769 A 709 711 Au FORMULA 23495911 A 1029 1037 chromium SYSTEMATIC 23495911 A 1290 1298 chromium SYSTEMATIC 23495911 A 181 189 chromium SYSTEMATIC 23495911 A 278 286 chromium SYSTEMATIC 23495911 T 0 8 Chromium SYSTEMATIC 23496305 A 298 309 fluorescein TRIVIAL 23496349 A 1065 1067 W3 FORMULA 23496349 A 1099 1105 W3(2-) FORMULA 23496349 A 122 133 tritungsten SYSTEMATIC 23496349 A 144 146 W3 FORMULA 23496349 A 148 153 W3(-) FORMULA 23496349 A 155 161 W3(2-) FORMULA 23496349 A 167 184 tritungsten oxide SYSTEMATIC 23496349 A 194 203 W3Ox(-/0) FAMILY 23496349 A 350 357 W3Ox(-) FAMILY 23496349 A 508 519 tritungsten SYSTEMATIC 23496349 A 632 634 W3 FORMULA 23496349 A 636 641 W3(-) FORMULA 23496349 A 646 652 W3(2-) FORMULA 23496349 A 672 678 W3O(-) FORMULA 23496349 A 683 686 W3O FORMULA 23496349 A 701 707 oxygen SYSTEMATIC 23496349 A 762 768 oxygen SYSTEMATIC 23496349 A 812 819 W3O2(-) FORMULA 23496349 A 824 828 W3O2 FORMULA 23496349 A 990 995 W3(-) FORMULA 23496349 A 999 1006 W3O2(-) FORMULA 23496349 T 104 110 W3(2-) FORMULA 23496349 T 37 46 W3Ox(-/0) FAMILY 23496349 T 61 67 W3(2-) FORMULA 23496349 T 97 99 W3 FORMULA 23496412 A 268 279 metal oxide FAMILY 23496412 A 439 456 calcium carbonate SYSTEMATIC 23496412 A 468 477 kaolinite TRIVIAL 23496412 A 597 606 kaolinite TRIVIAL 23496412 T 48 57 Kaolinite TRIVIAL 23496412 T 72 89 Calcium Carbonate SYSTEMATIC 23497227 A 104 112 tyrosine TRIVIAL 23497227 A 12 31 pyrido-quinazolines FAMILY 23497227 A 174 204 Alkylideno/arylideno-bis-ureas MULTIPLE 23497227 A 300 302 1H FORMULA 23497227 T 37 63 N-Aryl pyrido-quinazolines FAMILY 23497860 A 1012 1022 β-carotene TRIVIAL 23497860 A 972 983 astaxanthin TRIVIAL 23497860 A 985 991 lutein TRIVIAL 23497860 A 993 1006 canthaxanthin TRIVIAL 23497864 A 115 133 phenolic glycoside FAMILY 23497864 A 144 166 monoterpene glycosides FAMILY 23497864 A 178 211 1-O-β-d-(4-hydroxybenzoyl)glucose SYSTEMATIC 23497864 A 217 236 pyridylpaeoniflorin SYSTEMATIC 23497864 A 242 286 (8R)-piperitone-4-en-9-O-β-d-glucopyranoside SYSTEMATIC 23497864 A 292 307 oxypaeoniflorin SYSTEMATIC 23497864 A 313 344 6'-O-β-glucopyranosylalbiflorin SYSTEMATIC 23497864 A 350 360 albiflorin TRIVIAL 23497864 A 366 392 β-gentiobiosylpaeoniflorin TRIVIAL 23497864 A 402 414 paeoniflorin TRIVIAL 23497864 A 602 613 formic acid SYSTEMATIC 23497864 A 618 626 methanol SYSTEMATIC 23497864 T 41 76 phenolic and monoterpene glycosides MULTIPLE 23497866 A 131 141 flavonoids FAMILY 23497866 A 202 212 flavonoids FAMILY 23497866 A 301 311 flavonoids FAMILY 23497866 A 321 330 quercetin TRIVIAL 23497866 A 332 342 kaempferol TRIVIAL 23497866 A 347 359 isorhamnetin TRIVIAL 23497866 A 599 606 ethanol SYSTEMATIC 23497866 A 843 853 flavonoids FAMILY 23497866 T 70 80 flavonoids FAMILY 23497867 A 528 531 Thr FORMULA 23497867 A 544 547 Ser FORMULA 23497875 A 140 144 iron SYSTEMATIC 23497875 A 273 275 Fe FORMULA 23497875 A 302 308 FeEDTA FORMULA 23497875 A 357 359 Fe FORMULA 23497875 A 384 390 FeEDTA FORMULA 23497875 A 395 397 Fe FORMULA 23497875 A 434 440 FeEDTA FORMULA 23497875 A 460 462 Fe FORMULA 23497875 A 498 505 nitrate SYSTEMATIC 23497875 A 555 557 Fe FORMULA 23497875 A 646 655 ascorbate TRIVIAL 23497875 A 664 666 Fe FORMULA 23497875 A 705 707 Fe FORMULA 23497875 A 776 780 DPPH ABBREVIATION 23497875 A 809 811 Fe FORMULA 23497875 A 863 865 Fe FORMULA 23497875 A 919 921 Fe FORMULA 23497875 A 984 986 Fe FORMULA 23497875 T 5 7 Fe FORMULA 23497876 A 133 174 reduced nicotinamide adenine dinucleotide TRIVIAL 23497876 A 176 180 NADH ABBREVIATION 23497876 A 222 229 ethanol SYSTEMATIC 23497876 A 259 263 NADH ABBREVIATION 23497876 A 349 353 NADH ABBREVIATION 23497876 A 377 391 graphene oxide SYSTEMATIC 23497876 A 424 430 carbon SYSTEMATIC 23497876 A 596 602 Al(3+) FORMULA 23497876 A 623 645 tridecameric aluminium SYSTEMATIC 23497876 A 665 671 Al(13) FORMULA 23497876 A 706 712 Al(3+) FORMULA 23497876 A 722 728 Al(13) FORMULA 23497876 A 77 84 alcohol FAMILY 23497876 A 929 933 NADH ABBREVIATION 23497876 A 945 951 Al(3+) FORMULA 23497876 A 961 967 Al(13) FORMULA 23497876 T 118 125 alcohol FAMILY 23497876 T 23 37 graphene oxide SYSTEMATIC 23497876 T 42 48 carbon SYSTEMATIC 23497878 A 246 259 ethyl-acetate SYSTEMATIC 23497878 A 455 466 cholesterol TRIVIAL 23497879 A 784 789 MeAαC ABBREVIATION 23497879 A 916 920 HCAs ABBREVIATION 23497879 T 139 146 Trp-P-1 ABBREVIATION 23497879 T 148 155 Trp-P-2 ABBREVIATION 23497879 T 157 160 AαC ABBREVIATION 23497879 T 165 170 MeAαC ABBREVIATION 23497881 A 479 491 l-malic acid SYSTEMATIC 23497881 A 633 641 alcohols FAMILY 23497881 A 653 659 esters FAMILY 23497881 A 743 751 alcohols FAMILY 23497882 A 329 336 glucose TRIVIAL 23497882 A 338 347 galactose TRIVIAL 23497882 A 352 359 mannose TRIVIAL 23497882 A 461 468 glucose TRIVIAL 23497882 A 562 568 oxygen SYSTEMATIC 23497882 A 630 636 Trolox TRIVIAL 23497882 A 86 90 DEAE ABBREVIATION 23497887 A 246 254 carbonyl FAMILY 23497887 A 635 643 peroxide SYSTEMATIC 23497887 A 675 692 organic peroxides FAMILY 23497887 A 694 698 ROOH FAMILY 23497887 A 725 742 hydrogen peroxide SYSTEMATIC 23497887 A 744 748 H2O2 FORMULA 23497887 A 800 809 vitamin E FAMILY 23497887 A 814 823 carnosine TRIVIAL 23497887 T 120 129 peroxides FAMILY 23497894 A 150 172 short-chain fatty acid FAMILY 23497894 A 174 178 SCFA ABBREVIATION 23497894 A 631 639 hydroxyl SYSTEMATIC 23497894 A 660 670 superoxide TRIVIAL 23497894 A 691 721 1,1-diphenyl-2-picryl-hydrazyl SYSTEMATIC 23497894 A 822 826 SCFA ABBREVIATION 23497894 A 828 842 propionic acid SYSTEMATIC 23497894 A 847 861 n-butyric acid SYSTEMATIC 23497894 T 64 86 short-chain fatty acid FAMILY 23497896 A 0 6 Citral TRIVIAL 23497896 A 373 379 citral TRIVIAL 23497896 A 417 423 citral TRIVIAL 23497896 A 588 594 citral TRIVIAL 23497896 A 689 715 polyoxyethylene alkylether FAMILY 23497896 A 859 865 citral TRIVIAL 23497896 T 14 20 citral TRIVIAL 23497896 T 69 95 polyoxyethylene alkylether FAMILY 23497898 A 448 467 phosphatidylcholine FAMILY 23497908 A 46 53 mercury SYSTEMATIC 23499236 A 232 241 rhodanine FAMILY 23499236 A 60 65 enoyl FAMILY 23499236 T 57 62 enoyl FAMILY 23499237 A 335 339 zinc SYSTEMATIC 23499237 A 372 422 UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine SYSTEMATIC 23499237 A 512 515 UDP ABBREVIATION 23499237 A 636 647 hydroxamate SYSTEMATIC 23499237 A 722 725 UDP ABBREVIATION 23499237 A 761 773 α-amino acid FAMILY 23499237 T 14 17 UDP ABBREVIATION 23499237 T 41 51 amino acid FAMILY 23499664 A 0 15 Levomilnacipran TRIVIAL 23499664 A 1025 1028 LVM ABBREVIATION 23499664 A 1219 1229 Duloxetine TRIVIAL 23499664 A 1234 1245 venlafaxine TRIVIAL 23499664 A 127 138 milnacipran TRIVIAL 23499664 A 1346 1349 LVM ABBREVIATION 23499664 A 1430 1433 LVM ABBREVIATION 23499664 A 1477 1481 5-HT SYSTEMATIC 23499664 A 17 20 LVM ABBREVIATION 23499664 A 22 27 F2695 IDENTIFIER 23499664 A 222 225 LVM ABBREVIATION 23499664 A 267 277 duloxetine TRIVIAL 23499664 A 282 293 venlafaxine TRIVIAL 23499664 A 353 356 LVM ABBREVIATION 23499664 A 413 417 5-HT SYSTEMATIC 23499664 A 489 493 5-HT SYSTEMATIC 23499664 A 543 546 LVM ABBREVIATION 23499664 A 578 592 norepinephrine TRIVIAL 23499664 A 605 614 serotonin TRIVIAL 23499664 A 644 648 5-HT SYSTEMATIC 23499664 A 66 75 serotonin TRIVIAL 23499664 A 749 760 venlafaxine TRIVIAL 23499664 A 76 90 norepinephrine TRIVIAL 23499664 A 765 775 duloxetine TRIVIAL 23499664 A 791 794 LVM ABBREVIATION 23499664 A 849 852 LVM ABBREVIATION 23499664 A 903 907 5-HT SYSTEMATIC 23499664 A 92 96 5-HT SYSTEMATIC 23499664 T 0 15 Levomilnacipran TRIVIAL 23499664 T 17 22 F2695 IDENTIFIER 23499664 T 27 41 norepinephrine TRIVIAL 23499758 A 0 10 Raloxifene TRIVIAL 23499758 A 105 115 raloxifene TRIVIAL 23499758 A 1072 1082 raloxifene TRIVIAL 23499758 A 1144 1154 raloxifene TRIVIAL 23499758 A 1258 1268 raloxifene TRIVIAL 23499758 A 1333 1343 raloxifene TRIVIAL 23499758 A 1437 1447 raloxifene TRIVIAL 23499758 A 1538 1548 raloxifene TRIVIAL 23499758 A 1634 1651 mycophenolic acid TRIVIAL 23499758 A 191 194 UDP ABBREVIATION 23499758 A 2130 2140 raloxifene TRIVIAL 23499758 A 503 513 amino acid FAMILY 23499758 A 541 551 raloxifene TRIVIAL 23499758 A 704 714 Raloxifene TRIVIAL 23499758 A 982 992 raloxifene TRIVIAL 23499758 T 10 13 UDP ABBREVIATION 23499758 T 58 68 raloxifene TRIVIAL 23499823 A 117 133 4'-hydroxymethyl SYSTEMATIC 23499823 A 148 166 4'-methoxycarbonyl SYSTEMATIC 23499823 A 216 261 17α-bromo-21-iodo-3β-acetoxypregn-5-en-20-one SYSTEMATIC 23499823 A 24 104 (4'R)- and (4'S)- 2'-{[(E)-3β-hydroxyandrost-5-en-17-ylidene]-methyl} oxazolines MULTIPLE 23499823 A 274 297 (L)-serine methyl ester SYSTEMATIC 23499823 A 302 325 (D)-serine methyl ester SYSTEMATIC 23499823 A 338 405 methyl N-[3β-acetoxy-21-oxopregna-5,17(20)-dien-21-yl]-(L)-serinate SYSTEMATIC 23499823 A 410 477 methyl N-[3β-acetoxy-21-oxopregna-5,17(20)-dien-21-yl]-(D)-serinate SYSTEMATIC 23499823 A 561 567 amides FAMILY 23499823 A 575 681 methyl 2'-{[(E)-3β-acetoxyandrost-5-en-17-ylidene]methyl}-(4'S)-4',5'-dihydro-1',3'-oxazole-4'-carboxylate SYSTEMATIC 23499823 A 686 792 methyl 2'-{[(E)-3β-acetoxyandrost-5-en-17-ylidene]methyl}-(4'R)-4',5'-dihydro-1',3'-oxazole-4'-carboxylate SYSTEMATIC 23499823 T 36 120 (4'R)- and (4'S)- 4'-substituted 2'-{[(E)-androst-5-en-17-ylidene]-methyl}oxazolines MULTIPLE 23499925 A 1986 1987 N FORMULA 23500061 A 407 415 tyrosine TRIVIAL 23500061 A 562 579 polyethyleneimine SYSTEMATIC 23500061 A 594 610 deoxycholic acid TRIVIAL 23500061 T 108 124 deoxycholic acid TRIVIAL 23500061 T 155 172 polyethyleneimine SYSTEMATIC 23500065 A 105 121 proanthocyanidin FAMILY 23500065 A 626 629 Lys FORMULA 23500065 T 41 57 proanthocyanidin FAMILY 23500115 A 1051 1061 ketoprofen TRIVIAL 23500115 A 1152 1162 ketoprofen TRIVIAL 23500115 A 1186 1195 phosphate SYSTEMATIC 23500115 A 1236 1246 Ketoprofen TRIVIAL 23500115 A 1446 1456 ketoprofen TRIVIAL 23500115 A 1510 1520 ketoprofen TRIVIAL 23500115 A 161 171 Ketoprofen TRIVIAL 23500115 A 437 441 (1)H FORMULA 23500115 A 446 451 (31)P FORMULA 23500115 A 499 509 Ketoprofen TRIVIAL 23500115 A 599 609 ketoprofen TRIVIAL 23500115 A 73 83 ketoprofen TRIVIAL 23500115 A 760 770 Ketoprofen TRIVIAL 23500115 A 956 966 ketoprofen TRIVIAL 23500115 A 979 989 ketoprofen TRIVIAL 23500115 T 40 50 ketoprofen TRIVIAL 23500335 A 0 11 Bisphenol A TRIVIAL 23500335 A 1226 1229 BPA ABBREVIATION 23500335 A 1237 1240 BPA ABBREVIATION 23500335 A 13 16 BPA ABBREVIATION 23500335 A 1359 1362 BPA ABBREVIATION 23500335 A 1427 1430 BPA ABBREVIATION 23500335 A 1565 1568 BPA ABBREVIATION 23500335 A 188 191 BPA ABBREVIATION 23500335 A 320 323 BPA ABBREVIATION 23500335 A 394 397 BPA ABBREVIATION 23500335 A 624 633 estradiol TRIVIAL 23500335 A 63 76 polycarbonate FAMILY 23500335 A 781 784 BPA ABBREVIATION 23500335 A 87 92 epoxy SYSTEMATIC 23500335 A 949 957 tyrosine TRIVIAL 23500335 T 33 44 bisphenol A TRIVIAL 23500335 T 46 49 BPA ABBREVIATION 23500411 A 175 177 OH FORMULA 23500411 A 25 38 ritterazine G TRIVIAL 23500411 A 69 86 hecogenin acetate SYSTEMATIC 23500411 A 8 10 OH FORMULA 23500411 T 17 19 OH FORMULA 23500411 T 34 47 ritterazine G TRIVIAL 23500411 T 78 95 hecogenin acetate SYSTEMATIC 23500537 A 1036 1046 sitosterol TRIVIAL 23500537 A 1051 1062 campesterol TRIVIAL 23500537 A 107 121 oxyphytosterol FAMILY 23500537 A 1108 1121 oxysitosterol FAMILY 23500537 A 1126 1140 oxycampesterol FAMILY 23500537 A 1220 1234 oxyphytosterol FAMILY 23500537 A 1373 1387 oxyphytosterol FAMILY 23500537 A 1518 1522 iron SYSTEMATIC 23500537 A 1523 1529 copper SYSTEMATIC 23500537 A 1538 1550 α-tocopherol TRIVIAL 23500537 A 1675 1689 oxyphytosterol FAMILY 23500537 A 195 208 sterol esters FAMILY 23500537 A 276 288 stanol ester FAMILY 23500537 A 28 43 oxyphytosterols FAMILY 23500537 A 324 338 oxyphytosterol FAMILY 23500537 A 493 507 oxyphytosterol FAMILY 23500537 A 591 597 sterol FAMILY 23500537 A 599 605 stanol FAMILY 23500537 A 636 650 oxyphytosterol FAMILY 23500537 A 685 709 butylated hydroxytoluene SYSTEMATIC 23500537 A 711 714 BHT ABBREVIATION 23500537 A 725 729 EDTA ABBREVIATION 23500537 A 838 844 Trolox TRIVIAL 23500537 A 892 904 α-tocopherol TRIVIAL 23500537 A 924 928 iron SYSTEMATIC 23500537 A 929 935 copper SYSTEMATIC 23500537 T 0 14 Oxyphytosterol FAMILY 23500547 A 314 325 cholesterol TRIVIAL 23500547 A 72 83 cholesterol TRIVIAL 23500550 A 1037 1038 N FORMULA 23500550 A 1085 1086 C FORMULA 23500550 A 872 873 N FORMULA 23500768 A 0 11 Astaxanthin TRIVIAL 23500768 A 174 185 astaxanthin TRIVIAL 23500768 A 271 282 astaxanthin TRIVIAL 23500768 A 329 338 bleomycin FAMILY 23500768 A 412 423 astaxanthin TRIVIAL 23500768 A 557 568 astaxanthin TRIVIAL 23500768 A 664 678 hydroxyproline SYSTEMATIC 23500768 A 798 809 Astaxanthin TRIVIAL 23500768 A 958 969 astaxanthin TRIVIAL 23500768 T 0 11 Astaxanthin TRIVIAL 23500770 A 1071 1074 DON ABBREVIATION 23500770 A 42 56 deoxynivalenol TRIVIAL 23500770 A 431 434 DON ABBREVIATION 23500770 A 462 465 DON ABBREVIATION 23500770 A 58 61 DON ABBREVIATION 23500770 A 633 636 DON ABBREVIATION 23500770 A 816 819 DON ABBREVIATION 23500770 A 972 975 DON ABBREVIATION 23500770 T 40 54 deoxynivalenol TRIVIAL 23500772 A 143 150 ethanol SYSTEMATIC 23500772 A 152 156 EtOH FORMULA 23500772 A 207 211 EtOH FORMULA 23500772 A 293 297 EtOH FORMULA 23500772 A 354 361 glucose TRIVIAL 23500772 A 513 517 EtOH FORMULA 23500772 A 723 727 EtOH FORMULA 23500772 A 812 815 MDA ABBREVIATION 23500772 A 958 962 EtOH FORMULA 23500772 A 989 992 MDA ABBREVIATION 23500772 T 25 32 ethanol SYSTEMATIC 23500778 A 1057 1068 Hirsutenone TRIVIAL 23500778 A 1101 1105 NMDA ABBREVIATION 23500778 A 1164 1175 hirsutenone TRIVIAL 23500778 A 264 294 l-buthionine-(S,R)-sulfoximine SYSTEMATIC 23500778 A 296 299 BSO ABBREVIATION 23500778 A 30 41 hirsutenone TRIVIAL 23500778 A 306 315 glutamate TRIVIAL 23500778 A 372 388 propidium iodide TRIVIAL 23500778 A 445 448 MTT ABBREVIATION 23500778 A 467 478 hirsutenone TRIVIAL 23500778 A 549 552 BSO ABBREVIATION 23500778 A 569 580 Hirsutenone TRIVIAL 23500778 A 608 628 sodium nitroprusside SYSTEMATIC 23500778 A 630 633 SNP ABBREVIATION 23500778 A 718 729 hirsutenone TRIVIAL 23500778 A 747 767 N-methyl-d-aspartate SYSTEMATIC 23500778 A 769 773 NMDA ABBREVIATION 23500778 A 820 824 NMDA ABBREVIATION 23500778 A 968 972 dUTP ABBREVIATION 23501108 A 16 74 2-pyridyl hexahydrocycloocta [4,5]thieno[2,3-d]pyrimidines FAMILY 23501108 A 566 577 doxorubicin TRIVIAL 23501108 T 43 93 2-pyridyl hexahyrocyclooctathieno[2,3-d]pyrimidine SYSTEMATIC 23501109 A 18 31 pleuromutilin TRIVIAL 23501109 A 185 196 methicillin TRIVIAL 23501109 A 230 241 methicillin TRIVIAL 23501109 A 418 487 14-O-[(4-methoxybenzamide-2- methylpropane-2-yl) thioacetate] mutilin SYSTEMATIC 23501109 A 492 558 14-O-[(2-aminobenzamide-2-methylpropane-2-yl) thioacetate] mutilin SYSTEMATIC 23501109 A 566 632 14-O-[(4-aminobenzamide-2-methylpropane-2-yl) thioacetate] mutilin SYSTEMATIC 23501109 T 48 61 pleuromutilin TRIVIAL 23503472 A 1054 1066 cyclosporine TRIVIAL 23503472 A 1685 1697 cyclosporine TRIVIAL 23503472 A 1799 1811 cyclosporine TRIVIAL 23503472 A 265 277 cyclosporine TRIVIAL 23503472 A 4 16 Cyclosporine TRIVIAL 23503472 A 441 453 cyclosporine TRIVIAL 23503472 A 579 591 Cyclosporine TRIVIAL 23503472 A 694 706 cyclosporine TRIVIAL 23503472 A 818 830 cyclosporine TRIVIAL 23503472 T 66 78 cyclosporine TRIVIAL 23503923 A 473 499 poly(lactide-co-glycolide) SYSTEMATIC 23503923 A 501 505 PLGA ABBREVIATION 23503923 A 531 535 PLGA ABBREVIATION 23503923 A 599 617 poly(acrylic acid) SYSTEMATIC 23503923 A 619 622 PAA ABBREVIATION 23503923 A 834 837 PAA ABBREVIATION 23503927 A 1008 1017 potassium SYSTEMATIC 23503927 A 1042 1049 lithium SYSTEMATIC 23503927 A 109 112 DNB ABBREVIATION 23503927 A 1097 1103 tBuCQN ABBREVIATION 23503927 A 1114 1123 potassium SYSTEMATIC 23503927 A 113 124 S/R-leucine TRIVIAL 23503927 A 1170 1176 tBuCQN ABBREVIATION 23503927 A 158 163 Li(+) FORMULA 23503927 A 165 170 Na(+) FORMULA 23503927 A 172 176 K(+) FORMULA 23503927 A 28 62 (8S,9R)-tert-butylcarbamoylquinine SYSTEMATIC 23503927 A 298 309 carboxylate SYSTEMATIC 23503927 A 319 322 DNB ABBREVIATION 23503927 A 323 326 Leu FORMULA 23503927 A 377 403 [tBuCQN·DNB-S/R-Leu·Na](+) FORMULA 23503927 A 513 519 tBuCQN ABBREVIATION 23503927 A 570 573 DNB ABBREVIATION 23503927 A 574 579 S-Leu FORMULA 23503927 A 64 70 tBuCQN ABBREVIATION 23503927 A 73 107 N-3,5-dinitrobenzoyl-(S,R)-leucine SYSTEMATIC 23503927 A 744 747 DNB ABBREVIATION 23503927 A 748 753 R-Leu FORMULA 23503927 A 817 824 lithium SYSTEMATIC 23503927 A 853 859 sodium SYSTEMATIC 23503927 A 901 925 [tBuCQN·DNB-R-Leu·Li](+) FORMULA 23503927 A 934 958 [tBuCQN·DNB-S-Leu·Li](+) FORMULA 23504247 A 124 134 devazepide TRIVIAL 23504247 A 139 149 asperlicin TRIVIAL 23504247 A 19 45 1,3,4-benzotriazepin-5-one SYSTEMATIC 23504247 A 203 237 2-amino-1,3,4-benzotriazepin-5-one SYSTEMATIC 23504247 T 17 43 1,3,4-benzotriazepin-5-one SYSTEMATIC 23504356 A 405 417 fenfluramine TRIVIAL 23504356 A 655 663 oxytocin TRIVIAL 23504645 A 208 211 SO2 FORMULA 23504645 A 27 30 SO2 FORMULA 23504645 A 76 83 benzene SYSTEMATIC 23504923 A 0 10 BMS-690514 IDENTIFIER 23504923 A 1020 1032 ketoconazole TRIVIAL 23504923 A 1178 1190 ketoconazole TRIVIAL 23504923 A 1278 1290 ketoconazole TRIVIAL 23504923 A 357 369 ketoconazole TRIVIAL 23504923 A 373 383 BMS-690514 IDENTIFIER 23504923 A 440 450 BMS-690514 IDENTIFIER 23504923 A 476 486 BMS-690514 IDENTIFIER 23504923 A 492 504 ketoconazole TRIVIAL 23504923 A 556 566 BMS-690514 IDENTIFIER 23504923 A 599 611 ketoconazole TRIVIAL 23504923 A 642 652 BMS-690514 IDENTIFIER 23504923 A 697 707 BMS-690514 IDENTIFIER 23504923 A 724 734 BMS-690514 IDENTIFIER 23504923 A 742 754 ketoconazole TRIVIAL 23504923 A 836 846 BMS-690514 IDENTIFIER 23504923 T 103 113 BMS-690514 IDENTIFIER 23504923 T 21 33 Ketoconazole TRIVIAL 23504923 T 77 85 Tyrosine TRIVIAL 23505091 A 988 994 oxygen SYSTEMATIC 23505146 A 255 256 N FORMULA 23505146 A 463 470 glucose TRIVIAL 23505146 A 518 525 mannose TRIVIAL 23505344 A 242 244 CO FORMULA 23505344 A 288 291 H2O FORMULA 23505344 A 39 42 H2O FORMULA 23505344 A 420 423 Leu FORMULA 23505344 A 47 49 CO FORMULA 23505344 A 568 573 xenon SYSTEMATIC 23505344 A 599 602 H2O FORMULA 23505344 A 639 644 xenon SYSTEMATIC 23505344 A 655 658 Xe4 FORMULA 23505344 A 660 663 Xe2 FORMULA 23505344 A 669 672 Xe3 FORMULA 23505344 A 773 776 H2O FORMULA 23505344 A 794 803 histidine TRIVIAL 23505344 A 831 833 CO FORMULA 23505344 A 917 919 Xe FORMULA 23505344 A 978 980 CO FORMULA 23505344 T 35 37 CO FORMULA 23506052 A 1034 1039 TEMPO ABBREVIATION 23506052 A 1066 1071 TEMPO ABBREVIATION 23506052 A 1083 1086 DPH ABBREVIATION 23506052 A 1157 1160 DPH ABBREVIATION 23506052 A 122 126 DOPC ABBREVIATION 23506052 A 1244 1248 DOPC ABBREVIATION 23506052 A 1249 1253 DPPC ABBREVIATION 23506052 A 1263 1267 DOPC ABBREVIATION 23506052 A 1268 1272 DPPC ABBREVIATION 23506052 A 127 131 DPPC ABBREVIATION 23506052 A 1282 1286 DOPC ABBREVIATION 23506052 A 1303 1307 DOPC ABBREVIATION 23506052 A 1308 1312 DPPC ABBREVIATION 23506052 A 137 141 DOPC ABBREVIATION 23506052 A 142 153 cholesterol TRIVIAL 23506052 A 212 251 (2,2,6,6-tetramethylpiperidin-1-yl)oxyl SYSTEMATIC 23506052 A 253 258 TEMPO ABBREVIATION 23506052 A 307 311 DOPC ABBREVIATION 23506052 A 312 316 DPPC ABBREVIATION 23506052 A 352 381 1,6-diphenyl-1,3,5-hexatriene SYSTEMATIC 23506052 A 36 76 1,2-dioleoyl-sn-glycero-3-phosphocholine SYSTEMATIC 23506052 A 383 386 DPH ABBREVIATION 23506052 A 483 520 6-lauroyl-2-dimethylamino naphthalene SYSTEMATIC 23506052 A 522 529 Laurdan ABBREVIATION 23506052 A 593 597 DOPC ABBREVIATION 23506052 A 598 602 DPPC ABBREVIATION 23506052 A 77 120 1,2-dipalmitoyl-sn-glycero-3-phosphocholine SYSTEMATIC 23506052 A 799 803 DOPC ABBREVIATION 23506052 A 804 808 DPPC ABBREVIATION 23506052 A 813 817 DOPC ABBREVIATION 23506052 A 945 949 DOPC ABBREVIATION 23506052 A 950 954 DPPC ABBREVIATION 23506052 T 42 46 DOPC ABBREVIATION 23506052 T 47 51 DPPC ABBREVIATION 23506052 T 56 60 DOPC ABBREVIATION 23506073 A 1004 1007 FMN ABBREVIATION 23506073 A 1095 1103 quinones FAMILY 23506073 A 1139 1146 glyoxal TRIVIAL 23506073 A 1303 1311 quinones FAMILY 23506073 A 1316 1324 glyoxals FAMILY 23506073 A 264 280 N-ethylmaleimide SYSTEMATIC 23506073 A 32 40 glyoxals FAMILY 23506073 A 485 493 quinones FAMILY 23506073 A 498 506 glyoxals FAMILY 23506073 A 624 632 quinones FAMILY 23506073 A 637 645 glyoxals FAMILY 23506073 A 80 88 carbonyl FAMILY 23506073 A 815 825 disulphide SYSTEMATIC 23506073 A 931 938 glyoxal TRIVIAL 23506497 A 1093 1107 catecholamines FAMILY 23506497 A 1165 1175 dobutamine TRIVIAL 23506497 A 1207 1221 catecholamines FAMILY 23506497 A 1444 1456 levosimendan TRIVIAL 23506497 A 1458 1468 istaroxime TRIVIAL 23506497 A 1472 1490 omecamtiv mecarbil TRIVIAL 23506497 A 1527 1533 oxygen SYSTEMATIC 23506497 A 1569 1579 ivabradine TRIVIAL 23506497 A 1599 1605 oxygen SYSTEMATIC 23506497 A 1780 1788 pyruvate TRIVIAL 23506497 A 1790 1799 succinate TRIVIAL 23506497 A 710 717 calcium SYSTEMATIC 23506497 A 742 749 calcium SYSTEMATIC 23506497 A 995 1009 norepinephrine TRIVIAL 23506741 A 1076 1081 Fc11a FORMULA 23506741 A 1125 1132 Fc11a-2 FORMULA 23506741 A 1339 1346 Fc11a-2 FORMULA 23506741 A 269 315 1-ethyl-5-methyl-2-phenyl-1H-benzo[d]imidazole SYSTEMATIC 23506741 A 365 372 Fc11a-2 FORMULA 23506741 A 403 410 sulfate SYSTEMATIC 23506741 A 411 417 sodium SYSTEMATIC 23506741 A 745 752 Fc11a-2 FORMULA 23506741 A 926 933 Fc11a-2 FORMULA 23506741 T 79 85 sodium SYSTEMATIC 23506741 T 8 25 benzo[d]imidazole SYSTEMATIC 23507565 T 118 125 cocaine TRIVIAL 23507565 T 130 136 heroin TRIVIAL 23507573 A 455 463 tyrosine TRIVIAL 23508304 A 100 107 glucose TRIVIAL 23508304 T 109 116 glucose TRIVIAL 23508887 A 1198 1221 5-hydroxymethylcytosine SYSTEMATIC 23508887 A 1241 1257 5-methylcytosine SYSTEMATIC 23508961 A 1332 1341 leupeptin TRIVIAL 23508961 A 450 461 cholesterol TRIVIAL 23508961 A 782 793 cholesterol TRIVIAL 23509039 A 27 40 aminothiazole SYSTEMATIC 23509039 A 46 104 (4-biphenyl-4-ylthiazol-2-yl)-(6-methylpyridin-2-yl)-amine SYSTEMATIC 23509039 A 664 731 (6-methylpyridin-2-yl)-[4-(4-pyridin-3-yl-phenyl)thiazol-2-yl]amine SYSTEMATIC 23509039 A 736 793 cyclopropanecarboxylic acid (4-biphenylthiazol-2-yl)amide SYSTEMATIC 23509039 T 0 16 2-aminothiazoles FAMILY 23509853 A 1107 1117 pivalamido SYSTEMATIC 23509853 A 1148 1154 Cu(II) FORMULA 23509853 A 1155 1160 Cu(I) FORMULA 23509853 A 1256 1265 CF3COO(-) FORMULA 23509853 A 1364 1374 pivalamido SYSTEMATIC 23509853 A 1631 1635 H2O2 FORMULA 23509853 A 1765 1767 O2 FORMULA 23509853 A 18 42 [(PV-tmpa)Cu(II)](ClO4)2 FORMULA 23509853 A 190 192 O2 FORMULA 23509853 A 196 215 decamethylferrocene SYSTEMATIC 23509853 A 2 8 copper SYSTEMATIC 23509853 A 241 261 trifluoroacetic acid SYSTEMATIC 23509853 A 263 270 CF3COOH FORMULA 23509853 A 275 282 acetone SYSTEMATIC 23509853 A 318 324 copper SYSTEMATIC 23509853 A 343 353 pivalamido SYSTEMATIC 23509853 A 361 382 [(tmpa)Cu(II)](ClO4)2 FORMULA 23509853 A 388 392 tmpa ABBREVIATION 23509853 A 395 421 tris(2-pyridylmethyl)amine SYSTEMATIC 23509853 A 465 486 decamethylferrocenium SYSTEMATIC 23509853 A 48 55 PV-tmpa ABBREVIATION 23509853 A 544 546 O2 FORMULA 23509853 A 58 118 bis(pyrid-2-ylmethyl){[6-(pivalamido)pyrid-2-yl]methyl}amine SYSTEMATIC 23509853 A 588 595 CF3COOH FORMULA 23509853 A 600 602 O2 FORMULA 23509853 A 783 790 CF3COOH FORMULA 23509853 A 794 796 O2 FORMULA 23509853 A 941 943 O2 FORMULA 23509853 A 970 977 CF3COOH FORMULA 23509853 T 106 116 Copper(II) SYSTEMATIC 23509853 T 33 41 Dioxygen SYSTEMATIC 23509853 T 43 45 O2 FORMULA 23509853 T 64 81 Hydrogen Peroxide SYSTEMATIC 23509853 T 83 87 H2O2 FORMULA 23509904 A 654 662 aspartyl TRIVIAL 23510192 A 1255 1264 phosphate SYSTEMATIC 23510192 A 1671 1681 nucleotide FAMILY 23510479 A 254 273 poly(1,2-butadiene) SYSTEMATIC 23511016 A 302 304 Gd FORMULA 23511016 A 363 367 DOTA ABBREVIATION 23511016 A 375 387 pantoprazole TRIVIAL 23511016 A 491 495 DOTA ABBREVIATION 23511016 A 565 577 pantoprazole TRIVIAL 23511016 T 15 19 DOTA ABBREVIATION 23511016 T 21 27 Gd(3+) FORMULA 23511016 T 64 76 pantoprazole TRIVIAL 23511018 A 45 61 (+)-lycoricidine TRIVIAL 23511018 A 737 753 (+)-lycoricidine TRIVIAL 23511018 T 49 65 (+)-lycoricidine TRIVIAL 23511022 A 109 151 dimethoxyP(V)tetraphenylporphyrin chloride SYSTEMATIC 23511022 A 1124 1133 DMP(V)TPP ABBREVIATION 23511022 A 1163 1169 oxygen SYSTEMATIC 23511022 A 153 162 DMP(V)TPP ABBREVIATION 23511022 A 242 248 oxygen SYSTEMATIC 23511022 A 263 272 DMP(V)TPP ABBREVIATION 23511022 A 316 325 porphyrin FAMILY 23511022 A 421 430 DMP(V)TPP ABBREVIATION 23511022 A 498 507 DMP(V)TPP ABBREVIATION 23511022 A 520 530 amino acid FAMILY 23511022 A 628 638 tryptophan TRIVIAL 23511022 A 681 687 oxygen SYSTEMATIC 23511022 A 698 710 sodium azide SYSTEMATIC 23511022 A 870 876 oxygen SYSTEMATIC 23511022 A 934 943 DMP(V)TPP ABBREVIATION 23511022 A 94 107 P(V)porphyrin SYSTEMATIC 23511022 T 34 77 dimethoxyphosphorus(V) tetraphenylporphyrin SYSTEMATIC 23511088 A 285 298 alkylphenones FAMILY 23511088 A 645 651 butoxy SYSTEMATIC 23511125 A 1002 1011 donepezil TRIVIAL 23511125 A 1249 1258 donepezil TRIVIAL 23511125 A 1314 1323 donepezil TRIVIAL 23511125 A 1449 1458 Donepezil TRIVIAL 23511125 A 1519 1531 mecamylamine TRIVIAL 23511125 A 1540 1558 methyllycaconitine TRIVIAL 23511125 A 1650 1659 glutamate TRIVIAL 23511125 A 35 48 acetylcholine SYSTEMATIC 23511125 A 363 376 acetylcholine SYSTEMATIC 23511125 A 428 437 glutamate TRIVIAL 23511125 A 515 524 glutamate TRIVIAL 23511125 T 75 84 glutamate TRIVIAL 23511311 A 581 588 glucose TRIVIAL 23511711 A 1001 1010 midazolam TRIVIAL 23511711 A 1056 1065 midazolam TRIVIAL 23511711 A 158 167 midazolam TRIVIAL 23511711 A 222 231 midazolam TRIVIAL 23511711 A 419 431 ketoconazole TRIVIAL 23511711 A 482 491 midazolam TRIVIAL 23511711 A 627 639 Ketoconazole TRIVIAL 23511711 A 648 657 midazolam TRIVIAL 23511711 A 781 790 midazolam TRIVIAL 23511711 A 827 839 ketoconazole TRIVIAL 23511711 A 878 887 midazolam TRIVIAL 23511711 T 45 54 Midazolam TRIVIAL 23511718 A 1002 1005 PEG ABBREVIATION 23511718 A 1179 1182 PEG ABBREVIATION 23511718 A 1316 1319 PEG ABBREVIATION 23511718 A 1439 1442 PEG ABBREVIATION 23511718 A 516 535 polyethylene glycol SYSTEMATIC 23511718 A 537 540 PEG ABBREVIATION 23511718 A 640 643 PEG ABBREVIATION 23511718 A 833 836 PEG ABBREVIATION 23511718 A 874 877 PEG ABBREVIATION 23511718 T 0 3 PEG ABBREVIATION 23512337 A 113 127 polyamidoamine FAMILY 23512337 A 500 517 polyethyleneimine SYSTEMATIC 23512337 T 15 18 PAA ABBREVIATION 23512409 A 113 126 polythiophene FAMILY 23512409 A 458 471 polythiophene FAMILY 23512409 T 55 68 Polythiophene FAMILY 23512438 A 1030 1043 monocrotophos TRIVIAL 23512438 A 1048 1060 imidacloprid TRIVIAL 23512438 A 1149 1162 gluconic acid TRIVIAL 23512438 A 1175 1198 citric and acetic acids MULTIPLE 23512438 A 1369 1382 monocrotophos TRIVIAL 23512438 A 1387 1399 imidacloprid TRIVIAL 23512438 A 264 273 phosphate SYSTEMATIC 23512438 A 60 69 phosphate SYSTEMATIC 23512438 A 606 618 alphamethrin TRIVIAL 23512438 A 642 652 endosulfan TRIVIAL 23512438 A 743 756 monocrotophos TRIVIAL 23512438 A 761 773 imidacloprid TRIVIAL 23512438 A 920 933 gluconic acid TRIVIAL 23512438 T 23 33 phosphorus SYSTEMATIC 23512754 A 1007 1010 CDM ABBREVIATION 23512754 A 1134 1137 CDM ABBREVIATION 23512754 A 13 50 1-cinnamoyl-3,11-dihydroxymeliacarpin SYSTEMATIC 23512754 A 217 220 CDM ABBREVIATION 23512754 A 292 295 CDM ABBREVIATION 23512754 A 394 397 CDM ABBREVIATION 23512754 A 403 406 MTT ABBREVIATION 23512754 A 501 504 CDM ABBREVIATION 23512754 A 52 55 CDM ABBREVIATION 23512754 A 703 706 CDM ABBREVIATION 23512754 A 953 956 CDM ABBREVIATION 23512754 T 31 68 1-Cinnamoyl-3,11-Dihydroxymeliacarpin SYSTEMATIC 23512824 A 1064 1069 azide SYSTEMATIC 23512824 A 1086 1096 phosphines FAMILY 23512824 A 1132 1149 2,4-dinitrophenyl SYSTEMATIC 23512824 A 1151 1154 DNP ABBREVIATION 23512824 A 1317 1320 DNP ABBREVIATION 23512824 A 1356 1359 DNP ABBREVIATION 23512824 A 521 526 azide SYSTEMATIC 23512824 A 595 600 azide SYSTEMATIC 23512824 A 708 746 peracetylated N-azidoacetylglucosamine SYSTEMATIC 23512824 A 748 758 Ac4 GlcNAz FORMULA 23512824 A 803 813 Ac4 GlcNAz FORMULA 23512824 A 954 960 azides FAMILY 23512824 A 965 975 phosphines FAMILY 23512927 A 122 225 poly(ethylene glycol)-b-poly[styrene-co-(2-(1,2,3,4,5-pentaphenyl-1H-silol-1-yloxy)ethyl methacrylate)] SYSTEMATIC 23512927 A 227 247 PEG-b-P(S-co-PPSEMA) ABBREVIATION 23512927 A 278 289 doxorubicin TRIVIAL 23512927 A 291 294 DOX ABBREVIATION 23512927 A 454 460 PPSEMA ABBREVIATION 23512927 A 464 467 DOX ABBREVIATION 23512927 A 483 486 DOX ABBREVIATION 23512927 A 568 571 DOX ABBREVIATION 23512927 A 779 782 DOX ABBREVIATION 23512927 T 112 123 Doxorubicin TRIVIAL 23514378 A 104 113 serotonin TRIVIAL 23514378 A 115 119 5-HT SYSTEMATIC 23514378 A 1277 1281 5-HT SYSTEMATIC 23514378 A 627 631 5-HT SYSTEMATIC 23514378 A 706 710 5-HT SYSTEMATIC 23514378 T 32 41 serotonin TRIVIAL 23514599 A 12 50 4-(1-methyl-1H-pyrrol-3-yl)benzenamine SYSTEMATIC 23514599 A 195 228 pyrrolo[2,1-c][1,4]benzodiazepine SYSTEMATIC 23514599 A 230 233 PBD ABBREVIATION 23514599 A 265 272 PBD-MPB ABBREVIATION 23514599 A 52 55 MPB ABBREVIATION 23514599 A 661 670 KMR-28-39 IDENTIFIER 23514599 T 22 43 Pyrrolobenzodiazepine FAMILY 23514599 T 44 50 Biaryl FAMILY 23515282 A 1242 1253 cholesterol TRIVIAL 23515282 A 519 530 cholesterol TRIVIAL 23515282 A 52 63 cholesterol TRIVIAL 23515282 A 735 746 cholesterol TRIVIAL 23515497 A 1063 1067 PCBs ABBREVIATION 23515497 A 1157 1164 PCB 180 IDENTIFIER 23515497 A 1169 1174 mirex TRIVIAL 23515497 A 1296 1303 PCB 180 IDENTIFIER 23515497 A 1308 1318 endosulfan TRIVIAL 23515497 A 1386 1393 PCB 180 IDENTIFIER 23515497 A 1395 1407 Aroclor 1221 TRIVIAL 23515497 A 1412 1422 endosulfan TRIVIAL 23515497 A 384 394 oestradiol TRIVIAL 23515497 A 412 419 PCB 180 IDENTIFIER 23515497 A 421 433 Aroclor 1221 TRIVIAL 23515497 A 435 445 endosulfan TRIVIAL 23515497 A 450 455 mirex TRIVIAL 23515497 A 46 71 polychlorinated biphenyls FAMILY 23515497 A 634 646 formaldehyde SYSTEMATIC 23515497 A 73 77 PCBs ABBREVIATION 23515497 A 823 828 mirex TRIVIAL 23515497 A 83 100 organochlorinated FAMILY 23515497 A 924 936 Aroclor 1221 TRIVIAL 23515497 A 941 951 endosulfan TRIVIAL 23515497 T 36 61 polychlorinated biphenyls FAMILY 23515497 T 66 83 organochlorinated FAMILY 23515582 A 1135 1147 escitalopram TRIVIAL 23515582 A 1197 1209 escitalopram TRIVIAL 23515582 A 1411 1423 escitalopram TRIVIAL 23515582 A 1544 1556 Escitalopram TRIVIAL 23515582 A 456 465 serotonin TRIVIAL 23515582 A 485 497 escitalopram TRIVIAL 23515582 A 614 626 Escitalopram TRIVIAL 23515582 T 6 18 escitalopram TRIVIAL 23515934 A 1001 1009 formalin TRIVIAL 23515934 A 1027 1036 glutamate TRIVIAL 23515934 A 1093 1107 oleanolic acid TRIVIAL 23515934 A 207 218 acetic acid SYSTEMATIC 23515934 A 307 321 oleanolic acid TRIVIAL 23515934 A 31 45 oleanolic acid TRIVIAL 23515934 A 506 515 glutamate TRIVIAL 23515934 A 542 556 oleanolic acid TRIVIAL 23515934 A 599 607 naloxone TRIVIAL 23515934 A 640 652 methysergide TRIVIAL 23515934 A 654 658 5-HT SYSTEMATIC 23515934 A 73 87 Oleanolic acid TRIVIAL 23515934 A 738 752 oleanolic acid TRIVIAL 23515934 A 784 793 yohimbine TRIVIAL 23515934 A 869 883 oleanolic acid TRIVIAL 23515934 A 911 925 oleanolic acid TRIVIAL 23515934 T 74 88 oleanolic acid TRIVIAL 23517008 A 103 109 carbon SYSTEMATIC 23517008 A 1241 1247 carbon SYSTEMATIC 23517008 A 143 149 carbon SYSTEMATIC 23517008 A 256 264 graphene TRIVIAL 23517008 A 431 437 carbon SYSTEMATIC 23517008 A 571 579 graphite TRIVIAL 23517008 A 908 916 graphene TRIVIAL 23517008 T 67 73 carbon SYSTEMATIC 23517010 A 334 336 Au FORMULA 23517028 A 198 212 arylpiperazine FAMILY 23517028 A 486 492 indole SYSTEMATIC 23517028 A 500 509 quinoline SYSTEMATIC 23517028 T 94 108 Arylpiperazine FAMILY 23517093 A 1045 1059 thailanstatins FAMILY 23517093 A 128 136 FR901464 IDENTIFIER 23517093 A 393 407 thailanstatins FAMILY 23517093 A 503 517 Thailanstatins FAMILY 23517093 A 667 675 hydroxyl SYSTEMATIC 23517093 A 705 713 carboxyl SYSTEMATIC 23517093 A 746 760 thailanstatins FAMILY 23517093 A 820 829 phosphate SYSTEMATIC 23517093 A 876 890 thailanstatins FAMILY 23517093 T 29 55 Thailanstatins A, B, and C MULTIPLE 23517126 A 176 192 sesquiterpenoids FAMILY 23517126 A 194 228 1β-p-hydroxy-E-cinnamoyldrimeninol SYSTEMATIC 23517126 A 234 279 1β-p-hydroxy-E-cinnamoyl-5α-hydroxydrimeninol SYSTEMATIC 23517126 A 289 351 methyl ether of 1β-p-hydroxy-E-cinnamoyl-12α-methoxydrimeninol SYSTEMATIC 23517126 A 385 412 1β-p-coumaroyloxypolygodial SYSTEMATIC 23517126 A 439 449 tetralones FAMILY 23517126 A 451 472 3'-deoxyisozygolone A SYSTEMATIC 23517126 A 481 495 calothyrlone A TRIVIAL 23517126 A 525 538 isozygolone A TRIVIAL 23517126 A 544 554 zygolone A TRIVIAL 23517126 A 564 585 4'-O-methylzygolone A SYSTEMATIC 23517126 A 603 614 cinnamolide TRIVIAL 23517126 T 52 68 Sesquiterpenoids FAMILY 23517126 T 73 83 Tetralones FAMILY 23517145 A 106 159 3,11,15,23-tetraoxo-27ξ-lanosta-8,16-dien-26-oic acid SYSTEMATIC 23517145 A 177 184 lactone FAMILY 23517145 A 198 249 5-hydroxy-5-(methoxymethyl)-4-methylfuran-2(5H)-one SYSTEMATIC 23517145 A 23 41 ethyl lucidenate A SYSTEMATIC 23517145 A 258 305 3-(4-methoxy-2-oxo-2H-pyran-6-yl)propanoic acid SYSTEMATIC 23517145 A 347 400 11α-hydroxy-3,7-dioxolanost-8,24(E)-dien-26- oic acid SYSTEMATIC 23517145 A 406 455 3,7,11-trioxo-5α-lanosta-8,24(E)-dien-26-oic acid SYSTEMATIC 23517145 A 461 514 methyl 3,7,11,12,15,23-hexaoxo-5α-lanost-8-en-26-oate SYSTEMATIC 23517145 A 47 65 ethyl lucidenate F SYSTEMATIC 23517145 A 524 576 ethyl 3,7,11,12,15,23-hexaoxo-5α-lanost-8-en-26-oate SYSTEMATIC 23517145 A 71 96 15-O-acetylganolucidate A SYSTEMATIC 23517145 A 869 871 NO FORMULA 23517145 A 9 21 lanostanoids FAMILY 23517145 A 996 998 NO FORMULA 23517145 T 18 30 Lanostanoids FAMILY 23517145 T 35 42 Lactone FAMILY 23517379 A 101 109 graphene TRIVIAL 23517379 A 28 61 2,5-dialkoxy-phenylene-thienylene SYSTEMATIC 23517379 A 383 392 thiophene SYSTEMATIC 23517470 A 153 159 Ca(2+) FORMULA 23517470 A 237 243 Ca(2+) FORMULA 23517470 A 701 707 Ca(2+) FORMULA 23517470 A 95 101 Ca(2+) FORMULA 23517470 T 54 60 Ca(2+) FORMULA 23517474 A 1117 1122 amide FAMILY 23517474 A 1229 1235 Ca(2+) FORMULA 23517474 A 1238 1244 Mg(2+) FORMULA 23517474 A 1247 1252 Li(+) FORMULA 23517474 A 1255 1260 Na(+) FORMULA 23517474 A 1263 1267 K(+) FORMULA 23517474 A 1323 1329 Ca(2+) FORMULA 23517474 A 1410 1431 amide carbonyl oxygen SYSTEMATIC 23517474 A 1464 1469 Na(+) FORMULA 23517474 A 1474 1478 K(+) FORMULA 23517474 A 1567 1573 amides FAMILY 23517474 A 163 171 chloride SYSTEMATIC 23517474 A 309 314 amide FAMILY 23517474 A 39 49 butyramide SYSTEMATIC 23517474 A 546 552 Ca(2+) FORMULA 23517474 A 554 560 Mg(2+) FORMULA 23517474 A 562 567 Li(+) FORMULA 23517474 A 626 632 amides FAMILY 23517474 A 709 715 amides FAMILY 23517474 A 846 856 butyramide SYSTEMATIC 23517474 A 945 950 amide FAMILY 23517474 T 28 34 Amides FAMILY 23517541 A 1117 1125 nor-NOHA TRIVIAL 23517541 A 1318 1326 nor-NOHA TRIVIAL 23517541 A 357 365 nor-NOHA TRIVIAL 23517541 A 49 76 N(ω)-hydroxy-nor-L-arginine SYSTEMATIC 23517541 A 493 501 nor-NOHA TRIVIAL 23517541 A 78 86 nor-NOHA TRIVIAL 23517541 A 939 947 nor-NOHA TRIVIAL 23517541 T 32 59 N(ω)-hydroxy-nor-L-arginine SYSTEMATIC 23517546 A 1016 1020 GaAs FORMULA 23517546 A 1021 1030 (Ga,Mn)As FORMULA 23517546 A 115 124 (Ga,Mn)As FORMULA 23517546 A 158 169 zinc-blende SYSTEMATIC 23517546 A 175 179 GaAs FORMULA 23517546 A 180 189 (Ga,Mn)As FORMULA 23517546 A 214 216 Si FORMULA 23517546 A 241 245 GaAs FORMULA 23517546 A 319 321 Ga FORMULA 23517546 A 406 415 (Ga,Mn)As FORMULA 23517546 A 471 475 GaAs FORMULA 23517546 A 538 542 GaAs FORMULA 23517546 A 54 58 GaAs FORMULA 23517546 A 543 552 (Ga,Mn)As FORMULA 23517546 A 722 726 GaAs FORMULA 23517546 A 727 736 (Ga,Mn)As FORMULA 23517546 A 805 807 Mn FORMULA 23517546 T 16 20 GaAs FORMULA 23517546 T 21 30 (Ga,Mn)As FORMULA 23517546 T 4 15 Zinc-Blende SYSTEMATIC 23517565 A 455 475 dihydroquinazolinone SYSTEMATIC 23517565 T 0 28 N-Methyldihydroquinazolinone SYSTEMATIC 23517621 A 0 36 2,2,6,6-Tetramethylpiperidine-1-oxyl SYSTEMATIC 23517621 A 1120 1125 TEMPO ABBREVIATION 23517621 A 1280 1285 TEMPO ABBREVIATION 23517621 A 174 179 TEMPO ABBREVIATION 23517621 A 318 323 TEMPO ABBREVIATION 23517621 A 38 43 TEMPO ABBREVIATION 23517621 A 464 469 TEMPO ABBREVIATION 23517621 A 630 635 TEMPO ABBREVIATION 23517621 A 873 878 TEMPO ABBREVIATION 23517621 A 896 902 oxygen SYSTEMATIC 23517621 A 925 936 glutathione TRIVIAL 23517621 A 998 1003 TEMPO ABBREVIATION 23517621 T 0 9 Nitroxide SYSTEMATIC 23517621 T 10 15 TEMPO ABBREVIATION 23517636 A 1008 1023 androstenedione TRIVIAL 23517636 A 1025 1055 dehydroepiandrosterone sulfate SYSTEMATIC 23517636 A 1057 1063 DHEA-S ABBREVIATION 23517636 A 1151 1159 androgen FAMILY 23517636 A 14 26 Testosterone TRIVIAL 23517636 A 521 529 androgen FAMILY 23517636 A 984 1006 17-hydroxyprogesterone SYSTEMATIC 23517636 T 0 12 Testosterone TRIVIAL 23517729 A 1200 1211 Py3MeO-TBPo ABBREVIATION 23517729 A 140 151 Py3MeO-TBPo ABBREVIATION 23517729 A 1805 1816 Py3MeO-TBPo ABBREVIATION 23517729 A 1919 1925 oxygen SYSTEMATIC 23517729 A 2051 2057 oxygen SYSTEMATIC 23517729 A 2068 2080 sodium azide SYSTEMATIC 23517729 A 2151 2162 Py3MeO-TBPo ABBREVIATION 23517729 A 2500 2511 Py3MeO-TBPo ABBREVIATION 23517729 A 289 300 Py3MeO-TBPo ABBREVIATION 23517729 A 601 611 porphycene TRIVIAL 23517729 A 66 138 2,7,12-tris(α-pyridinio-p-tolyl)-17-(p-(methoxymethyl)phenyl) porphycene SYSTEMATIC 23517729 A 745 756 Py3MeO-TBPo ABBREVIATION 23517729 A 812 823 Py3MeO-TBPo ABBREVIATION 23517729 T 67 77 porphycene TRIVIAL 23518155 A 1121 1128 glucose TRIVIAL 23518155 A 1253 1260 glucose TRIVIAL 23518155 A 1393 1400 glucose TRIVIAL 23518155 A 1627 1634 glucose TRIVIAL 23518155 A 399 400 N FORMULA 23518155 A 657 661 cAMP ABBREVIATION 23518155 A 873 880 glucose TRIVIAL 23518155 A 996 1003 glucose TRIVIAL 23518321 A 0 13 Acetaminophen TRIVIAL 23518321 A 1167 1180 acetaminophen TRIVIAL 23518321 A 215 228 acetaminophen TRIVIAL 23518321 A 352 365 acetaminophen TRIVIAL 23518321 A 465 478 acetaminophen TRIVIAL 23518321 A 533 558 phorbol myristate acetate SYSTEMATIC 23518321 A 688 701 acetaminophen TRIVIAL 23518321 A 727 731 HOCl FORMULA 23518321 A 736 740 H2O2 FORMULA 23518321 A 808 821 Acetaminophen TRIVIAL 23518321 A 852 863 glutathione TRIVIAL 23518321 A 990 1003 acetaminophen TRIVIAL 23518321 T 0 13 Acetaminophen TRIVIAL 23518599 A 0 10 Rare-earth FAMILY 23518599 A 1168 1188 rare-earth phosphate FAMILY 23518599 A 1316 1319 P-O FORMULA 23518599 A 1324 1325 P FORMULA 23518599 A 1356 1357 O FORMULA 23518599 A 1375 1395 rare-earth phosphate FAMILY 23518599 A 1535 1555 rare-earth phosphate FAMILY 23518599 A 214 234 rare-earth phosphate FAMILY 23518599 A 244 272 (R2O3)x(R'2O3)y(P2O5)1-(x+y) FAMILY 23518599 A 297 299 Ce FORMULA 23518599 A 301 303 Er FORMULA 23518599 A 309 311 La FORMULA 23518599 A 313 315 Nd FORMULA 23518599 A 341 351 rare-earth FAMILY 23518599 A 395 408 metaphosphate FAMILY 23518599 A 410 415 RP3O9 FAMILY 23518599 A 421 435 ultraphosphate FAMILY 23518599 A 437 443 RP5O14 FAMILY 23518599 A 471 481 rare-earth FAMILY 23518599 A 726 736 rare-earth FAMILY 23518599 A 989 1009 rare-earth phosphate FAMILY 23518599 T 58 78 rare-earth phosphate FAMILY 23518857 A 203 215 formaldehyde SYSTEMATIC 23518857 A 228 231 FCF FORMULA 23518857 A 241 256 difluoromethane SYSTEMATIC 23518857 A 275 279 C-HF FORMULA 23518857 A 297 301 CH2O FORMULA 23518857 A 307 315 hydrogen SYSTEMATIC 23518857 A 463 475 formaldehyde SYSTEMATIC 23518857 A 75 90 difluoromethane SYSTEMATIC 23518857 A 95 107 formaldehyde SYSTEMATIC 23518857 T 50 59 CH2F2H2CO FORMULA 23519059 A 372 431 bis(4,6-difluorophenyl) pyridinato-N,C [dfppy] iridium(iii) SYSTEMATIC 23519059 A 509 524 acetylacetonate SYSTEMATIC 23519059 A 526 536 picolinate TRIVIAL 23519059 A 542 559 pyridylpyrazolate SYSTEMATIC 23519059 T 67 79 iridium(iii) SYSTEMATIC 23519153 A 1063 1067 iron SYSTEMATIC 23519153 A 1174 1196 S-adenosylhomocysteine TRIVIAL 23519153 A 1298 1320 S-adenosylhomocysteine TRIVIAL 23519153 A 1519 1525 Copper SYSTEMATIC 23519153 A 1598 1600 Fe FORMULA 23519153 A 1605 1625 adenosylhomocysteine TRIVIAL 23519153 A 265 271 copper SYSTEMATIC 23519153 A 691 697 copper SYSTEMATIC 23519153 A 989 995 copper SYSTEMATIC 23520074 A 101 107 serine TRIVIAL 23520074 A 1063 1070 phospho SYSTEMATIC 23520074 A 219 224 amino FAMILY 23520074 A 452 453 N FORMULA 23520074 A 501 502 C FORMULA 23520074 A 987 994 (125) I FORMULA 23521014 A 0 6 Carbon SYSTEMATIC 23521014 T 41 47 carbon SYSTEMATIC 