Author Report for: Chen RNo contact information in database for Chen R
Chen H, Mi J, Li S, Liu Z, Yang J, Chen R, Wang Y, Ban Y, Zhou Y and Sang Z <1 more author(s)> Chen H, Mi J, Li S, Liu Z, Yang J, Chen R, Wang Y, Ban Y, Zhou Y, Dong W, Sang Z (- 1) Ref: J Enzyme Inhib Med Chem, 38:2169682, 2023 : PubMed ESTHER: Chen_2023_J.Enzyme.Inhib.Med.Chem_38_2169682 PubMedSearch: Chen 2023 J.Enzyme.Inhib.Med.Chem 38 2169682 PubMedID: 36688444 Abstract A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer's disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The insvitro activities showed that compound 3f was a reversible dual eeAChE/eqBuChE inhibitor with IC(50) values of 1.3 microM and 0.81 microM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1beta and NO. In addition, compound 3f presented significant neuroprotective effect on Abeta(25-35)-induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes insvitro and plasma. Furthermore, compound 3f could improve AlCl(3)-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD. Title: Crystal structure of the GDSL family esterase EstL5 in complex with PMSF reveals a branch channel of the active site pocket Chen R, Gao X, Nie T, Wu J, Wang L, Osman A, Feng Y, Li X, Zhang Y Ref: Acta Biochim Biophys Sin (Shanghai), :, 2023 : PubMed ESTHER: Chen_2023_Acta.Biochim.Biophys.Sin.(Shanghai)__ PubMedSearch: Chen 2023 Acta.Biochim.Biophys.Sin.(Shanghai) PubMedID: 37705347 Abstract Esterases/lipases from the GDSL family have potential applications in the hydrolysis and synthesis of important esters of pharmaceutical, food, and biotechnical interests. However, the structural and functional understanding of GDSL enzymes is still limited. Here, we report the crystal structure of the GDSL family esterase EstL5 complexed with PMSF at 2.34 A resolution. Intriguingly, the PMSF binding site is not located at the active site pocket but is situated in a surface cavity. At the active site, we note that there is a trapped crystallization solvent 1,6-hexanediol, which mimics the bound ester chain, allowing for further definition of the active site pocket of EstL5. The most striking structural feature of EstL5 is the presence of a unique channel, which extends approximately 18.9 A, with a bottleneck radius of 6.8 A, connecting the active-site pocket and the surface cavity. Replacement of Ser205 with the bulk aromatic residue Trp or Phe could partially block the channel at one end and perturb its access. Reduced enzymatic activity is found in the EstL5 S205W and EstL5 S205F mutants, suggesting the functional relevance of the channel to enzyme catalysis. Our study provides valuable information regarding the properties of the GDSL-family enzymes for designing more efficient and robust biocatalysts. Title: Changes in the VOC of Fruits at Different Refrigeration Stages of 'Ruixue' and the Participation of Carboxylesterase MdCXE20 in the Catabolism of Volatile Esters Li D, Guo J, Ma H, Pei L, Liu X, Wang H, Chen R, Zhao Z, Gao H Ref: Foods, 12:1977, 2023 : PubMed ESTHER: Li_2023_Foods_12_1977 PubMedSearch: Li 2023 Foods 12 1977 PubMedID: 37238795 Abstract Aroma is a crucial quality attribute of apple fruit, which significantly impacts its commercial value and consumer choice. Despite its importance the volatile aroma substances produced by the new variety 'Ruixue' after harvest remain unclear. In this study, we utilized headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) to investigate the changes in volatile substances, fruit hardness, crispness, and related aroma synthase activity of commercially mature 'Ruixue' apples during cold storage. Our findings revealed a gradual decline in fruit firmness and brittleness of 'Ruixue' apples during cold storage, with hexyl acetate, hexyl caproate, and hexyl thiocyanate being the main hexyl esters detected. To gain a better understanding of the metabolic pathway of esters, we identified 42 MdCXE gene members that are associated with ester degradation. Through RT-qPCR analysis, we discovered that carboxylesterase MdCXE20 exhibited higher expression levels compared to other MdCXE genes during cold storage. To confirm the role of MdCXE20, we conducted a transient injection of apple fruits and observed that overexpression of MdCXE20 led to the degradation of esters such as hexyl hexanoate, butyl hexanoate, butyl 2-methylbutyrate, hexyl butyrate, and hexyl 2-methylbutyrate. The results of the study showed that the virus-induced gene silencing of MdCXE20 found the opposite results. Additionally, the esters of OE-MdCXE20 callus showed a lower content of ester VOC than the control callus, according to the homologous stable transformation of 'Wanglin' callus. Overall, these findings suggest that the MdCXE20 gene plays a crucial role in the decrease of esters in 'Ruixue' apples, which ultimately affects their flavor. Title: Association between the NEP rs701109 polymorphism and the clinical efficacy and safety of sacubitril/valsartan in Chinese patients with heart failure Luo HY, Gao LC, Long HZ, Zhou ZW, Xu SG, Li FJ, Li HL, Cheng Y, Li CX and Deng P <3 more author(s)> Luo HY, Gao LC, Long HZ, Zhou ZW, Xu SG, Li FJ, Li HL, Cheng Y, Li CX, Peng XY, Li L, Chen R, Deng P (- 3) Ref: European Journal of Clinical Pharmacology, :, 2023 : PubMed ESTHER: Luo_2023_Eur.J.Clin.Pharmacol__ PubMedSearch: Luo 2023 Eur.J.Clin.Pharmacol PubMedID: 36976322 Abstract OBJECTIVE: Sacubitril/valsartan is a commonly used medicine for treating heart failure (HF) patients, but the treatment effects significantly vary. Neprilysin (NEP) and carboxylesterase 1 (CES1) play an important role in the efficacy of sacubitril/valsartan. The purpose of this study was to explore the relationship between NEP and CES1 gene polymorphisms and the efficacy and safety of sacubitril/valsartan treatment in HF patients. METHODS: Genotyping of 10 single nucleotide polymorphisms (SNPs) of the NEP and CES1 genes in 116 HF patients was performed by the Sequenom MassARRAY method, and logistic regression and haplotype analysis were used to evaluate the associations between SNPs and the clinical efficacy and safety of sacubitril/valsartan in HF patients. RESULTS: A total of 116 Chinese patients with HF completed the whole trial, and T variations in rs701109 in NEP gene were an independent risk factor (P = 0.013, OR = 3.292, 95% CI:1.287-8.422) for the clinical efficacy of sacubitril/valsartan. Furthermore, haplotype analysis of 6 NEP SNPs (including rs701109) was performed and showed that the CGTACC and TGTACC haplotypes were significantly associated with clinical efficacy (OR = 0.095, 95%CI: 0.012-0.723, P = 0.003; OR = 5.586, 95% CI: 1.621-19.248, P = 0.005). Moreover, no association was found between SNPs of other selected genes in terms of efficacy in HF patients, and no association was observed between SNPs and symptomatic hypotension. CONCLUSION: Our results suggest an association between rs701109 and sacubitril/valsartan response in HF patients. Symptomatic hypotension is not associated with the presence of NEP polymorphisms. Title: Comparison of chemical compositions, antioxidant activities, and acetylcholinesterase inhibitory activities between coffee flowers and leaves as potential novel foods Shen X, Nie F, Fang H, Liu K, Li Z, Li X, Chen Y, Chen R, Zheng T, Fan J Ref: Food Sci Nutr, 11:917, 2023 : PubMed ESTHER: Shen_2023_Food.Sci.Nutr_11_917 PubMedSearch: Shen 2023 Food.Sci.Nutr 11 917 PubMedID: 36789063 Abstract This study aimed to compare chemical compositions, antioxidant activities, and acetylcholinesterase inhibitory activities of coffee flowers (ACF) and coffee leaves (ACL) with green coffee beans (ACGB) of Coffea Arabica L. The chemical compositions were determined by employing high-performance liquid chromatography-mass spectroscopy (HPLC-MS) and gas chromatography-mass spectroscopy (GC-MS) techniques. Antioxidant effects of the components were evaluated using DPPH and ABTS radical scavenging assays, and the ferric reducing antioxidant power (FRAP) assay. Their acetylcholinesterase inhibitory activities were also evaluated. The coffee sample extracts contained a total of 214 components identified by HPLC-MS and belonged to 12 classes (such as nucleotides and amino acids and their derivatives, tannins, flavonoids, alkaloids, benzene, phenylpropanoids, and lipids.), where phenylpropanoids were the dominant component (>30%). The contents of flavonoids, alkaloids, saccharides, and carboxylic acid and its derivatives in ACF and ACL varied significantly (p < .05) compared to similar components in ACGB. Meanwhile, 30 differentially changed chemical compositions (variable importance in projection [VIP] > 1, p < .01 and fold change [FC] > 4, or <0.25), that determine the difference in characteristics, were confirmed in the three coffee samples. Furthermore, among 25 volatile chemical components identified by GC-MS, caffeine, n-hexadecanoic acid, 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methyl-phenol], and quinic acid were common in these samples with caffeine being the highest in percentage. In addition, ACL showed the significantly highest (p < .05) DPPH radical scavenging capacity with IC(50) value of 0.491 +/- 0.148 mg/ml, and acetylcholinesterase inhibitory activity with inhibition ratio 25.18 +/- 2.96%, whereas ACF showed the significantly highest (p < .05) ABTS radical scavenging activity with 36.413 +/- 1.523 mmol trolox/g Ex. The results suggested that ACL and ACF had potential values as novel foods in the future. Title: The alteration of the expression level of neuropathy target esterase in human neuroblastoma SK-N-SH cells disrupts cellular phospholipids homeostasis Hou WY, Song X, Wang Y, Chang P, Chen R, Wu YJ Ref: Toxicol In Vitro, :105509, 2022 : PubMed ESTHER: Hou_2022_Toxicol.In.Vitro__105509 PubMedSearch: Hou 2022 Toxicol.In.Vitro 105509 PubMedID: 36336212 Abstract Neuropathy target esterase (NTE) has been proven to act as a lysophospholipase (LysoPLA) and phospholipase B (PLB) in mammalian cells. In this study, we took human neuroblastoma SK-N-SH cells as the research object and explored the effect of NTE on phospholipid homeostasis. The results showed that phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) levels significantly increased (> 40%), while glycerophosphocholine (GPC) decreased (below 60%) after NTE gene was knockdown in the cells (NTE < 30% of control), which were prepared by gene silencing with dsRNA-NTE. However, in the NTE-overexpressed cells (NTE > 50% of control), which were prepared by expressing recombinant catalytic domain of NTE, LPC remarkably decreased (below 80%) and GPC enhanced (> 40%). Mipafox, a neuropathic organophosphorus compound (OP), significantly inhibited NTE-LysoPLA and NTE-PLB activities (> 95-99% inhibition at 50 microM), which was accompanied with a decreased GPC level (below 40%) although no change of the PC and LPC levels was observed; while paraoxon, a non-neuropathic OP, suppresses neither the activities of NTE-phospholipases nor the levels of PC, LPC, and GPC. Thus, we concluded that both the stable up- or down-regulated expression of NTE gene and the loss of NTE-LysoPLA/PLB activities disrupts phospholipid homeostasis in the cells although the inhibition of NTE activity only decreased GPC content without altering PC and LPC levels. Title: Endocannabinoids regulate cocaine-associated memory through brain AEA-CB1R signalling activation Li H, Chen R, Zhou Y, Wang H, Sun L, Yang Z, Bai L, Zhang J Ref: Mol Metab, :101597, 2022 : PubMed ESTHER: Li_2022_Mol.Metab__101597 PubMedSearch: Li 2022 Mol.Metab 101597 PubMedID: 36096452 Abstract OBJECTIVE: Contextual drug-associated memory precipitates craving and relapse in substance users, and the risk of relapse is a major challenge in the treatment of substance