Author Report for: Ding YNo contact information in database for Ding Y
Dhakal D, Kallifidas D, Chen M, Kokkaliari S, Chen QY, Paul VJ, Ding Y, Luesch H Ref: Org Lett, 25:2238, 2023 : PubMed ESTHER: Dhakal_2023_Org.Lett_25_2238 PubMedSearch: Dhakal 2023 Org.Lett 25 2238 PubMedID: 36961224 Abstract A polyketide synthase subcluster of cytotoxic apratoxin A was isolated from a Moorena bouillonii environmental DNA library and engineered with a thioesterase II domain for heterologous expression in the filamentous cyanobacterium Anabaena sp. PCC7120. Further engineering with a rhamnose-inducible promoter led to the production of (2R,3R,5R,7R)-3,7-dihydroxy-2,5,8,8-tetramethylnonanoic acid, a stereogenically rich chiral building block that is important to the efficient synthesis of apratoxin analogues, representing the first synthetic biology attempt for this type of polyketide fragment. Title: Genome-wide exploration of the GDSL-type esterase/lipase gene family in rapeseed reveals several BnGELP proteins active during early seedling development Ding Y, Xing L, Xu J, Jiang T, Tang X, Wang Y, Huang S, Hao W, Zhou X and Xie CG <1 more author(s)> Ding Y, Xing L, Xu J, Jiang T, Tang X, Wang Y, Huang S, Hao W, Zhou X, Zhang Y, Xie CG (- 1) Ref: Front Plant Sci, 14:1139972, 2023 : PubMed ESTHER: Ding_2023_Front.Plant.Sci_14_1139972 PubMedSearch: Ding 2023 Front.Plant.Sci 14 1139972 PubMedID: 37008509 Abstract The Gly-Asp-Ser-Leu (GDSL)-type esterase/lipase proteins (GELP) are one of the most important families of lipolytic enzymes and play prominent roles in seed germination and early seedling establishment through mobilizing the lipids stored in seeds. However, there are no comprehensive studies systematically investigating the GELP gene family in Brassica napus (BnGELP), and their biological significance to these physiological processes are far from understood. In the present study, a total of 240 BnGELP genes were identified in B. napus cultivar "Zhongshuang 11" (ZS11), which is nearly 2.3-fold more GELP genes than in Arabidopsis thaliana. The BnGELP genes clustered into 5 clades based on phylogenetic analysis. Ten BnGELPs were identified through zymogram analysis of esterase activity followed by mass spectrometry, among which five clustered into the clade 5. Gene and protein architecture, gene expression, and cis-element analyses of BnGELP genes in clade 5 suggested that they may play different roles in different tissues and in response to different abiotic stresses. BnGELP99 and BnGELP159 were slightly induced by cold, which may be attributed to two low-temperature responsive cis-acting regulatory elements present in their promoters. An increased activity of esterase isozymes by cold was also observed, which may reflect other cold inducible esterases/lipases in addition to the ten identified BnGELPs. This study provides a systemic view of the BnGELP gene family and offers a strategy for researchers to identify candidate esterase/lipase genes responsible for lipid mobilization during seed germination and early seedling establishment. Title: Maize resistance to witchweed through changes in strigolactone biosynthesis Li C, Dong L, Durairaj J, Guan JC, Yoshimura M, Quinodoz P, Horber R, Gaus K, Li J and Bouwmeester HJ <21 more author(s)> Li C, Dong L, Durairaj J, Guan JC, Yoshimura M, Quinodoz P, Horber R, Gaus K, Li J, Setotaw YB, Qi J, De Groote H, Wang Y, Thiombiano B, Flokova K, Walmsley A, Charnikhova TV, Chojnacka A, Correia de Lemos S, Ding Y, Skibbe D, Hermann K, Screpanti C, De Mesmaeker A, Schmelz EA, Menkir A, Medema M, van Dijk ADJ, Wu J, Koch KE, Bouwmeester HJ (- 21) Ref: Science, 379:94, 2023 : PubMed ESTHER: Li_2023_Science_379_94 PubMedSearch: Li 2023 Science 379 94 PubMedID: 36603079 Abstract Maize (Zea mays) is a major staple crop in Africa, where its yield and the livelihood of millions are compromised by the parasitic witchweed Striga. Germination of Striga is induced by strigolactones exuded from maize roots into the rhizosphere. In a maize germplasm collection, we identified two strigolactones, zealactol and zealactonoic acid, which stimulate less Striga germination than the major maize strigolactone, zealactone. We then showed that a single cytochrome P450, ZmCYP706C37, catalyzes a series of oxidative steps in the maize-strigolactone biosynthetic pathway. Reduction in activity of this enzyme and two others involved in the pathway, ZmMAX1b and ZmCLAMT1, can change strigolactone composition and reduce Striga germination and infection. These results offer prospects for breeding Striga-resistant maize. Title: Mechanism and Structural Insights Into a Novel Esterase, E53, Isolated From Erythrobacter longus Ding Y, Nie L, Yang XC, Li Y, Huo YY, Li Z, Gao Y, Cui HL, Li J, Xu XW Ref: Front Microbiol, 12:798194, 2022 : PubMed ESTHER: Ding_2022_Front.Microbiol_12_798194 PubMedSearch: Ding 2022 Front.Microbiol 12 798194 PubMedID: 35069500 Gene_locus related to this paper: erylo-E53 Abstract Esterases are a class of enzymes that split esters into an acid and an alcohol in a chemical reaction with water, having high potential in pharmaceutical, food and biofuel industrial applications. To advance the understanding of esterases, we have identified and characterized E53, an alkalophilic esterase from a marine bacterium Erythrobacter longus. The crystal structures of wild type E53 and three variants were solved successfully using the X-ray diffraction method. Phylogenetic analysis classified E53 as a member of the family IV esterase. The enzyme showed highest activity against p-nitrophenyl butyrate substrate at pH 8.5 9.5 and 40 C. Based on the structural feature, the catalytic pocket was defined as R1 (catalytic center), R2 (pocket entrance), and R3 (end area of pocket) regions. Nine variants were generated spanning R1-R3 and thorough functional studies were performed. Detailed structural analysis and the results obtained from the mutagenesis study revealed that mutations in the R1 region could regulate the catalytic reaction in both positive and negative directions; expanding the bottleneck in R2 region has improved the enzymatic activity; and R3 region was associated with the determination of the pH pattern of E53. N166A in R3 region showed reduced activity only under alkaline conditions, and structural analysis indicated the role of N166 in stabilizing the loop by forming a hydrogen bond with L193 and G233. In summary, the systematic studies on E53 performed in this work provide structural and functional insights into alkaliphilic esterases and further our knowledge of these enzymes. Title: Esterase-Activated Precipitating Strategy to Achieve Highly Specific Detection and Long-Term Imaging of Calcium Ions by Aggregation-Induced Phosphorescence Probe Wang Z, Xiong Z, Liu W, Zhu Q, Zhang X, Ding Y, Huang C, Feng H, Zhang K and Qian Z <1 more author(s)> Wang Z, Xiong Z, Liu W, Zhu Q, Zhang X, Ding Y, Huang C, Feng H, Zhang K, Zhu E, Qian Z (- 1) Ref: Analytical Chemistry, :, 2022 : PubMed ESTHER: Wang_2022_Anal.Chem__ PubMedSearch: Wang 2022 Anal.Chem PubMedID: 35315662 Abstract Spatial and temporal monitoring of bioactive targets such as calcium ions is vitally significant for their essential roles in physiological and biochemical functions. Herein, we proposed an esterase-activated precipitating strategy to achieve highly specific identification and long-term bioimaging of calcium ions via lighting up the calcium ions by precipitation using a water-soluble aggregation-induced phosphorescence (AIP) probe. The designed probe CaP2 has an AIP behavior and can be efficiently aggregated by calcium ions through the coupling coordination of carboxylic acid and cyanide groups, which enables it to light up Ca(2+) by precipitating-triggered phosphorescence. Four hydrophilic groups of tetraethylene glycol were introduced to endow the resulting probe CaP3 with extraordinary water solubility as well as excellent cellular penetration. Only when the probe CaP3 penetrates inside the live cells the existing esterase in cells can activate the probe to be transformed active CaP2 probe selectively binding with calcium ion in the surroundings. The probe was used to further evaluate the imaging of intracellular calcium ions in model organisms. The excellent imaging performance of CaP3 in Arabidopsis thaliana seedling roots demonstrates that CaP3 has the excellent capability of monitoring calcium ions in live-cell imaging, and furthermore CaP3 exhibits much better photostability and thereby greater potential in long-term imaging. This work established a general esterase-activated precipitating strategy to achieve specific detection and bioimaging in situ triggered by esterase in live cells, and established a water-soluble aggregation-induced phosphorescence probe with high selectivity to achieve specific sensing and long-term imaging of calcium ions in live cells. Title: ((E)-N-(4-(((2-Amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) Ameliorated Abeta(1-42)-Induced Alzheimer's Disease in SD Rats by Inhibiting Oxidative Stress and Apoptosis Ding Y, Wang X, Ji J, Zhang X, Chen M, Li S, Zhang Q, Liu P Ref: ACS Chem Neurosci, :, 2021 : PubMed ESTHER: Ding_2021_ACS.Chem.Neurosci__ PubMedSearch: Ding 2021 ACS.Chem.Neurosci PubMedID: 33517657 Abstract Our study investigated the protective effects of ((E)-N-(4-(((2-amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) 9b, a novel glycogen synthase kinase-3beta (GSK-3beta) inhibitor, on the learning and memory function of rats with amyloid-beta(1-42) (Abeta(1-42))-induced Alzheimer's disease (AD) and explored the possible mechanisms. Sixty male Sprague-Dawley (SD) rats were randomly divided into five groups: the control, Abeta, donepezil, and low-dose and high-dose 9b groups. The rats in the Abeta, donepezil, and two 9b intervention groups received a single microinjection of 10 microg of Abeta(1-42) into the