Author Report for: Gu JNo contact information in database for Gu J
Lian B, Gu J, Zhang C, Zou Z, Yu M, Li F, Wu X, Zhao AZ Ref: Metabolic Brain Disease, :, 2022 : PubMed ESTHER: Lian_2022_Metab.Brain.Dis__ PubMedSearch: Lian 2022 Metab.Brain.Dis PubMedID: 35921056 Abstract BACKGROUND: Isofraxidin is a coumarin compound mainly isolated from several traditional and functional edible plants beneficial for neurodegenerative diseases, including Sarcandra glabra and Apium graveolens, and Siberian Ginseng. OBJECTIVE: This study aimed to assess effects of isofraxidin against memory impairments and cognition deficits in a scopolamine-induced mouse model. MATERIALS & METHODS: Animals were randomly divided into 6 groups, control, vehicle, donepezil (10 mg/kg, p.o.), and isofraxidin (3, 10, and 30 mg/kg, p.o.). Isofraxidin or donepezil was administered for 44 days, once per day. The scopolamine insults (1 mg/kg, i.p.) was given from the 21st day, once per day. Morris water maze test and Y-maze test were used for the behavioral test. After that, brain samples were collected for analysis. RESULTS: Firstly, isofraxidin significantly improved scopolamine-induced behavioral impairments and cognition deficits in Morris water maze and Y-maze test. Then, isofraxidin facilitated cholinergic activity via inhibiting acetylcholinesterase (AChE) activity. Besides, isofraxidin decreased lipid peroxidation level but enhanced levels of glutathione, glutathione peroxidase, and superoxide dismutase. Moreover, isofraxidin suppressed the expression of inflammatory mediators and cytokines. Further investigations showed that isofraxidin up-regulated expression of brain-derived neurotrophic factor (BDNF), and promoted phosphorylation of tropomyosin-related kinase B (TrkB), cyclic AMP-response element-binding protein (CREB), and extracellular signal-regulated kinase (ERK). DISCUSSION & CONCLUSIONS: These results suggested that isofraxidin ameliorated scopolamine-induced cognitive and memory impairments, possibly through regulating AChE activity, suppressing oxidative stress and inflammatory response, and modulating BDNF-CREB-ERK pathways. Title: Fenpropathrin exposure induces neurotoxicity in zebrafish embryos Yu T, Xu X, Mao H, Han X, Liu Y, Zhang H, Lai J, Gu J, Xia M and Li D <1 more author(s)> Yu T, Xu X, Mao H, Han X, Liu Y, Zhang H, Lai J, Gu J, Xia M, Hu C, Li D (- 1) Ref: Fish Physiol Biochem, :, 2022 : PubMed ESTHER: Yu_2022_Fish.Physiol.Biochem__ PubMedSearch: Yu 2022 Fish.Physiol.Biochem PubMedID: 36266516 Abstract Fenpropathrin has been a commonly used insecticide to control agricultural and household insects over a few decades. Up to now, fenpropathrin residue in soil and water has been often determined due to its widespread use, which poses serious threat to environment and aquatic organisms. The potential of fenpropathrin to affect aquatic lives is still poorly understood. In this study, we used zebrafish (Danio rerio) embryo as an experimental model system to evaluate the toxicity of fenpropathrin to the development of zebrafish nervous system. Zebrafish embryos were separately exposed to fenpropathrin at the dose of 0.016 mg/L, 0.032 mg/L, 0.064 mg/L, starting at 6 h post-fertilizationhpf (hpf) up to 96 hpf. The results showed that fenpropathrin exposure gives rise to physiological, behavioral, and neurodevelopmental impairments in zebrafish embryos, including enhanced acetylcholinesterase (AChE) activity, abnormal swimming behavior, karyopyknosis in brain cells, increased intercellular space, and uneven migration of neuron in brain area. In addition, the expressions of genes concerning neurodevelopment and neurotransmitter system were inhibited following fenpropathrin exposure. We also found that fenpropathrin exposure distinctly induced oxidative stress by increasing reactive oxygen species (ROS) generation and inhibiting the production of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). Expectedly, some apoptosis-associated genes were induced and the apoptosis appeared in the brain and heart cells of zebrafish embryos. Moreover, fenpropathrin exposure also inhibited the expressions of genes in Nrf2 signaling pathway, such as heme oxygenase-1 (HO-1) and SOD. In summary, the results of this study indicate that oxidative stress-triggered apoptosis may be an underlying fundamental of fenpropathrin-induced neurotoxicity in zebrafish embryos. Title: Synthesis, biological evaluation and molecular modeling of benzofuran piperidine derivatives as Abeta antiaggregant Chowdhury SR, Gu J, Hu Y, Wang J, Lei S, Tavallaie MS, Lam C, Lu D, Jiang F, Fu L Ref: Eur Journal of Medicinal Chemistry, 222:113541, 2021 : PubMed ESTHER: Chowdhury_2021_Eur.J.Med.Chem_222_113541 PubMedSearch: Chowdhury 2021 Eur.J.Med.Chem 222 113541 PubMedID: 34116326 Abstract A series of benzofuran piperidine derivatives were designed, synthesized and evaluated as multifunctional Abeta antiaggregant to treat Alzheimer's disease (AD). In vitro results revealed that all of them are very good Abeta antiaggregants and some of the compounds are potent acetylcholinesterase (AChE) inhibitors with moderate antioxidant property. Selected compounds were also tested for neuroprotection activity, LDH release, ATP production and inhibitory activity to prevent Abeta peptides binding to the cell membrane. The different modifications introduced in the structure of our lead compound 3 (hAChE IC(50) = 61 microM and self induced Abeta (25-35) aggregation 45.45%), to increase its activity toward AD related targets. The most interesting multifunctional Abeta antiaggregants were compounds 3a, 3h and 3i, highlighting 3h as potent Abeta antiaggregant and good antiacetylholinesterase inhibitor (self induced Abeta (25-35) aggregation 57.71% and hAChE IC(50) = 21 microM), with good neuroprotective and antioxidant activity. In addition, these three most promising compounds prevent intracellular reactive oxygen species (ROS) formation and cell