use disorders. Thus, understanding the neurobiological underpinnings of how this association memory is formed and maintained will inform future advances in the treatment of drug addiction. Brain endocannabinoids (eCBs) signalling has been associated with drug-induced neuroadaptations, but the role of lipases that mediate small lipid ligand biosynthesis and metabolism in regulating drug-associated memory has not been examined. Here, we explored how manipulation of the lipase fatty acid amide hydrolase (FAAH), which is involved in mediating the level of the lipid ligand anandamide (AEA), affects cocaine-associated memory formation. METHODS: We applied behavioural, pharmacological and biochemical methods to detect cocaine-associated memory formation, eCBs in the dorsal dentate gyrus (dDG), and the activity of related enzymes. We further examined the roles of abnormal FAAH activity and AEA-CB1R signalling in the regulation of cocaine-associated memory formation and granule neuron dendritic structure alterations in the dDG through Western blotting, electron microscopy and immunofluorescence. RESULTS: In the present study, we found that cocaine induced a decrease in the level of FAAH in the dDG and increased the level of AEA. A high level of AEA activated cannabinoid type 1 receptors (CB1Rs) and further triggered CB1R signalling activation and granule neuron dendritic remodelling, and these effects were reversed by blockade of CB1Rs in the brain. Furthermore, inhibition of FAAH in the dDG markedly increased AEA levels and promoted cocaine-associated memory formation through CB1R signalling activation. CONCLUSIONS: Together, our findings demonstrate that the lipase FAAH influences CB1R signalling activation and granule neuron dendritic structure alteration in the dDG by regulating AEA levels and that AEA and AEA metabolism play a key role in cocaine-associated memory formation. Manipulation of AEA production may serve as a potential therapeutic strategy for drug addiction and relapse prevention. Title: Enantioselective Metabolic Mechanism and Metabolism Pathway of Pydiflumetofen in Rat Liver Microsomes: In Vitro and In Silico Study Wang Z, Li R, Wu Q, Duan J, Tan Y, Sun X, Chen R, Shi H, Wang M Ref: Journal of Agricultural and Food Chemistry, 70:2520, 2022 : PubMed ESTHER: Wang_2022_J.Agric.Food.Chem_70_2520 PubMedSearch: Wang 2022 J.Agric.Food.Chem 70 2520 PubMedID: 35184556 Abstract Pydiflumetofen (PYD) has been used worldwide. However, the enantioselective fate of PYD within mammals is not clear. Thus, the enantioselective metabolism and its potential mechanisms of PYD were explored via in vitro and in silico. Consistent results were observed between metabolism and enzyme kinetics experiments, with S-PYD metabolizing faster than R-PYD in rat liver microsomes. Moreover, CYP3A1 and carboxylesterase 1 were found to be major enzymes participating in the metabolism of PYD. Based on the computational results, S-PYD bound with CYP3A1 and carboxylesterase 1 more tightly with lower binding free energy than R-PYD, explaining the mechanism of enantioselective metabolism. Nine phase I metabolites of PYD were identified, and metabolic pathways of PYD were speculated. This study is the first to clarify the metabolism of PYD in mammals, and further research to evaluate the toxicological implications of these metabolites will help in assessing the risk of PYD. Title: Biochemical toxicity and transcriptome aberration induced by dinotefuran in Bombyx mori Xu S, Hao Z, Li Y, Zhou Y, Shao R, Chen R, Zheng M, Xu Y, Wang H Ref: Environ Pollut, :119562, 2022 : PubMed ESTHER: Xu_2022_Environ.Pollut__119562 PubMedSearch: Xu 2022 Environ.Pollut 119562 PubMedID: 35659910 Abstract Dinotefuran is a third-generation neonicotinoid pesticide and is increasingly used in agricultural production, which has adverse effects on nontarget organisms. However, the research on the impact of dinotefuran on nontarget organisms is still limited. Here the toxic effects of dinotefuran on an economic lepidopteran model insect, Bombyx mori, were investigated. Exposure to different doses of dinotefuran caused physiological disorders or death. Cytochrome P450, glutathione S-transferase, carboxylesterase, and UDP glycosyl-transferase activities were induced in the fat body at early stages after dinotefuran exposure. By contrast, only glutathione S-transferase activity was increased in the midgut. To overcome the lack of sensitivity of the biological assays at the individual organism level, RNA sequencing was performed to measure differential expressions of mRNA from silkworm larvae after dinotefuran exposure. Differential gene expression profiling revealed that various detoxification enzyme genes were significantly increased after dinotefuran exposure, which was consistent with the upregulation of the detoxifying enzyme. The global transcriptional pattern showed that the physiological responses induced by dinotefuran toxicity involved multiple cellular processes, including energy metabolism, oxidative stress, detoxification, and other fundamental physiological processes. Many metabolism processes, such as carbon metabolism, fatty acid biosynthesis, pyruvate metabolism, and the citrate cycle, were partially repressed in the midgut or fat body. Furthermore, dinotefuran significantly activated the MAPK/CREB, CncC/Keap1, PI3K/Akt, and Toll/IMD pathways. The links between physiological, biochemical toxicity and comparative transcriptomic analysis facilitated the systematic understanding of the integrated biological toxicity of dinotefuran. This study provides a holistic view of the toxicity and detoxification metabolism of dinotefuran in silkworm and other organisms. Title: Design, synthesis, and evaluation of novel O-alkyl ferulamide derivatives as multifunctional ligands for treating Alzheimer's disease Zhu G, Bai P, Wang K, Mi J, Yang J, Hu J, Ban Y, Xu R, Chen R and Sang Z <2 more author(s)> Zhu G, Bai P, Wang K, Mi J, Yang J, Hu J, Ban Y, Xu R, Chen R, Wang C, Tang L, Sang Z (- 2) Ref: J Enzyme Inhib Med Chem, 37:1375, 2022 : PubMed ESTHER: Zhu_2022_J.Enzyme.Inhib.Med.Chem_37_1375 PubMedSearch: Zhu 2022 J.Enzyme.Inhib.Med.Chem 37 1375 PubMedID: 35549612 Abstract Herein, a series of novel O-alkyl ferulamide derivatives were designed and synthesised through the multi-target-directed ligands (MTDLs) strategy. The biological activities in vitro showed that compounds 5a, 5d, 5e, 5f, and 5h indicated significantly selective MAO-B inhibitory potency (IC(50) = 0.32, 0.56, 0.54, 0.73, and 0.86 microM, respectively) and moderate antioxidant activity. Moreover, compounds 5a, 5d, 5e, 5f, and 5h showed potent anti-inflammatory properties, remarkable effects on self-induced Abeta(1-42) aggregation, and potent neuroprotective effect on Abeta(1-42)-induced PC12 cell injury. Furthermore, compounds 5a, 5d, 5e, 5f, and 5h presented good blood-brain barrier permeation in vitro and drug-like properties. More interesting, the PET/CT images with [(11)C]5f demonstrated that [(11)C]5f could penetrate the BBB with a high brain uptake and exhibited good brain clearance kinetic property. Therefore, compound 5f would be a promising multi-functional agent for the treatment of AD. Title: Explainable machine learning model for predicting spontaneous bacterial peritonitis in cirrhotic patients with ascites Hu Y, Chen R, Gao H, Lin H, Wang J, Wang X, Liu J, Zeng Y Ref: Sci Rep, 11:21639, 2021 : PubMed ESTHER: Hu_2021_Sci.Rep_11_21639 PubMedSearch: Hu 2021 Sci.Rep 11 21639 PubMedID: 34737270 Abstract Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with cirrhosis. We aimed to develop an explainable machine learning model to achieve the early prediction and outcome interpretation of SBP. We used CatBoost algorithm to construct MODEL-1 with 46 variables. After dimensionality reduction, we constructed MODEL-2. We calculated and compared the sensitivity and negative predictive value (NPV) of MODEL-1 and MODEL-2. Finally, we used the SHAP (SHapley Additive exPlanations) method to provide insights into the model's outcome or prediction. MODEL-2 (AUROC: 0.822; 95% confidence interval [CI] 0.783-0.856), liked MODEL-1 (AUROC: 0.822; 95% CI 0.784-0.856), could well predict the risk of SBP in cirrhotic ascites patients. The 6 most influential predictive variables were total protein, C-reactive protein, prothrombin activity, cholinesterase, lymphocyte ratio and apolipoprotein A1. For binary classifier, the sensitivity and NPV of MODEL-1 were 0.894 and 0.885, respectively, while for MODEL-2 they were 0.927 and 0.904, respectively. We applied CatBoost algorithm to establish a practical and explainable prediction model for risk of SBP in cirrhotic patients with ascites. We also identified 6 important variables closely related to the occurrence of SBP. Title: Structural and Functional Characterization of Fibronectin in Extracellular Vesicles From Hepatocytes Li X, Chen R, Kemper S, Brigstock DR Ref: Front Cell Developmental Biology, 9:640667, 2021 : PubMed ESTHER: Li_2021_Front.Cell.Dev.Biol_9_640667 PubMedSearch: Li 2021 Front.Cell.Dev.Biol 9 640667 PubMedID: 33816490 Abstract Extracellular vesicles (EVs) are membrane-limited nanoparticles that are liberated by cells and contain a complex molecular payload comprising proteins, microRNA, RNAs, and lipids. EVs may be taken up by other cells resulting in their phenotypic or functional reprogramming. In the liver, EVs produced by non-injured hepatocytes are involved in the maintenance of hepatic homeostasis or therapeutic outcomes following injury while EVs produced by damaged hepatocytes may drive or exacerbate liver injury. In this study, we examined the contribution of EV fibronectin (FN1) to the biogenesis, release, uptake, and action of hepatocyte-derived EVs. While FN1 is classically viewed as a component of the extracellular matrix that regulates processes such as cell adhesion, differentiation, and wound healing and can exist in cell-associated or soluble plasma forms, we report that FN1 is also a constituent of hepatocyte EVs that functions in EV uptake by target cells such as hepatocytes and hepatic stellate cells (HSC). FN1 co-purified with EVs when EVs were enriched from conditioned medium of human or mouse hepatocytes and a direct association between FN1 and hepatocyte EVs was established by immunoprecipitation and proteinase protection. FN1 ablation in mouse hepatocytes using CRISPR-Cas9 did not alter EV biogenesis but EV uptake by HSC was significantly reduced for FN1 knockout EVs (EV(deltaFN1) ) as compared to EVs from wild type hepatocytes (EV(WT)). The uptake by hepatocytes or HSC of either EV(WT) or EV(deltaFN1) required clathrin- and caveolin-mediated endocytosis, cholesterol, lysosomal acidic lipase activity, and low pH, while macropinocytosis was also involved in EV(deltaFN1) uptake in HSC. Despite their differences in rate and mechanisms of uptake, EV(deltaFN1) functioned comparably to EV(WT) in ameliorating CCl(4)-induced hepatic fibrosis in mice. In conclusion, FN1 is a constituent of hepatocyte EVs that facilitates EV uptake by target cells but is dispensable for EV-mediated anti-fibrotic activity in vivo. Title: Residual behaviors and metabolic pathway of ethylparaben in Drosophila melanogaster Wang Y, Qin M, Wang X, Han J, Chen R, Zhang M, Gu W Ref: Ecotoxicology & Environmental Safety, 230:113124, 2021 : PubMed ESTHER: Wang_2021_Ecotoxicol.Environ.Saf_230_113124 PubMedSearch: Wang 2021 Ecotoxicol.Environ.Saf 230 113124 PubMedID: 34968799 Abstract OBJECTIVE: Parabens are commonly used as preservatives in foodstuffs, cosmetics, and pharmaceutical products. The widespread use of parabens has led to their leaking into the environment. Concerns about the safety of parabens have recently increased due to their potential