Liang Y

References (52)

Title : MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity - Zhou_2024_Theranostics_14_1583
Author(s) : Zhou S , Ling X , Zhu J , Liang Y , Feng Q , Xie C , Li J , Chen Q , Chen S , Miao J , Zhang M , Li Z , Shen W , Li X , Wu Q , Wang X , Liu R , Wang C , Hou FF , Kong Y , Liu Y , Zhou L
Ref : Theranostics , 14 :1583 , 2024
Abstract : Rationale: Renal fibrosis, with no therapeutic approaches, is a common pathological feature in various chronic kidney diseases (CKD). Tubular cell injury plays a pivotal role in renal fibrosis. Commonly, injured tubular cells exhibit significant lipid accumulation. However, the underlying mechanisms remain poorly understood. Methods: 2-arachidonoylglycerol (2-AG) levels in CKD patients and CKD model specimens were measured using mass spectrometry. 2-AG-loaded nanoparticles were infused into unilateral ureteral obstruction (UUO) mice. Lipid accumulation and renal fibrosis were tested. Furthermore, monoacylglycerol lipase (MAGL), the hydrolyzing enzyme of 2-AG, was assessed in CKD patients and models. Tubular cell-specific MAGL knock-in mice were generated. Moreover, MAGL recombination protein was also administered to unilateral ischemia reperfusion injury (UIRI) mice. Besides, a series of methods including RNA sequencing, metabolomics, primary cell culture, lipid staining, etc. were used. Results: 2-AG was increased in the serum or kidneys from CKD patients and models. Supplement of 2-AG further induced lipid accumulation and fibrogenesis through cannabinoid receptor type 2 (CB2)/beta-catenin signaling. beta-catenin knockout blocked 2-AG/CB2-induced fatty acid beta-oxidation (FAO) deficiency and lipid accumulation. Remarkably, MAGL significantly decreased in CKD, aligning with lipid accumulation and fibrosis. Specific transgene of MAGL in tubular cells significantly preserved FAO, inhibited lipid-mediated toxicity in tubular cells, and finally retarded fibrogenesis. Additionally, supplementation of MAGL in UIRI mice also preserved FAO function, inhibited lipid accumulation, and protected against renal fibrosis. Conclusion: MAGL is a potential diagnostic marker for kidney function decline, and also serves as a new therapeutic target for renal fibrosis through ameliorating lipotoxicity.
ESTHER : Zhou_2024_Theranostics_14_1583
PubMedSearch : Zhou_2024_Theranostics_14_1583
PubMedID: 38389852
Gene_locus related to this paper: human-MGLL , mouse-MGLL

Title : Mechanisms of biochar assisted di-2-ethylhexyl phthalate (DEHP) biodegradation in tomato rhizosphere by metabolic and metagenomic analysis - Lin_2024_Chemosphere__141520
Author(s) : Lin Z , Wu W , Yang C , Yang G , Wei T , Huang F , Li H , Ren L , Liang Y , Zhang D , Li Z , Zhen Z
Ref : Chemosphere , :141520 , 2024
Abstract : The intensive accumulation of di-2-ethylhexyl phthalate (DEHP) in agricultural soils has resulted in severe environmental pollution that endangers ecosystem and human health. Biochar is an eco-friendly material that can help in accelerating organic pollutant degradation; nevertheless, its roles in enhancing DEHP removal in rhizosphere remain unclear. This work investigated the impacts of biochar dosage (0%-2.0%) on DEHP degradation performance in tomato rhizosphere by comprehensively exploring the change in DEHP metabolites, bacterial communities and DEHP-degrading genes. Our results showed a significant increase of rhizosphere pH, organic matter and humus by biochar amendment, which achieved a satisfactorily higher DEHP removal efficiency, maximally 77.53% in treatments with 1.0% of biochar. Biochar addition also remarkably changed rhizosphere bacterial communities by enriching some potential DEHP degraders of Nocardioides, Sphingomonas, Bradyrhizobium and Rhodanobacter. The abundance of genes encoding key enzymes (hydrolase, esterase and cytochrome P450) and DEHP-degrading genes (pht3, pht4, pht5, benC-xylZ and benD-xylL) were increased after biochar amendment, leading to the change in DEHP degradation metabolism, primarily from benzoic acid pathway to protocatechuic acid pathway. Our findings evidenced that biochar amendment could accelerate DEHP degradation by altering rhizosphere soil physicochemical variables, bacterial community composition and metabolic genes, providing clues for the mechanisms of biochar-assisted DEHP degradation in organic contaminated farmland soils.
ESTHER : Lin_2024_Chemosphere__141520
PubMedSearch : Lin_2024_Chemosphere__141520
PubMedID: 38395368

Title : Human hepatocyte PNPLA3-148M exacerbates rapid non-alcoholic fatty liver disease development in chimeric mice - Kabbani_2022_Cell.Rep_40_111321
Author(s) : Kabbani M , Michailidis E , Steensels S , Fulmer CG , Luna JM , Le Pen J , Tardelli M , Razooky B , Ricardo-Lax I , Zou C , Zeck B , Stenzel AF , Quirk C , Foquet L , Ashbrook AW , Schneider WM , Belkaya S , Lalazar G , Liang Y , Pittman M , Devisscher L , Suemizu H , Theise ND , Chiriboga L , Cohen DE , Copenhaver R , Grompe M , Meuleman P , Ersoy BA , Rice CM , de Jong YP
Ref : Cell Rep , 40 :111321 , 2022
Abstract : Advanced non-alcoholic fatty liver disease (NAFLD) is a rapidly emerging global health problem associated with pre-disposing genetic polymorphisms, most strikingly an isoleucine to methionine substitution in patatin-like phospholipase domain-containing protein 3 (PNPLA3-I148M). Here, we study how human hepatocytes with PNPLA3 148I and 148M variants engrafted in the livers of broadly immunodeficient chimeric mice respond to hypercaloric diets. As early as four weeks, mice developed dyslipidemia, impaired glucose tolerance, and steatosis with ballooning degeneration selectively in the human graft, followed by pericellular fibrosis after eight weeks of hypercaloric feeding. Hepatocytes with the PNPLA3-148M variant, either from a homozygous 148M donor or overexpressed in a 148I donor background, developed microvesicular and severe steatosis with frequent ballooning degeneration, resulting in more active steatohepatitis than 148I hepatocytes. We conclude that PNPLA3-148M in human hepatocytes exacerbates NAFLD. These models will facilitate mechanistic studies into human genetic variant contributions to advanced fatty liver diseases.
ESTHER : Kabbani_2022_Cell.Rep_40_111321
PubMedSearch : Kabbani_2022_Cell.Rep_40_111321
PubMedID: 36103835

Title : Carthamus tinctorius L.: A natural neuroprotective source for anti-Alzheimer's disease drugs - Liang_2022_J.Ethnopharmacol__115656
Author(s) : Liang Y , Wang L
Ref : J Ethnopharmacol , :115656 , 2022
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a multicausal neurodegenerative disease clinically characterized by generalized dementia. The pathogenic process of AD not only is progressive and complex but also involves multiple factors and mechanisms, including beta-amyloid (Abeta) aggregation, tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. As the first-line treatment for AD, cholinesterase inhibitors can, to a certain extent, relieve AD symptoms and delay AD progression. Nonetheless, the current treatment strategies for AD are far from meeting clinical expectations, and more options for AD treatment should be applied in clinical practice. AIM OF THE REVIEW: The aim of this review was to investigate published reports of C. tinctorius L. and its active constituents in AD treatment through a literature review. MATERIALS AND METHODS: Information was retrieved from scientific databases including Web of Science, ScienceDirect, Scopus, Google Scholar, Chemical Abstracts Services and books, PubMed, dissertations and technical reports. Keywords used for the search engines were "Honghua" or "Carthamus tinctorius L." or "safflower" in conjunction with "(native weeds OR alien invasive)"AND "Chinese herbal medicine". RESULTS: A total of 47 literatures about C. tinctorius L. and its active constituents in AD treatment through signaling pathways, immune cells, and disease-related mediators and systematically elucidates potential mechanisms from the point of anti-Abeta aggregation, suppressing tau protein hyperphosphorylation, increasing cholinergic neurotransmitters levels, inhibiting oxidative stress, anti-neuroinflammation, ameliorating synaptic plasticity, and anti-apoptosis. CONCLUSIONS: Chinese herbal medicine (CHM) is a treasure endowed by nature to mankind. Emerging studies have confirmed that CHM and its active constituents play a positive role in AD treatment. Carthamus tinctorius L., the most commonly used CHM, can be used with medicine and food, with the effect of activating blood circulation and eliminating blood stasis. In the paper, we have concluded that the existing therapeutic mechanisms of C. tinctorius L. and summarized the potential mechanisms of C. tinctorius L. and its active constituents in AD treatment through a literature review.
ESTHER : Liang_2022_J.Ethnopharmacol__115656
PubMedSearch : Liang_2022_J.Ethnopharmacol__115656
PubMedID: 36041691

Title : Protein palmitoylation in cancer: molecular functions and therapeutic potential - Zhou_2022_Mol.Oncol__
Author(s) : Zhou B , Hao Q , Liang Y , Kong E
Ref : Mol Oncol , : , 2022
Abstract : Protein S-palmitoylation (hereinafter referred to as protein palmitoylation) is a reversible lipid post-translational modification catalyzed by the zinc finger DHHC-type containing (ZDHHC) protein family. The reverse reaction, depalmitoylation, is catalyzed by palmitoyl-protein thioesterases (PPTs) including acyl-protein thioesterases (APT1/2), palmitoyl protein thioesterases (PPT1/2) or alpha/beta hydrolase domain-containing protein 17A/B/C (ABHD17A/B/C). Proteins encoded by several oncogenes and tumor suppressors are modified by palmitoylation, which enhances the hydrophobicity of specific protein subdomains, and can confer changes in protein stability, membrane localization, protein-protein interaction and signal transduction. The importance for protein palmitoylation in tumorigenesis has just started to be elucidated in the past decade; palmitoylation appears to affect key aspects of cancer, including cancer cell proliferation and survival, cell invasion and metastasis, and anti-tumor immunity. Here, we review the current literature on protein palmitoylation in the various cancer types, and discuss the potential of targeting of palmitoylation enzymes or palmitoylated proteins for tumor treatment.
ESTHER : Zhou_2022_Mol.Oncol__
PubMedSearch : Zhou_2022_Mol.Oncol__
PubMedID: 36018061

Title : Thirteen cyathane diterpenoids with acetylcholinesterase inhibitory effects from the fungus Cyathus africanus - Yu_2021_Phytochemistry_193_112982
Author(s) : Yu M , Kang X , Li Q , Liang Y , Zhang M , Gong Y , Chen C , Zhu H , Zhang Y
Ref : Phytochemistry , 193 :112982 , 2021
Abstract : Eight undescribed cyathane diterpenoids, representative specialised metabolites of the genus Cyathus, named cyathins Q-X, along with five known congeners, were isolated from the liquid fermentation of Cyathus africanus. Their structures and absolute configurations were elucidated by integrating NMR spectroscopic analyses, electronic circular dichroism (ECD) calculations, and X-ray diffraction. Reasonable correction to the C-12 configuration of cyathin I was corroborated by the crystal data. The structural identification in this research expanded the number of candidates to allow for more bioactivity-screening options. Among them, (12S)-11alpha,14alpha-epoxy-13alpha,14beta,15-trihydroxycyath-3-ene displayed significant acetylcholinesterase (AChE) inhibitory effect with an IC(50) value of 4.60 +/- 0.85 microM. Molecular docking studies were also performed to unravel the underlying modes of interactions with the active sites of AChE for active compounds.
ESTHER : Yu_2021_Phytochemistry_193_112982
PubMedSearch : Yu_2021_Phytochemistry_193_112982
PubMedID: 34700067

Title : Design, Synthesis, and Evaluation of a Series of Novel Super Long-Acting DPP-4 Inhibitors for the Treatment of Type 2 Diabetes - Zhang_2020_J.Med.Chem_63_7108
Author(s) : Zhang C , Ye F , Wang J , He P , Lei M , Huang L , Huang A , Tang P , Lin H , Liao Y , Liang Y , Ni J , Yan P
Ref : Journal of Medicinal Chemistry , 63 :7108 , 2020
Abstract : In the present work, a novel series of trifluoromethyl-substituted tetrahydropyran derivatives were rationally designed and synthesized as potent DPP-4 inhibitors with significantly improved duration time of action over current commercially available DPP-4 inhibitors. The incorporation of the trifluoromethyl group on the 6-position of the tetrahydropyran ring of omarigliptin with the configuration of (2R,3S,5R,6S) not only significantly improves the overall pharmacokinetic profiles in mice but also maintains comparable DPP-4 inhibition activities. Further preclinical development of compound 2 exhibited its extraordinary efficacy in vivo and good safety profile. Clinical studies of compound 2 (Haisco HSK7653) are now ongoing in China, which revealed that inhibitor 2 could serve as an efficient candidate with a once-biweekly therapeutic regimen.
ESTHER : Zhang_2020_J.Med.Chem_63_7108
PubMedSearch : Zhang_2020_J.Med.Chem_63_7108
PubMedID: 32452679

