Zhu X

References (75)

Title : Expanding the clinical spectrum of anti-DPPX encephalitis: a multicenter retrospective study - Gao_2024_Front.Neurosci_18_1379933
Author(s) : Gao Y , Zhang Y , Chunyu H , Xu Y , Wang Y , Liu S , Chang J , Tang B , Xu C , Lu Y , Zhou J , Kong X , Zhu X , Chen S , Zhou Q , Meng H
Ref : Front Neurosci , 18 :1379933 , 2024
Abstract : OBJECTIVE: Anti-dipeptidyl-peptidase-like protein-6 (DPPX) encephalitis is a rare autoimmune encephalitis, and clinical and experimental information regarding this disease is limited. We conducted this study to comprehensively describe the clinical characteristics, ancillary test results, neuroimaging results, and treatment response in a group of Chinese patients with anti-DPPX encephalitis for better understanding this disease. METHODS: We recruited 14 patients who tested positive for anti-DPPX antibodies in the serum and/or cerebrospinal fluid from 11 medical centers between March 2021 and June 2023. This retrospective study evaluated data on symptoms, autoantibody test, auxiliary examinations, treatments, and outcomes. RESULTS: The average age at diagnosis was 45.93 +/- 4.62 years (range: 11-72 years), and 9 of the 14 patients were males. The main symptoms included cognitive impairment (50.0%, 7/14), central nervous system hyperexcitability (42.9%, 6/14), gastrointestinal dysfunction (35.7%, 5/14), and psychiatric disorders (35.7%, 5/14). Notably, we discovered specific findings on (18)F-fluorodeoxyglucose positron-emission tomography (PET)/magnetic resonance imaging in two patients. Co-existing autoantibodies were identified in two patients. Parainfection was identified in four patients. One patient had other autoimmune diseases, and one had tumor. Eleven patients received immunotherapy and most patients improved at discharge. Surprisingly, three male patients but no female patients relapsed during the 6 months of follow-up. CONCLUSION: The development and outcome of anti-DPPX encephalitis are variable. Male patients were predominant in our cohort. The most common symptoms were the classical triad of prodromal gastrointestinal dysfunction, cognitive and mental disorders, and central nervous system hyperexcitability. Infections, immune dysregulation, and tumors may be important etiologies. Long-term monitoring of disease development should be done in male patients. Overall, our results highlight novel clinical characteristics of anti-DPPX encephalitis.
ESTHER : Gao_2024_Front.Neurosci_18_1379933
PubMedSearch : Gao_2024_Front.Neurosci_18_1379933
PubMedID: 38756408
Gene_locus related to this paper: human-DPP6

Title : Inhibition of cannabinoid degradation enhances hippocampal contextual fear memory and exhibits anxiolytic effects - Zhang_2024_iScience_27_108919
Author(s) : Zhang J , Yuan R , Han W , Chang Y , Kong L , Wei C , Zheng Q , Zhu X , Liu Z , Ren W , Han J
Ref : iScience , 27 :108919 , 2024
Abstract : Recent studies have demonstrated the pivotal involvement of endocannabinoids in regulating learning and memory, but the conclusions obtained from different paradigms or contexts are somewhat controversial, and the underlying mechanisms remain largely elusive. Here, we show that JZL195, a dual inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase, can enhance the performance of mice in a contextual fear conditioning task and increase the time spent in open arms in the elevated zero maze (EZM). Although the effect of JZL195 on fear memory could not be inhibited by antagonists of cannabinoid receptors, the effect on the EZM seems to be mediated by CB1R. Simultaneously, hippocampal neurons are hyperactive, and theta oscillation power is significantly increased during the critical period of memory consolidation upon treatment with JZL195. These results suggest the feasibility of targeting the endocannabinoid system for the treatment of various mental disorders.
ESTHER : Zhang_2024_iScience_27_108919
PubMedSearch : Zhang_2024_iScience_27_108919
PubMedID: 38318362

Title : Inquiry lipaseoring the mechanism of pancreatic lipase inhibition by isovitexin based on multispectral method and enzyme inhibition assay - Yu_2024_Luminescence_39_e4765
Author(s) : Yu H , Xing Z , Jia K , Li S , Xu Y , Zhao P , Zhu X
Ref : Luminescence , 39 :e4765 , 2024
Abstract : Isovitexin is a main natural flavonoid component in various plants. Currently, the inhibitory effect of isovitexin on pancreatic lipase (PL) and its mechanism have not been elucidated yet. In the present study, we investigated the inhibitory effect of isovitexin on PL, as well as its interaction mechanism, using enzyme inhibition methods, spectroscopic analysis, and molecular simulations. Results showed that isovitexin possessed significant PL inhibitory activity, with IC(50) values of 0.26 +/- 0.02 mM. The interaction between isovitexin and PL was dominated by static quenching, and mainly through hydrogen bonding and hydrophobic interaction forces. Analysis of fluorescence spectroscopy confirmed that isovitexin binding altered the conformation of the PL. Circular dichroism (CD) spectrum indicated that isovitexin altered the secondary structure of PL by decreasing the alpha-helix content and increasing the beta-fold content. Molecular simulations further characterize the conformational changes produced by the interaction between isovitexin with PL. The performed study may provide a new insight into the inhibitory mechanism of isovitexin as a novel PL inhibitor.
ESTHER : Yu_2024_Luminescence_39_e4765
PubMedSearch : Yu_2024_Luminescence_39_e4765
PubMedID: 38769927

Title : Genome-Wide Identification and Characterization of Effector Candidates with Conserved Motif in Falciphora oryzae - Dai_2024_Int.J.Mol.Sci_25_
Author(s) : Dai M , Su Z , Zhu X , Li L , Ye Z , Tan X , Kong D , Liu X , Lin F
Ref : Int J Mol Sci , 25 : , 2024
Abstract : Microbes employ effectors to disrupt immune responses and promote host colonization. Conserved motifs including RXLR, LFLAK-HVLVxxP (CRN), Y/F/WxC, CFEM, LysM, Chitin-bind, DPBB_1 (PNPi), and Cutinase have been discovered to play crucial roles in the functioning of effectors in filamentous fungi. Nevertheless, little is known about effectors with conserved motifs in endophytes. This research aims to discover the effector genes with conserved motifs in the genome of rice endophyte Falciphora oryzae. SignalP identified a total of 622 secreted proteins, out of which 227 were predicted as effector candidates by EffectorP. By utilizing HMM features, we discovered a total of 169 effector candidates with conserved motifs and three novel motifs. Effector candidates containing LysM, CFEM, DPBB_1, Cutinase, and Chitin_bind domains were conserved across species. In the transient expression assay, it was observed that one CFEM and one LysM activated cell death in tobacco leaves. Moreover, two CFEM and one Chitin_bind inhibited cell death induced by Bax protein. At various points during the infection, the genes' expression levels were increased. These results will help to identify functional effector proteins involving omics methods using new bioinformatics tools, thus providing a basis for the study of symbiosis mechanisms.
ESTHER : Dai_2024_Int.J.Mol.Sci_25_
PubMedSearch : Dai_2024_Int.J.Mol.Sci_25_
PubMedID: 38203820

Title : Wwl70-induced ABHD6 inhibition attenuates memory deficits and pathological phenotypes in APPswe\/PS1dE9 mice - Xue_2023_Pharmacol.Res__106864
Author(s) : Xue Z , Ye L , Ge J , Lan Z , Zou X , Mao C , Bao X , Yu L , Xu Y , Zhu X
Ref : Pharmacol Res , :106864 , 2023
Abstract : Synaptic dysfunction plays a crucial role in the pathogenesis of Alzheimer's disease (AD). alpha/beta-hydrolase domain-containing 6 (ABHD6) contributes to synaptic dysfunctions, and ABHD6 inhibition has shown potential therapeutic value in neurological disorders. However, the role of ABHD6 in AD has not been fully defined. In this study, we demonstrated that adeno-associated virus (AAV) mediated shRNA targeting ABHD6 in hippocampal neurons attenuated synaptic dysfunction and memory impairment of APPswe/PS1dE9 (APP/PS1) mice, while it didn't affect the amyloid-beta (Abeta) levels and neuroinflammation in the brains. In addition, intraperitoneal injection of wwl70, a specific inhibitor of ABHD6, improved synaptic plasticity and memory function in APP/PS1 mice, which might attribute to the activation of endogenous cannabinoid signaling. Furthermore, wwl70 significantly decreased the Abeta levels and neuroinflammation in the hippocampus of AD mice, and enhanced Abeta phagocytized by microglia. In conclusion, for the first time our data have shown that ABHD6 inhibition might be a promising strategy for AD treatment, and wwl70 is a potential candidate for AD drug development pipeline.
ESTHER : Xue_2023_Pharmacol.Res__106864
PubMedSearch : Xue_2023_Pharmacol.Res__106864
PubMedID: 37480972
Gene_locus related to this paper: human-ABHD6 , mouse-ABHD6

Title : Pharmacological effect and mechanism of orlistat in anti-tumor therapy: A review - Hao_2023_Medicine.(Baltimore)_102_e34671
Author(s) : Hao X , Zhu X , Tian H , Lai G , Zhang W , Zhou H , Liu S
Ref : Medicine (Baltimore) , 102 :e34671 , 2023
Abstract : Research has demonstrated that obesity is an important risk factor for cancer progression. Orlistat is a lipase inhibitor with promising therapeutic effects on obesity. In addition to being regarded as a slimming drug, a growing number of studies in recent years have suggested that orlistat has anti-tumor activities, while the underlying mechanism is still not well elucidated. This paper reviewed recent pharmacological effects and mechanisms of orlistat against tumors and found that orlistat can target cancer cells through activation or suppression of multiple signaling pathways. It can induce tumor cells apoptosis or death, interfere with tumor cells' cycles controlling, suppress fatty acid synthase activity, increase ferroptosis, inhibit tumor angiogenesis, and improve tumor cells glycolytic. Thus, this review may shed new light on anti-tumor mechanism and drug repurposing of orlistat, and anti-tumor drug development.
ESTHER : Hao_2023_Medicine.(Baltimore)_102_e34671
PubMedSearch : Hao_2023_Medicine.(Baltimore)_102_e34671
PubMedID: 37682175

Title : Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase\/transferase - Wang_2023_Nat.Commun_14_4795
Author(s) : Wang C , Liu C , Zhu X , Peng Q , Ma Q
Ref : Nat Commun , 14 :4795 , 2023
Abstract : Although enzyme catalysis is typified by high specificity, enzymes can catalyze various substrates (substrate promiscuity) and/or different reaction types (catalytic promiscuity) using a single active site. This interesting phenomenon is widely distributed in enzyme catalysis, with both fundamental and applied importance. To date, the mechanistic understanding of enzyme promiscuity is very limited. Herein, we report the structural mechanism underlying the substrate and catalytic promiscuity of Vibrio dual lipase/transferase (VDLT). Crystal structures of the VDLT from Vibrio alginolyticus (ValDLT) and its fatty acid complexes were solved, revealing prominent structural flexibility. In particular, the "Ser-His-Asp" catalytic triad machinery of ValDLT contains an intrinsically flexible oxyanion hole. Analysis of ligand-bound structures and mutagenesis showed that the flexible oxyanion hole and other binding residues can undergo distinct conformational changes to facilitate substrate and catalytic promiscuity. Our study reveals a previously unknown flexible form of the famous catalytic triad machinery and proposes a "catalytic site tuning" mechanism to expand the mechanistic paradigm of enzyme promiscuity.
ESTHER : Wang_2023_Nat.Commun_14_4795
PubMedSearch : Wang_2023_Nat.Commun_14_4795
PubMedID: 37558668

Title : Microbiome dynamics during anaerobic digestion of food waste and the genetic potential for poly (lactic acid) co-digestion - Zhu_2023_Chem.Eng.J__145194
Author(s) : Zhu X , Zhu S , Zhao Z , Kang X , Ju F
Ref : Chemical Engineering Journal , :145194 , 2023
Abstract : Anaerobic digestion of food waste (FW) and potential co-digestion with biodegradable packaging material (i.e., bioplastics) have been promising resource recovery strategies. Unveiling the microbiome dynamics involved in the digestion process and exploring the genetic potential for poly (lactic acid) hydrolysis therein provide the fundamental basis for further process control and optimization. The current study has shown that the FW-digesting microbiome changed in both composition and activity-dormancy status while consuming available substrates. The microbiome assembly was mainly driven by homogeneous selection (36.7% on average) and drift (59.5% on average), and the homogeneous selection effect scaled with the availability of substrates. Based on the ratio between the relative activity and abundance, the microbiome was clustered into four groups. The Group (1) microbes, including Bacterioidetes_vadinHA17 and Syntrophomonadaceae, accumulated high relative abundance during the early stage of the digestion process but entered dormancy after the preferred substrate was consumed. Other members, i.e., the Group 4 Syntrophobacteraceae and Pseudomonadaceae, showed low abundance but disproportional activity during the later stage of the digestion process. The genome-centric metagenomics revealed that inherent AD microbes, especially the Group (1) microbes, harbored robust hydrolase genes, facilitating the PLA degradation. In fact, PLA addition to FW digestor led to significant methane production enhancement (14%) but negligible changes in microbiome composition. The outcome of this study provided the theoretical basis for developing microbiome management and engineering strategies that prospect efficient FW and PLA co-digestion processes.
ESTHER : Zhu_2023_Chem.Eng.J__145194
PubMedSearch : Zhu_2023_Chem.Eng.J__145194

Title : Exploration of the SIRT1-mediated BDNF-TrkB signaling pathway in the mechanism of brain damage and learning and memory effects of fluorosis - Wang_2023_Front.Public.Health_11_1247294
Author(s) : Wang F , Li Y , Tang D , Yang B , Tian T , Tian M , Meng N , Xie W , Zhang C , He Z , Zhu X , Ming D , Liu Y
Ref : Front Public Health , 11 :1247294 , 2023
Abstract : INTRODUCTION: Fluoride is considered an environmental pollutant that seriously affects organisms and ecosystems, and its harmfulness is a perpetual public health concern. The toxic effects of fluoride include organelle damage, oxidative stress, cell cycle destruction, inflammatory factor secretion, apoptosis induction, and synaptic nerve transmission destruction. To reveal the mechanism of fluorosis-induced brain damage, we analyzed the molecular mechanism and learning and memory function of the SIRT1-mediated BDNF-TrkB signaling pathway cascade reaction in fluorosis-induced brain damage through in vivo experiments. METHODS: This study constructed rat models of drinking water fluorosis using 50 mg/L, 100 mg/L, and 150 mg/L fluoride, and observed the occurrence of dental fluorosis in the rats. Subsequently, we measured the fluoride content in rat blood, urine, and bones, and measured the rat learning and memory abilities. Furthermore, oxidative stress products, inflammatory factor levels, and acetylcholinesterase (AchE) and choline acetyltransferase (ChAT) activity were detected. The pathological structural changes to the rat bones and brain tissue were observed. The SIRT1, BDNF, TrkB, and apoptotic protein levels were determined using western blotting. RESULTS: All rats in the fluoride exposure groups exhibited dental fluorosis; decreased learning and memory abilities; and higher urinary fluoride, bone fluoride, blood fluoride, oxidative stress product, and inflammatory factor levels compared to the control group. The fluoride-exposed rat brain tissue had abnormal AchE and ChAT activity, sparsely arranged hippocampal neurons, blurred cell boundaries, significantly fewer astrocytes, and swollen cells. Furthermore, the nucleoli were absent from the fluoride-exposed rat brain tissue, which also contained folded neuron membranes, deformed mitochondria, absent cristae, vacuole formation, and pyknotic and hyperchromatic chromatin. The fluoride exposure groups had lower SIRT1, BDNF, and TrkB protein levels and higher apoptotic protein levels than the control group, which were closely related to the fluoride dose. The findings demonstrated that excessive fluoride caused brain damage and affected learning and memory abilities. DISCUSSION: Currently, there is no effective treatment method for the tissue damage caused by fluorosis. Therefore, the effective method for preventing and treating fluorosis damage is to control fluoride intake.
ESTHER : Wang_2023_Front.Public.Health_11_1247294
PubMedSearch : Wang_2023_Front.Public.Health_11_1247294
PubMedID: 37711250