hippocampus followed by intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC-Na), 12 (mg/kg)/d donepezil hydrochloride and 6 or 18 (mg/kg)/d compound 9b for 28 days, while the rats in the control group were treated with the vehicles. Learning and memory impairment were attenuated, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), acetylcholinesterase (AChE), and adenosine triphosphatase (ATPase) in the brain tissue were significantly increased (p < 0.05), and the concentrations of Abeta(1-42), phospho-tau (p-tau), and malondialdehyde (MDA) in the brain tissue were significantly decreased (p < 0.05) in the compound 9b group compared to the Abeta group. In addition, compound 9b regulated the imbalance in the concentrations of neurotransmitters and alleviated severe damage and apoptosis in the brains of the rats exposed to Abeta(1-42). The novel GSK-3beta inhibitor 9b could improve learning and memory dysfunction caused by Abeta(1-42) through its antioxidant and antiapoptotic effects. Title: Discovery of soluble epoxide hydrolase inhibitors through DNA-encoded library technology (ELT) Ding Y, Belyanskaya S, DeLorey JL, Messer JA, Joseph Franklin G, Centrella PA, Morgan BA, Clark MA, Skinner SR and Israel DI <3 more author(s)> Ding Y, Belyanskaya S, DeLorey JL, Messer JA, Joseph Franklin G, Centrella PA, Morgan BA, Clark MA, Skinner SR, Dodson JW, Li P, Marino JP, Jr., Israel DI (- 3) Ref: Bioorganic & Medicinal Chemistry, 41:116216, 2021 : PubMed ESTHER: Ding_2021_Bioorg.Med.Chem_41_116216 PubMedSearch: Ding 2021 Bioorg.Med.Chem 41 116216 PubMedID: 34023664 Inhibitor(s) related to this paper: GSK2256294A Abstract Inhibition of soluble epoxide hydrolase (sEH) has recently emerged as a new approach to treat cardiovascular disease and respiratory disease. Inhibitors based on 1,3,5-triazine chemotype were discovered through affinity selection against two triazine-based DNA-encoded libraries. The structure and activity relationship study led to the expansion of the original 1,4-cycloalkyl series to related aniline, piperidine, quinoline, aryl-ether and benzylic series. The 1,3-cycloalkyl chemotype led to the discovery of a clinical candidate (GSK2256294) for COPD. 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: Design, synthesis and evaluation of novel ferulic acid derivatives as multi-target-directed ligands for the treatment of Alzheimer's disease Lan JS, Zeng RF, Jiang XY, Hou JW, Liu Y, Hu ZH, Li HX, Li Y, Xie SS and Zhang T <1 more author(s)> Lan JS, Zeng RF, Jiang XY, Hou JW, Liu Y, Hu ZH, Li HX, Li Y, Xie SS, Ding Y, Zhang T (- 1) Ref: Bioorg Chem, :103413, 2019 : PubMed ESTHER: Lan_2019_Bioorg.Chem__103413 PubMedSearch: Lan 2019 Bioorg.Chem 103413 PubMedID: 31791679 Abstract A series of new ferulic acid derivatives were designed, synthesized and evaluated as multi-target inhibitors against Alzheimer's disease. In vitro studies indicated that most compounds showed significant potency to inhibit self-induced beta-amyloid (Abeta) aggregation and acetylcholinesterase (AChE), and had good antioxidant activity. Specifically, compound 4g exhibited the potent ability to inhibit cholinesterase (ChE) (IC50, 19.7nM for hAChE and 0.66muM for hBuChE) and the good Abeta aggregation inhibition (49.2% at 20muM), and it was also a good antioxidant (1.26 trolox equivalents). Kinetic and molecular modeling studies showed that compound 4g was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Moreover, compound 4g could remarkably increase PC12 cells viability in hydrogen peroxide-induced oxidative cell damage and Abeta-induced cell damage. Finally, compound 4g had good ability to cross the BBB using the PAMPA-BBB assay. These results suggested that compound 4g was a promising multifunctional ChE inhibitor for the further investigation. Title: Thermostability of Lipase A and Dynamic Communication Based on Residue Interaction Network Xia Q, Ding Y Ref: Protein Pept Lett, 26:702, 2019 : PubMed ESTHER: Xia_2019_Protein.Pept.Lett_26_702 PubMedSearch: Xia 2019 Protein.Pept.Lett 26 702 PubMedID: 31215367 Gene_locus related to this paper: bacsu-lip Abstract OBJECTIVE: Dynamic communication caused by mutation affects protein stability. The main objective of this study is to explore how mutations affect communication and to provide further insight into the relationship between heat resistance and signal propagation of Bacillus subtilis lipase (Lip A). METHODS: The relationship between dynamic communication and Lip A thermostability is studied by long-time MD simulation and residue interaction network. The Dijkstra algorithm is used to get the shortest path of each residue pair. Subsequently, time-series frequent paths and spatio-temporal frequent paths are mined through an Apriori-like algorithm. RESULTS: Time-series frequent paths show that the communication between residue pairs, both in wild-type lipase (WTL) and mutant 6B, becomes chaotic with an increase in temperature; however, more residues in 6B can maintain stable communication at high temperature, which may be associated with the structural rigidity. Furthermore, spatio-temporal frequent paths reflect the interactions among secondary structures. For WTL at 300K, beta7, alphaC, alphaB, the longest loop, alphaA and alphaF contact frequently. The 310-helix between beta3 and alphaA is penetrated by spatio-temporal frequent paths. At 400K, only alphaC can be frequently transmitted. For 6B, when at 300K, alphaA and alphaF are in more tight contact by spatio-temporal frequent paths though I157M and N166Y. Moreover, the rigidity of the active site His156 and the C-terminal of Lip A are increased, as reflected by the spatio-temporal frequent paths. At 400K, alphaA and alphaF, 310-helix between beta3 and alphaA, the longest loop, and the loop where the active site Asp133 is located can still maintain stable communication. CONCLUSION: From the perspective of residue dynamic communication, it is obviously found that mutations cause changes in interactions between secondary structures and enhance the rigidity of the structure, contributing to the thermal stability and functional activity of 6B. Title: Reassembly of native components with donepezil to execute dual-missions in Alzheimer's disease therapy Zhang H, Zhao Y, Yu M, Zhao Z, Liu P, Cheng H, Ji Y, Jin Y, Sun B and Ding Y <1 more author(s)> Zhang H, Zhao Y, Yu M, Zhao Z, Liu P, Cheng H, Ji Y, Jin Y, Sun B, Zhou J, Ding Y (- 1) Ref: J Control Release, 296:14, 2019 : PubMed ESTHER: Zhang_2019_J.Control.Release_296_14 PubMedSearch: Zhang 2019 J.Control.Release 296 14 PubMedID: 30639387 Abstract Alzheimer's disease (AD) is a multifaceted and progressive neurodegenerative disease characterized by accumulation of amyloid-beta (Abeta) and deficits of acetylcholine. Accordingly, the intra-/extra-cerebral level of high density lipoprotein (HDL) is crucial on the pathogenesis of AD; and most of all, various HDL-protein subtypes play a double-edged role in AD pathology, of which apolipoprotein A-I (apoA-I) gives protective outcomes. Inspired from "HDL bionics", we proposed biologically reassembled nanodrugs, donepezil-loaded apolipoprotein A-I-reconstituted HDL (rHDL/Do) that concurrently executed dual-missions of Abeta-targeting clearance and acetylcholinesterase (AChE) inhibition in AD therapy. Once prepared, rHDL/Do nanodrug achieved high drug encapsulation efficiency of 90.47%, and mimicked the configurations and properties of natural lipoproteins aiming to significantly enhance BBB penetration and modulate Abeta-induced neuronal damage both in vitro and in vivo. Surface plasmon resonance (SPR) analysis confirmed that rHDL/Do facilitated microglial-mediated Abeta intake and degradation, demonstrating low KD value with Abeta affinity (2.45x10(-8) of Abeta monomer and 2.78x10(-8) of Abeta oligomer). In AD animal models, daily treatment of rHDL/Do efficiently inhibited AChE activity, ameliorated neurologic variation, promoted Abeta clearance, and rescued memory loss at a safe level. The collective findings indicated that the biological nanodrug was provided with the capacities of BBB penetration, Abeta capture and degradation via microglial cells, and cholinergic dysfunction amelioration after controlled donepezil release. In summary, rHDL/Do nanodrugs could offer a promising strategy to synergize both symptom control and disease modification in AD therapy. 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: Safety, efficacy, and pharmacokinetics of pradefovir for the treatment of chronic hepatitis B infection Zhang H, Liu J, Zhu X, Li X, Jin W, Chen H, Wu M, Li C, Liu C and Ding Y <1 more author(s)> Zhang H, Liu J, Zhu X, Li X, Jin W, Chen H, Wu M, Li C, Liu C, JunqiNiu, Ding Y (- 1) Ref: Antiviral Res, :104693, 2019 : PubMed ESTHER: Zhang_2019_Antiviral.Res__104693 PubMedSearch: Zhang 2019 Antiviral.Res 104693 PubMedID: 31838002 Abstract BACKGROUND & AIMS: Pradefovir is a liver targeted novel prodrug of adefovir (PMEA) developed to provide higher antiviral activity with reduced systemic toxicities. This study evaluated the tolerability, pharmacokinetics, and antiviral activity of pradefovir in patients with chronic hepatitis B (CHB) virus infection. METHODS: Non-cirrhotic, treatment-naive subjects with CHB were divided into five groups (10 patients each) and randomized within each group in a ratio of 6:2:2 to receive an ascending dose of 30, 60, 75, 90, or 120mg pradefovir, 10mg adefovir dipivoxil (ADV), or 300mg tenofovir disoproxil fumarate (TDF) once a day for 28 days. RESULTS: A total of 51 subjects were randomized and 49 subjects completed the study. The groups were well matched and included 39 males, of whom 71% were hepatitis B e-antigen-negative with a mean hepatitis B virus (HBV) DNA level of 6.4-7.16 log10 IU/mL. No subject experienced a serious adverse event or nephrotoxicity. The most frequently reported adverse event was asymptomatic reduction in blood cholinesterase levels in the pradefovir group which recovered without any treatment about 13+/-7 days after drug discontinuation. This adverse event was not observed in the ADV and TDF groups. The mean changes in serum HBV DNA were -2.78, -2.77, -3.08, -3.18, -3.44, -2.34, and -3.07 log10 IU/mL at 30, 60, 75, 90, and 120mg pradefovir, 10mg ADV and 300mg TDF, respectively, with plateau levels reached with 60mg pradefovir. Pradefovir and its metabolite PMEA showed linear pharmacokinetics proportional to the dose. The half-life of PMEA in the pradefovir group was 11.47-17.63h. CONCLUSIONS: Short-term use of pradefovir was well tolerated. A decline in HBV DNA levels was superior to TDF at higher doses of pradefovir. 