Title : Structural insights into the catalytic mechanism of lovastatin hydrolase - Liang_2020_J.Biol.Chem_295_1047
Author(s) : Liang Y , Lu X
Ref : Journal of Biological Chemistry , 295 :1047 , 2020
Abstract : The lovastatin hydrolase PcEST from the fungus Penicillium chrysogenum exhibits enormous potential for industrial-scale applications in single-step production of monacolin J, the key precursor for synthesis of the cholesterol-lowering drug simvastatin. This enzyme specifically and efficiently catalyzes the conversion of lovastatin to monacolin J but cannot hydrolyze simvastatin. Understanding the catalytic mechanism and the structure-function relationship of PcEST is therefore important for further lovastatin hydrolase screening, engineering, and commercial applications. Here, we solved four X-ray crystal structures, including apo PcEST (2.3 A), PcEST in complex with monacolin J (2.48 A), PcEST complexed with the substrate analog simvastatin (2.4 A), and an inactivated PcEST variant (S57A) with the lovastatin substrate (2.3 A). Structure-based biochemical analyses and mutagenesis assays revealed that the Ser(57) (nucleophile)-Tyr(170) (general base)-Lys(60) (general acid) catalytic triad, the hydrogen-bond network (Trp(344) and Tyr(127)) around the active site, and the specific substrate-binding tunnel together determine efficient and specific lovastatin hydrolysis by PcEST. Moreover, steric effects on nucleophilic attack caused by the 2',2-dimethybutyryl group of simvastatin resulted in no activity of PcEST on simvastatin. On the basis of structural comparisons, we propose several indicators to define lovastatin esterases. Furthermore, using structure-guided enzyme engineering, we developed a PcEST variant, D106A, having improved solubility and thermostability, suggesting a promising application of this variant in industrial processes. To our knowledge, this is the first report describing the mechanism and structure-function relationship of lovastatin hydrolase and providing insights that may guide rapid screening and engineering of additional lovastatin esterase variants.
ESTHER : Liang_2020_J.Biol.Chem_295_1047
PubMedSearch : Liang_2020_J.Biol.Chem_295_1047
PubMedID: 31839596

Title : Carboxylesterase catalyzed (18)O-labeling of carboxylic acid and its potential application in LC-MS\/MS based quantification of drug metabolites - Yu_2019_Drug.Metab.Pharmacokinet_34_308
Author(s) : Yu ZJ , Roesner JM , Lutz R , Liang Y , Baker J , Smith DM , Fan PW
Ref : Drug Metab Pharmacokinet , 34 :308 , 2019
Abstract : LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel (18)O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H2(18)O in the presence of the enzyme, generating singly- and doubly-(18)O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds - indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.
ESTHER : Yu_2019_Drug.Metab.Pharmacokinet_34_308
PubMedSearch : Yu_2019_Drug.Metab.Pharmacokinet_34_308
PubMedID: 31235362

Title : Vitisin B as a novel fatty acid synthase inhibitor induces human breast cancer cells apoptosis - Wang_2019_Am.J.Transl.Res_11_5096
Author(s) : Wang X , Jiang B , Lv H , Liang Y , Ma X
Ref : Am J Transl Res , 11 :5096 , 2019
Abstract : Breast cancer is one of the most common cancers and the second leading cause of cancer mortality in women worldwide. Novel therapies and chemo-therapeutic drugs are still in urgent need to be developed for the treatment of breast cancer. One of the most important metabolic hallmarks of breast cancer cells is enhanced lipogenesis. Increasing evidences suggest that fatty acid synthase (FAS) plays an important role in the development of human breast cancer, for the expression of FAS is significantly higher in breast cancer cells than in normal cells. In addition, FAS inhibitors, such as curcumin, ursolic acid, and resveratrol, have shown anti-cancer potential. In the present study, we discovered that vitisin B, a natural stilbene isolated from the seeds of Iris lactea Pall. var. chinensis (Fisch.), was a novel FAS inhibitor. We found that vitisin B could down-regulate FAS expression and inhibit intracellular FAS activity in MDA-MB-231 cells. Also, we reported for the first time that vitisin B exhibited apoptotic effect on human breast cancer cells. Given all of this, we proposed a hypothesis that vitisin B has an application potential in the chemoprevention and treatment of breast cancer.
ESTHER : Wang_2019_Am.J.Transl.Res_11_5096
PubMedSearch : Wang_2019_Am.J.Transl.Res_11_5096
PubMedID: 31497225

Title : Modified substrate specificity of a methyltransferase domain by protein insertion into an adenylation domain of the bassianolide synthetase - Xu_2019_J.Biol.Eng_13_65
Author(s) : Xu F , Butler R , May K , Rexhepaj M , Yu D , Zi J , Chen Y , Liang Y , Zeng J , Hevel J , Zhan J
Ref : J Biol Eng , 13 :65 , 2019
Abstract : BACKGROUND: Creating designer molecules using a combination of select domains from polyketide synthases and/or nonribosomal peptide synthetases (NRPS) continues to be a synthetic goal. However, an incomplete understanding of how protein-protein interactions and dynamics affect each of the domain functions stands as a major obstacle in the field. Of particular interest is understanding the basis for a class of methyltransferase domains (MT) that are found embedded within the adenylation domain (A) of fungal NRPS systems instead of in an end-to-end architecture. RESULTS: The MT domain from bassianolide synthetase (BSLS) was removed and the truncated enzyme BSLS-deltaMT was recombinantly expressed. The biosynthesis of bassianolide was abolished and N-desmethylbassianolide was produced in low yields. Co-expression of BSLS-deltaMT with standalone MT did not recover bassianolide biosynthesis. In order to address the functional implications of the protein insertion, we characterized the N-methyltransferase activity of the MT domain as both the isolated domain (MT(BSLS)) and as part of the full NRPS megaenzyme. Surprisingly, the MT(BSLS) construct demonstrated a relaxed substrate specificity and preferentially methylated an amino acid (L-Phe-SNAC) that is rarely incorporated into the final product. By testing the preference of a series of MT constructs (BSLS, MT(BSLS), cMT, XLcMT, and aMT) to L-Phe-SNAC and L-Leu-SNAC, we further showed that restricting and/or fixing the termini of the MT(BSLS) by crosslinking or embedding the MT within an A domain narrowed the substrate specificity of the methyltransferase toward L-Leu-SNAC, the preferred substrate for the BSLS megaenzyme. CONCLUSIONS: The embedding of MT into the A2 domain of BSLS is not required for the product assembly, but is critical for the overall yields of the final products. The substrate specificity of MT is significantly affected by the protein context within which it is present. While A domains are known to be responsible for selecting and activating the biosynthetic precursors for NRPS systems, our results suggest that embedding the MT acts as a secondary gatekeeper for the assembly line. This work thus provides new insights into the embedded MT domain in NRPSs, which will facilitate further engineering of this type of biosynthetic machinery to create structural diversity in natural products.
ESTHER : Xu_2019_J.Biol.Eng_13_65
PubMedSearch : Xu_2019_J.Biol.Eng_13_65
PubMedID: 31388353

Title : Bialternacins A-F, Aromatic Polyketide Dimers from an Endophytic Alternaria sp - Yang_2019_J.Nat.Prod_82_792
Author(s) : Yang CL , Wu HM , Liu CL , Zhang X , Guo ZK , Chen Y , Liu F , Liang Y , Jiao RH , Tan RX , Ge HM
Ref : Journal of Natural Products , 82 :792 , 2019
Abstract : Six novel aromatic polyketide dimers, bialternacins A-F (1-6), were isolated from a plant endophytic Alternaria sp. The structures of compounds 1-6 were elucidated on the basis of extensive spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism analysis. Compounds 1, 2, 5, and 6 were characterized as four pairs of racemic mixtures. Compound (+)-5 was demonstrated to show acetylcholinesterase inhibitory activity with an IC50 value of 15.5 muM. A putative biosynthetic pathway for these compounds was proposed.
ESTHER : Yang_2019_J.Nat.Prod_82_792
PubMedSearch : Yang_2019_J.Nat.Prod_82_792
PubMedID: 30794407

Title : Comparative transcriptome profiling reveals candidate genes related to insecticide resistance of Glyphodes pyloalis - Su_2019_Bull.Entomol.Res__1
Author(s) : Su H , Gao Y , Liu Y , Li X , Liang Y , Dai X , Xu Y , Zhou Y , Wang H
Ref : Bull Entomol Res , :1 , 2019
Abstract : Glyphodes pyloalis Walker (Lepidoptera: Pyralididae) is a common pest in sericulture and has developed resistance to different insecticides. However, the mechanisms involved in insecticide resistance of G. pyloalis are poorly understood. Here, we present the first whole-transcriptome analysis of differential expression genes in insecticide-resistant and susceptible G. pyloalis. Clustering and enrichment analysis of DEGs revealed several biological pathways and enriched Gene Ontology terms were related to detoxification or insecticide resistance. Genes involved in insecticide metabolic processes, including cytochrome P450, glutathione S-transferases and carboxylesterase, were identified in the larval midgut of G. pyloalis. Among them, CYP324A19, CYP304F17, CYP6AW1, CYP6AB10, GSTs5, and AChE-like were significantly increased after propoxur treatment, while CYP324A19, CCE001c, and AChE-like were significantly induced by phoxim, suggesting that these genes were involved in insecticide metabolism. Furthermore, the sequence variation analysis identified 21 single nucleotide polymorphisms within CYP9A20, CYP6AB47, and CYP6AW1. Our findings reveal many candidate genes related to insecticide resistance of G. pyloalis. These results provide novel insights into insecticide resistance and facilitate the development of insecticides with greater specificity to G. pyloalis.
ESTHER : Su_2019_Bull.Entomol.Res__1
PubMedSearch : Su_2019_Bull.Entomol.Res__1
PubMedID: 31217039

Title : The Structures and Bioactivities of Fatty Acid Synthase Inhibitors - Jiang_2019_Curr.Med.Chem_26_7081
Author(s) : Jiang H , Gan T , Zhang J , Ma Q , Liang Y , Zhao Y
Ref : Curr Med Chem , 26 :7081 , 2019
Abstract : BACKGROUND: Fatty Acid Synthase (FAS or FASN) is a vital enzyme which catalyzes the de novo synthesis of long chain fatty acids. A number of studies have recently been reported that FAS was combined targets for the discovery of anti-obesity and anti-cancer drugs. Great interest has been developed in finding novel FAS inhibitors, and result in more than 200 inhibitors being reported. METHODS: The reported research literature about the FAS inhibitors was collected and analyzedsised through major databases including Web of Science, and PubMed. Then the chemical stractures, FAS inhibitory activities, and Structure-Activity Relationships (SAR) were summarized focused on all these reported FAS inhibitors. RESULTS: The 248 FAS inhibitors, which were reported during the past 20 years, could be divided into thiolactone, butyrolactone and butyrolactam, polyphenols, alkaloids, terpenoids, and other structures, in view of their structure characteristics. And the SAR of high inhibitory structures of each type was proposed in this paper. CONCLUSION: A series of synthetic quinolinone derivatives show strongest inhibitory activity in the reported FAS inhibitors. Natural polyphenols, existing in food and herbs, show more adaptive in medicine exploration because of their safety and efficiency. Moreover, screening the FAS inhibitors from microorganism and marine natural products could be the hot research directions in the future.
ESTHER : Jiang_2019_Curr.Med.Chem_26_7081
PubMedSearch : Jiang_2019_Curr.Med.Chem_26_7081
PubMedID: 31538883