Title : Strigolactone and gibberellin signalling coordinately regulates metabolic adaptations to changes in nitrogen availability in rice - Sun_2023_Mol.Plant__
Author(s) : Sun H , Guo X , Zhu X , Gu P , Zhang W , Tao W , Wang D , Wu Y , Zhao Q , Xu G , Fu X , Zhang Y
Ref : Mol Plant , : , 2023
Abstract : Modern semi-dwarf rice varieties of the 'Green Revolution' require a high nitrogen (N) fertilizer supply to obtain a high yield. A better understanding of the interplay between N metabolic and developmental processes is required for improved N use efficiency (NUE) and agricultural sustainability. Here, we show that strigolactones (SLs) modulate root metabolic and developmental adaptations to low N availability, which ensure efficient uptake and translocation of available N. The key repressor DWARF 53 (D53) of the SL signalling interacts with the transcription factor GROWTH-REGULATING FACTOR 4 (GRF4) and prevents GRF4 from binding to its target gene promoters. N limitation induces the accumulation of SLs, which in turn promotes SL-mediated degradation of D53, leading to the release of GRF4 and thus promoting the genes expression associated with N metabolism. N limitation also induces degradation of the rice DELLA protein SLENDER RICE 1 (SLR1) in the D14- and D53-dependent manners, and that is effective for the release of GRF4 from the competitive inhibition caused by SLR1. Our findings reveal a previously unknown mechanism underlying SL and gibberellin crosstalk in response to N availability, which advances our understanding of plant growth-metabolic coordination that can be useful to improve NUE in high-yield crops.
ESTHER : Sun_2023_Mol.Plant__
PubMedSearch : Sun_2023_Mol.Plant__
PubMedID: 36683328

Title : Polyethylene Degradation by a Rhodococcous Strain Isolated from Naturally Weathered Plastic Waste Enrichment - Tao_2023_Environ.Sci.Technol__
Author(s) : Tao X , Ouyang H , Zhou A , Wang D , Matlock H , Morgan JS , Ren AT , Mu D , Pan C , Zhu X , Han A , Zhou J
Ref : Environ Sci Technol , : , 2023
Abstract : Polyethylene (PE) is the most widely produced synthetic polymer and the most abundant plastic waste worldwide due to its recalcitrance to biodegradation and low recycle rate. Microbial degradation of PE has been reported, but the underlying mechanisms are poorly understood. Here, we isolated a Rhodococcus strain A34 from 609 day enriched cultures derived from naturally weathered plastic waste and identified the potential key PE degradation enzymes. After 30 days incubation with A34, 1% weight loss was achieved. Decreased PE molecular weight, appearance of C-O and C=O on PE, palmitic acid in the culture supernatant, and pits on the PE surface were observed. Proteomics analysis identified multiple key PE oxidation and depolymerization enzymes including one multicopper oxidase, one lipase, six esterase, and a few lipid transporters. Network analysis of proteomics data demonstrated the close relationships between PE degradation and metabolisms of phenylacetate, amino acids, secondary metabolites, and tricarboxylic acid cycles. The metabolic roadmap generated here provides critical insights for optimization of plastic degradation condition and assembly of artificial microbial communities for efficient plastic degradation.
ESTHER : Tao_2023_Environ.Sci.Technol__
PubMedSearch : Tao_2023_Environ.Sci.Technol__
PubMedID: 37682848

Title : Chromone-based monoamine oxidase B inhibitor with potential iron-chelating activity for the treatment of Alzheimer's disease - Zhang_2023_J.Enzyme.Inhib.Med.Chem_38_100
Author(s) : Zhang C , Zhang Y , Lv Y , Guo J , Gao B , Lu Y , Zang A , Zhu X , Zhou T , Xie Y
Ref : J Enzyme Inhib Med Chem , 38 :100 , 2023
Abstract : Based on the multitarget-directed ligands (MTDLs) strategy, a series of chromone-hydroxypyridinone hybrids were designed, synthesised, and evaluated as potential multimodal anti-AD ligands. Prospective iron-chelating effects and favourable monoamine oxidase B (MAO-B) inhibitory activities were observed for most of the compounds. Pharmacological assays led to the identification of compound 17d, which exhibited favourable iron-chelating potential (pFe(3+) = 18.52) and selective hMAO-B inhibitory activity (IC(50) = 67.02 +/- 4.3 nM, SI = 11). Docking simulation showed that 17d occupied both the substrate and the entrance cavity of MAO-B, and established several key interactions with the pocket residues. Moreover, 17d was determined to cross the blood-brain barrier (BBB), and can significantly ameliorate scopolamine-induced cognitive impairment in AD mice. Despite its undesired pharmacokinetic property, 17d remains a promising multifaceted agent that is worth further investigation.
ESTHER : Zhang_2023_J.Enzyme.Inhib.Med.Chem_38_100
PubMedSearch : Zhang_2023_J.Enzyme.Inhib.Med.Chem_38_100
PubMedID: 36519319

Title : Physiologically based pharmacokinetic modeling of candesartan to predict the exposure in hepatic and renal impairment and elderly populations - Guo_2023_Ther.Adv.Drug.Saf_14_20420986231220222
Author(s) : Guo L , Zhu X , Zhang L , Xu Y
Ref : Ther Adv Drug Safety , 14 :20420986231220222 , 2023
Abstract : BACKGROUND: Candesartan cilexetil is a widely used angiotensin II receptor blocker with minimal adverse effects and high tolerability for the treatment of hypertension. Candesartan is administered orally as the prodrug candesartan cilexetil, which is wholly and swiftly converted to the active metabolite candesartan by carboxylesterase during absorption in the intestinal tract. In populations with renal or hepatic impairment, candesartan's pharmacokinetic (PK) behavior may be altered, necessitating dosage adjustments. OBJECTIVES: This study was conducted to examine how the physiologically based PK (PBPK) model characterizes the PKs of candesartan in adult and geriatric populations and to predict the PKs of candesartan in elderly populations with renal and hepatic impairment. DESIGN: After developing PBPK models using the reported physicochemical properties of candesartan and clinical data, these models were validated using data from clinical investigations involving various dose ranges. METHODS: Comparing predicted and observed blood concentration data and PK parameters was used to assess the fit performance of the models. RESULTS: Doses should be reduced to approximately 94% of Chinese healthy adults for the Chinese healthy elderly population; approximately 92%, 68%, and 64% of that of the Chinese healthy adult dose in elderly populations with mild, moderate, and severe renal impairment, respectively; and approximately 72%, 71%, and 52% of that of the Chinese healthy adult dose in elderly populations with Child-Pugh-A, Child-Pugh-B, and Child-Pugh-C hepatic impairment, respectively. CONCLUSION: The results suggest that the PBPK model of candesartan can be utilized to optimize dosage regimens for special populations.
ESTHER : Guo_2023_Ther.Adv.Drug.Saf_14_20420986231220222
PubMedSearch : Guo_2023_Ther.Adv.Drug.Saf_14_20420986231220222
PubMedID: 38157240

Title : Detecting the combined toxicity of 18 binary and 24 ternary pesticide combinations to carboxylesterase based on fluorescence probe technology - Zhu_2022_J.Environ.Sci.Health.B__1
Author(s) : Zhu X , Chen L , Liu T , He S , Zhao X , Tian Y , Fang Y , Cui J
Ref : J Environ Sci Health B , :1 , 2022
Abstract : A rapid test method for the determination of pesticide toxicity was established by using carboxylesterase (CES) and fluorescence probe ACE-NH based on the principle of enzyme inhibition, and this method was applied to detect the combined toxicity of 18 binary and 24 ternary pesticide combinations commonly used for fruits and vegetables to CES. The results show that chlorpyrifos + carbendazim, carbofuran + carbendazim, imidacloprid + carbendazim, imidacloprid + dimethomorph, dimethoate + dimethomorph, prochloraz + carbendazim and imidacloprid + acetamiprid + carbendazim had synergistic effects under three concentration gradients, it indicated that most binary combinations containing carbendazim or imidacloprid had synergistic effects. Based on structure-activity relationship between pesticides and CES, pesticides with phosphate ester bonds had great toxicity to CES, or though they have no toxicity to CES alone, they showed a strong synergistic effect when mixed with other pesticides. Pesticides with amide or ester bond had medium toxicity and little synergistic effect. Pesticides with urea, carbamate or nitrite nitrogen group had little or no toxicity, while there was a strong synergistic effect after mixing with other pesticides. The test method and results in this study can provide scientific basis for risk assessment of cumulative exposure to mixed pesticide residues.
ESTHER : Zhu_2022_J.Environ.Sci.Health.B__1
PubMedSearch : Zhu_2022_J.Environ.Sci.Health.B__1
PubMedID: 35287560

Title : Enhancing the methanol tolerance of Candida antarctica lipase B by saturation mutagenesis for biodiesel preparation - Tan_2022_3.Biotech_12_22
Author(s) : Tan Z , Li X , Shi H , Yin X , Zhu X , Bilal M , Onchari MM
Ref : 3 Biotech , 12 :22 , 2022
Abstract : Methanol tolerance of lipase is one of the important factors affecting its esterification ability in biodiesel preparation. By B factor indicated prediction of Candida antarctica lipase B (CalB) surface amino acids, eight sites (Val(139), Ala(146), Leu(147), Pro(218), Val(286), Ala(287), Val(306), and Gly(307)) with high B value indicating more flexibility were chosen to perform saturation mutagenesis. High-methanol-tolerant variants, CalB-P218W and -V306N, created larger haloes on emulsified tributyrin solid plate including 15% (v/v) methanol and showed 19% and 31% higher activity over wild-type CalB (CalB-WT), respectively. By modeling, a newly formed hydrogen bond in CalB-V306N and hydrophobic force in CalB-P218W contributing more stability in protein may have resulted in increased methanol tolerance. CalB-P218W and -V306N transesterified the soybean oil into biodiesel at 30 degreesC by 85% and 89% yield, respectively, over 82% by CalB-WT for 24 h reactions. These results may provide a basis for molecular engineering of CalB and expand its applications in fuel industries. The as-developed semi-rational method could be utilized to enhance the stabilities of many other industrial enzymes.
ESTHER : Tan_2022_3.Biotech_12_22
PubMedSearch : Tan_2022_3.Biotech_12_22
PubMedID: 35036270

Title : Adeno-associated virus-mediated in vivo suppression of expression of EPHX2 gene modulates the activity of paraventricular nucleus neurons in spontaneously hypertensive rats - Zhu_2022_Biochem.Biophys.Res.Commun_606_121
Author(s) : Zhu X , Li K , Gao Y
Ref : Biochemical & Biophysical Research Communications , 606 :121 , 2022
Abstract : BACKGROUND: Hypertension can be attributed to increased sympathetic activities. Presympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus are capable of modulating sympathetic outflow, thus contributing to the pathogenesis of neurogenic hypertension. Epoxyeicosatrienoic acids (EETs) were reported to have anti-hypertensive effects, which could be degraded by soluble epoxide hydrolase (sEH), encoded by EPHX2. However, the potential effect of EETs on PVN neuron activity and the underlying molecular mechanism are largely unknown. METHODS: Knockdown of EPHX2 in spontaneously hypertensive rats (SHRs) was achieved by tail-intravenous injection of AAV plasmid containing shRNA targeting EPHX2. Whole-cell patch clamp was used to record action potentials of PVN neurons. An LC-MS/MS System was employed to determine 14,15-EET levels in rat cerebrospinal fluid. qPCR and western blotting were applied to examine the expression level of EPHX2 in various tissues. ELISA and immunofluorescence staining were applied to examine the levels of ATP, D-serine and glial fibrillary acidic protein (GFAP) in isolated astrocytes. RESULTS: The expression level of EPHX2 was higher, while the level of 14,15-EET was lower in SHRs than normotensive Wistar-Kyoto rats (WKY) rats. The spike firing frequency of PNV neurons in SHRs was higher than in WKY rats at a given stimulus current, which could be reduced by either EPHX2 downregulation or 14,15-EET administration. In isolated hypothalamic astrocytes, the elevated intracellular ATP or D-serine induced by Angiotensin II (Ang II) treatment could be rescued by 14,15-EET addition or 14,15-EET combing serine racemase (SR) downregulation by siRNA, respectively. Furthermore, 14,15-EET treatment reduced the Ang II-induced elevation of GFAP immunofluorescence. CONCLUSIONS: The elevation of EET levels by EPHX2 downregulation reduced presympathetic neuronal activity in the PVN of SHRs, leading to a reduced sympathetic outflow in hypertension rats. The ATP/SR/D-serine pathway of astrocytes is involved in EET-mediated neuroprotection.
ESTHER : Zhu_2022_Biochem.Biophys.Res.Commun_606_121
PubMedSearch : Zhu_2022_Biochem.Biophys.Res.Commun_606_121
PubMedID: 35344709

Title : Phytochemical Properties and In Vitro Biological Activities of Phenolic Compounds from Flower of Clitoria ternatea L - Li_2022_Molecules_27_6336
Author(s) : Li C , Tang W , Chen S , He J , Li X , Zhu X , Li H , Peng Y
Ref : Molecules , 27 :6336 , 2022
Abstract : Phenolic compounds from the flower of Clitoria ternatea L. (PCFCTL) were extracted using a high-speed shearing extraction technique and purified by AB-8 macroporous resins, and the phytochemical composition of the purified phenolic compounds from the flower of Clitoria ternatea L. (PPCFCTL) was then analyzed. Subsequently, its bioactivities including antioxidant properties, enzyme inhibitory activities, and antiproliferative activities against several tumor cell lines were evaluated. Results indicated that the contents of total phenolics, flavonoids, flavonols, flavanols, and phenolic acids in PPCFCTL were increased by 3.29, 4.11, 2.74, 2.43, and 2.96-fold, respectively, compared with those before being purified by AB-8 macroporous resins. The results showed PPCFCTL have significant antioxidant ability (measured by reducing power, RP, and ferric reducing antioxidant power method, FRAP) and good DPPH, ABTS(+), and superoxide anion radical scavenging activities. They can also significantly inhibit lipase, alpha-amylase, and alpha-glucosidase. In addition, morphological changes of HeLa, HepG2, and NCI-H460 tumor cells demonstrated the superior antitumor performance of PPCFCTL. However, the acetylcholinesterase inhibitory activity was relatively weak. These findings suggest that PPCFCTL have important potential as natural antioxidant, antilipidemic, anti-glycemic and antineoplastic agents in health-promoting foods.
ESTHER : Li_2022_Molecules_27_6336
PubMedSearch : Li_2022_Molecules_27_6336
PubMedID: 36234873

Title : The impact of ABCB1 and CES1 polymorphisms on the safety of dabigatran in patients with non-valvular atrial fibrillation - Zhu_2022_BMC.Cardiovasc.Disord_22_481
Author(s) : Zhu Z , Qian C , Su C , Tao H , Mao J , Guo Z , Zhu X , Pan J
Ref : BMC Cardiovasc Disord , 22 :481 , 2022
Abstract : BACKGROUND: This study aimed to analyze associations between genetic variants and plasma concentrations along with clinical outcomes in dabigatran in patients with non-valvular atrial fibrillation (NVAF). METHODS: We conducted a prospective study and enrolled NVAF patients treated with dabigatran in the real world. A total of 86 patients treated with 110 mg DE twice daily were recruited for this study. Blood samples were obtained from each patient and used for genotyping and determination of plasma dabigatran concentration. All bleeding and thromboembolic complications were recorded during the 1.5 years of follow-up. RESULTS: Eighty-three patients provided samples at the trough plasma level of dabigatran, and 58 patients provided samples at the peak plasma level of dabigatran. There was a significant association between the CES1 SNP rs8192935 and trough plasma concentrations of dabigatran (P = 0.013). Our results showed that the CES1 SNP rs8192935 significantly influenced dabigatran trough concentrations in the Chinese population, and carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 SNP c.2482-2236G > A (rs4148738) was associated with major bleeding events in the addictive model (P = 0.046, OR = 3.29) and dominant model (P = 0.040, OR = 8.17). Additionally, the ABCB1 SNP c.3435 C > T (rs1045642) was associated with the incidence of major bleeding events in the addictive model (P = 0.043, OR = 3.34) and dominant model (P = 0.046, OR = 7.77). However, no significant associations were found between all the SNPs and the incidence of minor bleeding events. CONCLUSION: Our results indicated that the CES1 polymorphism rs8192935 was associated with trough plasma concentrations of dabigatran. Carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 polymorphisms rs4148738 and rs1045642 were associated with an increased risk for major bleeding events for the first time in a Chinese population.
ESTHER : Zhu_2022_BMC.Cardiovasc.Disord_22_481
PubMedSearch : Zhu_2022_BMC.Cardiovasc.Disord_22_481
PubMedID: 36368930