endocrine-disrupting effects as an emerging contaminant. Thus, it is necessary to study the metabolism of parabens in vivo. METHODS: In this study, Drosophila melanogaster in males and females were exposed to ethylparaben (EP) concentration group (300 mg/L, 700 mg/L, and 1000 mg/L), and control group (0 mg/L) by the capillary feeding assay (CAFE). We quantified the activity of the detoxification-related carboxylesterase (CarE). The contents of EP metabolites in D. melanogaster, including p-hydroxybenzoic acid (PHBA), methylparaben (MP), and intact EP were carried out by high-performance liquid chromatography (HPLC). The regression model between EP metabolites (PHBA and MP) and CarE was developed using the Fourier series fitting method. RESULTS: The general level of EP metabolites (PHBA, MP, and intact EP) accumulation was accounted for 5.6-11.5% in D. melanogaster. As EP accumulated, the activity of CarE increased, and the activity of CarE in females was higher than males, which is inconsistent with the result of EP intake dose. Additionally, there were significant differences in the proportion of EP metabolites between female and male flies, and the results of sex comparison were different depending on the EP treated groups and EP metabolites. In general, PHBA of EP hydrolytic product and MP of EP transesterification product in D. melanogaster were 41.4-63.9% and 10.4-24.6%, respectively. In terms of the rest of the EP existed in intact form and ranged from 22.4% to 34.0%. Moreover, the EP metabolites in the conjugated form were higher than those in the free form. The regression model between EP metabolites and CarE was established, showing that the CarE activity can be used to estimate the content of PHBA and MP. CONCLUSION: The result indicates that the EP can accumulate in the body through food. Hydrolysis is the main metabolic pathway of EP in D. melanogaster, and transesterification is another metabolic pathway of EP. Additionally, the EP metabolites in flies mainly exist in conjugated form. Furthermore, the Fourier series fitting method model between EP metabolites and CarE, providing theoretical support to study the dose-effect relationship between metabolites of parabens and CarE. This study not only provides a mathematical basis for the safety evaluation of parabens, but also provides support for the further study of the toxicological effects of parabens. Title: Cholinesterase homozygous genotype as susceptible biomarker of hypertriglyceridemia for pesticide-exposed agricultural workers Zhou X, Zhang M, Wang Y, Xia H, Zhu L, Li G, Rong L, Dong H, Chen R and Yu M <1 more author(s)> Zhou X, Zhang M, Wang Y, Xia H, Zhu L, Li G, Rong L, Dong H, Chen R, Tang S, Yu M (- 1) Ref: Biomarkers, :1, 2021 : PubMed ESTHER: Zhou_2021_Biomarkers__1 PubMedSearch: Zhou 2021 Biomarkers 1 PubMedID: 33617373 Abstract PURPOSE: Dyslipidemia is an emerging metabolic disorder among pesticide-exposed agricultural workers, and this study was aimed to explore biomarkers of hypertriglyceridemia susceptibility. METHODS: This cross-sectional study recruited 72 pesticide-exposed subjects and 78 non-exposed controls. Lipid profile, cholinesterase activity, and thyroid hormones were analyzed with routine assays. Six loci, including rs11206244 and rs2235544 for deiodinase 1, rs12885300 and rs225014 for deiodinase 2, rs1803274 for butyrylcholinesterase, and rs3757869 for acetylcholinesterase were genotyped using an improved multiplex ligation detection reaction technique. RESULTS: Pesticide-exposed subjects showed higher levels of triglyceride than controls (p = 0.009), although there were comparable cholinesterase activity and genotype frequencies of all six loci between pesticide-exposed subjects and controls. Pesticide-exposed subjects with homozygous genotype of cholinesterasehad increased triglyceride levels than controls (p < 0.05). The percentage of hypertriglyceridemia was 28.6% and 8.8% for pesticide-exposed subjects and controls with homozygous butyrylcholinesterase genotype (p = 0.007) and 20.8% and 14.3% with homozygous acetylcholinesterase genotype (p = 0.792), respectively. Multivariate logistic regression analyses found that odds ratio of hypertriglyceridemia is 21.92 and 4.56 for pesticide-exposed subjects with homozygous genotype of butyrylcholinesterase (p = 0.001) and acetylcholinesterase (p = 0.036), respectively. CONCLUSIONS: Cholinesterase homozygous genotype might be a potential susceptible biomarker in screening pesticide-exposed agricultural workers vulnerable to hypertriglyceridemia. Title: Enhanced Contextual Fear Memory and Elevated Astroglial Glutamate Synthase Activity in Hippocampal CA1 BChE shRNA Knockdown Mice Chen S, Lin Z, Tan KL, Chen R, Su W, Zhao H, Tan Q, Tan W Ref: Front Psychiatry, 11:564843, 2020 : PubMed ESTHER: Chen_2020_Front.Psychiatry_11_564843 PubMedSearch: Chen 2020 Front.Psychiatry 11 564843 PubMedID: 33061920 Abstract Butyrylcholinesterase (BChE) efficiently hydrolyzes acetylcholine (ACh) at high concentrations when acetylcholinesterase (AChE) is substrate-inhibited. Recent studies have shown that BChE also has a function that is independent of ACh, but it has not been fully explored. Low BChE expression is accompanied with higher stress-induced aggression and ghrelin levels in stress models, and BChE knockout mice exhibit cognitive and memory impairments. However, the role of BChE in posttraumatic stress disorder (PTSD) remains unclear. In the present study, we investigated the role of BChE in contextual fear memory and its regulatory effect on the expression of factors related to the glutamate (Glu)-glutamine (Gln) cycle via knockdown studies. We used AAVs and lentiviruses to knockdown BChE expression in the mouse hippocampal CA1 region and C8D1A astrocytes. Our behavioral data from those mice injected with AAV-shBChE in the hippocampal CA1 region showed strengthened fear memory and increased dendritic spine density. Elevated Glu levels and glutamine synthetase (GS) enzyme activity were detected in contextual fear conditioned-BChE knockdown animals and astrocytes. We observed that an AAV-shBChE induced lowering of BChE expression in the hippocampus CA1 region enhanced contextual fear memory expression and promoted the astrocytic Glu-Gln cycle but did not elevate ACh-hydrolyzing activity. This study provides new insight into the regulatory role of BChE in cognition and suggests potential target for stress-related psychiatric disorder such as PTSD where patients experience fear after exposure to severe life-threatening traumatic events. Title: HFIP-Functionalized Co3 O4 Micro-Nano-Octahedra/rGO as a Double-Layer Sensing Material for Chemical Warfare Agents Alali KT, Liu J, Chen R, Liu Q, Zhang H, Li J, Hou J, Li R, Wang J Ref: Chemistry, 25:11892, 2019 : PubMed ESTHER: Alali_2019_Chemistry_25_11892 PubMedSearch: Alali 2019 Chemistry 25 11892 PubMedID: 31309626 Abstract Semiconductor metal oxides (SMO)-based gas-sensing materials suffer from insufficient detection of a specific target gas. Reliable selectivity, high sensitivity, and rapid response-recovery times under various working conditions are the main requirements for optimal gas sensors. Chemical warfare agents (CWA) such as sarin are fatal inhibitors of acetylcholinesterase in the nerve system. So, sensing materials with high sensitivity and selectivity toward CWA are urgently needed. Herein, micro-nano octahedral Co3 O4 functionalized with hexafluoroisopropanol (HFIP) were deposited on a layer of reduced graphene oxide (rGO) as a double-layer sensing materials. The Co3 O4 micro-nano octahedra were synthesized by direct growth from electrospun fiber templates calcined in ambient air. The double-layer rGO/Co3 O4 -HFIP sensing materials presented high selectivity toward DMMP (sarin agent simulant, dimethyl methyl phosphonate) versus rGO/Co3 O4 and Co3 O4 sensors after the exposure to various gases owing to hydrogen bonding between the DMMP molecules and Co3 O4 -HFIP. The rGO/Co3 O4 -HFIP sensors showed high stability with a response signal around 11.8 toward 0.5 ppm DMMP at 125 degrees C, and more than 75 % of the initial response was maintained under a saturated humid environment (85 % relative humidity). These results prove that these double-layer inorganic-organic composite sensing materials are excellent candidates to serve as optimal gas-sensing materials. Title: Evaluation of the cholinesterase activity of a potential therapeutic cocaine esterase for cocaine overdose Hou S, Zhang Y, Zhu Y, Zhang C, Kong Y, Chen X, Chen R, Yin X, Xie T Ref: Drug Alcohol Depend, 202:168, 2019 : PubMed ESTHER: Hou_2019_Drug.Alcohol.Depend_202_168 PubMedSearch: Hou 2019 Drug.Alcohol.Depend 202 168 PubMedID: 31352306 Abstract BACKGROUND: Cocaine is a commonly abused drug and there is no approved medication specifically to treat its addiction or overdose. Bacterial cocaine esterase (CocE)-derived RBP-8000 is currently under clinical development for cocaine overdose treatment. It is proven to be effective for human use to accelerate cocaine metabolism into physiologically inactive products. Besides cocaine, RBP-8000 may hydrolyze the neurotransmitter acetylcholine (ACh), however, no study has reported its cholinesterase activity. The present study aims to examine RBP-8000's cholinesterase activity and substrate selectivity to address the potential concern that this enzyme therapy might produce cholinergic side-effects. METHODS: Both computational modeling and experimental kinetic analysis were carried out to characterize the potential cholinesterase activity of RBP-8000. Substrates interacting with RBP-8000 were modeled for their enzyme-substrate binding complexes. In vitro enzymatic kinetic parameters were measured using Ellman's colorimetric assay and analyzed by Michaelis-Menten kinetics. RESULTS: It is the first demonstration that RBP-8000 catalyzes the hydrolysis of acetylthiocholine (ATC). However, its catalytic efficiency (kcat/KM) against ATC is 1000-fold and 5000-fold lower than it against cocaine at 25 degrees C and 37 degrees C, respectively, suggesting RBP-8000 has the desired substrate selectivity for cocaine over ACh. CONCLUSION: Given the fact that clinically relevant dose of RBP-8000 displays insignificant cholinesterase activity relative to endogenous cholinesterases in human, administration of RBP-8000 is unlikely to produce any significant cholinergic side-effects. This study provides supplemental evidences in support of further development of RBP-8000 towards a clinically used pharmacotherapy for cocaine overdose. Title: Effective neutralization of chemical warfare agents (HD, VX) by Me-DABCOF: a small molecule with dual action Karton-Lifshin N, Katalan S, Columbus I, Chen R, Yehezkel L, Madmon M, Dagan S, Elias S, Fridkin G, Zafrani Y Ref: Chem Commun (Camb), 55:12471, 2019 : PubMed ESTHER: Karton-Lifshin_2019_Chem.Commun.(Camb)_55_12471 PubMedSearch: Karton-Lifshin 2019 Chem.Commun.