Title : Naringenin induces laxative effects by upregulating the expression levels of c-Kit and SCF, as well as those of aquaporin 3 in mice with loperamide-induced constipation - Yin_2018_Int.J.Mol.Med_41_649
Author(s) : Yin J , Liang Y , Wang D , Yan Z , Yin H , Wu D , Su Q
Ref : Int J Mol Med , 41 :649 , 2018
Abstract : Constipation is a common affliction which causes discomfort and affects the quality of life of affected individuals. Naringenin (NAR), a natural flavonoid widely found in citrus fruits and tomatoes, has been reported to exhibit various pharmacological effects, such as anti-inflammatory, anti-atherogenic, anti-mutagenic, hepatoprotective and anticancer effects. Increasing evidence has indicated that NAR has potential for use in the treatment of constipation. Thus, the aim of this study was to evaluate the laxative effects of NAR in mice with loperamide-induced (Lop-induced) constipation. The data indicated that NAR relieved Lop-induced constipation in mice based on the changes of fecal parameters (numbers, weight and water content), the intestinal charcoal transit ratio and the histological alteration. ELISA revealed that NAR regulated the production levels of gastrointestinal metabolic components, such as motilin (MTL), gastrin (Gas), endothelin (ET), substance P (SP), acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) in serum. The expression levels of enteric nerve-related factors, glial cell line-derived neurotrophic factor (GDNF), transient receptor potential vanilloid 1 (TRPV1), nitric oxide synthase (NOS), c-Kit, stem cell factor (SCF) and aquaporin 3 (AQP3) were examined by western blot analysis and RT-PCR analysis. The results of this study suggest that NAR relieves Lop-induced constipation by increasing the levels of interstitial cells of Cajal markers (c-Kit and SCF), as well as AQP3. Thus, NAR may be effective as a candidate in patients suffering from lifestyle-induced constipation.
ESTHER : Yin_2018_Int.J.Mol.Med_41_649
PubMedSearch : Yin_2018_Int.J.Mol.Med_41_649
PubMedID: 29207043

Title : Expression of soluble epoxide hydrolase in renal tubular epithelial cells regulates macrophage infiltration and polarization in IgA nephropathy - Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915
Author(s) : Wang Q , Liang Y , Qiao Y , Zhao X , Yang Y , Yang S , Li B , Zhao Q , Dong L , Quan S , Tian R , Liu Z
Ref : American Journal of Physiology Renal Physiol , 315 :F915 , 2018
Abstract : Tubulointerstitial inflammatory cell infiltration and activation contribute to kidney inflammation and fibrosis. Epoxyeicosatrienoic acids (EETs), which are rapidly metabolized to dihydroxyeicosatrienoic acids by the soluble epoxide hydrolase (sEH), have multiple biological functions, including vasodilation, anti-inflammatory action, and others. Inhibition of sEH has been demonstrated to attenuate inflammation in many renal disease models. However, the relationship between sEH expression and macrophage polarization in the kidney remains unknown. In this study, we investigated the relationships between the level of sEH and clinical and pathological parameters in IgA nephropathy. The level of sEH expression positively correlated with proteinuria and infiltration of macrophages. sEH-positive tubules were found to be surrounded by macrophages. Furthermore, we found that incubation of immortalized human proximal tubular HK-2 cells with total urinary protein and overexpression of sEH promoted inflammatory factor production, which was associated with M1 polarization. We also exposed RAW264.7 mouse leukemic monocytes/macrophages to different HK-2 cell culture media conditioned by incubation with various substances affecting sEH amount or activity. We found that the upregulation of sEH promoted M1 polarization. However, pharmacological inhibition of sEH and supplementation with EETs reversed the conditioning effects of urinary proteins by inhibiting M1 polarization through the NF-kappaB pathway and stimulating M2 polarization through the phosphatidylinositol 3-kinase pathway. These data suggest that inhibition of sEH could be a new strategy to prevent the progression of inflammation and to attenuate renal tubulointerstitial fibrosis.
ESTHER : Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915
PubMedSearch : Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915
PubMedID: 29717935

Title : Fatal poisoning by terbufos following occupational exposure - Liang_2017_Clin.Toxicol.(Phila)__1
Author(s) : Liang Y , Tong F , Zhang L , Li W , Huang W , Zhou Y
Ref : Clinical Toxicology (Phila) , :1 , 2017
Abstract : CONTEXT: Terbufos (TBF) is a class Ia (extremely hazardous) organophosphate pesticide (OP) and its distribution in industrialized countries has been severely restricted. Thus, acute occupational poisoning is rather uncommon. However, it still occurs in rural areas of some developing countries, where the sale of TBF is not controlled and its use is thus not properly regulated. We report a case of a 43-year-old female farmer who died after applying TBF granules. CASE: The patient died within 3 h after applying 20 bags of 5% TBF granules (900 g per bag). Investigation showed that her personal protective equipment (PPE) did not provide effective protection against dermal and inhalational exposure. Postmortem analysis revealed extremely low red blood cell acetylcholinesterase activity. Toxicological analysis of TBF showed 1.45 x 10-2 mug/ml in the heart blood and 0.17 mug/g in the liver. DISCUSSIONS: This patient died as a result of toxicity from dermal and inhalational exposure to TBF. Over-application, improper equipment, inadequate and defective PPE, and lack of hygienic precautions were all contributing factors.
CONCLUSIONS: TBF is a highly toxic OP. Inadequate regulatory control, improper environmental application, and ineffective PPE resulted in a fatal human exposure.
ESTHER : Liang_2017_Clin.Toxicol.(Phila)__1
PubMedSearch : Liang_2017_Clin.Toxicol.(Phila)__1
PubMedID: 28681657

Title : Toxic effects of glyphosate on diploid and triploid fin cell lines from Misgurnus anguillicaudatus - Qin_2017_Chemosphere_180_356
Author(s) : Qin Y , Li X , Xiang Y , Wu D , Bai L , Li Z , Liang Y
Ref : Chemosphere , 180 :356 , 2017
Abstract : We examined the toxic effects of glyphosate on diploid (DIMF) and triploid (TRMF) fin cell lines from the Oriental Weather Loach Misgurnus anguillicaudatus. The LC50 values of glyphosate estimated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay were 315.34 and 371.77 mg/L for DIMF and TRMF, respectively. Superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities in DIMF and TRMF cells gradually increased and then decreased with increasing glyphosate concentrations, reaching a maximum at 240 mg/L glyphosate. In contrast, acetylcholinesterase (AChE) activities in DIMF and TRMF decreased with increasing concentrations of glyphosate in a concentration-dependent manner. SOD and AChE activities were generally significantly higher in TRMF compared with DIMF cells (P < 0.05). The rates of micronucleus and abnormal nuclei were significantly higher in DIMF and TRMF groups treated with 80-560 mg/L glyphosate compared with the control groups (P < 0.01). The highest micronuclei rates in both DIMF and TRMF cells (both 4.30 per thousand) occurred at 400 mg/L glyphosate. There were no differences in the rates of micronuclei and abnormal nuclei between DIMF and TRMF cells at any glyphosate concentration. Cell damage, including chromatin condensation, nucleus distortion, and broken and reduced endoplasmic reticulum, mitochondria, and ribosomes, were found in both cells treated with the LC50 concentration of glyphosate. Moreover, vacuolization and apoptotic bodies occurred in glyphosate-exposed DIMF and TRMF cells, indicating apoptosis. These results indicate that glyphosate in the range of tested concentrations represent a potential risk to loach through inhibiting proliferation of diploid and triploid cell lines and induces micronuclei and apoptosis.
ESTHER : Qin_2017_Chemosphere_180_356
PubMedSearch : Qin_2017_Chemosphere_180_356
PubMedID: 28415036

Title : Dabigatran etexilate activation is affected by the CES1 genetic polymorphism G143E (rs71647871) and gender - Shi_2016_Biochem.Pharmacol_119_76
Author(s) : Shi J , Wang X , Nguyen JH , Bleske BE , Liang Y , Liu L , Zhu HJ
Ref : Biochemical Pharmacology , 119 :76 , 2016
Abstract : The oral anticoagulant prodrug dabigatran etexilate (DABE) is sequentially metabolized by intestinal carboxylesterase 2 (CES2) and hepatic carboxylesterase 1 (CES1) to form its active metabolite dabigatran (DAB). A recent genome-wide association study reported that the CES1 single nucleotide polymorphisms (SNPs) rs2244613 and rs8192935 were associated with lower DAB plasma concentrations in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) study participants. In addition, gender differences in exposure to DAB were observed in clinical studies. The aim of this study was to examine the effect of CES1 genetic polymorphisms and gender on DABE activation using several in vitro approaches. The genotypes of the CES1 SNPs rs2244613, rs8192935, and the known loss-of-function CES1 variant rs71647871 (G143E), and the activation of DABE and its intermediate metabolites M1 and M2 were determined in 104 normal human liver samples. DABE, M1, and M2 activations were found to be impaired in human livers carrying the G143E variant. However, neither rs2244613 nor rs8192935 was associated with the activation in human livers. The incubation study of DABE with supernatant fractions (S9) prepared from the G143E-transfected cells showed that the G143E is a loss-of-function variant for DABE metabolism. Moreover, hepatic CES1 activity on M2 activation was significantly higher in female liver samples than male. Our data suggest that CES1 genetic variants and gender are important contributing factors to variability in DABE activation in humans. A personalized DABE treatment approach based on patient-specific CES1 genotypes and sex may have the potential to improve the efficacy and safety of DABE pharmacotherapy.
ESTHER : Shi_2016_Biochem.Pharmacol_119_76
PubMedSearch : Shi_2016_Biochem.Pharmacol_119_76
PubMedID: 27614009
Gene_locus related to this paper: human-CES1

Title : Association of Oseltamivir Activation with Gender and Carboxylesterase 1 Genetic Polymorphisms - Shi_2016_Basic.Clin.Pharmacol.Toxicol_119_555
Author(s) : Shi J , Wang X , Eyler RF , Liang Y , Liu L , Mueller BA , Zhu HJ
Ref : Basic Clin Pharmacol Toxicol , 119 :555 , 2016
Abstract : Oseltamivir, an inactive anti-influenza virus prodrug, is activated (hydrolysed) in vivo by carboxylesterase 1 (CES1) to its active metabolite oseltamivir carboxylate. CES1 functions are significantly associated with certain CES1 genetic variants and some non-genetic factors. The purpose of this study was to investigate the effect of gender and several CES1 genetic polymorphisms on oseltamivir activation using a large set of individual human liver samples. CES1-mediated oseltamivir hydrolysis and CES1 genotypes, including the G143E (rs71647871), rs2244613, rs8192935, the -816A>C (rs3785161) and the CES1P1/CES1P1VAR, were determined in 104 individual human livers. The results showed that hepatic CES1 protein expression in females was 17.3% higher than that in males (p = 0.039), while oseltamivir activation rate in the livers from female donors was 27.8% higher than that from males (p = 0.076). As for CES1 genetic polymorphisms, neither CES1 protein expression nor CES1 activity on oseltamivir activation was significantly associated with the rs2244613, rs8192935, -816A>C or CES1P1/CES1P1VAR genotypes. However, oseltamivir hydrolysis in the livers with the genotype 143G/E was approximately 40% of that with the 143G/G genotype (0.7 +/- 0.2 versus 1.8 +/- 1.1 nmole/mg protein/min, p = 0.005). In summary, the results suggest that hepatic oseltamivir activation appears to be more efficient in females than that in males, and the activation can be impaired by functional CES1 variants, such as the G143E. However, clinical implication of CES1 gender differences and pharmacogenetics in oseltamivir pharmacotherapy warrants further investigations.
ESTHER : Shi_2016_Basic.Clin.Pharmacol.Toxicol_119_555
PubMedSearch : Shi_2016_Basic.Clin.Pharmacol.Toxicol_119_555
PubMedID: 27228223
Gene_locus related to this paper: human-CES1

Title : Relationship of paraoxonase-1 Q192R genotypes and in-stent restenosis and re-stenting in Chinese patients after coronary stenting - Ma_2016_Atherosclerosis_251_305
Author(s) : Ma W , Liang Y , Zhu J , Chen T , Feng G , Yang Y , Liu X , Wang X
Ref : Atherosclerosis , 251 :305 , 2016
Abstract : BACKGROUND AND AIMS: Asians have very different genotype distributions of cytochrome P450 2C19 (CYP2C19), ATP-binding cassette, sub-family B, member 1 (ABCB1), and paraoxonase-1 (PON1), in whom relevant studies based on large samples are scarce. The purpose of this study was to evaluate the effects of these genes on outcomes of in-stent restenosis and re-stenting in Chinese patients after coronary stenting.
METHODS: A total of 2569 acute coronary syndrome (ACS) patients were enrolled in a gene database study. Among the 1674 patients receiving coronary stenting, 504 patients performed repeated coronary angiography within the next year after discharge and were eligible to complete our final cohort.
RESULTS: The prevalence of the CYP2C19 loss-of-function carriers (had at least 1 allele of *2, *3 and *4) was considerable high (52.2%). During re-angiography, in-stent restenosis occurred in 106 (21.0%) out of the 504 patients; the mean restenosis degree was 71.3% and 152 (30.2%) patients received re-stenting treatment. In multivariate regression, only age and left ventricular ejection fraction (LVEF) were significantly associated with in-stent restenosis. As for predictors of re-stenting, multivariate regression identified variables of LVEF, coronary artery lesions, and PON1 Q192R genotype. Genotype RR of PON1 Q192R was an independent risk factor predicting re-stenting compared with genotypes of QQ and QR (OR 1.95, 95% CI 1.30-2.93, p = 0.001). The genotypes of CYP2C19, ABCB1 C3435T, and PON1 L55M showed no significant associations with in-stent restenosis or re-stenting.
CONCLUSIONS: Genotype RR of PON1 Q192R was an independent risk factor predicting re-stenting in Chinese ACS patients after coronary stenting.
ESTHER : Ma_2016_Atherosclerosis_251_305
PubMedSearch : Ma_2016_Atherosclerosis_251_305
PubMedID: 27450784

