Author Report for: Shen YNo contact information in database for Shen Y
Chen T, Jiang H, Shen Y, Cui T, Yang Z, Liu Y, Zhao J, Chen X Ref: Chemosphere, 340:139830, 2023 : PubMed ESTHER: Chen_2023_Chemosphere_340_139830 PubMedSearch: Chen 2023 Chemosphere 340 139830 PubMedID: 37597625 Abstract Health risks caused by widespread environmental pollutants such as nanopolystyrene (NP) and chrysene (CHR) in aquatic ecosystems have aroused considerable concern. The present study established juvenile Mandarin fish (Siniperca chuatsi) models of NP and/or CHR exposure at ambient concentrations for 21 days to systematically investigate the underlying neurotoxicity mechanisms. The results showed that single and combined exposure to NP and CHR not only reduced the density of small neuronal cells in the grey matter layer of the optic tectum, but also induced brain oxidative stress according to physiological parameters including CAT, GSH-Px, SOD, T-AOC, and MDA. The co-exposure alleviated the histopathological damage, compared to NP and CHR single exposure group. These results indicate that NP and/or CHR causes neurotoxicity in S. chuatsi, in accordance with decreased acetylcholinesterase activity and altered expression of several marker genes of nervous system functions and development including c-fos, shha, elavl3, and mbpa. Transcriptomics analysis was performed to further investigate the potential molecular mechanisms of neurotoxicity. We propose that single NP and co-exposure induced oxidative stress activates MMP, which degrades tight junction proteins according to decreased expression of claudin, JAM, caveolin and TJP, ultimately damaging the integrity of the blood-brain barrier in S. chuatsi. Remarkably, the co-exposure exacerbated the blood-brain barrier disruption. More importantly, single NP and co-exposure induced neuronal apoptosis mainly activates the expression of apoptosis-related genes through the death receptor apoptosis pathway, while CHR acted through both death receptor apoptosis and endoplasmic reticulum apoptosis pathways. Additionally, subchronic CHR exposure caused neuroinflammation, supported by activation of TNF/NF-kappaB and JAK-STAT signaling pathways via targeting-related genes, while the co-exposure greatly alleviated the neuroinflammation. Collectively, our findings illuminate the underlying neurotoxicity molecular mechanisms of NP and/or CHR exposure on aquatic organisms. Title: Amelioration of walnut-derived novel peptides against D-galactose-induced cognitive impairment by modulating the gut microbiota composition Li T, Lin L, Li C, Zheng J, Chen B, Shen Y, Ren D Ref: Food Funct, :, 2023 : PubMed ESTHER: Li_2023_Food.Funct__ PubMedSearch: Li 2023 Food.Funct PubMedID: 37067262 Abstract In this work, RLWPF (Arg-Leu-Trp-Pro-Phe) and VLRLF (Val-Leu-Arg-Leu-Phe) were investigated for the effects against D-galactose (D-gal) induced cognitive impairment by modulating the gut microbiota composition. The effects on serum metabolite production were further investigated. The two novel peptides derived from walnut protein alkaline protease hydrolysates were predicted by docking to acetylcholinesterase (AChE) with the highest binding affinities, -10.3 and -9.9 kcal mol(-1), considered as the potential neuroprotective peptides. In behavioral experiments, RLWPF and VLRLF treatment significantly restored spatial learning and memory impairment induced by D-gal. The results showed that RLWPF and VLRLF could alleviate cholinergic dysfunction, oxidative stress, and inflammation to varying degrees caused by D-gal-induced aging. Furthermore, 16S rRNA analysis revealed that RLWPF and VLRLF treatment improved cognitive impairment by regulating the composition of the gut microbiota and the abundance of harmful bacteria, including the ratio of Firmicutes to Bacteroidetes, Helicobacter, Allobaculum, Alistipes, Mucispirillum, and Odoribacter. In addition to the same regulation, RLWPF and VLRLF had their marker and regulatory flora. Studies based on the gut microbiota would allow a better understanding of the neuroprotective effects of walnut-derived peptides, supporting that walnut-derived peptides could be potential functional ingredients in foods and nutraceuticals or drug candidates in the treatment of cognitive dysfunction. Title: Ultrathin C(3)N(4) nanosheets-based oxidase-like 2D fluorescence nanozyme for dual-mode detection of organophosphorus pesticides Shen Y, Gao X, Chen H, Wei Y, Yang H, Gu Y Ref: J Hazard Mater, 451:131171, 2023 : PubMed ESTHER: Shen_2023_J.Hazard.Mater_451_131171 PubMedSearch: Shen 2023 J.Hazard.Mater 451 131171 PubMedID: 36913745 Abstract Engineering efficient dual-mode portable sensor with built-in cross reference correction is of great significance for onsite reliable and precise detection of organophosphorus pesticides (OPs) and evading the false-positive outputs, especially in emergency case. Currently, most nanozyme-based sensors for OPs monitoring primarily replied on the peroxidase-like activity, which involved unstable and toxic H(2)O(2). In this scenario, a hybrid oxidase-like 2D fluorescence nanozyme (PtPdNPs@g-C(3)N(4)) was yielded by in situ growing PtPdNPs in the ultrathin two-dimensional (2D) graphitic carbon nitride (g-C(3)N(4)) nanosheet. When acetylcholinesterase (AChE) hydrolyzed acetylthiocholine (ATCh) to thiocholine (TCh), it ablated O(2)(-) from the dissolved O(2) catalyzed by PtPdNPs@g-C(3)N(4)'s oxidase-like activity, hampering the oxidation of o-phenylenediamine (OPD) into 2,3-diaminophenothiazine (DAP). Consequently, with the increasing concentration of OPs which inhibited the blocking effect by inactivating AChE, the produced DAP caused an apparent color change and a dual-color ratiometric fluorescence change in the response system. Through integrating into a smartphone, a H(2)O(2)-free 2D nanozyme-based onsite colorimetric and fluorescence dual-mode visual imaging sensor for OPs was proposed with acceptable results in real samples, which holds vast promise for further development of commercial point-of-care testing platform in early warning and controlling of OPs pollution for safeguarding environmental health and food safety. Title: Emodin derivatives as promising multi-aspect intervention agents for amyloid aggregation: molecular docking/dynamics simulation, bioactivities evaluation, and cytoprotection Shen Y, Duan H, Yuan L, Asikaer A, Liu Y, Zhang R, Wang Y, Lin Z, Shen R and Kou X <4 more author(s)> Shen Y, Duan H, Yuan L, Asikaer A, Liu Y, Zhang R, Wang Y, Lin Z, Shen R, Zhao W, Li X, Liu J, Yang A, Kou X (- 4) Ref: Mol Divers, :, 2023 : PubMed ESTHER: Shen_2023_Mol.Divers__ PubMedSearch: Shen 2023 Mol.Divers PubMedID: 37523101 37737959 Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disease with complex pathogenesis. Despite the pathogenesis is unknown, the misfolding and accumulation of beta-amyloid (Abeta) peptide play the important role in the occurrence and development of AD. Hence, multi-aspect intervention of the misfolded Abeta peptides aggregation is a promising therapy for AD. In previous work, we obtained the emodin derivatives (a-d) with multifunctional anti-AD activities, including metal ions chelation, cholinesterase inhibition, and hydroxyl/superoxide anion radical elimination. In this work, we predicted the interaction of emodin derivatives (a-d) with Abeta by combining molecular docking simulation and molecular dynamics simulation, and evaluated the ability to intervene with the self-, Cu(2+)- and AChE-induced Abeta aggregation via in vitro methods. The results indicated that a-d could act as the potent multi-aspect intervention agents for Abeta aggregation. In addition, a-d could effectively eliminate peroxyl radical, had virtually no neurotoxicity, and protect cells from oxidative and Abeta-induced damage. The prediction results of ADMET properties showed that a-d had suitable pharmacokinetic characteristics. It suggested that a-d could act as the promising multi-targeted directed ligands (MTDLs) for AD. These results may provide meaningful information for the development of the potential MTDLs for AD which are modified from natural-origin scaffolds. Title: The diagnostic value of lipoprotein-associated phospholipase A2 in early diabetic nephropathy Zhai Y, Cao X, Liu S, Shen Y Ref: Ann Med, 55:2230446, 2023 : PubMed ESTHER: Zhai_2023_Ann.Med_55_2230446 PubMedSearch: Zhai 2023 Ann.Med 55 2230446 PubMedID: 37566692 Abstract OBJECTIVE: The aim of this study was to investigate diagnosis of lipoprotein-associated phospholipase A2 (Lp-PLA2) in early diabetic nephropathy (DN). METHODS: A total of 342 type 2 diabetes mellitus (T2DM) patients hospitalized in department of metabolism and nephrology in our hospital from January 2019 to December 2019 were randomly selected. Patients were divided into three groups via urine albumin level: diabetes mellitus (DM) group, simple diabetes group (114 patients, urinary albumin creatinine ratio (UACR) < 30 mg/g); DN1 group, early DN group (114 patients, UACR: 30-300 mg/g); DN2 group: clinical DN group (114 patients, UACR > 300mg/g). Eighty healthy adults were examined at the same time. Lp-PLA2, fasting blood glucose (FBG), creatinine (Cr), triglyceride (TG), total cholesterol (TCHOL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), haemoglobin A1c (HbA1c), blood urea nitrogen/creatinine (BUN/Cr), estimated glomerular filtration rate (eGFR), 24-h urine protein, albumin and creatinine of all subjects were detected and compared. Pearson's correlation analysis and multiple ordered logistic regression were used to investigate the correlation between serum Lp-PLA2 level and DN. The possibility of Lp-PLA2 in the diagnosis of early DN was studied by using the subject working curve. RESULTS: Lp-PLA2 level in DN1 and DN2 groups was significantly higher than that in DM group, with statistical difference (p < .05). With the progression of DN, the level of Lp-PLA2 gradually increased p < .05. Lp-PLA2 was positively correlated with FBG, TG, LDL and HbA1c (R = 0.637, p < .01; R = 0.314, p = .01; R = 0.213, p = .01; R = 0.661, p >= .01), was negatively correlated with HDL (r = -0.230, p < .01). The results showed that Lp-PLA2 was an independent factor in the evaluation of early DN. The area under the curve for the evaluation of serum Lp-PLA2 level in early DN was 0.841, the optimal critical value was 155.9 ng/mL, the sensitivity was 88% and the specificity was 76.2%. CONCLUSIONS: Lp-PLA2 is an independent factor for the evaluation of early DN, and can be used as an important potential specific indicator for the diagnosis of early DN, meanwhile monitoring the progression of DN. Title: Nanobodies as binding-chaperones stabilize the recombinant Bombyx mori acetylcholinesterase and protect the enzyme activity in pesticide detection Cai J, Romao E, Wu G, Li J, Li L, Wang Z, Li Y, Yang J, Shen Y and Wang H <2 more author(s)> Cai J, Romao E, Wu G, Li J, Li L, Wang Z, Li Y, Yang J, Shen Y, Xu Z, Muyldermans S, Wang H (- 2) Ref: Enzyme Microb Technol, 155:109992, 2022 : PubMed ESTHER: Cai_2022_Enzyme.Microb.Technol_155_109992 PubMedSearch: Cai 2022 Enzyme.Microb.Technol 155 109992 PubMedID: 35114480 Abstract In our previous study, the recombinant type II acetylcholinesterase from Bombyx mori (rBmAChE) presented outstanding sensitivity to pesticides, which exhibited great potential in pesticides detection. However, the poor stability of rBmAChE and also the unclear mechanism of its sensitivity hindered the applications in on-site testing of pesticides residues. In this study, we constructed an immune nanobody library, in which we obtained 48 rBmAChE-specific nanobodies. Among them, Nb4 and Nb9 were verified as the most prominent enhancers of the enzyme activity and stabilizers under thermal stress, which indicated their usage as protective reagents for rBmAChE. The simultaneously addition of the two Nbs enhanced the thermal-stability of rBmAChE against exposure to 50-70 degreesC, and also remained 100% residual activity after 30 days storage at - 20 degreesC or 4 degreesC, whereas 80% and 62% at - 80 degreesC and 25 degreesC. The homologous modeling and docking of Nb4 and Nb9 to rBmAChE indicated the stabilization of Nb4 to the peripheral anion site (PAS) of rBmAChE while Nb9 protected the C-terminal structure. Substrate docking demonstrated the importance of electrostatic attraction during catalytic process, that might be enhanced by Nbs. As a result, Nb4 and Nb9 were proved to have great potential on rBmAChE applications due to their regulation on enzyme activity and protection against thermal-inactivation and long-term storage of rBmAChE. Title: Covalent CES2 Inhibitors Protect against Reduced Formation of Intestinal Organoids by the Anticancer Drug Irinotecan Eades W, Liu W, Shen Y, Shi Z, Yan B Ref: Curr Drug Metab, :, 2022 : PubMed ESTHER: Eades_2022_Curr.Drug.Metab__ PubMedSearch: Eades 2022 Curr.Drug.Metab PubMedID: 36515038 Inhibitor(s) related to this paper: Sofosbuvir, SN-38 Abstract BACKGROUND: Irinotecan is widely used to treat various types of solid and metastatic cancer. It is an ester prodrug and its hydrolytic metabolite (SN-38) exerts potent anticancer activity. Irinotecan is hydrolyzed primarily by carboxylesterase-2 (CES2), a hydrolase abundantly present in the intestine such as the duodenum. We have identified