apoptosis induced by Abeta(25-35) peptides in SH-SY5Y cells. Molecular docking studies were also accomplished to understand the binding interaction of these compounds on Abeta monomer, Abeta fibril and AChE. Based on all data, compounds 3a, 3h and 3i were concluded as potent multifunctional Abeta antiaggregant, useful candidate for the treatment of AD. Title: Chlorpyrifos-induced toxicity has no gender selectivity in the early fetal brain Gu J, Xu S, Liu Y, Chen X Ref: J Environ Sci Health B, :1, 2020 : PubMed ESTHER: Gu_2020_J.Environ.Sci.Health.B__1 PubMedSearch: Gu 2020 J.Environ.Sci.Health.B 1 PubMedID: 32602772 Abstract Organophosphorus pesticides induce gender-specific developmental neurotoxicity after birth, especially in adolescents and adults. However, whether and when the selectivity occurs in fetus remains unclear. In this study, we analyzed chlorpyrifos (CPF)-induced neurotoxicity in the early fetal brains of male and female mice. The gestational dams were administered 0, 1, 3, and 5 mg/(kg.d) CPF during gestational days (GD)7-11, and brains from the fetuses were isolated and analyzed on GD12. Fetal gender was identified by PCR technique based on male-specific Sry gene and Myog control gene. The body weight and head weight, the activity of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and the content of malondialdehyde (MDA), as well as the oxidative stress-related gene expression were examined. Our results showed that CPF pretreatment induced AChE inhibition in GD12 fetal brain. CPF treatment activated SOD and GPX but not CAT and MDA. For oxidative stress-related gene expression, CPF pretreatment increased mRNA expression of Sod1, Cat, Gpx1, and Gpx2 in the fetal brain on GD12. The statistical analysis did not show gender-selective CPF-induced toxicity. Moreover, our results showed that although the gestational exposure to CPF could elicit abnormalities in the early fetal brain, the toxicity observed was not gender-specific. Title: Type 2 diabetes mellitus decreases systemic exposure of clopidogrel active metabolite through upregulation of P-glycoprotein in rats Yao H, Gu J, Shan Y, Wang Y, Chen X, Sun D, Guo Y Ref: Biochemical Pharmacology, :114142, 2020 : PubMed ESTHER: Yao_2020_Biochem.Pharmacol__114142 PubMedSearch: Yao 2020 Biochem.Pharmacol 114142 PubMedID: 32653591 Abstract Patients with diabetic mellitus tend to have a poor response to clopidogrel (Clop) due to reduced generation of active metabolite (Clop-AM). However, the underlying mechanism is not elucidated. A type 2 diabetic mellitus (T2DM) rat model was established by combining high-fat diet feeding and low-dose streptozotocin (STZ) injection. The reduced Clop-AM exposure was observed in T2DM rats after oral administration of Clop. However, in vitro liver microsomes incubated with Clop exhibited increased Clop-AM levels in T2DM rats due to a significant decrease in carboxylesterase (CES)1 expression and activity and a significant increase in the expression or activity of CYP1A2 and CYP3A. Interestingly, different from oral administration, the significantly increased Cmax of Clop-AM was observed in T2DM rats after intravenous injection, with no difference in AUC0-t and t1/2 values between the two strains. Meanwhile, in situ single -pass intestinal perfusion study showed lower absorption rate constant (Ka) and effective apparent permeability values (Peff) of Clop in T2DM rats than in control rats. It is explained by the increased expression or function of P-glycoprotein (P-gp) and pregnane X receptor (PXR) in duodenum and jejunum of T2DM rats. Moreover, the decreased Clop-AM level in T2DM rats was eliminated by the pretreatment of cyclosporin A, a P-gp inhibitor. It suggests that intestinal absorption, not hepatic metabolism is responsible for the reduced Clop-AM exposure in T2DM rats. P-gp might be the key factor causing the reduction of Clop absorption, consequently making less Clop available for Clop-AM formation. Title: Enhanced Platelet Response to Clopidogrel in Zucker Diabetic Fatty Rats due to Impaired Clopidogrel Inactivation by Carboxylesterase 1 and Increased Exposure to Active Metabolite Yao H, Bai R, Ren T, Wang Y, Gu J, Guo Y Ref: Drug Metabolism & Disposition: The Biological Fate of Chemicals, 47:794, 2019 : PubMed ESTHER: Yao_2019_Drug.Metab.Dispos_47_794 PubMedSearch: Yao 2019 Drug.Metab.Dispos 47 794 PubMedID: 31092394 Gene_locus related to this paper: ratno-Ces1d Abstract Clopidogrel (Clop), a thienopyridine antiplatelet prodrug, is metabolized by cytochrome P450s (CYPs) to an active metabolite, Clop-AM, and hydrolyzed by carboxylesterase (CES)1 to the inactive Clop-acid. Patients with type 2 diabetes (T2DM) tend to have a poor response to Clop due to reduced generation of Clop-AM. Whether a similar response occurs in the Zucker diabetic fatty (ZDF) rat, a commonly used animal model of T2DM, has not been explored. In this work, we compared ZDF and control rats for hepatic CES1- and CYP-mediated Clop metabolism; pharmacokinetics of Clop, Clop-AM, and Clop-acid; and the antiplatelet efficacy of Clop. In contrast to clinical findings, Clop-treated ZDF rats displayed significantly less (50%) maximum platelet aggregation at 4 hours than control rats; the enhanced efficacy was accompanied by higher formation of Clop-AM and lower formation of Clop-acid. In vitro studies showed that hepatic levels of CES1 protein and activity and Ces1e mRNA were significantly lower in ZDF than in control rats, as were the mRNA levels of CYP2B1/2, CYP2C11, and CYP3A2, and levels of CYP2B6-, CYP2C19-, and CYP3A4-related proteins and enzymatic activities in liver microsomes of ZDF rats. Interestingly, liver microsomes of ZDF rats produced higher levels of Clop-AM than that of control rats despite their lower CYP levels, although the addition of fluoride ion, an esterase inhibitor, enhanced Clop-AM formation in control rats more than in ZDF rats. These results suggest that the reduction in CES1-based