Title : CES1 genetic variation affects the activation of angiotensin-converting enzyme inhibitors - Wang_2016_Pharmacogenomics.J_16_220
Author(s) : Wang X , Wang G , Shi J , Aa JY , Comas R , Liang Y , Zhu HJ
Ref : Pharmacogenomics J , 16 :220 , 2016
Abstract : The aim of the study was to determine the effect of carboxylesterase 1 (CES1) genetic variation on the activation of angiotensin-converting enzyme inhibitor (ACEI) prodrugs. In vitro incubation study of human liver, intestine and kidney s9 fractions demonstrated that the ACEI prodrugs enalapril, ramipril, perindopril, moexipril and fosinopril are selectively activated by CES1 in the liver. The impact of CES1/CES1VAR and CES1P1/CES1P1VAR genotypes and diplotypes on CES1 expression and activity on enalapril activation was investigated in 102 normal human liver samples. Neither the genotypes nor the diplotypes affected hepatic CES1 expression and activity. Moreover, among several CES1 nonsynonymous variants studied in transfected cell lines, the G143E (rs71647871) was a loss-of-function variant for the activation of all ACEIs tested. The CES1 activity on enalapril activation in human livers with the 143G/E genotype was approximately one-third of that carrying the 143G/G. Thus, some functional CES1 genetic variants (for example, G143E) may impair ACEI activation, and consequently affect therapeutic outcomes of ACEI prodrugs.
ESTHER : Wang_2016_Pharmacogenomics.J_16_220
PubMedSearch : Wang_2016_Pharmacogenomics.J_16_220
PubMedID: 26076923
Gene_locus related to this paper: human-CES1

Title : Targeted absolute quantitative proteomics with SILAC internal standards and unlabeled full-length protein calibrators (TAQSI) - Wang_2016_Rapid.Commun.Mass.Spectrom_30_553
Author(s) : Wang X , Liang Y , Liu L , Shi J , Zhu HJ
Ref : Rapid Commun Mass Spectrom , 30 :553 , 2016
Abstract : RATIONALE: Liquid Chromatography/Mass Spectrometry (LC/MS)-based proteomics for absolute protein quantification has been increasingly utilized in both basic and clinical research. There is a great need to overcome some major hurdles of current absolute protein quantification methods, such as significant inter-assay variability and the high cost associated with the preparation of purified stable-isotope-labeled peptide/protein standards.
METHODS: We developed a novel targeted absolute protein quantification method, named TAQSI, utilizing full-length isotope-labeled protein internal standards generated from SILAC (stable isotope labeling by amino acid in cell culture) and unlabeled full-length protein calibrators. This approach was applied to absolute quantification of carboxylesterase 1 (CES1), the primary human hepatic hydrolase, in a large set of human liver samples. Absolute CES1 quantities were derived from the standard calibration curves established from unlabeled CES1 protein calibrators and the isotope-labeled CES1 internal standards obtained from SILAC HepG2 cells.
RESULTS: The TAQSI assay was found to be accurate, precise, reproducible, and cost-effective. Importantly, protein quantification was not affected by various protein extraction and digestion protocols, and measurement errors associated with nonsynonymous variants can be readily identified and avoided. Furthermore, the TAQSI approach significantly simplifies the procedure of identifying the best performance surrogate peptides.
CONCLUSIONS: The TAQSI assay can be widely used for targeted absolute protein quantification in various biomedical research and clinical practice settings. Copyright (c) 2016 John Wiley & Sons, Ltd.
ESTHER : Wang_2016_Rapid.Commun.Mass.Spectrom_30_553
PubMedSearch : Wang_2016_Rapid.Commun.Mass.Spectrom_30_553
PubMedID: 26842578

Title : SMAX1-LIKE7 Signals from the Nucleus to Regulate Shoot Development in Arabidopsis via Partially EAR Motif-Independent Mechanisms - Liang_2016_Plant.Cell_28_1581
Author(s) : Liang Y , Ward S , Li P , Bennett T , Leyser O
Ref : Plant Cell , 28 :1581 , 2016
Abstract : Strigolactones (SLs) are hormonal signals that regulate multiple aspects of shoot architecture, including shoot branching. Like many plant hormonal signaling systems, SLs act by promoting ubiquitination of target proteins and their subsequent proteasome-mediated degradation. Recently, SMXL6, SMXL7, and SMXL8, members of the SMAX1-LIKE (SMXL) family of chaperonin-like proteins, have been identified as proteolytic targets of SL signaling in Arabidopsis thaliana However, the mechanisms by which these proteins regulate downstream events remain largely unclear. Here, we show that SMXL7 functions in the nucleus, as does the SL receptor, DWARF14 (D14). We show that nucleus-localized D14 can physically interact with both SMXL7 and the MAX2 F-box protein in a SL-dependent manner and that disruption of specific conserved domains in SMXL7 affects its localization, SL-induced degradation, and activity. By expressing and overexpressing these SMXL7 protein variants, we show that shoot tissues are broadly sensitive to SMXL7 activity, but degradation normally buffers the effect of increasing SMXL7 expression. SMXL7 contains a well-conserved EAR (ETHYLENE-RESPONSE FACTOR Amphiphilic Repression) motif, which contributes to, but is not essential for, SMXL7 functionality. Intriguingly, different developmental processes show differential sensitivity to the loss of the EAR motif, raising the possibility that there may be several distinct mechanisms at play downstream of SMXL7.
ESTHER : Liang_2016_Plant.Cell_28_1581
PubMedSearch : Liang_2016_Plant.Cell_28_1581
PubMedID: 27317673

Title : Strigolactone regulates shoot development through a core signalling pathway - Bennett_2016_Biol.Open_5_1806
Author(s) : Bennett T , Liang Y , Seale M , Ward S , Muller D , Leyser O
Ref : Biol Open , 5 :1806 , 2016
Abstract : Strigolactones are a recently identified class of hormone that regulate multiple aspects of plant development. The DWARF14 (D14) alpha/beta fold protein has been identified as a strigolactone receptor, which can act through the SCF(MAX2) ubiquitin ligase, but the universality of this mechanism is not clear. Multiple proteins have been suggested as targets for strigolactone signalling, including both direct proteolytic targets of SCF(MAX2), and downstream targets. However, the relevance and importance of these proteins to strigolactone signalling in many cases has not been fully established. Here we assess the contribution of these targets to strigolactone signalling in adult shoot developmental responses. We find that all examined strigolactone responses are regulated by SCF(MAX2) and D14, and not by other D14-like proteins. We further show that all examined strigolactone responses likely depend on degradation of SMXL proteins in the SMXL6 clade, and not on the other proposed proteolytic targets BES1 or DELLAs. Taken together, our results suggest that in the adult shoot, the dominant mode of strigolactone signalling is D14-initiated, MAX2-mediated degradation of SMXL6-related proteins. We confirm that the BRANCHED1 transcription factor and the PIN-FORMED1 auxin efflux carrier are plausible downstream targets of this pathway in the regulation of shoot branching, and show that BRC1 likely acts in parallel to PIN1.
ESTHER : Bennett_2016_Biol.Open_5_1806
PubMedSearch : Bennett_2016_Biol.Open_5_1806
PubMedID: 27793831

Title : SMAX1-LIKE\/D53 Family Members Enable Distinct MAX2-Dependent Responses to Strigolactones and Karrikins in Arabidopsis - Soundappan_2015_Plant.Cell_27_3143
Author(s) : Soundappan I , Bennett T , Morffy N , Liang Y , Stanga JP , Abbas A , Leyser O , Nelson DC
Ref : Plant Cell , 27 :3143 , 2015
Abstract : The plant hormones strigolactones and smoke-derived karrikins are butenolide signals that control distinct aspects of plant development. Perception of both molecules in Arabidopsis thaliana requires the F-box protein MORE AXILLARY GROWTH2 (MAX2). Recent studies suggest that the homologous SUPPRESSOR OF MAX2 1 (SMAX1) in Arabidopsis and DWARF53 (D53) in rice (Oryza sativa) are downstream targets of MAX2. Through an extensive analysis of loss-of-function mutants, we demonstrate that the Arabidopsis SMAX1-LIKE genes SMXL6, SMXL7, and SMXL8 are co-orthologs of rice D53 that promote shoot branching. SMXL7 is degraded rapidly after treatment with the synthetic strigolactone mixture rac-GR24. Like D53, SMXL7 degradation is MAX2- and D14-dependent and can be prevented by deletion of a putative P-loop. Loss of SMXL6,7,8 suppresses several other strigolactone-related phenotypes in max2, including increased auxin transport and PIN1 accumulation, and increased lateral root density. Although only SMAX1 regulates germination and hypocotyl elongation, SMAX1 and SMXL6,7,8 have complementary roles in the control of leaf morphology. Our data indicate that SMAX1 and SMXL6,7,8 repress karrikin and strigolactone signaling, respectively, and suggest that all MAX2-dependent growth effects are mediated by degradation of SMAX1/SMXL proteins. We propose that functional diversification within the SMXL family enabled responses to different butenolide signals through a shared regulatory mechanism.
ESTHER : Soundappan_2015_Plant.Cell_27_3143
PubMedSearch : Soundappan_2015_Plant.Cell_27_3143
PubMedID: 26546447

Title : Soluble epoxide hydrolase inhibition ameliorates proteinuria-induced epithelial-mesenchymal transition by regulating the PI3K-Akt-GSK-3beta signaling pathway - Liang_2015_Biochem.Biophys.Res.Commun_463_70
Author(s) : Liang Y , Jing Z , Deng H , Li Z , Zhuang Z , Wang S , Wang Y
Ref : Biochemical & Biophysical Research Communications , 463 :70 , 2015
Abstract : Soluble epoxide hydrolase (sEH) plays an essential role in chronic kidney disease by hydrolyzing renoprotective epoxyeicosatrienoic acids to the corresponding inactive dihydroxyeicosatrienoic acids. However, there have been few mechanistic studies elucidating the role of sEH in epithelial-mesenchymal transition (EMT). The present study investigated, in vitro and in vivo, the role of sEH in proteinuria-induced renal tubular EMT and the underlying signaling pathway. We report that urinary protein (UP) induced EMT in cultured NRK-52E cells, as evidenced by decreased E-cadherin expression, increased alpha-smooth muscle actin (alpha-SMA) expression, and the morphological conversion to a myofibroblast-like phenotype. UP incubation also resulted in upregulated sEH, activated phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB/Akt) signaling and increased phosphorylated glycogen synthase kinase-3beta (GSK-3beta). The PI3K inhibitor LY-294002 inhibited phosphorylation of Akt and GSK-3beta as well as blocking EMT. Importantly, pharmacological inhibition of sEH with 12-(3-adamantan-1-yl- ureido)-dodecanoic acid (AUDA) markedly suppressed PI3K-Akt activation and GSK-3beta phosphorylation. EMT associated E-cadherin suppression, alpha-SMA elevation and phenotypic transition were also attenuated by AUDA. Furthermore, in rats with chronic proteinuric renal disease, AUDA treatment inhibited PI3K-Akt activation and GSK-3beta phosphorylation, while attenuating levels of EMT markers. Overall, our findings suggest that sEH inhibition ameliorates proteinuria-induced renal tubular EMT by regulating the PI3K-Akt-GSK-3beta signaling pathway. Targeting sEH might be a potential strategy for the treatment of EMT and renal fibrosis.
ESTHER : Liang_2015_Biochem.Biophys.Res.Commun_463_70
PubMedSearch : Liang_2015_Biochem.Biophys.Res.Commun_463_70
PubMedID: 25986738