Title : Cholinesterase is a Potential Biomarker with High Accuracy for the Nephrotic Syndrome Diagnosis in Minors - Zhu_2022_J.Multidiscip.Healthc_15_2375
Author(s) : Zhu X , Hu J
Ref : J Multidiscip Healthc , 15 :2375 , 2022
Abstract : BACKGROUND: Serum Cholinesterase (CHE) levels have been found to be elevated in individuals with nephrotic syndrome (NS); nevertheless, it is unknown whether CHE can serve as a biomarker for NS diagnosis and what its diagnostic relevance is for NS in minors. METHODS: In this study, 138 minors aged 1-17 years with NS were enrolled, including 101 patients with the first episode of NS and 37 patients with relapsing NS. One hundred and four minors suffering from nephritis and 109 healthy minors were included as control groups. The clinical information and laboratory data of all NS patients and the control group were obtained. Logistic regression, correlation analyses and receiver operator characteristic curve were used to examine the value of CHE for NS patients. RESULTS: Compared to patients diagnosed with nephritis and healthy minors in the control group, the serum CHE levels of total/first episode/relapsing NS patients were substantially higher (P < 0.05). The CHE was an independent risk predictor of total (adjusted odds ratio [OR] = 2.23, 95% confidence interval [CI]: 1.57-3.18)/first episode (adjusted OR = 4.02, 95% CI: 1.47-11.08)/relapsing (adjusted OR = 2.04, 95% CI: 1.42-2.93) NS, and was positively correlated with total cholesterol in total/first episode/relapsing NS patients, respectively. The optimal cutoff for total/first episode/relapsing NS all was 11 KU/L, but the diagnostic accuracy in first episode NS (area under the curve [AUC] = 0.96, 95% CI: 0.94-0.98) was higher than the total NS (AUC = 0.93, 95% CI: 0.91-0.96) and relapsing NS (AUC = 0.85, 95% CI: 0.78-0.92). CONCLUSION: CHE is a possible biomarker for NS and has good diagnostic accuracy for NS in minors, particularly for the first episode of NS in minors.
ESTHER : Zhu_2022_J.Multidiscip.Healthc_15_2375
PubMedSearch : Zhu_2022_J.Multidiscip.Healthc_15_2375
PubMedID: 36277118

Title : A hypothesis-driven study to comprehensively investigate the association between genetic polymorphisms in EPHX2 gene and cardiovascular diseases: findings from the UK Biobank - Zhu_2022_Gene_822_146340
Author(s) : Zhu X , Li Y , Yu T , Li S , Chen M
Ref : Gene , :146340 , 2022
Abstract : BACKGROUND: Epoxyeicosatrienoic acids (EETs) are protective factors against cardiovascular diseases (CVDs) because of their vasodilatory, cholesterol-lowering, and anti-inflammatory effects. Soluble epoxide hydrolase (sEH), encoded by the EPHX2 gene, degrades EETs into less biologically active metabolites. EPHX2 is highly polymorphic, and genetic polymorphisms in EPHX2 have been linked to various types of CVDs, such as coronary heart disease, essential hypertension, and atrial fibrillation recurrence. METHODS: Based on a priori hypothesis that EPHX2 genetic polymorphisms play an important role in the pathogenesis of CVDs, we comprehensively investigated the associations between 210 genetic polymorphisms in the EPHX2 gene and an array of 118 diseases in the circulatory system using a large sample from the UK Biobank (N=307,516). The diseases in electronic health records were mapped to the phecode system, which was more representative of independent phenotypes. Survival analyses were employed to examine the effects of EPHX2 variants on CVD incidence, and a phenome-wide association study was conducted to study the impact of EPHX2 polymorphisms on 62 traits, including blood pressure, blood lipid levels, and inflammatory indicators. RESULTS: A novel association between the intronic variant rs116932590 and the phenotype "aneurysm and dissection of heart" was identified. In addition, the rs149467044 and rs200286838 variants showed nominal evidence of association with arterial aneurysm and cerebrovascular disease, respectively. Furthermore, the variant rs751141, which was linked with a lower hydrolase activity of sEH, was significantly associated with metabolic traits, including blood levels of triglycerides, creatinine, and urate. CONCLUSIONS: Multiple novel associations observed in the present study highlight the important role of EPHX2 genetic variation in the pathogenesis of CVDs.
ESTHER : Zhu_2022_Gene_822_146340
PubMedSearch : Zhu_2022_Gene_822_146340
PubMedID: 35183688

Title : Old pesticide, new use: Smart and safe enantiomer of isocarbophos in locust control - Kong_2021_Ecotoxicol.Environ.Saf_225_112710
Author(s) : Kong Y , Ji C , Qu J , Chen Y , Wu S , Zhu X , Niu L , Zhao M
Ref : Ecotoxicology & Environmental Safety , 225 :112710 , 2021
Abstract : Locust plagues are still worldwide problems. Selecting active enantiomers from current chiral insecticides is necessary for controlling locusts and mitigating the pesticide pollution in agricultural lands. Herein, two enantiomers of isocarbophos (ICP) were separated and the enantioselectivity in insecticidal activity against the pest Locusta migratoria manilensis (L. migratoria) and mechanisms were investigated. The significant difference of LD(50) between (+)-ICP (0.609 mg/kg bw) and (-)-ICP (79.412 mg/kg bw) demonstrated that (+)-ICP was a more effective enantiomer. The enantioselectivity in insecticidal activity of ICP enantiomers could be attributed to the selective affinity to acetylcholinesterase (AChE). Results of in vivo and in vitro assays suggested that AChE was more sensitive to (+)-ICP. In addition, molecular docking showed that the -CDOKER energies of (+)-ICP and (-)-ICP were 25.6652 and 24.4169, respectively, which suggested a stronger affinity between (+)-ICP and AChE. Significant selectivity also occurred in detoxifying enzymes activities (carboxylesterases (CarEs) and glutathione S-transferases (GSTs)) and related gene expressions. Suppression of detoxifying enzymes activities with (+)-ICP treatment suggested that (-)-ICP may induce the detoxifying enzyme-mediated ICP resistance. A more comprehensive understanding of the enantioselectivity of ICP is necessary for improving regulation and risk assessment of ICP.
ESTHER : Kong_2021_Ecotoxicol.Environ.Saf_225_112710
PubMedSearch : Kong_2021_Ecotoxicol.Environ.Saf_225_112710
PubMedID: 34481357

Title : Deletion of soluble epoxide hydrolase suppressed chronic kidney disease-related vascular calcification by restoring Sirtuin 3 expression - He_2021_Cell.Death.Dis_12_992
Author(s) : He W , Huang J , Liu Y , Xie C , Zhang K , Zhu X , Chen J , Huang H
Ref : Cell Death Dis , 12 :992 , 2021
Abstract : Vascular calcification is common in chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD) without any effective therapies available up to date. The expression of soluble epoxide hydrolase (sEH) is different in patients with and without vascular calcification. The present study investigates the role of sEH as a potential mediator of vascular calcification in CKD. Both Ephx2(-)(/-) and wild-type (WT) mice fed with high adenine and phosphate (AP) diet were used to explore the vascular calcification in CKD. Compared with WT, deletion of sEH inhibited vascular calcification induced by AP. sEH deletion also abolished high phosphorus (Pi)-induced phenotypic transition of vascular smooth muscle cells (VSMCs) independent of its epoxyeicosatrienoic acids (EETs) hydrolysis. Further gene expression analysis identified the potential role of Sirtuin 3 (Sirt3) in the sEH-regulated VSMC calcification. Under high Pi treatment, sEH interacted with Sirt3, which might destabilize Sirt3 and accelerate the degradation of Sirt3. Deletion of sEH may preserve the expression of Sirt3, and thus maintain the mitochondrial adenosine triphosphate (ATP) synthesis and morphology, significantly suppressing VSMC calcification. Our data supported that sEH deletion inhibited vascular calcification and indicated a promising target of sEH inhibition in vascular calcification prevention.
ESTHER : He_2021_Cell.Death.Dis_12_992
PubMedSearch : He_2021_Cell.Death.Dis_12_992
PubMedID: 34689162

Title : Developmental neurotoxicity of antimony (Sb) in the early life stages of zebrafish - Xia_2021_Ecotoxicol.Environ.Saf_218_112308
Author(s) : Xia S , Zhu X , Yan Y , Zhang T , Chen G , Lei D , Wang G
Ref : Ecotoxicology & Environmental Safety , 218 :112308 , 2021
Abstract : Accumulating studies have revealed the toxicity of antimony (Sb) to soil-dwelling and aquatic organisms at the individual level. However, little is known about the neurotoxic effects of antimony and its underlying mechanisms. To assess this issue, we investigated the neurotoxicity of antimony (0, 200, 400, 600 and 800 mg/L) in zebrafish embryos. After exposure, zebrafish embryos showed abnormal phenotypes such as a shortened body length, morphological malformations, and weakened heart function. Behavioral experiments indicated that antimony caused neurotoxicity in zebrafish embryos, manifested in a decreased spontaneous movement frequency, delayed response to touch, and reduced movement distance. We also showed that antimony caused a decrease in acetylcholinesterase (AChE) levels in zebrafish embryos, along with decreased expression of neurofunctional markers such as gfap, nestin, mbp, and shha. Additionally, antimony significantly increased reactive oxygen species levels and significantly reduced glutathione (GSH) and superoxide dismutase (SOD) activity. In summary, our findings indicated that antimony can induce developmental toxicity and neurotoxicity in zebrash embryos by affecting neurotransmitter systems and oxidative stress, thus altering behavior. These outcomes will advance our understanding of antimony-induced neurotoxicity, environmental problems, and health hazards.
ESTHER : Xia_2021_Ecotoxicol.Environ.Saf_218_112308
PubMedSearch : Xia_2021_Ecotoxicol.Environ.Saf_218_112308
PubMedID: 33975224

Title : Susceptibility of Four Species of Aphids in Wheat to Seven Insecticides and Its Relationship to Detoxifying Enzymes - Gong_2020_Front.Physiol_11_623612
Author(s) : Gong P , Chen D , Wang C , Li M , Li X , Zhang Y , Zhu X
Ref : Front Physiol , 11 :623612 , 2020
Abstract : Sitobion avenae (Fabricius), Rhopalosiphum padi (Linnaeus), Schizaphis graminum (Rondani), and Metopolophium dirhodum (Walker) (Hemiptera: Aphididae) are important pests of wheat and other cereals worldwide. In this study, the susceptibilities of four wheat aphid species to seven insecticides were assessed. Furthermore, the activities of carboxylesterase (CarE), glutathione S-transferase (GSTs), and cytochrome P450 monooxygenase (P450s) were determined in imidacloprid treated and untreated aphids. The results showed that the susceptibilities of four wheat aphid species to tested insecticides are different and M. dirhodum has shown higher tolerance to most insecticides. Relatively higher CarE and GST activities were observed in M. dirhodum, and P450s activities increased significantly in response to imidacloprid treatment. Moreover, susceptibility to imidacloprid were increased by the oxidase inhibitor piperonyl butoxide in M. dirhodum (20-fold). The results we have obtained imply that P450s may play an important role in imidacloprid metabolic process in M. dirhodum. We suggest that a highly species-specific approach is essential for managing M. dirhodum.
ESTHER : Gong_2020_Front.Physiol_11_623612
PubMedSearch : Gong_2020_Front.Physiol_11_623612
PubMedID: 33536942

Title : 14,15-Epoxyeicosatrienoic Acid Alleviates Pathology in a Mouse Model of Alzheimer's Disease - Chen_2020_J.Neurosci_40_8188
Author(s) : Chen W , Wang M , Zhu M , Xiong W , Qin X , Zhu X
Ref : Journal of Neuroscience , 40 :8188 , 2020
Abstract : Alzheimer's disease (AD) is the leading cause of late-onset dementia, and there exists an unmet medical need for effective treatments for AD. The accumulation of neurotoxic amyloid-beta (Abeta) plaques contributes to the pathophysiology of AD. EPHX2 encoding soluble epoxide hydrolase (sEH)-a key enzyme for epoxyeicosatrienoic acid (EET) signaling that is mainly expressed in lysosomes of astrocytes in the adult brain-is cosited at a locus associated with AD, but it is unclear whether and how it contributes to the pathophysiology of AD. In this report, we show that the pharmacologic inhibition of sEH with 1-trifluoromethoxyphenyl- 3-(1-propionylpiperidin-4-yl) urea (TPPU) or the genetic deletion of Ephx2 reduces Abeta deposition in the brains of both male and female familial Alzheimer's disease (5xFAD) model mice. The inhibition of sEH with TPPU or the genetic deletion of Ephx2 alleviated cognitive deficits and prevented astrocyte reactivation in the brains of 6-month-old male 5xFAD mice. 14,15-EET levels in the brains of these mice were also increased by sEH inhibition. In cultured adult astrocytes treated with TPPU or 14,15-EET, astrocyte Abeta clearance was increased through enhanced lysosomal biogenesis. Infusion of 14,15-EET into the hippocampus of 5xFAD mice prevented the aggregation of Abeta. Notably, a higher concentration of 14,15-EET (200 ng/ml) infusion into the hippocampus reversed Abeta deposition in the brains of 6-month-old male 5xFAD mice. These results indicate that EET signaling, especially 14,15-EET, plays a key role in the pathophysiology of AD, and that targeting this pathway is a potential therapeutic strategy for the treatment of AD.SIGNIFICANCE STATEMENT There are limited treatment options for Alzheimer's disease (AD). EPHX2 encoding soluble epoxide hydrolase (sEH) is located at a locus that is linked to late-onset AD, but its contribution to the pathophysiology of AD is unclear. Here, we demonstrate that sEH inhibition or Ephx2 deletion alleviates pathology in familial Alzheimer's disease (5xFAD) mice. Inhibiting sEH or increasing 14,15-epoxyeicosatrienoic acid (EET) enhanced lysosomal biogenesis and amyloid-beta (Abeta) clearance in cultured adult astrocytes. Moreover, the infusion of 14,15-EET into the hippocampus of 5xFAD mice not only prevented the aggregation of Abeta, but also reversed the deposition of Abeta. Thus, 14,15-EET plays a key role in the pathophysiology of AD and therapeutic strategies that target this pathway may be an effective treatment.
ESTHER : Chen_2020_J.Neurosci_40_8188
PubMedSearch : Chen_2020_J.Neurosci_40_8188
PubMedID: 32973044

Title : Anti-dipeptidyl-peptidase-like protein 6 encephalitis, a rare cause of reversible rapid progressive dementia and insomnia - Zhou_2020_J.Neuroimmunol_339_577114
Author(s) : Zhou Q , Zhu X , Meng H , Zhang M , Chen S
Ref : Journal of Neuroimmunology , 339 :577114 , 2020
Abstract : Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare type of autoimmune encephalitis. We present a case of a 72-year-old male with anti-DPPX encephalitis who developed rapidly progressive cognitive decline, psychiatric and sleep problems, severe abdominal pain and diarrhea. Antibodies against DPPX were positive both in serum and cerebrospinal fluid. (18)F-FDG PET-MR imaging indicated hypometabolism in the bilateral temporal lobes and thalamus. No related tumors were found, and the patient responded to immunotherapy without relapse at the 3-year follow-up. The present case enriches the understanding of the clinical, imaging manifestations and prognosis of anti-DPPX encephalitis.
ESTHER : Zhou_2020_J.Neuroimmunol_339_577114
PubMedSearch : Zhou_2020_J.Neuroimmunol_339_577114
PubMedID: 31775073
Gene_locus related to this paper: human-DPP6

Title : Effects of Malania oleifera Chun Oil on the Improvement of Learning and Memory Function in Mice - Wu_2020_Evid.Based.Complement.Alternat.Med_2020_8617143
Author(s) : Wu R , Zhong S , Ni M , Zhu X , Chen Y , Chen X , Zhang L , Chen J
Ref : Evid Based Complement Alternat Med , 2020 :8617143 , 2020
Abstract : BACKGROUND: The fruits of Malania oleifera Chun & S. K. Lee have been highly sought after medically because its seeds have high oil content (>60%), especially the highest known proportion of nervonic acid (>55%). Objective of the Study. The objective was to explore the effects of different doses of Malania oleifera Chun oil (MOC oil) on the learning and memory of mice and to evaluate whether additional DHA algae oil and vitamin E could help MOC oil improve learning and memory and its possible mechanisms. METHODS: After 30 days of oral administration of the relevant agents to mice, behavioral tests were conducted as well as detection of oxidative stress parameters (superoxide dismutase, malondialdehyde, and glutathione peroxidase) and biochemical indicators (acetylcholine, acetyl cholinesterase, and choline acetyltransferase) in the hippocampus. RESULTS: Experimental results demonstrated that MOC oil treatment could markedly improve learning and memory of mouse models in behavioral experiments and increase the activity of GSH-PX in hippocampus and reduce the content of MDA, especially the dose of 46.27 mg/kg. The addition of DHA and VE could better assist MOC oil to improve the learning and memory, and its mechanism may be related to the inhibition of oxidative stress and restrain the activity of AChE and also increase the content of ACh. CONCLUSION: Our results demonstrated that MOC oil treatment could improve learning and memory impairments. Therefore, we suggest that MOC oil is a potentially important resource for the development of nervonic acid products.
ESTHER : Wu_2020_Evid.Based.Complement.Alternat.Med_2020_8617143
PubMedSearch : Wu_2020_Evid.Based.Complement.Alternat.Med_2020_8617143
PubMedID: 33014116