Clop inactivation indirectly enhances Clop efficacy in ZDF rats by making more Clop available for CYP-mediated Clop-AM formation. Title: Genome sequence of the Asian Tiger mosquito, Aedes albopictus, reveals insights into its biology, genetics, and evolution Chen XG, Jiang X, Gu J, Xu M, Wu Y, Deng Y, Zhang C, Bonizzoni M, Dermauw W and James AA <21 more author(s)> Chen XG, Jiang X, Gu J, Xu M, Wu Y, Deng Y, Zhang C, Bonizzoni M, Dermauw W, Vontas J, Armbruster P, Huang X, Yang Y, Zhang H, He W, Peng H, Liu Y, Wu K, Chen J, Lirakis M, Topalis P, Van Leeuwen T, Hall AB, Thorpe C, Mueller RL, Sun C, Waterhouse RM, Yan G, Tu ZJ, Fang X, James AA (- 21) Ref: Proc Natl Acad Sci U S A, 112:E5907, 2015 : PubMed ESTHER: Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907 PubMedSearch: Chen 2015 Proc.Natl.Acad.Sci.U.S.A 112 E5907 PubMedID: 26483478 Gene_locus related to this paper: aedae-q177c7, aedal-a0a182gwe3, aedal-a0a182gwt8, aedal-a0a023eq67 Abstract The Asian tiger mosquito, Aedes albopictus, is a highly successful invasive species that transmits a number of human viral diseases, including dengue and Chikungunya fevers. This species has a large genome with significant population-based size variation. The complete genome sequence was determined for the Foshan strain, an established laboratory colony derived from wild mosquitoes from southeastern China, a region within the historical range of the origin of the species. The genome comprises 1,967 Mb, the largest mosquito genome sequenced to date, and its size results principally from an abundance of repetitive DNA classes. In addition, expansions of the numbers of members in gene families involved in insecticide-resistance mechanisms, diapause, sex determination, immunity, and olfaction also contribute to the larger size. Portions of integrated flavivirus-like genomes support a shared evolutionary history of association of these viruses with their vector. The large genome repertory may contribute to the adaptability and success of Ae. albopictus as an invasive species. Title: Development of self-assembling peptide nanovesicle with bilayers for enhanced EGFR-targeted drug and gene delivery Liang X, Shi B, Wang K, Fan M, Jiao D, Ao J, Song N, Wang C, Gu J, Li Z Ref: Biomaterials, 82:194, 2015 : PubMed ESTHER: Liang_2015_Biomaterials_82_194 PubMedSearch: Liang 2015 Biomaterials 82 194 PubMedID: 26763734 Abstract Development of rational vectors for efficient drug and gene delivery is crucial for cancer treatment. In this study, epidermal growth factor receptor (EGFR)-binding peptide amphiphile (PA) were used as the primary bilayer skeleton material to construct ultra-stable self-assembling peptide nanovesicle (SPV). The resulted EGFR-targeted SPV (ESPV) could efficiently encapsulate therapeutic cargos (drugs or small interfering RNAs [siRNAs]) or labelled fluorescent cargo (quantum dots [QDs]) and exhibited excellent affinity for EGFR-positive cancer cells. Moreover, ESPV could deliver more drug or plasmid DNA to tumour sites and promote gene expression (a three-fold ratio of ESPVs vs cationic liposomes). Notably, the individual delivery or co-delivery of doxorubicin (DOX) and the acetylcholinesterase (AChE) gene via the ESPVs resulted in excellent drug/gene delivery both in vitro and in vivo and exerted a significant growth-suppressing effect on a liver cancer xenograft. This nanoscale, targeted cargo-packaging technology may provide a new strategy for the design of highly targeted cancer therapy vectors. Title: Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses Chu S, Gu J, Feng L, Liu J, Zhang M, Jia X, Liu M, Yao D Ref: Int Immunopharmacol, 19:317, 2014 : PubMed ESTHER: Chu_2014_Int.Immunopharmacol_19_317 PubMedSearch: Chu 2014 Int.Immunopharmacol 19 317 PubMedID: 24503167 Abstract Neuroinflammatory responses play a crucial role in the pathogenesis of Alzheimer's disease (AD). Ginsenoside Rg5 (Rg5), an abundant natural compound in Panax ginseng, has been found to be beneficial in treating AD. In the present study, we demonstrated that Rg5 improved cognitive dysfunction and attenuated neuroinflammatory responses in streptozotocin (STZ)-induced memory impaired rats. Cognitive deficits were ameliorated with Rg5 (5, 10 and 20mg/kg) treatment in a dose-dependent manner together with decreased levels of inflammatory cytokines TNF-alpha and IL-1beta (P<0.05) in brains of STZ rats. Acetylcholinesterase (AChE) activity was also significantly reduced by Rg5 whereas choline acetyltransferase (ChAT) activity was remarkably increased in the cortex and hippocampus of STZ-induced AD rats (P<0.05). In addition, Congo red and immunohistochemistry staining results showed that Rg5 alleviated Abeta deposition but enhanced the expressions of insulin-like growth factors 1 (IGF-1) and brain derived neurophic factor (BDNF) in the hippocampus and cerebral cortex (P<0.05). Western blot analysis also demonstrated that Rg5 increased remarkably BDNF and IGF-1 expressions whereas decreased significantly Abeta deposits (P<0.05). Furthermore, it was observed that the expressions of COX-2 and iNOS were significantly up-regulated in STZ-induced AD rats and down-regulated strongly (P<0.05) by Rg5 compared with control rats. These data demonstrated that STZ-induced learning and memory impairments in rats could be improved by Rg5, which was associated with attenuating neuroinflammatory responses. Our findings suggested that Rg5 could be a beneficial agent for the treatment of AD. Title: Controlling enantioselectivity of esterase in asymmetric hydrolysis of aryl prochiral diesters by introducing aromatic interactions Guo F, Franzen S, Ye L, Gu J, Yu H Ref: Biotechnol Bioeng, 111:1729, 2014 : PubMed ESTHER: Guo_2014_Biotechnol.Bioeng_111_1729 PubMedSearch: Guo 2014 Biotechnol.Bioeng 111 1729 PubMedID: 24737244 Abstract Aromatic interactions specific to aryl radicals were introduced into two esterases, BioH from Escherichia coli and RspE from Rhodobacter