Title : Fusaric acid induction of programmed cell death modulated through nitric oxide signalling in tobacco suspension cells - Jiao_2013_Planta_238_727
Author(s) : Jiao J , Zhou B , Zhu X , Gao Z , Liang Y
Ref : Planta , 238 :727 , 2013
Abstract : Fusaric acid (FA) is a nonhost-selective toxin mainly produced by Fusarium oxysporum, the causal agent of plant wilt diseases. We demonstrate that FA can induce programmed cell death (PCD) in tobacco suspension cells and the FA-induced PCD is modulated by nitric oxide (NO) signalling. Cells undergoing cell death induced by FA treatment exhibited typical characteristics of PCD including cytoplasmic shrinkage, chromatin condensation, DNA fragmentation, membrane plasmolysis, and formation of small cytoplasmic vacuoles. In addition, caspase-3-like activity was activated upon the FA treatment. The process of FA-induced PCD was accompanied by a rapid accumulation of NO in a FA dose-dependent manner. Pre-treatment of cells with NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) or NO synthase inhibitor N(G)-monomethyl-arginine monoacetate (L-NMMA) significantly reduced the rate of FA-induced cell death. Furthermore, the caspase-3-like activity and the expression of PAL and Hsr203J genes were alleviated by application of cPTIO or L-NMMA to FA-treated tobacco cells. This indicates that NO is an important factor involved in the FA-induced PCD. Our results also show that pre-treatment of tobacco cells with a caspase-3-specific inhibitor, Ac-DEVD-CHO, can reduce the rate of FA-induced cell death. These results demonstrate that the FA-induced cell death is a PCD and is modulated by NO signalling through caspase-3-like activation.
ESTHER : Jiao_2013_Planta_238_727
PubMedSearch : Jiao_2013_Planta_238_727
PubMedID: 23838885
Gene_locus related to this paper: gibf5-fub4 , gibf5-fub5

Title : Exceptional thermal stability and organic solvent tolerance of an esterase expressed from a thermophilic host - Mei_2012_Appl.Microbiol.Biotechnol_93_1965
Author(s) : Mei Y , Peng N , Zhao S , Hu Y , Wang H , Liang Y , She Q
Ref : Applied Microbiology & Biotechnology , 93 :1965 , 2012
Abstract : A protein expression system recently developed for the thermophilic crenarchaeon Sulfolobus islandicus was employed to produce recombinant protein for EstA, a thermophilic esterase encoded in the same organism. Large amounts of protein were readily obtained by an affinity protein purification, giving SisEstA. Upon Escherichia coli expression, only the thioredoxin-tagged EstA recombinant protein was soluble. The fusion protein was then purified, and removing the protein tag yielded EcSisEstA. Both forms of the thermophilic EstA enzyme were characterized. We found that SisEstA formed dimer exclusively in solution, whereas EcSisEstA appeared solely as monomer. The former exhibited a stronger resistance to organic solvents than the latter in general, having a much higher temperature optimum (90 degrees C vs. 65 degrees C). More strikingly, SisEstA exhibited a half-life that was more than 32-fold longer than that of EcSisEstA at 90 degrees C. This indicated that thermophilic enzymes yielded from homologous expression should be better biocatalysts than those obtained from mesophilic expression.
ESTHER : Mei_2012_Appl.Microbiol.Biotechnol_93_1965
PubMedSearch : Mei_2012_Appl.Microbiol.Biotechnol_93_1965
PubMedID: 21847512
Gene_locus related to this paper: sulir-f0ndq1

Title : [The relationship between carboxylesterase 1 gene polymorphisms and susceptibility to antituberculosis drug-induced hepatotoxicity] - Wu_2012_Zhonghua.Nei.Ke.Za.Zhi_51_524
Author(s) : Wu XQ , Zhu DL , Zhang JX , Zhong Y , Xi Y , An HR , Liang Y , Yang YR
Ref : Zhonghua Nei Ke Za Zhi , 51 :524 , 2012
Abstract : OBJECTIVE: To study the relationship between the genetic polymorphisms of carboxylesterase 1 gene (CES1) and the susceptibility to antituberculosis drug-induced hepatotoxicity (ATBDIH). METHODS: Genetic polymorphisms of CES1 in 473 tuberculosis patients with or without hepatotoxicity (200:273) after antituberculosis chemotherapy were analyzed by PCR-MassArray. RESULTS: In 4 tags of CES1 single nucleotide polymorphism (SNP), the frequency of the rs1968753 allele had statistical difference between the hepatotoxicity group and the no-hepatotoxicity group(P = 0.0236). The characteristics of anti-hepatotoxicity had been shown relationship with rs8192950 (P = 0.044, OR = 0.649, 95%CI = 0.426 - 0.989, AC/AA) and rs1968753 (P = 0.048, OR = 0.556, 95%CI = 0.311 - 0.995, GG/AA). The diplotypes with 'CGC' haplotype exhibited significant protection against hepatotoxicity at one copy (P = 0.048, OR = 0.654, 95%CI = 0.430 - 0.996). CONCLUSIONS: The genetic polymorphisms of CES1 might have significant association with ATBDIH. SNP rs8192950 AC genotype and rs1968753 GG genotype might be the candidates for risk prediction of ATBDIH.
ESTHER : Wu_2012_Zhonghua.Nei.Ke.Za.Zhi_51_524
PubMedSearch : Wu_2012_Zhonghua.Nei.Ke.Za.Zhi_51_524
PubMedID: 22943824

Title : Nicotine normalizes event related potentials in COMT-Val-tg mice and increases gamma and theta spectral density - Cao_2012_Behav.Neurosci_126_332
Author(s) : Cao YA , Featherstone RE , Gandal MJ , Liang Y , Jutzeler C , Saunders J , Tatard-Leitman V , Chen J , Weinberger DR , Lerman C , Siegel SJ
Ref : Behavioral Neuroscience , 126 :332 , 2012
Abstract : Regulation of dopamine neurotransmission is essential for cognitive processes. In humans and rodents, the relationship between dopamine signaling and cognitive performance is described as a dose-dependent, inverted-U curve whereby excess or insufficiency of dopamine in prefrontal cortex has detrimental effects. Previous studies have indicated that prefrontal dopamine levels are associated with genetic variation in catechol-O-methyltransferase (COMT), a regulatory enzyme that controls dopamine availability. Furthermore, smokers who carry the high-activity COMT-Val allele are more prone to cognitive deficits and have an increased risk of smoking relapse. The present study employed transgenic mice expressing the human COMT-Val variant to determine the effects of the high-activity COMT allele on electrophysiological markers, including the P20, N40, and P80 components of the auditory event-related potential, as well as baseline and auditory event-related power and phase-synchrony in theta and gamma ranges. We also examined the effects of nicotine on these measures to investigate the potential effects of smoking on COMT-mediated electrophysiological activity. COMT-Val-tg mice displayed increased N40 latency and decreased P80 amplitude as well as reduced baseline theta and gamma power. Nicotine increased P20 and P80 amplitudes, decreased N40 amplitude, increased P20 and N40 latencies, and reduced P80 latency. Nicotine also increased the event-related power and phase synchrony, yielding an increase in signal-to-noise ratio across theta and gamma ranges. COMT activity specifically alters long-latency components of the event-related response. Nicotine restored normal event-related activity among COMT-Val-tg mice, suggesting one mechanism through which nicotine may normalize cognitive function among people with the high-activity allele.
ESTHER : Cao_2012_Behav.Neurosci_126_332
PubMedSearch : Cao_2012_Behav.Neurosci_126_332
PubMedID: 22309446

Title : Complete genome sequence of Bacillus amyloliquefaciens TA208, a strain for industrial production of guanosine and ribavirin - Zhang_2011_J.Bacteriol_193_3142
Author(s) : Zhang G , Deng A , Xu Q , Liang Y , Chen N , Wen T
Ref : Journal of Bacteriology , 193 :3142 , 2011
Abstract : Here, we report the complete genome sequence of Bacillus amyloliquefaciens TA208, a strain for industrial production of guanosine and synthesis of ribavirin by assimilation of formamide. Comparison of its genome sequence with those of strains DSM7 and FZB42 revealed horizontal gene transfer represented by unique prophages and restriction-modification systems and indicated significant accumulation of guanosine.
ESTHER : Zhang_2011_J.Bacteriol_193_3142
PubMedSearch : Zhang_2011_J.Bacteriol_193_3142
PubMedID: 21515778
Gene_locus related to this paper: baca2-a7z811

Title : A neurotensin analog, NT69L, attenuates intravenous nicotine self-administration in rats - Boules_2011_Neuropeptides_45_9
Author(s) : Boules M , Oliveros A , Liang Y , Williams K , Shaw A , Robinson J , Fredrickson P , Richelson E
Ref : Neuropeptides , 45 :9 , 2011
Abstract : NT69L is a neurotensin analog that blocks nicotine-induced locomotor activity and has sustained efficacy in a rat model of nicotine-induced sensitization when administered peripherally. Additionally, NT69L attenuates food-reinforcement in rats. The present study tested the effect of acute administration of NT69L on nicotine self-infusion in Sprague-Dawley rats. Rats were trained to self-infuse nicotine intravenously (0.03mg/kg per infusion) following operant training. Once the rats acquired stable responding to nicotine self-infusion they were pretreated with NT69L (1mg/kg, i.p.) or saline 30min before being assessed for nicotine self-infusion. Pretreatment with NT69L significantly attenuated nicotine self-infusion under FR1 (fixed ratio of 1) and FR5 schedule of reinforcement as compared to saline pretreatment. Control rats that were response-independent "yoked" as well as rats that self-infused saline or NT69L showed minimal responses, indicating that nicotine served as a reinforcer. Additionally, NT69L modulated serum corticosterone; brain norepinephrine serotonin; and dopamine receptors mRNA levels altered in the nicotine self-infused rats after a 24h withdrawal period. Pretreatment with NT69L significantly decreased the nicotine-induced increase in serum corticosterone levels and striatal norepinephrine and increased the nicotine-induced reduction in serotonin in both the striatum and the prefrontal cortex (PFC). NT69L might modulate dopamine neurotransmission implicated in the reinforcing effects of nicotine by modulating tyrosine hydroxylase and dopamine receptor mRNA levels in the PFC and striatum. These data support further study of the effects of NT analogs on attenuating the reinforcing effects of psychostimulants.
ESTHER : Boules_2011_Neuropeptides_45_9
PubMedSearch : Boules_2011_Neuropeptides_45_9
PubMedID: 21047685

Title : Acetylcholinesterase inhibitors from Corydalis yanhusuo - Xiao_2011_Nat.Prod.Res_25_1418
Author(s) : Xiao HT , Peng J , Liang Y , Yang J , Bai X , Hao XY , Yang FM , Sun QY
Ref : Nat Prod Res , 25 :1418 , 2011
Abstract : In a bioassay-guided search for acetylcholinesterase (AChE) inhibitors from Chinese natural resources, eight isoquinoline alkaloids, tetrahydropalmatine (1), corydaline (2), protopine (3), berberine (4), palmatine (5), jatrorrhizine (6), coptisine (7) and dehydrocorydaline (8), were isolated from the methanolic extract of the tubers of Corydalis yanhusuo. Structures of these compounds were identified by spectroscopic techniques. Compounds 4-8 inhibited AChE activity in a dose-dependent manner, and the IC(5)(0) values were 0.47 +/- 0.01, 0.74 +/- 0.06, 2.08 +/- 0.09, 1.01 +/- 0.03 and 0.62 +/- 0.05 microM, respectively. Structure-activity relationship analysis suggested that aromatisation at ring C, as well as substitutions at C-2, C-3, C-9, C-10 and C-13 affect the AChE activity of protoberberine alkaloids.
ESTHER : Xiao_2011_Nat.Prod.Res_25_1418
PubMedSearch : Xiao_2011_Nat.Prod.Res_25_1418
PubMedID: 20234973

Title : Complete genome sequences of Yersinia pestis from natural foci in China - Shen_2010_J.Bacteriol_192_3551
Author(s) : Shen X , Wang Q , Xia L , Zhu X , Zhang Z , Liang Y , Cai H , Zhang E , Wei J , Chen C , Song Z , Zhang H , Yu D , Hai R
Ref : Journal of Bacteriology , 192 :3551 , 2010
Abstract : Yersinia pestis, the causative agent of plague, is a deadly bacterium that affects humans. Strain D106004 was isolated from a new plague focus in Yulong County, China, in 2006. To gain insights into the epidemic origin, we have sequenced the genomes of D106004 and strains Z176003 and D182038, isolated from neighboring regions.
ESTHER : Shen_2010_J.Bacteriol_192_3551
PubMedSearch : Shen_2010_J.Bacteriol_192_3551
PubMedID: 20453098
Gene_locus related to this paper: yerpe-dlhh , yerpe-PIP , yerpe-PLDB , yerpe-PTRB , yerpe-y1616 , yerpe-y3224 , yerpe-YPLA , yerpe-YPO0180 , yerpe-YPO0667 , yerpe-YPO0773 , yerpe-YPO0986 , yerpe-YPO2526 , yerpe-YPO2814