several potent and covalent CES2 inhibitors such as remdesivir and sofosbuvir. Remdesivir is the first small molecule drug approved for COVID-19, whereas sofosbuvir is a paradigm-shift medicine for hepatitis C viral infection. Irinotecan is generally well-tolerated but associated with severe/life-threatening diarrhea due to intestinal accumulation of SN-38. OBJECTIVE: This study was to test the hypothesis that remdesivir and sofosbuvir protect against irinotecan-induced epithelial injury associated with gastrointestinal toxicity. METHODS: To test this hypothesis, formation of organoids derived from mouse duodenal crypts, a robust cellular model for intestinal regeneration, was induced in the presence or absence of irinotecan +/- pretreatment with a CES2 drug inhibitor. RESULTS: Irinotecan profoundly inhibited the formation of intestinal organoids and the magnitude of the inhibition was greater with female crypts than their male counterparts. Consistently, crypts from female mice had significantly higher hydrolytic activity toward irinotecan. Critically, remdesivir and sofosbuvir both reduced irinotecan hydrolysis and reversed irinotecan-reduced formation of organoids. Human duodenal samples robustly hydrolyzed irinotecan, stable CES2 transfection induced cytotoxicity and the cytotoxicity was reduced by CES2 drug inhibitor. CONCLUSION: These findings establish a therapeutic rationale to reduce irinotecan-gastrointestinal injury and serve as a cellular foundation to develop oral formulations of irinotecan with high safety. Title: PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma Li H, Wu Z, Zhong R, Zhang Q, Chen Q, Shen Y Ref: Med Oncol, 39:250, 2022 : PubMed ESTHER: Li_2022_Med.Oncol_39_250 PubMedSearch: Li 2022 Med.Oncol 39 250 PubMedID: 36209344 Abstract Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The bifunctional protein peroxiredoxin 6 (PRDX6), which has both calcium-independent phospholipase A2 (iPLA2) and glutathione peroxidase (GPx) activity, participates in the development of multiple tumors. However, the function and clinical significance of PRDX6 in ICC remain unclear. In this study, we characterized PRDX6 in both human ICC and thioacetamide (TAA)-induced rat ICC. We found PRDX6 was significantly increased in ICC tissues, compared with the peritumoral tissues, and PRDX6 expression level was positively correlated with the malignant phenotype in ICC patients. Furthermore, PRDX6 genetic knockout significantly inhibited the tumor progression in rats. By using RNA sequencing analysis, we found 127 upregulated genes and 321 downregulated genes after PRDX6 knockout. In addition, we noticed a significant repression in the Wnt7a/b cascade, which has been shown to play an important role in the occurrence of ICC. We confirmed that gene expressions in the Wnt7a/b cascade were inhibited in ICC tissues after PRDX6 knockout by using qRT-PCR and immunohistochemistry analysis. Collectively, our findings suggest that PRDX6 may promote ICC by regulating the Wnt7a/b pathway, which could be a novel therapeutic target for ICC. Title: The Covid-19 oral drug Molnupiravir is a CES2 substrate: potential drug-drug interactions and impact of CES2 genetic polymorphism in vitro Shen Y, Eades W, Liu W, Yan B Ref: Drug Metabolism & Disposition: The Biological Fate of Chemicals, :, 2022 : PubMed ESTHER: Shen_2022_Drug.Metab.dispos__ PubMedSearch: Shen 2022 Drug.Metab.dispos PubMedID: 35790245 Abstract Molnupiravir is one of the two COVID-19 oral drugs that were recently granted the emergency use authorization by the Food and Drug Administration (FDA). Molnupiravir is an ester and requires hydrolysis to exert antiviral activity. Carboxylesterases constitute a class of hydrolases with high catalytic efficiency. Humans express two major carboxylesterases (CES1 and CES2) that differ in substrate specificity. Based on the structural characteristics of molnupiravir, this study was performed to test the hypothesis that molnupiravir is preferably hydrolyzed by CES2. Several complementary approaches were used to test this hypothesis. As many as 24 individual human liver samples were tested and the hydrolysis of molnupiravir was significantly correlated with the level of CES2 but not CES1. Microsomes from the intestine, kidney and liver but not lung all rapidly hydrolyzed molnupiravir and the magnitude of hydrolysis was related closely to the level of CES2 expression among these organs. Importantly, recombinant CES2 but not CES1 hydrolyzed molnupiravir, collectively establishing that molnupiravir is a CES2-selective substrate. In addition, several CES2 polymorphic variants (e.g., R180H) differed from the wild-type CES2 in the hydrolysis of molnupiravir. Molecular docking revealed that wild-type CES2 and its variant R180H used different sets of amino acids to interact with molnupiravir. Furthermore, molnupiravir hydrolysis was significantly inhibited by remdesivir, the first COVID-19 drug granted the full approval by the FDA. The results presented raise the possibility that CES2 expression and genetic variation may impact therapeutic efficacy in clinical situations and warrants further investigation. Significance Statement COVID-19 remains a global health crisis, and molnupiravir is one of the two recently approved oral COVID-19 therapeutics. In this study, we have shown that molnupiravir is hydrolytically activated by CES2, a major hydrolase whose activity is impacted by genetic polymorphic variants, disease mediators, and many potentially co-administered medicines. these results presented raise the possibility that CES2 expression and genetic variation may impact therapeutic efficacy in clinical situations and warrants further investigation. Title: Transcriptomic Identification and Expression Profile Analysis of Odorant-Degrading Enzymes from the Asian Corn Borer Moth, Ostrinia furnacalis Zhang L, Shen Y, Jiang X, Liu S Ref: Insects, 13:, 2022 : PubMed ESTHER: Zhang_2022_Insects_13_ PubMedSearch: Zhang 2022 Insects 13 PubMedID: 36354851 Abstract The Asian corn borer moth Ostrinia furnacalis is an important lepidopteran pest of maize in Asia. Odorant-degrading enzymes (ODEs), including carboxylesterases (CCEs), glutathione S-transferases (GSTs), cytochrome P450s (CYPs), UDP-glycosyltransferases (UGTs), and aldehyde oxidases (AOXs), are responsible for rapid inactivation of odorant signals in the insect antennae. In this study, we performed a transcriptome assembly for the antennae of O. furnacalis to identify putative ODE genes. Transcriptome sequencing revealed 35,056 unigenes, and 21,012 (59.94%) of these were annotated by searching against the reference sequences in the NCBI non-redundant (NR) protein database. For functional classification, these unigenes were subjected to Gene Ontology (GO), Eukaryotic Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations. We identified 79 genes encoding putative ODEs: 19 CCEs, 17 GSTs, 24 CYPs, 13 UGTs, and 6 AOXs. BLASTX best hit results indicated that these genes shared quite high amino acid identities with their respective orthologs from other lepidopteran species. Reverse transcription-quantitative PCR showed that OfurCCE2, OfurCCE5, and OfurCCE18 were enriched in male antennae, while OfurCCE7 and OfurCCE10 were enriched in female antennae. OfurCCE14 and OfurCCE15 were expressed at near-equal amounts in the antennae of both sexes. Our findings establish a solid foundation for future studies aimed at understanding the olfactory functions of these genes in O. furnacalis. Title: iTRAQ and PRM-based comparative proteomic profiling in gills of white shrimp Litopenaeus vannamei under copper stress Guo H, Chen T, Liang Z, Fan L, Shen Y, Zhou D Ref: Chemosphere, 263:128270, 2021 : PubMed ESTHER: Guo_2021_Chemosphere_263_128270 PubMedSearch: Guo 2021 Chemosphere 263 128270 PubMedID: 33297214 Abstract Crustaceans are particularly sensitive to heavy metal pollution. Copper (Cu) is one of typical heavy metal pollutants in aquatic ecosystems. However, limited attention has been paid on the proteomic responses of shrimp under Cu stress. White shrimp Litopenaeus vannamei held in 5 0/00 seawater were exposed to 5 mg L(-1) Cu for 3 h, and the regulatory mechanism in the gills was elucidated using iTRAQ-based quantitative proteomics. The results showed that a total of 5034 proteins were identified, 385 differentially expressed proteins (DEPs), including 147 differentially up-regulated proteins (DUPs) and 238 differentially down-regulated proteins (DDPs) were found. Bioinformatics analysis indicated the DEPs responding to Cu stress mainly involved in cytoskeleton, immune response, stress response, protein synthesis, detoxification, ion homeostasis and apoptosis. Furthermore, we still performed PRM analysis on sarcoplasmic calcium binding protein (SCP), serine proteinase inhibitor B3 (SPIB3), C-type lectin 4 (CTL4), cathepsin L (CATHL), JHE-like carboxylesterase 1 (CXE1) and paramyosin (PMY), and biochemical analysis on Cu/Zn-superoxide dismutase (Cu/Zn-SOD) to validate the iTRAQ results, respectively. The present proteome analysis revealed that Cu stress disrupted the ion homeostasis and protein synthesis, and L.vannamei mainly regulates a series of molecular pathways which contained many key proteins involved in the immune process to protect the organism from Cu stress. Our data provides more insight about the underlying mechanisms that related to the stress response of Cu exposure in crustacean. Title: Extraction and purification of total flavonoids from Eupatorium lindleyanum DC. and evaluation of their antioxidant and enzyme inhibitory activities Li C, Chen S, Sha J, Cui J, He J, Fu J, Shen Y Ref: Food Sci Nutr, 9:2349, 2021 : PubMed ESTHER: Li_2021_Food.Sci.Nutr_9_2349 PubMedSearch: Li 2021 Food.Sci.Nutr 9 2349 PubMedID: 34026054 Abstract The health benefits and promising medical treatment potential of total flavonoids from Eupatorium lindleyanum DC. (TFELDC) have been recognized. The process parameters of extracting total flavonoids from Eupatorium lindleyanum DC. by ultrasonic-microwave synergistic extraction (UMSE) were optimized, and they were purified by AB-8 macroporous resin in the current study. In addition, the antioxidant and enzyme inhibitory activities of the purified TFELDC (PTFELDC) were evaluated. The results showed that the optimal parameters of UMSE were as follows: ethanol volume fraction 71.5%, L/S ratio 12.2 ml/g, microwave power 318 W, and extraction time 143 s. After TFELDC were purified by AB-8 macroporous resin, the total flavonoid contents of PTFELDC increased from 208.18 +/- 1.60 to 511.19 +/- 3.21 mg RE/g FDS. Compared with TFELDC, the content of total flavonoids in PTFELDC was increased by 2.46 times. The antioxidant activities of PTFELDC were assessed using DPPH radical, superoxide anion radical, reducing power, and ferric reducing antioxidant power assays, and the IC(50) values were found to be 37.13, 19.62, 81.22, and 24.72 microg/ml, respectively. The enzyme inhibitory activities of PTFELDC were measured using lipase, alpha-amylase, alpha-glucosidase, and acetylcholinesterase assays with the IC(50) values 1.38, 2.08, 1.63, and 0.58 mg/ml, respectively. By comparing with their positive controls, it was found that PTFELDC had good antioxidant activities, and lipase, alpha-amylase, and alpha-glucosidase inhibitory activities, However, the acetylcholinesterase inhibitory activity was relatively weaker. These results suggested that PTFELDC have a promising potential as natural antioxidant, antilipidemic, and hypoglycemic drugs used in functional foods or pharmaceuticals. Title: TPPU Pre-Treatment Rescues Dendritic Spine Loss and Alleviates Depressive Behaviours during the Latent Period in the Lithium Chloride-Pilocarpine-Induced Status Epilepticus Rat Model Peng W, Shen Y, Wang Q, Ding J, Wang X Ref: Brain Sci, 11:, 2021 : PubMed ESTHER: Peng_2021_Brain.Sci_11_ PubMedSearch: Peng 2021 Brain.Sci 11 PubMedID: 34827464 Abstract Epileptogenesis may be responsible for both of recurrent seizures and comorbid depression in epilepsy. Disease-modifying treatments targeting the latent period before spontaneous recurrent seizures may contribute to the remission of seizures and comorbid depression. We hypothesized that pre-treatment with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase (sEH) inhibitor, which has anti-inflammatory and neuroprotective effects might rescue status epilepticus (SE)-induced dendritic spine loss and alleviate depressive behaviours. Rats were either pre-treated with TPPU (0.1 mg/kg/d) intragastrically or with vehicle (40% polyethylene glycol 400) from 7 days before to 7 days after SE that was induced with lithium chloride and pilocarpine intraperitoneally. Rats in the Control group were given saline instead. The forced swim test (FST) was performed on the 8th day after SE to evaluate the depression-like behaviours in rats. The results showed that seizures severity during SE was significantly decreased, and the immobility time during FST was significantly increased through TPPU pre-treatment. Moreover, pre-treatment with TPPU attenuated inflammations including microglial gliosis and the level of proinflammatory cytokine IL-1beta in the hippocampus; in addition, neuronal and dendritic spine loss in the subfields of hippocampus was selectively