sphaeroides to control their enantioselectivity in the asymmetric hydrolysis of prochiral aryl glutaric acid diesters. As a result, the enantiomeric excess (ee) of the S-product of dimethyl 3-phenylglutarate was increased from 25% (BioH wild type) to 96% (B_L83F/L86F) and from 13% (RspE wild type) to >99% (R_Y27R), respectively, while another variant of RspE R_M121F gave a reversed ee of 50% (R-product). Similar enhancement or reversion of enantioselectivity were also observed in the hydrolysis of three other prochiral aryl diesters (dimethyl 3-(4-flouro)-phenylglutarate, dimethyl 3-(4-cholo)-phenylglutarate and dimethyl 3-(3,4-dicholo)-phenylglutarate). Especially, the mutant R_Y27R was shown to be an excellent S-selective hydrolase for prochiral aryl diesters, with ee of all S-products >99%. In the mutants with altered enantioselectivity, the successful introduction of designed aromatic interactions was confirmed by molecular dynamics simulations and binding free energy analysis. These results demonstrate that aromatic interaction is one of the origins of enzyme enantioselectivity, the tuning of which leads to dramatic change in enantioselectivity. Besides, the successful engineering of the enantioselectivity in two different proteins toward four different substrates suggests that the introduction of aromatic interactions is a generally applicable strategy in the control of enantioselectivity toward aryl substrates. Biotechnol. Bioeng. 2014;111: 1729-1739. (c) 2014 Wiley Periodicals, Inc. Title: Free energy landscape for the binding process of Huperzine A to acetylcholinesterase Bai F, Xu Y, Chen J, Liu Q, Gu J, Wang X, Ma J, Li H, Onuchic JN, Jiang H Ref: Proc Natl Acad Sci U S A, 110:4273, 2013 : PubMed ESTHER: Bai_2013_Proc.Natl.Acad.Sci.U.S.A_110_4273 PubMedSearch: Bai 2013 Proc.Natl.Acad.Sci.U.S.A 110 4273 PubMedID: 23440190 Abstract Drug-target residence time (t = 1/k(off), where k(off) is the dissociation rate constant) has become an important index in discovering better- or best-in-class drugs. However, little effort has been dedicated to developing computational methods that can accurately predict this kinetic parameter or related parameters, k(off) and activation free energy of dissociation (DeltaG(off) not equal). In this paper, energy landscape theory that has been developed to understand protein folding and function is extended to develop a generally applicable computational framework that is able to construct a complete ligand-target binding free energy landscape. This enables both the binding affinity and the binding kinetics to be accurately estimated. We applied this method to simulate the binding event of the anti-Alzheimer's disease drug (-)-Huperzine A to its target acetylcholinesterase (AChE). The computational results are in excellent agreement with our concurrent experimental measurements. All of the predicted values of binding free energy and activation free energies of association and dissociation deviate from the experimental data only by less than 1 kcal/mol. The method also provides atomic resolution information for the (-)-Huperzine A binding pathway, which may be useful in designing more potent AChE inhibitors. We expect this methodology to be widely applicable to drug discovery and development. Title: Neuroprotective effect of Liuwei Dihuang decoction on cognition deficits of diabetic encephalopathy in streptozotocin-induced diabetic rat Liu JP, Feng L, Zhang MH, Ma DY, Wang SY, Gu J, Fu Q, Qu R, Ma SP Ref: J Ethnopharmacol, 150:371, 2013 : PubMed ESTHER: Liu_2013_J.Ethnopharmacol_150_371 PubMedSearch: Liu 2013 J.Ethnopharmacol 150 371 PubMedID: 24041458 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihuang decoction (LWDHD) is a well-known prescription of traditional Chinese medicine (TCM) and consists of six crude drugs including Rehmannia glutinosa Libosch. (family: Scrophulariaceae), Cornus officinalis Sieb. (family: Cornaceae), Dioscorea oppositifolia L. (family: Dioscoreaceae), Paoenia ostii (family: Paeoniaceae), Alisma orientale (G. Samuelsson) Juz (family: Alismataceae) and Poria cocos (Schw.) Wolf (family: Polyporaceae). It has been used for the treatment of "Kidney-Yin" deficiency syndrome in clinic in China for a long time. Recent studies found that LWDHD had a potential benefit for the treatment of diabetic complications. The aim of the present study is to investigate the neuroprotective effect of LWDHD on memory and cognition deficits in streptozotocin (STZ)-induced diabetic encephalopathy (DE) rats. MATERIALS AND Title: Enhanced enantioselectivity of a carboxyl esterase from Rhodobacter sphaeroides by directed evolution Ma J, Wu L, Guo F, Gu J, Tang X, Jiang L, Liu J, Zhou J, Yu H Ref: Applied Microbiology & Biotechnology, 97:4897, 2013 : PubMed ESTHER: Ma_2013_Appl.Microbiol.Biotechnol_97_4897 PubMedSearch: Ma 2013 Appl.Microbiol.Biotechnol 97 4897 PubMedID: 22987200 Gene_locus related to this paper: rhos4-q3j2v1 Abstract The present work created an esterase variant from Rhodobacter sphaeroides (RspE) with enhanced selectivity in hydrolytic kinetic resolutions by directed evolution. A "model" substrate, methyl mandelate, was introduced in the high-throughput screening procedure. E values of a variant CH (Asn62Cys/Leu145His) for six different esters were 10-83, which were a relative improvement compared to 2-20 for the wild type. Our subsequent crystal structure interpretation and molecular dynamics simulations helped shed light on the source of enantioselectivity modified by directed evolution. Though mutations displayed no "direct" interaction with the substrate, they were hypothesized to strengthen the intramolecular interaction in the catalytic cavity of variant. Conformation analysis revealed that the enhanced enantioselectivity of variant CH for the seven substrates applied in this study was derived from the decrease in size of the substrate binding pocket. Title: First genome sequence of a Burkholderia