30-60mg pradefovir is recommended for CHB treatment. CLINICAL TRIAL NUMBER: CTR20150224. Title: Long noncoding RNA ABHD11-AS1 functions as a competing endogenous RNA to regulate papillary thyroid cancer progression by miR-199a-5p/SLC1A5 axis Zhuang X, Tong H, Ding Y, Wu L, Cai J, Si Y, Zhang H, Shen M Ref: Cell Death Dis, 10:620, 2019 : PubMed ESTHER: Zhuang_2019_Cell.Death.Dis_10_620 PubMedSearch: Zhuang 2019 Cell.Death.Dis 10 620 PubMedID: 31409775 Gene_locus related to this paper: human-ABHD11 Abstract With the increasing incidence of papillary thyroid cancer (PTC), more attention has been paid to exploring the mechanism of PTC initiation and progression. In addition, ectopic expression of long noncoding RNAs (lncRNAs) is reported to play a pivotal role in multiple human cancers. Based on these findings, we examined lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) expression and its clinical significance, biological function and mechanism in PTC. First, we analyzed thyroid ABHD11-AS1 expression in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then, qRT-PCR was applied to detect the expression in paired PTC tissues and adjacent normal tissues, as well as in PTC cell lines (TPC-1 and K-1) and a normal thyroid follicular epithelium cell line (Nthy-ori3-1). In addition, we validated the relationship between ABHD11-AS1 expression and clinicopathological features by the Pearson X(2) test. The oncogenic role of ABHD11-AS1 and its regulation of miR-199a-5p in PTC were examined by biological assays. Finally, bioinformatics analysis and mechanism assays were used to elucidate the underlying mechanism. We found that ABHD11-AS1 was remarkably overexpressed in PTC, and high expression was related to tumor size, lymph node metastasis, extrathyroidal extension and advanced TNM stage. Moreover, ABHD11-AS1 enhanced the abilities of cell proliferation, migration, and invasion, inhibited apoptosis in vitro, promoted tumorigenesis in vivo via sponging miR-199a-5p and then induced SLC1A5 activation. In addition, rescue assays were performed to confirm the ABHD11-AS1/miR-199a-5p/SLC1A5 axis. Taken together, the data show that ABHD11-AS1 acts as a competing endogenous RNA (ceRNA) to exert malignant properties in PTC through the miR-199a-5p/SLC1A5 axis. Therefore, our study may shed light on PTC diagnosis and therapies. Title: A pH responsive AIE probe for enzyme assays Shi L, Liu Y, Wang Q, Wang T, Ding Y, Cao Y, Li Z, Wei H Ref: Analyst, 143:741, 2018 : PubMed ESTHER: Shi_2018_Analyst_143_741 PubMedSearch: Shi 2018 Analyst 143 741 PubMedID: 29323362 Abstract By combining leucine (Leu) and tetraphenylethene (TPE), a pH-sensitive aggregation induced emission (AIE) probe TPE-Leu was developed. The aliphatic amine in TPE-Leu was more easily protonated under acidic conditions, which made TPE-Leu more water soluble. Therefore, the protonated AIE probe showed weak fluorescence under acidic conditions. When the pH was changed to basic conditions, it showed strong fluorescence due to the hydrophobic nature of TPE-Leu. We demonstrated that the probe showed high selectivity toward pH changes with the coexistence of other potential species such as metal ions, redox agents, and biomolecules. In contrast, TPE-NH2 did not exhibit obvious pH-sensitive properties. Moreover, TPE-Leu was further utilized to develop a sensitive and selective sensing platform for urease and acetylcholinesterase (AChE) detection. The current study not only provides a new strategy for designing pH-sensitive fluorescent probes for bioassays but also broadens the applications of AIE probes. Title: Discovering Drugs with DNA-Encoded Library Technology: From Concept to Clinic with an Inhibitor of Soluble Epoxide Hydrolase Belyanskaya SL, Ding Y, Callahan JF, Lazaar AL, Israel DI Ref: Chembiochem, 18:837, 2017 : PubMed ESTHER: Belyanskaya_2017_Chembiochem_18_837 PubMedSearch: Belyanskaya 2017 Chembiochem 18 837 PubMedID: 28281333 Abstract DNA-encoded chemical library technology was developed with the vision of its becoming a transformational platform for drug discovery. The hope was that a new paradigm for the discovery of low-molecular-weight drugs would be enabled by combining the vast molecular diversity achievable with combinatorial chemistry, the information-encoding attributes of DNA, the power of molecular biology, and a streamlined selection-based discovery process. Here, we describe the discovery and early clinical development of GSK2256294, an inhibitor of soluble epoxide hydrolase (sEH, EPHX2), by using encoded-library technology (ELT). GSK2256294 is an orally bioavailable, potent and selective inhibitor of sEH that has a long half life and produced no serious adverse events in a first-time-in-human clinical study. To our knowledge, GSK2256294 is the first molecule discovered from this technology to enter human clinical testing and represents a realization of the vision that DNA-encoded chemical library technology can efficiently yield molecules with favorable properties that can be readily progressed into high-quality drugs. Title: Design, synthesis and biological activity of novel donepezil derivatives bearing N-benzyl pyridinium moiety as potent and dual binding site acetylcholinesterase inhibitors Lan JS, Zhang T, Liu Y, Yang J, Xie SS, Liu J, Miao ZY, Ding Y Ref: Eur Journal of Medicinal Chemistry, 133:184, 2017 : PubMed ESTHER: Lan_2017_Eur.J.Med.Chem_133_184 PubMedSearch: Lan 2017 Eur.J.Med.Chem 133 184 PubMedID: 28388521 Abstract A series of new donepezil derivatives were designed synthesized and evaluated as multifunctional cholinesterase inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of them exhibited significant potency to inhibit acetylcholinesterase and self-induced beta-amyloid (Abeta) aggregation, and moderate antioxidant activity. Especially, compound 5b presented the greatest ability to inhibit cholinesterase (IC50, 1.9 nM for eeAChE and 0.8 nM for hAChE), good inhibition of Abeta aggregation (53.7% at 20 muM) and good antioxidant activity (0.54 trolox equivalents). Kinetic and molecular modeling studies indicated that compound 5b was a mixed-type inhibitor, binding simultaneously to the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, compound 5b could reduce PC12 cells death induced by oxidative stress and Abeta (1-42). Moreover, in vivo experiments showed that compound 5b was nontoxic and tolerated at doses up to 2000 mg/kg. These results suggested that compound 5b might be an excellent multifunctional agent for AD treatment. Title: Design, synthesis and evaluation of novel cinnamic acid derivatives bearing N-benzyl pyridinium moiety as multifunctional cholinesterase inhibitors for Alzheimer's disease Lan JS, Hou JW, Liu Y, Ding Y, Zhang Y, Li L, Zhang T Ref: J Enzyme Inhib Med Chem, 32:776, 2017 : PubMed ESTHER: Lan_2017_J.Enzyme.Inhib.Med.Chem_32_776 PubMedSearch: Lan 2017 J.Enzyme.Inhib.Med.Chem 32 776 PubMedID: 28585866 Abstract A novel family of cinnamic acid derivatives has been developed to be multifunctional cholinesterase inhibitors against AD by fusing N-benzyl pyridinium moiety and different substituted cinnamic acids. In vitro studies showed that most compounds were endowed with a noteworthy ability to inhibit cholinesterase, self-induced Abeta (1-42) aggregation, and to chelate metal ions. Especially, compound 5l showed potent cholinesterase inhibitory activity (IC50, 12.1 nM for eeAChE, 8.6 nM for hAChE, 2.6 muM for eqBuChE and 4.4 muM for hBuChE) and the highest selectivity toward AChE over BuChE. It also showed good inhibition of Abeta (1-42) aggregation (64.7% at 20 muM) and good neuroprotection on PC12 cells against amyloid-induced cell toxicity. Finally, compound 5l could penetrate the BBB, as forecasted by the PAMPA-BBB assay and proved in OF1 mice by ex vivo experiments. Overall, compound 5l seems to be a promising lead compound for the treatment of Alzheimer's diseases. Title: Design, synthesis and biological evaluation of novel coumarin-N-benzyl pyridinium hybrids as multi-target agents for the treatment of Alzheimer's disease Lan JS, Ding Y, Liu Y, Kang P, Hou JW, Zhang XY, Xie SS, Zhang T Ref: Eur Journal of Medicinal Chemistry, 139:48, 2017 : PubMed ESTHER: Lan_2017_Eur.J.Med.Chem_139_48 PubMedSearch: Lan 2017 Eur.J.Med.Chem 139 48 PubMedID: 28797883 Abstract Combining N-benzyl pyridinium moiety and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activities were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for ChE and Abeta (1-42) self-aggregation, and clearly selective inhibition to MAO-B over MAO-A. Of these compounds, compound 7f was the most potent inhibitor for hMAO-B, and it was also a good and balanced inhibitor to ChEs and hMAO-B (0.0373 muM for eeAChE; 2.32 muM for eqBuChE; 1.57 muM for hMAO-B). Molecular modeling and kinetic studies revealed that compound 7f was a mixed-type inhibitor, which bond simultaneously to CAS and PAS of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, compound 7f with no toxicity on PC12 neuroblastoma cells, showed good ability to inhibit Abeta (1-42) self-aggregation and cross the BBB. Collectively, all these results suggested that