Title : Spatial variation of Yersinia pestis from Yunnan Province of China - Zhang_2009_Am.J.Trop.Med.Hyg_81_714
Author(s) : Zhang Z , Hai R , Song Z , Xia L , Liang Y , Cai H , Shen X , Zhang E , Xu J , Yu D , Yu XJ
Ref : American Journal of Tropical Medicine & Hygiene , 81 :714 , 2009
Abstract : Yunnan Province of China is considered the site of origin for modern plague. We analyzed the genotypes of eight Yersinia pestis strains isolated from three counties in Yunnan Province by pulse field gel electrophoresis (PFGE). PFGE showed that strains isolated from the same site were identical regardless of hosts or year of isolation. However, Y. pestis strains isolated from geographically distinct loci were genetically divergent. Whole genome sequences of two strains from two foci in Yunnan showed that the genetic variation of Y. pestis strains was caused by genome rearrangement. We concluded that Y. pestis strains in each epidemic focus in Yunnan were a clonal population and selected by host environments. The genomic variability of the Y. pestis strains from different foci were caused by genome rearrangement, which may provide a positive selective advantage for Y. pestis to adapt to its host environments.
ESTHER : Zhang_2009_Am.J.Trop.Med.Hyg_81_714
PubMedSearch : Zhang_2009_Am.J.Trop.Med.Hyg_81_714
PubMedID: 19815893
Gene_locus related to this paper: yerpe-BIOH , yerpe-dlhh , yerpe-PIP , yerpe-PLDB , yerpe-PTRB , yerpe-Y0507 , yerpe-y1616 , yerpe-y3224 , yerpe-YPLA , yerpe-YPO0180 , yerpe-YPO0667 , yerpe-YPO0773 , yerpe-YPO0986 , yerpe-YPO1501 , yerpe-YPO2526 , yerpe-YPO2814

Title : Effect of a novel neurotensin analog, NT69L, on nicotine-induced alterations in monoamine levels in rat brain - Liang_2008_Brain.Res_1231_6
Author(s) : Liang Y , Boules M , Shaw AM , Williams K , Fredrickson P , Richelson E
Ref : Brain Research , 1231 :6 , 2008
Abstract : NT69L, is a novel neurotensin (8-13) analog that participates in the modulation of the dopaminergic pathways implicated in addiction to psychostimulants. NT69L blocks nicotine-induced hyperactivity as well as the initiation and expression of sensitization in rats. Recent evidence suggests that stimulation of mesocorticolimbic dopamine system, with influences from the other monoamine systems, e.g. norepinephrine and serotonin, is involved in nicotine's reinforcing properties. The aim of the present study was to investigate the effect of pretreatment with NT69L on nicotine-induced changes in monoamine levels in the rat brain using in vivo microdialysis. Acute or chronic (0.4 mg/kg, sc, once daily for 2 weeks) administration of nicotine elicited increases in extracellular levels of dopamine, dopamine metabolites, norepinephrine, or serotonin in medial prefrontal cortex, nucleus accumbens shell, and core of rats. Pretreatment with NT69L (1 mg/kg, intraperitoneally, ip) administered 40 min before nicotine injection significantly attenuated the acute nicotine-evoked increases in norepinephrine levels in medial prefrontal cortex, dopamine and serotonin in nucleus accumbens shell. After chronic nicotine administration, pretreatment of NT69L markedly reversed the increase in dopamine levels in the nucleus accumbens core. NT69L's attenuation of some of the biochemical effects of acute and chronic nicotine is consistent with this peptide's attenuation of nicotine-induced behavioral effects. These data further support a role for NT69L or other neurotensin receptor agonists to treat nicotine addiction.
ESTHER : Liang_2008_Brain.Res_1231_6
PubMedSearch : Liang_2008_Brain.Res_1231_6
PubMedID: 18687313

Title : [Preliminary research of 3D reconstruction of short-segment common peroneal nerve functional fascicles] - Qi_2008_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_22_1031
Author(s) : Qi J , Liu X , Xiong Z , Zhou J , Li S , Liang Y , Zhang Y
Ref : Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi , 22 :1031 , 2008
Abstract : OBJECTIVE: To investigate the feasibility of building the 3D reconstruction of short segment common peroneal nerve functional fascicles based on serial histological sections and computer technology.
METHODS: Five cm of the common peroneal nerve in the popliteal fossa, donated by an adult, was made into the serial transverse freezing sections (n=200) at an interval of 0.25 mm and 10 microm in thickness per section. Acetylcholinesterase staining was adopted and the nerve fascicles were observed by microscope. 2D panorama images were acquired by high-resolution digital camera under microscope (x 100) and mosaic software. Different functional fascicles were distinguished and marked on each section. The topographic database was matched by image processing software. The 3D microstructure of the fascicular groups of 5 cm common peroneal nerve was reconstructed using Amira 3.1 3D reconstruction software.
RESULTS: Based on microanatomy and the results of acetylcholinesterase staining, this segmented common peroneal nerve functional fascicles was divided into sensory tract, motor tract, mixed tract and motor-predominating mixed tract. The cross merging was not evident in the nerve fascicles between deep peroneal nerve and superficial peroneal nerve, but existed within the functional fascicles of the deep peroneal nerve and the superficial peroneal nerve. The results of 3D reconstruction reflected the 3D structure of peripheral nerve and its interior functional fascicles factually, which displayed solely or in combination at arbitrary angles.
CONCLUSION: Based on serial histological sections and computer technology, the 3D microstructure of short-segment peripheral nerve functional fascicles can be reconstructed satisfactorily, indicating the feasibility of building 3D reconstruction of long-segmental peripheral nerve functional fascicles.
ESTHER : Qi_2008_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_22_1031
PubMedSearch : Qi_2008_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_22_1031
PubMedID: 18822721

Title : Regulation of hormone-sensitive lipase in islets - Shen_2007_Diabetes.Res.Clin.Pract_75_14
Author(s) : Shen WJ , Liang Y , Wang J , Harada K , Patel S , Michie SA , Osuga J , Ishibashi S , Kraemer FB
Ref : Diabetes Res Clin Pract , 75 :14 , 2007
Abstract : An unique isoform of hormone-sensitive lipase (HSL) is expressed in beta-cells. Recent findings suggest that HSL could be involved in the regulation of glucose stimulated insulin secretion (GSIS), however, these findings are controversial. To test the hypothesis that HSL is involved in control of normal GSIS via changes in its expression and/or activity in response to stimuli, we examined the effects of free fatty acid (FFA) loading and glucagon like peptide-1 (GLP-1) stimulation on the regulation of HSL expression and activity. With prolonged FFA loading, there was increased expression of beta-cell HSL and increased HSL hydrolytic activity in clonal beta-cells. Short-term treatment with GLP-1 increased HSL activity without changing the expression of the beta-cell isoform of HSL. Basal insulin secretion was increased, whereas GLP-1 potentiation of GSIS was decreased in islets isolated from HSL-/- mice, as compared to islets from wild type mice. Furthermore, using PancChip 2.2 cDNA microarrays (NIDDK consortium), the gene expression profile in the islets of HSL-/- mice was compared with wild type mice. Results showed changes in several metabolic pathways due to changes in lipid homeostasis caused by inactivation of HSL. Quantitative PCR for selected genes also revealed changes in genes that are related to insulin secretion, such as UCP-2. Therefore, these results suggest that the beta-cell isoform of HSL is involved in maintaining lipid homeostasis in islets and contributes to the proper control of GSIS.
ESTHER : Shen_2007_Diabetes.Res.Clin.Pract_75_14
PubMedSearch : Shen_2007_Diabetes.Res.Clin.Pract_75_14
PubMedID: 16765472

Title : Study of biochemical pathways and enzymes involved in pyrene degradation by Mycobacterium sp. strain KMS - Liang_2006_Appl.Environ.Microbiol_72_7821
Author(s) : Liang Y , Gardner DR , Miller CD , Chen D , Anderson AJ , Weimer BC , Sims RC
Ref : Applied Environmental Microbiology , 72 :7821 , 2006
Abstract : Pyrene degradation is known in bacteria. In this study, Mycobacterium sp. strain KMS was used to study the metabolites produced during, and enzymes involved in, pyrene degradation. Several key metabolites, including pyrene-4,5-dione, cis-4,5-pyrene-dihydrodiol, phenanthrene-4,5-dicarboxylic acid, and 4-phenanthroic acid, were identified during pyrene degradation. Pyrene-4,5-dione, which accumulates as an end product in some gram-negative bacterial cultures, was further utilized and degraded by Mycobacterium sp. strain KMS. Enzymes involved in pyrene degradation by Mycobacterium sp. strain KMS were studied, using 2-D gel electrophoresis. The first protein in the catabolic pathway, aromatic-ring-hydroxylating dioxygenase, which oxidizes pyrene to cis-4,5-pyrene-dihydrodiol, was induced with the addition of pyrene and pyrene-4,5-dione to the cultures. The subcomponents of dioxygenase, including the alpha and beta subunits, 4Fe-4S ferredoxin, and the Rieske (2Fe-2S) region, were all induced. Other proteins responsible for further pyrene degradation, such as dihydrodiol dehydrogenase, oxidoreductase, and epoxide hydrolase, were also found to be significantly induced by the presence of pyrene and pyrene-4,5-dione. Several nonpathway-related proteins, including sterol-binding protein and cytochrome P450, were induced. A pyrene degradation pathway for Mycobacterium sp. strain KMS was proposed and confirmed by proteomic study by identifying almost all the enzymes required during the initial steps of pyrene degradation.
ESTHER : Liang_2006_Appl.Environ.Microbiol_72_7821
PubMedSearch : Liang_2006_Appl.Environ.Microbiol_72_7821
PubMedID: 17041157

Title : Functional polymorphisms in the human beta4 subunit of nicotinic acetylcholine receptors - Liang_2005_Neurogenetics_6_37
Author(s) : Liang Y , Salas R , Marubio L , Bercovich D , De Biasi M , Beaudet AL , Dani JA
Ref : Neurogenetics , 6 :37 , 2005
Abstract : Human nicotinic acetylcholine receptor (nAChR) polymorphisms occur in different ethnic populations and may result in differences in nAChR ion channel properties. We have identified four nAChR beta 4 subunit (beta4) nucleotide variants: 392C-->T, 526C-->T, 538A-->G, and 1519A-->G. Their corresponding amino acid substitutions are: Thr to Ile at codon 91 (T91I), Arg to Trp at codon 136 (R136W), Ser to Gly at codon 140 (S140G), and Met to Val at codon 467 (M467V), respectively. The nAChR ion channel properties of these variants were studied and compared with the more-common (wild-type) allele as wild-types. The nAChRs (alpha4beta4 channels) were expressed heterologously in Xenopus oocytes and studied using the two-electrode voltage clamp technique to reveal functional differences between the wild-type and the variants. The receptors containing the R136W and M467V mutations (or variants) had a higher sensitivity to acetylcholine and lower EC50 than the wild-type. The T91I mutation had lower sensitivity to acetylcholine and the EC50 was larger than in wild-type nAChRs. The S140G mutation had a dose-response relationship that was similar to the wild-type. The T91I, R136W, and M467V mutations (or variants) also showed a slightly greater degree of steady-state desensitization than the wild-type in response to a 30-min exposure to one tenth of their EC50. The present results demonstrate that human beta4 nAChR DNA polymorphisms result in functional changes, and suggest that certain individuals with those variants may be more or less sensitive to cholinergic drugs or to dysfunctions associated with nicotinic cholinergic systems.
ESTHER : Liang_2005_Neurogenetics_6_37
PubMedSearch : Liang_2005_Neurogenetics_6_37
PubMedID: 15742216

Title : Specific inhibition of hormone-sensitive lipase improves lipid profile while reducing plasma glucose - Claus_2005_J.Pharmacol.Exp.Ther_315_1396
Author(s) : Claus TH , Lowe DB , Liang Y , Salhanick AI , Lubeski CK , Yang L , Lemoine L , Zhu J , Clairmont KB
Ref : Journal of Pharmacology & Experimental Therapeutics , 315 :1396 , 2005
Abstract : Elevation of plasma free fatty acids has been linked with insulin resistance and diabetes. Inhibition of lipolysis may provide a mechanism to decrease plasma fatty acids, thereby improving insulin sensitivity. Hormone-sensitive lipase (HSL) is a critical enzyme involved in the hormonally regulated release of fatty acids and glycerol from adipocyte lipid stores, and its inhibition may thus improve insulin sensitivity and blood glucose handling in type 2 diabetes. In rat adipocytes, forskolin-activated lipolysis was blocked by in vitro addition of a potent and selective HSL inhibitor or by prior treatment of the animals themselves. Antilipolytic effects also were demonstrated in overnight-fasted mice, rats, and dogs with species-dependent effects on plasma free fatty acid levels but with similar reductions in plasma glycerol being observed in all species. Inhibition of HSL also reduced hyperglycemia in streptozotocin-induced diabetic rats. The data support a connection between adipose tissue lipolysis and plasma glucose levels.
ESTHER : Claus_2005_J.Pharmacol.Exp.Ther_315_1396
PubMedSearch : Claus_2005_J.Pharmacol.Exp.Ther_315_1396
PubMedID: 16162821