23521318 A 489 500 α-terpineol TRIVIAL 23521318 A 810 821 α-terpineol TRIVIAL 23521360 A 10 40 methylated flavonol glucosides FAMILY 23521360 A 102 161 3,4'-dimethoxy-7-O-β-(6″-galloyl-glucopyranoside) quercetin SYSTEMATIC 23521360 A 170 225 3-methoxy-7-O-β-(6″-galloylgluco-pyranoside) kaempferol SYSTEMATIC 23521360 A 256 265 flavonols FAMILY 23521360 A 290 303 ethyl acetate SYSTEMATIC 23521360 A 42 96 3-methoxy-7-O-β-(6″-galloylgluco-pyranoside) quercetin SYSTEMATIC 23521360 T 4 34 methylated flavonol glucosides FAMILY 23521567 A 357 400 1,2-dipalmitoyl-sn-glycero-3-phosphocholine SYSTEMATIC 23521567 A 402 406 DPPC ABBREVIATION 23521567 A 522 526 DPPC ABBREVIATION 23521567 A 578 582 DPPC ABBREVIATION 23521567 T 34 38 DPPC ABBREVIATION 23522182 A 1044 1051 AZD1656 IDENTIFIER 23522182 A 1214 1221 AZD1656 IDENTIFIER 23522182 A 1322 1329 glucose TRIVIAL 23522182 A 1408 1415 AZD1656 IDENTIFIER 23522182 A 293 300 AZD1656 IDENTIFIER 23522182 A 496 503 glucose TRIVIAL 23522182 A 611 618 AZD1656 IDENTIFIER 23522182 A 705 712 AZD1656 IDENTIFIER 23522182 A 809 816 AZD1656 IDENTIFIER 23522182 A 90 97 AZD1656 IDENTIFIER 23522182 A 988 995 AZD1656 IDENTIFIER 23522182 T 50 57 AZD1656 IDENTIFIER 23522564 A 126 127 N FORMULA 23522564 A 246 247 C FORMULA 23522564 A 464 474 amino acid FAMILY 23522564 A 669 675 lysine TRIVIAL 23522564 A 680 683 Ile FORMULA 23522564 A 695 706 cholesterol TRIVIAL 23522564 A 723 724 C FORMULA 23522564 A 823 834 cholesterol TRIVIAL 23522833 A 0 8 Cu(OTf)2 FORMULA 23522833 A 138 144 isatin TRIVIAL 23522833 A 146 156 kojic acid TRIVIAL 23522833 A 168 178 methylenes FAMILY 23522833 A 42 76 spiropyrano[3,2-b]pyran-4(8H)-ones FAMILY 23522833 T 0 8 Cu(OTf)2 FORMULA 23522833 T 68 106 spiro[indoline-3,4'-pyrano[3,2-b]pyran SYSTEMATIC 23523142 A 0 9 Ginkgetin TRIVIAL 23523142 A 23 34 biflavonoid FAMILY 23523142 A 283 292 ginkgetin TRIVIAL 23523142 A 369 378 ginkgetin TRIVIAL 23523142 A 431 440 Ginkgetin TRIVIAL 23523142 A 602 611 Ginkgetin TRIVIAL 23523142 A 790 800 Z-DEVD-fmk ABBREVIATION 23523142 A 876 885 ginkgetin TRIVIAL 23523142 A 938 947 ginkgetin TRIVIAL 23523142 T 0 9 Ginkgetin TRIVIAL 23523258 A 1031 1040 midazolam TRIVIAL 23523258 A 111 116 Sch B ABBREVIATION 23523258 A 1189 1209 1'-hydroxy midazolam SYSTEMATIC 23523258 A 1427 1432 Sch B ABBREVIATION 23523258 A 1546 1551 Sch B ABBREVIATION 23523258 A 236 245 midazolam TRIVIAL 23523258 A 348 360 ketoconazole TRIVIAL 23523258 A 414 419 Sch B ABBREVIATION 23523258 A 565 574 midazolam TRIVIAL 23523258 A 579 599 1'-hydroxy midazolam SYSTEMATIC 23523258 A 678 683 Sch B ABBREVIATION 23523258 A 875 880 Sch B ABBREVIATION 23523258 A 96 109 Schisandrin B TRIVIAL 23523258 A 960 969 midazolam TRIVIAL 23523258 A 971 976 Sch B ABBREVIATION 23523258 T 18 31 Schisandrin B TRIVIAL 23523546 A 1104 1107 ITZ ABBREVIATION 23523546 A 121 124 ITZ ABBREVIATION 23523546 A 1224 1227 ITZ ABBREVIATION 23523546 A 20 23 ITZ ABBREVIATION 23523546 A 387 390 ITZ ABBREVIATION 23523546 A 496 499 ITZ ABBREVIATION 23523546 A 563 566 ITZ ABBREVIATION 23523546 A 6 18 Itraconazole TRIVIAL 23523546 A 90 98 mannitol TRIVIAL 23523546 T 48 60 itraconazole TRIVIAL 23523557 A 1211 1220 HC 030031 IDENTIFIER 23523557 A 1277 1293 cyclophosphamide TRIVIAL 23523557 A 1481 1497 cyclophosphamide TRIVIAL 23523557 A 161 177 cyclophosphamide TRIVIAL 23523557 A 264 280 cyclophosphamide TRIVIAL 23523557 A 417 426 HC 030031 IDENTIFIER 23523557 A 604 613 HC 030031 IDENTIFIER 23523557 A 673 689 cyclophosphamide TRIVIAL 23523557 A 818 834 cyclophosphamide TRIVIAL 23523557 A 867 876 HC 030031 IDENTIFIER 23523557 A 958 974 cyclophosphamide TRIVIAL 23523557 T 125 141 cyclophosphamide TRIVIAL 23523780 A 104 110 Ca(2+) FORMULA 23523780 A 1325 1336 bicuculline TRIVIAL 23523780 A 176 182 Ca(2+) FORMULA 23523780 A 40 46 Ca(2+) FORMULA 23523781 A 1320 1364 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine SYSTEMATIC 23523781 A 1366 1370 MPTP ABBREVIATION 23523781 A 1444 1449 DOPAC ABBREVIATION 23523781 A 1687 1691 MPTP ABBREVIATION 23523781 A 1745 1749 MPTP ABBREVIATION 23523781 A 2309 2317 dopamine TRIVIAL 23523781 A 403 411 dopamine TRIVIAL 23523781 A 418 435 homovanillic acid TRIVIAL 23523781 A 42 61 paraquat dichloride SYSTEMATIC 23523781 A 437 440 HVA ABBREVIATION 23523781 A 445 475 3,4-dihydroxyphenylacetic acid SYSTEMATIC 23523781 A 477 482 DOPAC ABBREVIATION 23523781 A 497 505 dopamine TRIVIAL 23523781 A 668 676 tyrosine TRIVIAL 23523781 A 900 906 silver SYSTEMATIC 23523781 A 942 950 tyrosine TRIVIAL 23523781 T 104 112 paraquat TRIVIAL 23523906 A 1044 1058 hydroxyproline SYSTEMATIC 23523906 A 1092 1101 bleomycin FAMILY 23523906 A 1138 1147 histamine TRIVIAL 23523906 A 1185 1194 berberine TRIVIAL 23523906 A 1196 1205 Berberine TRIVIAL 23523906 A 1342 1351 Berberine TRIVIAL 23523906 A 1366 1375 bleomycin FAMILY 23523906 A 1499 1511 nitric oxide SYSTEMATIC 23523906 A 1541 1550 berberine TRIVIAL 23523906 A 1755 1764 berberine TRIVIAL 23523906 A 1773 1782 bleomycin FAMILY 23523906 A 332 341 Berberine TRIVIAL 23523906 A 524 533 berberine TRIVIAL 23523906 A 542 551 bleomycin FAMILY 23523906 A 695 704 bleomycin FAMILY 23523906 A 715 724 Berberine TRIVIAL 23523906 A 805 814 Berberine TRIVIAL 23523906 A 860 869 bleomycin FAMILY 23523906 A 958 967 Berberine TRIVIAL 23523906 T 0 9 Berberine TRIVIAL 23523906 T 21 30 bleomycin FAMILY 23523949 A 1136 1142 Crocin TRIVIAL 23523949 A 1163 1172 vitamin E FAMILY 23523949 A 1219 1222 MDA ABBREVIATION 23523949 A 1244 1247 GSH ABBREVIATION 23523949 A 130 138 diazinon TRIVIAL 23523949 A 1381 1384 DZN ABBREVIATION 23523949 A 1398 1401 DZN ABBREVIATION 23523949 A 140 143 DZN ABBREVIATION 23523949 A 1497 1503 Crocin TRIVIAL 23523949 A 1558 1561 DZN ABBREVIATION 23523949 A 275 281 crocin TRIVIAL 23523949 A 318 321 DZN ABBREVIATION 23523949 A 323 332 vitamin E FAMILY 23523949 A 376 379 DZN ABBREVIATION 23523949 A 384 390 crocin TRIVIAL 23523949 A 456 464 Creatine TRIVIAL 23523949 A 491 506 malondealdehyde TRIVIAL 23523949 A 508 511 MDA ABBREVIATION 23523949 A 517 528 glutathione TRIVIAL 23523949 A 530 533 GSH ABBREVIATION 23523949 A 57 63 crocin TRIVIAL 23523949 A 792 795 DZN ABBREVIATION 23523949 A 923 926 MDA ABBREVIATION 23523949 A 957 960 GSH ABBREVIATION 23523949 T 21 27 crocin TRIVIAL 23523949 T 31 39 diazinon TRIVIAL 23523991 A 1051 1059 naloxone TRIVIAL 23523991 A 1064 1067 FNA ABBREVIATION 23523991 A 1376 1384 naloxone TRIVIAL 23523991 A 1633 1637 urea TRIVIAL 23523991 A 1649 1659 creatinine TRIVIAL 23523991 A 268 276 naloxone TRIVIAL 23523991 A 346 350 urea TRIVIAL 23523991 A 351 359 nitrogen SYSTEMATIC 23523991 A 377 387 creatinine TRIVIAL 23523991 A 524 532 naloxone TRIVIAL 23523991 A 611 621 creatinine TRIVIAL 23523991 A 638 646 naloxone TRIVIAL 23523991 A 694 702 morphine TRIVIAL 23523991 A 738 754 β-funaltrexamine TRIVIAL 23523991 A 756 759 FNA ABBREVIATION 23523991 A 844 854 creatinine TRIVIAL 23523991 A 866 874 tyrosine TRIVIAL 23523991 T 10 18 naloxone TRIVIAL 23524160 A 12 50 3-(1H-indol-3-yl)pyrrolidine-2,5-dione SYSTEMATIC 23524160 A 198 202 (1)H FORMULA 23524160 A 208 213 (13)C FORMULA 23524160 A 306 315 serotonin TRIVIAL 23524160 T 45 66 pyrrolidine-2,5-dione SYSTEMATIC 23524188 A 1070 1073 Dox ABBREVIATION 23524188 A 1131 1134 Dox ABBREVIATION 23524188 A 1199 1202 Dox ABBREVIATION 23524188 A 1309 1312 Dox ABBREVIATION 23524188 A 1338 1341 Dox ABBREVIATION 23524188 A 1390 1393 Dox ABBREVIATION 23524188 A 1428 1431 Dox ABBREVIATION 23524188 A 1480 1483 Dox ABBREVIATION 23524188 A 1537 1540 Dox ABBREVIATION 23524188 A 1595 1598 Dox ABBREVIATION 23524188 A 1658 1661 Dox ABBREVIATION 23524188 A 1718 1721 Dox ABBREVIATION 23524188 A 1769 1772 Dox ABBREVIATION 23524188 A 1820 1823 Dox ABBREVIATION 23524188 A 1907 1910 Dox ABBREVIATION 23524188 A 198 201 PEG ABBREVIATION 23524188 A 212 223 doxorubicin TRIVIAL 23524188 A 225 228 Dox ABBREVIATION 23524188 A 365 368 Dox ABBREVIATION 23524188 A 387 390 Dox ABBREVIATION 23524188 A 446 449 PEG ABBREVIATION 23524188 A 515 518 Dox ABBREVIATION 23524188 A 625 628 Dox ABBREVIATION 23524188 A 823 826 Dox ABBREVIATION 23524188 A 837 840 Dox ABBREVIATION 23524188 A 909 912 Dox ABBREVIATION 23524188 T 28 39 doxorubicin TRIVIAL 23524189 A 372 415 meso-tetrakis (4-sulfonatophenyl) porphyrin SYSTEMATIC 23524189 A 417 421 TPPS ABBREVIATION 23524189 A 709 713 TPPS ABBREVIATION 23524189 A 760 766 oxygen SYSTEMATIC 23524189 T 46 55 porphyrin FAMILY 23524254 A 1139 1146 PVP-K30 IDENTIFIER 23524254 A 1164 1167 PVP ABBREVIATION 23524254 A 1224 1229 (13)C FORMULA 23524254 A 1231 1236 (15)N FORMULA 23524254 A 1241 1245 (1)H FORMULA 23524254 A 1364 1373 vincamine TRIVIAL 23524254 A 141 150 vincamine TRIVIAL 23524254 A 1459 1466 PVP-K30 IDENTIFIER 23524254 A 1480 1488 hydrogen SYSTEMATIC 23524254 A 1576 1579 PVP ABBREVIATION 23524254 A 1622 1629 PVP-K30 IDENTIFIER 23524254 A 1688 1697 vincamine TRIVIAL 23524254 A 262 265 PVP ABBREVIATION 23524254 A 578 585 PVP-K30 IDENTIFIER 23524254 A 933 937 (1)H FORMULA 23524254 T 30 39 vincamine TRIVIAL 23524305 A 257 263 oxygen SYSTEMATIC 23524983 A 365 390 trifluoromethyloxadiazole SYSTEMATIC 23524983 A 392 396 TFMO ABBREVIATION 23524983 A 466 478 hydroxamates FAMILY 23524983 A 519 523 TFMO ABBREVIATION 23524983 A 631 635 TFMO ABBREVIATION 23524983 A 657 668 hydroxamate SYSTEMATIC 23524983 T 70 74 zinc SYSTEMATIC 23525092 A 910 922 levoglucosan TRIVIAL 23525092 A 938 966 phenyl α- and β-d-glucosides MULTIPLE 23525092 T 130 158 phenyl α- and β-d-glucosides MULTIPLE 23525092 T 91 107 1,6-anhydrosugar FAMILY 23525112 A 1010 1013 PMA ABBREVIATION 23525112 A 1122 1126 H2O2 FORMULA 23525112 A 118 124 oxygen SYSTEMATIC 23525112 A 1326 1329 PMA ABBREVIATION 23525112 A 1393 1396 PMA ABBREVIATION 23525112 A 1598 1612 trichostatin A TRIVIAL 23525112 A 1625 1629 H2O2 FORMULA 23525112 A 205 209 H2O2 FORMULA 23525112 A 314 318 H2O2 FORMULA 23525112 A 324 355 phorbol 12-myristate 13-acetate SYSTEMATIC 23525112 A 357 360 PMA ABBREVIATION 23525112 A 520 526 Ca(2+) FORMULA 23525112 A 645 651 Ca(2+) FORMULA 23525112 A 705 708 PMA ABBREVIATION 23525112 A 738 767 4α-phorbol 12, 13-didecanoate SYSTEMATIC 23525112 A 769 775 4α-PDD SYSTEMATIC 23525112 A 885 888 PMA ABBREVIATION 23525112 A 951 957 Gö6976 IDENTIFIER 23525112 T 106 112 Oxygen SYSTEMATIC 23525167 A 103 122 formoterol fumarate TRIVIAL 23525167 A 218 224 phenyl SYSTEMATIC 23525167 A 243 249 methyl SYSTEMATIC 23525167 A 306 311 (13)C FORMULA 23525167 A 356 360 (2)H FORMULA 23525167 A 365 370 (13)C FORMULA 23525167 A 474 482 fumarate TRIVIAL 23525167 A 56 63 ethanol SYSTEMATIC 23525167 T 63 82 formoterol fumarate TRIVIAL 23525215 A 1013 1017 CORT ABBREVIATION 23525215 A 1116 1120 CORT ABBREVIATION 23525215 A 1157 1161 CORT ABBREVIATION 23525215 A 1171 1175 CORT ABBREVIATION 23525215 A 1279 1283 CORT ABBREVIATION 23525215 A 1528 1532 zinc SYSTEMATIC 23525215 A 736 750 corticosterone TRIVIAL 23525215 A 752 756 CORT ABBREVIATION 23525215 A 912 916 CORT ABBREVIATION 23525215 A 974 978 CORT ABBREVIATION 23525330 A 1022 1057 Para-chloromercuribenzene sulfonate SYSTEMATIC 23525330 A 1059 1064 pCMBS ABBREVIATION 23525330 A 1104 1115 sulfhydryls FAMILY 23525330 A 1139 1143 GABA ABBREVIATION 23525330 A 1162 1171 Etomidate TRIVIAL 23525330 A 1294 1303 etomidate TRIVIAL 23525330 A 1350 1360 suflhydryl SYSTEMATIC 23525330 A 1446 1455 etomidate TRIVIAL 23525330 A 1533 1537 GABA ABBREVIATION 23525330 A 1609 1618 etomidate TRIVIAL 23525330 A 1759 1768 etomidate TRIVIAL 23525330 A 230 238 cysteine TRIVIAL 23525330 A 400 409 Etomidate TRIVIAL 23525330 A 637 641 GABA ABBREVIATION 23525330 A 673 682 etomidate TRIVIAL 23525330 A 693 697 GABA ABBREVIATION 23525330 A 729 738 etomidate TRIVIAL 23525330 A 905 914 etomidate TRIVIAL 23525330 T 82 90 Cysteine TRIVIAL 23525662 A 127 134 steroid FAMILY 23525674 A 1016 1028 polyethylene SYSTEMATIC 23525674 A 119 131 polyethylene SYSTEMATIC 23525674 A 463 475 polyethylene SYSTEMATIC 23525674 A 825 838 polypropylene SYSTEMATIC 23525674 A 88 101 polypropylene SYSTEMATIC 23525674 A 932 944 polyethylene SYSTEMATIC 23525674 T 67 80 polypropylene SYSTEMATIC 23525674 T 98 110 polyethylene SYSTEMATIC 23525786 A 1051 1067 methacrylic acid TRIVIAL 23525786 A 1238 1242 HEMA ABBREVIATION 23525786 A 1360 1364 HEMA ABBREVIATION 23525786 A 446 499 poly(2-hydroxyethyl methacrylate-co-methacrylic acid) SYSTEMATIC 23525786 A 501 517 poly(HEMA-co-MA) SYSTEMATIC 23525786 A 541 555 hydroxyapatite TRIVIAL 23525786 A 656 713 dimethacrylated poly(lactide-b-ethylene glycol-b-lactide) SYSTEMATIC 23525786 A 805 810 pHEMA ABBREVIATION 23525786 T 84 89 PHEMA ABBREVIATION 23525786 T 94 108 Hydroxyapatite TRIVIAL 23525902 A 1116 1122 RO3306 IDENTIFIER 23525902 A 547 557 phosphates FAMILY 23525902 A 814 817 ATP ABBREVIATION 23525902 A 838 844 1NMPP1 IDENTIFIER 23525902 A 873 879 RO3306 IDENTIFIER 23525902 A 888 894 1NMPP1 IDENTIFIER 23526144 A 1053 1055 Ca FORMULA 23526144 A 1060 1062 Mg FORMULA 23526144 A 1101 1103 Cu FORMULA 23526144 A 1149 1151 Cu FORMULA 23526144 A 1152 1154 Fe FORMULA 23526144 A 1212 1214 Mg FORMULA 23526144 A 1220 1222 Zn FORMULA 23526144 A 1240 1242 Mg FORMULA 23526144 A 1248 1250 Fe FORMULA 23526144 A 623 625 Ca FORMULA 23526144 A 627 629 Mg FORMULA 23526144 A 631 633 Cu FORMULA 23526144 A 635 637 Zn FORMULA 23526144 A 642 644 Fe FORMULA 23526144 A 851 853 Ca FORMULA 23526144 A 858 860 Mg FORMULA 23526144 A 917 919 Cu FORMULA 23526144 A 924 926 Zn FORMULA 23526144 A 970 972 Ca FORMULA 23526144 A 974 976 Mg FORMULA 23526144 A 981 983 Cu FORMULA 23526231 A 115 149 (+)-N-methoxylcarbonyl-nandigerine SYSTEMATIC 23526231 A 155 188 (+)-N-methoxycarbonyl-lindcarpine SYSTEMATIC 23526231 A 194 226 (+)-10-O-methylhernovine N-oxide SYSTEMATIC 23526231 A 236 273 (+)-3-hydroxy-anhydrolycorine N-oxide SYSTEMATIC 23526231 A 35 42 ethanol SYSTEMATIC 23526231 A 377 381 (1)H FORMULA 23526231 A 382 386 (1)H FORMULA 23526571 A 247 255 thiazole SYSTEMATIC 23526571 T 25 33 Thiazole SYSTEMATIC 23526674 A 1105 1115 vancomycin TRIVIAL 23526674 A 1169 1179 vancomycin TRIVIAL 23526674 A 1341 1351 vancomycin TRIVIAL 23526674 A 1568 1572 urea TRIVIAL 23526674 A 1573 1581 nitrogen SYSTEMATIC 23526674 A 1605 1615 vancomycin TRIVIAL 23526674 A 1721 1731 vancomycin TRIVIAL 23526674 A 1760 1770 vancomycin TRIVIAL 23526674 A 1880 1890 vancomycin TRIVIAL 23526674 A 361 371 vancomycin TRIVIAL 23526674 A 384 394 vancomycin TRIVIAL 23526674 A 490 500 vancomycin TRIVIAL 23526674 A 589 599 creatinine TRIVIAL 23526674 A 677 687 vancomycin TRIVIAL 23526674 A 69 79 vancomycin TRIVIAL 23526674 A 902 912 vancomycin TRIVIAL 23526674 T 27 37 Vancomycin TRIVIAL 23526745 A 171 183 thiostrepton TRIVIAL 23526745 A 195 204 cobalamin FAMILY 23526745 A 212 218 4Fe-4S FORMULA 23526745 A 240 258 2-methyltryptophan SYSTEMATIC 23526745 A 264 274 tryptophan TRIVIAL 23526745 A 75 85 tryptophan TRIVIAL 23526745 T 30 39 Cobalamin FAMILY 23526814 A 112 131 tert-butylcarbamate SYSTEMATIC 23526814 A 23 30 pyrrole SYSTEMATIC 23526814 A 291 303 hydroxamates FAMILY 23526814 A 36 43 benzene SYSTEMATIC 23526814 A 492 496 SAHA ABBREVIATION 23526814 A 50 62 hydroxamates FAMILY 23526814 A 515 530 pyrrole anilide SYSTEMATIC 23526814 A 75 91 2'-aminoanilides FAMILY 23526814 T 0 19 tert-Butylcarbamate SYSTEMATIC 23526919 T 13 25 Carbocyanine TRIVIAL 23527317 A 12 13 N FORMULA 23527317 A 146 155 monoamine FAMILY 23527317 A 206 220 [(3)H]dopamine SYSTEMATIC 23527317 A 26 34 lobelane TRIVIAL 23527317 A 261 285 N-1,2(R)-dihydroxypropyl SYSTEMATIC 23527317 A 368 383 methamphetamine TRIVIAL 23527317 A 85 111 [(3)H]dihydrotetrabenazine SYSTEMATIC 23527317 T 147 162 methamphetamine TRIVIAL 23527317 T 24 25 N FORMULA 23527317 T 42 54 nor-lobelane TRIVIAL 23527551 A 1123 1137 aryl diazonium FAMILY 23527551 A 183 197 aryl diazonium FAMILY 23527551 A 258 264 SO3(-) FORMULA 23527551 A 269 278 N(+)(Me)3 FORMULA 23527551 A 345 358 glassy carbon TRIVIAL 23527551 A 482 496 aryl diazonium FAMILY 23527551 A 680 694 aryl diazonium FAMILY 23527551 A 815 829 aryl diazonium FAMILY 23527551 A 922 928 phenyl SYSTEMATIC 23527551 T 205 219 Aryl Diazonium FAMILY 23527585 A 0 6 Copper SYSTEMATIC 23527585 A 1047 1053 copper SYSTEMATIC 23527585 A 1090 1096 PCB126 TRIVIAL 23527585 A 1229 1240 glutathione TRIVIAL 23527585 A 1277 1283 copper SYSTEMATIC 23527585 A 1377 1385 selenium SYSTEMATIC 23527585 A 1387 1396 manganese SYSTEMATIC 23527585 A 1398 1402 zinc SYSTEMATIC 23527585 A 1408 1412 iron SYSTEMATIC 23527585 A 143 149 copper SYSTEMATIC 23527585 A 1604 1610 PCB126 TRIVIAL 23527585 A 1678 1684 copper SYSTEMATIC 23527585 A 1714 1720 copper SYSTEMATIC 23527585 A 1773 1779 PCB126 TRIVIAL 23527585 A 1781 1787 PCB126 TRIVIAL 23527585 A 213 221 hydroxyl SYSTEMATIC 23527585 A 232 248 Aryl-hydrocarbon FAMILY 23527585 A 300 324 polychlorinated biphenyl FAMILY 23527585 A 326 329 PCB ABBREVIATION 23527585 A 341 372 3,3',4,4',5-pentachlorobiphenyl SYSTEMATIC 23527585 A 374 380 PCB126 TRIVIAL 23527585 A 392 398 copper SYSTEMATIC 23527585 A 517 520 PCB ABBREVIATION 23527585 A 604 610 copper SYSTEMATIC 23527585 A 793 799 PCB126 TRIVIAL 23527585 A 994 1000 copper SYSTEMATIC 23527585 T 13 19 Copper SYSTEMATIC 23527619 A 113 115 Au FORMULA 23527619 A 150 163 carboxylethyl SYSTEMATIC 23527619 A 239 245 Hg(2+) FORMULA 23527619 A 250 252 Au FORMULA 23527619 A 317 319 Au FORMULA 23527619 A 369 371 Au FORMULA 23527619 A 422 425 Cys FORMULA 23527619 A 472 474 Au FORMULA 23527619 A 593 599 Hg(2+) FORMULA 23527619 A 60 68 cysteine TRIVIAL 23527619 A 629 635 thiols FAMILY 23527619 A 641 643 Au FORMULA 23527619 A 673 676 Cys FORMULA 23527619 A 689 691 Au FORMULA 23527619 A 70 73 Cys FORMULA 23527619 A 79 85 Hg(2+) FORMULA 23527619 A 824 827 Cys FORMULA 23527619 A 832 838 Hg(2+) FORMULA 23527619 A 890 893 Cys FORMULA 23527619 A 898 904 Hg(2+) FORMULA 23527619 T 106 114 Cysteine TRIVIAL 23527619 T 119 130 Mercury(II) SYSTEMATIC 23528109 A 124 131 silicon SYSTEMATIC 23528109 A 195 207 organosilane FAMILY 23528109 A 216 221 Si3N4 FORMULA 23528109 A 27 31 POPC ABBREVIATION 23528109 A 769 774 CaCl2 FORMULA 23528109 A 88 103 silicon nitride SYSTEMATIC 23528109 A 970 977 silicon SYSTEMATIC 23528109 T 36 51 silicon nitride SYSTEMATIC 23528251 A 140 150 androstane TRIVIAL 23528251 A 215 221 5'-AMP SYSTEMATIC 23528251 A 35 41 5'-AMP SYSTEMATIC 23528251 A 367 380 Phenobarbital TRIVIAL 23528251 A 702 717 Cobalt chloride SYSTEMATIC 23528251 T 32 42 androstane TRIVIAL 23528252 A 1042 1050 androgen FAMILY 23528252 A 1141 1144 BPA ABBREVIATION 23528252 A 138 141 BPA ABBREVIATION 23528252 A 36 47 bisphenol A TRIVIAL 23528252 A 413 416 BPA ABBREVIATION 23528252 A 49 52 BPA ABBREVIATION 23528252 A 532 544 testosterone TRIVIAL 23528252 A 673 676 BPA ABBREVIATION 23528252 A 782 790 androgen FAMILY 23528252 A 961 964 BPA ABBREVIATION 23528252 T 10 18 androgen FAMILY 23528252 T 121 132 bisphenol A TRIVIAL 23528300 A 12 23 benzoxazole SYSTEMATIC 23528300 A 45 56 oxamic acid TRIVIAL 23528300 T 24 50 2-substituted benzoxazoles FAMILY 23528390 A 0 10 Quinolones FAMILY 23528390 A 159 169 quinolones FAMILY 23528390 A 227 237 Quinolones FAMILY 23528390 A 489 498 quinolone FAMILY 23528390 A 587 593 oxygen SYSTEMATIC 23528390 A 794 803 quinolone FAMILY 23528390 T 24 34 quinolones FAMILY 23528611 A 1125 1132 PKI-166 IDENTIFIER 23528611 A 1220 1227 PKI-166 IDENTIFIER 23528611 A 1232 1242 lisinopril TRIVIAL 23528611 A 1314 1327 phenylephrine TRIVIAL 23528611 A 445 452 PKI-166 IDENTIFIER 23528611 A 570 577 PKI-166 IDENTIFIER 23528611 A 581 591 lisinopril TRIVIAL 23528611 A 683 690 PKI-166 IDENTIFIER 23528611 A 718 725 PKI-166 IDENTIFIER 23528611 A 837 847 creatinine TRIVIAL 23528611 A 925 935 lisinopril TRIVIAL 23528611 A 993 1000 PKI-166 IDENTIFIER 23528611 T 43 50 PKI-166 IDENTIFIER 23529571 A 530 536 carbon SYSTEMATIC 23529571 A 548 556 graphene TRIVIAL 23529571 A 561 567 carbon SYSTEMATIC 23529671 A 1094 1101 glucose TRIVIAL 23529671 A 631 638 glucose TRIVIAL 23529894 A 167 178 flinderoles FAMILY 23529894 A 236 245 borrerine TRIVIAL 23529894 A 273 284 flinderoles FAMILY 23529894 A 290 302 borreverines FAMILY 23529894 A 347 358 flinderoles FAMILY 23529894 A 387 396 borrerine TRIVIAL 23529894 A 492 515 Flinderoles A, B, and C MULTIPLE 23529894 A 540 554 isoborreverine TRIVIAL 23529894 A 560 582 dimethylisoborreverine TRIVIAL 23529894 A 627 637 tryptamine TRIVIAL 23529894 A 708 731 flinderoles A, B, and C MULTIPLE 23529894 A 819 825 indole SYSTEMATIC 23529894 A 835 840 enone SYSTEMATIC 23529898 A 105 109 TiO2 FORMULA 23529898 A 326 330 TiO2 FORMULA 23529898 A 341 344 PHB ABBREVIATION 23529898 A 45 68 poly(3-hydroxybutyrate) SYSTEMATIC 23529898 A 70 73 PHB ABBREVIATION 23529898 A 86 90 TiO2 FORMULA 23529898 T 38 61 Poly(3-Hydroxybutyrate) SYSTEMATIC 23529898 T 63 67 TiO2 FORMULA 23529905 A 117 133 polycaprolactone SYSTEMATIC 23529905 A 134 160 poly(α,β)-DL-aspartic acid SYSTEMATIC 23529905 A 622 625 PCL ABBREVIATION 23529905 A 626 629 PAA ABBREVIATION 23530011 A 1111 1122 cholesterol TRIVIAL 23530011 A 1184 1191 glucose TRIVIAL 23530011 A 1208 1219 cholesterol TRIVIAL 23530011 A 1225 1236 cholesterol TRIVIAL 23530011 A 1238 1251 triglycerides FAMILY 23530011 A 1261 1272 fatty acids FAMILY 23530011 A 1433 1440 glucose TRIVIAL 23530011 A 1766 1773 glucose TRIVIAL 23530011 A 636 643 glucose TRIVIAL 23530011 A 763 775 Carbohydrate FAMILY 23530011 A 809 822 carbohydrates FAMILY 23530018 A 1066 1069 CGP ABBREVIATION 23530018 A 1210 1219 chalcogen FAMILY 23530018 A 1226 1228 Se FORMULA 23530018 A 1236 1238 Te FORMULA 23530018 A 1313 1320 methine SYSTEMATIC 23530018 A 1324 1334 trimethine SYSTEMATIC 23530018 A 1369 1377 pyrylium FAMILY 23530018 A 1538 1547 chalcogen FAMILY 23530018 A 182 200 chalcogenopyrylium FAMILY 23530018 A 207 211 CGPs ABBREVIATION 23530018 A 270 297 [(3)H]estradiol glucuronide SYSTEMATIC 23530018 A 299 305 E217βG SYSTEMATIC 23530018 A 405 409 CGPs ABBREVIATION 23530018 A 458 465 calcein TRIVIAL 23530018 A 49 52 ATP ABBREVIATION 23530018 A 494 498 CGPs ABBREVIATION 23530018 A 523 529 E217βG SYSTEMATIC 23530018 A 571 575 CGPs ABBREVIATION 23530018 A 704 708 CGPs ABBREVIATION 23530018 A 744 751 calcein TRIVIAL 23530018 A 849 853 CGPs ABBREVIATION 23530018 A 869 881 [(3)H]E217βG SYSTEMATIC 23530018 A 971 977 E217βG SYSTEMATIC 23530018 T 0 18 Chalcogenopyrylium FAMILY 23530019 A 0 8 Nicotine TRIVIAL 23530019 A 1000 1008 nicotine TRIVIAL 23530019 A 1013 1022 bupropion TRIVIAL 23530019 A 1049 1057 coumarin TRIVIAL 23530019 A 1077 1085 Nicotine TRIVIAL 23530019 A 1105 1113 cotinine TRIVIAL 23530019 A 1161 1169 Nicotine TRIVIAL 23530019 A 1174 1183 bupropion TRIVIAL 23530019 A 1213 1225 C-8-xanthate TRIVIAL 23530019 A 1365 1373 nicotine TRIVIAL 23530019 A 1399 1408 bupropion TRIVIAL 23530019 A 1473 1481 nicotine TRIVIAL 23530019 A 149 157 nicotine TRIVIAL 23530019 A 1565 1573 nicotine TRIVIAL 23530019 A 196 204 Nicotine TRIVIAL 23530019 A 209 217 cotinine TRIVIAL 23530019 A 289 297 nicotine TRIVIAL 23530019 A 364 372 nicotine TRIVIAL 23530019 A 448 456 nicotine TRIVIAL 23530019 A 542 550 nicotine TRIVIAL 23530019 A 561 569 Nicotine TRIVIAL 23530019 A 701 709 nicotine TRIVIAL 23530019 A 765 773 nicotine TRIVIAL 23530019 A 867 875 nicotine TRIVIAL 23530019 A 879 887 cotinine TRIVIAL 23530019 T 0 8 Nicotine TRIVIAL 23530020 A 0 10 Prilocaine TRIVIAL 23530020 A 1020 1049 bis-(4-nitrophenyl) phosphate SYSTEMATIC 23530020 A 1134 1144 prilocaine TRIVIAL 23530020 A 1149 1158 lidocaine TRIVIAL 23530020 A 1305 1316 o-toluidine SYSTEMATIC 23530020 A 1321 1333 2,6-xylidine SYSTEMATIC 23530020 A 1415 1426 o-Toluidine SYSTEMATIC 23530020 A 1431 1443 2,6-xylidine SYSTEMATIC 23530020 A 1482 1510 4- and 6-hydroxy-o-toluidine MULTIPLE 23530020 A 15 24 lidocaine TRIVIAL 23530020 A 1515 1537 4-hydroxy-2,6-xylidine SYSTEMATIC 23530020 A 168 178 prilocaine TRIVIAL 23530020 A 1781 1791 prilocaine TRIVIAL 23530020 A 1797 1806 lidocaine TRIVIAL 23530020 A 180 191 o-toluidine SYSTEMATIC 23530020 A 197 206 lidocaine TRIVIAL 23530020 A 208 220 2,6-xylidine SYSTEMATIC 23530020 A 421 431 prilocaine TRIVIAL 23530020 A 43 48 amide FAMILY 23530020 A 437 446 lidocaine TRIVIAL 23530020 A 504 514 prilocaine TRIVIAL 23530020 A 595 604 lidocaine TRIVIAL 23530020 A 668 678 prilocaine TRIVIAL 23530020 A 683 692 lidocaine TRIVIAL 23530020 A 843 853 prilocaine TRIVIAL 23530020 A 858 869 o-toluidine SYSTEMATIC 23530020 A 920 929 lidocaine TRIVIAL 23530020 A 934 946 2,6-xylidine SYSTEMATIC 23530020 A 988 1015 diisopropyl fluorophosphate SYSTEMATIC 23530020 T 0 10 Prilocaine TRIVIAL 23530020 T 16 25 Lidocaine TRIVIAL 23530036 A 577 585 tyrosine TRIVIAL 23530765 A 130 165 bis(l-histidinato)cadmium dihydrate SYSTEMATIC 23530765 A 204 210 copper SYSTEMATIC 23530765 A 453 459 copper SYSTEMATIC 23530765 A 610 619 histidine TRIVIAL 23530765 A 69 75 Cu(II) FORMULA 23530765 A 809 815 copper SYSTEMATIC 23530765 T 55 61 Copper SYSTEMATIC 23530765 T 79 114 Bis(l-histidinato)cadmium Dihydrate SYSTEMATIC 23531107 A 1153 1156 PbS FORMULA 23531107 A 1216 1219 PbS FORMULA 23531107 A 1220 1223 ZnO FORMULA 23531107 A 1309 1312 ZnO FORMULA 23531107 A 1322 1326 PbSe FORMULA 23531107 A 1330 1333 ZnO FORMULA 23531107 A 138 149 metal oxide FAMILY 23531107 A 1652 1663 metal oxide FAMILY 23531107 A 422 425 ZnO FORMULA 23531107 A 433 438 oxide SYSTEMATIC 23531107 A 487 490 ZnO FORMULA 23531107 A 623 626 PbS FORMULA 23531107 A 630 633 ZnO FORMULA 23531107 A 684 687 ZnO FORMULA 23531107 A 693 701 nitrogen SYSTEMATIC 23531107 A 763 766 ZnO FORMULA 23531107 A 801 805 PbSe FORMULA 23531107 A 809 812 ZnO FORMULA 23531107 T 88 99 Metal Oxide FAMILY 23531119 A 0 7 Uridine TRIVIAL 23531119 A 167 174 5-bromo SYSTEMATIC 23531119 A 179 187 5-fluoro SYSTEMATIC 23531119 A 208 214 uracil TRIVIAL 23531119 A 231 234 NHN FORMULA 23531119 A 235 243 hydrogen SYSTEMATIC 23531119 A 290 301 nucleosides FAMILY 23531119 A 315 323 halogens FAMILY 23531119 A 415 426 halouracils FAMILY 23531119 A 471 481 2-carbonyl SYSTEMATIC 23531119 A 515 523 hydrogen SYSTEMATIC 23531119 A 611 618 guanine TRIVIAL 23531119 A 63 71 hydrogen SYSTEMATIC 23531119 A 640 647 thymine TRIVIAL 23531119 A 664 669 (15)N FORMULA 23531119 A 678 692 5-bromouridine SYSTEMATIC 23531119 A 728 732 enol SYSTEMATIC 23531119 T 68 88 5-substituted uracil SYSTEMATIC 23531160 A 1054 1057 TRP ABBREVIATION 23531160 A 1062 1066 5-HT SYSTEMATIC 23531160 A 1076 1086 monoamines FAMILY 23531160 A 183 192 monoamine FAMILY 23531160 A 226 235 serotonin TRIVIAL 23531160 A 237 241 5-HT SYSTEMATIC 23531160 A 898 909 indoleamine SYSTEMATIC 23531160 A 963 973 tryptophan TRIVIAL 23531160 A 975 978 TRP ABBREVIATION 23531160 T 14 23 serotonin TRIVIAL 23531217 A 105 120 organophosphate FAMILY 23531217 A 122 139 organophosphonate FAMILY 23531217 A 24 52 bis-pyridinium mono-aldoxime SYSTEMATIC 23531217 A 358 374 octadecyl silica SYSTEMATIC 23532446 A 1256 1269 polypropylene SYSTEMATIC 23532446 A 180 196 titanium dioxide SYSTEMATIC 23532897 A 397 404 proline TRIVIAL 23532897 A 761 773 thiazolidine SYSTEMATIC 23532897 A 862 880 inositol phosphate SYSTEMATIC 23532897 T 14 21 Proline TRIVIAL 23533220 A 1139 1151 testosterone TRIVIAL 23533220 A 1405 1409 cAMP ABBREVIATION 23533220 A 1421 1425 cAMP ABBREVIATION 23533220 A 1563 1576 17β-estradiol SYSTEMATIC 23533220 A 332 345 17β-estradiol SYSTEMATIC 23533220 A 356 369 catecholamine TRIVIAL 23533220 A 619 627 dopamine TRIVIAL 23534412 A 144 151 seselin TRIVIAL 23534412 A 334 345 epinephrine TRIVIAL 23534412 A 407 423 arachidonic acid TRIVIAL 23534412 A 538 553 ferric chloride SYSTEMATIC 23534412 A 698 701 ADP ABBREVIATION 23534412 A 973 976 ADP ABBREVIATION 23534412 T 47 55 coumarin TRIVIAL 23534412 T 67 188 3-(5-hydroxy-2,2-dimethyl-chroman-6-yl)-N-{2-[3-(5-hydroxy-2,2-dimethyl-chroman-6-yl)-propionylamino]-ethyl}-propionamide SYSTEMATIC 23534413 A 1026 1036 flavonoids FAMILY 23534413 A 1067 1075 xanthine TRIVIAL 23534413 A 210 219 uric acid TRIVIAL 23534413 A 24 35 allopurinol TRIVIAL 23534413 A 302 310 xanthine TRIVIAL 23534413 A 40 53 benzbromarone TRIVIAL 23534413 A 409 419 flavonoids FAMILY 23534413 A 473 483 flavonoids FAMILY 23534413 A 530 538 xanthine TRIVIAL 23534413 A 674 682 xanthine TRIVIAL 23534413 A 713 722 Myricetin TRIVIAL 23534413 A 727 735 luteolin TRIVIAL 23534413 A 786 794 xanthine TRIVIAL 23534413 A 872 880 xanthine TRIVIAL 23534413 T 108 116 xanthine TRIVIAL 23534413 T 73 83 flavonoids FAMILY 23534413 T 88 99 isoflavones FAMILY 23534440 A 1144 1151 guanine TRIVIAL 23534440 A 1192 1200 cytosine TRIVIAL 23534440 A 1466 1476 nucleotide FAMILY 23534440 A 1555 1565 nucleotide FAMILY 23534440 A 1992 1997 sugar FAMILY 23534440 A 2003 2004 H FORMULA 23534440 A 2082 2088 Mg(2+) FORMULA 23534440 A 2209 2215 Mg(2+) FORMULA 23534440 A 834 841 guanine TRIVIAL 23534442 A 1025 1054 nitrooxyalkyl ester and ether MULTIPLE 23534442 A 12 44 3-substituted 1,5-diarylpyrroles FAMILY 23534442 A 138 145 pyrrole SYSTEMATIC 23534442 A 154 167 nitrooxyalkyl FAMILY 23534442 A 176 182 esters FAMILY 23534442 A 184 194 carbonates FAMILY 23534442 A 200 206 ethers FAMILY 23534442 A 248 250 NO FORMULA 23534442 A 351 371 nitrooxyalkyl ethers FAMILY 23534442 A 399 407 alcohols FAMILY 23534442 A 450 458 Nitrooxy SYSTEMATIC 23534442 A 478 480 NO FORMULA 23534442 A 55 68 nitrooxyalkyl FAMILY 23534442 A 922 926 (1)H FORMULA 23534442 A 932 937 (13)C FORMULA 23534442 T 134 146 nitric oxide SYSTEMATIC 23534442 T 42 80 1,5-diarylpyrrole nitrooxyalkyl ethers FAMILY 23534827 A 1009 1020 C-(N)-A-S-H ABBREVIATION 23534827 A 103 128 calcium (alumino)silicate SYSTEMATIC 23534827 A 1255 1263 silicate FAMILY 23534827 A 1268 1277 aluminate TRIVIAL 23534827 A 1377 1407 calcium-sodium aluminosilicate SYSTEMATIC 23534827 A 196 207 tobermorite TRIVIAL 23534827 A 347 385 calcium-sodium aluminosilicate hydrate SYSTEMATIC 23534827 A 387 398 C-(N)-A-S-H ABBREVIATION 23534827 A 507 518 C-(N)-A-S-H ABBREVIATION 23534827 A 573 584 tobermorite TRIVIAL 23534827 A 632 643 tobermorite TRIVIAL 23534827 A 992 1003 tobermorite TRIVIAL 23534827 T 112 123 tobermorite TRIVIAL 23534827 T 38 76 calcium-sodium aluminosilicate hydrate SYSTEMATIC 23535167 A 10 20 methionine TRIVIAL 23535167 A 1012 1020 ethylene SYSTEMATIC 23535167 A 1022 1035 nicotianamine SYSTEMATIC 23535167 A 1150 1153 Met FORMULA 23535167 A 188 191 Met FORMULA 23535167 A 26 29 SAM ABBREVIATION 23535167 A 293 299 sulfur SYSTEMATIC 23535167 A 31 51 S-adenosylmethionine TRIVIAL 23535167 A 341 350 aspartate TRIVIAL 23535167 A 359 370 amino acids FAMILY 23535167 A 404 407 SAM ABBREVIATION 23535167 A 409 412 SAM ABBREVIATION 23535167 A 424 432 ethylene SYSTEMATIC 23535167 A 434 447 nicotianamine SYSTEMATIC 23535167 A 5 8 Met FORMULA 23535167 A 501 507 methyl SYSTEMATIC 23535167 A 631 634 SAM ABBREVIATION 23535167 A 76 79 Met FORMULA 23535167 A 837 840 Met FORMULA 23535167 A 895 898 Met FORMULA 23535167 A 934 937 MTA ABBREVIATION 23535167 A 939 961 5'-methylthioadenosine SYSTEMATIC 23535167 A 964 967 MTA ABBREVIATION 23535167 T 0 10 Methionine TRIVIAL 23535167 T 23 43 S-adenosylmethionine TRIVIAL 23535167 T 69 75 sulfur SYSTEMATIC 23535167 T 77 85 ethylene SYSTEMATIC 23535185 A 1053 1061 galangin TRIVIAL 23535185 A 1084 1092 cromolyn TRIVIAL 23535185 A 1146 1154 galangin TRIVIAL 23535185 A 1232 1241 histamine TRIVIAL 23535185 A 1365 1373 galangin TRIVIAL 23535185 A 298 306 galangin TRIVIAL 23535185 A 378 386 Galangin TRIVIAL 23535185 A 397 406 histamine TRIVIAL 23535185 A 449 456 calcium SYSTEMATIC 23535185 A 460 489 phorbol 12-mystate 13-acetate SYSTEMATIC 23535185 A 495 502 calcium SYSTEMATIC 23535185 A 557 565 Galangin TRIVIAL 23535185 A 719 727 galangin TRIVIAL 23535185 A 788 789 N FORMULA 23535185 A 897 905 galangin TRIVIAL 23535185 A 982 991 histamine TRIVIAL 23535185 T 0 8 Galangin TRIVIAL 23535186 A 109 124 d-galactosamine TRIVIAL 23535186 A 1145 1151 d-GalN ABBREVIATION 23535186 A 1188 1197 scoparone TRIVIAL 23535186 A 1224 1233 scoparone TRIVIAL 23535186 A 1245 1251 d-GalN ABBREVIATION 23535186 A 126 132 d-GalN ABBREVIATION 23535186 A 264 270 d-GalN ABBREVIATION 23535186 A 338 347 scoparone TRIVIAL 23535186 A 358 364 d-GalN ABBREVIATION 23535186 A 395 401 d-GalN ABBREVIATION 23535186 A 559 568 scoparone TRIVIAL 23535186 A 585 591 d-GalN ABBREVIATION 23535186 A 756 757 N FORMULA 23535186 A 950 959 scoparone TRIVIAL 23535186 A 96 105 scoparone TRIVIAL 23535186 T 0 9 Scoparone TRIVIAL 23535186 T 21 36 d-galactosamine TRIVIAL 23535288 A 1195 1198 BHA ABBREVIATION 23535288 A 562 578 sulfadimethoxine TRIVIAL 23535288 A 580 583 SDM ABBREVIATION 23535288 A 603 629 phenylethyl isothiocyanate SYSTEMATIC 23535288 A 645 669 butylated hydroxyanisole SYSTEMATIC 23535288 A 671 674 BHA ABBREVIATION 23535288 A 696 704 catechol TRIVIAL 23535288 A 722 769 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine SYSTEMATIC 23535288 A 774 795 chenodeoxycholic acid TRIVIAL 23535288 A 846 857 caprolactam TRIVIAL 23535320 A 120 135 1,2,3-triazoles FAMILY 23535320 A 142 157 nor-β-lapachone TRIVIAL 23535320 A 164 179 1,2,3-triazoles FAMILY 23535320 A 188 199 α-lapachone TRIVIAL 23535320 A 206 221 1,2,3-triazoles FAMILY 23535320 A 622 637 Nor-α-lapachone TRIVIAL 23535320 A 89 108 1,4-naphthoquinones FAMILY 23535320 T 106 128 α- and nor-α-lapachone MULTIPLE 23535320 T 135 150 1,2,3-triazoles FAMILY 23535320 T 154 160 copper SYSTEMATIC 23535320 T 171 176 azide SYSTEMATIC 23535320 T 177 183 alkyne FAMILY 23535320 T 7 22 naphthoquinones FAMILY 23535321 A 107 123 diphenyl sulfone SYSTEMATIC 23535321 A 12 56 heterocyclic organobismuth(III) carboxylates FAMILY 23535321 A 174 185 carboxylate SYSTEMATIC 23535321 A 441 457 diphenyl sulfone SYSTEMATIC 23535321 A 470 497 ClBi(5-RC6H3-2-SO2C6H4-1'-) FAMILY 23535321 A 66 92 RCO2Bi(C6H4-2-SO2C6H4-1'-) FAMILY 23535321 A 699 706 bismuth SYSTEMATIC 23535321 A 732 743 carboxylate SYSTEMATIC 23535321 A 765 772 bismuth SYSTEMATIC 23535321 T 0 33 Heterocyclic bismuth carboxylates FAMILY 23535321 T 45 61 diphenyl sulfone SYSTEMATIC 23535326 A 307 315 BP1.4160 IDENTIFIER 23535326 A 317 329 cyclohexanol SYSTEMATIC 23535326 A 358 365 alcohol FAMILY 23535326 A 46 55 histamine TRIVIAL 23535326 A 96 104 hydroxyl SYSTEMATIC 23535326 T 24 33 histamine TRIVIAL 23535326 T 66 73 alcohol FAMILY 23535334 A 173 190 hydroxycinnamates FAMILY 23535334 A 234 276 p-coumaryl, coniferyl and sinapyl alcohols MULTIPLE 23535351 A 1236 1245 Asenapine TRIVIAL 23535351 A 1354 1363 asenapine TRIVIAL 23535351 A 411 420 Asenapine TRIVIAL 23535351 A 967 976 asenapine TRIVIAL 23535351 T 54 63 asenapine TRIVIAL 23535360 A 1239 1247 cysteine TRIVIAL 23535360 A 1252 1260 cysteine TRIVIAL 23535360 A 1261 1267 lysine TRIVIAL 23535360 A 1342 1348 lysine TRIVIAL 23535360 A 1588 1596 cysteine TRIVIAL 23535360 A 411 422 amino acids FAMILY 23535360 A 875 883 cysteine TRIVIAL 23535360 A 885 891 lysine TRIVIAL 23535360 A 896 904 cysteine TRIVIAL 23535360 A 905 911 lysine TRIVIAL 23535360 T 42 53 Amino Acids FAMILY 23535394 A 1014 1023 saxitoxin TRIVIAL 23535394 A 1063 1069 sodium SYSTEMATIC 23535394 A 1185 1194 saxitoxin TRIVIAL 23535394 A 156 162 sodium SYSTEMATIC 23535394 A 164 173 potassium SYSTEMATIC 23535394 A 178 185 calcium SYSTEMATIC 23535394 A 376 385 Saxitoxin TRIVIAL 23535394 A 950 959 saxitoxin TRIVIAL 23535394 T 38 47 saxitoxin TRIVIAL 23535516 A 1092 1095 Nle FORMULA 23535516 A 1100 1105 D-Phe FORMULA 23535516 A 1839 1844 AG490 TRIVIAL 23535516 A 1849 1854 U0126 IDENTIFIER 23535516 A 827 828 N FORMULA 23535870 T 12 21 potassium SYSTEMATIC 23535915 A 1056 1064 atrazine TRIVIAL 23535915 A 1165 1173 atrazine TRIVIAL 23535915 A 1283 1291 atrazine TRIVIAL 23535915 A 1492 1500 atrazine TRIVIAL 23535915 A 162 170 atrazine TRIVIAL 23535915 A 243 251 atrazine TRIVIAL 23535915 A 424 432 atrazine TRIVIAL 23535915 A 532 540 atrazine TRIVIAL 23535915 A 704 712 atrazine TRIVIAL 23535915 A 933 941 atrazine TRIVIAL 23535915 A 996 1004 atrazine TRIVIAL 23535915 T 80 88 atrazine TRIVIAL 23536271 A 0 8 β-Ionone TRIVIAL 23536271 A 1176 1184 β-ionone TRIVIAL 23536271 A 191 199 β-ionone TRIVIAL 23536271 A 575 583 β-ionone TRIVIAL 23536271 A 641 649 β-ionone TRIVIAL 23536271 A 789 794 amino FAMILY 23536271 A 842 850 β-Ionone TRIVIAL 23536271 T 0 8 β-Ionone TRIVIAL 23536315 A 1092 1095 ASA ABBREVIATION 23536315 A 1099 1110 BAY 11-7082 IDENTIFIER 23536315 A 1194 1207 dexamethasone TRIVIAL 23536315 A 1316 1319 ASA ABBREVIATION 23536315 A 329 342 dexamethasone TRIVIAL 23536315 A 363 383 acetylsalicylic acid SYSTEMATIC 23536315 A 385 388 ASA ABBREVIATION 23536315 A 471 482 BAY 11-7082 IDENTIFIER 23536315 A 487 498 Ro 106-9920 IDENTIFIER 23536315 A 587 590 ASA ABBREVIATION 23536315 A 592 603 BAY-11-7082 IDENTIFIER 23536315 A 608 619 Ro 106-9920 IDENTIFIER 23536582 A 224 231 glucose TRIVIAL 23536582 A 56 63 glucose TRIVIAL 23536582 T 15 22 Glucose TRIVIAL 23536584 A 1044 1051 glucose TRIVIAL 23536584 A 1192 1199 glucose TRIVIAL 23536584 A 1856 1865 metformin TRIVIAL 23536584 A 202 211 metformin TRIVIAL 23536584 T 123 132 Metformin TRIVIAL 23536728 T 56 64 Pregnane TRIVIAL 23537133 A 109 121 acetonitrile SYSTEMATIC 23537133 A 143 160 tetraalkyammonium FAMILY 23537133 A 220 221 C FORMULA 23537133 A 238 251 glassy carbon TRIVIAL 23537133 A 253 261 graphite TRIVIAL 23537133 A 266 275 fullerene TRIVIAL 23537133 A 346 348 Ag FORMULA 23537133 A 349 353 AgCl FORMULA 23537133 A 410 426 trimethylsilanes FAMILY 23537133 A 427 433 RSiMe3 FAMILY 23537133 A 459 473 trimethylsilyl SYSTEMATIC 23537133 A 481 487 TMS(+) ABBREVIATION 23537133 A 60 66 carbon SYSTEMATIC 23537133 A 761 767 benzyl SYSTEMATIC 23537133 A 772 777 allyl SYSTEMATIC 23537133 A 91 104 glassy carbon TRIVIAL 23537133 T 47 54 carbons FAMILY 23537133 T 61 66 allyl SYSTEMATIC 23537133 T 71 77 benzyl SYSTEMATIC 23537133 T 78 94 trimethylsilanes FAMILY 23537315 A 202 217 phosphoranimide SYSTEMATIC 23537315 A 260 268 nitrogen SYSTEMATIC 23537315 A 31 42 hydrocarbon FAMILY 23537315 A 354 365 hydrocarbon FAMILY 23537315 A 450 458 nitrogen SYSTEMATIC 23537315 A 89 94 Co(I) FORMULA 23537315 A 932 956 unsaturated hydrocarbons FAMILY 23537315 A 99 104 Ni(I) FORMULA 23537315 T 0 11 Hydrocarbon FAMILY 23537321 A 15 22 silicon SYSTEMATIC 23537321 A 184 191 silicon SYSTEMATIC 23537321 A 301 308 silicon SYSTEMATIC 23537321 A 487 494 silicon SYSTEMATIC 23537321 A 495 501 carbon SYSTEMATIC 23537321 A 531 538 silicon SYSTEMATIC 23537321 A 576 582 carbon SYSTEMATIC 23537321 A 632 638 carbon SYSTEMATIC 23537321 A 64 71 lithium SYSTEMATIC 23537321 A 676 683 silicon SYSTEMATIC 23537321 A 736 743 silicon SYSTEMATIC 23537321 T 57 64 silicon SYSTEMATIC 23537321 T 88 90 li FORMULA 23537339 A 164 185 α-azido-β-keto esters FAMILY 23537339 A 21 23 Fe FORMULA 23537339 A 255 284 3-substitued 3-azidooxindoles FAMILY 23537339 A 65 78 β-keto esters FAMILY 23537339 A 83 92 oxindoles FAMILY 23537339 T 17 21 Iron SYSTEMATIC 23537339 T 45 58 β-Keto Esters FAMILY 23537339 T 63 72 Oxindoles FAMILY 23537597 A 1056 1077 δ-aminolevulinic acid SYSTEMATIC 23537597 A 1144 1159 protoporphyrins FAMILY 23537597 A 174 183 vitamin C TRIVIAL 23537597 A 190 205 calcium lactate SYSTEMATIC 23537597 A 207 212 CaLac ABBREVIATION 23537597 A 215 230 ferrous sulfate SYSTEMATIC 23537597 A 232 237 FeSO4 FORMULA 23537597 A 243 255 zinc sulfate SYSTEMATIC 23537597 A 257 262 ZnSO4 FORMULA 23537599 A 106 116 methanabol TRIVIAL 23537599 A 92 101 turinabol TRIVIAL 23537599 A 943 953 methanabol TRIVIAL 23537661 A 1021 1037 PC-dibenzofurans FAMILY 23537661 A 623 648 polychlorinated biphenyls FAMILY 23537661 A 650 654 PCBs ABBREVIATION 23537661 A 657 671 organochlorine FAMILY 23537661 A 688 701 methylmercury SYSTEMATIC 23537661 A 946 957 hydrocarbon FAMILY 23537661 A 983 996 non-ortho PCB FAMILY 23537661 A 999 1016 PC-dibenzodioxins FAMILY 23537700 A 0 10 Oxysterols FAMILY 23537700 A 148 173 7 beta-hydroxycholesterol SYSTEMATIC 23537700 A 175 180 7b-HC SYSTEMATIC 23537700 A 404 409 7b-HC SYSTEMATIC 23537700 A 472 480 pyruvate TRIVIAL 23537700 A 506 526 phosphoenol pyruvate TRIVIAL 23537700 A 561 570 glutamine TRIVIAL 23537700 T 63 84 7β-hydroxycholesterol SYSTEMATIC 23537700 T 8 16 pyruvate TRIVIAL 23537700 T 89 98 glutamine TRIVIAL 23537747 A 1098 1107 nobiletin TRIVIAL 23537747 A 291 299 apigenin TRIVIAL 23537747 A 301 309 tricetin TRIVIAL 23537747 A 311 321 tangeretin TRIVIAL 23537747 A 327 336 nobiletin TRIVIAL 23537747 A 402 411 nobiletin TRIVIAL 23537747 A 628 637 nobiletin TRIVIAL 23537747 A 750 759 nobiletin TRIVIAL 23537747 A 897 906 nobiletin TRIVIAL 23537747 A 945 952 phospho SYSTEMATIC 23537747 A 962 969 phospho SYSTEMATIC 23537747 T 0 9 Nobiletin TRIVIAL 23537748 A 0 11 Methicillin TRIVIAL 23537748 A 1077 1080 CCM ABBREVIATION 23537748 A 1134 