compound 7f might be a promising multi-target lead candidate worthy of further pursuit. Title: The Relation Between Lipase Thermostability and Dynamics of Hydrogen Bond and Hydrogen Bond Network Based on Long Time Molecular Dynamics Simulation Zhang L, Ding Y Ref: Protein Pept Lett, 24:643, 2017 : PubMed ESTHER: Zhang_2017_Protein.Pept.Lett_24_643 PubMedSearch: Zhang 2017 Protein.Pept.Lett 24 643 PubMedID: 28464764 Abstract BACKGROUND: Compared with the wild type of lipase (WTL), mutant lipase 6B has twelve mutations (A15S, F17S, A20E, N89Y, G111D, L114P, A132D, M134E, M137P, I157M, S163P, N166Y). The melting temperature of 6B (78.2 degrees C) is much higher than that of WTL (56 degrees C). Hydrogen bond (HB) play an important role in stabilizing the protein. It is important to analyze how mutations affect hydrogen bond and hydrogen bond network and explain how hydrogen bond and hydrogen bond network affect lipase thermostability by the change of the intensity of HB and HB networks with temperature changing. OBJECTIVE: Study the dynamics of HB and HB networks to find that how HBs and HB networks change over time and over temperature in WTL and 6B. METHOD: Long time MD simulations of WTL and 6B are carried out to analyze how mutations affect hydrogen bond and hydrogen bond network. All proteins were simulated at 300K, 325K, 350K, 375K, 400K for 300ns respectively. The definition of HB is that the distance between acceptor and donor is smaller than a cutoff 3.0 A and the angle between Donor-H and H-Acceptor is larger than 120o. If two or more HBs connect together, they formed HB network. In the network, residues that formed HB represent nodes, the HB interactions between residues represent edges. The persistence value of HB is computed by . RESULTS: The persistence values of HBs formed by mutations A15S, A20E, G111D, M137P, N166Y are significantly different from that of WTL. HB Glu20-Ser24, Asp111-Asp144, Leu160-Tyr166 and Lys170-Tyr166 are important to stabilize 6B. In addition, the HB networks dynamics show that there are three HB networks are more stable in mutants than that in WTL. The first HB network makes beta3, beta5, loop and 310-helix closely connect with each other at mutants. The second HB network increases the rigidity of the loop, alphaC, beta3 and beta5. The third HB network enhances the interaction between loops, alphaB and alphaC. CONCLUSION: The higher HB persistence value generally means that the HB is more stable. These mutations directly improve the stability of these HBs referring to their persistence values, which show that mutations strengthen the ability of HBs to withstand high temperature and then stabilize the secondary structure. It is thus clear that the mutations change the stability of HBs and the HB networks, which are responsible for increasing protein thermostability. Title: Does cadmium affect the toxicokinetics of permethrin in Chironomus dilutus at sublethal level? Evidence of enzymatic activity and gene expression Chen X, Li H, Zhang J, Ding Y, You J Ref: Environ Pollut, 218:1005, 2016 : PubMed ESTHER: Chen_2016_Environ.Pollut_218_1005 PubMedSearch: Chen 2016 Environ.Pollut 218 1005 PubMedID: 27567170 Abstract Pyrethroids and metals were simultaneously detected in aquatic environment and showed antagonistic lethality to the benthic invertebrate, Chironomus dilutus. Accelerated biotransformation of pyrethroids in organism by the presence of metals was proposed as the likely reason for the antagonism. Mechanistic explanation for the role of toxicokinetics of pyrethroids in the antagonistic interaction would help better understanding the reasons for the joint toxicity. The goal was achieved in the current study by evaluating the impact of cadmium on toxicokinetic parameters of permethrin in C. dilutus, and by explaining the interaction through quantifying the activity and gene expression of biotransformation-related enzymes. Toxicokinetic parameters were simulated using a first-order kinetic model. Bioconcentration factors and uptake and elimination rate constants for permethrin were not significantly changed with the addition of cadmium at sublethal level, neither did the activity of enzymes, including glutathione S-transferase (GST), carboxylesterase (CarE), catalase and lipid peroxidation. Yet, the activities of metabolism-related enzymes (GST and CarE) showed an elevating tendency with adding cadmium. Furthermore, the expression of metabolism-related genes, including cytochrome P450 and glutathione S-transferase genes were significantly up-regulated in C. dilutus exposed to a mixture of permethrin and cadmium compared with permethrin only. Although co-exposure to cadmium did not induce toxicokinetic changes of permethrin in C. dilutus, it did enhance the activity of metabolic enzymes which were encoded by the metabolism-related genes, suggesting an acceleration of biotransformation of permethrin to less toxic metabolites in the midges. This possibly explained the antagonistic interaction for permethrin and cadmium. Title: Genome sequencing of the perciform fish Larimichthys crocea provides insights into molecular and genetic mechanisms of stress adaptation Ao J, Mu Y, Xiang LX, Fan D, Feng M, Zhang S, Shi Q, Zhu LY, Li T and Chen X <19 more author(s)> Ao J, Mu Y, Xiang LX, Fan D, Feng M, Zhang S, Shi Q, Zhu LY, Li T, Ding Y, Nie L, Li Q, Dong WR, Jiang L, Sun B, Zhang X, Li M, Zhang HQ, Xie S, Zhu Y, Jiang X, Wang X, Mu P, Chen W, Yue Z, Wang Z, Wang J, Shao JZ, Chen X (- 19) Ref: PLoS Genet, 11:e1005118, 2015 : PubMed ESTHER: Ao_2015_PLoS.Genet_11_E1005118 PubMedSearch: Ao 2015 PLoS.Genet 11 E1005118 PubMedID: 25835551 Gene_locus related to this paper: larcr-a0a0f8ay25, larcr-a0a0f8cf53, larcr-a0a0f8cir1, larcr-a0a0f8d1j2, larcr-a0a0f8alq6, larcr-a0a0f8bdu4, larcr-a0a0f8abw1, larcr-a0a0f8ahh1, larcr-a0a0f8avc6, larcr-a0a0f8al93, larcr-a0a0f8aed8, larcr-a0a0f7ir14, larcr-a0a0f8aje8, larcr-k9lsm3, larcr-a0a0f8but5, larcr-a0a0f8af44 Abstract The large yellow croaker Larimichthys crocea (L. crocea) is one of the most economically important marine fish in China and East Asian countries. It also exhibits peculiar behavioral and physiological characteristics, especially sensitive to various environmental stresses, such as hypoxia and air exposure. These traits may render L. crocea a good model for investigating the response mechanisms to environmental stress. To understand the molecular and genetic mechanisms underlying the adaptation and response of L. crocea to environmental stress, we sequenced and assembled the genome of L. crocea using a bacterial artificial chromosome and whole-genome shotgun hierarchical strategy. The final genome assembly was 679 Mb, with a contig N50 of 63.11 kb and a scaffold N50 of 1.03 Mb, containing 25,401 protein-coding genes. Gene families underlying adaptive behaviours, such as vision-related crystallins, olfactory receptors, and auditory sense-related genes, were significantly expanded in the genome of L. crocea relative to those of other vertebrates. Transcriptome analyses of the hypoxia-exposed L. crocea brain revealed new aspects of neuro-endocrine-immune/metabolism regulatory networks that may help the fish to avoid cerebral inflammatory injury and maintain energy balance under hypoxia. Proteomics data demonstrate that skin mucus of the air-exposed L. crocea had a complex composition, with an unexpectedly high number of proteins (3,209), suggesting its multiple protective mechanisms involved in antioxidant functions, oxygen transport, immune defence, and osmotic and ionic regulation. Our results reveal the molecular and genetic basis of fish adaptation and response to hypoxia and air exposure. The data generated by this study will provide valuable resources for the genetic improvement of stress resistance and yield potential in L. crocea. Title: Outbred genome sequencing and CRISPR/Cas9 gene editing in butterflies Li X, Fan D, Zhang W, Liu G, Zhang L, Zhao L, Fang X, Chen L, Dong Y and Wang W <14 more author(s)> Li X, Fan D, Zhang W, Liu G, Zhang L, Zhao L, Fang X, Chen L, Dong Y, Chen Y, Ding Y, Zhao R, Feng M, Zhu Y, Feng Y, Jiang X, Zhu D, Xiang H, Feng X, Li S, Wang J, Zhang G, Kronforst MR, Wang W (- 14) Ref: Nat Commun, 6:8212, 2015 : PubMed ESTHER: Li_2015_Nat.Commun_6_8212 PubMedSearch: Li 2015 Nat.Commun 6 8212 PubMedID: 26354079 Gene_locus related to this paper: papxu-a0a194pj15, papxu-a0a194q254, papma-a0a194rdx2, papxu-a0a194q858, papxu-a0a194pyl3, papxu-a0a194q337, papma-a0a194r1p9, papma-a0a194r6h1, papxu-a0a194q1w8, papma-a0a194ql80, papma-a0a0n1ipl3, papma-a0a194qm14 Abstract Butterflies are exceptionally diverse but their potential as an experimental system has been limited by the difficulty of deciphering heterozygous genomes and a lack of genetic manipulation technology. Here we use a hybrid assembly approach to construct high-quality reference genomes for Papilio xuthus (contig and scaffold N50: 492 kb, 3.4 Mb) and Papilio machaon (contig and scaffold N50: 81 kb, 1.15 Mb), highly heterozygous species that differ in host plant affiliations, and adult and larval colour patterns. Integrating comparative genomics and analyses of gene expression yields multiple insights into butterfly evolution, including potential roles of specific genes in recent diversification. To functionally test gene function, we develop an efficient (up to 92.5%) CRISPR/Cas9 gene editing method that yields obvious phenotypes with three genes, Abdominal-B, ebony and frizzled. Our results provide valuable genomic and technological resources for butterflies and unlock their potential as a genetic model system. Title: Polycyclic Polyprenylated Acylphloroglucinol Congeners Possessing Diverse Structures from Hypericum henryi Yang XW, Li MM, Liu X, Ferreira D, Ding Y, Zhang JJ, Liao Y, Qin HB, Xu G Ref: Journal of Natural Products, 78:885, 2015 : PubMed ESTHER: Yang_2015_J.Nat.Prod_78_885 