rescued, and the expression of NR1 subunit of N-methyl-D-aspartate (NMDA) receptor, ERK1/2, CREB, and their phosphorylated forms involved in the dendritic spine development were all significantly increased. We concluded that pre-treatment with TPPU attenuated seizures severity during SE and depressive behaviours during the period of epileptogenesis probably by rescuing dendritic spine loss in the hippocampus. Title: The COVID-19 medicine remdesivir is therapeutically activated by carboxylesterase-1 AND excessive hydrolysis increases cytotoxicity Shen Y, Eades W, Yan B Ref: Hepatol Commun, :, 2021 : PubMed ESTHER: Shen_2021_Hepatol.Commun__ PubMedSearch: Shen 2021 Hepatol.Commun PubMedID: 34230903 Inhibitor(s) related to this paper: Remdesivir Abstract The pandemic of coronavirus disease 2019 (COVID-19) has become a global health crisis with the death toll of over 14 million people. So far, there are limited options to treat COVID-19. Remdesivir was granted emergency use authorization earlier, and full use recently. Remdesivir was originally developed against Ebola viral infection and has since been shown to exert a broad antiviral activity against as many as seven viral families [1]. On the other hand, serious adverse events and mortality remained high even with remdesivir among COVID-19 patients [2-4]. Title: Remdesivir potently inhibits carboxylesterase-2 through covalent modifications: signifying strong drug-drug interactions Shen Y, Eades W, Yan B Ref: Fundamental & Clinical Toxicology, 35:432, 2021 : PubMed ESTHER: Shen_2021_Fundam.Clin.Pharmacol_35_432 PubMedSearch: Shen 2021 Fundam.Clin.Pharmacol 35 432 PubMedID: 33369768 Gene_locus related to this paper: human-CES2 Inhibitor(s) related to this paper: Remdesivir Abstract Remdesivir was recently approved to treat COVID-19. While this antiviral agent delivers clinical benefits, several safety concerns in many cases have been raised. This study reports that remdesivir at nanomolar concentrations inhibits carboxylesterase-2 (CES2) through covalent modifications. CES2 is a major drug-metabolizing enzyme. The combination of high potency with irreversible inhibition concludes that cautions must be exercised when remdesivir is used along with drugs hydrolyzed by CES2. Title: Functional expression of a novel methanol-stable esterase from Geobacillus subterraneus DSM13552 for biocatalytic synthesis of cinnamyl acetate in a solvent-free system Cai X, Lin L, Shen Y, Wei W, Wei DZ Ref: BMC Biotechnol, 20:36, 2020 : PubMed ESTHER: Cai_2020_BMC.Biotechnol_20_36 PubMedSearch: Cai 2020 BMC.Biotechnol 20 36 PubMedID: 32600313 Abstract BACKGROUND: Esterases are widely distributed in nature and have important applications in medical, industrial and physiological. Recently, the increased demand for flavor esters has prompted the search of catalysts like lipases and esterases. Esterases from thermophiles also show thermal stability at elevated temperatures and have become enzymes of special interest in biotechnological applications. Although most of esterases catalyzed reactions are carried out in toxic and inflammable organic solvents, the solvent-free system owning many advantages such as low cost and easy downstream processing. RESULTS: The gene estGSU753 from Geobacillus subterraneus DSM13552 was cloned, sequenced and overexpressed into Escherichia coli BL21 (DE3). The novel gene has an open reading frame of 753 bp and encodes 250-amino-acid esterase (EstGSU753). The sequence analysis showed that the protein contains a catalytic triad formed by Ser97, Asp196 and His226, and the Ser of the active site is located in the conserved motif Gly95-X-Ser97-X-Gly99 included in most esterases and lipases. The protein catalyzed the hydrolysis of pNP-esters of different acyl chain lengths, and the enzyme specific activity was 70 U/mg with the optimum substrate pNP-caprylate. The optimum pH and temperature of the recombinant enzyme were 8.0 and 60 degrees C respectively. The resulting EstGSU753 showed remarkable stability against methanol. After the incubation at 50% methanol for 9 days, EstGSU753 retained 50% of its original activity. Even incubation at 90% methanol for 35 h, EstGSU753 retained 50% of its original activity. Also, the preliminary study of the transesterification shows the potential value in synthesis of short-chain flavor esters in a solvent-free system, and more than 99% conversion was obtained in 6 h (substrate: cinnamyl alcohol, 1.0 M). CONCLUSIONS: This is the first report of esterase gene cloning from Geobacillus subterraneus with detailed enzymatic properties. This methanol-stable esterase showed potential value in industrial applications especially in the perfume industry. Title: Bioguided Isolation and Structure Identification of Acetylcholinesterase Enzyme Inhibitors from Drynariae Rhizome Liu MY, Zeng F, Shen Y, Wang YY, Zhang N, Geng F Ref: J Anal Methods Chem, 2020:2971841, 2020 : PubMed ESTHER: Liu_2020_J.Anal.Methods.Chem_2020_2971841 PubMedSearch: Liu 2020 J.Anal.Methods.Chem 2020 2971841 PubMedID: 32185082 Abstract Drynariae Rhizome, widely distributed in southern China, was clinically used as a traditional treatment for cognitive disfunction, such as Alzheimer's disease (AD). The aim of our work was to evaluate the AChE inhibition activities of extracts of Drynariae Rhizome and pure compounds using a bioguided fractionation procedure. The classical approach for screening potential AChE inhibitors was developed by Ellman. However, the background color of compounds or herb extracts remained uncertain and frequently interfered with the detection of the secondary reaction, thereby easily yielding false positive or false negative results. Here, a high-throughput assay monitoring the transformation of iodized choline from iodized acetylcholine catalyzed by AChE was established based on UPLC-MS/MS. The bioguided fractionation of the extract using this method resulted in the isolation of eight AChE inhibitory flavonoids, including naringenin, eriodictyol, kaempferol, luteolin, astragalin, luteolin-7-O-beta-D-glucoside, naringin, and neoeriocitrin, with the IC50 values of 3.81 +/- 0.21 muM, 7.19 +/- 0.62 muM, 11.09 +/- 1.02 muM, 17.26 +/- 0.23 muM, 18.24 +/- 2.33 muM, 17.13 +/- 1.02 muM, 26.4 +/- 1.17 muM, and 22.49 +/- 1.25 muM. It is assumed that the identified flavonoids contribute to the AChE inhibition activity of Drynariae Rhizome. These results are in agreement with the traditional uses of Drynariae Rhizome for AD. Title: Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer's Disease Shen Y, Zhang B, Pang X, Yang R, Chen M, Zhao J, Wang J, Wang Z, Yu Z and Du G <3 more author(s)> Shen Y, Zhang B, Pang X, Yang R, Chen M, Zhao J, Wang J, Wang Z, Yu Z, Wang Y, Li L, Liu A, Du G (- 3) Ref: Front Pharmacol, 11:595254, 2020 : PubMed ESTHER: Shen_2020_Front.Pharmacol_11_595254 PubMedSearch: Shen 2020 Front.Pharmacol 11 595254 PubMedID: 33390981 Abstract Alzheimer's disease (AD) has become a worldwide disease that is harmful to human health and brings a heavy economic burden to healthcare system. Xiao-Xu-Ming Decoction (XXMD) has been widely used to treat stroke and other neurological diseases for more than 1000 years in China. However, the synergistic mechanism of the constituents in XXMD for the potential treatment of AD is still unclear. Therefore, the present study aimed to predict the potential targets and uncover the material basis of XXMD for the potential treatment of AD. A network pharmacology-based method, which combined data collection, drug-likeness filtering and absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties filtering, target prediction and network analysis, was used to decipher the effect and potential targets of XXMD for the treatment of AD. Then, the acetylcholinesterase (AChE) inhibitory assay was used to screen the potential active constituents in XXMD for the treatment of AD, and the molecular docking was furtherly used to identify the binding ability of active constituents with AD-related target of AChE. Finally, three in vitro cell models were applied to evaluate the neuroprotective effects of potential lead compounds in XXMD. Through the China Natural Products Database, Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database, Traditional Chinese Medicine (TCM)-Database @Taiwan and literature, a total of 1481 compounds in XXMD were finally collected. After ADME/T properties filtering, 908 compounds were used for the further study. Based on the prediction data, the constituents in XXMD formula could interact with 41 AD-related targets. Among them, cyclooxygenase-2 (COX-2), estrogen receptor alpha (ERalpha) and AChE were the major targets. The constituents in XXMD were found to have the potential to treat AD through multiple AD-related targets. 62 constituents in it were found to interact with more than or equal to 10 AD-related targets. The prediction results were further validated by in vitro biology experiment, resulting in several potential anti-AD multitarget-directed ligands (MTDLs), including two AChE inhibitors with the IC(50) values ranging from 4.83 to 10.22 microM. Moreover, fanchinoline was furtherly found to prevent SH-SY5Y cells from the cytotoxicities induced by sodium nitroprusside, sodium dithionate and potassium chloride. In conclusion, XXMD was found to have the potential to treat AD by targeting multiple AD-related targets and canonical pathways. Fangchinoline and dauricine might be the potential lead compounds in XXMD for the treatment of AD. Title: Crystal structure and biochemical characterization of Striga hermonthica HYPO-SENSITIVE TO LIGHT 8 (ShHTL8) in strigolactone signaling pathway Zhang Y, Wang D, Shen Y, Xi Z Ref: Biochemical & Biophysical Research Communications, 523:1040, 2020 : PubMed ESTHER: Zhang_2020_Biochem.Biophys.Res.Commun_523_1040 PubMedSearch: Zhang 2020 Biochem.Biophys.Res.Commun 523 1040 PubMedID: 31973817 Gene_locus related to this paper: strhe-ShHTL8 Abstract Striga is a parasitic weed that disperses easily, and its seeds can persist in the soil for many years, presenting long-term threats to food security. If SLs stimulate the seed germination of root parasitic weeds before planting, weeds will wither due to no host. Therefore, it is necessary to determine the mechanism of strigolactone (SL) signaling in Striga to reduce the impacts of this parasitic weed. Striga has eleven different kinds of HYPO-SENSITIVE to LIGHT (ShHTL) hydrolases. Different ShHTL hydrolases exhibit distinct responses to SLs, despite these ShHTLs exhibiting more than 60% sequence identity. Currently, structural information is available for only five ShHTL proteins, and more structural information is needed to design Striga germination stimulants or inhibitors. In this paper, we report the crystal structure of ShHTL8, which is determined at a resolution of 1.4 A. Scanning fluorimetry and HPLC assays indicate that L125, M147, M154 and I194 are important binding sites, and of which L125 may act as a key holder involved in the catalytic reaction. Additionally, the corresponding residue, Y124 of ShHTL1 and F135 of ShHTL2 also play a significant role in the substrate recognition. Title: Identifying genes for resistant starch, slowly digestible starch, and rapidly digestible starch in rice using genome-wide association studies Zhang N, Wang M, Fu J, Shen Y, Ding Y, Wu D, Shu X, Song W Ref: Genes Genomics, 42:1227, 2020 : PubMed ESTHER: Zhang_2020_Genes.Genomics_42_1227 PubMedSearch: Zhang 2020 Genes.Genomics 42 1227 PubMedID: 32901332 Abstract BACKGROUND: The digestibility of starch is important for the nutritive value of staple food. Although several genes are responsible for resistant starch (RS) and slowly digestible starch (SDS), gaps persist concerning the molecular basis of RS and SDS formation due to the complex genetic mechanisms of starch digestibility. OBJECTIVES: The objective of this study was to identify new genes for starch digestibility in rice and interprete the genetic mechanisms of RS and SDS by GWAS. METHODS: Genome-wide association studies were conducted by associating the RS and SDS phenotypes of 104 re-sequenced rice lines to an SNP dataset of 2,288,867 sites using a compressed mixed linear model. Candidate genes were identified according to the position of the SNPs based on data from the MSU Rice Genome Annotation Project. RESULTS: Seven quantitative trait loci (QTLs) were detected to be associated with the RS content, among which the SNP 6 m1765761 was located on Waxy. Starch branching enzymes IIa (BEIIa) close to QTL qRS-I4 was detected and further identified as a specific candidate gene for RS in INDICA. Two QTLs were associated with SDS, and the LOC_Os09g09360 encoding lipase was identified as a causal gene for SDS. CONCLUSIONS: GWAS is a valid strategy to genetically dissect the formation of starch digestion properties in rice. RS formation in grains is dependent on the rice type; lipid might also contribute to starch digestibility and should be an alternative factor to improve rice starch digestibility. Title: Application and design of esterase-responsive nanoparticles for cancer therapy Dong H, Pang L, Cong H, Shen Y, Yu B Ref: Drug Deliv, 26:416, 2019 : PubMed ESTHER: Dong_2019_Drug.Deliv_26_416 PubMedSearch: Dong 2019 Drug.Deliv 26 416 PubMedID: 30929527 Abstract Nanoparticles have been