pseudomallei Isolate in China, strain BPC006, obtained from a melioidosis patient in Hainan Fang Y, Huang Y, Li Q, Chen H, Yao Z, Pan J, Gu J, Tang B, Wang HG and Mao XH <3 more author(s)> Fang Y, Huang Y, Li Q, Chen H, Yao Z, Pan J, Gu J, Tang B, Wang HG, Yu B, Tong YG, Zou QM, Mao XH (- 3) Ref: Journal of Bacteriology, 194:6604, 2012 : PubMed ESTHER: Fang_2012_J.Bacteriol_194_6604 PubMedSearch: Fang 2012 J.Bacteriol 194 6604 PubMedID: 23144371 Gene_locus related to this paper: burma-a5tq93, burma-q62mq7 Abstract Melioidosis, caused by Burkholderia pseudomallei, is considered to be endemic to Northern Australia and Southeast Asia, with high mortality and relapse rates, regardless of powerful antibiotic therapy. Here we report the first genome sequence of Burkholderia pseudomallei strain BPC006, obtained from a melioidosis patient in Hainan, China. The genome sizes of the 2 chromosomes were determined to be 4,001,777 bp and 3,153,284 bp. Title: Acetylcholinesterase, a key prognostic predictor for hepatocellular carcinoma, suppresses cell growth and induces chemosensitization Zhao Y, Wang X, Wang T, Hu X, Hui X, Yan M, Gao Q, Chen T, Li J and He X <4 more author(s)> Zhao Y, Wang X, Wang T, Hu X, Hui X, Yan M, Gao Q, Chen T, Li J, Yao M, Wan D, Gu J, Fan J, He X (- 4) Ref: Hepatology, 53:493, 2011 : PubMed ESTHER: Zhao_2011_Hepatology_53_493 PubMedSearch: Zhao 2011 Hepatology 53 493 PubMedID: 21274871 Abstract UNLABELLED: Acetylcholinesterase (ACHE) plays important roles in the cholinergic system, and its dysregulation is involved in a variety of human diseases. However, the roles and implications of ACHE in hepatocellular carcinoma (HCC) remain elusive. Here we demonstrate that ACHE was significantly down-regulated in the cancerous tissues of 69.2% of HCC patients, and the low ACHE expression in HCC was correlated with tumor aggressiveness, an elevated risk of postoperative recurrence, and a low survival rate. Both the recombinant ACHE protein and the enhanced expression of ACHE significantly inhibited HCC cell growth in vitro and tumorigenicity in vivo. Further study showed that ACHE suppressed cell proliferation via its enzymatic activity of acetylcholine catalysis and degradation. Moreover, ACHE could inactivate mitogen-activated protein kinase and phosphatidyl inositol-3'-phosphate kinase/protein kinase B pathways in HCC cells and thereby increase the activation of glycogen synthase kinase 3beta and lead to beta-catenin degradation and cyclin D1 suppression. In addition, increased ACHE expression could remarkably sensitize HCC cells to chemotherapeutic drugs (i.e., adriamycin and etoposide). CONCLUSION: For the first time, we describe the function of ACHE as a tumor growth suppressor in regulating cell proliferation, the relevant signaling pathways, and the drug sensitivity of HCC cells. ACHE is a promising independent prognostic predictor for HCC recurrence and the survival of HCC patients. These findings provide new insights into potential strategies for drug discovery and improved HCC treatment. Title: Heteromeric co-assembly of two insect nicotinic acetylcholine receptor alpha subunits: influence on sensitivity to neonicotinoid insecticides Liu Z, Han Z, Zhang Y, Song F, Yao X, Liu S, Gu J, Millar NS Ref: Journal of Neurochemistry, 108:498, 2009 : PubMed ESTHER: Liu_2009_J.Neurochem_108_498 PubMedSearch: Liu 2009 J.Neurochem 108 498 PubMedID: 19046356 Abstract Neonicotinoid insecticides, such as imidacloprid, are selective agonists of insect nicotinic acetylcholine receptors (nAChRs) and are used extensively in areas of crop protection and animal health to control a variety of insect pest species. Here, we describe studies performed with nAChR subunits Nlalpha1 and Nlalpha2 cloned from the brown planthopper Nilaparvata lugens, a major insect pest of rice crops in many parts of Asia. The influence of Nlalpha1 and Nlalpha2 subunits upon the functional properties of recombinant nAChRs has been examined by expression in Xenopus oocytes. In addition, the influence of a Nlalpha1 mutation (Y151S), which has been linked to neonicotinoid lab generated resistance in N. lugens, has been examined. As in previous studies of insect alpha subunits, functional expression has been achieved by co-expression with the mammalian beta2 subunit. This approach has revealed a significantly higher apparent affinity of imidacloprid for Nlalpha1/beta2 than for Nlalpha2/beta2 nAChRs. In addition, evidence has been obtained for the co-assembly of Nlalpha1 and Nlalpha2 subunits into 'triplet' nAChRs of subunit composition Nlalpha1/Nlalpha2/beta2. Evidence has also been obtained which demonstrates that the resistance-associated Y151S mutation has a significantly reduced effect on neonicotinoid agonist activity when Nlalpha1 is co-assembled with Nlalpha2 than when expressed as the sole alpha subunit in a heteromeric nAChR. These findings may be of importance in assessing the likely impact of the target-site mutations such as Y151S upon neonicotinoid insecticide resistance in insect field populations. Title: Molecular cloning and characterization of a juvenile hormone esterase gene from brown planthopper, Nilaparvata lugens Liu S, Yang B, Gu J, Yao X, Zhang Y, Song F, Liu Z Ref: J Insect Physiol, 54:1495, 2008 : PubMed ESTHER: Liu_2008_J.Insect.Physiol_54_1495 PubMedSearch: Liu 2008 J.Insect.Physiol 54 1495 PubMedID: 18804476 Gene_locus related to this paper: nillu-b8q962 Abstract Juvenile hormone (JH) plays key roles in the regulation of growth, development, diapause and reproduction in insects, and juvenile hormone esterase (JHE) plays an important role in regulating JH titers. We obtained a full-length cDNA encoding JHE in Nilaparvata lugens (NlJHE), the first JHE gene cloned from the hemipteran insects. The deduced protein sequence of Nljhe contains the five conserved motifs identified in JHEs of other insect species, including a consensus GQSAG motif that is required for the enzymatic activity