PubMedSearch: Yang 2015 J.Nat.Prod 78 885 PubMedID: 25871261 Abstract Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of hybrid natural products sharing the mevalonate/methylerythritol phosphate and polyketide biosynthetic pathways and showing considerable structural and bioactive diversity. In a systematic phytochemical investigation of Hypericum henryi, 40 PPAP-type derivatives, including the new compounds hyphenrones G-Q, were obtained. These compounds represent 12 different structural types, including four unusual skeletons exemplified by 5, 8, 10, and 17. The 12 different core structures found are explicable in terms of their biosynthetic origin. The structure of a known PPAP, perforatumone, was revised to hyphenrone A (5) by NMR spectroscopic and biomimetic synthesis methods. Several compounds exhibited inhibitory activities against acetylcholinesterase and human tumor cell lines. This study deals with the structural diversity, function, and biogenesis of natural PPAPs. Title: Tacrine induces apoptosis through lysosome- and mitochondria-dependent pathway in HepG2 cells Gao C, Ding Y, Zhong L, Jiang L, Geng C, Yao X, Cao J Ref: Toxicol In Vitro, 28:667, 2014 : PubMed ESTHER: Gao_2014_Toxicol.In.Vitro_28_667 PubMedSearch: Gao 2014 Toxicol.In.Vitro 28 667 PubMedID: 24560791 Abstract Tacrine (THA) is a competitive inhibitor of cholinesterase. Administration of THA for the treatment of Alzheimer's disease results in a reversible hepatotoxicity in 30-50% of patients, as indicated by elevated alanine aminotransferase levels. However, the intracellular mechanisms have not yet been elucidated. In our previous study, we found that THA induced cytotoxicity and mitochondria dysfunction by ROS generation and 8-OHdG formation in mitochondrial DNA in HepG2 cells. In this study, the mechanism underlying was further investigated. Our results demonstrated that THA induced dose-dependent apoptosis with cytochrome c release and activation of caspase-3. THA-induced apoptosis was inhibited by treating cells with a ROS inhibitor, YCG063. In addition, we observed that THA led to an early lysosomal membrane permeabilization and release of cathepsin B. Pretreatment with CA-074Me, a specific cathepsin B inhibitor resulted in a significant but not complete decrease in tacrine-induced apoptosis. These data suggest that tacrine-induced cell apoptosis involves both mitochondrial damage and lysosomal membrane destabilization, and ROS is the critical factor that integrates tacrine-induced mitochondrial and lysosomal death pathways. Title: Droplet-based microfluidics for dose-response assay of enzyme inhibitors by electrochemical method Gu S, Lu Y, Ding Y, Li L, Zhang F, Wu Q Ref: Anal Chim Acta, 796:68, 2013 : PubMed ESTHER: Gu_2013_Anal.Chim.Acta_796_68 PubMedSearch: Gu 2013 Anal.Chim.Acta 796 68 PubMedID: 24016585 Abstract A simple but robust droplet-based microfluidic system was developed for dose-response enzyme inhibition assay by combining concentration gradient generation method with electrochemical detection method. A slotted-vials array and a tapered tip capillary were used for reagents introduction and concentration gradient generation, and a polydimethylsiloxane (PDMS) microfluidic chip integrated with microelectrodes was used for droplet generation and electrochemical detection. Effects of oil flow rate and surfactant on electrochemical sensing were investigated. This system was validated by measuring dose-response curves of three types of acetylcholinesterase (AChE) inhibitors, including carbamate pesticide, organophosphorus pesticide, and therapeutic drugs regulating Alzheimer's disease. Carbaryl, chlorpyrifos, and tacrine were used as model analytes, respectively, and their IC50 (half maximal inhibitory concentration) values were determined. A whole enzyme inhibition assay was completed in 6min, and the total consumption of reagents was less than 5muL. This microfluidic system is applicable to many biochemical reactions, such as drug screening and kinetic studies, as long as one of the reactants or products is electrochemically active. Title: In vitro and in vivo characterization of a novel soluble epoxide hydrolase inhibitor Podolin PL, Bolognese BJ, Foley JF, Long E, 3rd, Peck B, Umbrecht S, Zhang X, Zhu P, Schwartz B and Callahan JF <16 more author(s)> Podolin PL, Bolognese BJ, Foley JF, Long E, 3rd, Peck B, Umbrecht S, Zhang X, Zhu P, Schwartz B, Xie W, Quinn C, Qi H, Sweitzer S, Chen S, Galop M, Ding Y, Belyanskaya SL, Israel DI, Morgan BA, Behm DJ, Marino JP, Jr., Kurali E, Barnette MS, Mayer RJ, Booth-Genthe CL, Callahan JF (- 16) Ref: Prostaglandins Other Lipid Mediat, 104-105:25, 2013 : PubMed ESTHER: Podolin_2013_Prostaglandins.Other.Lipid.Mediat_104-105_25 PubMedSearch: Podolin 2013 Prostaglandins.Other.Lipid.Mediat 104-105 25 PubMedID: 23434473 Inhibitor(s) related to this paper: GSK2256294A Abstract Soluble epoxide hydrolase (sEH, EPHX2) metabolizes eicosanoid epoxides, including epoxyeicosatrienoic acids (EETs) to the corresponding dihydroxyeicosatrienoic acids (DHETs), and leukotoxin (LTX) to leukotoxin diol (LTX diol). EETs, endothelium-derived hyperpolarizing factors, exhibit potentially beneficial properties, including anti-inflammatory effects and vasodilation. A novel, potent, selective inhibitor of recombinant human, rat and mouse sEH, GSK2256294A, exhibited potent cell-based activity, a concentration-dependent inhibition of the conversion of 14,15-EET to 14,15-DHET in human, rat and mouse whole blood in vitro, and a dose-dependent increase in the LTX/LTX diol ratio in rat plasma following oral administration. Mice receiving 10 days of cigarette smoke exposure concomitant with oral administration of GSK2256294A exhibited significant, dose-dependent reductions in pulmonary leukocytes and keratinocyte chemoattractant (KC, CXCL1) levels. Mice receiving oral administration of GSK2256294A following 10 days of cigarette smoke exposure exhibited significant reductions in pulmonary leukocytes compared to vehicle-treated mice. These data indicate that GSK2256294A attenuates cigarette smoke-induced inflammation by both inhibiting its initiation and/or maintenance and promoting its resolution. Collectively, these data indicate that GSK2256294A would be an appropriate agent to evaluate the role of sEH in clinical studies, for example in diseases where cigarette smoke is a risk factor, such as chronic obstructive pulmonary disease (COPD) and cardiovascular disease. Title: First case of E anophelis outbreak in an intensive-care unit Teo J, Tan SY, Tay M, Ding Y, Kjelleberg S, Givskov M, Lin RT, Yang L Ref: Lancet, 382:855, 2013 : PubMed ESTHER: Teo_2013_Lancet_382_855 PubMedSearch: Teo 2013 Lancet 382 855 PubMedID: 24012265 Gene_locus related to this paper: 9flao-h0kx79 Title: Discovery of 1-(1,3,5-triazin-2-yl)piperidine-4-carboxamides as inhibitors of soluble epoxide hydrolase Thalji RK, McAtee JJ, Belyanskaya S, Brandt M, Brown GD, Costell MH, Ding Y, Dodson JW, Eisennagel SH and Marino JP, Jr. <18 more author(s)> Thalji RK, McAtee JJ, Belyanskaya S, Brandt M, Brown GD, Costell MH, Ding Y, Dodson JW, Eisennagel SH, Fries RE, Gross JW, Harpel MR, Holt DA, Israel DI, Jolivette LJ, Krosky D, Li H, Lu Q, Mandichak T, Roethke T, Schnackenberg CG, Schwartz B, Shewchuk LM, Xie W, Behm DJ, Douglas SA, Shaw AL, Marino JP, Jr. (- 18) Ref: Bioorganic & Medicinal Chemistry Lett, 23:3584, 2013 : PubMed ESTHER: Thalji_2013_Bioorg.Med.Chem.Lett_23_3584 PubMedSearch: Thalji 2013 Bioorg.Med.Chem.Lett 23 3584 PubMedID: 23664879 Gene_locus related to this paper: human-EPHX2 Inhibitor(s) related to this paper: CHEMBL2392714 Abstract 1-(1,3,5-Triazin-yl)piperidine-4-carboxamide inhibitors of soluble epoxide hydrolase were identified from high through-put screening using encoded library technology. The triazine heterocycle proved to be a critical functional group, essential for high potency and P450 selectivity. Phenyl group substitution was important for reducing clearance, and establishing good oral exposure. Based on this lead optimization work, 1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-{[[4-bromo-2-(trifluoromethoxy) ]-phenyl]methyl}-4-piperidinecarboxamide (27) was identified as a useful tool compound for in vivo investigation. Robust effects on a serum biomarker, 9, 10-epoxyoctadec-12(Z)-enoic acid (the epoxide derived from linoleic acid) were observed, which provided evidence of robust in vivo target engagement and the suitability of 27 as a tool compound for study in various disease models. Title: The clinical study of precise hemihepatectomy guided by middle hepatic vein Qiu Y, Zhu X, Zhu R, Zhou J, Zhou T, Wang Y, Ding Y Ref: World J Surg, 36:2428, 2012 : PubMed ESTHER: Qiu_2012_World.J.Surg_36_2428 PubMedSearch: Qiu 2012 World.J.Surg 36 2428 PubMedID: 22714574 Abstract OBJECTIVE This study was designed to analyze the feasibility of classification for hepatic veins preoperatively and to evaluate the safety and therapeutic efficacy of precise hemihepatectomy guided by middle hepatic vein METHODS Thirty patients who underwent precise hemihepatectomy PH group were subjected to multi-slice helical CT hepatic venography preoperatively to achieve Nakamura's and Kawasaki's classification of hepatic veins The hemihepatectomy was performed precisely by the guidance of middle hepatic vein which was revealed by the hepatic venography and confirmed with intraoperative ultrasound The clinical data of these patients were compared with other 38 traditional hemihepatectomy patients control group The amount of intraoperative bleeding and blood transfusion liver function recovery postoperative complications and 1-year follow-up data were compared between two groups RESULTS The ratios of Nakamura's classification type I II and III of hepatic veins were 56.7 17/30 26.7 8/30 and 16.7 5/30 respectively The percentages of Kawasaki's classification