developed for tumor treatment due to the enhanced permeability and retention effects. However, lack of specific cancer cells selectivity results in low delivery efficiency and undesired side effects. In that case, the stimuli-responsive nanoparticles system designed for the specific structure and physicochemical properties of tumors have attracted more and more attention of researchers. Esterase-responsive nanoparticle system is widely used due to the overexpressed esterase in tumor cells. For a rational designed esterase-responsive nanoparticle, ester bonds and nanoparticle structures are the key characters. In this review, we overviewed the design of esterase-responsive nanoparticles, including ester bonds design and nano-structure design, and analyzed the fitness of each design for different application. In the end, the outlook of esterase-responsive nanoparticle is looking forward. Title: Early growth response-1 regulates acetylcholinesterase and its relation with the course of Alzheimer's disease Hu YT, Chen XL, Huang SH, Zhu QB, Yu SY, Shen Y, Sluiter A, Verhaagen J, Zhao J and Bao AM <1 more author(s)> Hu YT, Chen XL, Huang SH, Zhu QB, Yu SY, Shen Y, Sluiter A, Verhaagen J, Zhao J, Swaab D, Bao AM (- 1) Ref: Brain Pathology, 29:502, 2019 : PubMed ESTHER: Hu_2019_Brain.Pathol_29_502 PubMedSearch: Hu 2019 Brain.Pathol 29 502 PubMedID: 30511454 Abstract Our previous studies showed that the transcription factor early growth response-1 (EGR1) may play a role in keeping the brain cholinergic function intact in the preclinical stages of Alzheimer's disease (AD). In order to elucidate the mechanisms involved, we first performed data mining on our previous microarray study on postmortem human prefrontal cortex (PFC) for the changes in the expression of EGR1 and acetylcholinesterase (AChE) and the relationship between them during the course of AD. The study contained 49 patients, ranging from non-demented controls (Braak stage 0) to late AD patients (Braak stage VI). We found EGR1-mRNA was high in early AD and decreased in late AD stages, while AChE-mRNA was stable in preclinical AD and slightly decreased in late AD stages. A significant positive correlation was found between the mRNA levels of these two molecules. In addition, we studied the relationship between EGR1 and AChE mRNA levels in the frontal cortex of 3-12-months old triple-transgenic AD (3xTg-AD) mice. EGR1- and AChE-mRNA were lower in 3xTg-AD mice compared with wild-type (WT) mice. A significant positive correlation between these two molecules was present in the entire group and in each age group of either WT or 3xTg-AD mice. Subsequently, AChE expression was determined following up- or down-regulating EGR1 in cell lines and the EGR1 levels were found to regulate AChE at both the mRNA and protein levels. Dual-luciferase assay and electrophoretic mobility shift assay in the EGR1-overexpressing cells were performed to determine the functionally effective binding sites of the EGR1 on the AChE gene promoter. We conclude that the EGR1 can upregulate AChE expression by a direct effect on its gene promoter, which may contribute significantly to the changes in cholinergic function in the course of AD. The 3xTg-AD mouse model only reflects later stage AD. Title: Dietary choline supplementation attenuated high-fat diet-induced inflammation through regulation of lipid metabolism and suppression of NFkappaB activation in juvenile black seabream (Acanthopagrus schlegelii) Jin M, Pan T, Tocher DR, Betancor MB, Monroig O, Shen Y, Zhu T, Sun P, Jiao L, Zhou Q Ref: J Nutr Sci, 8:e38, 2019 : PubMed ESTHER: Jin_2019_J.Nutr.Sci_8_e38 PubMedSearch: Jin 2019 J.Nutr.Sci 8 e38 PubMedID: 32042405 Abstract The present study aimed to investigate whether dietary choline can regulate lipid metabolism and suppress NFkappaB activation and, consequently, attenuate inflammation induced by a high-fat diet in black sea bream (Acanthopagrus schlegelii). An 8-week feeding trial was conducted on fish with an initial weight of 8.16 +/- 0.01 g. Five diets were formulated: control, low-fat diet (11 %); HFD, high-fat diet (17 %); and HFD supplemented with graded levels of choline (3, 6 or 12 g/kg) termed HFD + C1, HFD + C2 and HFD + C3, respectively. Dietary choline decreased lipid content in whole body and tissues. Highest TAG and cholesterol concentrations in serum and liver were recorded in fish fed the HFD. Similarly, compared with fish fed the HFD, dietary choline reduced vacuolar fat drops and ameliorated HFD-induced pathological changes in liver. Expression of genes of lipolysis pathways were up-regulated, and genes of lipogenesis down-regulated, by dietary choline compared with fish fed the HFD. Expression of nfkappab and pro-inflammatory cytokines in liver and intestine was suppressed by choline supplementation, whereas expression of anti-inflammatory cytokines was promoted in fish fed choline-supplemented diets. In fish that received lipopolysaccharide to stimulate inflammatory responses, the expression of nfkappab and pro-inflammatory cytokines in liver, intestine and kidney were all down-regulated by dietary choline compared with the HFD. Overall, the present study indicated that dietary choline had a lipid-lowering effect, which could protect the liver by regulating intrahepatic lipid metabolism, reducing lipid droplet accumulation and suppressing NFkappaB activation, consequently attenuating HFD-induced inflammation in A. schlegelii. Title: Anti-inflammatory treatment with a soluble epoxide hydrolase inhibitor attenuates seizures and epilepsy-associated depression in the LiCl-pilocarpine post-status epilepticus rat model Shen Y, Peng W, Chen Q, Hammock BD, Liu J, Li D, Yang J, Ding J, Wang X Ref: Brain Behavior & Immunity, 81:535, 2019 : PubMed ESTHER: Shen_2019_Brain.Behav.Immun_81_535 PubMedSearch: Shen 2019 Brain.Behav.Immun 81 535 PubMedID: 31306773 Abstract PURPOSE: This study aimed to investigate whether 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase inhibitor with anti-inflammatory effects, could alleviate spontaneous recurrent seizures (SRS) and epilepsy-associated depressive behaviours in the lithium chloride (LiCl)-pilocarpine-induced post-status epilepticus (SE) rat model. METHODS: The rats were intraperitoneally (IP) injected with LiCl (127mg/kg) and pilocarpine (40mg/kg) to induce SE. A video surveillance system was used to monitor SRS in the post-SE model for 6weeks (from the onset of the 2nd week to the end of the 7th week after SE induction). TPPU (0.1mg/kg/d) was intragastrically given for 4weeks from the 21st day after SE induction in the SRS+0.1 TPPU group. The SRS+PEG 400 group was given the vehicle (40% polyethylene glycol 400) instead, and the control group was given LiCl and PEG 400 but not pilocarpine. The sucrose preference test (SPT) and forced swim test (FST) were conducted to evaluate the depression-like behaviours of rats. Immunofluorescent staining, enzyme-linked immunosorbent assay, and western blot analysis were performed to measure astrocytic and microglial gliosis, neuronal loss, and levels of soluble epoxide hydrolase (sEH), cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6], and cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB). RESULTS: The frequency of SRS was significantly decreased at 6weeks and 7weeks after SE induction in the 0.1TPP U group compared with the SRS+PEG 400 group. The immobility time (IMT) evaluated by FST was significantly decreased, whereas the climbing time (CMT) was increased, and the sucrose preference rate (SPR) evaluated by SPT was in an increasing trend. The levels of sEH, TNF-alpha, IL-1beta, and IL-6 in the hippocampus (Hip) and prefrontal cortex (PFC) were all significantly increased in the SRS+PEG 400 group compared with the control group; neuronal loss, astrogliosis, and microglial activation were also observed. The astrocytic and microglial activation and levels of the pro-inflammatory cytokines in the Hip and PFC were significantly attenuated in the TPPU group compared with the SRS+PEG 400 group; moreover, neuronal loss and the decreased CREB expression were significantly alleviated as well. CONCLUSION: TPPU treatment after SE attenuates SRS and epilepsy-associated depressive behaviours in the LiCl-pilocarpine induced post-SE rat model, and it also exerts anti-inflammatory effects in the brain. Our findings suggest a new therapeutic approach for epilepsy and its comorbidities, especially depression. Title: Excipient-free nanodispersion of 7-ethyl-10-hydroxycamptothecin exerts potent therapeutic effects against pancreatic cancer cell lines and patient-derived xenografts Zhang L, Zhou J, Yan Y, Zhou X, Zhou Q, Du R, Hu S, Ge W, Huang Y and Wang W <5 more author(s)> Zhang L, Zhou J, Yan Y, Zhou X, Zhou Q, Du R, Hu S, Ge W, Huang Y, Xu H, Kong Y, Zheng H, Ding Y, Shen Y, Wang W (- 5) Ref: Cancer Letters, 465:36, 2019 : PubMed ESTHER: Zhang_2019_Cancer.Lett_465_36 PubMedSearch: Zhang 2019 Cancer.Lett 465 36 PubMedID: 31479691 Abstract Irinotecan (CPT-11) is an anti-tumor drug and formulated as nanomedicines to reduce side effects and improve efficacy. In vivo, CPT-11 must be hydrolyzed by carboxylesterase to its active form 7-ethyl-10-hydroxycamptothecin (SN-38) to exert anti-tumor activity, but the lack of this enzyme in humans causes inefficient generation of SN-38. Thus, direct delivery of SN-38, not relying on carboxylesterase, will potentially achieve higher efficacy. However, it is difficult to effectively formulate SN-38 using current excipients due to its hydrophobicity and tendency to crystallize. Herein, we report the nanodispersion of SN-38 with its amphiphilic prodrug, CPT-11, as an effective treatment for pancreatic cancer (PC). SN-38 and CPT-11 formed stable nanoparticles without any other excipients, and showed potent cytotoxicity against PC cells in vitro, slowed tumor growth in vivo, namely subcutaneously and orthotopically xenografted mice, with minimal adverse effects, and prolonged their overall survival. Even in clinically-relevant patient-derived xenograft (PDX) models, the nanodispersion showed greater anti-tumor efficacy than CPT-11. Importantly, the nanodispersion directly released SN-38, resulting in carboxylesterase-independent anti-tumor activity, in contrast to carboxylesterase-dependent CPT-11. These characteristics may enable the excipient-free nanodispersion to exert potent therapeutic effects in patients. Title: Guided Evolution of Recombinant Bombyx mori Acetylcholinesterase II by Homology Modeling to Change Pesticide Sensitivity Cai J, Wang B, Li J, Chen Z, Rao M, Muyldermans S, Hua X, Xie X, Wang H and Sun Y <3 more author(s)> Cai J, Wang B, Li J, Chen Z, Rao M, Muyldermans S, Hua X, Xie X, Wang H, Yang J, Xu Z, Shen Y, Sun Y (- 3) Ref: Int J Mol Sci, 19:, 2018 : PubMed Title: Transfection of neurotrophin-3 into neural stem cells using ultrasound with microbubbles to treat denervated muscle atrophy Gong L, Jiang C, Liu L, Wan S, Tan W, Ma S, Jia X, Wang M, Hu A and Chen Y <4 more author(s)> Gong L, Jiang C, Liu L, Wan S, Tan W, Ma S, Jia X, Wang M, Hu A, Shi Y, Zhang Y, Shen Y, Wang F, Chen Y (- 4) Ref: Exp Ther Med, 15:620, 2018 : PubMed ESTHER: Gong_2018_Exp.Ther.Med_15_620 PubMedSearch: Gong 2018 Exp.Ther.Med 15 620 PubMedID: 29403547 Abstract Neurotrophin-3 (NT-3) has potential as a therapeutic agent for the treatment of patients with denervated muscle atrophy. However, the endogenous secretion of NT-3 is low and exogenous NT-3 lacks sufficient time to accumulate due to its short half-life. The transfection of NT-3 has been demonstrated to have a beneficial effect on denervated muscle and motor endplates. Neural stem cells (NSCs) differentiate into neurons and form motor endplate nerve-muscle connections. It has been previously demonstrated that local and noninvasive transfection can be performed using ultrasound with microbubbles (MBs). In the current study, hematoxylin and eosin, acetylcholinesterase and gold chloride staining, as well as transmission electron microscopy, were performed to verify the effects of this treatment strategy. The results demonstrated that using ultrasound with MBs for the transfection of NT-3 into NSCs, and their subsequent transplantation in vivo, attenuated the atrophy of denervated muscle and reduced motor endplate degeneration. This noninvasive, efficient and targeted treatment strategy may therefore be a potential treatment for patients with denervated muscle atrophy. Title: Suxiao Jiuxin pill promotes exosome secretion from mouse cardiac mesenchymal stem cells in vitro Ruan XF, Ju CW, Shen Y, Liu YT, Kim IM, Yu H, Weintraub N, Wang XL, Tang Y Ref: Acta Pharmacol Sin, 39:569, 2018 : PubMed ESTHER: Ruan_2018_Acta.Pharmacol.Sin_39_569 PubMedSearch: Ruan 2018 Acta.Pharmacol.Sin 39 569 PubMedID: 29542682 Abstract Cardiac mesenchymal stem cells (C-MSCs) are endogenous cardiac stromal cells that play a role in heart repair after injury. C-MSC-derived exosomes (Exo) have shown protective effects against apoptosis induced by acute myocardial ischemia/reperfusion. Suxiao Jiuxin pill (SJP) is a traditional Chinese medicine (TCM) formula used in China for the treatment of acute myocardial ischemia, which contains tetramethylpyrazine (TMP) and borneol (BOR) as major components. In this study, we investigated whether SJP treatment affected