Title : Potential applications of nicotinic ligands in the laboratory and clinic - Dani_2004_Bioorg.Med.Chem.Lett_14_1837
Author(s) : Dani JA , De Biasi M , Liang Y , Peterson J , Zhang L , Zhang T , Zhou FM
Ref : Bioorganic & Medicinal Chemistry Lett , 14 :1837 , 2004
Abstract : The nicotinic acetylcholine receptor (nAChR) is a receptor, ion channel complex composed of five polypeptide subunits. There are many different nAChR subtypes constructed from a variety of different subunit combinations. This structural diversity contributes to the varied roles of nAChRs in the peripheral and central nervous system, and this diversity offers an excellent opportunity for chemists who are producing ligands. Subunit specific ligands could have wide and varied effects in the laboratory as experimental tools and in the clinic as therapeutic agents. Because presynaptic nAChRs have been shown to enhance the release of many neurotransmitters, new nicotinic ligands that potentiate nAChR activity would be very useful. Such ligands could enhance the release of various neurotransmitters during degenerative diseases that cause neurotransmitter systems to decrease their output. For example, boosting the release from cholinergic neurons would help patients with Alzheimer's disease, and boosting the release from dopaminergic neurons would help patients with Parkinson's disease.
ESTHER : Dani_2004_Bioorg.Med.Chem.Lett_14_1837
PubMedSearch : Dani_2004_Bioorg.Med.Chem.Lett_14_1837
PubMedID: 15050611

Title : Nicotinic cholinergic synaptic mechanisms in the ventral tegmental area contribute to nicotine addiction - Pidoplichko_2004_Learn.Mem_11_60
Author(s) : Pidoplichko VI , Noguchi J , Areola OO , Liang Y , Peterson J , Zhang T , Dani JA
Ref : Learn Mem , 11 :60 , 2004
Abstract : Tobacco use is a major health problem that is estimated to cause 4 million deaths a year worldwide. Nicotine is the main addictive component of tobacco. It acts as an agonist to activate and desensitize nicotinic acetylcholine receptors (nAChRs). A component of nicotine's addictive power is attributable to actions on the mesolimbic dopaminergic system, which serves a fundamental role in the acquisition of behaviors that are inappropriately reinforced by addictive drugs. Here we show that nicotine, in the same concentration and time ranges as obtained from tobacco, has three main actions that regulate the activity of midbrain dopamine (DA) neurons. Nicotine first activates and then desensitizes nAChRs on the DA neurons. This process directly excites the DA neurons for a short period of time before the nAChRs desensitize. Nicotine also enhances glutamatergic excitation and decreases GABAergic inhibition onto DA neurons. These events increase the probability for synaptic plasticity, such as long-term potentiation. The short-lived direct excitation of the DA neurons coupled with the enhanced glutamatergic afferent activity provides the presynaptic and postsynaptic coincidence necessary to initiate synaptic potentiation. In total, these synaptic events lead to a relatively long-lasting heightened activity of midbrain DA neurons. Consistent with other summarized studies, this work indicates that the synaptic changes normally associated with learning and memory can be influenced and commandeered during the nicotine addiction process.
ESTHER : Pidoplichko_2004_Learn.Mem_11_60
PubMedSearch : Pidoplichko_2004_Learn.Mem_11_60
PubMedID: 14747518

Title : The genome sequence of the malaria mosquito Anopheles gambiae - Holt_2002_Science_298_129
Author(s) : Holt RA , Subramanian GM , Halpern A , Sutton GG , Charlab R , Nusskern DR , Wincker P , Clark AG , Ribeiro JM , Wides R , Salzberg SL , Loftus B , Yandell M , Majoros WH , Rusch DB , Lai Z , Kraft CL , Abril JF , Anthouard V , Arensburger P , Atkinson PW , Baden H , de Berardinis V , Baldwin D , Benes V , Biedler J , Blass C , Bolanos R , Boscus D , Barnstead M , Cai S , Center A , Chaturverdi K , Christophides GK , Chrystal MA , Clamp M , Cravchik A , Curwen V , Dana A , Delcher A , Dew I , Evans CA , Flanigan M , Grundschober-Freimoser A , Friedli L , Gu Z , Guan P , Guigo R , Hillenmeyer ME , Hladun SL , Hogan JR , Hong YS , Hoover J , Jaillon O , Ke Z , Kodira C , Kokoza E , Koutsos A , Letunic I , Levitsky A , Liang Y , Lin JJ , Lobo NF , Lopez JR , Malek JA , McIntosh TC , Meister S , Miller J , Mobarry C , Mongin E , Murphy SD , O'Brochta DA , Pfannkoch C , Qi R , Regier MA , Remington K , Shao H , Sharakhova MV , Sitter CD , Shetty J , Smith TJ , Strong R , Sun J , Thomasova D , Ton LQ , Topalis P , Tu Z , Unger MF , Walenz B , Wang A , Wang J , Wang M , Wang X , Woodford KJ , Wortman JR , Wu M , Yao A , Zdobnov EM , Zhang H , Zhao Q , Zhao S , Zhu SC , Zhimulev I , Coluzzi M , della Torre A , Roth CW , Louis C , Kalush F , Mural RJ , Myers EW , Adams MD , Smith HO , Broder S , Gardner MJ , Fraser CM , Birney E , Bork P , Brey PT , Venter JC , Weissenbach J , Kafatos FC , Collins FH , Hoffman SL
Ref : Science , 298 :129 , 2002
Abstract : Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency ("dual haplotypes") in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect.
ESTHER : Holt_2002_Science_298_129
PubMedSearch : Holt_2002_Science_298_129
PubMedID: 12364791
Gene_locus related to this paper: anoga-a0nb77 , anoga-a0nbp6 , anoga-a0neb7 , anoga-a0nei9 , anoga-a0nej0 , anoga-a0ngj1 , anoga-a7ut12 , anoga-a7uuz9 , anoga-ACHE1 , anoga-ACHE2 , anoga-agCG44620 , anoga-agCG44666 , anoga-agCG45273 , anoga-agCG45279 , anoga-agCG45511 , anoga-agCG46741 , anoga-agCG47651 , anoga-agCG47655 , anoga-agCG47661 , anoga-agCG47690 , anoga-agCG48797 , anoga-AGCG49362 , anoga-agCG49462 , anoga-agCG49870 , anoga-agCG49872 , anoga-agCG49876 , anoga-agCG50851 , anoga-agCG51879 , anoga-agCG52383 , anoga-agCG54954 , anoga-AGCG55021 , anoga-agCG55401 , anoga-agCG55408 , anoga-agCG56978 , anoga-ebiG239 , anoga-ebiG2660 , anoga-ebiG5718 , anoga-ebiG5974 , anoga-ebiG8504 , anoga-ebiG8742 , anoga-glita , anoga-nrtac , anoga-q5tpv0 , anoga-Q5TVS6 , anoga-q7pm39 , anoga-q7ppw9 , anoga-q7pq17 , anoga-Q7PQT0 , anoga-q7q8m4 , anoga-q7q626 , anoga-q7qa14 , anoga-q7qa52 , anoga-q7qal7 , anoga-q7qbj0 , anoga-f5hl20 , anoga-q7qkh2 , anoga-a0a1s4h1y7 , anoga-q7q887

Title : The sequence of the human genome - Venter_2001_Science_291_1304
Author(s) : Venter JC , Adams MD , Myers EW , Li PW , Mural RJ , Sutton GG , Smith HO , Yandell M , Evans CA , Holt RA , Gocayne JD , Amanatides P , Ballew RM , Huson DH , Wortman JR , Zhang Q , Kodira CD , Zheng XH , Chen L , Skupski M , Subramanian G , Thomas PD , Zhang J , Gabor Miklos GL , Nelson C , Broder S , Clark AG , Nadeau J , McKusick VA , Zinder N , Levine AJ , Roberts RJ , Simon M , Slayman C , Hunkapiller M , Bolanos R , Delcher A , Dew I , Fasulo D , Flanigan M , Florea L , Halpern A , Hannenhalli S , Kravitz S , Levy S , Mobarry C , Reinert K , Remington K , Abu-Threideh J , Beasley E , Biddick K , Bonazzi V , Brandon R , Cargill M , Chandramouliswaran I , Charlab R , Chaturvedi K , Deng Z , Di Francesco V , Dunn P , Eilbeck K , Evangelista C , Gabrielian AE , Gan W , Ge W , Gong F , Gu Z , Guan P , Heiman TJ , Higgins ME , Ji RR , Ke Z , Ketchum KA , Lai Z , Lei Y , Li Z , Li J , Liang Y , Lin X , Lu F , Merkulov GV , Milshina N , Moore HM , Naik AK , Narayan VA , Neelam B , Nusskern D , Rusch DB , Salzberg S , Shao W , Shue B , Sun J , Wang Z , Wang A , Wang X , Wang J , Wei M , Wides R , Xiao C , Yan C , Yao A , Ye J , Zhan M , Zhang W , Zhang H , Zhao Q , Zheng L , Zhong F , Zhong W , Zhu S , Zhao S , Gilbert D , Baumhueter S , Spier G , Carter C , Cravchik A , Woodage T , Ali F , An H , Awe A , Baldwin D , Baden H , Barnstead M , Barrow I , Beeson K , Busam D , Carver A , Center A , Cheng ML , Curry L , Danaher S , Davenport L , Desilets R , Dietz S , Dodson K , Doup L , Ferriera S , Garg N , Gluecksmann A , Hart B , Haynes J , Haynes C , Heiner C , Hladun S , Hostin D , Houck J , Howland T , Ibegwam C , Johnson J , Kalush F , Kline L , Koduru S , Love A , Mann F , May D , McCawley S , McIntosh T , McMullen I , Moy M , Moy L , Murphy B , Nelson K , Pfannkoch C , Pratts E , Puri V , Qureshi H , Reardon M , Rodriguez R , Rogers YH , Romblad D , Ruhfel B , Scott R , Sitter C , Smallwood M , Stewart E , Strong R , Suh E , Thomas R , Tint NN , Tse S , Vech C , Wang G , Wetter J , Williams S , Williams M , Windsor S , Winn-Deen E , Wolfe K , Zaveri J , Zaveri K , Abril JF , Guigo R , Campbell MJ , Sjolander KV , Karlak B , Kejariwal A , Mi H , Lazareva B , Hatton T , Narechania A , Diemer K , Muruganujan A , Guo N , Sato S , Bafna V , Istrail S , Lippert R , Schwartz R , Walenz B , Yooseph S , Allen D , Basu A , Baxendale J , Blick L , Caminha M , Carnes-Stine J , Caulk P , Chiang YH , Coyne M , Dahlke C , Mays A , Dombroski M , Donnelly M , Ely D , Esparham S , Fosler C , Gire H , Glanowski S , Glasser K , Glodek A , Gorokhov M , Graham K , Gropman B , Harris M , Heil J , Henderson S , Hoover J , Jennings D , Jordan C , Jordan J , Kasha J , Kagan L , Kraft C , Levitsky A , Lewis M , Liu X , Lopez J , Ma D , Majoros W , McDaniel J , Murphy S , Newman M , Nguyen T , Nguyen N , Nodell M , Pan S , Peck J , Peterson M , Rowe W , Sanders R , Scott J , Simpson M , Smith T , Sprague A , Stockwell T , Turner R , Venter E , Wang M , Wen M , Wu D , Wu M , Xia A , Zandieh A , Zhu X
Ref : Science , 291 :1304 , 2001
Abstract : A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.
ESTHER : Venter_2001_Science_291_1304
PubMedSearch : Venter_2001_Science_291_1304
PubMedID: 11181995
Gene_locus related to this paper: human-AADAC , human-ABHD1 , human-ABHD10 , human-ABHD11 , human-ACHE , human-BCHE , human-LDAH , human-ABHD18 , human-CMBL , human-ABHD17A , human-KANSL3 , human-LIPA , human-LYPLAL1 , human-NDRG2 , human-NLGN3 , human-NLGN4X , human-NLGN4Y , human-PAFAH2 , human-PREPL , human-RBBP9 , human-SPG21