type I and II of hepatic veins were 36.7 11/30 and 63.3 19/30 respectively The total 30 cases of precise hemihepatectomies were performed successfully including 13 cases of right hemihepatectomy without MHV 15 cases of left hemihepatectomy without MHV 1 case of right hemihepatectomy with MHV and 1 case of left hemihepatectomy with MHV There was no significant difference in operation-related mortality the amount of intraoperative bleeding and blood transfusion as well as serum alanine aminotransferase total bilirubin and cholinesterase of the third postoperative day between the two groups However negative resection margin and albumin level were more favorable in precise hemihepatectomy group than control group In addition the incidence of postoperative pleural effusion and seroperitoneum was decreased significantly in precise hemihepatectomy group The 1-year tumor-free survival rate was 79 15/19 In PH group which is 48 in control group CONCLUSIONS Preoperative evaluation of hepatic veins is of great value for individual operative program via determination of anatomical type of hepatic veins Precise hemihepatectomy could preserve functional liver tissue with complete venous return to a great extent resulting in fewer incidences of postoperative pleural effusion and seroperitoneum Precise hemihepatectomy also has the potential to achieve more adequate tumor-free resection margin which may result in higher tumor-free survival rate. Title: Complete genome sequence of Paenibacillus polymyxa SC2, a strain of plant growth-promoting Rhizobacterium with broad-spectrum antimicrobial activity Ma M, Wang C, Ding Y, Li L, Shen D, Jiang X, Guan D, Cao F, Chen H and Du B <7 more author(s)> Ma M, Wang C, Ding Y, Li L, Shen D, Jiang X, Guan D, Cao F, Chen H, Feng R, Wang X, Ge Y, Yao L, Bing X, Yang X, Li J, Du B (- 7) Ref: Journal of Bacteriology, 193:311, 2011 : PubMed ESTHER: Ma_2011_J.Bacteriol_193_311 PubMedSearch: Ma 2011 J.Bacteriol 193 311 PubMedID: 21037012 Gene_locus related to this paper: paep6-e0rmc7, paeps-e3e5s8, paeps-e3ebx3, paeps-e3e602 Abstract Paenibacillus polymyxa SC2 is an important plant growth-promoting rhizobacterium (PGPR). Here, we report the complete genome sequence of P. polymyxa SC2. Multiple sets of functional genes have been found in the genome. As far as we know, this is the first complete genome sequence of Paenibacillus polymyxa. Title: Biodiesel production in packed-bed reactors using lipase-nanoparticle biocomposite Wang X, Liu X, Zhao C, Ding Y, Xu P Ref: Bioresour Technol, 102:6352, 2011 : PubMed ESTHER: Wang_2011_Bioresour.Technol_102_6352 PubMedSearch: Wang 2011 Bioresour.Technol 102 6352 PubMedID: 21435865 Abstract The development of appropriate reactors is crucial for the production of biodiesel. In this study, a packed-bed reactor system using lipase-Fe(3)O(4) nanoparticle biocomposite catalyst was successfully developed for biodiesel production based on soybean oil methanolysis. Emulsification before methanolysis improved the reaction rate. The lipase-nanoparticle biocomposite showed high activity and stability in the single-packed-bed reactor at an optimal flow rate (0.25 mL min(-1)). After 240 h of reaction, the conversion rate was sustained as high as 45%. The conversion rate and stability achieved using the four-packed-bed reactor were much higher than those achieved using the single-packed-bed reactor. The conversion of biodiesel was maintained at a high rate of over 88% for 192 h, and it only slightly declined to approximately 75% after 240 h of reaction. The packed-bed reactor system, therefore, has a great potential for achieving the design and operation of enzymatic biodiesel production on the industrial scale. Title: Moving posttranslational modifications forward to biosynthesize the glycosylated thiopeptide nocathiacin I in Nocardia sp. ATCC202099 Ding Y, Yu Y, Pan H, Guo H, Li Y, Liu W Ref: Mol Biosyst, 6:1180, 2010 : PubMed ESTHER: Ding_2010_Mol.Biosyst_6_1180 PubMedSearch: Ding 2010 Mol.Biosyst 6 1180 PubMedID: 20473441 Gene_locus related to this paper: 9noca-e5dui2 Abstract Characterization of the biosynthetic gene cluster of glycosylated antibiotic nocathiacin I (NOC-I) here adds new insights to thiopeptide biosynthesis, showing the NOC-specific tailoring and unusual sugar formation. NOC-I biosynthesis shares the paradigm for forming a common thiopeptide core and the generality for converting to an e series member, as that of the parent compound nosiheptide (NOS). This may permit the production of NOC-I in the genetically amenable, NOS-producing strain by building NOC-specific genes for pathway engineering. Title: A catalog of reference genomes from the human microbiome Nelson KE, Weinstock GM, Highlander SK, Worley KC, Creasy HH, Wortman JR, Rusch DB, Mitreva M, Sodergren E and Zhu D <73 more author(s)> Nelson KE, Weinstock GM, Highlander SK, Worley KC, Creasy HH, Wortman JR, Rusch DB, Mitreva M, Sodergren E, Chinwalla AT, Feldgarden M, Gevers D, Haas BJ, Madupu R, Ward DV, Birren BW, Gibbs RA, Methe B, Petrosino JF, Strausberg RL, Sutton GG, White OR, Wilson RK, Durkin S, Giglio MG, Gujja S, Howarth C, Kodira CD, Kyrpides N, Mehta T, Muzny DM, Pearson M, Pepin K, Pati A, Qin X, Yandava C, Zeng Q, Zhang L, Berlin AM, Chen L, Hepburn TA, Johnson J, McCorrison J, Miller J, Minx P, Nusbaum C, Russ C, Sykes SM, Tomlinson CM, Young S, Warren WC, Badger J, Crabtree J, Markowitz VM, Orvis J, Cree A, Ferriera S, Fulton LL, Fulton RS, Gillis M, Hemphill LD, Joshi V, Kovar C, Torralba M, Wetterstrand KA, Abouellleil A, Wollam AM, Buhay CJ, Ding Y, Dugan S, Fitzgerald MG, Holder M, Hostetler J, Clifton SW, Allen-Vercoe E, Earl AM, Farmer CN, Liolios K, Surette MG, Xu Q, Pohl C, Wilczek-Boney K, Zhu D (- 73) Ref: Science, 328:994, 2010 : PubMed ESTHER: Nelson_2010_Science_328_994 PubMedSearch: Nelson 2010 Science 328 994 PubMedID: 20489017 Gene_locus related to this paper: strp2-q04l35, strpn-AXE1, strpn-pepx Abstract The human microbiome refers to the community of microorganisms, including prokaryotes, viruses, and microbial eukaryotes, that populate the human body. The National Institutes of Health launched an initiative that focuses on describing the diversity of microbial species that are associated with health and disease. The first phase of this initiative includes the sequencing of hundreds of microbial reference genomes, coupled to metagenomic sequencing from multiple body sites. Here we present results from an initial reference genome sequencing of 178 microbial genomes. From 547,968 predicted polypeptides that correspond to the gene complement of these strains, previously unidentified ("novel") polypeptides that had both unmasked sequence length greater than 100 amino acids and no BLASTP match to any nonreference entry in the nonredundant subset were defined. This analysis resulted in a set of 30,867 polypeptides, of which 29,987 (approximately 97%) were unique. In addition, this set of microbial genomes allows for approximately 40% of random sequences from the microbiome of the gastrointestinal tract to be associated with organisms based on the match criteria used. Insights into pan-genome analysis suggest that we are still far from saturating microbial species genetic data sets. In addition, the associated metrics and standards used by our group for quality assurance are presented. Title: Comparative genomics of Gardnerella vaginalis strains reveals substantial differences in metabolic and virulence potential Yeoman CJ, Yildirim S, Thomas SM, Durkin AS, Torralba M, Sutton G, Buhay CJ, Ding Y, Dugan-Rocha SP and Wilson BA <8 more author(s)> Yeoman CJ, Yildirim S, Thomas SM, Durkin AS, Torralba M, Sutton G, Buhay CJ, Ding Y, Dugan-Rocha SP, Muzny DM, Qin X, Gibbs RA, Leigh SR, Stumpf R, White BA, Highlander SK, Nelson KE, Wilson BA (- 8) Ref: PLoS ONE, 5:e12411, 2010 : PubMed ESTHER: Yeoman_2010_PLoS.ONE_5_e12411 PubMedSearch: Yeoman 2010 PLoS.ONE 5 e12411 PubMedID: 20865041 Gene_locus related to this paper: garv4-d2rbq6, garv4-d2rap1, garv3-e3d9p1 Abstract BACKGROUND: Gardnerella vaginalis is described as a common vaginal bacterial species whose presence correlates strongly with bacterial vaginosis (BV). Here we report the genome sequencing and comparative analyses of three strains of G. vaginalis. Strains 317 (ATCC 14019) and 594 (ATCC 14018) were isolated from the vaginal tracts of women with symptomatic BV, while Strain 409-05 was isolated from a healthy, asymptomatic individual with a Nugent score of 9. PRINCIPAL FINDINGS: Substantial genomic rearrangement and heterogeneity were observed that appeared to have resulted from both mobile elements and substantial lateral gene transfer. These genomic differences translated to differences in metabolic potential. All strains are equipped with significant virulence potential, including genes encoding the previously described vaginolysin, pili for cytoadhesion, EPS biosynthetic genes for biofilm formation, and antimicrobial resistance systems, We also observed systems promoting multi-drug and lantibiotic extrusion. All G. vaginalis strains possess a large number of genes that may enhance their ability to compete with and exclude other vaginal colonists. These include up to six toxin-antitoxin systems and up to nine additional antitoxins lacking cognate toxins, several of which are clustered within each genome. All strains encode bacteriocidal toxins, including two lysozyme-like toxins produced uniquely by strain 409-05. Interestingly, the BV isolates encode numerous proteins not found in strain 409-05 that likely increase their pathogenic potential. These include enzymes enabling mucin degradation, a trait previously described to strongly correlate with BV, although commonly attributed to non-G. vaginalis species. 