exosome release from C-MSCs in vitro. C-MSCs prepared from mice were treated with SJP (62.5 mug/mL), TMP (25 mug/mL) or BOR (15 mug/mL). Using an acetylcholinesterase activity assay, we found that both SJP and TMP treatment significantly increased exosome secretion compared to the control ethanol treatment. The neutral sphingomyelinase 2 (nSMase2) pathway was important in exosome formation and packaging. But neither the level of nSMase2 mRNA nor the level of protein changed following SJP, TMP or BOR treatment, suggesting that SJP stimulated exosome release via an nSMase2-independent pathway. The Rab27a and Rab27b GTPases controlled different steps of the exosome secretion pathway. We showed that SJP treatment significantly increased the protein levels of Rab27a, SYTL4 (Rab27a effector) and Rab27b compared with the control treatment. SJP treatment also significantly upregulated the mRNA level of Rab27b, rather than Rab27a. Moreover, SJP-induced increase of C-MSC-exosome release was inhibited by Rab27b knockdown, suggesting that SJP promotes exosome secretion from C-MSCs via a GTPase-dependent pathway. This study reveals a novel mechanism for SJP in modulating cardiac homeostasis. Title: Purification and characterization of a hydroxynitrile lyase from Amygdalus pedunculata Pall Yao L, Li H, Yang J, Li C, Shen Y Ref: Int J Biol Macromol, 118:189, 2018 : PubMed ESTHER: Yao_2018_Int.J.Biol.Macromol_118_189 PubMedSearch: Yao 2018 Int.J.Biol.Macromol 118 189 PubMedID: 29890248 Abstract Hydroxynitrile lyases (HNLs) are widely used in the asymmetric synthesis of cyanohydrins which are organic compounds used in the production of fine chemicals and pharmaceuticals, because these enzymes exhibit high catalytic efficiency and are very economical. In the present study, seeds of A. pedunculata Pall were identified as new potential source of HNLs. The HNL from A. pedunculata Pall (APHNL) was purified 138 fold and 4.20% yield with a specific activity of 661U/mg. SDS-PAGE result showed the enzyme to be present as a monomer and the relative molecular mass determined by MALDI-TOF MS was 61kDa. APHNL owned highest activity at pH6.0 and at 60 degrees C temperature, showing activity up to 80 degrees C and stable up to 60 degrees C. APHNL has a Km of 0.5mM, Vmax of 665.9mumolmg(-1)min(-1), Kcat of 676.5s(-1) and Kcat/Km of 1353s(-1)mM(-1) using mandelonitrile as substrate. Syntheses of (R)-mandelonitrile and (R)-2-Hydroxy-2-(3-phenoxy-phenyl)-acetonitrile were carried out using APHNL and molar conversion of (R)-mandelonitrile and (R)-2-Hydroxy-2-(3-phenoxy-phenyl)-acetonitrile were 90% and 98% with 94% and 93% ee, respectively. These results indicated that APHNL was an excellent biocatalyst and has very high potential for synthesis of enantiopure cyanohydrins. Title: Autotransporter domain-dependent enzymatic analysis of a novel extremely thermostable carboxylesterase with high biodegradability towards pyrethroid pesticides Cai X, Wang W, Lin L, He D, Huang G, Shen Y, Wei W, Wei D Ref: Sci Rep, 7:3461, 2017 : PubMed ESTHER: Cai_2017_Sci.Rep_7_3461 PubMedSearch: Cai 2017 Sci.Rep 7 3461 PubMedID: 28615636 Abstract The EstPS1 gene, which encodes a novel carboxylesterase of Pseudomonas synxantha PS1 isolated from oil well-produced water, was cloned and sequenced. EstPS1 has an open reading frame of 1923 bp and encodes the 640-amino acid carboxylesterase (EstPS1), which contains an autotransporter (AT) domain (357-640 amino acids). Homology analysis revealed that EstPS1 shared the highest identity (88%) with EstA from Pseudomonas fluorescens A506 (NCBI database) and belonged to the carboxylesterase family (EC 3.1.1.1). The optimum pH and temperature of recombinant EstPS1 were found to be 8.0 and 60 degrees C, respectively. EstPS1 showed high thermostability, and the half-lives (T1/2 thermal inactivation) at 60, 70, 80, 90, and 100 degrees C were 14 h, 2 h, 31 min, 10 min, and 1 min, respectively. To understand the role of the AT domain in carboxylesterase, AT domain-truncated carboxylesterase (EstPS1DeltaAT) was generated. EstPS1DeltaAT showed a clearly decreased secretion rate, owing to the AT domain strongly improved secretory expression in the heterogeneous system. EstPS1 degraded various pyrethroid pesticides, and hydrolysis efficiencies were dependent on the pyrethroid molecular structure. EstPS1 degraded all the tested pyrethroid pesticides and hydrolysed the p-nitrophenyl esters of medium-short-chain fatty acids, indicating that EstPS1 is an esterase with broad specificity. Title: Covalent inhibition of carboxylesterase-2 by sofosbuvir and its effect on the hydrolytic activation of tenofovir disoproxil Shen Y, Yan B Ref: Journal of Hepatology, 66:660, 2017 : PubMed Title: Novel chaetospirolactone and orsellide F from an endophytic fungus Chaetomium sp Xu QL, Xiao YS, Shen Y, Wu HM, Zhang X, Deng XZ, Wang TT, Li W, Tan RX and Ge HM <1 more author(s)> Xu QL, Xiao YS, Shen Y, Wu HM, Zhang X, Deng XZ, Wang TT, Li W, Tan RX, Jiao RH, Ge HM (- 1) Ref: J Asian Nat Prod Res, :1, 2017 : PubMed ESTHER: Xu_2017_J.Asian.Nat.Prod.Res__1 PubMedSearch: Xu 2017 J.Asian.Nat.Prod.Res 1 PubMedID: 28478698 Abstract Chaetospirolactone (1), a novel spiro-lactone bearing a rare 1-oxaspiro [4.4] non-7-ene-2,6-dione skeleton, and orsellide F (2), together with six known compounds (3-8), were isolated from an endophytic fungus Chaetomium sp. NF00754. Their structures were determined by interpretation of spectroscopic data. The absolute configurations of 1 and 2 were established by analysis of single X-ray crystallographic data and CD spectra. Compounds 3, 4, and 6 showed moderate acetylcholinesterase inhibitory activity with IC50 values of 7.34, 5.19, and 7.67 muM, respectively. 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: Increased Lipoprotein-associated phospholipase A2 activity portends an increased risk of resistant hypertension Li Z, Liu J, Shen Y, Zeng F, Zheng D Ref: Lipids Health Dis, 15:15, 2016 : PubMed ESTHER: Li_2016_Lipids.Health.Dis_15_15 PubMedSearch: Li 2016 Lipids.Health.Dis 15 15 PubMedID: 26801405 Abstract BACKGROUND: To investigate the relationship between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and incidence of resistant hypertension (RH). Title: Multitarget-directed oxoisoaporphine derivatives: Anti-acetylcholinesterase, anti-beta-amyloid aggregation and enhanced autophagy activity against Alzheimer's disease Wei S, Chen W, Qin J, Huangli Y, Wang L, Shen Y, Tang H Ref: Bioorganic & Medicinal Chemistry, 24:6031, 2016 : PubMed ESTHER: Wei_2016_Bioorg.Med.Chem_24_6031 PubMedSearch: Wei 2016 Bioorg.Med.Chem 24 6031 PubMedID: 27720328 Abstract A series of 8- and 11-substituted oxoisoaporphine derivatives have been designed, synthesized, and tested for their ability to inhibit cholinesterase (ChE) in vitro and in vivo, and self-induced beta-amyloid (Abeta) aggregation. Their autophagy activity and blood-brain barrier (BBB) permeability were also assessed. The new derivatives exhibited high AChE inhibitory activity in vivo and in intro. Over half the derivatives exhibited a significant in vitro inhibitory activity toward the self-induced Abeta aggregation. While, treatment of SH-SY5Y cells overexpressing the Swedish mutant form of human beta-amyloid precursor protein (APPsw) with derivatives was associated with significant reduction of Abeta secretion levels. Moreover, one-third of the synthetic compounds were predicted to be able to cross the BBB to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. Compounds 5b and 6b were chosen for assessing their autophagy activity. The fluorescence intensity of the BC12921 was decreased significantly after treatment with compounds. The result encourages us to study such compounds thoroughly and systematically. Title: Delayed diagnosis of congenital myasthenia due to associated mitochondrial enzyme defect Guo Y, Menezes MJ, Menezes MP, Liang J, Li D, Riley LG, Clarke NF, Andrews PI, Tian L and Xu X <9 more author(s)> Guo Y, Menezes MJ, Menezes MP, Liang J, Li D, Riley LG, Clarke NF, Andrews PI, Tian L, Webster R, Wang F, Liu X, Shen Y, Thorburn DR, Keating BJ, Engel A, Hakonarson H, Christodoulou J, Xu X (- 9) Ref: Neuromuscular Disorders, 25:257, 2015 : PubMed ESTHER: Guo_2015_Neuromuscul.Disord_25_257 PubMedSearch: Guo 2015 Neuromuscul.Disord 25 257 PubMedID: 25557462 Abstract Clinical phenotypes of congenital myasthenic syndromes and primary mitochondrial disorders share significant overlap in their clinical presentations, leading to challenges in making the correct diagnosis. Next generation sequencing is transforming molecular diagnosis of inherited neuromuscular disorders by identifying novel disease genes and by identifying previously known genes in undiagnosed patients. This is evident in two patients who were initially suspected to have a mitochondrial myopathy, but in whom a clear diagnosis of congenital myasthenic syndromes was made through whole exome sequencing. In patient 1, whole exome sequencing revealed compound heterozygous mutations c.1228C > T (p.Arg410Trp) and c.679C > T (p.Arg227*) in collagen-like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase (COLQ). In patient 2, in whom a deletion of exon 52 in Dystrophin gene was previously detected by multiplex ligation-dependent probe amplification, Sanger sequencing revealed an additional homozygous mutation c.1511_1513delCTT (p.Pro504Argfs*183) in docking protein7 (DOK7). These case reports highlight the need for careful diagnosis of clinically heterogeneous syndromes like congenital myasthenic syndromes, which are treatable, and for which delayed diagnosis is likely to have implications for patient health. The report also demonstrates that whole exome sequencing is an effective diagnostic tool in providing molecular diagnosis in patients with complex phenotypes. Title: A simple electrochemical biosensor based on AuNPs/MPS/Au electrode sensing layer for monitoring carbamate pesticides in real samples Song Y, Chen J, Sun M, Gong C, Shen Y, Wang L Ref: J Hazard Mater, 304:103, 2015 : PubMed ESTHER: Song_2015_J.Hazard.Mater_304_103 PubMedSearch: Song 2015 J.Hazard.Mater 304 103 PubMedID: 26547618 Abstract A simple electrochemical biosensor for quantitative determination of carbamate pesticide was developed based on a sensing interface of citrate-capped gold nanoparticles (AuNPs)/(3-mercaptopropyl)-trimethoxysilane (MPS)/gold electrode (Au). The biosensor was fabricated by firstly assembling three-dimensional (3D) MPS networks on Au electrode and subsequently assembling citrate-capped AuNPs on 3D MPS network via AuS bond. The interface of AuNPs/MPS/Au was negatively charged originating from the citrate coated on AuNPs that would repulse the negatively charged ferricyanide ([Fe(CN)6]3-/4-) to produce a negative response. In the presence of acetylcholinesterase (AChE) and acetylthiocholine (ATCl), the AChE catalyzes the hydrolysis of ATCl into positively charged thiocholine which would replace the citrate on AuNPs through the strong AuS bond and convert the negative charged surface to be positively charged. The resulted positively charged AuNPs/MPS/Au then attracted the [Fe(CN)6]3-/4- to produce a positive response. Based on the inhibition of carbamate pesticides on the activity of AChE, the pesticide could be quantitatively determined at a very low potential. The linear range was from 0.003 to 2.00muM. The sensing platform was also proved to be suitable for carbamate pesticides detection in practical sample. Title: Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism Corominas R, Yang X, Lin GN, Kang S, Shen Y, Ghamsari L, Broly M, Rodriguez M, Tam S and Iakoucheva LM <20 more author(s)> Corominas R, Yang X, Lin GN, Kang S, Shen Y, Ghamsari L, Broly M, Rodriguez M, Tam S, Trigg SA, Fan C, Yi S, Tasan M, Lemmens I, Kuang X, Zhao N, Malhotra D, Michaelson JJ, Vacic V, Calderwood MA, Roth FP, Tavernier J, Horvath S, Salehi-Ashtiani K, Korkin D, Sebat J, Hill DE, Hao T, Vidal M, Iakoucheva LM (- 20) Ref: Nat Commun, 5:3650, 2014 : PubMed ESTHER: Corominas_2014_Nat.Commun_5_3650 PubMedSearch: Corominas 2014 Nat.Commun 5 3650 PubMedID: 24722188 Gene_locus related to this paper: human-NLGN3 Abstract Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of genetic loci. The convergence of ASD variants have been investigated using various approaches, including protein interactions extracted from the published literature. However, these datasets are frequently incomplete, carry biases and are limited to interactions of a single splicing isoform, which may not be expressed in the disease-relevant tissue. Here we introduce a new interactome mapping approach by experimentally identifying interactions between brain-expressed alternatively spliced variants of ASD risk factors. The Autism Spliceform Interaction Network reveals that almost half of the detected interactions and about 30% of the newly identified interacting partners represent contribution from splicing variants, emphasizing the importance of isoform networks. Isoform interactions greatly contribute to establishing direct physical connections between proteins from the de novo autism CNVs. Our findings demonstrate the critical role of spliceform networks for translating genetic knowledge into a better understanding of human diseases. Title: Expression of DPP6 in