Title : Biological evaluation of 7-O-amide hesperetin derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease - Wu_2020_Chem.Biol.Interact_334_109350
Author(s) : Wu M , Zhu X , Zhang Y , Wang M , Liu T , Han J , Li J , Li Z
Ref : Chemico-Biological Interactions , 334 :109350 , 2020
Abstract : A series of 7-O-amide hesperetin derivatives were subjected to multi-target biological evaluation of anti-Alzheimer's disease. Most of the compounds showed good in vitro inhibitory activity against cholinesterase, of which compound 7c (7-O-(4-(morpholinoethyl)-acetamide) hesperetin) was the most effective anti-eqBuChE derivative (IC(50) = 0.28 +/- 0.05 M) and exerted neuroprotective effects. Further biological evaluation found that compounds 4d, 4e and 7c showed strong antioxidant, anti-Abeta self-aggregation and anti-neuroinflammatory activities. Compound 7c could inhibit the expression of iNOS and COX-2 proteins and prevent LPS-induced inflammatory response in BV2 cells. In addition, compound 7c could chelate biometal ions such as Cu(2+) and Zn(2+). In the vivo study, the MWM test confirmed that compound 7c could improve the cognitive impairment caused by scopolamine. In summary, the above studies have shown that the optimized compound 7c has great development potential as MTDL for the treatment of AD.
ESTHER : Wu_2020_Chem.Biol.Interact_334_109350
PubMedSearch : Wu_2020_Chem.Biol.Interact_334_109350
PubMedID: 33307048

Title : Lycosquarrines A-R, Lycopodium Alkaloids from Phlegmariurus squarrosus - Zhu_2020_J.Nat.Prod_83_2831
Author(s) : Zhu X , Xia D , Zhou Z , Xie S , Shi Z , Chen G , Wang L , Pan K
Ref : Journal of Natural Products , 83 :2831 , 2020
Abstract : Eighteen new Lycopodium alkaloids, lycosquarrines A-R (1-18), and eight known alkaloids were isolated from the aerial parts of Phlegmariurus squarrosus. Compounds 1-5 and 19, identified from natural sources for the first time, are uncommon lycopodine-type alkaloids with beta-oriented H-4. Pentacyclic 4 and 5 represent the first examples of 5,12- and 5,11-epoxy Lycopodium alkaloids, respectively, and an epoxide-opening cyclization reaction is suggested to be a key step in their biosynthesis. Compound 18 possesses the same carbon skeleton as carinatine A (22), which was previously reported as a unique Lycopodium alkaloid with a 5/6/6/6 ring system. X-ray crystallographic data analysis was used to determine the absolute configuration of 18, leading to the establishment of the absolute configuration of 22 by comparison of the ECD spectra. An anti-acetylcholinesterase activity assay showed that 11 and 20 exhibited inhibitory activities with IC(50) values of 4.2 and 2.1 microM, respectively.
ESTHER : Zhu_2020_J.Nat.Prod_83_2831
PubMedSearch : Zhu_2020_J.Nat.Prod_83_2831
PubMedID: 32941036

Title : Liver Function of Male Rats Exposed to Manganese at Different Time Points - Zhu_2020_Biol.Trace.Elem.Res__
Author(s) : Zhu X , Yang L , He Y , Sun Y , Shi W , Ou C
Ref : Biol Trace Elem Res , : , 2020
Abstract : As an essential trace element in the human body, manganese (Mn) is involved in many important biochemical reactions. However, excessive exposure to manganese can cause multiple systematic damages to the body. This study aims to investigate the effects of manganese exposure on serum hepatic enzymes in male rats at different time points. After adaptive feeding for 7 days, male Sprague-Dawley (SD) rats were injected intraperitoneally with 30 mg/kg MnCl2.4H2O once a day for 21 days at zeitgeber time point 2 (ZT2), ZT8, ZT14, and ZT20, respectively. We found that short-term repeated exposure to manganese caused slower body weight gain and increased relative liver and spleen weight index in male rats at different time points. Moreover, serum total bile acid (TBA) increased while aspartate aminotransferase (AST) decreased at ZT2, ZT8, and ZT20. Cholinesterase (ChE) decreased at ZT2 and ZT20, lactic dehydrogenase (LDH) decreased at ZT2, ZT14, and ZT20, and acid phosphatase (ACP) decreased at ZT2 and ZT14. Alkaline phosphatase (ALP) decreased at ZT2, ZT14, and ZT20, but increased at ZT8. Alanine amino transferase (ALT) decreased at ZT2 and ZT20, but increased at ZT8. There was a negative correlation between relative liver weight index with AST, ACP, ALP, and LDH, while a positive correlation with TBA. However, relative spleen weight index had a positive correlation with relative liver weight index and TBA, while a negative correlation with ALT, AST, ACP, ALP, LDH, and ChE. Our study shows that the injury of liver function is caused by short-term repeated manganese exposure at different time points. The time effect should be considered in manganese toxicity evaluation.
ESTHER : Zhu_2020_Biol.Trace.Elem.Res__
PubMedSearch : Zhu_2020_Biol.Trace.Elem.Res__
PubMedID: 32100273

Title : Structural insights into the putative bacterial acetylcholinesterase ChoE and its substrate inhibition mechanism - Pham_2020_J.Biol.Chem__
Author(s) : Pham VD , To TA , Gagne-Thivierge C , Couture M , Lague P , Yao D , Picard ME , Lortie LA , Attere SA , Zhu X , Levesque RC , Charette SJ , Shi R
Ref : Journal of Biological Chemistry , : , 2020
Abstract : Mammalian acetylcholinesterase (AChE) is well studied, being important in both cholinergic brain synapses and the peripheral nervous systems and also a key drug target for many diseases. In contrast, little is known about the structures and molecular mechanism of prokaryotic acetylcholinesterases. We report here the structural and biochemical characterization of ChoE, a putative bacterial acetylcholinesterase from Pseudomonas aeruginosa. Analysis of wild-type (WT) and mutant strains indicated that ChoE is indispensable for P. aeruginosa growth with acetylcholine as the sole carbon and nitrogen source. The crystal structure of ChoE at 1.35 A resolution revealed that this enzyme adopts a typical fold of the SGNH hydrolase family. Although ChoE and eukaryotic AChEs catalyze the same reaction, their overall structures bear no similarities constituting an interesting example of convergent evolution. Among Ser-38, Asp-285, and His-288 of the catalytic triad residues, only Asp-285 was not essential for ChoE activity. Combined with kinetic analyses of WT and mutant proteins, multiple crystal structures of ChoE complexed with substrates, products, or reaction intermediate revealed the structural determinants for substrate recognition, snapshots of the various catalytic steps, and the molecular basis of substrate inhibition at high substrate concentrations. Our results indicate that substrate inhibition in ChoE is due to acetate release being blocked by the binding of a substrate molecule in a nonproductive mode. Owing to the distinct overall folds and significant differences of the active site between ChoE and eukaryotic AChEs, these structures will serve as a prototype for other prokaryotic acetylcholinesterases.
ESTHER : Pham_2020_J.Biol.Chem__
PubMedSearch : Pham_2020_J.Biol.Chem__
PubMedID: 32371400

Title : ABAD\/17beta-HSD10 reduction contributes to the protective mechanism of huperzine a on the cerebral mitochondrial function in APP\/PS1 mice - Xiao_2019_Neurobiol.Aging_81_77
Author(s) : Xiao X , Chen Q , Zhu X , Wang Y
Ref : Neurobiology of Aging , 81 :77 , 2019
Abstract : Huperzine A (HupA) is a kind of Lycopodium alkaloid with potential disease-modifying qualities that has been reported to protect against beta-amyloid (Abeta)-mediated mitochondrial damage in Alzheimer's disease. However, the fundamental molecular mechanism underlying the protective action of HupA against Abeta-mediated mitochondrial malfunction is not completely understood. Recently, the mitochondrial enzyme amyloid-binding alcohol dehydrogenase (ABAD) protein has been reported to facilitate Abeta-induced mitochondrial damage, resulting in mitochondrial malfunction and cell death. Our study found that HupA, but not the acetylcholinesterase inhibitor tacrine, reduced the deposition of Abeta and the ABAD level, and further reduced Abeta-ABAD complexes, thereby improving cerebral mitochondrial function in APP/PS1 mice. This was accompanied by attenuated reactive oxygen species overload, as well as increases adenosine triphosphate levels. Moreover, HupA decreased the release of cytochrome-c from mitochondria and the level of cleaved caspase-3, thereby increasing dissociated brain cell viability in APP/PS1 mice. Thus, our study demonstrated that a reduction in ABAD was involved in the protective mechanism of HupA on the cerebral mitochondrial function in APP/PS1 mice.
ESTHER : Xiao_2019_Neurobiol.Aging_81_77
PubMedSearch : Xiao_2019_Neurobiol.Aging_81_77
PubMedID: 31252207

Title : Synthesis of cocoa butter substitutes from Cinnamomum camphora seed oil and fully hydrogenated palm oil by enzymatic interesterification - Ma_2019_J.Food.Sci.Technol_56_835
Author(s) : Ma X , Hu Z , Mao J , Xu Y , Zhu X , Xiong H
Ref : J Food Sci Technol , 56 :835 , 2019
Abstract : Cinnamomum camphora trees have a vast range of distribution in southern China and the seed oil has unique fatty acid (FA) properties and various bio-activities. In this work, Cinnamomum camphora seed oil (CCSO) was utilized to synthesize value-added cocoa butter substitute (CBS) by enzymatic interesterification. The synthesis was conducted in a solvent-free system by blending CCSO with fully hydrogenated palm oil under the catalysis of Lipozyme RM IM. The reacted products were assessed with physicochemical properties, i.e. FA composition, slip melting point (SMP), triacylglycerol (TAG), crystal polymorphism, microstructure, melting and crystallization properties and solid fat content (SFC). It showed that MCFAs (capric acid plus lauric acid) was the main fatty acid in products, accounting for over 45%. Comparing to physical blends, some novel TAG species such as LaLaLa and LaMLa/LaLaM were observed after enzymatic interesterification whereas SSS TAGs were reduced. IP presented a ball-like, well-distributed and nearly round crystal microstructure and a smaller crystal size. Moreover, it should be mentioned that SFC of IP ranging from 31.85 to 38.47% at 25 degreeC with most beta' crystal forms, was beneficial to improve the spreadability in term of confectionery products and baked goods. The SMP of the interesterified products was 35.75-36.15 degreeC which closed to the commercial CBS. Hence, the products synthesized can be used to as CBS, and the results in this study also showed CCSO have value-added applications.
ESTHER : Ma_2019_J.Food.Sci.Technol_56_835
PubMedSearch : Ma_2019_J.Food.Sci.Technol_56_835
PubMedID: 30906041

Title : The genome of broomcorn millet - Zou_2019_Nat.Commun_10_436
Author(s) : Zou C , Li L , Miki D , Li D , Tang Q , Xiao L , Rajput S , Deng P , Peng L , Jia W , Huang R , Zhang M , Sun Y , Hu J , Fu X , Schnable PS , Chang Y , Li F , Zhang H , Feng B , Zhu X , Liu R , Schnable JC , Zhu JK
Ref : Nat Commun , 10 :436 , 2019
Abstract : Broomcorn millet (Panicum miliaceum L.) is the most water-efficient cereal and one of the earliest domesticated plants. Here we report its high-quality, chromosome-scale genome assembly using a combination of short-read sequencing, single-molecule real-time sequencing, Hi-C, and a high-density genetic map. Phylogenetic analyses reveal two sets of homologous chromosomes that may have merged ~5.6 million years ago, both of which exhibit strong synteny with other grass species. Broomcorn millet contains 55,930 protein-coding genes and 339 microRNA genes. We find Paniceae-specific expansion in several subfamilies of the BTB (broad complex/tramtrack/bric-a-brac) subunit of ubiquitin E3 ligases, suggesting enhanced regulation of protein dynamics may have contributed to the evolution of broomcorn millet. In addition, we identify the coexistence of all three C4 subtypes of carbon fixation candidate genes. The genome sequence is a valuable resource for breeders and will provide the foundation for studying the exceptional stress tolerance as well as C4 biology.
ESTHER : Zou_2019_Nat.Commun_10_436
PubMedSearch : Zou_2019_Nat.Commun_10_436
PubMedID: 30683860
Gene_locus related to this paper: panmi-a0a3l6qvl9 , 9poal-a0a2s3hbt0 , panmi-a0a3l6sxg5 , 9poal-a0a2t7cdl4 , panmi-a0a3l6ta96 , panmi-a0a3l6qv47 , panmi-a0a3l6s688 , panmi-a0a3l6tph0

Title : Polysaccharide from Spirulina platensis ameliorates diphenoxylate-induced constipation symptoms in mice - Ma_2019_Int.J.Biol.Macromol_133_1090
Author(s) : Ma H , Xiong H , Zhu X , Ji C , Xue J , Li R , Ge B , Cui H
Ref : Int J Biol Macromol , 133 :1090 , 2019
Abstract : The aim of this study is to probe new functions of a polysaccharide from Spirulina platensis (PSP) on constipation and intestinal microbiota in mice. Diphenoxylate-induced constipation in mice was treated with different doses of PSP, followed by examining the defecation patterns, levels of acetyl cholinesterase (AchE), nitric oxide (NO), and tissue section histopathology. The composition of intestinal microbiota was determined by genome sequencing analysis of the 16S rDNA. This study found that the average molecular weight of PSP was 29, 600Da, and mainly monosaccharides of PSP were rhamnose (24.7%), glucose (16.15%) and galactose (13.32%). The beneficial effects of PSP treatment include defecation improvement, increase of AchE activity, reduction of NO concentration, renovation of the damaged intestinal villus and affection on the expression of some related genes in the constipated mice. In addition, PSP had significant effects on the gut microbiota, showing the enhancement in abundance of beneficial bacteria including Akkermansia, Lactobacillus, Butyricimonas, Candidatus Arthromitus and Prevotella, and the reduction in abundance of harmful bacteria such as Clostridium and Dorea. The present s uncovered a new function of PSP, indicating that PSP could be used in constipation therapies.
ESTHER : Ma_2019_Int.J.Biol.Macromol_133_1090
PubMedSearch : Ma_2019_Int.J.Biol.Macromol_133_1090
PubMedID: 31054300

Title : Safety, efficacy, and pharmacokinetics of pradefovir for the treatment of chronic hepatitis B infection - Zhang_2019_Antiviral.Res__104693
Author(s) : Zhang H , Liu J , Zhu X , Li X , Jin W , Chen H , Wu M , Li C , Liu C , JunqiNiu , Ding Y
Ref : Antiviral Res , :104693 , 2019
Abstract : BACKGROUND & AIMS: Pradefovir is a liver targeted novel prodrug of adefovir (PMEA) developed to provide higher antiviral activity with reduced systemic toxicities. This study evaluated the tolerability, pharmacokinetics, and antiviral activity of pradefovir in patients with chronic hepatitis B (CHB) virus infection. METHODS: Non-cirrhotic, treatment-naive subjects with CHB were divided into five groups (10 patients each) and randomized within each group in a ratio of 6:2:2 to receive an ascending dose of 30, 60, 75, 90, or 120mg pradefovir, 10mg adefovir dipivoxil (ADV), or 300mg tenofovir disoproxil fumarate (TDF) once a day for 28 days. RESULTS: A total of 51 subjects were randomized and 49 subjects completed the study. The groups were well matched and included 39 males, of whom 71% were hepatitis B e-antigen-negative with a mean hepatitis B virus (HBV) DNA level of 6.4-7.16 log10 IU/mL. No subject experienced a serious adverse event or nephrotoxicity. The most frequently reported adverse event was asymptomatic reduction in blood cholinesterase levels in the pradefovir group which recovered without any treatment about 13+/-7 days after drug discontinuation. This adverse event was not observed in the ADV and TDF groups. The mean changes in serum HBV DNA were -2.78, -2.77, -3.08, -3.18, -3.44, -2.34, and -3.07 log10 IU/mL at 30, 60, 75, 90, and 120mg pradefovir, 10mg ADV and 300mg TDF, respectively, with plateau levels reached with 60mg pradefovir. Pradefovir and its metabolite PMEA showed linear pharmacokinetics proportional to the dose. The half-life of PMEA in the pradefovir group was 11.47-17.63h. CONCLUSIONS: Short-term use of pradefovir was well tolerated. A decline in HBV DNA levels was superior to TDF at higher doses of pradefovir. 30-60mg pradefovir is recommended for CHB treatment. CLINICAL TRIAL NUMBER: CTR20150224.
ESTHER : Zhang_2019_Antiviral.Res__104693
PubMedSearch : Zhang_2019_Antiviral.Res__104693
PubMedID: 31838002