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: Thiopeptide biosynthesis featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications Liao R, Duan L, Lei C, Pan H, Ding Y, Zhang Q, Chen D, Shen B, Yu Y, Liu W Ref: Chemical Biology, 16:141, 2009 : PubMed ESTHER: Liao_2009_Chem.Biol_16_141 PubMedSearch: Liao 2009 Chem.Biol 16 141 PubMedID: 19246004 Gene_locus related to this paper: 9acto-c0jrv0, 9acto-c0jrv6, strlu-c0jry1, 9actn-c0jrw3, strlu-c0l0l7 Abstract Thiopeptides, with potent activity against various drug-resistant pathogens, contain a characteristic macrocyclic core consisting of multiple thiazoles, dehydroamino acids, and a 6-membered nitrogen heterocycle. Their biosynthetic pathways remain elusive, in spite of great efforts by in vivo feeding experiments. Here, cloning, sequencing, and characterization of the thiostrepton and siomycin A gene clusters unveiled a biosynthetic paradigm for the thiopeptide specific core formation, featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications. The paradigm generality for thiopeptide biosynthesis was supported by genome mining and ultimate confirmation of the thiocillin I production in Bacillus cereus ATCC 14579, a strain that was previously unknown as a thiopeptide producer. These findings set the stage to accelerate the discovery of thiopeptides by prediction at the genetic level and to generate structural diversity by applying combinatorial biosynthesis methods. Title: Nosiheptide biosynthesis featuring a unique indole side ring formation on the characteristic thiopeptide framework Yu Y, Duan L, Zhang Q, Liao R, Ding Y, Pan H, Wendt-Pienkowski E, Tang G, Shen B, Liu W Ref: ACS Chemical Biology, 4:855, 2009 : PubMed ESTHER: Yu_2009_ACS.Chem.Biol_4_855 PubMedSearch: Yu 2009 ACS.Chem.Biol 4 855 PubMedID: 19678698 Gene_locus related to this paper: stras-c6fx50 Abstract Nosiheptide (NOS), belonging to the e series of thiopeptide antibiotics that exhibit potent activity against various bacterial pathogens, bears a unique indole side ring system and regiospecific hydroxyl groups on the characteristic macrocyclic core. Here, cloning, sequencing, and characterization of the nos gene cluster from Streptomyces actuosus ATCC 25421 as a model for this series of thiopeptides has unveiled new insights into their biosynthesis. Bioinformatics-based sequence analysis and in vivo investigation into the gene functions show that NOS biosynthesis shares a common strategy with recently characterized b or c series thiopeptides for forming the characteristic macrocyclic core, which features a ribosomally synthesized precursor peptide with conserved posttranslational modifications. However, it apparently proceeds via a different route for tailoring the thiopeptide framework, allowing the final product to exhibit the distinct structural characteristics of e series thiopeptides, such as the indole side ring system. Chemical complementation supports the notion that the S-adenosylmethionine-dependent protein NosL may play a central role in converting tryptophan to the key 3-methylindole moiety by an unusual carbon side chain rearrangement, most likely via a radical-initiated mechanism. Characterization of the indole side ring-opened analogue of NOS from the nosN mutant strain is consistent with the proposed methyltransferase activity of its encoded protein, shedding light into the timing of the individual steps for indole side ring biosynthesis. These results also suggest the feasibility of engineering novel thiopeptides for drug discovery by manipulating the NOS biosynthetic machinery. Title: Large scale variation in Enterococcus faecalis illustrated by the genome analysis of strain OG1RF Bourgogne A, Garsin DA, Qin X, Singh KV, Sillanpaa J, Yerrapragada S, Ding Y, Dugan-Rocha S, Buhay C and Weinstock GM <18 more author(s)> Bourgogne A, Garsin DA, Qin X, Singh KV, Sillanpaa J, Yerrapragada S, Ding Y, Dugan-Rocha S, Buhay C, Shen H, Chen G, Williams G, Muzny D, Maadani A, Fox KA, Gioia J, Chen L, Shang Y, Arias CA, Nallapareddy SR, Zhao M, Prakash VP, Chowdhury S, Jiang H, Gibbs RA, Murray BE, Highlander SK, Weinstock GM (- 18) Ref: Genome Biol, 9:R110, 2008 : PubMed ESTHER: Bourgogne_2008_Genome.Biol_9_R110 PubMedSearch: Bourgogne 2008 Genome.Biol 9 R110 PubMedID: 18611278 Gene_locus related to this paper: entfa-EF0101, entfa-EF0449, entfa-EF1236, entfa-EF2618, entfa-q5j1l4, entfl-e2z7d4 Abstract BACKGROUND: Enterococcus faecalis has emerged as a major hospital pathogen. To explore its diversity, we sequenced E. faecalis strain OG1RF, which is commonly used for molecular manipulation and virulence studies. RESULTS: The 2,739,625 base pair chromosome of OG1RF was found to contain approximately 232 kilobases unique to this strain compared to V583, the only publicly available sequenced strain. Almost no mobile genetic elements were found in OG1RF. The 64 areas of divergence were classified into three categories. First, OG1RF carries 39 unique regions, including 2 CRISPR loci and a new WxL locus. Second, we found nine replacements where a sequence specific to V583 was substituted by a sequence specific to OG1RF. For example, the iol operon of OG1RF replaces a possible prophage and the vanB transposon in V583. Finally, we found 16 regions that were present in V583 but missing from OG1RF, including the proposed pathogenicity island, several probable prophages, and the cpsCDEFGHIJK capsular polysaccharide operon. OG1RF was more rapidly but less frequently lethal than V583 in the mouse peritonitis model and considerably outcompeted V583 in a murine model of urinary tract infections. CONCLUSION: E. faecalis OG1RF carries a number of unique loci compared to V583, but the almost complete lack of mobile genetic elements demonstrates that this is not a defining feature of the species. Additionally, OG1RF's effects in experimental models suggest that mediators of virulence may be diverse between different E. faecalis strains and that virulence is not dependent on the presence of mobile genetic elements. Title: A mutation upstream of an ATPase gene significantly increases magnetosome production in Magnetospirillum gryphiswaldense Liu J, Ding Y, Jiang W, Tian J, Li Y, Li J Ref: Applied Microbiology & Biotechnology, 81:551, 2008 : PubMed ESTHER: Liu_2008_Appl.Microbiol.Biotechnol_81_551 PubMedSearch: Liu 2008 Appl.Microbiol.Biotechnol 81 551 PubMedID: 18800186 Abstract A mutant of Magnetospirillum gryphiswaldense, NPHB, was obtained from a conjugation experiment. An aberrant recombination occurred between a putative elongation factor-G gene (fus-like) of the bacterial chromosome and the chloramphenicol resistant gene (cat) of a suicide vector, pSUP202. Complementary experiments and transcription analysis of genes around the recombinant site showed that the cat promoter enhanced the expression of adenosine triphosphatase gene downstream. Adenosine triphosphate hydrolyzing activity in NPHB was 35% higher than in the wild-type strain (M. gryphiswaldense MSR-1). NPHB accumulated 71% less poly-beta-hydroxybutyrate and consumed 56% more oxygen and 40% more lactate than MSR-1. The magnetosome content of NPHB was 69% higher than MSR-1 in flask culture. NPHB cultured in a 7.5-L bioreactor gave a maximum yield of 58.4 +/- 6.4 mg magnetosomes per liter. 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: Paradoxical DNA repair and peroxide resistance gene conservation in Bacillus pumilus SAFR-032 Gioia J, Yerrapragada S, Qin X, Jiang H, Igboeli OC, Muzny D, Dugan-Rocha S, Ding Y, Hawes A and Weinstock GM <31 more author(s)> Gioia J, Yerrapragada S, Qin X, Jiang H, Igboeli OC, Muzny D, Dugan-Rocha S, Ding Y, Hawes A, Liu W, Perez L, Kovar C, Dinh H, Lee S, Nazareth L, Blyth P, Holder M, Buhay C, Tirumalai MR, Liu Y, Dasgupta I, Bokhetache L, Fujita M, Karouia F, Eswara Moorthy P, Siefert J, Uzman A, Buzumbo P, Verma A, Zwiya H, McWilliams BD, Olowu A, Clinkenbeard KD, Newcombe D, Golebiewski L, Petrosino JF, Nicholson WL, Fox GE, Venkateswaran K, Highlander SK, Weinstock GM (- 31) Ref: PLoS ONE, 2:e928, 2007 : PubMed ESTHER: Gioia_2007_PLoS.ONE_2_E928 PubMedSearch: Gioia 2007 PLoS.ONE 2 E928 PubMedID: 17895969 Gene_locus related to this paper: bacp2-a8f9m3, bacp2-a8fa85, bacp2-a8fgk8, bacp2-a8fhg9, bacp2-a8fjc9, bacpu-AXE, bacpu-b4af62, bacpu-b4ail3, bacpu-b4ann4, bacpu-b4apa9, bacp2-a8f983, bacp2-a8fgz0 Abstract BACKGROUND: Bacillus spores are notoriously resistant to unfavorable conditions such as UV radiation, gamma-radiation, H2O2, desiccation, chemical disinfection, or starvation. Bacillus pumilus SAFR-032 survives standard decontamination procedures of the Jet Propulsion Lab spacecraft assembly facility, and both spores and vegetative cells of this strain exhibit elevated resistance to UV radiation and H2O2 compared to other Bacillus species. PRINCIPAL FINDINGS: The genome of B. pumilus SAFR-032 was sequenced and annotated. Lists of genes relevant to DNA repair and the oxidative stress response were generated and compared to B. subtilis and B. licheniformis. Differences in conservation of genes, gene order, and protein sequences are highlighted because they potentially explain the extreme resistance phenotype of B. pumilus. The B. pumilus genome includes genes not found in B. subtilis or B. licheniformis and conserved genes with sequence divergence, but paradoxically lacks several genes that function in UV or H2O2 resistance in other Bacillus species. SIGNIFICANCE: This study identifies several candidate genes for further research into UV and H2O2 resistance. These findings will help explain the resistance of B. pumilus and are applicable to understanding sterilization survival strategies of microbes. Title: Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus Highlander SK, Hulten KG, Qin X, Jiang H, Yerrapragada S, Mason EO, Jr., Shang Y, Williams TM, Fortunov RM and Weinstock GM <23 more author(s)> Highlander SK, Hulten KG, Qin X, Jiang H, Yerrapragada S, Mason EO, Jr., Shang Y, Williams TM, Fortunov RM, Liu Y, Igboeli O, Petrosino