Meckel's cartilage and tooth germs during mouse facial development Du J, Fan Z, Ma X, Wu Y, Liu S, Gao Y, Shen Y, Fan M, Wang S Ref: Biotech Histochem, 89:14, 2014 : PubMed ESTHER: Du_2014_Biotech.Histochem_89_14 PubMedSearch: Du 2014 Biotech.Histochem 89 14 PubMedID: 23750656 Abstract Dipeptidyl peptidase-like protein 6 (DPP6), a member of the dipeptidyl aminopeptidase family, plays distinct roles in brain development, but its expression in embryonic Meckel's cartilage and tooth germs development is unknown. We analyzed the expression pattern of DPP6 in Meckel's cartilage and tooth germs development using in situ hybridization. DPP6 was detected in different patterns in Meckel's cartilage and tooth germs during mouse facial development from 11.5 to 13.5 days post-coitus (dpc) embryos. The expression pattern of DPP6 suggests that it may be involved in mandible and tooth development. Title: Oil accumulation mechanisms of the oleaginous microalga Chlorella protothecoides revealed through its genome, transcriptomes, and proteomes Gao C, Wang Y, Shen Y, Yan D, He X, Dai J, Wu Q Ref: BMC Genomics, 15:582, 2014 : PubMed ESTHER: Gao_2014_BMC.Genomics_15_582 PubMedSearch: Gao 2014 BMC.Genomics 15 582 PubMedID: 25012212 Gene_locus related to this paper: auxpr-a0a087suf4, auxpr-a0a087sif8, auxpr-a0a087srm3 Abstract BACKGROUND: Microalgae-derived biodiesel is a promising substitute for conventional fossil fuels. In particular, the green alga Chlorella protothecoides sp. 0710 is regarded as one of the best candidates for commercial manufacture of microalgae-derived biofuel. This is due not only to its ability to live autotrophically through photosynthesis, but also to its capacity to produce a large amount of biomass and lipid through fermentation of glucose. However, until the present study, neither its genome sequence nor the platform required for molecular manipulations were available. Title: Sensitive detection of acetylcholine based on a novel boronate intramolecular charge transfer fluorescence probe Liu C, Shen Y, Yin P, Li L, Liu M, Zhang Y, Li H, Yao S Ref: Analytical Biochemistry, 465C:172, 2014 : PubMed ESTHER: Liu_2014_Anal.Biochem_465C_172 PubMedSearch: Liu 2014 Anal.Biochem 465C 172 PubMedID: 25132563 Abstract A highly sensitive and selective fluorescence method for the detection of acetylcholine (ACh) based on enzyme-generated hydrogen peroxide (H2O2) and a new boronate intramolecular charge transfer (ICT) fluorescence probe, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-butyl-1,8-naphthalimide (BN), was developed. This strategy involves the reaction of ACh with acetylcholinesterase (AChE) to produce choline, which is further oxidized by choline oxidase (ChOx) to obtain betaine and H2O2. The enzyme-generated H2O2 reacts with BN and results in hydrolytic deprotection of BN to generate fluorescent product (4-hydroxyl-N-butyl-1,8-naphthalimide, ON). Two consecutive linear response ranges allow determining ACh in a wide concentration range with a low detection limit of 2.7nM (signal/noise=3). Compared with other fluorescent probes based on the mechanism of nonspecific oxidation, this reported boronate probe has the advantage of no interference from other biologically relevant reactive oxygen species (ROS) on the detection of ACh. This study provides a new method for the detection of ACh with high selectivity and sensitivity. Title: Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M and Zhang Z <58 more author(s)> Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M, Luo Y, Yang Y, Wu Z, Mao L, Wu H, Ling-Hu C, Zhou H, Lin H, Gonzalez-Morales S, Trejo-Saavedra DL, Tian H, Tang X, Zhao M, Huang Z, Zhou A, Yao X, Cui J, Li W, Chen Z, Feng Y, Niu Y, Bi S, Yang X, Cai H, Luo X, Montes-Hernandez S, Leyva-Gonzalez MA, Xiong Z, He X, Bai L, Tan S, Liu D, Liu J, Zhang S, Chen M, Zhang L, Zhang Y, Liao W, Wang M, Lv X, Wen B, Liu H, Luan H, Yang S, Wang X, Xu J, Li X, Li S, Wang J, Palloix A, Bosland PW, Li Y, Krogh A, Rivera-Bustamante RF, Herrera-Estrella L, Yin Y, Yu J, Hu K, Zhang Z (- 58) Ref: Proc Natl Acad Sci U S A, 111:5135, 2014 : PubMed ESTHER: Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135 PubMedSearch: Qin 2014 Proc.Natl.Acad.Sci.U.S.A 111 5135 PubMedID: 24591624 Gene_locus related to this paper: capch-q75qh4, capan-a0a1u8fuf5, capan-a0a1u8gmz3, capan-a0a1u8f879, capan-a0a1u8ftr2, capan-a0a1u8g8s6 Abstract As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs. Title: The genome of the platyfish, Xiphophorus maculatus, provides insights into evolutionary adaptation and several complex traits Schartl M, Walter RB, Shen Y, Garcia T, Catchen J, Amores A, Braasch I, Chalopin D, Volff JN and Warren WC <9 more author(s)> Schartl M, Walter RB, Shen Y, Garcia T, Catchen J, Amores A, Braasch I, Chalopin D, Volff JN, Lesch KP, Bisazza A, Minx P, Hillier L, Wilson RK, Fuerstenberg S, Boore J, Searle S, Postlethwait JH, Warren WC (- 9) Ref: Nat Genet, 45:567, 2013 : PubMed ESTHER: Schartl_2013_Nat.Genet_45_567 PubMedSearch: Schartl 2013 Nat.Genet 45 567 PubMedID: 23542700 Gene_locus related to this paper: xipma-m4a796, xipma-a0a3b5r0c8, xipma-m3zmg6, xipma-m3zml4, xipma-m4a704, xipma-a0a3b5r3p5, xipma-a0a3b5rfa0, xipma-m3zns4, xipma-m4a5i1, xipma-m3zxe7, xipma-a0a3b5r7u3, xipma-m3zyp9, xipma-m4a7a2, xipma-m4a1z8, xipma-a0a3b5qbj2, xipma-m4azu0, xipma-a0a3b5q4l7 Abstract Several attributes intuitively considered to be typical mammalian features, such as complex behavior, live birth and malignant disease such as cancer, also appeared several times independently in lower vertebrates. The genetic mechanisms underlying the evolution of these elaborate traits are poorly understood. The platyfish, X. maculatus, offers a unique model to better understand the molecular biology of such traits. We report here the sequencing of the platyfish genome. Integrating genome assembly with extensive genetic maps identified an unexpected evolutionary stability of chromosomes in fish, in contrast to in mammals. Genes associated with viviparity show signatures of positive selection, identifying new putative functional domains and rare cases of parallel evolution. We also find that genes implicated in cognition show an unexpectedly high rate of duplicate gene retention after the teleost genome duplication event, suggesting a hypothesis for the evolution of the behavioral complexity in fish, which exceeds that found in amphibians and reptiles. Title: Design, synthesis, and biological evaluation of acetophenone derivatives as dual binding acetylcholinesterase inhibitors Shen Y, Li B, Xu H, Zhang G Ref: Pharmazie, 68:307, 2013 : PubMed ESTHER: Shen_2013_Pharmazie_68_307 PubMedSearch: Shen 2013 Pharmazie 68 307 PubMedID: 23802426 Abstract As part of a project aimed at developing new agents for potential application in Alzheimer's disease, a new series of acetophenone derivatives which possess alkylamine side chains were designed, synthesized and assayed as acetylcholinesterase (AChE) inhibitors that could simultaneously bind to the peripheral and catalytic sites of the enzyme. The compounds were synthesized, and the inhibitory activities toward AChE and butyrylcholinesterase (BCHE) in vitro were determined using a modified Ellman method. Of the compounds tested, 6 derivatives were found to inhibit AChE in the micromolar range. The best compound, 2e, had an 1C50 of 0.13 microM. A detailed molecular modeling study was performed to explore the interaction of 2e with AChE. Title: Type II thioesterase gene (ECO-orf27) from Amycolatopsis orientalis influences production of the polyketide antibiotic, ECO-0501 (LW01) Shen Y, Huang H, Zhu L, Luo M, Chen D Ref: Biotechnol Lett, 34:2087, 2012 : PubMed ESTHER: Shen_2012_Biotechnol.Lett_34_2087 PubMedSearch: Shen 2012 Biotechnol.Lett 34 2087 PubMedID: 22850790 Abstract ECO-orf27 associated with the cluster of ECO-0501 (LW01) from Amycolatopsis orientalis is deduced to encode a type II thioesterase. Disruption of ECO-orf27 reduced LW01 production by 95 %. Complementation of the disrupted mutant with intact ECO-orf27 restored the production of LW01 suggesting that ECO-orf27 is crucial for LW01 biosynthesis. ECO-TE I, the gene encoding type I thioesterase from LW01 polyketide synthases, cannot complement ECO-orf27 deficient mutant distinguishing ECO-orf27 from type I thioesterase gene. Type II thioesterase gene pikAV from Streptomyces venezuelae could complement ECO-orf27 in A. orientalis indicating that the two genes are equivalent in their function. Overexpression of ECO-orf27 resulted in a 20 % increase in LW01 production providing an alternative approach for yield improvement. Title: Expression of Dpp6 in mouse embryonic craniofacial development Du J, Fan Z, Ma X, Gao Y, Wu Y, Liu S, Shen Y, Fan M, Wang S Ref: Acta Histochemica, 113:636, 2011 : PubMed ESTHER: Du_2011_Acta.Histochem_113_636 PubMedSearch: Du 2011 Acta.Histochem 113 636 PubMedID: 20817268 Abstract Dipeptidyl-peptidase-like protein 6 (DPP6), a member of the dipeptidyl aminopeptidase family, plays distinct roles in brain development, but its expression in embryonic craniofacial development is unknown. The expression pattern of Dpp6 in the maxillofacial region during mouse embryonic craniofacial development was analyzed by whole-mount in situ hybridization on sections and by real-time PCR analysis. Dpp6 expression was detected during mouse embryonic craniofacial development in embryos 11-13.5 days post-coitum (dpc). Real-time PCR showed high Dpp6 expression present in 11.5-13.5dpc, and this then decreased as development of maxillofacial region progressed. The expression pattern of Dpp6 suggests that Dpp6 may be involved in embryonic craniofacial development. Title: In vivo toxicity and immunogenicity of wheat germ agglutinin conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles for intranasal delivery to the brain Liu Q, Shao X, Chen J, Shen Y, Feng C, Gao X, Zhao Y, Li J, Zhang Q, Jiang X Ref: Toxicol Appl Pharmacol, 251:79, 2011 : PubMed ESTHER: Liu_2011_Toxicol.Appl.Pharmacol_251_79 PubMedSearch: Liu 2011 Toxicol.Appl.Pharmacol 251 79 PubMedID: 21163285 Abstract Biodegradable polymer-based nanoparticles have been widely studied to deliver therapeutic agents to the brain after intranasal administration. However, knowledge as to the side effects of nanoparticle delivery system to the brain is limited. The aim of this study was to investigate the in vivo toxicity and immunogenicity of wheat germ agglutinin (WGA) conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles (WGA-NP) after intranasal instillation. Sprague-Dawley rats were intranasally given WGA-NP for 7 continuous days. Amino acid neurotransmitters, lactate dehydrogenase (LDH) activity, reduced glutathione (GSH), acetylcholine, acetylcholinesterase activity, tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) in rat olfactory bulb (OB) and brain were measured to estimate the in vivo toxicity of WGA-NP. Balb/C mice were intranasally immunized by WGA-NP and then WGA-specific antibodies in serum and nasal wash were detected by indirect ELISA. WGA-NP showed slight toxicity to brain tissue, as evidenced by increased glutamate level in rat brain and enhanced LDH activity in rat OB. No significant changes in acetylcholine level, acetylcholinesterase activity, GSH level, TNF-alpha level and IL-8 level were observed in rat OB and brain for the WGA-NP group. WGA-specific antibodies in mice serum and nasal wash were not increased after two intranasal immunizations of WGA-NP. These results demonstrate that WGA-NP is a safe carrier system for intranasal delivery of therapeutic agents to the brain. Title: Surrogate based accurate quantification of endogenous acetylcholine in murine brain by hydrophilic interaction liquid chromatography-tandem mass spectrometry Peng L, Jiang T, Rong Z, Liu T, Wang H, Shao B, Ma J, Yang L, Kang L and Chen H <3 more author(s)> Peng L, Jiang T, Rong Z, Liu T, Wang H, Shao B, Ma J, Yang L, Kang L, Shen Y, Li H, Qi H, Chen H (- 3) Ref: Journal of Chromatography B Analyt Technol Biomed Life Sciences, 879:3927, 2011 : PubMed ESTHER: Peng_2011_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_879_3927 PubMedSearch: Peng 2011 J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci 879 3927 PubMedID: 22088352 Abstract Cholinergic dysfunction is known as a hallmark feature of Alzheimer's disease (AD). Measurement of endogenous acetylcholine (ACh) in specific brain regions is important in understanding the pathology of AD and in designing and evaluating novel cholinomimetic agents for the treatment of AD. Since ACh is an endogenous neurotransmitter, there is no real blank matrix available to construct standard curves. It has been a challenging task to determine ACh in complex brain matrices. To overcome these difficulties, we employed a surrogate analyte strategy using ACh-d(4) instead of ACh to generate calibration curves and Ch-d(9) as internal standard (IS). The brain samples were deproteinized by acetonitrile with IS. Analytes and IS were separated by a HILIC column with the mobile phase composed of 20 mM ammonium formate in water-acetonitrile (30:70, v/v, adjusted to pH 3.0 with formic acid) and monitored in multiple reaction monitoring (MRM) mode using a positive electrospray source. The concentrations of endogenous ACh were calculated based on the peak area ratio of the analyte to the IS using a regression equation for the corresponding surrogate standard (ACh-d(4)). The lower limit of detection was 0.2 ng/mL and linearity was maintained over the range of 10-1000 ng/mL. Compared to other currently available methods, this approach offers improved accuracy and precision for efficient analysis of ACh. The proposed method was proved successfully by evaluating the action of typical acetylcholinesterase inhibitor huperzine A in senescence accelerated mouse prone 8 (SAMP8). Title: Click-based synthesis and proteomic profiling of lipstatin analogues Ngai MH, Yang PY, Liu K, Shen Y, Wenk MR, Yao SQ, Lear MJ Ref: Chem Commun (Camb), 46:8335, 2010 : PubMed ESTHER: Ngai_2010_Chem.Commun.