1137 CCM ABBREVIATION 23537748 A 1225 1228 CCM ABBREVIATION 23537748 A 1274 1283 oxacillin TRIVIAL 23537748 A 1285 1288 OXI ABBREVIATION 23537748 A 1291 1301 ampicillin TRIVIAL 23537748 A 1303 1306 AMP ABBREVIATION 23537748 A 1309 1322 ciprofloxacin TRIVIAL 23537748 A 1324 1327 CIP ABBREVIATION 23537748 A 1334 1345 norfloxacin TRIVIAL 23537748 A 1347 1350 NOR ABBREVIATION 23537748 A 1415 1418 CCM ABBREVIATION 23537748 A 1423 1426 OXI ABBREVIATION 23537748 A 1537 1540 CCM ABBREVIATION 23537748 A 1600 1603 OXI ABBREVIATION 23537748 A 1605 1608 AMP ABBREVIATION 23537748 A 1610 1613 CIP ABBREVIATION 23537748 A 1619 1622 NOR ABBREVIATION 23537748 A 1633 1636 CCM ABBREVIATION 23537748 A 505 513 Curcumin TRIVIAL 23537748 A 515 518 CCM ABBREVIATION 23537748 A 531 553 polyphenolic flavonoid FAMILY 23537748 A 746 754 curcumin TRIVIAL 23537748 A 825 828 CCM ABBREVIATION 23537748 A 890 893 CCM ABBREVIATION 23537748 T 36 44 curcumin TRIVIAL 23537748 T 53 64 methicillin TRIVIAL 23537942 A 168 190 thiazolidine-2,4-dione SYSTEMATIC 23537942 A 406 457 N-3-substituted-5-arylidene thiazolidine-2,4-diones FAMILY 23537942 A 471 491 α-bromoacryloylamido SYSTEMATIC 23537942 A 536 542 phenyl SYSTEMATIC 23537942 A 550 559 arylidene FAMILY 23537942 T 57 93 5-benzylidene thiazolidine-2,4-dione SYSTEMATIC 23538843 A 595 608 carbohydrates FAMILY 23538843 A 621 628 proline TRIVIAL 23538868 A 133 220 (3Z,6E)-1-N-methyl-3-benzylidene-6-(2R-methyl-3-hydroxypropylidene)piperazine-2,5-dione SYSTEMATIC 23538868 A 226 295 (3Z,6Z)-3- (4-hydroxybenzylidene)-6-isobutylidenepiperazine-2,5-dione SYSTEMATIC 23538868 A 301 377 (3Z,6Z)-3-((1H-imidazol-5-yl)-methylene)-6-isobutylidenepiperazine-2,5-dione SYSTEMATIC 23538868 A 387 444 (3Z,6S)-3-benzylidene-6-(2S-but-2-yl)piperazine-2,5-dione SYSTEMATIC 23538868 A 39 127 (3Z,6E)-1-N-methyl-3-benzy lidene-6-(2S-methyl-3-hydroxypropylidene)piperazine-2,5-dione SYSTEMATIC 23538868 A 9 25 diketopiperazine FAMILY 23538868 A 979 982 13C FORMULA 23538868 A 995 1047 (3Z,6S)-3-benzylidene-6-isobutylpiperazine-2,5-dione SYSTEMATIC 23538868 T 0 16 Diketopiperazine FAMILY 23538871 A 1010 1019 thiazolyl SYSTEMATIC 23538871 A 775 786 methicillin TRIVIAL 23538871 A 981 988 kocurin TRIVIAL 23538871 T 66 75 Thiazolyl SYSTEMATIC 23538871 T 95 102 Kocurin TRIVIAL 23539511 A 839 849 creatinine TRIVIAL 23539547 A 1336 1347 glutathione TRIVIAL 23539547 A 1348 1349 S FORMULA 23539547 A 1364 1365 N FORMULA 23539547 A 1391 1394 UDP ABBREVIATION 23539641 A 140 150 orvepitant TRIVIAL 23539641 A 152 160 GW823296 IDENTIFIER 23539641 A 401 416 [(11)C]GR205171 SYSTEMATIC 23539641 A 445 455 orvepitant TRIVIAL 23539641 A 658 668 orvepitant TRIVIAL 23539641 A 680 690 orvepitant TRIVIAL 23539641 T 98 108 orvepitant TRIVIAL 23540754 A 120 129 l-lactide SYSTEMATIC 23540754 A 407 416 l-lactide SYSTEMATIC 23540754 A 468 472 PLLA ABBREVIATION 23540754 A 48 63 poly(l-lactide) SYSTEMATIC 23540754 A 493 497 PLLA ABBREVIATION 23540754 A 65 69 PLLA ABBREVIATION 23540754 A 708 712 PLLA ABBREVIATION 23540754 A 733 737 PLLA ABBREVIATION 23540754 T 14 25 Polylactide SYSTEMATIC 23540754 T 50 61 Polylactide SYSTEMATIC 23541399 A 319 327 androgen FAMILY 23541399 A 41 53 testosterone TRIVIAL 23541399 A 589 597 androgen FAMILY 23541399 T 0 8 Androgen FAMILY 23541436 A 358 366 limonene TRIVIAL 23541436 A 380 391 γ-terpinene TRIVIAL 23541436 A 431 443 nitric oxide SYSTEMATIC 23541436 A 445 447 NO FORMULA 23541436 A 453 469 prostaglandin E2 TRIVIAL 23541436 A 471 475 PGE2 ABBREVIATION 23541436 A 528 540 nitric oxide SYSTEMATIC 23541637 A 0 11 Aldosterone TRIVIAL 23541637 A 1032 1037 Na(+) FORMULA 23541637 A 1038 1042 K(+) FORMULA 23541637 A 169 174 Na(+) FORMULA 23541637 A 175 179 K(+) FORMULA 23541637 A 197 208 Aldosterone TRIVIAL 23541637 A 22 27 Na(+) FORMULA 23541637 A 411 431 phosphatidylinositol TRIVIAL 23541637 A 700 707 ouabain TRIVIAL 23541637 A 756 761 Na(+) FORMULA 23541637 A 762 766 K(+) FORMULA 23541637 A 864 875 aldosterone TRIVIAL 23541637 A 935 946 aldosterone TRIVIAL 23541637 T 0 11 Aldosterone TRIVIAL 23541637 T 35 40 Na(+) FORMULA 23541637 T 41 45 K(+) FORMULA 23541637 T 87 107 phosphatidylinositol TRIVIAL 23541646 A 1055 1065 octylamide SYSTEMATIC 23541646 A 1169 1174 amide FAMILY 23541646 A 365 384 glycyrrhetinic acid TRIVIAL 23541646 A 646 649 MTT ABBREVIATION 23541646 A 765 777 benzyl amide SYSTEMATIC 23541646 A 873 876 MTT ABBREVIATION 23541646 T 0 19 Glycyrrhetinic acid TRIVIAL 23541670 A 107 132 5H-pyrrolo[2,3-b]pyrazine SYSTEMATIC 23541670 A 45 48 ATP ABBREVIATION 23541670 T 31 72 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers FAMILY 23541768 T 33 42 histidine TRIVIAL 23541949 A 0 25 RFamide-related peptide-3 SYSTEMATIC 23541949 A 179 185 RFRP-3 ABBREVIATION 23541949 A 239 245 RFRP-3 ABBREVIATION 23541949 A 27 33 RFRP-3 ABBREVIATION 23541949 A 467 473 RFRP-3 ABBREVIATION 23541949 A 545 551 RFRP-3 ABBREVIATION 23541949 A 567 574 steroid FAMILY 23541949 A 778 784 RFRP-3 ABBREVIATION 23541949 A 875 882 steroid FAMILY 23541949 T 15 21 RFRP-3 ABBREVIATION 23541950 A 311 341 dehydroepiandrosterone sulfate SYSTEMATIC 23541950 A 343 355 testosterone TRIVIAL 23541950 A 42 49 steroid FAMILY 23541950 A 520 527 steroid FAMILY 23541950 A 728 735 steroid FAMILY 23541950 T 45 52 steroid FAMILY 23542008 A 1070 1079 2'-fluoro SYSTEMATIC 23542008 A 1410 1418 hydrogen SYSTEMATIC 23542008 A 379 387 hydrogen SYSTEMATIC 23542008 A 403 414 2'-hydroxyl SYSTEMATIC 23542008 A 604 612 hydrogen SYSTEMATIC 23542008 A 825 834 2'-fluoro SYSTEMATIC 23542008 A 872 880 hydrogen SYSTEMATIC 23542039 A 137 148 Neutral Red TRIVIAL 23542039 A 491 499 glycerol TRIVIAL 23542039 A 651 662 polyphenols FAMILY 23542041 A 1214 1216 NO FORMULA 23542041 A 418 430 nitric oxide SYSTEMATIC 23542041 A 457 462 O2(-) FORMULA 23542041 A 844 846 NO FORMULA 23542041 A 865 870 O2(-) FORMULA 23542126 A 1126 1129 GSH ABBREVIATION 23542126 A 1156 1159 GSH ABBREVIATION 23542126 A 167 186 Thiobarbituric-acid TRIVIAL 23542126 A 244 253 carbonyls FAMILY 23542126 A 283 294 glutathione TRIVIAL 23542126 A 683 686 GSH ABBREVIATION 23542126 A 725 734 carbonyls FAMILY 23542126 A 953 962 carbonyls FAMILY 23542239 A 104 107 PEG ABBREVIATION 23542239 A 113 130 poly(amino acid)s FAMILY 23542239 A 484 494 iron oxide SYSTEMATIC 23542239 A 81 102 poly(ethylene glycol) SYSTEMATIC 23542440 A 0 9 Serotonin TRIVIAL 23542440 A 11 15 5-HT SYSTEMATIC 23542440 A 1256 1260 CORT ABBREVIATION 23542440 A 1345 1354 SB-656104 IDENTIFIER 23542440 A 1401 1405 CORT ABBREVIATION 23542440 A 1461 1470 SB-656104 IDENTIFIER 23542440 A 1539 1543 CORT ABBREVIATION 23542440 A 1817 1821 5-HT SYSTEMATIC 23542440 A 1826 1832 5-HIAA SYSTEMATIC 23542440 A 1889 1895 5-HIAA SYSTEMATIC 23542440 A 1896 1900 5-HT SYSTEMATIC 23542440 A 1946 1950 5-HT SYSTEMATIC 23542440 A 2229 2233 CORT ABBREVIATION 23542440 A 2367 2371 5-HT SYSTEMATIC 23542440 A 250 264 corticosterone TRIVIAL 23542440 A 266 270 CORT ABBREVIATION 23542440 A 317 326 SB-656104 IDENTIFIER 23542440 A 518 522 5-HT SYSTEMATIC 23542440 A 527 552 5-hydroxyindolacetic acid ABBREVIATION 23542440 A 554 560 5-HIAA SYSTEMATIC 23542440 A 567 573 5-HIAA SYSTEMATIC 23542440 A 574 578 5-HT SYSTEMATIC 23542440 A 607 611 5-HT SYSTEMATIC 23542440 A 635 639 5-HT SYSTEMATIC 23542440 A 654 664 tryptophan TRIVIAL 23542440 A 840 849 SB-656104 IDENTIFIER 23542440 T 35 49 corticosterone TRIVIAL 23542513 A 1007 1009 NO FORMULA 23542513 A 1035 1054 zinc protoporphyrin SYSTEMATIC 23542513 A 1056 1060 ZnPP FORMULA 23542513 A 1129 1134 5HHMF SYSTEMATIC 23542513 A 1150 1152 NO FORMULA 23542513 A 1174 1179 5HHMF SYSTEMATIC 23542513 A 1291 1296 5HHMF SYSTEMATIC 23542513 A 1305 1307 NO FORMULA 23542513 A 1415 1420 5HHMF SYSTEMATIC 23542513 A 1432 1434 NO FORMULA 23542513 A 160 162 NO FORMULA 23542513 A 217 219 NO FORMULA 23542513 A 267 272 5HHMF SYSTEMATIC 23542513 A 29 70 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone SYSTEMATIC 23542513 A 507 534 Pyrrolidine dithiocarbamate SYSTEMATIC 23542513 A 536 540 PDTC ABBREVIATION 23542513 A 698 703 5HHMF SYSTEMATIC 23542513 A 72 77 5HHMF SYSTEMATIC 23542513 A 785 790 5HHMF SYSTEMATIC 23542513 A 915 936 cobalt protoporphyrin SYSTEMATIC 23542513 A 938 942 CoPP FORMULA 23542513 T 0 41 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone SYSTEMATIC 23542513 T 51 63 nitric oxide SYSTEMATIC 23542608 A 0 6 Carbon SYSTEMATIC 23542608 A 333 339 carbon SYSTEMATIC 23542652 A 1128 1137 estrogens FAMILY 23542652 A 210 213 EE2 ABBREVIATION 23542652 A 24 45 17-α-ethinylestradiol SYSTEMATIC 23542652 A 369 372 EE2 ABBREVIATION 23542652 A 420 423 EE2 ABBREVIATION 23542652 A 47 50 EE2 ABBREVIATION 23542652 A 528 537 estradiol TRIVIAL 23542652 A 563 566 EE2 ABBREVIATION 23542652 A 619 622 EE2 ABBREVIATION 23542652 A 750 753 EE2 ABBREVIATION 23542652 T 15 36 17-α-ethinylestradiol SYSTEMATIC 23542652 T 38 41 EE2 ABBREVIATION 23543321 A 0 10 Polyamines FAMILY 23543321 A 1100 1109 polyamine FAMILY 23543321 A 1490 1500 polyamines FAMILY 23543321 A 176 196 S-adenosylmethionine TRIVIAL 23543321 A 243 252 polyamine FAMILY 23543321 T 38 58 S-adenosylmethionine TRIVIAL 23543413 A 0 9 Cisplatin TRIVIAL 23543413 A 1071 1079 platinum SYSTEMATIC 23543413 A 1099 1105 copper SYSTEMATIC 23543413 A 11 15 cDDP ABBREVIATION 23543413 A 1218 1226 platinum SYSTEMATIC 23543413 A 1560 1566 copper SYSTEMATIC 23543413 A 313 319 copper SYSTEMATIC 23543413 A 364 368 cDDP ABBREVIATION 23543413 A 763 767 cDDP ABBREVIATION 23543413 A 820 826 copper SYSTEMATIC 23543413 A 886 890 cDDP ABBREVIATION 23543413 A 958 960 Pt FORMULA 23543413 T 62 64 Cu FORMULA 23543413 T 80 82 Pt FORMULA 23543460 A 0 11 Radioiodide SYSTEMATIC 23543460 A 1194 1200 (131)I FORMULA 23543460 A 13 19 (131)I FORMULA 23543460 A 1429 1435 (131)I FORMULA 23543460 A 1569 1575 (131)I FORMULA 23543460 A 545 551 (131)I FORMULA 23543460 A 604 610 (131)I FORMULA 23543460 A 677 683 (131)I FORMULA 23543460 A 833 836 MTT ABBREVIATION 23543460 A 844 855 Radioiodide SYSTEMATIC 23543460 T 0 11 Radioiodide SYSTEMATIC 23544667 A 812 820 hydroxyl SYSTEMATIC 23544667 A 838 846 sulfates FAMILY 23544698 A 270 283 (NaNO3,1H2O)x FORMULA 23544698 A 528 541 (NaNO3,nH2O)3 FORMULA 23544698 A 74 79 NaNO3 SYSTEMATIC 23544698 A 88 102 (NaNO3, nH2O)x FORMULA 23544698 T 150 166 Hydrated Nitrate SYSTEMATIC 23545002 A 121 134 1,3-diketones FAMILY 23545002 A 35 40 steel TRIVIAL 23545002 A 407 420 1,3-diketones FAMILY 23545002 A 480 484 iron SYSTEMATIC 23545002 A 485 491 diketo SYSTEMATIC 23545002 A 565 575 1,3 diketo SYSTEMATIC 23545002 A 871 875 iron SYSTEMATIC 23545002 T 90 95 steel TRIVIAL 23545108 A 22 32 nucleoside FAMILY 23545108 T 35 45 nucleoside FAMILY 23545161 A 0 13 Acetaminophen TRIVIAL 23545161 A 1283 1299 prostaglandin E2 TRIVIAL 23545161 A 1318 1331 acetaminophen TRIVIAL 23545161 A 1370 1383 acetaminophen TRIVIAL 23545161 A 1396 1403 aspirin TRIVIAL 23545161 A 1566 1582 prostaglandin E2 TRIVIAL 23545161 A 171 184 acetaminophen TRIVIAL 23545161 A 346 359 prostaglandin FAMILY 23545161 A 722 737 prostaglandin E FAMILY 23545161 A 857 870 acetaminophen TRIVIAL 23545161 A 979 992 acetaminophen TRIVIAL 23545161 T 0 13 Acetaminophen TRIVIAL 23545348 A 892 895 ACh ABBREVIATION 23545348 A 913 916 KCl FORMULA 23545348 A 977 990 acetylcholine SYSTEMATIC 23545458 T 6 14 saponins FAMILY 23545806 A 1090 1099 methylone TRIVIAL 23545806 A 1132 1141 methylone TRIVIAL 23545806 A 263 272 methylone TRIVIAL 23545806 A 362 371 methylone TRIVIAL 23545806 A 37 46 methylone TRIVIAL 23545806 A 471 493 dihydroxymethcathinone SYSTEMATIC 23545806 A 48 75 methylenedioxymethcathinone SYSTEMATIC 23545806 A 526 545 N-hydroxy-methylone SYSTEMATIC 23545806 A 566 583 dihydro-methylone SYSTEMATIC 23545806 T 44 53 Methylone TRIVIAL 23545999 A 139 213 7-(2,3-dihydroxy-3-methylbutoxy)-3,5-dimethoxy-3',4'-methylenedioxyflavone SYSTEMATIC 23545999 A 21 76 5,8-dihydroxy-3,7-dimethoxy-3',4'-methylenedioxyflavone SYSTEMATIC 23545999 A 219 281 7-(2,3-dihydroxy-3-methylbutoxy)-3,3',4',5-tetramethoxyflavone SYSTEMATIC 23545999 A 291 355 7-(2,3-dihydroxy-3-methylbutoxy)-3,3',4',5,8-pentamethoxyflavone SYSTEMATIC 23545999 A 437 447 flavonoids FAMILY 23545999 A 463 505 3,4',5-trihydroxy-3',7,8-trimethoxyflavone SYSTEMATIC 23545999 A 511 562 5,7-dihydroxy-3-methoxy-3',4'-methylenedioxyflavone SYSTEMATIC 23545999 A 568 607 4',5,7-trihydroxy-3,3'-dimethoxyflavone SYSTEMATIC 23545999 A 613 656 4',7-dihydroxy-3,3',5,8-tetramethoxyflavone SYSTEMATIC 23545999 A 662 701 4',7-dihydroxy-3,3',5-trimethoxyflavone SYSTEMATIC 23545999 A 712 754 4',5,7-trihydroxy-3,3',8-trimethoxyflavone SYSTEMATIC 23545999 A 82 133 7-hydroxy-3,5-dimethoxy-3',4'-methylenedioxyflavone SYSTEMATIC 23545999 A 9 19 flavonoids FAMILY 23545999 T 22 32 Flavonoids FAMILY 23546003 A 0 11 Quinoxaline SYSTEMATIC 23546003 A 31 48 bis(fluoromethyl) SYSTEMATIC 23546003 A 422 433 quinoxaline SYSTEMATIC 23546003 A 488 498 halomethyl FAMILY 23546003 A 50 67 bis(chloromethyl) SYSTEMATIC 23546003 A 72 87 bis(iodomethyl) SYSTEMATIC 23546003 T 13 43 2,3-Bis(halomethyl)quinoxaline FAMILY 23546004 A 131 137 aldose FAMILY 23546004 A 187 204 acylated sucroses FAMILY 23546004 A 206 218 mumeoses F-J MULTIPLE 23546004 A 436 442 aldose FAMILY 23546004 A 477 497 Acylated quinic acid FAMILY 23546004 A 611 617 aldose FAMILY 23546004 A 644 657 mumeic acid-A TRIVIAL 23546004 T 42 59 Acylated Sucroses FAMILY 23546395 A 1085 1096 gallic acid TRIVIAL 23546395 A 1101 1116 (-)-epicatechin SYSTEMATIC 23546395 A 568 584 cyclophosphamide TRIVIAL 23546395 A 934 953 Thiobarbituric acid TRIVIAL 23546525 A 0 14 Azidoacetylene SYSTEMATIC 23546525 A 238 252 azidoacetylene SYSTEMATIC 23546525 T 0 14 Azidoacetylene SYSTEMATIC 23546600 A 1379 1387 androgen FAMILY 23546600 A 1634 1642 androgen FAMILY 23546600 A 256 264 androgen FAMILY 23546600 A 440 448 androgen FAMILY 23546600 T 115 123 androgen FAMILY 23546601 A 1017 1026 tamoxifen TRIVIAL 23546601 A 1074 1083 tamoxifen TRIVIAL 23546601 A 1111 1120 tamoxifen TRIVIAL 23546601 A 1317 1325 estrogen FAMILY 23546601 A 1509 1518 tamoxifen TRIVIAL 23546601 A 1595 1604 tamoxifen TRIVIAL 23546601 A 176 185 tamoxifen TRIVIAL 23546601 A 22 31 tamoxifen TRIVIAL 23546601 A 231 240 tamoxifen TRIVIAL 23546601 A 427 436 tamoxifen TRIVIAL 23546601 A 577 586 tamoxifen TRIVIAL 23546601 A 672 681 tamoxifen TRIVIAL 23546601 A 708 717 tamoxifen TRIVIAL 23546601 A 754 763 tamoxifen TRIVIAL 23546601 A 981 990 tamoxifen TRIVIAL 23546601 T 0 8 Estrogen FAMILY 23546601 T 52 61 Tamoxifen TRIVIAL 23546601 T 77 85 Estrogen FAMILY 23546605 A 1174 1186 progesterone TRIVIAL 23546605 A 1358 1371 estradiol-17β SYSTEMATIC 23546605 A 513 521 estrogen FAMILY 23546867 A 673 679 oxygen SYSTEMATIC 23546879 A 1107 1108 O FORMULA 23546879 A 1159 1165 GalNAc FORMULA 23546879 A 1180 1186 GalNAc FORMULA 23546879 A 1262 1268 GalNAc FORMULA 23546879 A 1392 1398 GalNAc FORMULA 23546879 A 1449 1450 C FORMULA 23546879 A 1472 1481 threonine TRIVIAL 23546879 A 1761 1762 O FORMULA 23546879 A 568 569 O FORMULA 23546879 A 633 641 cysteine TRIVIAL 23546879 A 647 648 N FORMULA 23546879 A 654 655 C FORMULA 23546879 A 868 869 N FORMULA 23546879 T 107 115 cysteine TRIVIAL 23546879 T 14 15 O FORMULA 23547584 A 142 151 hβ(3) Phe SYSTEMATIC 23547584 A 164 167 Phe FORMULA 23547584 A 47 55 Biphalin TRIVIAL 23547584 A 91 112 homo-β(3) amino acids FAMILY 23547584 T 50 58 Biphalin TRIVIAL 23547652 A 212 227 hydroxamic acid SYSTEMATIC 23547652 A 337 362 3-hydroxypyridin-2-thione SYSTEMATIC 23547652 A 364 369 3-HPT SYSTEMATIC 23547652 A 427 432 3-HPT SYSTEMATIC 23547652 A 47 51 zinc SYSTEMATIC 23547652 A 519 524 3-HPT SYSTEMATIC 23547652 A 601 605 3HPT SYSTEMATIC 23547652 T 0 25 3-Hydroxypyridin-2-thione SYSTEMATIC 23547652 T 35 39 Zinc SYSTEMATIC 23547706 A 123 130 PI-1833 IDENTIFIER 23547706 A 401 408 PI-1840 IDENTIFIER 23547706 A 482 487 amide FAMILY 23547706 A 505 511 phenyl SYSTEMATIC 23547706 A 584 590 propyl SYSTEMATIC 23547706 A 594 599 butyl SYSTEMATIC 23547706 A 662 674 meta-pyridyl SYSTEMATIC 23547706 A 94 119 oxadiazole-isopropylamide FAMILY 23547706 T 0 26 Oxadiazole-isopropylamides FAMILY 23547757 A 20 32 belactosin A TRIVIAL 23547757 A 44 62 trans-cyclopropane SYSTEMATIC 23547757 A 464 480 cis-cyclopropane SYSTEMATIC 23547757 A 938 947 threonine TRIVIAL 23547757 A 964 973 β-lactone SYSTEMATIC 23547757 T 56 72 Cis-Cyclopropane SYSTEMATIC 23547757 T 83 95 Belactosin A TRIVIAL 23547776 A 483 493 LDN-212854 IDENTIFIER 23547776 A 689 699 LDN-212854 IDENTIFIER 23547776 A 898 908 LDN-212854 IDENTIFIER 23547786 A 100 103 PGS ABBREVIATION 23547786 A 131 168 dodecyl triphenyl phosphonium bromide SYSTEMATIC 23547786 A 170 173 DTP ABBREVIATION 23547786 A 182 185 DTP ABBREVIATION 23547786 A 186 189 PGS ABBREVIATION 23547786 A 350 353 DTP ABBREVIATION 23547786 A 390 393 PGS ABBREVIATION 23547786 A 438 441 DTP ABBREVIATION 23547786 A 442 445 PGS ABBREVIATION 23547786 A 45 72 quaternary phosphonium salt FAMILY 23547786 A 482 485 PGS ABBREVIATION 23547786 A 490 493 DTP ABBREVIATION 23547786 A 638 641 PGS ABBREVIATION 23547786 A 86 98 palygorskite TRIVIAL 23547786 T 18 30 palygorskite TRIVIAL 23547786 T 46 73 quaternary phosphonium salt FAMILY 23548149 A 1117 1120 Ser FORMULA 23548149 A 113 123 Fru-2,6-P2 SYSTEMATIC 23548149 A 125 150 fructose-2,6-bisphosphate SYSTEMATIC 23548149 A 1350 1360 Fru-2,6-P2 SYSTEMATIC 23548149 A 275 287 carbohydrate FAMILY 23548149 A 509 513 NaCl FORMULA 23548149 A 515 519 H2O2 FORMULA 23548149 A 538 548 anisomycin TRIVIAL 23548896 A 298 313 phosphotyrosine SYSTEMATIC 23548896 A 332 343 amino acids FAMILY 23548896 A 460 461 C FORMULA 23548896 A 63 71 tyrosine TRIVIAL 23548896 A 693 708 phosphotyrosine SYSTEMATIC 23548896 T 84 85 C FORMULA 23548974 A 1038 1045 mercury SYSTEMATIC 23548974 A 1138 1145 mercury SYSTEMATIC 23548974 A 1338 1345 mercury SYSTEMATIC 23548974 A 1466 1479 methylmercury SYSTEMATIC 23548974 A 1664 1668 PUFA ABBREVIATION 23548974 A 21 34 methylmercury SYSTEMATIC 23548974 A 319 332 methylmercury SYSTEMATIC 23548974 A 428 441 methylmercury SYSTEMATIC 23548974 A 740 747 mercury SYSTEMATIC 23548974 A 935 962 polyunsaturated fatty acids FAMILY 23548974 A 964 969 PUFAs ABBREVIATION 23548974 T 59 72 methylmercury SYSTEMATIC 23549285 A 775 787 Spongiatriol TRIVIAL 23549285 A 798 815 furanoditerpenoid FAMILY 23549285 T 0 12 Spongiatriol TRIVIAL 23549672 A 623 641 11β-hydroxysteroid FAMILY 23549672 A 712 721 cortisone TRIVIAL 23549672 A 745 753 cortisol TRIVIAL 23549672 A 788 796 cortisol TRIVIAL 23549673 A 119 131 testosterone TRIVIAL 23549673 A 203 211 androgen FAMILY 23549673 A 351 374 testosterone propionate SYSTEMATIC 23549673 A 51 60 androgens FAMILY 23550066 A 0 8 Ketamine TRIVIAL 23550066 A 1262 1270 ThioTEPA SYSTEMATIC 23550066 A 1348 1362 troleandomycin TRIVIAL 23550066 A 1441 1449 ketamine TRIVIAL 23550066 A 1658 1666 ketamine TRIVIAL 23550066 A 1750 1758 ketamine TRIVIAL 23550066 A 324 332 ketamine TRIVIAL 23550066 A 37 48 norketamine TRIVIAL 23550066 A 391 399 ketamine TRIVIAL 23550066 A 658 669 norketamine TRIVIAL 23550066 A 958 966 ketamine TRIVIAL 23550066 T 64 72 Ketamine TRIVIAL 23550656 A 0 3 CO2 FORMULA 23550656 A 1057 1058 H FORMULA 23550656 A 1061 1064 CO2 FORMULA 23550656 A 1151 1154 CO2 FORMULA 23550656 A 130 133 CO2 FORMULA 23550656 A 1314 1317 CO2 FORMULA 23550656 A 1446 1449 HCO FORMULA 23550656 A 1513 1515 CO FORMULA 23550656 A 1525 1526 H FORMULA 23550656 A 1563 1566 H2O FORMULA 23550656 A 1612 1613 H FORMULA 23550656 A 1643 1646 H2O FORMULA 23550656 A 1670 1672 CO FORMULA 23550656 A 1705 1708 HCO FORMULA 23550656 A 247 249 CO FORMULA 23550656 A 250 253 H2O FORMULA 23550656 A 344 346 CO FORMULA 23550656 A 354 356 OH FORMULA 23550656 A 381 384 H2O FORMULA 23550656 A 463 466 CO2 FORMULA 23550656 A 666 670 HOCO FORMULA 23550656 A 705 708 CO2 FORMULA 23550656 A 785 787 CO FORMULA 23550656 A 823 826 CO2 FORMULA 23550656 A 832 834 CO FORMULA 23550656 A 87 90 H2O FORMULA 23550656 A 878 882 HOCO FORMULA 23550656 A 938 948 trans-HOCO SYSTEMATIC 23550656 A 95 97 CO FORMULA 23550656 T 34 37 CO2 FORMULA 23550722 A 119 122 NO2 FORMULA 23550722 A 166 183 C6F13CH2C(O)OONO2 FORMULA 23550722 A 17 36 CxF2x+1CH2C(O)OONO2 FAMILY 23550722 A 367 382 CF3CH2C(O)OONO2 FORMULA 23550722 A 539 559 peroxy acyl nitrates FAMILY 23550722 A 74 89 CxF2x+1CH2C(O)H FAMILY 23550722 T 114 117 NO2 FORMULA 23550722 T 21 41 Peroxy Acyl Nitrates FAMILY 23550722 T 69 84 CxF2x+1CH2C(O)H FAMILY 23551856 A 1343 1355 Pioglitazone TRIVIAL 23551856 A 140 147 glucose TRIVIAL 23551856 A 161 173 pioglitazone TRIVIAL 23551856 A 175 178 TZD ABBREVIATION 23551856 A 41 53 pioglitazone TRIVIAL 23551856 A 631 643 pioglitazone TRIVIAL 23551856 A 743 755 pioglitazone TRIVIAL 23551856 A 856 868 pioglitazone TRIVIAL 23551856 T 10 22 pioglitazone TRIVIAL 23552101 A 1004 1041 phosphatidylinositol-4,5-bisphosphate SYSTEMATIC 23552101 A 1043 1052 PI(4,5)P2 FORMULA 23552101 A 1136 1145 PI(4,5)P2 FORMULA 23552101 A 157 164 glucose TRIVIAL 23552101 A 807 839 phosphatidylinositol 4-phosphate SYSTEMATIC 23552101 A 950 982 phosphatidylinositol 4-phosphate SYSTEMATIC 23552101 A 984 990 PI(4)P FORMULA 23552264 A 14 20 carbon SYSTEMATIC 23552264 T 65 71 carbon SYSTEMATIC 23552268 A 0 7 Carvone TRIVIAL 23552268 A 1204 1207 CVN ABBREVIATION 23552268 A 1209 1269 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide SYSTEMATIC 23552268 A 1288 1291 CVN ABBREVIATION 23552268 A 1445 1448 CVN ABBREVIATION 23552268 A 19 41 monocyclic monoterpene FAMILY 23552268 A 285 288 CVN ABBREVIATION 23552268 A 432 435 CVN ABBREVIATION 23552268 A 598 601 CVN ABBREVIATION 23552268 A 687 690 CVN ABBREVIATION 23552268 A 851 854 CVN ABBREVIATION 23552268 A 9 12 CVN ABBREVIATION 23552268 T 33 40 carvone TRIVIAL 23552398 A 1286 1292 oxygen SYSTEMATIC 23552398 A 1398 1401 C-O FORMULA 23552398 A 151 159 hydrogen SYSTEMATIC 23552398 A 333 336 CO2 FORMULA 23552398 A 340 347 Pt(111) FORMULA 23552398 A 373 376 CO2 FORMULA 23552398 A 398 402 COOH FORMULA 23552398 A 405 407 CO FORMULA 23552398 A 410 413 H2O FORMULA 23552398 A 416 419 COH FORMULA 23552398 A 438 439 C FORMULA 23552398 A 442 445 H2O FORMULA 23552398 A 562 564 CO FORMULA 23552398 A 569 572 COH FORMULA 23552398 A 674 677 C-O FORMULA 23552398 A 77 80 CO2 FORMULA 23552398 A 84 91 Pt(111) FORMULA 23552398 T 26 33 Pt(111) FORMULA 23552398 T 9 12 CO2 FORMULA 23552482 A 1298 1300 RX FAMILY 23552482 A 1640 1651 cyclohexane SYSTEMATIC 23552482 A 1707 1712 ether SYSTEMATIC 23552482 A 1725 1731 phenol SYSTEMATIC 23552482 A 1733 1751 allyl phenyl ether SYSTEMATIC 23552482 A 1779 1781 RO FAMILY 23552482 A 1782 1787 allyl SYSTEMATIC 23552482 A 306 316 thiophenol SYSTEMATIC 23552482 A 318 336 p-methylthiophenol SYSTEMATIC 23552482 A 341 352 thioanisole SYSTEMATIC 23552482 A 354 373 p-methylthioanisole SYSTEMATIC 23552482 A 379 385 phenol SYSTEMATIC 23552482 A 404 415 cyclohexane SYSTEMATIC 23552482 A 468 472 RX-Y FAMILY 23552482 A 478 479 O FORMULA 23552482 A 481 482 S FORMULA 23552482 A 488 489 H FORMULA 23552482 A 491 494 CH3 FORMULA 23552482 A 971 982 cyclohexane SYSTEMATIC 23552830 A 849 859 amino acid FAMILY 23552843 A 262 268 silica TRIVIAL 23552843 A 346 352 silica TRIVIAL 23552843 A 372 381 disulfide SYSTEMATIC 23552843 A 400 439 poly(2-dimethylaminoethyl methacrylate) SYSTEMATIC 23552843 A 441 448 PDMAEMA ABBREVIATION 23552843 A 856 865 disulfide SYSTEMATIC 23552843 A 890 897 PDMAEMA ABBREVIATION 23552843 A 940 947 PDMAEMA ABBREVIATION 23552843 T 24 63 poly(2-dimethylaminoethyl methacrylate) SYSTEMATIC 23552843 T 90 96 silica TRIVIAL 23552852 A 1011 1022 flusilazole TRIVIAL 23552852 A 1141 1152 fluconazole TRIVIAL 23552852 A 233 239 azoles FAMILY 23552852 A 26 31 azole FAMILY 23552852 A 653 664 triadimefon TRIVIAL 23552852 A 669 677 imazalil TRIVIAL 23552852 A 688 699 triadimefon TRIVIAL 23552852 A 701 709 imazalil TRIVIAL 23552852 A 735 746 fluconazole TRIVIAL 23552852 A 942 953 triadimefon TRIVIAL 23552852 A 955 963 imazalil TRIVIAL 23552852 A 965 976 triadimenol TRIVIAL 23552852 A 978 991 cyproconazole TRIVIAL 23552852 A 993 1005 tebuconazole TRIVIAL 23552852 T 23 28 azole FAMILY 23552899 A 172 175 ZnO FORMULA 23552899 A 189 197 graphene TRIVIAL 23552899 A 353 361 graphene TRIVIAL 23552899 A 66 77 metal oxide FAMILY 23552899 A 91 99 graphene TRIVIAL 23552899 T 66 69 ZnO FORMULA 23552899 T 83 91 graphene TRIVIAL 23552908 A 136 139 DFA ABBREVIATION 23552908 A 177 184 benzene SYSTEMATIC 23552908 A 200 207 benzene SYSTEMATIC 23552908 A 333 342 acetylene SYSTEMATIC 23552908 A 378 388 ferrocenes FAMILY 23552908 A 40 61 diferrocenylacetylene SYSTEMATIC 23552908 A 593 596 DFA ABBREVIATION 23552908 A 63 66 DFA ABBREVIATION 23552908 A 804 807 DFA ABBREVIATION 23552908 A 84 91 benzene SYSTEMATIC 23552908 A 923 932 ferrocene TRIVIAL 23552908 A 95 102 Au(111) FORMULA 23552908 A 972 988 cyclopentadienyl SYSTEMATIC 23552908 T 14 35 diferrocenylacetylene SYSTEMATIC 23552908 T 39 46 Au(111) FORMULA 23553560 A 0 8 Axitinib TRIVIAL 23553560 A 1249 1257 axitinib TRIVIAL 23553560 A 1326 1334 axitinib TRIVIAL 23553560 A 180 188 Axitinib TRIVIAL 23553560 A 474 482 axitinib TRIVIAL 23553560 T 0 8 Axitinib TRIVIAL 23553595 A 437 459 fluticasone propionate SYSTEMATIC 23553595 A 504 510 Diskus TRIVIAL 23553595 A 819 825 Diskus TRIVIAL 23553632 A 458 464 biotin TRIVIAL 23553632 A 735 741 biotin TRIVIAL 23553632 A 815 816 N FORMULA 23553632 A 822 823 C FORMULA 23553655 A 1003 1012 nilotinib TRIVIAL 23553655 A 1014 1023 dasatinib TRIVIAL 23553655 A 1029 1038 bosutinib TRIVIAL 23553655 A 1322 1330 imatinib TRIVIAL 23553655 A 1332 1341 nilotinib TRIVIAL 23553655 A 1343 1352 dasatinib TRIVIAL 23553655 A 1358 1367 bosutinib TRIVIAL 23553655 A 153 161 imatinib TRIVIAL 23553655 A 163 172 nilotinib TRIVIAL 23553655 A 174 183 dasatinib TRIVIAL 23553655 A 189 198 bosutinib TRIVIAL 23553655 A 42 50 tyrosine TRIVIAL 23553655 A 993 1001 imatinib TRIVIAL 23553655 T 91 99 Tyrosine TRIVIAL 23553677 A 183 189 silver SYSTEMATIC 23553677 A 360 366 silver SYSTEMATIC 23553677 T 116 122 Silver SYSTEMATIC 23553679 A 1424 1434 gabapentin TRIVIAL 23553679 A 437 447 gabapentin TRIVIAL 23553679 A 503 513 gabapentin TRIVIAL 23553679 A 676 686 gabapentin TRIVIAL 23553679 A 811 821 gabapentin TRIVIAL 23553679 T 83 93 Gabapentin TRIVIAL 23553708 A 1127 1137 sildenafil TRIVIAL 23553708 A 1267 1277 sildenafil TRIVIAL 23553708 A 162 172 sildenafil TRIVIAL 23553708 A 43 53 sildenafil TRIVIAL 23553708 A 553 563 sildenafil TRIVIAL 23553708 A 633 643 sildenafil TRIVIAL 23553708 A 818 828 sildenafil TRIVIAL 23553708 A 979 989 sildenafil TRIVIAL 23553708 T 10 20 Sildenafil TRIVIAL 23553811 A 1163 1170 alcohol FAMILY 23553811 A 1354 1362 warfarin TRIVIAL 23553811 A 1405 1416 clopidogrel TRIVIAL 23553811 A 1422 1429 aspirin TRIVIAL 23553811 A 1485 1495 dabigatran TRIVIAL 23553811 A 1497 1508 rivaroxaban TRIVIAL 23553811 A 1514 1522 apixaban TRIVIAL 23553811 A 1524 1535 Vernakalant TRIVIAL 23553811 A 1666 1677 dronedarone TRIVIAL 23553811 A 1852 1863 aldosterone TRIVIAL 23553811 A 1872 1879 statins FAMILY 23553811 A 1885 1912 polyunsaturated fatty acids FAMILY 23553905 A 761 773 Alizarin red TRIVIAL 23553905 A 801 812 Alcian blue TRIVIAL 23553961 A 10 12 CO FORMULA 23553961 A 102 104 Pt FORMULA 23553961 A 297 299 Pt FORMULA 23553961 A 322 323 O FORMULA 23553961 A 353 359 oxides FAMILY 23553961 A 86 88 CO FORMULA 23553961 T 17 19 CO FORMULA 23553961 T 48 50 Pt FORMULA 23554029 A 797 812 malondialdehyde TRIVIAL 23554029 A 852 862 superoxide TRIVIAL 23554029 A 877 888 glutathione TRIVIAL 23554215 A 150 161 fluoroximes FAMILY 23554215 A 358 366 fluorine SYSTEMATIC 23554215 A 371 379 nitrogen SYSTEMATIC 23554215 T 76 87 fluoroximes FAMILY 23554335 A 1127 1145 2,4-dinitroaniline SYSTEMATIC 23554335 A 1324 1341 2,4-dinitrophenyl SYSTEMATIC 23554335 A 306 319 dodecanethiol SYSTEMATIC 23554335 A 323 325 Pt FORMULA 23554335 A 47 64 2,4-dinitrophenyl SYSTEMATIC 23554335 A 518 520 CH FORMULA 23554335 A 618 636 2,4-dinitroaniline SYSTEMATIC 23554335 A 692 694 CH FORMULA 23554335 T 51 68 2,4-dinitrophenyl SYSTEMATIC 23556445 A 250 261 hydroxyurea SYSTEMATIC 23556445 T 91 102 hydroxyurea SYSTEMATIC 23556446 T 15 18 ATP ABBREVIATION 23556448 A 1225 1240 methamphetamine TRIVIAL 23556448 A 1408 1423 methamphetamine TRIVIAL 23556448 A 1552 1567 methamphetamine TRIVIAL 23556448 A 360 375 methamphetamine TRIVIAL 23556448 A 388 403 methamphetamine TRIVIAL 23556448 A 549 564 methamphetamine TRIVIAL 23556448 A 989 1004 methamphetamine TRIVIAL 23556448 T 51 66 methamphetamine TRIVIAL 23557487 A 1040 1051 nitric acid SYSTEMATIC 23557487 A 1066 1068 OH FORMULA 23557487 A 1094 1097 NO2 FORMULA 23557487 A 1774 1785 nitric acid SYSTEMATIC 23557487 A 373 384 nitric acid SYSTEMATIC 23557487 A 57 68 nitric acid SYSTEMATIC 23557487 A 70 74 HNO3 FORMULA 23557487 T 39 43 HNO3 FORMULA 23557931 A 100 103 MPA ABBREVIATION 23557931 A 1041 1044 MPA ABBREVIATION 23557931 A 1046 1049 MPA ABBREVIATION 23557931 A 1464 1467 MPA ABBREVIATION 23557931 A 197 200 MPA ABBREVIATION 23557931 A 447 450 MPA ABBREVIATION 23557931 A 535 538 MPA ABBREVIATION 23557931 A 81 98 mycophenolic acid TRIVIAL 23557931 A 924 936 cyclosporine TRIVIAL 23557931 A 940 950 tacrolimus TRIVIAL 23557931 T 35 52 mycophenolic acid TRIVIAL 23557933 A 1395 1398 RES ABBREVIATION 23557933 A 1621 1624 RES ABBREVIATION 23557933 A 1744 1747 RES ABBREVIATION 23557933 A 234 237 RES ABBREVIATION 23557933 A 33 44 resveratrol TRIVIAL 23557933 A 431 434 RES ABBREVIATION 23557933 A 46 49 RES ABBREVIATION 23557933 A 468 471 RES ABBREVIATION 23557933 A 705 708 RES ABBREVIATION 23557933 A 751 754 RES ABBREVIATION 23557933 A 916 919 RES ABBREVIATION 23557933 A 964 971 glucose TRIVIAL 23557933 T 57 68 resveratrol TRIVIAL 23558233 A 105 109 MPTP ABBREVIATION 23558233 A 1209 1213 MPTP ABBREVIATION 23558233 A 251 255 MPTP ABBREVIATION 23558233 A 358 366 dopamine TRIVIAL 23558233 A 393 398 DOPAC ABBREVIATION 23558233 A 403 406 HVA ABBREVIATION 23558233 A 412 421 serotonin TRIVIAL 23558233 A 442 449 5-HIAAA ABBREVIATION 23558233 A 505 510 DOPAC ABBREVIATION 23558233 A 518 521 HVA ABBREVIATION 23558233 A 542 550 tyrosine TRIVIAL 23558233 A 612 616 iron SYSTEMATIC 23558233 A 666 674 dopamine TRIVIAL 23558233 A 774 778 MPTP ABBREVIATION 23558233 A 780 789 Serotonin TRIVIAL 23558233 A 884 888 MPTP ABBREVIATION 23558233 A 898 903 DOPAC ABBREVIATION 23558233 A 905 908 HVA ABBREVIATION 23558233 T 41 45 MPTP ABBREVIATION 23558236 A 257 260 MTT ABBREVIATION 23558236 A 37 50 rotundic acid TRIVIAL 23558236 T 62 75 rotundic acid TRIVIAL 23558446 A 69 77 tyrosine TRIVIAL 23558646 A 201 209 melamine TRIVIAL 23558646 A 214 237 N(3)-alkylated xanthine FAMILY 23558646 T 117 125 melamine TRIVIAL 23558646 T 126 134 xanthine TRIVIAL 23558646 T 15 16 H FORMULA 23558682 A 1055 1063 arginine TRIVIAL 23558682 A 1243 1251 carbonyl FAMILY 23558682 A 1292 1300 hydrogen SYSTEMATIC 23558682 A 1328 1337 histidine TRIVIAL 23558682 A 1380 1388 cysteine TRIVIAL 23558682 A 267 275 cysteine TRIVIAL 23558682 A 607 608 N FORMULA 23558682 A 683 691 cysteine TRIVIAL 23558682 A 772 777 sugar FAMILY 23558682 T 96 104 cysteine TRIVIAL 23558686 A 562 563 C FORMULA 23558747 A 11 17 methyl SYSTEMATIC 23558747 A 164 170 methyl SYSTEMATIC 23558747 A 634 635 N FORMULA 23558747 T 73 79 methyl SYSTEMATIC 23559221 A 1096 1103 glucose TRIVIAL 23559221 A 1193 1200 glucose TRIVIAL 23559221 A 1233 1240 glucose TRIVIAL 23559221 A 1373 1380 glucose TRIVIAL 23559221 A 140 147 glucose TRIVIAL 23559221 A 1481 1488 glucose TRIVIAL 23559221 A 1531 1538 glucose TRIVIAL 23559221 A 1657 1664 glucose TRIVIAL 23559221 A 238 245 glucose TRIVIAL 23559221 A 495 502 glucose TRIVIAL 23559221 A 56 63 glucose TRIVIAL 23559221 A 583 590 glucose TRIVIAL 23559221 A 617 624 glucose TRIVIAL 23559221 A 920 927 glucose TRIVIAL 23559221 T 0 7 Glucose TRIVIAL 23559436 A 161 173 hydrocarbons FAMILY 23559436 A 193 199 oxygen SYSTEMATIC 23559436 A 26 34 peroxide SYSTEMATIC 23559436 A 462 476 alkyl peroxide FAMILY 23559436 A 515 516 H FORMULA 23559436 A 531 559 (di)unsaturated hydrocarbons FAMILY 23559436 T 17 25 Peroxide SYSTEMATIC 23560557 A 1481 1494 catecholamine TRIVIAL 23560844 A 1031 1038 phospho SYSTEMATIC 23560844 A 1098 1105 phospho SYSTEMATIC 23560844 A 1245 1258 pThr-Glu-pTyr FORMULA 23560844 A 1281 1284 Lys FORMULA 23560844 A 1292 1295 Arg FORMULA 23560844 A 1374 1377 Gln FORMULA 23560844 A 1385 1388 Arg FORMULA 23560844 A 1466 1469 Arg FORMULA 23560844 A 1486 1489 Glu FORMULA 23560844 A 1508 1515 phospho SYSTEMATIC 23560844 A 1553 1560 phospho SYSTEMATIC 23560844 A 428 431 Thr FORMULA 23560844 A 439 442 Tyr FORMULA 23560989 A 0 21 Poly(ethylene glycol) SYSTEMATIC 23560989 A 217 252 2-(dimethylamino)ethyl methacrylate SYSTEMATIC 23560989 A 23 26 PEG ABBREVIATION 23560989 A 254 260 DMAEMA ABBREVIATION 23560989 A 266 296 ethylene glycol dimethacrylate SYSTEMATIC 23560989 A 298 303 EGDMA ABBREVIATION 23561072 A 128 131 DNJ ABBREVIATION 23561072 A 193 196 DNJ ABBREVIATION 23561072 A 286 289 DNJ ABBREVIATION 23561072 A 42 60 1-deoxynojirimycin SYSTEMATIC 23561072 A 452 455 DNJ ABBREVIATION 23561072 A 552 567 triacylglycerol FAMILY 23561072 A 62 65 DNJ ABBREVIATION 23561072 A 759 762 DNJ ABBREVIATION 23561072 A 797 800 DNJ ABBREVIATION 23561072 A 909 912 DNJ ABBREVIATION 23561075 A 0 16 Proanthocyanidin FAMILY 23561075 A 293 301 Catechin TRIVIAL 23561075 A 306 321 (epi)afzelechin TRIVIAL 23561075 A 337 348 flavan-3-ol FAMILY 23561075 A 563 575 flavan-3-ols FAMILY 23561075 A 630 652 catechin-7-O-glucoside SYSTEMATIC 23561075 T 0 16 Proanthocyanidin FAMILY 23561075 T 63 83 catechin-O-glucoside SYSTEMATIC 23561076 A 437 448 anthocyanin FAMILY 23561076 A 44 55 anthocyanin FAMILY 23561076 A 478 489 anthocyanin FAMILY 23561076 A 665 676 anthocyanin FAMILY 23561076 A 719 730 anthocyanin FAMILY 23561076 T 64 76 anthocyanins FAMILY 23561079 A 316 324 nitrogen SYSTEMATIC 23561079 A 466 474 nitrogen SYSTEMATIC 23561089 A 22 30 phenolic FAMILY 23561089 A 306 318 polyphenolic FAMILY 23561089 A 394 402 methanol SYSTEMATIC 23561089 A 404 411 ethanol SYSTEMATIC 23561089 A 549 557 methanol SYSTEMATIC 23561089 A 597 608 Gallic acid TRIVIAL 23561089 A 860 866 trolox TRIVIAL 23561091 A 10 22 eriocaulin A TRIVIAL 23561091 A 2 8 flavan FAMILY 23561091 A 251 259 flavones FAMILY 23561091 A 270 281 isoflavones FAMILY 23561091 A 298 308 flavonoids FAMILY 23561091 A 328 379 (2S)-3',4'-methylenedioxy-5-methoxy-7-hydroxyflavan SYSTEMATIC 23561091 A 38 61 flavone acyl glucosides FAMILY 23561091 A 385 434 hispidulin 7-O-β-d-(6-O-cinnamoyl)glucopyranoside SYSTEMATIC 23561091 A 440 491 jaceosidin 7-O-β-d-(6-O-p-coumaroyl)glucopyranoside SYSTEMATIC 23561091 A 497 553 jaceosidin 7-O-β-d-(6-O-p-hydroxybenzoyl)glucopyranoside SYSTEMATIC 23561091 A 604 614 flavonoids FAMILY 23561091 A 63 81 eriocaulosides A-C MULTIPLE 23561091 A 855 858 MTT ABBREVIATION 23561091 T 0 10 Flavonoids FAMILY 23561093 A 672 683 astaxanthin TRIVIAL 23561093 A 725 738 palmitic acid TRIVIAL 23561093 A 743 753 tocopherol FAMILY 23561093 A 828 849 eicosapentaenoic acid SYSTEMATIC 23561093 A 851 854 EPA ABBREVIATION 23561093 A 887 907 docosahexaenoic acid SYSTEMATIC 23561093 A 909 912 DHA ABBREVIATION 23561093 A 940 949 Anisidine TRIVIAL 23561093 A 954 973 thiobarbituric acid SYSTEMATIC 23561103 A 0 9 Vitamin A FAMILY 23561103 A 196 205 vitamin A FAMILY 23561103 A 484 494 β-carotene TRIVIAL 23561103 A 643 653 β-carotene TRIVIAL 23561103 A 693 703 β-carotene TRIVIAL 23561103 A 863 873 β-carotene TRIVIAL 23561103 A 984 993 vitamin A FAMILY 23561103 T 16 26 β-carotene TRIVIAL 23561109 A 722 726 DPPH ABBREVIATION 23561109 A 755 759 ABTS ABBREVIATION 23561113 A 501 514 Hoechst 33342 TRIVIAL 23561120 A 0 6 Phenol SYSTEMATIC 23561120 A 1224 1228 IPTG ABBREVIATION 23561120 A 146 153 tyrosol TRIVIAL 23561120 A 189 203 hydroxytyrosol SYSTEMATIC 23561120 A 222 228 Phenol SYSTEMATIC 23561120 A 326 330 NADH ABBREVIATION 23561120 A 335 338 FAD ABBREVIATION 23561120 A 514 520 phenol SYSTEMATIC 23561120 A 525 532 tyrosol TRIVIAL 23561120 A 539 543 IPTG ABBREVIATION 23561120 A 545 580 isopropyl-β-d-thiogalactopyranoside SYSTEMATIC 23561120 A 729 733 IPTG ABBREVIATION 23561120 A 779 785 phenol SYSTEMATIC 23561120 A 902 913 monophenols FAMILY 23561120 T 28 42 hydroxytyrosol SYSTEMATIC 23561120 T 95 101 phenol SYSTEMATIC 23561124 A 142 148 amines FAMILY 23561124 A 150 162 anthocyanins FAMILY 23561124 A 164 175 polyphenols FAMILY 23561124 A 590 595 amine SYSTEMATIC 23561124 A 702 711 histamine TRIVIAL 23561124 A 713 721 tyramine TRIVIAL 23561124 A 726 736 putrescine TRIVIAL 23561124 A 818 830 anthocyanins FAMILY 23561124 A 906 917 polyphenols FAMILY 23561124 T 23 28 amine SYSTEMATIC 23561124 T 33 43 polyphenol FAMILY 23561128 A 125 139 sodium nitrite SYSTEMATIC 23561128 A 545 551 sulfur SYSTEMATIC 23561128 A 668 675 nitrite SYSTEMATIC 23561128 A 790 796 sulfur SYSTEMATIC 23561128 T 10 17 nitrite SYSTEMATIC 23561131 A 102 111 minutin B TRIVIAL 23561131 A 1099 1113 clauslactone E TRIVIAL 23561131 A 1144 1153 minutin B TRIVIAL 23561131 A 1187 1222 8-hydroxyisocapnolactone-2',3'-diol SYSTEMATIC 23561131 A 183 192 coumarins FAMILY 23561131 A 194 245 8,4″-dihydroxy-3″,4″-dihydrocapnolactone-2',3'-diol SYSTEMATIC 23561131 A 247 282 8-hydroxyisocapnolactone-2',3'-diol SYSTEMATIC 23561131 A 284 330 8-hydroxy-3″,4″-dihydrocapnolactone-2',3'-diol SYSTEMATIC 23561131 A 336 350 clauslactone E TRIVIAL 23561131 A 375 384 minutin A TRIVIAL 23561131 A 386 395 minutin B TRIVIAL 23561131 A 397 432 8-hydroxyisocapnolactone-2',3'-diol SYSTEMATIC 23561131 A 437 451 clauslactone E TRIVIAL 23561131 A 586 636 8,4″-dihydroxy-3″4″-dihydrocapnolactone-2',3'-diol SYSTEMATIC 23561131 A 641 687 8-hydroxy-3″,4″-dihydrocapnolactone-2',3'-diol SYSTEMATIC 23561131 A 65 86 monoterpene coumarins FAMILY 23561131 A 88 97 minutin A TRIVIAL 23561131 A 887 901 clauslactone E TRIVIAL 23561131 A 903 912 minutin B TRIVIAL 23561131 A 917 952 8-hydroxyisocapnolactone-2',3'-diol SYSTEMATIC 23561131 T 17 38 monoterpene coumarins FAMILY 23561135 A 116 124 coumarin TRIVIAL 23561135 A 1163 1192 coumarinyl thiosemicarbazides FAMILY 23561135 A 271 297 7-hydroxy-4-methylcoumarin SYSTEMATIC 23561135 A 30 47 thiosemicarbazide SYSTEMATIC 23561135 A 382 400 thiosemicarbazides FAMILY 23561135 A 443 447 DPPH ABBREVIATION 23561135 A 452 462 galvinoxyl TRIVIAL 23561135 A 481 498 4-thiazolidinones FAMILY 23561135 A 52 66 thiazolidinone SYSTEMATIC 23561135 A 562 575 ascorbic acid TRIVIAL 23561135 A 787 795 coumarin TRIVIAL 23561135 A 932 949 4-thiazolidinones FAMILY 23561135 A 993 1011 thiosemicarbazides FAMILY 23561135 T 0 26 4-Methyl-7-hydroxycoumarin SYSTEMATIC 23561135 T 118 132 thiazolidinone SYSTEMATIC 23561135 T 96 113 thiosemicarbazide SYSTEMATIC 23561137 A 276 291 petroleum ether TRIVIAL 23561137 A 296 309 ethyl acetate SYSTEMATIC 23561137 A 373 375 NO FORMULA 23561137 A 634 644 lanosterol TRIVIAL 23561137 A 650 676 3β-hydroxy-8,24-dien-21-al SYSTEMATIC 23561137 A 682 692 ergosterol TRIVIAL 23561137 A 698 707 inotodiol TRIVIAL 23561137 A 713 732 ergosterol peroxide TRIVIAL 23561137 A 741 758 trametenolic acid TRIVIAL 23561137 A 773 783 ergosterol TRIVIAL 23561137 A 785 804 ergosterol peroxide TRIVIAL 23561137 A 809 826 trametenolic acid TRIVIAL 23561137 A 867 886 ergosterol peroxide TRIVIAL 23561137 A 891 908 trametenolic acid TRIVIAL 23561138 A 351 361 6-gingerol SYSTEMATIC 23561138 A 473 480 acetone SYSTEMATIC 23561138 A 530 538 gingerol TRIVIAL 23561138 A 600 608 gingerol TRIVIAL 23561138 A 685 692 ethanol SYSTEMATIC 23561138 A 718 726 gingerol TRIVIAL 23561138 A 818 825 ethanol SYSTEMATIC 23561138 A 88 98 6-Gingerol SYSTEMATIC 23561138 A 882 892 polyphenol FAMILY 23561138 A 924 934 6-gingerol SYSTEMATIC 23561138 A 936 945 6-paradol SYSTEMATIC 23561138 A 957 981 6- and 8-methyl shogaols MULTIPLE 23561139 A 583 591 vitamins FAMILY 23561139 A 596 606 acrylamide TRIVIAL 23561139 A 666 679 ascorbic acid TRIVIAL 23561139 A 694 708 glucosinolates FAMILY 23561139 A 769 779 acrylamide TRIVIAL 23561139 A 835 845 vitamins B FAMILY 23561140 A 550 561 anthocyanin FAMILY 23561140 A 618 630 anthocyanins FAMILY 23561140 A 632 652 quercetin rutinoside TRIVIAL 23561140 A 657 669 procyanidins FAMILY 23561140 A 776 788 procyanidins FAMILY 23561140 A 793 805 anthocyanins FAMILY 23561140 A 883 894 anthocyanin FAMILY 23561140 T 11 21 polyphenol FAMILY 23561141 A 1009 1020 astaxanthin TRIVIAL 23561141 A 13 24 astaxanthin TRIVIAL 23561141 A 184 195 astaxanthin TRIVIAL 23561141 A 601 612 astaxanthin TRIVIAL 23561141 A 669 680 astaxanthin TRIVIAL 23561141 A 694 705 astaxanthin TRIVIAL 23561141 A 790 801 astaxanthin TRIVIAL 23561141 A 881 892 astaxanthin TRIVIAL 