Title : Multi-level ecotoxicological effects of imidacloprid on earthworm (Eisenia fetida) - Wang_2018_Chemosphere_219_923
Author(s) : Wang X , Zhu X , Peng Q , Wang Y , Ge J , Yang G , Cai L , Shen W
Ref : Chemosphere , 219 :923 , 2018
Abstract : As a neurotoxic insecticide, imidacloprid (IMI) has been widely used for crop protection. However, continuous application of such pesticide in the environment may damage the non-target organisms in soil. In the present study, we aimed to investigate the effects of IMI on earthworms in terms of survival, avoidance behavior, reproduction, detoxification enzyme activity and gene expression using a systematic experimental approach. The results showed that the 14-day LC50 value of IMI was 2.26 (2.09-2.43) mg a.i. kg(-1), and the 2-day AC50 value (concentration inducing an avoidance rate of 50%) of IMI was 1.34 (1.02-1.91) mg a.i. kg(-1) to E. fetida. For reproduction, the 56-day EC50 value of IMI was 0.87 (0.66-1.33) mg a.i. kg(-1) to E. fetida, and there was a positive correlation between the growth rate of earthworms and the number of juveniles in IMI treatments. Activities of carboxylesterase (CarE) and glutathione-S-transferases (GST) in earthworms were disturbed by IMI exposure. Moreover, effects of IMI on the CarE activity in earthworms were more severe and sensitive compared with the GST activity. The expressions of annetocin (ann) and calreticulin (crt) at the transcriptional level were decreased upon IMI exposure, reaching the lowest levels of 0.09 fold and 0.16 fold on day 7 and day 14, respectively. Transcriptionally controlled tumor protein (tctp), heat shock protein 70 (hsp70) and gst exhibited relatively obvious variations (up-regulation or down-regulation) when the exposure duration was extended. Taken together, these results comprehensively contributed to further understandings of the impacts of IMI on earthworms.
ESTHER : Wang_2018_Chemosphere_219_923
PubMedSearch : Wang_2018_Chemosphere_219_923
PubMedID: 30572241

Title : Discovery of the leinamycin family of natural products by mining actinobacterial genomes - Pan_2017_Proc.Natl.Acad.Sci.U.S.A_114_E11131
Author(s) : Pan G , Xu Z , Guo Z , Hindra , Ma M , Yang D , Zhou H , Gansemans Y , Zhu X , Huang Y , Zhao LX , Jiang Y , Cheng J , Van Nieuwerburgh F , Suh JW , Duan Y , Shen B
Ref : Proc Natl Acad Sci U S A , 114 :E11131 , 2017
Abstract : Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm-type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.
ESTHER : Pan_2017_Proc.Natl.Acad.Sci.U.S.A_114_E11131
PubMedSearch : Pan_2017_Proc.Natl.Acad.Sci.U.S.A_114_E11131
PubMedID: 29229819
Gene_locus related to this paper: 9actn-a0a2m9jcs9 , 9actn-a0a2m9ijf7 , 9actn-a0a2m9iy91 , 9actn-a0a2m9k146 , 9actn-a0a2m9m5n6 , 9actn-a0a2m9ifq0 , 9actn-a0a1c4rpf7

Title : Association of Lp-PLA2 G994T gene polymorphism with risk of ischemic stroke in Chinese population - Ni_2017_J.Biochem.Mol.Toxicol_31_
Author(s) : Ni J , Gu H , Hu W , Zhou F , Zhu X , Wang K
Ref : J Biochem Mol Toxicol , 31 : , 2017
Abstract : The association between lipoprotein-associated phospholipase A2 (Lp-PLA2) G994T gene polymorphism and the risk of ischemic stroke is unclear. The aim of this study is to investigate the influence of Lp-PLA2 G994T genetic variant on the pathogenesis of ischemic stroke in Chinese population. A total of 348 patients with a clinical diagnosis of ischemic stroke and 260 gender-matched control subjects under physical examination were recruited from hospitals and genotyped for G994T gene polymorphism. The results showed that there was a significant difference in the genotype distribution between the two groups and people with GT or TT genotype were associated with the higher risk of ischemic stroke even after adjusting the effects of potential confounding factors. In addition, both ischemic stroke patients and control subjects carrying T allele showed relatively lower Lp-PLA2 activity and higher oxLDL level. Therefore, Lp-PLA2 G994T gene polymorphism may be an independent risk factor of ischemic stroke in Chinese population.
ESTHER : Ni_2017_J.Biochem.Mol.Toxicol_31_
PubMedSearch : Ni_2017_J.Biochem.Mol.Toxicol_31_
PubMedID: 28960681
Gene_locus related to this paper: human-PLA2G7

Title : Activation of mTOR signaling mediates the increased expression of AChE in high glucose condition: in vitro and in vivo evidences - Liu_2016_Mol.Neurobiol_53_4972
Author(s) : Liu YW , Zhang L , Li Y , Cheng YQ , Zhu X , Zhang F , Yin XX
Ref : Molecular Neurobiology , 53 :4972 , 2016
Abstract : Acetylcholinesterase (AChE) is impaired in brain of diabetic animals, which may be one of the reasons for diabetes-associated cognitive decline. However, the mechanism is still unknown. The present study was designed to investigate whether the increased expression of AChE in central neurons under high glucose (HG) condition was due to activation of mammalian target of rapamycin (mTOR) signaling. It was found that more production of reactive oxygen species, and higher levels of phospho-Akt, phospho-mTOR, phospho-p70S6K, and AChE were detected in HT-22 cells in HG group than normal glucose group after culture for 24 h, which were all attenuated by an antioxidant N-acetyl-L-cysteine. A PI3K inhibitor LY294002 significantly decreased the levels of phospho-Akt, phospho-mTOR, phospho-p70S6K, and AChE protein expression in HG-cultured HT-22 cells, and an mTOR inhibitor rapamycin markedly reduced the levels of phospho-mTOR, phospho-p70S6K, and AChE expression. Furthermore, compared with normal rats, diabetic rats showed remarkable increases in levels of AChE activity and expression, malondialdehyde, phospho-mTOR, phospho-p70S6K, and a significant decrease in total superoxide dismutase activity in both hippocampus and cerebral cortex. However, much lower levels of phospho-mTOR, phospho-p70S6K, and AChE expression occurred in both brain regions of diabetic rats treated with rapamycin when compared with untreated ones. These results indicated that mTOR signaling was activated through the activation of PI3K/Akt pathway mediated by oxidative stress in HG-cultured HT-22 cells and diabetic rat brains, which contributed to the elevated protein expression of AChE in central neurons under the condition of HG.
ESTHER : Liu_2016_Mol.Neurobiol_53_4972
PubMedSearch : Liu_2016_Mol.Neurobiol_53_4972
PubMedID: 26374551

Title : Strain Prioritization and Genome Mining for Enediyne Natural Products - Yan_2016_MBio_7_e02104
Author(s) : Yan X , Ge H , Huang T , Hindra , Yang D , Teng Q , Crnovcic I , Li X , Rudolf JD , Lohman JR , Gansemans Y , Zhu X , Huang Y , Zhao LX , Jiang Y , Van Nieuwerburgh F , Rader C , Duan Y , Shen B
Ref : MBio , 7 : , 2016
Abstract : The enediyne family of natural products has had a profound impact on modern chemistry, biology, and medicine, and yet only 11 enediynes have been structurally characterized to date. Here we report a genome survey of 3,400 actinomycetes, identifying 81 strains that harbor genes encoding the enediyne polyketide synthase cassettes that could be grouped into 28 distinct clades based on phylogenetic analysis. Genome sequencing of 31 representative strains confirmed that each clade harbors a distinct enediyne biosynthetic gene cluster. A genome neighborhood network allows prediction of new structural features and biosynthetic insights that could be exploited for enediyne discovery. We confirmed one clade as new C-1027 producers, with a significantly higher C-1027 titer than the original producer, and discovered a new family of enediyne natural products, the tiancimycins (TNMs), that exhibit potent cytotoxicity against a broad spectrum of cancer cell lines. Our results demonstrate the feasibility of rapid discovery of new enediynes from a large strain collection. IMPORTANCE: Recent advances in microbial genomics clearly revealed that the biosynthetic potential of soil actinomycetes to produce enediynes is underappreciated. A great challenge is to develop innovative methods to discover new enediynes and produce them in sufficient quantities for chemical, biological, and clinical investigations. This work demonstrated the feasibility of rapid discovery of new enediynes from a large strain collection. The new C-1027 producers, with a significantly higher C-1027 titer than the original producer, will impact the practical supply of this important drug lead. The TNMs, with their extremely potent cytotoxicity against various cancer cells and their rapid and complete cancer cell killing characteristics, in comparison with the payloads used in FDA-approved antibody-drug conjugates (ADCs), are poised to be exploited as payload candidates for the next generation of anticancer ADCs. Follow-up studies on the other identified hits promise the discovery of new enediynes, radically expanding the chemical space for the enediyne family.
ESTHER : Yan_2016_MBio_7_e02104
PubMedSearch : Yan_2016_MBio_7_e02104
PubMedID: 27999165
Gene_locus related to this paper: 9actn-a0a1q5ckn8 , 9actn-a0a1q5j3v0 , 9actn-a0a1q5kj90 , 9actn-a0a1q5jti2 , 9actn-a0a1q5luf4 , 9actn-a0a1q4w3c8 , 9actn-a0a1q4wvf2 , 9actn-a0a1q4yuw0 , 9actn-a0a1q5diu2 , 9actn-a0a1q5dxi1 , 9actn-a0a1q5ftj7 , 9actn-a0a1q5h9t1 , 9actn-a0a1q5k3r2 , 9actn-a0a1q5l4j4 , 9actn-a0a1q5l7v2 , 9actn-a0a1q5ltu8 , 9actn-a0a1q5m0p6 , 9actn-a0a1q5mza2 , 9pseu-a0a1q4yle9 , 9pseu-a0a1q4ylg6 , 9actn-a0a1q5hn40 , 9actn-a0a1q4zi93 , 9actn-a0a1q5d7w2 , 9actn-a0a1q5mn15 , 9pseu-a0a1q4xtq2 , 9actn-a0a1q5le62 , 9actn-a0a1q5fgx4 , strsp-TnmK1 , strsp-TnmK2 , strun-UcmK2 , 9actn-a0a1q4w6n9 , 9actn-a0a1q4yc91 , 9actn-a0a1q4yun2 , 9actn-a0a1q5g588 , 9actn-a0a1q5h571 , 9actn-a0a1q5kh06 , 9actn-a0a1q5lnf3 , 9actn-a0a1q5n7d1 , 9actn-a0a1q5n4g6

Title : Molecular mechanism of nicotine degradation by a newly isolated strain, Ochrobactrum sp. strain SJY1 - Yu_2015_Appl.Environ.Microbiol_81_272
Author(s) : Yu H , Tang H , Zhu X , Li Y , Xu P
Ref : Applied Environmental Microbiology , 81 :272 , 2015
Abstract : A newly isolated strain, SJY1, identified as Ochrobactrum sp., utilizes nicotine as a sole source of carbon, nitrogen, and energy. Strain SJY1 could efficiently degrade nicotine via a variant of the pyridine and pyrrolidine pathways (the VPP pathway), which highlights bacterial metabolic diversity in relation to nicotine degradation. A 97-kbp DNA fragment containing six nicotine degradation-related genes was obtained by gap closing from the genome sequence of strain SJY1. Three genes, designated vppB, vppD, and vppE, in the VPP pathway were cloned and heterologously expressed, and the related proteins were characterized. The vppB gene encodes a flavin-containing amine oxidase converting 6-hydroxynicotine to 6-hydroxy-N-methylmyosmine. Although VppB specifically catalyzes the dehydrogenation of 6-hydroxynicotine rather than nicotine, it shares higher amino acid sequence identity with nicotine oxidase (38%) from the pyrrolidine pathway than with its isoenzyme (6-hydroxy-l-nicotine oxidase, 24%) from the pyridine pathway. The vppD gene encodes an NADH-dependent flavin-containing monooxygenase, which catalyzes the hydroxylation of 6-hydroxy-3-succinoylpyridine to 2,5-dihydroxypyridine. VppD shows 62% amino acid sequence identity with the hydroxylase (HspB) from Pseudomonas putida strain S16, whereas the specific activity of VppD is approximately 10-fold higher than that of HspB. VppE is responsible for the transformation of 2,5-dihydroxypyridine. Sequence alignment and phylogenetic analysis suggested that the VPP pathway, which evolved independently from nicotinic acid degradation, might have a closer relationship with the pyrrolidine pathway. The proteins and functional pathway identified here provide a sound basis for future studies aimed at a better understanding of molecular principles of nicotine degradation.
ESTHER : Yu_2015_Appl.Environ.Microbiol_81_272
PubMedSearch : Yu_2015_Appl.Environ.Microbiol_81_272
PubMedID: 25344232
Gene_locus related to this paper: 9rhiz-a0a075xai2

Title : Prevalence of myasthenia gravis and associated autoantibodies in paraneoplastic pemphigus and their correlations with symptoms and prognosis - Wang_2015_Br.J.Dermatol_172_968
Author(s) : Wang R , Li J , Wang M , Hao H , Chen X , Li R , Zhu X
Ref : Br J Dermatol , 172 :968 , 2015
Abstract : BACKGROUND: Paraneoplastic pemphigus (PNP) involves multiple organs, but little is known about its neurological involvement. OBJECTIVES: To investigate the symptoms, prognosis and profiles of associated autoantibodies in myasthenia gravis (MG), and their correlations in patients with PNP.
METHODS: Fifty-eight patients with PNP were assessed for myasthenic symptoms and laboratory evidence. Serum autoantibodies against acetylcholine receptor (AChR), acetylcholinesterase (AChE), titin, ryanodine receptor (RyR) and muscle-specific kinase (MuSK) were measured by enzyme-linked immunosorbent assay. Patients with pemphigus vulgaris (PV), pemphigus foliaceus (PF), connective tissue disease (CTD) and non-PNP MG (NP-MG), and healthy donors, served as controls. These autoantibodies in PNP were also compared in the presence or absence of dyspnoea or muscle weakness. Cox regression and log-rank tests were used for survival analysis.
RESULTS: Overall 39% of patients with PNP experienced muscle weakness, and 35% were diagnosed with MG. Moreover, 35% had positive anti-AChR and 28% had anti-AChE antibodies, similarly to NP-MG (33% and 17%, respectively, P > 0.05). However, both were negative in all patients with PV, PF and CTD and healthy donors (P < 0.005). No other antibodies showed significant differences among groups. Anti-AChR and anti-AChE antibody levels were significantly increased in patients with PNP with dyspnoea, while anti-AChR, anti-titin and anti-RyR were significantly increased in patients with PNP with muscle weakness (P < 0.05). Nevertheless, levels and positive rates of these autoantibodies showed no significant differences between PNP with Castleman disease and thymoma. Although anti-AChE levels impacted survival duration (P = 0.027, odds ratio 3.14), MG complications did not affect the overall survival percentage in PNP.
CONCLUSIONS: MG is a complication of PNP. Anti-AChR and anti-AChE antibodies are prominent in patients with PNP, especially those with dyspnoea.
ESTHER : Wang_2015_Br.J.Dermatol_172_968
PubMedSearch : Wang_2015_Br.J.Dermatol_172_968
PubMedID: 25388377

Title : Key residues in the nicotinic acetylcholine receptor beta2 subunit contribute to alpha-conotoxin LvIA binding - Zhangsun_2015_J.Biol.Chem_290_9855
Author(s) : Zhangsun D , Zhu X , Wu Y , Hu Y , Kaas Q , Craik DJ , McIntosh JM , Luo S
Ref : Journal of Biological Chemistry , 290 :9855 , 2015
Abstract : alpha-Conotoxin LvIA (alpha-CTx LvIA) is a small peptide from the venom of the carnivorous marine gastropod Conus lividus and is the most selective inhibitor of alpha3beta2 nicotinic acetylcholine receptors (nAChRs) known to date. It can distinguish the alpha3beta2 nAChR subtype from the alpha6beta2* (* indicates the other subunit) and alpha3beta4 nAChR subtypes. In this study, we performed mutational studies to assess the influence of residues of the beta2 subunit versus those of the beta4 subunit on the binding of alpha-CTx LvIA. Although two beta2 mutations, alpha3beta2[F119Q] and alpha3beta2[T59K], strongly enhanced the affinity of LvIA, the beta2 mutation alpha3beta2[V111I] substantially reduced the binding of LvIA. Increased activity of LvIA was also observed when the beta2-T59L mutant was combined with the alpha3 subunit. There were no significant difference in inhibition of alpha3beta2[T59I], alpha3beta2[Q34A], and alpha3beta2[K79A] nAChRs when compared with wild-type alpha3beta2 nAChR. alpha-CTx LvIA displayed slower off-rate kinetics at alpha3beta2[F119Q] and alpha3beta2[T59K] than at the wild-type receptor, with the latter mutant having the most pronounced effect. Taken together, these data provide evidence that the beta2 subunit contributes to alpha-CTx LvIA binding and selectivity. The results demonstrate that Val(111) is critical and facilitates LvIA binding; this position has not previously been identified as important to binding of other 4/7 framework alpha-conotoxins. Thr(59) and Phe(119) of the beta2 subunit appear to interfere with LvIA binding, and their replacement by the corresponding residues of the beta4 subunit leads to increased affinity.
ESTHER : Zhangsun_2015_J.Biol.Chem_290_9855
PubMedSearch : Zhangsun_2015_J.Biol.Chem_290_9855
PubMedID: 25713061