(Camb)_46_8335 PubMedSearch: Ngai 2010 Chem.Commun.(Camb) 46 8335 PubMedID: 20577697 Abstract Using click chemistry to enable both structural diversity and proteome profiling within a natural product derived library, two out of nineteen lipstatin analogues showed similar activity to Orlistat against fatty acid synthase (FAS), but with an improved ability to induce tumour cell death. Title: Residue Tyr224 is critical for the thermostability of Geobacillus sp. RD-2 lipase Wu L, Liu B, Hong Y, Sheng D, Shen Y, Ni J Ref: Biotechnol Lett, 32:107, 2010 : PubMed ESTHER: Wu_2010_Biotechnol.Lett_32_107 PubMedSearch: Wu 2010 Biotechnol.Lett 32 107 PubMedID: 19763406 Abstract A thermophilic lipase (lipGRD) from Geobacillus sp. RD-2, isolated from a hot spring in Yunnan, China, was cloned and over-expressed in Escherichia coli. The function of the conserved residue, Tyr224, near the presumed temperature switch site was analyzed by site-directed saturation mutagenesis. The activity of the wild type lipGRD was optimal at 55 degrees C and pH 7.5, but that from mutant Y224C was optimally active at 35 degrees C, whereas Y224P lipase was optimally active at 65 degrees C. Furthermore, the latter lipase retained 60% of its activity after incubation at 65 degrees C for 5 h. The conserved residue Tyr224, which is close to the lid helix, is the key amino acid residue determining the thermostability of the thermostable lipase. Title: The genome sequence of taurine cattle: a window to ruminant biology and evolution Elsik CG, Tellam RL, Worley KC, Gibbs RA, Muzny DM, Weinstock GM, Adelson DL, Eichler EE, Elnitski L and Zhao FQ <297 more author(s)> Elsik CG, Tellam RL, Worley KC, Gibbs RA, Muzny DM, Weinstock GM, Adelson DL, Eichler EE, Elnitski L, Guigo R, Hamernik DL, Kappes SM, Lewin HA, Lynn DJ, Nicholas FW, Reymond A, Rijnkels M, Skow LC, Zdobnov EM, Schook L, Womack J, Alioto T, Antonarakis SE, Astashyn A, Chapple CE, Chen HC, Chrast J, Camara F, Ermolaeva O, Henrichsen CN, Hlavina W, Kapustin Y, Kiryutin B, Kitts P, Kokocinski F, Landrum M, Maglott D, Pruitt K, Sapojnikov V, Searle SM, Solovyev V, Souvorov A, Ucla C, Wyss C, Anzola JM, Gerlach D, Elhaik E, Graur D, Reese JT, Edgar RC, McEwan JC, Payne GM, Raison JM, Junier T, Kriventseva EV, Eyras E, Plass M, Donthu R, Larkin DM, Reecy J, Yang MQ, Chen L, Cheng Z, Chitko-McKown CG, Liu GE, Matukumalli LK, Song J, Zhu B, Bradley DG, Brinkman FS, Lau LP, Whiteside MD, Walker A, Wheeler TT, Casey T, German JB, Lemay DG, Maqbool NJ, Molenaar AJ, Seo S, Stothard P, Baldwin CL, Baxter R, Brinkmeyer-Langford CL, Brown WC, Childers CP, Connelley T, Ellis SA, Fritz K, Glass EJ, Herzig CT, Iivanainen A, Lahmers KK, Bennett AK, Dickens CM, Gilbert JG, Hagen DE, Salih H, Aerts J, Caetano AR, Dalrymple B, Garcia JF, Gill CA, Hiendleder SG, Memili E, Spurlock D, Williams JL, Alexander L, Brownstein MJ, Guan L, Holt RA, Jones SJ, Marra MA, Moore R, Moore SS, Roberts A, Taniguchi M, Waterman RC, Chacko J, Chandrabose MM, Cree A, Dao MD, Dinh HH, Gabisi RA, Hines S, Hume J, Jhangiani SN, Joshi V, Kovar CL, Lewis LR, Liu YS, Lopez J, Morgan MB, Nguyen NB, Okwuonu GO, Ruiz SJ, Santibanez J, Wright RA, Buhay C, Ding Y, Dugan-Rocha S, Herdandez J, Holder M, Sabo A, Egan A, Goodell J, Wilczek-Boney K, Fowler GR, Hitchens ME, Lozado RJ, Moen C, Steffen D, Warren JT, Zhang J, Chiu R, Schein JE, Durbin KJ, Havlak P, Jiang H, Liu Y, Qin X, Ren Y, Shen Y, Song H, Bell SN, Davis C, Johnson AJ, Lee S, Nazareth LV, Patel BM, Pu LL, Vattathil S, Williams RL, Jr., Curry S, Hamilton C, Sodergren E, Wheeler DA, Barris W, Bennett GL, Eggen A, Green RD, Harhay GP, Hobbs M, Jann O, Keele JW, Kent MP, Lien S, McKay SD, McWilliam S, Ratnakumar A, Schnabel RD, Smith T, Snelling WM, Sonstegard TS, Stone RT, Sugimoto Y, Takasuga A, Taylor JF, Van Tassell CP, Macneil MD, Abatepaulo AR, Abbey CA, Ahola V, Almeida IG, Amadio AF, Anatriello E, Bahadue SM, Biase FH, Boldt CR, Carroll JA, Carvalho WA, Cervelatti EP, Chacko E, Chapin JE, Cheng Y, Choi J, Colley AJ, de Campos TA, De Donato M, Santos IK, de Oliveira CJ, Deobald H, Devinoy E, Donohue KE, Dovc P, Eberlein A, Fitzsimmons CJ, Franzin AM, Garcia GR, Genini S, Gladney CJ, Grant JR, Greaser ML, Green JA, Hadsell DL, Hakimov HA, Halgren R, Harrow JL, Hart EA, Hastings N, Hernandez M, Hu ZL, Ingham A, Iso-Touru T, Jamis C, Jensen K, Kapetis D, Kerr T, Khalil SS, Khatib H, Kolbehdari D, Kumar CG, Kumar D, Leach R, Lee JC, Li C, Logan KM, Malinverni R, Marques E, Martin WF, Martins NF, Maruyama SR, Mazza R, McLean KL, Medrano JF, Moreno BT, More DD, Muntean CT, Nandakumar HP, Nogueira MF, Olsaker I, Pant SD, Panzitta F, Pastor RC, Poli MA, Poslusny N, Rachagani S, Ranganathan S, Razpet A, Riggs PK, Rincon G, Rodriguez-Osorio N, Rodriguez-Zas SL, Romero NE, Rosenwald A, Sando L, Schmutz SM, Shen L, Sherman L, Southey BR, Lutzow YS, Sweedler JV, Tammen I, Telugu BP, Urbanski JM, Utsunomiya YT, Verschoor CP, Waardenberg AJ, Wang Z, Ward R, Weikard R, Welsh TH, Jr., White SN, Wilming LG, Wunderlich KR, Yang J, Zhao FQ (- 297) Ref: Science, 324:522, 2009 : PubMed ESTHER: Elsik_2009_Science_324_522 PubMedSearch: Elsik 2009 Science 324 522 PubMedID: 19390049 Gene_locus related to this paper: bovin-2neur, bovin-a0jnh8, bovin-a5d7b7, bovin-ACHE, bovin-balip, bovin-dpp4, bovin-dpp6, bovin-e1bi31, bovin-e1bn79, bovin-est8, bovin-f1mbd6, bovin-f1mi11, bovin-f1mr65, bovin-f1n1l4, bovin-g3mxp5, bovin-q0vcc8, bovin-q2kj30, bovin-q3t0r6, bovin-thyro Abstract To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production. Title: Synthesis and biological evaluation of novel flavonoid derivatives as dual binding acetylcholinesterase inhibitors Shen Y, Zhang J, Sheng R, Dong X, He Q, Yang B, Hu Y Ref: J Enzyme Inhib Med Chem, 24:372, 2009 : PubMed ESTHER: Shen_2009_J.Enzyme.Inhib.Med.Chem_24_372 PubMedSearch: Shen 2009 J.Enzyme.Inhib.Med.Chem 24 372 PubMedID: 18830885 Abstract A new series of flavonoid derivatives have been designed, synthesised and evaluated as acetylcholinesterase inhibitors that could bind simultaneously to the peripheral and catalytic sites of the enzyme. Among them, fifteen derivatives were found to inhibit the enzyme in the micromolar range and isoflavone derivatives possessed more potent inhibitory activity than other flavonoid derivatives. The best compound 9a had its inhibitory activity (IC(50) = 0.093 microM) in the same range as the reference compound, donepezil (IC(50) = 0.025 microM). Preliminary structure-activity relationships and a molecular modeling study for 9a have revealed that the isoflavone moiety plays a key role in the interaction of this series of derivatives with AChE by acting as an anchor in its peripheral anionic site. Title: Characterization of ST-4821 complex, a unique Neisseria meningitidis clone Peng J, Yang L, Yang F, Yang J, Yan Y, Nie H, Zhang X, Xiong Z, Jiang Y and Jin Q <9 more author(s)> Peng J, Yang L, Yang F, Yang J, Yan Y, Nie H, Zhang X, Xiong Z, Jiang Y, Cheng F, Xu X, Chen S, Sun L, Li W, Shen Y, Shao Z, Liang X, Xu J, Jin Q (- 9) Ref: Genomics, 91:78, 2008 : PubMed ESTHER: Peng_2008_Genomics_91_78 PubMedSearch: Peng 2008 Genomics 91 78 PubMedID: 18031983 Gene_locus related to this paper: neigo-pip, neima-metx, neimb-q9k0t9, neime-ESD, neime-NMA2216, neime-NMB0276, neime-NMB1877 Abstract Ten outbreaks of a new serogroup C meningococcal disease emerged during 2003-2005 in China. The multilocus sequence typing results indicated that unique sequence type 4821 clone meningococci were responsible for these outbreaks. Herein, we determined the entire genomic DNA sequence of serogroup C isolate 053442, which belongs to ST-4821. Comparison of 053442 gene contents with other meningococcal genomes shows that they have similar characteristics, including thousands of repetitive elements and simple sequence repeats, numerous phase-variable genes, and similar virulence-related factors. However, many strain-specific regions were found in each genome. We also present the results of a genomic comparison of 28 ST-4821 complex isolates that were isolated from different serogroups using comparative genomic hybridization analysis. Genome comparison between the newly emerged hyperinvasive isolates belonging to different serogroups will further our understanding of their respective pathogenetic mechanisms. Title: 2-Phenoxy-indan-1-one derivatives as acetylcholinesterase inhibitors: a study on the importance of modifications at the side chain on the activity Shen Y, Sheng R, Zhang J, He Q, Yang B, Hu Y Ref: Bioorganic & Medicinal Chemistry, 16:7646, 2008 : PubMed ESTHER: Shen_2008_Bioorg.Med.Chem_16_7646 PubMedSearch: Shen 2008 Bioorg.Med.Chem 16 7646 PubMedID: 18662884 Abstract As a part of our project aimed at developing new agents of potential application in AD, a new series of 2-phenoxy-indan-1-one derivatives which possess alkylamine side chain were designed, synthesized, and evaluated for their inhibitory activity against AChE and BuChE. Most of the compounds were found to inhibit AChE in the nanomolar range. The optimum inhibitor 3g exhibited 34-fold increase in AChE inhibition than donepezil and displayed neuroprotective effect against H(2)O(2)-induced cell death. Title: The genome of a lepidopteran model insect, the silkworm Bombyx mori Xia Q, Wang J, Zhou Z, Li R, Fan W, Cheng D, Cheng T, Qin J, Duana J and Morishita S <88 more author(s)> Xia Q, Wang J, Zhou Z, Li R, Fan W, Cheng D, Cheng T, Qin J, Duana J, Xu H, Li Q, Li N, Wang M, Dai F, Liu C, Lin Y, Zhao P, Zhang H, Liu S, Zha X, Li C, Zhao A, Pan M, Pan G, Shen Y, Gao Z, Wang Z, Wang G, Wu Z, Hou Y, Chai C, Yu Q, He N, Zhang Z, Li S, Yang H, Lu C, Xiang Z, Mita K, Kasahara M, Nakatani Y, Yamamoto K, Abe H, Ahsan B, Daimoni T, Doi K, Fujii T, Fujiwara H, Fujiyama A, Futahashi R, Hashimotol S, Ishibashi J, Iwami M, Kadono-Okuda K, Kanamori H, Kataoka H, Katsuma S, Kawaoka S, Kawasaki H, Kohara Y, Kozaki T, Kuroshu RM, Kuwazaki S, Matsushima K, Minami H, Nagayasu Y, Nakagawa T, Narukawa J, Nohata J, Ohishi K, Ono Y, Osanai-Futahashi M, Ozaki K, Qu W, Roller L, Sasaki S, Sasaki T, Seino A, Shimomura M, Shin-I T, Shinoda T, Shiotsuki T, Suetsugu Y, Sugano S, Suwa M, Suzuki Y, Takiya S, Tamura T, Tanaka H, Tanaka Y, Touhara K, Yamada T, Yamakawa M, Yamanaka N, Yoshikawa H, Zhong YS, Shimada T, Morishita S (- 88) Ref: Insect Biochemistry & Molecular Biology, 38:1036, 2008 : PubMed ESTHER: Xia_2008_Insect.Biochem.Mol.Biol_38_1036 PubMedSearch: Xia 2008 Insect.Biochem.Mol.Biol 38 1036 PubMedID: 19121390 Gene_locus related to this paper: bommo-a0mnw6, bommo-a1yw85, bommo-a9ls22, bommo-ACHE1, bommo-ACHE2, bommo-b0fgv8, bommo-b1q137, bommo-b1q139, bommo-b1q140, bommo-b1q141, bommo-b2zdz0, bommo-b3gef6, bommo-b3gef7, bommo-b3gs55, bommo-b3gs56, bommo-d2ktu3, bommo-d2ktu5, bommo-d9ile0, bommo-e1cga5, bommo-e1cga6, bommo-g8fpz6, bommo-h9iu43, bommo-h9iu46, bommo-h9iu47.1, bommo-h9iu47.2, bommo-h9iue5, bommo-h9ivg2, bommo-h9iwj7, bommo-h9iwj8, bommo-h9ix58, bommo-h9ixi1.1, bommo-h9ixi1.2, bommo-h9iy47, bommo-h9izw1, bommo-h9j0s4, bommo-h9j1y0, bommo-h9j3r0, bommo-h9j3w6, bommo-h9j3w7, bommo-h9j5t0, bommo-h9j8g3, bommo-h9j9k9, bommo-h9j066, bommo-h9j067, bommo-h9j593, bommo-h9j594, bommo-h9j990, bommo-h9jde8, bommo-h9jde9, bommo-h9jdf0, bommo-h9jds4, bommo-h9jle7, bommo-h9jn83, bommo-h9jn85, bommo-h9jrg2, bommo-h9jyh9, bommo-JHE, bommo-m1rmh6, bommo-q1hq05, bommo-q4tte1, bommo-h9j592, bommo-h9j604, bommo-h9jpm8, bommo-h9iss4, bommo-h9j2c7 Abstract Bombyx mori, the domesticated silkworm, is a major insect model for research, and the first lepidopteran for which draft genome sequences became available in 2004. Two independent data sets from whole-genome shotgun sequencing were merged and assembled together with newly obtained fosmid- and BAC-end sequences. The remarkably improved new assembly is presented here. The 8.5-fold sequence coverage of an estimated 432 Mb genome was assembled into scaffolds with an N50 size of approximately 3.7 Mb; the largest scaffold was 14.5 million base pairs. With help of a high-density SNP linkage map, we anchored 87% of the scaffold sequences to all 28 chromosomes. A particular feature was the high repetitive sequence content estimated to be 43.6% and that consisted mainly of transposable elements. We predicted 14,623 gene models based on a GLEAN-based algorithm, a more accurate prediction than the previous gene models for this species. Over three thousand silkworm genes have no homologs in other insect or vertebrate genomes. Some insights into gene evolution and into characteristic biological processes are presented here and in other papers in this issue. The massive silk production correlates with the existence of specific tRNA clusters, and of several sericin genes assembled in a cluster. The silkworm's adaptation to feeding on mulberry leaves, which contain toxic alkaloids, is likely linked to the presence of new-type sucrase genes, apparently acquired from bacteria. The silkworm genome also revealed the cascade of genes involved in the juvenile hormone biosynthesis pathway, and a large number of cuticular protein genes. 