(Camb) 55 12471 PubMedID: 31566634 Abstract The ability of mono N-methyl-1,4-diazabicyclo[2.2.2]octane fluoride (Me-DABCOF, 1) to act as a bifunctional reagent that effectively and universally neutralizes both the persistent and extremely toxic blister agent HD and the nerve agent VX in nearly neutral aqueous solution, alumina powder or a hydrogel formulation, is described. Title: Impairment of Angiogenesis by Fatty Acid Synthase Inhibition Involves mTOR Malonylation Bruning U, Morales-Rodriguez F, Kalucka J, Goveia J, Taverna F, Queiroz KCS, Dubois C, Cantelmo AR, Chen R and Carmeliet P <22 more author(s)> Bruning U, Morales-Rodriguez F, Kalucka J, Goveia J, Taverna F, Queiroz KCS, Dubois C, Cantelmo AR, Chen R, Loroch S, Timmerman E, Caixeta V, Bloch K, Conradi LC, Treps L, Staes A, Gevaert K, Tee A, Dewerchin M, Semenkovich CF, Impens F, Schilling B, Verdin E, Swinnen JV, Meier JL, Kulkarni RA, Sickmann A, Ghesquiere B, Schoonjans L, Li X, Mazzone M, Carmeliet P (- 22) Ref: Cell Metab, 28:866, 2018 : PubMed ESTHER: Bruning_2018_Cell.Metab_28_866 PubMedSearch: Bruning 2018 Cell.Metab 28 866 PubMedID: 30146486 Abstract The role of fatty acid synthesis in endothelial cells (ECs) remains incompletely characterized. We report that fatty acid synthase knockdown (FASN(KD)) in ECs impedes vessel sprouting by reducing proliferation. Endothelial loss of FASN impaired angiogenesis insvivo, while FASN blockade reduced pathological ocular neovascularization, at >10-fold lower doses than used for anti-cancer treatment. Impaired angiogenesis was not due to energy stress, redox imbalance, or palmitate depletion. Rather, FASN(KD) elevated malonyl-CoA levels, causing malonylation (a post-translational modification) of mTOR at lysine 1218 (K1218). mTOR K-1218 malonylation impaired mTOR complex 1 (mTORC1) kinase activity, thereby reducing phosphorylation of downstream targets (p70S6K/4EBP1). Silencing acetyl-CoA carboxylase 1 (an enzyme producing malonyl-CoA) normalized malonyl-CoA levels and reactivated mTOR in FASN(KD) ECs. Mutagenesis unveiled the importance of mTOR K1218 malonylation for angiogenesis. This study unveils a novel role of FASN in metabolite signaling that contributes to explaining the anti-angiogenic effect of FASN blockade. Title: Aii810, a Novel Cold-Adapted N-Acylhomoserine Lactonase Discovered in a Metagenome, Can Strongly Attenuate Pseudomonas aeruginosa Virulence Factors and Biofilm Formation Fan X, Liang M, Wang L, Chen R, Li H, Liu X Ref: Front Microbiol, 8:1950, 2017 : PubMed ESTHER: Fan_2017_Front.Microbiol_8_1950 PubMedSearch: Fan 2017 Front.Microbiol 8 1950 PubMedID: 29067011 Gene_locus related to this paper: 9bact-Aii810 Abstract The pathogen Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence and biofilm formation. Enzymatic disruption of quorum sensing is a promising anti-infection therapeutic strategy that does not rely on antibiotics. Here, a novel gene (aii810) encoding an N-acylhomoserine lactonase was isolated from the Mao-tofu metagenome for the first time. Aii810 encoded a protein of 269 amino acids and was expressed in Escherichia coli BL21 (DE3) in soluble form. It showed the highest activity at 20 degrees C, and it maintained 76.5% of activity at 0 degrees C and more than 50% activity at 0-40 degrees C. The optimal pH was 8.0. It was stable in both neutral and slightly alkaline conditions and at temperatures below 40 degrees C. The enzyme hydrolyzed several rho-nitrophenyl esters, but its best substrate was rho-nitrophenyl acetate. Its kcat and Km values were 347.7 S(-1) and 205.1 muM, respectively. It efficiently degraded N-butyryl-L-homoserine lactone and N-(3-oxododecanoyl)-L-homoserine lactone, exceeding hydrolysis rates of 72.3 and 100%, respectively. Moreover, Aii810 strongly attenuated P. aeruginosa virulence and biofilm formation. This enzyme with high anti-QS activity was the most cold-adapted N-acylhomoserine lactonase reported, which makes it an attractive enzyme for use as a therapeutic agent against P. aeruginosa infection. Title: What is the impact of PCSK9 rs505151 and rs11591147 polymorphisms on serum lipids level and cardiovascular risk: a meta-analysis Qiu C, Zeng P, Li X, Zhang Z, Pan B, Peng ZYF, Li Y, Ma Y, Leng Y, Chen R Ref: Lipids Health Dis, 16:111, 2017 : PubMed ESTHER: Qiu_2017_Lipids.Health.Dis_16_111 PubMedSearch: Qiu 2017 Lipids.Health.Dis 16 111 PubMedID: 28606094 Abstract BACKGROUND: PCSK9 rs505151 and rs11591147 polymorphisms are identified as gain- and loss-of-function mutations, respectively. The effects of these polymorphisms on serum lipid levels and cardiovascular risk remain to be elucidated. Title: Thyroglobulin gene mutations in Chinese patients with congenital hypothyroidism Hu X, Chen R, Fu C, Fan X, Wang J, Qian J, Yi S, Li C, Luo J and Shen Y <9 more author(s)> Hu X, Chen R, Fu C, Fan X, Wang J, Qian J, Yi S, Li C, Luo J, Su J, Zhang S, Xie B, Zheng H, Lai Y, Chen Y, Li H, Gu X, Chen S, Shen Y (- 9) Ref: Mol Cell Endocrinol, 423:60, 2016 : PubMed ESTHER: Hu_2016_Mol.Cell.Endocrinol_423_60 PubMedSearch: Hu 2016 Mol.Cell.Endocrinol 423 60 PubMedID: 26777470 Gene_locus related to this paper: human-TG Abstract Mutations in Thyroglobulin (TG) are common genetic causes of congenital hypothyroidism (CH). But the TG mutation spectrum and its frequency in Chinese CH patients have not been investigated. Here we conducted a genetic screening of TG gene in a cohort of 382 Chinese CH patients. We identified 22 rare non-polymorphic variants including six truncating variants and 16 missense variants of unknown significance (VUS). Seven patients carried homozygous pathogenic variants, and three patients carried homozygous or compound heterozygous VUS. 48 out of 382 patients carried one of 18 heterozygous VUS which is significantly more often than their occurrences in control cohort (P < 0.0001). Unique to Asian population, the c.274+2T>G variant is the most common pathogenic variant with an allele frequency of 0.021. The prevalence of CH due to TG gene defect in Chinese population was estimated to be approximately 1/101,000. Our study uncovered ethnicity specific TG mutation spectrum and frequency. Title: The destruction box is involved in the degradation of the NTE family proteins by the proteasome Huang FF, Chang PA, Sun LX, Qin WZ, Han LP, Chen R Ref: Mol Biol Rep, 43:1285, 2016 : PubMed ESTHER: Huang_2016_Mol.Biol.Rep_43_1285 PubMedSearch: Huang 2016 Mol.Biol.Rep 43 1285 PubMedID: 27558092 Abstract Neuropathy target esterase (NTE) and NTE-related esterase (NRE) are endoplasmic reticulum (ER) membrane-anchored proteins belonging to the NTE protein family. NTE and NRE are degraded by macroautophagy and by the ubiquitin-proteasome pathway. However, the regulation of NTE and NRE by proteasome has not been well understood. Western blotting showed that the deletion of the regulatory region of NTE and NRE led to protein accumulation compared with that of the corresponding wild-type proteins. Further, deletion and site-directed mutagenesis experiments demonstrated that the destruction (D) box was required for the proteasomal degradation of NTE and NRE. However, unlike the deletion of the regulatory region, the deletion of the D box did not affect the subcellular localisation of NTE or NRE or disrupt the ER. Moreover, the deletion of the D box or the regulatory region of NTE has similar inhibitory effects on cell growth, which are greater than those produced by the full-length NTE. Here, for the first time, we show that the D box is involved in the regulation of NTE family proteins by the proteasome but not in their subcellular localisation. In addition, these results suggest that the NTE overexpression-mediated inhibition of cell growth is related to active protein levels but not to its ER disruption effect. Title: Fluoxetine reduces CES1, CES2, and CYP3A4 expression through decreasing PXR and increasing DEC1 in HepG2 cells Shang W, Liu J, Chen R, Ning R, Xiong J, Liu W, Mao Z, Hu G, Yang J Ref: Xenobiotica, 46:393, 2016 : PubMed ESTHER: Shang_2016_Xenobiotica_46_393 PubMedSearch: Shang 2016 Xenobiotica 46 393 PubMedID: 26340669 Gene_locus related to this paper: human-CES1 Abstract 1. This study investigated the mechanisms of the decreases of carboxylesterases (CES) and cytochrome P4503A4 (CYP3A4) and the enzymatic activities induced by fluoxetine (FLX) in HepG2 cells. We found that FLX decreased the carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2) expression and the hydrolytic activity. 2. FLX decreased the pregnane X receptor (PXR) expression which regulated the target genes such as CYP3A4, whereas increased the differentiated embryonic chondrocyte-expressed gene 1 (DEC1) expression. 3. FLX repressed the PXR at transcriptional level. 4. Overexpression of PXR alone increased the expression of CES1, CES2, and CYP3A4 and attenuated the decreases of CES1, CES2, and CYP3A4 induced by FLX. On the contrary, knockdown of PXR alone decreased the expression of CES1, CES2, and CYP3A4 and almost abolished the decreases of CES1, CES2, and CYP3A4 induced by FLX. 5. Knockdown of DEC1 alone increased the expression of PXR and CYP3A4 and almost abolished the decreases of CES1, CES2, and CYP3A4 induced by FLX. 6. Taken together, the decreases of CES and CYP3A4 expression and enzymatic activities induced by FLX are through decreasing PXR and increasing DEC1 in HepG2 cells. Title: A novel acetylcholinesterase inhibitor and calcium channel blocker SCR-1693 improves Abeta25-35-impaired mouse cognitive function Zhang Z, Chen R, An W, Wang C, Liao G, Dong X, Bi A, Yin Z, Luo L Ref: Psychopharmacology (Berl), 233:599, 2016 : PubMed ESTHER: Zhang_2016_Psychopharmacology.(Berl)_233_599 PubMedSearch: Zhang 2016 Psychopharmacology.(Berl) 233 599 PubMedID: 26554390 Abstract RATIONALE: The mechanism involved in AD is complex, which has prompted to develop compounds that could simultaneously interact with several potential targets. Here, we report a new synthesized compound SCR-1693 which is designed to target both AChE and calcium channels that are potential for AD therapy. OBJECTIVES: We investigated the effects of SCR-1693 on AChE and calcium channels, the effects of neuroprotection and anti-amnesia in icv-Abeta25-35-injected mice, and the potential mechanisms. Title: Enhancing the Thermostability of Feruloyl Esterase EstF27 by Directed Evolution and the Underlying Structural Basis Cao LC, Chen R, Xie W, Liu YH Ref: Journal of Agricultural and Food Chemistry, 63:8225, 2015 : PubMed ESTHER: Cao_2015_J.Agric.Food.Chem_63_8225 PubMedSearch: Cao 2015 J.Agric.Food.Chem 63 8225 PubMedID: 26329893 Gene_locus related to this paper: 9bact-e7djy5 Abstract To improve the thermostability of EstF27, two rounds of random mutagenesis were performed. A thermostable mutant, M6, with six amino acid substitutions was obtained. The half-life of M6 at 55 degrees C is 1680 h, while that of EstF27 is 0.5 h. The Kcat/Km value of M6 is 1.9-fold higher than that of EstF27. The concentrations of ferulic acid released from destarched wheat bran by EstF27 and M6 at their respective optimal temperatures were 223.2 +/- 6.8 and 464.8 +/- 11.9 muM, respectively. To further understand the structural basis of the enhanced thermostability, the crystal structure of M6 is determined at 2.0 A. Structural analysis shows that a new disulfide bond and hydrophobic interactions formed by the mutations may play an important role in stabilizing the protein. This study not only provides us with a robust catalyst, but also enriches our knowledge about the structure-function relationship of feruloyl esterase. Title: Decreased carboxylesterases expression and hydrolytic activity in type 2 diabetic mice through Akt/mTOR/HIF-1alpha/Stra13 pathway Chen R, Wang Y, Ning R, Hu J, Liu W, Xiong J, Wu L, Liu J, Hu G, Yang J Ref: Xenobiotica, 45:782, 2015 : PubMed ESTHER: Chen_2015_Xenobiotica_45_782 PubMedSearch: Chen 2015 Xenobiotica 45 782 PubMedID: 25801056 Abstract 1. This study investigated the alteration of carboxylesterases in type 2 diabetes. We found that the carboxylesterase 1d (Ces1d) and carboxylesterase 1e (Ces1e) expression and the capacity of hydrolytic activity of liver and intestine decreased, whereas the Akt/mTOR/HIF-1alpha/ Stra13 (DEC1) signaling was activated in T2D mice. Consistently, high insulin could give rise to the same results in the high-glucose DMEM condition, which mimicked T2D, in primary mouse hepatocytes. 2. Perifosine or rapamycin almost abolished the decrease of the Ces1d and Ces1e expression and the hydrolytic activity induced by the insulin in the primary mouse hepatocytes. 