Title : Soluble Epoxide Hydrolase Deficiency or Inhibition Attenuates MPTP-Induced Parkinsonism - Qin_2015_Mol.Neurobiol_52_187
Author(s) : Qin X , Wu Q , Lin L , Sun A , Liu S , Li X , Cao X , Gao T , Luo P , Zhu X , Wang X
Ref : Molecular Neurobiology , 52 :187 , 2015
Abstract : Soluble epoxide hydrolase (sEH) inhibition has been demonstrated to have beneficial effects on various diseases, such as hypertension, diabetes, and brain ischemia. However, whether sEH inhibition has therapeutic potential in Parkinson's disease is still unknown. In this paper, we found that sEH expression is increased in 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP)-treated mice, and sEH deficiency and inhibition significantly attenuated tyrosine hydroxylase (TH)-positive cell loss and improved rotarod performance. The substrate of sEH, 14,15-epoxyeicosatrienoic acid (14,15-EET), protected TH-positive cells and alleviated the rotarod performance deficits of wild-type mice but not sEH-knockout mice. Moreover, the 14,15-EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) abolished the neuronal protective effects of sEH deficiency. In primary cultured cortical neurons, MPP(+) induced significant Akt inactivation in neurons from sEH wild-type mice, and this effect was not observed in neurons from knockout mice. Our data indicate that sEH deficiency and inhibition increased 14,15-EET in MPTP-treated mice, which activated the Akt-mediated protection of TH-positive neurons and behavioral functioning. We also found that sEH deficiency attenuated TH-positive cell loss in a paraquat-induced mouse model of Parkinson's. Our data suggest that sEH inhibition might be a powerful tool to protect dopaminergic neurons in Parkinson's disease.
ESTHER : Qin_2015_Mol.Neurobiol_52_187
PubMedSearch : Qin_2015_Mol.Neurobiol_52_187
PubMedID: 25128026

Title : Cloning, synthesis, and characterization of alphaO-conotoxin GeXIVA, a potent alpha9alpha10 nicotinic acetylcholine receptor antagonist - Luo_2015_Proc.Natl.Acad.Sci.U.S.A_112_E4026
Author(s) : Luo S , Zhangsun D , Harvey PJ , Kaas Q , Wu Y , Zhu X , Hu Y , Li X , Tsetlin VI , Christensen S , Romero HK , McIntyre M , Dowell C , Baxter JC , Elmslie KS , Craik DJ , McIntosh JM
Ref : Proc Natl Acad Sci U S A , 112 :E4026 , 2015
Abstract : We identified a previously unidentified conotoxin gene from Conus generalis whose precursor signal sequence has high similarity to the O1-gene conotoxin superfamily. The predicted mature peptide, alphaO-conotoxin GeXIVA (GeXIVA), has four Cys residues, and its three disulfide isomers were synthesized. Previously pharmacologically characterized O1-superfamily peptides, exemplified by the US Food and Drug Administration-approved pain medication, ziconotide, contain six Cys residues and are calcium, sodium, or potassium channel antagonists. However, GeXIVA did not inhibit calcium channels but antagonized nicotinic AChRs (nAChRs), most potently on the alpha9alpha10 nAChR subtype (IC50 = 4.6 nM). Toxin blockade was voltage-dependent, and kinetic analysis of toxin dissociation indicated that the binding site of GeXIVA does not overlap with the binding site of the competitive antagonist alpha-conotoxin RgIA. Surprisingly, the most active disulfide isomer of GeXIVA is the bead isomer, comprising, according to NMR analysis, two well-resolved but uncoupled disulfide-restrained loops. The ribbon isomer is almost as potent but has a more rigid structure built around a short 310-helix. In contrast to most alpha-conotoxins, the globular isomer is the least potent and has a flexible, multiconformational nature. GeXIVA reduced mechanical hyperalgesia in the rat chronic constriction injury model of neuropathic pain but had no effect on motor performance, warranting its further investigation as a possible therapeutic agent.
ESTHER : Luo_2015_Proc.Natl.Acad.Sci.U.S.A_112_E4026
PubMedSearch : Luo_2015_Proc.Natl.Acad.Sci.U.S.A_112_E4026
PubMedID: 26170295

Title : A novel alpha4\/7-conotoxin LvIA from Conus lividus that selectively blocks alpha3beta2 vs. alpha6\/alpha3beta2beta3 nicotinic acetylcholine receptors - Luo_2014_FASEB.J_28_1842
Author(s) : Luo S , Zhangsun D , Schroeder CI , Zhu X , Hu Y , Wu Y , Weltzin MM , Eberhard S , Kaas Q , Craik DJ , McIntosh JM , Whiteaker P
Ref : FASEB Journal , 28 :1842 , 2014
Abstract : This study was performed to discover and characterize the first potent alpha3beta2-subtype-selective nicotinic acetylcholine receptor (nAChR) ligand. A novel alpha4/7-conotoxin, alpha-CTxLvIA, was cloned from Conus lividus. Its pharmacological profile at Xenopus laevis oocyte-expressed rat nAChR subtypes was determined by 2-electrode voltage-clamp electrophysiology, and its 3-dimensional (3D) structure was determined by NMR spectroscopy. alpha-CTx LvIA is a 16-aa C-terminally-amidated peptide with 2-disulfide bridges. Using rat subunits expressed in Xenopus oocytes, we found the highest affinity of alpha-CTxLvIA was for alpha3beta2 nAChRs (IC50 8.7 nM), where blockade was reversible within 2 min. IC50 values were >100 nM at alpha6/alpha3beta2beta3, alpha6/alpha3beta4, and alpha3beta4 nAChRs, and >/=3 muM at all other subtypes tested. alpha3beta2 vs. alpha6beta2 subtype selectivity was confirmed for human-subunit nAChRs with much greater preference (300-fold) for alpha3beta2 over alpha6beta2 nAChRs. This is the first alpha-CTx reported to show high selectivity for human alpha3beta2 vs. alpha6beta2 nAChRs. alpha-CTxLvIA adopts two similarly populated conformations water: one (assumed to be bioactive) is highly structured, whereas the other is mostly random coil in nature. Selectivity differences with the similarly potent, but less selective, alpha3beta2 nAChR antagonist alpha-CTx PeIA probably reside within the three residues, which differ in loop 2, given their otherwise similar 3D structures. alpha4/7-CTx LvIA is a new, potent, selective alpha3beta2 nAChR antagonist, which will enable detailed studies of alpha3beta2 nAChR structure, function, and physiological roles.-Luo, S., Zhangsun, D., Schroeder, C. I., Zhu, X., Hu, Y., Wu, Y., Weltzin, M. M., Eberhard, S., Kaas, Q., Craik, D. J., McIntosh, J. M., Whiteaker, P. A novel alpha4/7-conotoxin LvIA from Conus lividus that selectively blocks alpha3beta2 vs. alpha6/alpha3beta2beta3 nicotinic acetylcholine receptors.
ESTHER : Luo_2014_FASEB.J_28_1842
PubMedSearch : Luo_2014_FASEB.J_28_1842
PubMedID: 24398291

Title : Point Mutations Associated with Organophosphate and Carbamate Resistance in Chinese Strains of Culex pipiens quinquefasciatus (Diptera: Culicidae) - Zhao_2014_PLoS.One_9_e952607
Author(s) : Zhao M , Dong Y , Ran X , Wu Z , Guo X , Zhang Y , Xing D , Yan T , Wang G , Zhu X , Zhang H , Li C , Zhao T
Ref : PLoS ONE , 9 :e95260 , 2014
Abstract : Acetylcholinesterase resistance has been well documented in many insects, including several mosquito species. We tested the resistance of five wild, Chinese strains of the mosquito Culex pipiens quinquefasciatus to two kinds of pesticides, dichlorvos and propoxur. An acetylcholinesterase gene (ace1) was cloned and sequenced from a pooled sample of mosquitoes from these five strains and the amino acids of five positions were found to vary (V185M, G247S, A328S, A391T, and T682A). Analysis of the correlation between mutation frequencies and resistance levels (LC50) suggests that two point mutations, G247S (r2 = 0.732, P = 0.065) and A328S (r2 = 0.891, P = 0.016), are associated with resistance to propoxur but not to dichlorvos. Although the V185M mutation was not associated with either dichlorvos or propoxur resistance, its RS genotype frequency was correlated with propoxur resistance (r2 = 0.815, P = 0.036). And the HWE test showed the A328S mutation is linked with V185M, also with G247S mutation. This suggested that these three mutations may contribute synergistically to propoxur resistance. The T682A mutation was negatively correlated with propoxur (r2 = 0.788, P = 0.045) resistance. Knowledge of these mutations may help design strategies for managing pesticide resistance in wild mosquito populations.
ESTHER : Zhao_2014_PLoS.One_9_e952607
PubMedSearch : Zhao_2014_PLoS.One_9_e952607
PubMedID: 24788312
Gene_locus related to this paper: culpi-ACHE1

Title : Deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2 - Zhang_2014_Crit.Care.Med_42_e345
Author(s) : Zhang H , Wang T , Zhang K , Liu Y , Huang F , Zhu X , Wang MH , Tang W , Wang J , Huang H
Ref : Critical Care Medicine , 42 :e345 , 2014
Abstract : OBJECTIVE: Inhibition of soluble epoxide hydrolase (Ephx2) has been shown to play a protective role in cardiac hypertrophy, but the mechanism is not fully understood. We tested the hypothesis that deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2. DESIGN: Prospective, controlled, and randomized animal study. SETTING: University laboratory. SUBJECTS: Male wild-type C57BL/6 mice and Ephx2 (-/-) mice. INTERVENTIONS: Male wild-type or Ephx2 (-/-) mice were subjected to transverse aorta constriction surgery. MEASUREMENTS AND MAIN
RESULTS: Four weeks after transverse aorta constriction, Ephx2 (-/-) mice did not develop significant cardiac hypertrophy as that of wild-type mice, indicated by no changes in the ratio of heart weight/body weight and ventricular wall thickness after transverse aorta constriction. Cardiac fibroblast growth factor-2 increased in wild-type-transverse aorta constriction group but this did not change in Ephx2 (-/-)-transverse aorta constriction group, and the serum level of fibroblast growth factor-2 did not change in both groups. In vitro, cardiac fibroblasts were stimulated by angiotensin II to analyze the expression of fibroblast growth factor-2. The effect of increased fibroblast growth factor-2 from cardiac fibroblasts induced by angiotensin II was attenuated by soluble epoxide hydrolase deletion. ERK1/2, p38, and AKT kinase were involved in fibroblast growth factor-2 expression regulated by angiotensin II, and soluble epoxide hydrolase deletion lowered the phosphorylation of ERK1/2 not p38 or AKT to mediate fibroblast growth factor-2 expression. In addition, soluble epoxide hydrolase deletion did not attenuate cardiomyocytes hypertrophy induced by exogenous fibroblast growth factor-2.
CONCLUSIONS: Our present data demonstrated that deletion of soluble epoxide hydrolase prevented cardiac hypertrophy not only directly to cardiomyocytes but also to cardiac fibroblasts by reducing expression of fibroblast growth factor-2.
ESTHER : Zhang_2014_Crit.Care.Med_42_e345
PubMedSearch : Zhang_2014_Crit.Care.Med_42_e345
PubMedID: 24448199

Title : Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor expression changes in spiral ganglion neurons of the mouse - Tang_2014_Neurosci_259_184
Author(s) : Tang X , Zhu X , Ding B , Walton JP , Frisina RD , Su J
Ref : Neuroscience , 259 :184 , 2014
Abstract : Age-related hearing loss - presbycusis - is the number one communication disorder and most prevalent neurodegenerative condition of our aged population. Although speech understanding in background noise is quite difficult for those with presbycusis, there are currently no biomedical treatments to prevent, delay or reverse this condition. A better understanding of the cochlear mechanisms underlying presbycusis will help lead to future treatments. Objectives of the present study were to investigate GABAA receptor subunit alpha1, nicotinic acetylcholine (nACh) receptor subunit beta2, and N-methyl-d-aspartate (NMDA) receptor subunit NR1 mRNA and protein expression changes in spiral ganglion neurons (SGN) of the CBA/CaJ mouse cochlea, that occur in age-related hearing loss, utilizing quantitative immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) techniques. We found that auditory brainstem response (ABR) thresholds shifted over 40dB from 3 to 48kHz in old mice compared to young adults. DPOAE thresholds also shifted over 40dB from 6 to 49kHz in old mice, and their amplitudes were significantly decreased or absent in the same frequency range. SGN density decreased with age in basal, middle and apical turns, and SGN density of the basal turn declined the most. A positive correlation was observed between SGN density and ABR wave 1amplitude. mRNA and protein expression of GABAAR alpha1 and AChR beta2 decreased with age in SGNs in the old mouse cochlea. mRNA and protein expression of NMDAR NR1 increased with age in SGNs of the old mice. These findings demonstrate that there are functionally-relevant age-related changes of GABAAR, nAChR, NMDAR expression in CBA mouse SGNs reflecting their degeneration, which may be related to functional changes in cochlear synaptic transmission with age, suggesting biological mechanisms for peripheral age-related hearing loss.
ESTHER : Tang_2014_Neurosci_259_184
PubMedSearch : Tang_2014_Neurosci_259_184
PubMedID: 24316061

Title : Identification and characterization of a new erythromycin biosynthetic gene cluster in Actinopolyspora erythraea YIM90600, a novel erythronolide-producing halophilic actinomycete isolated from salt field - Chen_2014_PLoS.One_9_e108129
Author(s) : Chen D , Feng J , Huang L , Zhang Q , Wu J , Zhu X , Duan Y , Xu Z
Ref : PLoS ONE , 9 :e108129 , 2014
Abstract : Erythromycins (Ers) are clinically potent macrolide antibiotics in treating pathogenic bacterial infections. Microorganisms capable of producing Ers, represented by Saccharopolyspora erythraea, are mainly soil-dwelling actinomycetes. So far, Actinopolyspora erythraea YIM90600, a halophilic actinomycete isolated from Baicheng salt field, is the only known Er-producing extremophile. In this study, we have reported the draft genome sequence of Ac. erythraea YIM90600, genome mining of which has revealed a new Er biosynthetic gene cluster encoding several novel Er metabolites. This Er gene cluster shares high identity and similarity with the one of Sa. erythraea NRRL2338, except for two absent genes, eryBI and eryG. By correlating genotype and chemotype, the biosynthetic pathways of 3'-demethyl-erythromycin C, erythronolide H (EH) and erythronolide I have been proposed. The formation of EH is supposed to be sequentially biosynthesized via C-6/C-18 epoxidation and C-14 hydroxylation from 6-deoxyerythronolide B. Although an in vitro enzymatic activity assay has provided limited evidence for the involvement of the cytochrome P450 oxidase EryFAc (derived from Ac. erythraea YIM90600) in the catalysis of a two-step oxidation, resulting in an epoxy moiety, the attempt to construct an EH-producing Sa. erythraea mutant via gene complementation was not successful. Characterization of EryKAc (derived from Ac. erythraea YIM90600) in vitro has confirmed its unique role as a C-12 hydroxylase, rather than a C-14 hydroxylase of the erythronolide. Genomic characterization of the halophile Ac. erythraea YIM90600 will assist us to explore the great potential of extremophiles, and promote the understanding of EH formation, which will shed new insights into the biosynthesis of Er metabolites.
ESTHER : Chen_2014_PLoS.One_9_e108129
PubMedSearch : Chen_2014_PLoS.One_9_e108129
PubMedID: 25250723
Gene_locus related to this paper: 9acto-a0a099d7w4 , 9actn-a0a099d934