23561141 A 90 101 astaxanthin TRIVIAL 23561141 A 979 990 astaxanthin TRIVIAL 23561141 T 22 33 astaxanthin TRIVIAL 23561147 A 0 10 Fatty acid FAMILY 23561147 A 170 173 FAs ABBREVIATION 23561147 A 283 286 FAs ABBREVIATION 23561147 T 60 71 fatty acids FAMILY 23561152 A 0 7 Annatto TRIVIAL 23561152 A 185 193 norbixin TRIVIAL 23561152 A 227 233 sodium SYSTEMATIC 23561152 A 454 462 Norbixin TRIVIAL 23561152 A 591 599 norbixin TRIVIAL 23561152 A 628 636 norbixin TRIVIAL 23561152 A 717 725 norbixin TRIVIAL 23561152 A 792 800 norbixin TRIVIAL 23561152 A 9 17 norbixin TRIVIAL 23561152 T 28 36 norbixin TRIVIAL 23561157 A 205 208 KOH FORMULA 23561157 A 283 294 fatty acids FAMILY 23561157 A 317 327 oleic acid TRIVIAL 23561157 A 341 349 peroxide SYSTEMATIC 23561157 A 369 371 O2 FORMULA 23561157 A 396 400 (1)H FORMULA 23561157 A 429 433 (1)H FORMULA 23561157 A 484 490 iodine SYSTEMATIC 23561157 A 569 579 oleic acid TRIVIAL 23561157 A 602 615 palmitic acid TRIVIAL 23561157 A 626 638 stearic acid TRIVIAL 23561157 A 649 667 palmitelaidic acid TRIVIAL 23561157 A 680 693 myristic acid TRIVIAL 23561158 A 1206 1209 EPA ABBREVIATION 23561158 A 1214 1217 DHA ABBREVIATION 23561158 A 1247 1250 DHA ABBREVIATION 23561158 A 1307 1310 DHA ABBREVIATION 23561158 A 1322 1326 TAGs ABBREVIATION 23561158 A 1342 1345 EPA ABBREVIATION 23561158 A 1701 1705 TAGs ABBREVIATION 23561158 A 1768 1772 TAGs ABBREVIATION 23561158 A 1822 1836 diacylglycerol FAMILY 23561158 A 189 202 lithiated TAG ABBREVIATION 23561158 A 279 295 triacylglycerols FAMILY 23561158 A 297 301 TAGs ABBREVIATION 23561158 A 327 343 eicosapentaenoic SYSTEMATIC 23561158 A 345 348 EPA ABBREVIATION 23561158 A 360 381 docosahexaenoic acids FAMILY 23561158 A 383 386 DHA ABBREVIATION 23561158 A 492 502 fatty acid FAMILY 23561158 A 573 599 α,β-unsaturated fatty acid FAMILY 23561158 A 652 656 TAGs ABBREVIATION 23561158 A 719 728 Li-RACOOH FAMILY 23561158 A 729 740 R'BCHCHCOOH FAMILY 23561158 A 754 763 Li-RACOOH FAMILY 23561158 A 764 775 R'ACHCHCOOH FAMILY 23561158 A 850 854 acyl FAMILY 23561158 A 891 895 TAGs ABBREVIATION 23561158 T 51 83 polyunsaturated triacylglycerols FAMILY 23561161 A 105 116 fatty acids FAMILY 23561161 A 209 220 fatty acids FAMILY 23561161 A 25 32 calcium SYSTEMATIC 23561161 A 350 360 fatty acid FAMILY 23561161 A 409 416 calcium SYSTEMATIC 23561161 A 503 510 calcium SYSTEMATIC 23561161 A 554 563 phosphate SYSTEMATIC 23561161 A 573 580 calcium SYSTEMATIC 23561161 A 596 613 calcium gluconate SYSTEMATIC 23561161 A 615 630 calcium acetate SYSTEMATIC 23561161 A 635 640 CaCl2 FORMULA 23561161 A 693 703 fatty acid FAMILY 23561161 A 746 749 CaO FORMULA 23561161 A 754 759 CaSO4 FORMULA 23561161 A 796 803 calcium SYSTEMATIC 23561161 A 875 882 calcium SYSTEMATIC 23561161 A 933 944 fatty acids FAMILY 23561161 T 10 17 calcium SYSTEMATIC 23561161 T 42 52 fatty acid FAMILY 23561165 A 396 406 sulphydryl FAMILY 23561165 A 461 469 carbonyl FAMILY 23561169 A 293 303 β-carotene TRIVIAL 23561169 A 308 319 chlorophyll FAMILY 23561169 A 32 43 chlorophyll FAMILY 23561169 A 337 348 xanthophyll FAMILY 23561169 A 349 355 lutein TRIVIAL 23561169 A 426 432 lutein TRIVIAL 23561169 A 504 515 fatty acids FAMILY 23561169 A 521 527 C8-C16 MULTIPLE 23561169 A 590 596 lutein TRIVIAL 23561169 A 60 71 tocopherols FAMILY 23561169 A 609 615 lutein TRIVIAL 23561169 A 621 632 tocopherols FAMILY 23561169 A 761 772 tocopherols FAMILY 23561169 A 903 914 isoprenoids FAMILY 23561169 T 16 27 tocopherols FAMILY 23561171 A 1001 1013 ginsenosides FAMILY 23561171 A 294 302 saponins FAMILY 23561171 A 304 316 ginsenosides FAMILY 23561171 A 399 407 saponins FAMILY 23561171 A 464 465 H FORMULA 23561171 A 477 479 Na FORMULA 23561171 A 591 596 sugar FAMILY 23561171 A 664 672 saponins FAMILY 23561171 A 778 790 ginsenosides FAMILY 23561171 A 799 803 acyl FAMILY 23561171 A 823 830 malonyl SYSTEMATIC 23561171 A 843 845 OH FORMULA 23561171 A 850 860 di-malonyl SYSTEMATIC 23561171 A 949 964 protopanaxadiol TRIVIAL 23561171 A 979 995 protopanaxatriol TRIVIAL 23561171 T 28 36 saponins FAMILY 23561176 A 102 105 EGC ABBREVIATION 23561176 A 111 141 (-)-epigallocatechin-3-gallate TRIVIAL 23561176 A 143 147 EGCG ABBREVIATION 23561176 A 153 177 butylated hydroxytoluene SYSTEMATIC 23561176 A 179 182 BHT ABBREVIATION 23561176 A 221 240 phosphatidylcholine FAMILY 23561176 A 246 259 sphingomyelin FAMILY 23561176 A 49 61 (+)-catechin TRIVIAL 23561176 A 63 78 (-)-epicatechin SYSTEMATIC 23561176 A 645 646 H FORMULA 23561176 A 763 775 (+)-catechin TRIVIAL 23561176 A 777 792 (-)-epicatechin SYSTEMATIC 23561176 A 794 797 EGC ABBREVIATION 23561176 A 799 803 EGCG ABBREVIATION 23561176 A 80 100 (-)-epigallocatechin TRIVIAL 23561176 A 808 811 BHT ABBREVIATION 23561176 A 913 921 hydrogen SYSTEMATIC 23561176 A 935 938 BTH ABBREVIATION 23561176 T 10 19 flavonoid FAMILY 23561177 A 0 7 Folates FAMILY 23561177 A 1031 1038 folates FAMILY 23561177 A 125 132 folates FAMILY 23561177 A 318 325 folates FAMILY 23561177 A 429 436 folates FAMILY 23561177 A 561 568 Folates FAMILY 23561177 A 843 849 folate TRIVIAL 23561177 T 36 42 folate TRIVIAL 23561178 A 400 413 hydroperoxide FAMILY 23561178 A 430 443 linoleic acid TRIVIAL 23561178 A 448 462 linolenic acid TRIVIAL 23561178 A 816 827 amino acids FAMILY 23561183 A 1041 1044 PAC ABBREVIATION 23561183 A 225 243 Methylene chloride SYSTEMATIC 23561183 A 244 257 ethyl acetate SYSTEMATIC 23561183 A 258 269 formic acid SYSTEMATIC 23561183 A 311 332 vanillin hydrochloric SYSTEMATIC 23561183 A 39 47 catechin TRIVIAL 23561183 A 441 449 catechin TRIVIAL 23561183 A 451 457 PAC-A2 ABBREVIATION 23561183 A 462 468 PAC-B1 ABBREVIATION 23561183 A 49 65 proanthocyanidin FAMILY 23561183 A 663 671 Catechin TRIVIAL 23561183 A 67 70 PAC ABBREVIATION 23561183 A 673 679 PAC-A2 ABBREVIATION 23561183 A 684 690 PAC-B1 ABBREVIATION 23561183 A 753 756 PAC ABBREVIATION 23561183 A 79 85 PAC-B1 ABBREVIATION 23561185 A 1071 1081 β-carotene TRIVIAL 23561185 A 297 309 triglyceride FAMILY 23561185 A 330 342 triglyceride FAMILY 23561185 A 478 488 β-carotene TRIVIAL 23561185 A 675 691 triacylglycerols FAMILY 23561185 A 710 721 fatty acids FAMILY 23561185 A 877 887 β-carotene TRIVIAL 23561185 T 11 21 β-carotene TRIVIAL 23561188 A 1014 1042 C-20 oxygenated ent-kauranes FAMILY 23561188 A 1099 1110 Effusanin E TRIVIAL 23561188 A 1112 1120 lasiodin TRIVIAL 23561188 A 1125 1136 effusanin F TRIVIAL 23561188 A 123 130 ethanol SYSTEMATIC 23561188 A 201 216 petroleum ether TRIVIAL 23561188 A 218 231 ethyl acetate SYSTEMATIC 23561188 A 233 240 butanol SYSTEMATIC 23561188 A 280 287 ethanol SYSTEMATIC 23561188 A 486 499 ethyl acetate SYSTEMATIC 23561188 A 702 717 rosmarinic acid TRIVIAL 23561188 A 719 737 methyl rosmarinate SYSTEMATIC 23561188 A 742 751 pedalitin TRIVIAL 23561188 A 762 790 C-20 oxygenated ent-kauranes FAMILY 23561188 A 792 803 effusanin E TRIVIAL 23561188 A 805 813 lasiodin TRIVIAL 23561188 A 815 831 rabdosichuanin D TRIVIAL 23561188 A 858 869 effusanin F TRIVIAL 23561188 T 73 100 C-20 oxygenated ent-kaurane FAMILY 23561190 A 210 218 n-hexane SYSTEMATIC 23561190 A 219 231 acetonitrile SYSTEMATIC 23561190 A 265 286 cycloartenyl ferulate TRIVIAL 23561190 A 288 291 CAF ABBREVIATION 23561190 A 297 331 24-methylene cycloartanyl ferulate SYSTEMATIC 23561190 A 333 340 24-mCAF SYSTEMATIC 23561190 A 381 384 CAF ABBREVIATION 23561190 A 402 409 24-mCAF SYSTEMATIC 23561190 A 47 65 triterpene alcohol FAMILY 23561190 A 761 765 (1)H FORMULA 23561190 A 767 772 (13)C FORMULA 23561190 A 871 874 CAF ABBREVIATION 23561190 A 879 886 24-mCAF SYSTEMATIC 23561190 T 26 44 triterpene alcohol FAMILY 23561191 A 0 16 Alkylresorcinols FAMILY 23561191 A 26 34 phenolic FAMILY 23561191 A 444 469 3,5-dihydroxybenzoic acid SYSTEMATIC 23561191 A 474 514 3-(3,5-dihydroxyphenyl)-1-propanoic acid SYSTEMATIC 23561191 A 516 521 DHPPA ABBREVIATION 23561191 A 801 806 DHPPA ABBREVIATION 23561191 T 29 45 alkylresorcinols FAMILY 23561192 A 291 302 Anthocyanin FAMILY 23561192 A 30 45 sodium chloride SYSTEMATIC 23561192 A 470 476 sugars FAMILY 23561192 A 477 484 glucose TRIVIAL 23561192 A 486 494 fructose TRIVIAL 23561192 A 499 506 sucrose TRIVIAL 23561192 A 565 572 glucose TRIVIAL 23561192 A 577 585 fructose TRIVIAL 23561192 A 730 754 tartaric and malic acids MULTIPLE 23561192 A 882 886 NaCl FORMULA 23561192 T 59 63 NaCl FORMULA 23561194 A 14 20 Ca(2+) FORMULA 23561194 A 163 169 Ca(2+) FORMULA 23561194 A 352 363 oxalic acid TRIVIAL 23561194 A 383 394 quinic acid TRIVIAL 23561194 A 417 430 tartaric acid TRIVIAL 23561194 A 450 461 Oxalic acid TRIVIAL 23561194 A 489 495 Ca(2+) FORMULA 23561194 A 527 538 polyphenols FAMILY 23561194 A 575 581 Ca(2+) FORMULA 23561194 A 705 711 Ca(2+) FORMULA 23561194 A 739 750 oxalic acid TRIVIAL 23561194 A 752 763 quinic acid TRIVIAL 23561194 A 768 781 tartaric acid TRIVIAL 23561194 A 783 789 Ca(2+) FORMULA 23561194 A 794 801 oxalate SYSTEMATIC 23561194 T 14 20 Ca(2+) FORMULA 23561197 A 104 112 xanthine TRIVIAL 23561197 A 119 127 xanthine TRIVIAL 23561197 A 205 210 Fe3O4 FORMULA 23561197 A 823 836 ascorbic acid TRIVIAL 23561197 A 838 842 urea TRIVIAL 23561197 A 847 854 sucrose TRIVIAL 23561197 T 65 73 xanthine TRIVIAL 23561198 A 173 184 lactic acid TRIVIAL 23561198 A 487 493 carbon SYSTEMATIC 23561198 A 495 503 nitrogen SYSTEMATIC 23561198 A 76 82 carbon SYSTEMATIC 23561198 A 851 858 lactose TRIVIAL 23561198 A 871 879 thiamine TRIVIAL 23561198 A 896 901 FeCl3 FORMULA 23561198 A 92 100 nitrogen SYSTEMATIC 23561198 T 77 88 lactic acid TRIVIAL 23561203 A 147 157 Pyronine B TRIVIAL 23561203 A 163 169 Se(IV) FORMULA 23561203 A 194 217 sodium dodecyl sulphate SYSTEMATIC 23561203 A 219 222 SDS ABBREVIATION 23561203 A 450 456 Se(IV) FORMULA 23561203 A 505 511 Se(IV) FORMULA 23561203 A 74 82 selenium SYSTEMATIC 23561203 A 764 772 selenium SYSTEMATIC 23561203 T 44 52 selenium SYSTEMATIC 23561208 A 398 410 anthocyanins FAMILY 23561208 A 412 429 proanthocyanidins FAMILY 23561208 A 615 623 Vanillin TRIVIAL 23561208 A 625 639 syringaldehyde TRIVIAL 23561208 A 644 660 furfuryl alcohol TRIVIAL 23561208 A 781 798 proanthocyanidins FAMILY 23561213 A 104 120 chlorogenic acid TRIVIAL 23561213 A 1045 1052 neo-ChA TRIVIAL 23561213 A 1122 1141 feruloyl octopamine TRIVIAL 23561213 A 1153 1177 5-O-feruloyl quinic acid SYSTEMATIC 23561213 A 1189 1196 cis-ChA TRIVIAL 23561213 A 1208 1227 caffeoyl putrescine TRIVIAL 23561213 A 122 125 ChA ABBREVIATION 23561213 A 1239 1254 sinapoyl hexose FAMILY 23561213 A 1266 1307 N(1),N(14)-bis-(dihydrocaffeoyl) spermine SYSTEMATIC 23561213 A 128 138 crypto-ChA TRIVIAL 23561213 A 1319 1362 N(1),N(10)-bis-(dihydrocaffeoyl) spermidine SYSTEMATIC 23561213 A 1378 1425 N(1),N(5),N(14)-tris-(dihydrocaffeoyl) spermine SYSTEMATIC 23561213 A 144 151 neo-ChA TRIVIAL 23561213 A 158 169 anthocyanin FAMILY 23561213 A 17 29 caffeic acid TRIVIAL 23561213 A 177 181 HCAs ABBREVIATION 23561213 A 320 347 didydrohydroxycinnamic acid SYSTEMATIC 23561213 A 47 67 hydroxycinnamic acid SYSTEMATIC 23561213 A 629 633 HCAs ABBREVIATION 23561213 A 69 72 HCA ABBREVIATION 23561213 A 867 871 HCAs ABBREVIATION 23561213 T 13 43 (dihydro) hydroxycinnamic acid SYSTEMATIC 23561222 A 0 28 Caffeic acid phenethyl ester SYSTEMATIC 23561222 A 234 238 CAPE ABBREVIATION 23561222 A 30 34 CAPE ABBREVIATION 23561222 A 388 392 CAPE ABBREVIATION 23561222 A 40 52 caffeic acid TRIVIAL 23561222 A 576 580 CAPE ABBREVIATION 23561222 A 810 814 CAPE ABBREVIATION 23561222 T 58 86 caffeic acid phenethyl ester SYSTEMATIC 23561222 T 91 103 caffeic acid TRIVIAL 23562076 A 805 812 glucose TRIVIAL 23562245 A 123 131 cysteine TRIVIAL 23562245 A 163 178 iodoacetanilide SYSTEMATIC 23562245 A 180 183 IAA ABBREVIATION 23562245 A 192 198 (13)C7 FORMULA 23562245 A 207 222 iodoacetanilide SYSTEMATIC 23562245 A 224 230 (13)C7 FORMULA 23562245 A 231 234 IAA ABBREVIATION 23562245 A 243 259 N-ethylmaleimide SYSTEMATIC 23562245 A 261 264 NEM ABBREVIATION 23562245 A 273 275 d5 FORMULA 23562245 A 284 300 N-ethylmaleimide SYSTEMATIC 23562245 A 302 304 d5 FORMULA 23562245 A 305 308 NEM ABBREVIATION 23562245 T 36 42 (13)C7 FORMULA 23562245 T 51 66 iodoacetanilide SYSTEMATIC 23562245 T 71 73 d5 FORMULA 23562245 T 82 98 N-ethylmaleimide SYSTEMATIC 23562369 A 1109 1112 LPC ABBREVIATION 23562369 A 1163 1166 LPA ABBREVIATION 23562369 A 1322 1340 phosphatidylserine FAMILY 23562369 A 427 450 lysophosphatidylcholine FAMILY 23562369 A 452 455 LPC ABBREVIATION 23562369 A 462 483 lysophosphatidic acid TRIVIAL 23562369 A 485 488 LPA ABBREVIATION 23562369 A 494 501 choline FAMILY 23562369 A 589 602 sphingomyelin FAMILY 23562369 A 611 630 phosphatidylcholine FAMILY 23562369 A 887 891 EDTA ABBREVIATION 23562369 A 893 897 EGTA ABBREVIATION 23562369 A 903 922 1, 10-phenantroline SYSTEMATIC 23562597 A 0 12 Ilicicolin H TRIVIAL 23562597 A 395 407 ilicicolin H TRIVIAL 23562597 A 416 426 19-hydroxy SYSTEMATIC 23562597 A 495 504 4'-esters SYSTEMATIC 23562597 A 526 527 N FORMULA 23562597 A 533 534 O FORMULA 23562597 A 618 633 4',19-Diacetate SYSTEMATIC 23562597 A 638 660 19-cyclopropyl acetate SYSTEMATIC 23562597 T 96 108 ilicicolin H TRIVIAL 23562633 A 1226 1232 PEG-FA ABBREVIATION 23562633 A 1432 1438 PEG-FA ABBREVIATION 23562633 A 1577 1583 PEG-FA ABBREVIATION 23562633 A 1632 1638 PEG-FA ABBREVIATION 23562633 A 1831 1838 alanine TRIVIAL 23562633 A 1856 1865 aspartate TRIVIAL 23562633 A 1989 1992 PEG ABBREVIATION 23562633 A 2069 2075 PEG-FA ABBREVIATION 23562633 A 2183 2189 PEG-FA ABBREVIATION 23562633 A 546 565 polyethylene glycol SYSTEMATIC 23562633 A 567 570 PEG ABBREVIATION 23562633 A 579 589 folic acid TRIVIAL 23562633 A 693 696 PEG ABBREVIATION 23562633 A 714 720 PEG-FA ABBREVIATION 23562633 A 800 806 PEG-FA ABBREVIATION 23562633 A 817 823 folate TRIVIAL 23562633 A 916 919 PEG ABBREVIATION 23562633 A 935 941 PEG-FA ABBREVIATION 23562633 T 34 37 PEG ABBREVIATION 23562633 T 38 44 folate TRIVIAL 23562634 A 1319 1328 DP-TAT-59 IDENTIFIER 23562634 A 431 451 miproxifen phosphate TRIVIAL 23562634 A 453 459 TAT-59 IDENTIFIER 23562634 A 711 717 TAT-59 IDENTIFIER 23562634 A 812 818 TAT-59 IDENTIFIER 23562634 A 845 854 DP-TAT-59 IDENTIFIER 23562634 A 928 937 DP-TAT-59 IDENTIFIER 23562706 A 1045 1048 DON ABBREVIATION 23562706 A 1049 1052 NIV ABBREVIATION 23562706 A 1054 1057 DON ABBREVIATION 23562706 A 1058 1061 ZEA ABBREVIATION 23562706 A 1063 1066 DON ABBREVIATION 23562706 A 1067 1070 NIV ABBREVIATION 23562706 A 1071 1074 FB1 ABBREVIATION 23562706 A 1076 1079 DON ABBREVIATION 23562706 A 1080 1083 ZEA ABBREVIATION 23562706 A 1084 1087 FB1 ABBREVIATION 23562706 A 1089 1092 NIV ABBREVIATION 23562706 A 1093 1096 ZEA ABBREVIATION 23562706 A 1097 1100 FB1 ABBREVIATION 23562706 A 315 329 deoxynivalenol TRIVIAL 23562706 A 331 334 DON ABBREVIATION 23562706 A 337 346 nivalenol TRIVIAL 23562706 A 348 351 NIV ABBREVIATION 23562706 A 354 365 zearalenone TRIVIAL 23562706 A 367 370 ZEA ABBREVIATION 23562706 A 376 388 fumonisin B1 TRIVIAL 23562706 A 390 393 FB1 ABBREVIATION 23562706 A 533 536 MTT ABBREVIATION 23562706 A 831 834 NIV ABBREVIATION 23562706 A 835 838 DON ABBREVIATION 23562706 A 839 842 ZEA ABBREVIATION 23562706 A 843 846 FB1 ABBREVIATION 23562706 T 105 118 fumonisins B1 TRIVIAL 23562706 T 62 76 deoxynivalenol TRIVIAL 23562706 T 78 87 nivalenol TRIVIAL 23562706 T 89 100 zearalenone TRIVIAL 23562707 A 1086 1095 Sudan III TRIVIAL 23562707 A 1126 1129 azo SYSTEMATIC 23562707 A 148 163 aromatic amines FAMILY 23562707 A 206 209 azo SYSTEMATIC 23562707 A 284 297 ironporphyrin SYSTEMATIC 23562707 A 449 458 Sudan III TRIVIAL 23562707 A 46 55 Sudan III TRIVIAL 23562707 A 542 549 aniline SYSTEMATIC 23562707 A 551 562 o-anisidine TRIVIAL 23562707 A 564 589 2-methoxi-5-methylaniline SYSTEMATIC 23562707 A 591 606 4-aminobiphenyl SYSTEMATIC 23562707 A 608 625 4,4'-oxydianiline SYSTEMATIC 23562707 A 627 654 4,4'-diaminodiphenylmethane SYSTEMATIC 23562707 A 659 678 2,6-dimethylaniline SYSTEMATIC 23562707 A 775 784 Sudan III TRIVIAL 23562707 A 970 985 aromatic amines FAMILY 23562707 T 104 113 Sudan III TRIVIAL 23562707 T 56 71 aromatic amines FAMILY 23562707 T 96 99 azo SYSTEMATIC 23562765 A 0 11 Bisphenol A TRIVIAL 23562765 A 1053 1056 BPA ABBREVIATION 23562765 A 1061 1065 BPAF ABBREVIATION 23562765 A 1224 1227 BPA ABBREVIATION 23562765 A 1232 1236 BPAF ABBREVIATION 23562765 A 13 16 BPA ABBREVIATION 23562765 A 1315 1323 androgen FAMILY 23562765 A 1324 1329 R1881 IDENTIFIER 23562765 A 1331 1334 BPS ABBREVIATION 23562765 A 1404 1409 R1881 IDENTIFIER 23562765 A 1471 1474 BPA ABBREVIATION 23562765 A 1569 1582 17β-estradiol SYSTEMATIC 23562765 A 1615 1618 BPA ABBREVIATION 23562765 A 1715 1718 BPA ABBREVIATION 23562765 A 1792 1795 BPA ABBREVIATION 23562765 A 1908 1911 BPA ABBREVIATION 23562765 A 259 262 BPA ABBREVIATION 23562765 A 575 583 estrogen FAMILY 23562765 A 609 617 androgen FAMILY 23562765 A 649 652 BPA ABBREVIATION 23562765 A 711 714 BPA ABBREVIATION 23562765 A 914 917 BPA ABBREVIATION 23562765 A 927 939 bisphenol AF TRIVIAL 23562765 A 941 945 BPAF ABBREVIATION 23562765 A 951 962 bisphenol S TRIVIAL 23562765 A 964 967 BPS ABBREVIATION 23562765 T 0 11 Bisphenol A TRIVIAL 23562765 T 20 28 androgen FAMILY 23562995 A 284 287 ZnO FORMULA 23562995 A 8 11 ZnO FORMULA 23562995 T 22 25 ZnO FORMULA 23563049 A 0 10 Ketoprofen TRIVIAL 23563049 A 1220 1230 ketoprofen TRIVIAL 23563049 A 1319 1329 ketoprofen TRIVIAL 23563049 A 1404 1414 ketoprofen TRIVIAL 23563049 A 158 171 prostaglandin FAMILY 23563049 A 209 219 ketoprofen TRIVIAL 23563049 A 772 782 ketoprofen TRIVIAL 23563049 T 88 98 Ketoprofen TRIVIAL 23563055 A 1140 1169 2,2-diphenyl-1-picrylhydrazyl SYSTEMATIC 23563205 T 114 132 thiazolidinediones FAMILY 23563356 A 1005 1014 serotonin TRIVIAL 23563356 A 629 638 serotonin TRIVIAL 23563356 A 715 724 serotonin TRIVIAL 23563356 T 20 29 serotonin TRIVIAL 23564211 A 1108 1118 cetirizine TRIVIAL 23564211 A 1124 1133 verapamil TRIVIAL 23564211 A 1158 1168 cetirizine TRIVIAL 23564211 A 1238 1248 cetirizine TRIVIAL 23564211 A 1458 1468 cetirizine TRIVIAL 23564211 A 1473 1482 verapamil TRIVIAL 23564211 A 1541 1547 oxygen SYSTEMATIC 23564211 A 713 723 cetirizine TRIVIAL 23564211 A 750 759 verapamil TRIVIAL 23564211 A 802 812 cetirizine TRIVIAL 23564211 A 815 824 verapamil TRIVIAL 23564329 A 16 18 CO FORMULA 23564329 A 221 223 CO FORMULA 23564329 A 284 293 graphenes FAMILY 23564329 A 353 355 Al FORMULA 23564329 A 361 363 Si FORMULA 23564329 A 409 411 CO FORMULA 23564329 A 590 592 Al FORMULA 23564329 A 599 607 graphene TRIVIAL 23564329 A 650 652 CO FORMULA 23564329 A 728 736 graphene TRIVIAL 23564329 A 74 76 Al FORMULA 23564329 A 757 759 Al FORMULA 23564329 A 771 773 CO FORMULA 23564329 A 82 84 Si FORMULA 23564329 A 92 101 graphenes FAMILY 23564329 T 23 31 graphene TRIVIAL 23564329 T 61 63 CO FORMULA 23564329 T 71 73 Al FORMULA 23564643 A 0 30 Polybrominated diphenyl ethers FAMILY 23564643 A 111 118 PBDE-47 ABBREVIATION 23564643 A 1168 1180 6-OH-PBDE-47 SYSTEMATIC 23564643 A 1298 1310 6-OH-PBDE-47 SYSTEMATIC 23564643 A 1448 1460 6-OH-PBDE-47 SYSTEMATIC 23564643 A 148 152 PBDE ABBREVIATION 23564643 A 1660 1672 6-OH-PBDE-47 SYSTEMATIC 23564643 A 1754 1758 PBDE ABBREVIATION 23564643 A 249 261 6-OH-PBDE-47 SYSTEMATIC 23564643 A 294 301 PBDE-47 ABBREVIATION 23564643 A 32 37 PBDEs ABBREVIATION 23564643 A 392 397 PBDEs ABBREVIATION 23564643 A 469 474 PBDEs ABBREVIATION 23564643 A 54 67 organobromine FAMILY 23564643 A 616 621 PBDEs ABBREVIATION 23564643 A 755 767 6-OH-PBDE-47 SYSTEMATIC 23564643 A 797 804 PBDE-47 ABBREVIATION 23564643 A 911 923 6-OH-PBDE-47 SYSTEMATIC 23564643 T 45 52 PBDE-47 ABBREVIATION 23564646 A 1029 1033 DNCB ABBREVIATION 23564646 A 1213 1217 DNCB ABBREVIATION 23564646 A 1276 1280 CinA ABBREVIATION 23564646 A 155 161 oxygen SYSTEMATIC 23564646 A 700 708 cysteine TRIVIAL 23564646 A 719 743 2,4-dinitrochlorobenzene SYSTEMATIC 23564646 A 745 749 DNCB ABBREVIATION 23564646 A 755 769 cinnamaldehyde TRIVIAL 23564646 A 771 775 CinA ABBREVIATION 23564646 A 830 838 cysteine TRIVIAL 23564646 A 843 849 lysine TRIVIAL 23564646 A 860 883 isophorone diisocyanate SYSTEMATIC 23564646 A 885 889 IPDI ABBREVIATION 23564646 A 927 933 lysine TRIVIAL 23564646 A 944 965 trimellitic anhydride SYSTEMATIC 23564646 A 967 970 TMA ABBREVIATION 23564918 A 26 29 NH2 FORMULA 23564918 T 0 3 NH2 FORMULA 23565585 A 1019 1022 PLA ABBREVIATION 23565585 A 1023 1027 PLGA ABBREVIATION 23565585 A 214 233 polyethylene glycol SYSTEMATIC 23565585 A 235 238 PEG ABBREVIATION 23565585 A 288 295 glucose TRIVIAL 23565585 A 323 349 poly(lactide-co-glycolide) SYSTEMATIC 23565585 A 351 355 PLGA ABBREVIATION 23565585 A 360 377 poly(lactic acid) SYSTEMATIC 23565585 A 379 382 PLA ABBREVIATION 23565585 A 384 388 PLGA ABBREVIATION 23565585 A 740 743 PLA ABBREVIATION 23565585 A 754 758 PLGA ABBREVIATION 23565749 A 105 111 halide FAMILY 23565749 A 126 130 NaCl FORMULA 23565749 A 243 247 NaCl FORMULA 23565749 A 255 261 polyol FAMILY 23565749 A 275 277 Ag FORMULA 23565749 A 287 292 AgNO3 FORMULA 23565749 A 296 311 ethylene glycol SYSTEMATIC 23565749 A 346 350 AgCl FORMULA 23565749 A 38 44 polyol FAMILY 23565749 A 416 418 Ag FORMULA 23565749 A 440 442 Ag FORMULA 23565749 A 559 563 AgCl FORMULA 23565749 A 58 64 silver SYSTEMATIC 23565749 A 76 78 Ag FORMULA 23565749 T 0 15 Silver Chloride SYSTEMATIC 23565749 T 62 68 Silver SYSTEMATIC 23565753 A 0 9 Androgens FAMILY 23565753 A 1333 1341 androgen FAMILY 23565753 A 160 169 androgens FAMILY 23565753 A 18 26 androgen FAMILY 23565753 A 249 257 androgen FAMILY 23565753 A 553 561 androgen FAMILY 23565753 A 587 595 androgen FAMILY 23565753 A 808 816 androgen FAMILY 23565753 A 987 995 androgen FAMILY 23565753 T 0 8 Androgen FAMILY 23565754 A 1108 1109 N FORMULA 23565754 A 136 145 androgens FAMILY 23565754 A 155 164 androgens FAMILY 23565754 A 188 196 androgen FAMILY 23565754 A 311 320 androgens FAMILY 23565754 A 54 62 androgen FAMILY 23565754 A 579 588 androgens FAMILY 23565754 A 820 829 androgens FAMILY 23565754 T 38 46 androgen FAMILY 23565776 A 211 221 amino acid FAMILY 23565776 A 222 232 nucleotide FAMILY 23565776 A 259 272 phenylalanine TRIVIAL 23565776 A 277 286 thymidine TRIVIAL 23565776 A 300 340 saturated or unsaturated diacyl glycerol MULTIPLE 23565776 A 398 407 aminoacid FAMILY 23565776 A 591 604 phenylanaline TRIVIAL 23565776 A 605 616 amino acids FAMILY 23565776 A 652 662 nucleotide FAMILY 23565776 A 773 783 nucleotide FAMILY 23565776 T 0 10 Amino Acid FAMILY 23565776 T 11 21 nucleotide FAMILY 23565776 T 40 50 amino Acid FAMILY 23565822 A 119 129 perovskite TRIVIAL 23565822 A 142 152 perovskite TRIVIAL 23565822 A 28 34 oxygen SYSTEMATIC 23565822 A 479 483 LSCO ABBREVIATION 23565822 A 68 97 lanthanum strontium cobaltite SYSTEMATIC 23565822 A 99 103 LSCO ABBREVIATION 23565822 T 30 36 Oxygen SYSTEMATIC 23566174 A 116 124 bis-urea SYSTEMATIC 23566174 A 534 542 hydrogen SYSTEMATIC 23566174 A 83 91 hydrogen SYSTEMATIC 23566174 T 29 37 Hydrogen SYSTEMATIC 23566174 T 45 53 Bis-urea SYSTEMATIC 23566269 A 0 12 d-Amino acid FAMILY 23566269 A 1010 1038 3-hydroxy-pyridine-2(1H)-one SYSTEMATIC 23566269 A 1070 1130 6-[2-(3,5-Difluorophenyl)ethyl]-4-hydroxypyridazin-3(2H)-one SYSTEMATIC 23566269 A 108 128 N-methyl-d-aspartate SYSTEMATIC 23566269 A 1165 1171 MK-801 IDENTIFIER 23566269 A 165 193 4-hydroxypyridazin-3(2H)-one SYSTEMATIC 23566269 A 536 539 Tyr FORMULA 23566269 A 55 68 d-amino acids FAMILY 23566269 A 630 658 3-hydroxy-pyridine-2(1H)-one SYSTEMATIC 23566269 A 730 775 3-Hydroxy-5-(2-phenylethyl)pyridine-2(1H)-one SYSTEMATIC 23566269 A 79 87 d-serine TRIVIAL 23566269 A 940 968 4-hydroxypyridazin-3(2H)-one SYSTEMATIC 23566269 T 0 28 4-Hydroxypyridazin-3(2H)-one SYSTEMATIC 23566269 T 50 62 d-Amino Acid FAMILY 23566299 A 67 80 acetylcholine SYSTEMATIC 23566299 A 941 949 hydrogen SYSTEMATIC 23566299 T 75 88 Acetylcholine SYSTEMATIC 23566514 A 101 118 pyrrolopyrimidine SYSTEMATIC 23566514 A 178 191 benzimidazole SYSTEMATIC 23566514 A 212 225 benzimidazole SYSTEMATIC 23566514 A 252 277 4-amino-pyrrolopyrimidine SYSTEMATIC 23566514 A 291 301 ketophenyl SYSTEMATIC 23566514 A 340 350 ketophenyl SYSTEMATIC 23566514 A 452 485 ketophenyl pyrrolopyrimidine urea SYSTEMATIC 23566514 T 33 57 4-aminopyrrolopyrimidine SYSTEMATIC 23566899 A 628 641 acetaminophen TRIVIAL 23566899 T 144 157 acetaminophen TRIVIAL 23567034 A 1023 1031 methanol SYSTEMATIC 23567034 A 1042 1045 MTT ABBREVIATION 23567034 A 1090 1098 methanol SYSTEMATIC 23567034 A 1176 1184 methanol SYSTEMATIC 23567034 A 1442 1453 citronellol TRIVIAL 23567034 A 1458 1466 geraniol TRIVIAL 23567034 A 1510 1521 E-β-ocimene TRIVIAL 23567034 A 1582 1603 7,8-dimethoxycoumarin SYSTEMATIC 23567034 A 1608 1620 sinapic acid TRIVIAL 23567034 A 1628 1636 methanol SYSTEMATIC 23567034 A 1707 1715 methanol SYSTEMATIC 23567037 A 158 164 oxygen SYSTEMATIC 23567037 A 932 942 superoxide TRIVIAL 23567041 A 1203 1214 fluorescein TRIVIAL 23567041 A 1224 1235 Fluorescein TRIVIAL 23567041 A 1552 1563 fluorescein TRIVIAL 23567041 A 475 483 Nile red TRIVIAL 23567041 A 504 515 fluorescein TRIVIAL 23567041 A 897 908 fluorescein TRIVIAL 23567041 A 982 993 fluorescein TRIVIAL 23567045 A 254 301 N-lactobionyl-dioleoyl phosphatidylethanolamine SYSTEMATIC 23567045 A 303 311 Lac-DOPE ABBREVIATION 23567046 A 154 164 iron oxide SYSTEMATIC 23567046 A 222 224 Au FORMULA 23567046 A 660 671 doxorubicin TRIVIAL 23567046 A 673 676 DOX ABBREVIATION 23567046 A 780 783 DOX ABBREVIATION 23567046 A 928 931 DOX ABBREVIATION 23567046 T 47 58 doxorubicin TRIVIAL 23567046 T 68 78 iron oxide SYSTEMATIC 23567242 A 0 11 Bisphenol A TRIVIAL 23567242 A 1205 1208 BPA ABBREVIATION 23567242 A 1290 1293 BPA ABBREVIATION 23567242 A 13 16 BPA ABBREVIATION 23567242 A 173 176 BPA ABBREVIATION 23567242 A 267 270 BPA ABBREVIATION 23567242 A 36 49 polycarbonate FAMILY 23567242 A 430 433 BPA ABBREVIATION 23567242 A 63 68 epoxy SYSTEMATIC 23567242 A 632 635 BPA ABBREVIATION 23567242 A 681 684 BPA ABBREVIATION 23567242 A 787 790 BPA ABBREVIATION 23567242 A 837 840 BPA ABBREVIATION 23567242 T 0 11 Bisphenol A TRIVIAL 23567269 A 323 329 oxygen SYSTEMATIC 23567314 A 1223 1233 androstane TRIVIAL 23567314 A 1305 1310 PFAAs ABBREVIATION 23567314 A 155 175 perfluoroalkyl acids FAMILY 23567314 A 177 182 PFAAs ABBREVIATION 23567314 A 1928 1933 PFAAs ABBREVIATION 23567314 A 2146 2150 PFAA ABBREVIATION 23567314 A 2151 2163 carboxylates FAMILY 23567314 A 2241 2245 PFDA ABBREVIATION 23567314 A 2250 2254 PFOS ABBREVIATION 23567314 A 2309 2313 PFOA ABBREVIATION 23567314 A 30 34 PFOA ABBREVIATION 23567314 A 324 329 PFAAs ABBREVIATION 23567314 A 40 65 perfluorooctane sulfonate SYSTEMATIC 23567314 A 528 533 PFAAs ABBREVIATION 23567314 A 6 28 perfluorooctanoic acid SYSTEMATIC 23567314 A 67 71 PFOS ABBREVIATION 23567314 A 699 704 PFAAs ABBREVIATION 23567314 A 708 716 Wy14,643 IDENTIFIER 23567314 T 14 33 perfluoroalkyl acid FAMILY 23567318 A 1097 1109 carbohydrate FAMILY 23567318 A 334 335 N FORMULA 23567318 A 773 784 xylohexaose FAMILY 23567318 A 789 801 xylopentaose FAMILY 23567318 A 807 819 xylotetraose FAMILY 23567318 A 821 831 xylotriose FAMILY 23567318 A 836 845 xylobiose FAMILY 23567486 A 410 422 hydroxyethyl SYSTEMATIC 23567486 A 430 455 hydroxyethyl methacrylate SYSTEMATIC 23567486 A 457 465 HES-HEMA ABBREVIATION 23567486 A 468 480 hydroxyethyl SYSTEMATIC 23567486 A 488 500 methacrylate TRIVIAL 23567486 A 502 508 HES-MA ABBREVIATION 23567486 A 515 527 hydroxyethyl SYSTEMATIC 23567486 A 535 567 polyethylene glycol methacrylate SYSTEMATIC 23567486 A 569 581 HES-P(EG)6MA FORMULA 23567486 A 584 603 polyethylene glycol SYSTEMATIC 23567486 A 612 615 PEG ABBREVIATION 23567486 A 769 772 PEG ABBREVIATION 23567486 A 849 852 PEG ABBREVIATION 23567486 T 14 33 polyethylene glycol SYSTEMATIC 23567861 A 1384 1390 sterol FAMILY 23567861 A 1486 1498 nitric oxide SYSTEMATIC 23567861 A 1591 1592 N FORMULA 23567861 A 545 552 glucose TRIVIAL 23567861 A 632 645 triglycerides FAMILY 23567861 A 653 664 cholesterol TRIVIAL 23567861 A 681 692 fatty acids FAMILY 23567861 A 71 98 7-O-galloyl-d-sedoheptulose SYSTEMATIC 23567861 A 719 730 cholesterol TRIVIAL 23567861 A 761 772 cholesterol TRIVIAL 23567861 A 797 808 cholesterol TRIVIAL 23567861 A 819 825 oxygen SYSTEMATIC 23567861 A 845 864 thiobarbituric acid SYSTEMATIC 23567861 T 14 41 7-O-galloyl-d-sedoheptulose SYSTEMATIC 23567954 A 12 24 polysulfones FAMILY 23567954 A 300 304 iron SYSTEMATIC 23567954 A 305 314 ascorbate TRIVIAL 23567954 A 347 351 H2O2 FORMULA 23567954 A 372 383 polysulfone FAMILY 23567954 A 387 437 2,2-diallyl-1,1,3,3-tetraethylguanidinium chloride SYSTEMATIC 23567954 A 480 497 hydrogen peroxide SYSTEMATIC 23567954 A 647 658 polysulfone FAMILY 23567954 A 65 79 azanorbornenes FAMILY 23567954 A 662 688 N-benzyl-2-azanorbornene-5 SYSTEMATIC 23567954 A 81 182 2,2-diallyl-1,1,3,3-tetraethylguanidiniumchloride and tris(diethylamino)diallylaminophosphonium salts MULTIPLE 23567954 T 0 12 Polysulfones FAMILY 23567959 A 140 175 5-substituted-2-aminobenzimidazoles FAMILY 23567959 A 319 323 (1)H FORMULA 23567959 A 329 334 (13)C FORMULA 23567959 A 588 597 hydrazone FAMILY 23567959 A 768 775 acetate SYSTEMATIC 23567959 A 9 61 1,3,5-substituted-2,3-dihydro-2-imino-benzimidazoles FAMILY 23567959 A 978 987 hydrazone FAMILY 23567959 T 63 97 5-substituted-2-iminobenzimidazole FAMILY 23567999 A 1011 1017 τ-CnVA TRIVIAL 23567999 A 1230 1236 τ-CnVA TRIVIAL 23567999 A 569 575 τ-CnVA TRIVIAL 23567999 A 604 612 cysteine TRIVIAL 23567999 T 67 73 τ-CnVA TRIVIAL 23568274 A 1146 1154 tyrosine TRIVIAL 23568429 A 96 103 tritium SYSTEMATIC 23568429 T 44 51 tritium SYSTEMATIC 23568455 A 107 115 LY294002 IDENTIFIER 23568455 A 217 227 tetrazolyl SYSTEMATIC 23568455 A 60 80 phosphatidylinositol TRIVIAL 23568455 T 21 41 Phosphatidylinositol TRIVIAL 23568508 A 292 298 oxygen SYSTEMATIC 23568508 A 30 59 Rhenium(I) indolato complexes FAMILY 23568508 T 0 7 Rhenium SYSTEMATIC 23568512 A 0 10 Acrylamide TRIVIAL 23568512 A 1025 1031 AA-GSH ABBREVIATION 23568512 A 1037 1041 AAMA ABBREVIATION 23568512 A 1047 1051 GAMA ABBREVIATION 23568512 A 1129 1138 N7-GA-Gua FORMULA 23568512 A 1273 1279 AA-GSH ABBREVIATION 23568512 A 1509 1515 AA-GSH ABBREVIATION 23568512 A 1594 1603 N7-GA-Gua FORMULA 23568512 A 191 204 carbohydrates FAMILY 23568512 A 209 219 asparagine TRIVIAL 23568512 A 360 371 glycidamide TRIVIAL 23568512 A 447 485 N7-(2-carbamoyl-2-hydroxyethyl)guanine SYSTEMATIC 23568512 A 487 496 N7-GA-Gua FORMULA 23568512 A 613 624 glutathione TRIVIAL 23568512 A 626 629 GSH ABBREVIATION 23568512 A 636 639 GSH ABBREVIATION 23568512 A 711 728 mercapturic acids FAMILY 23568512 A 735 772 N-acetyl-S-(2-carbamoylethyl)cysteine SYSTEMATIC 23568512 A 774 778 AAMA ABBREVIATION 23568512 A 785 832 N-acetyl-S-(2-hydroxy-2-carbamoylethyl)cysteine SYSTEMATIC 23568512 A 834 838 GAMA ABBREVIATION 23568512 T 110 121 glycidamide TRIVIAL 23568512 T 18 28 acrylamide TRIVIAL 23568512 T 69 80 glutathione TRIVIAL 23568578 A 1022 1031 glutamine TRIVIAL 23568578 A 1097 1101 GABA ABBREVIATION 23568578 A 1103 1112 glutamine TRIVIAL 23568578 A 1118 1127 glutamate TRIVIAL 23568578 A 1202 1211 threonine TRIVIAL 23568578 A 1293 1300 alanine TRIVIAL 23568578 A 1460 1464 GABA ABBREVIATION 23568578 A 29 48 γ-aminobutyric acid SYSTEMATIC 23568578 A 419 430 amino acids FAMILY 23568578 A 50 54 GABA ABBREVIATION 23568578 A 716 726 amino acid FAMILY 23568578 A 860 864 GABA ABBREVIATION 23568578 A 929 938 glutamine TRIVIAL 23568578 T 29 40 amino acids FAMILY 23568579 A 1053 1060 cocaine TRIVIAL 23568579 A 1189 1196 cocaine TRIVIAL 23568579 A 1271 1278 cocaine TRIVIAL 23568579 A 1473 1480 cocaine TRIVIAL 23568579 A 1562 1569 cocaine TRIVIAL 23568579 A 203 210 cocaine TRIVIAL 23568579 A 508 515 cocaine TRIVIAL 23568579 A 571 578 cocaine TRIVIAL 23568579 A 98 105 cocaine TRIVIAL 23568579 T 22 29 cocaine TRIVIAL 23570266 A 51 57 silica TRIVIAL 23570266 T 40 46 silica TRIVIAL 23570328 A 275 292 4-acetamido-TEMPO SYSTEMATIC 23570328 A 303 308 TEMPO ABBREVIATION 23570328 A 311 347 2,2,6,6-tetramethylpiperidine-N-oxyl SYSTEMATIC 23570328 A 369 373 HNO3 FORMULA 23570328 A 378 381 HCl FORMULA 23570328 A 511 514 C-C FORMULA 23570328 A 86 103 benzylic alcohols FAMILY 23570394 A 268 276 graphene TRIVIAL 23570394 A 290 292 Ru FORMULA 23570394 A 322 330 graphene TRIVIAL 23570394 A 334 337 SiC FORMULA 23570394 A 339 340 O FORMULA 23570394 A 341 343 Ru FORMULA 23570394 A 354 358 SiO2 FORMULA 23570394 A 359 361 Ru FORMULA 23570394 A 397 399 Ru FORMULA 23570394 A 410 417 Pt(111) FORMULA 23570394 A 527 529 Ru FORMULA 23570394 A 594 596 Ru FORMULA 23570394 A 597 598 C FORMULA 23570394 A 61 69 graphene TRIVIAL 23570394 A 643 645 Ru FORMULA 23570394 A 707 715 graphene TRIVIAL 23570394 A 768 776 graphene TRIVIAL 23570394 T 39 47 Graphene TRIVIAL 23570451 A 285 310 poly(methyl methacrylate) SYSTEMATIC 23570451 A 312 316 PMMA ABBREVIATION 23570451 A 355 362 acetone SYSTEMATIC 23570500 A 1102 1106 (1)H FORMULA 23570500 A 1191 1196 PEO45 ABBREVIATION 23570500 A 1251 1256 PEO45 ABBREVIATION 23570500 A 1437 1448 doxorubicin TRIVIAL 23570500 A 1450 1453 DOX ABBREVIATION 23570500 A 1474 1500 fluorescein isothiocyanate TRIVIAL 23570500 A 1511 1515 FITC ABBREVIATION 23570500 A 1620 1624 FITC ABBREVIATION 23570500 A 1633 1636 DOX ABBREVIATION 23570500 A 164 209 trans-N-(2-ethoxy-1,3-dioxan-5-yl) acrylamide SYSTEMATIC 23570500 A 1802 1805 DOX ABBREVIATION 23570500 A 211 215 tNEA ABBREVIATION 23570500 A 225 245 poly(ethylene oxide) SYSTEMATIC 23570500 A 247 252 PEO45 ABBREVIATION 23570500 A 570 575 PtNEA ABBREVIATION 23570500 A 62 67 PEO45 ABBREVIATION 23570500 A 735 740 PtNEA ABBREVIATION 23570500 A 848 853 PtNEA ABBREVIATION 23570514 A 41 47 NAD(+) ABBREVIATION 23570514 A 683 694 carboxamide SYSTEMATIC 23570514 A 708 720 nicotinamide TRIVIAL 23570514 T 13 51 Thieno[3,2-d]pyrimidine-6-carboxamides FAMILY 23570533 A 1093 1099 Quartz TRIVIAL 23570533 A 171 177 lignin FAMILY 23570533 A 561 593 dodecyl 3,4,5-trihydroxybenzoate SYSTEMATIC 23570533 A 595 601 HB-C12 ABBREVIATION 23570533 A 821 827 HB-C12 ABBREVIATION 23570533 A 974 980 HB-C12 ABBREVIATION 23570552 A 0 14 Cinnamaldehyde TRIVIAL 23570552 A 434 448 cinnamaldehyde TRIVIAL 23570552 A 518 532 cinnamaldehyde TRIVIAL 23570552 A 628 642 Cinnamaldehyde TRIVIAL 23570552 T 25 39 Cinnamaldehyde TRIVIAL 23570561 A 358 362 urea TRIVIAL 23570561 A 791 795 urea TRIVIAL 23570561 T 39 43 Urea TRIVIAL 23570609 A 1076 1083 PEG-LαC ABBREVIATION 23570609 A 1236 1243 PEG-LαC ABBREVIATION 23570609 A 178 192 α-cyclodextrin TRIVIAL 23570609 A 194 213 polyethylene glycol SYSTEMATIC 23570609 A 215 218 PEG ABBREVIATION 23570609 A 249 256 lactose TRIVIAL 23570609 A 258 266 PEG-LαCs ABBREVIATION 23570609 A 350 357 PEG-LαC ABBREVIATION 23570609 A 394 397 PEG ABBREVIATION 23570609 A 464 472 PEG-LαCs ABBREVIATION 23570609 A 685 692 PEG-LαC ABBREVIATION 23570609 A 75 89 polyamidoamine FAMILY 23570609 A 779 793 α-cyclodextrin TRIVIAL 23570609 A 833 842 Lac-α-CDE ABBREVIATION 23570609 A 869 872 PEG ABBREVIATION 23570609 A 934 941 PEG-LαC ABBREVIATION 23570609 T 25 39 polyamidoamine FAMILY 23570609 T 65 68 PEG ABBREVIATION 23570609 T 70 84 α-cyclodextrin TRIVIAL 23570609 T 89 96 lactose TRIVIAL 23570839 A 227 235 n-hexane SYSTEMATIC 23570839 A 237 242 CHCl3 FORMULA 23570839 A 244 249 AcOEt FORMULA 23570839 A 251 256 CH3OH FORMULA 23570839 A 27 35 coumarin TRIVIAL 23570839 A 54 69 Daphneretusin A TRIVIAL 23570839 A 74 89 Daphneretusin B TRIVIAL 23570839 T 25 33 coumarin TRIVIAL 23570840 A 223 231 methanol SYSTEMATIC 23570840 A 266 274 n-hexane SYSTEMATIC 23570840 A 276 286 chloroform TRIVIAL 23570840 A 291 298 butanol SYSTEMATIC 23570840 A 386 413 goniolandrene-A (1), -B (2) MULTIPLE 23570840 A 445 460 goniolandrene B TRIVIAL 23570840 A 601 614 Goniothalamin TRIVIAL 23570840 T 0 21 Goniolandrene A and B MULTIPLE 23570914 A 1110 1138 caffeic acid phenethyl ester SYSTEMATIC 23570914 A 1168 1177 bleomycin FAMILY 23570914 A 380 389 bleomycin FAMILY 23570914 A 551 561 superoxide TRIVIAL 23570914 A 596 607 glutathione TRIVIAL 23570914 A 612 631 thiobarbituric acid SYSTEMATIC 23570914 A 682 691 bleomycin FAMILY 23570914 A 809 815 oxygen SYSTEMATIC 23570914 A 947 956 bleomycin FAMILY 23570914 T 116 125 bleomycin FAMILY 23570992 A 1046 1060 hydroxysteroid FAMILY 23570992 A 1147 1154 arsenic SYSTEMATIC 23570992 A 1234 1241 arsenic SYSTEMATIC 23570992 A 150 157 arsenic SYSTEMATIC 23570992 A 242 249 arsenic SYSTEMATIC 23570992 A 460 467 arsenic SYSTEMATIC 23570992 A 556 571 sodium arsenite SYSTEMATIC 23570992 A 94 101 arsenic SYSTEMATIC 23570992 T 22 29 Arsenic SYSTEMATIC 23570993 A 37 43 carbon SYSTEMATIC 23570993 T 108 114 Carbon SYSTEMATIC 23570998 A 0 9 Quercetin TRIVIAL 23570998 A 1166 1176 flavonoids FAMILY 23570998 A 1182 1187 rutin TRIVIAL 23570998 A 1192 1201 quercetin TRIVIAL 23570998 A 14 19 rutin TRIVIAL 23570998 A 141 151 flavonoids FAMILY 23570998 A 31 41 flavonoids FAMILY 23570998 A 373 383 flavonoids FAMILY 23570998 A 385 394 quercetin TRIVIAL 23570998 A 399 404 rutin TRIVIAL 23570998 A 456 465 quercetin TRIVIAL 23570998 A 470 475 rutin TRIVIAL 23570998 A 538 547 quercetin TRIVIAL 23570998 A 552 557 rutin TRIVIAL 23570998 A 704 713 Quercetin TRIVIAL 23570998 A 718 723 rutin TRIVIAL 23570998 A 928 938 flavonoids FAMILY 23570998 T 26 36 flavonoids FAMILY 23571415 A 634 652 sodium fluorescein SYSTEMATIC 23572409 A 0 12 Pomalidomide TRIVIAL 23572409 A 1010 1022 pomalidomide TRIVIAL 23572409 A 14 22 Pomalyst TRIVIAL 23572409 A 187 199 Pomalidomide TRIVIAL 23572409 A 286 299 dexamethasone TRIVIAL 23572409 A 432 444 lenalidomide TRIVIAL 23572409 A 449 459 bortezomib TRIVIAL 23572409 A 488 500 pomalidomide TRIVIAL 23572409 A 59 70 thalidomide TRIVIAL 23572409 A 754 766 Pomalidomide TRIVIAL 23572409 T 0 12 Pomalidomide TRIVIAL 23572520 A 0 1 S FORMULA 23572520 A 1051 1052 S FORMULA 23572520 A 1127 1130 GSH ABBREVIATION 23572520 A 1146 1148 NO FORMULA 23572520 A 1207 1209 NO FORMULA 23572520 A 1248 1250 NO FORMULA 23572520 A 1264 1276 nitric oxide SYSTEMATIC 23572520 A 430 441 glutathione TRIVIAL 23572520 A 555 556 S FORMULA 23572520 A 62 70 cysteine TRIVIAL 23572520 A 730 731 S FORMULA 23572520 A 998 1003 CysNO FORMULA 23572520 T 0 1 S FORMULA 23572520 T 17 28 glutathione TRIVIAL 23573957 A 24 34 E-stilbene TRIVIAL 23573957 A 281 292 prolinamide TRIVIAL 23573957 A 35 47 prolinamides FAMILY 23573990 A 1015 1018 PEO ABBREVIATION 23573990 A 102 120 polyethylene oxide SYSTEMATIC 23573990 A 1147 1150 PEO ABBREVIATION 23573990 A 122 125 PEO ABBREVIATION 23573990 A 177 180 sPS ABBREVIATION 23573990 A 348 351 sPS ABBREVIATION 23573990 A 44 68 syndiotactic polystyrene FAMILY 23573990 A 445 448 sPS ABBREVIATION 23573990 A 500 515 tetrahydrofuran SYSTEMATIC 23573990 A 535 538 PEO ABBREVIATION 23573990 A 674 682 nitrogen SYSTEMATIC 23573990 A 70 73 sPS ABBREVIATION 23573990 A 707 713 helium SYSTEMATIC 23573990 A 889 892 PEO ABBREVIATION 23573990 A 981 984 sPS ABBREVIATION 23573990 T 50 74 syndiotactic polystyrene FAMILY 23574008 A 1088 1099 C4-C-N-PEG9 NO CLASS 23574008 A 1200 1211 C4-C-N-PEG9 NO CLASS 23574008 A 1278 1289 C4-C-N-PEG9 NO CLASS 23574008 A 1343 1349 C12EO4 FORMULA 23574008 A 1363 1374 C4-C-N-PEG9 NO CLASS 23574008 A 1582 1593 C4-C-N-PEG9 NO CLASS 23574008 A 1621 1629 coumarin TRIVIAL 23574008 A 1657 1672 polyoxyethylene SYSTEMATIC 23574008 A 1758 1766 coumarin TRIVIAL 23574008 A 1803 1814 C4-C-N-PEG9 NO CLASS 23574008 A 187 195 coumarin TRIVIAL 23574008 A 1924 1939 polyoxyethylene SYSTEMATIC 23574008 A 1990 1997 PhyEO20 FORMULA 23574008 A 208 233 7-butoxy-2H-chromen-2-one SYSTEMATIC 23574008 A 251 266 polyoxyethylene SYSTEMATIC 23574008 A 314 325 C4-C-N-PEG9 NO CLASS 23574008 A 33 46 cinnamic acid TRIVIAL 23574008 A 444 477 polyoxyethylene phytosterol ether SYSTEMATIC 23574008 A 479 486 PhyEO20 FORMULA 23574008 A 492 522 tetraoxyethylene dodecyl ether SYSTEMATIC 23574008 A 524 530 C12EO4 FORMULA 23574008 A 546 553 PhyEO20 FORMULA 23574008 A 554 557 H2O FORMULA 23574008 A 569 575 C12EO4 FORMULA 23574008 A 676 687 C4-C-N-PEG9 NO CLASS 23574008 A 79 90 C4-C-N-PEG9 NO CLASS 23574008 A 798 809 C4-C-N-PEG9 NO CLASS 23574008 A 860 871 C4-C-N-PEG9 NO CLASS 23574008 A 899 910 C4-C-N-PEG9 NO CLASS 23574008 A 982 993 C4-C-N-PEG9 NO CLASS 23574014 A 147 151 DTPA ABBREVIATION 23574014 A 153 187 diethylenetriaminepentaacetic acid SYSTEMATIC 23574014 A 215 224 maleimide SYSTEMATIC 23574014 A 585 594 maleimide SYSTEMATIC 23574014 A 62 85 poly(N-alkylacrylamide) SYSTEMATIC 23574534 A 115 119 SnO2 FORMULA 23574534 A 1323 1327 SnO2 FORMULA 23574534 A 1448 1452 SnO2 FORMULA 23574534 A 254 256 He FORMULA 23574534 A 257 259 Cd FORMULA 23574534 A 326 330 SnO2 FORMULA 23574534 A 478 482 SnO2 FORMULA 23574534 A 