3. The responsiveness of human hepatoma (HepG2) cells to high insulin in high-glucose condition was similar to that of primary mouse hepatocytes in terms of the altered expression of carboxylesterases. 4. The knockdown of HIF-1alpha or DEC1 with shRNA construct abrogated the decrease of the CES1 and CES2 expression induced by the insulin in high glucose condition in HepG2 cells. 5. Taken together, the decreased carboxylesterases expression and hydrolytic activity in T2D mice are through the Akt/mTOR/HIF-1alpha/Stra13 (DEC1) pathway. Title: Association of and with Alzheimer's disease: Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls Ji H, Dai D, Wang Y, Jiang D, Zhou X, Lin P, Ji X, Li J, Zhang Y and Wang Q <5 more author(s)> Ji H, Dai D, Wang Y, Jiang D, Zhou X, Lin P, Ji X, Li J, Zhang Y, Yin H, Chen R, Zhang L, Xu M, Duan S, Wang Q (- 5) Ref: Exp Ther Med, 9:1831, 2015 : PubMed ESTHER: Ji_2015_Exp.Ther.Med_9_1831 PubMedSearch: Ji 2015 Exp.Ther.Med 9 1831 PubMedID: 26136901 Abstract Alzheimer's disease (AD) is a common neurodegenerative disorder that can destroy the memory of sufferers and lead to distress for the individual and society. Brain-derived neurotrophic factor (BDNF) and butyrylcholinesterase (BCHE) are two genes associated with beta-amyloid plaques and neurofibrillary tangles that are two key factors in the pathophysiology of AD. The aim of the current meta-analysis was to evaluate the association between BDNF Val66Met (rs6265), BDNF C270T (rs2030324) and BCHE-K (rs1803274) polymorphisms and AD. A comprehensive meta-analysis was performed using the online database PubMed without a time limitation. A total of 56 articles evaluating 12,563 cases and 12,622 controls were selected for the current meta-analysis. The results showed a moderate association of the BDNF C270T polymorphism with the risk of AD in Asians under a dominant model (P=0.03; odds ratio, 1.88; 95% confidence interval, 1.08-3.27). No other significant association was found during the meta-analysis for the other two polymorphisms (P>0.05). The current meta-analysis suggests that BDNF C270T is a risk factor for AD in Asians. This meta-analysis has been, to the best of our knowledge, the most comprehensive meta-analysis of BDNF Val66Met, BDNF C270T and BCHE-K to date. Title: Strigolactones contribute to shoot elongation and to the formation of leaf margin serrations in Medicago truncatula R108 Lauressergues D, Andre O, Peng J, Wen J, Chen R, Ratet P, Tadege M, Mysore KS, Rochange SF Ref: J Exp Bot, 66:1237, 2015 : PubMed ESTHER: Lauressergues_2015_J.Exp.Bot_66_1237 PubMedSearch: Lauressergues 2015 J.Exp.Bot 66 1237 PubMedID: 25472976 Abstract Strigolactones were recently identified as a new class of plant hormones involved in the control of shoot branching. The characterization of strigolactone mutants in several species has progressively revealed their contribution to several other aspects of development in roots and shoots. In this article, we characterize strigolactone-deficient and strigolactone-insensitive mutants of the model legume Medicago truncatula for aerial developmental traits. The most striking mutant phenotype observed was compact shoot architecture. In contrast with what was reported in other species, this could not be attributed to enhanced shoot branching, but was instead due to reduced shoot elongation. Another notable feature was the modified leaf shape in strigolactone mutants: serrations at the leaf margin were smaller in the mutants than in wild-type plants. This phenotype could be rescued in a dose-dependent manner by exogenous strigolactone treatments of strigolactone-deficient mutants, but not of strigolactone-insensitive mutants. Treatment with the auxin transport inhibitor N-1-naphthylphtalamic acid resulted in smooth leaf margins, opposite to the effect of strigolactone treatment. The contribution of strigolactones to the formation of leaf serrations in M. truncatula R108 line represents a novel function of these hormones, which has not been revealed by the analysis of strigolactone mutants in other species. Title: Oral treatment of rodents with soluble epoxide hydrolase inhibitor 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU): Resulting drug levels and modulation of oxylipin pattern Ostermann AI, Herbers J, Willenberg I, Chen R, Hwang SH, Greite R, Morisseau C, Gueler F, Hammock BD, Schebb NH Ref: Prostaglandins Other Lipid Mediat, 121:131, 2015 : PubMed ESTHER: Ostermann_2015_Prostaglandins.Other.Lipid.Mediat_121_131 PubMedSearch: Ostermann 2015 Prostaglandins.Other.Lipid.Mediat 121 131 PubMedID: 26117215 Inhibitor(s) related to this paper: TPPU Abstract Epoxides from polyunsaturated fatty acids (PUFAs) are potent lipid mediators. In vivo stabilization of these epoxides by blockade of the soluble epoxide hydrolase (sEH) leads to anti-inflammatory, analgesic and normotensive effects. Therefore, sEH inhibitors (sEHi) are a promising new class of drugs. Herein, we characterized pharmacokinetic (PK) and pharmacodynamic properties of a commercially available potent sEHi 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU). Cell culture studies suggest its high absorption and metabolic stability. Following administration in drinking water to rats (0.2, 1, and 5mg TPPU/L with 0.2% PEG400), TPPU's blood concentration increased dose dependently within the treatment period to reach an almost steady state after 8 days. TPPU was found in all the tissues tested. The linoleic epoxide/diol ratios in most tissues were dose dependently increased, indicating significant sEH inhibition. Overall, administration of TPPU with the drinking water led to systemic distribution as well as high drug levels and thus makes chronic sEH inhibition studies possible. Title: Quantitative-profiling of neurotransmitter abnormalities in the disease progression of experimental diabetic encephalopathy rat Zhou X, Zhu Q, Han X, Chen R, Liu Y, Fan H, Yin X Ref: Canadian Journal of Physiology & Pharmacology, 93:1007, 2015 : PubMed ESTHER: Zhou_2015_Can.J.Physiol.Pharmacol_93_1007 PubMedSearch: Zhou 2015 Can.J.Physiol.Pharmacol 93 1007 PubMedID: 26426748 Abstract Diabetic encephalopathy (DE) is one of the most prevalent chronic complications of diabetes mellitus (DM), with neither effective prevention nor proven therapeutic regimen. This study aims to uncover the potential dysregulation pattern of the neurotransmitters in a rat model of streptozotocin (STZ)-induced experimental DE. For that purpose, male Sprague-Dawley (SD) rats were treated with a single intraperitoneal injection of STZ. Cognitive performance was detected with the Morris water maze (MWM) test. Serum, cerebrospinal fluid (CSF), and brain tissues were collected to measure the levels of neurotransmitters. Compared with the control rats, the acetylcholine (ACh) levels in serum, CSF, hippocampus, and cortex were all significantly down-regulated as early as 6 weeks in the STZ treatment group. In contrast, the glutamate (Glu) levels were decreased in CSF and the hippocampus, but unaffected in the serum and cortex of STZ-treated rats. As for gamma-aminobutyric acid (GABA), it was down-regulated in serum, but up-regulated in CSF, hippocampus, and the cortex in the STZ-treated group. The mRNA expressions of neurotransmitter-related rate limiting enzymes (including AChE, GAD1, and GAD2) and pro-inflammatory cytokines (including IL-1beta and TNF-alpha) were all increased in the DE rats. Our data suggest that DM induces isoform-dependent and tissue-specific neurotransmitter abnormalities, and that neuroinflammation may underlay the nervous system dysfunction observed in the progression of DE. Title: The Report of Sustained Low-Efficiency Dialysis (SLED) Treatment in Fifteen Patients of Severe Snakebite Cheng J, Wang D, Hu S, Jiang H, Lu H, Lei Q, Liu J, Yuan F, Chen R Ref: Cell Biochem Biophys, 69:71, 2014 : PubMed ESTHER: Cheng_2014_Cell.Biochem.Biophys_69_71 PubMedSearch: Cheng 2014 Cell.Biochem.Biophys 69 71 PubMedID: 24068524 Abstract To investigate the therapeutic efficacy of sustained low-efficiency dialysis (SLED) in severe snakebite patients. Fifteen patients of severe snakebite was treated with SLED from July 2005 to August 2009 were included in the study. Central venous access was established in all patients. SLED was administered using Dialog(+) dialyzer (B. Braun, Germany). SLED sessions were 6-12 h in duration at a blood flow rate of 200 ml/min and a dialysate flow rate of 300 ml/min. Heparin or low molecular weight heparin was used as anticoagulant. Biochemical indicators, APACHE II scores before and after SLED, and clinical outcomes were evaluated. The levels of serum creatinine, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, creatine kinase isozyme MB, and creatine kinase were significantly lower than the level before SLED (P < 0.05); the level of cholinesterase was significantly higher after SLED (P < 0.01); the APACHE II score before SLED was 14.1 +/- 3.8, but decreased significantly to 7.9 +/- 1.4, 6.2 +/- 1.1, and 4.2 +/- 0.8 on days 1, 2, and 7 after SLED, respectively (P < 0.01). Three patients died on days 1, 3, and 4 after SLED, respectively. The remaining twelve patients were either cured or showed improvement at the time of discharge. The survival rate was 80 % where as mortality was 20 %. SLED may be an effective treatment option in severe snakebite patients. It can reduce mortality, thereby, resulting in increased survival rates. Title: Construction of genetically engineered bacteria that degrades organophosphorus pesticide residues and can be easily detected by the fluorescence Li Q, Wang P, Chen R, Li W, Wu YJ Ref: Environ Technol, 35:556, 2014 : PubMed ESTHER: Li_2014_Environ.Technol_35_556 PubMedSearch: Li 2014 Environ.Technol 35 556 PubMedID: 24645434 Abstract Organophosphorus compounds (OPs) are widely used in agriculture and industry and there is increased concern about their toxicological effects in the environment. Bioremediation can offer an efficient and cost-effective option for the removal of OPs. Herein, we describe the construction of a genetically engineered microorganism (GEM) that can degrade OPs and be directly detected and monitored in the environment using an enhanced green fluorescent protein (EGFP) fusion strategy. The coding regions of EGFP, a reporter protein that can fluoresce by itself, and organophosphorus hydrolase (OPH), which has a broad substrate specificity and is able to hydrolyse a number of organophosphorus pesticides, were cloned into the expression vector pET-28b. The fusion protein of EGFP-OPH was expressed in E. coli BL21 (DE3) and the protein expression reached the highest level at 11 h after isopropyl beta-D-thiogalactopyranoside induction. The fluorescence of the GEM was detected by fluorescence spectrophotometry and microscopy, and its ability to degrade OPs was determined by OPH activity assay. Those GEM that express the fusion protein (EGFP and OPH) exhibited strong fluorescence intensity and also potent hydrolase activity, which could be used to degrade organophosphorus pesticide residues in the environment and can also be directly monitored by fluorescence. Title: Novel Multipotent AChEI-CCB Attenuates Hyperhomocysteinemia-Induced Memory Deficits and Neuropathologies in Rats Xia Y, Liu R, Chen R, Tian Q, Zeng K, Hu J, Liu X, Wang Q, Wang P and Wang JZ <1 more author(s)> Xia Y, Liu R, Chen R, Tian Q, Zeng K, Hu J, Liu X, Wang Q, Wang P, Wang XC, Wang JZ (- 1) Ref: J Alzheimers Dis, 42:1029, 2014 : PubMed ESTHER: Xia_2014_J.Alzheimers.Dis_42_1029 PubMedSearch: Xia 2014 J.Alzheimers.Dis 42 1029 PubMedID: 25024319 Abstract Alzheimer's disease (AD) has multiple etiopathogenic factors, yet the definitive cause remains unclear and the therapeutic strategies have been elusive. Combination therapy, as one of the promising treatments, has