J, Tirumalai M, Uzman A, Fox GE, Cardenas AM, Muzny DM, Hemphill L, Ding Y, Dugan S, Blyth PR, Buhay CJ, Dinh HH, Hawes AC, Holder M, Kovar CL, Lee SL, Liu W, Nazareth LV, Wang Q, Zhou J, Kaplan SL, Weinstock GM (- 23) Ref: BMC Microbiol, 7:99, 2007 : PubMed ESTHER: Highlander_2007_BMC.Microbiol_7_99 PubMedSearch: Highlander 2007 BMC.Microbiol 7 99 PubMedID: 17986343 Gene_locus related to this paper: staa3-q2fkj0, staau-LIP, staau-lipas, staau-MW0741, staau-MW2456, staau-q6gfm6, staau-SA0011, staau-SA0569, staau-SA0572, staau-SA0897, staau-SA1143, staau-SA2240, staau-SA2306, staau-SA2367, staau-SA2422, staau-SAV0321, staau-SAV0446, staau-SAV0457, staau-SAV0655, staau-SAV1014, staau-SAV1765, staau-SAV1793, staau-SAV2188, staau-SAV2350, staau-SAV2594 Abstract BACKGROUND: Community acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) increasingly causes disease worldwide. USA300 has emerged as the predominant clone causing superficial and invasive infections in children and adults in the USA. Epidemiological studies suggest that USA300 is more virulent than other CA-MRSA. The genetic determinants that render virulence and dominance to USA300 remain unclear. RESULTS: We sequenced the genomes of two pediatric USA300 isolates: one CA-MRSA and one CA-methicillin susceptible (MSSA), isolated at Texas Children's Hospital in Houston. DNA sequencing was performed by Sanger dideoxy whole genome shotgun (WGS) and 454 Life Sciences pyrosequencing strategies. The sequence of the USA300 MRSA strain was rigorously annotated. In USA300-MRSA 2658 chromosomal open reading frames were predicted and 3.1 and 27 kilobase (kb) plasmids were identified. USA300-MSSA contained a 20 kb plasmid with some homology to the 27 kb plasmid found in USA300-MRSA. Two regions found in US300-MRSA were absent in USA300-MSSA. One of these carried the arginine deiminase operon that appears to have been acquired from S. epidermidis. The USA300 sequence was aligned with other sequenced S. aureus genomes and regions unique to USA300 MRSA were identified. CONCLUSION: USA300-MRSA is highly similar to other MRSA strains based on whole genome alignments and gene content, indicating that the differences in pathogenesis are due to subtle changes rather than to large-scale acquisition of virulence factor genes. The USA300 Houston isolate differs from another sequenced USA300 strain isolate, derived from a patient in San Francisco, in plasmid content and a number of sequence polymorphisms. Such differences will provide new insights into the evolution of pathogens. 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: The DNA sequence of the human X chromosome Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C and Bentley DR <272 more author(s)> Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C, Bird CP, Frankish A, Lovell FL, Howe KL, Ashurst JL, Fulton RS, Sudbrak R, Wen G, Jones MC, Hurles ME, Andrews TD, Scott CE, Searle S, Ramser J, Whittaker A, Deadman R, Carter NP, Hunt SE, Chen R, Cree A, Gunaratne P, Havlak P, Hodgson A, Metzker ML, Richards S, Scott G, Steffen D, Sodergren E, Wheeler DA, Worley KC, Ainscough R, Ambrose KD, Ansari-Lari MA, Aradhya S, Ashwell RI, Babbage AK, Bagguley CL, Ballabio A, Banerjee R, Barker GE, Barlow KF, Barrett IP, Bates KN, Beare DM, Beasley H, Beasley O, Beck A, Bethel G, Blechschmidt K, Brady N, Bray-Allen S, Bridgeman AM, Brown AJ, Brown MJ, Bonnin D, Bruford EA, Buhay C, Burch P, Burford D, Burgess J, Burrill W, Burton J, Bye JM, Carder C, Carrel L, Chako J, Chapman JC, Chavez D, Chen E, Chen G, Chen Y, Chen Z, Chinault C, Ciccodicola A, Clark SY, Clarke G, Clee CM, Clegg S, Clerc-Blankenburg K, Clifford K, Cobley V, Cole CG, Conquer JS, Corby N, Connor RE, David R, Davies J, Davis C, Davis J, Delgado O, Deshazo D, Dhami P, Ding Y, Dinh H, Dodsworth S, Draper H, Dugan-Rocha S, Dunham A, Dunn M, Durbin KJ, Dutta I, Eades T, Ellwood M, Emery-Cohen A, Errington H, Evans KL, Faulkner L, Francis F, Frankland J, Fraser AE, Galgoczy P, Gilbert J, Gill R, Glockner G, Gregory SG, Gribble S, Griffiths C, Grocock R, Gu Y, Gwilliam R, Hamilton C, Hart EA, Hawes A, Heath PD, Heitmann K, Hennig S, Hernandez J, Hinzmann B, Ho S, Hoffs M, Howden PJ, Huckle EJ, Hume J, Hunt PJ, Hunt AR, Isherwood J, Jacob L, Johnson D, Jones S, de Jong PJ, Joseph SS, Keenan S, Kelly S, Kershaw JK, Khan Z, Kioschis P, Klages S, Knights AJ, Kosiura A, Kovar-Smith C, Laird GK, Langford C, Lawlor S, Leversha M, Lewis L, Liu W, Lloyd C, Lloyd DM, Loulseged H, Loveland JE, Lovell JD, Lozado R, Lu J, Lyne R, Ma J, Maheshwari M, Matthews LH, McDowall J, Mclaren S, McMurray A, Meidl P, Meitinger T, Milne S, Miner G, Mistry SL, Morgan M, Morris S, Muller I, Mullikin JC, Nguyen N, Nordsiek G, Nyakatura G, O'Dell CN, Okwuonu G, Palmer S, Pandian R, Parker D, Parrish J, Pasternak S, Patel D, Pearce AV, Pearson DM, Pelan SE, Perez L, Porter KM, Ramsey Y, Reichwald K, Rhodes S, Ridler KA, Schlessinger D, Schueler MG, Sehra HK, Shaw-Smith C, Shen H, Sheridan EM, Shownkeen R, Skuce CD, Smith ML, Sotheran EC, Steingruber HE, Steward CA, Storey R, Swann RM, Swarbreck D, Tabor PE, Taudien S, Taylor T, Teague B, Thomas K, Thorpe A, Timms K, Tracey A, Trevanion S, Tromans AC, d'Urso M, Verduzco D, Villasana D, Waldron L, Wall M, Wang Q, Warren J, Warry GL, Wei X, West A, Whitehead SL, Whiteley MN, Wilkinson JE, Willey DL, Williams G, Williams L, Williamson A, Williamson H, Wilming L, Woodmansey RL, Wray PW, Yen J, Zhang J, Zhou J, Zoghbi H, Zorilla S, Buck D, Reinhardt R, Poustka A, Rosenthal A, Lehrach H, Meindl A, Minx PJ, Hillier LW, Willard HF, Wilson RK, Waterston RH, Rice CM, Vaudin M, Coulson A, Nelson DL, Weinstock G, Sulston JE, Durbin R, Hubbard T, Gibbs RA, Beck S, Rogers J, Bentley DR (- 272) Ref: Nature, 434:325, 2005 : PubMed ESTHER: Ross_2005_Nature_434_325 PubMedSearch: Ross 2005 Nature 434 325 PubMedID: 15772651 Gene_locus related to this paper: human-NLGN3, human-NLGN4X Abstract The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence. Title: Crystallization and preliminary crystallographic analysis of acylamino-acid releasing enzyme from the hyperthermophilic archaeon Aeropyrum pernix Wang G, Gao R, Ding Y, Yang H, Cao S, Feng Y, Rao Z Ref: Acta Crystallographica D Biol Crystallogr, 58:1054, 2002 : PubMed ESTHER: Wang_2002_Acta.Crystallogr.D.Biol.Crystallogr_58_1054 PubMedSearch: Wang 2002 Acta.Crystallogr.D.Biol.Crystallogr 58 1054 PubMedID: 12037315 Gene_locus related to this paper: aerpe-APE1547 Abstract Crystals of acylamino-acid releasing enzyme from the hyperthermophilic archaeon Aeropyrum pernix strain K1 have been grown at 291 K using ammonium phosphate as a precipitant. The diffraction pattern of the crystal extends to 2.4 A resolution at 100 K using Cu Kalpha radiation. The crystal belongs to space group P1, with unit-cell parameters a = 107.5, b = 109.9, c = 119.4 A, alpha = 108.1, beta = 109.8, gamma = 91.9 degrees. The presence of eight molecules per asymmetric unit gives a crystal volume per protein mass (V(M)) of 2.4 A(3) Da(-1) and a solvent content of 48% by volume. A full set of X-ray diffraction data was collected to 2.9 A from the native crystal. Title: Large-scale concatenation cDNA sequencing Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA Ref: Genome Res, 7:353, 1997 : PubMed ESTHER: Yu_1997_Genome.Res_7_353 PubMedSearch: Yu 1997 Genome.Res 7 353 PubMedID: 9110174 Gene_locus related to this paper: human-ABHD3 Abstract A total of 100 kb of DNA derived from 69 individual human brain cDNA clones of 0.7-2.0 kb were sequenced by concatenated cDNA sequencing (CCS), whereby multiple individual DNA fragments are sequenced simultaneously in a single shotgun library. The method yielded accurate sequences and a similar efficiency compared with other shotgun libraries constructed from single DNA fragments (> 20 kb). Computer analyses were carried out on 65 cDNA clone sequences and their corresponding end sequences to examine both nucleic acid and amino acid sequence similarities in the databases. Thirty-seven clones revealed no DNA database matches, 12 clones generated exact matches (> or = 98% identity), and 16 clones generated nonexact matches (57%-97% identity) to either known human or other species genes. Of those 28 matched clones, 8 had corresponding end sequences that failed to identify similarities. In a protein similarity search, 27 clone sequences displayed significant matches, whereas only 20 of the end sequences had matches to known protein sequences. Our data indicate that full-length cDNA insert sequences provide significantly more nucleic acid and protein sequence similarity matches than expressed sequence tags (ESTs) for database searching. Title: Clinical observation and comparison of the effectiveness of several oxime cholinesterase reactivators Xue SZ, Ding XJ, Ding Y Ref: Scandinavian Journal of Work, Environment & Health, 4:46, 1985 : PubMed ESTHER: Xue_1985_Scand.J.Work.Environ.Health_4_46 PubMedSearch: Xue 1985 Scand.J.Work.Environ.Health 4 46 PubMedID: 3914075 Abstract After passing toxicity and experimental therapeutic tests, four oxime cholinesterase reactivators [PAM (pyridine aldoxime methiodide), PAC (pralidoxime, pyridine aldoxime methylchloride), TMB4 (trimedoxime), and DMO4 (obidoxime, Toxogonin, LH6)] were compared in clinical trials. All of them proved capable of restoring erythrocyte cholinesterase activity and relieving symptoms and signs of organophosphate insecticide poisoning. Mildly and moderately poisoned patients can be treated by several injections of any one of these drugs alone, but severe cases need the synergistic action of atropine, as well as treatments for two to three consecutive days. Although response to treatment is stronger with TMB4 and DMO4, they are not recommended for routine treatment because of their dangerous adverse side effects. | |||||||
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