689 693 SnO2 FORMULA 23574534 A 934 938 SnO2 FORMULA 23574534 T 71 75 SnO2 FORMULA 23574984 A 526 537 acetic acid SYSTEMATIC 23574984 A 688 704 prostaglandin E2 TRIVIAL 23574984 A 706 710 PGE2 ABBREVIATION 23574984 A 825 833 Naloxone TRIVIAL 23575765 A 1301 1307 carbon SYSTEMATIC 23575765 A 437 440 ZnO FORMULA 23575765 A 644 654 zinc oxide SYSTEMATIC 23575765 A 655 661 silver SYSTEMATIC 23575765 A 66 82 indium tin oxide SYSTEMATIC 23575765 A 84 87 ITO ABBREVIATION 23575765 A 848 858 zinc oxide SYSTEMATIC 23575765 T 19 29 zinc oxide SYSTEMATIC 23575765 T 42 48 silver SYSTEMATIC 23576174 A 27 49 dimeric alkenylphenols FAMILY 23576174 A 490 505 sarmentosumol A TRIVIAL 23576174 A 58 79 sarmentosumols A to F MULTIPLE 23576174 T 0 21 Sarmentosumols A to F MULTIPLE 23576174 T 27 59 Mono- and Dimeric Alkenylphenols MULTIPLE 23576286 A 114 150 oligo(poly(ethylene glycol)fumarate) SYSTEMATIC 23576286 A 152 155 OPF ABBREVIATION 23576286 A 212 236 calcium glycerophosphate SYSTEMATIC 23576286 A 238 243 Ca-GP FORMULA 23576286 A 471 483 alizarin red TRIVIAL 23576286 A 600 607 calcium SYSTEMATIC 23576286 A 883 895 alizarin red TRIVIAL 23576286 T 58 94 Oligo(poly(ethylene glycol) Fumarate SYSTEMATIC 23576297 A 172 174 Pd FORMULA 23576297 A 192 201 porphyrin FAMILY 23576297 A 340 351 formic acid SYSTEMATIC 23576297 A 47 49 Pd FORMULA 23576297 A 75 84 porphyrin FAMILY 23576297 T 36 45 Palladium SYSTEMATIC 23576297 T 59 68 Porphyrin FAMILY 23576297 T 82 93 Formic Acid SYSTEMATIC 23576306 A 0 19 Tetramethylammonium SYSTEMATIC 23576306 A 130 136 amines FAMILY 23576306 A 142 157 methyl acrylate SYSTEMATIC 23576306 A 228 257 tetramethylammonium hydroxide SYSTEMATIC 23576306 A 263 266 CO2 FORMULA 23576306 A 346 349 CO2 FORMULA 23576306 A 382 389 alcohol FAMILY 23576306 A 400 406 (13) C FORMULA 23576306 A 467 470 CO2 FORMULA 23576306 A 49 61 β-amino acid FAMILY 23576306 A 497 500 CO2 FORMULA 23576306 A 575 586 bicarbonate SYSTEMATIC 23576306 A 616 637 hydroxyethylcarbonate SYSTEMATIC 23576306 A 642 657 methylcarbonate SYSTEMATIC 23576306 A 683 698 ethylene glycol SYSTEMATIC 23576306 A 703 711 methanol SYSTEMATIC 23576306 A 768 779 carboxylate SYSTEMATIC 23576306 A 854 857 CO2 FORMULA 23576306 A 874 882 hydrogen SYSTEMATIC 23576306 A 913 921 hydrogen SYSTEMATIC 23576306 A 935 940 amino FAMILY 23576306 T 0 11 Carboxylate SYSTEMATIC 23576306 T 103 115 β-Amino Acid FAMILY 23576306 T 34 48 Alkylcarbonate FAMILY 23576306 T 62 65 CO2 FORMULA 23576306 T 70 89 Tetramethylammonium SYSTEMATIC 23576341 A 1087 1095 biphenyl SYSTEMATIC 23576341 A 1379 1387 biphenyl SYSTEMATIC 23576341 A 300 308 biphenyl SYSTEMATIC 23576341 A 34 37 ATP ABBREVIATION 23576341 A 439 442 MTT ABBREVIATION 23576341 A 445 509 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide SYSTEMATIC 23576341 A 674 682 biphenyl SYSTEMATIC 23576341 A 787 795 biphenyl SYSTEMATIC 23576341 A 901 905 urea TRIVIAL 23576341 T 28 36 biphenyl SYSTEMATIC 23576355 A 10 21 tirucallane TRIVIAL 23576355 A 104 157 (23R,24S)-23,24,25-trihydroxytirucall-7-ene-3,6-dione SYSTEMATIC 23576355 A 163 175 piscidinol A TRIVIAL 23576355 A 181 199 24-epipiscidinol A SYSTEMATIC 23576355 A 205 226 21α-methylmelianodiol SYSTEMATIC 23576355 A 22 35 triterpenoids FAMILY 23576355 A 236 257 21β-methylmelianodiol SYSTEMATIC 23576355 A 285 289 EtOH FORMULA 23576355 A 37 53 brumollisols A-C MULTIPLE 23576355 A 696 698 NO FORMULA 23576355 T 0 11 Tirucallane TRIVIAL 23576355 T 12 25 Triterpenoids FAMILY 23576378 A 180 191 methicillin TRIVIAL 23576378 A 232 242 gentamicin FAMILY 23576378 A 25 43 demethylvancomycin SYSTEMATIC 23576378 A 282 293 methicillin TRIVIAL 23576378 A 340 350 vancomycin TRIVIAL 23576378 A 427 463 N-(6-phenylheptyl)demethylvancomycin SYSTEMATIC 23576378 A 533 543 vancomycin TRIVIAL 23576378 A 548 566 demethylvancomycin SYSTEMATIC 23576378 A 634 644 vancomycin TRIVIAL 23576378 A 870 880 vancomycin TRIVIAL 23576378 T 49 67 Demethylvancomycin SYSTEMATIC 23577042 A 147 153 biotin TRIVIAL 23577589 A 904 911 glucose TRIVIAL 23577701 A 138 147 friedelin TRIVIAL 23577701 A 153 165 apetalactone TRIVIAL 23577701 A 171 183 inophyllum C TRIVIAL 23577701 A 192 203 canophyllol TRIVIAL 23577701 A 24 46 α-hydroxytomentolide A TRIVIAL 23577701 A 298 302 (1)H FORMULA 23577701 A 308 313 (13)C FORMULA 23577701 A 6 22 dipyranocoumarin FAMILY 23577701 T 4 20 dipyranocoumarin FAMILY 23577749 A 545 556 gallic acid TRIVIAL 23577749 A 829 839 terpenoids FAMILY 23577749 A 841 848 phenols FAMILY 23577749 A 853 863 flavonoids FAMILY 23577749 A 879 887 phenolic FAMILY 23577749 A 902 912 flavonoids FAMILY 23578584 A 764 767 ATP ABBREVIATION 23578584 A 775 782 calcium SYSTEMATIC 23578610 A 886 895 baicalein TRIVIAL 23578623 A 551 555 NaCl FORMULA 23578627 A 0 25 3,4-Dihydroxyphenylglycol SYSTEMATIC 23578627 A 1008 1017 β-hydroxy SYSTEMATIC 23578627 A 1033 1045 verbascoside TRIVIAL 23578627 A 1050 1065 isoverbascoside TRIVIAL 23578627 A 1067 1085 β-hydroxyacteoside SYSTEMATIC 23578627 A 1090 1111 β-hydroxyisoacteoside SYSTEMATIC 23578627 A 1118 1138 2″-hydroxyoleuropein SYSTEMATIC 23578627 A 1163 1167 DHPG ABBREVIATION 23578627 A 120 124 DHPG ABBREVIATION 23578627 A 1242 1250 phenolic FAMILY 23578627 A 255 259 DHPG ABBREVIATION 23578627 A 27 31 DHPG ABBREVIATION 23578627 A 440 444 DHPG ABBREVIATION 23578627 A 528 532 DHPG ABBREVIATION 23578627 T 53 85 phenol 3,4-dihydroxyphenylglycol SYSTEMATIC 23578632 A 0 11 Polyphenols FAMILY 23578632 A 1070 1081 polyphenols FAMILY 23578632 A 115 149 omega-3 polyunsaturated fatty acid FAMILY 23578632 A 1176 1188 α-tocopherol TRIVIAL 23578632 A 1190 1214 butylated hydroxytoluene SYSTEMATIC 23578632 A 151 158 ω3 PUFA ABBREVIATION 23578632 A 310 317 ethanol SYSTEMATIC 23578632 A 558 564 ferric SYSTEMATIC 23578632 A 603 632 1,1-diphenyl-2-picrylhydrazyl SYSTEMATIC 23578632 A 642 646 DPPH ABBREVIATION 23578632 A 722 741 thiobarbituric acid SYSTEMATIC 23578632 A 777 788 Polyphenols FAMILY 23578632 A 872 879 DPPH(·) ABBREVIATION 23578633 A 236 261 perfluorooctane sulfonate SYSTEMATIC 23578633 A 263 267 PFOS ABBREVIATION 23578633 A 273 295 perfluorooctanoic acid SYSTEMATIC 23578633 A 297 301 PFOA ABBREVIATION 23578633 A 435 439 PFOS ABBREVIATION 23578633 A 509 513 PFOA ABBREVIATION 23578633 A 558 562 PFOS ABBREVIATION 23578633 A 829 833 PFOS ABBREVIATION 23578633 T 25 54 perfluorooctane sulfonic acid SYSTEMATIC 23578633 T 56 60 PFOS ABBREVIATION 23578633 T 66 88 perfluorooctanoic acid SYSTEMATIC 23578633 T 90 94 PFOA ABBREVIATION 23578634 A 344 348 NaCl FORMULA 23578634 A 350 353 KCl FORMULA 23578634 A 355 368 Ca-propionate SYSTEMATIC 23578634 A 373 409 FeNa-ethylenediaminetetraacetic acid SYSTEMATIC 23578634 A 411 420 FeNa-EDTA FORMULA 23578634 A 805 809 NaCl FORMULA 23578636 A 1209 1218 alcoholic FAMILY 23578636 A 1268 1275 alcohol FAMILY 23578636 A 1475 1487 Anthocyanins FAMILY 23578636 A 1567 1574 tannins FAMILY 23578636 A 684 692 phenolic FAMILY 23578642 A 256 273 ammonium sulphate SYSTEMATIC 23578643 A 1085 1090 5-HMF SYSTEMATIC 23578643 A 139 146 glucose TRIVIAL 23578643 A 235 242 glucose TRIVIAL 23578643 A 329 335 oxygen SYSTEMATIC 23578643 A 518 525 glucose TRIVIAL 23578643 A 552 557 5-HMF SYSTEMATIC 23578643 A 622 629 glucose TRIVIAL 23578643 A 66 71 5-HMF SYSTEMATIC 23578643 A 703 708 5-HMF SYSTEMATIC 23578643 A 732 739 glucose TRIVIAL 23578643 A 879 886 glucose TRIVIAL 23578643 A 994 1001 glucose TRIVIAL 23578643 T 10 33 5-hydroxymethylfurfural SYSTEMATIC 23578643 T 102 109 glucose TRIVIAL 23578651 A 144 160 ethylenethiourea SYSTEMATIC 23578651 A 162 165 ETU ABBREVIATION 23578651 A 286 289 ETU ABBREVIATION 23578651 A 331 339 methanol SYSTEMATIC 23578651 A 355 362 alumina TRIVIAL 23578651 T 30 46 ethylenethiourea SYSTEMATIC 23578651 T 76 84 methanol SYSTEMATIC 23578652 A 303 313 superoxide TRIVIAL 23578652 A 321 334 peroxynitrite SYSTEMATIC 23578652 A 346 353 peroxyl SYSTEMATIC 23578652 A 432 440 hydroxyl SYSTEMATIC 23578652 A 476 482 oxygen SYSTEMATIC 23578652 A 682 696 S-allylcystein SYSTEMATIC 23578652 A 85 99 hydroethanolic FAMILY 23578652 A 851 855 NMDA ABBREVIATION 23578652 A 949 952 ATP ABBREVIATION 23578652 T 38 52 hydroethanolic FAMILY 23578690 A 131 136 amine SYSTEMATIC 23578690 A 49 55 oxygen SYSTEMATIC 23578690 A 835 846 doxorubicin TRIVIAL 23578690 A 851 861 cytarabine TRIVIAL 23578690 T 37 51 tethered amine FAMILY 23578763 A 498 508 prednisone TRIVIAL 23578968 A 1052 1056 MEHP ABBREVIATION 23578968 A 1154 1161 steroid FAMILY 23578968 A 123 135 testosterone TRIVIAL 23578968 A 1283 1292 phthalate FAMILY 23578968 A 185 195 phthalates FAMILY 23578968 A 197 201 MEHP ABBREVIATION 23578968 A 203 206 MBP ABBREVIATION 23578968 A 222 232 phthalates FAMILY 23578968 A 234 237 MMP ABBREVIATION 23578968 A 242 245 MEP ABBREVIATION 23578968 A 373 385 testosterone TRIVIAL 23578968 A 438 441 MBP ABBREVIATION 23578968 A 450 454 MEHP ABBREVIATION 23578968 A 462 465 MEP ABBREVIATION 23578968 A 470 473 MMP ABBREVIATION 23578968 A 503 515 testosterone TRIVIAL 23578968 A 610 622 testosterone TRIVIAL 23578968 A 637 640 MBP ABBREVIATION 23578968 A 645 649 MEHP ABBREVIATION 23578968 A 804 814 monoesters FAMILY 23578968 A 844 848 MEHP ABBREVIATION 23578968 A 850 860 Monoesters FAMILY 23578968 A 883 890 carbons FAMILY 23578968 A 929 941 testosterone TRIVIAL 23578968 A 964 970 carbon SYSTEMATIC 23578968 T 80 96 phthalate esters FAMILY 23579044 A 1097 1104 cocaine TRIVIAL 23579044 A 1168 1171 MPD ABBREVIATION 23579044 A 1224 1231 cocaine TRIVIAL 23579044 A 1288 1295 cocaine TRIVIAL 23579044 A 1348 1351 MPD ABBREVIATION 23579044 A 1423 1430 cocaine TRIVIAL 23579044 A 153 160 cocaine TRIVIAL 23579044 A 1589 1592 MPD ABBREVIATION 23579044 A 1639 1648 monoamine FAMILY 23579044 A 1658 1671 d-amphetamine TRIVIAL 23579044 A 1736 1745 monoamine FAMILY 23579044 A 1769 1772 MPD ABBREVIATION 23579044 A 1793 1800 cocaine TRIVIAL 23579044 A 293 306 d-amphetamine TRIVIAL 23579044 A 320 327 cocaine TRIVIAL 23579044 A 427 442 methylphenidate SYSTEMATIC 23579044 A 444 447 MPD ABBREVIATION 23579044 A 501 508 cocaine TRIVIAL 23579044 A 598 605 cocaine TRIVIAL 23579044 A 65 73 dopamine TRIVIAL 23579044 A 755 762 cocaine TRIVIAL 23579044 A 83 97 norepinephrine TRIVIAL 23579044 A 858 865 cocaine TRIVIAL 23579044 A 991 994 MPD ABBREVIATION 23579044 T 19 34 methylphenidate SYSTEMATIC 23579044 T 38 45 cocaine TRIVIAL 23579182 A 643 644 N FORMULA 23579333 A 144 163 potassium phosphate SYSTEMATIC 23579333 A 208 210 Co FORMULA 23579333 A 211 213 Ni FORMULA 23579333 A 291 293 Co FORMULA 23579333 A 294 296 Ni FORMULA 23579333 A 297 306 hydroxide SYSTEMATIC 23579333 A 322 328 iodine SYSTEMATIC 23579333 A 34 36 Co FORMULA 23579333 A 37 39 Ni FORMULA 23579333 A 423 430 Co(iii) FORMULA 23579333 A 431 440 hydroxide SYSTEMATIC 23579333 A 55 65 hydroxides FAMILY 23579333 A 633 635 Co FORMULA 23579333 A 636 638 Ni FORMULA 23579333 A 782 788 oxygen SYSTEMATIC 23579333 A 852 854 Co FORMULA 23579333 A 855 857 Ni FORMULA 23579333 A 900 902 Co FORMULA 23579333 T 0 2 Co FORMULA 23579333 T 21 31 hydroxides FAMILY 23579333 T 3 5 Ni FORMULA 23579427 A 1011 1018 alcohol FAMILY 23579427 A 1044 1051 alcohol FAMILY 23579427 A 1134 1141 alcohol FAMILY 23579427 A 1217 1224 alcohol FAMILY 23579427 A 1307 1314 alcohol FAMILY 23579427 A 1428 1435 alcohol FAMILY 23579427 A 1493 1500 alcohol FAMILY 23579427 A 1614 1621 alcohol FAMILY 23579427 A 326 333 alcohol FAMILY 23579427 A 363 370 alcohol FAMILY 23579427 A 39 46 alcohol FAMILY 23579427 A 446 453 alcohol FAMILY 23579427 A 459 466 alcohol FAMILY 23579427 A 779 786 alcohol FAMILY 23579427 A 875 882 alcohol FAMILY 23579427 T 6 13 alcohol FAMILY 23579427 T 65 72 alcohol FAMILY 23579486 A 1084 1089 RU486 IDENTIFIER 23579486 A 1104 1109 APR19 IDENTIFIER 23579486 A 1159 1165 serine TRIVIAL 23579486 A 1347 1359 progesterone TRIVIAL 23579486 A 1361 1366 APR19 IDENTIFIER 23579486 A 1398 1406 hydrogen SYSTEMATIC 23579486 A 1543 1548 APR19 IDENTIFIER 23579486 A 1554 1559 RU486 IDENTIFIER 23579486 A 20 32 progesterone TRIVIAL 23579486 A 529 540 homosteroid FAMILY 23579486 A 541 546 APR19 IDENTIFIER 23579486 A 604 609 APR19 IDENTIFIER 23579486 A 619 631 progesterone TRIVIAL 23579486 A 68 80 mifepristone TRIVIAL 23579486 A 788 795 steroid FAMILY 23579486 A 82 87 RU486 IDENTIFIER 23579486 A 948 953 APR19 IDENTIFIER 23579486 T 42 54 Progesterone TRIVIAL 23579487 A 192 199 glucose TRIVIAL 23579487 A 933 953 phosphatidylinositol TRIVIAL 23580169 A 1035 1043 europium SYSTEMATIC 23580169 A 1198 1200 Eu FORMULA 23580169 A 191 193 Eu FORMULA 23580169 A 363 371 europium SYSTEMATIC 23580169 A 383 395 (Ca,Eu)2SiS4 FORMULA 23580169 A 42 50 europium SYSTEMATIC 23580169 A 57 64 Ca2SiS4 FORMULA 23580169 A 582 590 europium SYSTEMATIC 23580169 A 652 660 europium SYSTEMATIC 23580169 A 781 789 europium SYSTEMATIC 23580169 A 833 835 Ca FORMULA 23580169 A 960 978 monoclinic Eu2SiS4 FORMULA 23580169 T 31 33 Eu FORMULA 23580169 T 45 57 thiosilicate SYSTEMATIC 23580257 A 274 287 dexamethasone TRIVIAL 23580257 A 446 457 hematoxylin TRIVIAL 23580257 A 462 467 eosin FAMILY 23580257 A 70 78 baicalin TRIVIAL 23580257 T 26 34 Baicalin TRIVIAL 23580402 A 1281 1287 sodium SYSTEMATIC 23580402 A 1336 1342 sugars FAMILY 23580402 A 1344 1355 cholesterol TRIVIAL 23580402 A 837 846 vitamin C TRIVIAL 23580402 A 848 857 vitamin E FAMILY 23580402 A 863 873 β-carotene TRIVIAL 23580402 A 879 883 zinc SYSTEMATIC 23580404 A 0 3 PbS FORMULA 23580404 A 473 476 PbS FORMULA 23580404 T 78 81 PbS FORMULA 23580421 A 41 45 MnO2 FORMULA 23580421 T 53 67 Graphene Oxide SYSTEMATIC 23580421 T 68 85 Manganese Dioxide SYSTEMATIC 23580652 A 839 846 glycine TRIVIAL 23580652 A 861 874 aspartic acid TRIVIAL 23580652 A 915 922 calcium SYSTEMATIC 23581295 A 146 150 VCl4 FORMULA 23581295 A 156 168 superhydride TRIVIAL 23581295 A 170 177 LiBHEt3 FORMULA 23581295 A 198 220 4-octylphenyldiazonium SYSTEMATIC 23581295 A 415 423 V-N═N-Ar FORMULA 23581295 A 48 70 4-octylphenyldiazenido SYSTEMATIC 23581295 A 9 17 vanadium SYSTEMATIC 23581295 T 13 22 diazenido SYSTEMATIC 23581295 T 31 39 vanadium SYSTEMATIC 23581492 A 1164 1171 Arg-Arg FORMULA 23581492 A 1243 1250 Arg-Arg FORMULA 23581492 A 1264 1275 Arg-Arg-Asp FORMULA 23581492 A 1276 1279 Glu FORMULA 23581492 A 135 143 arginine TRIVIAL 23581492 A 144 152 arginine TRIVIAL 23581492 A 1457 1464 Arg-Arg FORMULA 23581492 A 154 161 Arg-Arg FORMULA 23581492 A 178 184 carbon SYSTEMATIC 23581492 A 187 193 carbon SYSTEMATIC 23581492 A 248 255 Arg-Arg FORMULA 23581492 A 454 461 Arg-Arg FORMULA 23581492 A 501 508 Arg-Arg FORMULA 23581492 A 561 572 Arg-Arg-Asp FORMULA 23581492 A 573 576 Glu FORMULA 23581492 A 720 727 Arg-Arg FORMULA 23581492 A 950 957 Arg-Arg FORMULA 23581492 T 52 70 acidic amino acids FAMILY 23581492 T 74 82 arginine TRIVIAL 23581492 T 83 91 arginine TRIVIAL 23581965 A 1173 1181 hematite TRIVIAL 23581965 A 1203 1206 ATO ABBREVIATION 23581965 A 222 230 hematite TRIVIAL 23581965 A 310 321 polystyrene SYSTEMATIC 23581965 A 48 72 antimony-doped tin oxide SYSTEMATIC 23581965 A 559 564 oxide SYSTEMATIC 23581965 A 572 580 hematite TRIVIAL 23581965 A 77 80 ATO ABBREVIATION 23581965 A 813 821 hematite TRIVIAL 23581965 A 936 939 ATO ABBREVIATION 23581965 A 979 987 hematite TRIVIAL 23581965 T 48 72 Antimony-Doped Tin Oxide SYSTEMATIC 23581965 T 9 17 Hematite TRIVIAL 23581993 A 222 225 ATP ABBREVIATION 23581993 A 818 824 carbon SYSTEMATIC 23582235 A 1066 1070 zinc SYSTEMATIC 23582235 A 1138 1142 zinc SYSTEMATIC 23582235 A 1178 1182 zinc SYSTEMATIC 23582235 A 1401 1405 zinc SYSTEMATIC 23582235 A 1588 1592 zinc SYSTEMATIC 23582235 A 184 188 zinc SYSTEMATIC 23582235 A 36 40 zinc SYSTEMATIC 23582235 A 371 375 zinc SYSTEMATIC 23582235 A 622 635 zinc chloride SYSTEMATIC 23582235 A 689 705 Poly(ADP-ribose) SYSTEMATIC 23582235 A 812 816 zinc SYSTEMATIC 23582235 A 938 942 zinc SYSTEMATIC 23582235 T 0 4 Zinc SYSTEMATIC 23582235 T 125 141 Poly(ADP-ribose) SYSTEMATIC 23582330 A 0 7 Glucose TRIVIAL 23582330 A 117 122 sugar FAMILY 23582330 A 162 175 phosphosugars FAMILY 23582330 A 249 257 haloacid FAMILY 23582330 A 359 372 phosphosugars FAMILY 23582330 A 490 497 glucose TRIVIAL 23582330 T 33 38 Sugar FAMILY 23582330 T 66 73 Glucose TRIVIAL 23582779 A 91 98 glucose TRIVIAL 23583168 A 403 413 fatty-acid FAMILY 23583203 A 1008 1011 TPP ABBREVIATION 23583203 A 141 150 celastrol TRIVIAL 23583203 A 317 326 celastrol TRIVIAL 23583203 A 381 384 TPP ABBREVIATION 23583203 A 684 687 TPP ABBREVIATION 23583203 A 766 769 TPP ABBREVIATION 23583203 A 872 881 celastrol TRIVIAL 23583203 A 970 979 celastrol TRIVIAL 23583437 A 146 275 (3β, 7β, 12β, 25R)-spirost-5-ene-3, 7, 12-triol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-O-β-d-glucopyranoside SYSTEMATIC 23583437 A 281 410 (2α, 3β, 12β, 25R)-spirost-5-ene-2, 3, 12-triol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-O-β-d-glucopyranoside SYSTEMATIC 23583437 A 440 560 (3β, 12β, 25R)-spirost-5-ene-3,12-diol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-O-β-d-glucopyranoside SYSTEMATIC 23583437 A 5 23 steroidal saponins FAMILY 23583437 A 567 682 (1α, 3β, 25R)-spirost-5-ene-2-diol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl(1→4)]-O-β-d-glucopyranoside SYSTEMATIC 23583437 A 79 83 EtOH FORMULA 23583437 A 894 912 steroidal saponins FAMILY 23583437 T 8 26 steroidal saponins FAMILY 23583454 A 1073 1077 METH ABBREVIATION 23583454 A 1082 1086 MDMA ABBREVIATION 23583454 A 1097 1118 4-fluoromethcathinone SYSTEMATIC 23583454 A 1156 1160 METH ABBREVIATION 23583454 A 1180 1194 methcathinones FAMILY 23583454 A 1286 1295 monoamine FAMILY 23583454 A 138 153 methamphetamine TRIVIAL 23583454 A 1515 1528 methcathinone TRIVIAL 23583454 A 1543 1552 serotonin TRIVIAL 23583454 A 155 159 METH ABBREVIATION 23583454 A 1554 1558 5-HT SYSTEMATIC 23583454 A 1649 1657 dopamine TRIVIAL 23583454 A 165 197 3,4-methylendioxymethamphetamine SYSTEMATIC 23583454 A 1780 1789 serotonin TRIVIAL 23583454 A 1791 1799 dopamine TRIVIAL 23583454 A 199 203 MDMA ABBREVIATION 23583454 A 21 35 methcathinones FAMILY 23583454 A 408 419 amphetamine TRIVIAL 23583454 A 434 464 3,4-Methylenedioxypyrovalerone SYSTEMATIC 23583454 A 469 478 naphyrone TRIVIAL 23583454 A 548 556 dopamine TRIVIAL 23583454 A 565 574 serotonin TRIVIAL 23583454 A 587 601 norepinephrine TRIVIAL 23583454 A 642 648 [(3)H] FORMULA 23583454 A 683 690 cocaine TRIVIAL 23583454 A 737 745 Butylone TRIVIAL 23583454 A 798 819 4-fluoromethcathinone SYSTEMATIC 23583454 A 821 831 mephedrone TRIVIAL 23583454 A 836 845 methylone TRIVIAL 23583454 A 949 955 [(3)H] FORMULA 23583454 T 12 26 methcathinones FAMILY 23583513 A 1029 1072 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione SYSTEMATIC 23583513 A 22 65 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione SYSTEMATIC 23583513 A 530 539 diazepine TRIVIAL 23583513 A 578 625 1,5-dihydro-benzo[f][1,3,5]triazepine-2,4-dione SYSTEMATIC 23583513 A 747 790 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione SYSTEMATIC 23583513 T 18 61 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione SYSTEMATIC 23583641 A 1024 1027 MTT ABBREVIATION 23583641 A 552 564 polyurethane SYSTEMATIC 23583641 A 760 768 methanol SYSTEMATIC 23583641 A 995 997 NO FORMULA 23583735 A 1121 1128 Realgar TRIVIAL 23583735 A 1229 1236 Realgar TRIVIAL 23583735 A 1345 1349 (1)H FORMULA 23583735 A 2167 2174 realgar TRIVIAL 23583735 A 2176 2181 As2S2 FORMULA 23583735 A 2247 2254 realgar TRIVIAL 23583735 A 2256 2261 As2S2 FORMULA 23583735 A 2440 2447 choline FAMILY 23583735 A 2460 2470 amino acid FAMILY 23583735 A 2517 2524 realgar TRIVIAL 23583735 A 2526 2531 As2S2 FORMULA 23583735 A 544 551 realgar TRIVIAL 23583735 A 553 558 As2S2 FORMULA 23583735 A 638 642 (1)H FORMULA 23583735 A 720 727 realgar TRIVIAL 23583735 A 729 734 As2S2 FORMULA 23583735 A 888 895 Realgar TRIVIAL 23583735 A 921 928 Realgar TRIVIAL 23583735 T 0 4 (1)H FORMULA 23583882 A 483 492 parathion TRIVIAL 23583882 A 497 512 organophosphate FAMILY 23583882 A 526 538 methoxychlor TRIVIAL 23583882 A 543 557 organochlorine FAMILY 23583882 A 600 618 piperonyl butoxide SYSTEMATIC 23583882 T 65 77 methoxychlor TRIVIAL 23583882 T 79 88 parathion TRIVIAL 23583882 T 93 111 piperonyl butoxide SYSTEMATIC 23583910 A 12 30 aminopropylindenes FAMILY 23583910 A 152 168 2,3-oxidosqualen TRIVIAL 23583910 A 172 182 lanosterol TRIVIAL 23583910 A 201 219 Grundmann's ketone TRIVIAL 23583910 A 347 370 N,N-dimethylaminopropyl SYSTEMATIC 23583910 A 509 520 cholesterol TRIVIAL 23583910 A 97 110 oxidosqualene FAMILY 23583910 T 0 18 Aminopropylindenes FAMILY 23583910 T 32 50 Grundmann's ketone TRIVIAL 23583928 A 1273 1281 VUF 8430 IDENTIFIER 23583928 A 1286 1298 JNJ 10191584 IDENTIFIER 23583928 A 4 13 histamine TRIVIAL 23583928 A 427 435 VUF 8430 IDENTIFIER 23583928 A 559 571 JNJ 10191584 IDENTIFIER 23583928 A 678 687 histamine TRIVIAL 23583928 A 859 867 diazepam TRIVIAL 23583928 A 934 942 VUF 8430 IDENTIFIER 23583928 A 956 967 scopolamine TRIVIAL 23583928 T 22 31 histamine TRIVIAL 23583929 A 597 612 quinolinic acid TRIVIAL 23584090 A 722 725 CpG ABBREVIATION 23584277 A 389 406 hydrogen peroxide SYSTEMATIC 23584277 A 4 10 oxygen SYSTEMATIC 23584277 A 95 142 diethylmethylammonium trifluoromethanesulfonate SYSTEMATIC 23584277 T 26 32 oxygen SYSTEMATIC 23584358 A 0 11 Paracetamol TRIVIAL 23584358 A 1098 1107 aspartate TRIVIAL 23584358 A 1126 1133 alanine TRIVIAL 23584358 A 121 130 melatonin TRIVIAL 23584358 A 1227 1241 8-iso-prostane TRIVIAL 23584358 A 1276 1286 superoxide TRIVIAL 23584358 A 1310 1321 glutathione TRIVIAL 23584358 A 1348 1359 paracetamol TRIVIAL 23584358 A 1379 1390 agomelatine TRIVIAL 23584358 A 1395 1398 NAC ABBREVIATION 23584358 A 1463 1474 agomelatine TRIVIAL 23584358 A 1516 1527 paracetamol TRIVIAL 23584358 A 294 303 melatonin TRIVIAL 23584358 A 390 401 agomelatine TRIVIAL 23584358 A 405 416 paracetamol TRIVIAL 23584358 A 517 528 agomelatine TRIVIAL 23584358 A 682 693 agomelatine TRIVIAL 23584358 A 709 725 N-acetylcysteine SYSTEMATIC 23584358 A 727 730 NAC ABBREVIATION 23584358 A 744 755 paracetamol TRIVIAL 23584358 A 768 779 paracetamol TRIVIAL 23584358 A 792 795 NAC ABBREVIATION 23584358 A 808 819 paracetamol TRIVIAL 23584358 A 831 842 agomelatine TRIVIAL 23584358 A 859 870 paracetamol TRIVIAL 23584358 A 882 893 agomelatine TRIVIAL 23584358 A 90 101 Agomelatine TRIVIAL 23584358 A 902 913 Paracetamol TRIVIAL 23584358 T 0 11 Agomelatine TRIVIAL 23584358 T 75 86 paracetamol TRIVIAL 23584418 A 0 9 Aluminium SYSTEMATIC 23584418 A 140 146 Al(3+) FORMULA 23584418 T 65 74 aluminium SYSTEMATIC 23584426 A 0 5 Fe3O4 FORMULA 23584426 A 1024 1029 Fe3O4 FORMULA 23584426 A 1098 1103 As(V) FORMULA 23584426 A 1108 1113 Fe3O4 FORMULA 23584426 A 1212 1217 As(V) FORMULA 23584426 A 1229 1234 Fe3O4 FORMULA 23584426 A 1315 1320 Fe3O4 FORMULA 23584426 A 137 144 arsenic SYSTEMATIC 23584426 A 1544 1549 Fe3O4 FORMULA 23584426 A 1566 1571 As(V) FORMULA 23584426 A 1589 1594 As(V) FORMULA 23584426 A 1644 1652 arsenics FAMILY 23584426 A 1699 1706 arsenic SYSTEMATIC 23584426 A 213 220 arsenic SYSTEMATIC 23584426 A 359 364 Fe3O4 FORMULA 23584426 A 389 394 As(V) FORMULA 23584426 A 51 58 arsenic SYSTEMATIC 23584426 A 559 564 As(V) FORMULA 23584426 A 613 618 As(V) FORMULA 23584426 A 650 655 Fe3O4 FORMULA 23584426 A 853 858 Fe3O4 FORMULA 23584426 A 894 899 As(V) FORMULA 23584426 A 93 98 Fe3O4 FORMULA 23584426 A 958 963 Fe3O4 FORMULA 23584426 T 21 38 ferroferric oxide SYSTEMATIC 23584426 T 57 64 arsenic SYSTEMATIC 23584427 A 0 19 Hexavalent chromium SYSTEMATIC 23584427 A 1304 1306 Cr FORMULA 23584427 A 1670 1672 Cr FORMULA 23584427 A 1786 1788 Cr FORMULA 23584427 A 1824 1830 oxygen SYSTEMATIC 23584427 A 20 26 Cr(VI) FORMULA 23584427 A 249 251 Cr FORMULA 23584427 A 393 395 Cr FORMULA 23584427 A 520 522 Cr FORMULA 23584427 A 602 608 Cr(VI) FORMULA 23584427 A 682 684 Cr FORMULA 23584427 A 746 752 Cr(VI) FORMULA 23584427 T 64 83 hexavalent chromium SYSTEMATIC 23584427 T 85 91 Cr(VI) FORMULA 23584541 A 209 223 betulinic acid TRIVIAL 23584541 A 241 255 1,2,3-triazole SYSTEMATIC 23584541 A 298 299 C FORMULA 23584541 A 517 582 3{1N(2-cyanophenyl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid SYSTEMATIC 23584541 A 591 663 3{1N(5-hydroxy-naphth-1yl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid SYSTEMATIC 23584541 T 13 69 3-O-propargylated betulinic acid and its 1,2,3-triazoles MULTIPLE 23584545 A 118 127 quinoline SYSTEMATIC 23584545 A 27 36 quinoline SYSTEMATIC 23584545 A 387 396 quinoline SYSTEMATIC 23584545 A 604 617 Schiff's base FAMILY 23584545 T 57 66 quinoline SYSTEMATIC 23584556 A 1178 1179 N FORMULA 23584556 A 1230 1231 C FORMULA 23584556 A 1780 1784 zinc SYSTEMATIC 23584556 A 2165 2175 amino acid FAMILY 23584556 A 979 989 amino acid FAMILY 23584636 A 112 115 ZnO FORMULA 23584636 A 195 200 Al2O3 FORMULA 23584636 A 357 359 Au FORMULA 23584636 A 364 380 indium-tin-oxide SYSTEMATIC 23584636 A 382 385 ITO ABBREVIATION 23584636 T 12 15 ZnO FORMULA 23584857 A 1063 1077 2-deoxyglucose SYSTEMATIC 23584886 A 0 12 Ketoconazole TRIVIAL 23584886 A 1125 1137 Ketoconazole TRIVIAL 23584886 A 1254 1263 midazolam TRIVIAL 23584886 A 1461 1473 ketoconazole TRIVIAL 23584886 A 310 322 ketoconazole TRIVIAL 23584886 A 397 409 ketoconazole TRIVIAL 23584886 A 410 419 midazolam TRIVIAL 23584886 A 765 774 midazolam TRIVIAL 23584886 A 804 813 midazolam TRIVIAL 23584886 A 997 1009 ketoconazole TRIVIAL 23584948 A 1252 1262 Vandetanib TRIVIAL 23584948 A 246 256 Vandetanib TRIVIAL 23584948 A 258 266 Caprelsa TRIVIAL 23584948 A 305 313 tyrosine TRIVIAL 23584948 A 403 411 tyrosine TRIVIAL 23584948 T 0 10 Vandetanib TRIVIAL 23585058 A 1023 1026 APV ABBREVIATION 23585058 A 1035 1039 NMDA ABBREVIATION 23585058 A 1086 1093 calcium SYSTEMATIC 23585058 A 1102 1110 BAPTA-AM ABBREVIATION 23585058 A 1147 1152 UO126 IDENTIFIER 23585058 A 1172 1176 NMDA ABBREVIATION 23585058 A 1215 1219 NMDA ABBREVIATION 23585058 A 1296 1300 Ca2+ FORMULA 23585058 A 456 460 NMDA ABBREVIATION 23585058 A 54 74 γ amino-butyric acid SYSTEMATIC 23585058 A 620 624 NMDA ABBREVIATION 23585058 A 829 833 NMDA ABBREVIATION 23585058 T 0 4 NMDA ABBREVIATION 23585058 T 75 79 GABA ABBREVIATION 23585235 A 1039 1041 HD FORMULA 23585235 A 1125 1133 hydrogen SYSTEMATIC 23585235 A 1244 1252 hydrogen SYSTEMATIC 23585235 A 1385 1393 hydrogen SYSTEMATIC 23585235 A 1471 1479 hydrogen SYSTEMATIC 23585235 A 1594 1602 hydrogen SYSTEMATIC 23585235 A 1659 1667 hydrogen SYSTEMATIC 23585235 A 166 168 H2 FORMULA 23585235 A 17 25 hydrogen SYSTEMATIC 23585235 A 170 172 D2 FORMULA 23585235 A 291 299 hydrogen SYSTEMATIC 23585235 A 353 361 hydrogen SYSTEMATIC 23585235 A 363 365 HD FORMULA 23585235 A 382 384 H2 FORMULA 23585235 A 389 391 D2 FORMULA 23585235 A 397 399 Pd FORMULA 23585235 A 45 52 Pd(111) FORMULA 23585235 A 526 528 HD FORMULA 23585235 A 620 628 hydrogen SYSTEMATIC 23585235 A 742 750 hydrogen SYSTEMATIC 23585235 A 827 835 hydrogen SYSTEMATIC 23585235 A 85 87 Pd FORMULA 23585235 A 861 863 HD FORMULA 23585235 T 105 112 Pd(111) FORMULA 23585235 T 66 67 H FORMULA 23585235 T 68 69 D FORMULA 23585235 T 84 86 Pd FORMULA 23585358 A 175 178 C-H FORMULA 23585358 A 353 362 diazonium SYSTEMATIC 23585380 A 101 132 poly(L-lactic-co-glycolic acid) SYSTEMATIC 23585380 A 1127 1131 PLGA ABBREVIATION 23585380 A 1164 1168 PLGA ABBREVIATION 23585380 A 134 138 PLGA ABBREVIATION 23585380 A 269 273 PLGA ABBREVIATION 23585380 A 362 366 PLGA ABBREVIATION 23585380 A 722 726 PLGA ABBREVIATION 23585383 A 232 234 Ag FORMULA 23585383 A 30 32 Ag FORMULA 23585383 A 33 39 Fe2 O3 FORMULA 23585383 A 331 333 Ag FORMULA 23585383 A 355 365 iron oxide SYSTEMATIC 23585383 A 391 393 Ag FORMULA 23585383 A 55 57 Ag FORMULA 23585383 A 58 64 Fe2 O3 FORMULA 23585383 T 62 64 Ag FORMULA 23585383 T 65 71 Fe2 O3 FORMULA 23585770 A 589 591 Ni FORMULA 23585770 T 31 33 Ni FORMULA 23586441 A 1063 1073 acridinium SYSTEMATIC 23586441 A 1240 1258 aliphatic ammonium FAMILY 23586441 A 1281 1289 acridine TRIVIAL 23586441 A 1304 1312 acridine TRIVIAL 23586441 A 1313 1321 nitrogen SYSTEMATIC 23586441 A 139 147 acridine TRIVIAL 23586441 A 438 442 (1)H FORMULA 23586441 A 597 607 tetraamine SYSTEMATIC 23586441 A 625 633 acridine TRIVIAL 23586441 A 634 642 nitrogen SYSTEMATIC 23586441 A 720 728 acridine TRIVIAL 23586441 A 76 96 triethylentetraamine SYSTEMATIC 23586441 T 93 101 Acridine TRIVIAL 23586519 A 1004 1007 THF ABBREVIATION 23586519 A 105 108 PFS ABBREVIATION 23586519 A 1146 1149 PFS ABBREVIATION 23586519 A 1268 1272 PDMS ABBREVIATION 23586519 A 1275 1295 polydimethylsiloxane SYSTEMATIC 23586519 A 1319 1329 2-propanol SYSTEMATIC 23586519 A 1331 1335 P2VP ABBREVIATION 23586519 A 1338 1358 poly(2-vinylpyridine SYSTEMATIC 23586519 A 1500 1503 PFS ABBREVIATION 23586519 A 1723 1726 PFS ABBREVIATION 23586519 A 719 722 PFS ABBREVIATION 23586519 A 73 103 poly(ferrocenyldimethylsilane) SYSTEMATIC 23586519 A 848 854 decane SYSTEMATIC 23586519 A 910 913 THF ABBREVIATION 23586519 A 919 922 PFS ABBREVIATION 23586638 A 0 13 Vinyl acetate SYSTEMATIC 23586638 A 1065 1066 H FORMULA 23586638 A 1085 1103 CH3C(O)O(•)CHCH2OH FORMULA 23586638 A 1114 1134 CH3C(O)OCH(OH)(•)CH2 FORMULA 23586638 A 1141 1143 OH FORMULA 23586638 A 1201 1203 O2 FORMULA 23586638 A 1216 1218 NO FORMULA 23586638 A 1894 1917 formic acetic anhydride SYSTEMATIC 23586638 A 19 29 CH3COOC2H3 FORMULA 23586638 A 1919 1930 acetic acid SYSTEMATIC 23586638 A 1936 1948 formaldehyde SYSTEMATIC 23586638 A 1956 1958 OH FORMULA 23586638 A 2004 2006 O2 FORMULA 23586638 A 2011 2013 NO FORMULA 23586638 A 206 208 OH FORMULA 23586638 A 322 324 OH FORMULA 23586638 A 360 362 O2 FORMULA 23586638 A 367 369 NO FORMULA 23586638 A 487 496 ethylenic SYSTEMATIC 23586638 A 497 498 C FORMULA 23586638 A 635 636 H FORMULA 23586638 A 708 710 OH FORMULA 23586638 A 997 999 OH FORMULA 23586638 T 56 69 Vinyl Acetate SYSTEMATIC 23586638 T 83 85 OH FORMULA 23586839 A 1096 1097 C FORMULA 23586839 A 1098 1100 2H FORMULA 23586839 A 1188 1189 H FORMULA 23586839 A 1191 1193 2H FORMULA 23586839 A 1210 1212 Ir FORMULA 23586839 A 1213 1214 C FORMULA 23586839 A 1215 1217 2H FORMULA 23586839 A 1364 1366 Pt FORMULA 23586839 A 1382 1389 carbene FAMILY 23586839 A 1405 1407 Ta FORMULA 23586839 A 1412 1413 W FORMULA 23586839 A 1415 1422 carbene FAMILY 23586839 A 1484 1491 carbyne FAMILY 23586839 A 1510 1512 Ir FORMULA 23586839 A 1526 1528 Ir FORMULA 23586839 A 1529 1536 carbyne FAMILY 23586839 A 162 169 Methane SYSTEMATIC 23586839 A 18 25 methane SYSTEMATIC 23586839 A 239 240 C FORMULA 23586839 A 241 243 2H FORMULA 23586839 A 250 252 H2 FORMULA 23586839 A 39 55 transition metal FAMILY 23586839 A 396 403 carbene FAMILY 23586839 A 430 433 CH2 FORMULA 23586839 A 469 472 CH2 FORMULA 23586839 A 480 487 carbyne FAMILY 23586839 A 489 508 hydrido-methylidyne SYSTEMATIC 23586839 A 532 534 CH FORMULA 23586839 A 541 549 hydrogen SYSTEMATIC 23586839 A 581 582 H FORMULA 23586839 A 586 588 CH FORMULA 23586839 A 707 714 carbene FAMILY 23586839 A 719 726 carbyne FAMILY 23586839 A 770 771 C FORMULA 23586839 A 772 774 2H FORMULA 23586839 A 782 784 Ta FORMULA 23586839 A 786 787 W FORMULA 23586839 A 789 791 Ir FORMULA 23586839 A 793 795 Pt FORMULA 23586839 T 46 53 Methane SYSTEMATIC 23586839 T 71 87 Transition Metal FAMILY 23587048 A 0 33 3-Hydroperoxy-N-nitrosomorpholine SYSTEMATIC 23587048 A 1012 1019 iminium SYSTEMATIC 23587048 A 1080 1085 imine SYSTEMATIC 23587048 A 1117 1130 hydroperoxide FAMILY 23587048 A 1150 1157 NaNCBH3 FORMULA 23587048 A 1468 1480 nicotinamide TRIVIAL 23587048 A 1495 1504 ascorbate TRIVIAL 23587048 A 160 180 α-hydroxynitrosamine SYSTEMATIC 23587048 A 196 205 diazonium SYSTEMATIC 23587048 A 281 288 hydride SYSTEMATIC 23587048 A 392 453 6-(2-{2-[(9H-purin-6-yl)amino]ethoxy}ethoxy)-9H-purin-2-amine SYSTEMATIC 23587048 A 510 519 diazonium SYSTEMATIC 23587048 A 530 543 3-oxapentanal SYSTEMATIC 23587048 A 556 557 O FORMULA 23587048 A 561 564 Gua ABBREVIATION 23587048 A 588 589 N FORMULA 23587048 A 593 596 Ade ABBREVIATION 23587048 A 769 780 borohydride SYSTEMATIC 23587048 A 793 800 NaNCBH3 FORMULA 23587048 A 878 885 hydride SYSTEMATIC 23587048 A 909 914 NaBH4 FORMULA 23587048 A 918 928 Na(AcO)3BH FORMULA 23587048 A 948 955 NaNCBH3 FORMULA 23587048 T 43 49 Purine TRIVIAL 23587048 T 91 110 N-Nitrosomorpholine SYSTEMATIC 23587423 A 98 104 lysine TRIVIAL 23587426 A 160 182 4-alkyloxybenzaldehyde FAMILY 23587426 A 188 228 2-amino-2-hydroxymethyl-propane-1,3-diol SYSTEMATIC 23587426 A 424 435 methicillin TRIVIAL 23587426 A 98 121 aromatic amino alcohols FAMILY 23587426 T 58 81 aromatic amino alcohols FAMILY 23587660 A 1102 1109 alcohol FAMILY 23587660 A 1206 1213 alcohol FAMILY 23587660 A 277 284 alcohol FAMILY 23587660 A 335 342 alcohol FAMILY 23587660 A 525 532 alcohol FAMILY 23587660 A 66 73 alcohol FAMILY 23587660 T 87 94 alcohol FAMILY 23588093 A 1042 1048 l-NAME ABBREVIATION 23588093 A 1050 1062 indomethacin TRIVIAL 23588093 A 1064 1082 tetraethylammonium SYSTEMATIC 23588093 A 1087 1100 glibenclamide TRIVIAL 23588093 A 1230 1235 CaCl2 FORMULA 23588093 A 1428 1442 norepinephrine TRIVIAL 23588093 A 1576 1582 Ca(2+) FORMULA 23588093 A 1659 1674 p-coumaric acid TRIVIAL 23588093 A 1676 1686 isovitexin TRIVIAL 23588093 A 1688 1696 luteolin TRIVIAL 23588093 A 1701 1712 chrysoeriol TRIVIAL 23588093 A 1725 1733 Luteolin TRIVIAL 23588093 A 1752 1763 chrysoeriol TRIVIAL 23588093 A 1786 1801 p-coumaric acid TRIVIAL 23588093 A 1919 1932 phenylephrine TRIVIAL 23588093 A 2206 2212 Ca(2+) FORMULA 23588093 A 2235 2242 calcium SYSTEMATIC 23588093 A 2294 2302 luteolin TRIVIAL 23588093 A 2304 2315 chrysoeriol TRIVIAL 23588093 A 2320 2335 p-coumaric acid TRIVIAL 23588093 A 771 784 phenylephrine TRIVIAL 23588093 A 826 845 5-hydroxytriptamine SYSTEMATIC 23588093 A 887 890 KCl FORMULA 23588093 A 963 976 phenylephrine TRIVIAL 23588094 A 1411 1418 styrene TRIVIAL 23588094 A 1428 1444 cinnamyl alcohol TRIVIAL 23588094 A 1456 1464 α-pinene TRIVIAL 23588094 A 698 708 chloroform TRIVIAL 23588094 A 713 722 n-butanol SYSTEMATIC 23588094 A 754 761 ethanol SYSTEMATIC 23588312 A 0 14 5-Fluorouracil SYSTEMATIC 23588312 A 1023 1027 5-FU SYSTEMATIC 23588312 A 136 140 5-FU SYSTEMATIC 23588312 A 16 20 5-FU SYSTEMATIC 23588312 A 284 301 dihydropyrimidine SYSTEMATIC 23588312 A 712 716 5-FU SYSTEMATIC 23588390 A 1227 1231 BrdU ABBREVIATION 23588390 A 1294 1306 GEM-C18-PLGA FORMULA 23588390 A 1558 1566 stearoyl TRIVIAL 23588390 A 407 418 gemcitabine TRIVIAL 23588390 A 608 619 gemcitabine TRIVIAL 23588390 A 627 641 4-(N)-stearoyl SYSTEMATIC 23588390 A 654 661 GEM-C18 FORMULA 23588390 A 714 718 PLGA ABBREVIATION 23588390 A 812 824 GEM-C18-PLGA FORMULA 23588390 T 134 154 stearoyl gemcitabine TRIVIAL 23588390 T 90 94 PLGA ABBREVIATION 23588558 T 24 30 statin FAMILY 23588560 A 10 20 Tacrolimus TRIVIAL 23588560 A 1247 1250 TAC ABBREVIATION 23588560 A 1360 1363 TAC ABBREVIATION 23588560 A 1479 1482 TAC ABBREVIATION 23588560 A 206 209 TAC ABBREVIATION 23588560 A 22 25 TAC ABBREVIATION 23588560 A 323 326 TAC ABBREVIATION 23588560 A 432 435 TAC ABBREVIATION 23588560 A 627 630 TAC ABBREVIATION 23588560 A 808 811 TAC ABBREVIATION 23588560 T 39 49 tacrolimus TRIVIAL 23588562 A 1582 1602 tetrahydrocannabinol SYSTEMATIC 23588562 A 1604 1607 THC ABBREVIATION 23588562 A 1613 1624 cannabidiol TRIVIAL 23588562 A 1626 1629 CBD ABBREVIATION 23588681 A 394 418 emodin-6-O-β-D-glucoside SYSTEMATIC 23588681 A 620 651 phorbol-12-myristate 13-acetate SYSTEMATIC 23588681 A 653 656 PMA ABBREVIATION 23588681 A 796 799 PMA ABBREVIATION 23588681 T 0 24 Emodin-6-O-β-D-glucoside SYSTEMATIC 23588682 A 1058 1069 venlafaxine TRIVIAL 23588682 A 1341 1352 venlafaxine TRIVIAL 23588682 A 246 257 venlafaxine TRIVIAL 23588682 A 316 327 venlafaxine TRIVIAL 23588682 A 520 527 carboxy SYSTEMATIC 23588682 A 548 569 polyvinyl pyrrolidone SYSTEMATIC 23588682 T 23 34 venlafaxine TRIVIAL 23588796 A 1045 1056 polyaniline SYSTEMATIC 23588796 A 1187 1198 polyaniline SYSTEMATIC 23588997 A 116 125 zirconium FAMILY 23588997 A 271 279 hydrogen SYSTEMATIC 23588997 A 45 63 zirconium hydrides FAMILY 23588997 A 564 568 ZrH2 FORMULA 23588997 T 10 28 zirconium hydrides FAMILY 23589223 A 1174 1183 fullerene TRIVIAL 23589223 A 534 543 fullerene TRIVIAL 23589223 A 545 548 C60 TRIVIAL 23589223 A 785 794 fullerene TRIVIAL 23589223 T 0 9 Fullerene TRIVIAL 23589329 A 1034 1038 tBHQ ABBREVIATION 23589329 A 1049 1056 arsenic SYSTEMATIC 23589329 A 1144 1151 arsenic SYSTEMATIC 23589329 A 1390 1397 arsenic SYSTEMATIC 23589329 A 516 523 Arsenic SYSTEMATIC 23589329 A 688 695 arsenic SYSTEMATIC 23589329 A 849 861 sulforaphane TRIVIAL 23589329 A 866 888 tert-butylhydroquinone SYSTEMATIC 23589329 A 976 980 tBHQ ABBREVIATION 23589329 T 0 7 Arsenic SYSTEMATIC 23589462 A 299 305 (13) C FORMULA 23589462 A 377 380 N-C FORMULA 23589462 A 40 45 (1) H FORMULA 23589462 A 46 52 (15) N FORMULA 23589462 A 59 65 (15) N FORMULA 23589462 A 647 658 amino acids FAMILY 23589462 A 66 72 (13) C FORMULA 23589462 A 690 696 Zn(II) FORMULA 23589462 A 717 723 Cu(II) FORMULA 23589462 A 726 732 Zn(II) FORMULA 23589462 T 0 6 (13) C FORMULA 23589476 A 206 213 glucose TRIVIAL 23589501 A 103 109 pyrene SYSTEMATIC 23589501 A 1032 1036 NaCl FORMULA 23589501 A 114 125 neocuproine TRIVIAL 23589501 A 232 234 Cu FORMULA 23589501 A 296 304 dioxygen SYSTEMATIC 23589501 A 323 325 Cu FORMULA 23589501 A 384 392 hydrogen SYSTEMATIC 23589501 A 530 532 O2 FORMULA 23589501 A 535 537 Cu FORMULA 23589501 A 687 693 pyrene SYSTEMATIC 23589501 A 699 710 neocuproine TRIVIAL 23589501 A 824 830 oxygen SYSTEMATIC 23589501 A 850 852 Cu FORMULA 23589501 T 31 33 O2 FORMULA 23589624 A 107 118 amino acids FAMILY 23589624 A 390 413 p-azido-l-phenylalanine SYSTEMATIC 23589624 A 415 419 pAzF ABBREVIATION 23589624 A 424 454 p-propargyloxy-l-phenylalanine SYSTEMATIC 23589624 A 456 460 pPaF ABBREVIATION 23589624 T 100 110 amino acid FAMILY 23590189 A 1042 1045 PVO ABBREVIATION 23590189 A 192 200 Vanillin TRIVIAL 23590189 A 404 412 vanillin TRIVIAL 23590189 A 421 443 poly(vanillin oxalate) SYSTEMATIC 23590189 A 445 448 PVO ABBREVIATION 23590189 A 462 465 PVO ABBREVIATION 23590189 A 47 64 hydrogen peroxide SYSTEMATIC 23590189 A 479 483 H2O2 FORMULA 23590189 A 493 509 peroxalate ester SYSTEMATIC 23590189 A 530 538 vanillin TRIVIAL 23590189 A 559 565 acetal SYSTEMATIC 23590189 A 652 655 PVO ABBREVIATION 23590189 A 66 70 H2O2 FORMULA 23590189 A 755 763 vanillin TRIVIAL 23590189 A 765 768 PVO ABBREVIATION 23590189 A 835 839 H2O2 FORMULA 23590189 A 88 92 H2O2 FORMULA 23590189 A 887 893 oxygen SYSTEMATIC 23590189 T 82 90 Vanillin TRIVIAL 23590386 A 1099 1103 P3AT SYSTEMATIC 23590386 A 143 166 poly(3-alkylthiophene)s FAMILY 23590386 A 168 173 P3ATs SYSTEMATIC 23590386 A 176 200 poly(3-dodecylthiophene) SYSTEMATIC 23590386 A 202 207 P3DDT SYSTEMATIC 23590386 A 210 246 poly(3,3‴-didodecyl-quaterthiophene) SYSTEMATIC 23590386 A 248 253 PQT12 ABBREVIATION 23590386 A 260 319 poly(2,5-bis(3-dodecylthiophen-2-yl)thieno[3,2-b]thiophene) SYSTEMATIC 23590386 A 321 328 pBTTT12 ABBREVIATION 23590386 A 366 381 dichloromethane SYSTEMATIC 23590386 A 383 393 chloroform TRIVIAL 23590386 A 395 410 tetrahydrofuran SYSTEMATIC 23590386 A 416 432 carbon disulfide SYSTEMATIC 23590386 A 434 437 CS2 FORMULA 23590386 A 440 443 CS2 FORMULA 23590386 A 544 548 P3AT SYSTEMATIC 23590386 A 596 599 CS2 FORMULA 23590386 A 714 718 P3AT SYSTEMATIC 23590386 A 771 776 P3DDT SYSTEMATIC 23590386 A 787 792 PQT12 ABBREVIATION 23590386 A 875 882 pBTTT12 ABBREVIATION 23590386 A 936 939 CS2 FORMULA 23590386 T 39 62 Poly(3-alkylthiophene)s FAMILY 23590473 A 638 645 alcohol FAMILY 23590667 A 12 16 MoS2 FORMULA 23590667 A 437 441 MoS2 FORMULA 23590667 T 10 14 MoS2 FORMULA 23590689 A 1132 1139 ClFn(+) FAMILY 23590689 A 1192 1195 SFn FAMILY 23590689 A 1286 1293 ClFn(+) FAMILY 23590689 A 1298 1301 SFn FAMILY 23590689 A 132 135 SFn FAMILY 23590689 A 1348 1355 ClFn(+) FAMILY 23590689 A 137 141 ClFn FAMILY 23590689 A 1404 1407 SFn FAMILY 23590689 A 143 146 PFn FAMILY 23590689 A 1460 1467 ClF2(+) FORMULA 23590689 A 148 152 SCln FAMILY 23590689 A 1511 1514 SF2 FORMULA 23590689 A 1563 1565 HF FORMULA 23590689 A 158 163 SFnCl FAMILY 23590689 A 1581 1588 ClFn(+) FAMILY 23590689 A 1593 1596 SFn FAMILY 23590689 A 1623 1624 F FORMULA 23590689 A 1709 1710 F FORMULA 23590689 A 1805 1806 F FORMULA 23590689 A 1816 1823 ClFn(+) FAMILY 23590689 A 1832 1835 SFn FAMILY 23590689 A 1860 1865 Cl(+) FORMULA 23590689 A 1897 1898 F FORMULA 23590689 A 1930 1935 Cl(+) FORMULA 23590689 A 1946 1947 S FORMULA 23590689 A 2042 2049 ClFn(+) FAMILY 23590689 A 636 643 ClFn(+) FAMILY 23590689 A 810 817 ClFn(+) FAMILY 23590689 A 861 865 ClFn FAMILY 23590689 T 38 45 ClFn(+) FAMILY 23590882 A 1192 1203 amino acids FAMILY 23590882 A 