been studied for years and may exert synergistic beneficial effects on AD through polytherapeutic targets. In this study, we tested the effects of a synthesized juxtaposition (named SCR1693) composed of an acetylcholinesterase inhibitor (AChEI) and a calcium channel blocker (CCB) on the hyperhomocysteinemia (HHcy)-induced AD rat model, and found that SCR1693 remarkably improved the HHcy-induced memory deficits and preserved dendrite morphologies as well as spine density by upregulating synapse-associated proteins PSD95 and synapsin-1. In addition, SCR1693 attenuated HHcy-induced tau hyperphosphorylation at multiple AD-associated sites by regulating the activity of protein phosphatase-2A and glycogen synthase kinase-3beta. Furthermore, SCR1693 was more effective than individual administration of both donepezil and nilvadipine which were used as AChEI and CCB, respectively, in the clinical practice. In conclusion, our data suggest that the polytherapeutic targeting juxtaposition SCR1693 (AChEI-CCB) is a promising therapeutic candidate for AD. Title: Glucose dominates the regulation of carboxylesterases induced by lipopolysaccharide or interleukin-6 in primary mouse hepatocytes Xiong J, Shang W, Wu L, Chen R, Liu W, Ning R, Hu G, Yang J Ref: Life Sciences, 112:41, 2014 : PubMed ESTHER: Xiong_2014_Life.Sci_112_41 PubMedSearch: Xiong 2014 Life.Sci 112 41 PubMedID: 25066929 Abstract AIMS: Altered drug disposition has been associated with inflammation and diabetes, leading to the alteration of drug efficacy and toxicity. Carboxylesterases are major hydrolytic enzymes in the liver, catalyzing the hydrolytic biotransformation of numerous therapeutic agents. Therefore, how glucose affects the regulation of carboxylesterases by interleukin-6 (IL-6) and lipopolysaccharide (LPS) were investigated. MAIN Title: Monoacylglycerol lipase is a therapeutic target for Alzheimer's disease Chen R, Zhang J, Wu Y, Wang D, Feng G, Tang YP, Teng Z, Chen C Ref: Cell Rep, 2:1329, 2012 : PubMed ESTHER: Chen_2012_Cell.Rep_2_1329 PubMedSearch: Chen 2012 Cell.Rep 2 1329 PubMedID: 23122958 Abstract Alzheimer's disease (AD) is the most common cause of dementia among older people. There are no effective medications currently available to prevent and treat AD and halt disease progression. Monoacylglycerol lipase (MAGL) is the primary enzyme metabolizing the endocannabinoid 2-arachidonoylglycerol in the brain. We show here that inactivation of MAGL robustly suppressed production and accumulation of beta-amyloid (Abeta) associated with reduced expression of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) in a mouse model of AD. MAGL inhibition also prevented neuroinflammation, decreased neurodegeneration, maintained integrity of hippocampal synaptic structure and function, and improved long-term synaptic plasticity, spatial learning, and memory in AD animals. Although the molecular mechanisms underlying the beneficial effects produced by MAGL inhibition remain to be determined, our results suggest that MAGL, which regulates endocannabinoid and prostaglandin signaling, contributes to pathogenesis and neuropathology of AD, and thus is a promising therapeutic target for the prevention and treatment of AD. Title: Sesquiterpenoids and lignans from the roots of Valeriana officinalis L Wang PC, Ran XH, Chen R, Luo HR, Ma QY, Liu YQ, Hu JM, Huang SZ, Jiang HZ and Zhao YX <2 more author(s)> Wang PC, Ran XH, Chen R, Luo HR, Ma QY, Liu YQ, Hu JM, Huang SZ, Jiang HZ, Chen ZQ, Zhou J, Zhao YX (- 2) Ref: Chem Biodivers, 8:1908, 2011 : PubMed ESTHER: Wang_2011_Chem.Biodivers_8_1908 PubMedSearch: Wang 2011 Chem.Biodivers 8 1908 PubMedID: 22006719 Abstract Two new guaiane-type sesquiterpenoids, valerol A (1) and kessyl 3-acetate (2), together with nine known compounds, valeracetate (3), anismol A (4), orientalol C (5), spatulenol (6), 4alpha,10alpha-epoxyaromadendrane (7), (+)-8-hydroxypinoresinol (8), pinorespiol (9), pinoresinol 4-O-beta-D-glucopyranoside (10), and 8-hydroxypinoresinol 4'-O-beta-D-glucopyranoside (11) were isolated from the roots of Valeriana officinalis. The structures and relative configurations of 1 and 2 were elucidated on the basis of spectroscopic methods (1D- and 2D-NMR, MS, UV, and IR). These compounds were evaluated for inhibitory activity on acetylcholinesterase (AChE) and enhancing activity on nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells. Title: Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques Yan G, Zhang G, Fang X, Zhang Y, Li C, Ling F, Cooper DN, Li Q, Li Y and Wang X <32 more author(s)> Yan G, Zhang G, Fang X, Zhang Y, Li C, Ling F, Cooper DN, Li Q, Li Y, van Gool AJ, Du H, Chen J, Chen R, Zhang P, Huang Z, Thompson JR, Meng Y, Bai Y, Wang J, Zhuo M, Wang T, Huang Y, Wei L, Li J, Wang Z, Hu H, Yang P, Le L, Stenson PD, Li B, Liu X, Ball EV, An N, Huang Q, Fan W, Zhang X, Wang W, Katze MG, Su B, Nielsen R, Yang H, Wang X (- 32) Ref: Nat Biotechnol, 29:1019, 2011 : PubMed ESTHER: Yan_2011_Nat.Biotechnol_29_1019 PubMedSearch: Yan 2011 Nat.Biotechnol 29 1019 PubMedID: 22002653 Gene_locus related to this paper: macfa-BCHE, macfa-g7nzc0, macfa-g7nze2, macfa-g7p4b9, macfa-g7pa87, macfa-g7pd01, macfa-g7q259, macfa-3neur, macfa-g8f585, macfa-KANSL3, macfa-q4r8p0, macfa-SPG21, macfa-TEX30, macmu-3neur, macmu-ACHE, macmu-BCHE, macmu-f6sz31, macmu-f6the6, macmu-f6zkq5, macmu-f7buk8, macmu-f7cfi8, macmu-f7flv1, macmu-f7ggk1, macmu-f7hir7, macmu-g7n054, macmu-g7npb8, macmu-g7nq39, macmu-KANSL3, macmu-TEX30, macfa-g7pgg6, macmu-g7n4x3, macfa-g7nzx2, macfa-g8f4f7, macmu-f7ba84, macfa-g7psx7, macmu-h9er02, macfa-g8f3k0, macfa-a0a2k5w1n7, macmu-g7mxj6, macfa-g7pbk1, macfa-a0a2k5urk5, macfa-a0a2k5wye4, macfa-g7pe14, macmu-f7hkw9, macmu-f7hm08, macmu-g7mke4, macfa-g7nxn9, macmu-a0a1d5rh04, macmu-h9fud6, macfa-g8f3e1, macfa-i7gcw6, macmu-f6qwx1, macmu-f7h4t2, macfa-a0a2k5wkd0, macfa-a0a2k5v7v4, macfa-g7p7y3, macfa-a0a2k5uqq3, macmu-i2cu80, macfa-g8f5i1, macmu-f7h550, macmu-f7gkb9, macfa-a0a2k5tui1 Abstract The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus macaque. Comparison with the previously sequenced Indian rhesus macaque reveals that all three macaques maintain abundant genetic heterogeneity, including millions of single-nucleotide substitutions and many insertions, deletions and gross chromosomal rearrangements. By assessing genetic regions with reduced variability, we identify genes in each macaque species that may have experienced positive selection. Genetic divergence patterns suggest that the cynomolgus macaque genome has been shaped by introgression after hybridization with the Chinese rhesus macaque. Macaque genes display a high degree of sequence similarity with human disease gene orthologs and drug targets. However, we identify several putatively dysfunctional genetic differences between the three macaque species, which may explain functional differences between them previously observed in clinical studies. Title: Germacrane-type sesquiterpenoids from the roots of Valeriana officinalis var. latifolia Wang PC, Ran XH, Chen R, Luo HR, Liu YQ, Zhou J, Zhao YX Ref: Journal of Natural Products, 73:1563, 2010 : PubMed ESTHER: Wang_2010_J.Nat.Prod_73_1563 PubMedSearch: Wang 2010 J.Nat.Prod 73 1563 PubMedID: 20812738 Abstract Eight new germacrane-type sesquiterpenoids, volvalerenals A-E (2-6) and volvalerenic acids A-C (7-9), along with four known compounds, were isolated from a chloroform extract of the roots of Valeriana officinalis var. latifolia. The structures and relative configurations of 2-9 were elucidated on the basis of spectroscopic data interpretation. The effects of all compounds isolated on acetylcholinesterase were evaluated. Title: The genome of the cucumber, Cucumis sativus L Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B and Du Y <77 more author(s)> Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B, Ni P, Ren Y, Zhu H, Li J, Lin K, Jin W, Fei Z, Li G, Staub J, Kilian A, van der Vossen EA, Wu Y, Guo J, He J, Jia Z, Tian G, Lu Y, Ruan J, Qian W, Wang M, Huang Q, Li B, Xuan Z, Cao J, Asan, Wu Z, Zhang J, Cai Q, Bai Y, Zhao B, Han Y, Li Y, Li X, Wang S, Shi Q, Liu S, Cho WK, Kim JY, Xu Y, Heller-Uszynska K, Miao H, Cheng Z, Zhang S, Wu J, Yang Y, Kang H, Li M, Liang H, Ren X, Shi Z, Wen M, Jian M, Yang H, Zhang G, Yang Z, Chen R, Ma L, Liu H, Zhou Y, Zhao J, Fang X, Fang L, Liu D, Zheng H, Zhang Y, Qin N, Li Z, Yang G, Yang S, Bolund L, Kristiansen K, Li S, Zhang X, Wang J, Sun R, Zhang B, Jiang S, Du Y (- 77) Ref: Nat Genet, 41:1275, 2009 : PubMed ESTHER: Huang_2009_Nat.Genet_41_1275 PubMedSearch: Huang 2009 Nat.Genet 41 1275 PubMedID: 19881527 Gene_locus related to this paper: cucsa-a0a0a0ktw5, cucsa-a0a0a0lnt6, cucsa-a0a0a0kpn7, cucsa-a0a0a0lvt9, cucsa-a0a0a0kdx8, cucsa-a0a0a0m228, cucsa-a0a0a0kz31, cucsa-a0a0a0k5t5, cucsa-a0a0a0kfs7, cucsa-a0a0a0kjj7, cucsa-a0a0a0kzs7, cucsa-a0a0a0l0a6, cucsa-a0a0a0l4w4, cucsa-a0a0a0lpz0, cucsa-a0a0a0ls66 Abstract Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system. Title: The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, Mills K, Rosler KM, Triggs WJ and Ziemann U <1 more author(s)> Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, Mills K, Rosler KM, Triggs WJ, Ugawa Y, Ziemann U (- 1) Ref: Clin Neurophysiol, 119:504, 2008 : PubMed ESTHER: Chen_2008_Clin.Neurophysiol_119_504 PubMedSearch: Chen 2008 Clin.Neurophysiol 119 504 PubMedID: 18063409 Abstract The review focuses on the clinical diagnostic utility of transcranial magnetic stimulation (TMS). The central motor conduction time (CMCT) is a sensitive method to detect myelopathy and abnormalities may be detected in the absence of radiological changes. CMCT may also detect upper motor neuron involvement in amyotrophic lateral sclerosis. The diagnostic sensitivity may be increased by using the triple stimulation technique (TST), by combining several parameters such as CMCT, motor threshold and silent period, or by studying multiple muscles. In peripheral facial nerve palsies, TMS may be used to localize the site of nerve dysfunction and clarify the etiology. TMS measures also have high sensitivity in detecting lesions in multiple sclerosis and abnormalities in CMCT or TST may correlate with motor impairment and disability. Cerebellar stimulation may detect lesions in the cerebellum or the cerebellar output pathway. TMS may detect upper motor neuron involvement in patients with atypical parkinsonism and equivocal signs. The ipsilateral silent period that measures transcallosal inhibition is a potential method to distinguish between different parkinsonian syndromes. Short latency afferent inhibition (SAI), which is related to central cholinergic transmission, is reduced in Alzheimer's disease. Changes in SAI following administration of cholinesterase inhibitor may be related to the long-term efficacy of this treatment. The results of MEP measurement in the first week after stroke correlate with functional outcome. We conclude that TMS measures have demonstrated diagnostic utility in myelopathy, amyotrophic lateral sclerosis and multiple sclerosis. TMS measures have potential clinical utility in cerebellar disease, dementia, facial nerve disorders, movement disorders, stroke, epilepsy, migraine and chronic pain. Title: Evolutionary and biomedical insights from the rhesus macaque genome Gibbs RA, Rogers J, Katze MG, Bumgarner R, Weinstock GM, Mardis ER, Remington KA, Strausberg RL, Venter JC and Zwieg AS <166 more author(s)> Gibbs RA, Rogers J, Katze MG, Bumgarner R, Weinstock GM, Mardis ER, Remington KA, Strausberg RL, Venter JC, Wilson RK, Batzer MA, Bustamante CD, Eichler EE, Hahn MW, Hardison RC, Makova KD, Miller W, Milosavljevic A, Palermo RE, Siepel A, Sikela JM, Attaway T, Bell S, Bernard KE, Buhay CJ, Chandrabose MN, Dao M, Davis C, Delehaunty KD, Ding