of JHE proteins. Nljhe showed high amino acid similarities with Athalia rosae JHE (40%) and Apis mellifera JHE (39%). Recombinant NlJHE protein expressed in the baculovirus expression system hydrolyzed [3H] JH III at high activity and yielded the specificity constants (kcat/KM=4.28x10(6) M(-1) s(-1)) close to those of the validated JHEs from other insect species, indicating that Nljhe cDNA encodes a functional JH esterase. The Nljhe transcript was expressed mainly in the fat body and the expression level reached a peak at 48 h after ecdysis of the 5th instar nymphs. In the 5th instar, macropterous insects showed significantly higher Nljhe mRNA levels and JHE activities, but much lower JH III levels, than those detected in the brachypterous insects soon after ecdysis and at 48 h after ecdysis. These data suggest that NlJHE might play important roles in regulation of JH levels and wing form differentiation. Title: Theoretical modeling study for the phosphonylation mechanisms of the catalytic triad of acetylcholinesterase by sarin Wang J, Gu J, Leszczynski J Ref: J Phys Chem B, 112:3485, 2008 : PubMed ESTHER: Wang_2008_J.Phys.Chem.B_112_3485 PubMedSearch: Wang 2008 J.Phys.Chem.B 112 3485 PubMedID: 18303880 Abstract Potential energy surfaces for the process of phosphonylation of the catalytic triad of acetylcholinesterase by sarin have been explored at the B3LYP/6-311G(d,p) level of theory through a computational study. It is concluded that the phosphonylation process involves a critical addition-elimination mechanism. The first nucleophilic addition process is the rate-determining step. The following elimination process of the fluoride ion comprises a composite reaction that includes several steps, and it occurs rapidly by comparison with the rate-determining step. The mobility characteristics of histidine play an important role in the reaction. A double proton-transfer mechanism is proposed for the catalytic triad during the phosphonylation process of sarin on AChE. The effect of aqueous solvation has been considered via the polarizable continuum model (PCM). One concludes that the energy barriers are generally lowered in solvent, compared to the gas-phase reactions. Title: The DNA sequence, annotation and analysis of human chromosome 3 Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A and Gibbs RA <100 more author(s)> Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA (- 100) Ref: Nature, 440:1194, 2006 : PubMed ESTHER: Muzny_2006_Nature_440_1194 PubMedSearch: Muzny 2006 Nature 440 1194 PubMedID: 16641997 Gene_locus related to this paper: human-AADAC, human-AADACL2, human-ABHD5, human-ABHD6, human-ABHD10, human-ABHD14A, human-APEH, human-BCHE, human-CIB, human-LIPH, human-MGLL, human-NLGN1, human-PLA1A Abstract After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion. Title: Phosphonylation mechanisms of sarin and acetylcholinesterase: a model DFT study Wang J, Gu J, Leszczynski J Ref: J Phys Chem B, 110:7567, 2006 : PubMed ESTHER: Wang_2006_J.Phys.Chem.B_110_7567 PubMedSearch: Wang 2006 J.Phys.Chem.B 110 7567 PubMedID: 16599539 Abstract Potential energy surfaces for the phosphonylation of sarin and acetylcholinesterase (AChE) have been theoretically studied at the B3LYP/6-311G(d,p) level of theory. The obtained results show that the phosphonylation process involves a two-step addition-elimination mechanism, with the first step (addition process) being the rate-determining step, while by comparison, the ensuing steps are very rapid. Stable trigonal bipyramidal intermediates are formed in the studied pathways. It is also revealed that the catalytic triad of acetylcholinesterase plays the catalytic role in the reaction by speeding up the phosphonylation process, as it does in the acylation reaction of ACh and AChE. The effect of aqueous solvation was accounted for via the polarizable continuum model. It is concluded that the enzymatic reaction here is influenced strongly by the solvent environment. Title: Hydrogen-bonding interactions in the binding of loop 1 of fasciculin 2 to Torpedo californica acetylcholinesterase: a density functional theory study Wang J, Gu J, Leszczynski J Ref: J Phys Chem B Condens Matter Mater Surf Interfaces Biophys, 109:13761, 2005 : PubMed ESTHER: Wang_2005_J.Phys.Chem.B.Condens.Matter.Mater.Surf.Interfaces.Biophys_109_13761 PubMedSearch: Wang 2005 J.Phys.Chem.B.Condens.Matter.Mater.Surf.Interfaces.Biophys 109 13761 PubMedID: 16852724 Abstract In the present study, the interactions of model complexes at the interface between loop1 of fasciculin 2 (Fas2) and acetylcholinesterase (AChE) are theoretically explored. Three interaction models based upon the crystal structure of the complex of Fas2 with AChE from Torpedo californica (PDB code ) were fully optimized at the B3LYP/6-311G(d,p) level of theory. The atoms-in-molecules (AIM) approach was employed to characterize the corresponding noncovalent hydrogen bonds through the densities and the Laplacians of electron densities at the bond critical points. The total interaction energy of loop 1 (Fas2) with AChE is predicted to be -99.4 kcal/mol. It is concluded that the Fas2 residue Thr8, which contributes more than half of the total binding energy, plays the most important role among the three binding sites. The energy decomposition results through the Kitaura-Morokuma scheme suggest that the electrostatic term is the major component of the entire interaction energy. The positive cooperativity effect revealed in the Thr8(F)-related models was confirmed through the geometry characteristics, AIM results, and the energy decomposition analysis. Title: Large-scale cDNA transfection screening for genes related to cancer development and progression Wan D, Gong Y, Qin W, Zhang P, Li J, Wei L, Zhou X, Li H, Qiu X and Gu J <15 more author(s)> Wan D, Gong Y, Qin W, Zhang P, Li J, Wei L, Zhou X, Li H, Qiu X, Zhong F, He L, Yu J, Yao G, Jiang H, Qian L, Yu Y, Shu H, Chen X, Xu H, Guo M, Pan Z, Chen