1290 1296 Ca(2+) FORMULA 23590882 A 148 158 amino acid FAMILY 23590882 A 165 171 Ca(2+) FORMULA 23590882 T 12 21 Glutamate TRIVIAL 23590892 A 0 8 Paraquat TRIVIAL 23590892 A 1020 1023 DHA ABBREVIATION 23590892 A 130 150 Docosahexaenoic acid SYSTEMATIC 23590892 A 152 155 DHA ABBREVIATION 23590892 A 298 301 DHA ABBREVIATION 23590892 A 506 509 DHA ABBREVIATION 23590892 A 600 603 DHA ABBREVIATION 23590892 A 748 762 hydroxyproline SYSTEMATIC 23590892 A 891 894 DHA ABBREVIATION 23590892 T 0 20 Docosahexaenoic acid SYSTEMATIC 23590892 T 22 25 DHA ABBREVIATION 23590892 T 39 47 paraquat TRIVIAL 23591044 A 1010 1017 ethanol SYSTEMATIC 23591044 A 1022 1029 ethanol SYSTEMATIC 23591044 A 1030 1039 melatonin TRIVIAL 23591044 A 1116 1123 ethanol SYSTEMATIC 23591044 A 1180 1189 melatonin TRIVIAL 23591044 A 1204 1211 Ethanol SYSTEMATIC 23591044 A 1216 1225 melatonin TRIVIAL 23591044 A 1318 1325 steroid FAMILY 23591044 A 192 199 ethanol SYSTEMATIC 23591044 A 211 220 melatonin TRIVIAL 23591044 A 282 289 steroid FAMILY 23591044 A 338 345 ethanol SYSTEMATIC 23591044 A 463 471 androgen FAMILY 23591044 A 473 481 estrogen FAMILY 23591044 A 483 495 progesterone TRIVIAL 23591044 A 500 509 melatonin TRIVIAL 23591044 A 582 591 Melatonin TRIVIAL 23591044 A 602 611 estradiol TRIVIAL 23591044 A 631 643 progesterone TRIVIAL 23591044 A 653 673 6-sulfatoxymelatonin SYSTEMATIC 23591044 A 675 680 6-STM SYSTEMATIC 23591044 A 692 699 ethanol SYSTEMATIC 23591044 A 700 709 melatonin TRIVIAL 23591044 A 8 15 ethanol SYSTEMATIC 23591044 A 830 837 ethanol SYSTEMATIC 23591044 A 838 847 melatonin TRIVIAL 23591044 A 927 934 ethanol SYSTEMATIC 23591044 A 938 947 melatonin TRIVIAL 23591044 A 94 103 melatonin TRIVIAL 23591044 T 0 9 Melatonin TRIVIAL 23591044 T 126 133 steroid FAMILY 23591044 T 14 21 ethanol SYSTEMATIC 23591044 T 67 76 estradiol TRIVIAL 23591044 T 81 93 progesterone TRIVIAL 23591111 A 122 126 zinc SYSTEMATIC 23591111 A 135 150 hydroxamic acid SYSTEMATIC 23591111 A 22 36 β-cyclodextrin TRIVIAL 23591111 A 275 279 SAHA ABBREVIATION 23591111 A 281 291 vorinostat TRIVIAL 23591111 A 38 41 βCD ABBREVIATION 23591111 A 396 400 SAHA ABBREVIATION 23591660 A 1142 1145 C60 TRIVIAL 23591660 A 1210 1213 C60 TRIVIAL 23591660 A 1229 1231 Ga FORMULA 23591660 A 408 411 C60 TRIVIAL 23591660 A 561 567 carbon SYSTEMATIC 23591777 A 1024 1027 MSM ABBREVIATION 23591777 A 1072 1076 CCl4 FORMULA 23591777 A 152 156 CCl4 FORMULA 23591777 A 246 250 CCl4 FORMULA 23591777 A 289 304 malondialdehyde TRIVIAL 23591777 A 306 309 MDA ABBREVIATION 23591777 A 342 352 superoxide TRIVIAL 23591777 A 35 56 methylsulfonylmethane SYSTEMATIC 23591777 A 58 61 MSM ABBREVIATION 23591777 A 594 598 CCl4 FORMULA 23591777 A 636 640 CCl4 FORMULA 23591777 A 66 86 carbon tetrachloride SYSTEMATIC 23591777 A 741 744 MSM ABBREVIATION 23591777 A 832 835 MDA ABBREVIATION 23591777 A 88 92 CCl4 FORMULA 23591777 A 880 884 CCl4 FORMULA 23591777 A 919 922 MSM ABBREVIATION 23591777 T 27 48 methylsulfonylmethane SYSTEMATIC 23591777 T 57 77 carbon tetrachloride SYSTEMATIC 23591995 A 1011 1021 ramiprilat TRIVIAL 23592429 A 31 39 androgen FAMILY 23592429 A 323 332 androgens FAMILY 23592429 A 375 384 androgens FAMILY 23592429 A 420 439 Abiraterone acetate SYSTEMATIC 23592429 A 444 452 androgen FAMILY 23592429 A 478 490 enzalutamide TRIVIAL 23592429 A 501 509 androgen FAMILY 23592429 A 574 583 androgens FAMILY 23592429 A 671 679 androgen FAMILY 23592429 A 797 805 androgen FAMILY 23592429 T 12 20 androgen FAMILY 23592516 A 1089 1096 choline FAMILY 23592516 A 1107 1119 L-amino acid FAMILY 23592516 A 1240 1243 OPZ ABBREVIATION 23592516 A 1247 1253 NK-252 IDENTIFIER 23592516 A 598 603 thiol FAMILY 23592516 A 619 627 oltipraz TRIVIAL 23592516 A 629 632 OPZ ABBREVIATION 23592516 A 693 697 urea TRIVIAL 23592516 A 715 721 NK-252 IDENTIFIER 23592516 A 723 729 NK-252 IDENTIFIER 23592516 A 780 783 OPZ ABBREVIATION 23592516 A 837 843 NK-252 IDENTIFIER 23592516 A 921 924 OPZ ABBREVIATION 23592516 A 963 969 NK-252 IDENTIFIER 23592516 A 990 993 OPZ ABBREVIATION 23592568 A 43 62 trimethine cyanines FAMILY 23592568 T 47 65 Trimethine Cyanine SYSTEMATIC 23592779 A 93 104 vitamin B12 TRIVIAL 23593923 A 594 600 serine TRIVIAL 23593960 A 148 172 toluene-2,4-diisocyanate SYSTEMATIC 23593960 A 174 177 TDI ABBREVIATION 23593960 A 31 39 diacetyl SYSTEMATIC 23593960 A 389 392 TDI ABBREVIATION 23593960 A 481 484 TDI ABBREVIATION 23593960 T 3 11 Diacetyl SYSTEMATIC 23594296 A 1005 1018 ethyl acetate SYSTEMATIC 23594296 A 1043 1048 taxol TRIVIAL 23594296 A 1103 1108 taxol TRIVIAL 23594296 A 1116 1131 dichloromethane SYSTEMATIC 23594296 A 1140 1150 chloroform TRIVIAL 23594296 A 1191 1192 C FORMULA 23594296 A 1193 1195 Cl FORMULA 23594296 A 1210 1218 hydrogen SYSTEMATIC 23594296 A 1236 1244 hydroxyl SYSTEMATIC 23594296 A 1260 1265 taxol TRIVIAL 23594296 A 182 191 phosphate SYSTEMATIC 23594296 A 237 245 methanol SYSTEMATIC 23594296 A 251 258 ethanol SYSTEMATIC 23594296 A 264 292 hydroxypropyl β-cyclodextrin SYSTEMATIC 23594296 A 294 300 HP-βCD ABBREVIATION 23594296 A 306 320 sodium citrate SYSTEMATIC 23594296 A 328 336 Tween 80 TRIVIAL 23594296 A 378 385 octanol SYSTEMATIC 23594296 A 391 406 dichloromethane SYSTEMATIC 23594296 A 412 422 chloroform TRIVIAL 23594296 A 431 444 ethyl acetate SYSTEMATIC 23594296 A 468 473 taxol TRIVIAL 23594296 A 56 61 taxol TRIVIAL 23594296 A 682 687 taxol TRIVIAL 23594296 A 775 783 Tween 80 TRIVIAL 23594296 A 837 842 taxol TRIVIAL 23594296 A 878 884 HP-βCD ABBREVIATION 23594296 A 899 904 taxol TRIVIAL 23594296 T 38 43 taxol TRIVIAL 23594789 A 0 16 Thyroid hormones FAMILY 23594789 A 639 642 PTU ABBREVIATION 23594789 A 644 667 6-n-propyl-2-thiouracil SYSTEMATIC 23594789 A 750 766 triiodothyronine TRIVIAL 23594789 A 781 784 PTU ABBREVIATION 23594789 A 884 887 PTU ABBREVIATION 23594789 T 30 45 thyroid hormone FAMILY 23595055 A 1093 1100 bromine SYSTEMATIC 23595055 A 1123 1127 MeOH FORMULA 23595055 A 1403 1410 bromine SYSTEMATIC 23595055 A 339 358 brominated tyrosine TRIVIAL 23595055 A 706 719 bromotyrosine SYSTEMATIC 23595055 A 928 932 MeOH FORMULA 23595419 A 1041 1048 lithium SYSTEMATIC 23595419 A 1159 1161 Na FORMULA 23595419 A 1162 1164 Li FORMULA 23595419 A 1173 1174 K FORMULA 23595419 A 1175 1177 Li FORMULA 23595419 A 1185 1187 Mg FORMULA 23595419 A 1188 1190 Li FORMULA 23595419 A 119 126 lithium SYSTEMATIC 23595419 A 15 22 lithium SYSTEMATIC 23595419 A 173 180 lithium SYSTEMATIC 23595419 A 310 317 lithium SYSTEMATIC 23595419 A 343 365 lithium iron phosphate SYSTEMATIC 23595419 A 434 441 lithium SYSTEMATIC 23595419 A 446 452 sodium SYSTEMATIC 23595419 A 511 520 magnesium SYSTEMATIC 23595419 A 656 663 lithium SYSTEMATIC 23595419 A 730 734 MnO2 FORMULA 23595419 A 760 768 chloride SYSTEMATIC 23595419 A 834 841 lithium SYSTEMATIC 23595419 A 877 886 magnesium SYSTEMATIC 23595419 A 941 948 lithium SYSTEMATIC 23595419 T 17 24 lithium SYSTEMATIC 23595419 T 55 59 MnO2 FORMULA 23595419 T 60 62 Ag FORMULA 23595510 A 1194 1199 (13)C FORMULA 23595510 A 1201 1205 (1)H FORMULA 23595510 A 1276 1282 carbon SYSTEMATIC 23595510 A 279 286 carbide FAMILY 23595510 A 295 302 carbons FAMILY 23595510 A 568 574 carbon SYSTEMATIC 23595510 A 57 63 carbon SYSTEMATIC 23595510 A 771 777 carbon SYSTEMATIC 23595510 T 66 73 carbide FAMILY 23595510 T 82 88 carbon SYSTEMATIC 23595554 A 477 487 difenacoum TRIVIAL 23595554 A 492 504 bromadiolone TRIVIAL 23595692 A 1030 1039 capsaicin TRIVIAL 23595692 A 1146 1154 pine-oil TRIVIAL 23595692 A 25 33 pine oil TRIVIAL 23595692 A 988 1010 adenosine triphosphate SYSTEMATIC 23595692 T 0 8 Pine Oil TRIVIAL 23596084 A 258 270 benzophenone SYSTEMATIC 23596084 A 75 96 poly(alkylacrylamide) FAMILY 23596084 T 57 81 Poly(N-alkyl Acrylamide) FAMILY 23596091 A 0 26 Fluorescein isothiocyanate SYSTEMATIC 23596091 A 144 152 mPEG-PCL ABBREVIATION 23596091 A 166 187 FITC-labeled mPEG-PCL ABBREVIATION 23596091 A 28 32 FITC ABBREVIATION 23596091 A 397 401 FITC ABBREVIATION 23596091 A 82 142 monomethoxy poly(ethylene glycol)-block-poly(ε-caprolactone) SYSTEMATIC 23596325 A 1096 1118 unsaturated fatty acid FAMILY 23596325 A 204 214 fatty acid FAMILY 23596325 A 419 426 glucose TRIVIAL 23596325 A 519 526 sucrose TRIVIAL 23596359 A 0 20 Cyclic tetrapeptides FAMILY 23596359 A 572 585 d-amino acids FAMILY 23596359 A 589 596 proline TRIVIAL 23596359 A 812 832 cyclic tetrapeptides FAMILY 23596359 A 928 936 hydrogen SYSTEMATIC 23596359 T 35 55 Cyclic Tetrapeptides FAMILY 23596972 A 1128 1132 VA64 IDENTIFIER 23596972 A 1677 1681 VA64 IDENTIFIER 23596972 A 659 663 VA64 IDENTIFIER 23597047 A 0 9 Adenosine TRIVIAL 23597047 A 1221 1232 nucleotides FAMILY 23597047 A 81 98 nucleosides/tides MULTIPLE 23597047 T 119 128 Adenosine TRIVIAL 23597071 A 488 494 biotin TRIVIAL 23597099 A 255 260 EtOAc FORMULA 23597099 A 289 305 2-methoxyjuglone SYSTEMATIC 23597099 A 606 622 propidium iodide TRIVIAL 23597099 A 64 71 ethanol SYSTEMATIC 23597099 A 747 763 propidium iodide TRIVIAL 23597099 T 0 16 2-Methoxyjuglone SYSTEMATIC 23597133 A 1027 1030 HCO FORMULA 23597133 A 1138 1141 HCO FORMULA 23597133 A 1147 1148 H FORMULA 23597133 A 1151 1153 CO FORMULA 23597133 A 1337 1338 H FORMULA 23597133 A 1339 1341 CO FORMULA 23597133 A 1362 1364 CO FORMULA 23597133 A 142 143 H FORMULA 23597133 A 148 150 CO FORMULA 23597133 A 42 55 H-CO(X̃(2)A') FAMILY 23597133 A 614 615 H FORMULA 23597133 A 616 618 CO FORMULA 23597133 A 77 79 CO FORMULA 23597133 T 57 70 H-CO(X̃(2)A') FAMILY 23597450 A 0 8 Prunetin TRIVIAL 23597450 A 1022 1030 prunetin TRIVIAL 23597450 A 1179 1187 prunetin TRIVIAL 23597450 A 1388 1396 prunetin TRIVIAL 23597450 A 148 156 prunetin TRIVIAL 23597450 A 15 38 O-methylated isoflavone FAMILY 23597450 A 212 220 prunetin TRIVIAL 23597450 A 324 336 nitric oxide SYSTEMATIC 23597450 A 781 789 prunetin TRIVIAL 23597450 A 862 870 prunetin TRIVIAL 23597450 A 892 904 nitric oxide SYSTEMATIC 23597450 A 909 925 prostaglandin E2 TRIVIAL 23597450 T 28 36 prunetin TRIVIAL 23597490 A 0 7 Embelin TRIVIAL 23597490 A 1174 1181 embelin TRIVIAL 23597490 A 1204 1211 embelin TRIVIAL 23597490 A 149 163 streptozotocin TRIVIAL 23597490 A 165 168 STZ ABBREVIATION 23597490 A 198 205 embelin TRIVIAL 23597490 A 252 255 STZ ABBREVIATION 23597490 A 346 353 glucose TRIVIAL 23597490 A 557 572 malondialdehyde TRIVIAL 23597490 A 592 603 glutathione TRIVIAL 23597490 A 626 636 superoxide TRIVIAL 23597490 A 706 709 STZ ABBREVIATION 23597490 A 745 752 embelin TRIVIAL 23597490 A 778 785 Embelin TRIVIAL 23597490 A 803 806 STZ ABBREVIATION 23597490 A 9 21 benzoquinone SYSTEMATIC 23597490 A 910 917 embelin TRIVIAL 23597490 T 26 33 embelin TRIVIAL 23597507 A 1090 1098 SB366791 IDENTIFIER 23597507 A 1136 1145 capsaicin TRIVIAL 23597507 A 1154 1160 Ca(2+) FORMULA 23597507 A 1233 1241 SB366791 IDENTIFIER 23597507 A 1256 1265 capsaicin TRIVIAL 23597507 A 1274 1280 Ca(2+) FORMULA 23597507 A 1395 1404 capsaicin TRIVIAL 23597507 A 275 282 calcium SYSTEMATIC 23597507 A 463 472 capsaicin TRIVIAL 23597507 A 518 524 Ca(2+) FORMULA 23597507 A 754 763 capsaicin TRIVIAL 23597507 A 796 804 SB366791 IDENTIFIER 23597507 A 846 856 nifedipine TRIVIAL 23597507 A 861 871 mibefradil TRIVIAL 23597507 A 935 944 capsaicin TRIVIAL 23597507 A 997 1003 Ca(2+) FORMULA 23597507 T 21 30 capsaicin TRIVIAL 23597510 A 1033 1041 nicotine TRIVIAL 23597510 A 1077 1084 cocaine TRIVIAL 23597510 A 109 117 nicotine TRIVIAL 23597510 A 1100 1108 nicotine TRIVIAL 23597510 A 1147 1155 nicotine TRIVIAL 23597510 A 1181 1188 cocaine TRIVIAL 23597510 A 121 128 alcohol FAMILY 23597510 A 1232 1240 nicotine TRIVIAL 23597510 A 1244 1251 cocaine TRIVIAL 23597510 A 1366 1374 nicotine TRIVIAL 23597510 A 1426 1457 Suberoylanilide hydroxamic acid SYSTEMATIC 23597510 A 1459 1463 SAHA ABBREVIATION 23597510 A 1531 1539 nicotine TRIVIAL 23597510 A 1607 1615 nicotine TRIVIAL 23597510 A 1816 1824 nicotine TRIVIAL 23597510 A 1828 1835 cocaine TRIVIAL 23597510 A 195 202 cocaine TRIVIAL 23597510 A 460 468 nicotine TRIVIAL 23597510 A 515 522 cocaine TRIVIAL 23597510 A 538 546 nicotine TRIVIAL 23597510 A 632 639 cocaine TRIVIAL 23597510 A 707 715 nicotine TRIVIAL 23597510 A 719 726 cocaine TRIVIAL 23597510 A 874 882 nicotine TRIVIAL 23597510 A 945 952 cocaine TRIVIAL 23597510 T 0 8 Nicotine TRIVIAL 23597510 T 30 37 cocaine TRIVIAL 23597793 A 1004 1007 Asp FORMULA 23597793 A 1030 1042 nicotinamide TRIVIAL 23597793 A 1051 1058 NADP(+) ABBREVIATION 23597793 A 146 150 (1)H FORMULA 23597793 A 152 157 (13)C FORMULA 23597793 A 2 11 tetrazole FAMILY 23597793 A 257 275 11β-hydroxysteroid FAMILY 23597793 A 34 48 clofibric acid TRIVIAL 23597793 A 424 434 clofibrate TRIVIAL 23597793 A 439 453 clofibric acid TRIVIAL 23597793 A 647 654 glucose TRIVIAL 23597793 A 986 989 Ser FORMULA 23597793 A 995 998 Tyr FORMULA 23597793 T 47 56 tetrazole FAMILY 23597793 T 69 83 clofibric acid TRIVIAL 23598462 A 305 313 graphene TRIVIAL 23598462 T 40 48 graphene TRIVIAL 23598904 A 1174 1180 Cd(2+) FORMULA 23598904 A 1185 1191 Mn(2+) FORMULA 23598904 A 162 169 cadmium SYSTEMATIC 23598904 A 174 183 manganese SYSTEMATIC 23598904 A 252 259 cadmium SYSTEMATIC 23598904 A 264 273 manganese SYSTEMATIC 23598904 A 292 294 Cd FORMULA 23598904 A 309 311 Mn FORMULA 23598904 A 388 393 CdCl2 FORMULA 23598904 A 398 403 MnCl2 FORMULA 23598904 A 435 437 Cd FORMULA 23598904 A 462 464 Mn FORMULA 23598904 A 538 543 CdCl2 FORMULA 23598904 A 548 553 MnCl2 FORMULA 23598904 A 659 666 cadmium SYSTEMATIC 23598904 A 671 680 manganese SYSTEMATIC 23598904 A 77 82 CdCl2 FORMULA 23598904 A 802 807 HgCl2 FORMULA 23598904 A 812 817 AgNO3 FORMULA 23598904 A 87 92 MnCl2 FORMULA 23598904 A 932 938 Cd(2+) FORMULA 23598904 A 943 949 Mn(2+) FORMULA 23598904 T 54 61 cadmium SYSTEMATIC 23598904 T 76 85 manganese SYSTEMATIC 23599006 A 1111 1118 alanine TRIVIAL 23599006 A 1140 1149 aspartate TRIVIAL 23599006 A 766 799 7-O-(β-D-glucopyranosyl)-galactin SYSTEMATIC 23599431 A 1013 1020 TC14012 IDENTIFIER 23599433 A 139 145 serine TRIVIAL 23599433 A 146 155 threonine TRIVIAL 23599433 T 62 68 serine TRIVIAL 23599433 T 69 78 threonine TRIVIAL 23600432 A 63 79 arachidonic acid TRIVIAL 23600432 A 789 808 1,5-diarylpyrazoles FAMILY 23600432 A 810 821 indolizines FAMILY 23600432 A 826 833 indoles FAMILY 23600486 A 181 186 ZnCl2 FORMULA 23600486 A 206 230 cyclic alkylaminocarbene FAMILY 23600486 A 232 236 cAAC ABBREVIATION 23600486 A 294 297 KC8 ABBREVIATION 23600486 A 302 315 LiB(sec-Bu)3H FORMULA 23600486 A 345 359 dicarbene zinc SYSTEMATIC 23600486 A 369 378 (cAAC)2Zn FORMULA 23600486 A 414 418 zinc SYSTEMATIC 23600486 A 428 438 (cAACH)2Zn FORMULA 23600486 A 751 754 CO2 FORMULA 23600486 A 795 799 cAAC ABBREVIATION 23600486 A 800 803 CO2 FORMULA 23600486 T 23 27 Zinc SYSTEMATIC 23600612 A 141 148 lignans FAMILY 23600612 A 150 157 visanol TRIVIAL 23600612 A 166 184 9-aldehydevibsanol SYSTEMATIC 23600612 A 19 43 8-dehydroxymethylvisanol SYSTEMATIC 23600612 A 217 221 EtOH FORMULA 23600612 A 374 381 lignans FAMILY 23600612 A 52 111 9-O-[3-O-acetyl-β-d-glucopyranosyl]-4-hydroxy-cinnamic acid SYSTEMATIC 23600626 A 235 242 polyHis ABBREVIATION 23600626 A 247 254 polyAsp ABBREVIATION 23600626 A 280 300 poly-l-glutamic acid SYSTEMATIC 23600626 A 302 309 polyGlu ABBREVIATION 23600626 A 335 342 polyHis ABBREVIATION 23600626 A 34 53 poly(aspartic acid) SYSTEMATIC 23600626 A 379 386 polyHis ABBREVIATION 23600626 A 387 394 polyAsp ABBREVIATION 23600626 A 462 469 polyHis ABBREVIATION 23600626 A 470 477 polyGlu ABBREVIATION 23600626 A 513 520 PolyHis ABBREVIATION 23600626 A 521 528 polyAsp ABBREVIATION 23600626 A 55 62 polyAsp ABBREVIATION 23600626 A 562 569 polyHis ABBREVIATION 23600626 A 570 577 polyGlu ABBREVIATION 23600626 A 68 84 poly-l-histidine SYSTEMATIC 23600626 A 831 846 ethylene glycol SYSTEMATIC 23600626 A 86 93 polyHis ABBREVIATION 23600646 A 140 144 TiO2 FORMULA 23600646 A 244 255 bisphenol A TRIVIAL 23600646 A 260 277 dibutyl phthalate SYSTEMATIC 23600646 A 34 39 Fe3O4 FORMULA 23600646 A 40 44 TiO2 FORMULA 23600646 A 492 497 Fe3O4 FORMULA 23600646 A 498 502 TiO2 FORMULA 23600646 A 786 790 TiO2 FORMULA 23600646 A 874 885 bisphenol A TRIVIAL 23600646 A 890 907 dibutyl phthalate SYSTEMATIC 23600646 A 987 992 Fe3O4 FORMULA 23600646 T 28 33 Fe3O4 FORMULA 23600646 T 34 38 TiO2 FORMULA 23600648 A 342 365 quinochalcone glycoside FAMILY 23600648 A 35 52 saffloquinoside C TRIVIAL 23600648 A 389 404 dioxaspirocycle FAMILY 23600648 A 61 136 (-)-4-hydroxybenzoic acid-4-O-[6'-O-(2″-methylbutyryl)-β-D-glucopyranoside] SYSTEMATIC 23600656 A 1236 1240 DPPC ABBREVIATION 23600656 A 1565 1569 DPPC ABBREVIATION 23600656 A 1582 1586 DPPC ABBREVIATION 23600656 A 223 242 phosphatidylcholine FAMILY 23600656 A 254 297 1,2-dipalmitoyl-sn-glycero-3-phosphacholine SYSTEMATIC 23600656 A 299 303 DPPC ABBREVIATION 23600656 A 354 361 Brucine TRIVIAL 23600656 A 442 446 DPPC ABBREVIATION 23600656 A 476 483 brucine TRIVIAL 23600656 A 655 659 DPPC ABBREVIATION 23600656 A 756 760 DPPC ABBREVIATION 23600656 A 865 869 DPPC ABBREVIATION 23600656 A 925 929 DPPC ABBREVIATION 23600656 T 0 7 Brucine TRIVIAL 23600717 A 106 118 fawcettimine TRIVIAL 23600717 A 146 163 lycobscurines A-C MULTIPLE 23600735 A 236 250 Anthraquinones FAMILY 23600735 A 252 262 flavonoids FAMILY 23600735 A 268 278 terpenoids FAMILY 23600754 A 129 209 3,4-secocycloarta-4(28),17(20),24(Z)-triene-7β-hydroxy-16β,26-lactone-3-oic acid SYSTEMATIC 23600754 A 218 303 3,4-secocycloarta-4(28),17(20)(Z),24(Z)-triene-7β-hydroxy-16β-methoxy-3,26-dioic acid SYSTEMATIC 23600754 A 53 67 nigranoic acid TRIVIAL 23600754 A 556 561 ester FAMILY 23600754 A 601 608 lactone FAMILY 23600754 A 638 657 3,4-secocycloartane SYSTEMATIC 23600754 A 69 120 3,4-secocycloarta-4(28),24(Z)-diene-3,26-dioic acid SYSTEMATIC 23600754 T 49 63 nigranoic acid TRIVIAL 23600800 A 0 3 ATP ABBREVIATION 23600800 A 1006 1012 MG-132 IDENTIFIER 23600800 A 249 256 calcium SYSTEMATIC 23600800 A 278 284 serine TRIVIAL 23600800 A 647 653 serine TRIVIAL 23600807 A 161 178 diketopiperazines FAMILY 23600807 A 19 31 rhodostegone FAMILY 23600807 A 85 104 cyclo-(l-Val-l-Leu) SYSTEMATIC 23600887 A 104 114 furostanol TRIVIAL 23600887 A 115 123 saponins FAMILY 23600887 A 158 176 steroidal saponins FAMILY 23600887 A 298 470 (25R)-26-O-[β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranosyl]-5-ene-furost-1β,3β,22α,26-tetraol-3-O-α-l-rhamnopyranosyl-(1 → 2)-[β-d-xylopyranosyl-(1 → 4)]-β-d-glucopyranoside SYSTEMATIC 23600887 A 475 489 ophiopogonin P TRIVIAL 23600887 A 495 667 (25R)-26-O-[β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyl]-5-ene-furost-1β,3β,22α,26-tetraol-3-O-α-l-rhamnopyranosyl-(1 → 2)-[β-d-xylopyranosyl-(1 → 4)]-β-d-glucopyranoside SYSTEMATIC 23600887 A 672 686 ophiopogonin Q TRIVIAL 23600887 A 689 699 Furostanol TRIVIAL 23600887 A 700 708 saponins FAMILY 23600887 A 718 730 disaccharide FAMILY 23600887 A 747 759 C-26 hydroxy SYSTEMATIC 23600887 T 10 20 furostanol TRIVIAL 23600887 T 21 29 saponins FAMILY 23600914 A 1201 1207 24-OHC SYSTEMATIC 23600914 A 1262 1268 24-OHC SYSTEMATIC 23600914 A 130 154 24(S)-hydroxycholesterol SYSTEMATIC 23600914 A 156 162 24-OHC SYSTEMATIC 23600914 A 363 369 24-OHC SYSTEMATIC 23600914 A 39 50 cholesterol TRIVIAL 23600914 A 488 494 24-OHC SYSTEMATIC 23600914 A 5 16 cholesterol TRIVIAL 23600914 A 507 515 TO901317 IDENTIFIER 23600914 A 520 533 retinoic acid TRIVIAL 23600914 A 639 645 24-OHC SYSTEMATIC 23600914 A 993 999 24-OHC SYSTEMATIC 23600914 T 0 24 24(S)-hydroxycholesterol SYSTEMATIC 23600925 A 177 192 diaminothiazole FAMILY 23600925 A 36 42 serine TRIVIAL 23600925 A 43 52 threonine TRIVIAL 23600925 T 43 58 Diaminothiazole FAMILY 23601387 A 162 172 vitamin D3 TRIVIAL 23601387 A 177 198 25-hydroxy-vitamin D3 SYSTEMATIC 23601387 A 200 206 25OHD3 SYSTEMATIC 23601387 A 316 325 vitamin D FAMILY 23601387 A 35 44 vitamin D FAMILY 23601387 A 438 448 vitamin D3 TRIVIAL 23601387 A 465 471 25OHD3 SYSTEMATIC 23601387 A 516 526 vitamin D3 TRIVIAL 23601387 A 538 544 25OHD3 SYSTEMATIC 23601387 A 593 603 vitamin D3 TRIVIAL 23601387 A 616 622 25OHD3 SYSTEMATIC 23601387 A 760 770 vitamin D3 TRIVIAL 23601387 T 50 60 vitamin D3 TRIVIAL 23601387 T 65 86 25-hydroxy-vitamin D3 SYSTEMATIC 23601391 A 30 35 sugar FAMILY 23601393 A 157 170 ascorbic acid TRIVIAL 23601393 A 401 414 Ascorbic acid TRIVIAL 23601393 A 521 525 zinc SYSTEMATIC 23601393 A 530 536 copper SYSTEMATIC 23601393 A 549 556 calcium SYSTEMATIC 23601393 A 558 567 magnesium SYSTEMATIC 23601393 A 572 583 phosphorous SYSTEMATIC 23601393 A 627 636 Potassium SYSTEMATIC 23601393 A 765 778 ascorbic acid TRIVIAL 23601396 A 156 169 carbohydrates FAMILY 23601396 A 219 223 iron SYSTEMATIC 23601396 A 225 229 zinc SYSTEMATIC 23601396 A 231 240 magnesium SYSTEMATIC 23601396 A 242 249 calcium SYSTEMATIC 23601396 A 251 261 phosphorus SYSTEMATIC 23601396 A 263 269 copper SYSTEMATIC 23601396 A 271 280 manganese SYSTEMATIC 23601396 A 282 291 potassium SYSTEMATIC 23601396 A 293 299 sodium SYSTEMATIC 23601396 A 304 312 selenium SYSTEMATIC 23601396 A 799 803 iron SYSTEMATIC 23601396 A 805 809 zinc SYSTEMATIC 23601396 A 814 823 magnesium SYSTEMATIC 23601409 A 1196 1203 ethanol SYSTEMATIC 23601409 A 724 738 monosaccharide FAMILY 23601409 A 803 810 Glucose TRIVIAL 23601409 A 840 854 monosaccharide FAMILY 23601409 A 868 877 arabinose TRIVIAL 23601409 A 879 888 galactose TRIVIAL 23601409 A 890 896 xylose TRIVIAL 23601409 A 901 908 mannose TRIVIAL 23601709 A 0 4 EMPA ABBREVIATION 23601709 A 1093 1104 [(11)C]EMPA SYSTEMATIC 23601709 A 337 341 EMPA ABBREVIATION 23601709 A 347 353 carbon SYSTEMATIC 23601709 A 376 478 [(11)C]N-ethyl-2-(N-(6-methoxypyridin-3-yl)-2-methylphenylsulfonamido)-N-(pyridin-3-ylmethyl)acetamide SYSTEMATIC 23601709 A 480 491 [(11)C]EMPA SYSTEMATIC 23601709 A 611 612 O FORMULA 23601709 A 651 655 EMPA ABBREVIATION 23601709 A 661 674 sodium iodide SYSTEMATIC 23601709 A 679 700 chlorotrimethylsilane SYSTEMATIC 23601709 A 712 713 O FORMULA 23601709 A 732 743 [(11)C]CH3I SYSTEMATIC 23601709 A 763 779 cesium carbonate SYSTEMATIC 23601709 A 783 787 DMSO ABBREVIATION 23601709 A 810 821 [(11)C]EMPA SYSTEMATIC 23601709 A 85 96 [(3)H]-EMPA SYSTEMATIC 23601709 A 881 892 [(11)C]CH3I SYSTEMATIC 23601709 T 33 44 [(11)C]EMPA SYSTEMATIC 23601710 A 134 177 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione SYSTEMATIC 23601710 A 417 432 benzotriazepine FAMILY 23601710 A 437 456 spirobenzodiazepine FAMILY 23601710 A 52 58 phenyl SYSTEMATIC 23601710 T 155 161 phenyl SYSTEMATIC 23601710 T 18 61 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione SYSTEMATIC 23601711 A 221 227 S14161 IDENTIFIER 23601711 A 28 75 8-ethoxy-2-(4-fluorophenyl)-3-nitro-2H-chromene SYSTEMATIC 23601711 A 342 351 l-proline SYSTEMATIC 23601711 A 356 369 triethylamine SYSTEMATIC 23601711 A 434 470 6-bromo-8-ethoxy-3-nitro-2H-chromene SYSTEMATIC 23601711 A 472 480 BENC-511 IDENTIFIER 23601711 A 587 593 S14161 IDENTIFIER 23601711 A 595 603 BENC-511 IDENTIFIER 23601711 A 692 700 BENC-511 IDENTIFIER 23601711 A 77 83 S14161 IDENTIFIER 23601711 T 15 21 S14161 IDENTIFIER 23601711 T 61 97 6-bromo-8-ethoxy-3-nitro-2H-chromene SYSTEMATIC 23602400 A 0 57 2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d]pyrimidine SYSTEMATIC 23602400 A 195 202 4-amino SYSTEMATIC 23602400 A 235 246 pyrimidines FAMILY 23602400 A 278 330 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine SYSTEMATIC 23602400 A 410 427 N-propylacetamide SYSTEMATIC 23602400 T 37 63 4-amino-2-phenylpyrimidine SYSTEMATIC 23602442 A 253 264 diarylureas FAMILY 23602442 A 285 290 amine SYSTEMATIC 23602442 A 57 67 diarylurea FAMILY 23602442 T 13 23 diarylurea FAMILY 23602516 A 0 9 Cisplatin TRIVIAL 23602516 A 1135 1144 Cisplatin TRIVIAL 23602516 A 1361 1370 cisplatin TRIVIAL 23602516 A 1459 1468 cisplatin TRIVIAL 23602516 A 1544 1553 cisplatin TRIVIAL 23602516 A 1579 1588 cisplatin TRIVIAL 23602516 A 1687 1696 cisplatin TRIVIAL 23602516 A 1785 1794 cisplatin TRIVIAL 23602516 A 416 425 cisplatin TRIVIAL 23602516 A 851 860 cisplatin TRIVIAL 23602516 A 961 970 cisplatin TRIVIAL 23602516 T 0 9 Cisplatin TRIVIAL 23602732 A 353 364 Salidroside TRIVIAL 23602732 A 369 376 tyrosol TRIVIAL 23602732 A 65 76 salidroside TRIVIAL 23602732 A 778 789 salidroside TRIVIAL 23602732 A 794 801 tyrosol TRIVIAL 23602732 A 81 88 tyrosol TRIVIAL 23602891 A 235 238 HCQ ABBREVIATION 23602891 A 43 61 hydroxychloroquine SYSTEMATIC 23602891 A 63 66 HCQ ABBREVIATION 23602891 A 845 848 HCQ ABBREVIATION 23602891 A 900 903 HCQ ABBREVIATION 23602891 T 49 67 Hydroxychloroquine SYSTEMATIC 23602903 A 0 21 Scrophularianines A-C MULTIPLE 23602903 A 406 426 monoterpene pyridine FAMILY 23602903 A 441 449 iridoids FAMILY 23602903 A 47 77 monoterpene pyridine alkaloids FAMILY 23602903 A 630 634 H2O2 FORMULA 23602903 A 83 106 cyclopenta [c] pyridine SYSTEMATIC 23602903 T 0 30 Monoterpene pyridine alkaloids FAMILY 23602903 T 35 44 phenolics FAMILY 23602986 A 1070 1078 nicotine TRIVIAL 23602986 A 114 117 MLA ABBREVIATION 23602986 A 1148 1156 nicotine TRIVIAL 23602986 A 123 147 dihydro-beta-eritroidine SYSTEMATIC 23602986 A 1264 1272 cotinine TRIVIAL 23602986 A 1279 1287 cotinine TRIVIAL 23602986 A 1288 1296 nicotine TRIVIAL 23602986 A 149 153 DHβE ABBREVIATION 23602986 A 42 50 nicotine TRIVIAL 23602986 A 52 55 NIC ABBREVIATION 23602986 A 58 66 cotinine TRIVIAL 23602986 A 604 612 nicotine TRIVIAL 23602986 A 633 641 Cotinine TRIVIAL 23602986 A 677 685 nicotine TRIVIAL 23602986 A 68 71 COT ABBREVIATION 23602986 A 74 86 mecamylamine TRIVIAL 23602986 A 792 800 cotinine TRIVIAL 23602986 A 809 817 nicotine TRIVIAL 23602986 A 88 91 MEC ABBREVIATION 23602986 A 94 112 methyllycaconitine TRIVIAL 23602986 A 991 999 Cotinine TRIVIAL 23602986 T 23 31 cotinine TRIVIAL 23602989 A 1018 1023 KN-62 IDENTIFIER 23602989 A 1090 1094 K(+) FORMULA 23602989 A 1176 1186 [(3)H]GABA FORMULA 23602989 A 1230 1235 KN-62 IDENTIFIER 23602989 A 1297 1307 PD 128,907 IDENTIFIER 23602989 A 1344 1353 SKF 38393 IDENTIFIER 23602989 A 1371 1376 KN-62 IDENTIFIER 23602989 A 1406 1414 dopamine TRIVIAL 23602989 A 1441 1451 [(3)H]GABA FORMULA 23602989 A 1461 1466 KN-62 IDENTIFIER 23602989 A 1484 1492 dopamine TRIVIAL 23602989 A 1512 1517 KN-62 IDENTIFIER 23602989 A 1670 1676 Ca(2+) FORMULA 23602989 A 1731 1735 GABA ABBREVIATION 23602989 A 1873 1881 dopamine TRIVIAL 23602989 A 425 431 Ca(2+) FORMULA 23602989 A 516 522 Ca(2+) FORMULA 23602989 A 524 533 ionomycin TRIVIAL 23602989 A 538 542 K(+) FORMULA 23602989 A 597 601 cAMP ABBREVIATION 23602989 A 650 658 dopamine TRIVIAL 23602989 A 702 707 KN-62 IDENTIFIER 23602989 A 742 751 ionomycin TRIVIAL 23602989 A 756 760 K(+) FORMULA 23602989 A 798 803 Ca(2) FORMULA 23602989 A 842 848 Ca(2+) FORMULA 23602989 A 857 867 nifedipine TRIVIAL 23602989 A 907 911 K(+) FORMULA 23602989 A 959 963 K(+) FORMULA 23602989 T 111 117 Ca(2+) FORMULA 23602989 T 30 38 dopamine TRIVIAL 23603053 A 0 30 Polybrominated diphenyl ethers FAMILY 23603053 A 1003 1011 OH-PBDEs FAMILY 23603053 A 1143 1151 OH-PBDEs FAMILY 23603053 A 1288 1295 OH-PBDE FORMULA 23603053 A 1378 1386 OH-PBDEs FAMILY 23603053 A 191 195 PBDE ABBREVIATION 23603053 A 197 204 OH-PBDE FORMULA 23603053 A 255 263 OH-PBDEs FAMILY 23603053 A 32 37 PBDEs ABBREVIATION 23603053 A 397 405 OH-PBDEs FAMILY 23603053 A 529 541 6-OH-BDE-047 SYSTEMATIC 23603053 A 542 555 4'-OH-BDE-049 SYSTEMATIC 23603053 A 556 569 4'-OH-BDE-017 SYSTEMATIC 23603053 A 570 583 6'-OH-BDE-099 SYSTEMATIC 23603053 A 584 597 5'-OH-BDE-099 SYSTEMATIC 23603053 A 598 611 2'-OH-BDE-007 SYSTEMATIC 23603053 A 612 625 3'-OH-BDE-028 SYSTEMATIC 23603053 A 686 694 OH-PBDEs FAMILY 23603053 A 69 77 estrogen FAMILY 23603053 A 824 837 4'-OH-BDE-049 SYSTEMATIC 23603053 A 838 851 4'-OH-BDE-017 SYSTEMATIC 23603053 A 852 865 2'-OH-BDE-007 SYSTEMATIC 23603053 A 866 879 3'-OH-BDE-028 SYSTEMATIC 23603053 A 880 892 3-OH-BDE-047 SYSTEMATIC 23603053 A 893 906 3'-OH-BDE-007 SYSTEMATIC 23603053 T 34 77 hydroxylated polybrominated diphenyl ethers FAMILY 23603053 T 87 95 estrogen FAMILY 23603059 A 1044 1053 SP6001325 IDENTIFIER 23603059 A 1213 1220 arsenic SYSTEMATIC 23603059 A 1289 1296 arsenic SYSTEMATIC 23603059 A 168 175 arsenic SYSTEMATIC 23603059 A 17 24 arsenic SYSTEMATIC 23603059 A 553 568 sodium arsenite SYSTEMATIC 23603059 A 663 669 oxygen SYSTEMATIC 23603059 A 803 804 N FORMULA 23603059 A 901 917 N-acetylcysteine SYSTEMATIC 23603059 A 919 922 NAC ABBREVIATION 23603059 T 0 7 Arsenic SYSTEMATIC 23603112 A 1143 1148 TMPCP ABBREVIATION 23603112 A 1153 1161 TMPCP-4P ABBREVIATION 23603112 A 1313 1323 porphyrins FAMILY 23603112 A 1523 1532 porphyrin FAMILY 23603112 A 237 309 tri-cationic meso-tri(4-N-methylpyridyl)-mono-(4-carboxyphenyl)porphyrin SYSTEMATIC 23603112 A 311 316 TMPCP ABBREVIATION 23603112 A 322 335 tetrapeptides FAMILY 23603112 A 347 352 TMPCP ABBREVIATION 23603112 A 354 362 TMPCP-4P ABBREVIATION 23603112 A 368 448 bi-cationic meso-5,10-bis(4-N-methylpyridyl)-15,20-di-(4-carboxyphenyl)porphyrin SYSTEMATIC 23603112 A 44 53 porphyrin FAMILY 23603112 A 450 459 BMPCP-4P2 ABBREVIATION 23603112 A 548 560 tetrapeptide FAMILY 23603112 A 584 594 porphyrins FAMILY 23603112 A 974 983 BMPCP-4P2 ABBREVIATION 23603112 T 24 33 porphyrin FAMILY 23603112 T 34 46 tetrapeptide FAMILY 23603193 A 1027 1030 Val ABBREVIATION 23603193 A 1152 1155 PTZ ABBREVIATION 23603193 A 1237 1240 Val ABBREVIATION 23603193 A 1273 1276 Val ABBREVIATION 23603193 A 1294 1306 nitric oxide SYSTEMATIC 23603193 A 1308 1310 NO FORMULA 23603193 A 1369 1372 PTZ ABBREVIATION 23603193 A 1424 1426 NO FORMULA 23603193 A 1443 1446 Val ABBREVIATION 23603193 A 1494 1497 MDA ABBREVIATION 23603193 A 1516 1519 PTZ ABBREVIATION 23603193 A 1579 1581 NO FORMULA 23603193 A 1713 1716 PTZ ABBREVIATION 23603193 A 1808 1811 Val ABBREVIATION 23603193 A 1844 1846 NO FORMULA 23603193 A 525 542 pentylenetetrazol TRIVIAL 23603193 A 544 547 PTZ ABBREVIATION 23603193 A 714 717 PTZ ABBREVIATION 23603193 A 785 788 PTZ ABBREVIATION 23603193 A 898 901 PTZ ABBREVIATION 23603193 A 941 950 Valproate TRIVIAL 23603193 A 952 955 Val ABBREVIATION 23603193 T 95 112 pentylenetetrazol TRIVIAL 23603293 A 0 10 Toluquinol TRIVIAL 23603293 A 1341 1351 toluquinol TRIVIAL 23603293 A 14 32 methylhydroquinone SYSTEMATIC 23603293 A 1630 1640 toluquinol TRIVIAL 23603293 A 212 222 toluquinol TRIVIAL 23603293 A 358 368 toluquinol TRIVIAL 23603293 A 448 458 Toluquinol TRIVIAL 23603293 A 673 683 Toluquinol TRIVIAL 23603293 A 931 941 toluquinol TRIVIAL 23603293 T 0 10 Toluquinol TRIVIAL 23603339 A 1019 1027 estrogen FAMILY 23603339 A 1040 1044 DHEA ABBREVIATION 23603339 A 1281 1285 DHEA ABBREVIATION 23603339 A 1376 1389 actinomycin D TRIVIAL 23603339 A 144 148 DHEA ABBREVIATION 23603339 A 1537 1541 DHEA ABBREVIATION 23603339 A 1565 1569 DHEA ABBREVIATION 23603339 A 1657 1661 DHEA ABBREVIATION 23603339 A 30 52 dehydroepiandrosterone TRIVIAL 23603339 A 392 396 DHEA ABBREVIATION 23603339 A 54 58 DHEA ABBREVIATION 23603339 A 554 558 DHEA ABBREVIATION 23603339 A 604 621 7-ethoxyresorufin SYSTEMATIC 23603339 A 622 623 O FORMULA 23603339 A 641 651 phenacetin TRIVIAL 23603339 A 652 653 O FORMULA 23603339 A 704 724 3-methylcholanthrene SYSTEMATIC 23603339 A 786 794 androgen FAMILY 23603339 A 829 833 DHEA ABBREVIATION 23603339 A 917 929 bicalutamide TRIVIAL 23603339 A 935 943 androgen FAMILY 23603339 T 0 22 Dehydroepiandrosterone TRIVIAL 23603339 T 82 90 androgen FAMILY 23603380 A 1006 1015 anabasine TRIVIAL 23603380 A 1020 1028 myosmine TRIVIAL 23603380 A 1056 1074 alpha conotoxin GI TRIVIAL 23603380 A 186 195 anabasine TRIVIAL 23603380 A 197 205 lobeline TRIVIAL 23603380 A 211 219 myosmine TRIVIAL 23603380 A 327 340 acetylcholine SYSTEMATIC 23603380 A 623 641 alpha conotoxin GI TRIVIAL 23603380 A 685 694 anabasine TRIVIAL 23603380 A 699 707 myosmine TRIVIAL 23603380 A 804 812 lobeline TRIVIAL 23603380 A 869 878 anabasine TRIVIAL 23603380 A 967 975 lobeline TRIVIAL 23603380 A 980 988 myosmine TRIVIAL 23603380 T 0 10 Piperidine SYSTEMATIC 23603380 T 12 29 pyridine alkaloid FAMILY 23603381 A 18 21 BLM ABBREVIATION 23603381 A 27 43 cyclophosphamide TRIVIAL 23603381 A 339 351 Ellagic acid TRIVIAL 23603381 A 620 623 BLM ABBREVIATION 23603381 A 7 16 bleomycin FAMILY 23603381 A 703 717 hydroxyproline SYSTEMATIC 23603381 A 771 783 nitric oxide SYSTEMATIC 23603381 A 807 815 carbonyl FAMILY 23603381 A 909 912 GSH ABBREVIATION 23603381 A 974 977 BLM ABBREVIATION 23603381 T 0 12 Ellagic acid TRIVIAL 23603381 T 24 33 bleomycin FAMILY 23603381 T 38 54 cyclophosphamide TRIVIAL 23603385 A 1665 1681 titanium dioxide SYSTEMATIC 23603385 A 1750 1754 TiO2 FORMULA 23603385 A 1970 1974 TiO2 FORMULA 23603385 A 2203 2207 TiO2 FORMULA 23603385 A 41 57 titanium dioxide SYSTEMATIC 23603385 A 464 468 TiO2 FORMULA 23603385 A 547 551 TiO2 FORMULA 23603385 A 750 766 titanium dioxide SYSTEMATIC 23603385 A 840 856 titanium dioxide SYSTEMATIC 23603385 T 79 95 titanium dioxide SYSTEMATIC 23603635 A 271 284 benzoquinones FAMILY 23603635 A 286 294 vanadium SYSTEMATIC 23603635 A 469 477 tyrosine TRIVIAL 23604140 A 1175 1181 Bodipy TRIVIAL 23604140 A 1182 1193 pirenzepine TRIVIAL 23604140 A 196 207 pirenzepine TRIVIAL 23604140 A 257 273 Bodipy [558/568] IDENTIFIER 23604140 A 724 730 Bodipy TRIVIAL 23604140 A 909 918 gallamine TRIVIAL 23604140 A 958 973 indocarbazolole SYSTEMATIC 23604592 A 1456 1458 As FORMULA 23604592 A 1460 1462 Cd FORMULA 23604592 A 1467 1469 Pb FORMULA 23604592 A 283 289 oxygen SYSTEMATIC 23604592 A 409 411 As FORMULA 23604592 A 422 424 Pb FORMULA 23604592 A 439 441 Cd FORMULA 23604592 A 59 61 As FORMULA 23604592 A 63 65 Cd FORMULA 23604592 A 70 72 Pb FORMULA 23604592 T 26 28 As FORMULA 23604592 T 30 32 Cd FORMULA 23604592 T 37 39 Pb FORMULA 23604719 A 115 119 β-CD ABBREVIATION 23604719 A 266 270 β-CD ABBREVIATION 23604719 A 373 383 flavonoids FAMILY 23604719 A 47 57 flavonoids FAMILY 23604719 A 502 506 β-CD ABBREVIATION 23604719 A 607 611 β-CD ABBREVIATION 23604719 A 99 113 β-cyclodextrin TRIVIAL 23604719 T 35 45 flavonoids FAMILY 23604721 A 232 240 methanol SYSTEMATIC 23604721 A 396 402 flavan FAMILY 23604721 T 35 44 flavonoid FAMILY 23604819 A 0 52 1-Substituted-N-tosyl-1,2,3,4-tetrahydroisoquinoline FAMILY 23604819 A 1109 1132 tetrahydroisoquinolines FAMILY 23604819 A 166 189 tetrahydroisoquinolines FAMILY 23604819 A 251 260 p-methoxy SYSTEMATIC 23604819 A 291 300 o-hydroxy SYSTEMATIC 23604819 A 467 477 Trimethoxy SYSTEMATIC 23604819 A 913 922 p-methoxy SYSTEMATIC 23604819 T 42 80 N-tosyl-1,2,3,4-tetrahydroisoquinoline SYSTEMATIC 23605905 A 706 714 thyroxin TRIVIAL 23605905 A 84 100 triiodothyronine TRIVIAL 23605905 T 132 148 triiodothyronine TRIVIAL 23606243 A 0 4 TiO2 FORMULA 23606243 A 143 147 TiO2 FORMULA 23606243 A 186 189 FTO ABBREVIATION 23606243 A 273 277 TiO2 FORMULA 23606243 A 332 336 TiO2 FORMULA 23606243 A 503 507 TiO2 FORMULA 23606243 A 761 765 CdSe FORMULA 23606243 A 780 784 TiO2 FORMULA 23606243 T 23 27 TiO2 FORMULA 23606278 A 115 126 cholesterol TRIVIAL 23606278 A 34 45 cholesterol TRIVIAL 23606278 A 515 522 statins FAMILY 23606278 T 7 14 Statins FAMILY 23606301 A 185 205 polydimethylsiloxane SYSTEMATIC 23606301 A 207 211 PDMS ABBREVIATION 23606301 A 341 347 oxygen SYSTEMATIC 23606301 T 98 104 Oxygen SYSTEMATIC 23606318 A 20 30 dabigatran TRIVIAL 23606318 A 35 46 rivaroxaban TRIVIAL 23606318 A 540 548 warfarin TRIVIAL 23606318 A 550 560 dabigatran TRIVIAL 23606318 A 566 577 rivaroxaban TRIVIAL 23606318 A 938 946 warfarin TRIVIAL 23606318 A 976 986 dabigatran TRIVIAL 23606318 A 991 1002 rivaroxaban TRIVIAL 23606463 A 284 292 carbonyl FAMILY 23606463 A 302 307 amino FAMILY 23606463 A 37 45 carbonyl FAMILY 23606463 A 514 522 carbonyl FAMILY 23606629 A 203 219 phosphoramidates FAMILY 23606629 A 321 336 phosphoramidate SYSTEMATIC 23606629 A 369 378 thymidine TRIVIAL 23606629 A 416 426 nucleoside FAMILY 23606629 A 438 453 Phosphoramidate SYSTEMATIC 23606629 A 469 505 (E)-5-(2-bromovinyl)-2'-deoxyuridine SYSTEMATIC 23606629 A 507 511 BVDU ABBREVIATION 23606629 A 526 535 L-alanine TRIVIAL 23606629 A 539 571 pivaloyloxymethyl iminodiacetate SYSTEMATIC 23606629 A 54 79 nucleoside monophosphates FAMILY 23606629 A 573 580 IDA-POM ABBREVIATION 23606629 A 735 746 nucleosides FAMILY 23606629 A 757 772 phosphoramidate SYSTEMATIC 23606629 A 816 827 nucleosides FAMILY 23606629 A 838 862 phosphoramidate triester FAMILY 23606629 A 945 955 nucleotide FAMILY 23606629 A 96 111 phosphoramidate SYSTEMATIC 23606629 A 976 992 phosphoramidates FAMILY 23606629 T 40 55 Phosphoramidate SYSTEMATIC 23607523 A 1043 1045 C7 FORMULA 23607523 A 1046 1054 cyclitol FAMILY 23607523 A 214 225 pyralomicin TRIVIAL 23607523 A 359 377 benzopyranopyrrole FAMILY 23607523 A 38 49 pyralomicin TRIVIAL 23607523 A 457 458 O FORMULA 23607523 A 485 486 N FORMULA 23607523 A 571 572 N FORMULA 23607523 A 625 632 glucose TRIVIAL 23607523 A 651 659 cyclitol FAMILY 23607523 A 703 705 C7 FORMULA 23607523 A 706 714 cyclitol FAMILY 23607523 A 767 785 benzopyranopyrrole FAMILY 23607523 A 846 847 N FORMULA 23607523 A 885 896 pyralomicin TRIVIAL 23607523 A 986 991 sugar FAMILY 23607523 A 992 1001 phosphate SYSTEMATIC 23607523 T 22 33 Pyralomicin TRIVIAL 23607578 A 164 170 carbon SYSTEMATIC 23607578 A 88 100 carbon black TRIVIAL 23607578 T 38 44 Carbon SYSTEMATIC 23607669 A 152 161 HB(C6F5)2 FORMULA 23607669 A 218 224 amines FAMILY 23607669 A 75 81 imines FAMILY 23607669 A 95 101 dienes FAMILY 23607669 T 31 37 borane SYSTEMATIC 23607669 T 7 13 dienes FAMILY 23607669 T 87 93 imines FAMILY 23607866 A 1089 1098 docetaxel TRIVIAL 23607866 A 1294 1304 paclitaxel TRIVIAL 23607866 A 1381 1391 paclitaxel TRIVIAL 23607866 A 1479 1481 1H FORMULA 23607866 A 1634 1644 paclitaxel TRIVIAL 23607866 A 387 423 N-(2-benzoyloxypropyl methacrylamide SYSTEMATIC 23607866 A 456 465 naphthoyl SYSTEMATIC 23607866 A 492 538 N-(2-hydroxypropyl) methacrylamide monolactate SYSTEMATIC 23607866 A 548 567 polyethylene glycol SYSTEMATIC 23607866 A 877 887 Paclitaxel TRIVIAL 23607866 A 892 901 docetaxel TRIVIAL 23607866 A 958 965 ethanol SYSTEMATIC 23607869 T 139 142 C-h FORMULA 23607869 T 144 147 C-C FORMULA 23607869 T 153 156 C-f FORMULA 23608109 A 577 587 crizotinib TRIVIAL 23608241 A 1099 1103 cAMP ABBREVIATION 23608241 A 1124 1132 foskolin TRIVIAL 23608241 A 1191 1199 morphine TRIVIAL 23608241 A 1205 1216 mitragynine TRIVIAL 23608241 A 1297 1305 morphine TRIVIAL 23608241 A 1361 1372 mitragynine TRIVIAL 23608241 A 1434 1442 morphine TRIVIAL 23608241 A 1486 1490 cAMP ABBREVIATION 23608241 A 1572 1583 mitragynine TRIVIAL 23608241 A 31 42 Mitragynine TRIVIAL 23608241 A 339 350 mitragynine TRIVIAL 23608241 A 365 373 morphine TRIVIAL 23608241 A 387 397 cyclic AMP TRIVIAL 23608241 A 399 403 cAMP ABBREVIATION 23608241 A 49 64 indole alkaloid FAMILY 23608241 A 518 529 Mitragynine TRIVIAL 23608241 A 620 624 cAMP ABBREVIATION 23608241 A 636 645 forskolin TRIVIAL 23608241 A 848 856 morphine TRIVIAL 23608241 A 861 872 mitragynine TRIVIAL 23608241 A 913 917 cAMP ABBREVIATION 23608241 A 952 960 nitrogen SYSTEMATIC 23608241 T 14 25 mitragynine TRIVIAL 23608241 T 29 33 cAMP ABBREVIATION 23608613 A 363 380 albuterol sulfate SYSTEMATIC 23608613 A 389 397 mannitol TRIVIAL 23608613 A 423 432 l-leucine TRIVIAL 23608613 A 459 472 poloxamer 188 TRIVIAL 23608699 A 1019 1022 EE2 ABBREVIATION 23608699 A 1034 1046 testosterone TRIVIAL 23608699 A 1114 1131 25-OH-cholesterol SYSTEMATIC 23608699 A 1140 1152 pregnenolone TRIVIAL 23608699 A 1160 1172 testosterone TRIVIAL 23608699 A 12 32 17α-ethinylestradiol SYSTEMATIC 23608699 A 1259 1264 11-KT ABBREVIATION 23608699 A 1375 1380 11-KT ABBREVIATION 23608699 A 1473 1476 EE2 ABBREVIATION 23608699 A 1596 1599 EE2 ABBREVIATION 23608699 A 310 313 EE2 ABBREVIATION 23608699 A 34 37 EE2 ABBREVIATION 23608699 A 491 494 EE2 ABBREVIATION 23608699 A 52 60 estrogen FAMILY 23608699 A 552 555 EE2 ABBREVIATION 23608699 A 688 691 EE2 ABBREVIATION 23608699 A 734 747 17β-estradiol SYSTEMATIC 23608699 A 878 883 11-KT ABBREVIATION 23608699 A 885 904 11-ketotestosterone SYSTEMATIC 23608699 A 918 921 EE2 ABBREVIATION 23608699 T 11 31 17α-ethinylestradiol SYSTEMATIC 23608699 T 33 36 EE2 ABBREVIATION 23608896 A 136 140 Cu2O FORMULA 23608896 A 141 143 Ni FORMULA 23608896 A 16 27 polystyrene SYSTEMATIC 23608896 A 202 206 Cu2O FORMULA 23608896 A 207 209 Ni FORMULA 23608896 T 40 44 Cu2O FORMULA 23608896 T 45 47 Ni FORMULA 23609128 A 1221 1230 hydronium SYSTEMATIC 23609128 A 1369 1380 (H2 O)5 (+) FORMULA 23609128 A 1443 1447 H2 O FORMULA 23609128 A 251 258 (H2 O)n FAMILY 23609128 A 746 755 hydronium SYSTEMATIC 23609128 A 771 778 H3 O(+) FORMULA 23609128 A 789 797 hydroxyl SYSTEMATIC 23609145 A 1031 1038 citrate FAMILY 23609145 A 1043 1050 glycine TRIVIAL 23609145 A 1279 1290 bicarbonate SYSTEMATIC 23609145 A 19 25 