Y, Dinh HH, Dugan-Rocha S, Fulton LA, Gabisi RA, Garner TT, Godfrey J, Hawes AC, Hernandez J, Hines S, Holder M, Hume J, Jhangiani SN, Joshi V, Khan ZM, Kirkness EF, Cree A, Fowler RG, Lee S, Lewis LR, Li Z, Liu YS, Moore SM, Muzny D, Nazareth LV, Ngo DN, Okwuonu GO, Pai G, Parker D, Paul HA, Pfannkoch C, Pohl CS, Rogers YH, Ruiz SJ, Sabo A, Santibanez J, Schneider BW, Smith SM, Sodergren E, Svatek AF, Utterback TR, Vattathil S, Warren W, White CS, Chinwalla AT, Feng Y, Halpern AL, Hillier LW, Huang X, Minx P, Nelson JO, Pepin KH, Qin X, Sutton GG, Venter E, Walenz BP, Wallis JW, Worley KC, Yang SP, Jones SM, Marra MA, Rocchi M, Schein JE, Baertsch R, Clarke L, Csuros M, Glasscock J, Harris RA, Havlak P, Jackson AR, Jiang H, Liu Y, Messina DN, Shen Y, Song HX, Wylie T, Zhang L, Birney E, Han K, Konkel MK, Lee J, Smit AF, Ullmer B, Wang H, Xing J, Burhans R, Cheng Z, Karro JE, Ma J, Raney B, She X, Cox MJ, Demuth JP, Dumas LJ, Han SG, Hopkins J, Karimpour-Fard A, Kim YH, Pollack JR, Vinar T, Addo-Quaye C, Degenhardt J, Denby A, Hubisz MJ, Indap A, Kosiol C, Lahn BT, Lawson HA, Marklein A, Nielsen R, Vallender EJ, Clark AG, Ferguson B, Hernandez RD, Hirani K, Kehrer-Sawatzki H, Kolb J, Patil S, Pu LL, Ren Y, Smith DG, Wheeler DA, Schenck I, Ball EV, Chen R, Cooper DN, Giardine B, Hsu F, Kent WJ, Lesk A, Nelson DL, O'Brien W E, Prufer K, Stenson PD, Wallace JC, Ke H, Liu XM, Wang P, Xiang AP, Yang F, Barber GP, Haussler D, Karolchik D, Kern AD, Kuhn RM, Smith KE, Zwieg AS (- 166) Ref: Science, 316:222, 2007 : PubMed ESTHER: Gibbs_2007_Science_316_222 PubMedSearch: Gibbs 2007 Science 316 222 PubMedID: 17431167 Gene_locus related to this paper: macmu-3neur, macmu-ACHE, macmu-BCHE, macmu-f6rul6, macmu-f6sz31, macmu-f6the6, macmu-f6unj2, macmu-f6wtx1, macmu-f6zkq5, macmu-f7aa58, macmu-f7ai42, macmu-f7aim4, macmu-f7buk8, macmu-f7cfi8, macmu-f7cnr2, macmu-f7cu68, macmu-f7flv1, macmu-f7ggk1, macmu-f7hir7, macmu-g7n054, macmu-KANSL3, macmu-TEX30, macmu-Y4neur, macmu-g7n4x3, macmu-i2cy02, macmu-f7ba84, macmu-CES2, macmu-h9er02, macmu-a0a1d5rbr3, macmu-a0a1d5q4k5, macmu-g7mxj6, macmu-f7dn71, macmu-f7hkw9, macmu-f7hm08, macmu-g7mke4, macmu-a0a1d5rh04, macmu-h9fud6, macmu-f6qwx1, macmu-f7h4t2, macmu-h9zaw9, macmu-f7h550, macmu-a0a1d5q9w1, macmu-f7gkb9, macmu-f7hp78, macmu-a0a1d5qvu5 Abstract The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species. Title: The DNA sequence, annotation and analysis of human chromosome 3 Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A and Gibbs RA <100 more author(s)> Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA (- 100) Ref: Nature, 440:1194, 2006 : PubMed ESTHER: Muzny_2006_Nature_440_1194 PubMedSearch: Muzny 2006 Nature 440 1194 PubMedID: 16641997 Gene_locus related to this paper: human-AADAC, human-AADACL2, human-ABHD5, human-ABHD6, human-ABHD10, human-ABHD14A, human-APEH, human-BCHE, human-CIB, human-LIPH, human-MGLL, human-NLGN1, human-PLA1A Abstract After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion. Title: Low levels of alpha7-nicotinic acetylcholine receptor mRNA on peripheral blood lymphocytes in schizophrenia and its association with illness severity Perl O, Strous RD, Dranikov A, Chen R, Fuchs S Ref: Neuropsychobiology, 53:88, 2006 : PubMed ESTHER: Perl_2006_Neuropsychobiology_53_88 PubMedSearch: Perl 2006 Neuropsychobiology 53 88 PubMedID: 16511340 Abstract BACKGROUND: There is evidence that the nicotinic alpha7-acetylcholine receptor (alpha7-AChR) is involved in the pathophysiology of schizophrenia. Several neurotransmitter receptors, including alpha7-AChR, have been demonstrated on peripheral blood lymphocytes (PBL) and it has been suggested that these peripheral receptors may reflect corresponding brain receptors. OBJECTIVE: In this study we compare alpha7 mRNA expression in PBL between schizophrenia patients and control individuals in order to determine whether any correlation exists between alpha7 mRNA expression in PBL and severity of schizophrenia. In addition, the isoforms of alpha7-AChR expressed are identified. METHOD: Peripheral venous blood samples were collected from individuals with schizophrenia (n = 44) and from healthy subjects (n = 16). Symptomatology and illness severity were assessed using standard clinical psychiatric evaluation scales. RNA was prepared from isolated lymphocytes and alpha7 mRNA was measured by RT-PCR. Title: A novel substitution at the translation initiator codon (ATG-->ATC) of the lipoprotein lipase gene is mainly responsible for lipoprotein lipase deficiency in a patient with severe hypertriglyceridemia and recurrent pancreatitis Yu XH, Zhao TQ, Wang L, Liu ZP, Zhang CM, Chen R, Li L, Liu G, Hu WC Ref: Biochemical & Biophysical Research Communications, 341:82, 2006 : PubMed ESTHER: Yu_2006_Biochem.Biophys.Res.Commun_341_82 PubMedSearch: Yu 2006 Biochem.Biophys.Res.Commun 341 82 PubMedID: 16431216 Gene_locus related to this paper: human-LPL Abstract A patient with severe hypertriglyceridemia and recurrent pancreatitis was found to have significantly decreased lipoprotein lipase (LPL) activity and normal apolipoprotein C-II concentration in post-heparin plasma. DNA analysis of the LPL gene revealed two mutations, one of which was a novel homozygous G-->C substitution, resulting in the conversion of a translation initiation codon methionine to isoleucine (LPL-1). The second was the previously reported heterozygous substitution of glutamic acid at residue 242 with lysine (LPL-242). In vitro expression of both mutations separately or in combination demonstrated that LPL-1 had approximately 3% protein mass and 2% activity, whereas LPL-242 had undetectable activity but normal mass. The combined mutation LPL-1-242 exhibited similar changes as for LPL-1, with markedly reduced mass, and for LPL-242, with undetectable activity. These results suggest that the homozygous initiator codon mutation rather than the heterozygous LPL-242 alteration was mainly responsible for the patient phenotypes. Title: Comparative genome sequencing of Drosophila pseudoobscura: chromosomal, gene, and cis-element evolution Richards S, Liu Y, Bettencourt BR, Hradecky P, Letovsky S, Nielsen R, Thornton K, Hubisz MJ, Chen R and Gibbs RA <42 more author(s)> Richards S, Liu Y, Bettencourt BR, Hradecky P, Letovsky S, Nielsen R, Thornton K, Hubisz MJ, Chen R, Meisel RP, Couronne O, Hua S, Smith MA, Zhang P, Liu J, Bussemaker HJ, van Batenburg MF, Howells SL, Scherer SE, Sodergren E, Matthews BB, Crosby MA, Schroeder AJ, Ortiz-Barrientos D, Rives CM, Metzker ML, Muzny DM, Scott G, Steffen D, Wheeler DA, Worley KC, Havlak P, Durbin KJ, Egan A, Gill R, Hume J, Morgan MB, Miner G, Hamilton C, Huang Y, Waldron L, Verduzco D, Clerc-Blankenburg KP, Dubchak I, Noor MA, Anderson W, White KP, Clark AG, Schaeffer SW, Gelbart W, Weinstock GM, Gibbs RA (- 42) Ref: Genome Res, 15:1, 2005 : PubMed ESTHER: Richards_2005_Genome.Res_15_1 PubMedSearch: Richards 2005 Genome.Res 15 1 PubMedID: 15632085 Gene_locus related to this paper: drome-BEM46, drome-GH02439, drops-ACHE, drops-b5dhd2, drops-b5di70, drops-b5djn7, drops-b5dk96, drops-b5dm12, drops-b5dpe3, drops-b5drp9, drops-b5du62, drops-b5dud8, drops-b5dwa7, drops-b5dwa8, drops-b5dy09, drops-b5dz85, drops-b5dz86, drops-b5e1k7, drops-CG4390, drops-est5a, drops-est5b, drops-est5c, drops-nrtac, drops-q2lyp3, drops-q2lyp4, drops-q2lyu3, drops-q2lz68, drops-q2m0u9, drops-q2m169, drops-q28wj5, drops-q28wt2, drops-q28wt8, drops-q28zi3, drops-q28zz1, drops-q29a22, drops-q29ad8, drops-q29ad9, drops-q29ae0, drops-q29ae1, drops-q29ay7, drops-q29ay8, drops-q29ay9, drops-q29bq2, drops-q29br3, drops-q29d59, drops-q29dc9, drops-q29dd7, drops-q29dp4, drops-q29dw3, drops-q29dw4, drops-q29e16, drops-q29ew0, drops-q29f35, drops-q29f66, drops-q29fi0, drops-q29fw0, drops-q29fw9, drops-q29g93, drops-q29gb0, drops-q29gs6, drops-q29h54, drops-b5dmp7, drops-q29hd2, drops-q29hu2, drops-q29hu3, drops-q29hv0, drops-q29i09, drops-q29js9, drops-q29jt5, drops-q29jt6, drops-q29jy5, drops-q29k25, drops-q29kd5, drops-q29kd6, drops-q29ke5, drops-q29kq9, drops-q29kr1, drops-q29kr3, drops-q29kr5, drops-q29kr8, drops-q29kr9, drops-q29ks6, drops-q29kz0, drops-q29kz1, drops-q29l31, drops-q29lf8, drops-q29lv0, drops-q29m07, drops-q29m08, drops-q29m27, drops-q29m66, drops-q29m81, drops-q29mj7, drops-q29mv2, drops-q29mx0, drops-q29n87, drops-q29na5, drops-q29na6, drops-q29pe4, drops-q29pk4, drops-q290i1, drops-q290k3, drops-q290v8, drops-q290v9, drops-q290w0, drops-q290z8, drops-q291d5, drops-q291e8, drops-q291y3, drops-q292f5, drops-q292g6, drops-q293n1, drops-q293n4, drops-q293n5, drops-q293n6, drops-q293y7, drops-q294n3, drops-q294n6, drops-q294n7, drops-q294n9, drops-q294p0, drops-q294p1, drops-q294p3, drops-q294p4, drops-q294u9, drops-q295h3, drops-q296h2, drops-q296x1, drops-q296x2, drops-q297h5, drops-q298u8, drope-b4gkk1 Abstract We have sequenced the genome of a second Drosophila species, Drosophila pseudoobscura, and compared this to the genome sequence of Drosophila melanogaster, a primary model organism. Throughout evolution the vast majority of Drosophila genes have remained on the same chromosome arm, but within each arm gene order has been extensively reshuffled, leading to a minimum of 921 syntenic blocks shared between the species. A repetitive sequence is found in the D. pseudoobscura genome at many junctions between adjacent syntenic blocks. Analysis of this novel repetitive element family suggests that recombination between offset elements may have given rise to many paracentric inversions, thereby contributing to the shuffling of gene order in the D. pseudoobscura lineage. Based on sequence similarity and synteny, 10,516 putative orthologs have been identified as a core gene set conserved over 25-55 million years (Myr) since the pseudoobscura/melanogaster divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome-wide average, consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than random and nearby sequences between the species--but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a pattern of repeat-mediated chromosomal rearrangement, and high coadaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence between these species of Drosophila. Title: The DNA sequence of the human X chromosome Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C and Bentley DR <272 more author(s)> Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C, Bird CP, Frankish A, Lovell FL, Howe KL, Ashurst JL, Fulton RS, Sudbrak R, Wen G, Jones MC, Hurles ME, Andrews TD, Scott CE, Searle S, Ramser J, Whittaker A, Deadman R, Carter NP, Hunt SE, Chen R, Cree A, Gunaratne P, Havlak P, Hodgson A, Metzker ML, Richards S, Scott G, Steffen D, Sodergren E, Wheeler DA, Worley KC, Ainscough R, Ambrose KD, Ansari-Lari MA, Aradhya S, Ashwell RI, Babbage AK, Bagguley CL, Ballabio A, Banerjee R, Barker GE, Barlow KF, Barrett IP, Bates KN, Beare DM, Beasley H, Beasley O, Beck A, Bethel G, Blechschmidt K, Brady N, Bray-Allen S, Bridgeman AM, Brown AJ, Brown MJ, Bonnin D, Bruford EA, Buhay C, Burch P, Burford D, Burgess J, Burrill W, Burton J, Bye JM, Carder C, Carrel L, Chako J, Chapman JC, Chavez D, Chen E, Chen G, Chen Y, Chen Z, Chinault C, Ciccodicola A, Clark SY, Clarke G, Clee CM, Clegg S, Clerc-Blankenburg K, Clifford K, Cobley V, Cole CG, Conquer JS, Corby N, Connor RE, David R, Davies J, Davis C, Davis J, Delgado O, Deshazo D, Dhami P, Ding Y, Dinh H, Dodsworth S, Draper H, Dugan-Rocha S, Dunham A, Dunn M, Durbin KJ, Dutta I, Eades T, Ellwood M, Emery-Cohen A, Errington H, Evans KL, Faulkner L, Francis F, Frankland J, Fraser AE, Galgoczy P, Gilbert J, Gill R, Glockner G, Gregory SG, Gribble S, Griffiths C, Grocock R, Gu Y, Gwilliam R, Hamilton C, Hart EA, Hawes A, Heath PD, Heitmann K, Hennig S, Hernandez J, Hinzmann B, Ho S, Hoffs M, Howden PJ, Huckle