Y, Ge C, Yang S, Gu J (- 15) Ref: Proc Natl Acad Sci U S A, 101:15724, 2004 : PubMed ESTHER: Wan_2004_Proc.Natl.Acad.Sci.U.S.A_101_15724 PubMedSearch: Wan 2004 Proc.Natl.Acad.Sci.U.S.A 101 15724 PubMedID: 15498874 Abstract A large-scale assay was performed by transfecting 29,910 individual cDNA clones derived from human placenta, fetus, and normal liver tissues into human hepatoma cells and 22,926 cDNA clones into mouse NIH 3T3 cells. Based on the results of colony formation in hepatoma cells and foci formation in NIH 3T3 cells, 3,806 cDNA species (8,237 clones) were found to possess the ability of either stimulating or inhibiting cell growth. Among them, 2,836 (6,958 clones) were known genes, 372 (384 clones) were previously unrecognized genes, and 598 (895 clones) were unigenes of uncharacterized structure and function. A comprehensive analysis of the genes and the potential mechanisms for their involvement in the regulation of cell growth is provided. The genes were classified into four categories: I, genes related to the basic cellular mechanism for growth and survival; II, genes related to the cellular microenvironment; III, genes related to host-cell systemic regulation; and IV, genes of miscellaneous function. The extensive growth-regulatory activity of genes with such highly diversified functions suggests that cancer may be related to multiple levels of cellular and systemic controls. The present assay provides a direct genomewide functional screening method. It offers a better understanding of the basic machinery of oncogenesis, including previously undescribed systemic regulatory mechanisms, and also provides a tool for gene discovery with potential clinical applications. Title: Liver-specific deletion of the NADPH-cytochrome P450 reductase gene: impact on plasma cholesterol homeostasis and the function and regulation of microsomal cytochrome P450 and heme oxygenase Gu J, Weng Y, Zhang QY, Cui H, Behr M, Wu L, Yang W, Zhang L, Ding X Ref: Journal of Biological Chemistry, 278:25895, 2003 : PubMed ESTHER: Gu_2003_J.Biol.Chem_278_25895 PubMedSearch: Gu 2003 J.Biol.Chem 278 25895 PubMedID: 12697746 Abstract A mouse model with liver-specific deletion of the NADPH-cytochrome P450 reductase (Cpr) gene (designated Alb-Cre/Cprlox mice) was generated and characterized in this study. Hepatic microsomal CPR expression was significantly reduced at 3 weeks and was barely detectable at 2 months of age in the Alb-Cre+/-/Cprlox+/+ (homozygous) mice, with corresponding decreases in liver microsomal cytochrome P450 (CYP) and heme oxygenase (HO) activities, in pentobarbital clearance, and in total plasma cholesterol level. Nevertheless, the homozygous mice are fertile and are normal in gross appearance and growth rate. However, at 2 months, although not at 3 weeks, the homozygotes had significant increases in liver weight, accompanied by hepatic lipidosis and other pathologic changes. Intriguingly, total microsomal CYP content was increased in the homozygotes about 2-fold at 3 weeks and about 3-fold at 2 months of age; at 2 months, there were varying degrees of induction in protein (1-5-fold) and mRNA expression (0-67-fold) for all CYPs examined. There was also an induction of HO-1 protein (nearly 9-fold) but no induction of HO-2. These data indicate the absence of significant alternative redox partners for liver microsomal CYP and HO, provide in vivo evidence for the significance of hepatic CPR-dependent enzymes in cholesterol homeostasis and systemic drug clearance, and reveal novel regulatory pathways of CYP expression associated with altered cellular homeostasis. The Alb-Cre/Cprlox mouse represents a unique model for studying the in vivo function of hepatic HO and microsomal CYP-dependent pathways in the biotransformation of endogenous and xenobiotic compounds. Title: Sequence and analysis of rice chromosome 4 Feng Q, Zhang Y, Hao P, Wang S, Fu G, Huang Y, Li Y, Zhu J, Liu Y and Han B <61 more author(s)> Feng Q, Zhang Y, Hao P, Wang S, Fu G, Huang Y, Li Y, Zhu J, Liu Y, Hu X, Jia P, Zhao Q, Ying K, Yu S, Tang Y, Weng Q, Zhang L, Lu Y, Mu J, Zhang LS, Yu Z, Fan D, Liu X, Lu T, Li C, Wu Y, Sun T, Lei H, Li T, Hu H, Guan J, Wu M, Zhang R, Zhou B, Chen Z, Chen L, Jin Z, Wang R, Yin H, Cai Z, Ren S, Lv G, Gu W, Zhu G, Tu Y, Jia J, Chen J, Kang H, Chen X, Shao C, Sun Y, Hu Q, Zhang X, Zhang W, Wang L, Ding C, Sheng H, Gu J, Chen S, Ni L, Zhu F, Chen W, Lan L, Lai Y, Cheng Z, Gu M, Jiang J, Li J, Hong G, Xue Y, Han B (- 61) Ref: Nature, 420:316, 2002 : PubMed ESTHER: Feng_2002_Nature_420_316 PubMedSearch: Feng 2002 Nature 420 316 PubMedID: 12447439 Gene_locus related to this paper: orysa-Q7XTC5, orysa-Q7F959, orysa-q7f9i3, orysa-q7x7y5, orysa-q7xkj9, orysa-q7xr62, orysa-q7xr63, orysa-q7xr64, orysa-q7xsg1, orysa-q7xsq2, orysa-Q7XTM8, orysa-q7xts6, orysa-q7xue7, orysa-q7xv53, orysa-Q7XVB5, orysa-Q7XVG5, orysj-q0jaf0, orysj-q7f8x1 Abstract Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis. Title: Expression of biotransformation enzymes in human fetal olfactory mucosa: potential roles in developmental toxicity Gu J, Su T, Chen Y, Zhang QY, Ding X Ref: Toxicol Appl Pharmacol, 165:158, 2000 : PubMed ESTHER: Gu_2000_Toxicol.Appl.Pharmacol_165_158 PubMedSearch: Gu 2000 Toxicol.Appl.Pharmacol 165 158 PubMedID: 10828211 Abstract High levels of cytochrome P450 are present in the olfactory mucosa (OM) in mammalian animals and contribute to the known tissue-selective toxicity of numerous chemical compounds. Olfactory toxicity in the perinatal period may have a greater impact on behavior, growth, and development than in adults. To establish a molecular basis for determining the risk of developmental toxicity in OM, the expression of several cytochrome P450 enzymes, as well as NADPH-cytochrome P450 reductase and microsomal epoxide hydrolase, was examined in hepatic and nasal microsomes prepared from human fetal tissues at gestational day 91-125. The relative microsomal concentrations of