Title : Rationally designed anion-responsive-organogels: sensing F(-) via reversible color changes in gel-gel states with specific selectivity - Lin_2014_Soft.Matter_10_5715
Author(s) : Lin Q , Zhu X , Fu YP , Zhang YM , Fang R , Yang LZ , Wei TB
Ref : Soft Matter , 10 :5715 , 2014
Abstract : Through the rational introduction of the multi self-assembly driving forces and F(-) sensing sites into a gelator molecule, low-molecular-weight organogelators L1 and L2 were designed and synthesized. L1 and L2 showed excellent gelation ability in DMF and DMSO. They could form stable organogels (OGL1 and OGL2) in DMF and DMSO with very low critical gelation concentrations. OGL1 and OGL2 could act as anion-responsive organogels (AROGs). Unlike most of the reported AROGs showing gel-sol phase transition according to the anions' stimulation, OGL1 could colorimetrically sense F(-) under gel-gel states. Upon addition of F(-), OGL1 showed dramatic color changes, while the color could be recovered by adding H(+). Moreover, OGL1 showed specific selectivity for F(-), other common anions and cations could not lead to any similar response. What deserves to be mentioned is that the report on specific sensing of anions under gel-gel states is very scarce. The gel-gel state recognition can endow the organogel OGL1 with the merits of facile and efficient properties for rapid detection of F(-). Therefore, OGL1 could act as a F(-) responsive smart material.
ESTHER : Lin_2014_Soft.Matter_10_5715
PubMedSearch : Lin_2014_Soft.Matter_10_5715
PubMedID: 24985608

Title : Cell debris self-immobilized thermophilic lipase: a biocatalyst for synthesizing aliphatic polyesters - Sun_2013_Appl.Biochem.Biotechnol_170_399
Author(s) : Sun Y , Yang Y , Wang C , Liu J , Shi W , Zhu X , Lu L , Li Q
Ref : Appl Biochem Biotechnol , 170 :399 , 2013
Abstract : The paper explored the catalytic activity of a cell debris self-immobilized thermophilic lipase for polyester synthesis, using the ring-opening polymerization of sigma-caprolactone as model. Effects of biocatalyst concentration, temperature, and reaction medium on monomer conversion and product molecular weight were systematically evaluated. The biocatalyst displayed high catalytic activity at high temperatures (70-90 degreesC), with 100 % monomer conversion. High monomer conversion values (>90 %) were achieved in both hydrophobic and hydrophilic solvents, and also in solvent-free system, with the exception of dichloromethane. Poly(sigma-caprolactone) was obtained in 100 % monomer conversion, with a number-average molecular weight of 1,680 g/mol and a polydispersity index of 1.35 in cyclohexane at 70 degreesC for 72 h. Furthermore, the biocatalyst exhibited excellent operational stability, with monomer conversion values exceeding 90 % over the course of 15 batch reactions.
ESTHER : Sun_2013_Appl.Biochem.Biotechnol_170_399
PubMedSearch : Sun_2013_Appl.Biochem.Biotechnol_170_399
PubMedID: 23536248

Title : Hopeahainol A attenuates memory deficits by targeting beta-amyloid in APP\/PS1 transgenic mice - Zhu_2013_Aging.Cell_12_85
Author(s) : Zhu X , Ye L , Ge H , Chen L , Jiang N , Qian L , Li L , Liu R , Ji S , Zhang S , Jin J , Guan D , Fang W , Tan R , Xu Y
Ref : Aging Cell , 12 :85 , 2013
Abstract : Increasing evidence demonstrates that amyloid beta (Abeta) elicits mitochondrial dysfunction and oxidative stress, which contributes to the pathogenesis of Alzheimer's disease (AD). Identification of the molecules targeting Abeta is thus of particular significance in the treatment of AD. Hopeahainol A (HopA), a polyphenol with a novel skeleton obtained from Hopea hainanensis, is potentially acetylcholinesterase-inhibitory and anti-oxidative in H(2) O(2) -treated PC12 cells. In this study, we reported that HopA might bind to Abeta(1-42) directly and inhibit the Abeta(1-42) aggregation using a combination of molecular dynamics simulation, binding assay, transmission electron microscopic analysis and staining technique. We also demonstrated that HopA decreased the interaction between Abeta(1-42) and Abeta-binding alcohol dehydrogenase, which in turn reduced mitochondrial dysfunction and oxidative stress in vivo and in vitro. In addition, HopA was able to rescue the long-term potentiation induction by protecting synaptic function and attenuate memory deficits in APP/PS1 mice. Our data suggest that HopA might be a promising drug for therapeutic intervention in AD.
ESTHER : Zhu_2013_Aging.Cell_12_85
PubMedSearch : Zhu_2013_Aging.Cell_12_85
PubMedID: 23107435

Title : Effects of muscarinic agents on chick choroids in intact eyes and eyecups: evidence for a muscarinic mechanism in choroidal thinning - Nickla_2013_Ophthalmic.Physiol.Opt_33_245
Author(s) : Nickla DL , Zhu X , Wallman J
Ref : Ophthalmic Physiol Opt , 33 :245 , 2013
Abstract : PURPOSE: In chicks, ocular growth inhibition is associated with choroidal thickening and growth stimulation with choroidal thinning, suggesting a mechanistic link between the two responses. Because muscarinic antagonists inhibit the development of myopia in animal models by a non-accommodative mechanism, we tested the hypothesis that agonists would stimulate eye growth and thin the choroid. We also hypothesized that the effective growth-inhibiting antagonists would thicken the choroid.
METHODS: Chicks, age 12-16 days, were used. In vivo: Agonists: Single intravitreal injections (20 muL) of oxotremorine (oxo), pilocarpine (pilo), carbachol (carb), or arecaidine (arec) were given to otherwise untreated eyes. A-scan ultrasonography was done prior to injections, and at 3, 24, 48 and 72 h. Antagonists: -10D lenses were worn on one eye for 4 days. Atropine (atro), pirenzepine (pirz), oxyphenonium (oxy) or dicyclomine (dicy) were injected (20 muL) daily into lens-wearing eyes; saline injections were done as controls. Ultrasonography was done on d1 and on d4; on d4 measurements were done before and 3 h after injections. In vitro: Paired eyecups of retinal pigment epithelium (RPE), choroid and sclera were made from 1-week old chicks. All drugs except atropine were tested on one eyecup, its pair in plain medium. Choroidal thickness was measured at various times over 48 h.
RESULTS: Agonists: In vivo, oxotremorine caused an increase in the rate of axial elongation (drug vs saline: 24-72 h: 338 mum vs 250 mum; p < 0.001). All except pilocarpine caused choroidal thinning by 24 h (oxo, carb and arec vs saline: -25, -35 and -46 mum vs 3 mum). In vitro, all agonists thinned choroids by 24 h (oxo: -6 vs 111 mum; pilo: 45 vs 212 mum; carb: -58 vs 65 mum; arec: 47 vs 139 mum; p < 0.05). Antagonists: Atropine, pirenzepine and oxyphenonium inhibited the development of myopia in negative lens-wearing eyes, and also caused choroidal thickening (drug vs saline: 42, 80, 88 vs 10 mum per 3 h). In vitro, pirenzepine thickened choroids by 3 h (77 vs 2 mum, p < 0.01).
CONCLUSIONS: Muscarinic agonists caused choroidal thinning in intact eyes and eyecups, supporting a role for acetylcholine in the choroidal response to hyperopic defocus or form deprivation. Only oxotremorine stimulated eye growth, which is inconsistent with a muscarinic receptor mechanism for antagonist-induced eye growth inhibition. The dissociation between choroidal thinning and ocular growth stimulation for the other agonists in vivo suggest separate pathways for the two.
ESTHER : Nickla_2013_Ophthalmic.Physiol.Opt_33_245
PubMedSearch : Nickla_2013_Ophthalmic.Physiol.Opt_33_245
PubMedID: 23662958

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 : The clinical study of precise hemihepatectomy guided by middle hepatic vein - Qiu_2012_World.J.Surg_36_2428
Author(s) : Qiu Y , Zhu X , Zhu R , Zhou J , Zhou T , Wang Y , Ding Y
Ref : World J Surg , 36 :2428 , 2012
Abstract : OBJECTIVE This study was designed to analyze the feasibility of classification for hepatic veins preoperatively and to evaluate the safety and therapeutic efficacy of precise hemihepatectomy guided by middle hepatic vein METHODS Thirty patients who underwent precise hemihepatectomy PH group were subjected to multi-slice helical CT hepatic venography preoperatively to achieve Nakamura's and Kawasaki's classification of hepatic veins The hemihepatectomy was performed precisely by the guidance of middle hepatic vein which was revealed by the hepatic venography and confirmed with intraoperative ultrasound The clinical data of these patients were compared with other 38 traditional hemihepatectomy patients control group The amount of intraoperative bleeding and blood transfusion liver function recovery postoperative complications and 1-year follow-up data were compared between two groups RESULTS The ratios of Nakamura's classification type I II and III of hepatic veins were 56.7 17/30 26.7 8/30 and 16.7 5/30 respectively The percentages of Kawasaki's classification type I and II of hepatic veins were 36.7 11/30 and 63.3 19/30 respectively The total 30 cases of precise hemihepatectomies were performed successfully including 13 cases of right hemihepatectomy without MHV 15 cases of left hemihepatectomy without MHV 1 case of right hemihepatectomy with MHV and 1 case of left hemihepatectomy with MHV There was no significant difference in operation-related mortality the amount of intraoperative bleeding and blood transfusion as well as serum alanine aminotransferase total bilirubin and cholinesterase of the third postoperative day between the two groups However negative resection margin and albumin level were more favorable in precise hemihepatectomy group than control group In addition the incidence of postoperative pleural effusion and seroperitoneum was decreased significantly in precise hemihepatectomy group The 1-year tumor-free survival rate was 79 15/19 In PH group which is 48 in control group CONCLUSIONS Preoperative evaluation of hepatic veins is of great value for individual operative program via determination of anatomical type of hepatic veins Precise hemihepatectomy could preserve functional liver tissue with complete venous return to a great extent resulting in fewer incidences of postoperative pleural effusion and seroperitoneum Precise hemihepatectomy also has the potential to achieve more adequate tumor-free resection margin which may result in higher tumor-free survival rate.
ESTHER : Qiu_2012_World.J.Surg_36_2428
PubMedSearch : Qiu_2012_World.J.Surg_36_2428
PubMedID: 22714574

Title : Identification and characterization of novel esterases from a deep-sea sediment metagenome - Jiang_2012_Arch.Microbiol_194_207
Author(s) : Jiang X , Xu X , Huo Y , Wu Y , Zhu X , Zhang X , Wu M
Ref : Arch Microbiol , 194 :207 , 2012
Abstract : A deep-sea sediment metagenomic library was constructed and screened for lipolytic enzymes by activity-based approach. Nine novel lipolytic enzymes were identified, and the amino acid sequences shared 56% to 84% identity to other lipolytic enzymes in the database. Phylogenetic analysis showed that these enzymes belonged to family IV lipolytic enzymes. One of the lipolytic enzymes, Est6, was successfully cloned and expressed in Escherichia coli Rosetta in a soluble form. The recombinant protein was purified by Ni-nitrilotriacetic affinity chromatography column and characterized using p-nitrophenyl esters with various chain lengths. The est6 gene consisted of 909 bp that encoded 302 amino acid residues. Est6 was most similar to a lipolytic enzyme from uncultured bacterium (ACL67845, 61% identity) isolated from the South China Sea marine sediment metagenome. The characterization of Est6 revealed that it was a cold-active esterase and exhibited the highest activity toward p-nitrophenyl butyrate (C4) at 20 degrees C and pH 7.5.
ESTHER : Jiang_2012_Arch.Microbiol_194_207
PubMedSearch : Jiang_2012_Arch.Microbiol_194_207
PubMedID: 21861153
Gene_locus related to this paper: 9bact-H6BDX1 , 9bact-h6bdx2

Title : Cloning, expression and characterization of a halotolerant esterase from a marine bacterium Pelagibacterium halotolerans B2T - Jiang_2012_Extremophiles_16_427
Author(s) : Jiang X , Huo Y , Cheng H , Zhang X , Zhu X , Wu M
Ref : Extremophiles , 16 :427 , 2012
Abstract : An esterase PE10 (279 aa) from Pelagibacterium halotolerans B2(T) was cloned and overexpressed in Escherichia coli Rosetta in a soluble form. The deduced protein was 29.91 kDa and the phylogenetic analysis of the deduced amino acids sequence showed it represented a new family of lipolytic enzymes. The recombinant protein was purified by Ni-NTA affinity chromatography column and the characterization showed its optimal temperature and pH were 45 degrees C and pH 7.5, respectively. Substrate specificity study showed PE10 preferred short chain p-nitrophenyl esters and exhibited maximum activity toward p-nitrophenyl acetate. In addition, PE10 was a halotolerant esterase as it was still active under 4 M NaCl. Three-dimensional modeling of PE10 suggested that the high negative electrostatic potential on the surface may relevant to its tolerance to high salt environment. With this halotolerance property, PE10 could be a candidate for industrial use.
ESTHER : Jiang_2012_Extremophiles_16_427
PubMedSearch : Jiang_2012_Extremophiles_16_427
PubMedID: 22481638
Gene_locus related to this paper: pelhb-g4rec9

Title : Effects of physostigmine on the conditioned hyperactivity and locomotor sensitization to morphine in rats - Li_2010_Behav.Brain.Res_206_223
Author(s) : Li X , Li JX , Zhu X , Cui R , Jiao J
Ref : Behavioural Brain Research , 206 :223 , 2010
Abstract : Repetitive exposure to opioids elicits sensitization to its psychomotor stimulating effect and environmental stimuli contribute to this effect. This study first developed a procedure that simultaneously measures conditioned hyperactivity and locomotor sensitization, and then investigated the effects of physostigmine on the development and expression of conditioned hyperactivity and locomotor sensitization in rats. Five groups of rats (10-12 rats each) were conditioned with a conditioned stimulus (CS) for 20 min and then drug or saline paired with CS for 2 h daily for 10 days. Rats were tested 20 min on day 18. On day 25, rats were tested 20 min and subsequently 2 h (immediately after morphine injection). Although the 20 min locomotion was not different among the rats on day 1, rats that received 5 mg/kg morphine during conditioning showed higher locomotion than those received saline or 5 mg/kg morphine in the home cage on day 18 and day 25. Rats received 0.1 mg/kg physostigmine and 5 mg/kg morphine during conditioning showed higher locomotion than those received 5 mg/kg morphine on day 18. On day 25, 0.1 mg/kg physostigmine attenuated the conditioned hyperactivity and expression of morphine locomotor sensitization. In contrast, rats received 0.1 mg/kg physostigmine and 5 mg/kg morphine during conditioning showed higher locomotion during 2 h test period than those received 5 mg/kg morphine. In conclusion, this study established a procedure that simultaneously study conditioned hyperactivity and locomotor sensitization. Physostigmine attenuates the expressions but enhances the development of conditioned hyperactivity and sensitization and the possible mechanisms are discussed.
ESTHER : Li_2010_Behav.Brain.Res_206_223
PubMedSearch : Li_2010_Behav.Brain.Res_206_223
PubMedID: 19761800

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 : Effects of dietary lipid levels on growth, survival and lipid metabolism during early ontogeny of Pelteobagrus vachelli larvae - Zheng_2010_Aquaculture_299_121
Author(s) : Zheng K , Zhu X , Han D , Yang Y , Lei W , Xie S
Ref : Aquaculture , 299 :121 , 2010
Abstract : A feeding trial was conducted to investigate the effect of dietary lipid level on darkbarbel catfish (Pelteobagrus vachelli) larvae during ontogeny with regard to growth, survival and lipid utilization. Larvae were fed, from mouth opening to 20days after hatching (DAH), with five isonitrogenous microdiets containing different lipid levels (58, 74, 111, 151 and 199gkg1 diet). Live prey (newly hatched Artemia, unenriched) was used as the control diet. The activities of lipoprotein lipase (LPL), hepatic lipase (HL), pancreatic lipase (PL) and LPL gene expression at 3 DAH (mouth opening), 6 DAH, 11 DAH and 20 DAH were examined. The results showed that dietary lipid significantly affected survival and growth of darkbarbel catfish larvae. At the end of the feeding trial, larvae fed diets containing 111 to 151glipidkg1 had significantly higher survival. Specific growth rate (SGR) of larvae fed the diet containing the highest dietary lipid (199gkg1) was significantly (P<0.05) lower while no significant differences were observed among other groups fed formulated diets. LPL mRNA level generally increased first with increasing dietary lipid levels and then reached a plateau at different sampling ages. A similar pattern was observed for LPL activity only at 6 DAH and 20 DAH. High dietary lipid increased HL activity at 20 DAH. At 6 DAH, highest PL activity was observed at 199glipidkg1 diet. Higher dietary lipid resulted in earlier elevated activities of LPL, PL and HL. The specific activities of the above three enzymes and LPL mRNA expression were detected at mouth opening and were significantly influenced by age. The activities of these enzymes increased first and then decreased or reached a plateau during development. The results suggest that dietary lipid could modify lipid utilization during ontogeny of darkbarbel catfish larvae.
ESTHER : Zheng_2010_Aquaculture_299_121
PubMedSearch : Zheng_2010_Aquaculture_299_121