folate TRIVIAL 23609145 A 202 208 folate TRIVIAL 23609145 A 306 317 bicarbonate SYSTEMATIC 23609145 A 410 419 Bisulfite SYSTEMATIC 23609145 A 424 431 nitrite SYSTEMATIC 23609145 A 484 491 sulfate SYSTEMATIC 23609145 A 493 500 nitrate SYSTEMATIC 23609145 A 505 514 phosphate SYSTEMATIC 23609145 A 564 573 bisulfite SYSTEMATIC 23609145 A 578 585 nitrite SYSTEMATIC 23609145 A 654 661 sulfate SYSTEMATIC 23609145 A 666 673 nitrate SYSTEMATIC 23609145 A 713 722 bisulfite SYSTEMATIC 23609145 A 727 734 nitrite SYSTEMATIC 23609145 A 76 82 folate TRIVIAL 23609145 A 922 938 Monocarboxylates FAMILY 23609145 A 947 955 pyruvate TRIVIAL 23609145 A 960 967 acetate SYSTEMATIC 23609145 T 33 39 Folate TRIVIAL 23609145 T 70 81 Bicarbonate SYSTEMATIC 23609438 A 1110 1116 Ca(2+) FORMULA 23609438 A 1641 1647 Ca(2+) FORMULA 23609438 A 29 36 calcium SYSTEMATIC 23609438 A 47 56 potassium SYSTEMATIC 23609438 A 482 488 Ca(2+) FORMULA 23609438 A 505 511 Ca(2+) FORMULA 23609438 A 546 552 Ca(2+) FORMULA 23609438 A 637 643 Ca(2+) FORMULA 23609438 A 695 699 cAMP ABBREVIATION 23609438 A 852 858 Ca(2+) FORMULA 23609438 T 140 147 Calcium SYSTEMATIC 23609438 T 29 36 Calcium SYSTEMATIC 23609438 T 47 56 Potassium SYSTEMATIC 23609606 A 1076 1081 UDPGA ABBREVIATION 23609606 A 1107 1112 UDPGA ABBREVIATION 23609606 A 1171 1185 fenclozic acid TRIVIAL 23609606 A 1537 1551 fenclozic acid TRIVIAL 23609606 A 26 40 fenclozic acid TRIVIAL 23609606 A 372 394 [(14)C]-fenclozic acid SYSTEMATIC 23609606 A 4 19 carboxylic acid SYSTEMATIC 23609606 A 512 517 NADPH ABBREVIATION 23609606 A 910 917 taurine TRIVIAL 23609606 A 966 982 acyl glucuronide SYSTEMATIC 23609606 T 87 101 fenclozic acid TRIVIAL 23609769 A 1121 1128 ecstasy TRIVIAL 23609769 A 1139 1146 ecstasy TRIVIAL 23609769 A 1149 1160 amphetamine TRIVIAL 23609769 A 1228 1235 ecstasy TRIVIAL 23609769 A 1245 1252 ecstasy TRIVIAL 23609769 A 1255 1266 amphetamine TRIVIAL 23609769 A 1306 1317 Amphetamine TRIVIAL 23609769 A 1328 1335 ecstasy TRIVIAL 23609769 A 1538 1545 ecstasy TRIVIAL 23609769 A 1548 1559 amphetamine TRIVIAL 23609769 A 1665 1672 ecstasy TRIVIAL 23609769 A 1688 1697 serotonin TRIVIAL 23609769 A 229 236 ecstasy TRIVIAL 23609769 A 238 266 methylendioxymethamphetamine SYSTEMATIC 23609769 A 300 309 serotonin TRIVIAL 23609769 A 366 377 amphetamine TRIVIAL 23609769 A 473 482 serotonin TRIVIAL 23609769 A 517 524 ecstasy TRIVIAL 23609769 A 692 703 amphetamine TRIVIAL 23609769 A 714 721 ecstasy TRIVIAL 23609769 A 72 79 ecstasy TRIVIAL 23609769 T 39 46 ecstasy TRIVIAL 23609769 T 48 52 MDMA ABBREVIATION 23609770 A 1535 1547 remifentanil TRIVIAL 23609770 A 1685 1697 remifentanil TRIVIAL 23609770 A 456 468 remifentanil TRIVIAL 23609770 A 635 647 remifentanil TRIVIAL 23609770 T 33 45 remifentanil TRIVIAL 23609782 A 2040 2045 BG-12 IDENTIFIER 23609782 A 2264 2274 Laquinimod TRIVIAL 23609782 A 2299 2304 BG-12 IDENTIFIER 23609782 A 2368 2381 Teriflunomide TRIVIAL 23609782 A 706 716 Fingolimod TRIVIAL 23609944 A 468 479 amino acids FAMILY 23609944 A 545 555 amino acid FAMILY 23609944 A 729 740 amino acids FAMILY 23609944 T 12 23 amino acids FAMILY 23609963 A 1266 1277 cholesterol TRIVIAL 23609963 A 1282 1292 fatty acid FAMILY 23609963 A 251 262 cholesterol TRIVIAL 23609963 A 367 378 cholesterol TRIVIAL 23609963 A 48 59 cholesterol TRIVIAL 23609963 A 638 649 cholesterol TRIVIAL 23609963 A 664 675 cholesterol TRIVIAL 23609963 A 684 694 fatty acid FAMILY 23609963 A 730 741 cholesterol TRIVIAL 23610077 A 0 7 Silanol SYSTEMATIC 23610077 A 20 26 silica TRIVIAL 23610077 A 227 234 silanol SYSTEMATIC 23610077 A 318 331 alkoxysilanes FAMILY 23610077 A 333 347 bis-silylamine SYSTEMATIC 23610077 A 358 371 chlorosilanes FAMILY 23610077 A 665 671 SBA-15 IDENTIFIER 23610077 A 821 833 nitrobenzene SYSTEMATIC 23610077 A 863 869 SBA-15 IDENTIFIER 23610077 T 19 25 SBA-15 IDENTIFIER 23610086 A 1066 1077 glutathione TRIVIAL 23610086 A 1104 1123 glutathione-S-oxide SYSTEMATIC 23610086 A 1151 1181 2-methylimidazo[2,1-b]thiazole SYSTEMATIC 23610086 A 1192 1203 glutathione TRIVIAL 23610086 A 1284 1292 thiazole SYSTEMATIC 23610086 A 1394 1397 18O FORMULA 23610086 A 1433 1450 potassium cyanide SYSTEMATIC 23610086 A 1621 1629 thiazole SYSTEMATIC 23610086 A 1642 1659 1,2,4-thiadiazole SYSTEMATIC 23610086 A 1675 1809 -(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)ethanone SYSTEMATIC 23610086 A 219 344 1-(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(2-methylimidazo[2,1-b]thiazol-6-yl)ethanone SYSTEMATIC 23610086 A 369 391 imidazo[2,1-b]thiazole SYSTEMATIC 23610086 A 470 475 NADPH ABBREVIATION 23610086 A 481 492 glutathione TRIVIAL 23610086 A 538 549 glutathione TRIVIAL 23610086 A 719 731 glutathionyl TRIVIAL 23610086 A 746 751 thiol FAMILY 23610086 A 774 782 thiazole SYSTEMATIC 23610086 A 812 823 glutathione TRIVIAL 23610086 A 859 881 imidazo[2,1-b]thiazole SYSTEMATIC 23610086 A 93 210 1-(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(imidazo[2,1-b]thiazol-6-yl)ethanone SYSTEMATIC 23610086 A 948 959 glutathione TRIVIAL 23610086 A 974 981 S-oxide SYSTEMATIC 23610086 T 40 83 Imidazo- and 2-Methylimidazo[2,1-b]thiazole MULTIPLE 23611120 A 118 129 polystyrene SYSTEMATIC 23611120 A 16 25 D-glucose SYSTEMATIC 23611120 A 281 290 D-glucose SYSTEMATIC 23611120 A 313 321 hydrogen SYSTEMATIC 23611120 A 432 440 hydrogen SYSTEMATIC 23611120 A 495 504 D-glucose SYSTEMATIC 23611120 A 575 584 D-glucose SYSTEMATIC 23611120 A 67 69 Ru FORMULA 23611120 A 731 739 hydrogen SYSTEMATIC 23611120 T 0 11 D - Glucose TRIVIAL 23611120 T 31 33 Ru FORMULA 23611120 T 88 99 Polystyrene SYSTEMATIC 23611124 A 448 468 indole-2-carboxamide SYSTEMATIC 23611124 T 95 112 Indolecarboxamide FAMILY 23611338 A 1042 1074 o-MitoPhB(OH)2 FORMULA 23611338 A 1079 1095 ONOO- FORMULA 23611338 A 1118 1124 phenyl SYSTEMATIC 23611338 A 1185 1231 o-MitoPhB(OH)2O•- FORMULA 23611338 A 1288 1294 phenyl SYSTEMATIC 23611338 A 1308 1334 •NO2 FORMULA 23611338 A 1451 1497 o-MitoPhB(OH)2O•- FORMULA 23611338 A 149 165 ONOO- FORMULA 23611338 A 1548 1594 m-MitoPhB(OH)2O•- FORMULA 23611338 A 1599 1645 p-MitoPhB(OH)2O•- FORMULA 23611338 A 1695 1711 ONOO- FORMULA 23611338 A 1717 1753 ortho-MitoPhB(OH)2 FORMULA 23611338 A 1790 1819 o-MitoPhNO2 FORMULA 23611338 A 1849 1857 phenolic FAMILY 23611338 A 1867 1884 o-MitoPhOH FORMULA 23611338 A 1946 1962 ONOO- FORMULA 23611338 A 247 263 ONOO- FORMULA 23611338 A 268 281 arylboronates FAMILY 23611338 A 283 302 PhB(OH)2 FORMULA 23611338 A 313 321 phenolic FAMILY 23611338 A 365 398 PhB(OH)2O•- FORMULA 23611338 A 399 425 •NO2 FORMULA 23611338 A 4 26 Aromatic boronic acids FAMILY 23611338 A 46 59 peroxynitrite SYSTEMATIC 23611338 A 555 575 triphenylphosphonium SYSTEMATIC 23611338 A 577 580 TPP ABBREVIATION 23611338 A 61 77 ONOO- FORMULA 23611338 A 612 628 ONOO- FORMULA 23611338 A 655 667 arylboronate FAMILY 23611338 A 677 735 o-, m-, and p-MitoPhB(OH)2 MULTIPLE 23611338 A 858 864 phenyl SYSTEMATIC 23611338 A 88 95 phenols FAMILY 23611338 A 979 1008 o-MitoPhNO2 FORMULA 23611338 T 17 30 peroxynitrite SYSTEMATIC 23611338 T 35 84 triphenylphosphonium-substituted arylboronic acid FAMILY 23611508 A 542 553 polystyrene SYSTEMATIC 23611538 A 1149 1153 EGCG ABBREVIATION 23611538 A 1178 1182 EGCG ABBREVIATION 23611538 A 1237 1241 EGCG ABBREVIATION 23611538 A 1268 1274 amines FAMILY 23611538 A 1326 1338 Schiff bases FAMILY 23611538 A 1534 1538 EGCG ABBREVIATION 23611538 A 1607 1611 EGCG ABBREVIATION 23611538 A 327 353 Epigallocatechin-3-gallate TRIVIAL 23611538 A 355 359 EGCG ABBREVIATION 23611538 A 376 386 polyphenol FAMILY 23611538 A 681 685 EGCG ABBREVIATION 23611538 A 776 780 EGCG ABBREVIATION 23611538 A 856 860 EGCG ABBREVIATION 23611538 A 886 890 EGCG ABBREVIATION 23611538 A 943 955 thioflavin T TRIVIAL 23611538 T 43 47 EGCG ABBREVIATION 23611809 A 1055 1076 tertiary cyclic amine MULTIPLE 23611809 A 1080 1095 trifluoperazine TRIVIAL 23611809 A 110 115 amine SYSTEMATIC 23611809 A 1170 1183 amitriptyline TRIVIAL 23611809 A 1185 1195 imipramine TRIVIAL 23611809 A 1201 1216 diphenhydramine TRIVIAL 23611809 A 1559 1567 nicotine TRIVIAL 23611809 A 1572 1581 hecogenin TRIVIAL 23611809 A 1708 1723 tertiary amines FAMILY 23611809 A 40 43 UDP ABBREVIATION 23611809 A 439 452 amitriptyline TRIVIAL 23611809 A 454 464 imipramine TRIVIAL 23611809 A 466 475 ketotifen TRIVIAL 23611809 A 477 486 pizotifen TRIVIAL 23611809 A 488 498 olanzapine TRIVIAL 23611809 A 500 515 diphenhydramine TRIVIAL 23611809 A 517 526 tamoxifen TRIVIAL 23611809 A 528 540 ketoconazole TRIVIAL 23611809 A 545 554 midazolam TRIVIAL 23611809 A 683 708 tertiary aliphatic amines FAMILY 23611809 A 710 723 cyclic amines FAMILY 23611809 A 731 740 imidazole SYSTEMATIC 23611809 A 795 806 desipramine TRIVIAL 23611809 A 808 821 nortriptyline TRIVIAL 23611809 A 823 836 carbamazepine TRIVIAL 23611809 A 841 852 afloqualone TRIVIAL 23611809 A 883 910 secondary or primary amines MULTIPLE 23611809 A 973 988 tertiary amines FAMILY 23612242 A 1161 1172 glutathione TRIVIAL 23612242 A 1173 1174 S FORMULA 23612242 A 646 678 polycyclic aromatic hydrocarbons FAMILY 23612242 A 764 775 glutathione TRIVIAL 23612242 A 950 960 superoxide TRIVIAL 23612421 A 1440 1447 adenine TRIVIAL 23612421 A 1463 1473 amino acid FAMILY 23612421 A 1532 1539 adenine TRIVIAL 23612421 A 1541 1558 L-acetylcarnitine SYSTEMATIC 23612421 A 1560 1576 8-hydroxyadenine SYSTEMATIC 23612421 A 1578 1590 hypoxanthine TRIVIAL 23612421 A 1592 1600 creatine TRIVIAL 23612421 A 1602 1612 methionine TRIVIAL 23612421 A 1614 1630 phytosphingosine TRIVIAL 23612421 A 1635 1648 phenylalanine TRIVIAL 23612421 A 1730 1750 2,8-dihydroxyadenine SYSTEMATIC 23612421 A 1752 1776 indole-3-carboxylic acid SYSTEMATIC 23612421 A 1778 1798 3-methyldioxyindole, SYSTEMATIC 23612421 A 1799 1828 ethyl-N2-acetyl-L-argininate, SYSTEMATIC 23612421 A 1829 1843 3-O-methyldopa SYSTEMATIC 23612421 A 1848 1864 xanthurenic acid TRIVIAL 23612421 A 2135 2142 adenine TRIVIAL 23612421 A 2158 2168 amino acid FAMILY 23612421 A 630 637 adenine TRIVIAL 23612423 A 1259 1262 MDA ABBREVIATION 23612423 A 1290 1298 creatine TRIVIAL 23612423 A 1307 1313 malate TRIVIAL 23612423 A 1329 1332 ATP ABBREVIATION 23612423 A 1435 1447 nitric oxide SYSTEMATIC 23612423 A 1764 1771 ethanol SYSTEMATIC 23612423 A 1852 1864 nitric oxide SYSTEMATIC 23612423 A 276 286 chloroform TRIVIAL 23612423 A 336 343 ethanol SYSTEMATIC 23612423 A 491 503 nitric oxide SYSTEMATIC 23612423 A 913 917 DPPH ABBREVIATION 23612487 A 0 23 Sphingosine-1-phosphate SYSTEMATIC 23612487 A 1104 1107 S1P ABBREVIATION 23612487 A 1292 1295 S1P ABBREVIATION 23612487 A 130 133 S1P ABBREVIATION 23612487 A 210 213 S1P ABBREVIATION 23612487 A 25 28 S1P ABBREVIATION 23612487 A 320 323 S1P ABBREVIATION 23612487 A 399 402 S1P ABBREVIATION 23612487 A 413 433 phosphatidylinositol TRIVIAL 23612487 A 56 68 sphingolipid FAMILY 23612487 A 751 754 S1P ABBREVIATION 23612487 T 0 23 Sphingosine-1-phosphate SYSTEMATIC 23612709 A 317 324 calcium SYSTEMATIC 23612720 A 185 194 graphenes FAMILY 23612720 A 212 220 graphene TRIVIAL 23612720 A 228 236 hydrogen SYSTEMATIC 23612720 A 384 392 graphene TRIVIAL 23612720 A 467 475 graphene TRIVIAL 23612720 A 571 579 graphane TRIVIAL 23612720 A 580 588 graphene TRIVIAL 23612720 A 61 69 graphene TRIVIAL 23612720 A 638 643 ferro TRIVIAL 23612720 A 782 791 graphenes FAMILY 23612720 A 929 938 graphenes FAMILY 23612720 T 40 48 graphene TRIVIAL 23613012 A 1108 1120 testosterone TRIVIAL 23613012 A 1304 1315 cholesterol TRIVIAL 23613012 A 1321 1332 cholesterol TRIVIAL 23613012 A 1556 1568 testosterone TRIVIAL 23613012 A 393 405 testosterone TRIVIAL 23613012 A 675 694 testosterone esters FAMILY 23613012 A 920 932 triglyceride FAMILY 23613012 A 982 993 cholesterol TRIVIAL 23613012 T 4 15 Cholesterol TRIVIAL 23613012 T 47 59 Testosterone TRIVIAL 23613080 A 120 123 FTO ABBREVIATION 23613080 A 53 56 NiO FORMULA 23613080 A 552 555 NiO FORMULA 23613080 A 592 595 WO3 FORMULA 23613080 T 13 16 NiO FORMULA 23613312 A 136 148 cyclopropane SYSTEMATIC 23613312 A 162 168 alkene FAMILY 23613312 A 187 199 cyclopropane SYSTEMATIC 23613312 A 21 33 cyclopropane SYSTEMATIC 23613312 A 248 271 4-benzyloxybenzaldehyde SYSTEMATIC 23613312 A 308 316 estrogen FAMILY 23613312 A 346 358 cyclopropane SYSTEMATIC 23613312 A 406 414 estrogen FAMILY 23613312 A 44 52 stilbene TRIVIAL 23613312 A 475 483 stilbene TRIVIAL 23613312 A 500 509 tamoxifen TRIVIAL 23613312 A 514 524 raloxifene TRIVIAL 23613312 A 536 548 cyclopropane SYSTEMATIC 23613312 A 591 599 estrogen FAMILY 23613312 A 86 94 estrogen FAMILY 23613312 T 142 150 estrogen FAMILY 23613312 T 48 59 cyclopropyl SYSTEMATIC 23613312 T 73 81 stilbene TRIVIAL 23613312 T 87 97 raloxifene TRIVIAL 23613425 A 220 231 doxorubicin TRIVIAL 23613425 A 233 236 DOX ABBREVIATION 23613425 A 269 276 methoxy SYSTEMATIC 23613425 A 277 298 poly(ethylene glycol) SYSTEMATIC 23613425 A 305 326 poly(D,L-lactic acid) SYSTEMATIC 23613425 A 328 332 mPEG ABBREVIATION 23613425 A 335 338 PLA ABBREVIATION 23613425 A 427 430 DOX ABBREVIATION 23613425 T 56 67 Doxorubicin TRIVIAL 23614379 A 254 292 ( - )-nectandrin B-β-d-glucopyranoside SYSTEMATIC 23614379 A 298 390 ( - )-(7R,7'R,8S,8'R)-4,4'-dihydroxy-3,3'-dimethoxy-7,7'-epoxylignan-4-O-β-d-glucopyranoside SYSTEMATIC 23614379 A 396 489 ( - )-(7R,7'R,8S,8'R)-4,4'-dihydroxy-3,3'-dimethoxy-7,7'-epoxylignan-4'-O-β-d-glucopyranoside SYSTEMATIC 23614379 A 495 574 ( - )-(8S,8'R)-4,4'-dihydroxy-3,3',5'-trimethoxylignan-4'-O-β-d-glucopyranoside SYSTEMATIC 23614379 A 580 634 ( - )-(7R,8R)-syringylglycerol-8-O-β-d-glucopyranoside SYSTEMATIC 23614379 A 644 729 ( - )-3-hydroxy-2-methyl-4-pyrone-3-O-β-d-xylopyranosyl-(1 → 6)-O-β-d-glucopyranoside SYSTEMATIC 23614492 A 10 18 pimarane TRIVIAL 23614492 A 128 160 11α-hydroxypimara-8(14),15-diene SYSTEMATIC 23614492 A 171 192 2,3-secoaromadendrane SYSTEMATIC 23614492 A 198 214 sesquiterpenoids FAMILY 23614492 A 237 260 ethyoxyplagiochiline A2 SYSTEMATIC 23614492 A 24 36 diterpenoids FAMILY 23614492 A 282 293 fusicoccane FAMILY 23614492 A 299 311 diterpenoids FAMILY 23614492 A 38 75 7β,11α-dihydroxypimara-8(14),15-diene SYSTEMATIC 23614492 A 81 118 1β,11α-dihydroxypimara-8(14),15-diene SYSTEMATIC 23614492 T 0 10 Terpenoids FAMILY 23614571 A 1015 1019 NMDA ABBREVIATION 23614571 A 119 129 (S)-CCG-IV ABBREVIATION 23614571 A 348 352 NMDA ABBREVIATION 23614571 A 54 58 NMDA ABBREVIATION 23614571 A 568 572 NMDA ABBREVIATION 23614571 A 719 723 NMDA ABBREVIATION 23614571 A 75 117 (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine SYSTEMATIC 23614571 A 944 954 (S)-CCG-IV ABBREVIATION 23614571 T 15 72 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine FAMILY 23614571 T 93 117 N-methyl-D-aspartic acid SYSTEMATIC 23614635 A 333 341 estrogen FAMILY 23614635 A 371 386 bisphosphonates FAMILY 23614635 A 402 420 strontium ranelate SYSTEMATIC 23614643 A 1163 1169 SU5402 IDENTIFIER 23614643 A 1274 1282 xyloside FAMILY 23614643 A 1515 1524 xylosides FAMILY 23614643 A 481 504 bis- and tris-xylosides MULTIPLE 23614643 A 725 748 bis- and tris-xylosides MULTIPLE 23614643 A 758 772 mono-xylosides FAMILY 23614652 A 0 19 Aristolochic acid I TRIVIAL 23614652 A 132 136 AA-I ABBREVIATION 23614652 A 177 182 nitro SYSTEMATIC 23614652 A 206 214 cysteine TRIVIAL 23614652 A 21 25 AA-I ABBREVIATION 23614652 A 218 229 glutathione TRIVIAL 23614652 A 238 252 aristolic acid TRIVIAL 23614652 A 440 444 AA-I ABBREVIATION 23614652 T 14 33 Aristolochic Acid I TRIVIAL 23614652 T 39 53 Aristolic Acid TRIVIAL 23614652 T 71 79 Cysteine TRIVIAL 23614652 T 84 95 Glutathione TRIVIAL 23614728 A 1184 1192 phosgene TRIVIAL 23614728 A 1378 1386 phosgene TRIVIAL 23614728 A 1515 1523 phosgene TRIVIAL 23614728 A 1671 1679 phosgene TRIVIAL 23614728 A 30 38 phosgene TRIVIAL 23614728 A 347 355 phosgene TRIVIAL 23614728 A 448 456 phosgene TRIVIAL 23614728 A 641 653 Haematoxylin TRIVIAL 23614728 A 654 659 Eosin FAMILY 23614728 T 50 58 phosgene TRIVIAL 23614815 A 604 614 disulphide SYSTEMATIC 23614815 A 752 762 amino-acid FAMILY 23614827 A 15 145 (7S,8R,7'R,8'R)-7-(3,4-methylenedioxyphenyl)-8,8'-dimethyl-8'-hydroxyl-7'-methoxyl-7'-(3',4'-methylenedioxyphenyl)-tetrahydrofuran SYSTEMATIC 23614827 A 173 206 2-hydroxy-11,12-dehydrocalamenene SYSTEMATIC 23614827 A 236 316 erythro-1-(3,4-dimethoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane SYSTEMATIC 23614827 A 336 343 lignans FAMILY 23614827 A 344 446 (+)-anwulignan(erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane) SYSTEMATIC 23614827 A 455 469 ( - )-zuonin-A TRIVIAL 23614831 A 1024 1042 N-vinylpyrrolidone SYSTEMATIC 23614831 A 1271 1279 Soluplus TRIVIAL 23614831 A 1281 1284 PVP ABBREVIATION 23614831 A 1286 1289 PVP ABBREVIATION 23614831 A 1417 1425 hydrogen SYSTEMATIC 23614831 A 1547 1550 PVP ABBREVIATION 23614831 A 1555 1563 Soluplus TRIVIAL 23614831 A 18 29 Cilnidipine TRIVIAL 23614831 A 299 302 PVP ABBREVIATION 23614831 A 304 307 PVP ABBREVIATION 23614831 A 315 323 Soluplus TRIVIAL 23614831 A 46 61 dihydropyridine SYSTEMATIC 23614831 A 62 69 calcium SYSTEMATIC 23614831 A 815 823 Soluplus TRIVIAL 23614831 A 825 828 PVP ABBREVIATION 23614831 A 833 836 PVP ABBREVIATION 23614831 A 985 993 hydrogen SYSTEMATIC 23614831 T 88 99 cilnidipine TRIVIAL 23614904 A 1042 1051 bile acid FAMILY 23614904 A 1163 1174 cholesterol TRIVIAL 23614904 A 1179 1188 bile acid FAMILY 23614904 A 1327 1338 cholesterol TRIVIAL 23614904 A 1344 1354 bile acids FAMILY 23614904 A 215 226 cholesterol TRIVIAL 23614904 A 231 240 bile acid FAMILY 23614904 A 359 371 atorvastatin TRIVIAL 23614904 A 384 396 Atorvastatin TRIVIAL 23614904 A 473 484 cholesterol TRIVIAL 23614904 A 486 503 cholesterol ester FAMILY 23614904 A 514 523 bile acid FAMILY 23614904 A 559 568 bile acid FAMILY 23614904 A 600 612 atorvastatin TRIVIAL 23614904 A 635 645 bile acids FAMILY 23614904 A 668 679 cholesterol TRIVIAL 23614904 A 785 795 bile acids FAMILY 23614904 A 922 931 bile acid FAMILY 23614904 A 993 1005 atorvastatin TRIVIAL 23614904 T 0 9 Bile Acid FAMILY 23614904 T 14 20 Sterol FAMILY 23615074 A 347 357 flavanoids FAMILY 23615074 A 374 384 flavanoids FAMILY 23615074 A 508 518 flavanoids FAMILY 23615074 A 566 572 oxygen SYSTEMATIC 23616238 A 1103 1106 Met FORMULA 23616238 A 1424 1433 metformin TRIVIAL 23616238 A 1437 1452 triacylglycerol FAMILY 23616238 A 1522 1537 triacylglycerol FAMILY 23616238 A 1556 1565 metformin TRIVIAL 23616238 A 384 393 metformin TRIVIAL 23616376 A 95 103 DPh-DNTT ABBREVIATION 23616387 A 134 142 triazole FAMILY 23616387 A 21 33 azide-alkyne FAMILY 23616387 A 294 303 triazoles FAMILY 23616387 A 4 10 copper SYSTEMATIC 23616387 A 426 435 triazoles FAMILY 23616387 A 556 565 triazoles FAMILY 23617226 A 126 137 [Cu(dmp)2]+ FORMULA 23617226 A 139 142 dmp ABBREVIATION 23617226 A 145 177 2,9-dimethyl-1,10-phenanthroline SYSTEMATIC 23617226 A 192 204 acetonitrile SYSTEMATIC 23617226 A 209 224 dichloromethane SYSTEMATIC 23617226 A 272 287 dichloromethane SYSTEMATIC 23617226 A 292 304 acetonitrile SYSTEMATIC 23617226 A 65 67 Cu FORMULA 23617226 A 78 124 Bis(2,9-dimethyl-1,10-phenanthroline)copper(I) SYSTEMATIC 23617226 A 933 945 acetonitrile SYSTEMATIC 23617226 T 100 124 Copper(I) Phenanthroline SYSTEMATIC 23617279 A 107 117 resorcinol TRIVIAL 23617279 A 1110 1116 carbon SYSTEMATIC 23617279 A 122 134 formaldehyde SYSTEMATIC 23617279 A 1239 1245 carbon SYSTEMATIC 23617279 A 1275 1281 carbon SYSTEMATIC 23617279 A 154 173 potassium carbonate SYSTEMATIC 23617279 A 454 460 carbon SYSTEMATIC 23617279 A 774 780 Carbon SYSTEMATIC 23617279 A 979 985 carbon SYSTEMATIC 23617279 T 0 6 Carbon SYSTEMATIC 23617279 T 47 57 Resorcinol TRIVIAL 23617279 T 58 70 Formaldehyde SYSTEMATIC 23617430 A 22 44 3-carboranyl thymidine SYSTEMATIC 23617430 A 628 652 N3-substituted thymidine FAMILY 23617430 A 67 72 boron SYSTEMATIC 23617430 A 761 770 carborane SYSTEMATIC 23617430 A 799 804 boron SYSTEMATIC 23617430 A 93 98 boron SYSTEMATIC 23617430 T 0 24 N3-substituted thymidine FAMILY 23617439 A 208 211 PZQ ABBREVIATION 23617439 A 35 47 praziquantel TRIVIAL 23617439 A 354 357 PZQ ABBREVIATION 23617439 A 441 448 bromine SYSTEMATIC 23617439 A 49 52 PZQ ABBREVIATION 23617439 A 493 505 praziquantel TRIVIAL 23617439 A 554 566 praziquentel TRIVIAL 23617439 T 0 12 Praziquantel TRIVIAL 23617462 A 101 111 bile salts FAMILY 23617462 A 1019 1023 NaTC FORMULA 23617462 A 1028 1033 NaGDC FORMULA 23617462 A 113 127 sodium cholate SYSTEMATIC 23617462 A 1201 1211 bile salts FAMILY 23617462 A 129 132 NaC ABBREVIATION 23617462 A 1342 1345 NaC ABBREVIATION 23617462 A 135 148 dexocycholate TRIVIAL 23617462 A 150 154 NaDC FORMULA 23617462 A 157 169 taurocholate TRIVIAL 23617462 A 1589 1599 bile salts FAMILY 23617462 A 171 175 NaTC FORMULA 23617462 A 181 198 glycodeoxycholate TRIVIAL 23617462 A 200 205 NaGDC FORMULA 23617462 A 311 321 amino acid FAMILY 23617462 A 323 327 NaTC FORMULA 23617462 A 332 337 NaGDC FORMULA 23617462 A 512 515 NaC ABBREVIATION 23617462 A 520 524 NaDC FORMULA 23617462 A 610 621 amino acids FAMILY 23617462 A 625 629 NaTC FORMULA 23617462 A 634 639 NaGDC FORMULA 23617462 A 69 75 sodium SYSTEMATIC 23617462 A 946 956 bile salts FAMILY 23617462 A 964 970 decane SYSTEMATIC 23617462 T 26 63 Di-hydroxy and Tri-hydroxy Bile Salts MULTIPLE 23617753 A 285 293 naphthyl SYSTEMATIC 23617753 A 299 308 quinoline SYSTEMATIC 23617753 A 40 47 BRD0476 IDENTIFIER 23617807 A 16 23 benzene SYSTEMATIC 23617807 A 28 47 hexahalogenbenzenes FAMILY 23617807 A 600 609 dihalogen FAMILY 23617807 A 634 667 hexachloro- and hexabromobenzenes MULTIPLE 23617807 A 805 814 dihalogen FAMILY 23617807 A 865 898 hexachloro- and hexabromobenzenes MULTIPLE 23617807 T 45 52 Benzene SYSTEMATIC 23617807 T 57 76 Hexahalogenbenzenes FAMILY 23618528 A 1378 1385 ethanol SYSTEMATIC 23618624 A 0 10 Squalamine TRIVIAL 23618624 A 193 202 polyamine FAMILY 23618624 A 21 32 aminosterol FAMILY 23618624 A 225 231 sterol FAMILY 23618624 A 262 270 hydroxyl SYSTEMATIC 23618624 A 305 337 tetraammonium spermine polyamine SYSTEMATIC 23618624 A 391 424 trisammonium spermidine polyamine SYSTEMATIC 23618624 A 456 464 hydroxyl SYSTEMATIC 23618624 A 603 617 7β-OH spermine SYSTEMATIC 23618624 T 36 47 aminosterol FAMILY 23618921 A 0 11 Glutathione TRIVIAL 23618921 A 1061 1068 fisetin TRIVIAL 23618921 A 1252 1259 fisetin TRIVIAL 23618921 A 1282 1285 GSH ABBREVIATION 23618921 A 13 16 GSH ABBREVIATION 23618921 A 1375 1378 GSH ABBREVIATION 23618921 A 146 149 GSH ABBREVIATION 23618921 A 1494 1497 GSH ABBREVIATION 23618921 A 1538 1545 fisetin TRIVIAL 23618921 A 1594 1597 GSH ABBREVIATION 23618921 A 22 25 GSH ABBREVIATION 23618921 A 244 247 GSH ABBREVIATION 23618921 A 413 416 GSH ABBREVIATION 23618921 A 645 648 GSH ABBREVIATION 23618921 A 691 700 flavonoid FAMILY 23618921 A 701 708 fisetin TRIVIAL 23618921 A 744 747 GSH ABBREVIATION 23618921 A 767 770 GSH ABBREVIATION 23618921 A 913 920 fisetin TRIVIAL 23618921 T 119 128 Flavonoid FAMILY 23618921 T 129 136 Fisetin TRIVIAL 23618921 T 93 104 Glutathione TRIVIAL 23619019 A 1583 1635 ginsenosides Rb1, Rg1, Rf, Rh1, Rc, Rb2, Ro, and Rg3 MULTIPLE 23619019 A 1694 1708 ginsenoside Ro TRIVIAL 23619019 A 1951 1963 ginsenosides FAMILY 23619019 A 800 809 Captopril TRIVIAL 23619611 A 1013 1024 rivaroxaban TRIVIAL 23619611 A 102 112 dabigatran TRIVIAL 23619611 A 1028 1036 apixaban TRIVIAL 23619611 A 1170 1178 Apixaban TRIVIAL 23619611 A 1235 1246 rivaroxaban TRIVIAL 23619611 A 1251 1261 dabigatran TRIVIAL 23619611 A 1463 1472 vitamin K FAMILY 23619611 A 1548 1559 rivaroxaban TRIVIAL 23619611 A 1561 1569 apixaban TRIVIAL 23619611 A 1571 1579 edoxaban TRIVIAL 23619611 A 1585 1595 dabigatran TRIVIAL 23619611 A 210 218 edoxaban TRIVIAL 23619611 A 297 308 rivaroxaban TRIVIAL 23619611 A 430 441 rivaroxaban TRIVIAL 23619611 A 443 451 apixaban TRIVIAL 23619611 A 457 467 dabigatran TRIVIAL 23619611 A 742 753 Rivaroxaban TRIVIAL 23619611 A 75 86 rivaroxaban TRIVIAL 23619611 A 755 763 apixaban TRIVIAL 23619611 A 769 779 dabigatran TRIVIAL 23619611 A 88 96 apixaban TRIVIAL 23619611 A 965 975 Dabigatran TRIVIAL 23619613 A 1131 1138 polySia ABBREVIATION 23619613 A 1160 1167 polySia ABBREVIATION 23619613 A 1399 1406 polySia ABBREVIATION 23619613 A 335 342 polySia ABBREVIATION 23619613 A 422 429 polySia ABBREVIATION 23619613 A 631 638 polySia ABBREVIATION 23619613 A 765 774 bleomycin FAMILY 23619613 A 78 93 polysialic acid SYSTEMATIC 23619613 A 907 914 polySia ABBREVIATION 23619613 A 95 102 polySia ABBREVIATION 23620060 A 1024 1031 glucose TRIVIAL 23620060 A 1159 1173 Diacylglycerol FAMILY 23620060 A 1359 1372 sphingomyelin FAMILY 23620060 A 391 398 glucose TRIVIAL 23620060 A 612 619 Glucose TRIVIAL 23620162 A 1058 1064 oxygen SYSTEMATIC 23620162 A 38 43 Al2O3 FORMULA 23620162 A 48 52 Y2O3 FORMULA 23620162 A 518 522 Y2O3 FORMULA 23620162 A 524 529 AlY20 FORMULA 23620162 A 783 789 Al(3+) FORMULA 23620162 A 794 799 Y(3+) FORMULA 23620162 A 847 852 Y(3+) FORMULA 23620162 A 853 858 Y(3+) FORMULA 23620162 T 34 39 Al2O3 FORMULA 23620162 T 40 44 Y2O3 FORMULA 23620199 A 1469 1475 taxane FAMILY 23620199 A 208 218 mertansine TRIVIAL 23620199 A 222 232 maytansine TRIVIAL 23620199 A 259 262 DM1 ABBREVIATION 23620199 A 386 396 mertansine TRIVIAL 23620199 A 542 551 thioether SYSTEMATIC 23620199 A 560 622 N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate SYSTEMATIC 23620199 A 624 628 SMCC ABBREVIATION 23620199 A 641 644 MCC ABBREVIATION 23620200 A 230 237 glucose TRIVIAL 23620200 A 341 348 glucose TRIVIAL 23620256 A 1516 1523 glucose TRIVIAL 23620256 A 1712 1719 glucose TRIVIAL 23620256 A 2114 2121 glucose TRIVIAL 23620256 A 802 810 yo pro-1 TRIVIAL 23620256 A 815 831 propidium iodide TRIVIAL 23620256 A 995 1002 glucose TRIVIAL 23620266 A 1005 1014 ibuprofen TRIVIAL 23620266 A 1016 1024 Naproxen TRIVIAL 23620266 A 258 263 amide FAMILY 23620266 A 317 339 (R)-1-phenylethylamine SYSTEMATIC 23620266 A 341 344 PEA ABBREVIATION 23620266 A 35 55 2-arylpropionic acid FAMILY 23620266 A 57 62 2-APA ABBREVIATION 23620266 A 572 581 ibuprofen TRIVIAL 23620266 A 71 80 ibuprofen TRIVIAL 23620266 A 722 732 ketoprofen TRIVIAL 23620266 A 82 90 naproxen TRIVIAL 23620266 A 893 903 ketoprofen TRIVIAL 23620266 A 96 106 ketoprofen TRIVIAL 23620266 T 39 60 2-arylpropionic acids FAMILY 23620283 A 1056 1057 C FORMULA 23620283 A 198 204 serine TRIVIAL 23620283 A 205 214 threonine TRIVIAL 23620487 A 1031 1041 omeprazole TRIVIAL 23620487 A 1292 1302 omeprazole TRIVIAL 23620487 A 148 158 omeprazole TRIVIAL 23620487 A 230 249 5-hydroxyomeprazole SYSTEMATIC 23620487 A 251 275 5'-O-desmethylomeprazole SYSTEMATIC 23620487 A 277 295 omeprazole sulfone TRIVIAL 23620487 A 300 317 carboxyomeprazole SYSTEMATIC 23620487 A 433 443 omeprazole TRIVIAL 23620487 A 535 545 omeprazole TRIVIAL 23620487 A 547 565 omeprazole sulfone TRIVIAL 23620487 A 570 594 5'-O-desmethylomeprazole SYSTEMATIC 23620487 A 650 660 omeprazole TRIVIAL 23620487 A 665 689 5'-O-desmethylomeprazole SYSTEMATIC 23620487 A 887 897 omeprazole TRIVIAL 23620487 T 36 46 Omeprazole TRIVIAL 23621358 A 1037 1040 GAL ABBREVIATION 23621358 A 114 126 carbohydrate FAMILY 23621358 A 181 221 galactosylated polylactide-polyaminoacid SYSTEMATIC 23621358 A 282 354 alpha,beta-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide SYSTEMATIC 23621358 A 356 364 PHEA-EDA ABBREVIATION 23621358 A 371 386 polylactic acid SYSTEMATIC 23621358 A 388 391 PLA ABBREVIATION 23621358 A 423 430 lactose TRIVIAL 23621358 A 442 458 PHEA-EDA-PLA-GAL ABBREVIATION 23621358 A 540 543 RBV ABBREVIATION 23621358 A 558 574 RBV tripalmitate TRIVIAL 23621358 A 62 71 ribavirin TRIVIAL 23621358 A 622 625 RBV ABBREVIATION 23621358 A 709 725 RBV tripalmitate TRIVIAL 23621358 A 73 76 RBV ABBREVIATION 23621358 A 780 796 PHEA-EDA-PLA-GAL ABBREVIATION 23621358 A 893 909 RBV tripalmitate TRIVIAL 23621358 A 917 933 PHEA-EDA-PLA-GAL ABBREVIATION 23621358 T 30 39 RIBAVIRIN TRIVIAL 23621493 A 0 13 Tetracyclines FAMILY 23621493 A 189 208 anhydrotetracycline SYSTEMATIC 23621493 A 218 233 oxytetracycline SYSTEMATIC 23621493 A 918 930 tetracycline FAMILY 23621493 T 56 71 Oxytetracycline SYSTEMATIC 23621616 A 13 21 graphene TRIVIAL 23621616 A 226 234 graphene TRIVIAL 23621616 A 365 373 graphene TRIVIAL 23621616 A 450 458 graphene TRIVIAL 23621616 A 551 559 graphene TRIVIAL 23621616 A 657 665 graphene TRIVIAL 23621616 A 829 837 graphene TRIVIAL 23621616 T 51 59 Graphene TRIVIAL 23621857 A 0 11 Brefeldin A TRIVIAL 23621857 A 1063 1066 BFA ABBREVIATION 23621857 A 13 16 BFA ABBREVIATION 23621857 A 201 204 BFA ABBREVIATION 23621857 A 276 284 hydroxyl SYSTEMATIC 23621857 A 370 373 BFA ABBREVIATION 23621857 A 431 462 monoacylated and diacylated BFA MULTIPLE 23621857 A 632 648 BFA 7-O-benzoate SYSTEMATIC 23621857 A 650 670 BFA 4,7-O-dibenzoate SYSTEMATIC 23621857 A 676 702 BFA 7-O-biotin carboxylate SYSTEMATIC 23621857 A 926 944 guanine nucleotide TRIVIAL 23621857 T 38 58 Acylated Brefeldin A TRIVIAL 23623416 A 0 13 Echinocandins FAMILY 23623416 A 18 31 pneumocandins FAMILY 23623416 A 314 325 caspofungin TRIVIAL 23623416 A 327 337 micafungin TRIVIAL 23623416 A 342 355 anidulafungin TRIVIAL 23623416 A 373 390 hydroxy-glutamine SYSTEMATIC 23623416 A 398 407 threonine TRIVIAL 23623416 A 412 441 unsaturated linear fatty acid FAMILY 23623416 A 449 484 branched chain saturated fatty acid FAMILY 23623416 A 47 68 lipocyclohexapeptides FAMILY 23623416 A 646 663 cyclohexapeptides FAMILY 23623416 A 700 704 acyl FAMILY 23623416 A 840 844 acyl FAMILY 23623416 A 859 876 hydroxy-glutamine SYSTEMATIC 23623416 T 39 49 pentyloxyl SYSTEMATIC 23623416 T 50 69 diphenylisoxazoloyl SYSTEMATIC 23623416 T 70 83 pneumocandins FAMILY 23623416 T 88 101 echinocandins FAMILY 23623419 A 136 151 1,2,3-triazoles FAMILY 23623419 A 700 708 diazepam TRIVIAL 23623419 A 76 105 2-arylimidazo[1,2-a]pyridines FAMILY 23623419 T 24 47 imidazo[1,2-a]pyridines FAMILY 23623419 T 57 72 1,2,3-triazoles FAMILY 23623493 A 18 28 titanocene TRIVIAL 23623493 T 81 96 half-titanocene TRIVIAL 23623743 A 1017 1031 polyacrylamide SYSTEMATIC 23623743 A 192 210 1,3-dinitrobenzene SYSTEMATIC 23623743 A 212 219 1,3-DNB SYSTEMATIC 23623743 A 222 243 3-nitropropionic acid SYSTEMATIC 23623743 A 245 250 3-NPA SYSTEMATIC 23623743 A 257 276 3-chloropropanediol SYSTEMATIC 23623743 A 278 283 3-CPD SYSTEMATIC 23623743 A 781 815 tetramethyl rhodamine methyl ester SYSTEMATIC 23623743 A 817 821 TMRM ABBREVIATION 23623743 A 903 915 deferoxamine TRIVIAL 23623743 A 953 957 TMRM ABBREVIATION 23623743 T 100 118 1,3-dinitrobenzene SYSTEMATIC 23623743 T 120 141 3-nitropropionic acid SYSTEMATIC 23623743 T 147 166 3-chloropropanediol SYSTEMATIC 23623751 A 103 118 Methylphenidate SYSTEMATIC 23623751 A 1055 1063 dopamine TRIVIAL 23623751 A 1142 1157 Methylphenidate SYSTEMATIC 23623751 A 1230 1245 methylphenidate SYSTEMATIC 23623751 A 1284 1299 methylphenidate SYSTEMATIC 23623751 A 1357 1372 methylphenidate SYSTEMATIC 23623751 A 136 144 dopamine TRIVIAL 23623751 A 149 163 norepinephrine TRIVIAL 23623751 A 1559 1574 methylphenidate SYSTEMATIC 23623751 A 1716 1723 cocaine TRIVIAL 23623751 A 358 373 methylphenidate SYSTEMATIC 23623751 A 411 418 cocaine TRIVIAL 23623751 A 698 705 cocaine TRIVIAL 23623751 A 839 854 methylphenidate SYSTEMATIC 23623751 T 101 109 Dopamine TRIVIAL 23623751 T 12 27 methylphenidate SYSTEMATIC 23623795 A 657 673 sodium phosphate SYSTEMATIC 23623843 A 1032 1036 CCl4 FORMULA 23623843 A 201 205 CCl4 FORMULA 23623843 A 339 354 monosaccharides FAMILY 23623843 A 388 394 ferric SYSTEMATIC 23623843 A 453 457 DPPH ABBREVIATION 23623843 A 459 461 OH FORMULA 23623843 A 466 471 O2(-) FORMULA 23623843 A 548 552 CCl4 FORMULA 23623843 A 595 599 CCl4 FORMULA 23623843 A 664 667 MDA ABBREVIATION 23623843 A 672 683 8-iso-PGF2a SYSTEMATIC 23623843 A 801 804 GSH ABBREVIATION 23623843 A 843 847 CCl4 FORMULA 23623843 T 64 84 carbon tetrachloride SYSTEMATIC 23624029 A 103 110 steroid FAMILY 23624029 A 240 248 androgen FAMILY 23624029 A 362 384 17-hydroxyprogesterone SYSTEMATIC 23624240 A 574 586 cobalt oxide SYSTEMATIC 23624240 A 588 593 Co3O4 FORMULA 23624240 A 731 737 cobalt SYSTEMATIC 23624240 T 23 35 cobalt oxide SYSTEMATIC 23624376 A 375 387 borosilicate SYSTEMATIC 23624376 A 405 437 linear methoxylated polyglycerol SYSTEMATIC 23624376 A 439 465 hyperbranched polyglycerol SYSTEMATIC 23624376 A 471 510 hyperbranched methoxylated polyglycerol SYSTEMATIC 23624376 T 0 12 Polyglycerol SYSTEMATIC 23624419 A 1134 1146 vildagliptin TRIVIAL 23624419 A 1147 1156 metformin TRIVIAL 23624419 A 1158 1170 Vildagliptin TRIVIAL 23624419 A 1187 1196 metformin TRIVIAL 23624419 A 220 231 vildaglipin TRIVIAL 23624419 A 263 272 metformin TRIVIAL 23624419 A 37 49 vildagliptin TRIVIAL 23624419 A 585 597 vildagliptin TRIVIAL 23624419 A 65 74 metformin TRIVIAL 23624419 A 698 706 arginine TRIVIAL 23624419 A 720 732 Vildagliptin TRIVIAL 23624419 A 733 742 metformin TRIVIAL 23624419 A 776 785 metformin TRIVIAL 23624419 A 892 904 Vildagliptin TRIVIAL 23624419 A 905 914 metformin TRIVIAL 23624419 T 112 121 metformin TRIVIAL 23624419 T 84 96 vildagliptin TRIVIAL 23624423 A 1125 1128 OHT FORMULA 23624423 A 131 144 17β-Estradiol SYSTEMATIC 23624423 A 1321 1324 OHT FORMULA 23624423 A 1436 1439 OHT FORMULA 23624423 A 228 237 Tamoxifen TRIVIAL 23624423 A 269 277 estrogen FAMILY 23624423 A 454 463 tamoxifen TRIVIAL 23624423 A 533 541 estrogen FAMILY 23624423 A 636 644 estrogen FAMILY 23624423 A 663 681 4-Hydroxytamoxifen SYSTEMATIC 23624423 A 683 686 OHT FORMULA 23624423 A 688 697 tamoxifen TRIVIAL 23624423 A 857 860 OHT FORMULA 23624423 T 0 18 4-Hydroxytamoxifen SYSTEMATIC 23624706 A 1002 1006 SnO2 FORMULA 23624706 A 1011 1016 Fe2O3 FORMULA 23624706 A 1017 1021 SnO2 FORMULA 23624706 A 1022 1023 C FORMULA 23624706 A 1045 1052 lithium SYSTEMATIC 23624706 A 1195 1202 lithium SYSTEMATIC 23624706 A 159 161 Li FORMULA 23624706 A 163 175 carbon black TRIVIAL 23624706 A 248 255 lithium SYSTEMATIC 23624706 A 333 344 molten salt FAMILY 23624706 A 40 45 Fe2O3 FORMULA 23624706 A 46 50 SnO2 FORMULA 23624706 A 51 52 C FORMULA 23624706 A 81 86 Fe2O3 FORMULA 23624706 A 91 95 SnO2 FORMULA 23624706 A 996 1001 Fe2O3 FORMULA 23624706 T 28 33 Fe2O3 FORMULA 23624706 T 34 38 SnO2 FORMULA 23624706 T 39 40 C FORMULA 23624706 T 9 16 lithium SYSTEMATIC 23624810 A 1140 1148 oxytocin TRIVIAL 23624810 A 1324 1332 oxytocin TRIVIAL 23624810 A 1722 1730 oxytocin TRIVIAL 23624810 A 342 350 oxytocin TRIVIAL 23624810 A 648 656 oxytocin TRIVIAL 23624810 A 661 669 oxytocin TRIVIAL 23624810 A 73 81 oxytocin TRIVIAL 23624810 A 746 754 oxytocin TRIVIAL 23624810 A 889 897 oxytocin TRIVIAL 23624810 T 35 43 oxytocin TRIVIAL 23624862 A 479 482 GTP ABBREVIATION 23624862 A 489 492 GTP ABBREVIATION 23624862 A 772 775 GTP ABBREVIATION 23624862 A 906 909 GDP ABBREVIATION 23625160 A 1010 1012 Fe FORMULA 23625160 A 106 110 iron SYSTEMATIC 23625160 A 133 137 iron SYSTEMATIC 23625160 A 312 315 MSG ABBREVIATION 23625160 A 411 413 Fe FORMULA 23625160 A 571 573 Fe FORMULA 23625160 A 68 90 monosodium L-glutamate SYSTEMATIC 23625160 A 697 700 MSG ABBREVIATION 23625160 A 711 713 Fe FORMULA 23625160 A 913 916 MSG ABBREVIATION 23625160 A 92 95 MSG ABBREVIATION 23625160 A 996 999 MSG ABBREVIATION 23625160 T 33 55 Monosodium L-Glutamate SYSTEMATIC 23625194 A 1101 1109 orlistat TRIVIAL 23625194 A 1322 1330 orlistat TRIVIAL 23625194 A 947 955 orlistat TRIVIAL 23625194 A 957 968 sibutramine TRIVIAL 23625194 A 974 984 rimonabant TRIVIAL 23625745 A 739 750 cholesterol TRIVIAL 23625745 A 758 769 cholesterol TRIVIAL 23625745 A 807 818 cholesterol TRIVIAL 23625745 A 824 837 triglycerides FAMILY 23625745 A 977 988 Cholesterol TRIVIAL 23625750 A 1118 1125 IB-MECA IDENTIFIER 23625750 A 12 21 adenosine TRIVIAL 23625750 A 1369 1376 IB-MECA IDENTIFIER 23625750 A 1497 1504 IB-MECA IDENTIFIER 23625750 A 1562 1571 adenosine TRIVIAL 23625750 A 1614 1633 sodium taurocholate SYSTEMATIC 23625750 A 208 217 adenosine TRIVIAL 23625750 A 398 407 adenosine TRIVIAL 23625750 A 445 464 sodium taurocholate SYSTEMATIC 23625750 A 678 687 adenosine TRIVIAL 23625750 A 708 715 IB-MECA IDENTIFIER 23625750 A 716 801 (1-deoxy-1-6[[(3-iodophenyl) methyl]amino]-9H-purin-9-yl)-N-methyl-B-D-ribofuronamide SYSTEMATIC 23625750 A 900 919 sodium taurocholate SYSTEMATIC 23625750 T 19 28 adenosine TRIVIAL 23625750 T 49 56 IB-MECA IDENTIFIER 23625750 T 60 79 sodium taurocholate SYSTEMATIC 23625769 A 1114 1124 furosemide TRIVIAL 23625769 A 1221 1231 furosemide TRIVIAL 23625769 A 439 449 furosemide TRIVIAL 23625769 A 668 678 furosemide TRIVIAL 23625769 A 839 849 furosemide TRIVIAL 23625769 A 907 917 furosemide TRIVIAL 23625769 A 935 944 torsemide TRIVIAL 23625769 A 986 996 furosemide TRIVIAL 23625769 T 17 27 Furosemide TRIVIAL 23625779 A 1032 1040 saponins FAMILY 23625779 A 1593 1599 MCM-41 IDENTIFIER 23625779 A 1600 1606 silica TRIVIAL 23625779 A 199 204 amino FAMILY 23625779 A 300 305 Amino SYSTEMATIC 23625779 A 321 327 MCM-41 IDENTIFIER 23625779 A 475 481 MCM-41 IDENTIFIER 23625779 A 495 501 MCM-41 IDENTIFIER 23625779 A 80 86 MCM-41 IDENTIFIER 23625779 A 98 104 silica TRIVIAL 23625779 T 11 17 Silica TRIVIAL 23625787 A 1320 1328 warfarin TRIVIAL 23625787 A 1541 1549 warfarin TRIVIAL 23625787 A 1803 1811 warfarin TRIVIAL 23625787 A 181 189 warfarin TRIVIAL 23625787 A 441 449 warfarin TRIVIAL 23625787 A 652 660 warfarin TRIVIAL 23625787 A 865 873 warfarin TRIVIAL 23625787 T 79 87 Warfarin TRIVIAL 23625887 A 14 41 5'-triphenylmethyl (trityl) SYSTEMATIC 23625887 A 299 365 3'-O-(isoleucylisoleucyl)-5'-O-(3,3,3-triphenylpropanoyl)thymidine SYSTEMATIC 23625887 A 527 543 tritylthymidines FAMILY 23625887 A 54 63 thymidine TRIVIAL 23625887 A 635 645 superoxide TRIVIAL 23625887 T 0 9 5'-Trityl SYSTEMATIC 23625887 T 22 31 Thymidine TRIVIAL 23625905 A 1084 1103 thiobarbituric acid SYSTEMATIC 23625905 A 1169 1180 glutathione TRIVIAL 23625905 A 1182 1185 GSH ABBREVIATION 23625905 A 1228 1239 glutathione TRIVIAL 23625905 A 1302 1304 Cr FORMULA 23625905 A 1337 1341 zinc SYSTEMATIC 23625905 A 1343 1349 copper SYSTEMATIC 23625905 A 1355 1359 iron SYSTEMATIC 23625905 A 1378 1384 Cr(VI) FORMULA 23625905 A 143 149 Cr(VI) FORMULA 23625905 A 1515 1518 GSH ABBREVIATION 23625905 A 1652 1658 Cr(VI) FORMULA 23625905 A 1738 1744 Cr(VI) FORMULA 23625905 A 188 194 Cr(VI) FORMULA 23625905 A 1946 1952 Cr(VI) FORMULA 23625905 A 25 44 hexavalent chromium SYSTEMATIC 23625905 A 327 333 Cr(VI) FORMULA 23625905 A 396 402 Cr(VI) FORMULA 23625905 A 453 464 glutathione TRIVIAL 23625905 A 46 52 Cr(VI) FORMULA 23625905 A 572 578 Cr(VI) FORMULA 23625905 A 808 814 Cr(VI) FORMULA 23625905 A 839 845 Cr(VI) FORMULA 23625905 A 86 88 Cr FORMULA 23625905 A 887 894 K2Cr2O7 FORMULA 23625905 T 10 23 chromium (VI) SYSTEMATIC 23625909 A 1140 1144 alum FAMILY 23625909 A 894 898 alum FAMILY 23625912 A 0 8 Aluminum SYSTEMATIC 23625912 A 10 12 Al FORMULA 23625912 A 1043 1045 Cu FORMULA 23625912 A 1065 1067 Fe FORMULA 23625912 A 1211 1213 Al FORMULA 23625912 A 258 260 Al FORMULA 23625912 A 548 559 Al chloride SYSTEMATIC 23625912 A 561 566 AlCl3 FORMULA 23625912 A 674 676 Al FORMULA 23625912 A 678 682 iron SYSTEMATIC 23625912 A 684 686 Fe FORMULA 23625912 A 689 695 copper SYSTEMATIC 23625912 A 697 699 Cu FORMULA 23625912 A 706 710 zinc SYSTEMATIC 23625912 A 712 714 Zn FORMULA 23625912 A 934 936 Al FORMULA 23625912 A 985 987 Al FORMULA 23625912 A 992 994 Fe FORMULA 23625912 T 11 28 aluminum chloride SYSTEMATIC 23627275 A 132 169 2-(2-methoxyethoxy)ethyl methacrylate SYSTEMATIC 23627275 A 171 177 MEO2MA ABBREVIATION 23627275 A 183 218 oligo(ethylene glycol) methacrylate SYSTEMATIC 23627275 A 220 225 OEGMA ABBREVIATION 23627275 A 232 244 polydopamine TRIVIAL 23627275 A 246 250 Pdop ABBREVIATION 23627275 A 259 263 SiO2 FORMULA 23627275 A 373 377 SiO2 FORMULA 23627275 A 563 575 rhodamine 6G TRIVIAL 23627275 A 577 581 Rh6G ABBREVIATION 23627275 A 677 681 Rh6G ABBREVIATION 23627275 A 853 866 methyl orange TRIVIAL 23627396 A 271 282 tyroscherin TRIVIAL 23627396 A 287 306 N-methyltyroscherin SYSTEMATIC 23627396 A 378 389 tyroscherin TRIVIAL 23627396 A 421 440 N-methyltyroscherin SYSTEMATIC 23627438 A 171 183 thioflavin-T TRIVIAL 23627438 A 204 217 sciadopitysin TRIVIAL 23627438 A 347 360 sciadopitysin TRIVIAL 23627438 A 46 53 ethanol SYSTEMATIC 23627438 A 5 24 taxane diterpenoids FAMILY 23627438 A 574 587 sciadopitysin TRIVIAL 23627438 T 0 13 Sciadopitysin TRIVIAL 23627443 A 2138 2152 amphotericin B TRIVIAL 23627443 A 371 385 amphotericin B TRIVIAL 23627443 A 47 61 amphotericin B TRIVIAL 23627443 A 527 532 Tween FAMILY 23627443 A 795 809 amphotericin B TRIVIAL 23627597 A 153 184 1,6-diyne carbonates and esters MULTIPLE 23627597 A 30 55 2,4a-dihydro-1H-fluorenes FAMILY 23627597 A 363 375 cyclopropene SYSTEMATIC 23627597 