these biotransformation enzymes were determined on immunoblots. Expression of CYP2A, CYP2J2, the reductase, and epoxide hydrolase was detected in both OM and liver. The microsomal levels of these enzymes were generally lower in OM than in liver of the same fetuses, except for the CYP2A-related proteins, which were expressed in OM at much higher levels. OM expression of CYP2A6, CYP2A13, CYP2B6, and CYP2J2 mRNAs was detected using RNA-PCR. These results document, for the first time, prenatal expression of xenobiotic-bioactivating cytochrome P450 enzymes in human OM and suggest that the human fetal OM may be a preferred target tissue for the toxicity of maternally derived chemical compounds that are activated by the CYP2A enzymes. Title: Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB and Chen JL <19 more author(s)> Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL (- 19) Ref: Proc Natl Acad Sci U S A, 97:9543, 2000 : PubMed ESTHER: Hu_2000_Proc.Natl.Acad.Sci.U.S.A_97_9543 PubMedSearch: Hu 2000 Proc.Natl.Acad.Sci.U.S.A 97 9543 PubMedID: 10931946 Gene_locus related to this paper: human-ESD Abstract The primary neuroendocrine interface, hypothalamus and pituitary, together with adrenals, constitute the major axis responsible for the maintenance of homeostasis and the response to the perturbations in the environment. The gene expression profiling in the human hypothalamus-pituitary-adrenal axis was catalogued by generating a large amount of expressed sequence tags (ESTs), followed by bioinformatics analysis (http://www.chgc.sh.cn/ database). Totally, 25,973 sequences of good quality were obtained from 31,130 clones (83.4%) from cDNA libraries of the hypothalamus, pituitary, and adrenal glands. After eliminating 5,347 sequences corresponding to repetitive elements and mtDNA, 20,626 ESTs could be assembled into 9, 175 clusters (3,979, 3,074, and 4,116 clusters in hypothalamus, pituitary, and adrenal glands, respectively) when overlapping ESTs were integrated. Of these clusters, 2,777 (30.3%) corresponded to known genes, 4,165 (44.8%) to dbESTs, and 2,233 (24.3%) to novel ESTs. The gene expression profiles reflected well the functional characteristics of the three levels in the hypothalamus-pituitary-adrenal axis, because most of the 20 genes with highest expression showed statistical difference in terms of tissue distribution, including a group of tissue-specific functional markers. Meanwhile, some findings were made with regard to the physiology of the axis, and 200 full-length cDNAs of novel genes were cloned and sequenced. All of these data may contribute to the understanding of the neuroendocrine regulation of human life. Title: Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY and Chen Z <11 more author(s)> Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (- 11) Ref: Genome Res, 10:1546, 2000 : PubMed ESTHER: Zhang_2000_Genome.Res_10_1546 PubMedSearch: Zhang 2000 Genome.Res 10 1546 PubMedID: 11042152 Gene_locus related to this paper: human-LYPLA1 Abstract Three hundred cDNAs containing putatively entire open reading frames (ORFs) for previously undefined genes were obtained from CD34+ hematopoietic stem/progenitor cells (HSPCs), based on EST cataloging, clone sequencing, in silico cloning, and rapid amplification of cDNA ends (RACE). The cDNA sizes ranged from 360 to 3496 bp and their ORFs coded for peptides of 58-752 amino acids. Public database search indicated that 225 cDNAs exhibited sequence similarities to genes identified across a variety of species. Homology analysis led to the recognition of 50 basic structural motifs/domains among these cDNAs. Genomic exon-intron organization could be established in 243 genes by integration of cDNA data with genome sequence information. Interestingly, a new gene named as HSPC070 on 3p was found to share a sequence of 105bp in 3' UTR with RAF gene in reversed transcription orientation. Chromosomal localizations were obtained using electronic mapping for 192 genes and with radiation hybrid (RH) for 38 genes. Macroarray technique was applied to screen the gene expression patterns in five hematopoietic cell lines (NB4, HL60, U937, K562, and Jurkat) and a number of genes with differential expression were found. The resource work has provided a wide range of information useful not only for expression genomics and annotation of genomic DNA sequence, but also for further research on the function of genes involved in hematopoietic development and differentiation. Title: Cytochrome P450 and steroid hydroxylase activity in mouse olfactory and vomeronasal mucosa Gu J, Dudley C, Su T, Spink DC, Zhang QY, Moss RL, Ding X Ref: Biochemical & Biophysical Research Communications, 266:262, 1999 : PubMed ESTHER: Gu_1999_Biochem.Biophys.Res.Commun_266_262 PubMedSearch: Gu 1999 Biochem.Biophys.Res.Commun 266 262 PubMedID: 10581200 Abstract The aims of this study are to identify the sex steroid-metabolizing cytochrome P450 enzymes of the vomeronasal organ (VNO) and to determine the activities of VNO microsomes to metabolize estradiol, progesterone, and testosterone. Several P450 isoforms, including CYP1A2, CYP2A, CYP2B, CYP2C, CYP2G1, and CYP3A, NADPH P450-reductase, and microsomal epoxide hydrolase were detected in mouse VNO, although their expression levels were much lower than those in the main olfactory epithelium. VNO microsomes were active toward the three steroid hormones, producing metabolite profiles similar to those seen with olfactory mucosal microsomes. Thus, the mammalian VNO, a steroid hormone target tissue, contains multiple steroid-metabolizing P450 isoforms and is capable of metabolic disposition of the three major sex steroid hormones. These findings support the proposed roles of olfactory mucosal and VNO microsomal P450 enzymes in maintaining cellular hormonal homeostasis and other perireceptor processes associated with olfactory chemosensory function. | |||||||
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