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: Complete genome sequence of Shigella flexneri 5b and comparison with Shigella flexneri 2a Nie H, Yang F, Zhang X, Yang J, Chen L, Wang J, Xiong Z, Peng J, Sun L and Jin Q <6 more author(s)> Nie H, Yang F, Zhang X, Yang J, Chen L, Wang J, Xiong Z, Peng J, Sun L, Dong J, Xue Y, Xu X, Chen S, Yao Z, Shen Y, Jin Q (- 6) Ref: BMC Genomics, 7:173, 2006 : PubMed ESTHER: Nie_2006_BMC.Genomics_7_173 PubMedSearch: Nie 2006 BMC.Genomics 7 173 PubMedID: 16822325 Gene_locus related to this paper: shifl-AES, shifl-BIOH, shifl-entf, shifl-FES, shifl-PTRB, shifl-S2753, shifl-SF1808, shifl-SF3046, shifl-yafa, shifl-YBFF, shifl-YCDJ, shifl-ycfp, shifl-YCJY, shifl-YFBB, shifl-YHET, shifl-YIEL, shifl-YJFP, shifl-YPFH, shiss-yeiG, shiss-yqia Abstract BACKGROUND: Shigella bacteria cause dysentery, which remains a significant threat to public health. Shigella flexneri is the most common species in both developing and developed countries. Five Shigella genomes have been sequenced, revealing dynamic and diverse features. To investigate the intra-species diversity of S. flexneri genomes further, we have sequenced the complete genome of S. flexneri 5b strain 8401 (abbreviated Sf8401) and compared it with S. flexneri 2a (Sf301). Title: Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery Yang F, Yang J, Zhang X, Chen L, Jiang Y, Yan Y, Tang X, Wang J, Xiong Z and Jin Q <17 more author(s)> Yang F, Yang J, Zhang X, Chen L, Jiang Y, Yan Y, Tang X, Wang J, Xiong Z, Dong J, Xue Y, Zhu Y, Xu X, Sun L, Chen S, Nie H, Peng J, Xu J, Wang Y, Yuan Z, Wen Y, Yao Z, Shen Y, Qiang B, Hou Y, Yu J, Jin Q (- 17) Ref: Nucleic Acids Research, 33:6445, 2005 : PubMed ESTHER: Yang_2005_Nucleic.Acids.Res_33_6445 PubMedSearch: Yang 2005 Nucleic.Acids.Res 33 6445 PubMedID: 16275786 Gene_locus related to this paper: ecoli-yeiG, shidy-IROD, shidy-q67dv1, shifl-AES, shifl-BIOH, shifl-entf, shifl-FES, shifl-PLDB, shifl-PTRB, shifl-S2753, shifl-SF1334, shifl-SF1808, shifl-SF3046, shifl-SF3908, shifl-yafa, shifl-YBFF, shifl-YCDJ, shifl-ycfp, shifl-YCJY, shifl-YFBB, shifl-YHET, shifl-YJFP, shifl-YPFH, shiss-yaim, shiss-yeiG, shiss-yqia Abstract The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300 approximately 700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features. Title: Two-dimensional protein database of human pancreas Hu L, Evers S, Lu ZH, Shen Y, Chen J Ref: Electrophoresis, 25:512, 2004 : PubMed ESTHER: Hu_2004_Electrophoresis_25_512 PubMedSearch: Hu 2004 Electrophoresis 25 512 PubMedID: 14760645 Abstract We report here the two-dimensional protein database of human pancreas. The proteins were analyzed by two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). Totally, 302 proteins were identified, of which about 27% were enzymes with a broad range of catalytic activities. Several of these are specifically expressed in pancreas, such as pancreatic amylase, pancreatic stone protein, pancreatitis-associated protein, pancreatic lipase, pancreatic elastase, etc. Structural and cytoskeletal proteins are also strongly represented on the gels. Thus, the pancreatic proteome reflects the organ's function. This work paves the way for further studies on pancreatic protein expression in health and disease, such as diabetes and pancreatic cancer. Title: Lipoprotein lipase gene is in linkage with blood pressure phenotypes in Chinese pedigrees Yang W, Huang J, Ge D, Yao C, Duan X, Shen Y, Qiang B, Gu D Ref: Hum Genet, 115:8, 2004 : PubMed ESTHER: Yang_2004_Hum.Genet_115_8 PubMedSearch: Yang 2004 Hum.Genet 115 8 PubMedID: 15127290 Abstract To elucidate the mechanism of lipid metabolism in the genesis of essential hypertension (EH), we linked blood pressure (BP) phenotypes with the lipoprotein lipase (LPL) gene. Variance component and sib-pair linkage models were used to test the relationship of the polymorphisms in the LPL gene region and EH in 148 Chinese hypertensive families. Linkage evidence with systolic BP (SBP) and diastolic BP (DBP) was observed in a total population of 148 pedigrees with seven flanking microsatellite markers of the LPL gene, with a maximum two-point LOD score of 2.68 and a maximum multipoint LOD score (MLS) of 2.37 for SBP and a maximum MLS of 1.54 for DBP. Suggestive linkage results around this region were also obtained in northern and southern subsets by geographic distribution. In addition, quantitative-transmission/disequilibrium-test analyses showed that there was linkage between DBP and two single nucleotide polymorphisms in the LPL gene. This is the first report of linkage between LPL gene and DBP in the Chinese population. The LPL gene itself might explain our results or the LPL gene region might harbor some genes to explain the observed results to some degree and might contribute to the variation of BP in the Chinese population. Title: Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing Ren SX, Fu G, Jiang XG, Zeng R, Miao YG, Xu H, Zhang YX, Xiong H, Lu G and Zhao GP <29 more author(s)> Ren SX, Fu G, Jiang XG, Zeng R, Miao YG, Xu H, Zhang YX, Xiong H, Lu G, Lu LF, Jiang HQ, Jia J, Tu YF, Jiang JX, Gu WY, Zhang YQ, Cai Z, Sheng HH, Yin HF, Zhang Y, Zhu GF, Wan M, Huang HL, Qian Z, Wang SY, Ma W, Yao ZJ, Shen Y, Qiang BQ, Xia QC, Guo XK, Danchin A, Saint Girons I, Somerville RL, Wen YM, Shi MH, Chen Z, Xu JG, Zhao GP (- 29) Ref: Nature, 422:888, 2003 : PubMed ESTHER: Ren_2003_Nature_422_888 PubMedSearch: Ren 2003 Nature 422 888 PubMedID: 12712204 Gene_locus related to this paper: lepin-AXEA, lepin-ESTA, lepin-LA0357, lepin-LA0587, lepin-LA0823, lepin-LA0932, lepin-LA1069, lepin-LA1345, lepin-LA1541, lepin-LA1702, lepin-LA1861, lepin-LA1902, lepin-LA1936, lepin-LA1955, lepin-LA2034, lepin-LA2132, lepin-LA2501, lepin-LA2505, lepin-LA2526, lepin-LA2544, lepin-LA2857, lepin-LA2958, lepin-LA3100, lepin-LA3107, lepin-LA3147, lepin-LA3604, lepin-LA3661, lepin-LA3669, lepin-LA3672, lepin-LA3770, lepin-LA3788, lepin-LA3851, lepin-LA3897, lepin-LA3998, lepin-LA4247, lepin-LB147, lepin-LB264, lepin-LB265, lepin-METX, lepin-q8f7a8, lepin-q72tt9 Abstract Leptospirosis is a widely spread disease of global concern. Infection causes flu-like episodes with frequent severe renal and hepatic damage, such as haemorrhage and jaundice. In more severe cases, massive pulmonary haemorrhages, including fatal sudden haemoptysis, can occur. Here we report the complete genomic sequence of a representative virulent serovar type strain (Lai) of Leptospira interrogans serogroup Icterohaemorrhagiae consisting of a 4.33-megabase large chromosome and a 359-kilobase small chromosome, with a total of 4,768 predicted genes. In terms of the genetic determinants of physiological characteristics, the facultatively parasitic L. interrogans differs extensively from two other strictly parasitic pathogenic spirochaetes, Treponema pallidum and Borrelia burgdorferi, although similarities exist in the genes that govern their unique morphological features. A comprehensive analysis of the L. interrogans genes for chemotaxis/motility and lipopolysaccharide synthesis provides a basis for in-depth studies of virulence and pathogenesis. The discovery of a series of genes possibly related to adhesion, invasion and the haematological changes that characterize leptospirosis has provided clues about how an environmental organism might evolve into an important human pathogen. Title: Genome-based analysis of virulence genes in a non-biofilm-forming Staphylococcus epidermidis strain (ATCC 12228) Zhang YQ, Ren SX, Li HL, Wang YX, Fu G, Yang J, Qin ZQ, Miao YG, Wang WY and Wen YM <7 more author(s)> Zhang YQ, Ren SX, Li HL, Wang YX, Fu G, Yang J, Qin ZQ, Miao YG, Wang WY, Chen RS, Shen Y, Chen Z, Yuan ZH, Zhao GP, Qu D, Danchin A, Wen YM (- 7) Ref: Molecular Microbiology, 49:1577, 2003 : PubMed ESTHER: Zhang_2003_Mol.Microbiol_49_1577 PubMedSearch: Zhang 2003 Mol.Microbiol 49 1577 PubMedID: 12950922 Gene_locus related to this paper: staep-GEHD, staep-lipas, staep-SE0011, staep-SE0226, staep-SE0386, staep-SE0389, staep-SE0424, staep-SE0564, staep-SE0714, staep-SE0745, staep-SE0980, staep-SE1436, staep-SE1460, staep-SE1510, staep-SE1780, staep-SE1929, staep-SERP2035, staep-SE2050, staep-SE2095, staep-SE2213, staep-SE2328, staep-SE2403 Abstract Staphylococcus epidermidis strains are diverse in their pathogenicity; some are invasive and cause serious nosocomial infections, whereas others are non-pathogenic commensal organisms. To analyse the implications of different virulence factors in Staphylococcus epidermidis infections, the complete genome of Staphylococcus epidermidis strain ATCC 12228, a non-biofilm forming, non-infection associated strain used for detection of residual antibiotics in food products, was sequenced. This strain showed low virulence by mouse and rat experimental infections. The genome consists of a single 2499 279 bp chromosome and six plasmids. The chromosomal G + C content is 32.1% and 2419 protein coding sequences (CDS) are predicted, among which 230 are putative novel genes. Compared to the virulence factors in Staphylococcus aureus, aside from delta-haemolysin and beta-haemolysin, other toxin genes were not found. In contrast, the majority of adhesin genes are intact in ATCC 12228. Most strikingly, the ica operon coding for the enzymes synthesizing interbacterial cellular polysaccharide is missing in ATCC 12228 and rearrangements of adjacent genes are shown. No mec genes, IS256, IS257, were found in ATCC 12228. It is suggested that the absence of the ica operon is a genetic marker in commensal Staphylococcus epidermidis strains which are less likely to become invasive. 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: Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY and Chen Z <11 more author(s)> Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (- 11) Ref: Genome Res, 10:1546, 2000 : PubMed ESTHER: Zhang_2000_Genome.Res_10_1546 PubMedSearch: Zhang 2000 Genome.Res 10 1546 PubMedID: 11042152 Gene_locus related to this paper: human-LYPLA1 Abstract Three hundred cDNAs containing putatively entire open reading frames (ORFs) for previously undefined genes were obtained from CD34+ hematopoietic stem/progenitor cells (HSPCs), based on EST cataloging, clone sequencing, in silico cloning, and rapid amplification of cDNA ends (RACE). The cDNA sizes ranged from 360 to 3496 bp and their ORFs coded for peptides of 58-752 amino acids. Public database search indicated that 225 cDNAs exhibited sequence similarities to genes identified across a variety of species. Homology analysis led to the recognition of 50 basic structural motifs/domains among these cDNAs. Genomic exon-intron organization could be established in 243 genes by integration of cDNA data with genome sequence information. Interestingly, a new gene named as HSPC070 on 3p was found to share a sequence of 105bp in 3' UTR with RAF gene in reversed transcription orientation. Chromosomal localizations were obtained using electronic mapping for 192 genes and with radiation hybrid (RH) for 38 genes. Macroarray technique was applied to screen the gene expression patterns in five hematopoietic cell lines (NB4, HL60, U937, K562, and Jurkat) and a number of genes with differential expression were found. The resource work has provided a wide range of information useful not only for expression genomics and annotation of genomic DNA sequence, but also for further research on the function of genes involved in hematopoietic development and differentiation. Title: [Study on Na(+)-K(+)-ATPase of the spiral ganglion neuron and acetylcholinesterase of the cochlea efferent nerve after electric stimulation in the scale media]. [Chinese] Wang Z, Shen Y Ref: Chinese Journal of Otorhinolaryngology, 29:92, 1994 : PubMed ESTHER: Wang_1994_Zhonghua.Er.Bi.Yan.Hou.Ke.Za.Zhi_29_92 PubMedSearch: Wang 1994 Zhonghua.Er.Bi.Yan.Hou.Ke.Za.Zhi 29 92 PubMedID: 7803098 Abstract In this study, it was found the concentration of Na(+)-K(+)-ATPase of the spiral ganglion neuron (SGN) increased 3 months after electric stimulation (0.1 mA) for 3 hours. However, current at 1.0 mA would destroy the enzyme production mechanism of SGN. Therefore 0.4 mA might be thought as a critical level because the concentration of the enzyme decreased with just above this level of stimulation. We suggest that the appropriate intensity range of the current stimulation of SGN should be controlled from 0.1 mA-0.4 mA. Acetylcholinesterase of the cochlea efferent nerve would increase with weak current stimulation (0.1 mA) which might play an important role in the protection of SGN during ototoxicity. This experimental results led to the conclusion that Na(+)-K(+)-ATPase of the SGN could be taken as an objective indicator presenting the functional changes of SGN quantitatively. | |||||||
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