Title : Characterization of the functional interaction of adipocyte lipid-binding protein with hormone-sensitive lipase - Shen_2001_J.Biol.Chem_276_49443
Author(s) : Shen WJ , Liang Y , Hong R , Patel S , Natu V , Sridhar K , Jenkins A , Bernlohr DA , Kraemer FB
Ref : Journal of Biological Chemistry , 276 :49443 , 2001
Abstract : Hormone-sensitive lipase (HSL) is an intracellular lipase that plays an important role in the hydrolysis of triacylglycerol in adipose tissue. HSL has been shown to interact with adipocyte lipid-binding protein (ALBP), a member of the family of intracellular lipid-binding proteins that bind fatty acids and other hydrophobic ligands. The current studies have addressed the functional significance of the association and mapped the site of interaction between HSL and ALBP. Incubation of homogeneous ALBP with purified, recombinant HSL in vitro resulted in a 2-fold increase in substrate hydrolysis. Moreover, the ability of oleate to inhibit HSL hydrolytic activity was attenuated by co-incubation with ALBP. Co-transfection of Chinese hamster ovary cells with HSL and ALBP resulted in greater hydrolytic activity than transfection of cells with HSL and vector alone. Deletional mutations of HSL localized the region of HSL that interacts with ALBP to amino acids 192-200, and site-directed mutagenesis of individual amino acids in this region identified His-194 and Glu-199 as critical for mediating the interaction of HSL with ALBP. Interestingly, HSL mutants H194L and E199A, each of which retained normal basal hydrolytic activity, failed to display an increase in hydrolytic activity when co-transfected with wild type ALBP. Therefore, ALBP increases the hydrolytic activity of HSL through its ability to bind and sequester fatty acids and via specific protein-protein interaction. Thus, HSL and ALBP constitute a functionally important lipolytic complex.
ESTHER : Shen_2001_J.Biol.Chem_276_49443
PubMedSearch : Shen_2001_J.Biol.Chem_276_49443
PubMedID: 11682468

Title : Endogenous nicotinic cholinergic activity regulates dopamine release in the striatum - Zhou_2001_Nat.Neurosci_4_1224
Author(s) : Zhou FM , Liang Y , Dani JA
Ref : Nat Neurosci , 4 :1224 , 2001
Abstract : Dopamine is vital for coordinated motion and for association learning linked to behavioral reinforcement. Here we show that the precise overlap of striatal dopaminergic and cholinergic fibers underlies potent control of dopamine release by ongoing nicotinic receptor activity. In mouse striatal slices, nicotinic antagonists or depletion of endogenous acetylcholine decreased evoked dopamine release by 90%. Nicotine at the concentration experienced by smokers also regulated dopamine release. In mutant mice lacking the beta2 nicotinic subunit, evoked dopamine release was dramatically suppressed, and those mice did not show cholinergic regulation of dopamine release. The results offer new perspectives when considering nicotine addiction and the high prevalence of smoking in schizophrenics.
ESTHER : Zhou_2001_Nat.Neurosci_4_1224
PubMedSearch : Zhou_2001_Nat.Neurosci_4_1224
PubMedID: 11713470

Title : Importance of arginines 63 and 423 in modulating the bile salt-dependent and bile salt-independent hydrolytic activities of rat carboxyl ester lipase - Liang_2000_J.Biol.Chem_275_24040
Author(s) : Liang Y , Medhekar R , Brockman HL , Quinn DM , Hui DY
Ref : Journal of Biological Chemistry , 275 :24040 , 2000
Abstract : Previous studies using chemical modification approach have shown the importance of arginine residues in bile salt activation of carboxyl ester lipase (CEL) activity. However, the x-ray crystal structure of CEL failed to show the involvement of arginine residues in CEL-bile salt interaction. The current study used a site-specific mutagenesis approach to determine the role of arginine residues 63 and 423 in bile salt-dependent and bile salt-independent hydrolytic activities of rat CEL. Mutations of Arg(63) to Ala(63) (R63A) and Arg(423) to Gly(423) (R423G) resulted in enzymes with increased bile salt-independent hydrolytic activity against lysophosphatidylcholine, having 6.5- and 2-fold higher k(cat) values, respectively, in comparison to wild type CEL. In contrast, the R63A and R423A mutant enzymes displayed 5- and 11-fold decreases in k(cat), in comparison with wild type CEL, for bile salt-dependent cholesteryl ester hydrolysis. Although taurocholate induced similar changes in circular dichroism spectra for wild type, R63A, and R423G proteins, this bile salt was less efficient in protecting the mutant enzymes against thermal inactivation in comparison with control CEL. Lipid binding studies revealed less R63A and R423G mutant CEL were bound to 1,2-diolein monolayer at saturation compared with wild type CEL. These results, along with computer modeling of the CEL protein, indicated that Arg(63) and Arg(423) are not involved directly with monomeric bile salt binding. However, these residues participate in micellar bile salt modulation of CEL enzymatic activity through intramolecular hydrogen bonding with the C-terminal domain. These residues are also important, probably through similar intramolecular hydrogen bond formation, in stabilizing the enzyme in solution and at the lipid-water interface.
ESTHER : Liang_2000_J.Biol.Chem_275_24040
PubMedSearch : Liang_2000_J.Biol.Chem_275_24040
PubMedID: 10811659

Title : A whole-genome assembly of Drosophila - Myers_2000_Science_287_2196
Author(s) : Myers EW , Sutton GG , Delcher AL , Dew IM , Fasulo DP , Flanigan MJ , Kravitz SA , Mobarry CM , Reinert KH , Remington KA , Anson EL , Bolanos RA , Chou HH , Jordan CM , Halpern AL , Lonardi S , Beasley EM , Brandon RC , Chen L , Dunn PJ , Lai Z , Liang Y , Nusskern DR , Zhan M , Zhang Q , Zheng X , Rubin GM , Adams MD , Venter JC
Ref : Science , 287 :2196 , 2000
Abstract : We report on the quality of a whole-genome assembly of Drosophila melanogaster and the nature of the computer algorithms that accomplished it. Three independent external data sources essentially agree with and support the assembly's sequence and ordering of contigs across the euchromatic portion of the genome. In addition, there are isolated contigs that we believe represent nonrepetitive pockets within the heterochromatin of the centromeres. Comparison with a previously sequenced 2.9- megabase region indicates that sequencing accuracy within nonrepetitive segments is greater than 99. 99% without manual curation. As such, this initial reconstruction of the Drosophila sequence should be of substantial value to the scientific community.
ESTHER : Myers_2000_Science_287_2196
PubMedSearch : Myers_2000_Science_287_2196
PubMedID: 10731133

Title : The genome sequence of Drosophila melanogaster - Adams_2000_Science_287_2185
Author(s) : Adams MD , Celniker SE , Holt RA , Evans CA , Gocayne JD , Amanatides PG , Scherer SE , Li PW , Hoskins RA , Galle RF , George RA , Lewis SE , Richards S , Ashburner M , Henderson SN , Sutton GG , Wortman JR , Yandell MD , Zhang Q , Chen LX , Brandon RC , Rogers YH , Blazej RG , Champe M , Pfeiffer BD , Wan KH , Doyle C , Baxter EG , Helt G , Nelson CR , Gabor GL , Abril JF , Agbayani A , An HJ , Andrews-Pfannkoch C , Baldwin D , Ballew RM , Basu A , Baxendale J , Bayraktaroglu L , Beasley EM , Beeson KY , Benos PV , Berman BP , Bhandari D , Bolshakov S , Borkova D , Botchan MR , Bouck J , Brokstein P , Brottier P , Burtis KC , Busam DA , Butler H , Cadieu E , Center A , Chandra I , Cherry JM , Cawley S , Dahlke C , Davenport LB , Davies P , de Pablos B , Delcher A , Deng Z , Mays AD , Dew I , Dietz SM , Dodson K , Doup LE , Downes M , Dugan-Rocha S , Dunkov BC , Dunn P , Durbin KJ , Evangelista CC , Ferraz C , Ferriera S , Fleischmann W , Fosler C , Gabrielian AE , Garg NS , Gelbart WM , Glasser K , Glodek A , Gong F , Gorrell JH , Gu Z , Guan P , Harris M , Harris NL , Harvey D , Heiman TJ , Hernandez JR , Houck J , Hostin D , Houston KA , Howland TJ , Wei MH , Ibegwam C , Jalali M , Kalush F , Karpen GH , Ke Z , Kennison JA , Ketchum KA , Kimmel BE , Kodira CD , Kraft C , Kravitz S , Kulp D , Lai Z , Lasko P , Lei Y , Levitsky AA , Li J , Li Z , Liang Y , Lin X , Liu X , Mattei B , McIntosh TC , McLeod MP , McPherson D , Merkulov G , Milshina NV , Mobarry C , Morris J , Moshrefi A , Mount SM , Moy M , Murphy B , Murphy L , Muzny DM , Nelson DL , Nelson DR , Nelson KA , Nixon K , Nusskern DR , Pacleb JM , Palazzolo M , Pittman GS , Pan S , Pollard J , Puri V , Reese MG , Reinert K , Remington K , Saunders RD , Scheeler F , Shen H , Shue BC , Siden-Kiamos I , Simpson M , Skupski MP , Smith T , Spier E , Spradling AC , Stapleton M , Strong R , Sun E , Svirskas R , Tector C , Turner R , Venter E , Wang AH , Wang X , Wang ZY , Wassarman DA , Weinstock GM , Weissenbach J , Williams SM , WoodageT , Worley KC , Wu D , Yang S , Yao QA , Ye J , Yeh RF , Zaveri JS , Zhan M , Zhang G , Zhao Q , Zheng L , Zheng XH , Zhong FN , Zhong W , Zhou X , Zhu S , Zhu X , Smith HO , Gibbs RA , Myers EW , Rubin GM , Venter JC
Ref : Science , 287 :2185 , 2000
Abstract : The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.
ESTHER : Adams_2000_Science_287_2185
PubMedSearch : Adams_2000_Science_287_2185
PubMedID: 10731132
Gene_locus related to this paper: drome-1vite , drome-2vite , drome-3vite , drome-a1z6g9 , drome-abhd2 , drome-ACHE , drome-b6idz4 , drome-BEM46 , drome-CG5707 , drome-CG5704 , drome-CG1309 , drome-CG1882 , drome-CG1986 , drome-CG2059 , drome-CG2493 , drome-CG2528 , drome-CG2772 , drome-CG3160 , drome-CG3344 , drome-CG3523 , drome-CG3524 , drome-CG3734 , drome-CG3739 , drome-CG3744 , drome-CG3841 , drome-CG4267 , drome-CG4382 , drome-CG4390 , drome-CG4572 , drome-CG4582 , drome-CG4851 , drome-CG4979 , drome-CG5068 , drome-CG5162 , drome-CG5355 , drome-CG5377 , drome-CG5397 , drome-CG5412 , drome-CG5665 , drome-CG5932 , drome-CG5966 , drome-CG6018 , drome-CG6113 , drome-CG6271 , drome-CG6283 , drome-CG6295 , drome-CG6296 , drome-CG6414 , drome-CG6431 , drome-CG6472 , drome-CG6567 , drome-CG6675 , drome-CG6753 , drome-CG6847 , drome-CG7329 , drome-CG7367 , drome-CG7529 , drome-CG7632 , drome-CG8058 , drome-CG8093 , drome-CG8233 , drome-CG8424 , drome-CG8425 , drome-CG9059 , drome-CG9186 , drome-CG9287 , drome-CG9289 , drome-CG9542 , drome-CG9858 , drome-CG9953 , drome-CG9966 , drome-CG10116 , drome-CG10163 , drome-CG10175 , drome-CG10339 , drome-CG10357 , drome-CG10982 , drome-CG11034 , drome-CG11055 , drome-CG11309 , drome-CG11319 , drome-CG11406 , drome-CG11598 , drome-CG11600 , drome-CG11608 , drome-CG11626 , drome-CG11935 , drome-CG12108 , drome-CG12869 , drome-CG13282 , drome-CG13562 , drome-CG13772 , drome-CG14034 , drome-nlg3 , drome-CG14717 , drome-CG15101 , drome-CG15102 , drome-CG15106 , drome-CG15111 , drome-CG15820 , drome-CG15821 , drome-CG15879 , drome-CG17097 , drome-CG17099 , drome-CG17101 , drome-CG17191 , drome-CG17192 , drome-CG17292 , drome-CG18258 , drome-CG18284 , drome-CG18301 , drome-CG18302 , drome-CG18493 , drome-CG18530 , drome-CG18641 , drome-CG18815 , drome-CG31089 , drome-CG31091 , drome-CG32333 , drome-CG32483 , drome-CG33174 , drome-dnlg1 , drome-este4 , drome-este6 , drome-GH02384 , drome-GH02439 , drome-glita , drome-KRAKEN , drome-lip1 , drome-LIP2 , drome-lip3 , drome-MESK2 , drome-nrtac , drome-OME , drome-q7k274 , drome-Q9VJN0 , drome-Q8IP31 , drome-q9vux3

Title : Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. -
Author(s) : Sherrington R , Rogaev EI , Liang Y , Rogaeva EA , Levesque G , Ikeda M , Chi H , Lin C , Li G , Holman K , Tsuda T , Mar L , Foncin J-F , Bruni AC , Montesi MP , Sorbi S , Rainero I , Pinessi L , Nee L , Chumakov I , Pollen D , Brookes A , Sanseau P , Polinsky RJ , Wasco W , da Silva HAR , Haines JL , Pericak-Vance MA , Tanzi RE , Roses AD , Fraser PE , Rommens JM , St George-Hyslop PH
Ref : Nature , 375 :754 , 1995
PubMedID: 7596406
Gene_locus related to this paper: human-ACOT2