A 594 596 Au FORMULA 23627597 A 73 80 gold(I) SYSTEMATIC 23627597 A 91 102 1,2-acyloxy SYSTEMATIC 23627597 T 37 68 1,6-Diyne Carbonates and Esters MULTIPLE 23627597 T 72 97 2,4a-Dihydro-1H-fluorenes FAMILY 23627605 A 1051 1059 graphene TRIVIAL 23627605 A 161 169 graphene TRIVIAL 23627605 A 245 253 graphene TRIVIAL 23627605 A 333 341 graphene TRIVIAL 23627605 A 399 407 graphene TRIVIAL 23627605 A 630 634 SiO2 FORMULA 23627605 A 674 682 graphene TRIVIAL 23627605 A 718 726 graphene TRIVIAL 23627605 A 73 81 graphene TRIVIAL 23627605 A 816 824 graphene TRIVIAL 23627605 A 872 880 graphene TRIVIAL 23627605 T 103 107 SiO2 FORMULA 23627605 T 4 12 Graphene TRIVIAL 23627605 T 90 98 Graphene TRIVIAL 23627685 A 114 120 carbon SYSTEMATIC 23627685 A 140 148 hydrogen SYSTEMATIC 23627685 A 337 342 oxide SYSTEMATIC 23627685 A 459 461 Zn FORMULA 23627685 A 57 59 Zn FORMULA 23627685 A 60 63 ZnO FORMULA 23627685 A 808 810 Zn FORMULA 23627685 A 938 940 Zn FORMULA 23627685 T 49 53 Zinc SYSTEMATIC 23627717 A 101 138 octaethylene glycol monododecyl ether SYSTEMATIC 23627717 A 1033 1062 cyclodextrin (i.e. ,  or ) MULTIPLE 23627717 A 61 96 di-n-decyldimethylammonium chloride SYSTEMATIC 23627717 T 59 94 di-n-decyldimethylammonium chloride SYSTEMATIC 23627717 T 95 132 octaethylene glycol monododecyl ether SYSTEMATIC 23627806 A 102 112 iron oxide SYSTEMATIC 23627806 A 190 202 acrylic acid TRIVIAL 23627806 A 207 235 2-methacryloylethyl acrylate SYSTEMATIC 23627806 A 262 283 poly(ethylene glycol) SYSTEMATIC 23627806 A 288 315 poly(N-isopropylacrylamide) SYSTEMATIC 23627806 A 477 480 MEA ABBREVIATION 23627806 A 65 76 citric acid TRIVIAL 23627834 A 1019 1022 Dox ABBREVIATION 23627834 A 1052 1072 p(NIPAM)55-b-p(His)n FAMILY 23627834 A 1283 1286 Dox ABBREVIATION 23627834 A 143 163 p(NIPAM)55-b-p(His)n FAMILY 23627834 A 291 296 NIPAM ABBREVIATION 23627834 A 341 373 α-amino acid N-carboxyanhydrides FAMILY 23627834 A 464 484 p(NIPAM)55-b-p(His)n FAMILY 23627834 A 645 665 p(NIPAM)55-b-p(His)n FAMILY 23627834 A 752 763 doxorubicin TRIVIAL 23627834 A 765 768 Dox ABBREVIATION 23627834 A 834 837 Dox ABBREVIATION 23627834 A 87 141 poly(N-isopropylacrylamide)55-block-poly(l-histidine)n FAMILY 23627834 A 939 942 Dox ABBREVIATION 23627834 T 122 133 Doxorubicin TRIVIAL 23627834 T 24 71 Poly(N-isopropylacrylamide)-b-poly(l-histidine) SYSTEMATIC 23627902 A 1071 1076 (13)C FORMULA 23627902 A 114 120 phenyl SYSTEMATIC 23627902 A 1187 1192 (13)C FORMULA 23627902 A 1193 1197 (1)H FORMULA 23627902 A 144 149 cyano FAMILY 23627902 A 173 179 phenyl SYSTEMATIC 23627902 A 204 211 dodecyl SYSTEMATIC 23627902 A 275 280 cyano FAMILY 23627902 A 43 48 (13)C FORMULA 23627902 T 110 115 (13)C FORMULA 23628154 A 1082 1091 berberine TRIVIAL 23628154 A 1093 1102 palmatine TRIVIAL 23628154 A 1104 1112 baicalin TRIVIAL 23628154 A 1117 1126 baicalein TRIVIAL 23628154 A 1197 1208 gardenoside TRIVIAL 23628154 A 163 172 berberine TRIVIAL 23628154 A 174 182 baicalin TRIVIAL 23628154 A 187 198 gardenoside TRIVIAL 23628154 A 457 466 berberine TRIVIAL 23628154 A 468 477 palmatine TRIVIAL 23628154 A 479 487 baicalin TRIVIAL 23628154 A 489 498 baicalein TRIVIAL 23628154 A 503 514 gardenoside TRIVIAL 23628154 A 944 953 berberine TRIVIAL 23628154 A 955 964 palmatine TRIVIAL 23628154 A 966 974 baicalin TRIVIAL 23628154 A 976 985 baicalein TRIVIAL 23628154 A 990 1001 gardenoside TRIVIAL 23628332 A 1156 1166 idescarpin TRIVIAL 23628332 A 1341 1351 idescarpin TRIVIAL 23628332 A 287 295 methanol SYSTEMATIC 23628332 A 477 553 6-(oxymethyl)-2-hydroxyphenyl-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside SYSTEMATIC 23628332 A 624 629 CHCl3 FORMULA 23628332 A 634 640 n-BuOH FORMULA 23628332 A 658 666 methanol SYSTEMATIC 23628332 A 711 721 idescarpin TRIVIAL 23628332 A 731 771 1-hydroxy-6-oxo-2-cyclohexenecarboxylate SYSTEMATIC 23628332 A 879 889 Idescarpin TRIVIAL 23628333 A 372 376 NADH ABBREVIATION 23628333 A 73 80 lactate FAMILY 23628333 A 8 42 2-thio-6-oxo-1,6-dihydropyrimidine SYSTEMATIC 23628333 T 30 65 2-thio-6-oxo-1,6-dihydropyrimidines FAMILY 23628333 T 89 96 lactate FAMILY 23628455 A 1086 1097 aldosterone TRIVIAL 23628455 A 1304 1310 sodium SYSTEMATIC 23628455 A 277 281 NaCl FORMULA 23628455 A 392 405 acetylcholine SYSTEMATIC 23628455 A 407 410 ACh ABBREVIATION 23628455 A 442 448 L-NAME ABBREVIATION 23628455 A 460 472 enalaprilate TRIVIAL 23628455 A 481 489 losartan TRIVIAL 23628455 A 502 516 spironolactone TRIVIAL 23628455 A 753 765 enalaprilate TRIVIAL 23628455 A 770 778 losartan TRIVIAL 23628455 A 892 900 losartan TRIVIAL 23628455 A 925 928 ACh ABBREVIATION 23628455 A 957 971 Spironolactone TRIVIAL 23628508 A 0 10 Aspidin BB TRIVIAL 23628508 A 1014 1024 aspidin BB TRIVIAL 23628508 A 1196 1206 aspidin BB TRIVIAL 23628508 A 211 221 aspidin BB TRIVIAL 23628508 A 25 39 phloroglucinol TRIVIAL 23628508 A 266 276 Aspidin BB TRIVIAL 23628508 A 469 479 aspidin BB TRIVIAL 23628508 A 610 626 propidium iodide TRIVIAL 23628508 A 694 704 aspidin BB TRIVIAL 23628508 A 919 934 poly ADP-ribose SYSTEMATIC 23628508 T 0 10 Aspidin BB TRIVIAL 23628508 T 14 28 phloroglucinol TRIVIAL 23628509 A 1092 1099 CP[c]Ph ABBREVIATION 23628509 A 1171 1185 benzo[a]pyrene SYSTEMATIC 23628509 A 1187 1192 B[a]P ABBREVIATION 23628509 A 1248 1255 CP[c]Ph ABBREVIATION 23628509 A 1393 1400 CP[c]Ph ABBREVIATION 23628509 A 1420 1425 B[a]P ABBREVIATION 23628509 A 1536 1544 estrogen FAMILY 23628509 A 1609 1616 CP[c]Ph ABBREVIATION 23628509 A 1700 1708 CP[c]Phs ABBREVIATION 23628509 A 1873 1880 CP-PAHs ABBREVIATION 23628509 A 282 308 cyclopenta[c]phenanthrenes FAMILY 23628509 A 310 317 CP[c]Ph ABBREVIATION 23628509 A 474 481 CP-PAHs ABBREVIATION 23628509 A 516 523 CP[c]Ph ABBREVIATION 23628509 A 59 66 CP-PAHs ABBREVIATION 23628509 A 591 598 CP[c]Ph ABBREVIATION 23628509 A 659 671 cyclopentane SYSTEMATIC 23628509 A 747 753 B[c]Ph ABBREVIATION 23628509 A 763 775 phenanthrene SYSTEMATIC 23628509 A 8 57 cyclopenta-fused polycyclic aromatic hydrocarbons FAMILY 23628509 A 809 814 alkyl FAMILY 23628509 A 932 939 CP[c]Ph ABBREVIATION 23628509 T 0 26 Cyclopenta[c]phenanthrenes FAMILY 23628605 A 1282 1293 cholesterol TRIVIAL 23628605 A 1342 1353 cholesterol TRIVIAL 23628605 A 1574 1585 cholesterol TRIVIAL 23628605 A 161 172 cholesterol TRIVIAL 23628605 A 315 326 cholesterol TRIVIAL 23628605 A 330 342 pregnenolone TRIVIAL 23628605 A 37 44 steroid FAMILY 23628605 A 496 513 3β-hydroxysteroid FAMILY 23628605 A 549 560 aldosterone TRIVIAL 23628605 A 725 734 vitamin D FAMILY 23628605 A 750 761 cholesterol TRIVIAL 23628605 T 0 7 Steroid FAMILY 23628621 A 1358 1369 cholesterol TRIVIAL 23628621 A 847 858 cholesterol TRIVIAL 23628674 A 1271 1281 tacrolimus TRIVIAL 23628674 A 1304 1314 tacrolimus TRIVIAL 23628674 A 1368 1378 tacrolimus TRIVIAL 23628674 A 1422 1431 tacolimus TRIVIAL 23628674 A 1485 1495 Tacrolimus TRIVIAL 23628674 A 150 161 schisandrin TRIVIAL 23628674 A 1614 1623 tacolimus TRIVIAL 23628674 A 163 176 schisandrol B TRIVIAL 23628674 A 1747 1757 tacrolimus TRIVIAL 23628674 A 178 193 schisantherin A TRIVIAL 23628674 A 1801 1811 tacrolimus TRIVIAL 23628674 A 195 207 schisanhenol TRIVIAL 23628674 A 212 227 deoxyshisandrin TRIVIAL 23628674 A 237 247 tacrolimus TRIVIAL 23628674 A 43 50 ethanol SYSTEMATIC 23628674 A 450 460 tacrolimus TRIVIAL 23628674 A 559 569 tacrolimus TRIVIAL 23628674 A 694 704 tacrolimus TRIVIAL 23628674 A 777 787 tacrolimus TRIVIAL 23628674 A 821 831 tacrolimus TRIVIAL 23628674 A 979 989 tacrolimus TRIVIAL 23628674 T 77 87 Tacrolimus TRIVIAL 23629055 A 103 150 meta di-tert-butylphenyl-substituted porphyrins FAMILY 23629055 A 1192 1206 ortho-octyloxy SYSTEMATIC 23629055 A 1225 1237 meso-phenyls FAMILY 23629055 A 15 24 porphyrin FAMILY 23629055 A 1671 1688 cyanoacrylic acid SYSTEMATIC 23629055 A 432 459 meta-substituted porphyrins FAMILY 23629055 A 500 510 dioctyloxy SYSTEMATIC 23629055 A 554 565 meso-phenyl SYSTEMATIC 23629055 A 592 600 carboxyl SYSTEMATIC 23629055 A 608 625 cyanoacrylic acid SYSTEMATIC 23629055 A 795 804 porphyrin FAMILY 23629055 A 829 830 C FORMULA 23629055 A 85 97 meso-phenyls FAMILY 23629055 A 861 862 C FORMULA 23629055 T 0 9 Porphyrin FAMILY 23629516 A 0 33 Tris(1-chloro-2-propyl) phosphate SYSTEMATIC 23629516 A 1040 1044 TCPP ABBREVIATION 23629516 A 1052 1057 TDCPP ABBREVIATION 23629516 A 1195 1199 TCPP ABBREVIATION 23629516 A 1203 1208 TDCPP ABBREVIATION 23629516 A 1325 1329 TCPP ABBREVIATION 23629516 A 1334 1339 TDCPP ABBREVIATION 23629516 A 1476 1481 TDCPP ABBREVIATION 23629516 A 274 278 TCPP ABBREVIATION 23629516 A 282 287 TDCPP ABBREVIATION 23629516 A 35 39 TCPP ABBREVIATION 23629516 A 45 82 tris(1,3-dichloro-2-propyl) phosphate SYSTEMATIC 23629516 A 646 650 TCPP ABBREVIATION 23629516 A 745 750 TDCPP ABBREVIATION 23629516 A 84 89 TDCPP ABBREVIATION 23629516 T 22 37 organophosphate FAMILY 23629516 T 56 60 TCPP ABBREVIATION 23629516 T 65 70 TDCPP ABBREVIATION 23629675 A 1054 1061 proline TRIVIAL 23629675 A 1201 1208 proline TRIVIAL 23629675 A 1562 1569 proline TRIVIAL 23629675 A 333 339 lysine TRIVIAL 23629675 A 383 391 ethylene SYSTEMATIC 23629675 A 621 627 lysine TRIVIAL 23629675 A 741 747 lysine TRIVIAL 23629675 A 86 92 lysine TRIVIAL 23629675 A 912 916 NaCl FORMULA 23629675 A 97 107 tryptophan TRIVIAL 23629675 T 113 119 Lysine TRIVIAL 23630043 A 106 138 5-(1,2,4-triazol-3-yl)tetrazoles FAMILY 23630043 A 1120 1128 triazole FAMILY 23630043 A 1139 1142 CC FORMULA 23630043 A 1159 1167 triazole FAMILY 23630043 A 1251 1260 tetrazole FAMILY 23630043 A 183 188 nitro SYSTEMATIC 23630043 A 190 199 nitrimino SYSTEMATIC 23630043 A 205 210 azido SYSTEMATIC 23630043 T 34 66 5-(1,2,4-Triazol-3-yl)tetrazoles FAMILY 23631351 A 119 141 biflavonoid glycosides FAMILY 23631351 A 143 236 5,3',5″,4″'-tetrahydroxy-3″',5″'dimethoxy-biflavone (4' → 8″)-7-O-((2-rhamnoside) rhamnoside) SYSTEMATIC 23631351 A 264 277 ethyl acetate SYSTEMATIC 23631351 A 302 310 methanol SYSTEMATIC 23631351 A 37 104 trans-2',6'-dihydroxy-4'-O-(4″-acetyl-rhamnoside)-4-methoxychalcone SYSTEMATIC 23631351 A 472 476 (1)H FORMULA 23631351 A 485 490 (13)C FORMULA 23631351 A 552 565 ethyl acetate SYSTEMATIC 23631351 A 591 620 1,1-diphenyl-2-picrylhydrazyl SYSTEMATIC 23631351 A 6 35 acetylated chalcone glycoside FAMILY 23631351 A 655 668 ethyl acetate SYSTEMATIC 23631351 T 30 52 biflavonoid glycosides FAMILY 23631351 T 6 25 acetylated chalcone FAMILY 23631427 A 16 25 adenosine TRIVIAL 23631427 A 240 256 benzothiazinones FAMILY 23631427 A 263 326 2-(3-chlorophenoxy)-N-(4-oxo-4H-3,1-benzothiazin-2-yl)acetamide SYSTEMATIC 23631427 A 422 438 Benzothiazinones TRIVIAL 23631427 A 487 494 methoxy SYSTEMATIC 23631427 A 495 509 cinnamoylamino SYSTEMATIC 23631427 A 511 529 phenylbutyrylamino SYSTEMATIC 23631427 A 534 566 chlorobenzylpiperazinylbenzamido SYSTEMATIC 23631427 A 63 72 monoamine FAMILY 23631427 A 687 703 benzothiazinones FAMILY 23631427 A 785 793 xanthine TRIVIAL 23631427 A 844 897 N-(4-oxo-4H-3,1-benzothiazin-2-yl)-4-phenylbutanamide SYSTEMATIC 23631427 T 22 31 Adenosine TRIVIAL 23631427 T 50 59 Monoamine SYSTEMATIC 23631490 A 55 66 polyphenols FAMILY 23631490 T 10 21 Polyphenols FAMILY 23631493 A 1036 1044 lycopene TRIVIAL 23631493 A 1089 1097 Lycopene TRIVIAL 23631493 A 1225 1233 Lycopene TRIVIAL 23631493 A 1367 1375 lycopene TRIVIAL 23631493 A 142 150 lycopene TRIVIAL 23631493 A 347 355 lycopene TRIVIAL 23631493 A 829 837 lycopene TRIVIAL 23631493 A 9 17 Lycopene TRIVIAL 23631493 T 10 18 Lycopene TRIVIAL 23631499 A 1036 1049 acetylcholine SYSTEMATIC 23631499 A 1280 1285 AlCl3 FORMULA 23631499 A 642 654 rivastigmine TRIVIAL 23631553 A 1251 1266 Polybenzoxazine FAMILY 23631553 A 180 191 benzoxazine FAMILY 23631553 A 253 264 bisphenol-A TRIVIAL 23631553 A 271 293 tetraethylenepentamine SYSTEMATIC 23631553 A 295 299 TEPA ABBREVIATION 23631553 A 305 313 formalin TRIVIAL 23631553 A 415 417 1H FORMULA 23631553 A 563 574 acetic acid SYSTEMATIC 23631553 A 694 705 benzoxazine FAMILY 23631553 A 71 82 benzoxazine FAMILY 23631553 A 891 902 benzoxazine FAMILY 23631553 A 904 912 Hydrogen SYSTEMATIC 23631553 A 929 944 polybenzoxazine FAMILY 23631553 T 19 34 Polybenzoxazine FAMILY 23632007 A 229 290 1,5-bis(4-allyldimethylammoniumphenyl) pentan-3-one dibromide SYSTEMATIC 23632007 A 292 324 tetraisopropyl pyrophosphoramide SYSTEMATIC 23632007 A 329 340 neostigmine TRIVIAL 23632007 A 378 394 organophosphorus FAMILY 23632007 A 396 406 dichlorvos TRIVIAL 23632007 A 408 420 chlorpyrifos TRIVIAL 23632007 A 425 433 diazinon TRIVIAL 23632007 A 443 452 carbamate FAMILY 23632007 A 454 462 carbaryl TRIVIAL 23632007 A 467 477 carbofuran TRIVIAL 23632007 A 658 668 dichlorvos TRIVIAL 23632007 A 681 693 chlorpyrifos TRIVIAL 23632007 A 707 715 carbaryl TRIVIAL 23632007 A 730 740 carbofuran TRIVIAL 23632081 A 0 9 Serotonin TRIVIAL 23632081 A 1182 1191 serotonin TRIVIAL 23632081 A 1237 1246 serotonin TRIVIAL 23632081 A 1313 1322 serotonin TRIVIAL 23632081 A 1381 1419 3,4-methylenedioxy-N-methylamphetamine SYSTEMATIC 23632081 A 1421 1425 MDMA ABBREVIATION 23632081 A 374 383 serotonin TRIVIAL 23632081 A 528 539 amino acids FAMILY 23632081 A 755 762 leucine TRIVIAL 23632081 A 90 99 serotonin TRIVIAL 23632081 T 45 54 Serotonin TRIVIAL 23632082 A 1044 1049 Na(+) FORMULA 23632082 A 1258 1263 2-APB SYSTEMATIC 23632082 A 1265 1280 flufenamic acid TRIVIAL 23632082 A 1285 1290 ML204 IDENTIFIER 23632082 A 1304 1310 La(3+) FORMULA 23632082 A 136 147 thyrotropin TRIVIAL 23632082 A 1378 1389 capsazepine TRIVIAL 23632082 A 1395 1400 Na(+) FORMULA 23632082 A 1402 1408 Ca(2+) FORMULA 23632082 A 1427 1435 KB-R7943 IDENTIFIER 23632082 A 1437 1440 TRH ABBREVIATION 23632082 A 1562 1567 2-APB SYSTEMATIC 23632082 A 1571 1576 ML204 IDENTIFIER 23632082 A 1612 1615 TRH ABBREVIATION 23632082 A 167 170 TRH ABBREVIATION 23632082 A 1719 1723 K(+) FORMULA 23632082 A 257 260 TRH ABBREVIATION 23632082 A 420 423 TRH ABBREVIATION 23632082 A 460 463 TRH ABBREVIATION 23632082 A 483 486 TTX ABBREVIATION 23632082 A 543 546 TRH ABBREVIATION 23632082 A 630 633 TRH ABBREVIATION 23632082 A 772 775 TRH ABBREVIATION 23632082 A 821 826 Na(+) FORMULA 23632082 A 843 847 K(+) FORMULA 23632082 A 950 956 Ba(2+) FORMULA 23632082 A 999 1008 SCH 23390 IDENTIFIER 23632082 T 45 56 thyrotropin TRIVIAL 23632158 A 1200 1209 glutamate TRIVIAL 23632309 A 1307 1316 flavonoid FAMILY 23633521 A 226 233 glucose TRIVIAL 23633529 A 1019 1028 phosphate SYSTEMATIC 23633529 A 1069 1079 phosphates FAMILY 23633529 A 1162 1171 oxymethyl SYSTEMATIC 23633529 A 1398 1417 ritonavir phosphate SYSTEMATIC 23633529 A 1531 1543 fosphenytoin TRIVIAL 23633529 A 1548 1569 clindamycin phosphate SYSTEMATIC 23633529 A 267 276 phosphate SYSTEMATIC 23633529 A 755 767 fosphenytoin TRIVIAL 23633529 A 769 790 clindamycin phosphate SYSTEMATIC 23633529 A 792 815 dexamethasone phosphate SYSTEMATIC 23633529 A 817 836 ritonavir phosphate SYSTEMATIC 23633529 A 841 870 ritonavir oxymethyl phosphate SYSTEMATIC 23633532 A 1133 1147 corticosterone TRIVIAL 23633532 A 1149 1153 CORT ABBREVIATION 23633532 A 1159 1164 11DHC SYSTEMATIC 23633532 A 1193 1197 CORT ABBREVIATION 23633532 A 1207 1212 11DHC SYSTEMATIC 23633532 A 1255 1259 CORT ABBREVIATION 23633532 A 1264 1269 11DHC SYSTEMATIC 23633532 A 1298 1302 CORT ABBREVIATION 23633532 A 1312 1317 11DHC SYSTEMATIC 23633532 A 1362 1365 Ser FORMULA 23633532 A 1383 1386 Thr FORMULA 23633532 A 1417 1432 diacylglyderide FAMILY 23633532 A 1638 1653 diacylglyderide FAMILY 23633532 A 450 468 11β-hydroxysteroid FAMILY 23633532 A 542 555 Dexamethasone TRIVIAL 23633532 A 642 645 Ser FORMULA 23633532 A 656 666 acetyl-CoA SYSTEMATIC 23633532 A 709 712 Thr FORMULA 23633532 A 720 723 AMP ABBREVIATION 23633532 A 786 799 dexamethasone TRIVIAL 23633532 A 842 855 dexamethasone TRIVIAL 23633532 A 921 945 11-dehydrocorticosterone SYSTEMATIC 23633532 A 947 952 11DHC SYSTEMATIC 23633563 A 1053 1060 glucose TRIVIAL 23633563 A 1683 1690 glucose TRIVIAL 23633563 A 298 305 glucose TRIVIAL 23633563 A 391 398 glucose TRIVIAL 23633563 A 517 524 glucose TRIVIAL 23633563 A 805 812 glucose TRIVIAL 23633563 A 89 96 glucose TRIVIAL 23634786 A 174 178 MeOH FORMULA 23634786 A 289 312 lanostane triterpenoids FAMILY 23634786 A 477 503 3-hydroxy-3-methylglutaryl SYSTEMATIC 23634786 A 640 652 fasciculol G TRIVIAL 23634786 A 876 888 nitric oxide SYSTEMATIC 23634786 T 0 23 Lanostane Triterpenoids FAMILY 23634899 A 22 24 OH FORMULA 23634899 A 291 300 $^{17}$OH FORMULA 23634899 A 433 442 $^{17}$OH FORMULA 23634899 A 544 546 OH FORMULA 23634899 T 24 32 Hydroxyl SYSTEMATIC 23635005 A 1004 1016 carbohydrate FAMILY 23635005 A 1196 1208 carbohydrate FAMILY 23635005 A 269 281 carbohydrate FAMILY 23635005 A 388 396 β-D-Galp ABBREVIATION 23635005 A 444 452 β-D-Galp ABBREVIATION 23635005 A 547 555 α-L-Araf ABBREVIATION 23635005 A 593 601 α-L-Araf ABBREVIATION 23635005 A 606 614 β-D-Galp ABBREVIATION 23635005 A 639 664 esterified phenolic acids FAMILY 23635005 A 757 769 carbohydrate FAMILY 23635005 A 851 864 phenolic acid FAMILY 23635005 T 17 29 Carbohydrate FAMILY 23635023 A 30 34 GaAs FORMULA 23635023 A 328 334 AlGaAs FORMULA 23635023 A 361 365 GaAs FORMULA 23635023 T 76 80 GaAs FORMULA 23636303 A 1055 1063 MDL72222 IDENTIFIER 23636303 A 1111 1123 methiothepin TRIVIAL 23636303 A 1141 1151 citalopram TRIVIAL 23636303 A 1174 1182 MDL72222 IDENTIFIER 23636303 A 1266 1276 citalopram TRIVIAL 23636303 A 1358 1366 MDL72222 IDENTIFIER 23636303 A 1390 1400 citalopram TRIVIAL 23636303 A 1485 1494 serotonin TRIVIAL 23636303 A 21 30 serotonin TRIVIAL 23636303 A 315 324 serotonin TRIVIAL 23636303 A 503 513 citalopram TRIVIAL 23636303 A 541 554 noradrenaline TRIVIAL 23636303 A 722 729 RS79948 IDENTIFIER 23636303 A 747 757 citalopram TRIVIAL 23636303 A 836 846 citalopram TRIVIAL 23636303 A 975 985 citalopram TRIVIAL 23636303 T 15 24 serotonin TRIVIAL 23636303 T 92 101 serotonin TRIVIAL 23636446 A 588 602 hydrocortisone TRIVIAL 23636584 A 552 558 biotin TRIVIAL 23636886 A 870 877 glucose TRIVIAL 23636886 A 898 903 MgCl2 FORMULA 23637306 A 144 151 benzene SYSTEMATIC 23637306 A 153 160 toluene TRIVIAL 23637306 A 165 171 xylene FAMILY 23637306 A 384 391 benzene SYSTEMATIC 23637306 A 393 400 toluene TRIVIAL 23637306 A 405 411 xylene FAMILY 23637306 A 705 715 superoxide TRIVIAL 23637306 A 841 848 alanine TRIVIAL 23637306 A 870 879 aspartate TRIVIAL 23637306 A 967 977 creatinine TRIVIAL 23637306 A 982 993 cholesterol TRIVIAL 23638641 A 0 8 Shogaols FAMILY 23638641 A 1053 1059 thiols FAMILY 23638641 A 1099 1125 5-glutathionyl-[6]-shogaol SYSTEMATIC 23638641 A 1449 1454 thiol FAMILY 23638641 A 1586 1616 5-N-acetylcystenyl-[6]-shogaol SYSTEMATIC 23638641 A 180 196 mercapturic acid TRIVIAL 23638641 A 1863 1871 cysteine TRIVIAL 23638641 A 1897 1908 [6]-shogaol TRIVIAL 23638641 A 206 229 5-cysteinyl-[6]-shogaol SYSTEMATIC 23638641 A 304 315 [6]-shogaol TRIVIAL 23638641 A 478 483 thiol FAMILY 23638641 A 906 917 glutathione TRIVIAL 23638641 T 0 8 Cysteine TRIVIAL 23638641 T 51 62 [6]-shogaol TRIVIAL 23638641 T 86 97 [6]-shogaol TRIVIAL 23638658 A 0 7 CuInSe2 FORMULA 23638658 A 266 273 CuInSe2 FORMULA 23638658 A 675 677 Cu FORMULA 23638658 A 678 680 In FORMULA 23638658 A 681 683 Se FORMULA 23638658 A 771 777 copper SYSTEMATIC 23638658 A 786 792 indium SYSTEMATIC 23638658 T 35 47 Chalcopyrite TRIVIAL 23638658 T 48 72 Copper Indium Diselenide SYSTEMATIC 23638985 A 154 162 saponins FAMILY 23638985 A 163 177 ginsenoside Rf TRIVIAL 23638985 A 18 28 triterpene FAMILY 23638985 A 186 201 ginsenoside Re5 TRIVIAL 23638985 A 206 219 panajaponol A TRIVIAL 23638985 A 275 279 (1)H FORMULA 23638985 A 280 284 (1)H FORMULA 23638985 A 29 36 saponin FAMILY 23638985 A 363 370 saponin FAMILY 23638985 A 389 482 3β,12β,20S,26-tetrahydroxydammar-24E-en-6α-O-β-d-glucopyranosyl-(1 → 2)-O-β-d-glucopyranoside SYSTEMATIC 23638985 A 43 56 ginsenjilinol TRIVIAL 23638985 A 512 520 saponins FAMILY 23638985 A 532 544 nitric oxide SYSTEMATIC 23638985 A 642 650 saponins FAMILY 23638985 A 8 17 dammarane TRIVIAL 23638985 A 912 924 indomethacin TRIVIAL 23638985 T 0 13 Ginsenjilinol TRIVIAL 23638985 T 21 37 protopanaxatriol TRIVIAL 23638985 T 43 50 saponin FAMILY 23638985 T 93 95 NO FORMULA 23639075 A 218 237 patriheterdoid B, C NO CLASS 23639075 A 30 49 patriheterdoid B, C NO CLASS 23639075 A 327 331 (1)H FORMULA 23639075 A 336 341 (13)C FORMULA 23639075 A 8 22 iridoid esters FAMILY 23639075 T 18 32 iridoid esters FAMILY 23639096 A 1223 1231 catechol TRIVIAL 23639096 A 1386 1393 calcium SYSTEMATIC 23639096 A 575 583 dopamine TRIVIAL 23639096 A 685 693 catechol TRIVIAL 23639096 A 712 721 catechols FAMILY 23639096 A 861 869 catechol TRIVIAL 23639096 A 993 1001 catechol TRIVIAL 23639096 T 14 21 Calcium SYSTEMATIC 23639188 A 230 241 anthranoids FAMILY 23639188 A 438 450 altersolanol FAMILY 23639188 T 28 39 anthranoids FAMILY 23639192 A 0 8 Puerarin TRIVIAL 23639192 A 1112 1120 puerarin TRIVIAL 23639192 A 1237 1245 puerarin TRIVIAL 23639192 A 1416 1424 estrogen FAMILY 23639192 A 1437 1445 puerarin TRIVIAL 23639192 A 19 39 isoflavone glycoside FAMILY 23639192 A 231 239 puerarin TRIVIAL 23639192 A 372 380 puerarin TRIVIAL 23639192 A 562 570 puerarin TRIVIAL 23639192 A 627 636 cisplatin TRIVIAL 23639192 A 704 712 estrogen FAMILY 23639192 A 737 745 Puerarin TRIVIAL 23639192 A 813 821 puerarin TRIVIAL 23639192 A 932 943 ICI 182,780 IDENTIFIER 23639192 A 975 983 puerarin TRIVIAL 23639192 T 0 8 Puerarin TRIVIAL 23639248 A 1063 1069 silica TRIVIAL 23639248 A 1246 1252 silica TRIVIAL 23639248 A 1402 1408 silica TRIVIAL 23639248 A 1475 1481 silica TRIVIAL 23639248 A 219 225 silica TRIVIAL 23639248 A 355 361 silica TRIVIAL 23639248 A 481 487 silica TRIVIAL 23639248 A 503 509 silica TRIVIAL 23639248 A 543 549 silica TRIVIAL 23639248 A 587 593 silica TRIVIAL 23639248 A 747 761 hydroxyproline SYSTEMATIC 23639248 A 886 900 hydroxyproline SYSTEMATIC 23639248 A 968 974 silica TRIVIAL 23639248 T 38 44 silica TRIVIAL 23639361 A 1043 1051 naringin TRIVIAL 23639361 A 1057 1067 naringenin TRIVIAL 23639361 A 1076 1083 calcium SYSTEMATIC 23639361 A 1108 1116 naringin TRIVIAL 23639361 A 1121 1131 naringenin TRIVIAL 23639361 A 1290 1298 naringin TRIVIAL 23639361 A 1303 1313 naringenin TRIVIAL 23639361 A 622 629 calcium SYSTEMATIC 23639361 A 801 808 calcium SYSTEMATIC 23639361 A 869 877 naringin TRIVIAL 23639361 A 882 892 naringenin TRIVIAL 23639361 A 918 925 calcium SYSTEMATIC 23639361 A 975 988 cortistatin-8 TRIVIAL 23639361 T 33 41 naringin TRIVIAL 23639361 T 46 56 naringenin TRIVIAL 23639430 A 1044 1051 quinine TRIVIAL 23639430 A 1194 1201 cocaine TRIVIAL 23639430 A 1478 1485 cocaine TRIVIAL 23639430 A 1578 1585 quinine TRIVIAL 23639430 A 1698 1705 cocaine TRIVIAL 23639430 A 1847 1855 dopamine TRIVIAL 23639430 A 1887 1894 cocaine TRIVIAL 23639430 A 1984 1991 quinine TRIVIAL 23639430 A 2042 2049 cocaine TRIVIAL 23639430 A 2076 2083 cocaine TRIVIAL 23639430 A 2170 2178 dopamine TRIVIAL 23639430 A 2203 2210 cocaine TRIVIAL 23639430 A 2358 2365 cocaine TRIVIAL 23639430 A 24 31 cocaine TRIVIAL 23639430 A 757 766 saccharin TRIVIAL 23639430 A 809 816 cocaine TRIVIAL 23639430 A 977 984 cocaine TRIVIAL 23639430 T 136 143 cocaine TRIVIAL 23639437 A 0 8 Nicotine TRIVIAL 23639437 A 412 420 nicotine TRIVIAL 23639437 A 966 974 nicotine TRIVIAL 23639437 T 26 34 Nicotine TRIVIAL 23639437 T 64 72 Nicotine TRIVIAL 23639537 A 6 44 indeno[1,2-d]thiazole hydroxamic acids FAMILY 23639537 T 47 68 indeno[1,2-d]thiazole SYSTEMATIC 23639543 A 0 26 Ribonucleoside phosphonate FAMILY 23639543 A 151 171 diphosphophosphonate SYSTEMATIC 23639543 A 173 185 triphosphate SYSTEMATIC 23639543 A 198 205 adenine TRIVIAL 23639543 A 210 218 cytidine TRIVIAL 23639543 A 387 410 nucleoside phosphonates FAMILY 23639543 A 48 59 2'-α-fluoro SYSTEMATIC 23639543 T 14 27 2'-α-fluorine SYSTEMATIC 23639543 T 37 60 nucleoside phosphonates FAMILY 23639545 A 102 107 amino FAMILY 23639545 A 108 117 acetamido FAMILY 23639545 A 183 187 (1)H FORMULA 23639545 A 384 407 l-α-phosphatidylcholine FAMILY 23639545 A 46 64 p-phenylenediamine SYSTEMATIC 23639545 A 583 588 amino FAMILY 23639545 A 6 18 bis(choloyl) FAMILY 23639545 A 640 645 Na(+) FORMULA 23639545 A 646 651 Li(+) FORMULA 23639545 A 65 90 p-bis(aminomethyl)benzene SYSTEMATIC 23639545 A 652 656 K(+) FORMULA 23639545 A 657 662 Rb(+) FORMULA 23639545 A 663 668 Cs(+) FORMULA 23639545 A 693 702 acetamido FAMILY 23639545 A 736 741 Li(+) FORMULA 23639545 A 742 747 Na(+) FORMULA 23639545 A 748 752 K(+) FORMULA 23639545 A 753 758 Rb(+) FORMULA 23639545 A 759 764 Cs(+) FORMULA 23639545 T 54 66 bis(choloyl) FAMILY 23639627 A 0 13 Anthracycline TRIVIAL 23639627 A 521 532 doxorubicin TRIVIAL 23639627 A 534 537 DXR ABBREVIATION 23639627 A 786 789 DXR ABBREVIATION 23639627 A 953 956 DXR ABBREVIATION 23639627 A 993 996 DXR ABBREVIATION 23639627 T 0 11 Doxorubicin TRIVIAL 23639652 A 391 399 chalcone FAMILY 23639652 A 420 431 sulfonamide SYSTEMATIC 23639652 T 10 19 chalcones FAMILY 23639652 T 24 36 sulfonamides FAMILY 23639652 T 84 92 tyrosine TRIVIAL 23639738 A 0 11 Cholesterol TRIVIAL 23639738 A 106 109 PEC ABBREVIATION 23639738 A 335 338 PEC ABBREVIATION 23639738 A 408 411 PEC ABBREVIATION 23639738 A 436 439 PEC ABBREVIATION 23639738 A 448 451 PEC ABBREVIATION 23639738 A 475 478 PEC ABBREVIATION 23639738 A 529 532 PEC ABBREVIATION 23639738 A 53 77 poly(ethylene carbonate) SYSTEMATIC 23639738 A 579 582 PEC ABBREVIATION 23639738 A 647 650 PEC ABBREVIATION 23639738 A 772 775 PEC ABBREVIATION 23639738 A 79 82 PEC ABBREVIATION 23639738 A 800 803 PEC ABBREVIATION 23639738 A 914 917 PEC ABBREVIATION 23639738 T 37 61 poly(ethylene carbonate) SYSTEMATIC 23639739 A 736 742 6-OHDA SYSTEMATIC 23639741 A 202 208 sodium SYSTEMATIC 23639741 A 213 222 potassium SYSTEMATIC 23639741 A 871 874 HCl FORMULA 23639741 T 34 36 Na FORMULA 23639741 T 41 42 K FORMULA 23639992 A 239 259 polydimethylsiloxane SYSTEMATIC 23639992 A 261 265 PDMS ABBREVIATION 23640282 A 244 249 Fe3O4 FORMULA 23640282 A 254 258 FePt FORMULA 23640471 A 150 177 1-butyl-3-methylimidazolium SYSTEMATIC 23640471 A 179 189 [C4MIM](+) FORMULA 23640471 A 329 334 C4MIM ABBREVIATION 23640471 A 353 360 [Cl](-) FORMULA 23640471 A 362 370 [BF4](-) FORMULA 23640471 A 372 380 [PF6](-) FORMULA 23640471 A 382 390 [OTf](-) FORMULA 23640471 A 392 401 [NTf2](-) FORMULA 23640471 A 406 419 [B(hfip)4](-) FORMULA 23640471 A 922 932 [C4MIM](+) FORMULA 23640722 A 334 380 2-chloro-3-(4-methylpiperazin-1-yl)quinoxaline SYSTEMATIC 23640722 A 382 390 VUF10166 IDENTIFIER 23640722 A 458 476 [(3) H]granisetron SYSTEMATIC 23640722 A 575 583 VUF10166 IDENTIFIER 23640722 A 588 629 3-(4-methylpiperazin-1-yl)quinoxalin-2-ol SYSTEMATIC 23640722 A 872 917 2-amino-3-(4-methylpiperazin-1-yl)quinoxaline SYSTEMATIC 23640722 A 982 1019 2-(4-methylpiperazin-1-yl)quinoxaline SYSTEMATIC 23640722 T 36 47 Quinoxaline SYSTEMATIC 23640867 A 252 260 arginine TRIVIAL 23640867 A 316 324 arginine TRIVIAL 23640867 A 569 576 trypsin TRIVIAL 23640867 A 752 762 citrulline TRIVIAL 23640872 A 286 293 tropane TRIVIAL 23640872 A 297 306 scopoline TRIVIAL 23640872 A 32 39 scopine TRIVIAL 23640872 A 352 359 scopine TRIVIAL 23640872 A 45 54 scopoline TRIVIAL 23640872 A 527 536 scopoline TRIVIAL 23640872 A 56 62 oscine TRIVIAL 23640872 A 607 614 scopine TRIVIAL 23640872 A 642 647 epoxy SYSTEMATIC 23640872 A 691 708 7β-hydroxytropane SYSTEMATIC 23640872 A 728 735 hydroxy SYSTEMATIC 23640872 A 780 783 OH FORMULA 23640872 A 786 787 N FORMULA 23640872 A 803 811 hydrogen SYSTEMATIC 23640872 A 845 853 N-methyl SYSTEMATIC 23640872 T 14 21 Tropane TRIVIAL 23640872 T 25 34 Scopoline TRIVIAL 23640962 A 1166 1179 isoflavonoids FAMILY 23640962 A 1190 1198 saponins FAMILY 23640962 A 628 640 nitric oxide SYSTEMATIC 23640962 A 927 943 prostaglandin E2 TRIVIAL 23641017 A 1100 1111 cholesterol TRIVIAL 23641017 A 1117 1129 triglyceride FAMILY 23641017 A 722 733 cholesterol TRIVIAL 23641017 A 755 768 triglycerides FAMILY 23641017 A 801 812 cholesterol TRIVIAL 23641685 A 1185 1188 HMP ABBREVIATION 23641685 A 145 156 hydroperoxy SYSTEMATIC 23641685 A 1519 1522 HMP ABBREVIATION 23641685 A 166 169 HO2 FORMULA 23641685 A 175 187 formaldehyde SYSTEMATIC 23641685 A 189 193 HCHO FORMULA 23641685 A 1943 1946 HMP ABBREVIATION 23641685 A 215 217 OH FORMULA 23641685 A 2231 2234 HMP ABBREVIATION 23641685 A 2277 2281 OCOH FORMULA 23641685 A 2287 2291 OOCO FORMULA 23641685 A 2639 2642 HMP ABBREVIATION 23641685 A 271 274 HMP ABBREVIATION 23641685 A 2749 2752 HMP ABBREVIATION 23641685 A 2910 2913 HMP ABBREVIATION 23641685 A 2994 2997 HMP ABBREVIATION 23641685 A 3006 3009 HMP ABBREVIATION 23641685 A 413 416 HMP ABBREVIATION 23641685 A 455 459 HCHO FORMULA 23641685 A 465 468 HO2 FORMULA 23641685 A 52 74 hydroxyl-methyl-peroxy SYSTEMATIC 23641685 A 544 547 Cl2 FORMULA 23641685 A 567 571 HCHO FORMULA 23641685 A 576 578 O2 FORMULA 23641685 A 84 91 HOCH2OO FORMULA 23641685 A 96 99 HMP ABBREVIATION 23641685 A 984 988 HOOH FORMULA 23641685 A 993 998 HCOOH FORMULA 23641685 T 36 57 Hydroxy-Methyl-Peroxy SYSTEMATIC 23641955 A 118 137 uridine diphosphate SYSTEMATIC 23641955 A 444 455 laropiprant TRIVIAL 23641955 A 51 67 prostaglandin D2 TRIVIAL 23641955 A 520 531 laropiprant TRIVIAL 23641955 A 795 806 laropiprant TRIVIAL 23641955 A 90 101 laropiprant TRIVIAL 23641955 T 134 145 laropiprant TRIVIAL 23641955 T 147 154 MK-0524 IDENTIFIER 23641955 T 24 27 UDP ABBREVIATION 23642029 A 0 12 Brevetoxin B FAMILY 23642029 A 1066 1076 brevetoxin FAMILY 23642029 A 123 147 α,β-unsaturated aldehyde SYSTEMATIC 23642029 A 1364 1374 brevetoxin FAMILY 23642029 A 14 19 BTX-B ABBREVIATION 23642029 A 1404 1417 dihydro-BTX-B SYSTEMATIC 23642029 A 1474 1489 S-desoxy-BTX-B2 SYSTEMATIC 23642029 A 1543 1570 N-palmitoyl-S-desoxy-BTX-B2 SYSTEMATIC 23642029 A 1706 1716 brevetoxin FAMILY 23642029 A 1756 1766 amino acid FAMILY 23642029 A 1783 1793 fatty acid FAMILY 23642029 A 1806 1811 BTX-B ABBREVIATION 23642029 A 342 352 brevetoxin FAMILY 23642029 A 423 428 BTX-B ABBREVIATION 23642029 A 451 456 BTX-B ABBREVIATION 23642029 A 485 503 [3H] dihydro-BTX-B SYSTEMATIC 23642029 A 505 525 [3H] S-desoxy-BTX-B2 SYSTEMATIC 23642029 A 527 548 cysteine brevetoxin B TRIVIAL 23642029 A 576 581 BTX-B ABBREVIATION 23642029 A 600 608 cysteine TRIVIAL 23642029 A 620 628 olefinic FAMILY 23642029 A 641 645 [3H] FORMULA 23642029 A 666 674 aldehyde SYSTEMATIC 23642029 A 686 719 [14C] N-palmitoyl-S-desoxy-BTX-B2 SYSTEMATIC 23642029 A 739 754 S-desoxy-BTX-B2 SYSTEMATIC 23642029 A 801 806 [14C] FORMULA 23642029 A 820 830 fatty acid FAMILY 23642029 A 839 847 cysteine TRIVIAL 23642029 A 848 853 amide FAMILY 23642029 A 909 929 [3H] S-desoxy-BTX-B2 SYSTEMATIC 23642029 A 931 964 [14C] N-palmitoyl-S-desoxy-BTX-B2 SYSTEMATIC 23642029 A 969 987 [3H] dihydro-BTX-B SYSTEMATIC 23642029 T 31 41 amino acid FAMILY 23642029 T 52 62 brevetoxin FAMILY 23642965 A 6 39 7-oxabicyclo[2.2.1]hept-5-en-2-yl SYSTEMATIC 23642965 A 80 114 boron trifluoride diethyl etherate SYSTEMATIC 23642965 T 13 46 7-oxabicyclo[2.2.1]hept-5-en-2-yl SYSTEMATIC 23643542 A 1634 1646 glycyrrhizin TRIVIAL 23643542 A 1685 1691 18β-GA FORMULA 23643542 A 2489 2495 18β-GA FORMULA 23643542 A 867 879 glycyrrhizin TRIVIAL 23643542 A 884 907 18β-glycyrrhetinic acid SYSTEMATIC 23643542 A 909 915 18β-GA FORMULA 23643664 A 1052 1060 tyrosine TRIVIAL 23643664 A 1218 1222 MPTP ABBREVIATION 23643664 A 1567 1571 MPTP ABBREVIATION 23643664 A 166 174 dopamine TRIVIAL 23643664 A 285 329 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine SYSTEMATIC 23643664 A 32 40 dopamine TRIVIAL 23643664 A 331 335 MPTP ABBREVIATION 23643664 A 376 380 MPTP ABBREVIATION 23643664 A 445 452 carboxy SYSTEMATIC 23643664 A 556 560 MPTP ABBREVIATION 23643664 A 594 598 MPTP ABBREVIATION 23643664 A 670 674 MPTP ABBREVIATION 23643664 A 816 820 MPTP ABBREVIATION 23643664 A 904 908 MPTP ABBREVIATION 23643664 T 30 34 MPTP ABBREVIATION 23643664 T 60 68 dopamine TRIVIAL 23643700 A 1042 1051 vitamin C TRIVIAL 23643700 A 1156 1165 vitamin C TRIVIAL 23643700 A 1255 1264 vitamin C TRIVIAL 23643700 A 207 220 Ascorbic acid TRIVIAL 23643700 A 356 369 ascorbic acid TRIVIAL 23643700 A 452 461 vitamin C TRIVIAL 23643700 A 651 660 vitamin C TRIVIAL 23643700 A 738 747 vitamin C TRIVIAL 23643700 A 974 983 vitamin C TRIVIAL 23643700 T 0 9 Vitamin C TRIVIAL 23643725 A 1340 1351 oxyfluorfen TRIVIAL 23643725 A 1416 1427 oxyfluorfen TRIVIAL 23643725 A 274 285 oxyfluorfen TRIVIAL 23643725 A 418 427 ascorbate TRIVIAL 23643725 A 532 543 glutathione TRIVIAL 23643725 A 620 631 oxyfluorfen TRIVIAL 23643725 A 856 867 oxyfluorfen TRIVIAL 23643725 A 903 908 chl-a ABBREVIATION 23643730 A 0 7 Juglone TRIVIAL 23643730 A 1017 1024 juglone TRIVIAL 23643730 A 1074 1082 androgen FAMILY 23643730 A 117 124 juglone TRIVIAL 23643730 A 1236 1255 dihydrotestosterone SYSTEMATIC 23643730 A 1257 1260 DHT ABBREVIATION 23643730 A 1308 1315 juglone TRIVIAL 23643730 A 1433 1440 juglone TRIVIAL 23643730 A 1482 1490 androgen FAMILY 23643730 A 404 411 juglone TRIVIAL 23643730 A 415 423 androgen FAMILY 23643730 A 463 466 MTT ABBREVIATION 23643730 A 531 538 juglone TRIVIAL 23643730 A 580 593 Hoechst 33342 TRIVIAL 23643730 A 650 657 juglone TRIVIAL 23643730 A 689 696 juglone TRIVIAL 23643730 A 817 824 juglone TRIVIAL 23643730 A 852 865 Hoechst 33342 TRIVIAL 23643730 T 0 7 Juglone TRIVIAL 23643737 A 254 260 acetyl SYSTEMATIC 23643737 A 347 360 acetylcholine SYSTEMATIC 23643737 A 558 601 1,4-substituted 4-(1H)-pyridylene-hydrazone FAMILY 23643737 T 0 43 1,4-Substituted 4-(1H)-pyridylene-hydrazone FAMILY 23643739 A 1181 1189 glycerol TRIVIAL 23643739 A 1194 1198 urea TRIVIAL 23643739 A 1311 1319 glycerol TRIVIAL 23643739 A 1325 1329 urea TRIVIAL 23643739 A 141 149 Glycerol TRIVIAL 23643739 A 154 158 urea TRIVIAL 23643739 A 294 302 glycerol TRIVIAL 23643739 A 307 311 urea TRIVIAL 23643739 A 349 362 metronidazole TRIVIAL 23643739 A 925 933 glycerol TRIVIAL 23643739 A 938 942 urea TRIVIAL 23643739 T 0 8 Glycerol TRIVIAL 23643739 T 13 17 urea TRIVIAL 23643744 A 106 110 NMDA ABBREVIATION 23643744 A 1186 1190 THIP ABBREVIATION 23643744 A 1202 1205 PCP ABBREVIATION 23643744 A 1306 1310 THIP ABBREVIATION 23643744 A 1328 1336 ADX47273 IDENTIFIER 23643744 A 1378 1382 THIP ABBREVIATION 23643744 A 1448 1456 ADX47273 IDENTIFIER 23643744 A 1461 1470 SSR180711 IDENTIFIER 23643744 A 1651 1659 ADX47273 IDENTIFIER 23643744 A 1663 1672 SSR180711 IDENTIFIER 23643744 A 1737 1740 PCP ABBREVIATION 23643744 A 367 371 NMDA ABBREVIATION 23643744 A 398 411 phencyclidine TRIVIAL 23643744 A 413 416 PCP ABBREVIATION 23643744 A 578 587 glutamate TRIVIAL 23643744 A 663 676 acetylcholine SYSTEMATIC 23643744 A 698 707 SSR180711 IDENTIFIER 23643744 A 750 753 PCP ABBREVIATION 23643744 A 906 914 ADX47273 IDENTIFIER 23643744 A 918 927 SSR180711 IDENTIFIER 23643744 T 184 197 phencyclidine TRIVIAL 23643744 T 199 202 PCP ABBREVIATION 23643744 T 42 51 glutamate TRIVIAL 23643744 T 89 102 acetylcholine SYSTEMATIC 23643745 A 109 117 dopamine TRIVIAL 23643745 A 1287 1298 pramipexole TRIVIAL 23643745 A 1509 1517 dopamine TRIVIAL 23643745 A 435 443 SCH23390 IDENTIFIER 23643745 A 453 463 raclopride TRIVIAL 23643745 A 465 476 amisulpride TRIVIAL 23643745 A 486 492 S33084 IDENTIFIER 23643745 A 705 715 raclopride TRIVIAL 23643745 A 756 767 amisulpride TRIVIAL 23643745 A 769 780 Amisulpride TRIVIAL 23643745 A 854 865 pramipexole TRIVIAL 23643745 A 870 878 dopamine TRIVIAL 23643745 A 889 917 L-3,4-dihydroxyphenylalanine SYSTEMATIC 23643745 A 927 937 raclopride TRIVIAL 23643745 A 943 949 S33084 IDENTIFIER 23643748 A 1041 1049 oxytocin TRIVIAL 23643748 A 1197 1205 oxytocin TRIVIAL 23643748 A 1554 1562 oxytocin TRIVIAL 23643748 A 32 40 oxytocin TRIVIAL 23643748 A 646 654 oxytocin TRIVIAL 23643748 A 706 714 oxytocin TRIVIAL 23643748 A 779 787 oxytocin TRIVIAL 23643748 A 915 923 oxytocin TRIVIAL 23643748 A 970 978 oxytocin TRIVIAL 23643748 T 21 29 oxytocin TRIVIAL 23643792 A 1123 1131 Tween 80 TRIVIAL 23643792 A 1402 1410 Tween-80 TRIVIAL 23643792 A 352 371 poly(-caprolactone) SYSTEMATIC 23643792 A 731 739 Tween 80 TRIVIAL 23643839 A 179 186 glucose TRIVIAL 23643839 A 202 208 serine TRIVIAL 23643839 A 209 218 threonine TRIVIAL 23643839 A 52 58 serine TRIVIAL 23643839 A 59 68 threonine TRIVIAL 23643933 A 1013 1016 TSA ABBREVIATION 23643933 A 1028 1031 TSA ABBREVIATION 23643933 A 1273 1276 TSA ABBREVIATION 23643933 A 1362 1365 TSA ABBREVIATION 23643933 A 1454 1457 TSA ABBREVIATION 23643933 A 1501 1504 TSA ABBREVIATION 23643933 A 197 211 Trichostatin A TRIVIAL 23643933 A 213 216 TSA ABBREVIATION 23643933 A 345 348 TSA ABBREVIATION 23643933 T 84 96 trichostatin TRIVIAL 23644192 A 207 214 rhenium SYSTEMATIC 23644192 A 417 424 (99m)Tc FORMULA 23644192 A 5 41 (99m)Tc-labeled dibenzylideneacetone SYSTEMATIC 23644192 A 677 684 (99m)Tc FORMULA 23644192 A 72 79 rhenium SYSTEMATIC 23644192 T 0 36 (99m)Tc-labeled dibenzylideneacetone SYSTEMATIC 23644195 A 1017 1028 carboxylate SYSTEMATIC 23644195 A 1032 1039 RVX-208 IDENTIFIER 23644195 A 1136 1140 (1)H FORMULA 23644195 A 1266 1282 primary hydroxyl FAMILY 23644195 A 1292 1299 RVX-208 IDENTIFIER 23644195 A 1303 1318 carboxylic acid SYSTEMATIC 23644195 A 344 351 RVX-208 IDENTIFIER 23644195 A 532 539 RVX-208 IDENTIFIER 23644195 A 65 72 RVX-208 IDENTIFIER 23644195 A 708 712 (1)H FORMULA 23644195 A 784 800 primary hydroxyl FAMILY 23644195 A 810 817 RVX-208 IDENTIFIER 23644195 A 822 837 glucuronic acid TRIVIAL 23644195 T 161 168 RVX-208 IDENTIFIER 23644195 T 83 159 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one SYSTEMATIC 23644200 A 248 255 mannose TRIVIAL 23644200 A 260 269 galactose TRIVIAL 23644200 A 28 57 glycosylated isomalyngamide A FAMILY 23644200 A 476 483 lactose TRIVIAL 23644200 A 548 562 monosaccharide FAMILY 23644200 A 575 587 disaccharide FAMILY 23644200 A 606 622 isomalyngamide A TRIVIAL 23644200 T 56 72 isomalyngamide A TRIVIAL 23644201 A 118 159 2-oxo-1,2-dihydroquinoline-3-carbaldehyde SYSTEMATIC 23644201 A 171 172 H FORMULA 23644201 A 178 180 Me FORMULA 23644201 A 186 188 Et FORMULA 23644201 A 197 199 Ph FORMULA 23644201 A 45 67 [Ni(H2-Qtsc-R)2](NO3)2 FAMILY 23644201 A 69 78 H2-Qtsc-R FAMILY 23644201 A 81 114 4N-substituted thiosemicarbazones FAMILY 23644201 A 9 15 Ni(II) FORMULA 23644201 T 109 142 4N-substituted thiosemicarbazones FAMILY 23644201 T 146 187 2-oxo-1,2-dihydroquinoline-3-carbaldehyde SYSTEMATIC 23644201 T 89 95 Ni(II) FORMULA 23644214 A 102 106 PCl5 FORMULA 23644214 A 125 126 C FORMULA 23644214 A 148 155 nitrile SYSTEMATIC 23644214 A 273 279 chloro SYSTEMATIC 23644214 A 298 304 amines FAMILY 23644214 A 327 372 4-aminothieno[2,3-d]pyrimidine-6-carbonitrile SYSTEMATIC 23644214 A 44 84 oxothieno[2,3-d]pyrimidine-6-carboxamide SYSTEMATIC 23644214 A 830 840 ampicillin TRIVIAL 23644214 A 908 920 greseofulvin TRIVIAL 23644214 A 92 97 POCl3 FORMULA 23644214 T 34 79 4-aminothieno[2,3-d]pyrimidine-6-carbonitrile SYSTEMATIC 23644256 A 1406 1409 IBU ABBREVIATION 23644256 A 1410 1414 ISDN ABBREVIATION 23644256 A 298 301 IBU ABBREVIATION 23644256 A 306 310 ISDN ABBREVIATION 23644256 A 33 42 ibuprofen TRIVIAL 23644256 A 44 47 IBU ABBREVIATION 23644256 A 497 500 IBU ABBREVIATION 23644256 A 514 518 ISDN ABBREVIATION 23644256 A 53 73 isosorbide dinitrate SYSTEMATIC 23644256 A 75 79 ISDN ABBREVIATION 23644256 A 946 949 IBU ABBREVIATION 23644256 A 950 954 ISDN ABBREVIATION 23644256 T 0 9 Ibuprofen TRIVIAL 23644256 T 15 35 Isosorbide Dinitrate SYSTEMATIC 23644525 A 245 251 carbon SYSTEMATIC 23645248 A 1014 1031 17beta-oestradiol SYSTEMATIC 23645248 A 1195 1208 sodium iodide SYSTEMATIC 23645248 A 1251 1268 17beta-oestradiol SYSTEMATIC 23645248 A 1284 1293 oestrogen FAMILY 23645248 A 139 148 oestrogen FAMILY 23645248 A 1511 1520 oestrogen FAMILY 23645248 A 334 343 oestrogen FAMILY 23645248 A 429 446 17beta-oestradiol SYSTEMATIC 23645248 A 498 507 oestrogen FAMILY 23645248 A 536 553 17beta-oestradiol SYSTEMATIC 23645248 A 675 688 sodium iodide SYSTEMATIC 23645248 A 726 743 17beta-oestradiol SYSTEMATIC 23645248 A 869 878 oestrogen FAMILY 23645248 A 945 954 oestrogen FAMILY 23645248 T 0 9 Oestrogen FAMILY 23645249 A 1077 1086 genistein TRIVIAL 23645249 A 1134 1146 triglyceride FAMILY 23645249 A 1175 1185 fatty acid FAMILY 23645249 A 1214 1223 Genistein TRIVIAL 23645249 A 1291 1299 estrogen FAMILY 23645249 A 1388 1427 2,3-bis (4-hydroxyphenyl)-propionitrile SYSTEMATIC 23645249 A 1429 1432 DPN ABBREVIATION 23645249 A 1606 1615 genistein TRIVIAL 23645249 A 1624 1627 DPN ABBREVIATION 23645249 A 1653 1662 genistein TRIVIAL 23645249 A 1847 1856 genistein TRIVIAL 23645249 A 605 615 isoflavone FAMILY 23645249 A 616 625 genistein TRIVIAL 23645249 A 784 793 genistein TRIVIAL 23645249 A 898 907 genistein TRIVIAL 23645249 T 38 47 genistein TRIVIAL