EJ, Hume J, Hunt PJ, Hunt AR, Isherwood J, Jacob L, Johnson D, Jones S, de Jong PJ, Joseph SS, Keenan S, Kelly S, Kershaw JK, Khan Z, Kioschis P, Klages S, Knights AJ, Kosiura A, Kovar-Smith C, Laird GK, Langford C, Lawlor S, Leversha M, Lewis L, Liu W, Lloyd C, Lloyd DM, Loulseged H, Loveland JE, Lovell JD, Lozado R, Lu J, Lyne R, Ma J, Maheshwari M, Matthews LH, McDowall J, Mclaren S, McMurray A, Meidl P, Meitinger T, Milne S, Miner G, Mistry SL, Morgan M, Morris S, Muller I, Mullikin JC, Nguyen N, Nordsiek G, Nyakatura G, O'Dell CN, Okwuonu G, Palmer S, Pandian R, Parker D, Parrish J, Pasternak S, Patel D, Pearce AV, Pearson DM, Pelan SE, Perez L, Porter KM, Ramsey Y, Reichwald K, Rhodes S, Ridler KA, Schlessinger D, Schueler MG, Sehra HK, Shaw-Smith C, Shen H, Sheridan EM, Shownkeen R, Skuce CD, Smith ML, Sotheran EC, Steingruber HE, Steward CA, Storey R, Swann RM, Swarbreck D, Tabor PE, Taudien S, Taylor T, Teague B, Thomas K, Thorpe A, Timms K, Tracey A, Trevanion S, Tromans AC, d'Urso M, Verduzco D, Villasana D, Waldron L, Wall M, Wang Q, Warren J, Warry GL, Wei X, West A, Whitehead SL, Whiteley MN, Wilkinson JE, Willey DL, Williams G, Williams L, Williamson A, Williamson H, Wilming L, Woodmansey RL, Wray PW, Yen J, Zhang J, Zhou J, Zoghbi H, Zorilla S, Buck D, Reinhardt R, Poustka A, Rosenthal A, Lehrach H, Meindl A, Minx PJ, Hillier LW, Willard HF, Wilson RK, Waterston RH, Rice CM, Vaudin M, Coulson A, Nelson DL, Weinstock G, Sulston JE, Durbin R, Hubbard T, Gibbs RA, Beck S, Rogers J, Bentley DR (- 272) Ref: Nature, 434:325, 2005 : PubMed ESTHER: Ross_2005_Nature_434_325 PubMedSearch: Ross 2005 Nature 434 325 PubMedID: 15772651 Gene_locus related to this paper: human-NLGN3, human-NLGN4X Abstract The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence. Title: Genome sequence of the Brown Norway rat yields insights into mammalian evolution Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC and Collins F <218 more author(s)> Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, de Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Alba M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hubner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Payseur BA, Bourque G, Lopez-Otin C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F (- 218) Ref: Nature, 428:493, 2004 : PubMed ESTHER: Gibbs_2004_Nature_428_493 PubMedSearch: Gibbs 2004 Nature 428 493 PubMedID: 15057822 Gene_locus related to this paper: rat-abhea, rat-abheb, rat-cd029, rat-d3zaw4, rat-dpp9, rat-d3zhq1, rat-d3zkp8, rat-d3zuq1, rat-d3zxw8, rat-d4a4w4, rat-d4a7w1, rat-d4a9l7, rat-d4a071, rat-d4aa31, rat-d4aa33, rat-d4aa61, rat-dglb, rat-f1lz91, rat-Kansl3, rat-nceh1, rat-Tex30, ratno-1hlip, ratno-1neur, ratno-1plip, ratno-2neur, ratno-3neur, ratno-3plip, ratno-ABH15, ratno-ACHE, ratno-balip, ratno-BCHE, ratno-cauxin, ratno-Ces1d, ratno-Ces1e, ratno-Ces2f, ratno-d3ze31, ratno-d3zp14, ratno-d3zxi3, ratno-d3zxq0, ratno-d3zxq1, ratno-d4a3d4, ratno-d4aa05, ratno-dpp4, ratno-dpp6, ratno-est8, ratno-FAP, ratno-hyep, ratno-hyes, ratno-kmcxe, ratno-lmcxe, ratno-LOC246252, ratno-MGLL, ratno-pbcxe, ratno-phebest, ratno-Ppgb, ratno-q4qr68, ratno-q6ayr2, ratno-q6q629, ratno-SPG21, ratno-thyro, rat-m0rc77, rat-a0a0g2k9y7, rat-a0a0g2kb83, rat-d3zba8, rat-d3zbj1, rat-d3zcr8, rat-d3zxw5, rat-d4a340, rat-f1lvg7, rat-m0r509, rat-m0r5d4, rat-b5den3, rat-d3zxk4, rat-d4a1b6, rat-d3zmg4, rat-ab17c Abstract The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution. Title: A complete sequence of the T. tengcongensis genome Bao Q, Tian Y, Li W, Xu Z, Xuan Z, Hu S, Dong W, Yang J, Chen Y and Yang H <11 more author(s)> Bao Q, Tian Y, Li W, Xu Z, Xuan Z, Hu S, Dong W, Yang J, Chen Y, Xue Y, Xu Y, Lai X, Huang L, Dong X, Ma Y, Ling L, Tan H, Chen R, Wang J, Yu J, Yang H (- 11) Ref: Genome Res, 12:689, 2002 : PubMed ESTHER: Bao_2002_Genome.Res_12_689 PubMedSearch: Bao 2002 Genome.Res 12 689 PubMedID: 11997336 Gene_locus related to this paper: thete-DAP2, thete-LIPA3, thete-MHPC, thete-MHPC2, thete-MHPC3, thete-MHPC4, thete-PLDB, thete-TTE1809, thetn-DAP2.2 Abstract Thermoanaerobacter tengcongensis is a rod-shaped, gram-negative, anaerobic eubacterium that was isolated from a freshwater hot spring in Tengchong, China. Using a whole-genome-shotgun method, we sequenced its 2,689,445-bp genome from an isolate, MB4(T) (Genbank accession no. AE008691). The genome encodes 2588 predicted coding sequences (CDS). Among them, 1764 (68.2%) are classified according to homology to other documented proteins, and the rest, 824 CDS (31.8%), are functionally unknown. One of the interesting features of the T. tengcongensis genome is that 86.7% of its genes are encoded on the leading strand of DNA replication. Based on protein sequence similarity, the T. tengcongensis genome is most similar to that of Bacillus halodurans, a mesophilic eubacterium, among all fully sequenced prokaryotic genomes up to date. Computational analysis on genes involved in basic metabolic pathways supports the experimental discovery that T. tengcongensis metabolizes sugars as principal energy and carbon source and utilizes thiosulfate and element sulfur, but not sulfate, as electron acceptors. T. tengcongensis, as a gram-negative rod by empirical definitions (such as staining), shares many genes that are characteristics of gram-positive bacteria whereas it is missing molecular components unique to gram-negative bacteria. A strong correlation between the G + C content of tDNA and rDNA genes and the optimal growth temperature is found among the sequenced thermophiles. It is concluded that thermophiles are a biologically and phylogenetically divergent group of prokaryotes that have converged to sustain extreme environmental conditions over evolutionary timescale. Title: Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157 Jin Q, Yuan Z, Xu J, Wang Y, Shen Y, Lu W, Wang J, Liu H, Yang J and Yu J <23 more author(s)> Jin Q, Yuan Z, Xu J, Wang Y, Shen Y, Lu W, Wang J, Liu H, Yang J, Yang F, Zhang X, Zhang J, Yang G, Wu H, Qu D, Dong J, Sun L, Xue Y, Zhao A, Gao Y, Zhu J, Kan B, Ding K, Chen S, Cheng H, Yao Z, He B, Chen R, Ma D, Qiang B, Wen Y, Hou Y, Yu J (- 23) Ref: Nucleic Acids Research, 30:4432, 2002 : PubMed ESTHER: Jin_2002_Nucleic.Acids.Res_30_4432 PubMedSearch: Jin 2002 Nucleic.Acids.Res 30 4432 PubMedID: 12384590 Gene_locus related to this paper: ecoli-Aes, ecoli-yafa, ecoli-ycfp, ecoli-yqia, ecoli-YfhR, shifl-AES, shifl-BIOH, shifl-entf, shifl-FES, shifl-PLDB, shifl-PTRB, shifl-SF1334, shifl-SF1808, shifl-SF3046, shifl-SF3908, shifl-yafa, shifl-YBFF, shifl-YCDJ, shifl-YCJY, shifl-YFBB, shifl-YHET, shifl-YIEL, shifl-YJFP, shifl-YPFH Abstract We have sequenced the genome of Shigella flexneri serotype 2a, the most prevalent species and serotype that causes bacillary dysentery or shigellosis in man. The whole genome is composed of a 4 607 203 bp chromosome and a 221 618 bp virulence plasmid, designated pCP301. While the plasmid shows minor divergence from that sequenced in serotype 5a, striking characteristics of the chromosome have been revealed. The S.flexneri chromosome has, astonishingly, 314 IS elements, more than 7-fold over those possessed by its close relatives, the non-pathogenic K12 strain and enterohemorrhagic O157:H7 strain of Escherichia coli. There are 13 translocations and inversions compared with the E.coli sequences, all involve a segment larger than 5 kb, and most are associated with deletions or acquired DNA sequences, of which several are likely to be bacteriophage-transmitted pathogenicity islands. Furthermore, S.flexneri, resembling another human-restricted enteric pathogen, Salmonella typhi, also has hundreds of pseudogenes compared with the E.coli strains. All of these could be subjected to investigations towards novel preventative and treatment strategies against shigellosis. Title: Determination of therapeutic doses of bisquaternary oximes in large animals Chen R, Raveh L, Zomber G, Rabinovitz I, Cohen G, Adani R, Amitai G Ref: J Appl Toxicol, 21:285, 2001 : PubMed ESTHER: Chen_2001_J.Appl.Toxicol_21_285 PubMedSearch: Chen 2001 J.Appl.Toxicol 21 285 PubMedID: 11481661 Abstract This report presents a non-lethal method for estimating a range of therapeutic doses of bisquaternary oximes that serve as antidotes against organophosphorus poisoning. We have estimated therapeutic oxime doses that are equivalent in their relative toxicity rather than selecting arbitrary fractions of their LD(50). Thus, toxic signs of the oximes HI-6, HLo-7, Toxogonin, AB-8 and AB-13 were monitored quantitatively in baboon monkeys and beagle dogs. Using Toxogonin as a reference oxime, a calculated unit of equivalent dose (CED) was defined as the oxime dose equal to the ratio between its minimal toxic dose (MTD) and the therapeutic ratio (TR) of Toxogonin i.e. CED = MTD/TR. Assuming that the tails of dose-response curves of toxicity for bisquaternary oximes are shallow and similar to one another, one could substitute the ED(10) for the MTD. The ED(10) values for bisquaternary oximes were estimated using the log-log model following experimental observations and quantitative scoring of toxic signs in dogs and monkeys. The MTD values then were calculated using the ED(10) values and the experimental therapeutic dose of the reference oxime Toxogonin. The following CED values were obtained for AB-8, AB-13, Toxogonin, HI-6 and HLo-7 in dogs (d) and monkeys (m): 98.7, 74.2, 30.0, 14.5 and 12.1 (d) and 281.9, 232.1, 41.7, 192.9 and 92.9 (m) micromol kg(-1), respectively. The antidotal efficacy of these oximes against poisoning by the nerve agent tabun was determined in dogs and monkeys. These dose-dependent efficacy data were obtained at 0.3 x CED, 1 x CED and 3 x CED of oximes in combination with atropine. These data provide comparative therapeutic values using oxime doses based on their relative toxicity. The highest antidotal efficacy against tabun in dogs was obtained for toxogonin, whereas HLo-7 and AB-13 were most efficacious in monkeys. Title: [A gene analysis of familial lipoprotein lipase deficiency in China] Shen J, Chen R, Hu W, Bingshen KE, Li L, Du Y, Liu Y Ref: Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 16:233, 1999 : PubMed ESTHER: Shen_1999_Zhonghua.Yi.Xue.Yi.Chuan.Xue.Za.Zhi_16_233 PubMedSearch: Shen 1999 Zhonghua.Yi.Xue.Yi.Chuan.Xue.Za.Zhi 16 233 PubMedID: 10431049 Abstract OBJECTIVE: To investigate the gene mutation of lipoprotein lipase(LPL) of familial LPL deficiency in China. Title: Bisquaternary Oximes as Antidotes against Tabun and Soman Poisoning Amitai G, Rabinovitz I, Zomber G, Chen R, Cohen G, Adani R, Raveh L Ref: In Enzyme of the Cholinesterase Family - Proceedings of Fifth International Meeting on Cholinesterases, (Quinn, D.M., Balasubramanian, A.S., Doctor, B.P., Taylor, P., Eds) Plenum Publishing Corp.:345, 1995 : PubMed Title: Enantioselective detoxication of optical isomers of glycidyl ethers Chen R, Nguyen P, You Z, Sinsheimer JE Ref: Chirality, 5:501, 1993 : PubMed ESTHER: Chen_1993_Chirality_5_501 PubMedSearch: Chen 1993 Chirality 5 501 PubMedID: 8240926 Abstract The detoxication of the enantiomers of glycidyl 4-nitrophenyl ether (GNPE), (-)-(R)- and (+)-(S)-GNPE, and glycidyl 1-naphthyl ether (GNE), (-)-(R)- and (+)-(S)-GNE, by rat liver glutathione transferase and epoxide hydrolase was studied. Enantioselectivity was observed with both enzymes favoring the (R)-isomers as determined by the formation of conjugate, diol, and remaining substrate measured by HPLC. Enantiomers of GNE were detoxified by cytosolic epoxide hydrolase but those of GNPE were not. Substantial nonenzymatically formed conjugates of enantiomers of GNPE were detected showing (S)-GNPE the more reactive of the pair. | |||||||
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