Title : Protection of PMS777, a new AChE inhibitor with PAF antagonism, against amyloid-beta-induced neuronal apoptosis and neuroinflammation - Li_2009_Cell.Mol.Neurobiol_29_589
Author(s) : Li J , Hu J , Shao B , Zhou W , Cui Y , Dong C , Ezoulin JM , Zhu X , Ding W , Heymans F , Chen H
Ref : Cellular Molecular Neurobiology , 29 :589 , 2009
Abstract : Amyloid-beta (Abeta) plays a central role in the neuroinflammation and cholinergic neuronal apoptosis in Alzheimer's disease, and thus has been considered as a main determinant of this disease. In the previous study, we reported that PMS777, a novel bis-interacting ligand for acetylcholinesterase (AChE) inhibition and platelet-activating factor (PAF) receptor antagonism, could significantly attenuate PAF-induced neurotoxicity. Continuing our efforts, we further investigated the protective effect of PMS777 on Abeta-induced neuronal apoptosis in vitro and neuroinflammation in vivo. PMS777 (1-100 microM) was found to inhibit Abeta-induced human neuroblastoma SH-SY5Y cell apoptosis in a concentration-dependent manner. Concurrently, PMS777 increased ratio of bcl-2 to bax mRNA, and inhibited both mRNA expression and activity of caspase-3 in SH-SY5Y cells after the exposure with Abeta. In vivo experimental study demonstrated that PMS777 could attenuate Abeta-induced microglial and astrocytic activation in the rat hippocampus after systemic administration. These results suggest that PMS777 potently protects against Abeta-induced neuronal apoptosis and neuroinflammation, and warrants further investigations in connection with its potential value in the treatment of Alzheimer's disease.
ESTHER : Li_2009_Cell.Mol.Neurobiol_29_589
PubMedSearch : Li_2009_Cell.Mol.Neurobiol_29_589
PubMedID: 19194797

Title : Bis-(-)-nor-meptazinols as novel nanomolar cholinesterase inhibitors with high inhibitory potency on amyloid-beta aggregation - Xie_2008_J.Med.Chem_51_2027
Author(s) : Xie Q , Wang H , Xia Z , Lu M , Zhang W , Wang X , Fu W , Tang Y , Sheng W , Li W , Zhou W , Zhu X , Qiu Z , Chen H
Ref : Journal of Medicinal Chemistry , 51 :2027 , 2008
Abstract : Bis-(-)-nor-meptazinols (bis-(-)-nor-MEPs) 5 were designed and synthesized by connecting two (-)-nor-MEP monomers with alkylene linkers of different lengths via the secondary amino groups. Their acetylcholinesterase (AChE) inhibitory activities were more greatly influenced by the length of the alkylene chain than butyrylcholinesterase (BChE) inhibition. The most potent nonamethylene-tethered dimer 5h exhibited low-nanomolar IC 50 values for both ChEs, having a 10 000-fold and 1500-fold increase in inhibition of AChE and BChE compared with (-)-MEP. Molecular docking elucidated that 5h simultaneously bound to the catalytic and peripheral sites in AChE via hydrophobic interactions with Trp86 and Trp286. In comparison, it folded in the large aliphatic cavity of BChE because of the absence of peripheral site and the enlargement of the active site. Furthermore, 5h and 5i markedly prevented the AChE-induced Abeta aggregation with IC 50 values of 16.6 and 5.8 microM, similar to that of propidium (IC 50 = 12.8 microM), which suggests promising disease-modifying agents for the treatment of AD patients.
ESTHER : Xie_2008_J.Med.Chem_51_2027
PubMedSearch : Xie_2008_J.Med.Chem_51_2027
PubMedID: 18333606

Title : A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates - Chen_2007_PLoS.One_2_e315
Author(s) : Chen C , Tang J , Dong W , Wang C , Feng Y , Wang J , Zheng F , Pan X , Liu D , Li M , Song Y , Zhu X , Sun H , Feng T , Guo Z , Ju A , Ge J , Dong Y , Sun W , Jiang Y , Yan J , Yang H , Wang X , Gao GF , Yang R , Yu J
Ref : PLoS ONE , 2 :e315 , 2007
Abstract : BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. METHODS AND FINDINGS: To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of approximately 89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence. CONCLUSIONS: To our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections.
ESTHER : Chen_2007_PLoS.One_2_e315
PubMedSearch : Chen_2007_PLoS.One_2_e315
PubMedID: 17375201
Gene_locus related to this paper: strsu-a4vws4 , strsu-q302y4 , strsy-a4vus4 , strsy-a4vwf6

Title : Therapeutic options in Alzheimer's disease - Moreira_2006_Expert.Rev.Neurother_6_897
Author(s) : Moreira PI , Zhu X , Nunomura A , Smith MA , Perry G
Ref : Expert Rev Neurother , 6 :897 , 2006
Abstract : Alzheimer's disease (AD) places an enormous burden on individuals, families and society. Consequently, a tremendous effort is being devoted to the development of drugs that prevent or delay neurodegeneration. Current pharmacological treatments are based on the use of acetylcholinesterase inhibitors or memantine, a N-methyl-D-aspartate channel blocker. However, new therapeutic approaches, including those more closely targeted to the pathogenesis of the disease, are being developed. These potentially disease-modifying therapeutics include secretase inhibitors, cholesterol-lowering drugs, amyloid-beta immunotherapy, nonsteroidal anti-inflammatory drugs, hormonal modulation and the use of antioxidants. The possibility that oxidative stress is a primary event in AD indicates that antioxidant-based therapies are perhaps the most promising weapons against this devastating neurodegenerative disorder.
ESTHER : Moreira_2006_Expert.Rev.Neurother_6_897
PubMedSearch : Moreira_2006_Expert.Rev.Neurother_6_897
PubMedID: 16784412

Title : Thyroid hormone receptor beta mutants: Dominant negative regulators of peroxisome proliferator-activated receptor gamma action - Araki_2005_Proc.Natl.Acad.Sci.U.S.A_102_16251
Author(s) : Araki O , Ying H , Furuya F , Zhu X , Cheng SY
Ref : Proc Natl Acad Sci U S A , 102 :16251 , 2005
Abstract : Thyroid hormone (T3) and peroxisome proliferators have overlapping metabolic effects in the maintenance of lipid homeostasis. Their actions are mediated by their respective receptors: thyroid hormone receptors (TR) and peroxisome proliferator-activated receptors (PPAR). We recently found that a dominantly negative TRbeta mutant (PV) that causes a genetic disease, resistance to thyroid hormone, acts to repress the ligand (troglitazone)-mediated transcriptional activity of PPARgamma in cultured thyroid cells. This finding suggests that TRbeta mutants could crosstalk with PPARgamma-signaling pathways. The present study explored the molecular mechanisms by which PV represses the PPARgamma transcriptional activity. Gel-shift assays show that the PV, similar to wild-type TRbeta, bound to the peroxisome proliferator response element (PPRE) as homodimers and heterodimers with PPARgamma or the retinoid X receptor (RXR), thereby competing with PPARgamma for binding to PPRE and for sequestering RXR. Association of PPRE-bound PV with corepressors [e.g., nuclear receptor corepressor (NCoR)] that led to transcriptional repression was independent of T3 and troglitazone. Chromatin immunoprecipitation assay further demonstrated that, despite the presence of ligands, NCoR was recruited to PPRE-bound PV on a PPARgamma-target gene, the lipoprotein lipase, in vivo, suggesting the dominant action of PV on PPARgamma-mediated transcriptional activity. Thus, the dominant negative action of PV is not limited on the wild-type TRs. The findings that TRbeta mutants affect PPARgamma functions through dominant negative action provide insights into the molecular mechanisms by which TR regulates the PPARgamma-target genes involved in metabolic pathways, lipid homeostasis, and carcinogenesis.
ESTHER : Araki_2005_Proc.Natl.Acad.Sci.U.S.A_102_16251
PubMedSearch : Araki_2005_Proc.Natl.Acad.Sci.U.S.A_102_16251
PubMedID: 16260719

Title : Molecularly imprinted polymer for monocrotophos and its binding characteristics for organophosphorus pesticides - Zhu_2005_Ann.Chim_95_877
Author(s) : Zhu X , Yang J , Su Q , Cai J , Gao Y
Ref : Ann Chim , 95 :877 , 2005
Abstract : In this study, molecular imprinting was used to develop a method based on noncovalent interaction for the synthesis of a monocrotophos-specific polymer. The selective binding characteristics of the template polymer were evaluated by 1H NMR study. The result was consistent with the existence of multi-molecular complexes formed by hydrogen-bonding interactions. Batch rebinding studies in acetonitrile were undertaken to quantitatively evaluate the affinity of the polymer for monocrotophos. The experimental binding isotherms were fitted to the Freundlich isotherm and the total number of binding sites of the polymer can be calculated to be 4.046 micromol g(-1). The induced affinity and selectivity by imprinting were examined chromatographically. The polymer gave more than 15 times longer retention for monocrotophos than the nonimprinted polymer with the same chemical composition. Other organophosphorus pesticides under study were eluted close to the void volume on the polymer column.
ESTHER : Zhu_2005_Ann.Chim_95_877
PubMedSearch : Zhu_2005_Ann.Chim_95_877
PubMedID: 16398351

Title : Crystallographic and biochemical analysis of cocaine-degrading antibody 15A10 - Larsen_2004_Biochemistry_43_8067
Author(s) : Larsen NA , de Prada P , Deng SX , Mittal A , Braskett M , Zhu X , Wilson IA , Landry DW
Ref : Biochemistry , 43 :8067 , 2004
Abstract : Catalytic antibody 15A10 hydrolyzes the benzoyl ester of cocaine to form the nonpsychoactive metabolites benzoic acid and ecgonine methylester. Here, we report biochemical and structural studies that characterize the catalytic mechanism. The crystal structure of the cocaine-hydrolyzing monoclonal antibody (mAb) 15A10 has been determined at 2.35 A resolution. The binding pocket is fairly shallow and mainly hydrophobic but with a cluster of three hydrogen-bond donating residues (TrpL96, AsnH33, and TyrH35). Computational docking of the transition state analogue (TSA) indicates that these residues are appropriately positioned to coordinate the phosphonate moiety of the TSA and, hence, form an oxyanion hole. Tyrosine modification of the antibody with tetranitromethane reduced hydrolytic activity to background level. The contribution from these and other residues to catalysis and TSA binding was explored by site-directed mutagenesis of 15A10 expressed in a single chain fragment variable (scFv) format. The TyrH35Phe mutant had 4-fold reduced activity, and TrpL96Ala, TrpL96His, and AsnH33Ala mutants were all inactive. Comparison with an esterolytic antibody D2.3 revealed a similar arrangement of tryptophan, asparagine, and tyrosine residues in the oxyanion hole that stabilizes the transition state for ester hydrolysis. Furthermore, the crystal structure of the bacterial cocaine esterase (cocE) also showed that the cocE employs a tyrosine hydroxyl in the oxyanion hole. Thus, the biochemical and structural data are consistent with the catalytic antibody providing oxyanion stabilization as its major contribution to catalysis.
ESTHER : Larsen_2004_Biochemistry_43_8067
PubMedSearch : Larsen_2004_Biochemistry_43_8067
PubMedID: 15209502

Title : Alzheimer's disease and the cell cycle - Raina_2004_Acta.Neurobiol.Exp.(Wars)_64_107
Author(s) : Raina AK , Zhu X , Smith MA
Ref : Acta Neurobiol Exp (Wars) , 64 :107 , 2004
Abstract : Current views associate the reappearance of cell cycle markers with early events in Alzheimer's disease. Even though, the cell cycle was implicated early in the study of this disease, only recently has it been associated with selective early vulnerability of neurons. The pathological hallmarks of Alzheimer's disease namely tau and amyloid have been associated with having effects on or being affected by cell cycle progression. Indeed the mitogenic component looms large early in the onset of Alzheimer's disease. Although quite a number of markers of reentry have been catalogued, the common denominator is abortosis, the unalterable march towards neuronal dysfunction, stasis and eventually death. We feel that complete understanding of the mechanisms, acting either positively by stimulation or through removal of inhibitory signals will provide promising molecular targets for pharmacological interventions which have been static for a number of years by being relegated to inhibition of the enzyme cholinesterase. In our opinion, investigating more proximal mechanisms will provide answers to changing the natural course of this illness.
ESTHER : Raina_2004_Acta.Neurobiol.Exp.(Wars)_64_107
PubMedSearch : Raina_2004_Acta.Neurobiol.Exp.(Wars)_64_107
PubMedID: 15190685

Title : Anticholinesterase activity of compounds related to geneserine tautomers. N-Oxides and 1,2-oxazines - Yu_2002_J.Med.Chem_45_3684
Author(s) : Yu QS , Zhu X , Holloway HW , Whittaker NF , Brossi A , Greig NH
Ref : Journal of Medicinal Chemistry , 45 :3684 , 2002
Abstract : A series of phenylcarbamate analogues of geneserine (8, 10, 12, 14) were synthesized from their counterparts, the phenylcarbamate analogues of physostigmine (2-5), by oxidation. The geneserine analogues can undergo tautomerism between N-oxide and 1,2-oxazine structures in a pH- and time-dependent manner. Assessment by (1)H NMR indicated that the N-oxide structure is adopted at neutral pH and that the compound exists in an equilibrium between several epimers. Evaluation of their biological action to inhibit human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), ex vivo, demonstrated that the N-oxide (7, 9, 11, 13, 15) and 1,2-oxazine (6, 8, 10, 12, 14) structures possessed similar potencies against AChE, but the latter structures were more potent against BChE. With the exception of the BChE selective inhibitor, 12, none of the geneserine analogues were as potent or enzyme subtype selective as their physostigmine analogue counterparts.
ESTHER : Yu_2002_J.Med.Chem_45_3684
PubMedSearch : Yu_2002_J.Med.Chem_45_3684
PubMedID: 12166941

Title : Observation of an arsenic adduct in an acetyl esterase crystal structure - Zhu_2003_J.Biol.Chem_278_2008
Author(s) : Zhu X , Larsen NA , Basran A , Bruce NC , Wilson IA
Ref : Journal of Biological Chemistry , 278 :2008 , 2002
Abstract : The crystal structures of an acetyl esterase, HerE, and its complex with an inhibitor dimethylarsinic acid have been determined at 1.30- and 1.45-A resolution, respectively. Although the natural substrate for the enzyme is unknown, HerE hydrolyzes the acetyl groups from heroin to yield morphine and from phenyl acetate to yield phenol. Recently, the activity of the enzyme toward heroin has been exploited to develop a heroin biosensor, which affords higher sensitivity than other currently available detection methods. The crystal structure reveals a single domain with the canonical alpha/beta hydrolase fold with an acyl binding pocket that snugly accommodates the acetyl substituent of the substrate and three backbone amides that form a tripartite oxyanion hole. In addition, a covalent adduct was observed between the active site serine and dimethylarsinic acid, which inhibits the enzyme. This crystal structure provides the first example of an As-containing compound in a serine esterase active site and the first example of covalent modification of serine by arsenic. Thus, the HerE complex reveals the structural basis for the broad scope inhibition of serine hydrolases by As(V)-containing organic compounds.
ESTHER : Zhu_2003_J.Biol.Chem_278_2008
PubMedSearch : Zhu_2003_J.Biol.Chem_278_2008
PubMedID: 12421810
Gene_locus related to this paper: rhosp-hercx

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 : A new therapeutic target in Alzheimer's disease treatment: attention to butyrylcholinesterase - Greig_2001_Curr.Med.Res.Opin_17_159
Author(s) : Greig NH , Utsuki T , Yu Q , Zhu X , Holloway HW , Perry T , Lee B , Ingram DK , Lahiri DK
Ref : Curr Med Res Opin , 17 :159 , 2001
Abstract : Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly, characterised by widespread loss of central cholinergic function. The only symptomatic treatment proven effective to date is the use of cholinesterase (ChE) inhibitors to augment surviving cholinergic activity. ChE inhibitors act on the enzymes that hydrolyse acetylcholine (ACh) following synaptic release. In the healthy brain, acetylcholinesterase (AChE) predominates (80%) and butyrylcholinesterase (BuChE) is considered to play a minor role in regulating brain ACh levels. In the AD brain, BuChE activity rises while AChE activity remains unchanged or declines. Therefore both enzymes are likely to have involvement in regulating ACh levels and represent legitimate therapeutic targets to ameliorate the cholinergic deficit. The two enzymes differ in location, substrate specificity and kinetics. Recent evidence suggests that BuChE may also have a role in the aetiology and progression of AD beyond regulation of synaptic ACh levels. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine, MF-8622) and ChE inhibitors such as rivastigmine, which have a dual inhibitory action on both AChE and BuChE, indicate potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. The development of specific BuChE inhibitors and the continued use of ChE inhibitors with the ability to inhibit BuChE in addition to AChE should lead to improved clinical outcomes.
ESTHER : Greig_2001_Curr.Med.Res.Opin_17_159
PubMedSearch : Greig_2001_Curr.Med.Res.Opin_17_159
PubMedID: 11900310

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